FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hitosugi, T Kang, SK Heiden, MGV Chung, TW Elf, S Lythgoe, K Dong, SZ Lonial, S Wang, X Chen, GZ Xie, JX Gu, TL Polakiewicz, RD Roesel, JL Boggon, TJ Khuri, FR Gilliland, DG Cantley, LC Kaufman, J Chen, J AF Hitosugi, Taro Kang, Sumin Heiden, Matthew G. Vander Chung, Tae-Wook Elf, Shannon Lythgoe, Katherine Dong, Shaozhong Lonial, Sagar Wang, Xu Chen, Georgia Z. Xie, Jianxin Gu, Ting-Lei Polakiewicz, Roberto D. Roesel, Johannes L. Boggon, Titus J. Khuri, Fadlo R. Gilliland, D. Gary Cantley, Lewis C. Kaufman, Jonathan Chen, Jing TI Tyrosine Phosphorylation Inhibits PKM2 to Promote the Warburg Effect and Tumor Growth SO SCIENCE SIGNALING LA English DT Article ID KINASE TYPE M2; PYRUVATE-KINASE; FACTOR RECEPTOR; HUMAN BREAST; CANCER; EXPRESSION; FGFR1; METABOLISM; PROTEIN; ZNF198 AB The Warburg effect describes a pro-oncogenic metabolism switch such that cancer cells take up more glucose than normal tissue and favor incomplete oxidation of glucose even in the presence of oxygen. To better understand how tyrosine kinase signaling, which is commonly increased in tumors, regulates the Warburg effect, we performed phosphoproteomic studies. We found that oncogenic forms of fibroblast growth factor receptor type 1 inhibit the pyruvate kinase M2 (PKM2) isoform by direct phosphorylation of PKM2 tyrosine residue 105 (Y(105)). This inhibits the formation of active, tetrameric PKM2 by disrupting binding of the PKM2 cofactor fructose-1,6-bisphosphate. Furthermore, we found that phosphorylation of PKM2 Y(105) is common in human cancers. The presence of a PKM2 mutant in which phenylalanine is substituted for Y(105) (Y105F) in cancer cells leads to decreased cell proliferation under hypoxic conditions, increased oxidative phosphorylation with reduced lactate production, and reduced tumor growth in xenografts in nude mice. Our findings suggest that tyrosine phosphorylation regulates PKM2 to provide a metabolic advantage to tumor cells, thereby promoting tumor growth. C1 [Hitosugi, Taro; Kang, Sumin; Chung, Tae-Wook; Elf, Shannon; Lythgoe, Katherine; Dong, Shaozhong; Lonial, Sagar; Wang, Xu; Chen, Georgia Z.; Khuri, Fadlo R.; Kaufman, Jonathan; Chen, Jing] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USA. [Heiden, Matthew G. Vander; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. [Heiden, Matthew G. Vander; Gilliland, D. Gary; Cantley, Lewis C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Xie, Jianxin; Gu, Ting-Lei; Polakiewicz, Roberto D.] Cell Signaling Technol Inc, Danvers, MA 01923 USA. [Roesel, Johannes L.] Novartis Pharma AG, CH-4002 Basel, Switzerland. [Boggon, Titus J.] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA. [Gilliland, D. Gary] Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Chen, J (reprint author), Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USA. EM jchen@emory.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [R01 CA120272-03, CA120272, R01 CA120272, R01 CA120272-01, R01 CA120272-02, R01 CA120272-04, R01 CA140515, T32 CA009172]; NIGMS NIH HHS [R01 GM056203] NR 25 TC 288 Z9 301 U1 9 U2 60 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD NOV 17 PY 2009 VL 2 IS 97 AR ra73 DI 10.1126/scisignal.2000431 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 570AZ UT WOS:000275645300003 PM 19920251 ER PT J AU Susa, M Iyer, AK Ryu, K Hornicek, FJ Mankin, H Amiji, MM Duan, ZF AF Susa, Michiro Iyer, Arun K. Ryu, Keinosuke Hornicek, Francis J. Mankin, Henry Amiji, Mansoor M. Duan, Zhenfeng TI Doxorubicin loaded Polymeric Nanoparticulate Delivery System to overcome drug resistance in osteosarcoma SO BMC CANCER LA English DT Article ID COPOLYMER-BOUND DOXORUBICIN; MULTIDRUG-RESISTANCE; OVARIAN-CARCINOMA; CYCLOSPORINE-A; CANCER-CELLS; MDR1 GENE; TUMOR; DAUNOMYCIN; REVERSAL; ACCUMULATION AB Background: Drug resistance is a primary hindrance for the efficiency of chemotherapy against osteosarcoma. Although chemotherapy has improved the prognosis of osteosarcoma patients dramatically after introduction of neo-adjuvant therapy in the early 1980's, the outcome has since reached plateau at approximately 70% for 5 year survival. The remaining 30% of the patients eventually develop resistance to multiple types of chemotherapy. In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure incurred from multidrug resistant (MDR) tumor cells, we explored the possibility of loading doxorubicin onto biocompatible, lipid-modified dextran-based polymeric nanoparticles and evaluated the efficacy. Methods: Doxorubicin was loaded onto a lipid-modified dextran based polymeric nano-system. The effect of various concentrations of doxorubicin alone or nanoparticle loaded doxorubicin on KHOS, KHOS(R2), U-2OS, and U-2OS(R2) cells was analyzed. Effects on drug retention, immunofluorescence, Pgp expression, and induction of apoptosis were also analyzed. Results: Dextran nanoparticles loaded with doxorubicin had a curative effect on multidrug resistant osteosarcoma cell lines by increasing the amount of drug accumulation in the nucleus via Pgp independent pathway. Nanoparticles loaded with doxorubicin also showed increased apoptosis in osteosarcoma cells as compared with doxorubicin alone. Conclusion: Lipid-modified dextran nanoparticles loaded with doxorubicin showed pronounced anti-proliferative effects against osteosarcoma cell lines. These findings may lead to new treatment options for MDR osteosarcoma. C1 [Susa, Michiro; Ryu, Keinosuke; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Susa, Michiro; Ryu, Keinosuke; Hornicek, Francis J.; Mankin, Henry; Duan, Zhenfeng] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, Boston, MA 02114 USA. [Iyer, Arun K.; Amiji, Mansoor M.] Northeastern Univ, Sch Pharm, Dept Pharmaceut Sci, Boston, MA 02115 USA. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. EM msusa@partners.org; arun.iyer@radiology.ucsf.edu; kryu@partners.org; fhornicek@partners.org; hmankin@partners.org; m.amiji@neu.edu; zduan@partners.org RI Susa, Michiro/L-2291-2013; Amiji, Mansoor/A-4365-2014; OI Amiji, Mansoor/0000-0001-6170-881X; Iyer, Arun/0000-0002-4428-0222 FU National Cancer Institute, NIH [R01-CA119617]; Sarcoma Foundation of America; Gattegno and Wechsler funds FX This project was supported, in part, by a grant from the National Cancer Institute, NIH (Nanotechnology Platform Partnership), R01-CA119617. Dr. Duan is supported, in part, through a grant from Sarcoma Foundation of America. Support has also been provided by the Gattegno and Wechsler funds. NR 45 TC 74 Z9 76 U1 8 U2 45 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD NOV 16 PY 2009 VL 9 AR 399 DI 10.1186/1471-2407-9-399 PG 12 WC Oncology SC Oncology GA 527AR UT WOS:000272338700003 PM 19917123 ER PT J AU Ganz, DA Yano, EM Saliba, D Shekelle, PG AF Ganz, David A. Yano, Elizabeth M. Saliba, Debra Shekelle, Paul G. TI Design of a continuous quality improvement program to prevent falls among community-dwelling older adults in an integrated healthcare system SO BMC HEALTH SERVICES RESEARCH LA English DT Article ID VULNERABLE ELDERS; MOBILITY PROBLEMS; CONTROLLED-TRIAL; METAANALYSIS; MANAGEMENT; PEOPLE; RISK; IMPLEMENTATION; ORGANIZATIONS; INTERVENTIONS AB Background: Implementing quality improvement programs that require behavior change on the part of health care professionals and patients has proven difficult in routine care. Significant randomized trial evidence supports creating fall prevention programs for community-dwelling older adults, but adoption in routine care has been limited. Nationally-collected data indicated that our local facility could improve its performance on fall prevention in community-dwelling older people. We sought to develop a sustainable local fall prevention program, using theory to guide program development. Methods: We planned program development to include important stakeholders within our organization. The theory-derived plan consisted of 1) an initial leadership meeting to agree on whether creating a fall prevention program was a priority for the organization, 2) focus groups with patients and health care professionals to develop ideas for the program, 3) monthly workgroup meetings with representatives from key departments to develop a blueprint for the program, 4) a second leadership meeting to confirm that the blueprint developed by the workgroup was satisfactory, and also to solicit feedback on ideas for program refinement. Results: The leadership and workgroup meetings occurred as planned and led to the development of a functional program. The focus groups did not occur as planned, mainly due to the complexity of obtaining research approval for focus groups. The fall prevention program uses an existing telephonic nurse advice line to 1) place outgoing calls to patients at high fall risk, 2) assess these patients' risk factors for falls, and 3) triage these patients to the appropriate services. The workgroup continues to meet monthly to monitor the progress of the program and improve it. Conclusion: A theory-driven program development process has resulted in the successful initial implementation of a fall prevention program. C1 [Ganz, David A.; Yano, Elizabeth M.; Saliba, Debra; Shekelle, Paul G.] VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA 91343 USA. [Ganz, David A.; Saliba, Debra] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Ganz, David A.; Saliba, Debra; Shekelle, Paul G.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90095 USA. [Saliba, Debra] Univ Calif Los Angeles, Borun Ctr Gerontol Res, Los Angeles, CA 90095 USA. RP Ganz, DA (reprint author), VA Greater Los Angeles HSR&D Ctr Excellence, 16111 Plummer St, Sepulveda, CA 91343 USA. EM David.Ganz@va.gov; Elizabeth.Yano@va.gov; Debra.Saliba@va.gov; Paul.Shekelle@va.gov FU U. S. Department of Veterans Affairs; 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]; UCLA Older Americans Independence Center; NIH/NIA [P30-AG028748]; Greater Los Angeles VA Health Services Research & Development Center of Excellence [LIP 65-150] FX The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the U. S. Department of Veterans NR 30 TC 11 Z9 12 U1 4 U2 13 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 NOV 16 PY 2009 VL 9 AR 206 DI 10.1186/1472-6963-9-206 PG 11 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 521LA UT WOS:000271921700001 PM 19917122 ER PT J AU Johnson, AS Fisher, RJ Weir, GC Colton, CK AF Johnson, Amy S. Fisher, Robert J. Weir, Gordon C. Colton, Clark K. TI Oxygen consumption and diffusion in assemblages of respiring spheres: Performance enhancement of a bioartificial pancreas SO CHEMICAL ENGINEERING SCIENCE LA English DT Article DE Bioartificial pancreas; Islets; Oxygen consumption; Reaction-diffusion models; Encapsulation; Biomedical engineering; Mathematical modeling; Numerical analysis ID ISLET CELLS; INSULIN RELEASE; MASS-TRANSFER; BLOOD-FLOW; BETA-CELLS; RAT; TRANSPLANTATION; ENCAPSULATION; LANGERHANS; TENSION AB Microencapsulation provides an immune barrier for transplanted islets of Langerhans to treat diabetes, but it imposes oxygen diffusional limitations that can result in loss of viability and function. We investigate two methods to reduce oxygen transport limitations: (1) enhancement of the encapsulant oxygen permeability, for example, by combination of a highly concentrated perfluorocarbon (PFC) emulsion with alginate (PFC alginate); and (2) reduction of islet tissue size, for example, by dispersing the islets into single cells followed by reaggregation into cell clusters smaller than the original islet. A theoretical reaction-diffusion model is used to predict the three-dimensional distribution of oxygen partial pressure in a spherical microcapsule and a planar slab containing islet tissue, from which the loss of cell viability and the reduction in insulin secretion rate is estimated. Numerical simulations are carried out for normal alginate and PFC alginate to examine the effect of surface oxygen partial pressure, capsule diameter, slab thickness, and the size and density of dispersed islet tissue. Results show that hypoxic conditions can be reduced, thereby enhancing islet viability and substantially maintaining insulin secretion rate when PFC emulsion is incorporated in the encapsulation material or when smaller islet cell aggregates are used in both types of geometries. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Johnson, Amy S.; Fisher, Robert J.; Colton, Clark K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Weir, Gordon C.] Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. RP Colton, CK (reprint author), MIT, Dept Chem Engn, Room 66-452,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM amyl@mit.edu; rjfisher@mit.edu; gordon.weir@joslin.harvard.edu; ckcolton@mit.edu FU NIH [R01 DK50657, R01-DK063108-01A1]; NCRR ICR [U4Z 16606]; JDRF Center for Islet Transplantation FX This work was supported by grants from the NIH (R01 DK50657, R01-DK063108-01A1, and NCRR ICR U4Z 16606) and the JDRF Center for Islet Transplantation at Harvard Medical School. NR 59 TC 25 Z9 25 U1 2 U2 25 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0009-2509 J9 CHEM ENG SCI JI Chem. Eng. Sci. PD NOV 16 PY 2009 VL 64 IS 22 SI SI BP 4470 EP 4487 DI 10.1016/j.ces.2009.06.028 PG 18 WC Engineering, Chemical SC Engineering GA 513CG UT WOS:000271299200003 ER PT J AU Merchant, FM Noseworthy, PA Weiner, RB Singh, SM Ruskin, JN Reddy, VY AF Merchant, Faisal M. Noseworthy, Peter A. Weiner, Rory B. Singh, Sheldon M. Ruskin, Jeremy N. Reddy, Vivek Y. TI Ability of Terminal QRS Notching to Distinguish Benign from Malignant Electrocardiographic Forms of Early Repolarization SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MONOMORPHIC VENTRICULAR-TACHYCARDIA; BRUGADA-SYNDROME; CLINICAL-SIGNIFICANCE; CELLULAR BASIS AB Recent studies have suggested that early repolarization (ER) might be associated with up to 1/3 of idiopathic ventricular tachycardia/ventricular fibrillation (VT/VF) cases ("malignant" ER). We sought to identify electrocardiographic features to distinguish benign from malignant variants of ER. We reviewed the medical records for implantable-cardioverter defibrillators implanted at a single institution (1988 to 2008) to identify cases of idiopathic VT/VF. The electrocardiograms were scored for ER, defined as a >= 0.1-mV elevation of the QRS-ST junction manifesting as J-point slurring or notching in 2 contiguous leads. We also identified a cohort of 200 healthy age- and gender-matched controls with electrocardiographic findings previously identified as normal ER ("benign" ER cohort). Of 1,224 consecutive implantable-cardioverter defibrillator implants, we identified 39 cases of idiopathic VT/VF. Of the 39 cases, 9 (23%) demonstrated ER. During a mean follow-up of 7.2 +/- 4.6 years, the combined end point of appropriate implantable-cardioverter defibrillator shocks or all-cause mortality occurred less frequently in cases of idiopathic VT/VF with ER than in those without ER (11% vs 30%, odds ratio 0.29, 95% confidence interval 0.03 to 2.69, p = 0.40). A comparison of the electrocardiograms between those with malignant ER and controls demonstrated that QRS notching was significantly more prevalent among cases when present in leads V4 (44% vs 5%, p = 0.001) and V5 (44% vs 8%, p = 0.006), with a similar trend in lead V6 (33% vs 5%, p = 0.013). In conclusion, left precordial terminal QRS notching is more prevalent in malignant variants of ER than in benign cases. These findings could have important implications for risk stratification of patients with ER. (c) 2009 Elsevier Inc. All rights reserved. (Am J Cardiol 2009;104:1402-1406) C1 [Reddy, Vivek Y.] Mt Sinai Sch Med, Div Cardiol, New York, NY USA. [Merchant, Faisal M.; Noseworthy, Peter A.; Weiner, Rory B.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Singh, Sheldon M.; Ruskin, Jeremy N.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Singh, Sheldon M.; Ruskin, Jeremy N.] Harvard Univ, Sch Med, Boston, MA USA. RP Reddy, VY (reprint author), Mt Sinai Sch Med, Div Cardiol, New York, NY USA. EM vivek.reddy@mountsinai.org NR 14 TC 57 Z9 61 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 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 2009 VL 104 IS 10 BP 1402 EP 1406 DI 10.1016/j.amjcard.2009.06.062 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 522LE UT WOS:000271998500015 PM 19892058 ER PT J AU Holmes, MD Chen, WY Hankinson, SE Willett, WC AF Holmes, Michelle D. Chen, Wendy Y. Hankinson, Susan E. Willett, Walter C. TI Physical Activity's Impact on the Association of Fat and Fiber Intake With Survival After Breast Cancer SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE breast neoplasms; dietary fats; dietary fiber; exercise; survival ID DIETARY-FAT; LIVING WHEL; WEIGHT-LOSS; DIAGNOSIS; WOMEN; MORTALITY; FRUIT; QUESTIONNAIRE; RECURRENCE; VEGETABLES AB This study examined whether, after a breast cancer diagnosis, high intake of animal fat was associated with increased breast cancer mortality and high intake of fiber was associated with decreased breast cancer mortality. Participants were 3,846 US female nurses diagnosed with stages I-III breast cancer between 1976 and 2001 and followed until death or May 2006. Breast cancer mortality was calculated according to dietary intake quintiles first assessed at least 12 months after diagnosis and was cumulatively averaged and updated. There were 446 breast cancer deaths. In simple models adjusted for time since diagnosis, age, and energy intake, animal fat intake was associated with increased breast cancer death, and cereal fiber intake was associated with reduced breast cancer death. However, no associations were found in fully adjusted models: for animal fat, the relative risks for increasing quintiles were 1.00, 0.89, 0.86, 0.85, and 0.89 (95% confidence interval: 0.61, 1.28), P = 0.68; for cereal fiber, they were 1.00, 0.95, 0.76, 0.81, and 1.00 (95% confidence interval: 0.71, 1.40), P = 0.59. Results of simple models adjusted additionally for physical activity were similar to those for full multivariate models. Results show that physical activity strongly confounds the association between diet and survival. C1 [Holmes, Michelle D.; Chen, Wendy Y.; Hankinson, Susan E.; Willett, Walter C.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Holmes, Michelle D.; Chen, Wendy Y.; Hankinson, Susan E.; Willett, Walter C.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Holmes, Michelle D.; Hankinson, Susan E.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Holmes, MD (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM michelle.holmes@channing.harvard.edu FU National Institutes of Health [CA87969] FX This work was supported by the National Institutes of Health (grant CA87969). NR 36 TC 13 Z9 14 U1 1 U2 3 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 NOV 15 PY 2009 VL 170 IS 10 BP 1250 EP 1256 DI 10.1093/aje/kwp291 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 514FN UT WOS:000271379800007 PM 19850626 ER PT J AU Sadreyev, RI Feramisco, JD Tsao, H Grishin, NV AF Sadreyev, Ruslan I. Feramisco, Jamison D. Tsao, Hensin Grishin, Nick V. TI Phenotypic categorization of genetic skin diseases reveals new relations between phenotypes, genes and pathways SO BIOINFORMATICS LA English DT Article ID MESANGIAL CELLS; OXIDATIVE STRESS; NADPH OXIDASE; HUMAN PHENOME; HIGH GLUCOSE; GLUCOSE-6-PHOSPHATE-DEHYDROGENASE; ANGIOGENESIS; NETWORK; DECREASES; MUTATIONS AB Motivation: Systematic analysis of connection between proteins, their cellular function and phenotypic manifestations in disease is a central problem of biological and clinical research. The solution to this problem requires the development of new approaches to link the rapidly growing dataset of gene-disease associations with the many complex and overlapping phenotypes of human disease. Results: We analyze genetic skin disorders and suggest a manually designed set of elementary phenotypes whose combinations define diseases as points in a multidimensional space, providing a basis for phenotypic disease clustering. Placing the known gene-disease associations in the context of this space reveals new patterns that suggest previously unknown functional links between proteins, signaling pathways and disease phenotypes. For example, analysis of telangiectasias (spider vein diseases) reveals a previously unrecognized interplay between the TGF-beta signaling pathway and pentose phosphate pathway. This interaction may mediate glucose-dependent regulation of TGF-beta signaling, providing a clue to the known association between angiopathies and diabetes and implying new gene candidates for mutational analysis and drug targeting. C1 [Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. [Sadreyev, Ruslan I.; Grishin, Nick V.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA. [Feramisco, Jamison D.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94115 USA. [Grishin, Nick V.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, 55 Fruit St, Boston, MA 02114 USA. EM grishin@chop.swmed.edu FU National Institutes of Health [GM67165]; Welch Foundation [I1505]; American Cancer Society FX National Institutes of Health ( GM67165 to N. V. G.); Welch Foundation ( I1505 to N. V. G.); American Cancer Society ( to H. T.). NR 27 TC 3 Z9 3 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD NOV 15 PY 2009 VL 25 IS 22 BP 2891 EP 2896 DI 10.1093/bioinformatics/btp538 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 516SY UT WOS:000271564300001 PM 19744994 ER PT J AU Berriz, GF Beaver, JE Cenik, C Tasan, M Roth, FP AF Berriz, Gabriel F. Beaver, John E. Cenik, Can Tasan, Murat Roth, Frederick P. TI Next generation software for functional trend analysis SO BIOINFORMATICS LA English DT Article ID GENOME DATABASE; GENE; INFORMATION; RESOURCES; BIOLOGY AB FuncAssociate is a web application that discovers properties enriched in lists of genes or proteins that emerge from large-scale experimentation. Here we describe an updated application with a new interface and several new features. For example, enrichment analysis can now be performed within multiple gene-and protein-naming systems. This feature avoids potentially serious translation artifacts to which other enrichment analysis strategies are subject. C1 [Berriz, Gabriel F.; Beaver, John E.; Cenik, Can; Tasan, Murat; Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Roth, Frederick P.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Roth, FP (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave, Boston, MA 02115 USA. EM fritz_roth@hms.harvard.edu RI Roth, Frederick/H-6308-2011; OI Cenik, Can/0000-0001-6370-0889; Roth, Frederick/0000-0002-6628-649X FU US National Institutes of Health [NS054052, NS035611, HL081341, HG0017115, HG004233, HG003224]; Canadian Institute for Advanced Research Fellowship FX US National Institutes of Health (grants NS054052, NS035611, HL081341, HG0017115, HG004233 and HG003224, in part); Canadian Institute for Advanced Research Fellowship (to F. P. R.). NR 14 TC 145 Z9 146 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD NOV 15 PY 2009 VL 25 IS 22 BP 3043 EP 3044 DI 10.1093/bioinformatics/btp498 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 516SY UT WOS:000271564300026 PM 19717575 ER PT J AU Peng, LF Stanton, BZ Maloof, N Wang, X Schreiber, SL AF Peng, Lee F. Stanton, Benjamin Z. Maloof, Nicole Wang, Xiang Schreiber, Stuart L. TI Syntheses of aminoalcohol-derived macrocycles leading to a small-molecule binder to and inhibitor of Sonic Hedgehog SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Sonic Hedgehog; Robotnikinin; Macrocycle; Small-molecule microarray; Surface plasmon resonance; Shh-LIGHT2; Ptch1(-/-) ID STOCK SOLUTION APPROACH; IMMUNOSUPPRESSANT FK506; CHEMICAL GENETICS; ONE-BEAD; MICROARRAYS; DISCOVERY; SYNTHASE; PATHWAY AB We report the synthesis and biological activity of a library of aminoalcohol-derived macrocycles from which robotnikinin (17), a binder to and inhibitor of Sonic Hedgehog, was derived. Using an asymmetric alkylation to set a key stereocenter and an RCM reaction to close the macrocycle, we were able to synthesize compounds for testing. High-throughput screening via small-molecule microarray (SMM) technology led to the discovery of a compound capable of binding ShhN. Follow-up chemistry led to a library of macrocycles with enhanced biological activity relative to the original hit compounds. Differences in ring size and stereochemistry, leading to alterations in the mode of binding, may account for differences in the degree of biological activity. These compounds are the first ones reported that inhibit Shh signaling at the ShhN level. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Peng, Lee F.] Massachusetts Gen Hosp, Dept Med, GI Unit, Boston, MA 02114 USA. [Peng, Lee F.; Stanton, Benjamin Z.; Maloof, Nicole; Wang, Xiang; Schreiber, Stuart L.] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. [Peng, Lee F.; Stanton, Benjamin Z.; Maloof, Nicole; Wang, Xiang; Schreiber, Stuart L.] Broad Inst, Cambridge, MA 02142 USA. [Schreiber, Stuart L.] Broad Inst Harvard & MIT, Howard Hughes Med Inst, Cambridge, MA 02142 USA. RP Peng, LF (reprint author), Massachusetts Gen Hosp, Dept Med, GI Unit, 55 Fruit St, Boston, MA 02114 USA. EM lpeng@partners.org FU National Pancreas Foundation; American Gastroenterological Association; American Liver Foundation; National Institute of General Medical Sciences [GM-38627] FX We thank Dr. Douglas M. Ho and Dr. Shao-Liang Zheng of the Center for Crystallographic Studies at Harvard University for the X-ray crystallographic analysis. We thank James K. Chen, Kazuo Nakai, Andrew M. Stern, Gregory T. Copeland, Damian W. Young, and Timothy A. Lewis for their helpful suggestions. L. F. P. is supported by grants from the National Pancreas Foundation, the American Gastroenterological Association, and the American Liver Foundation. This research was supported by the National Institute of General Medical Sciences (GM-38627, awarded to S. L. S.) S. L. S. is an investigator with the Howard Hughes Medical Institute. NR 21 TC 43 Z9 43 U1 1 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 15 PY 2009 VL 19 IS 22 BP 6319 EP 6325 DI 10.1016/j.bmcl.2009.09.089 PG 7 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 509PH UT WOS:000271029600014 PM 19819139 ER PT J AU Phillips, KA Marshall, DA Haas, JS Elkin, EB Liang, SY Hassett, M Ferrusi, I Brock, JE Van Bebber, SL AF Phillips, Kathryn A. Marshall, Deborah A. Haas, Jennifer S. Elkin, Elena B. Liang, Su-Ying Hassett, MichaelJ. Ferrusi, Ilia Brock, Jane E. Van Bebber, Stephanie L. TI Clinical Practice Patterns and Cost Effectiveness of Human Epidermal Growth Receptor 2 Testing Strategies in Breast Cancer Patients SO CANCER LA English DT Article DE personalized medicine; targeted therapies; genomics; HER2; trastuzumab; breast cancer; utilization; cost effectiveness; clinical practice patterns ID ADJUVANT TRASTUZUMAB; CONCORDANCE; MEDICINE; THERAPY AB BACKGROUND: Testing technologies are increasingly used to target cancer therapies. Human epidermal growth factor receptor 2 (HER2) testing to target trastuzumab for patients with breast cancer provides insights into the evidence needed for emerging testing technologies. METHODS: The authors reviewed literature on HER2 test utilization and cost effectiveness of HER2 testing for patients with breast cancer. They examined available evidence on: percentage of eligible patients tested for HER2; test methods used; concordance of test results between community and central/reference laboratories; use of trastuzumab by HER2 test result; and cost effectiveness of testing strategies. RESULTS: Little evidence was available to determine whether all eligible patients are tested, how many are retested to confirm results, and how many with negative HER2 test results still receive trastuzumab. Studies suggested that up to 66% of eligible patients had no documentation of testing in claims records, up to 20% of patients receiving trastuzumab were not tested or had no documentation of a positive test, and 20% of HER2 results may be incorrect. Few cost-effectiveness analyses of trastuzumab explicitly considered the economic implications of various testing strategies. CONCLUSIONS: There was little information about the actual use of HER2 testing in clinical practice, but evidence suggested important variations in testing practices and key gaps in knowledge exist. Given the increasing use of targeted therapies, it is critical to build an evidence base that supports informed decision making on emerging testing technologies in cancer care. Cancer 2009;115:5166-74. (C) 2009 American Cancer Society. C1 [Phillips, Kathryn A.; Liang, Su-Ying; Van Bebber, Stephanie L.] Univ Calif San Francisco, Dept Clin Pharm, Ctr Translat & Policy Res Personalized Med TRANSP, San Francisco, CA 94143 USA. [Marshall, Deborah A.; Ferrusi, Ilia] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Haas, Jennifer S.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. [Elkin, Elena B.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Hassett, MichaelJ.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Ferrusi, Ilia] St Josephs Healthcare, Ctr Evaluat Med, Hamilton, ON, Canada. [Brock, Jane E.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Phillips, KA (reprint author), Univ Calif San Francisco, Dept Clin Pharm, Ctr Translat & Policy Res Personalized Med TRANSP, 3333 Calif St 420, San Francisco, CA 94143 USA. EM PhillipsK@pharmacy.ucsf.edu RI Marshall, Deborah/J-7248-2015 OI Marshall, Deborah/0000-0002-8467-8008 FU National Cancer Institute [R01CA101849, P01CA130818]; Blue Shield Foundation of California FX This Study was funded by, 2 grants to Dr. Phillips from the National Cancer Institute (R01CA101849 and P01CA130818) and a grant from the Blue Shield Foundation of California (oil restricted). Funding agencies had no review of any portion of this work. NR 28 TC 37 Z9 39 U1 0 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 2009 VL 115 IS 22 BP 5166 EP 5174 DI 10.1002/cncr.24574 PG 9 WC Oncology SC Oncology GA 516SW UT WOS:000271564100009 PM 19753618 ER PT J AU Jayachandran, J Banez, LL Aronson, WJ Terris, MK Presti, JC Amling, CL Kane, CJ Freedland, SJ AF Jayachandran, Jayakrishnan Banez, Lionel L. Aronson, William J. Terris, Martha K. Presti, Joseph C., Jr. Amling, Christopher L. Kane, Christopher J. Freedland, Stephen J. CA SEARCH Database Study Grp TI Obesity as a Predictor of Adverse Outcome Across Black and White Race Results From the Shared Equal Access Regional Cancer Hospital (SEARCH) Database SO CANCER LA English DT Article DE prostatic neoplasms; prostatectomy; recurrence; obesity; continental population groups ID PROSTATE-CANCER; RADICAL PROSTATECTOMY; STEROID-HORMONES; UNITED-STATES; WEIGHT CHANGE; RISK; RECURRENCE; MORTALITY; MEN; IMPACT AB BACKGROUND: Across multiple studies, obesity has been associated with an increased risk of higher grade disease and prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). Whether these associations vary by race is unknown. In the current study, the authors examined the association between obesity and outcome after RID stratified by race. METHODS: A retrospective analysis was performed on 1415 men in the Shared Equal Access Regional Cancer Hospital (SEARCH) database who underwent RID between 1989 and 2008. The association between increased body mass index (BMI) and adverse pathology and biochemical recurrence was examined using multivariate logistic regression and Cox models, respectively. Data were examined stratified by race. RESULTS: After adjusting for preoperative clinical characteristics, higher BMI was associated with higher tumor grade (P = .008) and positive surgical margins (P < .001) in white men, and similar but statistically nonsignificant trends were observed in black men. No significant interaction was noted between race and BMI for associations with adverse pathology (P(interaction)>=.12). After adjusting for preoperative clinical characteristics, higher BMI was associated with an increased risk of recurrence in both white men (P = .001) and black men (P = .03). After further adjusting for pathologic variables, higher BMI was associated with significantly increased risk of recurrence in white men (P = .002) and black men (P = .01). No significant interactions were observed between race and BMI for predicting biochemical progression adjusting either for preoperative factors (P(interaction) = .35) or for preoperative and pathologic features (P(interaction) = .47). CONCLUSIONS: Obesity was associated with a greater risk of recurrence among both black men and white men. Obesity did not appear to be more or less influential in 1 race than another but, rather, was identified as a risk factor for aggressive cancer regardless of race. Cancer 2009;115:5263-71. (C) 2009 American Cancer Society. C1 [Jayachandran, Jayakrishnan; Banez, Lionel L.; Freedland, Stephen J.] Duke Univ, Sch Med, Dept Surg, Div Urol Surg, Durham, NC 27710 USA. [Jayachandran, Jayakrishnan; Banez, Lionel L.; Freedland, Stephen J.] Duke Univ, Sch Med, Dept Pathol, Div Urol Surg, Durham, NC 27710 USA. [Jayachandran, Jayakrishnan; Banez, Lionel L.; Freedland, Stephen J.] Duke Univ, Sch Med, Duke Prostate Ctr, Durham, NC 27710 USA. [Jayachandran, Jayakrishnan; Banez, Lionel L.; Freedland, Stephen J.] Vet Affairs Med Ctr, Urol Sect, Durham, NC USA. [Aronson, William J.] Vet Affairs Greater Los Angeles Healthcare Syst, Urol Sect, Los Angeles, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Terris, Martha K.] Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. [Presti, Joseph C., Jr.] Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. [Presti, Joseph C., Jr.] Vet Affairs Med Ctr, Urol Sect, Palo Alto, CA 94304 USA. [Amling, Christopher L.] Univ Alabama, Div Urol, Birmingham, AL USA. [Amling, Christopher L.] Birmingham Vet Affairs Med Ctr, Urol Sect, Birmingham, AL USA. [Kane, Christopher J.] Univ Calif San Diego, Sch Med, Div Urol, San Diego, CA 92103 USA. RP Freedland, SJ (reprint author), Duke Univ, Sch Med, Med Ctr, Div Urol, Box 2626, Durham, NC 27710 USA. EM steve.freedland@duke.edu OI Terris, Martha/0000-0002-3843-7270 FU Department of Veterans Affairs, National Institutes of Health (NIH) [RO1CA100938]; NIH Specialized Programs of Research Excellence [P50 CA92131-01A1]; Georgia Cancer Coalition; Department of Defense, Prostate Cancer Research Program; American Urological Association Foundation/Astellas Rising Star in Urology Award FX Supported by the Department of Veterans Affairs, National Institutes of Health (NIH) Grant RO1CA100938 (to W.J.A.); NIH Specialized Programs of Research Excellence Grant P50 CA92131-01A1 (to W.J.A.); the Georgia Cancer Coalition (to M.K.T.); the Department of Defense, Prostate Cancer Research Program, (to S.J.F. and J.J.); and the American Urological Association Foundation/Astellas Rising Star in Urology Award (to S.J.F.). NR 22 TC 38 Z9 38 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 2009 VL 115 IS 22 BP 5263 EP 5271 DI 10.1002/cncr.24571 PG 9 WC Oncology SC Oncology GA 516SW UT WOS:000271564100020 PM 19670453 ER PT J AU Chu, K Lee, SW AF Chu, Kiki Lee, Sam W. TI Revisiting calcein AM Alternative tool for identifying dye-effluxing cancer stem cells? SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE cancer stem cells; side-population; hoechst 33342; calcein AM; C(lo)P; cell surface markers; cell sorting ID SIDE-POPULATION PHENOTYPE; ACUTE MYELOID-LEUKEMIA; IDENTIFICATION; LINES; MICE C1 [Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Lee, SW (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. EM swlee@partners.org NR 28 TC 0 Z9 0 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD NOV 15 PY 2009 VL 8 IS 22 BP 2205 EP 2207 DI 10.4161/cbt.8.22.10714 PG 3 WC Oncology SC Oncology GA 645PZ UT WOS:000281477800025 ER PT J AU Chen, YF Chou, CY Wilkins, RJ Ellory, JC Mount, DB Shen, MR AF Chen, Yih-Fung Chou, Cheng-Yang Wilkins, Robert J. Ellory, J. Clive Mount, David B. Shen, Meng-Ru TI Motor Protein-Dependent Membrane Trafficking of KCl Cotransporter-4 Is Important for Cancer Cell Invasion SO CANCER RESEARCH LA English DT Article ID K-CL COTRANSPORTER; EPITHELIAL-MESENCHYMAL TRANSITION; H EXCHANGER NHE1; CERVICAL-CANCER; MATRIX METALLOPROTEINASES; OVARIAN-CANCER; BREAST-CANCER; UP-REGULATION; GROWTH; RECEPTOR AB The KCl cotransporter (KCC) is a major determinant of osmotic homeostasis and plays an emerging role in tumor biology. This study stresses the important role of KCC4 in tumor malignant behavior. Real-time reverse transcription-PCR on samples collected by laser microdissection and immunofluorescent stainings with different KCC isoform antibodies indicate that KCC4 is abundant in metastatic cervical and ovarian cancer tissues. Insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) stimulate KCC4 recruitment from a presumably inactive cytoplasmic pool of endoplasmic reticulum and Golgi to plasma membrane along actin cytoskeleton that is significantly inhibited by LY294002 and wortmannin. Throughout the trafficking process, KCC4 is incorporated into lipid rafts that function as a platform for the association between KCC4 and myosin Va, an actin-dependent motor protein. KCC4 and ezrin, a membrane cytoskeleton linker, colocalize at lamellipodia of migratory cancer cells. Interference with KCC activity by either an inhibitor or a dominant-negative loss-of-function mutant profoundly suppressed the IGF-I-induced membrane trafficking of KCC4 and the structural interaction between KCC4 and ezrin near the cell surface. Endogenous cancer cell invasiveness was significantly attenuated by small interfering RNA targeting KCC4, and the residual invasiveness was much less sensitive to IGF-I or EGF stimulation. In the metastatic cancer tissues, KCC4 colocalizes with IGF-I or EGF, indicating a likely in vivo stimulation of KCC4 function by growth factors. Thus, blockade of KCC4 trafficking and surface expression may provide a potential target for the prevention of IGF-I- or EGF-dependent cancer spread. [Cancer Res 2009;69(22):8585-93] C1 [Chou, Cheng-Yang; Shen, Meng-Ru] Natl Cheng Kung Univ, Coll Med, Dept Obstet & Gynecol, Tainan 704, Taiwan. [Chen, Yih-Fung] Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci, Tainan 704, Taiwan. [Chen, Yih-Fung; Shen, Meng-Ru] Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, Tainan 704, Taiwan. [Wilkins, Robert J.; Ellory, J. Clive] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England. [Mount, David B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Renal, Boston, MA 02115 USA. [Mount, David B.] Harvard Univ, VA Boston Healthcare Syst, Sch Med, Div Renal, Boston, MA 02115 USA. RP Shen, MR (reprint author), Natl Cheng Kung Univ, Coll Med, Dept Obstet & Gynecol, 138 Sheng Li Rd, Tainan 704, Taiwan. EM mrshen@mail.ncku.edu.tw FU National Science Council, Taiwan; Center of Excellence for Clinical Trial and Research [DOH-TD-B-111-OG4]; Department of Health, Executive Yuan, Taiwan; Center for Gene Regulation and Signal Transduction Research and Center for Micro/Nano Science and Technology; National Cheng Kong University, Taiwan; Medical Research Council [G0700759]; United Kingdom; NIH [DK57708] FX National Science Council, Taiwan; Center of Excellence for Clinical Trial and Research (DOH-TD-B-111-OG4), Department of Health, Executive Yuan, Taiwan; Center for Gene Regulation and Signal Transduction Research and Center for Micro/Nano Science and Technology, National Cheng Kong University, Taiwan; Medical Research Council (MRC grant G0700759). United Kingdom; and NIH grant (DK57708). NR 42 TC 17 Z9 18 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2009 VL 69 IS 22 BP 8585 EP 8593 DI 10.1158/0008-5472.CAN-09-2284 PG 9 WC Oncology SC Oncology GA 520JC UT WOS:000271839200009 PM 19887603 ER PT J AU Myers, AP Meyerhardt, JA Cantley, LC AF Myers, Andrea P. Meyerhardt, Jeffrey A. Cantley, Lewis C. TI Getting Knit-PI3Ky: PIK3CA Mutation Status to Direct Multimodality Therapy? SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID RECTAL-CANCER; RANDOMIZED TRIAL; RADIOTHERAPY AB There is high morbidity associated with local recurrence of rectal cancer. However, the adjuvant therapies given to prevent such recurrences also have significant side effects and associated risks. The ability to select patients with the highest risk of recurrence and greatest therapeutic response will improve rectal cancer care. (Clin Cancer Res 2009;15(22):6748-50) C1 [Myers, Andrea P.; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. [Myers, Andrea P.; Meyerhardt, Jeffrey A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Cantley, LC (reprint author), Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. EM lewis_cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIGMS NIH HHS [R01 GM041890, R37 GM041890, R01 GM036624] NR 11 TC 1 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2009 VL 15 IS 22 BP 6748 EP 6750 DI 10.1158/1078-0432.CCR-09-2305 PG 3 WC Oncology SC Oncology GA 520EJ UT WOS:000271822600002 PM 19903790 ER PT J AU Yanagawa, J Walser, TC Zhu, LX Hong, LS Fishbein, MC Mah, V Chia, D Goodglick, L Elashoff, DA Luo, J Magyar, CE Dohadwala, M Lee, JM St John, MA Strieter, RM Sharma, S Dubinett, SM AF Yanagawa, Jane Walser, Tonya C. Zhu, Li X. Hong, Longsheng Fishbein, Michael C. Mah, Vei Chia, David Goodglick, Lee Elashoff, David A. Luo, Jie Magyar, Clara E. Dohadwala, Mariam Lee, Jay M. St John, Maie A. Strieter, Robert M. Sharma, Sherven Dubinett, Steven M. TI Snail Promotes CXCR2 Ligand-Dependent Tumor Progression in Non-Small Cell Lung Carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; E-CADHERIN EXPRESSION; TRANSCRIPTION FACTOR; CANCER-CELLS; COLON-CANCER; KAPPA-B; SURVIVAL; ANGIOGENESIS; METASTASIS; INVASION AB Purpose: As a transcriptional repressor of E-cadherin, Snail has predominantly been associated with epithelial-mesenchymal transition, invasion, and metastasis. However, other important Snail-dependent malignant phenotypes have not been fully explored. Here, we investigate the contributions of Snail to the progression of non-small cell lung cancer (NSCLC). Experimental Design: Immunohistochemistry was done to quantify and localize Snail in human lung cancer tissues, and tissue microarray analysis was used to correlate these findings with survival. NSCLC cell lines gene-modified to stably overexpress Snail were evaluated in vivo in two severe combined immunodeficiency murine tumor models. Differential gene expression between Snail-overexpressing and control cell lines was evaluated using gene expression microarray analysis. Results: Snail is upregulated in human NSCLC tissue, and high levels of Snail expression correlate with decreased survival (P < 0.026). In a heterotopic model, mice bearing Snail-overexpressing tumors developed increased primary tumor burden (P = 0.008). In an orthotopic model, mice bearing Snail-overexpressing tumors also showed a trend toward increased metastases. In addition, Snail overexpression led to increased angiogenesis in primary tumors as measured by MECA-32 (P < 0.05) positivity and CXCL8 (P = 0.002) and CXCL5 (P = 0.0003) concentrations in tumor homogenates. Demonstrating the importance of these proangiogenic chemokines, the Snail-mediated increase in tumor burden was abrogated with CXCR2 blockade. Gene expression analysis also revealed Snail-associated differential gene expression with the potential to affect angiogenesis and diverse aspects of lung cancer progression. Conclusion: Snail upregulation plays a role in human NSCLC by promoting tumor progression mediated by CXCR2 ligands. (Clin Cancer Res 2009;15(22):6820-9) C1 [Dubinett, Steven M.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Lung Canc Res Program, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. [Yanagawa, Jane; Walser, Tonya C.; Elashoff, David A.; Luo, Jie; Dohadwala, Mariam; Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Hong, Longsheng; Fishbein, Michael C.; Mah, Vei; Chia, David; Goodglick, Lee; Magyar, Clara E.; Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Elashoff, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biostat, Los Angeles, CA 90095 USA. [Yanagawa, Jane; Lee, Jay M.; St John, Maie A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Zhu, Li X.; Dohadwala, Mariam; Sharma, Sherven; Dubinett, Steven M.] VA Greater Los Angeles Hlth Care Ctr, Los Angeles, CA USA. [Strieter, Robert M.] Univ Virginia, Dept Med, Charlottesville, VA USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Lung Canc Res Program, Div Pulm & Crit Care Med, 10833 Le Conte Ave,37-131 CHS, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu FU National Cancer Institute [CA90388]; University of California [NIH/NHLBI T32 HL72752]; Reiss Family and Piansky Family Trust; Early Detection Research Network [NCI CA-86366] FX Specialized Programs of Research Excellence in Lung Cancer grant P50-CA90388, National Cancer Institute, LUNGevity/Thoracic Surgery Foundation for Research and Education Research Fellowship, University of California at Los Angeles Pulmonary & Critical Care Training Grant, NIH/NHLBI T32 HL72752, Department of Veteran Affairs Medical Research Funds, Tobacco Related Disease Program Award Program of the University of California, Reiss Family and Piansky Family Trust, and the Early Detection Research Network, NCI CA-86366. NR 50 TC 57 Z9 59 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2009 VL 15 IS 22 BP 6820 EP 6829 DI 10.1158/1078-0432.CCR-09-1558 PG 10 WC Oncology SC Oncology GA 520EJ UT WOS:000271822600011 PM 19887480 ER PT J AU Zwicker, JI Liebman, HA Neuberg, D Lacroix, R Bauer, KA Furie, BC Furie, B AF Zwicker, Jeffrey I. Liebman, Howard A. Neuberg, Donna Lacroix, Romaric Bauer, Kenneth A. Furie, Barbara C. Furie, Bruce TI Tumor-Derived Tissue Factor-Bearing Microparticles Are Associated With Venous Thromboembolic Events in Malignancy SO CLINICAL CANCER RESEARCH LA English DT Article ID FACTOR-POSITIVE MICROPARTICLES; CANCER-PATIENTS; HEMOSTATIC ABNORMALITIES; PANCREATIC-CANCER; SOLID TUMORS; RISK-FACTORS; ENDOTHELIAL MICROPARTICLES; COAGULATION ACTIVATION; DOUBLE-BLIND; THROMBOSIS AB Purpose: Despite the strong association between malignant disease and thromboembolic disorders, the molecular and cellular basis of this relationship remains uncertain. We evaluated the hypothesis that tumor-derived tissue factor-bearing microparticles in plasma contribute to cancer-associated thrombosis. Experimental Design: We developed impedance-based flow cytometry to detect, quantitate, and size microparticles in platelet-poor plasma. We evaluated the number of tissue factor-bearing microparticles in a cohort of cancer patients of different histologies (N = 96) and conducted a case-control study of 30 cancer patients diagnosed with an acute venous thromboembolic event (VTE) compared with 60 cancer patients of similar age, stage, sex, and diagnosis without known VTE, as well as 22 patients with an idiopathic VTE. Results: Tissue factor-bearing microparticles were detected in patients with advanced malignancy, including two thirds of patients with pancreatic carcinoma. Elevated levels of tissue factor-bearing microparticles were associated VTE in cancer patients (adjusted odds ratio, 3.72; 95% confidence interval, 1.18-11.76; P = 0.01). In cancer patients without VTE, a retrospective analysis revealed a 1-year cumulative incidence of VTE of 34.8% in patients with tissue factor-bearing microparticles versus 0% in those without detectable tissue factor-bearing microparticles (Gray test P = 0.002). The median number of tissue factor-bearing microparticles in the cancer VTE cohort (7.1 x 10(4) microparticles/mu L) was significantly greater than both the idiopathic VTE and cancer-no VTE groups (P = 0.002 and P = 0.03, respectively). Pancreatectomy in three patients eliminated or nearly eliminated these microparticles which coexpressed the epithelial tumor antigen, MUC-1. Conclusion: We conclude that tumor-derived tissue factor-bearing microparticles are associated with VTE in cancer patients and may be central to the pathogenesis of cancer-associated thrombosis. (Clin Cancer Res 2009;15(22):6830-40) C1 [Zwicker, Jeffrey I.; Lacroix, Romaric; Bauer, Kenneth A.; Furie, Barbara C.; Furie, Bruce] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Zwicker, Jeffrey I.; Lacroix, Romaric; Bauer, Kenneth A.; Furie, Barbara C.; Furie, Bruce] Harvard Univ, Sch Med, Boston, MA USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Liebman, Howard A.] Univ So Calif, Keck Sch Med, Div Hematol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. RP Zwicker, JI (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. EM jzwicker@bidmc.harvard.edu OI Zwicker, Jeffrey/0000-0001-5810-6893 FU NIH [K23 HL084052, HL095084] FX NIH grants K23 HL084052 (J. Zwicker) and HL095084 (B.C. Furie, B. Furie). NR 45 TC 239 Z9 249 U1 2 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2009 VL 15 IS 22 BP 6830 EP 6840 DI 10.1158/1078-0432.CCR-09-0371 PG 11 WC Oncology SC Oncology GA 520EJ UT WOS:000271822600012 PM 19861441 ER PT J AU Al-Shakfa, F Dulucq, S Brukner, I Milacic, I Ansari, M Beaulieu, P Moghrabi, A Laverdiere, C Sallan, SE Silverman, LB Neuberg, D Kutok, JL Sinnett, D Krajinovic, M AF Al-Shakfa, Fidaa Dulucq, Stephanie Brukner, Ivan Milacic, Iva Ansari, Marc Beaulieu, Patrick Moghrabi, Albert Laverdiere, Caroline Sallan, Stephen E. Silverman, Lewis B. Neuberg, Donna Kutok, Jeffery L. Sinnett, Daniel Krajinovic, Maja TI DNA Variants in Region for Noncoding Interfering Transcript of Dihydrofolate Reductase Gene and Outcome in Childhood Acute Lymphoblastic Leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID METHOTREXATE RESISTANCE; HAPLOTYPE RECONSTRUCTION; PROGNOSTIC-SIGNIFICANCE; ACQUIRED-RESISTANCE; INDUCED APOPTOSIS; EXPRESSION; RNA; CHILDREN; P53; CHEMOTHERAPY AB Purpose: Dihydrofolate reductase (DHFR) is the major target of methotrexate, a key component in childhood acute lymphoblastic leukemia (ALL) treatment. We recently reported an association of DHFR promoter polymorphisms with ALL outcome. Lower event-free survival correlated with haplotype *1, defined by A(-317) and C(-1610) alleles. Haplotype *1 was also associated higher DHFR expression. Experimental Design: Here, we analyzed adjacent 400-bp region participating in DHFR regulation as both a major promoter and a noncoding minor transcript. Results: Six polymorphisms were identified, of which five were single nucleotide polymorphisms and one was length polymorphism composed of variable number of 9-bp elements and 9-bp insertion/deletion. Haplotype analysis including all promoter polymorphisms revealed diversification of haplotype *1 into five subtypes (*1a-*1e). DNA variations of major promoter/noncoding transcript region and haplotype *1 subtypes were subsequently analyzed for the association with ALL outcome. Lower event-free survival was associated with an A allele of G(308)A polymorphism (P = 0.02) and with *1b haplotype (P = 0.01). This association was particularly striking in high-risk patients (P = 0.001) and was subsequently confirmed in independent patient cohort (P = 0.02). Haplotype *1b was the only haplotype *1 subtype associated with higher mRNA levels. Conclusions: The study provides a new insight into DHFR regulatory variations predisposing to an event in ALL patients. (Clin Cancer Res 2009;15(22):6931-8) C1 [Al-Shakfa, Fidaa; Dulucq, Stephanie; Brukner, Ivan; Milacic, Iva; Ansari, Marc; Beaulieu, Patrick; Moghrabi, Albert; Laverdiere, Caroline; Sinnett, Daniel; Krajinovic, Maja] CHU St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada. [Moghrabi, Albert; Laverdiere, Caroline; Sinnett, Daniel; Krajinovic, Maja] Univ Montreal, Dept Pediat, Montreal, PQ H3C 3J7, Canada. [Al-Shakfa, Fidaa; Krajinovic, Maja] Univ Montreal, Dept Pharmacol, Montreal, PQ H3C 3J7, Canada. [Sallan, Stephen E.; Silverman, Lewis B.; Neuberg, Donna] Dana Farber Canc Inst, Dept Pediat Oncol Biostat & Computat Biol, Boston, MA 02115 USA. [Sallan, Stephen E.; Silverman, Lewis B.] Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Kutok, Jeffery L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Krajinovic, M (reprint author), CHU St Justine, Res Ctr, 3175 Chemin Cote Ste Catherine, Montreal, PQ H3T 1C5, Canada. EM maja.krajinovic@umontreal.ca FU Canadian Institutes of Health Research; Leukemia Lymphoma Society of Canada; CHU Sainte Justine; Charles Bruneau Foundation; Centre d'excellence en Oncologie pediatrique et en soins palliatifs; National Cancer Institute/NIH [P01 CA 68484]; Fonds de la Recherche en Sante du Quebec FX Canadian Institutes of Health Research, Leukemia Lymphoma Society of Canada, Research Center of CHU Sainte Justine, Charles Bruneau Foundation, and Centre d'excellence en Oncologie pediatrique et en soins palliatifs. Dana-Farber Cancer Institute ALL treatment protocols are supported by the National Cancer Institute/NIH grant P01 CA 68484. M. Krajinovic and D. Sinnett are scholars of the Fonds de la Recherche en Sante du Quebec. NR 30 TC 18 Z9 22 U1 0 U2 2 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 NOV 15 PY 2009 VL 15 IS 22 BP 6931 EP 6938 DI 10.1158/1078-0432.CCR-09-0641 PG 8 WC Oncology SC Oncology GA 520EJ UT WOS:000271822600022 PM 19861437 ER PT J AU Taplin, ME Regan, MM Ko, YJ Bubley, GJ Duggan, SE Werner, L Beer, TM Ryan, CW Mathew, P Tu, SM Denmeade, SR Oh, WK Sartor, O Mantzoros, CS Rittmaster, R Kantoff, PW Balk, SP AF Taplin, Mary-Ellen Regan, Meredith M. Ko, Yoo-Joung Bubley, Glenn J. Duggan, Stephen E. Werner, Lillian Beer, Tomasz M. Ryan, Christopher W. Mathew, Paul Tu, Shi-Ming Denmeade, Samuel R. Oh, William K. Sartor, Oliver Mantzoros, Christos S. Rittmaster, Roger Kantoff, Philip W. Balk, Steven P. TI Phase II Study of Androgen Synthesis Inhibition with Ketoconazole, Hydrocortisone, and Dutasteride in Asymptomatic Castration-Resistant Prostate Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID ANTIANDROGEN WITHDRAWAL; ABIRATERONE ACETATE; HORMONAL-THERAPY; RECEPTOR GENE; PROGRESSION; EXPRESSION; MECHANISM; CYP17; TESTOSTERONE; BICALUTAMIDE AB Purpose: Increasing evidence indicates that enhanced intratumoral androgen synthesis contributes to prostate cancer progression after androgen deprivation therapy. This phase II study was designed to assess responses to blocking multiple steps in androgen synthesis with inhibitors of CYP17A1 (ketoconazole) and type I and II 5 alpha-reductases (dutasteride) in patients with castration-resistant prostate cancer (CRPC). Experimental Design: Fifty-seven men with CRPC were continued on gonadal suppression and treated with ketoconazole (400 mg thrice daily), hydrocortisone (30 mg/AM, 10 mg/PM), and dutasteride (0.5 mg/d). Results: Prostate-specific antigen response rate (>= 50% decline) was 56% (32 of 57; 95% confidence interval, 42.4-69.3%); the median duration of response was 20 months. In patients with measurable disease, 6 of 20 (30%) responded by the Response Evaluation Criteria in Solid Tumors. Median duration of treatment was 8 months; 9 patients remained on therapy with treatment durations censored at 18 to 32 months. Median time to progression was 14.5 months. Grade 3 toxicities occurred in 32% with only one reported grade 4 (thrombosis) toxicity. Dehydroepiandrosterone sulfate declined by 89%, androstenedione by 56%, and testosterone by 66%, and dihydrotestosterone declined to below detectable levels compared with baseline levels with testicular suppression alone. Median baseline levels and declines in dehydroepiandrosterone sulfate, androstenedione, testosterone, and dihydrotestosterone were not statistically different in the responders versus nonresponders, and hormone levels were not significantly increased from nadir levels at relapse. Conclusion: The response proportion to ketoconazole, hydrocortisone, and dutasteride was at least comparable with previous studies of ketoconazole alone, whereas time to progression was substantially longer. Combination therapies targeting multiple steps in androgen synthesis warrant further investigation. (Clin Cancer Res 200915(22):7099-105) C1 [Bubley, Glenn J.; Duggan, Stephen E.; Mantzoros, Christos S.; Balk, Steven P.] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Taplin, Mary-Ellen; Regan, Meredith M.; Werner, Lillian; Oh, William K.; Sartor, Oliver; Kantoff, Philip W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Taplin, Mary-Ellen; Regan, Meredith M.; Bubley, Glenn J.; Oh, William K.; Mantzoros, Christos S.; Kantoff, Philip W.; Balk, Steven P.] Harvard Univ, Sch Med, Boston, MA USA. [Taplin, Mary-Ellen; Regan, Meredith M.; Bubley, Glenn J.; Werner, Lillian; Oh, William K.; Kantoff, Philip W.; Balk, Steven P.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Taplin, Mary-Ellen; Bubley, Glenn J.; Beer, Tomasz M.; Ryan, Christopher W.; Mathew, Paul; Tu, Shi-Ming; Denmeade, Samuel R.; Oh, William K.; Kantoff, Philip W.; Balk, Steven P.] Dept Def Prostate Canc Clin Trials Consortium, New York, NY USA. [Ko, Yoo-Joung] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Beer, Tomasz M.; Ryan, Christopher W.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Mathew, Paul; Tu, Shi-Ming] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Denmeade, Samuel R.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Sartor, Oliver] Tulane Canc Ctr, New Orleans, LA USA. [Rittmaster, Roger] GlaxoSmithKline Inc, Res Triangle Pk, NC USA. RP Balk, SP (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02115 USA. EM sbalk@bidmc.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU GlaxoSmithKline; Department of Defense Prostate Cancer Research Program [PC060807]; NIH [R01CA111803, P01CA89021]; Prostate Cancer Foundation Challenge FX Grant support: GlaxoSmithKline, Department of Defense Prostate Cancer Research Program grant PC060807, NIH grants R01CA111803 and P01CA89021, and Prostate Cancer Foundation Challenge grant. NR 30 TC 49 Z9 50 U1 0 U2 5 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 NOV 15 PY 2009 VL 15 IS 22 BP 7099 EP 7105 DI 10.1158/1078-0432.CCR-09-1722 PG 7 WC Oncology SC Oncology GA 520EJ UT WOS:000271822600043 PM 19887483 ER PT J AU Weil, AA Khan, AI Chowdhury, F LaRocque, RC Faruque, ASG Ryan, ET Calderwood, SB Qadri, F Harris, JB AF Weil, Ana A. Khan, Ashraful I. Chowdhury, Fahima LaRocque, Regina C. Faruque, A. S. G. Ryan, Edward T. Calderwood, Stephen B. Qadri, Firdausi Harris, Jason B. TI Clinical Outcomes in Household Contacts of Patients with Cholera in Bangladesh SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ANTI-MICROBIAL AGENTS; EL-TOR STRAINS; VIBRIO-CHOLERAE; ENDEMIC CHOLERA; FAMILY CONTACTS; RAPID DIAGNOSIS; SUSCEPTIBILITY; INFECTION; O1; TETRACYCLINE AB Background. Multiple Vibrio cholerae infections in the same household are common. The objective of this study was to examine the incidence of V. cholerae infection and associated clinical symptoms in household contacts of patients with cholera and to identify risk factors for development of severe dehydration in this cohort. Methods. Household contacts of hospitalized patients with cholera were observed with frequent clinical assessments and collection of serum and rectal swab samples for culture for a period of 21 days after presentation of the index case. Results. One-half (460 of 944) of all contacts reported diarrhea during the study period, and symptoms most frequently began 2 days after presentation of the index case. Antibiotics were used by 199 (43%) of 460 contacts with diarrhea. Results of rectal swab cultures for V. cholerae were positive for 202 (21%) of 944 contacts, and 148 (73%) infected contacts experienced diarrhea. Significant dehydration developed in 26 contacts; predictors of dehydration included vomiting, each additional day of diarrhea, and blood group O status. Conclusions. In urban Bangladesh, the burden of diarrheal illness among household contacts of patients with cholera is higher than was previously estimated, and prophylactic intervention is feasible, because the majority of symptomatic cases of V. cholerae infection in contacts begin soon after presentation of the index case. Re-evaluation of targeted chemoprophylaxis for household contacts of patients with cholera may be warranted. C1 [LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.; Harris, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Weil, Ana A.; Khan, Ashraful I.; Chowdhury, Fahima; Faruque, A. S. G.; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res Dhaka, Dhaka, Bangladesh. [LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Med, Dept Immunol & Infect Dis, Boston, MA USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Harris, JB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM jbharris@partners.org FU International Centre for Diarrhoeal Disease Research, Bangladesh; Centre for Health and Population Research [U01 AI058935, RO3 AI063079, U01 AI077883]; International Research Scientist Development Award [K01 TW07409]; National Institutes of Health; Fogarty International Center through Vanderbilt University [R24 TW007988] FX International Centre for Diarrhoeal Disease Research, Bangladesh, Centre for Health and Population Research (U01 AI058935 to S. B. C., RO3 AI063079 to F. Q., U01 AI077883 to E. T. R., International Research Scientist Development Award K01 TW07144 to R. C. L., and International Research Scientist Development Award K01 TW07409 to J.B.H.); and National Institutes of Health, Fogarty International Center through Vanderbilt University (R24 TW007988 to S. B. C. and A. A. W.). NR 27 TC 41 Z9 41 U1 3 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2009 VL 49 IS 10 BP 1473 EP 1479 DI 10.1086/644779 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 511EH UT WOS:000271146200002 PM 19842974 ER PT J AU Lipsky, BA Hoey, C AF Lipsky, Benjamin A. Hoey, Christopher TI Topical Antimicrobial Therapy for Treating Chronic Wounds SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ANTIBIOTIC-RESISTANT BACTERIA; DIABETIC FOOT ULCERS; VENOUS LEG ULCERS; SKIN INFECTIONS; IN-VITRO; COLONIZATION; RETAPAMULIN; HONEY; MICROBIOLOGY; MANAGEMENT AB Various agents have been applied topically to treat infected wounds for millennia, but their proper role remains unclear. Topical therapy affords many potential advantages but also has disadvantages. Opinions differ on which clinical signs define wound infection and on whether quantitative microbiological studies are useful. Clinically infected wounds usually require systemic antibiotic therapy, whereas clinically uninfected wounds that are healing as expected do not require antimicrobials. There is controversy over how to treat poorly healing wounds with "secondary" signs suggesting infection; these may benefit from topical antimicrobial agents. Some evidence supports using topical agents for malodorous or burn wounds. Meta-analyses and systematic reviews suggest there are few proven indications for topical antimicrobials. Use of a newer, relatively nontoxic antiseptic (eg, cadexomer iodine or silver dressings) is preferable to use of topical antibiotics, especially agents that are available for systemic use. We provide clinically relevant information on currently available topical antimicrobial agents. C1 [Lipsky, Benjamin A.; Hoey, Christopher] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Lipsky, Benjamin A.] Univ Washington, Sch Med, Seattle, WA USA. RP Lipsky, BA (reprint author), VA Puget Sound Hlth Care Syst, S-111-PCC 1660 S Columbian Way, Seattle, WA 98108 USA. EM balipsky@u.washington.edu OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 53 TC 113 Z9 119 U1 6 U2 50 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2009 VL 49 IS 10 BP 1541 EP 1549 DI 10.1086/644732 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 511EH UT WOS:000271146200015 PM 19842981 ER PT J AU Carneiro, HA Mylonakis, E AF Carneiro, Herman Anthony Mylonakis, Eleftherios TI Google Trends: A Web-Based Tool for Real-Time Surveillance of Disease Outbreaks SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID WEST-NILE-VIRUS; SYNDROMIC SURVEILLANCE; INFLUENZA SURVEILLANCE; EPIDEMIC AB Google Flu Trends can detect regional outbreaks of influenza 7-10 days before conventional Centers for Disease Control and Prevention surveillance systems. We describe the Google Trends tool, explain how the data are processed, present examples, and discuss its strengths and limitations. Google Trends shows great promise as a timely, robust, and sensitive surveillance system. It is best used for surveillance of epidemics and diseases with high prevalences and is currently better suited to track disease activity in developed countries, because to be most effective, it requires large populations of Web search users. Spikes in search volume are currently hard to interpret but have the benefit of increasing vigilance. Google should work with public health care practitioners to develop specialized tools, using Google Flu Trends as a blueprint, to track infectious diseases. Suitable Web search query proxies for diseases need to be established for specialized tools or syndromic surveillance. This unique and innovative technology takes us one step closer to true real-time outbreak surveillance. C1 [Carneiro, Herman Anthony; Mylonakis, Eleftherios] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Carneiro, Herman Anthony] Univ London Imperial Coll Sci Technol & Med, Sch Med, London, England. RP Mylonakis, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Gray Jackson 5,Rm GRJ-504, Boston, MA 02114 USA. EM emylonakis@partners.org NR 29 TC 166 Z9 178 U1 8 U2 69 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2009 VL 49 IS 10 BP 1557 EP 1564 DI 10.1086/630200 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 511EH UT WOS:000271146200017 PM 19845471 ER PT J AU Losina, E Schackman, BR Sadownik, SN Gebo, KA Walensky, RP Chiosi, JJ Weinstein, MC Hicks, PL Aaronson, WH Moore, RD Paltiel, AD Freedberg, KA AF Losina, Elena Schackman, Bruce R. Sadownik, Sara N. Gebo, Kelly A. Walensky, Rochelle P. Chiosi, John J. Weinstein, Milton C. Hicks, Perrin L. Aaronson, Wendy H. Moore, Richard D. Paltiel, A. David Freedberg, Kenneth A. TI Racial and Sex Disparities in Life Expectancy Losses among HIV-Infected Persons in the United States: Impact of Risk Behavior, Late Initiation, and Early Discontinuation of Antiretroviral Therapy SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INJECTING DRUG-USERS; COST-EFFECTIVENESS; CONTROLLED-TRIAL; MEDICAL-CARE; TENOFOVIR DF; HEALTH-CARE; COHORT; AIDS; MORTALITY AB Background. Most persons with human immunodeficiency virus (HIV) infection in the United States present to care with advanced disease, and many patients discontinue therapy prematurely. We sought to evaluate sex and racial/ethnic disparities in life-years lost as a result of risk behavior, late presentation, and early discontinuation of HIV care, and we compared these survival losses for HIV-infected persons with losses attributable to high-risk behavior and HIV disease itself. Methods. With use of a state-transition model of HIV disease, we simulated cohorts of HIV-infected persons and compared them with uninfected individuals who had similar demographic characteristics. We estimated non-HIV-related mortality with use of risk-adjusted standardized mortality ratios, as well as years of life lost because of late presentation and early discontinuation of antiretroviral therapy (ART) for HIV infection. Data from the national HIV Research Network, stratified by sex and race/ethnicity, were used for estimating CD4(+) cell counts at ART initiation. Results. For HIV-uninfected persons in the United States who have risk profiles similar to those of individuals with HIV infection, the projected life expectancy, starting at 33 years of age, was 34.58 years, compared with 42.91 years for the general US population. Those with HIV infection lost an additional 11.92 years of life if they received HIV care concordant with guidelines; late treatment initiation resulted in 2.60 additional years of life lost, whereas premature ART discontinuation led to 0.70 more years of life lost. Losses from late initiation and early discontinuation were greatest for Hispanic individuals (3.90 years). Conclusions. The high-risk profile of HIV-infected persons, HIV infection itself, as well as late initiation and early discontinuation of care, all lead to substantial decreases in life expectancy. Survival disparities resulting from late initiation and early discontinuation of therapy are most pronounced for Hispanic HIV-infected men and women. Interventions focused on risk behaviors, as well as on earlier linkage to and better retention in care, will lead to improved survival for HIV-infected persons in the United States. C1 [Losina, Elena; Sadownik, Sara N.; Walensky, Rochelle P.; Chiosi, John J.; Aaronson, Wendy H.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Losina, Elena; Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Sadownik, Sara N.; Weinstein, Milton C.; Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Schackman, Bruce R.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA. [Gebo, Kelly A.; Hicks, Perrin L.; Moore, Richard D.] Johns Hopkins Univ, Dept Med, Sch Med, Baltimore, MD USA. [Paltiel, A. David] Yale Univ, Dept Epidemiol & Publ Hlth, Sch Med, New Haven, CT 06520 USA. RP Losina, E (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Med, 50 Staniford St,9th Flr, Boston, MA 02114 USA. EM elosina@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Allergy and Infectious Diseases [K23 AI01794, K24 AI062476, K25 AI50436, R37 AI42006]; National Institute on Drug Abuse [K23 DA000523, K01 DA017179, K24 DA00432]; National Institute of Mental Health [MH065879]; Agency for Healthcare Research and Quality [290-01-012]; Doris Duke Charitable Foundation; Johns Hopkins University FX National Institute of Allergy and Infectious Diseases (K23 AI01794, K24 AI062476, K25 AI50436, and R37 AI42006), National Institute on Drug Abuse (K23 DA000523, K01 DA017179, and K24 DA00432), National Institute of Mental Health (MH065879), Agency for Healthcare Research and Quality (290-01-012), Doris Duke Charitable Foundation (Clinical Scientist Development Award to R.P.W.), and Johns Hopkins University (Richard S. Ross Clinical Scientist Award to K.A.G.). NR 67 TC 106 Z9 106 U1 2 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2009 VL 49 IS 10 BP 1570 EP 1578 DI 10.1086/644772 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 511EH UT WOS:000271146200019 PM 19845472 ER PT J AU Chen, TY Ding, EL Seage, GR Kim, AY AF Chen, Ting-Yi Ding, Eric L. Seage, George R., III Kim, Arthur Y. TI Meta-Analysis: Increased Mortality Associated with Hepatitis C in HIV-Infected Persons Is Unrelated to HIV Disease Progression SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-DEFINING EVENTS; INJECTION-DRUG USERS; LIVER-DISEASE; CLINICAL PROGRESSION; POSITIVE PATIENTS; FIBROSIS PROGRESSION; COINFECTED PATIENTS; SURVIVAL AB Background. It is unclear whether coinfection with hepatitis C virus (HCV) increases mortality in patients with human immunodeficiency virus (HIV) infection during the era of highly active antiretroviral therapy (HAART). With use of a meta-analysis, we estimated the effect of HCV infection on HIV disease progression and overall mortality in the pre-HAART and HAART eras. Method. The PubMed and EMBASE databases were searched for studies published through 30 April 2008. Additional studies were identified from cited references. Studies reporting disease progression or mortality among HCV-HIV coinfected patients were selected. Cross-sectional studies, studies without HCV-negative control subjects, and studies involving children and/or patients who had undergone liver transplantation were excluded. Two authors reviewed articles and extracted data on the demographic characteristics of study populations and risk estimates. Meta-regression was used to explore heterogeneity. Results. Ten studies from the pre-HAART era and 27 studies from the HAART era were selected. In the pre-HAART era, the risk ratio for overall mortality among patients with HCV-HIV coinfection, compared with that among patients with HIV infection alone, was 0.68 (95% confidence interval [CI], 0.53-0.87). In the HAART era, the risk ratio was 1.12 (95% CI, 0.82-1.51) for AIDS-defining events and 1.35 (95% CI, 1.11-1.63) for overall mortality among coinfected patients, compared with that among patients with HIV monoinfection. Conclusions. HCV coinfection did not increase mortality among patients with HIV infection before the introduction of HAART. In contrast, in the HAART era, HCV coinfection, compared with HIV infection alone, increases the risk of mortality, but not the risk of AIDS-defining events. Future studies should determine whether successful treatment of HCV infection could reduce this excess risk of mortality in coinfected patients. C1 [Chen, Ting-Yi] Wayne State Univ, Detroit Med Ctr, Detroit, MI 48201 USA. [Ding, Eric L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kim, Arthur Y.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Chen, TY (reprint author), Wayne State Univ, Detroit Med Ctr, 4201 St Antoine,2E, Detroit, MI 48201 USA. EM tchen2@med.wayne.edu RI Chen, Ting-Yi/B-3144-2013; OI Ding, Eric/0000-0002-5881-8097 FU The Paul and Daisy Soros Foundation; National Institutes of Health/National Institute of Allergy and Infectious Diseases [U19 AI066345, K23 AI054379] FX The Paul and Daisy Soros Foundation (fellowship to E.L.D) and the National Institutes of Health/National Institute of Allergy and Infectious Diseases (grants U19 AI066345 and K23 AI054379 to A.Y.K.). NR 73 TC 94 Z9 101 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2009 VL 49 IS 10 BP 1605 EP 1615 DI 10.1086/644771 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 511EH UT WOS:000271146200024 PM 19842982 ER PT J AU Aujesky, D McCausland, JB Whittle, J Obrosky, DS Yealy, DM Fine, MJ AF Aujesky, Drahomir McCausland, Julie B. Whittle, Jeff Obrosky, D. Scott Yealy, Donald M. Fine, Michael J. TI Reasons Why Emergency Department Providers Do Not Rely on the Pneumonia Severity Index to Determine the Initial Site of Treatment for Patients with Pneumonia SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; LOW-RISK PATIENTS; RESEARCH TEAM COHORT; PREDICTION RULE; ADMISSION DECISION; CLINICAL JUDGMENT; RANDOMIZED-TRIAL; HOSPITALIZATION; OUTCOMES; CARE AB Background. Many emergency department (ED) providers do not follow guideline recommendations for the use of the pneumonia severity index (PSI) to determine the initial site of treatment for patients with community-acquired pneumonia (CAP). We identified the reasons why ED providers hospitalize low-risk patients or manage higher-risk patients as outpatients. Methods. As a part of a trial to implement a PSI-based guideline for the initial site of treatment of patients with CAP, we analyzed data for patients managed at 12 EDs allocated to a high-intensity guideline implementation strategy study arm. The guideline recommended outpatient care for low-risk patients (nonhypoxemic patients with a PSI risk classification of I, II, or III) and hospitalization for higher-risk patients (hypoxemic patients or patients with a PSI risk classification of IV or V). We asked providers who made guideline-discordant decisions on site of treatment to detail the reasons for nonadherence to guideline recommendations. Results. There were 1,306 patients with CAP (689 low-risk patients and 617 higher-risk patients). Among these patients, physicians admitted 258 (37.4%) of 689 low-risk patients and treated 20 (3.2%) of 617 higher-risk patients as outpatients. The most commonly reported reasons for admitting low-risk patients were the presence of a comorbid illness (178 [71.5%] of 249 patients); a laboratory value, vital sign, or symptom that precluded ED discharge (73 patients [29.3%]); or a recommendation from a primary care or a consulting physician (48 patients [19.3%]). Higher-risk patients were most often treated as outpatients because of a recommendation by a primary care or consulting physician (6 [40.0%] of 15 patients). Conclusion. ED providers hospitalize many low-risk patients with CAP, most frequently for a comorbid illness. Although higher-risk patients are infrequently treated as outpatients, this decision is often based on the request of an involved physician. C1 [Aujesky, Drahomir] Univ Lausanne, Dept Med, Div Gen Internal Med, Lausanne, Switzerland. [McCausland, Julie B.; Yealy, Donald M.] Univ Pittsburgh, Dept Emergency Med, Pittsburgh, PA USA. [Obrosky, D. Scott; Fine, Michael J.] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Obrosky, D. Scott; Fine, Michael J.] Vet Affairs Pittsburgh Healthcare Syst, Vet Affairs Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Whittle, Jeff] Med Coll Wisconsin, Clement J Zablocki Vet Affairs Med Ctr, Primary Care Div, Milwaukee, WI 53226 USA. [Whittle, Jeff] Med Coll Wisconsin, Dept Med, Div Gen Internal Med, Milwaukee, WI 53226 USA. RP Aujesky, D (reprint author), CHU Vaudois, Serv Med Interne, BH 10-622, CH-1011 Lausanne, Switzerland. EM drahomir.aujesky@chuv.ch FU Agency for Healthcare Research and Quality [R01 HS10049]; National Institute of Allergy and Infectious Diseases [K24 AI001769] FX Financial support. This research was conducted as part of the project entitled "Guideline to Improve Quality of Initial Pneumonia Care," funded by the Agency for Healthcare Research and Quality (grant R01 HS10049). M.J.F. received support in part from a career development award from the National Institute of Allergy and Infectious Diseases (grant K24 AI001769). NR 25 TC 38 Z9 39 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2009 VL 49 IS 10 BP E100 EP E108 DI 10.1086/644741 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 511EH UT WOS:000271146200032 PM 19842971 ER PT J AU Lefebvre, L Mar, L Bogutz, A Oh-McGinnis, R Mandegar, MA Paderova, J Gertsenstein, M Squire, JA Nagy, A AF Lefebvre, Louis Mar, Lynn Bogutz, Aaron Oh-McGinnis, Rosemary Mandegar, Mohammad A. Paderova, Jana Gertsenstein, Marina Squire, Jeremy A. Nagy, Andras TI The interval between Ins2 and AscI2 is dispensable for imprinting centre function in the murine Beckwith-Wiedemann region SO HUMAN MOLECULAR GENETICS LA English DT Article ID MOUSE DISTAL CHROMOSOME-7; H19 GENE; TARGETED DISRUPTION; CRE RECOMBINASE; MICE LACKING; IGF2 GENE; YOLK-SAC; DOMAIN; EXPRESSION; METHYLATION AB Imprinted genes are commonly clustered in domains across the mammalian genome, suggesting a degree of coregulation via long-range coordination of their monoallelic transcription. The distal end of mouse chromosome 7 (Chr 7) contains two clusters of imprinted genes within a similar to 1 Mb domain. This region is conserved on human 11p15.5 where it is implicated in the Beckwith-Wiedemann syndrome. In both species, imprinted regulation requires two critical cis-acting imprinting centres, carrying different germline epigenetic marks and mediating imprinted expression in the proximal and distal sub-domains. The clusters are separated by a region containing the gene for tyrosine hydroxylase (Th) as well as a high density of short repeats and retrotransposons in the mouse. We have used the Cre-loxP recombination system in vivo to engineer an interstitial deletion of this similar to 280-kb intervening region previously proposed to participate in the imprinting mechanism or to act as a boundary between the two sub-domains. The deletion allele, Del(7AI), is silent with respect to epigenetic marking at the two flanking imprinting centres. Reciprocal inheritance of Del(7AI) demonstrates that the deleted region, which represents more than a quarter of the previously defined imprinted domain, is associated with intrauterine growth restriction in maternal heterozygotes. In homozygotes, the deficiency behaves as a Th null allele and can be rescued pharmacologically by bypassing the metabolic requirement for TH in utero. Our results show that the deleted interval is not required for normal imprinting on distal Chr 7 and uncover a new imprinted growth phenotype. C1 [Lefebvre, Louis; Bogutz, Aaron; Oh-McGinnis, Rosemary; Mandegar, Mohammad A.] Univ British Columbia, Dept Med Genet, Inst Life Sci, Vancouver, BC V6T 1Z3, Canada. [Lefebvre, Louis; Bogutz, Aaron; Oh-McGinnis, Rosemary; Mandegar, Mohammad A.] Univ British Columbia, Mol Epigenet Grp, Inst Life Sci, Vancouver, BC V6T 1Z3, Canada. [Mar, Lynn] Dana Farber Canc Inst, Boston, MA 02115 USA. [Paderova, Jana; Squire, Jeremy A.] Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada. [Paderova, Jana; Squire, Jeremy A.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada. [Gertsenstein, Marina; Nagy, Andras] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Gertsenstein, Marina; Nagy, Andras] Univ Toronto, Dept Med Genet, Toronto, ON M5G 1X5, Canada. RP Lefebvre, L (reprint author), Univ British Columbia, Dept Med Genet, Inst Life Sci, Vancouver, BC V6T 1Z3, Canada. EM louis.lefebvre@ubc.ca RI Nagy, Andras/G-6465-2013; Lefebvre, Louis/O-9309-2016 OI Lefebvre, Louis/0000-0001-5664-9480 FU Canadian Institutes of Health [MOP-82863, FRN 13687]; Canada Research Chair; Michael Smith Foundation for Health Research (MSFHR) FX This work was supported in part by the Canadian Institutes of Health Research (MOP-82863 to L.L. and FRN 13687 to A.N.). L.L. holds a Canada Research Chair and was also supported by a Michael Smith Foundation for Health Research (MSFHR) Scholar Award. NR 60 TC 7 Z9 7 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 15 PY 2009 VL 18 IS 22 BP 4255 EP 4267 DI 10.1093/hmg/ddp379 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 510RB UT WOS:000271107300003 PM 19684026 ER PT J AU Berger, AK Cortese, GP Amodeo, KD Weihofen, A Letai, A LaVoie, MJ AF Berger, Alison K. Cortese, Giuseppe P. Amodeo, Katherine D. Weihofen, Andreas Letai, Anthony LaVoie, Matthew J. TI Parkin selectively alters the intrinsic threshold for mitochondrial cytochrome c release SO HUMAN MOLECULAR GENETICS LA English DT Article ID RECESSIVE JUVENILE PARKINSONISM; OXIDATIVE STRESS; CELL-DEATH; DISEASE; MUTATIONS; APOPTOSIS; GENE; ACTIVATION; MUTANTS; BAX AB Autosomal-recessive mutations in the Parkin gene are the second most common cause of familial Parkinson's disease (PD). Parkin deficiency leads to the premature demise of the catecholaminergic neurons of the ventral midbrain in familial PD. Thus, a better understanding of parkin function may elucidate molecular aspects of their selective vulnerability in idiopathic PD. Numerous lines of evidence suggest a mitochondrial function for parkin and a protective effect of ectopic parkin expression. Since mitochondria play a critical role in cell survival/cell death through regulated cytochrome c release and control of apoptosis, we sought direct evidence of parkin function in this pathway. Mitochondria were isolated from cells expressing either excess levels of human parkin or shRNA directed against endogenous parkin and then treated with peptides corresponding to the active Bcl-2 homology 3 (BH3) domains of pro-apoptotic proteins and the threshold for cytochrome c release was analyzed. Data obtained from both rodent and human neuroblastoma cell lines showed that the expression levels of parkin were inversely correlated with cytochrome c release. Parkin was found associated with isolated mitochondria, but its binding per se was not sufficient to inhibit cytochrome c release. In addition, pathogenic parkin mutants failed to influence cytochrome c release. Furthermore, PINK1 expression had no effect on cytochrome c release, suggesting a divergent function for this autosomal recessive PD-linked gene. In summary, these data demonstrate a specific autonomous effect of parkin on mitochondrial mechanisms governing cytochrome c release and apoptosis, which may be relevant to the selective vulnerability of certain neuronal populations in PD. C1 [Berger, Alison K.; Cortese, Giuseppe P.; Amodeo, Katherine D.; Weihofen, Andreas; LaVoie, Matthew J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Berger, Alison K.; Weihofen, Andreas; Letai, Anthony; LaVoie, Matthew J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Weihofen, Andreas] Neurimmune Therapeut AG, Schlieren, Switzerland. [Letai, Anthony] Dana Farber Canc Inst, Boston, MA 02115 USA. RP LaVoie, MJ (reprint author), Harvard Inst Med, Room 764,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM mlavoie@rics.bwh.harvard.edu RI Weihofen, Andreas/A-1566-2011 FU National Institutes of Health [AG023094, AG00222]; The Smith Family Foundation; Ludke Foundation; American Parkinson's Disease Association; The Parkinson's Disease Foundation; Brigham and Women's Hospital [P50 NS03875] FX This work was supported by the National Institutes of Health (AG023094 to M.J.L., AG00222 to A.K.B.); The Smith Family Foundation; the Ludke Foundation to M.J.L and A.G.L.; the American Parkinson's Disease Association to M.J.L.; and The Parkinson's Disease Foundation to M.J.L. and the Brigham and Women's Hospital Udall Center of Excellence in Parkinson's Disease Research (P50 NS03875). NR 48 TC 46 Z9 47 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 15 PY 2009 VL 18 IS 22 BP 4317 EP 4328 DI 10.1093/hmg/ddp384 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 510RB UT WOS:000271107300008 PM 19679562 ER PT J AU Won, JY Gifford, E Smith, RS Yi, HQ Ferreira, PA Hicks, WL Li, TS Naggert, JK Nishina, PM AF Won, Jungyeon Gifford, Elaine Smith, Richard S. Yi, Haiqing Ferreira, Paulo A. Hicks, Wanda L. Li, Tiansen Naggert, Juergen K. Nishina, Patsy M. TI RPGRIP1 is essential for normal rod photoreceptor outer segment elaboration and morphogenesis SO HUMAN MOLECULAR GENETICS LA English DT Article ID LEBER CONGENITAL AMAUROSIS; REGULATOR (RPGR)-INTERACTING PROTEIN; RDS MUTANT MICE; RETINITIS-PIGMENTOSA; RETINAL DEGENERATION; MOUSE MODEL; SUBCELLULAR-LOCALIZATION; GENE-EXPRESSION; IDENTIFICATION; MUTATIONS AB The function of the retinitis pigmentosa GTPase regulator interacting protein 1 (RPGRIP1) gene is currently not known. However, mutations within the gene lead to Leber Congenital Amaurosis and autosomal recessive retinitis pigmentosa in human patients. In a previously described knockout mouse model of the long splice variant of Rpgrip1, herein referred to as Rpgrip1(tm1Tili) mice, mislocalization of key outer segment proteins and dysmorphogenesis of outer segment discs preceded subsequent photoreceptor degeneration. In this report, we describe a new mouse model carrying a splice acceptor site mutation in Rpgrip1, herein referred to as Rpgrip1(nmf247) that is phenotypically distinct from Rpgrip1(tm1Tili) mice. Photoreceptor degeneration in homozygous Rpgrip1(nmf247) mice is earlier in onset and more severe when compared with Rpgrip1(tm1Tili) mice. Also, ultrastructural studies reveal that whereas Rpgrip1(nmf247) mutants have a normal structure and number of connecting cilia, unlike Rpgrip1(tm1Tili) mice, they do not elaborate rod outer segments (OS). Therefore, in addition to its role in OS disc morphogenesis, RPGRIP1 is essential for rod OS formation. Our study indicates the absence of multiple Rpgrip1 isoforms in Rpgrip1(nmf247) mice, suggesting different isoforms may play different roles in photoreceptors and underscores the importance of considering splice variants when generating targeted null mutations. C1 [Won, Jungyeon; Gifford, Elaine; Smith, Richard S.; Hicks, Wanda L.; Naggert, Juergen K.; Nishina, Patsy M.] Jackson Lab, Bar Harbor, ME 04609 USA. [Yi, Haiqing; Ferreira, Paulo A.] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA. [Ferreira, Paulo A.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. [Li, Tiansen] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Nishina, PM (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM patsy.nishina@jax.org RI Ferreira, Paulo/S-4209-2016 OI Ferreira, Paulo/0000-0003-4585-1717 FU National Institutes of Health [EY016501, 2P30-EY005722-21]; TJL institutional core grant [CA34196] FX This study was supported by National Institutes of Health grant, EY016501 (P.M.N.), National Institutes of Health core grant, 2P30-EY005722-21 (P.A.F.), a TJL institutional core grant, CA34196, and the Jules & Doris Stein Research to Prevent Blindness Professor (P.A.F.). NR 49 TC 25 Z9 25 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 15 PY 2009 VL 18 IS 22 BP 4329 EP 4339 DI 10.1093/hmg/ddp385 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 510RB UT WOS:000271107300009 PM 19679561 ER PT J AU Antoniou, AC Sinilnikova, OM McGuffog, L Healey, S Nevanlinna, H Heikkinen, T Simard, J Spurdle, AB Beesley, J Chen, XQ Neuhausen, SL Ding, YC Couch, FJ Wang, XS Fredericksen, Z Peterlongo, P Peissel, B Bonanni, B Viel, A Bernard, L Radice, P Szabo, CI Foretova, L Zikan, M Claes, K Greene, MH Mai, PL Rennert, G Lejbkowicz, F Andrulis, IL Ozcelik, H Glendon, G Gerdes, AM Thomassen, M Sunde, L Caligo, MA Laitman, Y Kontorovich, T Cohen, S Kaufman, B Dagan, E Baruch, RG Friedman, E Harbst, K Barbany-Bustinza, G Rantala, J Ehrencrona, H Karlsson, P Domchek, SM Nathanson, KL Osorio, A Blanco, I Lasa, A Benitez, J Hamann, U Hogervorst, FBL Rookus, MA Collee, JM Devilee, P Ligtenberg, MJ van der Luijt, RB Aalfs, CM Waisfisz, Q Wijnen, J van Roozendaal, CEP Peock, S Cook, M Frost, D Oliver, C Platte, R Evans, DG Lalloo, F Eeles, R Izatt, L Davidson, R Chu, C Eccles, D Cole, T Hodgson, S Godwin, AK Stoppa-Lyonnet, D Buecher, B Leone, M Bressac-de Paillerets, B Remenieras, A Caron, O Lenoir, GM Sevenet, N Longy, M Ferrer, SF Prieur, F Goldgar, D Miron, A John, EM Buys, SS Daly, MB Hopper, JL Terry, MB Yassin, Y Singer, C Gschwantler-Kaulich, D Staudigl, C Hansen, TVO Barkardottir, RB Kirchhoff, T Pal, P Kosarin, K Offit, K Piedmonte, M Rodriguez, GC Wakeley, K Boggess, JF Basil, J Schwartz, PE Blank, SV Toland, AE Montagna, M Casella, C Imyanitov, EN Allavena, A Schmutzler, RK Versmold, B Engel, C Meindl, A Ditsch, N Arnold, N Niederacher, D Deissler, H Fiebig, B Suttner, C Schonbuchner, I Gadzicki, D Caldes, T de la Hoya, M Pooley, KA Easton, DF Chenevix-Trench, G AF Antoniou, Antonis C. Sinilnikova, Olga M. McGuffog, Lesley Healey, Sue Nevanlinna, Heli Heikkinen, Tuomas Simard, Jacques Spurdle, Amanda B. Beesley, Jonathan Chen, Xiaoqing Neuhausen, Susan L. Ding, Yuan C. Couch, Fergus J. Wang, Xianshu Fredericksen, Zachary Peterlongo, Paolo Peissel, Bernard Bonanni, Bernardo Viel, Alessandra Bernard, Loris Radice, Paolo Szabo, Csilla I. Foretova, Lenka Zikan, Michal Claes, Kathleen Greene, Mark H. Mai, Phuong L. Rennert, Gad Lejbkowicz, Flavio Andrulis, Irene L. Ozcelik, Hilmi Glendon, Gord Gerdes, Anne-Marie Thomassen, Mads Sunde, Lone Caligo, Maria A. Laitman, Yael Kontorovich, Tair Cohen, Shimrit Kaufman, Bella Dagan, Efrat Baruch, Ruth Gershoni Friedman, Eitan Harbst, Katja Barbany-Bustinza, Gisela Rantala, Johanna Ehrencrona, Hans Karlsson, Per Domchek, Susan M. Nathanson, Katherine L. Osorio, Ana Blanco, Ignacio Lasa, Adriana Benitez, Javier Hamann, Ute Hogervorst, Frans B. L. Rookus, Matti A. Collee, J. Margriet Devilee, Peter Ligtenberg, Marjolijn J. van der Luijt, Rob B. Aalfs, Cora M. Waisfisz, Quinten Wijnen, Juul van Roozendaal, Cornelis E. P. Peock, Susan Cook, Margaret Frost, Debra Oliver, Clare Platte, Radka Evans, D. Gareth Lalloo, Fiona Eeles, Rosalind Izatt, Louise Davidson, Rosemarie Chu, Carol Eccles, Diana Cole, Trevor Hodgson, Shirley Godwin, Andrew K. Stoppa-Lyonnet, Dominique Buecher, Bruno Leone, Melanie Bressac-de Paillerets, Brigitte Remenieras, Audrey Caron, Olivier Lenoir, Gilbert M. Sevenet, Nicolas Longy, Michel Ferrer, Sandra Fert Prieur, Fabienne Goldgar, David Miron, Alexander John, Esther M. Buys, Saundra S. Daly, Mary B. Hopper, John L. Terry, Mary Beth Yassin, Yosuf Singer, Christian Gschwantler-Kaulich, Daphne Staudigl, Christine Hansen, Thomas V. O. Barkardottir, Rosa Bjork Kirchhoff, Tomas Pal, Prodipto Kosarin, Kristi Offit, Kenneth Piedmonte, Marion Rodriguez, Gustavo C. Wakeley, Katie Boggess, John F. Basil, Jack Schwartz, Peter E. Blank, Stephanie V. Toland, Amanda E. Montagna, Marco Casella, Cinzia Imyanitov, Evgeny N. Allavena, Anna Schmutzler, Rita K. Versmold, Beatrix Engel, Christoph Meindl, Alfons Ditsch, Nina Arnold, Norbert Niederacher, Dieter Deissler, Helmut Fiebig, Britta Suttner, Christian Schoenbuchner, Ines Gadzicki, Dorothea Caldes, Trinidad de la Hoya, Miguel Pooley, Karen A. Easton, Douglas F. Chenevix-Trench, Georgia CA Kathleen Cuningham Fdn Consortium OCGN HEBON EMBRACE GEMO Breast Canc Family Registry CIMBA TI Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; ESTROGEN-RECEPTOR; OVARIAN-CANCER; SUSCEPTIBILITY; GENE; POPULATION; EXPRESSION; ALLELES AB Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 x 10(-4)]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not. C1 [Antoniou, Antonis C.; McGuffog, Lesley; Peock, Susan; Cook, Margaret; Frost, Debra; Oliver, Clare; Platte, Radka; Pooley, Karen A.; Easton, Douglas F.; EMBRACE] Univ Cambridge, Dept Publ Hlth & Primary Care, Canc Res UK Genet Epidemiol Unit, Cambridge, England. [Sinilnikova, Olga M.; Leone, Melanie] Univ Lyon, CNRS, Hosp Civils Lyon,Ctr Leon Berard,UMR5201, Unite Mixte Genet Constitut Canc Frequents, Lyon, France. [Healey, Sue; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4029, Australia. [Nevanlinna, Heli; Heikkinen, Tuomas] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Simard, Jacques] Univ Laval, Quebec City, PQ, Canada. [Simard, Jacques] Univ Quebec, Ctr Hosp, Canada Res Chair Oncogenet, Canc Genom Lab, Quebec City, PQ, Canada. [Kathleen Cuningham Fdn Consortium] Peter MacCallum Canc Inst, Melbourne, Vic 3002, Australia. [Neuhausen, Susan L.; Ding, Yuan C.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Couch, Fergus J.; Wang, Xianshu; Fredericksen, Zachary] Mayo Clin, Rochester, MN USA. [Peterlongo, Paolo; Peissel, Bernard; Radice, Paolo] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Peterlongo, Paolo; Radice, Paolo] Fdn Ist FIRC Oncol Molecolare, Milan, Italy. [Bonanni, Bernardo; Bernard, Loris] Ist Europeo Oncol, Milan, Italy. [Viel, Alessandra] IRCCS, Ctr Riferimento Oncol, Aviano, Italy. [Bernard, Loris] Cogentech, Consortium Genom Technol, Milan, Italy. [Szabo, Csilla I.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA. [Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Zikan, Michal] Charles Univ Prague, Dept Biochem & Expt Oncol, Fac Med 1, Prague, Czech Republic. [Claes, Kathleen] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium. [Greene, Mark H.; Mai, Phuong L.] US Natl Canc Inst, Clin Genet Branch, Rockville, MD USA. [Rennert, Gad; Lejbkowicz, Flavio] CHS Natl Canc Control Ctr, Haifa, Israel. [Rennert, Gad; Lejbkowicz, Flavio] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel. [Rennert, Gad; Lejbkowicz, Flavio] B Rappaport Fac Med, Haifa, Israel. [Andrulis, Irene L.; Glendon, Gord; OCGN] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON M5G 2L7, Canada. [Andrulis, Irene L.] Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Samuel Lunenfeld Res Inst, Toronto, ON, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Gerdes, Anne-Marie; Thomassen, Mads] Odense Univ Hosp, Dept Biochem Pharmacol & Genet, DK-5000 Odense, Denmark. [Sunde, Lone] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark. [Caligo, Maria A.] Univ Pisa, Div Surg Mol & Ultrastructural Pathol, Dept Oncol, Pisa, Italy. [Caligo, Maria A.] Pisa Univ Hosp, Pisa, Italy. [Laitman, Yael; Kontorovich, Tair; Cohen, Shimrit; Friedman, Eitan] Chaim Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel. [Kaufman, Bella] Chaim Sheba Med Ctr, Inst Oncol, IL-52621 Tel Hashomer, Israel. [Kaufman, Bella; Friedman, Eitan] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Dagan, Efrat; Baruch, Ruth Gershoni] Rambam Med Ctr, Genet Inst, Haifa, Israel. [Harbst, Katja] Lund Univ, Dept Oncol, S-22100 Lund, Sweden. [Barbany-Bustinza, Gisela; Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Ehrencrona, Hans] Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden. [Karlsson, Per] Sahlgrenska Univ, Dept Oncol, Gothenburg, Sweden. [Domchek, Susan M.; Nathanson, Katherine L.] Univ Penn, Philadelphia, PA 19104 USA. [Osorio, Ana; Benitez, Javier] Ctr Invest Biomed Red Enfermedades Raras CIBERERE, Inst Salud Carlos III, Madrid, Spain. [Osorio, Ana; Benitez, Javier] Spanish Natl Canc Ctr CNIO, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain. [Blanco, Ignacio] Catalan Inst Oncol ICO, Canc Genet Counseling Program, Barcelona, Spain. [Lasa, Adriana] Hosp Santa Creu & Sant Pau, Genet Serv, Barcelona, Spain. [Hamann, Ute] Deutsch Krebsforschungszentrum, Neuenheimer Feld 580 69120, D-6900 Heidelberg, Germany. [Hogervorst, Frans B. L.] Netherlands Canc Inst, Dept Pathol, Family Canc Clin, NL-1066 CX Amsterdam, Netherlands. [Rookus, Matti A.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [Collee, J. Margriet] Erasmus Univ, Dept Clin Genet, Rotterdam Family Canc Clin, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Devilee, Peter] Dept Genet Epidemiol, Leiden, Netherlands. [Wijnen, Juul] Leiden Univ, Med Ctr, Ctr Human & Clin Genet, Leiden, Netherlands. [Ligtenberg, Marjolijn J.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [van der Luijt, Rob B.] Univ Utrecht, Med Ctr, Dept Clin Mol Genet, NL-3508 TC Utrecht, Netherlands. [Aalfs, Cora M.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. [Waisfisz, Quinten] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [van Roozendaal, Cornelis E. P.] Univ Med Ctr, Dept Clin Genet, Maastricht, Netherlands. [Evans, D. Gareth; Lalloo, Fiona] Cent Manchester Univ Hosp, NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Eeles, Rosalind] Inst Canc Res, Translat Canc Genet Team, London SW3 6JB, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, London, England. [Izatt, Louise] Guys Hosp, Clin Genet, London SE1 9RT, England. [Davidson, Rosemarie] Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland. [Chu, Carol] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Eccles, Diana] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England. [Cole, Trevor] Birmingham Womens Hosp Healthcare, NHS Trust, W Midlands Reg Genet Serv, Birmingham, W Midlands, England. [Hodgson, Shirley] Univ London, Dept Canc Genet, St Georges Hosp, London, England. [Godwin, Andrew K.; Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Stoppa-Lyonnet, Dominique] Univ Paris 05, Paris, France. [Stoppa-Lyonnet, Dominique; GEMO] Inst Curie, INSERM U509, Serv Genet Oncol, Paris, France. [Buecher, Bruno] Inst Curie, Dept Genet, Paris, France. [Bressac-de Paillerets, Brigitte; Remenieras, Audrey; Lenoir, Gilbert M.] Inst Cancrol Gustave Roussy, Dept Genet, Villejuif, France. [Bressac-de Paillerets, Brigitte] Inst Cancerol Gustave Roussy, INSERM U946, Villejuif, France. [Caron, Olivier] Inst Cancerol Gustave Roussy, Dept Med, Villejuif, France. [Lenoir, Gilbert M.] Inst Cancerol Gustave Roussy, CNRS FRE2939, Villejuif, France. [Sevenet, Nicolas; Longy, Michel] Inst Bergonie, Lab Genet Constitutionnelle, Bordeaux, France. [Longy, Michel] Inst Bergonie, INSERM U916, Bordeaux, France. [Ferrer, Sandra Fert] Hop Hotel Dieu, Ctr Hosp, Lab Genet Chromosom, Chambery, France. [Prieur, Fabienne] CHU St Etienne, Serv Genet Clin Chromosom, St Etienne, France. [Goldgar, David] Univ Utah, Dept Dermatol, Salt Lake City, UT 84112 USA. [Miron, Alexander; Yassin, Yosuf] Dana Farber Canc Inst, Boston, MA 02115 USA. [John, Esther M.] No Calif Canc Ctr, Fremont, CA USA. [John, Esther M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Buys, Saundra S.] Univ Utah, Hlth Sci Ctr, Huntsman Canc Inst, Salt Lake City, UT USA. [Hopper, John L.] Univ Melbourne, Melbourne, Australia. [Terry, Mary Beth] Columbia Univ, New York, NY USA. [Singer, Christian; Gschwantler-Kaulich, Daphne; Staudigl, Christine] Med Univ Vienna, Div Special Gynecol, Dept OB GYN, Vienna, Austria. [Hansen, Thomas V. O.] Univ Copenhagen, Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark. [Barkardottir, Rosa Bjork] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland. [Kirchhoff, Tomas; Pal, Prodipto; Kosarin, Kristi; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA. [Piedmonte, Marion] Roswell Pk Canc Inst, GOG Stat & Data Ctr, Buffalo, NY 14263 USA. [Rodriguez, Gustavo C.] Evanston NW Healthcare, NorthShore Univ Hlth Syst, Evanston, IL 60201 USA. [Wakeley, Katie] Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. [Boggess, John F.] Univ N Carolina, Chapel Hill, NC 27599 USA. [Basil, Jack] St Elizabeth Hosp, Edgewood, KY 41017 USA. [Schwartz, Peter E.] Yale Univ, Sch Med, New Haven, CT 06510 USA. [Blank, Stephanie V.] NYU, Sch Med, New York, NY 10016 USA. [Toland, Amanda E.] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. [Toland, Amanda E.] Ohio State Univ, Div Human Canc Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Montagna, Marco; Casella, Cinzia] IRCCS, Ist Oncologico Veneto, Immunol & Mol Oncol Unit, Padua, Italy. [Imyanitov, Evgeny N.] NN Petrov Inst Res Inst, St Petersburg, Russia. [Allavena, Anna] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy. [Schmutzler, Rita K.; Versmold, Beatrix; Arnold, Norbert] Univ Cologne, Dept Obstet & Gynaecol, Div Mol Gynaeco Oncol, Cologne, Germany. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany. [Meindl, Alfons] Tech Univ Munich, Dept Obstet & Gynaecol, Munich, Germany. [Ditsch, Nina] Univ Munich, Dept Obstet & Gynecol, Munich, Germany. Univ Schleswig Holstein, Dept Obstet & Gynaecol, Campus Kiel, Germany. [Niederacher, Dieter] Univ Duesseldorf, Dept Obstet & Gynaecol, Mol Genet Lab, Dusseldorf, Germany. [Deissler, Helmut] Univ Ulm, Dept Obstet & Gynaecol, Ulm, Germany. [Fiebig, Britta] Univ Regensburg, Inst Human Genet, Regensburg, Germany. [Suttner, Christian] Univ Heidelberg, Inst Human Genet, Heidelberg, Germany. [Schoenbuchner, Ines] Univ Wurzburg, Inst Human Genet, D-8700 Wurzburg, Germany. [Gadzicki, Dorothea] Med Univ, Inst Cellular & Mol Pathol, Hannover, Germany. [Caldes, Trinidad; de la Hoya, Miguel] Hosp Clinico San Carlos 28040, Madrid, Spain. RP Antoniou, AC (reprint author), Strangeways Res Lab, CR UK Genet Epidemiol, Cambridge CB1 8RN, England. EM antonis@srl.cam.ac.uk RI Spurdle, Amanda/A-4978-2011; Ehrencrona, Hans/M-5619-2014; Arnold, Norbert/E-3012-2010; Toland, Amanda/E-4202-2011; montagna, marco/E-2225-2012; Andrulis, Irene/E-7267-2013; Sunde, Lone/H-7402-2013; Hoogerbrugge, Nicoline/O-1016-2013; Radice, Paolo/O-3119-2013; Blanco, Ignacio/D-2565-2013; Ditsch, Nina/F-6267-2014; Osorio, Ana/I-4324-2014; Bernard, Loris/K-5953-2014; GLADIEFF, Laurence/O-5129-2014; Ligtenberg, Marjolijn/N-9666-2013; Peissel, Bernard/E-8187-2017; OI Spurdle, Amanda/0000-0003-1337-7897; Ehrencrona, Hans/0000-0002-5589-3622; Arnold, Norbert/0000-0003-4523-8808; montagna, marco/0000-0002-4929-2150; Blanco, Ignacio/0000-0002-7414-7481; Osorio, Ana/0000-0001-8124-3984; GLADIEFF, Laurence/0000-0002-6980-9719; Ligtenberg, Marjolijn/0000-0003-1290-1474; Peissel, Bernard/0000-0001-9233-3571; Nordling, Margareta/0000-0002-4047-4994; Nathanson, Katherine/0000-0002-6740-0901; Eeles, Rosalind/0000-0002-3698-6241; Sunde, Lone/0000-0002-8479-165X; Nevanlinna, Heli/0000-0002-0916-2976; Kirchhoff, Tomas/0000-0002-9055-2364; Evans, Gareth/0000-0002-8482-5784 FU Cancer Research UK; Associazione Italiana per la Ricerca sul Cancro FX The CIMBA genotyping, data management and statistical analysis are supported by Cancer Research UK. A.C.A. is a Cancer Research UK Senior Cancer Research Fellow. We thank Ellen Goode for organizing the distribution of the standard DNA plates. NR 26 TC 72 Z9 74 U1 4 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 15 PY 2009 VL 18 IS 22 BP 4442 EP 4456 DI 10.1093/hmg/ddp372 PG 15 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 510RB UT WOS:000271107300019 PM 19656774 ER PT J AU Videtic, GMM Gaspar, LE Aref, AM Germano, IM Goldsmith, BJ Imperato, JP Marcus, KJ McDermott, MW McDonald, MW Patchell, RA Robins, HI Rogers, CL Suh, JH Wolfson, AH Wippold, FJ AF Videtic, Gregory M. M. Gaspar, Laurie E. Aref, Amr M. Germano, Isabelle M. Goldsmith, Brian J. Imperato, Joseph P. Marcus, Karen J. McDermott, Michael W. McDonald, Mark W. Patchell, Roy A. Robins, H. Ian Rogers, C. Leland Suh, John H. Wolfson, Aaron H. Wippold, Franz J. CA Expert Panel Radiation Oncology TI AMERICAN COLLEGE OF RADIOLOGY APPROPRIATENESS CRITERIA ON MULTIPLE BRAIN METASTASES SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Appropriateness criteria; Multiple brain metastases; Whole-brain radiotherapy; Radiosurgery; Surgery ID THERAPY ONCOLOGY GROUP; RANDOMIZED CLINICAL-TRIAL; RADIATION-THERAPY; PHASE-III; STEREOTACTIC RADIOSURGERY; NEUROCOGNITIVE FUNCTION; MOTEXAFIN GADOLINIUM; PROGNOSTIC-FACTORS; RADIOTHERAPY; RTOG C1 [Videtic, Gregory M. M.] Cleveland Clin Fdn, Dept Radiat Oncol T28, Cleveland, OH 44195 USA. [Gaspar, Laurie E.] Univ Colorado Denver, Aurora, CO USA. [Aref, Amr M.] Van Elslander Canc Ctr, Grosse Point, MI USA. [Germano, Isabelle M.] Mt Sinai Sch Med, New York, NY USA. [Goldsmith, Brian J.] Radiol Associates Sacramento, Sacramento, CA USA. [Imperato, Joseph P.] Lake Forest Hosp, Lake Forest, IL USA. [Marcus, Karen J.] Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Ctr, Boston, MA 02115 USA. [McDermott, Michael W.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [McDonald, Mark W.] Emory Univ, Atlanta, GA 30322 USA. [Patchell, Roy A.] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Robins, H. Ian] Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI USA. [Rogers, C. Leland] GammaW Brachytherapy, Salt Lake City, UT USA. [Wolfson, Aaron H.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Wippold, Franz J.] Washington Univ, Sch Med, St Louis, MO USA. RP Videtic, GMM (reprint author), Cleveland Clin Fdn, Dept Radiat Oncol T28, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM videtig@ccf.org NR 34 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 2009 VL 75 IS 4 BP 961 EP 965 DI 10.1016/j.ijrobp.2009.07.1720 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 515RF UT WOS:000271489600001 ER PT J AU Rodrigues, NA Killion, L Hickey, G Silver, B Martin, C Stevenson, MA Mauch, PM Ng, AK AF Rodrigues, Neesha A. Killion, Leah Hickey, Gail Silver, Barbara Martin, Chrystalla Stevenson, Mary Ann Mauch, Peter M. Ng, Andrea K. TI A PROSPECTIVE STUDY OF SALIVARY GLAND FUNCTION IN LYMPHOMA PATIENTS RECEIVING HEAD AND NECK IRRADIATION SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Lymphoma; Head and neck; Quality of Life; Xerostomia; Amifostine ID INTENSITY-MODULATED RADIOTHERAPY; STAGE NASOPHARYNGEAL CARCINOMA; DOSE-RESPONSE RELATIONSHIPS; MANTLE FIELD RADIOTHERAPY; RADIATION-THERAPY; PAROTID-GLAND; HODGKINS-DISEASE; PHASE-II; CANCER; AMIFOSTINE AB Purpose: To determine the radiation dose-response relationship on salivary dysfunction and quality of life (QOL) over time in patients With lymphoma receiving radiation therapy (RT) to the head and neck (H&N). Methods and Materials: We conducted a prospective study on salivary-gland function in lymphoma patients jeceiving RT to the H&N. Fifteen patients were enrolled on the study. Dose-volume histograms and mean doses to the salivary glands were generated. Radiation-related toxicities and H&N-specific QOL were assessed before treatment and at prespecified time points posttreatment. Factors predicting a decrement in QOL were explored using Fisher's exact test. Results: During RT, 47% of patients experienced Grade >= 2 acute toxicity of the salivary gland, mucous membrane, or both. QOL scores improved over time, but up to one third of patients continued to have persistent oral symptoms at 2 years. At 6 months, a mean dose to at least one of the parotids of > 31 Gy was significantly associated with persistent dry mouth (100% vs. 17%, p = 0.02) and sticky saliva (100% vs. 25 %, p = 0.04); a mean dose of > I I Gy to the minor salivary glands was significantly associated with persistent sticky saliva (100% vs. 25 %, p = 0.04), although the difference was no longer significant at 1 year. Conclusions: Limiting the mean parotid dose to <= 31 Gy and mean minor salivary gland dose to <= 11 Gy in lymphoma patients treated to the H&N may help reduce the risk of subacute xerostomia. (C) 2009 Elsevier Inc. C1 [Rodrigues, Neesha A.; Killion, Leah; Hickey, Gail; Silver, Barbara; Mauch, Peter M.; Ng, Andrea K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Martin, Chrystalla; Stevenson, Mary Ann] Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. RP Ng, AK (reprint author), 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM ang@lroc.harvard.edu FU MedImmune, Inc. FX MedImmune, Inc., provided partial salary support for one of the research nurses in this study (G.H.). NR 23 TC 7 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 2009 VL 75 IS 4 BP 1079 EP 1083 DI 10.1016/j.ijrobp.2008.12.053 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 515RF UT WOS:000271489600019 PM 19327910 ER PT J AU Sperduto, CM Chakravarti, A Aldape, K Burger, P Papermaster, GB Sperduto, P AF Sperduto, Christina Maria Chakravarti, Arnab Aldape, Ken Burger, Peter Papermaster, Gail Bender Sperduto, Paul TI TWENTY-YEAR SURVIVAL IN GLIOBLASTOMA: A CASE REPORT AND MOLECULAR PROFILE SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Glioblastoma; Molecular Profile; Survival; Outcomes ID LONG-TERM SURVIVORS; PROGNOSTIC-SIGNIFICANCE; MALIGNANT GLIOMA; MULTIFORME; RADIOTHERAPY; TEMOZOLOMIDE AB Background: The prognosis for patients with glioblastoma (GB) remains grim. Historically, the median survival has been 6 to 9 months. Recent research has improved the outcome slightly. A computer search of the literature reveals few long-term survivors. Method: Presented here is a case report of a 20-year survivor of GB, with pathologic review to confirm the diagnosis. A battery of molecular studies was performed to develop a molecular profile of this unique patient. Results: The results of the molecular genetic testing for this most unusual patient were as follows: (1) methylguanine methyl transferase (MGMT) was methylated, (2) p53 positive, (3) PTEN tumor suppressor gene positive, (4) protein kinase AKT (pAKT) negative, and (5) epidermal growth factor receptor negative. Conclusion: To our knowledge, this is the longest survival of any patient in the literature whose initial diagnosis was GB. Triple-positive GBM patients (MGMT methylated, PTEN, and p53 positive) are uncommon but may be associated with a better prognosis. Further research is needed to confirm whether this molecular profile is prognostic of prolonged survival. Molecular genetics will determine future treatment and prognosis in GB. (C) 2009 Elsevier Inc. C1 [Sperduto, Paul] Univ Minnesota, Gamma Knife Ctr, Dept Radiat Oncol, Med Ctr, Minneapolis, MN 55113 USA. [Sperduto, Christina Maria] Minneapolis Radiat Oncol, Res Associate, Minneapolis, MN USA. [Chakravarti, Arnab] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Aldape, Ken] UT MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA. [Burger, Peter] Johns Hopkins Sch Med, Div Neuropathol, Baltimore, MD USA. [Papermaster, Gail Bender] Ridgeview Med Ctr, Dept Med Oncol, Waconia, MN USA. RP Sperduto, P (reprint author), Univ Minnesota, Gamma Knife Ctr, Dept Radiat Oncol, Med Ctr, 420 Delaware St,MMC 494, Minneapolis, MN 55113 USA. EM psperduto@mropa.com NR 16 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 2009 VL 75 IS 4 BP 1162 EP 1165 DI 10.1016/j.ijrobp.2008.12.054 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 515RF UT WOS:000271489600031 PM 19327897 ER PT J AU Arvold, ND Lessell, S Bussiere, M Beaudette, K Rizzo, JF Loeffler, JS Shih, HA AF Arvold, Nils D. Lessell, Simmons Bussiere, Marc Beaudette, Kevin Rizzo, Joseph F. Loeffler, Jay S. Shih, Helen A. TI VISUAL OUTCOME AND TUMOR CONTROL AFTER CONFORMAL RADIOTHERAPY FOR PATIENTS WITH OPTIC NERVE SHEATH MENINGIOMA SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Optic nerve sheath meningioma; Vision; Local control; Radiotherapy; Proton ID FRACTIONATED STEREOTACTIC RADIOTHERAPY; RADIATION-THERAPY; MANAGEMENT; SURGERY; PROTON; BEAMS AB Purpose: Optic nerve sheath meningioma (ONSM) is a rare tumor that almost uniformly leads to visual dysfunction and even blindness without intervention. Because surgical extirpation carries a high risk of postoperative blindness, vision-sparing treatment strategies are desirable. Methods and Materials: We retrospectively reviewed the outcomes of 25 patients (25 optic nerves) with ONSM, treated at a single institution with conformal fractionated radiotherapy by either stereotactic photon or proton radiation. Primary endpoints were local control and visual acuity. Results: The patients presented with symptoms of visual loss (21) or orbital pain (3) or were incidentally diagnosed by imaging (3). The mean age was 44 years, and 64% were female patients. The indication for treatment was the development or progression of symptoms. Of the patients, 13 were treated with photons, 9 were treated with protons, and 3 received a combination of photons and protons. The median dose delivered was 50.4 gray equivalents (range, 45-59.4 gray equivalents). Median follow-up after radiotherapy was 30 months (range, 3-168 months), with 3 patients lost to follow-up. At most recent follow-up, 21 of 22 patients (95%) had improved (14) or stable (7) visual acuity. One patient had worsened visual acuity after initial postirradiation improvement. Of the 22 patients, 20 (95%) had no radiographic progression. Three patients had evidence of asymptomatic, limited retinopathy on ophthalmologic examination, and one had recurrent ONSM 11 years after treatment. Conclusions: Highly conformal, fractionated radiation therapy for symptomatic primary ONSM provides tumor control and improvement in visual function in most cases, with minimal treatment-induced morbidity. Longer follow-up is needed to assess the durability of tumor control and treatment-related late effects. (C) 2009 Elsevier Inc. C1 [Arvold, Nils D.] Massachusetts Gen Hosp, Harvard Radiat Oncol Program, Boston, MA 02114 USA. [Arvold, Nils D.; Bussiere, Marc; Beaudette, Kevin; Loeffler, Jay S.; Shih, Helen A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Lessell, Simmons; Rizzo, Joseph F.] Massachusetts Eye & Ear Infirm, Dept Neuroophthalmol, Boston, MA 02114 USA. [Arvold, Nils D.; Lessell, Simmons; Bussiere, Marc; Beaudette, Kevin; Rizzo, Joseph F.; Loeffler, Jay S.; Shih, Helen A.] Harvard Univ, Sch Med, Boston, MA USA. RP Arvold, ND (reprint author), Massachusetts Gen Hosp, Harvard Radiat Oncol Program, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM narvold@partners.org NR 23 TC 28 Z9 28 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 2009 VL 75 IS 4 BP 1166 EP 1172 DI 10.1016/j.ijrobp.2008.12.056 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 515RF UT WOS:000271489600032 PM 19406585 ER PT J AU Dai, J Kateneva, AV Higgins, JMG AF Dai, Jun Kateneva, Anna V. Higgins, Jonathan M. G. TI Studies of haspin-depleted cells reveal that spindle-pole integrity in mitosis requires chromosome cohesion SO JOURNAL OF CELL SCIENCE LA English DT Article DE Chromosome cohesion; Centrosome; Mitosis; Gsg2 Spindle assembly; Kinesin-5 ID SISTER-CHROMATID COHESION; XENOPUS EGG EXTRACTS; MAMMALIAN-CELLS; MITOTIC SPINDLE; AURORA-A; CENTROMERIC COHESION; MOTOR PROTEINS; GAMMA-TUBULIN; KINETOCHORE; MICROTUBULES AB Cohesins and their regulators are vital for normal chromosome cohesion and segregation. A number of cohesion proteins have also been localized to centrosomes and proposed to function there. We show that RNAi-mediated depletion of factors required for cohesion, including haspin, Sgo1 and Scc1, leads to the generation of multiple acentriolar centrosome-like foci and disruption of spindle structure in mitosis. Live-cell imaging reveals that, in haspin-depleted cells, these effects occur only as defects in chromosome cohesion become manifest, and they require ongoing microtubule dynamics and kinesin-5 (also known as Eg5) activity. Inhibition of topoisomerase Pi in mitosis, which prevents decatenation and separation of chromatids, circumvents the loss of cohesion and restores integrity of the spindle poles. Although these results do not rule out roles for cohesin proteins at centrosomes, they suggest that when cohesion is compromised, spindle-pole integrity can be disrupted as an indirect consequence of the failure to properly integrate chromosome-and centrosome-initiated pathways for spindle formation. C1 [Dai, Jun; Kateneva, Anna V.; Higgins, Jonathan M. G.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. RP Dai, J (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM jdai@partners.org; jhiggins@rics.bwh.harvard.edu RI Dai, Jun/J-9718-2015 FU NIGMS NIH HHS [R01 GM074210, R01 GM074210-04] NR 52 TC 27 Z9 27 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD NOV 15 PY 2009 VL 122 IS 22 BP 4168 EP 4176 DI 10.1242/jcs.054122 PG 9 WC Cell Biology SC Cell Biology GA 518HJ UT WOS:000271681300018 PM 19910498 ER PT J AU Nguyen, DP Wilson, MA Brown, EN Barbieri, R AF Nguyen, David P. Wilson, Matthew A. Brown, Emery N. Barbieri, Riccardo TI Measuring instantaneous frequency of local field potential oscillations using the Kalman smoother SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Autoregressive model; Kalman smoother; Frequency modulation; Adaptive filter; Hippocampus; Ripple oscillation ID SLOW-WAVE SLEEP; TIME-SERIES; IN-VITRO; EEG; STATE; HIPPOCAMPUS; RAT; NETWORKS; TRACKING; RIPPLES AB Rhythmic local field potentials (LFPs) arise from coordinated neural activity. Inference of neural function based on the properties of brain rhythms remains a challenging data analysis problem. Algorithms that characterize non-stationary rhythms with high temporal and spectral resolution may be useful for interpreting LFP activity on the timescales in which they are generated. We propose a Kalman smoother based dynamic autoregressive model for tracking the instantaneous frequency (iFreq) and frequency modulation (FM) of noisy and non-stationary sinusoids such as those found in LFP data. We verify the performance of our algorithm using simulated data with broad spectral content, and demonstrate its application using real data recorded from behavioral learning experiments. In analyses of ripple oscillations (100-250 Hz) recorded from the rodent hippocampus, our algorithm identified novel repetitive, short timescale frequency dynamics. Our results suggest that iFreq and FM may be useful measures for the quantification of small timescale LFP dynamics. (C) 2009 Elsevier B.V. All rights reserved. C1 [Nguyen, David P.] MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Brown, Emery N.; Barbieri, Riccardo] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Brown, Emery N.; Barbieri, Riccardo] MIT, Dept Hlth & Sci Technol, Boston, MA 02139 USA. RP Nguyen, DP (reprint author), MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Bldg 46,Room 5233,43 Vassar St, Cambridge, MA 02139 USA. EM dpnguyen@neurostat.mit.edu; mwilson@mit.edu; enb@neurostat.mit.edu; barbieri@neurostat.mit.edu OI Barbieri, Riccardo/0000-0001-9381-3833 FU NIH/NIMH [R01 MH59733]; NIH/NIHLB [R01 HL084502]; Singleton Graduate Student Fellowship FX This work was funded in part by the following grants: NIH/NIMH R01 MH59733, NIH/NIHLB R01 HL084502, and the Singleton Graduate Student Fellowship. We thank members of the Wilson Lab, Brown Lab, and Tonegawa Lab for helpful comments. NR 47 TC 10 Z9 10 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD NOV 15 PY 2009 VL 184 IS 2 BP 365 EP 374 DI 10.1016/j.jneumeth.2009.08.012 PG 10 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 521IN UT WOS:000271914400021 PM 19699763 ER PT J AU Li, XY Standley, C Sapp, E Valencia, A Qin, ZH Kegel, KB Yoder, J Comer-Tierney, LA Esteves, M Chase, K Alexander, J Masso, N Sobin, L Bellve, K Tuft, R Lifshitz, L Fogarty, K Aronin, N DiFiglia, M AF Li, Xueyi Standley, Clive Sapp, Ellen Valencia, Antonio Qin, Zheng-Hong Kegel, Kimberly B. Yoder, Jennifer Comer-Tierney, Laryssa A. Esteves, Miguel Chase, Kathryn Alexander, Jonathan Masso, Nicholas Sobin, Lindsay Bellve, Karl Tuft, Richard Lifshitz, Lawrence Fogarty, Kevin Aronin, Neil DiFiglia, Marian TI Mutant Huntingtin Impairs Vesicle Formation from Recycling Endosomes by Interfering with Rab11 Activity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PERIPHERAL-BLOOD CELLS; PLASMA-MEMBRANE; AXONAL-TRANSPORT; INTRACELLULAR TRAFFICKING; ENDOCYTIC PATHWAY; IN-VITRO; DISEASE; PROTEIN; NEURONS; DROSOPHILA AB Huntingtin (Htt) localizes to endosomes, but its role in the endocytic pathway is not established. Recently, we found that Htt is important for the activation of Rab11, a GTPase involved in endosomal recycling. Here we studied fibroblasts of healthy individuals and patients with Huntington's disease (HD), which is a movement disorder caused by polyglutamine expansion in Htt. The formation of endocytic vesicles containing transferrin at plasma membranes was the same in control and HD patient fibroblasts. However, HD fibroblasts were delayed in recycling biotin-transferrin back to the plasma membrane. Membranes of HD fibroblasts supported less nucleotide exchange on Rab11 than did control membranes. Rab11-positive vesicular and tubular structures in HD fibroblasts were abnormally large, suggesting that they were impaired in forming vesicles. We used total internal reflection fluorescence imaging of living fibroblasts to monitor fluorescence-labeled transferrin-carrying transport intermediates that emerged from recycling endosomes. HD fibroblasts had fewer small vesicles and more large vesicles and long tubules than did control fibroblasts. Dominant active Rab11 expressed in HD fibroblasts normalized the recycling of biotin-transferrin. We propose a novel mechanism for cellular dysfunction by the HD mutation arising from the inhibition of Rab11 activity and a deficit in vesicle formation at recycling endosomes. C1 [Chase, Kathryn; Aronin, Neil] Univ Massachusetts, Sch Med, Dept Med & Cell Biol, Worcester, MA 01655 USA. [Li, Xueyi; Sapp, Ellen; Valencia, Antonio; Qin, Zheng-Hong; Kegel, Kimberly B.; Yoder, Jennifer; Comer-Tierney, Laryssa A.; Esteves, Miguel; Alexander, Jonathan; Masso, Nicholas; Sobin, Lindsay; DiFiglia, Marian] Massachusetts Gen Hosp, Cellular Neurobiol Lab, Charlestown, MA 02129 USA. [Li, Xueyi; Sapp, Ellen; Valencia, Antonio; Qin, Zheng-Hong; Kegel, Kimberly B.; Yoder, Jennifer; Comer-Tierney, Laryssa A.; Esteves, Miguel; Alexander, Jonathan; Masso, Nicholas; Sobin, Lindsay; DiFiglia, Marian] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Li, Xueyi; Sapp, Ellen; Valencia, Antonio; Qin, Zheng-Hong; Kegel, Kimberly B.; Yoder, Jennifer; Comer-Tierney, Laryssa A.; Esteves, Miguel; Alexander, Jonathan; Masso, Nicholas; Sobin, Lindsay; DiFiglia, Marian] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Standley, Clive; Bellve, Karl; Tuft, Richard; Lifshitz, Lawrence; Fogarty, Kevin] Univ Massachusetts, Sch Med, Biomed Imaging Grp, Dept Physiol, Worcester, MA 01655 USA. RP Aronin, N (reprint author), Univ Massachusetts, Sch Med, Dept Med & Cell Biol, Worcester, MA 01655 USA. EM Neil.Aronin@umassmed.edu FU NIH [NS R0138194]; DANA Foundation; High Q Foundation; Huntington's Disease Society of America; Diabetes Endocrinology Research Center [DK P3032520]; Hereditary Disease Foundation FX This work was supported by grants from the NIH (grant NS R0138194 to N. A., Philip D. Zamore, and M. D.), the DANA Foundation (to N. A. and M. D.), the High Q Foundation (to M. D.), and the Huntington's Disease Society of America (to M. D.). Core resources supported by Diabetes Endocrinology Research Center grant DK P3032520 (University of Massachusetts Medical School [UMMS]) were also used. X.-L. is supported by a John J. Wasmuth postdoctoral fellowship from the Hereditary Disease Foundation and DANA Foundation. We declare no conflict of interests. NR 55 TC 34 Z9 35 U1 0 U2 2 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 NOV 15 PY 2009 VL 29 IS 22 BP 6106 EP 6116 DI 10.1128/MCB.00420-09 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 511ZB UT WOS:000271209600012 PM 19752198 ER PT J AU Lovrecic, L Kastrin, A Kobal, J Pirtosek, Z Krainc, D Peterlin, B AF Lovrecic, Luca Kastrin, Andrej Kobal, Jan Pirtosek, Zvezdan Krainc, Dimitri Peterlin, Borut TI Gene Expression Changes in Blood as a Putative Biomarker for Huntington's Disease SO MOVEMENT DISORDERS LA English DT Article DE biomarkers; gene expression; Huntington's disease; neurodegeneration; transcriptomics ID MICROARRAY AB Several studies demonstrated alterations of gene expression in blood in various neurological disorders including Huntington's disease (HD). Using microarray technology, a recent study identified a large number of significantly altered mRNAs in HD blood, from which a 12-gene set was selected as classifier for discriminating controls and HD patients. The aim of our study was to validate expression changes of these 12 genes in an independent cohort of HD patients and evaluate their sensitivity and specificity. Four different subject groups were included-patients with HD, Parkinson's disease (PD), acute ischemic stroke (AS) and healthy controls. Although the previous results were successfully validated, gene expression changes in HD blood partly overlapped with those observed in blood from PD and AS patients. Predictive value of the selected biomarker set for HD group was 78%, with 82% sensitivity and 53% specificity. Further gene expression analyses in longitudinal studies are needed to validate and refine possible transcriptomic blood biomarkers in HD. (C) 2009 Movement Disorder Society C1 [Lovrecic, Luca; Kastrin, Andrej; Peterlin, Borut] UMC, Inst Med Genet, Ljubljana 1000, Slovenia. [Kobal, Jan; Pirtosek, Zvezdan] UMC, Dept Neurol, Ljubljana 1000, Slovenia. [Krainc, Dimitri] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodegenerat, Charlestown, MA USA. RP Peterlin, B (reprint author), UMC, Inst Med Genet, Slajmerjeva 3, Ljubljana 1000, Slovenia. EM Borut.Peterlin@guest.arnes.si RI peterlin, borut/C-6086-2011 OI peterlin, borut/0000-0001-7824-4978 FU Ministry of Science and Technology, Ljubljana [J3-7411]; Republic of Slovenia FX This research was supported by grant J3-7411 from the Ministry of Science and Technology, Ljubljana, Republic of Slovenia. The authors express special gratitude to the participants in this study. NR 12 TC 17 Z9 17 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV 15 PY 2009 VL 24 IS 15 BP 2277 EP 2281 DI 10.1002/mds.22477 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 530DU UT WOS:000272570000015 PM 19844910 ER PT J AU Schwab, JH Healey, JH Rose, P Casas-Ganem, J Boland, PJ AF Schwab, Joseph H. Healey, John H. Rose, Peter Casas-Ganem, Jorge Boland, Patrick J. TI The Surgical Management of Sacral Chordomas SO SPINE LA English DT Article DE sacrum; chordoma ID SACROCOCCYGEAL CHORDOMA; UNILATERAL SACRIFICE; MAJOR RESECTIONS; BONE-TUMORS; CRYOSURGERY; SACRECTOMY; NERVES AB Study Design. Retrospective case series. Objective. The purpose of this study was to evaluate factors that contribute to improved local control and survival. In addition, we sought to define the expected morbidity associated with treatment. Summary of Background Data. Sacral chordomas are rare tumors presumed to arise from notochordal cells. Local recurrence presents a major problem in the management of these tumors and it has been correlated with survival. Resection of sacral tumors is associated with significant morbidity. Methods. Forty-two patients underwent resection for sacral chordoma between 1990 and 2005. Twelve patients had their initial surgery elsewhere. There were 12 female and 30 male patients. The proximal extent of the sacrectomy was at least S2 in 32 patients. Results. Median survival was 84 months, and 5-year disease-free (DFS) and disease-specific survival (DSF) were 56% and 77%, respectively. Local recurrence (LR) and metastasis occurred in 17 (40%) and 13 (31%) patients, respectively. Local recurrence (P = 0.0001), metastasis (P = 0.0001), prior resection (P = 0.046), and higher grade (P = 0.05) were associated with a worse DSF. Prior resections (P = 0.0001) and intralesional resections (P = 0.01) were associated with a higher rate of LR. Intralesional resections were associated with a lower DSF (P = 0.0001). Wide contaminated margins treated with cryosurgery and/or radiation were not associated with a higher LR rate. Rectus abdominus flaps were associated with decreased wound complications (P = 0.01). Thirty-one (74%) patients reported that they self catheterize; and 16 (38%) patients required bowel training, while an additional twelve (29%) patients had a colostomy. Twenty-eight (67%) patients reported sexual dysfunction. Two (5%) patients died due to sepsis. Conclusions. Intralesional resection should be avoided as it is associated with a higher LR rate and worse survival. Rectus abdominus flaps ought to be considered as they lower the wound complication rate. Sacral resection is associated with significant morbidity. C1 [Schwab, Joseph H.; Healey, John H.; Rose, Peter; Casas-Ganem, Jorge; Boland, Patrick J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Schwab, JH (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Yawkey 3,55 Fruit St, Boston, MA 02114 USA. EM jhschwab@partners.org NR 20 TC 51 Z9 53 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD NOV 15 PY 2009 VL 34 IS 24 BP 2700 EP 2704 PG 5 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 520YD UT WOS:000271884700015 PM 19910774 ER PT J AU Tilney, NL Delmonico, FL Murray, JE Thistlethwaite, R Leichtman, AB Hanto, DW Shapiro, R Danovitch, GM Sayegh, MH Brennan, DC Harmon, WE Salvatierra, O Pomfret, EA McDiarmid, SV Stock, PG Metzger, R Bennett, WM Conti, D Norman, DJ Sarwal, MM Cosimi, BA AF Tilney, Nicholas L. Delmonico, Francis L. Murray, Joseph E. Thistlethwaite, Richard Leichtman, Alan B. Hanto, Douglas W. Shapiro, Ronald Danovitch, Gabriel M. Sayegh, Mohamed H. Brennan, Daniel C. Harmon, William E. Salvatierra, Oscar Pomfret, Elizabeth A. McDiarmid, Sue V. Stock, Peter G. Metzger, Robert Bennett, William Michael Conti, David Norman, Douglas J. Sarwal, Minnie M. Cosimi, Benedict A. TI Promotion of Altruistic Donation (vol 88, pg 847, 2009) SO TRANSPLANTATION LA English DT Correction C1 [Tilney, Nicholas L.; Murray, Joseph E.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Delmonico, Francis L.; Cosimi, Benedict A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Thistlethwaite, Richard] Univ Chicago, Dept Surg, Chicago, IL 60637 USA. [Leichtman, Alan B.] Univ Michigan, Med Ctr, Dept Internal Med, Ann Arbor, MI 48109 USA. [Hanto, Douglas W.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Shapiro, Ronald] Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA. [Danovitch, Gabriel M.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Sayegh, Mohamed H.] Brigham & Womens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. [Brennan, Daniel C.] Washington Univ, Sch Med, Renal Div Internal Med, St Louis, MO USA. [Harmon, William E.] Childrens Hosp, Boston, MA 02115 USA. [Salvatierra, Oscar] Stanford Univ, Sch Med, Dept Surg, Palo Alto, CA 94304 USA. [Pomfret, Elizabeth A.] Lahey Clin Med Ctr, Burlington, MA 01803 USA. [McDiarmid, Sue V.] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. [McDiarmid, Sue V.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Stock, Peter G.] Univ Calif San Francisco, Dept Surg, Div Transplantat, San Francisco, CA 94143 USA. [Bennett, William Michael] Legacy Good Samaritan Hosp, Transplant Serv & NW Renal Clin, Portland, OR USA. [Conti, David] Albany Med Ctr, Albany, NY USA. [Norman, Douglas J.] Oregon Hlth & Sci Univ, Dept Transplantat Immunogenet, Portland, OR 97201 USA. [Sarwal, Minnie M.] Stanford Univ, Dept Pediat, Palo Alto, CA 94304 USA. RP Tilney, NL (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 15 PY 2009 VL 88 IS 9 BP 1145 EP 1147 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 519OM UT WOS:000271776500017 ER PT J AU Bray, GA Chatellier, A Duncan, C Greenway, FL Levy, E Ryan, DH Polonsky, KS Tobian, J Ehrmann, D Matulik, MJ Clark, B Czech, K DeSandre, C Hilbrich, R McNabb, W Semenske, AR Goldstein, BJ Smith, KA Wildman, W Pepe, C Goldberg, RB Calles, J Ojito, J Castillo-Florez, S Florez, HJ Giannella, A Lara, O Veciana, B Haffner, SM Montez, MG Lorenzo, C Martinez, A Hamman, RF Testaverde, L Bouffard, A Dabelea, D Jenkins, T Lenz, D Perreault, L Price, DW Steinke, SC Horton, ES Poirier, CS Swift, K Caballero, E Jackson, SD Lambert, L Lawton, KE Ledbury, S Kahn, SE Montgomery, BK Fujimoto, W Knopp, RH Lipkin, EW Marr, M Murillo, A Trence, D Kitabchi, AE Murphy, ME Applegate, WB Bryer-Ash, M Dagogo-Jack, S Frieson, SL Lambeth, H Lichtermann, LC Otkaei, H Rutledge, LMK Sherman, AR Smith, CM Soberman, JE Williams-Cleaves, B Metzger, BE Molitch, ME Johnson, MK Giles, MM Larsen, D Niznik, C Pen, SC Schinleber, PA Nathan, DM McKitrick, C Turgeon, H Abbott, K Altshuler, D Anderson, E Bissett, L Cagliero, E D'Anna, K Delahanty, L Florez, JC Goldman, V Poulos, A Tseng, B Barrett-Connor, E Carrion-Petersen, ML Horne, J Leos, D Mudaliar, S Smith, J Vejvoda, K Pi-Sunyer, FX Lee, JE Foo, ST Hagamen, S Marrero, DG Kelly, SM Ackermann, RT Fineberg, ES Hadden, A Jackson, MA Kirkman, MS Mather, KJ Roach, PJ Wheeler, ML Ratner, RE Aroda, V Shapiro, S Bavido-Arrage, C Gibbs, P Uwaifo, G Wiggins, R Saad, MF Watson, K Botrous, M Jinagouda, S Budget, M Conzues, C Magpuri, P Ngo, K Xapthalamous, K White, NH Das, S Santiago, A Brown, AL Wernimont, C Saudek, CD Whittington, T Clark, JM Greene, A Jiggetts, D Mosley, H Reusing, J Rubin, RR Stephen, S Utsey, E Schade, DS Adams, KS Hemphill, C Hyde, P Butler, L Canady, JL Colleran, K Gonzales, Y Hernandez-McGinnis, DA Katz, P King, C Crandall, J Brown-Friday, JO Adorno, E Duffy, H Martinez, H Pompi, D Shamoon, H Walker, EA Wylie-Rosett, J Orchard, T Jeffries, S Kramer, MK Smith, M Kriska, A Pettigrew, J Semler, L Venditti, E Weinzierl, V Arakaki, RF Baker-Ladao, NK Isonaga, MK Bermudez, NE Mau, MK Knowler, WC Cooeyate, N Hoskin, MA Natewa, C Percy, CA Acton, KJ Andre, VL Begay, S Bucca, BC Cook, S Doughty, MS Glass, J Glass, M Hanson, RL Hassenpflug, D Ingraham, LE Kobus, KM Krakoff, J Manus, C McCabe, C Michaels, S Morgan, T Nelson, JA Roy, RJ Smart, M Tonemah, DP Wilson, C Fowler, S Brenneman, T Abebe, S Bamdad, J Callaghan, J Christophi, CA Edelstein, SL Gao, Y Gooding, R Gottlieb, A Grover, N Hoffman, H Jablonski, K Katz, R Kolinjivadi, P Lachin, JM Ma, Y Reamer, S Sapozhnikova, A Sherif, H Temprosa, M Venditti, EM Kriska, AM Semler, L Weinzierl, V Marcovina, S Strylewicz, G Albers, J Prineas, RJ Alexander, T Campbell, C Hall, S Hensley, S Li, Y Mills, M Soliman, E Zhang, Z Fradkin, J Garfield, S Mayer-Davis, E Moran, RR Ganiats, T Sarkin, AJ AF Bray, G. A. Chatellier, A. Duncan, C. Greenway, F. L. Levy, E. Ryan, D. H. Polonsky, K. S. Tobian, J. Ehrmann, D. Matulik, M. J. Clark, B. Czech, K. DeSandre, C. Hilbrich, R. McNabb, W. Semenske, A. R. Goldstein, B. J. Smith, K. A. Wildman, W. Pepe, C. Goldberg, R. B. Calles, J. Ojito, J. Castillo-Florez, S. Florez, H. J. Giannella, A. Lara, O. Veciana, B. Haffner, S. M. Montez, M. G. Lorenzo, C. Martinez, A. Hamman, R. F. Testaverde, L. Bouffard, A. Dabelea, D. Jenkins, T. Lenz, D. Perreault, L. Price, D. W. Steinke, S. C. Horton, E. S. Poirier, C. S. Swift, K. Caballero, E. Jackson, S. D. Lambert, L. Lawton, K. E. Ledbury, S. Kahn, S. E. Montgomery, B. K. Fujimoto, W. Knopp, R. H. Lipkin, E. W. Marr, M. Murillo, A. Trence, D. Kitabchi, A. E. Murphy, M. E. Applegate, W. B. Bryer-Ash, M. Dagogo-Jack, S. Frieson, S. L. Lambeth, H. Lichtermann, L. C. Otkaei, H. Rutledge, L. M. K. Sherman, A. R. Smith, C. M. Soberman, J. E. Williams-Cleaves, B. Metzger, B. E. Molitch, M. E. Johnson, M. K. Giles, M. M. Larsen, D. Niznik, C. Pen, S. C. Schinleber, P. A. Nathan, D. M. McKitrick, C. Turgeon, H. Abbott, K. Altshuler, D. Anderson, E. Bissett, L. Cagliero, E. D'Anna, K. Delahanty, L. Florez, J. C. Goldman, V. Poulos, A. Tseng, B. Barrett-Connor, E. Carrion-Petersen, M. L. Horne, J. Leos, D. Mudaliar, S. Smith, J. Vejvoda, K. Pi-Sunyer, F. X. Lee, J. E. Foo, S. T. Hagamen, S. Marrero, D. G. Kelly, S. M. Ackermann, R. T. Fineberg, E. S. Hadden, A. Jackson, M. A. Kirkman, M. S. Mather, K. J. Roach, P. J. Wheeler, M. L. Ratner, R. E. Aroda, V. Shapiro, S. Bavido-Arrage, C. Gibbs, P. Uwaifo, Gl Wiggins, R. Saad, M. F. Watson, K. Botrous, M. Jinagouda, S. Budget, M. Conzues, C. Magpuri, P. Ngo, K. Xapthalamous, K. White, N. H. Das, S. Santiago, A. Brown, A. L. Wernimont, C. Saudek, C. D. Whittington, T. Clark, J. M. Greene, A. Jiggetts, D. Mosley, H. Reusing, J. Rubin, R. R. Stephen, S. Utsey, E. Schade, D. S. Adams, K. S. Hemphill, C. Hyde, P. Butler, L. Canady, J. L. Colleran, K. Gonzales, Y. Hernandez-McGinnis, D. A. Katz, P. King, C. Crandall, J. Brown-Friday, J. O. Adorno, E. Duffy, H. Martinez, H. Pompi, D. Shamoon, H. Walker, E. A. Wylie-Rosett, J. Orchard, T. Jeffries, S. Kramer, M. K. Smith, M. Kriska, A. Pettigrew, J. Semler, L. Venditti, E. Weinzierl, V. Arakaki, R. F. Baker-Ladao, N. K. Isonaga, M. K. Bermudez, N. E. Mau, M. K. Knowler, W. C. Cooeyate, N. Hoskin, M. A. Natewa, C. Percy, C. A. Acton, K. J. Andre, V. L. Begay, S. Bucca, B. C. Cook, S. Doughty, M. S. Glass, J. Glass, M. Hanson, R. L. Hassenpflug, D. Ingraham, L. E. Kobus, K. M. Krakoff, J. Manus, C. McCabe, C. Michaels, S. Morgan, T. Nelson, J. A. Roy, R. J. Smart, M. Tonemah, D. P. Wilson, C. Fowler, S. Brenneman, T. Abebe, S. Bamdad, J. Callaghan, J. Christophi, C. A. Edelstein, S. L. Gao, Y. Gooding, R. Gottlieb, A. Grover, N. Hoffman, H. Jablonski, K. Katz, R. Kolinjivadi, P. Lachin, J. M. Ma, Y. Reamer, S. Sapozhnikova, A. Sherif, H. Temprosa, M. Venditti, E. M. Kriska, A. M. Semler, L. Weinzierl, V. Marcovina, S. Strylewicz, G. Albers, J. Prineas, R. J. Alexander, T. Campbell, C. Hall, S. Hensley, S. Li, Y. Mills, M. Soliman, E. Zhang, Z. Fradkin, J. Garfield, S. Mayer-Davis, E. Moran, R. R. Ganiats, T. Sarkin, A. J. CA Diabet Prevention Program Res Grp TI 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study SO LANCET LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; COST-EFFECTIVENESS; RISK-FACTORS; METFORMIN; MELLITUS; PEOPLE; TRIAL; REDUCTION; DIAGNOSIS AB Background In the 2.8 years of the Diabetes Prevention Program (DPP) randomised clinical trial, diabetes incidence in high-risk adults was reduced by 58% with intensive lifestyle intervention and by 31% with metformin, compared with placebo. We investigated the persistence of these effects in the long term. Methods All active DPP participants were eligible for continued follow-up. 2766 of 3150 (88%) enrolled for a median additional follow-up of 5.7 years (IQR 5.5-5.8). 910 participants were from the lifestyle, 924 from the metformin, and 932 were from the original placebo groups. On the basis of the benefits from the intensive lifestyle intervention in the DPP, all three groups were offered group-implemented lifestyle intervention. Metformin treatment was continued in the original metformin group (850 mg twice daily as tolerated), with participants unmasked to assignment, and the original lifestyle intervention group was offered additional lifestyle support. The primary outcome was development of diabetes according to American Diabetes Association criteria. Analysis was by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00038727. Findings During the 10.0-year (IQR 9.0-10.5) follow-up since randomisation to DPP, the original lifestyle group lost, then partly regained weight. The modest weight loss with metformin was maintained. Diabetes incidence rates during the DPP were 4.8 cases per 100 person-years (95% CI 4.1-5.7) in the intensive lifestyle intervention group, 7.8 (6.8-8.8) in the metformin group, and 11.0 (9.8-12.3) in the placebo group. Diabetes incidence rates in this follow-up study were similar between treatment groups: 5.9 per 100 person-years (5.1-6.8) for lifestyle, 4.9 (4.2-5.7) for metformin, and 5.6 (4.8-6.5) for placebo. Diabetes incidence in the 10 years since DPP randomisation was reduced by 34% (24-42) in the lifestyle group and 18% (7-28) in the metformin group compared with placebo. Interpretation During follow-up after DPP, incidences in the former placebo and metformin groups fell to equal those in the former lifestyle group, but the cumulative incidence of diabetes remained lowest in the lifestyle group. Prevention or delay of diabetes with lifestyle intervention or metformin can persist for at least 10 years. C1 [Bray, G. A.; Fowler, S.; Brenneman, T.; Abebe, S.; Bamdad, J.; Callaghan, J.; Christophi, C. A.; Edelstein, S. L.; Gao, Y.; Gooding, R.; Gottlieb, A.; Grover, N.; Hoffman, H.; Jablonski, K.; Katz, R.; Kolinjivadi, P.; Lachin, J. M.; Ma, Y.; Reamer, S.; Sapozhnikova, A.; Sherif, H.; Temprosa, M.] George Washington Univ, Diabet Prevent Program Coordinating Ctr, Ctr Biostat, Rockville, MD 20852 USA. [Bray, G. A.; Chatellier, A.; Duncan, C.; Greenway, F. L.; Levy, E.; Ryan, D. H.] Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Polonsky, K. S.; Tobian, J.; Ehrmann, D.; Matulik, M. J.; Clark, B.; Czech, K.; DeSandre, C.; Hilbrich, R.; McNabb, W.; Semenske, A. R.] Univ Chicago, Chicago, IL 60637 USA. [Goldstein, B. J.; Smith, K. A.; Wildman, W.; Pepe, C.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Goldberg, R. B.; Calles, J.; Ojito, J.; Castillo-Florez, S.; Florez, H. J.; Giannella, A.; Lara, O.; Veciana, B.] Univ Miami, Miami, FL USA. [Haffner, S. M.; Montez, M. G.; Lorenzo, C.; Martinez, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Hamman, R. F.; Testaverde, L.; Bouffard, A.; Dabelea, D.; Jenkins, T.; Lenz, D.; Perreault, L.; Price, D. W.; Steinke, S. C.] Univ Colorado, Denver, CO 80202 USA. [Horton, E. S.; Poirier, C. S.; Swift, K.; Caballero, E.; Jackson, S. D.; Lambert, L.; Lawton, K. E.; Ledbury, S.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Kahn, S. E.; Montgomery, B. K.; Fujimoto, W.; Knopp, R. H.; Lipkin, E. W.; Marr, M.; Murillo, A.; Trence, D.] Univ Washington, Seattle, WA 98195 USA. [Kitabchi, A. E.; Murphy, M. E.; Applegate, W. B.; Bryer-Ash, M.; Dagogo-Jack, S.; Frieson, S. L.; Lambeth, H.; Lichtermann, L. C.; Otkaei, H.; Rutledge, L. M. K.; Sherman, A. R.; Smith, C. M.; Soberman, J. E.; Williams-Cleaves, B.] Univ Tennessee, Memphis, TN USA. [Metzger, B. E.; Molitch, M. E.; Johnson, M. K.; Giles, M. M.; Larsen, D.; Niznik, C.; Pen, S. C.; Schinleber, P. A.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Nathan, D. M.; McKitrick, C.; Turgeon, H.; Abbott, K.; Altshuler, D.; Anderson, E.; Bissett, L.; Cagliero, E.; D'Anna, K.; Delahanty, L.; Florez, J. C.; Goldman, V.; Poulos, A.; Tseng, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Barrett-Connor, E.; Carrion-Petersen, M. L.; Horne, J.; Leos, D.; Mudaliar, S.; Smith, J.; Vejvoda, K.] Univ Calif San Diego, San Diego, CA 92103 USA. [Pi-Sunyer, F. X.; Lee, J. E.; Foo, S. T.; Hagamen, S.] St Lukes Roosevelt Hosp, New York, NY 10025 USA. [Marrero, D. G.; Kelly, S. M.; Ackermann, R. T.; Fineberg, E. S.; Hadden, A.; Jackson, M. A.; Kirkman, M. S.; Mather, K. J.; Roach, P. J.; Wheeler, M. L.] Indiana Univ, Indianapolis, IN 46204 USA. [Ratner, R. E.; Aroda, V.; Shapiro, S.; Bavido-Arrage, C.; Gibbs, P.; Uwaifo, Gl; Wiggins, R.] Medstar Res Inst, Washington, DC USA. [Saad, M. F.; Watson, K.; Botrous, M.; Jinagouda, S.; Budget, M.; Conzues, C.; Magpuri, P.; Ngo, K.; Xapthalamous, K.] Univ Calif Los Angeles, Univ So Calif, Res Ctr, Alhambra, CA USA. [White, N. H.; Das, S.; Santiago, A.; Brown, A. L.; Wernimont, C.] Washington Univ, St Louis, MO USA. [Saudek, C. D.; Whittington, T.; Clark, J. M.; Greene, A.; Jiggetts, D.; Mosley, H.; Reusing, J.; Rubin, R. R.; Stephen, S.; Utsey, E.] Johns Hopkins Sch Med, Baltimore, MD USA. [Schade, D. S.; Adams, K. S.; Hemphill, C.; Hyde, P.; Butler, L.; Canady, J. L.; Colleran, K.; Gonzales, Y.; Hernandez-McGinnis, D. A.; Katz, P.; King, C.] Univ New Mexico, Albuquerque, NM 87131 USA. [Crandall, J.; Brown-Friday, J. O.; Adorno, E.; Duffy, H.; Martinez, H.; Pompi, D.; Shamoon, H.; Walker, E. A.; Wylie-Rosett, J.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Orchard, T.; Jeffries, S.; Kramer, M. K.; Smith, M.; Kriska, A.; Pettigrew, J.; Semler, L.; Venditti, E.; Weinzierl, V.] Univ Pittsburgh, Pittsburgh, PA USA. [Arakaki, R. F.; Baker-Ladao, N. K.; Isonaga, M. K.; Bermudez, N. E.; Mau, M. K.] Univ Hawaii, Honolulu, HI 96822 USA. [Knowler, W. C.; Cooeyate, N.; Hoskin, M. A.; Natewa, C.; Percy, C. A.; Acton, K. J.; Andre, V. L.; Begay, S.; Bucca, B. C.; Cook, S.; Doughty, M. S.; Glass, J.; Glass, M.; Hanson, R. L.; Hassenpflug, D.; Ingraham, L. E.; Kobus, K. M.; Krakoff, J.; Manus, C.; McCabe, C.; Michaels, S.; Morgan, T.; Nelson, J. A.; Roy, R. J.; Smart, M.; Tonemah, D. P.; Wilson, C.] SW Amer Indian Ctr, Phoenix, AZ USA. [Knowler, W. C.; Cooeyate, N.; Hoskin, M. A.; Natewa, C.; Percy, C. A.; Acton, K. J.; Andre, V. L.; Begay, S.; Bucca, B. C.; Cook, S.; Doughty, M. S.; Glass, J.; Glass, M.; Hanson, R. L.; Hassenpflug, D.; Ingraham, L. E.; Kobus, K. M.; Krakoff, J.; Manus, C.; McCabe, C.; Michaels, S.; Morgan, T.; Nelson, J. A.; Roy, R. J.; Smart, M.; Tonemah, D. P.; Wilson, C.] SW Amer Indian Ctr, Shiprock, NM USA. [Knowler, W. C.; Cooeyate, N.; Hoskin, M. A.; Natewa, C.; Percy, C. A.; Acton, K. J.; Andre, V. L.; Begay, S.; Bucca, B. C.; Cook, S.; Doughty, M. S.; Glass, J.; Glass, M.; Hanson, R. L.; Hassenpflug, D.; Ingraham, L. E.; Kobus, K. M.; Krakoff, J.; Manus, C.; McCabe, C.; Michaels, S.; Morgan, T.; Nelson, J. A.; Roy, R. J.; Smart, M.; Tonemah, D. P.; Wilson, C.] SW Amer Indian Ctr, Zuni, NM USA. [Marcovina, S.; Strylewicz, G.; Albers, J.] Cent Biochem Lab, Seattle, WA USA. [Prineas, R. J.; Alexander, T.; Campbell, C.; Hall, S.; Hensley, S.; Li, Y.; Mills, M.; Soliman, E.; Zhang, Z.] Epidemiol Cardiol Res Ctr Epicare, Winston Salem, NC USA. [Fradkin, J.; Garfield, S.] NIDDK, NIH, Bethesda, MD USA. [Mayer-Davis, E.; Moran, R. R.] Nutr Coding Ctr, Columbia, SC USA. [Ganiats, T.; Sarkin, A. J.] Qual Well Being Ctr, La Jolla, CA USA. RP Bray, GA (reprint author), George Washington Univ, Diabet Prevent Program Coordinating Ctr, Ctr Biostat, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM dppmail@biostat.bsc.gwu.edu RI Altshuler, David/A-4476-2009; Uwaifo, Gabriel/M-2361-2016 OI Altshuler, David/0000-0002-7250-4107; Uwaifo, Gabriel/0000-0002-6962-9304 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health FX This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) as a cooperative agreement. We thank the participants of the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study for their commitment and dedication; the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health for funding to the clinical and coordinating centres that designed and undertook the study, and collected, managed, analysed and interpreted the data; and the General Clinical Research Center Program and the National Center for Research Resources for support of data collection at many of the clinical centres. The Southwestern American Indian Centers were supported directly by the NIDDK, including its Intramural Research Program, and by the Indian Health Service. Funding was also provided by the National Institute of Child Health and Human Development, the National Institute on Aging, the National Eye Institute, the National Heart Lung and Blood Institute, the Office of Women's Health, the National Center for Minority Health and Human Disease, the Centers for Disease Control and Prevention, and the American Diabetes Association. Lipha (Merck-Sante) provided medicines, and LifeScan donated materials. The opinions expressed are those of the investigators and do not necessarily reflect the views of the funding agencies. NR 28 TC 800 Z9 806 U1 12 U2 82 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 NOV 14 PY 2009 VL 374 IS 9702 BP 1677 EP 1686 DI 10.1016/S0140-6736(09)61457-4 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 522LP UT WOS:000271999700023 ER PT J AU Eurich, K Segawa, M Toei-Shimizu, S Mizoguchi, E AF Eurich, Katrin Segawa, Mayuko Toei-Shimizu, Satoko Mizoguchi, Emiko TI Potential role of chitinase 3-like-1 in inflammation-associated carcinogenic changes of epithelial cells SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material DE Mammals; Chitinase 3-like 1; Colon; Epithelial cells; Inflammation; Colitis; Colon neoplasms; Inflammatory bowel disease ID HUMAN CARTILAGE GLYCOPROTEIN-39; ACIDIC MAMMALIAN CHITINASE; SERUM YKL-40 LEVEL; ADVANCED BREAST-CANCER; SMOOTH-MUSCLE-CELLS; FATTY LIVER-DISEASE; HIGH-GRADE GLIOMAS; GENE-EXPRESSION; OVARIAN-CANCER; BOWEL-DISEASE AB The family of mammalian chitinases includes members both with and without glycohydrolase enzymatic activity against chitin, a polymer of N-acetylglucosamine. Chitin is the structural component of fungi, crustaceans, insects and parasitic nematodes, but is completely absent in mammals. Exposure to antigens containing chitin- or chitin-like structures sometimes induces strong T helper type-I responses in mammals, which may be associated with the induction of mammalian chitinases. Chitinase 3-like-1 (CHI3L1), a member of the mammalian chitinase family, is induced specifically during the course of inflammation in such disorders as inflammatory bowel disease, hepatitis and asthma In addition, CHI3L1 is expressed and secreted by several types of solid tumors including glioblastoma, colon cancer, breast cancer and malignant melanoma. Although the exact function of CHI3L1 in inflammation and cancer is still largely unknown, CHI3L1 plays a pivotal role in exacerbating the inflammatory processes and in promoting angiogenesis and remodeling of the extracellular matrix. CHI3L1 may be highly involved in the chronic engagement of inflammation which potentiates development of epithelial tumorigenesis presumably by activating the mitogen-activated protein kinase and the protein kinase B signaling pathways. Anti-CHI3L1 antibodies or pan-chitinase inhibitors may have the potential to suppress CHI3L1-mediated chronic inflammation and the subsequent carcinogenic change in epithelial cells. (C) 2009 The WJG Press and Baishideng. All rights reserved. C1 [Eurich, Katrin; Segawa, Mayuko; Toei-Shimizu, Satoko; Mizoguchi, Emiko] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Gastrointestinal Unit, Boston, MA 02114 USA. [Mizoguchi, Emiko] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Mizoguchi, E (reprint author), Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Gastrointestinal Unit, GRJ 702,55 Fruit St, Boston, MA 02114 USA. EM emizoguchi@partners.org FU NIDDK NIH HHS [K08 DK064289-04, P30 DK043351, R01 DK080070, R01 DK080070-01A2, K08 DK064289, R01 DK080070-01A2S1, R03 DK074454, R03 DK074454-02, K08 DK064289-05] NR 192 TC 41 Z9 41 U1 1 U2 4 PU W J G PRESS PI BEIJING PA APT 1066, YISHOU GARDEN, NO 58, NORTH LANGXINZHUANG RD, PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD NOV 14 PY 2009 VL 15 IS 42 BP 5249 EP 5259 DI 10.3748/wjg.15.5249 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 520PI UT WOS:000271857200001 PM 19908331 ER PT J AU Rossen, RD Rubio, JA Porter, WJ Trial, J Orson, FM Rodriguez-Barradas, MC Birdsall, HH AF Rossen, Roger D. Rubio, Jose A. Porter, Wendy J. Trial, JoAnn Orson, Frank M. Rodriguez-Barradas, Maria C. Birdsall, Holly H. TI Monocyte CD49e and 110-120 kDa fibronectin fragments: HIV prognostic indicators independent of viral load and CD4 T-cell counts SO AIDS LA English DT Article DE cell-binding 110-120 kDa fibronectin fragments; inflammation; monocytes; patient survival; protease-antiprotease balance ID HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSENDOTHELIAL MIGRATION; PROTEASE INHIBITORS; SECRETION; ALPHA(1)-ANTITRYPSIN; INFECTIVITY; ACTIVATION; EXPRESSION; LEUKOCYTES; TYPE-1 AB Objective: To investigate the prognostic impact of chronic inflammation associated with HIV infections. Previously, we had observed that proteases, released in the course of HIV infections, cause 110-120 kDa fibronectin fragments (FNf) to appear in the blood of many patients. In vitro, at concentrations within the range found in patients' plasma, FNf stimulate monocytes to release proteolytic enzymes that remove CD49e from the cell surface and produce cytokines that suppress proliferation of activated T cells when stimulated by agents that crosslink their antigen receptors. Design: A long-term observational study of patients whose plasma FNf and monocyte CD49e had been measured at 90-day intervals for 1.4 +/- 0.5 years. Methods: Plasma FNf was measured by a quantitative western blot assay and monocyte CD49e expression by flow cytometry. Patients were monitored clinically for up to 5 years after enrollment. Results: All-cause mortality was significantly higher in patients who had at least 5 mu g/ml FNf in more than 50% of plasma samples and/or persistent depletion of monocyte CD49e. Persistence of FNf and depletion of monocyte CD49e were not associated with changes in viral load or CD4 T-cell counts. Conclusion: Persistently reduced expression of blood monocyte CD49e and/or the persistent presence of FNf in plasma are adverse prognostic markers in HIV-infected patients. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins C1 [Rossen, Roger D.; Rubio, Jose A.; Porter, Wendy J.; Trial, JoAnn; Orson, Frank M.; Rodriguez-Barradas, Maria C.; Birdsall, Holly H.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Rossen, Roger D.; Rubio, Jose A.; Porter, Wendy J.; Trial, JoAnn; Orson, Frank M.; Rodriguez-Barradas, Maria C.; Birdsall, Holly H.] Baylor Coll Med, Houston, TX 77030 USA. RP Rossen, RD (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Bldg 109,Room 228,2002 Holcombe Blvd, Houston, TX 77030 USA. EM rrossen@bcm.tmc.edu FU Department of Veterans Affairs Merit Review Program; National Institutes of Health [RO1-AI46285, RO1-MH63035] FX The support for this study was provided by the Department of Veterans Affairs Merit Review Program and National Institutes of Health grants: RO1-AI46285 and RO1-MH63035. NR 30 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 13 PY 2009 VL 23 IS 17 BP 2247 EP 2253 DI 10.1097/QAD.0b013e3283318ff4 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 517CF UT WOS:000271589700002 PM 19710592 ER PT J AU Lo, J Looby, SED Wei, J Adler, GK Grinspoon, SK AF Lo, Janet Looby, Sara E. D. Wei, Jeffrey Adler, Gail K. Grinspoon, Steven K. TI Increased aldosterone among HIV-infected women with visceral fat accumulation SO AIDS LA English DT Article ID CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; OBESITY AB Increased aldosterone has been associated with obesity and the metabolic syndrome in non-HIV-infected individuals, but aldosterone has not been investigated among HIV-infected patients with increased visceral adipose tissue (VAT). Twenty-four-hour urine aldosterone was assessed among age and BMI-matched HIV-infected women with increased VAT, HIV-infected women without increased VAT and healthy controls. Twenty-four hour urine aldosterone was higher in HIV-infected women with increased VAT and was associated with SBP, VAT and hemoglobin A1c. Increased aldosterone may contribute to the detrimental effects of excess visceral adiposity on blood pressure and glucose homeostasis among HIV patients. C1 [Lo, Janet; Looby, Sara E. D.; Wei, Jeffrey; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Adler, Gail K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. RP Lo, J (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. FU National Institutes of Health (NIH) [K23 HL092792, NIH RO1 DK 59535, NIH K24 DK064545, NIH M01 RR01066-2551] FX This study is supported by National Institutes of Health (NIH) K23 HL092792, NIH RO1 DK 59535, NIH K24 DK064545 and NIH M01 RR01066-2551. NR 14 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 13 PY 2009 VL 23 IS 17 BP 2366 EP 2370 DI 10.1097/QAD.0b013e3283328d3b PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 517CF UT WOS:000271589700017 PM 19770620 ER PT J AU Sosnovik, DE Wang, RP Dai, GP Reese, TG Wedeen, VJ AF Sosnovik, David E. Wang, Ruopeng Dai, Guangping Reese, Timothy G. Wedeen, Van J. TI Diffusion MR tractography of the heart SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Review ID MAGNETIC-RESONANCE; TENSOR MRI; IN-VIVO; LAMINAR STRUCTURE; CARDIAC FIBER; HYPERTROPHIC CARDIOMYOPATHY; MYOCARDIAL MICROSTRUCTURE; TISSUE ARCHITECTURE; WATER DIFFUSION; BOVINE TONGUE AB Histological studies have shown that the myocardium consists of an array of crossing helical fiber tracts. Changes in myocardial fiber architecture occur in ischemic heart disease and heart failure, and can be imaged non-destructively with diffusion-encoded MR. Several diffusion- encoding schemes have been developed, ranging from scalar measurements of mean diffusivity to a 6-dimensional imaging technique known as diffusion spectrum imaging or DSI. The properties of DSI make it particularly suited to the generation of 3-dimensional tractograms of myofiber architecture. In this article we review the physical basis of diffusion-tractography in the myocardium and the attributes of the available techniques, placing particular emphasis on DSI. The application of DSI in ischemic heart disease is reviewed, and the requisites for widespread clinical translation of diffusion MR tractography in the heart are discussed. C1 [Sosnovik, David E.; Wang, Ruopeng; Dai, Guangping; Reese, Timothy G.; Wedeen, Van J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. [Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. [Sosnovik, David E.; Wedeen, Van J.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Sosnovik, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. EM sosnovik@nmr.mgh.harvard.edu; rpwang@nmr.mgh.harvard.edu; dai@nmr.mgh.harvard.edu; reese@nmr.mgh.harvard.edu; van@nmr.mgh.harvard.edu FU National Institutes of Health [R01 HL093038, K08 HL079984]; VJW [RO1 MH64044]; NCRR [P41RR14075] FX This study was supported in part by the following grant from the National Institutes of Health: DES (R01 HL093038 and K08 HL079984), VJW ( RO1 MH64044), and (NCRR P41RR14075) to the Martinos Center for Biomedical Imaging. NR 63 TC 69 Z9 70 U1 1 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1097-6647 J9 J CARDIOVASC MAGN R JI J. Cardiov. Magn. Reson. PD NOV 13 PY 2009 VL 11 AR 47 DI 10.1186/1532-429X-11-47 PG 15 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 525XF UT WOS:000272250200001 PM 19912654 ER PT J AU Xiu, MH Hui, L Dang, YF De Hou, T Zhang, CX Zheng, YL Chen, DC Kosten, TR Zhang, XY AF Xiu, Mei Hong Hui, Li Dang, Yu Feng De Hou, Tian Zhang, Chong Xi Zheng, You Lan Chen, Da Chun Kosten, Thomas R. Zhang, Xiang Yang TI Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE Antipsychotic drug; Brain-derived neurotrophic factor; Neurotrophin; Psychopathology; Schizophrenia ID NEUROTROPHIC FACTOR; RAT HIPPOCAMPUS; MESSENGER-RNA; GROWTH-FACTOR; PREFRONTAL CORTEX; BIPOLAR DISORDER; WEIGHT-GAIN; BRAIN; EXPRESSION; PLASMA AB Accumulating evidence showed that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. Decreased BDNFlevels have been found in the serum of schizophrenic patients with mixed results. In the present study, we assessed serum BDNF levels in a large group of 364 schizophrenic patients (157 on clozapine, 89 on risperidone and 118 on typical antipsychotics), compared to 323 healthy control subjects matched for age and gender. The schizophrenia symptomatology was assessed by the Positive and Negative Syndrome Scale (PANSS), and serum BDNF levels were measured by sandwich ELISA. The results showed that BDNF levels were significantly lower in chronic patients with schizophrenia than in healthy control subjects (9.9 +/- 2.0 ng/ml vs. 11.9 +/- 23 ng/ml, p < 0.0001). Lower BDNF levels were observed in patients treated with risperidone (9.3 +/- 2.3 ng/ml) compared to those with clozapine (10.2 +/- 2.0 ng/ml, p < 0.001) and typical antipsychotics(10.0 +/- 2.1 ng/ml,p <0.01). Furthermore, a stepwise multiple regression analysis identified types of antipsychotic drugs (beta=-0.37, t=-3.15, p=0.001) and BDNF levels (beta=-0.26, t=-2.51, p = 0.014) as the influencing factor for the positive symptom subscore of PANSS. In addition, there was a sex difference in BDNF levels inpatients with schizophrenia (9.7 +/- 1.9 ng/ml for males vs. 10.4 +/- 2.1 ng/ml for female, p<0.005). but not in normal controls. Our findings indicated decreased BDNF serum levels in chronic patients with schizophrenia, which may be related to clinical phenotypes, including gender, antipsychotic treatment and the severity of psychotic symptoms. (C) 2009 Elsevier Inc. All rights reserved. C1 [Kosten, Thomas R.; Zhang, Xiang Yang] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Xiu, Mei Hong; Chen, Da Chun] Beijing HuiLongGuan Hosp, Ctr Biol Psychiat, Beijing, Peoples R China. [Hui, Li; De Hou, Tian] NW Normal Univ Lanzhou, Coll Life Sci, Lanzhou, Gansu, Peoples R China. [Dang, Yu Feng; Zheng, You Lan] Jilin Agr Univ, Coll Chinese Med Mat, Changchun, Peoples R China. [Zhang, Chong Xi] Shandong Univ Weihai Shandong, Weihai 264209, Peoples R China. 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 34 TC 71 Z9 73 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD NOV 13 PY 2009 VL 33 IS 8 BP 1508 EP 1512 DI 10.1016/j.pnpbp.2009.08.011 PG 5 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 532RL UT WOS:000272767100030 PM 19720106 ER PT J AU Nemoto, T Yamazawa, R Kobayashi, H Fujita, N Chino, B Fujii, C Kashima, H Rassovsky, Y Green, MF Mizuno, M AF Nemoto, Takahiro Yamazawa, Ryoko Kobayashi, Hiroyuki Fujita, Nobuharu Chino, Bun Fujii, Chiyo Kashima, Haruo Rassovsky, Yuri Green, Michael F. Mizuno, Masafumi TI Cognitive training for divergent thinking in schizophrenia: A pilot study SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE Cognitive training; Divergent thinking; Negative symptoms; Schizophrenia; Social functioning ID NEUROCOGNITIVE DEFICITS; REMEDIATION; SCALE AB Individuals with schizophrenia demonstrate deficits in divergent thinking. This ability is indispensable for generating creative solutions and navigating the complexities of social interactions. In a pilot study, seventeen stable schizophrenia outpatients were randomly assigned to a training program for divergent thinking or a control program on convergent thinking. After eight weeks of training, participants in the divergent thinking program had significantly greater improvements on measures of idea fluency, negative symptoms, and interpersonal relations than did participants receiving the control program. These preliminary results suggest that interventions for divergent thinking in schizophrenia may lead to improvements in patients' social functioning. (C) 2009 Elsevier Inc. All rights reserved. C1 [Nemoto, Takahiro] Keio Univ, Sch Med, Dept Neuropsychiat, Shinjuku Ku, Tokyo 1608582, Japan. [Nemoto, Takahiro] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Nemoto, Takahiro; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Fujii, Chiyo] Saitama Prefectural Univ, Dept Social Work, Saitama, Japan. [Rassovsky, Yuri; Green, Michael F.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Mizuno, Masafumi] Toho Univ, Sch Med, Dept Neuropsychiat, Tokyo, Japan. RP Nemoto, T (reprint author), Keio Univ, Sch Med, Dept Neuropsychiat, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan. EM nemotaka@aol.com FU Research Group for Schizophrenia, Japan FX We thank Mr. Ryosuke Ito, who kindly consulted on the development of the tasks in the study, and Dr. Jin Hwan Choi for help in interpretation of the data. Funding for this study was provided by a grant to Takahiro Nemoto from the Research Group for Schizophrenia, Japan. NR 26 TC 7 Z9 7 U1 1 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD NOV 13 PY 2009 VL 33 IS 8 BP 1533 EP 1536 DI 10.1016/j.pnpbp.2009.08.015 PG 4 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 532RL UT WOS:000272767100035 PM 19733608 ER PT J AU Jacobsohn, DA Gilman, AL Rademaker, A Browning, B Grimley, M Lehmann, L Nemecek, ER Thormann, K Schultz, KR Vogelsang, GB AF Jacobsohn, David A. Gilman, Andrew L. Rademaker, Alfred Browning, Brittan Grimley, Michael Lehmann, Leslie Nemecek, Eneida R. Thormann, Kimberly Schultz, Kirk R. Vogelsang, Georgia B. TI Evaluation of pentostatin in corticosteroid-refractory chronic graft-versus-host disease in children: a Pediatric Blood and Marrow Transplant Consortium study SO BLOOD LA English DT Article ID CONSENSUS DEVELOPMENT PROJECT; STEM-CELL TRANSPLANTATION; WORKING GROUP-REPORT; AUTOIMMUNE HEMOLYTIC-ANEMIA; CLINICAL-TRIALS; CHRONIC GVHD; EXTRACORPOREAL PHOTOCHEMOTHERAPY; MYCOPHENOLATE-MOFETIL; CRITERIA; THERAPY AB There is no standard therapy for steroid-refractory chronic graft-versus-host disease (GVHD). This problem is particularly daunting in children with chronic GVHD, whereby the effects of the disease and its treatment may impair normal growth and development. Children are also particularly vulnerable to failure and/or toxicity of therapy; for example, joint contractures or joint damage may result in lifelong disability. The Pediatric Blood and Marrow Transplant Consortium performed a phase 2 trial of pentostatin for steroid-refractory chronic GVHD in 51 children (median age, 9.8 years) from 24 institutions. Overall response was 53% (95% confidence interval, 40%-64%), with a response of 59% (95% confidence interval, 42%-75%) in sclerosis. Thirteen subjects (25%) had toxicity requiring them to stop pentostatin. The drug had a significant steroid-sparing effect in those that responded. A trend was also observed toward increased survival at 3 years in responders versus nonresponders (69% vs 50%; P = .06). The intravenous administration of the drug ensures compliance in a patient group in which oral therapy is difficult to monitor. Pentostatin has activity in refractory chronic GVHD in children, and future studies, including treatment of children newly diagnosed with high-risk chronic GVHD, are warranted. The trial was registered at www.Clinicaltrials.gov as #NCT00144430. (Blood. 2009;114: 4354-4360) C1 [Jacobsohn, David A.; Rademaker, Alfred; Thormann, Kimberly] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60614 USA. [Gilman, Andrew L.] Levine Childrens Hosp, Charlotte, NC USA. [Browning, Brittan] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. [Grimley, Michael] Methodist Childrens Hosp, San Antonio, TX USA. [Lehmann, Leslie] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nemecek, Eneida R.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Schultz, Kirk R.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Vogelsang, Georgia B.] Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD USA. RP Jacobsohn, DA (reprint author), Northwestern Univ, Sch Med, Stem Cell Transplant Program, Childrens Mem Hosp, 2300 Childrens Plaza,Box 30, Chicago, IL 60614 USA. EM djacobsohn@childrensmemorial.org NR 36 TC 18 Z9 19 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 12 PY 2009 VL 114 IS 20 BP 4354 EP 4360 DI 10.1182/blood-2009-05-224840 PG 7 WC Hematology SC Hematology GA 518WW UT WOS:000271727500006 PM 19745067 ER PT J AU Kubota, Y Osawa, M Jakt, LM Yoshikawa, K Nishikawa, SI AF Kubota, Yasushi Osawa, Masatake Jakt, Lars Martin Yoshikawa, Kazuaki Nishikawa, Shin-Ichi TI Necdin restricts proliferation of hematopoietic stem cells during hematopoietic regeneration SO BLOOD LA English DT Article ID PRADER-WILLI-SYNDROME; NEURONAL GROWTH SUPPRESSOR; GENE-EXPRESSION; IN-VIVO; DIFFERENTIATION; TRANSCRIPTION; PROTEIN; QUIESCENCE; INTERACTS; APOPTOSIS AB Hematopoietic stem cell (HSC) proliferation is tightly regulated by a poorly understood complex of positive and negative cell-cycle regulatory mechanisms. Necdin (Ndn) is an evolutionally conserved multifunctional protein that has been implicated in cell-cycle regulation of neuronal cells. Here, we provide evidence that necdin plays an important role in restricting excessive HSC proliferation during hematopoietic regeneration. We identify Ndn as being preferentially expressed in the HSC population on the basis of gene expression profiling and demonstrate that mice deficient in Ndn show accelerated recovery of the hematopoietic system after myelosuppressive injury, whereas no overt abnormality is seen in steady-state hematopoiesis. In parallel, after myelosuppression, Ndn-deficient mice exhibit an enhanced number of proliferating HSCs. Based on these findings, we propose that necdin functions in a negative feedback loop that prevents excessive proliferation of HSCs during hematopoietic regeneration. These data suggest that the inhibition of necdin after clinical myelosuppressive treatment (eg, chemotherapy, HSC transplantation) may provide therapeutic benefits by accelerating hematologic recovery. (Blood. 2009;114:4383-4392) C1 [Kubota, Yasushi; Osawa, Masatake; Jakt, Lars Martin; Nishikawa, Shin-Ichi] RIKEN, Ctr Dev Biol, Lab Stem Cell Biol, Chuo Ku, Kobe, Hyogo 6500047, Japan. [Osawa, Masatake] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Osawa, Masatake] Harvard Univ, Sch Med, Charlestown, MA USA. [Yoshikawa, Kazuaki] Osaka Univ, Inst Prot Res, Osaka, Japan. RP Kubota, Y (reprint author), RIKEN, Ctr Dev Biol, Lab Stem Cell Biol, Chuo Ku, Kobe, Hyogo 6500047, Japan. EM kubotay@cdb.riken.jp FU Grant-in-aid for Scientific Research Priority Areas [17045037]; Ministry of Education, Culture, Sports, Science, and Technology of Japan FX This work was supported by in part by a Grant-in-aid for Scientific Research Priority Areas (17045037) (M.O.) and a grant for Regenerative Medicine Realization Project (S.-I.N.) from Ministry of Education, Culture, Sports, Science, and Technology of Japan. NR 50 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 12 PY 2009 VL 114 IS 20 BP 4383 EP 4392 DI 10.1182/blood-2009-07-230292 PG 10 WC Hematology SC Hematology GA 518WW UT WOS:000271727500010 PM 19770359 ER PT J AU McGrath, CL Glatt, SJ Sklar, P Le-Niculescu, H Kuczenski, R Doyle, AE Biederman, J Mick, E Faraone, SV Niculescu, AB Tsuang, MT AF McGrath, Casey L. Glatt, Stephen J. Sklar, Pamela Le-Niculescu, Helen Kuczenski, Ronald Doyle, Alysa E. Biederman, Joseph Mick, Eric Faraone, Stephen V. Niculescu, Alexander B. Tsuang, Ming T. TI Evidence for genetic association of RORB with bipolar disorder SO BMC PSYCHIATRY LA English DT Article ID CONVERGENT FUNCTIONAL GENOMICS; DEFICIT HYPERACTIVITY DISORDER; CIRCADIAN-RHYTHM; CANDIDATE GENES; WIDE ASSOCIATION; MOOD DISORDERS; CLOCK GENES; STRESS; SYMPTOMS; ONSET AB Background: Bipolar disorder, particularly in children, is characterized by rapid cycling and switching, making circadian clock genes plausible molecular underpinnings for bipolar disorder. We previously reported work establishing mice lacking the clock gene D-box binding protein (DBP) as a stress-reactive genetic animal model of bipolar disorder. Microarray studies revealed that expression of two closely related clock genes, RAR-related orphan receptors alpha (RORA) and beta (RORB), was altered in these mice. These retinoid-related receptors are involved in a number of pathways including neurogenesis, stress response, and modulation of circadian rhythms. Here we report association studies between bipolar disorder and single-nucleotide polymorphisms ( SNPs) in RORA and RORB. Methods: We genotyped 355 RORA and RORB SNPs in a pediatric cohort consisting of a family-based sample of 153 trios and an independent, non-overlapping case-control sample of 152 cases and 140 controls. Bipolar disorder in children and adolescents is characterized by increased stress reactivity and frequent episodes of shorter duration; thus our cohort provides a potentially enriched sample for identifying genes involved in cycling and switching. Results: We report that four intronic RORB SNPs showed positive associations with the pediatric bipolar phenotype that survived Bonferroni correction for multiple comparisons in the case-control sample. Three RORB haplotype blocks implicating an additional 11 SNPs were also associated with the disease in the case-control sample. However, these significant associations were not replicated in the sample of trios. There was no evidence for association between pediatric bipolar disorder and any RORA SNPs or haplotype blocks after multiple-test correction. In addition, we found no strong evidence for association between the age-at-onset of bipolar disorder with any RORA or RORB SNPs. Conclusion: Our findings suggest that clock genes in general and RORB in particular may be important candidates for further investigation in the search for the molecular basis of bipolar disorder. C1 [Le-Niculescu, Helen; Niculescu, Alexander B.] Indiana Univ, Sch Med, Dept Psychiat, Lab Neurophen, Indianapolis, IN 46202 USA. [McGrath, Casey L.; Sklar, Pamela] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [McGrath, Casey L.] Indiana Univ, Dept Biol, Bloomington, IN USA. [Glatt, Stephen J.; Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Kuczenski, Ronald; Tsuang, Ming T.] UC San Diego, Dept Psychiat, La Jolla, CA USA. [Doyle, Alysa E.; Biederman, Joseph; Mick, Eric] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Doyle, Alysa E.; Biederman, Joseph; Mick, Eric] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Psychopharmacol Unit, Boston, MA USA. RP Niculescu, AB (reprint author), Indiana Univ, Sch Med, Dept Psychiat, Lab Neurophen, Indianapolis, IN 46202 USA. EM mcgrath.casey@gmail.com; glatts@upstate.edu; sklar@broad.mit.edu; hlenicul@iupui.edu; rkuczenski@ucsd.edu; doylea@helix.mgh.harvard.edu; biederman@helix.mgh.harvard.edu; emick1@partners.org; faraones@upstate.edu; anicules@iupui.edu; mtsuang@ucsd.edu OI Glatt, Stephen/0000-0002-0360-7567; Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU U. S. National Institute of Mental Health [1 R01 MH 071912]; NARSAD FX This work was supported by a grant ( 1 R01 MH 071912) from the U. S. National Institute of Mental Health to MTT and NARSAD Mogens Schou Young Investigator award to ABN. NR 51 TC 53 Z9 53 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-244X J9 BMC PSYCHIATRY JI BMC Psychiatry PD NOV 12 PY 2009 VL 9 AR 70 DI 10.1186/1471-244X-9-70 PG 8 WC Psychiatry SC Psychiatry GA 525MQ UT WOS:000272220600001 PM 19909500 ER PT J AU Moellering, RE Cornejo, M Davis, TN Del Bianco, C Aster, JC Blacklow, SC Kung, AL Gilliland, DG Verdine, GL Bradner, JE AF Moellering, Raymond E. Cornejo, Melanie Davis, Tina N. Del Bianco, Cristina Aster, Jon C. Blacklow, Stephen C. Kung, Andrew L. Gilliland, D. Gary Verdine, Gregory L. Bradner, James E. TI Direct inhibition of the NOTCH transcription factor complex SO NATURE LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; GAMMA-SECRETASE INHIBITORS; T-CELL LEUKEMIA; PROGENITOR CELLS; HUMAN HOMOLOG; C-MYC; MUTATIONS; GENE; MASTERMIND; ACTIVATION AB Direct inhibition of transcription factor complexes remains a central challenge in the discipline of ligand discovery. In general, these proteins lack surface involutions suitable for high-affinity binding by small molecules. Here we report the design of synthetic, cell-permeable, stabilized alpha-helical peptides that target a critical protein-protein interface in the NOTCH transactivation complex. We demonstrate that direct, high-affinity binding of the hydrocarbon-stapled peptide SAHM1 prevents assembly of the active transcriptional complex. Inappropriate NOTCH activation is directly implicated in the pathogenesis of several disease states, including T-cell acute lymphoblastic leukaemia (T-ALL). The treatment of leukaemic cells with SAHM1 results in genome-wide suppression of NOTCH-activated genes. Direct antagonism of the NOTCH transcriptional program causes potent, NOTCH-specific anti-proliferative effects in cultured cells and in a mouse model of NOTCH1-driven T-ALL. C1 [Moellering, Raymond E.; Bradner, James E.] Broad Inst Harvard & MIT, Chem Biol Program, Cambridge, MA 02142 USA. [Moellering, Raymond E.; Verdine, Gregory L.] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. [Moellering, Raymond E.; Verdine, Gregory L.; Bradner, James E.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. [Cornejo, Melanie; Gilliland, D. Gary] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Del Bianco, Cristina; Aster, Jon C.; Blacklow, Stephen C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Davis, Tina N.; Kung, Andrew L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Davis, Tina N.; Kung, Andrew L.] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. [Gilliland, D. Gary] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. RP Bradner, JE (reprint author), Broad Inst Harvard & MIT, Chem Biol Program, Cambridge, MA 02142 USA. EM gregory_verdine@harvard.edu; james_bradner@dfci.harvard.edu RI Del Bianco, Cristina/J-4665-2012; OI Kung, Andrew/0000-0002-9091-488X FU Leukaemia & Lymphoma Society; AACR Centennial Pre-doctoral Research Fellowship in Cancer Research; American Society of Hematology; MCCB-NIH [5T32GM007598]; Human Frontier Science Program; Harvard & Dana Farber Program in Cancer Chemical Biology; National Cancer Institute's Initiative for Chemical Genetics, National Institutes of Health [N01-CO-12400] FX We thank S. Schreiber and the Broad Institute Chemical Biology Program for discussions and access to instrumentation; J. Rocnik for assistance in the establishment of the T-ALL murine model; A. Ferrando for providing GSI microarray data; M. Hancock and Invitrogen for providing beta-lactamase HeLa reporter clones; K. Ross and A. Subramanian for conversations and guidance about GSEA; and S. Gupta and the Broad Institute Microarray Core. This work was supported by a Specialized Center of Research grant from the Leukaemia & Lymphoma Society (to J. E. B., J. C. A., S. C. B.), an AACR Centennial Pre-doctoral Research Fellowship in Cancer Research (to R. E. M.), the American Society of Hematology (to J. E. B.), MCCB-NIH Training Grant No. 5T32GM007598 (to R. E. M.), the Human Frontier Science Program (to C. D.), and the Harvard & Dana Farber Program in Cancer Chemical Biology (to J. E. B., R. E. M., G. L. V.). The project has been funded in part with Federal funds from the National Cancer Institute's Initiative for Chemical Genetics, National Institutes of Health, under Contract No. N01-CO-12400. Histology and immunohistochemical staining was performed in the Dana Farber/Harvard Cancer Center Specialized Histopathology Services Core Laboratory. NR 50 TC 410 Z9 419 U1 1 U2 72 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 12 PY 2009 VL 462 IS 7270 BP 182 EP U57 DI 10.1038/nature08543 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 517YM UT WOS:000271655100035 PM 19907488 ER PT J AU Baden, LR Digumarthy, SR Guimaraes, ASR Branda, JA AF Baden, Lindsey R. Digumarthy, Subba R. Guimaraes, Alexander S. R. Branda, John A. TI Case 35-2009: A 60-Year-Old Male Renal-Transplant Recipient with Renal Insufficiency, Diabetic Ketoacidosis, and Mental-Status Changes. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID COCCIDIOIDES-IMMITIS; NECROSIS-FACTOR; INFECTION; SEROLOGY; DISEASE C1 [Baden, Lindsey R.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Digumarthy, Subba R.; Guimaraes, Alexander S. R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Branda, John A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Baden, Lindsey R.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Digumarthy, Subba R.; Guimaraes, Alexander S. R.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Branda, John A.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Baden, LR (reprint author), Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. NR 23 TC 2 Z9 2 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 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 12 PY 2009 VL 361 IS 20 BP 1980 EP 1989 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 518AI UT WOS:000271660500015 PM 19907046 ER PT J AU Kujawa, SG Liberman, MC AF Kujawa, Sharon G. Liberman, M. Charles TI Adding Insult to Injury: Cochlear Nerve Degeneration after "Temporary" Noise-Induced Hearing Loss SO JOURNAL OF NEUROSCIENCE LA English DT Article ID KAINIC ACID EXCITOTOXICITY; GUINEA-PIG COCHLEA; CARBOPLATIN-TREATED CHINCHILLAS; MAMMALIAN COCHLEA; CAT COCHLEA; SERIAL SECTIONS; HAIR-CELLS; INNER-EAR; SYNAPSES; AFFERENT AB Overexposure to intense sound can cause temporary or permanent hearing loss. Postexposure recovery of threshold sensitivity has been assumed to indicate reversal of damage to delicate mechano-sensory and neural structures of the inner ear and no persistent or delayed consequences for auditory function. Here, we show, using cochlear functional assays and confocal imaging of the inner ear in mouse, that acoustic overexposures causing moderate, but completely reversible, threshold elevation leave cochlear sensory cells intact, but cause acute loss of afferent nerve terminals and delayed degeneration of the cochlear nerve. Results suggest that noise-induced damage to the ear has progressive consequences that are considerably more widespread than are revealed by conventional threshold testing. This primary neurodegeneration should add to difficulties hearing in noisy environments, and could contribute to tinnitus, hyperacusis, and other perceptual anomalies commonly associated with inner ear damage. C1 [Kujawa, Sharon G.; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Kujawa, Sharon G.; Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Kujawa, Sharon G.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. [Kujawa, Sharon G.; Liberman, M. Charles] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA. RP Kujawa, SG (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM sharon_kujawa@meei.harvard.edu FU National Institute on Deafness and Other Communicative Disorders [R01 DC8577, RO1 DC0188, P30 DC5209] FX Research was supported by grants from the National Institute on Deafness and Other Communicative Disorders (R01 DC8577, RO1 DC0188, P30 DC5209) and by a generous donation from Steve and Andrea Kaneb. NR 56 TC 573 Z9 588 U1 10 U2 72 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 NOV 11 PY 2009 VL 29 IS 45 BP 14077 EP 14085 DI 10.1523/JNEUROSCI.2845-09.2009 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 518BD UT WOS:000271664000003 PM 19906956 ER PT J AU Goebel, M Stengel, A Wang, LX Tache, Y AF Goebel, Miriam Stengel, Andreas Wang, Lixin Tache, Yvette TI Restraint stress activates nesfatin-1-immunoreactive brain nuclei in rats SO BRAIN RESEARCH LA English DT Article DE Fos; Nesfatin-1; NUCB2; Restraint; Hypothalamus; Medulla ID CORTICOTROPIN-RELEASING-FACTOR; DORSAL VAGAL COMPLEX; FOS EXPRESSION; C-FOS; PARAVENTRICULAR NUCLEUS; NEUROENDOCRINE RESPONSES; EMOTIONAL STRESSOR; SUPRAOPTIC NUCLEI; FACTOR RECEPTORS; CELL RESPONSES AB Nesfatin-1 is a newly discovered peptide that was reported to reduce food intake when injected centrally. We recently described its wide distribution in rat brain autonomic nuclei which implies potential recruitment of nesfatin-1 by stress. We investigated whether restraint, a mixed psychological and physical stressor, activates nesfatin-1-immunoreactive (ir) neurons in the rat brain. Male Sprague-Dawley rats were either subjected to 30 min restraint or left undisturbed and 90 min later brains were processed for double immunohistochemical labeling of Fos and nesfatin-1. Restraint induced significant Fos expression in neurons of the supraoptic nucleus (SON), paraventricular nucleus (PVN), locus coeruleus (LC), rostral raphe pallidus (rRPa), nucleus of the solitary tract (NTS), and ventrolateral medulla (VLM). Double Fos/nesfatin-1 labeling revealed that Fos-ir neurons comprised 95% of nesfatin-1-ir cells in the SON, 90% in the VLM, 80% in the LC, 48% in the caudal NTS, 57% in the rRPa, 48% in the anterior parvicellular PVN, 27% in the medial magnocellular PVN, 18% in the lateral magnocellular PVN and 10% in the medial parvicellular PVN. These data demonstrate that nesfatin-1 neurons are part of the hypothalamic and hindbrain neuronal cell groups activated by restraint suggesting a possible role of nesfatin-1 in the response to stress. Published by Elsevier B.V. C1 [Tache, Yvette] VA Greater Los Angeles Healthcare Syst, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr,Ctr Neurobiol Stress, Digest Dis Div,Dept Med, Los Angeles, CA 90095 USA. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Neurovisceral Sci & Womens Hlth, CURE Bldg 115,Room 117, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU German Research Foundation fellowship [Go 1718/1-1, STE 1765/1-1]; VA Research Career Scientist Award; Department of Veterans Affairs; NIHDK [33061]; Center [DK41301] FX This work was supported by German Research Foundation fellowship grants Go 1718/1-1 (M.G.) and STE 1765/1-1 (A.S.), the VA Research Career Scientist Award, Department of Veterans Affairs, NIHDK 33061 (Y.T.) and Center grant DK41301 (Animal Core, Y.T.). We are grateful to Mrs. Honghui Liang for her excellent technical support and Ms. Eugenia Hu for reviewing the manuscript. NR 53 TC 63 Z9 63 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 10 PY 2009 VL 1300 BP 114 EP 124 DI 10.1016/j.brainres.2009.08.082 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 520DC UT WOS:000271819200012 PM 19733157 ER PT J AU Weiner, RB Kiernan, TJ Yan, BP Rosenfield, K Jaff, MR AF Weiner, Rory B. Kiernan, Thomas J. Yan, Bryan P. Rosenfield, Kenneth Jaff, Michael R. TI Adventitial Fibromuscular Dysplasia of the Renal Artery Management Challenges of Nonatherosclerotic Renal Artery Stenosis SO CIRCULATION LA English DT Editorial Material ID RENOVASCULAR HYPERTENSION C1 [Weiner, Rory B.; Kiernan, Thomas J.; Rosenfield, Kenneth; Jaff, Michael R.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Sect Vasc Med, Boston, MA 02114 USA. [Yan, Bryan P.] Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Yan, Bryan P.] Prince Wales Hosp, Dept Med & Therapeut, Div Cardiol, Hong Kong, Hong Kong, Peoples R China. [Yan, Bryan P.] Monash Univ, Dept Epidemiol & Prevent Med, Ctr Cardiovasc Res & Educ Therapeut, Melbourne, Vic 3004, Australia. RP Weiner, RB (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Sect Vasc Med, Yawkey 5,55 Fruit St, Boston, MA 02114 USA. EM rweiner@partners.org RI Yan, Bryan/P-5928-2015 NR 4 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 10 PY 2009 VL 120 IS 19 BP E157 EP E158 DI 10.1161/CIRCULATIONAHA.109.872853 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 516WS UT WOS:000271574600016 PM 19901199 ER PT J AU Ligibel, JA AF Ligibel, Jennifer A. TI Could Modification of Lifestyle Factors Prevent Second Primary Breast Cancers? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID PHYSICAL-ACTIVITY; POOLED ANALYSIS; RISK-FACTORS; WOMEN; TAMOXIFEN; DIAGNOSIS; PROGNOSIS; SURVIVAL; ALCOHOL; OBESITY C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ligibel, JA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 18 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2009 VL 27 IS 32 BP 5301 EP 5302 DI 10.1200/JCO.2009.24.4517 PG 2 WC Oncology SC Oncology GA 516GT UT WOS:000271530900001 PM 19738104 ER PT J AU Harris, JR Morrow, M AF Harris, Jay R. Morrow, Monica TI Clinical Dilemma of Ductal Carcinoma in Situ SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID BREAST-CANCER; LOCAL RECURRENCE; RADIOTHERAPY; SURGERY; WOMEN; EXCISION; INSITU C1 [Harris, Jay R.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol,Med Sch, Boston, MA 02115 USA. [Morrow, Monica] Mem Sloan Kettering Canc Ctr, Dept Surg, Breast Serv, New York, NY 10021 USA. RP Harris, JR (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol,Med Sch, Boston, MA 02115 USA. NR 18 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 J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2009 VL 27 IS 32 BP 5303 EP 5305 DI 10.1200/JCO.2009.24.1489 PG 3 WC Oncology SC Oncology GA 516GT UT WOS:000271530900002 PM 19826109 ER PT J AU Hughes, LL Wang, ML Page, DL Gray, R Solin, LJ Davidson, NE Lowen, MA Ingle, JN Recht, A Wood, WC AF Hughes, Lorie L. Wang, Molin Page, David L. Gray, Robert Solin, Lawrence J. Davidson, Nancy E. Lowen, Mary Ann Ingle, James N. Recht, Abram Wood, William C. TI Local Excision Alone Without Irradiation for Ductal Carcinoma In Situ of the Breast: A Trial of the Eastern Cooperative Oncology Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SURGICAL ADJUVANT BREAST; NUYS PROGNOSTIC INDEX; RANDOMIZED CONTROLLED-TRIAL; CONSERVING TREATMENT; MARGIN WIDTH; CANCER; RADIOTHERAPY; RECURRENCE; TAMOXIFEN; SURGERY AB Purpose To determine the risk of ipsilateral breast events in patients with ductal carcinoma in situ ( DCIS) treated with local excision without irradiation. Patients and Methods Patients with either low- or intermediate-grade DCIS measuring 2.5 cm or smaller, or high-grade DCIS measuring 1 cm or smaller who had microscopic margin widths of 3 mm or wider and no residual calcifications on postoperative mammograms were eligible for a prospective trial conducted from 1997 to 2002 by the Eastern Cooperative Oncology Group and North Central Cancer Treatment Group. Patients entered in 2000 and later could take tamoxifen if they wished. Median age at last surgery for the entire population was 60 years (range, 28 to 88 years), and median tumor sizes in the two strata were 6 mm and 5 mm, respectively. Results With a median follow-up of 6.2 years, the 5-year rate of ipsilateral breast events in the 565 eligible patients in the low/intermediate grade stratum was 6.1% (95% CI, 4.1% to 8.2%). With a median follow-up of 6.7 years, this incidence for the 105 eligible patients in the high-grade stratum was 15.3% (95% CI, 8.2% to 22.5%). Conclusion Rigorously evaluated and selected patients with low- to intermediate-grade DCIS with margins 3 mm or wider had an acceptably low rate of ipsilateral breast events at 5 years after excision without irradiation. Patients with high-grade lesions had a much higher rate, suggesting that excision alone is inadequate treatment. Further follow-up is necessary to document long-term results. C1 N Georgia Radiat Therapy Hope Ctr, Cartersville, GA USA. Emory Univ, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Vanderbilt Univ, Nashville, TN USA. Univ Penn, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Baystate Med Ctr, Springfield, MA USA. Mayo Clin, Rochester, MN USA. RP Hughes, LL (reprint author), Hope Ctr, 100 Market Pl Blvd,Ste 102, Cartersville, GA 30121 USA. EM lhughesmd@aol.com FU National Cancer Institute, National Institutes of Health [CA23318, CA66636, CA21115, CA40057, CA07190, CA25224, CA16116]; Department of Health and Human Services FX Supported in part by Public Health Service Grants No. CA23318, CA66636, CA21115, CA40057, CA07190, CA25224, and CA16116 and from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. NR 24 TC 164 Z9 176 U1 0 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 NOV 10 PY 2009 VL 27 IS 32 BP 5319 EP 5324 DI 10.1200/JCO.2009.21.8560 PG 6 WC Oncology SC Oncology GA 516GT UT WOS:000271530900006 PM 19826126 ER PT J AU Kornblith, AB Huang, HQ Walker, JL Spirtos, NM Rotmensch, J Cella, D AF Kornblith, Alice B. Huang, Helen Q. Walker, Joan L. Spirtos, Nick M. Rotmensch, Jacob Cella, David TI Quality of Life of Patients With Endometrial Cancer Undergoing Laparoscopic International Federation of Gynecology and Obstetrics Staging Compared With Laparotomy: A Gynecologic Oncology Group Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FUNCTIONAL ASSESSMENT; OPEN COLECTOMY; MANAGEMENT; CARCINOMA; WOMEN; COST AB Purpose The study's objective was to compare the quality of life (QoL) of patients with endometrial cancer undergoing surgical staging via laparoscopy versus laparotomy. Patients and Methods The first 802 eligible patients (laparoscopy, n = 535; laparotomy, n = 267) participated in the QoL study in a Gynecologic Oncology Group (GOG) randomized trial of laparoscopy versus laparotomy (GOG 2222). Patients completed QoL assessments at baseline; at 1, 3, and 6 weeks; and at 6 months postsurgery. Results In an intent-to-treat analysis, laparoscopy patients reported significantly higher Functional Assessment of Cancer Therapy-General (FACT-G) scores (P = .001), better physical functioning (P = .006), better body image (BI; P < .001), less pain (P < .001) and its interference with QoL (P < .001), and an earlier resumption of normal activities (P = .003) and return to work (P = .04) over the 6-week postsurgery period, as compared with laparotomy patients. However, the differences in BI and return to work between groups were modest, and the adjusted FACT-G scores did not meet the minimally important difference ( MID) between the two surgical arms over 6 weeks. By 6 months, except for better BI in laparoscopy patients (P < .001), the difference in QoL between the two surgical techniques was not statistically significant. Conclusion Although the FACT-G did not show a MID between the two surgical groups, and only modest differences in return to work and BI were found between the two groups, statistically significantly better QoL across many parameters in the laparoscopy arm at 6 weeks provides modest support for the QoL advantage of using laparoscopy to stage patients with early endometrial cancer. C1 [Kornblith, Alice B.] Dana Farber Canc Inst, Div Womens Cancers, Boston, MA 02115 USA. Roswell Pk Canc Inst, Gynecol Oncol Grp Stat, Buffalo, NY 14263 USA. Roswell Pk Canc Inst, Ctr Data, Buffalo, NY 14263 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Oklahoma City, OK 73190 USA. Univ Nevada, Sch Med, Womens Canc Ctr Nevada, Las Vegas, NV 89154 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Ctr Outcomes Res & Educ, Evanston, IL USA. RP Kornblith, AB (reprint author), Dana Farber Canc Inst, Div Womens Cancers, 44 Binney St,LW 231, Boston, MA 02115 USA. EM alice_kornblith@dfci.harvard.edu FU National Cancer Institute [CA 27469, CA 37517]; GOG FX Supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office (Grant No. CA 27469) and the GOG Statistical and Data Center (Grant No. CA 37517). J.L.W. was supported by GOG. NR 19 TC 114 Z9 121 U1 1 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 NOV 10 PY 2009 VL 27 IS 32 BP 5337 EP 5342 DI 10.1200/JCO.2009.22.3529 PG 6 WC Oncology SC Oncology GA 516GT UT WOS:000271530900009 PM 19805678 ER PT J AU Chen, AB Punglia, RS Kuntz, KM Mauch, PM Ng, AK AF Chen, Aileen B. Punglia, Rinaa S. Kuntz, Karen M. Mauch, Peter M. Ng, Andrea K. TI Cost Effectiveness and Screening Interval of Lipid Screening in Hodgkin's Lymphoma Survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; LONG-TERM SURVIVORS; TREATMENT PANEL-III; ARTERY-DISEASE; MEDIASTINAL IRRADIATION; RADIATION-THERAPY; DATA-BASE; MORTALITY; CHOLESTEROL AB Purpose Survivors of Hodgkin's lymphoma (HL) who received mediastinal irradiation have an increased risk of coronary heart disease. We evaluated the cost effectiveness of lipid screening in survivors of HL and compared different screening intervals. Methods We developed a decision-analytic model to evaluate lipid screening in a hypothetical cohort of 30-year-old survivors of HL who survived 5 years after mediastinal irradiation. We compared the following strategies: no screening, and screening at 1-, 3-, 5-, or 7-year intervals. Screen-positive patients were treated with statins. Markov models were used to calculate life expectancy, quality-adjusted life expectancy, and lifetime costs. Baseline probabilities, transition probabilities, and utilities were derived from published studies and US population data. Costs were estimated from Medicare fee schedules and the medical literature. Sensitivity analyses were performed. Results Using an incremental cost-effectiveness ratio (ICER) threshold of $100,000 per quality-adjusted life-year (QALY) saved, lipid screening at every interval was cost effective relative to a strategy of no screening. When comparing screening intervals, a 3- year interval was cost effective relative to a 5- year interval, but annual screening, relative to screening every 3 years, had an ICER of more than $100,000/QALY saved. Factors with the most influence on the results included risk of cardiac events/death after HL, efficacy of statins in reducing cardiac events/death, and costs of statins. Conclusion Lipid screening in survivors of HL, with statin therapy for screen-positive patients, improves survival and is cost effective. A screening interval of 3 years seems reasonable in the long-term follow-up of survivors of HL. C1 [Chen, Aileen B.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA. RP Chen, AB (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St,Smith 255, Boston, MA 02115 USA. EM achen7@partners.org OI Chen, Aileen/0000-0002-5385-3360 NR 53 TC 13 Z9 13 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2009 VL 27 IS 32 BP 5383 EP 5389 DI 10.1200/JCO.2009.22.8460 PG 7 WC Oncology SC Oncology GA 516GT UT WOS:000271530900016 PM 19752333 ER PT J AU Bilimoria, KY Raval, MV Bentrem, DJ Wayne, JD Balch, CM Ko, CY AF Bilimoria, Karl Y. Raval, Mehul V. Bentrem, David J. Wayne, Jeffrey D. Balch, Charles M. Ko, Clifford Y. TI National Assessment of Melanoma Care Using Formally Developed Quality Indicators SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CANCER DATA-BASE; COLORECTAL-CANCER; UNITED-STATES; APPROPRIATENESS METHOD; PERFORMANCE-MEASURES; MALIGNANT-MELANOMA; ASSESSMENT TOOLS; CARDIAC-SURGERY; SURGICAL CARE; HEALTH-CARE AB Purpose There is considerable variation in the quality of cancer care delivered in the United States. Assessing care by using quality indicators could help decrease this variability. The objectives of this study were to formally develop valid quality indicators for melanoma and to assess hospital-level adherence with these measures in the United States. Methods Quality indicators were identified from available literature, consensus guidelines, and melanoma experts. Thirteen experts ranked potential measures for validity on the basis of the RAND/University of California, Los Angeles Appropriateness Methodology. Adherence with individual valid indicators and a composite measure of all indicators were assessed at 1,249 Commission on Cancer hospitals by using the National Cancer Data Base (NCDB; 2004 through 2005). Results Of 55 proposed quality indicators, 26 measures (47%) were rated as valid. These indicators assessed structure (n = 1), process (n = 24), and outcome (n = 1). Of the 26 measures, 10 are readily assessable by using cancer registry data. Adherence with valid indicators ranged from 11.8% to 96.5% at the patient level and 3.7% to 83.0% at the hospital level. (Adherence required that > 90% of patients at a hospital receive concordant care.) Most hospitals were adherent with 50% or fewer of the individual indicators (median composite score, five; interquartile range, four to seven). Adherence was higher for diagnosis and staging measures and was lower for treatment indicators. Conclusion There is considerable variation in the quality of melanoma care in the United States. By using these formally developed quality indicators, hospitals can assess their adherence with current melanoma care guidelines through feedback mechanisms from the NCDB and can better direct quality improvement efforts. C1 [Bilimoria, Karl Y.] Amer Coll Surg, Canc Programs, Chicago, IL 60611 USA. Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. Johns Hopkins Sch Med, Dept Surg, Baltimore, MD USA. Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Bilimoria, KY (reprint author), Amer Coll Surg, Canc Programs, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM kbilimoria@facs.org OI Raval, Mehul/0000-0002-1527-2661 FU American College of Surgeons Clinical Scholars in Residence program; American College of Surgeons; Commission on Cancer; American Cancer Society (National Cancer Data Base) FX Supported by the American College of Surgeons Clinical Scholars in Residence program (K.Y.B. and M.V.R.); and by the American College of Surgeons, the Commission on Cancer, and the American Cancer Society (National Cancer Data Base). NR 51 TC 36 Z9 36 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2009 VL 27 IS 32 BP 5445 EP 5451 DI 10.1200/JCO.2008.20.9965 PG 7 WC Oncology SC Oncology GA 516GT UT WOS:000271530900025 PM 19826131 ER PT J AU Lane, AA Chabner, BA AF Lane, Andrew A. Chabner, Bruce A. TI Histone Deacetylase Inhibitors in Cancer Therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID T-CELL LYMPHOMA; SUBEROYLANILIDE HYDROXAMIC ACID; REFRACTORY SOLID TUMORS; ACUTE MYELOID-LEUKEMIA; PHASE-II TRIAL; FRIEND ERYTHROLEUKEMIA CELLS; HDAC INHIBITORS; MYELODYSPLASTIC SYNDROMES; HEMATOLOGIC MALIGNANCIES; GENE-EXPRESSION AB Purpose Epigenetic processes are implicated in cancer causation and progression. The acetylation status of histones regulates access of transcription factors to DNA and influences levels of gene expression. Histone deacetylase (HDAC) activity diminishes acetylation of histones, causing compaction of the DNA/histone complex. This compaction blocks gene transcription and inhibits differentiation, providing a rationale for developing HDAC inhibitors. Methods In this review, we explore the biology of the HDAC enzymes, summarize the pharmacologic properties of HDAC inhibitors, and examine results of selected clinical trials. We consider the potential of these inhibitors in combination therapy with targeted drugs and with cytotoxic chemotherapy. Results HDAC inhibitors promote growth arrest, differentiation, and apoptosis of tumor cells, with minimal effects on normal tissue. In addition to decompaction of the histone/DNA complex, HDAC inhibition also affects acetylation status and function of nonhistone proteins. HDAC inhibitors have demonstrated antitumor activity in clinical trials, and one drug of this class, vorinostat, is US Food and Drug Administration approved for the treatment of cutaneous T-cell lymphoma. Other inhibitors in advanced stages of clinical development, including depsipeptide and MGCD0103, differ from vorinostat in structure and isoenzyme specificity, and have shown activity against lymphoma, leukemia, and solid tumors. Promising preclinical activity in combination with cytotoxics, inhibitors of heat shock protein 90, and inhibitors of proteasome function have led to combination therapy trials. Conclusion HDAC inhibitors are an important emerging therapy with single-agent activity against multiple cancers, and have significant potential in combination use. C1 [Lane, Andrew A.; Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02214 USA. RP Chabner, BA (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02214 USA. EM bchabner@partners.org RI qiao, zhixin/I-3408-2012 NR 130 TC 486 Z9 500 U1 6 U2 70 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 NOV 10 PY 2009 VL 27 IS 32 BP 5459 EP 5468 DI 10.1200/JCO.2009.22.1291 PG 10 WC Oncology SC Oncology GA 516GT UT WOS:000271530900027 PM 19826124 ER PT J AU Marzocchetti, A Tompkins, T Clifford, DB Gandhi, RT Kesari, S Berger, JR Simpson, DM Prosperi, M De Luca, A Koralnik, IJ AF Marzocchetti, A. Tompkins, T. Clifford, D. B. Gandhi, R. T. Kesari, S. Berger, J. R. Simpson, D. M. Prosperi, M. De Luca, A. Koralnik, I. J. TI Determinants of survival in progressive multifocal leukoencephalopathy SO NEUROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; CYTOTOXIC T-LYMPHOCYTES; JC VIRUS EPITOPE; PROLONGED SURVIVAL; CLINICAL-COURSE; PML-IRIS; ASSOCIATION; FREQUENCY; STEROIDS; HAART AB Background: We sought to characterize the role of immunologic, virologic, and radiologic determinants of survival in patients with progressive multifocal leukoencephalopathy (PML). Methods: We recorded the clinical outcome of 60 patients with PML (73% HIV+) who were prospectively evaluated between 2000 and 2007 for the presence of JC virus (JCV)-specific CD8+ cytotoxic T-lymphocytes (CTL) in blood. Results: Estimated probability of survival at 1 year was 52% for HIV+/PML and 58% for HIV-patients with PML. Patients with PML with detectable CTL within 3 months of diagnosis had a 1-year estimated survival of 73% compared to 46% for those without CTL ( hazard ratio [HR] for death = 0.47, 95% confidence interval [CI] 0.13-1.75, p = 0.26). Patients with CTL response had an increased likelihood of having contrast enhancement of PML lesions and immune reconstitution inflammatory syndrome (odds ratio 3.7 and 7.8). Estimated 1-year survival was 48% in HIV-patients with PML with CD4 count <200/mu L at PML diagnosis compared to 67% in those with CD4 >200/mu L (HR for death 1.41, 95% CI 0.27-7.38, p = 0.68). JCV DNA was detected in the urine of 48% and in the blood of 56% of patients with PML, but viruria and viremia were not associated with survival. Conclusions: The presence of JC virus (JCV)-specific cytotoxic T-lymphocytes ( CTL) was associated with a trend toward longer survival in patients with progressive multifocal leukoencephalopathy ( PML), which was more pronounced than the impact of CD4 count in HIV-patients with PML early after diagnosis. Despite the association of contrast enhancement and immune reconstitution inflammatory syndrome with JCV-specific CTL, these cannot be considered as surrogate markers for the prognostic value of the CTL. Strategies aiming at improving the cellular immune response may improve the course of PML. Neurology (R) 2009; 73: 1551-1558 C1 [Marzocchetti, A.; Tompkins, T.; Koralnik, I. J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis, Boston, MA 02215 USA. [Koralnik, I. J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Clifford, D. B.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Gandhi, R. T.] Harvard Univ, Sch Med, MGH, Dept Infect Dis, Boston, MA USA. [Kesari, S.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Neurol,Med Sch, Boston, MA 02115 USA. [Berger, J. R.] Univ Kentucky, Coll Med, Dept Neurol, Lexington, KY 40506 USA. [Simpson, D. M.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Prosperi, M.] Natl Inst Infect Dis L Spallanzani, Dept Virol, Rome, Italy. [De Luca, A.] Catholic Univ, Div Infect Dis, Rome, Italy. RP Koralnik, IJ (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis, E CLS 1005,330 Brookline Ave, Boston, MA 02215 USA. EM ikoralni@bidmc.harvard.edu RI De Luca, Andrea/G-8810-2011; Kesari, Santosh/E-8461-2013 FU NIH [UO1 NS32228, UO1 AI69495, NIMH 22005, RO3 DA022137, NIMH MH058076, R21 385753187, K08CA124804]; Gilead Sciences, Inc.; Tibotec Therapeutics; Enzon Pharmaceuticals, Inc.; Sontag Foundation; EMD Serono, Inc.; GlaxoSmithKline, Allergan, Inc.; Merz Pharmaceuticals, LLC, and Torrey Pines Institute for Molecular Studies FX Dr. Marzocchetti reports no disclosures. T. Tompkins holds stock options in BioMarin Pharmaceutical, Inc. Dr. Clifford serves/has served on scientific advisory boards for Biogen Idec, Elan Corporation, Roche, Forest Laboratories, Inc., Genentech, Inc., GlaxoSmithKline, Millennium Pharmaceuticals, Inc., Schering-Plough Corp., Bristol-Meyers Squibb, and Genzyme Corporation; received speaker honorarium and funding for travel from GlaxoSmithKline; has received research support from Pfizer Inc., Schering-Plough Corp., Bavarian Nordic, NeurogesX, GlaxoSmithKline, Tibotec Therapeutics, Boehringer Ingelheim, and Gilead Sciences, Inc.; and receives research support from the NIH [UO1 NS32228 ( PI), UO1 AI69495 ( PI), NIMH 22005 CHARTER Project ( Site PI), NIDA RO3 DA022137 (Co-I), NIMH MH058076 ( Site PI), and R21 385753187 ( PI)]. Dr. Gandhi serves on the editorial board of Journal Watch Infectious Diseases, received speaker honorarium from GlaxoSmithKline, received educational support from Gilead Sciences, Inc. and Abbott, and receives research support from Tibotec Therapeutics. Dr. Kesari serves on scientific advisory boards for Bristol-Meyers Squibb and Genentech, Inc.; serves on editorial boards for the Journal of Neuro-Oncology and the International Journal of Biomedical Nanoscience and Nanotechnology; receives royalties from publishing Cancer Neurology in Clinical Practice (Humana, 2008); served on a speakers' bureau for Enzon Pharmaceuticals, Inc.; and receives research support from GE Healthcare, the NIH [K08CA124804 ( PI)], and the Sontag Foundation. Dr. Berger serves/has served on scientific advisory boards for Millennium Pharmaceuticals, Inc., Bayer Schering Pharma, Merck Serono, Genentech, Inc., Astellas Pharma Inc., and Asphelia Pharmaceuticals; has received speaker honoraria from EMD Serono, Inc., Teva Pharmaceutical Industries Ltd., and Bayer Schering Pharma; and receives research support from Bayer Schering Pharma, EMD Serono, Inc., Biogen Idec, Sanofi-Aventis, Genentech Inc., and UCB. Dr. Simpson has served on scientific advisory boards for Boehringer Ingelheim, Cephalon, Inc., Pfizer Inc., Endo Pharmaceuticals, GlaxoSmithKline, Merz Pharmaceuticals, LLC, MEDA Pharmaceuticals Inc., Alpharma Pharmaceuticals LLC, and Biogen Idec; serves on the editorial boards of the Clinical Journal of Pain and AIDS Patient Care; has served as a consultant to NeurogesX, Eli Lilly and Company, Regeneron Pharmaceuticals Inc., GlaxoSmithKline, Allergan, Inc., Merz Pharmaceuticals, LLC, and Torrey Pines Institute for Molecular Studies; served on speakers' NR 22 TC 86 Z9 86 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 10 PY 2009 VL 73 IS 19 BP 1551 EP 1558 DI 10.1212/WNL.0b013e3181c0d4a1 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 517FO UT WOS:000271598800007 PM 19901246 ER PT J AU Lopez, L Weissman, JS Schneider, EC Weingart, SN Cohen, AP Epstein, AM AF Lopez, Lenny Weissman, Joel S. Schneider, Eric C. Weingart, Saul N. Cohen, Amy P. Epstein, Arnold M. TI Disclosure of Hospital Adverse Events and Its Association With Patients' Ratings of the Quality of Care SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HARMFUL MEDICAL ERRORS; DRUG EVENTS; PHYSICIANS ATTITUDES; PATIENTS WANT; EXPERIENCES; MISTAKES; MANAGEMENT; DOCTORS; SAFETY; VIEWS AB Background: Little is known about how the characteristics of adverse events (AEs) affect the likelihood of disclosure or how the disclosure of an AE relates to patients' perception of quality of care. Methods: The study included a random sample of medical and surgical acute care adult patients in Massachusetts hospitals between April I and October 1, 2003. The unit of analysis was the AE, and multivariable regression analyses accounted for clustering at the patient level. Results: Overall, 603 patients reported 845 AEs, and 40% of AEs were disclosed. The AEs that required additional treatment (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.16-2.32) or affected patients who reported good health (OR, 2.04; 95% CI, 1.29-3.24) were more likely to be disclosed. Disclosure was less likely if the events were preventable (OR, 0.58; 95% CI, 0.41-0.83) or if the patients were still affected by the AE at the time of survey (OR, 0.49; 95% CI, 0.31-0.78). Higher-quality ratings were associated with disclosure (OR, 2.04; 95% CI, 1.39-2.99) of preventable and nonpreventable events and with patients who felt that they were able to protect themselves from AEs (OR, 1.98; 95% CI, 1.21-3.24). Lower-quality ratings were associated with events that were preventable (OR, 0.55; 95% CI, 0.40-0.76), with events that caused increased discomfort (OR, 0.62; 95% CI, 0.46-0.86), or with events that still adversely affected the patient at the time of the survey (OR, 0.68; 95% CI, 0.46-0.98). Conclusions: Rates of disclosure of AEs by medical personnel remain low in hospitalized patients. Disclosure of some of these events is associated with higher ratings of quality by patients. C1 [Lopez, Lenny; Weissman, Joel S.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Lopez, Lenny; Weissman, Joel S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Schneider, Eric C.; Epstein, Arnold M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Sect Hlth Serv & Policy Res,Div Gen Med, Boston, MA 02115 USA. [Weissman, Joel S.; Epstein, Arnold M.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Cohen, Amy P.] Harvard Univ, Sch Publ Hlth, Dept Informat Technol, Boston, MA 02115 USA. [Weingart, Saul N.] Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02115 USA. [Weissman, Joel S.] Massachusetts Execut Off Hlth & Human Serv, Boston, MA USA. RP Lopez, L (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM llopez1@partners.org OI Schneider, Eric/0000-0002-1132-5084 FU Agency for Healthcare Research and Quality to the Massachusetts Department of Public Health [U18 HS11928]; Institutional National Research Service Award [5 T32 HP11001-19] FX This work was supported by a Cooperative Agreement from the Agency for Healthcare Research and Quality to the Massachusetts Department of Public Health (U18 HS11928). Dr Lopez acknowledges the support of an Institutional National Research Service Award (5 T32 HP11001-19). NR 42 TC 36 Z9 36 U1 3 U2 5 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 NOV 9 PY 2009 VL 169 IS 20 BP 1888 EP 1894 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 516BX UT WOS:000271517800010 PM 19901141 ER PT J AU Paik, JH Ding, ZH Narurkar, R Ramkissoon, S Muller, F Kamoun, WS Chae, SS Zheng, HW Ying, HQ Mahoney, J Hiller, D Jiang, S Protopopov, A Wong, WH Chin, L Ligon, KL DePinho, RA AF Paik, Ji-hye Ding, Zhihu Narurkar, Rujuta Ramkissoon, Shakti Muller, Florian Kamoun, Walid S. Chae, Sung-Suk Zheng, Hongwu Ying, Haoqiang Mahoney, Jed Hiller, David Jiang, Shan Protopopov, Alexei Wong, Wing H. Chin, Lynda Ligon, Keith L. DePinho, Ronald A. TI FoxOs Cooperatively Regulate Diverse Pathways Governing Neural Stem Cell Homeostasis SO CELL STEM CELL LA English DT Article ID FORKHEAD TRANSCRIPTION FACTORS; SELF-RENEWAL; OXIDATIVE STRESS; ADULT NEUROGENESIS; DOWN-REGULATION; IN-VIVO; DIFFERENTIATION; PROLIFERATION; FOREBRAIN; BRAIN AB The PI3K-AKT-FoxO pathway is integral to lifespan regulation in lower organisms and essential for the stability of long-lived cells in mammals. Here, we report the impact of combined FoxO1, 3, and 4 deficiencies on mammalian brain physiology with a particular emphasis on the study of the neural stem/progenitor cell (NSC) pool. We show that the FoxO family plays a prominent role in NSC proliferation and renewal. FoxO-deficient mice show initial increased brain size and proliferation of neural progenitor cells during early postnatal life, followed by precocious significant decline in the NSC pool and accompanying neurogenesis in adult brains. Mechanistically, integrated transcriptomic, promoter, and functional analyses of FoxO-deficient NSC cultures identified direct gene targets with known links to the regulation of human brain size and the control of cellular proliferation, differentiation, and oxidative defense. Thus, the FoxO family coordinately regulates diverse genes and pathways to govern key aspects of NSC homeostasis in the mammalian brain. C1 [Paik, Ji-hye; Ding, Zhihu; Narurkar, Rujuta; Muller, Florian; Zheng, Hongwu; Ying, Haoqiang; Mahoney, Jed; Jiang, Shan; Protopopov, Alexei; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Dept Med Oncol, Boston, MA 02115 USA. [Paik, Ji-hye; Ding, Zhihu; Narurkar, Rujuta; Muller, Florian; Zheng, Hongwu; Ying, Haoqiang; Mahoney, Jed; Jiang, Shan; Protopopov, Alexei; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Dept Med, Boston, MA 02115 USA. [Paik, Ji-hye; Ding, Zhihu; Narurkar, Rujuta; Muller, Florian; Zheng, Hongwu; Ying, Haoqiang; Mahoney, Jed; Jiang, Shan; Protopopov, Alexei; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Dept Genet, Boston, MA 02115 USA. [Ramkissoon, Shakti; Ligon, Keith L.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Ramkissoon, Shakti; Ligon, Keith L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kamoun, Walid S.; Chae, Sung-Suk] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Kamoun, Walid S.; Chae, Sung-Suk] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hiller, David; Wong, Wing H.] Stanford Univ, Dept Stat, Stanford, CA 94305 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Dept Med Oncol, Boston, MA 02115 USA. EM ron_depinho@dfci.harvard.edu OI Zheng, Hongwu/0000-0002-5823-4913 FU Damon Runyon Cancer Research Foundation [DRG 1900-06]; Claudia Adam Barr Foundation; ACS; ABTA; Ellison Medical Foundation; Robert A. and Renee E. Belfer Foundation Institute for Applied Cancer Science; [5P01CA95616] FX J.-h.P. is Damon Runyon Fellow was supported by the Damon Runyon Cancer Research Foundation (DRG 1900-06). Grant support includes the Claudia Adam Barr Foundation (J.-h.P.), ACS fellowship (F.M.), ABTA fellowship (H.Y.), Ellison Medical Foundation (R.A.D.), and 5P01CA95616 (R.A.D., K.L.L., L.C.). R.A.D. is an American Cancer Society Research Professor and supported by the Robert A. and Renee E. Belfer Foundation Institute for Applied Cancer Science. We thank D. Pellman and S. Yoshida for the deconvolution microscope use and advice, R. Maser for MSCV-puro-v5 gateway vector, W. Hahn for shRNA constructs, and J. Ling for technical assistance. NR 50 TC 180 Z9 186 U1 2 U2 13 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 NOV 6 PY 2009 VL 5 IS 5 BP 540 EP 553 DI 10.1016/j.stem.2009.09.013 PG 14 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 522SR UT WOS:000272019500015 PM 19896444 ER PT J AU Bujak, M Dobaczewski, M Gonzalez-Quesada, C Xia, Y Leucker, T Zymek, P Veeranna, V Tager, AM Luster, AD Frangogiannis, NG AF Bujak, Marcin Dobaczewski, Marcin Gonzalez-Quesada, Carlos Xia, Ying Leucker, Thorsten Zymek, Pawel Veeranna, Vikas Tager, Andrew M. Luster, Andrew D. Frangogiannis, Nikolaos G. TI Induction of the CXC Chemokine Interferon-gamma-Inducible Protein 10 Regulates the Reparative Response Following Myocardial Infarction SO CIRCULATION RESEARCH LA English DT Article DE infarction; remodeling; chemokines; fibrosis; wound healing ID PULMONARY-FIBROSIS; IP-10 CHEMOKINE; RECEPTOR; MICE; ANGIOGENESIS; REPERFUSION; EXPRESSION; INHIBITOR; ISCHEMIA; EFFECTOR AB Rationale: Interferon-gamma-inducible protein (IP)-10/CXCL10, an angiostatic and antifibrotic chemokine with an important role in T-cell trafficking, is markedly induced in myocardial infarcts, and may regulate the reparative response. Objective: To study the role of IP-10 in cardiac repair and remodeling. Methods and Results: We studied cardiac repair in IP-10-null and wild-type (WT) mice undergoing reperfused infarction protocols and examined the effects of IP-10 on cardiac fibroblast function. IP-10-deficient and WT animals had comparable acute infarct size. However, the absence of IP-10 resulted in a hypercellular early reparative response and delayed contraction of the scar. Infarcted IP-10(-/-) hearts exhibited accentuated early dilation, followed by rapid wall thinning during infarct maturation associated with systolic dysfunction. Although IP-10-null and WT mice had comparable cytokine expression, the absence of IP-10 was associated with marked alterations in the cellular content of the infarct. IP-10(-/-) infarcts had more intense infiltration with CD45(+) leukocytes, Mac-2(+) macrophages, and alpha-smooth muscle actin (alpha-SMA)(+) myofibroblasts than WT infarcts but exhibited reduced recruitment of the subpopulations of leukocytes, T lymphocytes and alpha-SMA(+) cells that expressed CXCR3, the IP-10 receptor. IP-10 did not modulate cardiac fibroblast proliferation and apoptosis but significantly inhibited basic fibroblast growth factor-induced fibroblast migration. In addition, IP-10 enhanced growth factor-mediated wound contraction in fibroblast-populated collagen lattices. Conclusions: Endogenous IP-10 is an essential inhibitory signal that regulates the cellular composition of the healing infarct and promotes wound contraction, attenuating adverse remodeling. IP-10-mediated actions may be due, at least in part, to direct effects on fibroblast migration and function. (Circ Res. 2009;105:973-983.) C1 [Bujak, Marcin; Dobaczewski, Marcin; Gonzalez-Quesada, Carlos; Xia, Ying; Leucker, Thorsten; Zymek, Pawel; Veeranna, Vikas; Frangogiannis, Nikolaos G.] Baylor Coll Med, Dept Med, Cardiovasc Sci Sect, Houston, TX 77030 USA. [Tager, Andrew M.; Luster, Andrew D.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. [Tager, Andrew M.; Luster, Andrew D.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Frangogiannis, NG (reprint author), Baylor Coll Med, Dept Med, Cardiovasc Sci Sect, 1 Baylor Plaza BCM620, Houston, TX 77030 USA. EM ngf@bcm.tmc.edu FU NIH [R01 HL-76246, R01 HL-85440, R01 CA-69212]; Alkek Foundation; Medallion Foundation FX This work was supported by NIH grants R01 HL-76246 and R01 HL-85440, the Alkek Foundation, and the Medallion Foundation (to N.G.F.); and NIH grant R01 CA-69212 (to A.D.L.). NR 27 TC 50 Z9 52 U1 2 U2 4 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 NOV 6 PY 2009 VL 105 IS 10 BP 973 EP 983 DI 10.1161/CIRCRESAHA.109.199471 PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 515XE UT WOS:000271505400006 PM 19797174 ER PT J AU Finn, AV John, M Nakazawa, G Polavarapu, R Karmali, V Xu, X Cheng, Q Davis, T Raghunathan, C Acampado, E Ezell, T Lajoie, S Eppihimer, M Kolodgie, FD Virmani, R Gold, HK AF Finn, Aloke V. John, Michael Nakazawa, Gaku Polavarapu, Rohini Karmali, Vinit Xu, Xin Cheng, Qi Davis, Talina Raghunathan, Chitra Acampado, Eduardo Ezell, Tucker Lajoie, Scott Eppihimer, Michael Kolodgie, Frank D. Virmani, Renu Gold, Herman Kalman TI Differential Healing After Sirolimus, Paclitaxel, and Bare Metal Stent Placement in Combination With Peroxisome Proliferator-Activator Receptor gamma Agonists Requirement for mTOR/Akt2 in PPAR gamma Activation SO CIRCULATION RESEARCH LA English DT Article DE stents; thrombosis; endothelium; pharmacology ID DRUG-ELUTING STENTS; ENDOTHELIAL-CELLS; PROTEIN-SYNTHESIS; MAMMALIAN TARGET; RAPAMYCIN; EXPRESSION; GROWTH; MTOR; ROSIGLITAZONE; PGC-1-ALPHA AB Rationale: Sirolimus-eluting coronary stents (SESs) and paclitaxel-eluting coronary stents (PESs) are used to reduce restenosis but have different sites of action. The molecular targets of sirolimus overlap with those of the peroxisome proliferator-activated receptor (PPAR)gamma agonist rosiglitazone (RSG) but the consequence of this interaction on endothelialization is unknown. Objective: Using the New Zealand white rabbit iliac model of stenting, we examined the effects of RSG on SESs, PESs, and bare metal stents endothelialization. Methods and Results: Animals receiving SESs, PESs, or bare metal stents and either RSG (3 mg/kg per day) or placebo were euthanized at 28 days, and arteries were evaluated by scanning electron microscopy. Fourteen-day organ culture and Western blotting of iliac arteries and tissue culture experiments were conducted. Endothelialization was significantly reduced by RSG in SESs but not in PESs or bare metal stents. Organ culture revealed reduced vascular endothelial growth factor in SESs receiving RSG compared to RSG animals receiving bare metal stent or PESs. Quantitative polymerase chain reaction in human aortic endothelial cells (HAECs) revealed that sirolimus (but not paclitaxel) inhibited RSG-induced vascular endothelial growth factor transcription. Western blotting demonstrated that inhibition of molecular signaling in SES+RSG-treated arteries was similar to findings in HAECs treated with RSG and small interfering RNA to PPAR gamma, suggesting that sirolimus inhibits PPAR gamma. Transfection of HAECs with mTOR (mammalian target of rapamycin) short hairpin RNA and with Akt2 small interfering RNA significantly inhibited RSG-mediated transcriptional upregulation of heme oxygenase-1, a PPAR gamma target gene. Chromatin immunoprecipitation assay demonstrated sirolimus interferes with binding of PPAR gamma to its response elements in heme oxygenase-1 promoter. Conclusions: mTOR/Akt2 is required for optimal PPAR gamma activation. Patients who receive SESs during concomitant RSG treatment may be at risk for delayed stent healing. (Circ Res. 2009;105:1003-1012.) C1 [Finn, Aloke V.; John, Michael; Polavarapu, Rohini; Karmali, Vinit; Davis, Talina; Raghunathan, Chitra; Ezell, Tucker; Lajoie, Scott] Emory Univ, Sch Med, Dept Med, Heart & Vasc Ctr, Atlanta, GA USA. [Nakazawa, Gaku; Xu, Xin; Cheng, Qi; Acampado, Eduardo; Kolodgie, Frank D.; Virmani, Renu] CVPath Inst Inc, Gaithersburg, MD USA. [Gold, Herman Kalman] Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Eppihimer, Michael] Boston Sci, Natick, MA USA. RP Finn, AV (reprint author), Emory Midtown Hosp, 550 Peachtree St NE, Atlanta, GA 30308 USA. EM avfinn@emory.edu FU Caryle Fraser Heart Center at Emory University FX This study was supported in part by a grant from Boston Scientific. A. V. F. is supported by the Caryle Fraser Heart Center at Emory University. NR 28 TC 21 Z9 21 U1 0 U2 2 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 NOV 6 PY 2009 VL 105 IS 10 BP 1003 EP 1012 DI 10.1161/CIRCRESAHA.109.200519 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 515XE UT WOS:000271505400009 PM 19797172 ER PT J AU Liang, HY Yoo, SE Na, R Walter, CA Richardson, A Ran, QT AF Liang, Hanyu Yoo, Si-Eun Na, Ren Walter, Christi A. Richardson, Arlan Ran, Qitao TI Short Form Glutathione Peroxidase 4 Is the Essential Isoform Required for Survival and Somatic Mitochondrial Functions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OXIDATIVE DAMAGE; LIPID-PEROXIDATION; CELLS; EXPRESSION; PHGPX; GPX4; GLUTATHIONE-PEROXIDASE-4; APOPTOSIS; PROTECTS; SEQUENCE AB Glutathione peroxidase 4 (Gpx4) is an essential antioxidant enzyme having multiple functions. A long form Gpx4 protein and a short form Gpx4 protein, which are distinguishable by the presence or lack of a mitochondrial signal peptide at the N terminus, are generated from the Gpx4 gene. In this study, we generated transgenic mice using mutated GPX4 genes encoding either the long form Gpx4 (lPX4 gene) or the short form Gpx4 (sGPX4 gene). Our results showed that transgenic mice with the sGPX4 gene had increased Gpx4 protein in all tissues and were protected against diquat-induced apoptosis in liver. Moreover, the sGPX4 gene was able to rescue the lethal phenotype of the mouse Gpx4-null mutation. In contrast, transgenic mice with the lGPX4 gene had increased Gpx4 protein only in the testes, and the lGPX4 gene failed to rescue the lethal phenotype of the mouse Gpx4-null mutation. In Gpx4-null mice rescued by the sGPX4 gene, the Gpx4 protein was present in mitochondria isolated from somatic tissues, and the submitochondrial distribution pattern of the Gpx4 protein in these mice was identical to that in wild-type mice. Interestingly, the male Gpx4-null mice rescued by the sGPX4 gene were infertile and exhibited sperm malformation. Together, our results demonstrated for the first time that the short form Gpx4 protein is present in somatic tissue mitochondria and is essential for survival and protection against apoptosis in mice, whereas the long form Gpx4 protein is important for male fertility. C1 Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Yoo, Si-Eun] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Walter, Christi A.; Richardson, Arlan; Ran, Qitao] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Walter, Christi A.; Richardson, Arlan; Ran, Qitao] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Ran, QT (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM ran@uthscsa.edu RI Liang, Hanyu/A-1066-2010 FU National Institutes of Health [P01AG19316, R37 AG026557, AG021163]; San Antonio Nathan Shock Aging Center [1P30-AG13319]; Veterans Affairs Merit FX This work was supported, in whole or in part, by National Institutes of Health Grants P01AG19316, R37 AG026557, and AG021163, San Antonio Nathan Shock Aging Center Grant 1P30-AG13319, and Veterans Affairs Merit grants (to A. R. and Q. R.). NR 26 TC 34 Z9 35 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 6 PY 2009 VL 284 IS 45 BP 30836 EP 30844 DI 10.1074/jbc.M109.032839 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 514EZ UT WOS:000271378400011 PM 19744930 ER PT J AU Kim, ST Takeuchi, K Sun, ZYJ Touma, M Castro, CE Fahmy, A Lang, MJ Wagner, G Reinherz, EL AF Kim, Sun Taek Takeuchi, Koh Sun, Zhen-Yu J. Touma, Maki Castro, Carlos E. Fahmy, Amr Lang, Matthew J. Wagner, Gerhard Reinherz, Ellis L. TI The alpha beta T Cell Receptor Is an Anisotropic Mechanosensor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID THYMIC SELECTION; FG LOOP; CD3-EPSILON-GAMMA HETERODIMER; ECTODOMAIN FRAGMENT; CRYSTAL-STRUCTURE; TCR; COMPLEX; ACTIVATION; THYMOCYTES; MODEL AB Thymus-derived lymphocytes protect mammalian hosts against virus- or cancer-related cellular alterations through immune surveillance, eliminating diseased cells. In this process, T cell receptors (TCRs) mediate both recognition and T cell activation via their dimeric alpha beta, CD3 epsilon gamma, CD3 epsilon delta, and CD3 zeta zeta subunits using an unknown structural mechanism. Here, site-specific binding topology of anti-CD3 monoclonal antibodies (mAbs) and dynamic TCR quaternary change provide key clues. Agonist mAbs footprint to the membrane distal CD3 epsilon lobe that they approach diagonally, adjacent to the lever-like C beta FG loop that facilitates antigen (pMHC)-triggered activation. In contrast, a non-agonist mAb binds to the cleft between CD3 epsilon and CD3 gamma in a perpendicular mode and is stimulatory only subsequent to an external tangential but not a normal force (similar to 50 piconewtons) applied via optical tweezers. Specific pMHC but not irrelevant pMHC activates a T cell upon application of a similar force. These findings suggest that the TCR is an anisotropic mechanosensor, converting mechanical energy into a biochemical signal upon specific pMHC ligation during immune surveillance. Activating anti-CD3 mAbs mimic this force via their intrinsic binding mode. A common TCR quaternary change rather than conformational alterations can better facilitate structural signal initiation, given the vast array of TCRs and their specific pMHC ligands. C1 [Kim, Sun Taek; Touma, Maki; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Lab Immunobiol, Boston, MA 02115 USA. [Kim, Sun Taek; Touma, Maki; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Takeuchi, Koh; Sun, Zhen-Yu J.; Fahmy, Amr; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Castro, Carlos E.; Lang, Matthew J.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Lang, Matthew J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. RP Reinherz, EL (reprint author), 77 Ave Louis Pasteur,HIM 419, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu RI Takeuchi, Koh/B-4971-2010; Castro, Carlos/D-8756-2016 OI Castro, Carlos/0000-0001-7023-6105 FU National Institutes of Health [AI19807, AI37581, GM47467, EB002026] FX This work was supported, in whole or in part, by National Institutes of Health Grants AI19807 (to E. L. R.) and AI37581, GM47467, and EB002026 (to G. W.). NR 46 TC 117 Z9 117 U1 1 U2 14 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 NOV 6 PY 2009 VL 284 IS 45 BP 31028 EP 31037 DI 10.1074/jbc.M109.052712 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 514EZ UT WOS:000271378400032 PM 19755427 ER PT J AU Wade, CM Giulotto, E Sigurdsson, S Zoli, M Gnerre, S Imsland, F Lear, TL Adelson, DL Bailey, E Bellone, RR Blocker, H Distl, O Edgar, RC Garber, M Leeb, T Mauceli, E MacLeod, JN Penedo, MCT Raison, JM Sharpe, T Vogel, J Andersson, L Antczak, DF Biagi, T Binns, MM Chowdhary, BP Coleman, SJ Della Valle, G Fryc, S Guerin, G Hasegawa, T Hill, EW Jurka, J Kiialainen, A Lindgren, G Liu, J Magnani, E Mickelson, JR Murray, J Nergadze, SG Onofrio, R Pedroni, S Piras, MF Raudsepp, T Rocchi, M Roed, KH Ryder, OA Searle, S Skow, L Swinburne, JE Syvanen, AC Tozaki, T Valberg, SJ Vaudin, M White, JR Zody, MC Lander, ES Lindblad-Toh, K AF Wade, C. M. Giulotto, E. Sigurdsson, S. Zoli, M. Gnerre, S. Imsland, F. Lear, T. L. Adelson, D. L. Bailey, E. Bellone, R. R. Bloecker, H. Distl, O. Edgar, R. C. Garber, M. Leeb, T. Mauceli, E. MacLeod, J. N. Penedo, M. C. T. Raison, J. M. Sharpe, T. Vogel, J. Andersson, L. Antczak, D. F. Biagi, T. Binns, M. M. Chowdhary, B. P. Coleman, S. J. Della Valle, G. Fryc, S. Guerin, G. Hasegawa, T. Hill, E. W. Jurka, J. Kiialainen, A. Lindgren, G. Liu, J. Magnani, E. Mickelson, J. R. Murray, J. Nergadze, S. G. Onofrio, R. Pedroni, S. Piras, M. F. Raudsepp, T. Rocchi, M. Roed, K. H. Ryder, O. A. Searle, S. Skow, L. Swinburne, J. E. Syvanen, A. C. Tozaki, T. Valberg, S. J. Vaudin, M. White, J. R. Zody, M. C. Lander, E. S. Lindblad-Toh, K. CA Broad Inst Genome Sequencing Perfo Broad Inst Whole Genome Assembly T TI Genome Sequence, Comparative Analysis, and Population Genetics of the Domestic Horse SO SCIENCE LA English DT Article ID STATIONARY NIGHT BLINDNESS; CENTROMERES; APPALOOSA; EVOLUTION; CATTLE AB We report a high-quality draft sequence of the genome of the horse ( Equus caballus). The genome is relatively repetitive but has little segmental duplication. Chromosomes appear to have undergone few historical rearrangements: 53% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary new centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise before satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds. C1 [Wade, C. M.; Sigurdsson, S.; Gnerre, S.; Garber, M.; Mauceli, E.; Sharpe, T.; Biagi, T.; Fryc, S.; Onofrio, R.; White, J. R.; Zody, M. C.; Lander, E. S.; Lindblad-Toh, K.; Broad Inst Genome Sequencing Perfo; Broad Inst Whole Genome Assembly T] Broad Inst, Cambridge, MA 02142 USA. [Wade, C. M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Wade, C. M.] Univ Sydney, Fac Vet Sci, Sydney, NSW 2006, Australia. [Giulotto, E.; Magnani, E.; Nergadze, S. G.; Piras, M. F.] Univ Pavia, Dipartimento Genet & Microbiol, I-27100 Pavia, Italy. [Sigurdsson, S.; Imsland, F.; Andersson, L.; Zody, M. C.; Lindblad-Toh, K.] Uppsala Univ, Dept Med Biochem & Microbiol, SE-75124 Uppsala, Sweden. [Zoli, M.; Della Valle, G.] Univ Bologna, Dipartimento Biol, I-40126 Bologna, Italy. [Lear, T. L.; Bailey, E.; MacLeod, J. N.; Coleman, S. J.] Univ Kentucky, Dept Vet Sci, Maxwell H Gluck Equine Res Ctr, Lexington, KY 40546 USA. [Adelson, D. L.; Raison, J. M.; Chowdhary, B. P.; Raudsepp, T.] Univ Adelaide, Adelaide, SA 5005, Australia. [Bellone, R. R.; Roed, K. H.] Univ Tampa, Tampa, FL 33606 USA. [Bloecker, H.] Helmholtz Ctr Infect Res, Braunschweig, Germany. [Distl, O.; Leeb, T.] Univ Vet Med Hannover, Inst Genet & Anim Breeding, D-30559 Hannover, Germany. [Leeb, T.] Univ Bern, Vetsuisse Fac, Inst Genet, CH-3001 Bern, Switzerland. [Penedo, M. C. T.; Pedroni, S.] Univ Calif Davis, Vet Genet Lab, Davis, CA 95616 USA. [Vogel, J.; Searle, S.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Antczak, D. F.] Cornell Univ, Coll Vet Med, James A Baker Inst Anim Hlth, Ithaca, NY 14853 USA. [Binns, M. M.] Univ London Royal Vet Coll, London NW1 0TU, England. [Skow, L.] Texas A&M Univ, Coll Vet Med, College Stn, TX 77843 USA. [Guerin, G.] INRA, UMR 1313, F-44078350 Jouy En Josas, France. [Hasegawa, T.] Japan Racing Assoc, Equine Res Inst, Utsunomiya, Tochigi 3200856, Japan. [Hill, E. W.] Univ Coll Dublin, Sch Agr Food Sci & Vet Med, Anim Genom Lab, Dublin 4, Ireland. [Jurka, J.] Genet Informat Res Inst, Mountain View, CA 94043 USA. [Kiialainen, A.; Syvanen, A. C.] Uppsala Univ, Dept Med Sci, S-75185 Uppsala, Sweden. [Lindgren, G.] Swedish Univ Agr Sci, Dept Anim Breeding & Genet, SE-75124 Uppsala, Sweden. [Liu, J.] Univ Kentucky, Dept Comp Sci, Lexington, KY 40506 USA. [Mickelson, J. R.; Valberg, S. J.] Univ Minnesota, Coll Vet Med, St Paul, MN 55108 USA. [Murray, J.] Univ Calif Davis, Sch Vet Med, Davis, CA 95616 USA. [Rocchi, M.] Univ Bari, Dept Genet & Microbiol, I-70126 Bari, Italy. Norwegian Sch Vet Sci, Dept Basic Sci & Aquat Med, N-0033 Oslo, Norway. [Ryder, O. A.] San Diego Zoos Inst Conservat Res, Escondido, CA 92029 USA. [Swinburne, J. E.; Vaudin, M.] Anim Hlth Trust, Newmarket CB8 7UU, Suffolk, England. [Tozaki, T.] Lab Racing Chem, Dept Mol Genet, Utsunomiya, Tochigi 3200851, Japan. [Lander, E. S.] MIT, Dept Biol, Cambridge, MA 02142 USA. RP Wade, CM (reprint author), Broad Inst, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM c.wade@usyd.edu.au; kersli@broadinstitute.org RI Leeb, Tosso/G-3187-2014; Adelson, David/E-5506-2011; OI Leeb, Tosso/0000-0003-0553-4880; Adelson, David/0000-0003-2404-5636; GIULOTTO, ELENA/0000-0002-4705-2049; Hill, Emmeline/0000-0002-1805-2250 FU National Human Genome Research Institute; Dorothy Russell Havemeyer Foundation; Volkswagen Foundation; Morris Animal Foundation; Centro di Eccellenza di Genomica in Campo Biomedico e Agrario; Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale [PRIN-2006]; European Science Foundation FX We thank the Kentucky Horse Park and L. Chemnick for samples, L. Gaffney for graphics, and M. Daly for useful discussions. Supported by the National Human Genome Research Institute, the Dorothy Russell Havemeyer Foundation, the Volkswagen Foundation, the Morris Animal Foundation, the Centro di Eccellenza di Genomica in Campo Biomedico e Agrario, and the Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale (PRIN-2006). K. L. T. is the recipient of a European Young Investigator award funded by the European Science Foundation. Sequences have GenBank accession numbers AAWR02000001 to AAWR02055316. 1,163,466 discovery SNPs have accession numbers rs6844103 to rs69617090 in dbSNP 130. NR 17 TC 301 Z9 324 U1 5 U2 110 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 NOV 6 PY 2009 VL 326 IS 5954 BP 865 EP 867 DI 10.1126/science.1178158 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 515KG UT WOS:000271468000047 PM 19892987 ER PT J AU Chirnomas, D Smith, AL Braunstein, J Finkelstein, Y Pereira, L Bergmann, AK Grant, FD Paley, C Shannon, M Neufeld, EJ AF Chirnomas, Deborah Smith, Amber Lynn Braunstein, Jennifer Finkelstein, Yaron Pereira, Luis Bergmann, Anke K. Grant, Frederick D. Paley, Carole Shannon, Michael Neufeld, Ellis J. TI Deferasirox pharmacokinetics in patients with adequate versus inadequate response SO BLOOD LA English DT Article ID BETA-THALASSEMIA MAJOR; ORAL IRON CHELATOR; PHASE-II; ICL670; TRANSFUSION; BIOAVAILABILITY; OVERLOAD; ANEMIA AB Tens of thousands of transfusion-dependent (eg, thalassemia) patients worldwide suffer from chronic iron overload and its potentially fatal complications. The oral iron chelator deferasirox has become commercially available in many countries since 2006. Although this alternative to parenteral deferoxamine has been a major advance for patients with transfusional hemosiderosis, a proportion of patients have suboptimal response to the maximum approved doses (30 mg/kg per day), and do not achieve negative iron balance. We performed a prospective study of oral deferasirox pharmacokinetics (PK), comparing 10 transfused patients with inadequate deferasirox response (rising ferritin trend or rising liver iron on deferasirox doses >30 mg/kg per day) with control transfusion-dependent patients (n = 5) with adequate response. Subjects were admitted for 4 assessments: deferoxamine infusion and urinary iron measurement to assess readily chelatable iron; quantitative hepatobiliary scintigraphy to assess hepatic uptake and excretion of chelate; a 24-hour deferasirox PK study following a single 35-mg/kg dose of oral deferasirox; and pharmacogenomic analysis. Patients with inadequate response to deferasirox had significantly lower systemic drug exposure compared with control patients (P <.00001). Cmax, volume of distribution/bioavailability (Vd/F), and elimination half-life (t(1/2)) were not different between the groups, suggesting bioavailability as the likely discriminant. Effective dosing regimens for inadequately responding patients to deferasirox must be determined. This trial has been registered at http://www.clinicaltrials.gov under identifier NCT00749515. (Blood. 2009; 114: 4009-4013) C1 [Neufeld, Ellis J.] Childrens Hosp, Div Hematol, Boston, MA 02115 USA. [Chirnomas, Deborah; Finkelstein, Yaron; Bergmann, Anke K.; Grant, Frederick D.; Shannon, Michael; Neufeld, Ellis J.] Harvard Univ, Sch Med, Boston, MA USA. [Chirnomas, Deborah; Neufeld, Ellis J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Finkelstein, Yaron; Pereira, Luis; Shannon, Michael] Childrens Hosp, Clin Pharmacol Unit, Boston, MA 02115 USA. [Finkelstein, Yaron] Univ Toronto, Hosp Sick Children, Div Clin Pharmacol & Toxicol, Toronto, ON M5G 1X8, Canada. [Grant, Frederick D.] Childrens Hosp, Div Nucl Med, Boston, MA 02115 USA. [Paley, Carole] Novartis Pharmaceut, E Hanover, NJ USA. RP Neufeld, EJ (reprint author), Childrens Hosp, Div Hematol, 300 Longwood Ave,Rm Karp 08210, Boston, MA 02115 USA. EM ellis.neufeld@childrens.harvard.edu RI Neufeld, Ellis/F-9331-2011 FU National Heart, Lung, and Blood Institute [NHLBI] [K12 HL087164, K24 HL004184]; Novartis; Harvard Catalyst Clinical and Translational Science Center [UL1RR025758]; National Institutes of Health (NIH) FX C. P. is a full-time employee of Novartis Pharmaceutical Corporation. The remaining authors declare no competing financial interests. The study was an investigator-initiated trial partially funded by Novartis, which provided the study drug and paid for and conducted the high-performance liquid chromatography analysis of deferasirox and deferasirox-iron levels. The remainder of the study, including salary support for D. C. and E. J. N., was provided by National Institutes of Health (NIH) funding, K12 and K24 (see "Acknowledgements" for fund numbers). NR 17 TC 39 Z9 39 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 NOV 5 PY 2009 VL 114 IS 19 BP 4009 EP 4013 DI 10.1182/blood-2009-05-222729 PG 5 WC Hematology SC Hematology GA 515TJ UT WOS:000271495500011 PM 19724055 ER PT J AU Giles, F Vey, N DeAngelo, D Seiter, K Stock, W Stuart, R Boskovic, D Pigneux, A Tallman, M Brandwein, J Kell, J Robak, T Staib, P Thomas, X Cahill, A Albitar, M O'Brien, S AF Giles, Francis Vey, Norbert DeAngelo, Daniel Seiter, Karen Stock, Wendy Stuart, Robert Boskovic, Darinka Pigneux, Arnaud Tallman, Martin Brandwein, Joseph Kell, Jonathan Robak, Tadeusz Staib, Peter Thomas, Xavier Cahill, Ann Albitar, Maher O'Brien, Susan TI Phase 3 randomized, placebo-controlled, double-blind study of high-dose continuous infusion cytarabine alone or with laromustine (VNP40101M) in patients with acute myeloid leukemia in first relapse SO BLOOD LA English DT Article ID SULFONYLHYDRAZINE ALKYLATING AGENT; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; CLORETAZINE VNP40101M; REFRACTORY LEUKEMIA; PRODRUG CLORETAZINE; INHIBITION; THERAPY; CANCER; TRIAL AB Laromustine is a sulfonylhdrazine alkylator with significant antileukemia activity. An international, randomized (2: 1), double-blind, placebo-controlled study was conducted to compare complete remission (CR) rates and overall survival (OS) in patients with first relapse acute myeloid leukemia (AML) treated with laromustine and high-dose cytarabine (HDAC) versus HDAC/placebo. Patients received 1.5 g/m(2) per day cytarabine continuous infusion for 3 days and laromustine 600 mg/m(2) (n = 177) or placebo (n = 86) on day 2. Patients in CR received consolidation with laromustine/HDAC or HDAC/placebo as per initial randomization. After interim analysis at 50% enrollment, the Data Safety Monitoring Board (DSMB) expressed concern that any advantage in CR would be compromised by the observed on-study mortality, and enrollment was held. The CR rate was significantly higher for the laromustine/HDAC group (35% vs 19%, P = .005). However, the 30-day mortality rate and median progression-free survival were significantly worse in this group compared with HDAC/placebo (11% vs 2%; P = .016; 54 days vs 34; P = .002). OS and median response durations were similar in both groups. Laromustine/HDAC induced significantly more CR than HDAC/placebo, but OS was not improved due to mortality associated with myelosuppression and its sequelae. The DSMB subsequently approved a revised protocol with laromustine dose reduction and recombinant growth factor support. The study was registered as NCT00112554 at http://www.clinicaltrials.gov. (Blood. 2009; 114: 4027-4033) C1 [Giles, Francis] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Vey, Norbert] Inst J Paoli I Calmettes, F-13009 Marseille, France. [DeAngelo, Daniel] Dana Farber Canc Inst, Boston, MA 02115 USA. [Seiter, Karen] New York Med Coll, Valhalla, NY 10595 USA. [Stock, Wendy] Univ Chicago, Chicago, IL 60637 USA. [Stuart, Robert] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Boskovic, Darinka] Clin Ctr Serbia, Belgrade, Serbia. [Pigneux, Arnaud] Hop Haut Leveque, Bordeaux, France. [Tallman, Martin] Robert H Lurie Comprehens Canc Ctr, Chicago, IL USA. [Brandwein, Joseph] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Kell, Jonathan] Univ Wales Hosp, Cardiff CF4 4XW, S Glam, Wales. [Robak, Tadeusz] Med Univ Lodz, Lodz, Poland. [Staib, Peter] Klinikum Univ Koln, Cologne, Germany. [Thomas, Xavier] Hop Edouard Herriot, Lyon, France. [Cahill, Ann] Vion Pharmaceut, New Haven, CT USA. [Albitar, Maher] Quest Diagnost Nichols Inst, San Juan Capistrano, CA USA. [O'Brien, Susan] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Giles, F (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, 7979 Wurzbach Rd,Mail Code 8026,Urschel Tower,Sui, San Antonio, TX 78229 USA. EM frankgiles@aol.com OI Stuart, Robert/0000-0001-7549-8008 NR 30 TC 25 Z9 25 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 NOV 5 PY 2009 VL 114 IS 19 BP 4027 EP 4033 DI 10.1182/blood-2009-06-229351 PG 7 WC Hematology SC Hematology GA 515TJ UT WOS:000271495500014 PM 19710500 ER PT J AU Rodriguez, S Chora, A Goumnerov, B Mumaw, C Goebel, WS Fernandez, L Baydoun, H HogenEsch, H Dombkowski, DM Karlewicz, CA Rice, S Rahme, LG Carlesso, N AF Rodriguez, Sonia Chora, Angelo Goumnerov, Boyan Mumaw, Christen Goebel, W. Scott Fernandez, Luis Baydoun, Hasan HogenEsch, Harm Dombkowski, David M. Karlewicz, Carol A. Rice, Susan Rahme, Laurence G. Carlesso, Nadia TI Dysfunctional expansion of hematopoietic stem cells and block of myeloid differentiation in lethal sepsis SO BLOOD LA English DT Article ID LINEAGE COMMITMENT; VIRULENCE FACTORS; GAMMA-INTERFERON; MECHANISMS; MODEL; INFLAMMATION; NEUTROPHILS; QUIESCENCE; PROGENITOR; INFECTION AB Severe sepsis is one of the leading causes of death worldwide. High mortality rates in sepsis are frequently associated with neutropenia. Despite the central role of neutrophils in innate immunity, the mechanisms causing neutropenia during sepsis remain elusive. Here, we show that neutropenia is caused in part by apoptosis and is sustained by a block of hematopoietic stem cell (HSC) differentiation. Using a sepsis murine model, we found that the human opportunistic bacterial pathogen Pseudomonas aeruginosa caused neutrophil depletion and expansion of the HSC pool in the bone marrow. "Septic" HSCs were significantly impaired in competitive repopulation assays and defective in generating common myeloid progenitors and granulocyte-monocyte progenitors, resulting in lower rates of myeloid differentiation in vitro and in vivo. Delayed myeloid-neutrophil differentiation was further mapped using a lysozyme-green fluorescent protein (GFP) reporter mouse. Pseudomonas's lipopolysaccharide was necessary and sufficient to induce myelosuppresion and required intact TLR4 signaling. Our results establish a previously unrecognized link between HSC regulation and host response in severe sepsis and demonstrate a novel role for TLR4. (Blood. 2009; 114: 4064-4076) C1 [Rodriguez, Sonia; Mumaw, Christen; Goebel, W. Scott; Karlewicz, Carol A.; Rice, Susan; Carlesso, Nadia] Indiana Univ, Sch Med, Simon Canc Ctr, Herman B Wells Ctr, Indianapolis, IN 46202 USA. [Chora, Angelo; Goumnerov, Boyan; Fernandez, Luis; Baydoun, Hasan; Dombkowski, David M.; Rahme, Laurence G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Baydoun, Hasan; Rahme, Laurence G.] Shriners Burn Inst, Boston, MA 02114 USA. [HogenEsch, Harm] Purdue Univ, Sch Vet Med, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA. RP Carlesso, N (reprint author), Indiana Univ, Sch Med, Herman B Wells Ctr Pediat Res, 1044 Walnut,Bldg R4,Rm 421, Indianapolis, IN 46202 USA. EM ncarless@iupui.edu OI Ferreira Chora, Angelo/0000-0002-7941-7196; HogenEsch, Harm/0000-0002-2738-9189 FU National Institutes of Health [R01-HL068256-05A2]; Shawalter; Shriners [8710] FX This work was supported by the National Institutes of Health (grant no. R01-HL068256-05A2 to N. C.), the Shawalter grant (N. C.), and Shriners grant no. 8710 (to L. G. R.). NR 39 TC 59 Z9 59 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 5 PY 2009 VL 114 IS 19 BP 4064 EP 4076 DI 10.1182/blood-2009-04-214916 PG 13 WC Hematology SC Hematology GA 515TJ UT WOS:000271495500018 PM 19696201 ER PT J AU Sharma, S Lichtenstein, A AF Sharma, Sanjai Lichtenstein, Alan TI Aberrant splicing of the E-cadherin transcript is a novel mechanism of gene silencing in chronic lymphocytic leukemia cells SO BLOOD LA English DT Article ID MESSENGER-RNA DECAY; CANCER; EXPRESSION; MUTATIONS; TRANSACTIVATION; SURVEILLANCE; INHIBITION; FAMILY; BRCA1; FORM AB Premature termination codon (PTC) mutations are due to insertion or deletion of nucleotides causing a frameshift and premature termination codon in RNA. These transcripts are degraded by the nonsense-mediated decay pathway and have a very short half-life. We used a microarray technique to screen for genes that up-regulate their RNA signal upon nonsense-mediated decay pathway blockade in chronic lymphocytic leukemia (CLL) specimens and identified an Ecadherin transcript with PTC. Sequencing revealed an aberrant E-cadherin transcript lacking exon 11, resulting in a frameshift and PTC. The aberrant E-cadherin transcript was also identified in normal B cells, but occurred at a much lower level compared with CLL cells. In CLL specimens, E-cadherin expression was depressed more than 50% in 62% cases (relative to normal B cells). By real-time polymerase chain reaction analysis, the relative amounts of wild-type transcript inversely correlated with amounts of aberrant transcript (P = .018). Ectopic expression of E-cadherin in CLL specimens containing high amounts of aberrant transcript resulted in down-regulation of the wnt-beta-catenin pathway reporter, a pathway known to be up-regulated in CLL. Our data point to a novel mechanism of E-cadherin gene inactivation, with CLL cells displaying a higher proportion of aberrant nonfunctional transcripts and resulting up-regulation of the wnt-beta-catenin pathway. (Blood. 2009; 114: 4179-4185) C1 [Sharma, Sanjai; Lichtenstein, Alan] Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Div Hematol Oncol, Los Angeles, CA 90073 USA. RP Sharma, S (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Div Hematol Oncol, Bldg 304,Rm E1-115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM sasharma@mednet.ucla.edu FU American Society of Clinical Oncology (ASCO) Foundation [CA96920, CA111448]; Veterans Administration FX S.S. is a recipient of a grant from Flight Attendants Medical Research Institute and an American Society of Clinical Oncology (ASCO) Foundation Young Investigator Award. A. L. was supported by Grants CA96920 and CA111448, and research funds from the Veterans Administration. NR 33 TC 23 Z9 24 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 NOV 5 PY 2009 VL 114 IS 19 BP 4179 EP 4185 DI 10.1182/blood-2009-03-206482 PG 7 WC Hematology SC Hematology GA 515TJ UT WOS:000271495500031 PM 19745069 ER PT J AU Huang, SC Cho, A Norton, S Liu, ES Park, J Zhou, AY Munagala, ID Ou, AC Yang, G Wickrema, A Tang, TK Benz, EJ AF Huang, Shu-Ching Cho, Aeri Norton, Stephanie Liu, Eva S. Park, Jennie Zhou, Anyu Munagala, Indira D. Ou, Alexander C. Yang, Guang Wickrema, Amittha Tang, Tang K. Benz, Edward J., Jr. TI Coupled transcription-splicing regulation of mutually exclusive splicing events at the 5 ' exons of protein 4.1R gene SO BLOOD LA English DT Article ID PRE-MESSENGER-RNA; ALTERNATIVE 1ST EXONS; ERYTHROID-DIFFERENTIATION; POLYMERASE-II; MAMMALIAN-CELLS; PROMOTER USAGE; SR PROTEINS; SITE AG; IN-VIVO; EXPRESSION AB The tightly regulated production of distinct erythrocyte protein 4.1R isoforms involves differential splicing of 3 mutually exclusive first exons (1A, 1B, 1C) to the alternative 3' splice sites (ss) of exon 2'/2. Here, we demonstrate that exon 1 and 2'/2 splicing diversity is regulated by a transcription-coupled splicing mechanism. We also implicate distinctive regulatory elements that promote the splicing of exon 1A to the distal 3' ss and exon 1B to the proximal 3' ss in murine erythroleukemia cells. A hybrid minigene driven by cytomegalovirus promoter mimicked 1B-promoter-driven splicing patterns but differed from 1A-promoter-driven splicing patterns, suggesting that promoter identity affects exon 2'/2 splicing. Furthermore, splicing factor SF2/ASF ultraviolet (UV) cross- linked to the exon 2'/2 junction CAGAGAA, a sequence that overlaps the distal U2AF35-binding 3'ss. Consequently, depletion of SF2/ASF allowed exon 1B to splice to the distal 3' ss but had no effect on exon 1A splicing. These findings identify for the first time that an SF2/ASF binding site also can serve as a 3' ss in a transcript-dependent manner. Taken together, our results suggest that 4.1R gene expression involves transcriptional regulation coupled with a complex splicing regulatory network. (Blood. 2009; 114:4233-4242) C1 [Huang, Shu-Ching; Cho, Aeri; Norton, Stephanie; Liu, Eva S.; Park, Jennie; Zhou, Anyu; Munagala, Indira D.; Ou, Alexander C.; Yang, Guang; Benz, Edward J., Jr.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Huang, Shu-Ching; Zhou, Anyu; Yang, Guang; Benz, Edward J., Jr.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Wickrema, Amittha] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Tang, Tang K.] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. [Benz, Edward J., Jr.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Benz, Edward J., Jr.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Benz, Edward J., Jr.] Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. RP Huang, SC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM shu-ching_huang@dfci.harvard.edu FU National Institutes of Health [HL24385] FX This study was supported by the National Institutes of Health grant HL24385 (to E.J.B.) and Claudia BarrAward (to S.C.H.). NR 49 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 5 PY 2009 VL 114 IS 19 BP 4233 EP 4242 DI 10.1182/blood-2009-02-206219 PG 10 WC Hematology SC Hematology GA 515TJ UT WOS:000271495500036 PM 19729518 ER PT J AU Barbie, DA Tamayo, P Boehm, JS Kim, SY Moody, SE Dunn, IF Schinzel, AC Sandy, P Meylan, E Scholl, C Frohling, S Chan, EM Sos, ML Michel, K Mermel, C Silver, SJ Weir, BA Reiling, JH Sheng, Q Gupta, PB Wadlow, RC Le, H Hoersch, S Wittner, BS Ramaswamy, S Livingston, DM Sabatini, DM Meyerson, M Thomas, RK Lander, ES Mesirov, JP Root, DE Gilliland, DG Jacks, T Hahn, WC AF Barbie, David A. Tamayo, Pablo Boehm, Jesse S. Kim, So Young Moody, Susan E. Dunn, Ian F. Schinzel, Anna C. Sandy, Peter Meylan, Etienne Scholl, Claudia Froehling, Stefan Chan, Edmond M. Sos, Martin L. Michel, Kathrin Mermel, Craig Silver, Serena J. Weir, Barbara A. Reiling, Jan H. Sheng, Qing Gupta, Piyush B. Wadlow, Raymond C. Le, Hanh Hoersch, Sebastian Wittner, Ben S. Ramaswamy, Sridhar Livingston, David M. Sabatini, David M. Meyerson, Matthew Thomas, Roman K. Lander, Eric S. Mesirov, Jill P. Root, David E. Gilliland, D. Gary Jacks, Tyler Hahn, William C. TI Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1 SO NATURE LA English DT Article ID NF-KAPPA-B; TUMOR-CELL SURVIVAL; LUNG ADENOCARCINOMA; ESSENTIAL GENES; K-RAS; ACTIVATION; SCREEN; PHOSPHORYLATION; CLASSIFICATION; APOPTOSIS AB The proto-oncogene KRAS is mutated in a wide array of human cancers, most of which are aggressive and respond poorly to standard therapies. Although the identification of specific oncogenes has led to the development of clinically effective, molecularly targeted therapies in some cases, KRAS has remained refractory to this approach. A complementary strategy for targeting KRAS is to identify gene products that, when inhibited, result in cell death only in the presence of an oncogenic allele(1,2). Here we have used systematic RNA interference to detect synthetic lethal partners of oncogenic KRAS and found that the non-canonical I kappa B kinase TBK1 was selectively essential in cells that contain mutant KRAS. Suppression of TBK1 induced apoptosis specifically in human cancer cell lines that depend on oncogenic KRAS expression. In these cells, TBK1 activated NF-kappa B anti-apoptotic signals involving c-Rel and BCL-XL (also known as BCL2L1) that were essential for survival, providing mechanistic insights into this synthetic lethal interaction. These observations indicate that TBK1 and NF-kappa B signalling are essential in KRAS mutant tumours, and establish a general approach for the rational identification of co-dependent pathways in cancer. C1 [Barbie, David A.; Kim, So Young; Moody, Susan E.; Dunn, Ian F.; Schinzel, Anna C.; Mermel, Craig; Sheng, Qing; Livingston, David M.; Meyerson, Matthew; Gilliland, D. Gary; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kim, So Young; Meyerson, Matthew; Hahn, William C.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Barbie, David A.; Tamayo, Pablo; Boehm, Jesse S.; Moody, Susan E.; Dunn, Ian F.; Schinzel, Anna C.; Chan, Edmond M.; Mermel, Craig; Silver, Serena J.; Weir, Barbara A.; Gupta, Piyush B.; Wadlow, Raymond C.; Le, Hanh; Wittner, Ben S.; Ramaswamy, Sridhar; Sabatini, David M.; Meyerson, Matthew; Lander, Eric S.; Mesirov, Jill P.; Root, David E.; Gilliland, D. Gary; Jacks, Tyler; Hahn, William C.] Broad Inst Harvard, Cambridge, MA 02142 USA. [Barbie, David A.; Tamayo, Pablo; Boehm, Jesse S.; Moody, Susan E.; Dunn, Ian F.; Schinzel, Anna C.; Chan, Edmond M.; Mermel, Craig; Silver, Serena J.; Weir, Barbara A.; Gupta, Piyush B.; Wadlow, Raymond C.; Le, Hanh; Wittner, Ben S.; Ramaswamy, Sridhar; Sabatini, David M.; Meyerson, Matthew; Lander, Eric S.; Mesirov, Jill P.; Root, David E.; Gilliland, D. Gary; Jacks, Tyler; Hahn, William C.] MIT, Cambridge, MA 02142 USA. [Barbie, David A.; Wadlow, Raymond C.; Wittner, Ben S.; Ramaswamy, Sridhar] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Dunn, Ian F.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Scholl, Claudia; Froehling, Stefan; Gilliland, D. Gary; Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sandy, Peter; Meylan, Etienne; Reiling, Jan H.; Sabatini, David M.; Lander, Eric S.; Jacks, Tyler] MIT, Dept Biol, Cambridge, MA 02139 USA. [Sandy, Peter; Meylan, Etienne; Hoersch, Sebastian; Jacks, Tyler] Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA. [Sos, Martin L.; Michel, Kathrin; Thomas, Roman K.] Max Planck Soc, Max Planck Inst Neurol Res, Klaus Joachim Zulch Labs, D-50931 Cologne, Germany. [Sos, Martin L.; Michel, Kathrin; Thomas, Roman K.] Univ Cologne, Fac Med, D-50931 Cologne, Germany. [Reiling, Jan H.; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Sabatini, David M.; Gilliland, D. Gary; Jacks, Tyler] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Thomas, Roman K.] Univ Cologne, Ctr Integrated Oncol, D-50931 Cologne, Germany. [Thomas, Roman K.] Univ Cologne, Dept Internal Med 1, D-50931 Cologne, Germany. [Thomas, Roman K.] Max Planck Soc, Chem Genom Ctr, D-44227 Dortmund, Germany. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_hahn@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; OI Boehm, Jesse/0000-0002-6795-6336 FU US National Cancer Institute [R33 CA128625, R01 CA130988]; NIH [T32 CA09172-33]; Starr Cancer Consortium [I1-A11]; Susan Madden Fund; ASCO YIA; Department of Defense Prostate Cancer Postdoctoral Fellowship; Brain Science Foundation Fellowship; Deutsche Krebshilfe [107954]; Fritz-Thyssen-Stiftung [10.08.2.175]; German Ministry of Science and Education [01GS08100] FX This work was supported in part by grants from the US National Cancer Institute (R33 CA128625, R01 CA130988) (W. C. H.) and NIH T32 CA09172-33 (D. A. B., S. E. M.), the Starr Cancer Consortium (I1-A11; W. C. H., D. G. G.), the Susan Madden Fund and an ASCO YIA (D. A. B.), a Department of Defense Prostate Cancer Postdoctoral Fellowship (S. Y. K.), a Brain Science Foundation Fellowship (I. F. D.), the Deutsche Krebshilfe (grant 107954) (R. K. T.), the Fritz-Thyssen-Stiftung (grant 10.08.2.175; R. K. T.) and the NGFNplus-program of the German Ministry of Science and Education (BMBF, grant 01GS08100; R. K. T.). We thank C. Yu, G. Wei and members of the Hahn laboratory for discussions. High-throughput RNAi screening was conducted at the RNAi Platform of the Broad Institute of MIT and Harvard. NR 31 TC 531 Z9 542 U1 12 U2 37 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 5 PY 2009 VL 462 IS 7269 BP 108 EP U122 DI 10.1038/nature08460 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 514TT UT WOS:000271419200042 PM 19847166 ER PT J AU Abate, JP Blackwell, TK AF Abate, Jess Porter Blackwell, T. Keith TI Life Is Short, if Sweet SO CELL METABOLISM LA English DT Editorial Material ID MECHANISMS; SPAN AB Insulin is essential for glucose homeostasis, but reducing its activity delays the aging process in model organisms. In this issue of Cell Metabolism, Lee et al. (2009) show how these effects of insulin signaling intersect when glucose is fed to C. elegans. C1 [Abate, Jess Porter; Blackwell, T. Keith] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Joslin Diabet Ctr,Sect Dev & Stem Cell Biol,Dept, Boston, MA 02215 USA. RP Blackwell, TK (reprint author), Harvard Univ, Sch Med, Harvard Stem Cell Inst, Joslin Diabet Ctr,Sect Dev & Stem Cell Biol,Dept, Boston, MA 02215 USA. EM keith.blackwell@joslin.harvard.edu NR 8 TC 8 Z9 8 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD NOV 4 PY 2009 VL 10 IS 5 BP 338 EP 339 DI 10.1016/j.cmet.2009.10.006 PG 2 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 515UP UT WOS:000271498700002 ER PT J AU O'Rourke, EJ Soukas, AA Carr, CE Ruvkun, G AF O'Rourke, Eyleen J. Soukas, Alexander A. Carr, Christopher E. Ruvkun, Gary TI C. elegans Major Fats Are Stored in Vesicles Distinct from Lysosome-Related Organelles SO CELL METABOLISM LA English DT Article ID ABC TRANSPORTER PGP-2; CAENORHABDITIS-ELEGANS; NILE RED; LIPID DROPLETS; LIFE-SPAN; BIOGENESIS; STORAGE; GENE; METABOLISM; LONGEVITY AB Genetic conservation allows ancient features of fat storage endocrine pathways to be explored in C. elegans. Multiple studies have used Nile red or BODIPY-labeled fatty acids to identify regulators of fat mass. When mixed with their food, E coli bacteria, Nile red, and BODIPY-labeled fatty acids stain multiple spherical cellular structures in the C. elegans major fat storage organ, the intestine. However, here we demonstrate that, in the conditions previously reported, the lysosome-related organelles stained by Nile red and BODIPY-labeled fatty acids are not the C. elegans major fat storage compartment. We show that the major fat stores are contained in a distinct cellular compartment that is not stained by Nile red. Using biochemical assays, we validate oil red 0 staining as a method to assess major fat stores in C. elegans, allowing for efficient and accurate genetic and functional genomic screens for genes that control fat accumulation at the organismal level. C1 [O'Rourke, Eyleen J.; Soukas, Alexander A.; Carr, Christopher E.; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [O'Rourke, Eyleen J.; Soukas, Alexander A.; Carr, Christopher E.; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu OI Carr, Christopher/0000-0002-7946-5622 FU National Institute of Diabetes and Digestive and Kidney Diseases [R01DK070147, F32DK080607]; Human Frontiers Science Program FX We would like to thank Sean Curran and Buck Samuel for creative input and reading of the manuscript. We also thank other members of the Ruvkun, Kaplan, and Ausubel labs for creative exchanges, and especially Jihong Bai for taking confocal microscopy images. We thank Mason Freeman for the use of his GCMS for lipid analysis. We want to thank Ho Yi Mak and Marc Van-Gilst for sharing their experiences with lipid histochemistry and biochemistry. Thanks to Kaveh Ashrafi and Kevin Jones for sharing their experience with the neutral lipid dye LipidTOX. Thanks to the Caenorhabditis Genome Center and Greg Hermann for providing strains. This work was supported by Award Numbers R01DK070147 (to G.R.) and F32DK080607 (to A.A.S.) from the National Institute of Diabetes and Digestive and Kidney Diseases, and the Human Frontiers Science Program (to E.J.O.). NR 26 TC 152 Z9 157 U1 4 U2 24 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD NOV 4 PY 2009 VL 10 IS 5 BP 430 EP 435 DI 10.1016/j.cmet.2009.10.002 PG 6 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 515UP UT WOS:000271498700011 PM 19883620 ER PT J AU Khan, M Im, YB Shunmugavel, A Gilg, AG Dhindsa, RK Singh, AK Singh, I AF Khan, Mushfiquddin Im, Yeong-Bin Shunmugavel, Anandakumar Gilg, Anne G. Dhindsa, Ramanpreet K. Singh, Avtar K. Singh, Inderjit TI Administration of S-nitrosoglutathione after traumatic brain injury protects the neurovascular unit and reduces secondary injury in a rat model of controlled cortical impact SO JOURNAL OF NEUROINFLAMMATION LA English DT Article ID NITRIC-OXIDE SYNTHASE; FOCAL CEREBRAL-ISCHEMIA; RECEPTOR AGONIST 8-OH-DPAT; ISCHEMIA/REPERFUSION INJURY; MATRIX METALLOPROTEINASES; ENDOTHELIAL DYSFUNCTION; EXPERIMENTAL STROKE; COGNITIVE DEFICITS; FLAP SURVIVAL; HEAD-INJURY AB Background: Traumatic brain injury (TBI) is a major cause of preventable death and serious morbidity in young adults. This complex pathological condition is characterized by significant blood brain barrier (BBB) leakage that stems from cerebral ischemia, inflammation, and redox imbalances in the traumatic penumbra of the injured brain. Once trauma has occurred, combating these exacerbations is the keystone of an effective TBI therapy. Following other brain injuries, nitric oxide modulators such as S-nitrosoglutathione (GSNO) maintain not only redox balance but also inhibit the mechanisms of secondary injury. Therefore, we tested whether GSNO shows efficacy in a rat model of experimental TBI. Methods: TBI was induced by controlled cortical impact (CCI) in adult male rats. GSNO (50 mu g/kg body weight) was administered at two hours after CCI. GSNO-treated injured animals (CCI+GSNO group) were compared with vehicle-treated injured animals (CCI+VEH group) in terms of tissue morphology, BBB leakage, edema, inflammation, cell death, and neurological deficit. Results: Treatment of the TBI animals with GSNO reduced BBB disruption as evidenced by decreased Evan's blue extravasation across brain, infiltration/activation of macrophages (ED1 positive cells), and reduced expression of ICAM-1 and MMP-9. The GSNO treatment also restored CCI-mediated reduced expression of BBB integrity proteins ZO-1 and occludin. GSNO-mediated improvements in tissue histology shown by reduction of lesion size and decreased loss of both myelin (measured by LFB staining) and neurons (assayed by TUNEL) further support the efficacy of GSNO therapy. GSNO-mediated reduced expression of iNOS in macrophages as well as decreased neuronal cell death may be responsible for the histological improvement and reduced exacerbations. In addition to these biochemical and histological improvements, GSNO-treated injured animals recovered neurobehavioral functions as evaluated by the rotarod task and neurological score measurements. Conclusion: GSNO is a promising candidate to be evaluated in humans after brain trauma because it not only protects the traumatic penumbra from secondary injury and improves overall tissue structure but also maintains the integrity of BBB and reduces neurologic deficits following CCI in a rat model of experimental TBI. C1 [Khan, Mushfiquddin; Im, Yeong-Bin; Shunmugavel, Anandakumar; Gilg, Anne G.; Dhindsa, Ramanpreet K.; Singh, Inderjit] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Singh, Avtar K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 171 Ashley Ave, Charleston, SC 29425 USA. EM khanm@musc.edu; imyb@musc.edu; anandak@musc.edu; gilg@musc.edu; mushfiquddinkhan@gmail.com; singha@musc.edu; singhi@musc.edu FU Betty and Guy Beatty Foundation; National Institutes of Health [NS-22576, NS-34741, NS-37766]; Veteran Administration Merit; National Center for Research Resources [C06 RR018823, C06 RR015455] FX These studies were supported by grants from Betty and Guy Beatty Foundation, National Institutes of Health (NS-22576, NS-34741 and NS-37766) and Veteran Administration Merit Award. This work was also supported by the NIH, Grants C06 RR018823 and No C06 RR015455 from the Extramural Research Facilities Program of the National Center for Research Resources. We thank Dr Md Nasrul Hoda and Dr Bilgen Mehmet for their valuable technical assistance. We are grateful to Dr Tom Smith from the MUSC Writing Center for his valuable editing and correction of the manuscript. We would like to thank Ms. Joyce Bryan for procurement of animals and chemicals and Chara Williams for secretarial assistance. NR 77 TC 70 Z9 73 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD NOV 4 PY 2009 VL 6 AR 32 DI 10.1186/1742-2094-6-32 PG 12 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 525XX UT WOS:000272252200001 PM 19889224 ER PT J AU Wen, B Wang, GI Dean, I Delgutte, B AF Wen, Bo Wang, Grace I. Dean, Isabel Delgutte, Bertrand TI Dynamic Range Adaptation to Sound Level Statistics in the Auditory Nerve SO JOURNAL OF NEUROSCIENCE LA English DT Article ID SHORT-TERM ADAPTATION; CELL AFFERENT SYNAPSE; INTENSITY DISCRIMINATION; INFERIOR COLLICULUS; FIBER RESPONSES; RIBBON SYNAPSE; NOISE; SUPPRESSION; STIMULI; NEURONS AB The auditory system operates over a vast range of sound pressure levels (100-120 dB) with nearly constant discrimination ability across most of the range, well exceeding the dynamic range of most auditory neurons (20-40 dB). Dean et al. (2005) have reported that the dynamic range of midbrain auditory neurons adapts to the distribution of sound levels in a continuous, dynamic stimulus by shifting toward the most frequently occurring level. Here, we show that dynamic range adaptation, distinct from classic firing rate adaptation, also occurs in primary auditory neurons in anesthetized cats for tone and noise stimuli. Specifically, the range of sound levels over which firing rates of auditory nerve (AN) fibers grows rapidly with level shifts nearly linearly with the most probable levels in a dynamic sound stimulus. This dynamic range adaptation was observed for fibers with all characteristic frequencies and spontaneous discharge rates. As in the midbrain, dynamic range adaptation improved the precision of level coding by the AN fiber population for the prevailing sound levels in the stimulus. However, dynamic range adaptation in the AN was weaker than in the midbrain and not sufficient (0.25 dB/dB, on average, for broadband noise) to prevent a significant degradation of the precision of level coding by the AN population above 60 dB SPL. These findings suggest that adaptive processing of sound levels first occurs in the auditory periphery and is enhanced along the auditory pathway. C1 [Wen, Bo; Wang, Grace I.; Delgutte, Bertrand] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Wen, Bo; Wang, Grace I.; Delgutte, Bertrand] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Wang, Grace I.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Dean, Isabel] UCL, Ear Inst, London WC1X 8EE, England. RP Wen, B (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM bwen@mit.edu OI , /0000-0003-1349-9608 FU National Institutes of Health [RO1 DC002258, P30 DC005209]; Royal Society Dorothy Hodgkin Fellowship FX This work was supported by National Institutes of Health Grants RO1 DC002258 and P30 DC005209 (B. D.) and a Royal Society Dorothy Hodgkin Fellowship (I. D.). We thank K. Hancock for developing the experimental software, C. Miller for expert surgical assistance, and N. Harper for providing the code for computing the Fisher information. J. Guinan and two anonymous reviewers made valuable comments on this manuscript. NR 43 TC 68 Z9 71 U1 0 U2 9 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 NOV 4 PY 2009 VL 29 IS 44 BP 13797 EP 13808 DI 10.1523/JNEUROSCI.5610-08.2009 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 515LG UT WOS:000271471400007 PM 19889991 ER PT J AU Panizzi, P Nahrendorf, M Wildgruber, M Waterman, P Figueiredo, JL Aikawa, E McCarthy, J Weissleder, R Hilderbrand, SA AF Panizzi, Peter Nahrendorf, Matthias Wildgruber, Moritz Waterman, Peter Figueiredo, Jose-Luiz Aikawa, Elena McCarthy, Jason Weissleder, Ralph Hilderbrand, Scott A. TI Oxazine Conjugated Nanoparticle Detects in Vivo Hypochlorous Acid and Peroxynitrite Generation SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; NITRIC-OXIDE; HYDROGEN-PEROXIDE; FLUORESCENT-PROBE; MYELOPEROXIDASE ACTIVITY; REACTIVE NITROGEN; LIVING CELLS; MYOCARDIAL-INFARCTION; OXIDATIVE STRESS; PROSTATE-CANCER AB The current lack of suitable probes has limited the in vivo imaging of reactive oxygen/nitrogen species (ROS/RNS). ROS/RNS are often generated by ischemia-induced inflammation; defining the extent of tissue involvement or ROS/RNS-related damage would have a significant clinical impact. We present the preparation and demonstration of a fluorogenic sensor for monitoring peroxynitrite (ONOO(-)) and myeloperoxidase (MIPO) mediated hypochlorous acid (HOCl/OCl(-)) production. The sensor consists of a long circulating biocompatible nanoparticle that targets phagocytic cells in vivo and is coated with similar to 400 quenched oxazine fluorophores that are released by reaction with HOCl or ONOO(-) but are stable toward oxidants such as hydroxyl radical, hydrogen peroxide, and superoxide. MPO-dependent probe activation is chloride ion dependent and is negated in flow cytometry studies of MPO inhibitor treated neutrophils. Fluorescence reflectance imaging and microscopic fluorescence imaging in mouse hearts after myocardial infarction showed probe release into neutrophil-rich ischemic areas, making this ROS/RNS sensor a novel prognostic indicator. C1 [Hilderbrand, Scott A.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Hilderbrand, SA (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM scoff_hilderbrand@hms.harvard.edu OI Panizzi, Peter/0000-0003-0141-8807 FU NIH [R24-CA92782, U0114L080731]; American Heart Association [0835623D] FX The authors acknowledge Cory Siegel, M.D. for help with image acquisition; Vima Cortez-Retamozo, Ph.D. for help with FACS isolation of neutrophils; Nikolai Sergeyev, Ph.D. for nanoparticle synthesis, Yoshiko Iwamoto for help with histology; and Ned Keliher, Ph.D. for helpful suggestions. This work was funded in part by NIH grants to R.W. (R24-CA92782, U0114L080731), and an American Heart Association scientist development grant to M.N. (0835623D). NR 54 TC 101 Z9 101 U1 9 U2 64 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 NOV 4 PY 2009 VL 131 IS 43 BP 15739 EP 15744 DI 10.1021/ja903922u PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 516AI UT WOS:000271513600044 PM 19817443 ER PT J AU Ke, YG Douglas, SM Liu, MH Sharma, J Cheng, AC Leung, A Liu, Y Shih, WM Yan, H AF Ke, Yonggang Douglas, Shawn M. Liu, Minghui Sharma, Jaswinder Cheng, Anchi Leung, Albert Liu, Yan Shih, William M. Yan, Hao TI Multilayer DNA Origami Packed on a Square Lattice SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID DOUBLE-CROSSOVER MOLECULES; NANOSCALE SHAPES; FOLDING DNA; NANOFABRICATION; INTEGRATION; ASSEMBLIES; OCTAHEDRON; PROTEINS; DESIGN AB Molecular self-assembly using DNA as a structural building block has proven to be an efficient route to the construction of nanoscale objects and arrays of increasing complexity. Using the remarkable "scaffolded DNA origami" strategy, Rothemund demonstrated that a long single-stranded DNA from a viral genome (M13) can be folded into a variety of custom two-dimensional (2D) shapes using hundreds of short synthetic DNA molecules as staple strands. More recently, we generalized a strategy to build custom-shaped, three-dimensional (3D) objects formed as pleated layers of helices constrained to a honeycomb lattice, with precisely controlled dimensions ranging from 10 to 100 nm. Here we describe a more compact design for 3D origami, with layers of helices packed on a square lattice, that can be folded successfully into structures of designed dimensions in a one-step annealing process, despite the increased density of DNA helices. A square lattice provides a more natural framework for designing rectangular structures, the option for a more densely packed architecture, and the ability to create surfaces that are more flat than is possible with the honeycomb lattice. Thus enabling the design and construction of custom 3D shapes from helices packed on a square lattice provides a general foundational advance for increasing the versatility and scope of DNA nanotechnology. C1 [Douglas, Shawn M.; Shih, William M.] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Douglas, Shawn M.; Shih, William M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Douglas, Shawn M.; Shih, William M.] Wyss Inst Biologically Inspired Engn Harvard, Cambridge, MA 02138 USA. [Ke, Yonggang; Liu, Minghui; Sharma, Jaswinder; Liu, Yan; Yan, Hao] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. [Ke, Yonggang; Liu, Minghui; Sharma, Jaswinder; Liu, Yan; Yan, Hao] Arizona State Univ, Biodesign Inst, Tempe, AZ 85287 USA. [Cheng, Anchi; Leung, Albert] Scripps Res Inst, Natl Resource Automated Mol Microscopy, La Jolla, CA 92037 USA. RP Shih, WM (reprint author), Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. EM William_Shih@dfci.harvard.edu; hao.yan@asu.edu RI Liu, Yan/K-1999-2014; OI Liu, Yan/0000-0003-0906-2606; Douglas, Shawn/0000-0001-5398-9041 FU NSF; NIH [IDP2OD004641-01]; ONR; ARO; AFOSR; DOE; Sloan Research; Claudia Adams Barr Program Investigator; Wyss Institute; National Institutes of Health [RR17573] FX This work was supported by grants from NSF, NIH, ONR, ARO, AFOSR, and DOE and a Sloan Research Fellowship to H.Y. and grants from NSF, ARO, and ONR to Y.L. This work was also supported by Claudia Adams Barr Program Investigator, Wyss Institute for Biologically Inspired Engineering, and NIH New Innovator (IDP2OD004641-01) grants to W.M.S. National Resource for Automated Molecular Microscopy is supported by the National Institutes of Health though the National Center for Research Resources' P41 program (RR17573). We thank Erica Jacovetty for technical assistance. NR 31 TC 149 Z9 151 U1 11 U2 97 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 NOV 4 PY 2009 VL 131 IS 43 BP 15903 EP 15908 DI 10.1021/ja906381y PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 516AI UT WOS:000271513600062 PM 19807088 ER PT J AU Qaseem, A Snow, V Denberg, TD Casey, DE Forciea, MA Owens, DK Shekelle, P AF Qaseem, Amir Snow, Vincenza Denberg, Thomas D. Casey, Donald E., Jr. Forciea, Mary Ann Owens, Douglas K. Shekelle, Paul CA Amer Coll Phys TI Hormonal Testing and Pharmacologic Treatment of Erectile Dysfunction: A Clinical Practice Guideline From the American College of Physicians SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID PLACEBO-CONTROLLED TRIAL; SILDENAFIL CITRATE VIAGRA((R)); SPARING RADICAL PROSTATECTOMY; RANDOMIZED CONTROLLED-TRIAL; URINARY-TRACT SYMPTOMS; ON-DEMAND TADALAFIL; PHOSPHODIESTERASE TYPE-5 INHIBITOR; BENIGN PROSTATIC HYPERPLASIA; EXTERNAL-BEAM RADIOTHERAPY; INCREASES PENILE RIGIDITY AB Description: The American College of Physicians developed this guideline to present the available evidence on hormonal testing in and pharmacologic management of erectile dysfunction. Current pharmacologic therapies include phosphodiesterase-5 (PDE-5) inhibitors, such as sildenafil, vardenafil, tadalafil, mirodenafil, and udenafil, and hormonal treatment. Methods: Published literature on this topic was identified by using MEDLINE (1966 to May 2007), EMBASE (1980 to week 22 of 2007), Cochrane Central Register of Controlled Trials (second quarter of 2007), PsycINFO (1985 to June 2007), AMED (1985 to June 2007), and SCOPUS (2006). The literature search was updated by searching for articles in MEDLINE and EMBASE published between May 2007 and April 2009. Searches were limited to English-language publications. This guideline grades the evidence and recommendations by using the American College of Physicians' clinical practice guidelines grading system. Recommendation 1: The American College of Physicians recommends that clinicians initiate therapy with a PDE-5 inhibitor in men who seek treatment for erectile dysfunction and who do not have a contraindication to PDE-5 inhibitor use (Grade: strong recommendation; high-quality evidence). Recommendation 2: The American College of Physicians recommends that clinicians base the choice of a specific PDE-5 inhibitor on the individual preferences of men with erectile dysfunction, including ease of use, cost of medication, and adverse effects profile (Grade: weak recommendation; low-quality evidence). Recommendation 3: The American College of Physicians does not recommend for or against routine use of hormonal blood tests or hormonal treatment in the management of patients with erectile dysfunction (Grade: insufficient evidence to determine net benefits and harms). C1 [Qaseem, Amir] Amer Coll Physicians, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Colorado, Aurora, CO USA. Atlantic Hlth, Morristown, NJ USA. Vet Affairs Palo Alto Hlth Care Syst, Stanford, CA USA. Stanford Univ, Stanford, CA 94305 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Qaseem, A (reprint author), Amer Coll Physicians, 190 N Independence Mall W, Philadelphia, PA 19104 USA. EM aqaseem@acponline.org FU American College of Physicians' operating budget FX Financial support for the development of this guideline comes exclusively from the American College of Physicians' operating budget. NR 211 TC 42 Z9 43 U1 2 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 3 PY 2009 VL 151 IS 9 BP 639 EP W208 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 514IM UT WOS:000271387700006 PM 19884625 ER PT J AU Sattler, M Griffin, JD AF Sattler, Martin Griffin, James D. TI JAK2 Gets Histone H3 Rolling SO CANCER CELL LA English DT Editorial Material ID FERM DOMAIN; TRANSCRIPTION; DISORDERS AB Activation of JAK2 is implicated in normal hematopoiesis as well as oncogenic transformation. A paper in the recent issue of Nature demonstrates that phosphorylation of histone H3 by JAK2 releases the transcriptional repressor HP1 alpha from chromatin, resulting in gene transcription. C1 [Sattler, Martin; Griffin, James D.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Sattler, Martin; Griffin, James D.] Harvard Univ, Dept Med, Boston, MA 02115 USA. [Sattler, Martin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Griffin, JD (reprint author), Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. EM james_griffin@dfci.harvard.edu FU NCI NIH HHS [P01 CA066996] NR 9 TC 6 Z9 6 U1 0 U2 1 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 NOV 3 PY 2009 VL 16 IS 5 BP 365 EP 366 DI 10.1016/j.ccr.2009.10.009 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 519HG UT WOS:000271755100004 PM 19878867 ER PT J AU Friedlander, SYG Chu, GC Snyder, EL Girnius, N Dibelius, G Crowley, D Vasile, E DePinho, RA Jacks, T AF Friedlander, Sharon Y. Gidekel Chu, Gerald C. Snyder, Eric L. Girnius, Nomeda Dibelius, Gregory Crowley, Denise Vasile, Eliza DePinho, Ronald A. Jacks, Tyler TI Context-Dependent Transformation of Adult Pancreatic Cells by Oncogenic K-Ras SO CANCER CELL LA English DT Article ID INTRAEPITHELIAL NEOPLASIA; BETA-CELLS; MALIGNANT-TRANSFORMATION; DUCTAL ADENOCARCINOMA; TRANSGENIC MICE; BREAST-CANCER; MOUSE MODEL; IN-VIVO; EXPRESSION; LET-7 AB Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies. To investigate the cellular origin(s) of this cancer, we determined the effect of PDAC-relevant gene mutations in distinct cell types of the adult pancreas. We show that a subpopulation of Pdx1-expressing cells is susceptible to oncogenic K-Ras-induced transformation without tissue injury, whereas insulin-expressing endocrine cells are completely refractory to transformation under these conditions. However, chronic pancreatic injury can alter their endocrine fate and allow them to serve as the cell of origin for exocrine neoplasia. These results suggest that one mechanism by which inflammation and/or tissue damage can promote neoplasia is by altering the fate of differentiated cells that are normally refractory to oncogenic stimulation. C1 [Friedlander, Sharon Y. Gidekel; Snyder, Eric L.; Girnius, Nomeda; Dibelius, Gregory; Crowley, Denise; Vasile, Eliza; Jacks, Tyler] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Jacks, Tyler] MIT, Dept Biol, Cambridge, MA 02139 USA. [Crowley, Denise; Jacks, Tyler] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Chu, Gerald C.; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chu, Gerald C.; Snyder, Eric L.] Brigham & Womans Hosp, Dept Pathol, Boston, MA 02115 USA. [Chu, Gerald C.; DePinho, Ronald A.] Belfer Fdn Inst Innovat Canc Sci, Ctr Appl Canc Sci, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. RP Jacks, T (reprint author), MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. EM tjacks@mit.edu RI Vasile, Eugeniu/F-8276-2010 FU National Institutes of Health (NIH) [1-PO1-CA117969-01]; Cancer Center Support; National Cancer Institute (NCI) [P30-CA14051] FX We are grateful to D. Melton for gifts of the Pdx1CreER (TM), proCPA1CreERT2, and RipCreER (TM) strains and stimulating discussions. We thank A. Berns (Netherlands Cancer Institute) for providing the Trp53flox mice; C. Wright for the anti-Pdx1 antibody; S. Hoersch for statistical analysis; and N. Bardeesy for critical reading of the manuscript. T.J. is a Howard Hughes Medical Institute Investigator and a Daniel K. Ludwig Scholar. S.Y.G.F. is an Anna Fuller fund of New Haven Fellow. R.A.D. is an American Cancer Society Research Professor. This work was supported by grant 1-PO1-CA117969-01 from the National Institutes of Health (NIH) and in part by Cancer Center Support (core) grant P30-CA14051 from the National Cancer Institute (NCI). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NCI or the NIH. NR 57 TC 108 Z9 108 U1 2 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 NOV 3 PY 2009 VL 16 IS 5 BP 379 EP 389 DI 10.1016/j.ccr.2009.09.027 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 519HG UT WOS:000271755100007 ER PT J AU Zhang, Q Gu, JM Li, LJ Liu, JY Luo, B Cheung, HW Boehm, JS Ni, M Geisen, C Root, DE Polyak, K Brown, M Richardson, AL Hahn, WC Kaelin, WG Bommi-Reddy, A AF Zhang, Qing Gu, Jinming Li, Lianjie Liu, Jiayun Luo, Biao Cheung, Hiu-Wing Boehm, Jesse S. Ni, Min Geisen, Christoph Root, David E. Polyak, Kornelia Brown, Myles Richardson, Andrea L. Hahn, William C. Kaelin, William G., Jr. Bommi-Reddy, Archana TI Control of Cyclin D1 and Breast Tumorigenesis by the EgIN2 Prolyl Hydroxylase SO CANCER CELL LA English DT Article ID HYPOXIA-INDUCIBLE-FACTOR; TUMOR-SUPPRESSOR; ESTROGEN-RECEPTOR; GENE-EXPRESSION; CANCER; HIF; PROTEIN; HIF-1-ALPHA; PATHWAY; GROWTH AB 2-Oxoglutarate-dependent dioxygenases, including the EgIN prolyl hydroxylases that regulate HIF, can be inhibited with drug-like molecules. EgIN2 is estrogen inducible in breast carcinoma cells and the lone Drosophila EgIN interacts genetically with Cyclin D1. Although EgIN2 is a nonessential gene, we found that EgIN2 inactivation decreases Cyclin D1 levels and suppresses mammary gland proliferation in vivo. Regulation of Cyclin D1 is a specific attribute of EgIN2 among the EgIN proteins and is HIF independent. Loss of EgIN2 catalytic activity inhibits estrogen-dependent breast cancer tumorigenesis and can be rescued by exogenous Cyclin D1. EgIN2 depletion also impairs the fitness of lung, brain, and hematopoietic cancer lines. These findings support the exploration of EgIN2 inhibitors as therapeutics for estrogen-dependent breast cancer and other malignancies. C1 [Zhang, Qing; Gu, Jinming; Li, Lianjie; Liu, Jiayun; Ni, Min; Geisen, Christoph; Polyak, Kornelia; Brown, Myles; Hahn, William C.; Kaelin, William G., Jr.; Bommi-Reddy, Archana] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Richardson, Andrea L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Cell Biol, Boston, MA 02115 USA. [Hahn, William C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Genome Discovery, Boston, MA 02115 USA. [Richardson, Andrea L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Luo, Biao; Cheung, Hiu-Wing; Boehm, Jesse S.; Root, David E.; Hahn, William C.] Broad Inst, Cambridge, MA 02142 USA. [Li, Lianjie; Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu FU National Cancer Institute Dana-Farber/Harvard SPORE in Breast Cancer; Breast Cancer Research Foundation; Terri Brodeur Breast Cancer Foundation; Howard Hughes Medical Institute Investigator; Doris Duke Distinguished Clinical Investigator; National Institutes of Health [5R01CA068490-14] FX We thank Regeneron Pharmaceuticals for the EgIN2-/- mice, Oliver Hankinson for the ARNT-/- cells, Silvia Giordano for the inducible shRNA vector, Yen Geng for help with mammary gland analysis, Margaret McLaughlin-Drubin for help with E7 immunoblots, Mariela Jaskelioff for help with xenograft studies, and members of the Kaelin Laboratory for useful discussions. This work was supported by National Cancer Institute Dana-Farber/Harvard SPORE in Breast Cancer (A.L.R.) and the Breast Cancer Research Foundation (A.L.R. and W.G.K.). QZ is supported by a postdoctoral fellowship from Terri Brodeur Breast Cancer Foundation. W.G.K. is a Howard Hughes Medical Institute Investigator and a Doris Duke Distinguished Clinical Investigator. This work is supported in part by a National Institutes of Health grant (5R01CA068490-14) to W.G.K. W.G.K. owns equity in Fibrogen, Inc., which is developing prolyl hydroxylase inhibitors as potential therapeutics. NR 52 TC 59 Z9 60 U1 0 U2 2 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 NOV 3 PY 2009 VL 16 IS 5 BP 413 EP 424 DI 10.1016/j.ccr.2009.09.029 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 519HG UT WOS:000271755100010 PM 19878873 ER PT J AU Zhou, DW Conrad, C Xia, F Park, JS Payer, B Yin, Y Lauwers, GY Thasler, W Lee, JT Avruch, J Bardeesy, N AF Zhou, Dawang Conrad, Claudius Xia, Fan Park, Ji-Sun Payer, Bernhard Yin, Yi Lauwers, Gregory Y. Thasler, Wolfgang Lee, Jeannie T. Avruch, Joseph Bardeesy, Nabeel TI Mst1 and Mst2 Maintain Hepatocyte Quiescence and Suppress Hepatocellular Carcinoma Development through Inactivation of the Yap1 Oncogene SO CANCER CELL LA English DT Article ID NF2 TUMOR-SUPPRESSOR; CELL-PROLIFERATION; PROMOTES APOPTOSIS; KINASE MST1; MUSCLE DIFFERENTIATION; CONTACT INHIBITION; CASPASE CLEAVAGE; GROWTH-CONTROL; HIPPO PATHWAY; ORGAN SIZE AB Hippo-Lats-Yorkie signaling regulates tissue overgrowth and tumorigenesis in Drosophila. We show that the Mst1 and Mst2 protein kinases, the mammalian Hippo orthologs, are cleaved and constitutively activated in the mouse liver. Combined Mst1/2 deficiency in the liver results in loss of inhibitory Ser127 phosphorylation of the Yorkie ortholog, Yap1, massive overgrowth, and hepatocellular carcinoma (HCC). Reexpression of Mst1 in HCC-derived cell lines promotes Yap1 Ser127 phosphorylation and inactivation and abrogates their tumorigenicity. Notably, Mst1/2 inactivates Yap1 in liver through an intermediary kinase distinct from Lats1/2. Approximately 30% of human HCCs show low Yap1 (Ser127) phosphorylation and a majority exhibit loss of cleaved, activated Mst1. Mst1/2 inhibition of Yap1 is an important pathway for tumor suppression in liver relevant to human HCC. C1 [Zhou, Dawang; Xia, Fan; Payer, Bernhard; Yin, Yi; Lee, Jeannie T.; Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Zhou, Dawang; Xia, Fan; Yin, Yi; Avruch, Joseph] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Conrad, Claudius; Park, Ji-Sun; Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Conrad, Claudius] Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Payer, Bernhard; Lee, Jeannie T.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Avruch, Joseph; Bardeesy, Nabeel] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Lauwers, Gregory Y.; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Thasler, Wolfgang] LM Univ Munich, Hosp Grosshadern, Dept Surg, D-81377 Munich, Germany. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu; nelbardeesy@partners.org RI Payer, Bernhard/F-7353-2010; OI Payer, Bernhard/0000-0002-4694-2082; Zhou, Dawang/0000-0002-9053-5249 FU Sidney Kimmel Foundation for Cancer Research [DK17776, K01CA104647]; Linda J. Verville Cancer Research Foundation; [T32DK007028] FX This work was supported in part by DK17776 (J.A.), K01CA104647, the Sidney Kimmel Foundation for Cancer Research (N.B.), the Linda J. Verville Cancer Research Foundation (NB), and institutional funds. D.Z. is supported by T32DK007028. The study was designed by J.A., D.Z., and N.B. and carried out by D.Z., with contributions from C.C., J.-S.P., F.X., Y.Y., B.P., and G.Y.L. N.B. and J.A. wrote the manuscript with contributions by D.Z., C.C., B.P., and J.T.L. W.T. provided essential materials. The authors thank S. Liebhaber for analysis of the human HCC data, T. Weiss (University of Regensburg, Germany) for human liver samples used in preliminary studies, and R.T. Bronson for histologic analyses. NR 43 TC 362 Z9 368 U1 3 U2 40 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 NOV 3 PY 2009 VL 16 IS 5 BP 425 EP 438 DI 10.1016/j.ccr.2009.09.026 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 519HG UT WOS:000271755100011 PM 19878874 ER PT J AU Patton, KK Ellinor, PT Heckbert, SR Christenson, RH DeFilippi, C Gottdiener, JS Kronmal, RA AF Patton, Kristen K. Ellinor, Patrick T. Heckbert, Susan R. Christenson, Robert H. DeFilippi, Christopher Gottdiener, John S. Kronmal, Richard A. TI N-Terminal Pro-B-Type Natriuretic Peptide Is a Major Predictor of the Development of Atrial Fibrillation The Cardiovascular Health Study SO CIRCULATION LA English DT Article DE arrhythmia; atrial fibrillation; natriuretic peptides ID RISK; DISEASE; SYSTEM AB Background-Atrial fibrillation (AF), the most common cardiac rhythm abnormality, is associated with significant morbidity, mortality, and healthcare expenditures. Elevated B-type natriuretic peptide levels have been associated with the risk of heart failure, AF, and mortality. Methods and Results-The relation between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and AF was studied in 5445 Cardiovascular Health Study participants with the use of relative risk regression for predicting prevalent AF and Cox proportional hazards for predicting incident AF. NT-proBNP levels were strongly associated with prevalent AF, with an unadjusted prevalence ratio of 128 for the highest quintile (95% confidence interval, 17.9 to 913.3; P<0.001) and adjusted prevalence ratio of 147 for the highest quintile ( 95% confidence interval, 20.4 to 1064.3; P<0.001) compared with the lowest. After a median follow-up of 10 years (maximum of 16 years), there were 1126 cases of incident AF (a rate of 2.2 per 100 person-years). NT-proBNP was highly predictive of incident AF, with an unadjusted hazard ratio of 5.2 ( 95% confidence interval, 4.3 to 6.4; P<0.001) for the development of AF for the highest quintile compared with the lowest; for the same contrast, NT-proBNP remained the strongest predictor of incident AF after adjustment for an extensive number of covariates, including age, sex, medication use, blood pressure, echocardiographic parameters, diabetes mellitus, and heart failure, with an adjusted hazard ratio of 4.0 (95% confidence interval, 3.2 to 5.0; P<0.001). Conclusions-In a community-based population of older adults, NT-proBNP was a remarkable predictor of incident AF, independent of any other previously described risk factor. (Circulation. 2009; 120: 1768-1774.) C1 [Kronmal, Richard A.] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Dept Biostat, Seattle, WA 98115 USA. [Patton, Kristen K.] Univ Washington, Div Cardiol, Seattle, WA 98115 USA. [Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98115 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Christenson, Robert H.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [DeFilippi, Christopher; Gottdiener, John S.] Univ Maryland, Med Ctr, Div Cardiol, Baltimore, MD 21201 USA. RP Kronmal, RA (reprint author), Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Dept Biostat, Bldg 29,Suite 310,6200 NE 74th St, Seattle, WA 98115 USA. EM kronmal@u.washington.edu OI Patton, Kristen K./0000-0002-9034-6966 FU National Heart, Lung, and Blood Institute [HL080295]; National Institute of Neurological Disorders and Stroke. Roche Diagnostics; [N01-HC-85079]; [N01-HC-85086]; [N01-HC-35129]; [N01HC-15103]; [N01 HC-55222]; [N01-HC-75150]; [N01-HC-45133] FX The research reported in this article was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, and grant number U01 HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. Roche Diagnostics provided funding and laboratory reagents for the NT pro-BNP assay. NR 26 TC 126 Z9 134 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 BP 1768 EP 1774 DI 10.1161/CIRCULATIONAHA.109.873265 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 514YD UT WOS:000271431800005 PM 19841297 ER PT J AU Tonelli, M Curhan, G Pfeffer, M Sacks, F Thadhani, R Melamed, ML Wiebe, N Muntner, P AF Tonelli, Marcello Curhan, Gary Pfeffer, Marc Sacks, Frank Thadhani, Ravi Melamed, Michal L. Wiebe, Natasha Muntner, Paul TI Relation Between Alkaline Phosphatase, Serum Phosphate, and All-Cause or Cardiovascular Mortality SO CIRCULATION LA English DT Article DE kidney failure, chronic; cardiovascular diseases; myocardial infarction; cohort studies; metabolism ID CORONARY-ARTERY CALCIFICATION; CHRONIC KIDNEY-DISEASE; HEMODIALYSIS-PATIENTS; VASCULAR CALCIFICATION; MYOCARDIAL-INFARCTION; CHOLESTEROL LEVELS; EVENT RATE; PHOSPHORUS; CALCIUM; PEOPLE AB Background-Higher levels of serum alkaline phosphatase (AlkP) are associated with excess mortality in dialysis patients, but whether AlkP is associated with adverse outcomes among people without kidney failure is unknown. Methods and Results-We first analyzed the association between AlkP and cardiovascular outcomes among 4115 participants with a previous myocardial infarction (the Cholesterol And Recurrent Events [CARE] study). Results were validated by analyzing the association between AlkP and mortality in an independent sample of 14 716 adults from the general US population (the Third National Health and Nutrition Examination Survey). A graded, independent association was noted between baseline tertile of AlkP and the adjusted hazard ratio of all-cause mortality in CARE participants (P(trend)=0.02). After adjustment for serum phosphate, hepatic enzymes, and other potential confounders, participants with AlkP in the highest tertile had an adjusted hazard ratio of 1.43 (95% confidence interval 1.08 to 1.89) compared with those in the lowest tertile. Multivariable-adjusted associations between higher AlkP and all-cause and cardiovascular mortality were present in the Third National Health and Nutrition Examination Survey (P(trend) across tertiles of AlkP=0.006 and 0.038, respectively). Findings from both CARE and the Third National Health and Nutrition Examination Survey were similar among individuals with and without evidence of kidney disease, defined by estimated glomerular filtration rate <60 mL . min(-1) . 1.73 m(-2). Conclusions-We found an independent relation between higher levels of AlkP and adverse outcomes among survivors of myocardial infarction and in a general population sample. The excess risk of death was present in people without evidence of kidney disease and was particularly high among people with higher levels of both AlkP and serum phosphate. (Circulation. 2009;120:1784-1792.) C1 [Tonelli, Marcello; Wiebe, Natasha] Univ Alberta, Dept Med, Edmonton, AB T6B 2B7, Canada. [Tonelli, Marcello] Univ Alberta, Dept Crit Care, Edmonton, AB T6B 2B7, Canada. [Curhan, Gary] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Pfeffer, Marc] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Sacks, Frank] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Melamed, Michal L.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Muntner, Paul] Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY USA. RP Tonelli, M (reprint author), Univ Alberta, Dept Med, 7-129 Clinical Sci Bldg,8440 112 St, Edmonton, AB T6B 2B7, Canada. EM mtonelli-admin@med.ualberta.ca RI Tonelli, Marcello/B-3028-2009 FU Bristol-Myers Squibb; Alberta Heritage Foundation for Medical Research; Canadian Institutes of Health Research; National Institute of Diabetes, Digestive, and Kidney Diseases of the National Institutes of Health [K23DK078774]; National Institutes of Health [HL093954] FX The CARE study was an investigator-initiated study funded by Bristol-Myers Squibb. This substudy on AlkP was not financially supported by industry. Dr Tonelli was supported by a Population Health Investigator Award from Alberta Heritage Foundation for Medical Research and a New Investigator Award from the Canadian Institutes of Health Research. Dr Melamed was supported by grant K23DK078774 from the National Institute of Diabetes, Digestive, and Kidney Diseases of the National Institutes of Health, and Dr Thadhani was supported by grant HL093954 from the National Institutes of Health. NR 31 TC 100 Z9 103 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 BP 1784 EP 1792 DI 10.1161/CIRCULATIONAHA.109.851873 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 514YD UT WOS:000271431800007 PM 19841303 ER PT J AU Ahmed, H Neuzil, P d'Avila, A Donaldson, DM Laragy, M Reddy, VY AF Ahmed, Humera Neuzil, Petr d'Avila, Andre Donaldson, David M. Laragy, Margaret Reddy, Vivek Y. TI The Permanency of PV Isolation With a Cryoballoon Catheter During AF Ablation SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Ahmed, Humera; d'Avila, Andre; Reddy, Vivek Y.] Mt Sinai Hosp, New York, NY 10029 USA. [Neuzil, Petr] Homolka Hosp, Prague, Czech Republic. [Donaldson, David M.; Laragy, Margaret] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009 OI d'Avila, Andre Luiz/0000-0001-8769-1411; NR 0 TC 1 Z9 1 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 NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S657 EP S657 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501658 ER PT J AU Atochin, D Buys, E Li, Q Yuzawa, I Rauwerdink, K Ayata, C Moskowitz, M Brouckaert, P Bloch, KD Huang, P AF Atochin, Dmitriy Buys, Emmanuel Li, Qian Yuzawa, Izumi Rauwerdink, Kristen Ayata, Cenk Moskowitz, Michael Brouckaert, Peter Bloch, Kenneth D. Huang, Paul TI Soluble Guanylate Cyclase Alpha 1 Beta 1 Limits Stroke Size and Attenuates Neurological Injury in a Mouse Model of Cerebral Ischemia-reperfusion SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Atochin, Dmitriy; Yuzawa, Izumi; Moskowitz, Michael; Huang, Paul] Massachusetts Gen Hosp, Charlestown, MA USA. [Buys, Emmanuel; Rauwerdink, Kristen; Bloch, Kenneth D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Li, Qian] Joslin Diabet Ctr, Boston, MA 02215 USA. [Brouckaert, Peter] Univ Ghent, B-9000 Ghent, Belgium. [Brouckaert, Peter] Flanders Inst Biotechnol, Ghent, Belgium. RI Atochin, Dmitriy/Q-3150-2016 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1158 EP S1158 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831504278 ER PT J AU Bangalore, S Sawhney, S Kinlay, S Faxon, DP AF Bangalore, Sripal Sawhney, Sabrina Kinlay, Scott Faxon, David P. TI Complete Revascularization versus Culprit-only Revascularization in Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Disease: A Meta-Analysis SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Bangalore, Sripal; Kinlay, Scott; Faxon, David P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sawhney, Sabrina] St Raphaels Hasp, New Haven, CT USA. [Kinlay, Scott] VA Boston Healthcare Syst, Boston, MA USA. RI Bangalore, Sripal/B-6246-2013 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S987 EP S987 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503355 ER PT J AU Bangalore, S Bhatt, DL Rother, J Thornton, J Wolski, K Goto, S Cannon, CP Steg, PG AF Bangalore, Sripal Bhatt, Deepak L. Roether, Joachim Thornton, Julie Wolski, Kathy Goto, Shinya Cannon, Christopher P. Steg, Philippe Gabriel TI Carotid Endarterectomy versus Carotid Artery Stenting: Insights From a Propensity Matched Analysis of the REduction of Atherothrombosis for Continued Health (REACH) Registry SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Roether, Joachim] Univ Hannover, Klinikum Minden, Minden, Germany. [Thornton, Julie; Wolski, Kathy] Cleveland Clin, Cleveland, OH 44106 USA. [Goto, Shinya] Tokai Univ, Kanagawa 2591100, Japan. [Steg, Philippe Gabriel] Univ Paris 07, AP HP, Paris, France. RI Bangalore, Sripal/B-6246-2013 NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S954 EP S955 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503226 ER PT J AU Bao, FP Liang, YF Kimball, WR Zapol, WM Kacmarek, RM Jiang, YD AF Bao, Fangping Liang, Yafen Kimball, William R. Zapol, Warren M. Kacmarek, Robert M. Jiang, Yandong TI Mouth-to-nose Breathing Provides more Effective Ventilation than Mouth-to-mouth Breathing SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Bao, Fangping; Liang, Yafen; Kimball, William R.; Zapol, Warren M.; Kacmarek, Robert M.; Jiang, Yandong] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1476 EP S1476 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831505157 ER PT J AU Bautista, LE Vera, L Herrera, V Casas, J Orostegui, M Miranda, J Perel, P Pichardo, R Gonzalez, A Sanchez, J Ferreccio, C Aguilera, X Silva, E Gomez, L Chirinos, J Medina-Lezama, J Perez, C Suarez, E Ortiz, A Rosero, L Schapochnik, N Ortiz, Z Ferrante, D AF Bautista, Leonelo E. Vera, Lina Herrera, Victor Casas, Juan Orostegui, Myriam Miranda, Jaime Perel, Pablo Pichardo, Rafael Gonzalez, Angel Sanchez, Jose Ferreccio, Catterina Aguilera, Ximena Silva, Egle Gomez, Luis Chirinos, Julio Medina-Lezama, Josefina Perez, Cynthia Suarez, Erick Ortiz, Ana Rosero, Luis Schapochnik, Norberto Ortiz, Zulma Ferrante, Daniel TI Hypertension Awareness, Treatment and Control in Latin America SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Bautista, Leonelo E.; Vera, Lina; Herrera, Victor] Univ Wisconsin, Madison, WI USA. [Casas, Juan; Miranda, Jaime; Perel, Pablo] London Sch Hyg & Trop Med, London WC1, England. [Orostegui, Myriam] Univ Ind Santander, Bucaramanga, Colombia. [Pichardo, Rafael; Gonzalez, Angel] Inst Dominicano Cardiol, Santo Domingo, Dominican Rep. [Sanchez, Jose] Inst Nacl Salud, Ctr Nacl Alimentac & Nutr, Lima, Peru. [Ferreccio, Catterina] Pontificia Univ Catolica Chile, Santiago, Chile. [Aguilera, Ximena] Minist Salud Chile, Santiago, Chile. [Silva, Egle] Univ Zulia, Maracaibo 4011, Venezuela. [Gomez, Luis] Fdn FES Social, Bogota, Colombia. [Chirinos, Julio] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Chirinos, Julio] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Medina-Lezama, Josefina] Santa Maria Catholic Univ, Arequipa, Peru. [Medina-Lezama, Josefina] Santa Maria Res Inst, Arequipa, Peru. [Perez, Cynthia; Suarez, Erick; Ortiz, Ana] Univ Puerto Rico, San Juan, PR 00936 USA. [Rosero, Luis] Univ Costa Rica, San Jose, Costa Rica. [Schapochnik, Norberto] Minist Salud Prov Tierra del Fuego, Ushuaia, Argentina. [Ortiz, Zulma] Acad Nacl med, Inst Invest Epidemiol, Buenos Aires, DF, Argentina. [Ferrante, Daniel] Minist Salud & Ambiente, Buenos Aires, DF, Argentina. RI Herrera, Victor/C-5602-2008; Miranda, J. Jaime/A-8482-2008 OI Miranda, J. Jaime/0000-0002-4738-5468 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S439 EP S440 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500555 ER PT J AU Beinart, R Heist, K Singh, S Kabra, R Blendea, D Donaldson, D Koruth, J Barrett, C Ruskin, J Mansour, M AF Beinart, Roy Heist, Kevin Singh, Sheldon Kabra, Rajesh Blendea, Dan Donaldson, David Koruth, Jacob Barrett, Conor Ruskin, Jeremy Mansour, Moussa TI Regional Differences in Left Atrial Wall Thickness in Patients With Atrial Fibrillation SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Beinart, Roy; Heist, Kevin; Singh, Sheldon; Kabra, Rajesh; Blendea, Dan; Donaldson, David; Koruth, Jacob; Barrett, Conor; Ruskin, Jeremy; Mansour, Moussa] Massachusetts Gen Hosp, 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S707 EP S707 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831502033 ER PT J AU Buys, ES Raher, MJ Rauwerdink, KM Sips, PY Brouckaert, P Bloch, KD AF Buys, Emmanuel S. Raher, Michael J. Rauwerdink, Kristen M. Sips, Patrick Y. Brouckaert, Peter Bloch, Kenneth D. TI Hypertension in Soluble Guanylate Cyclase alpha(1)-Deficient Mice is Associated With Hyperaldosteronism SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Buys, Emmanuel S.; Raher, Michael J.; Rauwerdink, Kristen M.; Sips, Patrick Y.; Bloch, Kenneth D.] Mass Gen Hosp, Boston, MA USA. [Buys, Emmanuel S.; Raher, Michael J.; Rauwerdink, Kristen M.; Sips, Patrick Y.; Bloch, Kenneth D.] Harvard Univ, Sch Med, Boston, MA USA. [Brouckaert, Peter] Flanders Inst Biotechnol, Ghent, Belgium. [Brouckaert, Peter] Univ Ghent, B-9000 Ghent, Belgium. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1045 EP S1045 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503593 ER PT J AU Carson, P Komajda, M Zile, M Johnson, RH Hetzel, S Mckelvie, R McMurray, J Staiger, C Ptaszynska, A Massie, B AF Carson, Peter Komajda, Michel Zile, Michael Johnson, Ralph H. Hetzel, Scott Mckelvie, Robert McMurray, John Staiger, Christoph Ptaszynska, Agata Massie, Barry TI The Relation of Quality of Life Score to Outcome in Heart Failure With Preserved Ejection Fraction: Findings From the Irbesartan in Heart Failure With Preserved Ejection Fraction Trial (I-PRESERVE) SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Carson, Peter] Washington VA Med Ctr, Washington, DC USA. [Komajda, Michel] Univ Paris 06, Paris, France. [Komajda, Michel] Hosp Pitie Salpetriere, Paris, France. [Zile, Michael; Johnson, Ralph H.] Vet Affairs Med Ctr, Charleston, SC 29403 USA. [Zile, Michael; Johnson, Ralph H.] Med Univ S Carolina, Charleston, SC 29425 USA. [Hetzel, Scott] Univ Wisconsin, Madison, WI USA. [Mckelvie, Robert] McMaster Univ, Hamilton, ON, Canada. [McMurray, John] Univ Glasgow, British Heart Fdn, Glasgow Cardiovasc Rsch Ctr, Glasgow, Lanark, Scotland. [Staiger, Christoph] Sanofi Aventis, Bridgewater, NJ USA. [Ptaszynska, Agata] Bristol Myers Squibb Co, Princeton, NJ USA. [Massie, Barry] San Francisco VA Med Ctr, San Francisco, CA USA. [Massie, Barry] Univ Calif San Francisco, San Francisco, CA 94143 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S749 EP S749 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831502208 ER PT J AU Chan, SY Zhang, YY Hemann, C Zweier, JL Loscalzo, J AF Chan, Stephen Y. Zhang, Ying-Yi Hemann, Craig Zweier, Jay L. Loscalzo, Joseph TI MicroRNA-210 Controls Metabolic Adaptation During Hypoxia in Pulmonary Vascular Endothelium SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Chan, Stephen Y.] Brigham & Womens Hosp, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Zhang, Ying-Yi; Loscalzo, Joseph] Harvard Univ, Sch Med, Boston, MA USA. [Hemann, Craig; Zweier, Jay L.] Ohio State Univ, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S743 EP S743 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831502184 ER PT J AU Chiuve, SE Korngold, EC Januzzi, JJ Gantzer, ML Albert, CM AF Chiuve, Stephanie E. Korngold, Ethan C. Januzzi, James J., Jr. Gantzer, Mary Lou Albert, Christine M. TI Plasma Magnesium as a Predictor of Sudden Cardiac Death: Findings From the Nurses' Health Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Chiuve, Stephanie E.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Korngold, Ethan C.; Januzzi, James J., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gantzer, Mary Lou] Siemens Healthcare Diagnost Inc, Newark, DE USA. [Albert, Christine M.] Brigham & Womens Hosp, Boston, MA 02115 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S417 EP S417 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500469 ER PT J AU Christen, T Rocha, V Sheikine, Y Goldfine, A Di Carli, M Libby, P AF Christen, Thomas Rocha, Viviane Sheikine, Yuri Goldfine, Allison Di Carli, Marcelo Libby, Peter TI Increased Glucose Uptake in Visceral versus Subcutaneous Adipose Tissue Revealed by PET Imaging SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Christen, Thomas; Rocha, Viviane; Sheikine, Yuri; Di Carli, Marcelo; Libby, Peter] Brigham & Womens Hosp, Boston, MA 02115 USA. [Goldfine, Allison] Joslin Diabet Ctr, Boston, MA 02215 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1051 EP S1051 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503615 ER PT J AU Das, S Aiba, T Xiao, CY Hessler, K Rosenberg, M Tomaselli, G Rosenzweig, A AF Das, Saumya Aiba, Takeshi Xiao, Chunyang Hessler, Katherine Rosenberg, Michael Tomaselli, Gordon Rosenzweig, Anthony TI SGK1 Activation in Cardiomyocytes Leads to Alteration of SCN5a Function, Electrical Remodeling and Left Ventricular Dysfunction SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Das, Saumya] Mass Gen Hosp, Boston, MA USA. [Aiba, Takeshi; Tomaselli, Gordon] Johns Hopkins Med Sch, Baltimore, MD USA. [Xiao, Chunyang; Hessler, Katherine; Rosenberg, Michael; Rosenzweig, Anthony] Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S693 EP S694 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501805 ER PT J AU Duval, S Jaff, MR Boden, WE Alberts, MJ Califf, RM Eagle, KA O'Agostino, RB Massaro, JM Pedley, A Steg, PG Bhatt, DL Hirsch, AT AF Duval, Susan Jaff, Michael R. Boden, William E. Alberts, Mark J. Califf, Robert M. Eagle, Kim A. O'Agostino, Ralph B., Sr. Massaro, Joseph M. Pedley, Alison Steg, P. Gabriel Bhatt, Deepak L. Hirsch, Alan T. TI A New Score to Improve the Detection of Peripheral Artery Disease SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Duval, Susan] Univ Minnesota, Minneapolis, MN USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boden, William E.] SUNY Buffalo, Sch Med, Buffalo, NY 14260 USA. [Boden, William E.] SUNY Buffalo, Sch Publ Hlth, Buffalo, NY 14260 USA. [Boden, William E.] SUNY Buffalo, Buffalo Gen Hosp, Buffalo, NY 14260 USA. [Boden, William E.] SUNY Buffalo, Millard Fillmore Hosp, Buffalo, NY 14260 USA. [Alberts, Mark J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Alberts, Mark J.] Northwestern Univ, NW Mem Hosp, Chicago, IL 60611 USA. [Califf, Robert M.] Duke Univ, Med Ctr, Durham, NC USA. [Califf, Robert M.] Duke Univ, Duke Clin Rsch Inst, Durham, NC USA. [Eagle, Kim A.] Univ Michigan, Cardiovasc Cntr, Ann Arbor, MI 48109 USA. [O'Agostino, Ralph B., Sr.; Massaro, Joseph M.; Pedley, Alison] Boston Univ, Sch Publ Hlth, Boston, MA USA. [O'Agostino, Ralph B., Sr.; Massaro, Joseph M.; Pedley, Alison] Boston Univ, Harvard Clin Rsch Inst, Boston, MA USA. [Steg, P. Gabriel] Univ Paris 07, INSERM, U698, Paris, France. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Hirsch, Alan T.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Hirsch, Alan T.] Minneapolis Heart Inst Fdn, Minneapolis, MN 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1149 EP S1149 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831504238 ER PT J AU Eijgelsheim, M Newton-Cheh, C Sotoodehnia, N de Bakker, PI Muller, M Morrison, AC Smith, AV Isaacs, A Sanna, S Dorr, M Navarro, P Fuchsberger, C Wilson, JF Pramstaller, PP van Duijn, CM Lakatta, EG Felix, SB Gudnason, V Pfeufer, A Heckbert, SR Stricker, BH Boerwinkle, E O'Donnell, CJ AF Eijgelsheim, Mark Newton-Cheh, Christpher Sotoodehnia, Nona de Bakker, Paul I. Mueller, Martina Morrison, Alanna C. Smith, Albert V. Isaacs, Aaron Sanna, Serena Doerr, Marcus Navarro, Pau Fuchsberger, Christian Wilson, James F. Pramstaller, Peter P. van Duijn, Cornelia M. Lakatta, Edward G. Felix, Stephan B. Gudnason, Vilmundur Pfeufer, Arne Heckbert, Susan R. Stricker, Bruno H. Boerwinkle, Eric O'Donnell, Christopher J. TI Genome-wide Association Analysis of 25,330 Individuals Identifies Multiple Loci Associated With Resting Heart Rate SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Eijgelsheim, Mark; Isaacs, Aaron; van Duijn, Cornelia M.; Stricker, Bruno H.] Erasmus MC, Rotterdam, Netherlands. [Newton-Cheh, Christpher] Massachusetts Gen Hosp, Ctr Human Genet Res, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Sotoodehnia, Nona; Heckbert, Susan R.] Univ Washington, Seattle, WA 98195 USA. [de Bakker, Paul I.] Broad Inst Harvard & MIT, Program Med Populat Genet, Boston, MA USA. [Mueller, Martina] Helmholtz Ctr Munich, Munich, Germany. [Morrison, Alanna C.; Boerwinkle, Eric] Univ Texas Houston, Houston, TX USA. [Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc Res Inst, Kopavagur, Iceland. [Sanna, Serena] Ist Neurogenet & Neurofarmacol, Monserrato, Italy. [Doerr, Marcus] Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany. [Navarro, Pau] Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland. [Fuchsberger, Christian; Pramstaller, Peter P.] European Acad Bozen, Bolzano, Italy. [Wilson, James F.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Lakatta, Edward G.] NIA, Baltimore, MD 21224 USA. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. RI Fuchsberger, Christian/C-9646-2010; Pfeufer, Arne/B-6634-2013; Pramstaller, Peter/C-2357-2008; de Bakker, Paul/B-8730-2009; Gudnason, Vilmundur/K-6885-2015 OI de Bakker, Paul/0000-0001-7735-7858; Gudnason, Vilmundur/0000-0001-5696-0084 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S579 EP S579 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501330 ER PT J AU Faxon, DP Kinlay, S Hernandez, RK Gaziano, JM Lawler, E AF Faxon, David P. Kinlay, Scott Hernandez, Rohini K. Gaziano, J. Michael Lawler, Elizabeth TI Prolonged Use of Clopidogrel Reduces Death and Myocardial Infarction Following Drug Eluting Stent but Not Bare Metal Stent Placement: The VA DES Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Faxon, David P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kinlay, Scott; Hernandez, Rohini K.; Gaziano, J. Michael; Lawler, Elizabeth] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S978 EP S979 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503322 ER PT J AU Feng, Y Zou, L Si, R Nagasaka, Y Shen, SQ Chao, W AF Feng, Yan Zou, Lin Si, Rui Nagasaka, Yasuko Shen, Shiqian Chao, Wei TI Bone Marrow MyD88 Contributes to Myocardial Infarction and Modulates Neutrophil Function and Chemokine Receptor Expression SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Feng, Yan; Zou, Lin; Si, Rui; Nagasaka, Yasuko; Shen, Shiqian; Chao, Wei] Massachusetts Gen Hosp, 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1489 EP S1489 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831505213 ER PT J AU Feng, Y Zou, L Si, R Nagasaka, Y Shen, SQ Chao, W AF Feng, Yan Zou, Lin Si, Ri Nagasaka, Yasuko Shen, Shiqian Chao, Wei TI Bone Marrow MyD88 Contributes to Ischemic Myocardial Infarction and Modulates Neutrophil Function and Chemokine Receptor Expression SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Feng, Yan; Zou, Lin; Si, Ri; Nagasaka, Yasuko; Shen, Shiqian; Chao, Wei] Massachusetts Gen Hosp, 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1041 EP S1041 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503574 ER PT J AU Ferencik, M Schleft, CL Nasir, K Ghoshhajra, BB Kriegel, MF Joshi, SB Rogers, I Truong, QA Banerji, D Bamberg, F Brady, TJ Nagumey, JT Hoffmann, U AF Ferencik, Maros Schleft, Christopher L. Nasir, Khurram Ghoshhajra, Brian B. Kriegel, Matthias F. Joshi, Subodh B. Rogers, Ian Truong, Quynh A. Banerji, Dahlia Bamberg, Fabian Brady, Thomas J. Nagumey, John T. Hoffmann, Udo TI A Computed Tomography Based Score to Identify Culprit Coronary Lesions Among Patients With Acute Chest Pain and Low to Intermediate Likelihood of Acute Coronary Syndrome SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Ferencik, Maros; Schleft, Christopher L.; Nasir, Khurram; Ghoshhajra, Brian B.; Kriegel, Matthias F.; Joshi, Subodh B.; Rogers, Ian; Truong, Quynh A.; Banerji, Dahlia; Bamberg, Fabian; Brady, Thomas J.; Nagumey, John T.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 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 NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S317 EP S317 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500073 ER PT J AU Fernandez-Pereira, C Rubilar, B Mieres, J Rodriguez-Pagani, C Santaera, O Rodriguez-Granillo, AM Antoniucci, D Palacios, IF Serruys, PW Rodriguez, AE AF Fernandez-Pereira, Carlos Rubilar, Bibiana Mieres, Juan Rodriguez-Pagani, Carlos Santaera, Omar Rodriguez-Granillo, Alfredo M. Antoniucci, David Palacios, Igor F. Serruys, Patrick W. Rodriguez, Alfredo E. TI Percutaneous Coronary Intervention With Bare Metal Stents and Oral Sirolimus Has Comparable Safety and Efficacy to Treatment With Drug Eluting Stents but With Significant Lower Cost: 31 Months Cost Saving and Clinical Events Analysis From the Randomized, Controlled ORAR III (Oral Rapamycin in Argentina) Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Fernandez-Pereira, Carlos; Rubilar, Bibiana; Mieres, Juan; Rodriguez-Pagani, Carlos; Rodriguez, Alfredo E.] Otamendi Hosp, Buenos Aires, DF, Argentina. [Santaera, Omar] Argentina Soc Cardiovasc Intervent CACI, Buenos Aires, DF, Argentina. [Rodriguez-Granillo, Alfredo M.] Cardiovasc Res Ctr CECI, Buenos Aires, DF, Argentina. [Palacios, Igor F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Antoniucci, David] Careggi Hosp, Florence, Italy. [Serruys, Patrick W.] Erasmus Thorax Ctr, Rotterdam, Netherlands. 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S967 EP S967 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503275 ER PT J AU Figueroa, AL Cury, RC Hoffmann, U Brady, TJ Tawakol, A AF Figueroa, Amparo L. Cury, Ricardo C. Hoffmann, Udo Brady, Thomas J. Tawakol, Ahmed TI Characterization of Carotid Atherosclerosis: A Comparison Between PET Activity, Plaque Morphology and Histopathology SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Figueroa, Amparo L.; Cury, Ricardo C.; Hoffmann, Udo; Brady, Thomas J.; Tawakol, Ahmed] Massachusetts Gen Hosp, 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S349 EP S350 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500202 ER PT J AU Fonarow, GC Smith, EE Reeves, MJ Pan, WQ Olson, D Hernandez, AF Peterson, ED Schwamm, LH AF Fonarow, Gregg C. Smith, Eric E. Reeves, Matthew J. Pan, Wenqin Olson, DaiWai Hernandez, Adrian F. Peterson, Eric D. Schwamm, Lee H. CA Guidelines Steering Comm Hosps TI Early Antithrombotic Therapy Performance Measure in Ischemic Stroke and Clinical Outcomes SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Smith, Eric E.] Univ Calgary, Calgary, AB, Canada. [Reeves, Matthew J.] Michigan State Univ, E Lansing, MI 48824 USA. [Pan, Wenqin; Olson, DaiWai; Hernandez, Adrian F.; Peterson, Eric D.] DCRI, Durham, NC USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1129 EP S1129 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831504155 ER PT J AU Fonarow, GC Smith, EE Reeves, MJ Pan, WQ Olson, D Hernandez, AF Peterson, ED Schwamm, LH AF Fonarow, Gregg C. Smith, Eric E. Reeves, Matthew J. Pan, Wenqin Olson, DaiWai Hernandez, Adrian F. Peterson, Eric D. Schwamm, Lee H. CA Get With Guidelines Steering Commi TI Antithrombotic Therapy at Hospital Discharge Performance Measure in Ischemic Stroke and Clinical Outcomes SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Fonarow, Gregg C.] Univ Calif Los Angeles, Ctr Med, Los Angeles, CA 90024 USA. [Smith, Eric E.] Univ Calgary, Calgary, AB, Canada. [Reeves, Matthew J.] Michigan State Univ, E Lansing, MI 48824 USA. [Pan, Wenqin; Olson, DaiWai; Hernandez, Adrian F.; Peterson, Eric D.] DCRI, Durham, NC USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S472 EP S473 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500692 ER PT J AU Fox, CS Massaro, JM Schlett, CL Lehman, S O'Donnell, CJ Hoffmann, U Murabito, JM AF Fox, Caroline S. Massaro, Joseph M. Schlett, Christopher L. Lehman, Sam O'Donnell, Christopher J. Hoffmann, Udo Murabito, Joanne M. TI Peri-vascular Fat Deposition is Associated With Peripheral Arterial Disease: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Fox, Caroline S.; O'Donnell, Christopher J.] Framingham Heart Dis Epidemiol Study, Sch Med, Framingham, MA 02215 USA. [Murabito, Joanne M.] Boston Univ, Boston, MA 02114 USA. [Schlett, Christopher L.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 5042 USA. [Lehman, Sam] Flinders Univ S Australia, Bedford Pk, SA, Australia. 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S509 EP S509 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501050 ER PT J AU Fukuda, D Aikawa, E Yamazaki, H Yagita, H Aikawa, M AF Fukuda, Daiju Aikawa, Elena Yamazaki, Hiroyuki Yagita, Hideo Aikawa, Masanori TI Blockade of the Notch Ligand Delta-like 4 (DII4) Prevents the Cardiometabolic Syndrome SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Fukuda, Daiju; Yamazaki, Hiroyuki; Aikawa, Masanori] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Aikawa, Elena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. [Yagita, Hideo] Juntendo Univ, Sch Med, Tokyo 113, Japan. 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1166 EP S1166 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831504316 ER PT J AU Gibson, CM Mega, JL Jennings, LK Mohanavelu, S Misselwitz, F Plotnikov, A Sun, X Zolynas, R Braunwald, E AF Gibson, C. Michael Mega, Jessica L. Jennings, Lisa K. Mohanavelu, Satishkumar Misselwitz, Frank Plotnikov, Alexei Sun, Xiang Zolynas, Robert Braunwald, Eugene TI Effect of Rivaroxaban on Markers of Coagulation in Patients With Acute Coronary Syndromes: An ATLAS ACS-TIMI 46 Substudy SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Gibson, C. Michael] Beth Israel Hosp, Boston, MA USA. [Mega, Jessica L.; Braunwald, Eugene] Brigham & Womens Hosp, Boston, MA USA. [Jennings, Lisa K.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Mohanavelu, Satishkumar] TIMI Study Grp, Boston, MA USA. [Misselwitz, Frank] Bayer HealthCare, Wuppertal, Germany. [Plotnikov, Alexei; Sun, Xiang; Zolynas, Robert] Johnson & Johnson, Raritan, NJ USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1035 EP S1035 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503550 ER PT J AU Gleva, MJ Holcomb, R Uslan, D Chung, M Mela, T Gottipaty, V Borge, R Dan, D Shinn, T AF Gleva, Marye J. Holcomb, Richard Uslan, Daniel Chung, Mina Mela, Theofanie Gottipaty, Venkateshwar Borge, Richard Dan, Dan Shinn, Timothy TI Charlson Comorbidity Index and Risk of Cardiac Rhythm Device Generator Replacement: Results From the REPLACE Registry SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Gleva, Marye J.] Washington Univ, St Louis, MO USA. [Uslan, Daniel] Univ Calif Los Angeles, Los Angeles, CA USA. [Chung, Mina] Cleveland Clin, Cleveland, OH 44106 USA. [Mela, Theofanie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gottipaty, Venkateshwar] S Carolina Heart Cntr, Columbia, SC USA. [Borge, Richard] Abington Med Specialists, Abington, PA USA. [Dan, Dan] Piedmont Heart Inst, Atlanta, GA USA. [Shinn, Timothy] Michigan Heart, Ypsilanti, MI USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S637 EP S637 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501572 ER PT J AU Goldman, A Curtis, JP Wang, YF Maisel, WH AF Goldman, Alena Curtis, Jeptha P. Wang, Yongfei Maisel, William H. TI Impact of Anticoagulation and Anti-platelet Therapy on ICD Implant-Related Bleeding and Thromboembolic Events in Patients Enrolled in the NCDR ICD Registry SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Goldman, Alena; Maisel, William H.] BIDMC, Boston, MA USA. [Curtis, Jeptha P.; Wang, Yongfei] Yale Univ, New Haven, CT 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S638 EP S638 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501576 ER PT J AU Goyal, A Bhatt, DL Steg, PG Gersh, BJ Alberts, MJ Ohman, EM Corbalan, R Eagle, KA Gaxiola, E Gao, RL Goto, S D'Agostino, RB Califf, RM Smith, SC Wilson, PW AF Goyal, Abhinav Bhatt, Deepak L. Steg, Ph. Gabriel Gersh, Bernard J. Alberts, Mark J. Ohman, E. Magnus Corbalan, Ramon Eagle, Kim A. Gaxiola, Efrain Gao, Runlin Goto, Shinya D'Agostino, Ralph B. Califf, Robert M. Smith, Sidney C., Jr. Wilson, Peter W. TI The Impact Of Attained Educational Level On Incident Cardiovascular Events Differs Between High-Income Countries and Low-and-Middle-Income Countries SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Goyal, Abhinav] Emory Rollins Sch Publ Hlth, Atlanta, GA USA. [Goyal, Abhinav; Wilson, Peter W.] Emory Sch Med, Atlanta, GA USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Steg, Ph. Gabriel] Univ Paris 07, AP HP, INSERM, U698, Paris, France. [Gersh, Bernard J.] Mayo Clin, Rochester, MN USA. [Alberts, Mark J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Ohman, E. Magnus; Califf, Robert M.] Duke Clin Rsch Inst, Durham, NC USA. [Corbalan, Ramon] Pontificia Univ Catolica Chile, Santiago, Chile. [Eagle, Kim A.] Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. [Gaxiola, Efrain] Jandines Hosp cle Especialidades, Cntr Especializado Terapia Endovasc, Guadalajara, Mexico. [Gao, Runlin] Fuwai Hosp, Beijing, Peoples R China. [Goto, Shinya] Tokai Univ, Sch Med, Kanagawa 2591100, Japan. [D'Agostino, Ralph B.] Boston Univ, Boston, MA 02215 USA. [Smith, Sidney C., Jr.] Univ N Carolina, UNC Cntr Cardiovasc Sci & Med, Chapel Hill, NC USA. RI Goyal, Abhinav/J-5086-2012 OI Goyal, Abhinav/0000-0002-6286-2349 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S415 EP S415 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500463 ER PT J AU Grabowski, M Szymanski, FM Januzzi, JL Wu, AH Hrynkiewicz-Szymanska, A Cacko, A Filipiak, KJ Kochman, J Karpinski, G Opolski, G AF Grabowski, Marcin Szymanski, Filip M. Januzzi, James L. Wu, Alan H. Hrynkiewicz-Szymanska, Anna Cacko, Andrzej Filipiak, Krzysztof J. Kochman, Janusz Karpinski, Grzegorz Opolski, Grzegorz TI Prognostic Utility of Serial Measurements of a Novel Biomarker ST2 in Stemi Patients Treated With Primary PCI SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Grabowski, Marcin; Szymanski, Filip M.; Hrynkiewicz-Szymanska, Anna; Cacko, Andrzej; Filipiak, Krzysztof J.; Kochman, Janusz; Karpinski, Grzegorz; Opolski, Grzegorz] Med Univ Warsaw, Warsaw, Poland. [Januzzi, James L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wu, Alan H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 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 NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S808 EP S808 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831502449 ER PT J AU Greyson, C Ahmad, H Schwartz, GG Lu, L Ye, SY Xu, Y AF Greyson, Clifford Ahmad, Hasan Schwartz, Gregory G. Lu, Li Ye, Shuyu Xu, Ya TI Calpain Inhibition Attenuates Right Heart Failure and Prevents Talin Degradation During Acute Pressure Overload SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Greyson, Clifford; Ahmad, Hasan; Schwartz, Gregory G.; Lu, Li; Ye, Shuyu; Xu, Ya] Denver VAMC, Denver, CO USA. NR 0 TC 1 Z9 1 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 NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S805 EP S805 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831502436 ER PT J AU Harkness, JR Morrow, DA Braunwald, E Qin, J Belardinelli, L Wang, W Karwatowska-Prokopczuk, E Lopez-Sendon, J Bode, C Scirica, BM AF Harkness, James R. Morrow, David A. Braunwald, Eugene Qin, Jie Belardinelli, Luiz Wang, Whedy Karwatowska-Prokopczuk, Ewa Lopez-Sendon, Jose Bode, Christophe Scirica, Benjamin M. TI Presence of Ischemia and Non-Sustained Ventricular Tachycardia is Strongly Associated With the Risk of Cardiovascular Outcomes: Observations From the MERLIN-TIMI 36 Trial SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Harkness, James R.; Morrow, David A.; Braunwald, Eugene; Qin, Jie; Scirica, Benjamin M.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Belardinelli, Luiz; Wang, Whedy; Karwatowska-Prokopczuk, Ewa] CV Therapeut Gilead, Palo Alto, CA USA. [Lopez-Sendon, Jose] Hosp Univ La Paz, Madrid, Spain. [Bode, Christophe] Univ Freiburg, Freiburg, Germany. 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1086 EP S1087 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503773 ER PT J AU Januzzi, J Bajwa, EK Gong, MN Thompson, T Christiani, DC AF Januzzi, James Bajwa, Ednan K. Gong, Michelle N. Thompson, Taylor Christiani, David C. TI Plasma Levels of Interleukin Receptor Soluble ST2 Predict Disease Severity and Mortality in Patients With Acute Respiratory Distress Syndrome (ARDS) SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Januzzi, James; Bajwa, Ednan K.; Thompson, Taylor; Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gong, Michelle N.] Mt Sinai Sch Med, New York, NY 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1466 EP S1467 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831505114 ER PT J AU Januzzi, JL Bamberg, F Lee, H Truong, QA Nichols, J Karakas, M Mohammed, AA Schlett, CL Nagurney, JT Hoffmann, U Koenig, W AF Januzzi, James L. Bamberg, Fabian Lee, Hang Truong, Quynh A. Nichols, John Karakas, Mahir Mohammed, Asim A. Schlett, Christopher L. Nagurney, John T. Hoffmann, Udo Koenig, Wolfgang TI Correlates of High Sensitivity Troponin T Concentrations in Chest Pain Patients With and Without Acute Coronary Syndrome SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Januzzi, James L.; Bamberg, Fabian; Lee, Hang; Truong, Quynh A.; Nichols, John; Mohammed, Asim A.; Schlett, Christopher L.; Nagurney, John T.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Karakas, Mahir; Koenig, Wolfgang] Univ Ulm, Ulm, Germany. 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1036 EP S1036 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503553 ER PT J AU Johri, AM Palacios, IF Cubeddu, RJ Inglessis, I Passeri, J AF Johri, Amer M. Palacios, Igor F. Cubeddu, Roberto J. Inglessis, Ignacio Passeri, Jonathan TI Assessment of Atrial Septal Defect Anatomy by Real-Time Three-dimensional Transesophageal Echocardiography and Residual Shunting After Transcatheter Atrial Septal Defect Closure SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Johri, Amer M.; Palacios, Igor F.; Cubeddu, Roberto J.; Inglessis, Ignacio; Passeri, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S392 EP S392 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500368 ER PT J AU Kadakia, MB Fox, CS Scirica, BM Murphy, SA Bonaca, MP Morrow, DA AF Kadakia, Mitul B. Fox, Caroline S. Scirica, Benjamin M. Murphy, Sabina A. Bonaca, Marc P. Morrow, David A. TI Central Obesity and Cardiovascular Outcomes in Patients With Acute Coronary Syndromes: Observations From the MERLIN-TIMI 36 Trial SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Kadakia, Mitul B.; Scirica, Benjamin M.; Murphy, Sabina A.; Bonaca, Marc P.; Morrow, David A.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Kadakia, Mitul B.; Scirica, Benjamin M.; Murphy, Sabina A.; Bonaca, Marc P.; Morrow, David A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S510 EP S510 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501052 ER PT J AU Kaab, S Lunetta, KL Glazer, NL Pfeufer, A Alonso, A Chung, MK Sinner, MF Darbar, D von Noord, C Smith, AV Gudnason, V Roden, DM Witteman, JC Barnard, J Arking, DE Benjamin, EJ Heckbert, SR Ellinor, PT AF Kaeaeb, Stefan Lunetta, Kathryn L. Glazer, Nicole L. Pfeufer, Arne Alonso, Alvaro Chung, Mina K. Sinner, Moritz F. Darbar, Dawood von Noord, Charlotte Smith, Albert V. Gudnason, Vilmundur Roden, Dan M. Witteman, Jacqueline C. Barnard, John Arking, Dan E. Benjamin, Emilia J. Heckbert, Susan R. Ellinor, Patrick T. TI Common Variants in KCNN3 Are Associated With Early-Onset Atrial Fibrillation SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Kaeaeb, Stefan; Sinner, Moritz F.] Univ Munich, Klinikum Grosshadern, LMU Munich, D-8000 Munich, Germany. [Lunetta, Kathryn L.; Benjamin, Emilia J.] Boston Univ, Boston, MA 02215 USA. [Glazer, Nicole L.; Heckbert, Susan R.] Univ Washington, Seattle, WA 98195 USA. [Pfeufer, Arne] Helmholtz Zentrum Munich, Neuherberg, Germany. [Alonso, Alvaro] Univ Minnesota, Minneapolis, MN USA. [Chung, Mina K.; Barnard, John] Cleveland Clin, Cleveland, OH 44106 USA. [Darbar, Dawood; Roden, Dan M.] Vanderbilt Univ, Nashville, TN USA. [von Noord, Charlotte; Witteman, Jacqueline C.] Erasmus MC, Rotterdam, Netherlands. [Smith, Albert V.; Gudnason, Vilmundur] Icelandic Heart Assoc, Kopavogur, Iceland. [Arking, Dan E.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Benjamin, Emilia J.] Boston Univ, Boston, MA 02215 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Pfeufer, Arne/B-6634-2013; Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 1 Z9 1 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 NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S578 EP S579 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501328 ER PT J AU Kalogeropoulos, AP Georgiopoulou, VV Psaty, BM Rodondi, N Smith, AL Harrison, DG Liu, YM Hoffmann, U Bauer, DC Newman, AB Kritchevsky, SB Harris, TB Butler, J AF Kalogeropoulos, Andreas P. Georgiopoulou, Vasiliki V. Psaty, Bruce M. Rodondi, Nicolas Smith, Andreas L. Harrison, David G. Liu, Yongmei Hoffmann, Udo Bauer, Douglas C. Newman, Anne B. Kritchevsky, Stephen B. Harris, Tamara B. Butler, Javed TI Inflammatory Markers and Incident Heart Failure Risk in Older Adults: The Health, Aging, and Body Composition Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Kalogeropoulos, Andreas P.; Georgiopoulou, Vasiliki V.; Smith, Andreas L.; Harrison, David G.; Butler, Javed] Emory Univ, Atlanta, GA 30322 USA. [Psaty, Bruce M.] Univ Washington, Seattle, WA 98195 USA. [Rodondi, Nicolas] Univ Lausanne, Lausanne, Switzerland. [Liu, Yongmei; Kritchevsky, Stephen B.] Wake Forest Univ, Winston Salem, SC USA. [Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Bauer, Douglas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA USA. [Harris, Tamara B.] NIA, Intramural Rsch Program, Bethesda, MD 20892 USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S505 EP S505 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501036 ER PT J AU Kasahara, H Briggs, L Lu, JT Chien, KR Yang, TP Bungert, J AF Kasahara, Hideko Briggs, Laura Lu, Jonathan T. Chien, Kenneth R. Yang, Thomas P. Bungert, Jorg TI Nkx2-5-dependent Transcriptional Regulation of ANF and BNP Through a Common Distal Enhancer SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Kasahara, Hideko; Briggs, Laura; Yang, Thomas P.; Bungert, Jorg] Univ Florida, Gainesville, FL USA. [Lu, Jonathan T.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Chien, Kenneth R.] Massachusetts Gen Hosp, 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S571 EP S571 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501299 ER PT J AU Kathiresan, S Voight, BF AF Kathiresan, Sekar Voight, Benjamin F. CA Myocardial Infarction Genetics Con TI DNA Sequence Variants Related to Plasma Triglycerides or High-Density Lipoprotein Cholesterol and Risk of Myocardial Infarction SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Kathiresan, Sekar; Voight, Benjamin F.] Massachusetts Gen Hosp, 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S559 EP S559 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501248 ER PT J AU Kim, DH Seo, JS Na, JO Song, JM Kang, DH Song, JK Handschumacher, MD Levine, RA AF Kim, Dae-Hee Seo, Jung-Suk Na, Jin-Oh Song, Jong-Min Kang, Duk-Hyun Song, Jae-Kwan Handschumacher, Mark D. Levine, Robert A. TI Determinants of Left Ventricular Outflow Tract Obstruction in Patients With Asymmetric Septal Hypertrophy: Insights From Geometric Analysis Using 3D Echocardiography SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Kim, Dae-Hee; Seo, Jung-Suk; Na, Jin-Oh; Song, Jong-Min; Kang, Duk-Hyun; Song, Jae-Kwan] Asan Med Cntr, Seoul, South Korea. [Handschumacher, Mark D.; Levine, Robert A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S315 EP S315 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500066 ER PT J AU Kim, S Park, C Han, JW Kim, SW Kim, H Choi, YJ Lee, E Patel, R Park, IH Daley, GQ Quyyumi, A Yoon, YS AF Kim, Sinae Park, Changwon Han, Ji Woong Kim, Sung-Whan Kim, Hyongbum Choi, Yong Jin Lee, Eugine Patel, Riyaz Park, In-Hyun Daley, George Q. Quyyumi, Arshed Yoon, Young-sup TI Generation of Induced Pluripotent Stem Cells From Peripheral Blood of Coronary Artery Disease Patients SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Kim, Sinae; Park, Changwon; Han, Ji Woong; Kim, Sung-Whan; Kim, Hyongbum; Choi, Yong Jin; Lee, Eugine; Patel, Riyaz; Quyyumi, Arshed; Yoon, Young-sup] Emory Univ, Decatur, GA USA. [Park, In-Hyun; Daley, George Q.] Childrens Hosp, Boston, MA 02115 USA. [Park, In-Hyun; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1091 EP S1091 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503794 ER PT J AU Kim, S Park, C Han, JW Kim, SW Kim, H Choi, YJ Lee, E Patel, R Park, IH Daley, GQ Quyyumi, A Yoon, YS AF Kim, Sinae Park, Changwon Han, Ji Woong Kim, Sung-Whan Kim, Hyongbum Choi, Yong Jin Lee, Eugine Patel, Riyaz Park, In-Hyun Daley, George Q. Quyyumi, Arshed Yoon, Young-sup TI Directed Differentiation of Endothelial Cells From Coronary Artery Disease (CAD) Patients-derived iPS Cells SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Kim, Sinae; Park, Changwon; Han, Ji Woong; Kim, Sung-Whan; Kim, Hyongbum; Choi, Yong Jin; Lee, Eugine; Patel, Riyaz; Quyyumi, Arshed; Yoon, Young-sup] Emory Univ, Decatur, GA USA. [Park, In-Hyun; Daley, George Q.] Childrens Hosp, Boston, MA 02115 USA. [Park, In-Hyun; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1092 EP S1092 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503796 ER PT J AU Kitzman, DW Haas, MM Carson, PE Hetzel, S Komajda, M Zile, M Mckelvie, R Mcmurray, JJ Demets, D Staiger, C Ptaszynska, A Massie, B AF Kitzman, Dalane W. Haas, Marcus M. Carson, Peter E. Hetzel, Scott Komajda, Michael Zile, Michael Mckelvie, Robert Mcmurray, John J. Demets, D. Staiger, C. Ptaszynska, Agata Massie, Barry TI Obesity and Its Relationship to Adverse Cardiovascular Outcomes in Older Patients With Heart Failure and Preserved Ejection Fraction in the I-PRESERVE Trial SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Kitzman, Dalane W.] Wake Forest Univ Hlth Sci, F-75634 Winston Salem, NC USA. [Haas, Marcus M.] Theresienkrankenhaus, Mannheim, Germany. [Carson, Peter E.] Washington VAMC, Washington, DC 29425 USA. [Carson, Peter E.] Georgetown Univ, Washington, DC USA. [Hetzel, Scott; Demets, D.] Univ Wisconsin, Madison, WI USA. [Komajda, Michael] Univ Paris 06, Paris, France. [Komajda, Michael] Grp Hosp Pitie Salpetriere, Paris, France. [Zile, Michael] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Zile, Michael] Med Univ S Carolina, Charleston, SC 94143 USA. [Mckelvie, Robert] McMaster Univ, Hamilton, ON, Canada. [Mcmurray, John J.] British Heart Fdn, Glasgow Cardiovasc Rsch Cntr, Glasgow, Lanark, Scotland. [Ptaszynska, Agata] Bristol Myers Squibb Co, Princeton, NJ USA. [Staiger, C.] Sanofi Aventis, Bridgeport, CT USA. [Massie, Barry] San Francisco VA Med Ctr, San Francisco, CA USA. [Massie, Barry] Univ Calif San Francisco, San Francisco, CA 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S757 EP S758 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831502242 ER PT J AU Klein, L Chae, CU Greenland, P Ning, HY Kang, J Limacher, MC Margolis, KL Howard, BV Robinson, JG Wong, ND Gulati, M Dupree, CS LaCroix, AZ Lloyd-Jones, DM AF Klein, Liviu Chae, Claudia U. Greenland, Philip Ning, Hongyan Kang, Joseph Limacher, Marian C. Margolis, Karen L. Howard, Barbara V. Robinson, Jennifer G. Wong, Nathan D. Gulati, Martha Dupree, Carla S. LaCroix, Andrea Z. Lloyd-Jones, Donald M. TI Hormone Therapy and Heart Failure Incidence and Prognosis in Post-Menopausal Women: The Women's Health Initiative Hormone Therapy Randomized Trials SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Klein, Liviu; Greenland, Philip; Ning, Hongyan; Kang, Joseph; Gulati, Martha; Lloyd-Jones, Donald M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Chae, Claudia U.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Limacher, Marian C.] Univ Florida, Gainesville, FL USA. [Margolis, Karen L.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Howard, Barbara V.] MedStar Rsch Inst, Washington, DC USA. [Robinson, Jennifer G.] Univ Iowa, Iowa City, IA USA. [Wong, Nathan D.] Univ Calif Irvine, Irvine, CA USA. [Dupree, Carla S.] Univ N Carolina, Chapel Hill, NC USA. [LaCroix, Andrea Z.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RI Lloyd-Jones, Donald/C-5899-2009 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S504 EP S504 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501031 ER PT J AU Klein, L Lloyd-Jones, DM Greenland, P Ning, HY Kang, J Limacher, MC Margolis, KL Howard, BV Robinson, JG Wong, ND Gulati, M Dupree, CS LaCroix, AZ Chae, CU AF Klein, Liviu Lloyd-Jones, Donald M. Greenland, Philip Ning, Hongyan Kang, Joseph Limacher, Marian C. Margolis, Karen L. Howard, Barbara V. Robinson, Jennifer G. Wong, Nathan D. Gulati, Martha Dupree, Carla S. LaCroix, Andrea Z. Chae, Claudia U. TI Heart Failure Incidence and Prognosis in Post-Menopausal Women According to Different Diagnostic Criteria: The Women's Health Initiative Hormone Therapy Randomized Trials SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Klein, Liviu; Lloyd-Jones, Donald M.; Greenland, Philip; Ning, Hongyan; Kang, Joseph; Gulati, Martha] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Limacher, Marian C.] Univ Florida, Gainesville, FL USA. [Margolis, Karen L.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Howard, Barbara V.] MedStar Rsch Inst, Washington, DC USA. [Robinson, Jennifer G.] Univ Iowa, Iowa City, IA USA. [Wong, Nathan D.] Univ Calif Irvine, Irvine, CA USA. [Dupree, Carla S.] Univ N Carolina, Chapel Hill, NC USA. [LaCroix, Andrea Z.] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Chae, Claudia U.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 0 TC 1 Z9 1 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 NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S399 EP S399 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500395 ER PT J AU Lakdawala, N Thune, JJ Cirino, A Havndrupm, O Christiansen, M Bundgaard, H MacRae, CA Carlsen, CM Colan, SD Kober, LV Ho, CY AF Lakdawala, Neal Thune, Jens J. Cirino, Allison Havndrupm, Ole Christiansen, Michael Bundgaard, Henning MacRae, Calum A. Carlsen, Christian M. Colan, Steven D. Kober, Lars V. Ho, Carolyn Y. TI Electrocardiographic Manifestations of Sarcomere Mutations in Hypertrophic Cardiomyopathy: Incremental Value in the Prediction Genetic Risk SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Lakdawala, Neal; Cirino, Allison; Ho, Carolyn Y.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Thune, Jens J.; Havndrupm, Ole; Bundgaard, Henning; Kober, Lars V.] Copenhagen Univ Hosp, Copenhagen, Denmark. [Christiansen, Michael] Statens Serum Inst, DK-2300 Copenhagen, Denmark. [MacRae, Calum A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carlsen, Christian M.] Bispebjerg Hosp, DK-2400 Copenhagen, Denmark. [Colan, Steven D.] Childrens Hosp, Boston, MA 02115 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S566 EP S566 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501276 ER PT J AU Leyton, P Beppu, H Yu, PB Bloch, KD AF Leyton, Patricio Beppu, Hideyuki Yu, Paul B. Bloch, Kenneth D. TI Heterozygous Mutation in the Carboxyl-Terminal Domain of the Type 2 Bone Morphogenetic Protein Receptor Leads to Ligand-Specific Gain of Function SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Leyton, Patricio; Beppu, Hideyuki; Yu, Paul B.; Bloch, Kenneth D.] Massachusetts Gen Hosp, 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1135 EP S1136 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831504182 ER PT J AU Li, Q Atochin, D Kashiwagi, S Earle, J Wang, A Sessa, W Huang, P AF Li, Qian Atochin, Dmitriy Kashiwagi, Satoshi Earle, John Wang, Annie Sessa, William Huang, Paul TI Phosphorylation of eNOS Corrects Diabetic Vascular Dysfunction and Improves Outcome to Stroke SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Li, Qian; Atochin, Dmitriy; Kashiwagi, Satoshi; Earle, John; Wang, Annie; Huang, Paul] Massachusetts Gen Hosp, Charlestown, MA USA. [Sessa, William] Yale Univ, Sch Med, New Haven, CT USA. RI Atochin, Dmitriy/Q-3150-2016 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1037 EP S1038 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503560 ER PT J AU Liu, YH Rawnsley, D Zeng, M Yu, E Pijnappels, D Thibault, H Scherrer-Crosbie, M Wu, SM AF Liu, Yuan-Hung Rawnsley, David Zeng, Ming Yu, Esther Pijnappels, Daniel Thibault, Helene Scherrer-Crosbie, Marielle Wu, Sean M. TI Myocardial Injury Induces the Expansion and Cardiomyogenic Differentiation of Postnatal Nkx2.5 Progenitor Cells via Inflammatory Signals SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Liu, Yuan-Hung] Far Eastern Mem Hosp, Taipei, Taiwan. [Rawnsley, David] Massachusetts Gen Hosp, Taipei, MA, Taiwan. [Zeng, Ming; Yu, Esther; Pijnappels, Daniel; Thibault, Helene; Scherrer-Crosbie, Marielle; Wu, Sean M.] Massachusetts Gen Hosp, 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S756 EP S756 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831502235 ER PT J AU Lo, J Abbara, S Shturman, L Soni, A Rocha, J Wei, J Grinspoon, S AF Lo, Janet Abbara, Suhny Shturman, Leon Soni, Anand Rocha-Filho, Jose Wei, Jeffrey Grinspoon, Steven TI Increased Prevalence of Subclinical Coronary Atherosclerosis Detected by Coronary Computed Tomography Angiography in HIV-Infected Men SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Lo, Janet; Abbara, Suhny; Shturman, Leon; Soni, Anand; Rocha-Filho, Jose; Wei, Jeffrey; Grinspoon, Steven] Massachusetts Gen Hosp, 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S463 EP S463 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500653 ER PT J AU Losordo, DW Henry, T Schatz, RA Lee, JS Costa, M Bass, T Schaer, G Niederman, A Mendelsohn, F Davidson, C Waksman, R Soukas, PA Simon, D Chronos, N Fortuin, FD Huang, PP Weintraub, N Yeung, A Rosenfield, K Wong, SC Taussig, A Rava, AN Sherman, W Kereiakes, D Strumpf, RK Port, S Pieper, K Adams, PX Harrington, R AF Losordo, Douglas W. Henry, Tim Schatz, Richard A. Lee, Joon Sup Costa, Marco Bass, Theodore Schaer, Gary Niederman, Alan Mendelsohn, Farrell Davidson, Charles Waksman, Ron Soukas, Peter A. Simon, Daniel Chronos, Nicolas Fortuin, F. David Huang, Paul P. Weintraub, Neal Yeung, Alan Rosenfield, Kenneth Wong, S. Chiu Taussig, Andrew Rava, Amish N. Sherman, Warren Kereiakes, Dean Strumpf, Robert K. Port, Steven Pieper, Karen Adams, Peter X. Harrington, Robert TI Autologous CD34+Cell Therapy for Refractory Angina: 12 Month Results of the Phase II ACT34-CMI Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Losordo, Douglas W.; Davidson, Charles] Northwestern Univ, Chicago, IL 60611 USA. [Henry, Tim] Minneapolis Heart Insitute, Minneapolis, MN USA. [Schatz, Richard A.] Scripps Green Hosp, San Diego, CA USA. [Lee, Joon Sup] UPMC, Pittsburgh, PA USA. [Costa, Marco; Bass, Theodore; Simon, Daniel] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Schaer, Gary] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Niederman, Alan] Holy Cross Hosp, Ft Lauderdale, FL USA. [Mendelsohn, Farrell] Cardiol PC, Birmingham, AL USA. [Waksman, Ron] Washington Hosp Ctr, Washington, DC 20010 USA. [Soukas, Peter A.] St Elizabeths, Boston, MA USA. [Chronos, Nicolas] St Josephs Rsch Inst, Atlanta, GA USA. [Fortuin, F. David] Mayo Clin, Scottsdale, AZ USA. [Huang, Paul P.] Swedish Seattle Hosp, Seattle, WA USA. [Weintraub, Neal] Univ Cincinnati, Med Ctr, Univ Iowa Healthcare, Cincinnati, OH 45267 USA. [Yeung, Alan] Stanford Univ, Stanford, CA 94305 USA. [Rosenfield, Kenneth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wong, S. Chiu] Cornell Univ, Ithaca, NY USA. [Taussig, Andrew] Florida Hosp, Orlando, FL USA. [Rava, Amish N.] Univ Wisconsin, Madison, WI USA. [Sherman, Warren] Columbia Univ, New York, NY USA. [Kereiakes, Dean] Lindner Clin Trial Ctr, Cincinnati, OH USA. [Strumpf, Robert K.] Arizona Heart, Phoenix, AZ USA. [Port, Steven] St Lukes, Kansas City, MO USA. [Pieper, Karen; Harrington, Robert] Duke Clin Rsch Inst, Durham, NC USA. [Adams, Peter X.] Baxter Healthcare Corp, Deerfield, IL 60015 USA. NR 0 TC 4 Z9 4 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 NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1132 EP S1132 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831504167 ER PT J AU Lubitz, SA Makino, S Sinner, MF Lunetta, KL Pfeufer, A Rahman, R Danik, SP Sonni, A Shea, MA del Monte, F Perz, S Peters, A Greenberg, SM Furie, KL Benjamin, EJ Rosand, J Arking, DE Alonso, A Boerwinkle, E Kaab, S Ellinor, PT AF Lubitz, Steven A. Makino, Seiko Sinner, Moritz F. Lunetta, Kathryn L. Pfeufer, Arne Rahman, Rosanna Danik, Stephan P. Sonni, Akshata Shea, Marisa A. del Monte, Frederica Perz, Siegfried Peters, Annette Greenberg, Steven M. Furie, Karen L. Benjamin, Emelia J. Rosand, Jonathan Arking, Dan E. Alonso, Alvaro Boerwinkle, Eric Kaab, Stefan Ellinor, Patrick T. TI Additional Independent Susceptibility Markers for Atrial Fibrillation on Chromosome 4q25 SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Lubitz, Steven A.; Makino, Seiko; Ellinor, Patrick T.] Massachusetts Gen Hosp, Charlestown, MA USA. [Sinner, Moritz F.; Kaab, Stefan] Univ Munich, Univ Hosp Grosshadern, Munich, Germany. [Lunetta, Kathryn L.; Benjamin, Emelia J.] Boston Univ, Sch Med, Framingham, MA USA. [Pfeufer, Arne] Tech Univ Munich, Munich, Germany. [Rahman, Rosanna; Danik, Stephan P.; Sonni, Akshata; Shea, Marisa A.; del Monte, Frederica; Greenberg, Steven M.; Furie, Karen L.; Rosand, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Perz, Siegfried; Peters, Annette] German Res Ctr Environm Hlth, Neuherberg, Germany. [Arking, Dan E.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Alonso, Alvaro] Univ Minnesota, Minneapolis, MN USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Charlestown, TX USA. RI Kaab, Stefan/H-3915-2012; Pfeufer, Arne/B-6634-2013; Peters, Annette/A-6117-2011 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S579 EP S579 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501329 ER PT J AU Mahoney, EM Wang, KJ Porath, A Corbalan, R Steg, PG Bhatt, DL AF Mahoney, Elizabeth M. Wang, Kaijun Porath, Avi Corbalan, Ramon Steg, Ph. G. Bhatt, Deepak L. TI Cholesterol Control in Patients With a History of Hyperlipidemia and Established Vascular Disease Reflects National Economic/Health System Characteristics SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Mahoney, Elizabeth M.; Wang, Kaijun] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Porath, Avi] Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel. [Corbalan, Ramon] Catholic Univ, Sch Med, Santiago, Chile. [Steg, Ph. G.] Ctr Hosp Bichat Claude Bernard, Paris, France. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S405 EP S406 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500423 ER PT J AU Maurovich-Horvat, P Kriegel, ML Schlett, CL Nakazawa, G Vorpahl, M Nakano, M Bamberg, F Virmani, R Hoffmann, U AF Maurovich-Horvat, Pal Kriegel, Matthias L. Schlett, Christopher L. Nakazawa, Gaku Vorpahl, Marc Nakano, Masataka Bamberg, Fabian Virmani, Renu Hoffmann, Udo TI Assessment of Coronary Atherosclerotic Plaque by High-Definition Computed Tomography: An ex vivo Study in Human Hearts SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Maurovich-Horvat, Pal; Kriegel, Matthias L.; Schlett, Christopher L.; Bamberg, Fabian; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nakazawa, Gaku; Vorpahl, Marc; Nakano, Masataka; Virmani, Renu] CVPath Inst, Gaithersburg, MD 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S303 EP S303 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500021 ER PT J AU Mega, JL Iakoubova, OA Devlin, JJ Qin, J Cannon, CP Braunwald, E Sabatine, MS AF Mega, Jessica L. Iakoubova, Olga A. Devlin, James J. Qin, Jie Cannon, Christopher P. Braunwald, Eugene Sabatine, Marc S. TI 9p21 Genetic Variant and Benefit From Intensive Statin Therapy After an Acute Coronary Syndrome SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Mega, Jessica L.; Cannon, Christopher P.; Braunwald, Eugene; Sabatine, Marc S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Iakoubova, Olga A.; Devlin, James J.] Celera, Alameda, CA USA. [Qin, Jie] TIMI Study Grp, Boston, MA USA. NR 0 TC 1 Z9 1 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 NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1144 EP S1144 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831504218 ER PT J AU Mega, JL Braunwald, E Lee, M Misselwitz, F Mohanavelu, S Notani, R Peters, G Gibson, CM AF Mega, Jessica L. Braunwald, Eugene Lee, Mary Misselwitz, Frank Mohanavelu, Satishkumar Notani, Ravi Peters, Gary Gibson, C. Michael TI Cessation of Rivaroxaban in Post-ACS Patients is Not Associated With Clinical Evidence of Rebound Hypercoagulability: An ATLAS ACS-TIMI 46 Substudy SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Mega, Jessica L.; Braunwald, Eugene] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lee, Mary; Notani, Ravi; Peters, Gary] Johnson & Johnson, Raritan, NJ USA. [Gibson, C. Michael] Beth Israel Hosp, Boston, MA USA. [Mohanavelu, Satishkumar] TIMI Study Grp, Boston, MA USA. [Misselwitz, Frank] Bayer HealthCare, Wuppertal, Germany. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1002 EP S1002 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503413 ER PT J AU Mehdi, H Frangiskakis, JM Grimley, S Gutmann, R Bloom, HL Dudley, SC Ellinor, PT Shalaby, A Weiss, R Saba, S McNamara, DM London, B AF Mehdi, Haider Frangiskakis, J. M. Grimley, Sara Gutmann, Rebecca Bloom, Heather L. Dudley, Samuel C. Ellinor, Patrick T. Shalaby, Alaa Weiss, Raul Saba, Samir McNamara, Dennis M. London, Barry TI NOS1AP is Associated With Arrhythmias in a Heart Failure Population With Severe LV Dysfunction SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Mehdi, Haider; Frangiskakis, J. M.; Grimley, Sara; Gutmann, Rebecca; Saba, Samir; McNamara, Dennis M.; London, Barry] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Bloom, Heather L.] Emory Univ, Sch Med, Atlanta, GA USA. [Dudley, Samuel C.] Univ Illinois, Chicago, IL USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shalaby, Alaa] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Weiss, Raul] Ohio State Univ, Columbus, OH 43210 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S571 EP S572 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501301 ER PT J AU Mela, T Chung, M Venkateshwar, G Borge, R Shinn, T Dan, D Uslan, D Gleva, M Holcomb, R Mitchell, K Poole, J AF Mela, Theofanie Chung, Mina Venkateshwar, Gottipaty Borge, Richard Shinn, Timothy Dan, Dan Uslan, Daniel Gleva, Marye Holcomb, Richard Mitchell, Kevin Poole, Jeanne TI Replacement of Cardiac Rhythm Devices: Is the Risk Different When Performed by Trained Electrophysiologists, in Academic or Private Practice? Results From the REPLACE Registry SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Mela, Theofanie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chung, Mina] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Venkateshwar, Gottipaty] S Carolina Heart Ctr, Columbia, SC USA. [Borge, Richard] Abington Vied Specialists, Abington, PA USA. [Shinn, Timothy] Michigan Heart, Ann Arbor, MI USA. [Dan, Dan] Piedmont Heart Inst, Atlanta, GA USA. [Uslan, Daniel] Univ Calif Los Angeles, Los Angeles, CA USA. [Gleva, Marye; Poole, Jeanne] Washington Univ, Sch Med, St Louis, MO USA. [Mitchell, Kevin] Biotronik, Lake Oswego, OR 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S637 EP S637 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501571 ER PT J AU Merchant, RM Abotsi, EJ Long, JA Trudeau, ME Groeneveld, PW Becker, LB Abella, BS Asch, DA AF Merchant, Raina M. Abotsi, Edam J. Long, Judith A. Trudeau, Marti E. Groeneveld, Peter W. Becker, Lance B. Abella, Benjamin S. Asch, David A. TI Real Time Cardiopulmonary Resuscitation Instructions via Cellular Phone SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Merchant, Raina M.; Abotsi, Edam J.; Long, Judith A.; Groeneveld, Peter W.; Becker, Lance B.; Abella, Benjamin S.; Asch, David A.] Univ Penn, Philadelphia, PA 19104 USA. [Trudeau, Marti E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1455 EP S1456 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831505066 ER PT J AU Miller, PS Evangelista, LS Giger, JN Martinez-Maza, O Corvera-Tindel, T Esmailian, F Doering, LV AF Miller, Pamela S. Evangelista, Lorraine S. Giger, Joyce N. Martinez-Maza, Otoniel Corvera-Tindel, Teresita Esmailian, Fardad Doering, Lynn V. TI Running on Exhaustion: Pathogen Burden, Immune Dysregulation, and Endothelial Activation After Coronary Artery Bypass Graft Surgery SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Miller, Pamela S.; Evangelista, Lorraine S.; Giger, Joyce N.; Martinez-Maza, Otoniel; Esmailian, Fardad; Doering, Lynn V.] Univ Calif Los Angeles, Los Angeles, CA USA. [Corvera-Tindel, Teresita] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S416 EP S416 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500466 ER PT J AU Mitchell, K Gupte, S Wright, J Minae, A Sasson, J Kehoe, K Fiocchi, F Oetgen, W Rumsfeld, JS AF Mitchell, Kristi Gupte, Sunil Wright, Janet Minae, Ashley Sasson, Joe Kehoe, Katie Fiocchi, Fran Oetgen, William Rumsfeld, John S. TI Electronic Medical Record Adoption in Cardiology Practices: A 2009 Snapshot From the American College of Cardiology's IC3 (Improving Continuous Cardiac Care) Program SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Mitchell, Kristi; Gupte, Sunil; Wright, Janet; Minae, Ashley; Kehoe, Katie; Fiocchi, Fran] Amer Coll Cardiol, Washington, DC USA. [Sasson, Joe] MedAxiom, Tallahassee, FL USA. [Oetgen, William] Georgetown Univ, Washington, DC USA. [Rumsfeld, John S.] Univ Colorado, Denver, CO 80202 USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S438 EP S438 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500550 ER PT J AU Miyazaki, T Yamazaki, H Morishige, K Aikawa, E Aikawa, M AF Miyazaki, Tetsuro Yamazaki, Hiroyuki Morishige, Kunio Aikawa, Elena Aikawa, Masanori TI Notch3 Signaling in Macrophages Promotes Obesity and Atherosclerosis in Hypercholesterolemic Mice SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Miyazaki, Tetsuro; Yamazaki, Hiroyuki; Morishige, Kunio; Aikawa, Masanori] Brigham & Womens Hosp, Boston, MA 02115 USA. [Aikawa, Elena] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1051 EP S1051 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503617 ER PT J AU Myrmel, T Tsai, TT Isselbacher, EM Eagle, KA Froehlich, JB Montgomery, DG Cooper, JV Sundt, T Pyeritz, RE Hutchison, S Bartnes, K Ehrlich, M Demertzis, S Evangelista, A Nienaber, CA AF Myrmel, Truls Tsai, Thomas T. Isselbacher, Eric M. Eagle, Kim A. Froehlich, James B. Montgomery, Daniel G. Cooper, Jeanna V. Sundt, Thoralf, III Pyeritz, Reed E. Hutchison, Stuart Bartnes, Kristian Ehrlich, Marek Demertzis, Stefanos Evangelista, Arturo Nienaber, Christoph A. CA IRAD Investigators TI Partial Thrombosis of the False Lumen is Not a Predictor of Follow-up Mortality in Patients With Acute Type A Aortic Dissection SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Myrmel, Truls; Bartnes, Kristian] Univ Hosp N Norway, Tromso, Norway. [Tsai, Thomas T.] Univ Colorado, Denver, CO 80202 USA. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Eagle, Kim A.; Froehlich, James B.; Montgomery, Daniel G.; Cooper, Jeanna V.] Univ Michigan, Ann Arbor, MI 48109 USA. [Sundt, Thoralf, III] Mayo Clin, Rochester, MN USA. [Pyeritz, Reed E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Hutchison, Stuart] Univ Calgary, Calgary, AB, Canada. [Ehrlich, Marek] Univ Vienna, Vienna, Austria. [Demertzis, Stefanos] Cardioctr Ticino, Lugano, Switzerland. [Evangelista, Arturo] Hosp Gen Univ Vall Hebron, Barcelona, Spain. [Nienaber, Christoph A.] Univ Hosp Rostock, Rostock, Germany. 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S965 EP S965 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503267 ER PT J AU Nabavi, V Ahmadi, N Saeed, A Hajsadeghi, F Flores, F Sourayanezhad, S Mendoza, H Ebrahimi, R Ahmdi, A Levenstein, S Budoff, M AF Nabavi, Vahid Ahmadi, Naser Saeed, Anila Hajsadeghi, Fereshteh Flores, Ferdinand Sourayanezhad, Souraya Mendoza, Helen Ebrahimi, Ramin Ahmdi, Ahmad Levenstein, Susan Budoff, Matthew TI Association of the Extent of Perceived Mental Stress and Physical Inactivity, and the Extent of Coronary Artery Disease Diagnosed by Computed Tomography SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Nabavi, Vahid; Ahmadi, Naser; Saeed, Anila; Hajsadeghi, Fereshteh; Flores, Ferdinand; Sourayanezhad, Souraya; Mendoza, Helen; Ahmdi, Ahmad; Budoff, Matthew] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Ebrahimi, Ramin] Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Levenstein, Susan] Aventino Med Grp, Rome, Italy. 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S494 EP S494 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500778 ER PT J AU Nazer, B Ray, KK Sloan, S Scirica, BM Morrow, DA Cannon, CP Braunwald, E AF Nazer, Babak Ray, Kausik K. Sloan, Sarah Scirica, Benjamin M. Morrow, David A. Cannon, Christopher P. Braunwald, Eugene TI Neopterin Levels Improve Risk Prediction for Heart Failure Hospitalization Over and Above C-reactive Protein and B-type Natriuretic Peptide in the PROVE IT-TIMI 22 Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Nazer, Babak] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ray, Kausik K.] Univ Cambridge, Cambridge, England. [Sloan, Sarah; Scirica, Benjamin M.; Morrow, David A.; Cannon, Christopher P.; Braunwald, Eugene] TIMI Study Grp, 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S808 EP S808 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831502448 ER PT J AU Okada, DR Blankstein, R Ghoshhajra, BB Rocha, JA Shturman, LD Rogers, IS Bezerra, HG Sarwar, A Gewirtz, H Hoffmann, U Mamuya, WS Brady, TJ Cury, RC AF Okada, David R. Blankstein, Ron Ghoshhajra, Brian B. Rocha-Filho, Jose A. Shturman, Leonid D. Rogers, Ian S. Bezerra, Hiram G. Sarwar, Ammar Gewirtz, Henry Hoffmann, Udo Mamuya, Wilfred S. Brady, Thomas J. Cury, Ricardo C. TI Direct Comparison of Rest and Adenosine Stress Myocardial Perfusion CT With Rest and Stress SPECT SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Okada, David R.; Ghoshhajra, Brian B.; Rocha-Filho, Jose A.; Shturman, Leonid D.; Rogers, Ian S.; Sarwar, Ammar; Gewirtz, Henry; Hoffmann, Udo; Brady, Thomas J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Blankstein, Ron] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bezerra, Hiram G.] Harrington McLaughlin Heart & Vasc Inst, Cleveland, OH USA. [Mamuya, Wilfred S.] Lown Cardiovasc Grp, Brookline, MA USA. [Cury, Ricardo C.] Baptist Cardiac & Vasc Inst, Miami, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S374 EP S374 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500297 ER PT J AU Peacock, JM Keo, HH Yu, XH Oldenburg, N Duval, S Henry, TD Jaff, MR Baumgartner, I Hirsch, AT AF Peacock, James M. Keo, Hong H. Yu, Xinhua Oldenburg, Niki Duval, Sue Henry, Timothy D. Jaff, Michael R. Baumgartner, Iris Hirsch, Alan T. TI The Incidence and Health Economic Burden of Critical Limb Ischemia and Ischemic Amputation in Minnesota: 2005-2007 SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Peacock, James M.; Yu, Xinhua; Oldenburg, Niki] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Keo, Hong H.; Duval, Sue; Hirsch, Alan T.] Univ Minnesota, Sch Publ Hlth, Abbott NW Hosp, Minneapolis Heart Inst Fdn, Minneapolis, MN USA. [Jaff, Michael R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Baumgartner, Iris] Swiss Cardiovasc Cntr, Bern, Switzerland. NR 0 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1148 EP S1148 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831504235 ER PT J AU Qadir, S Brady, TJ Tawakol, A AF Qadir, Sadia Brady, Thomas J. Tawakol, Ahmed TI F-18-FDG PET Imaging Predicts Progression of Carotid Stenosis: A Prospective 2-Year Follow-up Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Qadir, Sadia; Brady, Thomas J.; Tawakol, Ahmed] Massachusetts Gen Hosp, 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S388 EP S388 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500351 ER PT J AU Qi, S van Dam, RM Meigs, JB Franco, OH Mantzoros, CS Hu, FB AF Qi Sun van Dam, Rob M. Meigs, James B. Franco, Oscar H. Mantzoros, Christos S. Hu, Frank B. TI Leptin and Soluble Leptin Receptor Levels in Plasma and Risk of Type 2 Diabetes in US Women: A Prospective Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Qi Sun; van Dam, Rob M.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Meigs, James B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Franco, Oscar H.] Univ Warwick, Coventry CV4 7AL, W Midlands, England. [Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S415 EP S415 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500461 ER PT J AU Riegel, B Potashnik, S Goldberg, L Weaver, T Weintraub, W Fleck, D Sayers, S AF Riegel, Barbara Potashnik, Sheryl Goldberg, Lee Weaver, Terri Weintraub, William Fleck, Desiree Sayers, Steven TI Is There a Better Way to Screen for Sleep Disordered Breathing in Adults With Heart Failure? SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Riegel, Barbara; Potashnik, Sheryl; Goldberg, Lee; Weaver, Terri; Fleck, Desiree] Univ Penn, Philadelphia, PA 19104 USA. [Weintraub, William] Christiana Care Hlth Syst, Newark, DE USA. [Sayers, Steven] Philadelphia VA Med Ctr, Philadelphia, PA 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S864 EP S864 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831502678 ER PT J AU Rivera, JJ Budoff, M O'Leary, DH Hoffman, U Wasserman, B Szklo, M Burke, G Blumenthal, RS Nasir, K AF Rivera, Juan J. Budoff, Matthew O'Leary, Daniel H. Hoffman, Udo Wasserman, Bruce Szklo, Moyses Burke, Gregory Blumenthal, Roger S. Nasir, Khurram TI Relationship Between Carotid Intima Media Thickness and Coronary Artery Calcium Progression in the Multi-ethnic Study of Atherosclerosis (MESA) SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Rivera, Juan J.; Wasserman, Bruce; Szklo, Moyses; Blumenthal, Roger S.] Johns Hopkins Univ, Baltimore, MD 02114 USA. [Budoff, Matthew] Harbor UCLA Med Ctr, Los Angeles Biomed Rsch Inst, Los Angeles, CA USA. [O'Leary, Daniel H.] Caritas Carney Hosp, Dorchester, MA USA. [Hoffman, Udo] Massachusetts Gen Hosp, Boston, MA USA. [Burke, Gregory] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Nasir, Khurram] Boston Univ Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S343 EP S343 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500179 ER PT J AU Rogers, IS Joshi, SB Johnson, JR Ferencik, M Shturman, LD Abbara, S Gaber, MS Sciortino, N Williams, J Hachamovitch, R Di Carli, MF Hoffmann, U AF Rogers, Ian S. Joshi, Subodh B. Johnson, James R. Ferencik, Maros Shturman, Leon D. Abbara, Suhny Gaber, Mariya S. Sciortino, Nathan Williams, Julie Hachamovitch, Rory Di Carli, Marcelo F. Hoffmann, Udo TI Reliability of Cardiac CT for the Detection of Significant Luminal Narrowing: Results From the Study of Myocardial Perfusion and Coronary Anatomy Imaging Roles in CAD (SPARC) Trial SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Rogers, Ian S.; Joshi, Subodh B.; Ferencik, Maros; Shturman, Leon D.; Abbara, Suhny; Sciortino, Nathan; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Johnson, James R.; Gaber, Mariya S.; Williams, Julie; Hachamovitch, Rory; Di Carli, Marcelo F.] Brigham & Womens Hosp, Boston, MA 02115 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S301 EP S302 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500015 ER PT J AU Rusanescu, G Aikawa, M Weissleder, R Aikawa, E AF Rusanescu, Gabriel Aikawa, Masanori Weissleder, Ralph Aikawa, Elena TI Novel Roles of Notch2 and Notch3 in Differential Regulation of Cardiovascular Calcification SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Rusanescu, Gabriel; Weissleder, Ralph; Aikawa, Elena] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. [Aikawa, Masanori] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 1 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 NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S307 EP S307 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500040 ER PT J AU Sakhuja, R Rame, JE Brown, C Ordovas, K Ursell, P De Marco, T AF Sakhuja, Rahul Rame, J. Eduardo Brown, Colleen Ordovas, Karen Ursell, Philip De Marco, Teresa TI A 22-Year-Old Female With Non-Hypertrophic Hypertrophic Cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Sakhuja, Rahul] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rame, J. Eduardo; Brown, Colleen; Ordovas, Karen; Ursell, Philip; De Marco, Teresa] Univ Calif San Francisco, San Francisco, CA 94143 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S746 EP S747 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831502196 ER PT J AU Schlett, CL Banerji, D Siegel, EL Lehman, SJ Bamberg, F Ferencik, M Rogers, IS Brady, TJ Nagumey, JT Hoffmann, U Truong, QA AF Schlett, Christopher L. Banerji, Dahlia Siegel, Emily L. Lehman, Sam J. Bamberg, Fabian Ferencik, Maros Rogers, Ian S. Brady, Thomas J. Nagumey, John T. Hoffmann, Udo Truong, Quynh A. TI Computed Tomography Angiography Results Predict Long-term Major Adverse Cardiac Events in Patients With Chest Pain From the Emergency Department: Two-year Outcome of the ROMICAT (Rule Out Myocardial Infarction Using Computer Assisted Tomography) Trial SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Schlett, Christopher L.; Banerji, Dahlia; Siegel, Emily L.; Lehman, Sam J.; Bamberg, Fabian; Ferencik, Maros; Rogers, Ian S.; Brady, Thomas J.; Nagumey, John T.; Hoffmann, Udo; Truong, Quynh A.] Massachusetts Gen Hosp, 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S317 EP S317 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500072 ER PT J AU Schnabel, RB Baumert, J Barbalic, M Dupuis, J Ellinor, PT Durda, P Dehghan, A Bis, JC Witteman, JC Hoogeveen, RC Benjamin, EJ Koenig, W Tracy, RP AF Schnabel, Renate B. Baumert, Jens Barbalic, Maja Dupuis, Josee Ellinor, Patrick T. Durda, Peter Dehghan, Abbas Bis, Joshua C. Witteman, Jacqueline C. Hoogeveen, Ron C. Benjamin, Emelia J. Koenig, Wolfgang Tracy, Russell P. CA CHARGE Consortium TI Duffy Antigen Receptor for Chemokines (Darc) Polymorphism Regulates Circulating Concentrations of Monocyte Chemoattractant Protein-1 and Other Circulating Inflammatory Mediators SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Schnabel, Renate B.] Johannes Gutenberg Univ Mainz, Mainz, 02114, Germany. [Baumert, Jens] German Rsch Cntr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, 05405, Germany. [Barbalic, Maja; Hoogeveen, Ron C.] Univ Texas Hlth Sci Ctr, Human Genet Cntr, Houston, TX USA. [Barbalic, Maja; Hoogeveen, Ron C.] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX 98195 USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Rsch Cntr, Boston, MA USA. [Durda, Peter] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT USA. [Dehghan, Abbas] Erasmus Med Cntr, Dept Epidemiol, D-7900 Rotterdam, Netherlands. [Bis, Joshua C.] Univ Washington, Seattle, WA 05405 USA. [Witteman, Jacqueline C.] Erasmus Med Cntr, Rotterdam, Netherlands. [Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Koenig, Wolfgang] Univ Ulm, Dept Internal Med 2, Med Cntr, Ulm, Germany. [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S559 EP S559 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501249 ER PT J AU Sibley, CT Gottlieb, I Cox, C Godoy, G Spooner, AE Bluemke, DA Lima, JA AF Sibley, Christopher T. Gottlieb, Ilan Cox, Christopher Godoy, Gustavo Spooner, Amy E. Bluemke, David A. Lima, Joao A. TI Comparative Effect of Statins vs Niacin on MRI Measured Regression of Carotid Atherosclerosis in a Randomized Clinical Trial: The NIA Plaque Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Sibley, Christopher T.; Godoy, Gustavo; Lima, Joao A.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Gottlieb, Ilan] Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil. [Cox, Christopher] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Spooner, Amy E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bluemke, David A.] NIH, Bethesda, MD 20892 USA. RI Sibley, Christopher/C-9900-2013 NR 0 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S376 EP S376 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500305 ER PT J AU Smith, EE Reeves, MJ Hernandez, AF Saver, JL Pan, WQ Dai, D Olson, DM Fonarow, GC Schwamm, LH AF Smith, Eric E. Reeves, Mathew J. Hernandez, Adrian F. Saver, Jeffrey L. Pan, Wenqin Dai, David Olson, DaiWai M. Fonarow, Gregg C. Schwamm, Lee H. TI Prediction of In-Hospital Mortality in Ischemic Stroke Using Data From Get With the Guidelines Stroke SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Reeves, Mathew J.] Michigan State Univ, E Lansing, MI 48824 USA. [Smith, Eric E.] Univ Calgary, Calgary, AB, Canada. [Hernandez, Adrian F.; Pan, Wenqin; Dai, David; Olson, DaiWai M.] Duke Univ, Durham, NC USA. [Saver, Jeffrey L.; Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S522 EP S522 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501101 ER PT J AU Sosnovik, DE Garanger, E Aikawa, E Nahrendorf, M Figueiredo, JL Dai, GP Reynolds, F Rosenzweig, A Weissleder, R Josephson, L AF Sosnovik, David E. Garanger, Elisabeth Aikawa, Elena Nahrendorf, Matthias Figueiredo, Jose-Luiz Dai, Guangping Reynolds, Fred Rosenzweig, Anthony Weissleder, Ralph Josephson, Lee TI Molecular MRI of Cardiomyocyte Apoptosis With Simultaneous Delayed Enhancement MRI Distinguishes Apoptotic and Necrotic Myocytes in vivo: Potential for Midmyocardial Salvage in Acute Ischemia SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Sosnovik, David E.; Garanger, Elisabeth; Aikawa, Elena; Nahrendorf, Matthias; Figueiredo, Jose-Luiz; Dai, Guangping; Reynolds, Fred; Rosenzweig, Anthony; Weissleder, Ralph; Josephson, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 1 Z9 1 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 NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S367 EP S367 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500270 ER PT J AU Steinhaus, D Moffatt, E Vittinghoff, E Whiteman, D Tseng, ZH AF Steinhaus, Daniel Moffatt, Ellen Vittinghoff, Eric Whiteman, Dean Tseng, Zian H. TI Contemporary Burden of Sudden Cardiac Death in San Francisco County, 2007: Substantial Differences in Rates by Race and Gender SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Steinhaus, Daniel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moffatt, Ellen; Vittinghoff, Eric; Whiteman, Dean; Tseng, Zian H.] Univ Calif San Francisco, San Francisco, CA 94143 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S417 EP S418 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500472 ER PT J AU Stolker, JM McGuire, DK Spertus, JA Inzucchi, SE Rathore, SS Maddox, TM Masoudi, FA Tang, F Jones, PG Kosiborod, M AF Stolker, Joshua M. McGuire, Darren K. Spertus, John A. Inzucchi, Silvio E. Rathore, Saif S. Maddox, Thomas M. Masoudi, Frederick A. Tang, Fengming Jones, Philip G. Kosiborod, Mikhail TI In-Hospital Assessment of Hemoglobin A(1c) in Patients With Diabetes Treated for Myocardial Infarction: Variability Between Hospitals and Relationship With Established Quality Indicators SO CIRCULATION LA English DT Meeting Abstract CT 82nd National Conference and Exhibitions and Annual Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Stolker, Joshua M.; Spertus, John A.; Tang, Fengming; Jones, Philip G.; Kosiborod, Mikhail] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [McGuire, Darren K.] Univ Texas Southwestern Sch Med, Dallas, TX USA. [Inzucchi, Silvio E.; Rathore, Saif S.] Yale Univ, Sch Med, New Haven, CT USA. [Maddox, Thomas M.; Masoudi, Frederick A.] Univ Colorado, Denver VAMC, Denver, CO 80202 USA. [Masoudi, Frederick A.] Denver Hlth Med Ctr, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S485 EP S485 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500744 ER PT J AU Thanassoulis, G Massaro, JM O'Donnell, CJ Levy, D Hoffman, U Ellinor, PT Wang, TJ Vasan, RS Fox, CS Benjamin, EJ AF Thanassoulis, George Massaro, Joseph M. O'Donnell, Christopher J. Levy, Daniel Hoffman, Udo Ellinor, Patrick T. Wang, Thomas J. Vasan, Ramachandran S. Fox, Caroline S. Benjamin, Emelia J. TI Pericardial Fat is Associated With Prevalent AF - The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Thanassoulis, George; O'Donnell, Christopher J.; Vasan, Ramachandran S.; Fox, Caroline S.; Benjamin, Emelia J.] NHLBI, NIH, Framingham Heart Study, Framingham, MA USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Hoffman, Udo; Ellinor, Patrick T.; Wang, Thomas J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S519 EP S519 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501091 ER PT J AU Tofler, GH Massaro, J O'Donnell, CJ Wilson, PW Vasan, RS Sutherland, PA Lipinska, I Meigs, JB Levy, D D'Agostino, RB AF Tofler, Geoffrey H. Massaro, Joseph O'Donnell, Christopher J. Wilson, Peter W. Vasan, Ramachandran S. Sutherland, Patrice A. Lipinska, Izabela Meigs, James B. Levy, Daniel D'Agostino, Ralph B. TI Plasminogen Activator Inhibitor (PAI-1) and Risk of Cardiovascular Disease: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Tofler, Geoffrey H.] Royal N Shore Hosp, Sydney, NSW 02215, Australia. [Massaro, Joseph; Vasan, Ramachandran S.; Lipinska, Izabela; D'Agostino, Ralph B.] Boston Univ, Boston, MA USA. [O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Framingham, MA USA. [O'Donnell, Christopher J.; Sutherland, Patrice A.; Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA 30322 USA. [Wilson, Peter W.] Emory Univ, Atlanta, GA 02114 USA. [Meigs, James B.] Massachusetts Gen Hosp, 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S454 EP S454 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500614 ER PT J AU Tsai, TT Maddox, TM Roe, MT Dai, D Casserly, IP Ho, PM Messenger, JC Nallamothu, BK Peterson, ED Rumsfeld, JS AF Tsai, Thomas T. Maddox, Thomas M. Roe, Matthew T. Dai, David Casserly, Ivan P. Ho, P. Michael Messenger, John C. Nallamothu, Brahmajee K. Peterson, Eric D. Rumsfeld, John S. TI Contemporary Risk of In-Hospital Events in Dialysis Patients Undergoing Percutaneous Coronary Interventions: Insights From the NCDR Cath-PCI Registry SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Tsai, Thomas T.; Maddox, Thomas M.; Casserly, Ivan P.; Ho, P. Michael; Rumsfeld, John S.] Univ Colorado, Denver VAMC, Denver, CO 80202 USA. [Roe, Matthew T.; Dai, David; Peterson, Eric D.] Duke Univ, Med Cntr, Durham, NC USA. [Nallamothu, Brahmajee K.] Univ Michigan Hosp, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1101 EP S1101 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831504029 ER PT J AU Tsang, ZH Steinhaus, D Vittinghoff, E Whiteman, D Moffatt, E AF Tsang, Zian H. Steinhaus, Daniel Vittinghoff, Eric Whiteman, Dean Moffatt, Ellen TI Sudden Cardiac Death in San Francisco County, 2007: Coronary Artery Disease Accounts for Only 40% of SCDs but is Associated With a 3-Fold Higher Risk SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Tsang, Zian H.; Vittinghoff, Eric; Whiteman, Dean; Moffatt, Ellen] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Steinhaus, Daniel] Massachusetts Gen Hosp, 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S418 EP S418 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500473 ER PT J AU van der Giessen, AG Toepker, MH Donelly, PM Bamberg, F Raffle, C Lee, H Gijsen, FJ Wentzel, JJ Hoffmann, U AF van der Giessen, Alina G. Toepker, Michael H. Donelly, Patrick M. Bamberg, Fabian Raffle, Christopher Lee, Hang Gijsen, Frank J. Wentzel, Jolanda J. Hoffmann, Udo TI The Detection of Non-Calcified Coronary Plaques by Dual Source Computed Tomography is Related to the Plaque Thickness SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [van der Giessen, Alina G.; Gijsen, Frank J.; Wentzel, Jolanda J.] ErasmusMC, Rotterdam, Netherlands. [Toepker, Michael H.; Donelly, Patrick M.; Bamberg, Fabian; Raffle, Christopher; Lee, Hang; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MRI PET CT Program, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S325 EP S325 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500107 ER PT J AU Vandenwijngaert, S Pokreisz, P Pellens, M Gillijns, H Veulemans, P Liu, XS Herijgers, P D'hooge, J Bloch, KD Janssens, S AF Vandenwijngaert, Sara Pokreisz, Peter Pellens, Marijke Gillijns, Hilde Veulemans, Paul Liu, Xiaoshun Herijgers, Paul D'hooge, Jan Bloch, Kenneth D. Janssens, Stefan TI Myocardial Phosphodiesterase 5 Expression Contributes to Left Ventricular Dysfunction in the Pressure-Overloaded Heart SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Vandenwijngaert, Sara; Pokreisz, Peter; Veulemans, Paul; Liu, Xiaoshun; Herijgers, Paul; D'hooge, Jan; Janssens, Stefan] Katholieke Univ Leuven, Leuven, Belgium. [Pellens, Marijke; Gillijns, Hilde] VIB, Leuven, Belgium. [Bloch, Kenneth D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Herijgers, Paul/B-8064-2013 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S820 EP S820 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831502498 ER PT J AU Velagaleti, RS Gona, P Chuang, ML Yeon, SB Salton, CJ Fox, CS Massaro, J Hoffmann, U Manning, WJ O'Donnell, CJ AF Velagaleti, Raghava S. Gona, Philimon Chuang, Michael L. Yeon, Susan B. Salton, Carol J. Fox, Caroline S. Massaro, Joseph Hoffmann, Udo Manning, Warren J. O'Donnell, Christopher J. TI Aortic Atherosclerosis and Left Ventricular Structure in the Community SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Velagaleti, Raghava S.; Gona, Philimon; Fox, Caroline S.; Massaro, Joseph; O'Donnell, Christopher J.] NHLBI, Framingham, MA USA. [Chuang, Michael L.; Yeon, Susan B.; Salton, Carol J.; Manning, Warren J.] Beth Israel Deaconess Med Cntr, Boston, MA USA. [Hoffmann, Udo] Massachusetts Gen Hosp, 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S380 EP S380 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500321 ER PT J AU Wang, CC Lu, L Xu, Y Grayson, C Jacobs, S Reusch, JE Gianani, R Draznin, B Schwartz, GG AF Wang, Cecilia C. Lu, Li Xu, Ya Grayson, Clifford Jacobs, Susanna Reusch, Jane E. Gianani, Roberto Draznin, Boris Schwartz, Gregory G. TI Diet-Induced Insulin Resistance Causes Isoform-Specific Abnormalities of Akt Signaling in Arterial Wall of Pigs SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Wang, Cecilia C.; Lu, Li; Xu, Ya; Grayson, Clifford; Jacobs, Susanna; Reusch, Jane E.; Draznin, Boris; Schwartz, Gregory G.] Denver VA Med Ctr, Denver, CO USA. [Wang, Cecilia C.; Lu, Li; Xu, Ya; Grayson, Clifford; Jacobs, Susanna; Reusch, Jane E.; Gianani, Roberto; Draznin, Boris; Schwartz, Gregory G.] Univ Colorado, Denver, CO 80202 USA. [Gianani, Roberto] Childrens Hosp, Denver, CO 80218 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S443 EP S444 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500570 ER PT J AU Wann, LS Thompson, RC Allam, AH Miyamoto, MI Amer, HA Badr, I Abdel-maksoud, G Nureldin, A Thomas, JJ Thomas, GS AF Wann, L. S. Thompson, Randall C. Allam, Adel H. Miyamoto, Michael I. Amer, Hany A. Badr, Ibrahem Abdel-maksoud, Gomma Nureldin, Abdelhalium Thomas, Jennifer J. Thomas, Gregory S. TI Atherosclerosis: Not Just a Disease of Contemporary Humans SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Wann, L. S.] Wisconsin Heart Hosp, Milwaukee, WI USA. [Thompson, Randall C.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Allam, Adel H.] Al Azhar Med Sch, Cairo, Egypt. [Miyamoto, Michael I.] Univ Calif San Diego, San Diego, CA 92103 USA. [Amer, Hany A.] Natl Rsch Cntr, Giza, Egypt. [Badr, Ibrahem; Abdel-maksoud, Gomma; Nureldin, Abdelhalium] Cairo Univ, Cairo, Egypt. [Thomas, Jennifer J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thomas, Gregory S.] Univ Calif Irvine, Orange, CA 92668 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S354 EP S354 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500220 ER PT J AU Weiner, RB Kanayama, G Hudson, JI Hutter, AM Picard, MH Pope, HG Baggish, AL AF Weiner, Rory B. Kanayama, Gen Hudson, James I. Hutter, Adolph M., Jr. Picard, Michael H. Pope, Harrison G., Jr. Baggish, Aaron L. TI Chronic Anabolic Androgenic Steroid Use is Associated With Left Ventricular Systolic and Diastolic Dysfunction SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Weiner, Rory B.; Hutter, Adolph M., Jr.; Picard, Michael H.; Baggish, Aaron L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kanayama, Gen; Hudson, James I.; Pope, Harrison G., Jr.] McLean Hosp, Belmont, MA 02178 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S741 EP S741 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831502174 ER PT J AU Weiss, E Merchant, F Laferriere, S Mela, T Armoundas, A AF Weiss, Eric Merchant, Faisal Laferriere, Shawna Mela, Theofanie Armoundas, Antonis TI A Novel Intracardiac Pacing Method to Induce and Suppress Repolarization Altemans SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Weiss, Eric; Merchant, Faisal; Laferriere, Shawna; Mela, Theofanie; Armoundas, Antonis] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 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 NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S710 EP S710 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831502046 ER PT J AU Wilson, SR Angiolillo, DJ Frelinger, AL O'Donoghue, M Neumann, FJ Michelson, AD Miller, DL Luo, JX McCabe, CH Antman, EM Braunwald, E Wiviott, S AF Wilson, Sean R. Angiolillo, Dominick J. Frelinger, Andrew L., III O'Donoghue, Michelle Neumann, Franz-Josef Michelson, Alan D. Miller, Debra L. Luo, Junxiang McCabe, Carolyn H. Antman, Elliott M. Braunwald, Eugene Wiviott, Stephen TI Platelet Function in Diabetes Mellitus: Observations From the PRINCIPLE-TIMI 44 Trial SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Wilson, Sean R.; O'Donoghue, Michelle; McCabe, Carolyn H.; Antman, Elliott M.; Braunwald, Eugene; Wiviott, Stephen] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Angiolillo, Dominick J.] Univ Florida, Jacksonville, FL USA. [Frelinger, Andrew L., III; Michelson, Alan D.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Neumann, Franz-Josef] Herz Zentrum, Bad Krozingen, Germany. [Miller, Debra L.; Luo, Junxiang] Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 0 TC 1 Z9 1 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 NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S548 EP S549 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501207 ER PT J AU Winterfield, JR Werdich, A MacRae, CA Milan, DJ AF Winterfield, Jeffrey R. Werdich, Andreas MacRae, Calum A. Milan, David J. TI Stim1 Modulates Pacemaking and Contractility via Regulation of Calcium Stores in the Embryonic Heart SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Winterfield, Jeffrey R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Werdich, Andreas; MacRae, Calum A.; Milan, David J.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S779 EP S779 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831502328 ER PT J AU Yu, PB Zamanian, RT Malhotra, R Schmidt, J Deng, DY Lai, CS Parker, W Bloch, KD Elliott, CG AF Yu, Paul B. Zamanian, Roham T. Malhotra, Rajeev Schmidt, Jonathan Deng, Donna Y. Lai, Carol S. Parker, William Bloch, Kenneth D. Elliott, C. Gregory TI Circulating Soluble Endoglin is a Sensitive Predictor of Pulmonary Arterial Hypertension and Exercise Function SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Yu, Paul B.; Malhotra, Rajeev; Deng, Donna Y.; Lai, Carol S.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zamanian, Roham T.] Stanford Univ, Stanford, CA 94305 USA. [Schmidt, Jonathan; Elliott, C. Gregory] Univ Utah, Sch Med, Salt Lake City, UT USA. [Parker, William] Duke Univ, Durham, NC 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1137 EP S1137 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831504187 ER PT J AU Zahid, M Single, I Good, C Stone, RA Kim, S Fine, MJ Sonel, AF AF Zahid, Maliha Single, Ish Good, Chester Stone, Roslyn A. Kim, Sunghee Fine, Michael J. Sonel, Ali F. TI Association Between Pneumococcal Vaccination and Fewer Adverse Outcomes in Patients Hospitalized With Acute Coronary Syndromes SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Zahid, Maliha; Single, Ish; Good, Chester; Stone, Roslyn A.; Kim, Sunghee; Fine, Michael J.; Sonel, Ali F.] Univ Pittsburgh, Pittsburgh, PA USA. [Good, Chester; Stone, Roslyn A.; Kim, Sunghee; Fine, Michael J.; Sonel, Ali F.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Rsch & Promot, Pittsburgh, PA 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1173 EP S1173 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831504349 ER PT J AU Zou, L Feng, Y Chen, YJ Si, R Scherrer-Crosbie, M Shen, SQ Ichinose, F Chao, W AF Zou, Lin Feng, Yen Chen, Yu-Jung Si, Rui Scherrer-Crosbie, Marielle Shen, Shiqian Ichinose, Fumito Chao, We TI Toll-like Receptor 2 Signaling Contributes to Cardiac Dysfunction and High Mortality During Experimental Sepsis SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1443 EP S1443 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831505010 ER PT J AU Dieplinger, B Januzzi, JL Steinmair, M Gabriel, C Poelz, W Haltmayer, M Mueller, T AF Dieplinger, Benjamin Januzzi, James L., Jr. Steinmair, Martin Gabriel, Christian Poelz, Werner Haltmayer, Meinhard Mueller, Thomas TI Analytical and clinical evaluation of a novel high-sensitivity assay for measurement of soluble ST2 in human plasma - The Presage (TM) ST2 assay SO CLINICA CHIMICA ACTA LA English DT Article DE Heart failure; Inflammation; Interleukin-1 receptor family; Natriuretic peptides; Pneumonia; Sepsis ID RESPIRATORY-DISTRESS-SYNDROME; FAMILY-MEMBER ST2; HEART-FAILURE; MYOCARDIAL-INFARCTION; BIOLOGICAL VARIATION; NATRIURETIC PEPTIDE; 1-YEAR MORTALITY; BIOMARKER; RECEPTOR; PROTEIN AB Background: The protein ST-2 is a member of the interleukin-1 receptor family. Blood concentrations of the soluble isoform of M (sST2) are increased in inflammatory diseases and in heart disease and are considered a prognostic marker in both. The aim of this study was the analytical and clinical evaluation of the novel Presage (TM) ST2 assay for the determination of sST2 in human plasma. Methods: We evaluated precision and linearity of the assay, analyte stability, and biological variability, determined reference values, performed a method comparison with an established ELISA and quantified sST2 concentrations in various diseases. Results: Within-run and total coefficients of variation were <2.5% and <4.0%. The method was linear across the whole measurement range of the assay. The analyte was stable for 48 h at room temperature, for 7 days at 4 degrees C, and for at least 2 months at -20 degrees C and -80 degrees C. The reference change value for healthy individuals was 30%. Age-independent reference values were 3-28 U/mL in males, and 2-16 U/mL in females. The method comparison revealed a high proportional bias. sST2 plasma concentrations were increased modestly in heart failure and moderately in pneumonia and chronic obstructive pulmonary disease. Patients with sepsis exhibited highly elevated sST2 values. In patients with chronic renal disease, however, there was no difference compared to healthy individuals. Conclusion: The Presage (TM) ST2 assay meets the needs of quality specifications of laboratory medicine. The results of the clinical assay evaluation are novel with respect to sST2 in various diseases and should initiate further studies. (C) 2009 Elsevier B.V. All rights reserved. C1 [Dieplinger, Benjamin; Steinmair, Martin; Haltmayer, Meinhard; Mueller, Thomas] Konventhosp Barmherzige Brueder, Dept Lab Med, A-4020 Linz, Austria. [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Gabriel, Christian] Red Cross Transfus Serv Upper Austria, Linz, Austria. [Poelz, Werner] Univ Linz, Inst Appl Syst Sci & Stat, A-4040 Linz, Austria. RP Mueller, T (reprint author), Konventhosp Barmherzige Brueder, Dept Lab Med, Seilerstaette 2-A, A-4020 Linz, Austria. EM thomas.mueller@bs-lab.at RI Gabriel, Christian/A-1689-2014 OI Gabriel, Christian/0000-0003-2043-9320 FU Abbott Diagnostics; B.R.A.H.M.S AG; Roche Diagnostics; Presage(TM) FX Funding: Critical Diagnostics, holder of the license for ST2 cardiac testing, provided reagents for sST2 measurements with the Presage (TM) ST2 assay and the MBL assay free of charge. The company did not play a role in (1) the design of the study; (2) data collection, analysis and interpretation; and (3) preparation of the manuscript. NR 32 TC 101 Z9 106 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD NOV 3 PY 2009 VL 409 IS 1-2 BP 33 EP 40 DI 10.1016/j.cca.2009.08.010 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 516SS UT WOS:000271563600007 PM 19699192 ER PT J AU Maherali, N Hochedlinger, K AF Maherali, Nimet Hochedlinger, Konrad TI Tgf beta Signal Inhibition Cooperates in the Induction of iPSCs and Replaces Sox2 and cMyc SO CURRENT BIOLOGY LA English DT Article ID PLURIPOTENT STEM-CELLS; HUMAN FIBROBLASTS; SOMATIC-CELLS; DIFFERENTIATION; GENERATION; MOUSE; EXPRESSION; SYSTEM; OCT4 AB Ectopic expression of 004, Sox2, cMyc, and Klf4 confers a pluripotent state upon several differentiated cell types, generating induced pluripotent stem cells (IPSCs) [1-8]. iPSC derivation is highly inefficient, and the underlying mechanisms are largely unknown. This low efficiency suggests the existence of additional cooperative factors whose identification is critical for understanding reprogramming. In addition, the therapeutic use of iPSCs relies on the development of efficient nongenetic means of factor delivery, and although a handful of replacement molecules have been identified, their use yields a further reduction to the already low reprogramming efficiency [9-11]. Thus, the identification of compounds that enhance rather than solely replace the function of the reprogramming factors will be of great use. Here, we demonstrate that inhibition of Tgfb beta signaling cooperates in the reprogramming of murine fibroblasts by enabling faster, more efficient induction of iPSCs, whereas activation of Tgf beta signaling blocks reprogramming. In addition to exhibiting a strong cooperative effect, the Tgf beta receptor inhibitor bypasses the requirement for exogenous cMyc or Sox2, highlighting its dual role as a cooperative and replacement factor. The identification of a highly characterized pathway operating in iPSC induction will open new avenues for mechanistic dissection of the reprogramming process. C1 [Maherali, Nimet; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Regenerat Med, Harvard Stem Cell Inst, Boston, MA 02114 USA. [Maherali, Nimet; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Maherali, Nimet] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Maherali, Nimet; Hochedlinger, Konrad] Dept Stem Cell & Regenerat Biol, Boston, MA 02114 USA. RP Hochedlinger, K (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Harvard Stem Cell Inst, 185 Cambridge St, Boston, MA 02114 USA. EM khochedlinger@helix.mgh.harvard.edu FU Natural Sciences and Engineering Research Council of Canada; Alberta Scholarships Program; National Institutes of Health Director's Innovator Award; Harvard Stem Cell Institute; Massachusetts General Hospital FX We thank Matthias Stadtfeld for the pilot experiments that led to conception of the study, as well as insightful discussion and critical reading of the manuscript; we also thank Jose Polo for insightful discussion. N.M. is supported by a graduate scholarship from the Natural Sciences and Engineering Research Council of Canada and a Sir James Lougheed Award from the Alberta Scholarships Program. K.H. is supported by a National Institutes of Health Director's Innovator Award, the Harvard Stem Cell Institute, and Massachusetts General Hospital. NR 24 TC 197 Z9 203 U1 4 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD NOV 3 PY 2009 VL 19 IS 20 BP 1718 EP 1723 DI 10.1016/j.cub.2009.08.025 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 515UM UT WOS:000271498400027 PM 19765992 ER PT J AU Jaffer, FA AF Jaffer, Farouc A. TI Assessing Niacin as an Atherosclerosis Therapeutic Agent Valuable Insights Provided by High-Resolution Vascular Magnetic Resonance Imaging SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE niacin; atherosclerosis; magnetic resonance imaging; high-density lipoprotein; carotid ID EXTENDED-RELEASE NIACIN; SIMVASTATIN; COMBINATION; PREVENTION; DISEASE; MRI C1 [Jaffer, Farouc A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Jaffer, Farouc A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Jaffer, FA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Simches Res Bldg,Room 3206,185 Cambridge St, Boston, MA 02114 USA. EM fjaffer@mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X NR 15 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 3 PY 2009 VL 54 IS 19 BP 1795 EP 1796 DI 10.1016/j.jacc.2009.07.026 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 512OO UT WOS:000271259700007 PM 19874993 ER PT J AU Liao, SL Luthra, M Rogers, KM AF Liao, Steve L. Luthra, Munish Rogers, Kevin M. TI Leriche Syndrome SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material C1 [Liao, Steve L.; Luthra, Munish] James J Peters Vet Affairs Med Ctr, Dept Med, Bronx, NY USA. [Rogers, Kevin M.] James J Peters Vet Affairs Med Ctr, Dept Radiol, Bronx, NY USA. [Liao, Steve L.] Mt Sinai Sch Med, Dept Med Cardiol, New York, NY USA. RP Liao, SL (reprint author), James J Peters Vet Affairs Med Ctr, Dept Med, Bronx, NY USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 3 PY 2009 VL 54 IS 19 BP E11 EP E11 DI 10.1016/j.jacc.2009.06.037 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 512OO UT WOS:000271259700013 PM 19874987 ER PT J AU Uc, EY McDermott, MP Marder, KS Anderson, SW Litvan, I Como, PG Auinger, P Chou, KL Growdon, JC AF Uc, E. Y. McDermott, M. P. Marder, K. S. Anderson, S. W. Litvan, I. Como, P. G. Auinger, P. Chou, K. L. Growdon, J. C. CA Parkinson Study Grp DATATOP Invest TI Incidence of and risk factors for cognitive impairment in an early Parkinson disease clinical trial cohort SO NEUROLOGY LA English DT Article ID MENTAL-STATE-EXAMINATION; RATING-SCALE; DEMENTIA; LEVODOPA; DEPRENYL; DYSFUNCTION; PROGRESSION; DISABILITY; TOCOPHEROL; MULTICENTER AB Objective: To investigate the incidence of and risk factors for cognitive impairment in a large, well-defined clinical trial cohort of patients with early Parkinson disease (PD). Methods: The Mini-Mental State Examination (MMSE) was administered periodically over a median follow-up period of 6.5 years to participants in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism trial and its extension studies. Cognitive impairment was defined as scoring 2 standard deviations below age-and education-adjusted MMSE norms. Results: Cumulative incidence of cognitive impairment in the 740 participants with clinically confirmed PD (baseline age 61.0 +/- 9.6 years, Hoehn-Yahr stage 1-2.5) was 2.4% (95% confidence interval: 1.2%-3.5%) at 2 years and 5.8% (3.7%-7.7%) at 5 years. Subjects who developed cognitive impairment (n = 46) showed significant progressive decline on neuropsychological tests measuring verbal learning and memory, visuospatial working memory, visuomotor speed, and attention, while the performance of the nonimpaired subjects (n = 694) stayed stable. Cognitive impairment was associated with older age, hallucinations, male gender, increased symmetry of parkinsonism, increased severity of motor impairment (except for tremor), speech and swallowing impairments, dexterity loss, and presence of gastroenterologic/urologic disorders at baseline. Conclusions: The relatively low incidence of cognitive impairment in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism study may reflect recruitment bias inherent to clinical trial volunteers (e.g., younger age) or limitations of the Mini-Mental State Examination-based criterion. Besides confirming known risk factors for cognitive impairment, we identified potentially novel predictors such as bulbar dysfunction and gastroenterologic/urologic disorders (suggestive of autonomic dysfunction) early in the course of the disease. Neurology (R) 2009;73:1469-1477 C1 [Uc, E. Y.] Univ Iowa, Dept Neurol, Carver Coll Med, Iowa City, IA 52242 USA. [Uc, E. Y.] Vet Affairs Med Ctr, Neurol Serv, Iowa City, IA 52242 USA. [McDermott, M. P.] Univ Rochester, Dept Biostat & Computat Biol, Rochester, NY USA. [McDermott, M. P.; Como, P. G.; Auinger, P.] Univ Rochester, Dept Neurol, Rochester, NY USA. [Marder, K. S.] Columbia Univ, Dept Neurol, New York, NY USA. [Litvan, I.] Univ Louisville, Dept Neurol, Louisville, KY 40292 USA. [Chou, K. L.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Growdon, J. C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Uc, EY (reprint author), Univ Iowa, Dept Neurol, Carver Coll Med, 200 Hawkins Dr 2RCP, Iowa City, IA 52242 USA. EM ergun-uc@uiowa.edu OI Chou, Kelvin/0000-0002-2597-7315; Litvan, Irene/0000-0002-3485-3445 FU Parkinson's Disease Foundation; US Public Health Service (National Institute of Neurological Disorders and Stroke) [NS 24778]; Parkinson Study Group; NIH [NINDS NS044930, NS42372, HD44430, DE16280, NS52619, NS45686, NS46487, NS50095, NS49639, AR52274, NS50573, HL80107, RR24160, NS58259, NS48843, NS36630, 1UL1 RR024156-01, PO412196-G, NIA 5 R01 PAS-03-092, 1 R13 NS062643-01, NINDS NPTUNE (Site PI)]; US Department of Veterans Affairs [B6261R, 1 I01 RX000170]; Parkinson Disease Foundation; Medivation, Inc.; Boehringer Ingelheim; NeuroSearch Sweden AB; Forest Laboratories, Inc.; US Food and Drug Administration; Michael J. Fox Foundation; Spinal Muscular Atrophy Foundation; Muscular Dystrophy Association; Amarin Corporation; Huntington's Disease Society of America; Kyowa Hakko Kirin Pharma, Inc.; University of Louisville; Center for Environmental Genomics and Integrative Biology; Parkinson Support Center of Kentuckiana; National Parkinson Foundation; Movement Disorder Society; CurePSP FX Growdon serves on a scientific advisory board for Neuroimmune Therapeutics AG; serves on editorial boards for Archives of Neurology and Neurodegenerative Diseases; receives royalties from publishing The Dementias (Elsevier, 2007); and receives reserch support from the NIH [NIA P50 AG05134 (Co-PI), NINDS P50 NS037372 (Co-PI), and NINDS R21 NS60310 (PI)] and from the Michael J. Fox Foundation. NR 40 TC 69 Z9 71 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 3 PY 2009 VL 73 IS 18 BP 1469 EP 1477 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 514XN UT WOS:000271429900008 PM 19884574 ER PT J AU Gerstner, ER Yip, S Wang, DL Louis, DN Iafrate, AJ Batchelor, TT AF Gerstner, E. R. Yip, S. Wang, D. L. Louis, D. N. Iafrate, A. J. Batchelor, T. T. TI MGMT METHYLATION IS A PROGNOSTIC BIOMARKER IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA SO NEUROLOGY LA English DT Editorial Material ID METHYLTRANSFERASE; TEMOZOLOMIDE; CELLS C1 [Gerstner, E. R.; Wang, D. L.; Batchelor, T. T.] Massachusetts Gen Hosp, Ctr Canc, Dept Neurol, Boston, MA 02114 USA. [Batchelor, T. T.] Massachusetts Gen Hosp, Ctr Canc, Dept Radiat Oncol, Boston, MA 02114 USA. [Yip, S.; Louis, D. N.; Iafrate, A. J.] Massachusetts Gen Hosp, Ctr Canc, Dept Pathol, Boston, MA 02114 USA. [Gerstner, E. R.; Batchelor, T. T.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gerstner, ER (reprint author), Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM egerstner@partners.org FU NCI NIH HHS [R01CA57683] NR 6 TC 48 Z9 49 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 3 PY 2009 VL 73 IS 18 BP 1509 EP 1510 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 514XN UT WOS:000271429900014 PM 19884580 ER PT J AU Lefkimmiatis, K Moyer, MP Curci, S Hofer, AM AF Lefkimmiatis, Konstantinos Moyer, Mary Pat Curci, Silvana Hofer, Aldebaran M. TI "cAMP Sponge": A Buffer for Cyclic Adenosine 3 ', 5 '-Monophosphate SO PLOS ONE LA English DT Article ID DEPENDENT PROTEIN-KINASE; CELLS; EPAC; PHOSPHORYLATION; COMMUNICATION; INHIBITION; ACTIVATION; INDICATORS; DYNAMICS; CHANNELS AB Background: While intracellular buffers are widely used to study calcium signaling, no such tool exists for the other major second messenger, cyclic AMP (cAMP). Methods/Principal Findings: Here we describe a genetically encoded buffer for cAMP based on the high-affinity cAMP-binding carboxy-terminus of the regulatory subunit RI beta of protein kinase A (PKA). Addition of targeting sequences permitted localization of this fragment to the extra-nuclear compartment, while tagging with mCherry allowed quantification of its expression at the single cell level. This construct (named "cAMP sponge") was shown to selectively bind cAMP in vitro. Its expression significantly suppressed agonist-induced cAMP signals and the downstream activation of PKA within the cytosol as measured by FRET-based sensors in single living cells. Point mutations in the cAMP-binding domains of the construct rendered the chimera unable to bind cAMP in vitro or in situ. Cyclic AMP sponge was fruitfully applied to examine feedback regulation of gap junction-mediated transfer of cAMP in epithelial cell couplets. Conclusions: This newest member of the cAMP toolbox has the potential to reveal unique biological functions of cAMP, including insight into the functional significance of compartmentalized signaling events. RP Lefkimmiatis, K (reprint author), Brigham & Womens Hosp, VA Boston Healthcare Syst, W Roxbury, MA USA. EM ahofer@rics.bwh.harvard.edu RI Lefkimmiatis, Konstantinos/I-1239-2016 OI Lefkimmiatis, Konstantinos/0000-0001-7137-7866 NR 32 TC 12 Z9 12 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 NOV 3 PY 2009 VL 4 IS 11 AR e7649 DI 10.1371/journal.pone.0007649 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 514RY UT WOS:000271414500001 PM 19888343 ER PT J AU Lee, S Verdine, GL AF Lee, Seongmin Verdine, Gregory L. TI Atomic substitution reveals the structural basis for substrate adenine recognition and removal by adenine DNA glycosylase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE base-excision repair; general acid catalysis; substrate recognition ID MISMATCH REPAIR ENZYME; ESCHERICHIA-COLI DNA; C-TERMINAL DOMAIN; EXCISION-REPAIR; CRYSTAL-STRUCTURES; DUPLEX DNA; MUTY; 8-OXOGUANINE; BASES; SPECIFICITY AB Adenine DNA glycosylase catalyzes the glycolytic removal of adenine from the promutagenic A.oxoG base pair in DNA. The general features of DNA recognition by an adenine DNA glycosylase, Bacillus stearothermophilus MutY, have previously been revealed via the X-ray structure of a catalytically inactive mutant protein bound to an A: oxoG-containing DNA duplex. Although the structure revealed the substrate adenine to be, as expected, extruded from the DNA helix and inserted into an extrahelical active site pocket on the enzyme, the substrate adenine engaged in no direct contacts with active site residues. This feature was paradoxical, because other glycosylases have been observed to engage their substrates primarily through direct contacts. The lack of direct contacts in the case of MutY suggested that either MutY uses a distinctive logic for substrate recognition or that the X-ray structure had captured a noncatalytically competent state in lesion recognition. To gain further insight into this issue, we crystallized wild-type MutY bound to DNA containing a catalytically inactive analog of 2'-deoxyadenosine in which a single 2'-H atom was replaced by fluorine. The structure of this fluorinated lesion-recognition complex (FLRC) reveals the substrate adenine buried more deeply into the active site pocket than in the prior structure and now engaged in multiple direct hydrogen bonding and hydrophobic interactions. This structure appears to capture the catalytically competent state of adenine DNA glycosylases, and it suggests a catalytic mechanism for this class of enzymes, one in which general acid-catalyzed protonation of the nucleobase promotes glycosidic bond cleavage. C1 [Lee, Seongmin; Verdine, Gregory L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Verdine, Gregory L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Verdine, Gregory L.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Verdine, Gregory L.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. RP Verdine, GL (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, 12 Oxford St, Cambridge, MA 02138 USA. EM gregory_verdine@harvard.edu FU NCI NIH HHS [CA100742, R01 CA100742] NR 45 TC 37 Z9 39 U1 1 U2 7 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 NOV 3 PY 2009 VL 106 IS 44 BP 18497 EP 18502 DI 10.1073/pnas.0902908106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 514XM UT WOS:000271429800018 PM 19841264 ER PT J AU Rioux, JD Goyette, P Vyse, TJ Hammarstrom, L Fernando, MMA Green, T De Jager, PL Foisy, S Wang, J de Bakker, PIW Leslie, S McVean, G Padyukov, L Alfredsson, L Annese, V Hafler, DA Pan-Hammarstrom, Q Matell, R Sawcer, SJ Compston, AD Cree, BAC Mirel, DB Daly, MJ Behrens, TW Klareskog, L Gregersen, PK Oksenberg, JR Hauser, SL AF Rioux, John D. Goyette, Philippe Vyse, Timothy J. Hammarstroem, Lennart Fernando, Michelle M. A. Green, Todd De Jager, Philip L. Foisy, Sylvain Wang, Joanne de Bakker, Paul I. W. Leslie, Stephen McVean, Gilean Padyukov, Leonid Alfredsson, Lars Annese, Vito Hafler, David A. Pan-Hammarstroem, Qiang Matell, Ritva Sawcer, Stephen J. Compston, Alastair D. Cree, Bruce A. C. Mirel, Daniel B. Daly, Mark J. Behrens, Tim W. Klareskog, Lars Gregersen, Peter K. Oksenberg, Jorge R. Hauser, Stephen L. CA Int MHC Autoimmunity Genetics Netw TI Mapping of multiple susceptibility variants within the MHC region for 7 immune-mediated diseases SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoimmunity; genes; genetics ID MAJOR HISTOCOMPATIBILITY COMPLEX; SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENOME-WIDE ASSOCIATION; INFLAMMATORY-BOWEL-DISEASE; SELECTIVE IGA DEFICIENCY; CLASS-II REGION; RHEUMATOID-ARTHRITIS; LINKAGE-DISEQUILIBRIUM; ULCERATIVE-COLITIS; MYASTHENIA-GRAVIS AB The human MHC represents the strongest susceptibility locus for autoimmune diseases. However, the identification of the true predisposing gene(s) has been handicapped by the strong linkage disequilibrium across the region. Furthermore, most studies to date have been limited to the examination of a subset of the HLA and non-HLA genes with a marker density and sample size insufficient for mapping all independent association signals. We genotyped a panel of 1,472 SNPs to capture the common genomic variation across the 3.44 megabase (Mb) classic MHC region in 10,576 DNA samples derived from patients with systemic lupus erythematosus, Crohn's disease, ulcerative colitis, rheumatoid arthritis, myasthenia gravis, selective IgA deficiency, multiple sclerosis, and appropriate control samples. We identified the primary association signals for each disease and performed conditional regression to identify independent secondary signals. The data demonstrate that MHC associations with autoimmune diseases result from complex, multilocus effects that span the entire region. C1 [Rioux, John D.; Goyette, Philippe; Foisy, Sylvain] Univ Montreal, Res Ctr, Montreal, PQ H1T 1C8, Canada. [Rioux, John D.; Goyette, Philippe; Foisy, Sylvain] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Vyse, Timothy J.; Fernando, Michelle M. A.] Hammersmith Hosp, Div Med, Rheumatol Sect, London W12 0NN, England. [Vyse, Timothy J.; Fernando, Michelle M. A.] Univ London Imperial Coll Sci Technol & Med, London W12 0NN, England. [Hammarstroem, Lennart; Pan-Hammarstroem, Qiang] Karolinska Inst, Div Clin Immunol, SE-14186 Huddinge, Sweden. [Green, Todd; De Jager, Philip L.; Mirel, Daniel B.] Broad Inst, External Projects, Program Med & Populat Genet, Cambridge, MA 02142 USA. [De Jager, Philip L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Program Translat Neuropsychiat Genom, Boston, MA 02115 USA. [de Bakker, Paul I. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Genet, Boston, MA 02115 USA. [Wang, Joanne; Cree, Bruce A. C.; Oksenberg, Jorge R.; Hauser, Stephen L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Leslie, Stephen; McVean, Gilean] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Padyukov, Leonid] Karolinska Inst, Dept Med, Rheumatol Unit, S-17176 Stockholm, Sweden. [Alfredsson, Lars] Karolinska Inst, Inst Environm Med, Cardiovasc Epidemiol Unit, SE-17177 Solna, Sweden. [Annese, Vito] IRCCS CSS Hosp, Dept Med Sci, Ist Ricovero & Cura Carattere Sci Endoscopy & IBD, I-71013 San Giovanni Rotondo, Italy. [Hafler, David A.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA. [Matell, Ritva] Karolinska Univ Hosp Solna, Dept Neurol, SE-17176 Stockholm, Sweden. [Sawcer, Stephen J.; Compston, Alastair D.] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England. [Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Behrens, Tim W.] Genentech Inc, Exploratory Clin Dev Immunol Tissue Growth & Repa, San Francisco, CA 94080 USA. [Klareskog, Lars] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, SE-17177 Solna, Sweden. [Gregersen, Peter K.] N Shore Univ Hosp, Feinstein Inst Med Res, Robert S Boas Ctr Genom & Human Genet, Manhasset, NY 11030 USA. RP Rioux, JD (reprint author), Univ Montreal, Res Ctr, Montreal, PQ H1T 1C8, Canada. EM john.david.rioux@umontreal.ca; hausers@neurology.ucsf.edu RI Fernando, Michelle/F-5554-2012; de Bakker, Paul/B-8730-2009; Rioux, John/A-9599-2015; Hauser, Stephen/J-2978-2016; OI de Bakker, Paul/0000-0001-7735-7858; Rioux, John/0000-0001-7560-8326; Alfredsson, Lars/0000-0003-1688-6697; Klareskog, Lars/0000-0001-9601-6186; Padyukov, Leonid/0000-0003-2950-5670 FU National Institutes of Allergy and Infectious Diseases [AI067152]; National Institute of Diabetes and Digestive and Kidney Diseases [DK064869, DK062432]; National Institute of Neurological Disease and Stroke [NS21799]; Swedish National Research Counci; Medical Research Council [G0000934]; Wellcome Trust [068545/Z/02]; National Center for Research Resources [U54 RR020278] FX This work was supported primarily by Grant AI067152 from the National Institutes of Allergy and Infectious Diseases. Additional support was supplied by Grants DK064869 and DK062432 from the National Institute of Diabetes and Digestive and Kidney Diseases (to J.D.R.), by Grant NS21799 from the National Institute of Neurological Disease and Stroke (to SLH.), and by the Swedish National Research Council. We also thank the disease-specific societies and foundations for support in DNA collections. We acknowledge the use of DNA from the British 1958 Birth Cohort collection (D. Strachan, S. Ring, W. McArdle, and M. Pembrey), funded by the Medical Research Council Grant G0000934 and Wellcome Trust Grant 068545/Z/02. The Broad Institute Center for Genotyping and Analysis is supported by Grant U54 RR020278 from the National Center for Research Resources. NR 61 TC 122 Z9 127 U1 3 U2 14 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 NOV 3 PY 2009 VL 106 IS 44 BP 18680 EP 18685 DI 10.1073/pnas.0909307106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 514XM UT WOS:000271429800049 ER PT J AU Siegrist, MS Unnikrishnan, M McConnell, MJ Borowsky, M Cheng, TY Siddiqi, N Fortune, SM Moody, DB Rubin, EJ AF Siegrist, M. Sloan Unnikrishnan, Meera McConnell, Matthew J. Borowsky, Mark Cheng, Tan-Yun Siddiqi, Noman Fortune, Sarah M. Moody, D. Branch Rubin, Eric J. TI Mycobacterial Esx-3 is required for mycobactin-mediated iron acquisition SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE secretion; siderophore ID GENE-EXPRESSION; PATHOGENIC MYCOBACTERIA; SECRETION SYSTEM; CALMETTE-GUERIN; DNA TRANSFER; TUBERCULOSIS; VIRULENCE; SMEGMATIS; SIDEROPHORE; RD1 AB The Esx secretion pathway is conserved across Gram-positive bacteria. Esx-1, the best-characterized system, is required for virulence of Mycobacterium tuberculosis, although its precise function during infection remains unclear. Esx-3, a paralogous system present in all mycobacterial species, is required for growth in vitro. Here, we demonstrate that mycobacteria lacking Esx-3 are defective in acquiring iron. To compete for the limited iron available in the host and the environment, these organisms use mycobactin, high-affinity iron-binding molecules. In the absence of Esx-3, mycobacteria synthesize mycobactin but are unable to use the bound iron and are impaired severely for growth during macrophage infection. Mycobacteria thus require a specialized secretion system for acquiring iron from siderophores. C1 [Siegrist, M. Sloan; Unnikrishnan, Meera; Siddiqi, Noman; Fortune, Sarah M.; Rubin, Eric J.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [McConnell, Matthew J.; Cheng, Tan-Yun; Moody, D. Branch] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy,Dept Med, Boston, MA 02115 USA. [Borowsky, Mark] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Rubin, EJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM erubin@hsph.harvard.edu OI Rubin, Eric/0000-0001-5120-962X FU Burroughs Wellcome Fund; National Institutes of Health Grants [R01 AI48704, R0171155] FX We gratefully acknowledge Dr. Colin Ratledge for helpful advice and for providing ferri-mycobactin S and ferri-carboxymycobactin S. We also thank Dr. Alfred Goldberg for providing the anti-ClpP1P2 antibody. This work was supported by the Burroughs Wellcome Fund and the National Institutes of Health Grants R01 AI48704 and R0171155. NR 45 TC 113 Z9 123 U1 2 U2 11 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 NOV 3 PY 2009 VL 106 IS 44 BP 18792 EP 18797 DI 10.1073/pnas.0900589106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 514XM UT WOS:000271429800068 PM 19846780 ER PT J AU Brunelle, JK Ryan, J Yecies, D Opferman, JT Letai, A AF Brunelle, Joslyn K. Ryan, Jeremy Yecies, Derek Opferman, Joseph T. Letai, Anthony TI MCL-1-dependent leukemia cells are more sensitive to chemotherapy than BCL-2-dependent counterparts SO JOURNAL OF CELL BIOLOGY LA English DT Article ID MYC-INDUCED LYMPHOMAGENESIS; C-MYC; TRANSGENIC MICE; BH3 DOMAINS; MEMBRANE PERMEABILIZATION; MITOCHONDRIAL APOPTOSIS; ANTIAPOPTOTIC BCL-2; ANTAGONIST ABT-737; BH3-ONLY PROTEINS; IN-VIVO AB Myeloid cell leukemia sequence 1 (MCL-1) and B cell leukemia/lymphoma 2 (BCL-2) are antiapoptotic proteins in the BCL-2 protein family often expressed in cancer. To compare the function of MCL-1 and BCL-2 in maintaining cancer survival, we constructed complementary mouse leukemia models based on E(mu)-Myc expression in which either BCL-2 or MCL-1 are required for leukemia maintenance. We show that the principal anti-apoptotic mechanism of both BCL-2 and MCL- 1 in these leukemias is to sequester pro-death BH3-only proteins rather than BAX and BAK. We find that the MCL-1-dependent leukemias are more sensitive to a wide range of chemotherapeutic agents acting by disparate mechanisms. In common across these varied treatments is that MCL-1 protein levels rapidly decrease in a proteosome-dependent fashion, whereas those of BCL-2 are stable. We demonstrate for the first time that two anti-apoptotic proteins can enable tumorigenesis equally well, but nonetheless differ in their influence on chemosensitivity. C1 [Brunelle, Joslyn K.; Ryan, Jeremy; Yecies, Derek; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02052 USA. [Opferman, Joseph T.] St Jude Childrens Hosp, Dept Biochem, Memphis, TN 38105 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02052 USA. EM Anthony_Letai@dfci.harvard.edu FU National Institutes of Health [P01 CA068484, U01 CA105423, R01 CA129974] FX The authors gratefully acknowledge financial support from National Institutes of Health grants P01 CA068484, U01 CA105423, and R01 CA129974. A. Letai is a Leukemia and Lymphoma Society Scholar. A. Letai is inventor on a patent application regarding BH3 profiling. A. Letai is a founder and head of the scientific advisory board for Eutropics Pharmaceuticals. NR 38 TC 44 Z9 44 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 2 PY 2009 VL 187 IS 3 BP 429 EP 442 DI 10.1083/jcb.200904049 PG 14 WC Cell Biology SC Cell Biology GA 514DJ UT WOS:000271374200013 PM 19948485 ER PT J AU Khan, AM Janneck, LM Bhatt, J Panjabi, R Marjoua, Y Bharwani, A AF Khan, Ali M. Janneck, Laura M. Bhatt, Jay Panjabi, Rajesh Marjoua, Youssra Bharwani, Aleem TI Building a Health-Peace Movement: Academic Medicine's Role in Generating Solutions to Global Problems SO ACADEMIC MEDICINE LA English DT Editorial Material C1 [Khan, Ali M.] Virginia Commonwealth Univ, Off Student Affairs, Sch Med, Richmond, VA 23298 USA. [Khan, Ali M.; Marjoua, Youssra; Bharwani, Aleem] Harvard Kennedy Sch, Cambridge, MA USA. [Janneck, Laura M.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Janneck, Laura M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bhatt, Jay; Panjabi, Rajesh] Harvard Univ, Sch Med, Boston, MA USA. [Bhatt, Jay] Cambridge Hlth Alliance, Cambridge, MA USA. [Panjabi, Rajesh] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Marjoua, Youssra] Yale Univ, Sch Med, New Haven, CT USA. [Bharwani, Aleem] Univ Calgary, Dept Med, Calgary, AB, Canada. RP Khan, AM (reprint author), Virginia Commonwealth Univ, Off Student Affairs, Sch Med, 1101 E Marshall St, Richmond, VA 23298 USA. EM khanam@vcu.edu NR 3 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD NOV PY 2009 VL 84 IS 11 BP 1486 EP 1486 DI 10.1097/ACM.0b013e3181bab2bf PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA V15EV UT WOS:000207786200013 PM 19858797 ER PT J AU Schlozman, SC AF Schlozman, Steven C. TI Using a Socratic Dialogue to Tackle Thorny Issues of Psychiatry SO ACADEMIC MEDICINE LA English DT Article AB Medical students often experience significant cognitive dissonance as they attempt to understand psychiatry. After the security of lab values and medical tests that characterize much of medical practice, the ambiguity of seemingly subjectively obtained information characteristic of psychiatry often leaves students somewhat uncomfortable with how psychiatric diagnoses are made and understood. This is, at its root, an issue of epistemology: How do we know what we say we know? Psychiatry can seem "fuzzy" to medical students, and it behooves psychiatry educators to explicitly address this discomfort but, at the same time, not apologize for the differences between psychiatry and "the rest of medicine." In this article, the author strives to emphasize that this kind of epistemological challenge is ancient and esteemed, represented to some extent in the writings of Plato (who believed that we measure the world by comparing our experience with our innate sense of what we know is true) and Aristotle (who insisted that what we know is based largely on what we can measurably experience). Using humor, an imagined conversation among these ancient philosophers and a modern psychiatrist-medical educator might help to dispel some of the discomfort that psychiatry education sometimes engenders among future physicians. The author presents an example of such a conversation. After a brief discussion of the epistemological differences characteristic of Platonic and Aristotelian views, students could be shown a script similar to the example script and then asked to discuss and debate the arguments elucidated. Perhaps even better, students could be asked to write their own debates based on how Plato or Aristotle would be expected to behave. C1 [Schlozman, Steven C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Schlozman, Steven C.] Harvard Univ, Sch Med, Boston, MA USA. [Schlozman, Steven C.] MGH Hosp, Boston, MA USA. [Schlozman, Steven C.] McLean Hosp, Boston, MA USA. [Schlozman, Steven C.] Harvard Univ, Grad Sch Educ, Boston, MA 02115 USA. RP Schlozman, SC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Yawkey 6900,55 Fruit St, Boston, MA 02114 USA. EM Sschlozman@partners.org NR 24 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD NOV PY 2009 VL 84 IS 11 BP 1562 EP 1566 DI 10.1097/ACM.0b013e3181bb2593 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA V15EV UT WOS:000207786200033 PM 19858818 ER PT J AU Schlozman, SC AF Schlozman, Steven C. TI Using a Socratic Dialogue to Tackle Thorny Issues of Psychiatry SO ACADEMIC MEDICINE LA English DT Article AB Medical students often experience significant cognitive dissonance as they attempt to understand psychiatry. After the security of lab values and medical tests that characterize much of medical practice, the ambiguity of seemingly subjectively obtained information characteristic of psychiatry often leaves students somewhat uncomfortable with how psychiatric diagnoses are made and understood. This is, at its root, an issue of epistemology: How do we know what we say we know? Psychiatry can seem "fuzzy" to medical students, and it behooves psychiatry educators to explicitly address this discomfort but, at not apologize for the differences between psychiatry and "the rest of medicine." In this article, the author strives to emphasize that this kind of epistemological challenge is ancient and esteemed, represented to some extent in the writings of Plato (who believed that we measure the world by comparing our experience with our innate sense of what we know is true) and Aristotle (who insisted that what we know is based largely on what we can measurably experience). Using humor, an imagined conversation among these ancient philosophers and a modern psychiatrist-medical educator might help to dispel some of the discomfort that psychiatry education sometimes engenders among future physicians. The author presents an example of such a conversation. After a brief discussion of the epistemological differences characteristic of Platonic and Aristotelian views, students could be shown a script similar to the example script and then asked to discuss and debate the arguments elucidated. Perhaps even better, students could be asked to write their own debates based on how Plato or Aristotle would be expected to behave. C1 [Schlozman, Steven C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Schlozman, Steven C.] Harvard Univ, Sch Med, Boston, MA USA. [Schlozman, Steven C.] MGH Hosp, Boston, MA USA. [Schlozman, Steven C.] McLean Hosp, Boston, MA USA. [Schlozman, Steven C.] Harvard Univ, Grad Sch Educ, Boston, MA 02115 USA. RP Schlozman, SC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Yawkey 6900,55 Fruit St, Boston, MA 02114 USA. EM Sschlozman@partners.org NR 24 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 NOV PY 2009 VL 84 IS 11 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA V15EV UT WOS:000207786200034 ER PT J AU Abujudeh, HH Kaewlai, R Farsad, K Orr, E Gilman, M Shepard, JAO AF Abujudeh, Hani H. Kaewlai, Rathachai Farsad, Khashayar Orr, Esther Gilman, Matthew Shepard, Jo-Anne O. TI Computed Tomography Pulmonary Angiography: An Assessment of the Radiology Report SO ACADEMIC RADIOLOGY LA English DT Article DE Quality of radiology report; limitations; computed tomographic pulmonary angiography; pulmonary embolism ID NEGATIVE SPIRAL CT; DIAGNOSTIC STRATEGY; CLINICAL-OUTCOMES; THIN-COLLIMATION; PREDICTIVE VALUE; MULTISLICE CT; HELICAL CT; EMBOLISM; OUTPATIENTS; MANAGEMENT AB Rationale and Objective. The aim of this study was to evaluate the uncertainty in computed tomographic pulmonary angiography (CTPA) radiology reports, manifested by descriptions of report limitations and image quality. Materials and Methods. CTPA reports between 2004 and 2006 were reviewed for patient demographic data (age, gender, pregnancy state), radiologist data (years of experience, subspecialty, final dictation by an attending radiologist vs a resident being present and dictating the report), the presence of pulmonary embolism (PE), and key words describing examination quality and limitations. Results. There were 2151 CTPA reports. Patterns of reporting CTPA in the impression sections of radiology reports were as follows: (1) PE conclusively positive (10%), (2) PE conclusively negative (29%), (3) PE negative to segmental arteries (27%), (4) PE negative to central Pulmonary arteries (21%), (5) PE negative but suboptimal examination (8%), and (6) nondiagnostic examination (5%). Among the last three categories, seven PEs were not initially diagnosed but were found on subsequent imaging examinations. Limitations in image quality, respiratory motion artifact, and contrast enhancement were most frequently mentioned as limitations in image quality (62% and 28% of all reports, respectively). Radiologists tended to report limitations in image quality if they were thoracic radiology subspecialists, had >10 years of experience, or worked independently (P < .001). Conclusion. Different patterns of reporting CTPA exist and vary on the basis of individual radiologists' subspecialties, experience, and whether they work independently or with residents. Certain wording regarding the presence of PE may falsely imply negativity of PE in a limited examination. C1 [Abujudeh, Hani H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Abujudeh, HH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM habujudeh@partners.org NR 36 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 2009 VL 16 IS 11 BP 1309 EP 1315 DI 10.1016/j.acra.2009.06.012 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 513EA UT WOS:000271304000002 PM 19692272 ER PT J AU Lee, JM Halpern, EF Rafferty, EA Gazelle, GS AF Lee, Janie M. Halpern, Elkan F. Rafferty, Elizabeth A. Gazelle, G. Scott TI Evaluating the Correlation between Film Mammography and MRI for Screening Women with Increased Breast Cancer Risk SO ACADEMIC RADIOLOGY LA English DT Article DE Mammography; MRI; screening; technology assessment ID HIGH FAMILIAL RISK; BRCA MUTATION CARRIERS; 2 DIAGNOSTIC-TESTS; SURVEILLANCE; MASTECTOMY; ULTRASOUND AB Rationale and Objectives. Breast magnetic resonance imaging (MRI) is increasingly being added to mammography for screening asymptomatic women at increased risk of breast cancer. Because the direction and extent of correlation between mammography and MRI could potentially result in over- or underestimation of the diagnostic gain related to using MRI as an adjunct to mammographic screening, we performed an analysis to evaluate the extent of correlation between mammography and MRI. Materials and Methods. We reviewed the published literature to identify multimodality breast cancer screening studies reporting the sensitivity of mammography and MRi, alone and in combination, for breast cancer diagnosis. After calculating the expected sensitivity of combined mammography and MRI under conditions of test independence (no correlation), we compared the calculated and observed sensitivities for combined mammography and MRI. We then calculated correlation coefficients for mammography and MRI. Results. Seven studies of multimodality screening in women at increased risk of developing breast cancer were included for analysis. Of these studies, the correlation between film mammography and MRI was positive in three studies, negative in two studies, and not identified in two studies. The calculated correlation coefficients ranged from -0.38 to 0.18. In six of seven studies, the 95% confidence interval for the correlation coefficient included 0.0, indicating no significant correlation. Conclusions. Evidence from published trials of multimodality breast cancer screening identified no statistically significant correlation between film mammography and MRI. Using both tests for breast cancer screening is likely to improve the early detection of breast cancer in women at increased risk. C1 [Lee, Janie M.; Halpern, Elkan F.; Rafferty, Elizabeth A.; Gazelle, G. Scott] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA 02114 USA. RP Lee, JM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM jlee45@partners.org FU National Cancer Institute [1K07CA128816] FX Supported by grant funding from the National Cancer Institute (author JML, 1K07CA128816). The authors thank Dr. Etta Pisano and Dr. Constantine Gatsonis for their thoughtful comments on the draft manuscript. NR 24 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 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 2009 VL 16 IS 11 BP 1323 EP 1328 DI 10.1016/j.acra.2009.05.011 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 513EA UT WOS:000271304000004 PM 19632865 ER PT J AU Nagata, K Singh, AK Sangwaiya, MJ Nappi, J Zalis, ME Cai, WL Yoshida, H AF Nagata, Koichi Singh, Anand Kumar Sangwaiya, Minal Jagtiani Naeppi, Janne Zalis, Michael E. Cai, Wenli Yoshida, Hiroyuki TI Comparative Evaluation of the Fecal-Tagging Quality in CT Colonography: Barium vs. Iodinated Oral Contrast Agent SO ACADEMIC RADIOLOGY LA English DT Article DE Computed tomography; virtual colonoscopy; tagging; iodinated contrast; barium ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; SMALL-BOWEL OBSTRUCTION; CONVENTIONAL COLONOSCOPY; CATHARTIC PREPARATION; VIRTUAL COLONOSCOPY; PATIENT ACCEPTANCE; PERFORMANCE; IOHEXOL; MEDIA; FEASIBILITY AB Rationale and Objectives. The purpose of this evaluation was to compare the tagging quality of a barium-based regimen with that of iodine-based regimens for computed tomographic (CT) colonography. Materials and Methods. Tagging quality was assessed retrospectively in three different types of fecal-tagging CT colonographic cases: 24 barium-based cases, 22 nonionic iodine-based cases, and 24 ionic iodine-based cases. For the purpose of evaluation, the large intestine was divided into six segments, and the tagging homogeneity of a total of 420 segments (70 patients) was graded by three blinded readers from 0 (heterogeneous) to 4 (homogeneous). Results. For barium-based cases, the average score for the three readers was 2.4, whereas it was 3.4 for nonionic iodine and 3.6 for ionic iodine. The percentages of segments that were assigned scores of 4 (excellent tagging [100%]) were 11.6%, 61.9%, and 72.9% for the barium-based, nonionic iodine-based, and ionic iodine-based regimens, respectively. The homogeneity scores of iodine-based fecal-tagging regimens were significantly higher than those of the barium-based fecal-tagging regimen (P < .001). The CT attenuation values of tagging in the cases were also assessed: the minimum and maximum values were significantly higher for the iodine-based regimens than for the barium-based regimen (P < .001). Conclusions. The iodine-based fecal-tagging regimens provide significantly greater homogeneity in oral-tagging fecal material than the barium-based fecal-tagging regimen. Iodine-based fecal-tagging regimens can provide an appropriate method for use in nonlaxative or minimum-laxative CT colonography. C1 [Nagata, Koichi; Singh, Anand Kumar; Naeppi, Janne; Cai, Wenli; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Imaging Lab 3D, Dept Radiol, Boston, MA 02114 USA. [Sangwaiya, Minal Jagtiani; Zalis, Michael E.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Nagata, K (reprint author), Massachusetts Gen Hosp, Imaging Lab 3D, Dept Radiol, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM nagata7@aol.com RI Nappi, Janne/B-9424-2008 OI Nappi, Janne/0000-0002-0108-0992 FU GE (Milwaukee, WI) FX Dr Zalis received a research grant from GE (Milwaukee, WI). NR 35 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 2009 VL 16 IS 11 BP 1393 EP 1399 DI 10.1016/j.acra.2009.05.003 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 513EA UT WOS:000271304000013 PM 19596591 ER PT J AU Collinger, JL Gagnon, D Jacobson, J Impink, BG Boninger, ML AF Collinger, Jennifer L. Gagnon, Dany Jacobson, Jon Impink, Bradley G. Boninger, Michael L. TI Reliability of Quantitative Ultrasound Measures of the Biceps and Supraspinatus Tendons SO ACADEMIC RADIOLOGY LA English DT Article DE Ultrasound; reliability; tendon; biceps; supraspinatus ID ROTATOR CUFF; SONOGRAPHY; SHOULDER; TENDINOPATHY; CHILDREN; MUSCLES; DISEASE; IMAGES; INDEX AB Rationale and Objectives. Ultrasound is a proven method for examining soft tissue structures, including tendons, and recently quantitative ultrasound has become more prevalent in research settings. However, limited reliability data have been published for these new quantitative ultrasound measures. The main objective of this study was to quantify the reliability and measurement error of multiple quantitative ultrasound imaging protocols for the biceps and supraspinatus tendons. Materials and Methods. Two examiners captured ultrasound images of the non-dominant long head of the biceps tendon and supraspinatus tendon from 15 able-bodied participants and five manual wheelchair users. Each examiner captured two images per subject under two different preparations, which included subject positioning and reference marker placement. Image processing (reading) was performed twice to compute nine quantitative ultrasound measures of grayscale tendon appearance using first-order statistics and texture analysis. Generalizability theory was applied to compute interrater and intrarater reliability using the coefficient of dependability (Phi) for multiple study design protocols. Results. Interrater reliability was generally low (0.26 < Phi < 0.82), and it is recommended that a single evaluator capture all images for quantitative ultrasound protocols. Most of the quantitative ultrasound measures (n = 14 of 18) exhibited at least moderate (Phi > 0.50) intrarater reliability for a single image captured under one preparation and read once. Conclusion. By following a protocol designed to minimize measurement error, one can increase the reliabdity of quantitative ultrasound measures. An appropriately designed protocol will allow quantitative ultrasound to be used as an outcome measure to identify structural changes within tendons. C1 [Collinger, Jennifer L.; Gagnon, Dany; Impink, Bradley G.; Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. [Collinger, Jennifer L.; Gagnon, Dany; Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Collinger, Jennifer L.; Impink, Bradley G.; Boninger, Michael L.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Gagnon, Dany] Univ Montreal, Fac Med, Sch Rehabil, Montreal, PQ H3C 3J7, Canada. [Jacobson, Jon] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. RP Boninger, ML (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 7180 Highland Dr,Bldg 4,151R-1, Pittsburgh, PA 15206 USA. EM boninger@pitt.edu OI Jacobson, Jon/0000-0002-3676-6628; Boninger, Michael/0000-0001-6966-919X FU Office of Research and Development, Rehabilitation Research & Development Service, US Department of Veterans Affairs (Washington, DC) [B3142C]; National Institutes of Health (Bethesda, MD) [R21HD054529]; National Institute on Disability and Rehabilitation Research's Rehabilitation Engineering Research Center on Spinal Cord Injury (Arlington, VA) [H133E070024]; National Science Foundation; Fonds de la Recherche en Sante du Quebec (Montreal, QC, Canada) FX This material is based on work supported by grant B3142C from the Office of Research and Development, Rehabilitation Research & Development Service, US Department of Veterans Affairs (Washington, DC); grant R21HD054529 from the National Institutes of Health (Bethesda, MD); grant H133E070024 the National Institute on Disability and Rehabilitation Research's Rehabilitation Engineering Research Center on Spinal Cord Injury (Arlington, VA); and a National Science Foundation graduate research fellowship. D.G. held a postdoctoral scholarship from Fonds de la Recherche en Sante du Quebec (Montreal, QC, Canada) at the time of this study. NR 22 TC 22 Z9 23 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 2009 VL 16 IS 11 BP 1424 EP 1432 DI 10.1016/j.acra.2009.05.001 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 513EA UT WOS:000271304000017 PM 19596592 ER PT J AU Johansen, KL AF Johansen, Kirsten L. TI Anabolic and Catabolic Mechanisms in End-Stage Renal Disease SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE Muscle catabolism; End-Stage Renal Disease (ESRD); Catabolism ID INTRADIALYTIC PARENTERAL-NUTRITION; MALNOURISHED HEMODIALYSIS-PATIENTS; UBIQUITIN-PROTEASOME PATHWAY; SKELETAL-MUSCLE HYPERTROPHY; HUMAN GROWTH-HORMONE; BODY PROTEIN-DEGRADATION; CHRONIC KIDNEY-DISEASE; P70 S6 KINASE; AMINO-ACID; WHOLE-BODY AB Muscle wasting is a prominent feature of end-stage renal disease and is associated with muscle weakness and poor physical functioning. Potential reasons for muscle wasting include advancing age, sedentary behavior, inflammation, poor nutritional intake, androgen deficiency, oxidative stress, metabolic acidosis, and insulin resistance. Each of these conditions can be associated with decreased protein synthesis, increased protein degradation, or both. The primary muscle protein synthesis pathway is the insulin insulin-like growth factor-1/phosphatidyl inositol-3 kinase/Akt pathway, which results in the phosphorylation of the mammalian target of rapamycin and subsequent increased protein synthesis. The major protein degradation pathway is the ubiquitin-proteasome system. This review discusses the ways in which end-stage renal disease tips the balance of protein turnover towards catabolism and the mechanisms by which various interventions may work to mitigate wasting or even cause anabolism. (C) 2009 by the National Kidney Foundation, Inc. All rights reselved. C1 [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, Box 111J,4150 Clement St, San Francisco, CA 94121 USA. EM Kirsten.johansen@ucsf.edu NR 68 TC 12 Z9 13 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 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD NOV PY 2009 VL 16 IS 6 BP 501 EP 510 DI 10.1053/j.ackd.2009.07.007 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 508LJ UT WOS:000270932500010 PM 19801138 ER PT J AU Thomas, MA Yaremchuk, MJ AF Thomas, Mathew A. Yaremchuk, Michael J. TI Masseter Muscle Reattachment After Mandibular Angle Surgery SO AESTHETIC SURGERY JOURNAL LA English DT Article AB Background: Altering the dimensions of the mandibular angle by alloplastic augmentation or skeletal reduction requires elevation of the insertion of the masseter muscle, including the pterygomasseteric sling. Disruption of the pterygomasseteric sling during exposure of the inferior border of the mandible can cause the masseter muscle to retract superiorly, resulting in a loss of soft tissue volume over the angle of the mandible and a skeletonized appearance. Subsequent contraction of the masseter elevates the disinserted edge of the muscle and not only increases the skeletonized area, but also exaggerates the deficiency by causing a soft tissue bulge above it. Objective: The authors describe the disinsertion of the masseter and the resulting deformity as a potential complication of mandibular angle surgery and review the technique for repair. Methods: The records of 60 patients (44 primary, 16 secondary) who presented for alloplastic mandible augmentation between 2003 and 2008 were reviewed. Results: Nine patients presented with clinical signs of disruption of the pterygomasseteric sling after mandibular angle surgery. Five patients had clinical signs consistent with complete disruption. Two of these patients requested reconstruction. The other four had signs consistent with partial disruption. Through a Risdon approach, the masseter was successfully reinserted using drill holes placed at the inferior border of the mandible. Conclusions: Masseter disinsertion is a previously unreported sequelae after aesthetic surgery for the angle of the mandible. The resultant static and dynamic contour deformity can be corrected by reattaching the muscle to the inferior border of the mandible. (Aesthet Surg J; 29:473-476.) C1 [Thomas, Mathew A.; Yaremchuk, Michael J.] Massachusetts Gen Hosp, Dept Surg, Div Plast Surg, Boston, MA 02114 USA. [Thomas, Mathew A.; Yaremchuk, Michael J.] Harvard Univ, Sch Med, Boston, MA USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Plast Surg, 15 Parkman St,Wang 435, Boston, MA 02114 USA. EM dr.y@dryaremchuk.com NR 15 TC 3 Z9 3 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-820X J9 AESTHET SURG J JI Aesthet. Surg. J. PD NOV PY 2009 VL 29 IS 6 BP 473 EP 476 DI 10.1016/j.asj.2009.09.006 PG 4 WC Surgery SC Surgery GA V20LC UT WOS:000208140500005 PM 19944991 ER PT J AU Lawrence, I Moy, R AF Lawrence, Ira Moy, Ronald TI An Evaluation of Neutralizing Antibody Induction During Treatment of Glabellar Lines with a New US Formulation of Botulinum Neurotoxin Type A SO AESTHETIC SURGERY JOURNAL LA English DT Article AB BACKGROUND: The induction of neutralizing antibodies during the aesthetic application of botulinum neurotoxin type A is rare, but of potential clinical concern. Phase III studies of a new US formulation of botulinum neurotoxin type A, Dysport (BoNTA-ABO [abobotulinumtoxinA]; Medicis Aesthetics, Scottsdale, AZ), have not identified any cases of neutralizing antibody formation during the treatment of glabellar lines in patients who received up to nine treatments. OBJECTIVE: To provide an in-depth analysis of the potential for induction of neutralizing antibodies in the study population enrolled in phase III trials of BoNTA-ABO in the treatment of glabellar lines. METHODS: First and last available serum samples from patients in the BoNTA-ABO Glabellar Lines Development Program were screened for BoNTA-ABO antibodies with a radioimmunoprecipitation assay (RIPA), followed by a confirmatory competitive assay (RIPA-C). Confirmed RIPA-C-positive samples were further evaluated for the presence of neutralizing antibodies using a mouse protection assay (MPA), a highly specific bioassay for neutralizing antibodies. We conducted safety and efficacy evaluations, including day 30 responder rate (a rating of no or mild glabellar lines) and duration of response in the last treatment cycle. RESULTS: Of 1554 patients who received at least one BoNTA-ABO treatment (10 units at five injection points, for a total dose of 50 units/treatment; range one to nine treatments), five (0.32%) were antibody positive on the RIPA-C assay-two at baseline and three at the last treatment cycle. None of the RIPA-C-positive samples tested positive for neutralizing antibodies upon further evaluation using the highly specific MPA. Of note, the RIPA-C-positive group had a responder rate of 100% and a mean response of 103.3 days, while the RIPA-C-negative group had a responder rate of 90% and a mean response of 89.4 days. The safety of BoNTA-ABO did not appear to be altered in the RIPA-C-positive group. CONCLUSIONS: At the dose and treatment interval used in the correction of glabellar lines, induction of neutralizing antibodies to BoNTA-ABO was not observed. None of the five samples that initially gave positive results in a RIPA-C assay were positive when further evaluated using the MPA. Clinically, RIPA-C-positive status did not correlate with any reduction in efficacy or an altered safety profile, although the small numbers prevent definitive conclusions. These data suggest that the five RIPA-C-positive samples represented false positives. (Aesthetic Surg J 2009;29:S66-S71.) C1 [Lawrence, Ira] Medicis Pharmaceut Corp, Res & Dev, Scottsdale, AZ USA. [Moy, Ronald] W Los Angeles Vet Affairs Med Ctr, Fincher Med Grp, Los Angeles, CA 90073 USA. [Moy, Ronald] Univ Calif Los Angeles, David Geffen Sch Med, Moy Fincher Med Grp, Los Angeles, CA 90024 USA. RP Moy, R (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Moy Fincher Med Grp, 100 UCLA Med Plaza,Suite 590, Los Angeles, CA 90024 USA. EM rmoy@ucla.edu FU Medicis Aesthetics (Scottsdale, AZ) FX The authors were compensated for their contributions in preparing this manuscript and as investigators for this study. The writing of this manuscript was funded by Medicis Aesthetics (Scottsdale, AZ). Dr. Lawrence is employed by Medicis Pharmaceutical, the distributor of Dysport for aesthetic use in the United States. Dr. Moy was a paid investigator for Inamed (Santa Barbara, CA). He has no financial arrangements with Medicis Aesthetics. NR 22 TC 8 Z9 8 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-820X J9 AESTHET SURG J JI Aesthet. Surg. J. PD NOV PY 2009 VL 29 IS 6 SU S BP S66 EP S71 DI 10.1016/j.asj.2009.09.009 PG 6 WC Surgery SC Surgery GA V20LB UT WOS:000208140400007 PM 19945007 ER PT J AU Federman, AD Cole, H Sano, M AF Federman, Alex D. Cole, Helen Sano, Mary TI Cognitive performance in community-dwelling English- and Spanish-speaking seniors SO AGE AND AGEING LA English DT Article DE elderly; cognition; language; Spanish ID NEUROPSYCHOLOGICAL TEST-PERFORMANCE; MINI-MENTAL-STATE; VERBAL FLUENCY; NORMATIVE DATA; EDUCATION; ELDERS; AGE; IMPAIRMENT; DISABILITY; AMERICAN AB Design: cross-sectional. Setting: community-based settings in New York City, including senior centres and residential complexes. Subjects: four hundred and twenty independently living adults aged 60 or older (mean 73.8 years). Methods: participants completed the Mini-Mental State Exam (MMSE), animal naming test (ANT) and Wechsler Memory Scale III (WMS) Story A immediate and delayed subtests. Scores were examined by strata of language, age or education and for different thresholds of the MMSE. We tested the association of language and cognitive test performance using multivariable linear regression. Results: twenty-one per cent of subjects were interviewed in Spanish and 16.2% reported poor-fair English proficiency. The mean WMS scores were not statistically different between English and Spanish groups (immediate recall, 9.9 vs 9.5, P = 0.44; delayed recall, 8.0 vs 7.6, P = 0.36, respectively), whereas ANT scores did differ (16.6 vs 14.3, P < 0.0001). These associations were consistent across MMSE thresholds. The association of language and ANT score was not significant after accounting for education. Conclusions: we found little difference in performance on the Story A subtests from the WMS suggesting that this test may be used for both English- and Spanish-speaking populations. Results suggest that variations in ANT performance may be accounted for by adjusting for the level of education. These results have important implications for the generalisability of test scores among diverse older populations. C1 [Federman, Alex D.; Cole, Helen] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY 10029 USA. [Sano, Mary] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Sano, Mary] Bronx Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. RP Federman, AD (reprint author), Mt Sinai Sch Med, Div Gen Internal Med, 1 Gustave L Levy Pl,Box 1087, New York, NY 10029 USA. EM alex.federman@mssm.edu FU National Institute on Aging [1K23AG028955-01]; Mount Sinai School of Medicine Alzheimer's Disease Research Center (NIH) [AG0051318] FX This study was supported by a Paul B. Beeson Career Development Award in Aging from the National Institute on Aging (Dr. Federman, 1K23AG028955-01). Additional support was provided by the Mount Sinai School of Medicine Alzheimer's Disease Research Center (NIH AG0051318). NR 29 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0002-0729 J9 AGE AGEING JI Age Ageing PD NOV PY 2009 VL 38 IS 6 BP 669 EP 675 DI 10.1093/ageing/afp127 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 510QQ UT WOS:000271106000006 PM 19651699 ER PT J AU Thomas, B Mimiaga, MJ Mayer, KH Johnson, CV Menon, S Chandrasekaran, V Murugesan, P Swaminathan, S Safren, SA AF Thomas, Beena Mimiaga, Matthew J. Mayer, Kenneth H. Johnson, Carey V. Menon, Sunil Chandrasekaran, V. Murugesan, P. Swaminathan, Soumya Safren, Steven A. TI HIV Prevention Interventions in Chennai, India: Are Men Who Have Sex with Men Being Reached? SO AIDS PATIENT CARE AND STDS LA English DT Article ID BASE-LINE DATA; RISK BEHAVIORS; PREVALENCE; INFECTION; EXPLORE; STATES AB India has the greatest number of HIV infections in Asia and the third highest total number of infected persons globally. Men who have sex with men (MSM) are considered by the Government of India's National AIDS Control Organization (NACO) a "core risk group" for HIV in need of HIV prevention efforts. However there is a dearth of information on the frequency of participation in HIV prevention interventions and subsequent HIV risk and other correlates among MSM in India. Recruited through peer outreach workers, word of mouth and snowball sampling techniques, 210 MSM in Chennai completed an interviewer-administered assessment, including questions about participating in any HIV prevention interventions in the past year, sexual risk taking, demographics, MSM identities, and other psychosocial variables. Bivariate and multivariable logistic regression procedures were used to examine behavioral and demographic correlates with HIV prevention intervention participation. More than a quarter (26%) of the sample reported participating in an HIV prevention intervention in the year prior to study participation. Participants who reported engaging in unprotected anal sex (UAS; odds ratio [OR] = 0.28; p = 0.01) in the 3 months prior to study enrollment were less likely to have participated in an HIV prevention program in the past year. MSM who were older (OR = 1.04; p = 0.05), kothis (feminine acting/appearing and predominantly receptive partners in anal sex) compared to panthis (masculine appearing, predominantly insertive partners; OR = 5.52, p = 0.0004), those with higher educational attainment (OR = 1.48, p = 0.01), being "out" about having sex with other men (OR = 4.03, p = 0.0001), and MSM who reported ever having been paid in exchange for sex (OR = 2.92, p = 0.001) were more likely to have reported participation in an HIV prevention intervention in the preceding year. In a multivariable model, MSM reporting UAS in the prior 3 months were less likely to have participated in an HIV prevention intervention (AOR = 0.34, p = 0.04). MSM who were older (AOR = 1.05, p = 0.05), those with higher educational attainment (AOR = 1.92, p = 0.0009), and MSM who were "out" about having sex with other men (AOR = 2.71, p = 0.04) were more likely to have reported participating in an HIV prevention program. Findings suggest that exposure to HIV prevention interventions may be protective against engaging in UAS for some MSM in India. Understanding predictors of participation in an HIV prevention intervention is helpful for identifying Indian MSM who might have had no exposure to HIV prevention information and skills building, hence allowing researchers and prevention workers to focus efforts on individuals at greatest need. C1 [Thomas, Beena; Chandrasekaran, V.; Murugesan, P.; Swaminathan, Soumya] Indian Council Med Res, TB Res Ctr, Madras, Tamil Nadu, India. [Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Mimiaga, Matthew J.; Mayer, Kenneth H.; Johnson, Carey V.; Safren, Steven A.] Fenway Inst, Boston, MA USA. [Mayer, Kenneth H.] Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA. [Menon, Sunil] Sahodaran, Madras, Tamil Nadu, India. RP Mimiaga, MJ (reprint author), Harvard MGH Behav Med, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM mmimiaga@partners.org FU [P30A1060354]; [MH085314] FX Funding for data collection for this project was supported by a supplement to grant P30A1060354 on which Bruce Walker, M. D. is the PI, and Steven A. Safren, Ph. D. was the PI of the supplement. Support for some staff time for analysis and manuscript preparation was from grant MH085314 (Safren). NR 35 TC 22 Z9 22 U1 1 U2 3 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 NOV PY 2009 VL 23 IS 11 BP 981 EP 986 DI 10.1089/apc.2009.0092 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 522KD UT WOS:000271995700010 PM 19821722 ER PT J AU Marinkovic, K Oscar-Berman, M Urban, T O'Reilly, CE Howard, JA Sawyer, K Harris, GJ AF Marinkovic, Ksenija Oscar-Berman, Marlene Urban, Trinity O'Reilly, Cara E. Howard, Julie A. Sawyer, Kayle Harris, Gordon J. TI Alcoholism and Dampened Temporal Limbic Activation to Emotional Faces SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE Alcoholism; Emotion; Faces; Amygdala; Functional Magnetic Resonance Imaging ID FACIAL EXPRESSION RECOGNITION; AFFECTIVE PROSODY COMPREHENSION; SURFACE-BASED ANALYSIS; PREFRONTAL CORTEX; CORTICAL SURFACE; FUNCTIONAL MRI; HUMAN AMYGDALA; HIPPOCAMPAL VOLUME; COORDINATE SYSTEM; HUMAN BRAIN AB Background: Excessive chronic drinking is accompanied by a broad spectrum of emotional changes ranging from apathy and emotional flatness to deficits in comprehending emotional information, but their neural bases are poorly understood. Methods: Emotional abnormalities associated with alcoholism were examined with functional magnetic resonance imaging in abstinent long-term alcoholic men in comparison to healthy demographically matched controls. Participants were presented with emotionally valenced words and photographs of faces during deep (semantic) and shallow (perceptual) encoding tasks followed by recognition. Results: Overall, faces evoked stronger activation than words, with the expected material-specific laterality (left hemisphere for words, and right for faces) and depth of processing effects. However, whereas control participants showed stronger activation in the amygdala and hippocampus when viewing faces with emotional (relative to neutral) expressions, the alcoholics responded in an undifferentiated manner to all facial expressions. In the alcoholic participants, amygdala activity was inversely correlated with an increase in lateral prefrontal activity as a function of their behavioral deficits. Prefrontal modulation of emotional function as a compensation for the blunted amygdala activity during a socially relevant face appraisal task is in agreement with a distributed network engagement during emotional face processing. Conclusions: Deficient activation of amygdala and hippocampus may underlie impaired processing of emotional faces associated with long-term alcoholism and may be a part of the wide array of behavioral problems including disinhibition, concurring with previously documented interpersonal difficulties in this population. Furthermore, the results suggest that alcoholics may rely on prefrontal rather than temporal limbic areas in order to compensate for reduced limbic responsivity and to maintain behavioral adequacy when faced with emotionally or socially challenging situations. C1 [Marinkovic, Ksenija] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Urban, Trinity] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02215 USA. [Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Oscar-Berman, Marlene; Howard, Julie A.; Sawyer, Kayle] VA Healthcare Syst, Psychol Res Serv, Boston, MA USA. [Urban, Trinity; Harris, Gordon J.] Massachusetts Gen Hosp, Radiol Comp Aided Diagnost Lab, Boston, MA 02114 USA. [O'Reilly, Cara E.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Marinkovic, K (reprint author), Univ Calif San Diego, Dept Radiol, 9500 Gilman Dr 0841, La Jolla, CA 92093 USA. EM xenia@ucsd.edu OI Sawyer, Kayle/0000-0001-7767-5688 FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [R01-AA07112, K05-AA00219, K01-AA13402, R01-AA016624]; Medical Research Service of the US Department of Veterans Affairs; Alcoholic Beverage Medical Research Foundation; MIND Institute; [P41RR14075] FX This research was supported by funds from the National Institute on Alcohol Abuse and Alcoholism (NIAAA), grants R01-AA07112 and K05-AA00219, and Medical Research Service of the US Department of Veterans Affairs to Dr. Marlene Oscar-Berman; NIAAA K01-AA13402, R01-AA016624, and Alcoholic Beverage Medical Research Foundation to Dr. Ksenija Marinkovic, by P41RR14075, and MIND Institute. We thank Diane Merritt for recruitment assistance and Sheeva Azma and Susan Mosher for help with data collection and analysis. NR 113 TC 48 Z9 49 U1 6 U2 7 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 NOV PY 2009 VL 33 IS 11 BP 1880 EP 1892 DI 10.1111/j.1530-0277.2009.01026.x PG 13 WC Substance Abuse SC Substance Abuse GA 509YA UT WOS:000271054000005 PM 19673745 ER PT J AU Griffin, WC Lopez, MF Becker, HC AF Griffin, William C., III Lopez, Marcelo F. Becker, Howard C. TI Intensity and Duration of Chronic Ethanol Exposure Is Critical for Subsequent Escalation of Voluntary Ethanol Drinking in Mice SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Dependence; Excessive Drinking; Alcohol; Mouse ID ALCOHOL-USE DISORDERS; C57BL/6J MICE; REPEATED CYCLES; ANIMAL-MODELS; INTERMITTENT; DEPENDENCE; WITHDRAWAL; CONSUMPTION; ANTAGONIST; ALLOSTASIS AB Background: Excessive alcohol drinking continues to be an important health problem. Recent studies from our laboratory and others have demonstrated that animal models of ethanol dependence and relapse can contribute to understanding factors that contribute to excessive drinking. In this study, we tested the hypothesis that the amount and duration of ethanol exposure is critical for promoting the escalation in drinking by mice given access to ethanol in a limited access paradigm. Methods: We used several methods of chronic intermittent ethanol exposure in male C57BL/6J mice that would vary in the amount and duration of exposure to ethanol as indicated by blood ethanol concentrations (BEC). After establishing baseline drinking in the mice using a 2 hours, 2 bottle choice drinking paradigm, each study involved alternating between periods of ethanol exposure and periods of limited access to ethanol (1 cycle) for a total of 3 cycles. In Study 1, mice were allowed extended access (16 hours) to ethanol for oral consumption or remained in the home cage. In Study 2, the ethanol exposure consisted of intragastric gavage of increasing doses of ethanol or isocaloric sucrose as the control. Study 3 compared intragastric gavage combined with pyrazole, an alcohol dehydrogenase inhibitor, with vapor inhalation of ethanol using procedures known to lead to increased drinking in mice. Finally, Study 4 was a retrospective review of several studies conducted in our laboratory using inhalation procedures. The retrospective review encompassed a range of postvapor chamber BEC values and ethanol intakes that would allow a relationship between increased drinking and BEC to be examined. Results: Allowing mice to drink for longer periods of time did not cause increased drinking in subsequent limited access sessions. Likewise, gastric intubation of ethanol which produced high BEC (> 300 mg/dl) with or without pyrazole did not increase drinking. Only the vapor inhalation procedure, which was associated with sustained BEC above 175 mg/dl for the entire exposure period resulted in increased drinking. The retrospective study provided further evidence that sustained BEC levels above 175 mg/dl was critical to the escalation in drinking. Conclusions: We found that the intensity (amount) and duration of ethanol exposure, indexed by BEC, is critical to produce increased drinking in mice. Specifically, BEC must regularly exceed 175 mg/dl for the escalation in drinking to occur. Future studies will examine neurobiological adaptations that may underlie the increased drinking behavior caused by chronic intermittent ethanol exposure. C1 [Griffin, William C., III; Lopez, Marcelo F.; Becker, Howard C.] Med Univ S Carolina, Ctr Drug & Alcohol Programs, Dept Psychiat & Behav Sci, Charleston Alcohol Res Ctr, Charleston, SC 29425 USA. [Becker, Howard C.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Becker, Howard C.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Griffin, WC (reprint author), Med Univ S Carolina, Ctr Drug & Alcohol Programs, Dept Psychiat & Behav Sci, Charleston Alcohol Res Ctr, MSC 861, Charleston, SC 29425 USA. EM griffinw@musc.edu FU NIH [AA10716, AA14095, AA13885] FX This work was supported by NIH grants AA10716, AA14095, and AA13885. The authors acknowledge the expert technical assistance of Melissa Overstreet, Laura Ralston, and Kay Fernandes in conducting these studies. NR 25 TC 60 Z9 61 U1 2 U2 2 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 NOV PY 2009 VL 33 IS 11 BP 1893 EP 1900 DI 10.1111/j.1530-0277.2009.01027.x PG 8 WC Substance Abuse SC Substance Abuse GA 509YA UT WOS:000271054000006 PM 19673744 ER PT J AU Thomas, D Giugliano, RP AF Thomas, Deepak Giugliano, Robert P. TI Management of ST-segment elevation myocardial infarction: Comparison of the updated guidelines from North America and Europe SO AMERICAN HEART JOURNAL LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; CONVERTING-ENZYME INHIBITORS; PLACEBO-CONTROLLED TRIAL; FIBRINOLYTIC THERAPY; RESCUE ANGIOPLASTY; FOLLOW-UP; UNFRACTIONATED HEPARIN; THROMBUS ASPIRATION; RANDOMIZED-TRIALS; MULTICENTER TRIAL AB The American College of Cardiology/American Heart Association and the European Society of Cardiology each recently published updated guidelines for management of patients with acute ST elevation myocardial infarction. In this article, we highlight the most important new recommendations, review their supporting data, and describe differences between the guidelines. Key aspects of these updates include detailed guidance regarding the selection of a reperfusion strategy and the incorporation of newer adjunctive antithrombotic agents. Both new guidelines suggest caution in the administration of intravenous beta-blockers, avoidance of nonsteroidal anti-inflammatory agents, and support a more aggressive approach to secondary risk factor management. The 2 guidelines have some nuanced differences as well as some recommendations that are unique to each guideline. They present different levels of support for the 4 available adjunctive parenteral anticoagulants, vary in their endorsement of routine elective coronary angiography after fibrinolysis, and cite different targets for low density lipoprotein long-term. Major unique recommendations include the American College of Cardiology/American Heart Assocaition's emphasis of a stepped approach to analgesia in patients with musculoskeletal pain beginning with acetaminophen or aspirin and a lower target international normalized ratio in patients receiving warfarin, aspirin, and clopidogrel. Meanwhile, unique recommendations in the European Society of Cardiology guidelines include measures to prevent/treat microvascular obstruction and reperfusion injury associated with percutaneous coronary intervention and greater emphasis on maintaining eugylcemia. As these guidelines represent an evidence based approach, health care providers should become familiar with the new data and the resultant updated recommendations to ensure optimal treatment of their patients with ST-elevation myocardial infarction. (Am Heart J 2009;158:695-705.) C1 [Thomas, Deepak; Giugliano, Robert P.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. RP Giugliano, RP (reprint author), TIMI Study Off, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM rgiugliano@partners.org NR 51 TC 8 Z9 8 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 2009 VL 158 IS 5 BP 695 EP 705 DI 10.1016/j.ahj.2009.08.023 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 512UD UT WOS:000271275400001 PM 19853685 ER PT J AU Bamberg, F Truong, QA Blankstein, R Nasir, K Lee, H Rogers, IS Achenbach, S Brady, TJ Nagurney, JT Reiser, MF Hoffmann, U AF Bamberg, Fabian Truong, Quynh A. Blankstein, Ron Nasir, Khurram Lee, Hang Rogers, Ian S. Achenbach, Stephan Brady, Thomas J. Nagurney, John T. Reiser, Maximilian F. Hoffmann, Udo TI Usefulness of Age and Gender in the Early Triage of Patients With Acute Chest Pain Having Cardiac Computed Tomographic Angiography SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; ELEVATION MYOCARDIAL-INFARCTION; PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; EMERGENCY-DEPARTMENT; PRACTICAL IMPLEMENTATION; SCIENTIFIC STATEMENT; CLINICAL CARDIOLOGY; COST-EFFECTIVENESS; AMERICAN-COLLEGE AB To identify the age- and gender-specific subpopulations of patients with acute chest pain in whom coronary computed tomograpbic angiography (CTA) will yield the greatest diagnostic benefit. Subjects with acute chest pain and an inconclusive initial evaluation (non-diagnostic electrocardiograhic findings, negative cardiac biomarkers) underwent contrast-enhanced 64-slice coronary CTA as a part of an observational cohort study. Independent investigators determined the presence of significant coronary stenosis (>50% luminal narrowing) and the occurrence of acute coronary syndrome (ACS) during the index hospitalization. We determined the diagnostic accuracy and effect on pretest probability of ACS using Bayes' theorem by age and gender. Of 368 patients (age 52.7 +/- 12 years, 61% men), 8% had ACS. The presence of significant coronary stenosis on CTA and the occurrence of ACS increased with age for both men and women (p < 0.001). Cardiac CTA was highly sensitive and specific in women <65 years of age (sensitivity 100% and specificity >87%) and men <55 years of age (sensitivity 100% for men <45 years and 80% for men 45 to 54 years old; specificity >88.2%). Moreover, in these patients, coronary CTA led to restratification from low to high risk (for positive findings on CTA) or from low to very low risk (for negative findings on CTA). In contrast, a negative result on CTA did not result in restratification to a low-risk category in women >65 years and men >55 years old. In conclusion, the present analysis provides initial evidence that men <55 years and women <65 years might benefit more from cardiac CTA than older patients. Thus, age and gender might serve as simple criteria to appropriately select patients who would derive the greatest diagnostic benefit from coronary CTA in the setting of acute chest pain. (C) 2009 Elsevier Inc. All rights reserved. (Am J Cardiol 2009;104:1165-1170) C1 [Bamberg, Fabian; Truong, Quynh A.; Blankstein, Ron; Nasir, Khurram; Rogers, Ian S.; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Bamberg, Fabian; Blankstein, Ron; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Truong, Quynh A.; Rogers, Ian S.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Bamberg, Fabian; Reiser, Maximilian F.] Univ Munich, Dept Clin Radiol, Munich, Germany. [Achenbach, Stephan] Univ Erlangen Nurnberg, Dept Cardiol, Erlangen, Germany. RP Bamberg, F (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. EM fbamberg@post.harvard.edu FU NHLBI NIH HHS [R01 HL080053, R01 HL080053-03, T32 HL076136, T32 HL076136-05] NR 28 TC 4 Z9 4 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 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 2009 VL 104 IS 9 BP 1165 EP 1170 DI 10.1016/j.amjcard.2009.06.029 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 515QI UT WOS:000271487100001 PM 19840556 ER PT J AU Depta, JP Cannon, CP Fonarow, GC Zhao, X Peacock, WF Bhatt, DL AF Depta, Jeremiah P. Cannon, Christopher P. Fonarow, Gregg C. Zhao, Xin Peacock, W. Frank Bhatt, Deepak L. CA Get Guidelines Steering Comm Inves TI Patient Characteristics Associated With the Choice of Triple Antithrombotic Therapy in Acute Coronary Syndromes SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID AMERICAN-HEART-ASSOCIATION; ATRIAL-FIBRILLATION; ANTIPLATELET THERAPY; STROKE PREVENTION; BLEEDING RISK; WARFARIN; ANTICOAGULATION; INTERVENTION; OUTCOMES; CLOPIDOGREL AB Evidence regarding the use of dual antiplatelet therapy and oral anticoagulation (i.e., triple therapy) in acute coronary syndromes (ACS) is limited. We evaluated the characteristics associated with the choice of triple therapy in ACS. Using the Get With The Guidelines (GWTG) Coronary Artery Disease national registry, we studied patients with ACS at 361 sites in the United States from 2004 to 2007. Both univariate analysis and multivariate logistic regression analysis were used to assess the factors associated using triple therapy on discharge. The Generalized Estimating Equation method was used to account for within-hospital clustering in modeling. A total of 86,304 patients presented with ACS during the study period. At discharge, 3,933 patients (4.6%) were prescribed triple therapy, 60,716 patients (70.4%) received dual antiplatelet therapy, 2,348 patients (2.7%) received single antiplatelet therapy plus oral anticoagulation, 19,065 patients (22.1%) received antiplatelet monotherapy, and 242 patients (0.3%) received oral anticoagulation alone. Patients with a history of atrial fibrillation (odds ratio 7.01, 95% confidence interval 6.06 to 8.12; p<0.001), documented new-onset atrial fibrillation (odds ratio 3.76, 95% confidence interval 2.87 to 4.93; p<0.001), or history of atrial flutter (odds ratio 3.38, 95% confidence interval 2.15 to 5.32; p<0.001) were more frequently discharged with triple therapy. In conclusion, for patients with ACS, atrial fibrillation and atrial flutter were most strongly associated with the use of triple therapy; however, this therapy was used less often than dual or single antiplatelet therapy. Published by Elsevier Inc. (Am J Cardiol 2009;104:1171-1178) C1 [Bhatt, Deepak L.] Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Depta, Jeremiah P.] Cleveland Clin, Inst Med, Dept Internal Med, Cleveland, OH 44106 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Zhao, Xin] Duke Clin Res Inst, Durham, NC USA. [Peacock, W. Frank] Cleveland Clin, Dept Emergency Med, Cleveland, OH 44106 USA. RP Bhatt, DL (reprint author), Vet Affairs Boston Healthcare Syst, Boston, MA USA. EM dlbhattmd@alum.mit.edu NR 20 TC 12 Z9 12 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 NOV 1 PY 2009 VL 104 IS 9 BP 1171 EP 1178 DI 10.1016/j.amjcard.2009.06.027 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 515QI UT WOS:000271487100002 PM 19840557 ER PT J AU Shea, MK Gundberg, CM Meigs, JB Dallal, GE Saltzman, E Yoshida, M Jacques, PF Booth, SL AF Shea, M. Kyla Gundberg, Caren M. Meigs, James B. Dallal, Gerard E. Saltzman, Edward Yoshida, Makiko Jacques, Paul F. Booth, Sarah L. TI gamma-Carboxylation of osteocalcin and insulin resistance in older men and women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID VITAMIN-K SUPPLEMENTATION; HOMEOSTASIS MODEL ASSESSMENT; BONE-MINERAL DENSITY; PLASMA-GLUCOSE; BETA-CELL; ADIPONECTIN; METABOLISM AB Background: The skeletal protein osteocalcin is gamma-carboxylated by vitamin K. High serum uncarboxylated osteocalcin reflects low vitamin K status. In vitro and animal studies indicate that high uncarboxylated osteocalcin is associated with reduced insulin resistance. However, associations between osteocalcin and measures of insulin resistance in humans are less clear. Objective: Our aim was to examine cross-sectional and longitudinal associations between circulating forms of osteocalcin (total, uncarboxylated, and carboxylated) and insulin resistance in older men and women. Design: Cross-sectional associations between serum measures of total osteocalcin, carboxylated osteocalcin, and uncarboxylated osteocalcin and insulin resistance were examined in 348 nondiabetic men and women (mean age: 68 y; 58% female) by using the homeostasis model assessment of insulin resistance (HOMA-IR). Associations between each form of osteocalcin at baseline and 3-y change in HOMA-IR were examined in 162 adults (mean age: 69 y; 63% female) who did not receive vitamin K supplementation. Results: Lower circulating uncarboxylated osteocalcin was not associated with higher HOMA-IR at baseline or at 3-y follow-up. Those in the lowest tertiles of total osteocalcin and carboxylated osteocalcin at baseline had higher baseline HOMA-IR (P = 0.006 and P = 0.02, respectively). The concentration of carboxylated osteocalcin at baseline was inversely associated with a 3-y change in HOMA-IR (P = 0.002). Conclusions: In older adults, circulating uncarboxylated osteocalcin was not associated with insulin resistance. In contrast, elevated carboxylated osteocalcin and total osteocalcin were associated with lower insulin resistance, which supports a potential link between skeletal physiology and insulin resistance in humans. The role of vitamin K status in this association remains unclear and merits further investigation. This trial is registered at clinicaltrials.gov as NCT00183001. Am J Clin Nutr 2009; 90: 1230-5. C1 [Shea, M. Kyla; Dallal, Gerard E.; Saltzman, Edward; Yoshida, Makiko; Jacques, Paul F.; Booth, Sarah L.] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Gundberg, Caren M.] Yale Univ, Sch Med, Dept Orthopaed, New Haven, CT 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. RP Booth, SL (reprint author), Tufts Univ, USDA, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA. EM sarah.booth@tufts.edu FU GlaxoSmithKline; Sanofi-Aventis FX The authors' responsibilities were as follows-SLB: designed the study and contributed to the design of the analyses, the interpretation of the data, and the writing of the manuscript; MKS: performed the statistical analyses and drafted the manuscript; and CMG, JBM, GED, ES, MY, and PFJ: contributed to the design of the analyses, the interpretation of the data, and the writing of the manuscript. JBM currently has research grants from GlaxoSmithKline and Sanofi-Aventis and serves on consultancy boards for Eli Lilly, Interleukin Genetics, Kalypsis, and Outcomes Sciences. MKS, CMG, ES, PFJ, MY, GED, and SLB had no conflicts of interest. NR 19 TC 102 Z9 105 U1 0 U2 3 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 NOV 1 PY 2009 VL 90 IS 5 BP 1230 EP 1235 DI 10.3945/ajcn.2009.28151 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 508TO UT WOS:000270959500017 PM 19776145 ER PT J AU Wilbur, DC Black-Schaffer, WS Luff, RD Abraham, KP Kemper, C Molina, JT Tench, WD AF Wilbur, David C. Black-Schaffer, W. Stephen Luff, Ronald D. Abraham, Kurian P. Kemper, Cynthia Molina, James T. Tench, William D. TI The Becton Dickinson FocalPoint GS Imaging System Clinical Trials Demonstrate Significantly Improved Sensitivity for the Detection of Important Cervical Lesions SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol DE Cervical cytology; Computer-assisted screening; Cytology imaging system ID PRIMARY SCREENING SYSTEM; QUALITY-CONTROL; AUTOPAP SYSTEM; INTENDED-USE; CYTOLOGY; SMEARS; PERFORMANCE; NO; CLASSIFICATION; FEASIBILITY AB Location-guided screening in cervical cytology offers a potentially significant advance over routine manual screening. A prospective, 2-armed, masked clinical trial of the BD FocalPoint GS Imaging System using SurePath slides (BD Diagnostics-TriPath, Burlington, NC) compared routine manual screening and quality control rescreening with computer-assisted, field-of-view screening and device-directed quality control rescreening. The results obtained in the 2 arms were compared with adjudicated reference diagnoses for each slide. Sensitivity, specificity, and negative predictive value were calculated for the detection of atypical squamous cells of undetermined significance and greater (ASC-US+), low-grade squamous intraepithelial lesion and greater (LSIL+), and high-grade squamous intraepithelial lesion and greater (HSIL+) groups. We evaluated 12,313 slides. The detection sensitivities for HSIL+ were increased by 19.6% (P < .0001) and for LSIL+ were increased by 9.8% (P < .0001) in the computer assisted arm, with small statistically significant decreases in specificity. For ASC-US+ sensitivity and specificity, the study arms were not statistically cl fferent. Use of this system might be expected to improve accuracy for clinically important entities without increasing equivocal case detection. C1 [Wilbur, David C.; Black-Schaffer, W. Stephen] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Wilbur, David C.; Black-Schaffer, W. Stephen] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Luff, Ronald D.] Quest Diagnost, Teterboro, NJ USA. [Abraham, Kurian P.] Quest Diagnost, Schaumburg, IL USA. [Kemper, Cynthia] Boyce & Bynum Pathol Labs PC, Columbia, MO USA. [Tench, William D.] Palomar Med Ctr, Escondido, CA USA. [Molina, James T.] Cyto Labs, San Antonio, TX USA. RP Wilbur, DC (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, 55 Fruit St, Boston, MA 02114 USA. NR 32 TC 34 Z9 34 U1 1 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 NOV PY 2009 VL 132 IS 5 BP 767 EP 775 DI 10.1309/AJCP8VE7AWBZCVQT PG 9 WC Pathology SC Pathology GA 509CA UT WOS:000270988600017 PM 19846820 ER PT J AU Tsai, CL Rowe, BH Cydulka, RK Camargo, CA AF Tsai, Chu-Lin Rowe, Brian H. Cydulka, Rita K. Camargo, Carlos A., Jr. TI ED visit volume and quality of care in acute exacerbations of chronic obstructive pulmonary disease SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID EMERGENCY-DEPARTMENTS; MANAGEMENT; DIAGNOSIS; OUTCOMES AB Objective: The purpose of this study is to determine whether emergency department (ED) visit volume is associated with ED quality of care in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD). Methods: We performed a prospective multicenter cohort study involving 29 EDs in the United States and Canada. Using a standard protocol, we interviewed consecutive ED patients with COPD exacerbation, reviewed their charts, and completed a 2-week telephone follow-up. The associations between ED visit volume and quality of care (process and outcome measures) were examined at both the ED and patient levels. Results: After adjustment for patient mix in the multivariable analyses, chest radiography was less frequent among patients with COPD exacerbations in the low-volume (odds ratio [OR], 0.2; 95% confidence interval [CI], 0.1-0.4) and high-volume EDs (OR, 0.1; 95% CI, 0.05-0.5), with medium-volume EDs as the reference. Arterial blood gas testing was less frequent in the low-volume EDs (OR, 0.1; 95% CI, 0.02-0.8). Medication use was similar across volume tertiles. With respect to outcome measures, patients in high-volume EDs were more likely to be discharged (OR, 4.2; 95% CI, 2.2-7.7) and to report ongoing exacerbation at a 2-week follow-up (OR, 1.9; 95% CI, 1.02-3.5). Conclusions: Traditional positive volume-quality relationships did not apply to emergency care of COPD exacerbation. High-volume EDs used less guideline-recommended diagnostic procedures, had a higher admission threshold, and had a worse short-term patient-centered outcome. (C) 2009 Elsevier Inc. All rights reserved. C1 [Tsai, Chu-Lin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med,EMNet Coordinating Ctr, Boston, MA 02114 USA. [Tsai, Chu-Lin; Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rowe, Brian H.] Univ Alberta, Dept Emergency Med, Edmonton, AB T6G 2B7, Canada. [Cydulka, Rita K.] Case Western Reserve Univ, Metrohlth Med Ctr, Dept Emergency Med, Cleveland, OH 44109 USA. RP Tsai, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med,EMNet Coordinating Ctr, Boston, MA 02114 USA. EM ctsai2@partners.org OI TSAI, CHU-LIN/0000-0003-4639-1513 FU Boehringer Ingelheim FX The present cohort studies were supported by an unrestricted grant from Boehringer Ingelheim (Ridgefield, Conn, and Burlington, Ontario, Canada). NR 30 TC 2 Z9 2 U1 1 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD NOV PY 2009 VL 27 IS 9 BP 1040 EP 1049 DI 10.1016/j.ajem.2008.07.034 PG 10 WC Emergency Medicine SC Emergency Medicine GA 527XB UT WOS:000272403400003 PM 19931748 ER PT J AU Soremekun, OA Shear, ML Patel, S Kim, GJ Biddinger, PD Parry, BA Yialamas, MA Thomas, SH AF Soremekun, Olanrewaju A. Shear, Melissa L. Patel, Sagar Kim, Gina J. Biddinger, Paul D. Parry, Blair A. Yialamas, Maria A. Thomas, Stephen H. TI Rapid vascular glucose uptake via enzyme-assisted subcutaneous infusion: Enzyme-Assisted Subcutaneous Infusion Access Study SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID RECOMBINANT HUMAN HYALURONIDASE; RESUSCITATION; SKIN; VENIPUNCTURE AB Background: Enzyme-assisted subcutaneous infusion (EASI), with subcutaneous human recombinant hyaluronidase pretreatment, may offer an alternative to standard intravenous (IV) access. Objectives: This study's objectives were to assess paramedic (Emergency Medical Technician-Paramedic [EMTP])-placed EASI access in volunteers to determine (1) feasibility of EMTP EASI access placement; (2) subject/EMTP ratings of placement ease, discomfort, and overall EASI vs IV preference; and (3) speed of intravascular uptake of EASI infusate. Methods: Twenty adults underwent 20-gauge IV placement by 4 EMTPs, receiving a 250-mL maximal-rate IV bolus of normal saline. Next, each subject received in the other arm a 20-gauge EASI access line (with 1-mL injection of 150 U of human recombinant hyaluronidase), through which was infused 250 mL D5NS (1 g glucose was labeled with stable tracer 13C). Blood draws enabled gas chromatography/mass spectrometry (GC/MS) assessment of 13C-glucose uptake. Intravenous access and EASI access were compared for time parameters and subject/EMTP ratings. Data were analyzed with median and interquartile range, Kruskal-Wallis testing, Fisher exact test, and regression (GC/MS data). Results: Intravenous access and EASI access were successful in all 20 subjects. Compared with EASI access (all placed in <15 seconds), IV access took longer; but the 250-mL bolus was given more quickly via IV access. EMTPs rated EASI easier to place than IV; pain ratings were similar for Wand EASI. The GC/MS showed intravascular uptake at all time points. C1 [Soremekun, Olanrewaju A.; Shear, Melissa L.; Patel, Sagar; Kim, Gina J.; Biddinger, Paul D.; Parry, Blair A.; Thomas, Stephen H.] Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. [Soremekun, Olanrewaju A.; Shear, Melissa L.; Patel, Sagar; Kim, Gina J.; Biddinger, Paul D.; Parry, Blair A.; Yialamas, Maria A.; Thomas, Stephen H.] Harvard Univ, Sch Med, Boston, MA USA. [Yialamas, Maria A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Soremekun, Olanrewaju A.] Brigham & Womens Hosp, Harvard Affiliated EM Residency Program, Boston, MA 02115 USA. RP Thomas, SH (reprint author), Massachusetts Gen Hosp, Dept Emergency Serv, 0 Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM thomas.stephen@mgh.harvard.edu FU Baxter FX Project supported by an unrestricted grant from Baxter, the company that markets the human recombinant hyaluronidase used in the study. NR 27 TC 3 Z9 3 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD NOV PY 2009 VL 27 IS 9 BP 1072 EP 1080 DI 10.1016/j.ajem.2008.08.028 PG 9 WC Emergency Medicine SC Emergency Medicine GA 527XB UT WOS:000272403400008 PM 19931753 ER PT J AU Friedman, LS Gores, GJ Vargo, JJ Brandt, LJ Katz, PO Stolar, MH Elta, GH Kuemmerle, JF Fitz, JG Pardi, DS AF Friedman, Lawrence S. Gores, Gregory J. Vargo, John J. Brandt, Lawrence J. Katz, Philip O. Stolar, Michael H. Elta, Grace H. Kuemmerle, John F. Fitz, J. Gregory Pardi, Darrell S. TI Report of the Multisociety Task Force on GI Training SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material C1 [Friedman, Lawrence S.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Friedman, Lawrence S.] Tufts Univ, Sch Med, Medford, MA 02155 USA. [Friedman, Lawrence S.] Newton Wellesley Hosp, Newton, MA USA. [Friedman, Lawrence S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gores, Gregory J.; Pardi, Darrell S.] Mayo Clin, Coll Med Rochester, Rochester, MN 55905 USA. [Vargo, John J.] Cleveland Clin, Lerner Coll Med, Cleveland, OH USA. [Vargo, John J.] Cleveland Clin Fdn, Inst Digest Dis, Cleveland, OH USA. [Brandt, Lawrence J.] Albert Einstein Coll Med, Montefiore Med Ctr, New York, NY USA. [Katz, Philip O.] Thomas Jefferson Univ, Albert Einstein Med Ctr, Philadelphia, PA USA. [Elta, Grace H.] Univ Michigan, Ann Arbor, MI 48109 USA. [Kuemmerle, John F.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. RP Friedman, LS (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. OI Vargo, John/0000-0001-7638-5283 NR 0 TC 3 Z9 3 U1 0 U2 0 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 NOV PY 2009 VL 104 IS 11 BP 2659 EP 2663 DI 10.1038/ajg.2009.570 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 519YC UT WOS:000271805100001 ER PT J AU Tukey, M Pleskow, D Legnani, P Cheifetz, AS Moss, AC AF Tukey, Melissa Pleskow, Doug Legnani, Peter Cheifetz, Adam S. Moss, Alan C. TI The Utility of Capsule Endoscopy in Patients With Suspected Crohn's Disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CHRONIC ABDOMINAL-PAIN; ENTEROCLYSIS; TRIAL; INDEX AB OBJECTIVES: In patients with suspected Crohn's disease (CD), little is known about the test characteristics of capsule endoscopy (CE) in the diagnosis of this condition. We sought to determine the utility of CE for the subsequent diagnosis of CD in patients suspected to have this condition. METHODS: All patients who underwent CE at a single tertiary-care center for investigation of suspected small bowel CD, and who had a 12-month follow-up, were included in the study. All patients had undergone other investigations that were normal or equivocal. The test characteristics of CE were determined on the basis of capsule findings of small bowel ulcers and a subsequent new diagnosis of CD within 12 months of CE. RESULTS: The study included 102 patients with 12-month follow-up data. The majority (75%) met the established criteria to define "suspected Crohn's disease" as an indication for CE. Most had undergone computed tomography scan or small bowel follow-through (92%) and colonoscopy (99%) before CE. There were abnormal CE findings suggestive of CD in 39 patients. The prevalence rate of a new diagnosis of CD by 12 months in the study population was 13%. Using the presence of more than 3 ulcers as the criterion for an abnormal CE study, the sensitivity of CE for the diagnosis of CD was 77%, the specificity was 89%, the positive predictive value (PPV) was 50%, and the negative predictive value (NPV) was 96%. CONCLUSIONS: In patients with suspected CD, CE has a high sensitivity and a NPV for this condition. The PPV varies depending on the patient population and the criteria for a CE diagnosis of CD. C1 [Moss, Alan C.] Beth Israel Deaconess Med Ctr, Ctr Inflammatory Bowel Dis, Div Gastroenterol, Boston, MA 02215 USA. [Tukey, Melissa; Pleskow, Doug; Cheifetz, Adam S.; Moss, Alan C.] Harvard Univ, Sch Med, Boston, MA USA. [Legnani, Peter] Mt Sinai Sch Med, Div Gastroenterol, New York, NY USA. RP Moss, AC (reprint author), Beth Israel Deaconess Med Ctr, Ctr Inflammatory Bowel Dis, Div Gastroenterol, Rose 1 E,BIDMC,330 Brookline Ave, Boston, MA 02215 USA. EM amoss@bidmc.harvard.edu OI Pleskow, Douglas/0000-0003-0092-9496 NR 22 TC 46 Z9 49 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2009 VL 104 IS 11 BP 2734 EP 2739 DI 10.1038/ajg.2009.404 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 519YC UT WOS:000271805100015 PM 19584828 ER PT J AU Mavandadi, S Nazem, S Ten Have, TR Siderowf, AD Duda, JE Stern, MB Weintraub, D AF Mavandadi, Shahrzad Nazem, Sarra Ten Have, Thomas R. Siderowf, Andrew D. Duda, John E. Stern, Matthew B. Weintraub, Daniel TI Use of Latent Variable Modeling to Delineate Psychiatric and Cognitive Profiles in Parkinson Disease SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Parkinson disease; neuropsychology; psychiatry; cognition; depression ID QUALITY-OF-LIFE; NEUROPSYCHIATRIC DISTURBANCES; DEPRESSION; SYMPTOMS; DEMENTIA; PREVALENCE; INVENTORY; SCALE; COMORBIDITY; DISORDERS AB Objectives: A range of psychiatric symptoms and cognitive deficits occur in Parkinson disease (PD), and symptom overlap and comorbidity complicate the classification of nonmotor symptoms. The objective of this study was to use analytic-based approaches to classify psychiatric and cognitive symptoms in PD. Design: Cross-sectional evaluation of a convenience sample of patients in specialty care. Setting: Two outpatient movement disorders centers at the University of Pennsylvania and Philadelphia Veterans Affairs Medical Center. Participants: One hundred seventy-seven patients with mild-moderate idiopathic PD and without significant global cognitive impairment. Measurements: Subjects were assessed with an extensive psychiatric, neuropsychological, and neurological battery. Latent class analysis (LCA) was used to statistically delineate group-level symptom profiles across measures of psychiatric and cognitive functioning. Predictors of class membership were also examined. Results: Results from the LCA indicated that a four-class solution best fit the data. The 32.3% of the sample had good psychiatric and normal cognitive functioning, 17.5% had significant psychiatric comorbidity but normal cognition, 26.0% had few psychiatric symptoms but had poorer cognitive functioning across a range of cognitive domains, and 24.3% had both significant psychiatric comorbidity and poorer cognitive functioning. Age, disease severity, and medication use predicted class membership. Conclusions: LCA delineates four classes of patients in mild-moderate PD, three of which experience significant nonmotor impairments and comprise over two thirds of patients. Neuropsychiatric symptoms and cognitive deficits follow distinct patterns in PD, and further study is needed to determine whether these classes are generalizable, stable, predict function, quality of life, and long-term outcomes and are amenable to treatment at a class level. (Am J Geriatr Psychiatry 2009; 17:986-995) C1 [Mavandadi, Shahrzad; Weintraub, Daniel] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Mavandadi, Shahrzad; Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Ten Have, Thomas R.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Siderowf, Andrew D.; Duda, John E.; Stern, Matthew B.; Weintraub, Daniel] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Duda, John E.; Stern, Matthew B.; Weintraub, Daniel] Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. RP Weintraub, D (reprint author), 3615 Chestnut St,Room 330, Philadelphia, PA 19104 USA. EM daniel.weintraub@uphs.upenn.edu FU National Institute of Mental Health (NIMH) [067894] FX This work was supported by National Institute of Mental Health (NIMH) grant no. 067894. NR 42 TC 15 Z9 15 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD NOV PY 2009 VL 17 IS 11 BP 986 EP 995 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 517ZG UT WOS:000271657200009 PM 19855199 ER PT J AU Harley, AE Katz, ML Heaney, CA Duncan, DT Buckworth, J Odoms-Young, A Willis, SK AF Harley, Amy E. Katz, Mira L. Heaney, Catherine A. Duncan, Dustin T. Buckworth, Janet Odoms-Young, Angela Willis, Sharla K. TI Social Support and Companionship Among Active African American Women SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE physical activity; African Americans; women; qualitative research; social support ID PHYSICAL-ACTIVITY PARTICIPATION; ENVIRONMENTAL-INFLUENCES; SEDENTARY WOMEN; UNITED-STATES; WALKING; COMMUNITY; EXERCISE; OUTCOMES; MEMBERS; HEALTH AB Objective: To examine the role of physical activity (PA) companions in supporting PA participation among African American women. Methods: Data were collected through in-depth interviews and focus groups. Fifteen physically active African American women participated in the study. Grounded theory data analysis techniques were used to develop a taxonomy depicting roles of PA companions for African American women. Results: PA companions functioned in 4 different roles: motivational, social, facilitative, and instructional. Supportive behaviors associated with each role were also elucidated. Conclusions: These findings provide an understanding for the function of companions in sustaining active lifestyle that can be used to inform intervention development. C1 [Harley, Amy E.] Univ Wisconsin, Coll Hlth Sci, Ctr Urban Populat Hlth, Milwaukee, WI 53233 USA. [Katz, Mira L.] Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA. [Heaney, Catherine A.] Stanford Prevent Res Ctr, Stanford, CA USA. [Duncan, Dustin T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Buckworth, Janet] Ohio State Univ, Sch Phys Act & Educ Serv, Columbus, OH 43210 USA. [Odoms-Young, Angela] Univ Illinois, Coll Appl Hlth Sci, Chicago, IL USA. RP Harley, AE (reprint author), Univ Wisconsin, Coll Hlth Sci, Ctr Urban Populat Hlth, Milwaukee, WI 53233 USA. EM harley@uwm.edu RI Buckworth, Janet/B-5932-2012 NR 47 TC 12 Z9 12 U1 1 U2 7 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD NOV-DEC PY 2009 VL 33 IS 6 BP 673 EP 685 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 517FB UT WOS:000271597500005 PM 19320616 ER PT J AU Romley, JA Hussey, PS de Vries, H Wang, MC Shekelle, PG McGlynn, EA AF Romley, John A. Hussey, Peter S. de Vries, Han Wang, Margaret C. Shekelle, Paul G. McGlynn, Elizabeth A. TI Efficiency and Its Measurement: What Practitioners Need to Know SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID HEALTH-CARE; QUALITY AB Objective: To help health professionals understand and evaluate the concept of efficiency and its measurement in practice. Study Design: We reviewed conceptual and practical analyses of healthcare efficiency and its measurement and describe our findings. Methods: We searched the following 3 sources: the MEDLINE and EconLit databases for articles published from 1990 to 2008 using the keywords efficiency, inefficiency, productivity, and economic profiling; seminal economic studies of efficiency identified in MEDLINE or EconLit or in economics reference materials; and the "gray literature" on efficiency measures developed by private organizations. Results: An essential element of efficiency is that healthcare outputs are as large as possible given their inputs. An efficiency measure specifies outputs and inputs appropriate to the goals of the assessment. Participants in the healthcare system have differing perspectives about the goals of efficiency assessments, relevant outputs and inputs, and validity of measures. Conclusion: The broad meaning and the value of healthcare efficiency seem uncontroversial, yet any particular application may be confronted with conflicting perspectives and with practical challenges. (Am J Manag Care. 2009;15(11):842-845) C1 [Romley, John A.; Hussey, Peter S.; Wang, Margaret C.; Shekelle, Paul G.; McGlynn, Elizabeth A.] RAND Corp, Santa Monica, CA 90407 USA. [Romley, John A.] Occidental Coll, Dept Econ, Los Angeles, CA 90041 USA. [de Vries, Han] RAND Europe, Cambridge, England. [Shekelle, Paul G.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Romley, JA (reprint author), RAND Corp, 1776 Main St,POB 2138, Santa Monica, CA 90407 USA. EM romley@rand.org FU Agency for Healthcare research and Quality [282-00-0005-21] FX This research was funded by the Agency for Healthcare research and Quality, contract number 282-00-0005-21. NR 13 TC 2 Z9 2 U1 0 U2 1 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD NOV PY 2009 VL 15 IS 11 BP 842 EP 845 PG 4 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 521QI UT WOS:000271936800010 PM 19895189 ER PT J AU Chen, RC Khorsandi, AS Shatzkes, DR Holliday, RA AF Chen, R. C. Khorsandi, A. S. Shatzkes, D. R. Holliday, R. A. TI The Radiology of Referred Otalgia SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Review ID RHEUMATOID-ARTHRITIS; PAIN; EAR; NEURALGIA; VAGUS AB Pain referred to the ear is a well-documented phenomenon, which can be due to a multitude of disease processes. With the recent and rapid progression of CT and MR imaging technology, radiologists have played an increasing role in solving this potentially difficult diagnostic dilemma. Essentially any pathology residing within the sensory net of cranial nerves V, VII, IX, and X and the upper cervical nerves C2 and C3 can potentially cause referred otalgia. This article will attempt to outline the various sensorineural pathways that dually innervate the ear and other sites within the head and neck, as well as discuss various disease processes that are known to result in referred otalgia. C1 [Chen, R. C.; Khorsandi, A. S.] Beth Israel Deaconess Med Ctr, Dept Radiol, New York, NY 10003 USA. [Shatzkes, D. R.] St Lukes Roosevelt Hosp, Dept Radiol, New York, NY USA. [Holliday, R. A.] New York Eye & Ear Infirm, Dept Radiol, New York, NY 10003 USA. RP Chen, RC (reprint author), Massachusetts Gen Hosp, Gray Bldg 273A,55 Fruit St, Boston, MA 02114 USA. EM chenner23@gmail.com NR 44 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV-DEC PY 2009 VL 30 IS 10 BP 1817 EP 1823 DI 10.3174/ajnr.A1605 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 527IV UT WOS:000272361600005 PM 19797791 ER PT J AU Cuaron, JJ Hirsch, JA Medich, DC Rosenstein, BS Martel, CB Hirsch, AE AF Cuaron, J. J. Hirsch, J. A. Medich, D. C. Rosenstein, B. S. Martel, C. B. Hirsch, A. E. TI A Proposed Methodology to Select Radioisotopes for Use in Radionuclide Therapy SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID HEPATIC RADIOEMBOLIZATION; VERTEBRAL AUGMENTATION; COMPRESSION FRACTURES; CANCER; BRACHYTHERAPY; RADIATION; AT-211; Y-90 AB The American Journal of Neuroradiology has played a seminal role in the history of vertebral augmentation (VA). Because VA is increasingly being included in the multidisciplinary management of malignant vertebral compression fractures (VCFs), combined therapeutic approaches that include strategies to treat metastatic disease along with the fracture have become appealing options for patients. To that end, we recently investigated the closimetric feasibility of treating malignant VCFs with radionuclide therapy. The goal would be to provide local control of the systemic disease beyond the pain relief and structural support provided by polymethylmethacrylate cement. The purpose of this article is to propose a methodology for evaluating radionuclides for use in radiation therapy that takes into account a number of factors including radiation characteristics, biochemical effects, production capacity, and safety, The goal of such a methodology is to introduce a systematic approach to selecting radionuclides in designing treatment regimens and future investigations and also to stimulate discussion and experimentation involving new radionuclides that may provide more effective treatments than the current isotopes in widespread use. C1 [Cuaron, J. J.; Hirsch, A. E.] Boston Univ, Med Ctr, Dept Radiat Oncol, Sch Med, Boston, MA 02118 USA. [Hirsch, J. A.] Massachusetts Gen Hosp, Dept Radiol, Div Intervent Neuroradiol, Boston, MA 02114 USA. [Medich, D. C.] Univ Massachusetts, Radiat Lab, Lowell, MA USA. [Rosenstein, B. S.] Mt Sinai Sch Med, Dept Radiat Oncol, New York, NY USA. [Rosenstein, B. S.] Mt Sinai Sch Med, Dept Dermatol, New York, NY USA. [Rosenstein, B. S.] Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY USA. [Rosenstein, B. S.] NYU, Sch Med, Dept Radiat Oncol, New York, NY USA. [Martel, C. B.] Brigham & Womens Hosp, Dept Hlth Phys, Boston, MA 02115 USA. RP Hirsch, AE (reprint author), Boston Univ, Med Ctr, Dept Radiat Oncol, Massachusetts Gen Hosp, 830 Harrison Ave,Moakley Bldg LL, Boston, MA 02118 USA. EM Ariel.hirsch@bmc.org RI Medich, David/B-6006-2013 NR 34 TC 4 Z9 5 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV-DEC PY 2009 VL 30 IS 10 BP 1824 EP 1829 DI 10.3174/ajnr.A1773 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 527IV UT WOS:000272361600006 PM 19661172 ER PT J AU Eichler, F Grodd, W Grant, E Sessa, M Biffi, A Bley, A Kohlschuetter, A Loes, DJ Kraegeloh-Mann, I AF Eichler, F. Grodd, W. Grant, E. Sessa, M. Biffi, A. Bley, A. Kohlschuetter, A. Loes, D. J. Kraegeloh-Mann, I. TI Metachromatic Leukodystrophy: A Scoring System for Brain MR Imaging Observations SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID ADRENOLEUKODYSTROPHY; PHENOTYPE; MUTATION; ONSET AB BACKGROUND AND PURPOSE: Metachromatic leukodystrophy (MLD) is a devastating demyelinating disease for which novel therapies are being tested. We hypothesized that MR imaging of brain lesion involvement in MLD could be quantified along a scale. MATERIALS AND METHODS: Thirty-four brain MR images in 28 patients with proved biochemical and genetic defects for MLD were reviewed: 10 patients with late infantile, 16 patients with juvenile, and 2 patients with adult MLD. All MR images were reviewed by experienced neuroradiologists and neurologists (2 readers in Germany, 2 readers in the United States) for global disease burden, as seen on the T2 and fluid-attenuated inversion recovery images. A visual scoring method was based on a point system (range, 0-34) derived from the location of white matter involvement and the presence of global atrophy, aralogous to the scoring system developed for adrenoleukodystrophy. The readers were blinded to the neurologic findings. RESULTS: Thirty-three of 34 MR images showed confluent T2 hyperintensities of white matter. The inter-rater reliability coefficient was 0.988. Scores between readers were within 2 points of each other. Serial MR imaging studies in 6 patients showed significant progressive disease in 3 patients (initial score average, 4; mean follow-up, 24.3) and no change or I point progression in 3 patients (initial score average, 12; mean follow-up, 12.66). Projection fibers and the cerebellum tended to be involved only in advanced stages of disease. CONCLUSIONS: The MLD MR severity scoring method can be used to provide a measure of brain MR imaging involvement in MLD patients. C1 [Eichler, F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Eichler, F.; Grant, E.] AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Kraegeloh-Mann, I.] Univ Tubingen, Dept Pediat, Tubingen, Germany. [Grodd, W.] Univ Tubingen, Dept Radiol, Tubingen, Germany. [Sessa, M.; Biffi, A.] Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, I-20132 Milan, Italy. [Bley, A.; Kohlschuetter, A.] Univ Med Ctr Hamburg Eppendorf, Dept Pediat, Hamburg, Germany. [Loes, D. J.] Suburban Radiol Consultants, Minneapolis, MN USA. RP Eichler, F (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 55 Fruit St,ACC 708, Boston, MA 02114 USA. EM feichler@partners.org FU National Institutes of Health [W08NS52550]; Fondazione Telethon FX This work was supported by grant the National Institutes of Health grant W08NS52550. NR 13 TC 38 Z9 38 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV-DEC PY 2009 VL 30 IS 10 BP 1893 EP 1897 DI 10.3174/ajnr.A1739 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 527IV UT WOS:000272361600017 PM 19797797 ER PT J AU Bhat, PV Jakobiec, FA Kurbanyan, K Zhao, TZ Foster, CS AF Bhat, Pooja V. Jakobiec, Frederick A. Kurbanyan, Kristina Zhao, Tongzhen Foster, C. Stephen TI Chronic Herpes Simplex Scleritis: Characterization of 9 Cases of an Underrecognized Clinical Entity SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID NECROTIZING SCLEROKERATITIS; WEGENERS-GRANULOMATOSIS; ACYCLOVIR; DISEASE; EPISCLERITIS; INFECTION; KERATITIS; MANIFESTATIONS; BLEPHARITIS; DIAGNOSIS AB PURPOSE: To characterize in detail persistent and recalcitrant infectious scleritis resulting from herpes simplex virus (HSV). DESIGN: Retrospective and interventional clinical and immunopathologic case series. METHODS: Nine patients with chronic scleral redness, edema, and pain refractory to conventional therapy underwent a scleroconjunctival biopsy for routine histopathologic evaluation and definitive immunodiagnosis for the presence of HSV. Immunofluorescent probing for HSV was performed on the patient specimens. Negative controls for HSV included elimination of anti-HSV and anti-varicella zoster virus antibody in the probing process and the use of normal human conjunctiva and sclera as substrates. Response to therapy with acyclovir was monitored and recorded. RESULTS: The average age of the affected patients was 50.2 years, and the average duration of symptoms before tissue diagnosis of herpetic scleritis was 3.2 years (me, dian, 4 years). Three histopathologic patterns were discovered: granulomatous inflammation (2 cases), plasma cell-rich pyogenic granuloma-like pattern (1 case), and reactive fibroinflammatory pattern (6 cases). Herpes antigen was demonstrated uniformly by immunofluorescence in a perivascular distribution and less commonly in the interstitium. Varicella zoster virus was not detected, and all controls for nonspecific antibody reagent binding to tissue showed negative results. Acyclovir caused a dramatic improvement in the chronic or recurrent ocular inflammation in all instances, with an average duration of improvement of inflammation of 15.3 months. CONCLUSIONS: Unrecognized HSV infection can cause longstanding scleritis. Histopathologic features of HSV scleritis are varied and nonspecific; immunofluorescent demonstration of HSV protein can make a definitive diagnosis. Prolonged administration of acyclovir is required for effective therapy. (Am J Ophthalmol 2009;148:779-789. (C) 2009 by Elsevier Inc. All rights reserved.) C1 [Bhat, Pooja V.; Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Bhat, Pooja V.; Jakobiec, Frederick A.; Kurbanyan, Kristina; Foster, C. Stephen] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Zhao, Tongzhen; Foster, C. Stephen] Ocular Immunol & Uveitis Fdn, Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, David G Cogan Lab Ophthalm Pathol, Suite 321,243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 49 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV PY 2009 VL 148 IS 5 BP 779 EP 789 DI 10.1016/j.ajo.2009.06.025 PG 11 WC Ophthalmology SC Ophthalmology GA 518DA UT WOS:000271669300021 PM 19674728 ER PT J AU Chung, ES Chauhan, SK Jin, YP Nakao, S Hafezi-Moghadam, A van Rooijen, N Zhang, Q Chen, L Dana, R AF Chung, Eui-Sang Chauhan, Sunil Kumar Jin, Yiping Nakao, Shintaro Hafezi-Moghadam, Ali van Rooijen, Nico Zhang, Qiang Chen, Lu Dana, Reza TI Contribution of Macrophages to Angiogenesis Induced by Vascular Endothelial Growth Factor Receptor-3-Specific Ligands SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID VEGF-C; LYMPHATIC REGENERATION; TUMOR ANGIOGENESIS; FACTOR RECEPTOR-1; TRANSGENIC MICE; EXPRESSION; LYMPHANGIOGENESIS; MOUSE; BLOOD; ACTIVATION AB Vascular endothelial growth factor receptor (VEGFR)-2 is a major stimulator of hemangiogenesis (HA), whereas VEGFR-3 stimulates lymphangiogenesis (LA). Contrary to this understanding, we demonstrate that implantation of pellets containing VEGFR-3-specific ligands (VEGF-C156S and recombinant murine VEGF-D) into the corneal stroma induce not only LA but also robust HA characterized by blood vessels that are positive for VEGFR-3 expression. The implantation of pellets containing VEGFR-3-specific ligands also leads to the recruitment of VEGF-A-secreting macrophages. Depletion of these infiltrating macrophages using clodronate-liposome administration shows a significant reduction in HA as well as LA. Blockade of either VEGFR-2 or VEGFR-3 signaling reduces both HA and LA; however, the percent reduction of HA is greater in the VEGFR-2 blockade group. In addition, in the VEGFR-3 blockade group, the percent reduction of RA is significantly greater with VEGFR-3-specific ligands than that by VEGF-A or VEGF-C. Collectively, our data suggest that VEGFR-3-specific signaling can induce new blood vessels, to which macrophages contribute a major role, and signify its potential as an additional therapeutic target to the existing VEGF-A/VEGFR-2 signaling-based antiangiogenesis strategies. (Am J Pathol 2009, 175:1984-1992; DOI: 10.2353/ajpath.2009.080515) C1 [Dana, Reza] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA. [Chung, Eui-Sang] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Ophthalmol, Seoul, South Korea. [Hafezi-Moghadam, Ali; Dana, Reza] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [van Rooijen, Nico] Vrije Univ Amsterdam, Ctr Med, Dept Mol Cell Biol, Amsterdam, Netherlands. RP Dana, R (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu OI Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU National Institutes of Health [NEI-RO1-12963]; U.S. Department of Defense [W81XWH-07-2-0038]; New England Transplant Research Fund FX Supported in part by National Institutes of Health grant NEI-RO1-12963, U.S. Department of Defense grant W81XWH-07-2-0038, and New England Transplant Research Fund (to R.D.). NR 43 TC 45 Z9 47 U1 0 U2 5 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 NOV PY 2009 VL 175 IS 5 BP 1984 EP 1992 DI 10.2353/ajpath.2009.080515 PG 9 WC Pathology SC Pathology GA 515BH UT WOS:000271440800020 PM 19808642 ER PT J AU Panda, D Goltzman, D Juppner, H Karaplis, AC AF Panda, Dibiyendu Goltzman, David Jueppner, Harald Karaplis, Andrew C. TI TIP39/parathyroid hormone type 2 receptor signaling is a potent inhibitor of chondrocyte proliferation and differentiation SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE growth plate; cell cycle; osteoarthritis; secondary ossification center; Sox9 ID OLIGOMERIC MATRIX PROTEIN; TRANSCRIPTION FACTOR SOX9; PTH-RELATED PEPTIDE; PARATHYROID-HORMONE; TUBEROINFUNDIBULAR PEPTIDE; PTH/PTHRP RECEPTOR; 39 RESIDUES; BLOMSTRAND-CHONDRODYSPLASIA; GROWTH-PLATE; CATHEPSIN-D AB Panda D, Goltzman D, Juppner H, Karaplis AC. TIP39/parathyroid hormone type 2 receptor signaling is a potent inhibitor of chondrocyte proliferation and differentiation. Am J Physiol Endocrinol Metab 297: E1125-E1136, 2009. First published August 25, 2009; doi: 10.1152/ajpendo.00254.2009.-Tuberoinfundibular peptide of 39 residues (TIP39) is a member of the parathyroid hormone (PTH) family of peptide hormones that exerts its function by interacting with the PTH type 2 receptor (PTH2R). Presently, no known function has been attributed to this signaling pathway in the developing skeleton. We observed that TIP39 and PTH2R were present in the newborn mouse growth plate, with the receptor localizing in the resting zone whereas ligand expression was restricted exclusively in prehypertrophic and hypertrophic chondrocytes. By 8 wk of life, PTH2R, and to a lesser degree TIP39, immunoreactivity was present in articular chondrocytes. We therefore sought to investigate the role of TIP39/PTH2R signaling in chondrocytes by generating stably transfected CFK2 chondrocytic cells overexpressing PTH2R (CFK2R). TIP39 treatment of CFK2R clones in culture inhibited their proliferation by restricting cells at the G(0)/G(1) phase of the cell cycle, coupled with decreased expression and activity of cyclin-dependent kinases Cdk2 and Cdk4, while p21, an inhibitor of Cdks, was upregulated. In addition, TIP39 treatment decreased expression of differentiation markers in these cells associated with marked alterations in extracellular matrix and metalloproteinase expression. Transcription of Sox9, the master regulator of cartilage differentiation, was reduced in TIP39-treated CFK2R clones. Moreover, Sox9 promoter activity, as measured by luciferase reporter assay, was markedly diminished after TIP39 treatment. In summary, our results show that TIP39/PTH2R signaling inhibits proliferation and alters differentiation of chondrocytes by modulating SOX9 expression, thereby substantiating the functional significance of this signaling pathway in chondrocyte biology. C1 [Panda, Dibiyendu; Karaplis, Andrew C.] McGill Univ, Div Endocrinol, Dept Med, Sir Mortimer B Davis Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. [Panda, Dibiyendu; Karaplis, Andrew C.] McGill Univ, Lady Davis Inst Med Res, Sir Mortimer B Davis Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. [Goltzman, David] McGill Univ Hlth Ctr, Calcium Res Lab, Dept Med, Montreal, PQ, Canada. [Jueppner, Harald] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA USA. RP Karaplis, AC (reprint author), McGill Univ, Div Endocrinol, Dept Med, Sir Mortimer B Davis Jewish Gen Hosp, 3755 Cote Ste Catherine Rd, Montreal, PQ H3T 1E2, Canada. EM akarapli@ldi.jgh.mcgill.ca FU Canadian Institutes of Health Research (CIHR); National Institute of Diabetes and Digestive and Kidney Diseases [DK-11794]; Fonds de la Recherche en Sante du Quebec FX This work was supported by grants from the Canadian Institutes of Health Research (CIHR) (D. Goltzman and A. C. Karaplis) and National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-11794, project IV (H. Juppner). A. C. Karaplis is recipient of a Bourse de Chercheurs Nationaux from the Fonds de la Recherche en Sante du Quebec. NR 43 TC 9 Z9 9 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV PY 2009 VL 297 IS 5 BP E1125 EP E1136 DI 10.1152/ajpendo.00254.2009 PG 12 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 509CL UT WOS:000270990500018 PM 19706789 ER PT J AU Mani, SK Balasubramanian, S Zavadzkas, JA Jeffords, LB Rivers, WT Zile, MR Mukherjee, R Spinale, FG Kuppuswamy, D AF Mani, Santhosh K. Balasubramanian, Sundaravadivel Zavadzkas, Juozas A. Jeffords, Laura B. Rivers, William T. Zile, Michael R. Mukherjee, Rupak Spinale, Francis G. Kuppuswamy, Dhandapani TI Calpain inhibition preserves myocardial structure and function following myocardial infarction SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cardiomyocytes; cell death ID ENDOPLASMIC-RETICULUM STRESS; CARDIAC MYOCYTE APOPTOSIS; SMOOTH-MUSCLE-CELLS; HEART-FAILURE; DEGRADED COLLAGEN; CROSS-TALK; ACTIVATION; DEATH; PATHOGENESIS; HYPERTROPHY AB Mani SK, Balasubramanian S, Zavadzkas JA, Jeffords LB, Rivers WT, Zile MR, Mukherjee R, Spinale FG, Kuppuswamy D. Calpain inhibition preserves myocardial structure and function following myocardial infarction. Am J Physiol Heart Circ Physiol 297: H1744-H1751, 2009. First published September 4, 2009; doi:10.1152/ajpheart.00338.2009.-Cardiac pathology, such as myocardial infarction (MI), activates intracellular proteases that often trigger programmed cell death and contribute to maladaptive changes in myocardial structure and function. To test whether inhibition of calpain, a Ca(2+)-dependent cysteine protease, would prevent these changes, we used a mouse MI model. Calpeptin, an aldehydic inhibitor of calpain, was intravenously administered at 0.5 mg/kg body wt before MI induction and then at the same dose subcutaneously once per day. Both calpeptin-treated (n = 6) and untreated (n = 6) MI mice were used to study changes in myocardial structure and function after 4 days of MI, where end-diastolic volume (EDV) and left ventricular ejection fraction (EF) were measured by echocardiography. Calpain activation and programmed cell death were measured by immunohistochemistry, Western blotting, and TdT-mediated dUTP nick-end labeling (TUNEL). In MI mice, calpeptin treatment resulted in a significant improvement in EF [EF decreased from 67 +/- 2% pre-MI to 30 +/- 4% with MI only vs. 41 +/- 2% with MI + calpeptin] and attenuated the increase in EDV [EDV increased from 42 +/- 2 mu l pre-MI to 73 +/- 4 mu l with MI only vs. 55 +/- 4 mu l with MI + calpeptin]. Furthermore, calpeptin treatment resulted in marked reduction in calpain-and caspase-3-associated changes and TUNEL staining. These studies indicate that calpain contributes to MI-induced alterations in myocardial structure and function and that it could be a potential therapeutic target in treating MI patients. C1 [Mani, Santhosh K.; Balasubramanian, Sundaravadivel; Zile, Michael R.; Kuppuswamy, Dhandapani] Med Univ S Carolina, Dept Med, Div Cardiol, Charleston, SC 29425 USA. [Zavadzkas, Juozas A.; Jeffords, Laura B.; Rivers, William T.; Mukherjee, Rupak; Spinale, Francis G.] Med Univ S Carolina, Dept Surg, Div Cardiothorac Surg, Charleston, SC 29425 USA. [Zile, Michael R.; Spinale, Francis G.; Kuppuswamy, Dhandapani] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Kuppuswamy, D (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, 114 Doughty St, Charleston, SC 29425 USA. EM kuppusd@musc.edu FU National Heart, Lung, and Blood Institute (NHLBI) [PPG HL-48788, R01 HL-092124]; Research Service of the Department of Veterans Affairs FX This study was supported by National Heart, Lung, and Blood Institute (NHLBI) Grant PPG HL-48788, a Merit Award from the Research Service of the Department of Veterans Affairs, and NHLBI Grant R01 HL-092124 (to D. Kuppuswamy). NR 59 TC 28 Z9 32 U1 0 U2 4 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 NOV PY 2009 VL 297 IS 5 BP H1744 EP H1751 DI 10.1152/ajpheart.00338.2009 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 511DF UT WOS:000271143400024 PM 19734364 ER PT J AU Johnson, M Allen, L Dobbs, L AF Johnson, Meshell Allen, Lennell Dobbs, Leland TI Characteristics of Cl- uptake in rat alveolar type I cells SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE chloride transport; cystic fibrosis transmembrane regulator; CLC5 ID TRANSMEMBRANE CONDUCTANCE REGULATOR; POSTNATAL LUNG DEVELOPMENT; NASAL EPITHELIAL-CELLS; CHLORIDE-CHANNEL; ION-TRANSPORT; TRACHEAL EPITHELIUM; ANION-EXCHANGERS; SODIUM-CHANNELS; XENOPUS OOCYTES; FETAL LAMB AB Johnson M, Allen L, Dobbs L. Characteristics of Cl- uptake in rat alveolar type I cells. Am J Physiol Lung Cell Mol Physiol 297: L816-L827, 2009. First published August 14, 2009; doi: 10.1152/ajplung.90466.2008. Although Cl- transport in fetal lung is important for fluid secretion and normal lung development, the role of Cl- transport in adult lung is not well understood. In physiological studies, the cystic fibrosis transmembrane regulator (CFTR) plays a role in fluid absorption in the distal air spaces of adult lung, and alveolar type II cells cultured for 5 days have the capacity to transport Cl-. Although both alveolar type I and type II cells express CFTR, it has previously not been known whether type I cells transport Cl-. We studied Cl- uptake in isolated type I cells directly, using either radioisotopic tracers or halide-sensitive fluorescent indicators. By both methods, type I cells take up Cl-. In the presence of beta-adrenergic agonist stimulation, Cl- uptake can be inhibited by CFTR antagonists. Type I cells express both the Cl-/HCO3- anion exchanger AE2 and the voltage-gated Cl- channels CLC5 and CLC2. Inhibitors of AE2 also block Cl- uptake in type I cells. Together, these results demonstrate that type I cells are capable of Cl- uptake and suggest that the effects seen in whole lung studies establishing the importance of Cl- movement in alveolar fluid clearance may be, in part, the result of Cl- transport across type I cells. C1 [Johnson, Meshell; Dobbs, Leland] Univ Calif San Francisco, Dept Med, San Francisco, CA 94118 USA. [Allen, Lennell; Dobbs, Leland] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94118 USA. [Dobbs, Leland] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94118 USA. [Johnson, Meshell] San Francisco VA Med Ctr, San Francisco, CA USA. RP Johnson, M (reprint author), Univ Calif San Francisco, Dept Med, 3333 Calif St,Suite 150,Box 1245, San Francisco, CA 94118 USA. EM meshell.johnson@ucsf.edu FU National Heart, Lung, and Blood Institute [HL-24075, HL-57426, HL-088025]; Robert Wood Johnson Foundation Amos Medical Faculty Development Program FX This study was supported by National Heart, Lung, and Blood Institute Grants HL-24075 and HL-57426 (L. Dobbs) and HL-088025 (M. Johnson) and the Robert Wood Johnson Foundation Amos Medical Faculty Development Program (M. Johnson). NR 65 TC 8 Z9 8 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD NOV PY 2009 VL 297 IS 5 BP L816 EP L827 DI 10.1152/ajplung.90466.2008 PG 12 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 511CN UT WOS:000271141600005 PM 19684200 ER PT J AU Williams, DL Baskin, DG Schwartz, MW AF Williams, Diana L. Baskin, Denis G. Schwartz, Michael W. TI Hindbrain leptin receptor stimulation enhances the anorexic response to cholecystokinin SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE nucleus of the solitary tract; satiety signals; adiposity signals; food intake ID CENTRAL-NERVOUS-SYSTEM; CAUDAL BRAIN-STEM; FOOD-INTAKE; MEAL SIZE; SOLITARY TRACT; GENE-EXPRESSION; BLOOD-GLUCOSE; OB PROTEIN; LEAN MICE; C-FOS AB Williams DL, Baskin DG, Schwartz MW. Hindbrain leptin receptor stimulation enhances the anorexic response to cholecystokinin. Am J Physiol Regul Integr Comp Physiol 297: R1238-R1246, 2009. First published September 2, 2009; doi: 10.1152/ajpregu.00182.2009.-Leptin is thought to reduce food intake, in part, by increasing sensitivity to satiation signals, including CCK. Leptin action in both forebrain and hindbrain reduces food intake, and forebrain leptin action augments both the anorexic and neuronal activation responses to CCK. Here, we asked whether leptin signaling in hindbrain also enhances these responses to CCK. We found that food intake was strongly inhibited at 30 min after a combination of 4th-intracerebroventricular (4th-icv) leptin injection and intraperitoneal CCK administration, whereas neither hormone affected intake during this period when given alone. Leptin injections targeted directly at the dorsal vagal complex (DVC) similarly enhanced the anorexic response to intraperitoneal CCK. Intra-DVC leptin injection also robustly increased the number of neurons positive for phospho-STAT3 staining in the area surrounding the site of injection, confirming local leptin receptor activation. Conversely, the anorexic response to 4th-icv leptin was completely blocked by IP devazepide, a CCKA-R antagonist, suggesting that hindbrain leptin reduces intake via a mechanism requiring endogenous CCK signaling. We then asked whether hindbrain leptin treatment enhances the dorsomedial hindbrain, hypothalamus, or amygdala c-Fos responses to IP CCK. We found that, in contrast to the effects of forebrain leptin administration, 4th-icv leptin injection had no effect on CCK-induced c-Fos in any structures examined. We conclude that leptin signaling in either forebrain or hindbrain areas can enhance the response to satiation signals and that multiple distinct neural circuits likely contribute to this interaction. C1 [Williams, Diana L.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. [Williams, Diana L.] Florida State Univ, Program Neurosci, Tallahassee, FL 32306 USA. [Baskin, Denis G.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Baskin, Denis G.; Schwartz, Michael W.] Univ Washington, Dept Med, Ctr Excellence, Seattle, WA USA. [Baskin, Denis G.] Univ Washington, Dept Biol Struct, Ctr Excellence, Seattle, WA 98195 USA. [Baskin, Denis G.; Schwartz, Michael W.] Univ Washington, Dept Diabet & Obes, Ctr Excellence, Seattle, WA 98195 USA. RP Williams, DL (reprint author), Florida State Univ, Dept Psychol, POB 3064301, Tallahassee, FL 32306 USA. EM williams@psy.fsu.edu RI Schwartz, Michael/H-9950-2012; Williams, Diana/C-1699-2014 OI Williams, Diana/0000-0002-3548-7440 FU NIH [K99DK078779, DK52989, NS032273, DK68384, P30DK035816, P30DK17047]; Office of Research and Development Medical Research Service, Department of Veterans Affairs FX These studies were supported by NIH grants K99DK078779 to DLW and DK52989, NS032273 and DK68384 to MWS. This material is also based upon work supported in part by the Office of Research and Development Medical Research Service, Department of Veterans Affairs. Dr. Baskin is Senior Research Career Scientist, Research and Development Service, Department of Veterans Affairs Puget Sound Health Care System, Seattle, WA. This research was also supported by the Clinical Nutrition Research Unit at the University of Washington, supported by NIH grant P30DK035816, and the facilities of the Cellular and Molecular Imaging Core of the University of Washington NIH Diabetes Endocrinology Research Center, supported by NIH grant P30DK17047. NR 30 TC 23 Z9 23 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD NOV PY 2009 VL 297 IS 5 BP R1238 EP R1246 DI 10.1152/ajpregu.00182.2009 PG 9 WC Physiology SC Physiology GA 514CR UT WOS:000271371900003 PM 19726710 ER PT J AU Bauer, MS Biswas, K Kilbourne, AM AF Bauer, Mark S. Biswas, Kousick Kilbourne, Amy M. TI Enhancing Multiyear Guideline Concordance for Bipolar Disorder Through Collaborative Care SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT Annual Meeting of the VA-Health-Services-Research-and-Development CY FEB 11-13, 2009 CL Baltimore, MD SP VA Hlth Serv Res & Dev ID IMPROVING PRIMARY-CARE; MEDICATION-ALGORITHM-PROJECT; CLINICAL-PRACTICE GUIDELINES; RANDOMIZED CONTROLLED-TRIAL; LATE-LIFE DEPRESSION; QUALITY-OF-CARE; MENTAL-HEALTH; THERAPEUTIC DRUG; CHRONIC ILLNESS; I DISORDER AB Objective: Implementation of evidence-based care for serious mental illnesses such as bipolar disorder has been suboptimal. Improving and sustaining concordance with clinical practice guidelines has been a cornerstone of efforts to enhance evidence-based care and improve outcomes. For bipolar disorder, however, there has been only one regional controlled trial reporting guideline concordance, and no data are available for time periods longer than 1 year. In a multiregion effectiveness trial in veterans with bipolar disorder, the authors assessed the effects of a collaborative care model for this disorder on guideline concordance in care over a 3-year period. Method: A total of 306 participants with bipolar disorder were randomly assigned at hospital discharge to 3 years of follow-up treatment with a collaborative care model or to usual care. The collaborative care model included provider support through simplified practice guidelines, patient skills management enhancement through group psychoeducation, and facilitated access and continuity via nurse care management. Concordance with guideline-recommended antimanic pharmacotherapy was assessed at baseline and prospectively over six 6-month epochs. Group differences were assessed with generalized estimating equations that controlled for relevant covariates. Results: The collaborative care model achieved significantly higher rates of guideline-concordant antimanic treatment than usual care over the entire follow-up period. Baseline guideline concordance, but not patient age or bipolar type, was associated with higher concordance. Conclusions: Multicomponent collaborative care models, which include not only provider support for guideline implementation but also patient self-management skill enhancement and facilitated treatment access and continuity, can improve guideline concordance over the long term, even in severely impaired patients. C1 Harvard Univ, Sch Med, Boston, MA USA. Boston VA Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. Perry Point VA Cooperat Studies Coordinating Ctr, Perry Point, MD USA. VA Natl Serious Mental Illness Treatment Res & Ev, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. RP Bauer, MS (reprint author), VA Boston Healthcare Syst, Brockton Campus 116A7,940 Belmont St, Brockton, MA 02301 USA. EM mark.bauer@va.gov NR 37 TC 33 Z9 33 U1 2 U2 14 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 NOV PY 2009 VL 166 IS 11 BP 1244 EP 1250 DI 10.1176/appi.ajp.2009.09030342 PG 7 WC Psychiatry SC Psychiatry GA 514XL UT WOS:000271429600011 PM 19797436 ER PT J AU Rashid, JR Spengler, RF Wagner, RM Melanson, C Skillen, EL Mays, RA Heurtin-Roberts, S Long, JA AF Rashid, Jamila R. Spengler, Robert F. Wagner, Robin M. Melanson, Cindi Skillen, Elizabeth L. Mays, Robert A., Jr. Heurtin-Roberts, Suzanne Long, Judith A. TI Eliminating Health Disparities Through Transdisciplinary Research, Cross-Agency Collaboration, and Public Participation SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID UNITED-STATES; TRENDS; SCIENCE; DISEASE AB Despite efforts to the contrary, disparities in health and health care persist in the United States. To solve this problem, federal agencies representing different disciplines and perspectives are collaborating on a variety of transdisciplinary research initiatives. The most recent of these initiatives was launched in 2006 when the Centers for Disease Control and Prevention's Office of Public Health Research and the Department of Health and Human Services' Office of Minority Health brought together federal partners representing a variety of disciplines to form the Federal Collaboration on Health Disparities Research (FCHDR). FCHDR collaborates with a wide variety of federal and nonfederal partners to support and disseminate research that aims to reduce or eliminate disparities in health and health care. Given the complexity involved in eliminating health disparities, there is a need for more transdisciplinary, collaborative research, and facilitating that research is FCHDR's mission. (Am J Public Health. 2009;99:1955-1961. doi:10.2105/AJPH.2009.167932) C1 [Rashid, Jamila R.; Spengler, Robert F.; Wagner, Robin M.; Melanson, Cindi; Skillen, Elizabeth L.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Heurtin-Roberts, Suzanne] Off Minor Hlth, Dept Hlth & Human Serv, Rockville, MD USA. [Mays, Robert A., Jr.] NIH, Bethesda, MD 20892 USA. [Long, Judith A.] Philadelphia VA Ctr Hlth Equ Res & Promot, Dept Vet Affairs, Philadelphia, PA USA. RP Rashid, JR (reprint author), HHS, Off Minor Hlth, 1101 Wootton Pkwy,Suite 600, Rockville, MD 20852 USA. EM jamila.rashid@hhs.gov RI Heurtin-Roberts, Suzanne/D-7274-2013 NR 31 TC 16 Z9 16 U1 0 U2 9 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 2009 VL 99 IS 11 BP 1955 EP 1961 DI 10.2105/AJPH.2009.167932 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 511ZD UT WOS:000271209900012 PM 19762652 ER PT J AU Silverman, JB Prasittivatechakool, K Busaba, NY AF Silverman, Joshua B. Prasittivatechakool, Kajohnkiat Busaba, Nicolas Y. TI An evidence-based review of endoscopic frontal sinus surgery SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Review DE Draf procedure; endoscopic frontal surgery; evidence-based medicine; frontal sinus; frontal sinusitis; Lothrop procedure; osteoplastic frontal sinus obliteration ID MODIFIED LOTHROP PROCEDURE; FOLLOW-UP; OSTEOPLASTIC FLAP; SURGICAL OUTCOMES; EXPERIENCE; OBLITERATION; MANAGEMENT; REVISION; DRILLOUT; SALVAGE AB Background: Endoscopic approaches to treat frontal sinus disease gained in popularity over the past 20 years with a plethora of published studies that emphasize the high success rate of such surgeries. This study was designed to determine the levels of clinical evidence in the otolaryngology literature that address the efficacy of endoscopic approaches in the management of frontal sinus disease including frontal sinusitis. Methods: Twenty-three publications that reported the surgical outcomes of endoscopic approaches to treat frontal sinus disease were reviewed. Data were collected regarding the study design, operative technique, number of patients, duration of follow-up, diagnostic method, surgical success rate, and method(s) used to assess surgical outcome. Results: The study designs were a retrospective case series without control (16 articles), prospective case series without control (3 articles), and retrospective case series with internal control (4 articles). Eighty-three percent of the published articles provide an evidence level of IV, while the remaining 17% provide an evidence level of III. The surgical technique was described as frontal sinusotomy (n = 4), frontal sinusotomy or frontal sinus drillout (n = 1), frontal sinus drillout alone (n = 1), endoscopic modified Lothrop procedure (n = 9), Draf types I, II, or III (n = 6); trans-septal frontal sinusotomy (n = 1); and frontal sinus rescue procedure (n = 1). The mean number of subjects was 44, and the average follow-up period was 23.6 months. Surgical success rate ranged from 50 to 100%. Conclusion: Despite the number of reports in the literature that address the surgical outcome of endoscopic approaches for treatment of frontal sinus disease, the majority of these studies have a small population size, short follow-up period, and provide a low clinical evidence level. (Am J Rhinol Allergy 23, e59-e62, 2009; doi: 10.2500/ajra.2009.23.3406) C1 [Silverman, Joshua B.; Prasittivatechakool, Kajohnkiat; Busaba, Nicolas Y.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Busaba, Nicolas Y.] VA Boston HealthCare Syst, Div Otolaryngol, Boston, MA USA. [Silverman, Joshua B.; Busaba, Nicolas Y.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Prasittivatechakool, Kajohnkiat] Phramongkutklao Hosp, Dept Otorhinolaryngol, Bangkok, Thailand. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM Nicolas_busaba@meei.harvard.edu NR 28 TC 11 Z9 12 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD NOV-DEC PY 2009 VL 23 IS 6 BP E59 EP E62 DI 10.2500/ajra.2009.23.3406 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA V17NR UT WOS:000207944400014 PM 19958599 ER PT J AU Kligerman, S Digumarthy, S AF Kligerman, Seth Digumarthy, Subba TI Staging of Non-Small Cell Lung Cancer Using Integrated PET/CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE non-small cell lung cancer; PET/CT ID POSITRON-EMISSION-TOMOGRAPHY; CT; METASTASES C1 [Kligerman, Seth; Digumarthy, Subba] Massachusetts Gen Hosp, Dept Thorac Radiol, Boston, MA 02111 USA. [Kligerman, Seth; Digumarthy, Subba] Harvard Univ, Sch Med, Boston, MA 02111 USA. RP Digumarthy, S (reprint author), Massachusetts Gen Hosp, Dept Thorac Radiol, 55 Fruit St,Founders 202, Boston, MA 02111 USA. EM sdigumarthy@partners.org NR 21 TC 29 Z9 33 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 NOV PY 2009 VL 193 IS 5 BP 1203 EP 1211 DI 10.2214/AJR.09.3193 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 508ST UT WOS:000270956700002 PM 19843732 ER PT J AU Argo, JL Vick, CC Graham, LA Itani, KMF Bishop, MJ Hawn, MT AF Argo, Joshua L. Vick, Catherine C. Graham, Laura A. Itani, Kamal M. F. Bishop, Michael J. Hawn, Mary T. TI Elective surgical case cancellation in the Veterans Health Administration system: identifying areas for improvement SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Surgery; Operating room efficiency; Case cancellation; Quality; Quality improvement ID OPERATING-ROOM EFFICIENCY; PREOPERATIVE EVALUATION; SURGERY; TIME AB BACKGROUND: This study evaluated elective surgical case cancellation (CC) rates, reasons for these cancellations, and identified areas for improvement within the Veterans Health Administration (VA) system. METHODS: CC data for 2006 were collected from the scheduling software for 123 VA facilities. Surveys were distributed to 40 facilities (10 highest and 10 lowest CC rates for high- and low-volume facilities). CC reasons were standardized and piloted at 5 facilities. RESULTS: 017 329,784 cases scheduled by 9 surgical specialties, 40,988 (12.4%) were cancelled. CC reasons (9,528) were placed into 6 broad categories: patient (35%), work-up/medical condition change (28%), facility (20%), surgeon (8%), anesthesia (1%), and miscellaneous (8%). Survey results show areas for improvement at the facility level and a standardized list of 28 CC reasons was comprehensive. CONCLUSIONS: Interventions that decrease cancellations caused by patient factors, inadequate work-Lip, and facility factors are needed to reduce overall elective surgical case cancellations. Published by Elsevier Inc. C1 [Argo, Joshua L.; Vick, Catherine C.; Graham, Laura A.; Hawn, Mary T.] Birmingham Vet Adm Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA. [Argo, Joshua L.; Vick, Catherine C.; Hawn, Mary T.] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. [Itani, Kamal M. F.] VA Boston Hlth Care Syst, Dept Surg, W Roxbury, MA USA. [Itani, Kamal M. F.] Boston Univ, Dept Surg, Boston, MA 02215 USA. [Bishop, Michael J.] Cent Off, Dept Vet Affairs, Washington, DC USA. [Bishop, Michael J.] Puget Sound VA Hlth Care Syst, Seattle, WA USA. [Bishop, Michael J.] Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. RP Hawn, MT (reprint author), Birmingham Vet Adm Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA. EM mary.hawn@ccc.uab.edu FU Agency for Healthcare Research and Quality [5 T32 HS013852]; Office of Patient Care Services of the Department of Veterans Affairs FX This project was supported in part by grant number 5 T32 HS013852 from the Agency for Healthcare Research and Quality and a contract from the Office of Patient Care Services of the Department of Veterans Affairs. NR 24 TC 33 Z9 34 U1 1 U2 4 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 NOV PY 2009 VL 198 IS 5 BP 600 EP 606 DI 10.1016/j.amjsurg.2009.07.005 PG 7 WC Surgery SC Surgery GA 522KY UT WOS:000271997900005 PM 19887185 ER PT J AU Dhaliwal, AS Chu, D Huh, J Ghadir, M Sansgiry, S Atluri, P LeMaire, SA Coselli, JS Bakaeen, FG AF Dhaliwal, Amandeep S. Chu, Danny Huh, Joseph Ghadir, Mued Sansgiry, Shubhada Atluri, Prasad LeMaire, Scott A. Coselli, Joseph S. Bakaeen, Faisal G. TI Prognostic impact of intra-aortic balloon pump insertion before versus after cardiac surgical intervention in a veteran population SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Intra-aortic balloon pump; Morbidity; Mortality; Cardiac surgery; Outcomes ID CORONARY-BYPASS SURGERY; GRAFT-SURGERY; RISK; OUTCOMES AB BACKGROUND: The relative prognostic impact of intra-aortic balloon pump (IABP) placement before versus after cardiac surgery is not well defined. METHODS: We reviewed data from all cardiac surgical patients who received perioperative IABP support at a veterans' hospital between April 1992 and April 2008. We compared outcomes between patients who received an IABP before surgery (BS, n = 36) and after surgery (AS, n = 28). RESULTS: The AS group had higher operative morbidity (71% vs 42%) and mortality (43% vs 14%) rates than the BS aroup (P < .02 for both). Furthermore, survival rates were lower in the AS group than in the BS group at 1 year (50% vs 83%) and 3 years (46% vs 80%) (log-rank test, P < .004). CONCLUSIONS: Patients who require IABP after cardiac surgery may have worse outcomes than patients who receive IABP support before surgery. In both groups, after an early peak in mortality, the midterm outcomes were characterized by a reassuring plateau in the survival rates. Published by Elsevier Inc. C1 [Chu, Danny; Huh, Joseph; Ghadir, Mued; LeMaire, Scott A.; Coselli, Joseph S.; Bakaeen, Faisal G.] Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX 77030 USA. [Dhaliwal, Amandeep S.] Baylor Coll Med, Dept Med, Div Cardiol, Houston, TX 77030 USA. [Chu, Danny; Huh, Joseph; Sansgiry, Shubhada; Atluri, Prasad; Bakaeen, Faisal G.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Chu, Danny; Huh, Joseph; LeMaire, Scott A.; Coselli, Joseph S.; Bakaeen, Faisal G.] St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX USA. RP Bakaeen, FG (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX 77030 USA. EM fbakaeen@bcm.edu NR 14 TC 6 Z9 8 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 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2009 VL 198 IS 5 BP 628 EP 632 DI 10.1016/j.amjsurg.2009.07.011 PG 5 WC Surgery SC Surgery GA 522KY UT WOS:000271997900010 PM 19887190 ER PT J AU Kaafarani, HMA Hur, K Hirter, A Kim, LT Thomas, A Berger, DH Reda, D Itani, KMF AF Kaafarani, Haytham M. A. Hur, Kwan Hirter, Angie Kim, Lawrence T. Thomas, Anthony Berger, David H. Reda, Domenic Itani, Kamal M. F. TI Seroma in ventral incisional herniorrhaphy: incidence, predictors and outcome SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Seroma; Ventral hernia; Postoperative wound infection ID HERNIA REPAIR; EXPANDED POLYTETRAFLUOROETHYLENE; LAPAROSCOPIC REPAIR; TRIAL; MESH AB BACKGROUND: Factors leading to seroma following ventral incisional herniorrhaphy (VIH) are poorly understood. METHODS: Between 2004 and 2006, patients were prospectively randomized at 4 Veterans Affairs hospitals to undergo laparoscopic or open VIH. Patients who developed seromas within 8 weeks postoperatively were compared with those who did not. Multivariate analyses were per-formed to identify predictors of scroma. RESULTS: Of 145 patients who underwent VIH, 24 (16.6%) developed seromas. Patients who underwent Open VIH had more seromas than those who underwent laparoscopic VIH (23.3% vs 6.8%, P = .011). Seroma patients had hernias that were never spontaneously reducible (0% vs 21%, P = .015), had more abdominal incisions preoperatively (mean, 2.4 vs 1.8; P = .037), and were less likely to have drain catheters placed than those without seromas (30.0% vs 63.1%, P = .011). In multivariate analyses, open VIH predicted seroma (odds ratio, 5.5; 95% confidence interval, 1.6-18.8), as well as the specific hospital at which the procedure was performed. Spontaneous resolution occurred in 71% of seromas; 29% required aspiration. CONCLUSIONS: Procedural characteristics and hernia characteristics rather than patient comorbidities predicted seroma in VIH. Published by Elsevier Inc. C1 [Kaafarani, Haytham M. A.; Itani, Kamal M. F.] VA Boston Healthcare Syst, W Roxbury, MA USA. [Kaafarani, Haytham M. A.] Univ S Florida, Tampa, FL USA. [Kaafarani, Haytham M. A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Hur, Kwan; Hirter, Angie; Reda, Domenic] Coordinating Ctr, VA Cooperat Studies Program, Hines, IL USA. [Kim, Lawrence T.] Cent Arkansas Vet Hlth Care Syst, Little Rock, AR USA. [Kim, Lawrence T.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Thomas, Anthony] N Texas VA Hlth Care Syst, Dallas, TX USA. [Berger, David H.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Thomas, Anthony] Southwestern Univ, Dallas, TX USA. [Berger, David H.] Baylor Coll Med, Houston, TX 77030 USA. [Itani, Kamal M. F.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. RP Itani, KMF (reprint author), VA Boston Healthcare Syst, W Roxbury, MA USA. EM kitani@med.va.gov OI Hirter, Angie/0000-0001-6616-2123 NR 18 TC 23 Z9 24 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 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2009 VL 198 IS 5 BP 639 EP 644 DI 10.1016/j.amjsurg.2009.07.019 PG 6 WC Surgery SC Surgery GA 522KY UT WOS:000271997900012 PM 19887192 ER PT J AU Kougias, P Chen, A Cagiannos, C Bechara, CF Huynh, TT Lin, PH AF Kougias, Panagiotis Chen, Aaron Cagiannos, Catherine Bechara, Carlos F. Huynh, Tam T. Lin, Peter H. TI Subintimal placement of covered stent versus subintimal balloon angioplasty in the treatment of long-segment superficial femoral artery occlusion SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Subintimal angioplasty; Covered stent; Superficial femoral artery; Endovascular ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; FEMOROPOPLITEAL ARTERY; LIMB ISCHEMIA; DISEASE; GRAFT; ENDOPROSTHESIS; OBSTRUCTIONS; MULTICENTER; EXPERIENCE; BYPASS AB BACKGROUND: Subintimal endovascular intervention has been used widely in the treatment of symptomatic superficial femoral artery (SFA) Occlusion. The relative effectiveness of subintimal placement of a covered stent (CS) versus balloon-only subintimal angioplasty (SIA) remains uncertain. METHODS: We performed a retrospective cohort study of consecutive patients with symptomatic SFA occlusions (> 15 cm) who underwent subintimal endovascular intervention, either CS or SIA, in a single institution. Primary patency was the primary outcome. Secondary outcomes included complication rates, freedom from re-intervention, and limb salvage rates. Patency was ascertained with followup duplex or clinically. RESULTS: We evaluated 57 patients in the SIA group and 31 patients in the CS group. At 1 year the SFA primary patency for the SIA and CS groups was 28% versus 75% (P < .001), whereas the primary assisted patency was 37% versus 84% (P < .001), respectively. Need for bypass was 13% versus 0% (P = .05) in the SIA and CS groups, respectively. CONCLUSIONS: Placement of a covered stent improves patency after subintimal intervention for long SFA Occlusion. Published by Elsevier Inc. C1 [Kougias, Panagiotis; Chen, Aaron; Cagiannos, Catherine; Bechara, Carlos F.; Huynh, Tam T.; Lin, Peter H.] Baylor Coll Med, Div Vasc Surg & Endovasc Therapy, Michael E DeBakey Dept Surg, Houston VAMC, Houston, TX 77030 USA. RP Kougias, P (reprint author), Baylor Coll Med, Div Vasc Surg & Endovasc Therapy, Michael E DeBakey Dept Surg, Houston VAMC, 2002 Holcombe Blvd 112, Houston, TX 77030 USA. EM pkougias@bcm.edu NR 16 TC 18 Z9 20 U1 1 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 NOV PY 2009 VL 198 IS 5 BP 645 EP 649 DI 10.1016/j.amjsurg.2009.07.017 PG 5 WC Surgery SC Surgery GA 522KY UT WOS:000271997900013 PM 19887193 ER PT J AU Leong, M Chike-Obi, CJ Basu, CB Lee, EI Albo, D Netscher, DT AF Leong, Mimi Chike-Obi, Chuma J. Basu, C. Bob Lee, Edward I. Albo, Daniel Netscher, David T. TI Effective breast reconstruction in female veterans SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Breast reconstruction; Female veterans; Multidisciplinary teams ID PATIENT SATISFACTION; CANCER; OUTCOMES; AFFAIRS; IMPACT; MASTECTOMY; IMMEDIATE; CARE AB BACKGROUND: Despite increasing female veteran numbers, literature regarding reconstruction after breast cancer is lacking. The purpose of this study was to examine breast reconstruction referral rates and reconstruction outcomes at a tertiary Veterans Affairs hospital. METHODS: Female breast cancer patients (1997-2008) were identified. Demographics, tumor stage, oncologic therapies, reconstructive timings and procedures, and complications were noted. RESULTS: Eighty-two women underwent mastectomy (46%) or breast conservation (43%). The referral rates to plastic surgery were 61% (mastectomy) and 32% (overall). Reconstruction rates were 42% (mastectomy) and 22% (overall). Sixty-nine percent were suitable candidates and chose immediate (67%) or delayed (33%) reconstruction, with implant-based (44%), autologous (39%), or autologous plus implants (17%). There were complications (28%) but no mortalities. Comorbidifies were not correlated with outcomes. CONCLUSIONS: Breast reconstruction can be effectively delivered within the Veterans Affairs system. It is essential that sufficient Veterans Affairs resources be deployed to address the increasing reconstructive needs of female veterans. Published by Elsevier Inc. C1 [Leong, Mimi; Netscher, David T.] Michael E DeBakey Vet Affairs Med Ctr, Sect Plast Surg, Houston, TX USA. [Albo, Daniel] Michael E DeBakey Vet Affairs Med Ctr, Sect Gen Surg, Houston, TX USA. [Leong, Mimi; Chike-Obi, Chuma J.; Lee, Edward I.; Netscher, David T.] Baylor Coll Med, Div Plast Surg, Houston, TX 77030 USA. [Basu, C. Bob] Inst Adv Breast Reconstruct, Houston, TX USA. RP Leong, M (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Sect Plast Surg, Houston, TX USA. EM mimi.leong@va.gov NR 19 TC 1 Z9 1 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 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2009 VL 198 IS 5 BP 658 EP 663 DI 10.1016/j.amjsurg.2009.07.020 PG 6 WC Surgery SC Surgery GA 522KY UT WOS:000271997900015 PM 19887195 ER PT J AU Wilks, JA Balentine, CJ Berger, DH Anaya, D Awad, S Lee, L Haderxhanaj, K Albo, D AF Wilks, Jonathan A. Balentine, Courtney J. Berger, David H. Anaya, Daniel Awad, Samir Lee, Liz Haderxhanaj, Kujtim Albo, Daniel TI Establishment of a minimally invasive program at a Veterans' Affairs Medical Center leads to improved care in colorectal cancer patients SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Colorectal cancer; Minimally invasive; Laparoscopic surgery; Veterans; Clinical outcomes; Hand-assisted laparoscopic surgery ID MRC CLASICC TRIAL; LAPAROSCOPIC-ASSISTED COLECTOMY; COST STUDY-GROUP; RANDOMIZED-TRIAL; COLON-CANCER; LEARNING-CURVE; SURGERY; RESECTION; OUTCOMES; METAANALYSIS AB BACKGROUND: Despite significant advantages to patients, less than 5% of all colorectal Surgeries for cancer are performed laparoscopically. A minimally invasive colorectal cancer program was created in our Veterans' Affairs hospital with the intent of increasing access and improving quality of patient care while maintaining patient safety and oncologic standards. METHODS: Sixty consecutive laparoscopic colorectal cancer resections and 60 age-matched open resections were identified. Our prospective database was queried for demographic, clinical outcomes, and oncologic data. RESULTS: Patients undergoing laparoscopic resections experienced a shorter hospital stay and a quicker return of bowel function. Both groups had similar intraoperative blood loss and surgical times. Laparoscopic resections achieved equivalent lymph node retrieval and resection completeness compared with open resections. Laparoscopic resections resulted in fewer wounds and fewer complications requiring reoperation. CONCLUSIONS: Establishment of a minimally invasive colorectal cancer program in a Veterans Affairs Medical Center leads to increased access to laparoscopic colorectal resections and improved patient care while maintaining patient safety. Published by Elsevier Inc. C1 [Wilks, Jonathan A.; Balentine, Courtney J.; Berger, David H.; Anaya, Daniel; Awad, Samir; Lee, Liz; Haderxhanaj, Kujtim; Albo, Daniel] Michael E DeBakey Vet Affairs Med Ctr, Div Gen Surg & Surg Oncol, Houston, TX 77030 USA. [Wilks, Jonathan A.; Balentine, Courtney J.; Berger, David H.; Anaya, Daniel; Awad, Samir; Lee, Liz; Albo, Daniel] Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. RP Albo, D (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Div Gen Surg & Surg Oncol, 2002 Holcombe Blvd,OCL 112-A, Houston, TX 77030 USA. EM dalbo@bcm.edu NR 27 TC 9 Z9 9 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 NOV PY 2009 VL 198 IS 5 BP 685 EP 692 DI 10.1016/j.amjsurg.2009.07.016 PG 8 WC Surgery SC Surgery GA 522KY UT WOS:000271997900020 PM 19887200 ER PT J AU Bush, RL DePalma, RG Itani, KMF Henderson, WG Smith, TS Gunnar, WP AF Bush, Ruth L. DePalma, Ralph G. Itani, Kamal M. F. Henderson, William G. Smith, Tracy S. Gunnar, William P. TI Outcomes of care of abdominal aortic aneurysm in Veterans Health Administration facilities: results from the National Surgical Quality Improvement Program SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Abdominal aortic aneurysm; Endovascular aneurysm repair; EVAR; Veterans; NSQIP; Ruptured abdominal aneurysm; Quality improvement ID RANDOMIZED CONTROLLED-TRIAL; ENDOVASCULAR REPAIR; OPERATIVE MORTALITY; PROVIDER VOLUME; LEARNING-CURVE; AAA REPAIRS; RISK; PERFORMANCE; EXPERIENCE; SURVIVAL AB This-report describes outcomes of care for abdominal aortic aneurysms (AAAs), along with methods used by the Veterans Affairs (VA) National Surgical Quality Improvement Program (NSQIP) in tracking, monitoring, and improving surgical results in VA facilities. Since the inception of NSQIP in 1994, a continual drop in overall surgical mortality, along with decreased morbidity, has occurred. A parallel improvement in results of vascular surgery and AAA repair was also observed. Soon after introduction of endovascular aneurysm repair (EVAR), with Food and Drug Administration device approval in 1999, robust electronic NSQIP records immediately began to capture individual facility performances and outcomes for both types of AAA repair. The NSQIP data center provided actual and risk-adjusted analyses for both procedures semiannually. These analyses have been used by its executive board to provide recommendations, often based on site visits, to improve outcomes. Requirements for reporting of facility-specific data and feedback, paper audits, and site visits appear to relate directly to improved AAA care. Veterans Health Administration (VHA) outcomes of AAA repair are comparable to those reported nationally and internationally and have continued to improve in recent years. National VHA initiatives, based on data feedback and active oversight, relate to some of the lowest AAA mortality rates available. This review describes past, present, and possible future NSQIP strategies to improve outcomes for AAA repair with general comments about recent alternative proposals. (C) 2009 Published by Elsevier Inc. C1 [Bush, Ruth L.] Texas A&M Hlth Sci Ctr, Olin E Teague Vet Affairs Med Ctr, Temple, TX USA. [DePalma, Ralph G.; Gunnar, William P.] Affairs Cent Off, Dept Vet, Washington, DC USA. [Itani, Kamal M. F.] Boston Univ, Vet Affairs Boston Hlth Care Syst, Boston, MA 02215 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. [Henderson, William G.] Univ Colorado, Med Ctr, Denver, CO 80202 USA. [Smith, Tracy S.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Bush, RL (reprint author), Texas A&M Hlth Sci Ctr, Olin E Teague Vet Affairs Med Ctr, Temple, TX USA. EM ruth.bush@va.gov NR 31 TC 4 Z9 5 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 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2009 VL 198 IS 5A BP S41 EP S48 DI 10.1016/j.amjsurg.2009.08.005 PG 8 WC Surgery SC Surgery GA 522KZ UT WOS:000271998000007 PM 19874934 ER PT J AU Kaafarani, HMA Rosen, AK AF Kaafarani, Haytham M. A. Rosen, Amy K. TI Using administrative data to identify surgical adverse events: an introduction to the Patient Safety Indicators SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Adverse events; Patient safety; Quality indicators; Patient safety indicators; Quality improvement; Complications; Administrative data ID QUALITY IMPROVEMENT PROGRAM; SURGERY REPORT CARDS; MORTALITY CONFERENCE; COMPLICATIONS; MORBIDITY AB BACKGROUND: The Patient Safety Indicators (PSIs) are algorithms based on the International Classification of Diseases, Ninth Revision, Clinical Modification, aimed at identifying potential safety-related adverse events through the automated screening of readily available administrative databases. Many of these indicators focus on surgical care, and a few have been endorsed by the National Quality Forum as performance measures. The aim of this report is to give a brief overview of the development and definitions of the PSIs as well as the current evidence for their validity, compared with the National Surgical Quality Improvement Program and chart abstraction designed for the. purpose of PSI validation. METHODS: Several articles published in the past few years, in addition to primary data collected from an ongoing study of PSI validation in the Veterans Health Administration, were examined. RESULTS: Selected surgical PSIs have positive predictive values ranging from 22% to 89%, depending on the nature of the PSI and the method of validation used. CONCLUSIONS: With adequate coding revisions, PSI performance can be substantially improved. (C) 2009 Published by Elsevier Inc. C1 [Kaafarani, Haytham M. A.; Rosen, Amy K.] Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Kaafarani, Haytham M. A.] VA Boston Healthcare Syst, Dept Surg, W Roxbury, MA USA. [Rosen, Amy K.] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Rosen, AK (reprint author), Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. EM akrosen@bu.edu NR 13 TC 22 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 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2009 VL 198 IS 5A BP S63 EP S68 DI 10.1016/j.amjsurg.2009.08.008 PG 6 WC Surgery SC Surgery GA 522KZ UT WOS:000271998000010 PM 19874937 ER PT J AU Graham, JA Wilkinson, RA Hirohashi, T Chase, CM Colvin, RB Madsen, JC Fishman, JA Russell, PS AF Graham, J. A. Wilkinson, R. A. Hirohashi, T. Chase, C. M. Colvin, R. B. Madsen, J. C. Fishman, J. A. Russell, P. S. TI Viral Infection Induces De Novo Lesions of Coronary Allograft Vasculopathy Through a Natural Killer Cell-Dependent Pathway SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Allograft arteriopathy; cardiac transplant; coronary artery disease; graft rejection; NK-cells; viral; vasculopathy ID MHC CLASS-I; DENDRITIC CELLS; NK CELLS; CARDIAC ALLOGRAFTS; T-CELLS; VIRUS-INFECTION; MICE; REJECTION; ACTIVATION; IMMUNITY AB Viral infections including those due to cytomegalovirus have been associated with accelerated cardiac allograft vasculopathy (CAV) in clinical trials and some animal models. Evidence demonstrating a direct causal relationship between such infections and de novo formation of coronary vascular lesions is lacking. Heterotopic murine cardiac transplants were performed in a parental to F1 combination in animals lacking both T- and B-lymphocytes (RAG-/-). Coronary vasculopathy developed almost exclusively in the presence of recipient infection with lymphocytic choriomeningitis virus but not in uninfected controls. This process was also dependent upon the presence of natural killer (NK) cells as depletion of NK cells abrogated the process. These data show that a viral infection in its native host, and not previously implicated in the production of CAV, can contribute to the development of advanced coronary vascular lesions in cardiac allotransplants in mice. These data also suggest that virus-induced CAV can develop via an NK-cell-dependent pathway in the absence of T- and B-lymphocytes. C1 [Graham, J. A.; Hirohashi, T.; Chase, C. M.; Madsen, J. C.; Russell, P. S.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Transplantat Res Div, Boston, MA 02115 USA. [Graham, J. A.; Hirohashi, T.; Chase, C. M.; Madsen, J. C.; Russell, P. S.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Cardiac Surg Div, Boston, MA 02115 USA. [Wilkinson, R. A.; Fishman, J. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Infect Dis Program,Infect Dis Div, Boston, MA USA. [Colvin, R. B.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Graham, JA (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Transplantat Res Div, Boston, MA 02115 USA. EM jfishman@partners.org RI Graham, Jay/A-4896-2014 OI Graham, Jay/0000-0003-2054-1253 FU National Heart Blood and Lung Institute [NIH-NHLBI-RO1 HL071932]; National Institute of Allergy and Infectious Disease (NIH-NIAID) [PO1-AI45897]; Roche Organ Transplant Research Foundation; American Society of Transplantation FX This work was funded in part by Public Health Services grants from the National Heart Blood and Lung Institute (NIH-NHLBI-RO1 HL071932), National Institute of Allergy and Infectious Disease (NIH-NIAID PO1-AI45897) and a grant from the Roche Organ Transplant Research Foundation. T.H. is the recipient of a Basic Science Grant from the American Society of Transplantation. We thank Tricia DellaPelle for expert preparation and staining of histological material. NR 33 TC 21 Z9 21 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD NOV PY 2009 VL 9 IS 11 BP 2479 EP 2484 DI 10.1111/j.1600-6143.2009.02801.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 508AT UT WOS:000270899900009 PM 19843029 ER PT J AU Echeverria, GJ McGrath, K Bottino, R Hara, H Dons, EM van der Windt, DJ Ekser, B Casu, A Houser, S Ezzelarab, M Wagner, R Trucco, M Lakkis, FG Cooper, DKC AF Echeverria, G. J. McGrath, K. Bottino, R. Hara, H. Dons, E. M. van der Windt, D. J. Ekser, B. Casu, A. Houser, S. Ezzelarab, M. Wagner, R. Trucco, M. Lakkis, F. G. Cooper, D. K. C. TI Endoscopic Gastric Submucosal Transplantation of Islets (ENDO-STI): Technique and Initial Results in Diabetic Pigs SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Endoscopy; gastric submucosal space; pig; portal vein; transplantation; islets ID PANCREATIC-ISLETS; XENOTRANSPLANTATION; HYPOGLYCEMIA; IMPLANTATION; STRATEGIES; CELLS; MODEL; SITE; AUTO AB The results of transplantation of human donor islets into the portal vein (PV) in patients with diabetes are encouraging. However, there are complications, for example, hemorrhage, thrombosis and an immediate loss of islets through the 'instant blood-mediated inflammatory reaction' (IBMIR). The gastric submucosal space (GSMS) offers potential advantages. Islets were isolated from adult pigs. Recipient pigs were made diabetic by streptozotocin. Donor islets were injected into the GSMS through a laparotomy (Group 1A, n = 4) or endoscopically (Group 1B, n = 8) or into the PV through a laparotomy (Group 2, n = 3). The pigs were followed for a maximum of 28 days. Monitoring of C-peptide in Group 1 indicated that there was minimal immediate loss of islets whereas in Group 2 there was considerable loss from IBMIR. In Group 1, there were significant reductions in mean blood glucose and mean exogenous insulin requirement between pretransplantation and 20 days posttransplantation. In Group 2, there was no significant reduction in either parameter. Insulin-positive cells were seen in the GSMS in Group 1, but not in the liver in Group 2. Endoscopic gastric submucosal transplantation of islets (ENDO-STI) offers a minimally invasive and quick approach to islet transplantation, avoids IBMIR and warrants further exploration. C1 [Echeverria, G. J.; Hara, H.; Dons, E. M.; van der Windt, D. J.; Ekser, B.; Ezzelarab, M.; Lakkis, F. G.; Cooper, D. K. C.] Univ Pittsburgh, Dept Surg, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15260 USA. [Echeverria, G. J.] Fdn Clin Valle del Lili, Transplantat Unit, Cali, Colombia. [McGrath, K.] Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Bottino, R.; van der Windt, D. J.; Casu, A.; Trucco, M.] Univ Pittsburgh, Dept Pediat, Div Immunogenet, Pittsburgh, PA 15260 USA. [Dons, E. M.; van der Windt, D. J.] Erasmus MC, Dept Surg, Rotterdam, Netherlands. [Houser, S.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ekser, B.] Univ Padua, Dept Surg & Organ Transplantat, Padua, Italy. [Wagner, R.] Univ Pittsburgh, Div Lab Anim Resources, Pittsburgh, PA USA. RP Cooper, DKC (reprint author), Univ Pittsburgh, Dept Surg, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15260 USA. EM cooperdk@upmc.edu OI ECHEVERRI, GABRIEL/0000-0001-6432-0327; Ezzelarab, Mohamed/0000-0002-3919-5250 FU Royal Netherlands Academy of Arts and Sciences; NIH [U01AI068642, R21-A1074844]; US Department of Defense; University of Pittsburgh and Revivicor, Inc., Blacksburg, VA; Thomas E. Starzl Transplantation Institute, University of Pittsburgh FX Funding source: Thomas E. Starzl Transplantation Institute, University of Pittsburgh. NR 32 TC 41 Z9 42 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD NOV PY 2009 VL 9 IS 11 BP 2485 EP 2496 DI 10.1111/j.1600-6143.2009.02815.x PG 12 WC Surgery; Transplantation SC Surgery; Transplantation GA 508AT UT WOS:000270899900010 PM 19775318 ER PT J AU Kelly, JX O'Neil, M Melendez, V Harris, E Ager, A Smilkstein, M Forquer, I Dodean, R Winter, R Hinrichs, D Riscoe, M AF Kelly, Jane X. O'Neil, Michael Melendez, Victor Harris, Erin Ager, Arba Smilkstein, Martin Forquer, Isaac Dodean, Rosie Winter, Rolf Hinrichs, Dave Riscoe, Mike TI A NOVEL ANTIMALARIAL CHEMOTYPE WITH EFFICACY AGAINST BOTH EXOERYTHROCYTIC AND ERYTHROCYTIC STAGES SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Kelly, Jane X.; Forquer, Isaac; Dodean, Rosie; Winter, Rolf; Hinrichs, Dave; Riscoe, Mike] Portland VA Med Ctr, Portland, OR USA. [O'Neil, Michael; Melendez, Victor; Harris, Erin] Walter Reed Army Inst Res, Div Expt Therapeut, Silver Spring, MD USA. [Ager, Arba] Univ Miami, Sch Med, Miami, FL USA. [Smilkstein, Martin] Oregon Translat Res & Drug Dev Inst, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2009 VL 81 IS 5 SU S MA 295 BP 83 EP 83 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700295 ER PT J AU Weil, AA Khan, AI Chowdhury, F LaRocque, RC Faruque, AS Ryan, ET Calderwood, SB Qadri, F Harris, JB AF Weil, Ana A. Khan, Ashraful I. Chowdhury, Fahima LaRocque, Regina C. Faruque, A. S. Ryan, Edward T. Calderwood, Stephen B. Qadri, Firdausi Harris, Jason B. TI CLINICAL OUTCOMES IN HOUSEHOLD CONTACTS OF PATIENTS WITH CHOLERA IN BANGLADESH SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Weil, Ana A.; Khan, Ashraful I.; Chowdhury, Fahima; Faruque, A. S.; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.; Harris, Jason B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2009 VL 81 IS 5 SU S MA 323 BP 92 EP 92 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700323 ER PT J AU Anstead, GM Zhang, Q Melby, PC AF Anstead, Gregory M. Zhang, Qiong Melby, Peter C. TI INSULIN-LIKE GROWTH FACTOR-1 ENHANCES THE INNATE IMMUNE RESPONSE OF MACROPHAGES FROM WELL-NOURISHED MICE BUT CAN NOT RECTIFY THE DEFECTIVE IMMUNE RESPONSE OF MACROPHAGES FROM MALNOURISHED MICE SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Anstead, Gregory M.; Zhang, Qiong; Melby, Peter C.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2009 VL 81 IS 5 SU S MA 480 BP 137 EP 137 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700479 ER PT J AU Noah, JW Citorik, R Wallace, C Lebrun, L Nebane, M McKellip, S Sosa, M Rasmussen, L Ryan, E White, EL Jonsson, C Harris, J AF Noah, James W. Citorik, Robert Wallace, Carrie Lebrun, Lauren Nebane, Miranda McKellip, Sara Sosa, Melinda Rasmussen, Lynn Ryan, Edward White, E. Lucile Jonsson, Colleen Harris, Jason TI A COMPARATIVE HIGH-THROUGHPUT SCREEN OF 300,000 COMPOUNDS FOR REGULATORS OF THE SALMONELLA ENTERICA PHOP REGULON BY THE MOLECULAR LIBRARIES PROBE CENTERS NETWORK SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Noah, James W.; Wallace, Carrie; Nebane, Miranda; McKellip, Sara; Sosa, Melinda; Rasmussen, Lynn; White, E. Lucile; Jonsson, Colleen] So Res Inst, So Res Specialized Biocontainment Screening Ctr, Birmingham, AL 35255 USA. [Citorik, Robert; Lebrun, Lauren; Ryan, Edward; Harris, Jason] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2009 VL 81 IS 5 SU S MA 610 BP 174 EP 174 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701026 ER PT J AU Osorio, EY Zhao, WG Espitia, CM Saldarriaga, OA Hawel, L Byus, CV Travi, BL Melby, PC AF Osorio, Elvia Y. Zhao, Weiguo Espitia, Claudia M. Saldarriaga, Omar A. Hawel, Leo Byus, Craig V. Travi, Bruno L. Melby, Peter C. TI DOMINANT ALTERNATIVE MACROPHAGE ACTIVATION IN PROGRESSIVE VISCERAL LEISHMANIASIS IS MEDIATED BY PARASITE-INDUCED STAT6 ACTIVATION AND ARGINASE EXPRESSION SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Osorio, Elvia Y.; Zhao, Weiguo; Espitia, Claudia M.; Saldarriaga, Omar A.; Travi, Bruno L.; Melby, Peter C.] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Hawel, Leo; Byus, Craig V.] Univ Calif Riverside, Riverside, CA 92521 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2009 VL 81 IS 5 SU S BP 189 EP 189 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701077 ER PT J AU Singh, N Singh, MP Wylie, BJ Shukla, MM Hussain, M Dash, AP Yeboah-Antwi, K Sabin, L Udhayakumar, V Desai, M Hamer, DH AF Singh, Neeru Singh, Mrigendra P. Wylie, Blair J. Shukla, Manmohan M. Hussain, Mobassir Dash, Aditya P. Yeboah-Antwi, Kojo Sabin, Lora Udhayakumar, Venkatachalam Desai, Meghna Hamer, Davidson H. TI BURDEN OF MALARIA IN PREGNANCY IN WOMEN PRESENTING TO DELIVERY UNITS IN AREAS WITH STABLE AND UNSTABLE MALARIA TRANSMISSION IN CHHATTISGARH, INDIA SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Singh, Neeru] Reg Med Res Ctr ICMR, Jabalpur, India. [Singh, Mrigendra P.; Shukla, Manmohan M.; Hussain, Mobassir] Natl Inst Malaria Res Field Stn, Jabalpur, India. [Wylie, Blair J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dash, Aditya P.] Natl Inst Malaria Res, Delhi, India. [Yeboah-Antwi, Kojo; Sabin, Lora] Boston Univ, Ctr Int Hlth & Dev, Boston, MA 02215 USA. [Udhayakumar, Venkatachalam; Desai, Meghna] Ctr Dis Control & Prevent, Malaria Branch, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2009 VL 81 IS 5 SU S BP 191 EP 191 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701082 ER PT J AU Chowdhury, F Begum, YA Alam, M Khan, AI Ahmed, T LaRocque, RC Harris, JB Faruque, ASG Calderwood, SB Ryan, ET Svennerholm, AM Qadri, F AF Chowdhury, Fahima Begum, Yasmin Ara Alam, Murshid Khan, Ashraful Islam Ahmed, Tanvir LaRocque, Regina C. Harris, Jason B. Faruque, A. S. G. Calderwood, Stephen B. Ryan, Edward T. Svennerholm, Ann-Mari Qadri, Firdausi TI CONCOMITANT INFECTION WITH VIBRIO CHOLERAE O1 AND ENTEROTOXIGENIC ESCHERICHIA COLI INDUCES A MORE ROBUST IMMUNE RESPONSE TO CHOLERA ANTIGENS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Chowdhury, Fahima; Begum, Yasmin Ara; Alam, Murshid; Khan, Ashraful Islam; Ahmed, Tanvir; Faruque, A. S. G.; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [LaRocque, Regina C.; Harris, Jason B.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Svennerholm, Ann-Mari] Univ Gothenburg, Gothenburg, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2009 VL 81 IS 5 SU S MA 715 BP 206 EP 206 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701131 ER PT J AU LaRocque, RC Sabeti, P Duggal, P Chowdhury, F Khan, AI Lebrun, LM Harris, JB Ryan, ET Qadri, F Calderwood, SB AF LaRocque, Regina C. Sabeti, Pardis Duggal, Priya Chowdhury, Fahima Khan, Ashraful I. Lebrun, Lauren M. Harris, Jason B. Ryan, Edward T. Qadri, Firdausi Calderwood, Stephen B. TI A VARIANT IN LONG PALATE, LUNG AND NASAL EPITHELIUM CLONE 1 IS ASSOCIATED WITH CHOLERA IN A BANGLADESHI POPULATION SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [LaRocque, Regina C.; Lebrun, Lauren M.; Harris, Jason B.; Ryan, Edward T.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sabeti, Pardis] Broad Inst, Cambridge, MA USA. [Duggal, Priya] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Chowdhury, Fahima; Khan, Ashraful I.; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2009 VL 81 IS 5 SU S MA 716 BP 206 EP 206 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701132 ER PT J AU Dong, C Urgaonkar, S Cortese, J Francisco, J Garcia-Bustos, JF Gomez-de-las-Heras, FM Patel, V Ross, L Dvorin, JD Duraisingh, MT Wirth, D Mazitschek, R Clardy, J AF Dong, Carolyn Urgaonkar, Sameer Cortese, Joe Francisco, Javier Garcia-Bustos, Jose F. Gomez-de-las-Heras, Frederico M. Patel, Vishal Ross, Leila Dvorin, Jeffrey D. Duraisingh, Manoj T. Wirth, Dyann Mazitschek, Ralph Clardy, Jon TI TETRACYCLIC BENZOTHIAZEPINES: A NOVEL CLASS OF PLASMODIUM FALCIPARUM CYTOCHROME BC1 INHIBITORS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Dong, Carolyn; Patel, Vishal; Duraisingh, Manoj T.; Wirth, Dyann] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Urgaonkar, Sameer; Cortese, Joe; Mazitschek, Ralph] Broad Inst Infect Dis Initiat, Boston, MA USA. [Francisco, Javier; Garcia-Bustos, Jose F.; Gomez-de-las-Heras, Frederico M.] GlaxoSmithKline R&D, Dis Developing World Ctr, Drug Discovery Biol Grp, Madrid, Spain. [Patel, Vishal; Ross, Leila; Mazitschek, Ralph; Clardy, Jon] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Dvorin, Jeffrey D.] Childrens Hosp Boston, Div Infect Dis, Boston, MA USA. [Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RI Mazitschek, Ralph/E-3741-2013 OI Mazitschek, Ralph/0000-0002-1105-689X NR 0 TC 0 Z9 0 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 NOV PY 2009 VL 81 IS 5 SU S BP 252 EP 253 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701293 ER PT J AU Singh, N Singh, MP Shukla, MM Hussain, M Dash, AP Wylie, BJ Yeboah-Antwi, K Sabin, L Udhayakumar, V Desai, M Hamer, DH AF Singh, Neeru Singh, Mrigendra P. Shukla, Manmohan M. Hussain, Mohassir Dash, Aditya P. Wylie, Blair J. Yeboah-Antwi, Kojo Sabin, Lora Udhayakumar, Venkatachalam Desai, Meghna Hamer, Davidson H. TI BURDEN OF MALARIA IN PREGNANCY IN AREAS OF STABLE AND UNSTABLE MALARIA TRANSMISSION IN CHHATTISGARH, INDIA SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Singh, Neeru] Reg Med Res Ctr ICMR, Jabalpur, India. [Singh, Mrigendra P.; Shukla, Manmohan M.; Hussain, Mohassir] Natl Inst Malaria Res Field Stn, Jabalpur, India. [Dash, Aditya P.] Natl Inst Malaria Res, Delhi, India. [Wylie, Blair J.] Massachusetts Gen Hosp, Dept Obstet, Boston, MA 02114 USA. [Yeboah-Antwi, Kojo; Sabin, Lora; Hamer, Davidson H.] Ctr Int Hlth & Dev, Boston, MA USA. [Udhayakumar, Venkatachalam; Desai, Meghna] Ctr Dis Control & Prevent, Malaria Branch, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2009 VL 81 IS 5 SU S MA 900 BP 259 EP 259 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701315 ER PT J AU Charles, RC Sheikh, A Rollins, S Harris, JB Bhuiyan, MS Khanam, F Bukka, A Kalsy, A Porwollik, S Brooks, WA LaRocque, R McClelland, M Logvinenko, T Cravioto, A Calderwood, SB Graham, JE Qadri, F Ryan, ET AF Charles, Richelle C. Sheikh, Alaullah Rollins, Sean Harris, Jason B. Bhuiyan, Md. Saruar Khanam, Farhana Bukka, Archana Kalsy, Anuj Porwollik, Steffen Brooks, W. Abdullah LaRocque, Regina McClelland, Michael Logvinenko, Tanya Cravioto, Alejandro Calderwood, Stephen B. Graham, James E. Qadri, Firdausi Ryan, Edward T. TI HIGH THROUGHPUT GENE EXPRESSION PROFILING OF SALMONELLA ENTERICA SEROVAR PARATYPHI A IN THE BLOOD OF BACTEREMIC PATIENTS IN BANGLADESH SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Charles, Richelle C.; Rollins, Sean; Harris, Jason B.; Kalsy, Anuj; LaRocque, Regina; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sheikh, Alaullah; Bhuiyan, Md. Saruar; Khanam, Farhana; Brooks, W. Abdullah; Cravioto, Alejandro; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka, Bangladesh. [Bukka, Archana; Graham, James E.] Univ Louisville, Louisville, KY 40292 USA. [Porwollik, Steffen; McClelland, Michael] Sidney Kimmel Canc Ctr, San Diego, CA USA. [Logvinenko, Tanya] Tufts Univ, Med Ctr, Boston, MA 02111 USA. RI McClelland, Michael/A-8583-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2009 VL 81 IS 5 SU S MA 1145 BP 331 EP 331 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701559 ER PT J AU Sheikh, A Khanam, F Rahman, T Pacek, M Hu, YH Baresch, A Bhuiyan, MS Rollins, S Citorik, R Kalsy, A Charles, R LaRocque, RC LaBaer, J Calderwood, SB Harris, JB Qadri, F Ryan, ET AF Sheikh, Alaullah Khanam, Farhana Rahman, Taibur Pacek, Martin Hu, Yanhui Baresch, Andrea Bhuiyan, Md. Saruar Rollins, Sean Citorik, Robert Kalsy, Anuj Charles, Richelle LaRocque, Regina C. LaBaer, Joshua Calderwood, Stephen B. Harris, Jason B. Qadri, Firdausi Ryan, Edward T. TI EVALUATION OF INTERFERON-Gamma RESPONSES IN PATIENTS WITH SALMONELLA ENTERICA SEROVAR TYPHI BACTEREMIA IN DHAKA, BANGLADESH SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Sheikh, Alaullah; Khanam, Farhana; Rahman, Taibur; Bhuiyan, Md. Saruar; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka, Bangladesh. [Pacek, Martin; Hu, Yanhui; LaBaer, Joshua] Harvard Inst Prote, Boston, MA USA. [Baresch, Andrea; Rollins, Sean; Citorik, Robert; Kalsy, Anuj; Charles, Richelle; LaRocque, Regina C.; Calderwood, Stephen B.; Harris, Jason B.; Ryan, Edward T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2009 VL 81 IS 5 SU S MA 1144 BP 331 EP 331 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701558 ER PT J AU Moss, DR Bartels, K Peterfreund, GL Lovich, MA Sims, NM Peterfreund, RA AF Moss, David R. Bartels, Karsten Peterfreund, Gregory L. Lovich, Mark A. Sims, Nathaniel M. Peterfreund, Robert A. TI An In Vitro Analysis of Central Venous Drug Delivery by Continuous Infusion: The Effect of Manifold Design and Port Selection SO ANESTHESIA AND ANALGESIA LA English DT Article ID DEAD-VOLUME; SYRINGE PUMPS; DYNAMICS; DELAYS; SET AB BACKGROUND: Central venous catheters are used extensively in anesthesia and critical care. Multiport manifolds allow for simultaneous administration of multiple medication infusions into a common central venous catheter lumen. The structures of such manifolds vary considerably. In this study, we quantitatively compared, in a laboratory model of continuous drug infusion, the drug delivery dynamics of a traditional stopcock manifold and a microinfusion manifold constructed to minimize dead volume. METHODS: A syringe pump infused a saline carrier solution at a low flow rate frequently used in an intensive care unit (10 mL/h) through a multiport manifold connected to the 16-gauge lumen of a standard 16-cm triple-lumen catheter. The model drug methylene blue (3 mL/h) joined the carrier flow at the first, second, or fourth stopcock of a traditional manifold or 1 of 2 positions in a microinfusion manifold, a new device designed to minimize dead volume. Effluent samples were collected every minute for quantitative spectrophotometric analysis of delivery onset and offset. RESULTS: Onset and offset times differed significantly among individual ports of the traditional 4-stopcock manifold. There was also a significant difference between the 2 ports of the microinfusion manifold, but this was less pronounced. Both ports of the microinfusion manifold yielded delivery dynamics that were similar to the most downstream port of the 4-stopcock manifold. There was good correlation between dynamic data and dead volume for each of the manifolds. CONCLUSIONS: Using a traditional stopcock manifold, port selection significantly affects drug delivery dynamics for continuous infusions. The findings provide quantitative support for the concept that the most critical infusion should join the system at the manifold port closest to the patient. Port selection was less important for the microinfusion manifold and dynamics were faster compared with the second and fourth ports of the stopcock manifold. The smaller dead volumes of the microinfusion manifold minimize unwanted delays in drug delivery onset and offset allowing more precise control over drug delivery by continuous infusion. (Anesth Analg 2009;109:1524-9) C1 [Moss, David R.; Bartels, Karsten; Peterfreund, Gregory L.; Sims, Nathaniel M.; Peterfreund, Robert A.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Lovich, Mark A.] Caritas St Elizabeths Med Ctr, Dept Anesthesiol & Pain Med, Boston, MA USA. RP Peterfreund, RA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Jackson 439,55 Fruit St, Boston, MA 02114 USA. EM rpeterfreund@partners.org FU Departments of Anesthesia and Critical Care, Massachusetts General Hospital FX Supported by Institutional funds from the Departments of Anesthesia and Critical Care, Massachusetts General Hospital. NR 10 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD NOV PY 2009 VL 109 IS 5 BP 1524 EP 1529 DI 10.1213/ANE.0b013e3181b7c359 PG 6 WC Anesthesiology SC Anesthesiology GA 509QF UT WOS:000271032500030 PM 19843791 ER PT J AU Guan, ZH Baker, K Sandberg, WS AF Guan, Zhonghui Baker, Keith Sandberg, Warren S. TI Misalignment of Disposable Pulse Oximeter Probes Results in False Saturation Readings That Influence Anesthetic Management SO ANESTHESIA AND ANALGESIA LA English DT Article AB We report a small case series in which misaligned disposable pulse oximeter sensors gave falsely low saturation readings. In each instance, the sensor performed well during preinduction oxygen administration and the early part of the case, most notably by producing a plethysmographic trace rated as high quality by the oximeter software. The reported pulse oximeter oxygen saturation eventually decreased to concerning levels in each instance, but the anesthesiologists, relying on the reported high-quality signal, initially sought other causes for apparent hypoxia. They undertook maneuvers and diagnostic procedures later deemed unnecessary. When the malpositioned sensors were discovered and repositioned, the apparent hypoxia was quickly relieved in each case. We then undertook a survey of disposable oximeter sensors as patients entered the recovery room, and discovered malposition of more than 1 cm in approximately 20% of all sensors, without apparent consequence. We conclude that the technology is quite robust, but that the diagnosis of apparent hypoxia should include a quick check of oximeter position early on. (Anesth Analg 2009;109:1530-3) C1 [Guan, Zhonghui; Baker, Keith; Sandberg, Warren S.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Guan, Zhonghui; Baker, Keith; Sandberg, Warren S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Sandberg, WS (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Jackson 4, Boston, MA 02114 USA. EM wsandberg@partners.org OI Sandberg, Warren/0000-0002-9246-777X FU Department of Anesthesia and Critical Care, Massachusetts General Hospital FX Supported by the Department of Anesthesia and Critical Care, Massachusetts General Hospital. NR 4 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD NOV PY 2009 VL 109 IS 5 BP 1530 EP 1533 DI 10.1213/ANE.0b013e3181b9a814 PG 4 WC Anesthesiology SC Anesthesiology GA 509QF UT WOS:000271032500031 PM 19843792 ER PT J AU Costa, ELV Melo, MFV AF Costa, Eduardo L. V. Melo, Marcos F. Vidal TI Lung Water What You See (with Computed Tomography) and What You Get (with a Bedside Device) SO ANESTHESIOLOGY LA English DT Editorial Material ID SINGLE TRANSPULMONARY THERMODILUTION; REGIONAL PULMONARY PERFUSION; CRITICALLY-ILL; NITRIC-OXIDE; THERMAL-DYE; INJURY; VENTILATION; INDICATOR; SEPSIS; MANAGEMENT C1 [Costa, Eduardo L. V.; Melo, Marcos F. Vidal] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Costa, Eduardo L. V.; Melo, Marcos F. Vidal] Harvard Univ, Sch Med, Boston, MA USA. [Costa, Eduardo L. V.] Univ Sao Paulo, Sch Med, Resp Intens Care Unit, Sao Paulo, Brazil. RP Costa, ELV (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM mvidalmelo@partners.org RI Costa, Eduardo/K-5841-2012 OI Costa, Eduardo/0000-0002-6941-3626 FU NHLBI NIH HHS [R01 HL086827, R01 HL086827-03] NR 33 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 2009 VL 111 IS 5 BP 933 EP 935 PG 3 WC Anesthesiology SC Anesthesiology GA 511NN UT WOS:000271172500002 PM 19858867 ER PT J AU Payne, SJ Selb, J Boas, DA AF Payne, S. J. Selb, J. Boas, D. A. TI Effects of Autoregulation and CO2 Reactivity on Cerebral Oxygen Transport SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE Autoregulation; Cerebral blood flow; CO2; Transfer function; Mathematical model; Stroke ID ACUTE ISCHEMIC-STROKE; NONLINEAR PHYSIOLOGICAL SYSTEMS; BLOOD-FLOW; SLOW DYNAMICS; HEMODYNAMICS; HUMANS; FLUCTUATIONS; ARTERIAL; MODEL AB Both autoregulation and CO2 reactivity are known to have significant effects on cerebral blood flow and thus on the transport of oxygen through the vasculature. In this paper, a previous model of the autoregulation of blood flow in the cerebral vasculature is expanded to include the dynamic behavior of oxygen transport through binding with hemoglobin. The model is used to predict the transfer functions for both oxyhemoglobin and deoxyhemoglobin in response to fluctuations in arterial blood pressure and arterial CO2 concentration. It is shown that only six additional nondimensional groups are required in addition to the five that were previously found to characterize the cerebral blood flow response. A resonant frequency in the pressure-oxyhemoglobin transfer function is found to occur in the region of 0.1 Hz, which is a frequency of considerable physiological interest. The model predictions are compared with results from the published literature of phase angle at this frequency, showing that the effects of changes in breathing rate can significantly alter the inferred phase dynamics between blood pressure and hemoglobin. The question of whether dynamic cerebral autoregulation is affected under conditions of stenosis or stroke is then examined. C1 [Payne, S. J.] Univ Oxford, Dept Engn Sci, Inst Biomed Engn, Oxford OX1 3PJ, England. [Selb, J.; Boas, D. A.] Massachusetts Gen Hosp, Photon Migrat Imaging Lab, Charlestown, MA USA. RP Payne, SJ (reprint author), Univ Oxford, Dept Engn Sci, Inst Biomed Engn, Parks Rd, Oxford OX1 3PJ, England. EM sjp@robots.ox.ac.uk FU NCRR NIH HHS [P41 RR014075, P41 RR014075-075756]; NIBIB NIH HHS [R01 EB006385, R01 EB006385-03] NR 24 TC 13 Z9 14 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD NOV PY 2009 VL 37 IS 11 BP 2288 EP 2298 DI 10.1007/s10439-009-9763-5 PG 11 WC Engineering, Biomedical SC Engineering GA 502HL UT WOS:000270448300010 PM 19629692 ER PT J AU Granpeesheh, D Tarbox, J Dixon, DB Carr, E Herbert, M AF Granpeesheh, Doreen Tarbox, Jonathan Dixon, Dennis B. Carr, Edward Herbert, Martha TI Retrospective analysis of clinical records in 38 cases of recovery from autism SO ANNALS OF CLINICAL PSYCHIATRY LA English DT Article DE autism; ASD; recovery; EIBI; ABA AB BACKGROUND: Twenty years of research on early intensive treatment using applied behavior analysis (ABA) for children with autism has consistently produced robust effects. There appears to be a subset of children whose response to intensive ABA treatments includes achieving a level of functioning that is indistinguishable from typically developing peers. The purpose of this study was to describe a subset of children who recovered from autism following intensive ABA interventions. METHODS: We reviewed the clinical files of 38 children with autism who achieved an optimal outcome after receiving intensive ABA services. RESULTS: The mean age at intake was 40 months. Average IQ was 83.6 at intake and 107.9 at discharge. Mean adaptive skills were 68.04 at intake and 88.87 at discharge. CONCLUSIONS: Our study corroborates the finding that some children with autism who receive early intensive behavioral intervention achieve functioning in the average range. C1 [Granpeesheh, Doreen; Tarbox, Jonathan; Dixon, Dennis B.] Ctr Autism & Related Disorders, Tarzana, CA 91356 USA. [Carr, Edward] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Herbert, Martha] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Granpeesheh, D (reprint author), Ctr Autism & Related Disorders, 19019 Ventura Blvd,3rd Floor, Tarzana, CA 91356 USA. EM D.Granpeesheh@centerforautism.com NR 28 TC 12 Z9 12 U1 4 U2 11 PU DOWDEN HEALTH MEDIA PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 1040-1237 J9 ANN CLIN PSYCHIATRY JI Ann. Clin. Psychiatry PD NOV PY 2009 VL 21 IS 4 BP 195 EP 204 PG 10 WC Psychiatry SC Psychiatry GA V16WR UT WOS:000207900200002 PM 19917210 ER PT J AU Beslija, S Bonneterre, J Burstein, HJ Cocquyt, V Gnant, M Heinemann, V Jassem, J Kostler, WJ Krainer, M Menard, S Petit, T Petruzelka, L Possinger, K Schmid, P Stadtmauer, E Stockler, M Van Belle, S Vogel, C Wilcken, N Wiltschke, C Zielinski, CC Zwierzina, H AF Beslija, S. Bonneterre, J. Burstein, H. J. Cocquyt, V. Gnant, M. Heinemann, V. Jassem, J. Koestler, W. J. Krainer, M. Menard, S. Petit, T. Petruzelka, L. Possinger, K. Schmid, P. Stadtmauer, E. Stockler, M. Van Belle, S. Vogel, C. Wilcken, N. Wiltschke, C. Zielinski, C. C. Zwierzina, H. CA CECOG TI Third consensus on medical treatment of metastatic breast cancer SO ANNALS OF ONCOLOGY LA English DT Review DE diagnosis; metastatic breast cancer; prognosis; treatment ID PHASE-II TRIAL; PEGYLATED LIPOSOMAL DOXORUBICIN; HEAVILY PRETREATED PATIENTS; IN-SITU HYBRIDIZATION; REPLACEMENT THERAPY WITHDRAWAL; EVERY-2-WEEK DARBEPOETIN-ALPHA; CHEMOTHERAPY-INDUCED ANEMIA; COLONY-STIMULATING FACTOR; PLACEBO-CONTROLLED TRIAL; WEEKLY EPOETIN-ALPHA AB Design: To provide timely and evidence-based recommendations for the diagnostic workup and treatment of patients with MBC, an international expert panel reviewed and discussed the evidence available from clinical trials regarding diagnostic, therapeutic and supportive measures with emphasis on their impact on the quality of life and overall survival of patients with MBC. Results: Evidence-based recommendations for the diagnostic workup, endocrine therapy, chemotherapy, use of targeted therapies and bisphosphonates, surgical treatment and supportive care measures in the management of patients with MBC were formulated. Conclusions: The present consensus manuscript updates evidence-based recommendations for state-of-the-art treatment of MBC depending on disease-associated and biological variables. C1 [Koestler, W. J.; Krainer, M.; Wiltschke, C.; Zielinski, C. C.] Med Univ Vienna, Dept Med 1, Div Clin Oncol, A-1090 Vienna, Austria. [Beslija, S.] Inst Oncol, Sarajevo, Bosnia & Herceg. [Bonneterre, J.] Ctr Oscar Lambret, F-59020 Lille, France. [Burstein, H. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cocquyt, V.; Van Belle, S.] Univ Ziekenhuis St Rafael, Oncolog Centrum, Ghent, Belgium. [Gnant, M.] Med Univ Vienna, Dept Surg, Vienna, Austria. [Heinemann, V.] Univ Munich, Klinikum Grosshadern, Med Klin & Poliklin 3, D-8000 Munich, Germany. [Jassem, J.] Med Univ, Dept Radiotherapy & Oncol, Gdansk, Poland. [Menard, S.] Ist Tumori, Milan, Italy. [Petit, T.] Ctr Paul Strauss, Strasbourg, France. [Petruzelka, L.] Charles Univ Prague, Dept Oncol, Prague, Czech Republic. [Possinger, K.] Med Klin Charite, Berlin, Germany. [Schmid, P.] Univ London Imperial Coll Sci Technol & Med, Charing Cross Hosp, London, England. [Stadtmauer, E.] Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. [Stockler, M.] Univ Sydney, Concord Hosp, Sydney, NSW 2006, Australia. [Stockler, M.] Royal Prince Alfred Hosp, Sydney Canc Ctr, Sydney, NSW, Australia. [Vogel, C.] Breast Canc Aptium Oncol Lynn Canc Inst W, Boca Raton, FL USA. [Wilcken, N.] Westmead Hosp, Dept Med Oncol & Palliat Care, Sydney, NSW, Australia. [Zielinski, C. C.] Cent European Cooperat Oncol Grp, Vienna, Austria. [Zwierzina, H.] Med Univ Innsbruck, Dept Med 1, Innsbruck, Austria. RP Zielinski, CC (reprint author), Med Univ Vienna, Dept Med 1, Div Clin Oncol, 18-20 Waehringer Guertel, A-1090 Vienna, Austria. EM christoph.zielinski@meduniwien.ac.at RI Stockler, Martin/N-3859-2016; Petruzelka, Lubos/A-2750-2017; OI Stockler, Martin/0000-0003-3793-8724; Petruzelka, Lubos/0000-0002-4397-0635; Gnant, Michael/0000-0003-1002-2118; Krainer, Michael/0000-0002-7011-4957 FU Bristol Myers-Squibb; Eli Lilly; Roche FX Bristol Myers-Squibb; Eli Lilly; Roche. NR 193 TC 95 Z9 98 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2009 VL 20 IS 11 BP 1771 EP 1785 DI 10.1093/annonc/mdp261 PG 15 WC Oncology SC Oncology GA 514GB UT WOS:000271381300003 PM 19608616 ER PT J AU Sher, DJ Mauch, PM Van Den Abbeele, A LaCasce, AS Czerminski, J Ng, AK AF Sher, D. J. Mauch, P. M. Van Den Abbeele, A. LaCasce, A. S. Czerminski, J. Ng, A. K. TI Prognostic significance of mid- and post-ABVD PET imaging in Hodgkin's lymphoma: the importance of involved-field radiotherapy SO ANNALS OF ONCOLOGY LA English DT Article DE Hodgkin's lymphoma; involved-field radiotherapy; PET; radiotherapy; response-adapted therapy ID POSITRON-EMISSION-TOMOGRAPHY; DISEASE; RADIATION; CHEMOTHERAPY; PROGRESSION; THERAPY; RELAPSE; INTERIM AB Methods: Patients with HL treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD)-based CT and radiotherapy (RT) at our institution from January 2000 to March 2007 were eligible. All patients had either a post-treatment PET or PET-CT before initiation of RT or a negative midtreatment PET or PET-CT. The primary end point was failure-free survival (FFS) for patients with and without residual FDG avidity after ABVD. The treatment outcome of patients with interim PET positivity during CT was also reported. Results: Seventy-three patients were included in this study. Twenty patients (out of 46) were PET positive on interim PET, and 13 patients (out of 73) were PET positive at the conclusion of CT. At a median follow-up of 3.4 years for surviving patients, the 2-year FFSs for patients PET-negative versus PET-positive disease after ABVD were 95% and 69%, respectively (P < 0.01). On bivariable Cox regression, post-ABVD positivity (hazard ratio 4.8, P = 0.05) was predictive of disease recurrence after controlling for bulky disease. Of the 20 patients with interim PET positivity, three recurred, with a 2-year FFS of 85%. Among the 13 patients with interim PET positivity, but became PET negative at the completion of CT, the 2-year FFS was 92%. Conclusion: Sixty-nine per cent of patients with residual FDG avidity after ABVD were free of disease after consolidative RT, indicating a majority of patients with persistent lymphoma can be cured by sterilizing this PET-positive disease. C1 [Sher, D. J.; Mauch, P. M.; Czerminski, J.; Ng, A. K.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Sher, D. J.; Mauch, P. M.; Czerminski, J.; Ng, A. K.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Van Den Abbeele, A.] Dana Farber Canc Inst, Dept Nucl Med, Boston, MA 02115 USA. [LaCasce, A. S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Sher, DJ (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM dsher@lroc.harvard.edu NR 17 TC 41 Z9 42 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2009 VL 20 IS 11 BP 1848 EP 1853 DI 10.1093/annonc/mdp071 PG 6 WC Oncology SC Oncology GA 514GB UT WOS:000271381300013 PM 19541793 ER PT J AU Mcgee, S Mardirossian, V Elackattu, A Mirkovic, J Pistey, R Gallagher, G Kabani, S Yu, CC Wang, Z Badizadegan, K Grillone, G Feld, MS AF McGee, Sasha Mardirossian, Vartan Elackattu, Alphi Mirkovic, Jelena Pistey, Robert Gallagher, George Kabani, Sadru Yu, Chung-Chieh Wang, Zimmern Badizadegan, Kamran Grillone, Gregory Feld, Michael S. TI Anatomy-Based Algorithms for Detecting Oral Cancer Using Reflectance and Fluorescence Spectroscopy SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE diagnosis; fluorescence; oral cancer; reflectance; spectroscopy ID NATIVE CELLULAR FLUORESCENCE; AERODIGESTIVE TRACT CANCER; IN-VIVO; AUTOFLUORESCENCE SPECTROSCOPY; EXCITATION WAVELENGTHS; OPTICAL SPECTROSCOPY; INCISIONAL BIOPSY; LIGHT-SCATTERING; DIAGNOSIS; LESIONS AB Objectives: We used reflectance and fluorescence spectroscopy to noninvasively and quantitatively distinguish benign from dysplastic/malignant oral lesions. We designed diagnostic algorithms to account for differences in the spectral properties among anatomic sites (gingiva, buccal mucosa, etc). Methods: In vivo reflectance and fluorescence spectra were collected from 71 patients with oral lesions. The tissue was then biopsied and the specimen evaluated by histopathology. Quantitative parameters related to tissue morphology and biochemistry were extracted from the spectra. Diagnostic algorithms specific for combinations of sites with similar spectral properties were developed. Results: Discrimination of benign from dysplastic/malignant lesions was most successful when algorithms were designed for individual sites (area under the receiver operator characteristic curve [ROC-AUC], 0.75 for the lateral surface of the tongue) and was least accurate when all sites were combined (ROC-AUC, 0.60). The combination of sites with similar spectral properties (floor of mouth and lateral surface of the ton-Lie) yielded an ROC-AUC of 0.71. Conclusions: Accurate spectroscopic detection of oral disease must account for spectral variations among anatomic sites. Anatomy-based algorithms for single sites or combinations of sites demonstrated good diagnostic performance in distinguishing benign lesions from dysplastic/malignant lesions and consistently performed better than algorithms developed for all sites combined. C1 [Mardirossian, Vartan; Elackattu, Alphi; Wang, Zimmern; Grillone, Gregory] Boston Med Ctr, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. [Pistey, Robert] Boston Med Ctr, Dept Anat Pathol, Boston, MA USA. [McGee, Sasha; Mirkovic, Jelena; Yu, Chung-Chieh; Badizadegan, Kamran; Feld, Michael S.] MIT, GR Harrison Spect Lab, Boston, MA USA. [Gallagher, George; Kabani, Sadru] Boston Univ, Goldman Sch Dent Med, Dept Oral & Maxillofacial Pathol, Boston, MA 02215 USA. [Badizadegan, Kamran] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Badizadegan, Kamran] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mcgee, S (reprint author), MIT, GR Harrison Spect Lab, Bldg 6-205,77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Mirkovic, Jelena/A-6253-2013 FU National Institutes of Health [R01-CA097966, P41-RR02594-21] FX From the G. R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology (McGee, Mirkovic, Yu, Badizadegan, Feld), the Departments of Otolaryngology-Head and Neck Surgery (Mardirossian, Elackattu, Wang, Grillone) and Anatomic Pathology (Pistey), Boston Medical Center, the Department of Oral and Maxillofacial Pathology, Boston University Goldman School of Dental Medicine (Gallagher, Kabani), and the Department of Pathology, Harvard Medical School and Massachusetts General Hospital (Badizadegan), Boston. Massachusetts. This research was supported by National Institutes of Health grants R01-CA097966 and P41-RR02594-21. NR 44 TC 20 Z9 20 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD NOV PY 2009 VL 118 IS 11 BP 817 EP 826 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA 523YX UT WOS:000272112100012 PM 19999369 ER PT J AU Chambers, JA Ray, PD AF Chambers, James Alan Ray, Peter Damian TI Achieving Growth and Excellence in Medicine The Case History of Armed Conflict and Modem Reconstructive Surgery SO ANNALS OF PLASTIC SURGERY LA English DT Article DE plastic surgery; reconstructive surgery; war; history; military; surgery ID PLASTIC-SURGERY; HAND SURGERY; WAR; SPECIALTY; EVOLUTION; STORY AB November 11, 2009 will mark over 90 years of commemorating Armistice Day, the end of World War I. Although conflict in the Middle East reminds us that WWI failed to end all wars, it did serve as both substrate and catalyst for the development of modem plastic and reconstructive surgery. This article will outline those ingredients most directly responsible for the growth of the specialty, tracing its development in response to armed conflict, and implications for continued excellence both in reconstructive Surgery and other fields in the future. C1 [Chambers, James Alan] Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Ray, Peter Damian] Univ Alabama, Craniofacial Serv, Birmingham, AL USA. RP Chambers, JA (reprint author), Massachusetts Gen Hosp, Hand & Upper Extrem Serv, 55 Fruit St,Yawkey 2100, Boston, MA 02114 USA. EM j.alan.chambers@gmail.com NR 58 TC 5 Z9 5 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD NOV PY 2009 VL 63 IS 5 BP 473 EP 478 DI 10.1097/SAP.0b013e3181bc327a PG 6 WC Surgery SC Surgery GA 512QV UT WOS:000271266100002 PM 20431512 ER PT J AU Zischek, C Niess, H Ischenko, I Conrad, C Huss, R Jauch, KW Nelson, PJ Bruns, C AF Zischek, Christoph Niess, Hanno Ischenko, Ivan Conrad, Claudius Huss, Ralf Jauch, Karl-Walter Nelson, Peter J. Bruns, Christiane TI Targeting Tumor Stroma Using Engineered Mesenchymal Stem Cells Reduces the Growth of Pancreatic Carcinoma SO ANNALS OF SURGERY LA English DT Article AB Objective: To analyze the efficacy of engineered mesenchymal stem cell based therapy directed towards pancreatic tumor stroma. Summary Background Data: Mesenchymal stem cells (MSC) are actively recruited to tumor stroma where they enhance tumor growth and metastases. Upregulation of chemotactic cytokine (CCL5) by MSCs within the tumor stroma has been shown to play a central role in this process. Murine MSCs were engineered to express reporter genes or therapeutic genes under control of the CCL5 promoter and adoptively transferred into mice with growing pancreatic tumors. The effect on tumor growth and metastases was then evaluated. Methods: MSCs isolated from bone marrow of C57/Bl6 p53(-/-) mice were stably transfected with red fluorescent protein (RFP), enhanced green fluorescent protein (eGFP), or herpes simplex virus (HSV) thymidine kinase (Tk) gene driven by the RANTES promoter. MSCs were intravenously applied once per week over 3 weeks to mice carrying an orthotopic, syngeneic pancreatic Panc02 tumor. Results: eGFP and RFP signals driven by the CCL5 promoter were detected by fluorescence in treated pancreatic tumor samples. The HSV-Tk therapy group treated intraperitoneal with the prodrug ganciclovir 5 to 7 days after stem cell application lead to a 50% reduction of primary pancreatic tumor growth (P < 0.0003, student t test) and reduced liver metastases (0% vs. 60%). Conclusion: The active homing of MSCs into primary pancreatic tumor stroma and activation of the CCL5 promoter was verified using eGFP- and RFP-reporter genes. In the presence of ganciclovir, HSV-Tk transfected MSCs led to a significant reduction of primary pancreatic tumor growth and incidence of metastases. (Ann Surg 2009;250: 747-753) C1 [Zischek, Christoph; Nelson, Peter J.] Univ Munich, Med Policlin, Clin Biochem Grp, Munich, Germany. [Zischek, Christoph; Niess, Hanno; Ischenko, Ivan; Conrad, Claudius; Jauch, Karl-Walter; Bruns, Christiane] Univ Munich, Dept Surg, Munich, Germany. [Conrad, Claudius] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Conrad, Claudius; Huss, Ralf] Harvard Stem Cell Inst, Cambridge, MA USA. [Huss, Ralf] Univ Munich, Inst Pathol, D-80539 Munich, Germany. [Conrad, Claudius; Huss, Ralf] Roche Diagnost GmbH, Pharma Res, Stem Cell Therapy Strategy Penzberg, Penzberg, Germany. RP Bruns, C (reprint author), Univ Munich, Dept Surg, Munich, Germany. EM christiane.bruns@med.uni-muenchen.de FU Deutsche Forschungsgemeinschaft [SPP1190, SFB-TR36/B6]; EU FX Supported by grants from the Deutsche Forschungsgemeinschaft, SPP1190 (to C.B. and P.J.N.); SFB-TR36/B6 (to P.J.N.); EU P6 "INNOCHEM" (to P.J.N.). NR 44 TC 65 Z9 71 U1 1 U2 6 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 NOV PY 2009 VL 250 IS 5 BP 747 EP 753 DI 10.1097/SLA.0b013e3181bd62d0 PG 7 WC Surgery SC Surgery GA V28FT UT WOS:000208667400012 PM 19826249 ER PT J AU Merritt, RE Mathisen, DJ Wain, JC Gaissert, HA Donahue, D Lanuti, M Allan, JS Morse, CR Wright, CD AF Merritt, Robert E. Mathisen, Douglas J. Wain, John C. Gaissert, Henning A. Donahue, Dean Lanuti, Michael Allan, James S. Morse, Christopher R. Wright, Cameron D. TI Long-Term Results of Sleeve Lobectomy in the Management of Non-Small Cell Lung Carcinoma and Low-Grade Neoplasms SO ANNALS OF THORACIC SURGERY LA English DT Article ID LYMPH-NODE INVOLVEMENT; BRONCHOPLASTIC PROCEDURES; INDUCTION THERAPY; CANCER; SURVIVAL; PNEUMONECTOMY; MORBIDITY; MORTALITY; COMPLICATIONS; CHEMOTHERAPY AB Background. The objective of this study was to evaluate the operative mortality, morbidity, and long-term survival of sleeve lobectomy for non-small cell lung cancer and low-grade neoplasms. We evaluated the effects of neoadjuvant therapy on the bronchial anastomotic complication rate and determined whether sleeve lobectomy performed in patients with N1 disease resulted in decreased overall survival. Methods. This study is a retrospective review of 196 patients who underwent sleeve lobectomy. One hundred twenty-five patients had non-small cell lung cancer. There were 117 men (59.7%) and 79 women (40.3%) with a mean age of 54 years. Sixteen patients (13%) received neoadjuvant therapy. Fifty-six patients with N1 disease underwent sleeve lobectomy. Results. There were 4 (2.0%) postoperative deaths. The postoperative morbidity rate was 36.7%. Four patients (2.0%) experienced bronchopleural fistulas. Multivariate analysis demonstrated that age older than 70 years (p = 0.02) and the diagnosis of non-small cell lung cancer (p = 0.0002) were risk factors for postoperative complications. Multivariate analysis also demonstrated that neoadjuvant therapy predicted anastomotic complications (p = 0.01). For non-small cell lung cancer patients, the 5-year survival rate was 44%. The 5-year survival rates for patients with pathologic N0 disease and N1 disease were 52.6% versus 39.3%, respectively (p = 0.205). Conclusions. Sleeve lobectomy can be performed with minimal bronchial anastomotic complications and low postoperative mortality. In our study, neoadjuvant therapy for non-small cell lung cancer adversely influenced the rate of anastomotic complications. Performing sleeve lobectomy for patients with N1 disease was not associated with decreased overall survival rates. (Ann Thorac Surg 2009;88:1574-82) (C) 2009 by The Society of Thoracic Surgeons C1 [Wright, Cameron D.] Massachusetts Gen Hosp, Dept Thorac Surg, Gen Thorac Surg Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Dept Thorac Surg, Gen Thorac Surg Div, 32 Fruit St,Blake 1570, Boston, MA 02114 USA. EM cdwright@partners.org NR 22 TC 19 Z9 20 U1 0 U2 2 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 NOV PY 2009 VL 88 IS 5 BP 1574 EP 1582 DI 10.1016/j.athoracsur.2009.07.060 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 512AZ UT WOS:000271215700028 PM 19853115 ER PT J AU Armstrong, AW Watson, AJ Makredes, M Frangos, JE Kimball, AB Kvedar, JC AF Armstrong, April W. Watson, Alice J. Makredes, Maryanne Frangos, Jason E. Kimball, Alexandra B. Kvedar, Joseph C. TI Text-Message Reminders to Improve Sunscreen Use A Randomized, Controlled Trial Using Electronic Monitoring SO ARCHIVES OF DERMATOLOGY LA English DT Article ID SKIN-CANCER PREVENTION; ULTRAVIOLET-RADIATION; REDUCING EXPOSURE; SUN SAFETY; ADHERENCE; PROTECTION; POPULATION; MEDICATION; SCHOOLS; PATIENT AB Objective: To evaluate the effectiveness of cellular telephone text messaging as a reminder tool for improving adherence to sunscreen application. Design: We conducted a randomized, controlled trial of the effect of an electronic text- message reminder system on adherence to sunscreen application. Adherence to daily sunscreen use was evaluated using a novel electronic monitoring device. Setting: Participants were recruited from the general community. Participants: Seventy participants constituted a volunteer sample from the general community. The inclusion criteria required participants to be 18 years or older, to own a cellular telephone with text-message features, and to know how to retrieve text messages. Intervention: Half of the participants received daily text-message reminders via cellular telephone for 6 weeks, and the other half did not receive reminders. The text-message reminders consisted of 2 components: a "hook" text detailing daily local weather information and a "prompt" text reminding users to apply sunscreen. Main Outcome Measure: The primary end point of the study was adherence to sunscreen application measured by the number of days participants applied sunscreen during the 6-week study period. Results: All 70 participants completed the 6-week study. There were no statistically significant differences in baseline characteristics between the 2 study groups. At the end of the study period, the 35 participants who did not receive reminders had a mean daily adherence rate of 30.0% (95% confidence interval, 23.1%-36.9%). In comparison, the 35 participants who received daily text-message reminders had a mean daily adherence rate of 56.1% (95% confidence interval, 48.1%-64.1%) (P<.001). Among the participants in the reminder group, 24 (69%) reported that they would keep using the text-message reminders after the study, and 31 (89%) reported that they would recommend the text-message reminder system to others. Subgroup analysis did not reveal any significant demographic factors that predicted adherence. Conclusions: Despite awareness of the benefits of sunscreen, adherence is low, even in this population, for whom adherence was knowingly monitored. Shortterm data demonstrate that using existing cellular telephone text-message technology offers an innovative, low-cost, and effective method of improving adherence to sunscreen application. The use of ubiquitous communications technology, such as text messaging, may have implications for large-scale public health initiatives. C1 [Armstrong, April W.] Univ Calif Davis Hlth Syst, Dept Dermatol, Teledermatol Program, Sacramento, CA 95816 USA. [Watson, Alice J.] Massachusetts Gen Hosp, Ctr Connected Hlth, Boston, MA 02114 USA. [Kimball, Alexandra B.] Massachusetts Gen Hosp, Clin Unit Res Trials Skin, Boston, MA 02114 USA. [Watson, Alice J.; Kimball, Alexandra B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Makredes, Maryanne] Beth Israel Deaconess Med Ctr, Dept Internal Med, New York, NY 10003 USA. [Frangos, Jason E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kimball, Alexandra B.; Kvedar, Joseph C.] Harvard Univ, Sch Med, Dept Dermatol, Cambridge, MA 02138 USA. [Watson, Alice J.; Kvedar, Joseph C.] Partners HealthCare Syst, Ctr Connected Hlth, Boston, MA USA. RP Armstrong, AW (reprint author), Univ Calif Davis Hlth Syst, Dept Dermatol, Teledermatol Program, 3301 C St,Ste 1400, Sacramento, CA 95816 USA. FU Information Systems Council of Massachusetts General Hospital; Brigham and Women's Hospital FX Funding/Support: This study was supported by an institutional grant from Information Systems Council of Massachusetts General Hospital and Brigham and Women's Hospital. Study sunscreen was provided by Neutrogena. Dr Makredes was a Doris Duke Clinical Research Fellow and Dr Armstrong was a Stiefel/Connetics Research Fellow for Improving Access to Dermatologic Care at the time of the study. NR 40 TC 110 Z9 111 U1 3 U2 17 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD NOV PY 2009 VL 145 IS 11 BP 1230 EP 1236 PG 7 WC Dermatology SC Dermatology GA 520ZS UT WOS:000271889100003 PM 19917951 ER PT J AU Mollica, RF Lyoo, IK Chernoff, MC Bui, HX Lavelle, J Yoon, SJ Kim, JE Renshaw, PF AF Mollica, Richard F. Lyoo, In Kyoon Chernoff, Miriam C. Bui, Hoan X. Lavelle, James Yoon, Sujung J. Kim, Jieun E. Renshaw, Perry F. TI Brain Structural Abnormalities and Mental Health Sequelae in South Vietnamese Ex-Political Detainees Who Survived Traumatic Head Injury and Torture SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; HOPKINS SYMPTOM CHECKLIST-25; CONCENTRATION CAMP SURVIVORS; COLLEGIATE FOOTBALL PLAYERS; MAGNETIC-RESONANCE IMAGES; MAJOR DEPRESSIVE DISORDER; SURFACE-BASED ANALYSIS; POW SURVIVORS; PREFRONTAL CORTEX; PSYCHOLOGICAL SEQUELAE AB Context: A pilot study of South Vietnamese ex political detainees who had been incarcerated in Vietnamese reeducation camps and resettled in the United States disclosed significant mental health problems associated with torture and traumatic head injury (THI). Objectives: To identify structural brain alterations associated with THI and to investigate whether these deficits are associated with posttraumatic stress disorder and depression. Design: Cross-sectional neuroimaging study. Setting: Massachusetts General Hospital and McLean Hospital. Participants: A subsample of Vietnamese ex-political detainees (n=42) and comparison subjects (n=16) selected from a community study of 337 ex-political detainees and 82 comparison subjects. Main Outcome Measures: Scores on the Vietnamese versions of the Hopkins Symptom Checklist-25 (HSCL) and Harvard Trauma Questionnaire for depression and posttraumatic stress disorder, respectively; cerebral regional cortical thickness; and manual volumetric morphometry of the amygdala, hippocampus, and thalamus. Results: Ex-political detainees exposed to THI (n=16) showed a higher rate of depression (odds ratio, 10.2; 95% confidence interval, 1.2-90.0) than those without THI exposure (n=26). Ex-political detainees with THI had thinner prefrontotemporal cortices than those without THI exposure (P<.001 by the statistical difference brain map) in the left dorsolateral prefrontal and bilateral superior temporal cortices, controlling for age, handedness, and number of trauma/torture events (left superior frontal cortex [SFC], P=.006; left middle frontal cortex, P=.01; left superior temporal cortex [STC], P=.007; right STC, P=.01). Trauma/ torture events were associated with bilateral amygdala volume loss ( left, P=.045; right, P=.003). Cortical thinning associated with THI in the left SFC and bilateral STC was related to HSCL depression scores in THI-exposed (vs non THI-exposed) ex-political detainees (left SFC, P for interaction=.007; left STC, P for interaction=.03; right STC, P for interaction=.02). Conclusions: Structural deficits in prefrontotemporal brain regions are linked to THI exposures. These brain lesions are associated with the symptom severity of depression in Vietnamese ex-political detainees. C1 [Mollica, Richard F.; Lavelle, James] Massachusetts Gen Hosp, Harvard Program Refugee Trauma, Dept Psychiat, Cambridge, MA 02139 USA. [Lyoo, In Kyoon; Kim, Jieun E.] Seoul Natl Univ, Dept Psychiat, Seoul, South Korea. [Lyoo, In Kyoon] Seoul Natl Univ, Dept Neurosci, Seoul, South Korea. [Lyoo, In Kyoon] Harvard Univ, McLean Hosp, Sch Med, Brain Imaging Ctr, Belmont, MA 02178 USA. [Lyoo, In Kyoon] Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. [Chernoff, Miriam C.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Bui, Hoan X.] Vietnamese Amer Civic Assoc, Dorchester, MA USA. [Yoon, Sujung J.] Catholic Univ, Coll Med, Dept Psychiat, Seoul, South Korea. [Renshaw, Perry F.] Univ Utah, Dept Psychiat, Salt Lake City, UT USA. [Renshaw, Perry F.] Univ Utah, Inst Brain, Salt Lake City, UT USA. [Renshaw, Perry F.] VISN 19 Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs, Salt Lake City, UT USA. RP Mollica, RF (reprint author), Massachusetts Gen Hosp, Harvard Program Refugee Trauma, Dept Psychiat, 22 Putnam Ave, Cambridge, MA 02139 USA. EM rmollica@partners.org FU National Institutes of Health [MH R01-059559-04]; Brain Research Center of the 21st Century Frontier Research Program [2009K001272]; Ministry of Education, Science, and Technology of South Korea FX Research for this report was supported by grants MH R01-059559-04 from the National Institutes of Health and 2009K001272 from the Brain Research Center of the 21st Century Frontier Research Program, Ministry of Education, Science, and Technology of South Korea. NR 111 TC 32 Z9 33 U1 3 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 2009 VL 66 IS 11 BP 1221 EP 1232 PG 12 WC Psychiatry SC Psychiatry GA 514WS UT WOS:000271427500008 PM 19884610 ER PT J AU Hayden, KM Zandi, PP West, NA Tschanz, JT Norton, MC Corcoran, C Breitner, JCS Welsh-Bohmer, KA AF Hayden, Kathleen M. Zandi, Peter P. West, Nancy A. Tschanz, JoAnn T. Norton, Maria C. Corcoran, Chris Breitner, John C. S. Welsh-Bohmer, Kathleen A. CA Cache Cty Study Grp TI Effects of Family History and Apolipoprotein E epsilon 4 Status on Cognitive Decline in the Absence of Alzheimer Dementia The Cache County Study SO ARCHIVES OF NEUROLOGY LA English DT Article ID APOE GENOTYPE; DISEASE LOCUS; POPULATION-SAMPLE; TYPE-4 ALLELE; ONSET; PERFORMANCE; MEMORY; RISK; AGE; APOE-EPSILON-4 AB Objective: To evaluate the influences of a family history of Alzheimer dementia (FHxAD) and the apolipoprotein E epsilon 4 genotype (APOE epsilon 4) on cognitive decline. Design, Setting, and Participants: Residents of Cache County, Utah, aged 65 years or older, were invited to participate. At baseline, 2957 participants provided DNA for genotyping of APOE and a detailed FHxAD. They also completed the Modified Mini-Mental State Examination. Cognitive status was reexamined after 3 and 7 years. We used mixed-effects models to examine the association among FHxAD, APOE epsilon 4, and cognitive trajectories. Main Outcome Measure: Modified Mini-Mental State Examination score trajectories over time. Results: Compared with participants who did not have APOE epsilon 4 or an FHxAD, those with APOE epsilon 4 scored lower on the Modified Mini-Mental State Examination at base-line (-0.70 points; 95% confidence interval [CI], -1.15 to -0.24). Participants with an FHxAD and APOE epsilon 4 differed less, if at all, in baseline score (-0.46 points; 95% CI, -1.09 to 0.16) but declined faster during the 7-year study (-9.75 points [95% CI, -10.82 to -8.67] vs -2.91 points [95% CI, -3.37 to -2.44]). After exclusion of participants who developed prodromal AD or incident dementia, the group with an FHxAD and APOE epsilon 4 declined much less during the 7-year study (-1.54; 95% CI, -2.59 to -0.50). Conclusions: Much of the association among FHxAD, APOE epsilon 4, and cognitive decline may be attributed to undetected incipient (latent) disease. In the absence of latent disease, the 2 factors do not appear individually to be associated with cognitive decline, although they may be additive. C1 [Hayden, Kathleen M.; Welsh-Bohmer, Kathleen A.] Duke Univ, Med Ctr, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Dept Med,Div Neurol, Durham, NC 27705 USA. [Hayden, Kathleen M.; Welsh-Bohmer, Kathleen A.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27705 USA. [Zandi, Peter P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [West, Nancy A.] Univ Colorado, Dept Epidemiol, Denver, CO 80202 USA. [Norton, Maria C.] Utah State Univ, Dept Family Consumer & Human Dev, Logan, UT 84322 USA. [Tschanz, JoAnn T.; Norton, Maria C.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA. [Corcoran, Chris] Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA. [Breitner, John C. S.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Breitner, John C. S.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Hayden, KM (reprint author), Duke Univ, Med Ctr, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Dept Med,Div Neurol, 2200 W Main St,Ste A-200, Durham, NC 27705 USA. EM khayden@duke.edu RI Corcoran, Chris/F-2155-2010; Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013 FU National Institutes of Health [R01-AG-11380, K01-AG-029336] FX This work was supported by grants R01-AG-11380 (Dr Welsh-Bohmer) and K01-AG-029336 (Dr Hayden) from the National Institutes of Health. NR 49 TC 22 Z9 22 U1 4 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 NOV PY 2009 VL 66 IS 11 BP 1378 EP 1383 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 517AF UT WOS:000271584400011 PM 19901170 ER PT J AU Crothers, BA Tench, WD Schwartz, MR Bentz, JS Moriarty, AT Clayton, AC Fatheree, LA Chmara, BA Wilbur, DC AF Crothers, Barbara A. Tench, William D. Schwartz, Mary R. Bentz, Joel S. Moriarty, Ann T. Clayton, Amy C. Fatheree, Lisa A. Chmara, Beth Anne Wilbur, David C. TI Guidelines for the Reporting of Nongynecologic Cytopathology Specimens SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID OF-AMERICAN-PATHOLOGISTS; SURGICAL PATHOLOGY; IMPROVE COMMUNICATION; PAPANICOLAOU SOCIETY; CANCER; STANDARDIZATION; RECOMMENDATIONS; CYTOLOGY; BREAST; IMMUNOHISTOCHEMISTRY AB Context.-Gynecologic cytology terminology and report formatting have been nationally standardized since the implementation of The Bethesda System of 1988, but standard reporting for nongynecologic cytology has never been formally addressed on the same scale. Objectives.-To promote patient safety through uniform reporting in nongynecologic cytology (including fine-needle aspiration cytology) and to improve communication between laboratories and health care providers. Data Sources.-Sources include the College of American Pathologists Cytopathology Resource Committee; the College of American Pathologists Council on Scientific Affairs Ad Hoc Committee on Pathology Report Standardization; the College of American Pathologists Laboratory Accreditation Program inspection checklists; the Joint Commission for Accreditation of Healthcare Organizations; and the Clinical Laboratory Improvement Amendments of 1988. Conclusions.-We describe the major elements of quality nongynecologic cytology reporting and discuss areas of controversy in cytology reporting. Standardized nongynecologic specimen reporting will expand the concept of common report elements already widely implemented in gynecologic cytology reporting. The intent is to improve communication with the health care team while remaining in compliance with federal mandates and accreditation guidelines. (Arch Pathol Lab Med. 2009; 133: 1743-1756) C1 [Crothers, Barbara A.] Walter Reed Army Med Ctr, Dept Pathol, Washington, DC 20307 USA. [Crothers, Barbara A.] Walter Reed Army Med Ctr, Area Lab Serv, Washington, DC 20307 USA. [Tench, William D.] Palomar Med Ctr Lab, Escondido, CA USA. [Schwartz, Mary R.] Methodist Hosp, Dept Pathol, Houston, TX 77030 USA. [Bentz, Joel S.] Univ Utah, Dept Pathol, Salt Lake City, UT USA. [Moriarty, Ann T.] AmeriPath Indiana, Dept Pathol, Indianapolis, IN USA. [Clayton, Amy C.] Mayo Clin, Dept Anat Pathol, Rochester, MN USA. [Fatheree, Lisa A.; Chmara, Beth Anne] Coll Amer Pathologists, Dept Cytol Surveys, Northfield, IL USA. [Wilbur, David C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Crothers, BA (reprint author), Walter Reed Army Med Ctr, Dept Pathol, MCHL UAP Ward 47,6900 Georgia Ave NW, Washington, DC 20307 USA. EM barbara.crothers@us.army.mil NR 43 TC 6 Z9 6 U1 0 U2 0 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 NOV PY 2009 VL 133 IS 11 BP 1743 EP 1756 PG 14 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 520WP UT WOS:000271880500002 PM 19886707 ER PT J AU Moriarty, AT Crothers, BA Bentz, JS Souers, RJ Fatheree, LA Wilbur, DC AF Moriarty, Ann T. Crothers, Barbara A. Bentz, Joel S. Souers, Rhona J. Fatheree, Lisa A. Wilbur, David C. TI Automatic Failure in Gynecologic Cytology Proficiency Testing Results From the College of American Pathologists Proficiency Testing Program SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID INTERLABORATORY COMPARISON PROGRAM; SQUAMOUS INTRAEPITHELIAL LESION; CERVICOVAGINAL CYTOLOGY; VALIDATION CRITERIA; FEATURES; SLIDES; WELL AB Context.-Automatic failure in gynecologic cytology proficiency testing occurs when a high-grade lesion or carcinoma (HSIL+, Category D) is misinterpreted as negative for intraepithelial lesion or malignancy (Category B). Objectives.-To document the automatic failure rate in 2006 and 2007 from the College of American Pathologists proficiency testing program (PAP PT) and compare them to projected values from 2004. Design.-Identify automatic failures from PAP PT in 2006 and 2007 and compare the rates of failure regarding participant and preparation type to validated slides in the College of American Pathologists Interlaboratory Comparison Program in 2004. Results.-There were 65 264 participant responses for HSIL+ slides included in this analysis from 2006 and 2007. Overall, 1% (666 of 65 264) of the HSIL+ responses were classified as negative, resulting in automatic failure for the participant. There were significantly fewer automatic failures in 2007 as compared with either 2006 or projected from 2004 data (P<.001). Conventional preparations had a lower automatic failure rate than liquid-based preparations but only for 2006. Both pathologists and cytotechnologists interpreting liquid-based preparations faired better than projected from 2004 data. Conclusions.-The automatic failure rate in PAP PT is lower than expected based on 2004 data from the College of American Pathologists Interlaboratory Comparison Program. Automatic failures are a relatively small component (1% or less) of proficiency testing failures. The rate of automatic failure decreased from 2006 to 2007 and may be due to loss of poor performers in the testing pool, the test-taking environment, or removal of less robust slides from the program. (Arch Pathol Lab Med. 2009; 133: 1757-1760) C1 [Moriarty, Ann T.] AmeriPath Indiana, Dept Pathol, Indianapolis, IN 46219 USA. [Crothers, Barbara A.] Walter Reed Army Med Ctr, Dept Pathol, Washington, DC 20307 USA. [Crothers, Barbara A.] Walter Reed Army Med Ctr, Area Lab Serv, Washington, DC 20307 USA. [Bentz, Joel S.] Univ Utah, Dept Pathol, Salt Lake City, UT USA. [Souers, Rhona J.] Coll Amer Pathologists, Dept Stat, Northfield, IL USA. [Wilbur, David C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Moriarty, AT (reprint author), AmeriPath Indiana, Dept Pathol, 2560 N Shadeland Ave,Suite A, Indianapolis, IN 46219 USA. EM amoriarty@ameripath.com NR 13 TC 3 Z9 3 U1 0 U2 0 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 NOV PY 2009 VL 133 IS 11 BP 1757 EP 1760 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 520WP UT WOS:000271880500003 PM 19886708 ER PT J AU Kesselheim, JC Lehmann, LE Styron, NF Joffe, S AF Kesselheim, Jennifer C. Lehmann, Leslie E. Styron, Nancy Frumer Joffe, Steven TI The Ethics of Hematopoietic Stem Cell Donation by Minors Reply SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Editorial Material C1 [Kesselheim, Jennifer C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kesselheim, JC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jennifer_kesselheim@dfci.harvard.edu OI Joffe, Steven/0000-0002-0667-7384 NR 1 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD NOV PY 2009 VL 163 IS 11 BP 1065 EP 1066 PG 2 WC Pediatrics SC Pediatrics GA 514WU UT WOS:000271427700016 ER PT J AU De Jesus, M Parast, L Shelton, RC Kokkinogenis, K Othus, MKD Li, Y Allen, JD AF De Jesus, Maria Parast, Layla Shelton, Rachel C. Kokkinogenis, Kerry Othus, Megan K. D. Li, Yi Allen, Jennifer D. TI Actual vs Preferred Sources of Human Papillomavirus Information Among Black, White, and Hispanic Parents SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Editorial Material C1 [De Jesus, Maria] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP De Jesus, M (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St,LW 703, Boston, MA 02115 USA. EM maria_dejesus@dfci.harvard.edu RI Allen, Jennifer/M-2113-2015 FU NCI NIH HHS [P30 CA006516, P30 CA006516-44, T32 CA009337, P30CA006516] NR 5 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 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD NOV PY 2009 VL 163 IS 11 BP 1066 EP 1067 PG 5 WC Pediatrics SC Pediatrics GA 514WU UT WOS:000271427700017 PM 19884601 ER PT J AU Saunders, LL Selassie, AW Hill, EG Horner, MD Nicholas, JS Lackland, DT Corrigan, JD AF Saunders, Lee L. Selassie, Anbesaw W. Hill, Elizabeth G. Horner, Michael D. Nicholas, Joyce S. Lackland, Daniel T. Corrigan, John D. TI Pre-existing Health Conditions and Repeat Traumatic Brain Injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Brain injuries; Epilepsy; Rehabilitation; Seizures ID PROFESSIONAL FOOTBALL PLAYERS; RECURRENT CONCUSSION; SOCIOECONOMIC-STATUS; UNITED-STATES; HEAD-INJURY; ALCOHOL-USE; POPULATION; EPILEPSY; SEIZURES; PREVALENCE AB Objective: To assess and compare the effect of Pre-existing epilepsy/seizure disorder and drug/alcohol problem on the hazard of repeat traumatic brain injury (TBI) in persons with TBI who participated in a follow-up study. Design: Retrospective cohort. Setting: Acute care hospitals in South Carolina. Participants: Participants were from the South Carolina Traumatic Brain Injury Follow-up Registry cohort of persons (N=2118) who were discharged from an acute care hospital in South Carolina and who participated in a year-1 follow-up interview. Interventions: Not applicable. Main Outcome Measures: Repeat TBI was defined by 2 isolated events of TBI in the same person at least 72 hours apart and recorded in hospital discharge or emergency department records from 1999 through 2005. Results: A Cox proportional hazards model was used to assess the associations of Pre-existing epilepsy/seizure disorder and drug/alcohol problem with time to repeat TBI, controlling for other confounding factors. There were 2099 persons with information on both Pre-existing conditions. There were 147 (7%) persons who sustained repeat TBI after recruitment to the follow-up study, and 82 (3.9%) had a previous TBI before recruitment for which they were seen in the hospital discharge or emergency department since 1996. The hazard of repeat TBI for persons with Pre-existing epilepsy/seizure disorder was 2.3 times the hazard for those without (hazard ratio, 2.3; 95% confidence interval, 1.2-4.4; P=.011). Pre-existing drug/alcohol problem was not associated with repeat TBI. Other variables significantly associated with repeat TBI were having a prior TBI. being insured under Medicaid, and having no insurance. Conclusions: Pre-existing epilepsy/seizure disorder predisposes to repeat TBI. Appropriate management of seizure control may be an important strategy to allay the occurrence of repeat TBI. C1 [Saunders, Lee L.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Selassie, Anbesaw W.; Hill, Elizabeth G.; Nicholas, Joyce S.; Lackland, Daniel T.] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. [Horner, Michael D.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Horner, Michael D.] Ralph H Johnson Dept Vet Affairs, Med Ctr, Mental Hlth Serv, Charleston, SC USA. [Corrigan, John D.] Ohio State Univ, Dept Phys Med & Rehabil, Columbus, OH 43210 USA. RP Saunders, LL (reprint author), Med Univ S Carolina, Dept Rehabil Sci, 77 President St,Ste 117,MSC 700, Charleston, SC 29425 USA. EM saundel@musc.edu FU Division of Injury Response [U17/CCU421926]; National Center for Injury Prevention and Control (NCIPC); Centers for Disease Control and Prevention (CDC); Social Security Administration (SSA); Office of Disability Income and Support Programs FX Supported by the Division of Injury Response (grant no. U17/CCU421926), National Center for Injury Prevention and Control (NCIPC), Centers for Disease Control and Prevention (CDC). The study was performed pursuant to a jointly financed cooperative arrangement between the NCIPC, the National Center for Chronic Discase Prevention and Health Promotion, CDC, and the Social Security Administration (SSA), Office of Disability Income and Support Programs. NR 39 TC 3 Z9 3 U1 4 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2009 VL 90 IS 11 BP 1853 EP 1859 DI 10.1016/j.apmr.2009.05.020 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 520XC UT WOS:000271881900006 PM 19887208 ER PT J AU Koontz, AM Roche, BM Collinger, JL Cooper, RA Boninger, ML AF Koontz, Alicia M. Roche, Bailey M. Collinger, Jennifer L. Cooper, Rory A. Boninger, Michael L. TI Manual Wheelchair Propulsion Patterns on Natural Surfaces During Start-Up Propulsion SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Biomechanics; Kinetics; Rehabilitation; Wheelchairs ID STROKE PATTERN; BIOMECHANICS; EFFICIENCY; SPEEDS AB Objectives: To classify propulsion patterns over surfaces encountered in the natural environment during start-up and compare selected biomechanical variables between pattern types. Design: Case series. Setting: National Veterans Wheelchair Games, Minneapolis, MN, 2005. Participants: Manual wheelchair users (N=29). Intervention: Subjects pushed their wheelchairs from a resting position over high-pile carpet, over linoleum, and up a ramp with a 5 degrees incline while propulsion kinematics and kinetics were recorded with a motion capture system and an instrumented wheel. Main Outcome Measures: Three raters classified the first 3 strokes as 1 of 4 types on each surf-ace: arc, semicircular (SC), single looping over propulsion (SC), and double looping over propulsion (DC). The Fisher exact test was used to assess pattern changes between strokes and surface type. A multiple analysis of variance test was used to compare peak and average resultant force and moment about the hub, average wheel velocity, stroke frequency, contact angle, and distance traveled between stroke patterns. Results: SL was the most common pattern used during start-up propulsion (44.9%), followed by arc (35.9%), DL (14.1%), and SC (5.1%). Subjects who dropped their hands below the rim during recovery achieved faster velocities and covered greater distances (.016 <= P <=.075) during start-up on linoleum and carpet and applied more force during start-up on the ramp compared with those who used an arc pattern (P=.066). Conclusions: Classifying propulsion patterns is a difficult task that should use multiple raters. In addition, propulsion patterns change during start-up, with an arc pattern most prevalent initially. The biomechanical findings in this study agree with current clinical guidelines that recommend training users to drop the hand below the pushrim during recovery. C1 [Koontz, Alicia M.; Roche, Bailey M.; Collinger, Jennifer L.; Cooper, Rory A.; Boninger, Michael L.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Collinger, Jennifer L.; Cooper, Rory A.; Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Koontz, Alicia M.; Cooper, Rory A.; Boninger, Michael L.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Koontz, Alicia M.; Roche, Bailey M.; Collinger, Jennifer L.; Cooper, Rory A.; Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. RP Koontz, AM (reprint author), VA Pittsburgh Hlth Care Syst, Human Engn Res Labs 151R1 H, 7180 Highland Dr,151R1-H, Pittsburgh, PA 15206 USA. EM akoontz@pitt.edu OI Boninger, Michael/0000-0001-6966-919X FU Department of Veterans Affairs Rehabilitation Research and Development Service [B3142C]; National Science Foundation [EEC 0552351]; Paralyzed veterans of America FX Supported by the Department of Veterans Affairs Rehabilitation Research and Development Service (project no. B3142C), the National Science Foundation (project no. EEC 0552351), and the Paralyzed veterans of America. NR 22 TC 14 Z9 14 U1 3 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2009 VL 90 IS 11 BP 1916 EP 1923 DI 10.1016/j.apmr.2009.05.022 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 520XC UT WOS:000271881900015 PM 19887217 ER PT J AU Burnett, J Dyer, CB Naik, AA AF Burnett, Jason Dyer, Carmel B. Naik, Aanand A. TI Convergent Validation of the Kohlman Evaluation of Living Skills as a Screening Tool of Older Adults' Ability to Live Safely and Independently in the Community SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Activities of daily living; Comprehensive geriatric assessment; Older persons or elders; Rehabilitation; Restorative care ID COGNITIVE IMPAIRMENT; PHYSICAL-PERFORMANCE; SELF-NEGLECT; INSTRUMENTAL ACTIVITIES; EXECUTIVE DYSFUNCTION; FUNCTIONAL DECLINE; DWELLING ELDERS; FREEDOM HOUSE; FOLLOW-UP; DISABILITY AB Objective: To evaluate the convergent validity of the Kohlman Evaluation of Living Skills (KELS) to screen older adults' ability to live safely and independently. Design: Cross-sectional study correlating KELS with components of a Comprehensive Geriatric Assessment. Setting: Participants' homes. Participants: Community-dwelling older adults (N=200) 65 years and older including 100 persons referred by Adult Protective Services (APS) and 100 ambulatory patients matched on age, race, sex, and socioeconomic status. Interventions: In-home comprehensive assessment. Main Outcome Measures: KELS, Geriatric Depression Scale (GDS), modified Physical Performance Test (mPPT), Mini-Mental State Examination (MMSE), Knee Extensor Break Test, Executive Cognitive Test (EXIT25). executive clock-drawing test (CLOX) 1 and 2, and an 8-foot walk test. Results: Older adults with abnormal KELS scores performed significantly worse on all tests except for the Knee Extensor Break Test. Accordingly, among the entire group, the KELS correlated with measures of executive function (EXIT25, r=.705, P<.001; CLOX 1, r=-.629, P<.001), cognitive function (MMSE, r=-.508, P<.001), affect (GDS, r=.318, P<.001), and physical function (mPPT, r=-.472, P<.001) but did not correlate with the Knee Extensor Break Test (r=-.068, P=.456). Among those referred by APS, the KELS failed to correlate with only the 8-foot walk test (r=.175, P=.153) and GDS (r=.080, P=.450). Conclusions: This study demonstrated the convergent validity of KELS with a battery of cognitive, affective, executive, and functional measures often used to determine older adults' ability to live safely and independently in the community. KELS may be a valid and pragmatic alternative to screen for the capacity to live safely and independently among older adults. C1 [Naik, Aanand A.] Baylor Coll Med, Alkek Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. [Burnett, Jason; Dyer, Carmel B.] Univ Texas Hlth Sci Ctr Houston, Div Geriatr & Palliat Med, Dept Internal Med, Houston, TX USA. [Burnett, Jason; Dyer, Carmel B.; Naik, Aanand A.] Consortium Res Elder Self Neglect Texas, Houston, TX USA. [Burnett, Jason; Dyer, Carmel B.; Naik, Aanand A.] Harris Cty Hosp Dist, Houston, TX USA. RP Naik, AA (reprint author), Michael E DeBakey VAMC 152, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe, Houston, TX 77030 USA. EM anaik@bcm.tmc.edu FU Houston Center for Quality of Care & Utilization Studies [HFP90-020]; Michael E. DeBakey Veterans Affairs Medical Center; Consortium for Research in Elder Self-Neglect of Texas [NIH P20-RR020626]; Greenwall Foundation; National Institute of Aging [K23AG027144]; Doris Duke Charitable Foundation FX Supported by the Houston Center for Quality of Care & Utilization Studies (grant no. HFP90-020) with resources and the use of facilities; Michael E. DeBakey Veterans Affairs Medical Center, the Consortium for Research in Elder Self-Neglect of Texas (grant no. NIH P20-RR020626): a bioethics grant from the Greenwall Foundation: and the National Institute of Aging (grant no. K23AG027144) and a Doris Duke Charitable Foundation Clinical Scientist Development Award. NR 30 TC 10 Z9 10 U1 4 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2009 VL 90 IS 11 BP 1948 EP 1952 DI 10.1016/j.apmr.2009.05.021 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 520XC UT WOS:000271881900020 PM 19887222 ER PT J AU Bentrem, DJ Cohen, ME Hynes, DM Ko, CY Bilimoria, KY AF Bentrem, David J. Cohen, Mark E. Hynes, Denise M. Ko, Clifford Y. Bilimoria, Karl Y. TI Identification of Specific Quality Improvement Opportunities for the Elderly Undergoing Gastrointestinal Surgery SO ARCHIVES OF SURGERY LA English DT Article ID SURGICAL OUTCOMES; UNITED-STATES; COLORECTAL-CANCER; GASTRIC-CANCER; POPULATION; RISK; CARE; RESECTION; OCTOGENARIANS; ESOPHAGUS AB Hypothesis: Specific complications occur more frequently in elderly patients undergoing major gastrointestinal (GI) tract operations that may represent opportunities for quality improvement. Design: Retrospective cohort study. Setting: One hundred twenty-one hospitals participating in American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Patients: Using the ACS-NSQIP participant use file (2005-2006), patients undergoing upper gastrointestinal tract (n=4115), hepatobiliary or pancreatic (n=3364), and colorectal (n=17 268) operations at 121 hospitals were examined. Main Outcome Measures: Risk-adjusted 30-day outcomes were assessed using regression modeling adjusting for patient characteristics, comorbidities, and surgical procedures. The elderly were defined as those older than 75 years. Results: Between January 1, 2005, and December 31, 2006, a total of 54 747 patients who underwent major GI tract operations were identified from the ACS-NSQIP data file. In the elderly, overall perioperative morbidity was 1.2 to 2 times higher and mortality was 2.9 to 6.7 times higher than in younger patients after adjusting for differences in preoperative comorbidities. Irrespective of procedure type, the elderly were significantly more likely to experience cardiac ( acute myocardial infarction and cardiac arrest), pulmonary ( pneumonia, pulmonary embolism, and respiratory failure), and urologic ( urinary tract infection and renal failure) complications. However, surgical site infections, postoperative bleeding events, deep venous thromboses, and rates of return to the operating room did not differ significantly by age. Conclusions: Morbidity and mortality are markedly higher in older patients. Quality measures for the elderly currently address only myocardial infarction, surgical site infection, and deep venous thrombosis. If care for the elderly is to be improved, quality improvement initiatives need to be expanded to include postoperative pulmonary and renal complications. C1 [Cohen, Mark E.; Ko, Clifford Y.; Bilimoria, Karl Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Hynes, Denise M.] Univ Illinois, Coll Med, Dept Med, Sch Publ Hlth, Chicago, IL USA. [Hynes, Denise M.] Univ Illinois, Sch Publ Hlth, Dept Hlth Policy Adm, Chicago, IL USA. [Hynes, Denise M.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Bentrem, David J.; Bilimoria, Karl Y.] Northwestern Univ, Dept Surg, Sch Med, Chicago, IL 60611 USA. RP Bilimoria, KY (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM k-bilimoria@northwestern.edu FU American Cancer Society Illinois Division and by the Barnum Foundation [ACSIRG 93-037-12]; Department of Veterans Affairs Health Services Research and Development Service Research Career Scientist Award; American College of Surgeons Clinical Scholars FX This study was funded in part by grant ACSIRG 93-037-12 from the American Cancer Society Illinois Division and by the Barnum Foundation ( Dr Bentrem). Dr Hynes is supported by the Department of Veterans Affairs Health Services Research and Development Service Research Career Scientist Award. Dr Bilimoria is supported by the American College of Surgeons Clinical Scholars in Residence program. NR 41 TC 48 Z9 52 U1 0 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 NOV PY 2009 VL 144 IS 11 BP 1013 EP 1020 PG 8 WC Surgery SC Surgery GA 521AG UT WOS:000271890500007 PM 19917937 ER PT J AU Velmahos, GC AF Velmahos, George C. TI Patient Safety Systems: A Long Way to Go INVITED CRITIQUE SO ARCHIVES OF SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Dept Surg, 165 Cambridge St,Ste 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2009 VL 144 IS 11 BP 1034 EP 1034 PG 1 WC Surgery SC Surgery GA 521AG UT WOS:000271890500011 PM 19928295 ER PT J AU Paterson, AD Lopes-Virella, MF Waggott, D Boright, AP Hosseini, SM Carter, RE Shen, EQ Mirea, L Bharaj, B Sun, L Bull, SB AF Paterson, Andrew D. Lopes-Virella, Maria F. Waggott, Daryl Boright, Andrew P. Hosseini, S. Mohsen Carter, Rickey E. Shen, Enqing Mirea, Lucia Bharaj, Bhupinder Sun, Lei Bull, Shelley B. CA Diabet Control Complications Trial TI Genome-Wide Association Identifies the ABO Blood Group as a Major Locus Associated With Serum Levels of Soluble E-Selectin SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE E-selectin; ABO blood group; genome-wide association; SNP ID PLASMODIUM-FALCIPARUM MALARIA; CELLULAR ADHESION MOLECULES; LEUKOCYTE-ENDOTHELIAL ADHESION; VON-WILLEBRAND-FACTOR; RISK-FACTORS; CARDIOVASCULAR-DISEASE; MACROVASCULAR COMPLICATIONS; DIABETES-MELLITUS; VASCULAR-DISEASE; MARKERS AB Background-Elevated serum soluble E-selectin levels have been associated with a number of diseases. Although E-selectin levels are heritable, little is known about the specific genetic factors involved. E-selectin levels have been associated with the ABO blood group phenotype. Methods and Results-We performed a high-resolution genome-wide association study of serum soluble E-selectin levels in 685 white individuals with type 1 diabetes from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Intervention and Complications (EDIC) study to identify major loci influencing levels. Highly significant evidence for association (P = 10(-29)) was observed for rs579459 near the ABO blood group gene, accounting for 19% of the variance in E-selectin levels. Levels of E-selectin were higher in O/O than O/A heterozygotes, which were likewise higher than A/A genotypes. Analysis of subgroups of A alleles reveals heterogeneity in the association, and even after this was accounted for, an intron 1 SNP remained significantly associated. We replicate the ABO association in nondiabetic individuals. Conclusion-ABO is a major locus for serum soluble E-selectin levels. We excluded population stratification, fine-mapped the association to sub-A alleles, and also document association with additional variation in the ABO region. (Arterioscler Thromb Vasc Biol. 2009; 29: 1958-1967.) C1 [Paterson, Andrew D.; Hosseini, S. Mohsen; Bharaj, Bhupinder] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1L7, Canada. [Waggott, Daryl; Shen, Enqing; Mirea, Lucia; Bull, Shelley B.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [Boright, Andrew P.] Univ Toronto, Dept Med, Univ Hlth Network, Toronto, ON M5S 1A1, Canada. [Paterson, Andrew D.; Mirea, Lucia; Sun, Lei; Bull, Shelley B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada. [Lopes-Virella, Maria F.] Med Univ S Carolina, Dept Med & Lab Serv, Charleston, SC USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Carter, Rickey E.] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC USA. RP Paterson, AD (reprint author), Hosp Sick Children, Program Genet & Genome Biol, TMDT Bldg E Tower,Rm 15-707,101 Coll St, Toronto, ON M5G 1L7, Canada. EM andrew.paterson@utoronto.ca RI Bull, Shelley/A-1920-2013; Hosseini, Mohsen/K-7133-2013; Paterson, Andrew/A-4088-2011 OI Hosseini, Mohsen/0000-0003-3626-9928; Paterson, Andrew/0000-0002-9169-118X FU Department of Veterans Affairs; National Institutes of Health; Juvenile Diabetes Research Foundation [PO1 HL55782]; National Institute of Diabetes and Digestive and Kidney Diseases [N01-DK-6-2204, R01-DK-077510]; Canadian Network of Centers of Excellence in Mathematics; Canadian Institutes of Health Research (CIHR) FX This research was supported by funding of the Merit Review Program of the Department of Veterans Affairs, by joint funding of the National Institutes of Health and Juvenile Diabetes Research Foundation (PO1 HL55782), National Institute of Diabetes and Digestive and Kidney Diseases Contract N01-DK-6-2204, National Institute of Diabetes and Digestive and Kidney Diseases Grant R01-DK-077510, and support from the Canadian Network of Centers of Excellence in Mathematics. The DCCT/EDIC Research Group is sponsored through research contracts from the National Institute of Diabetes, Endocrinology, and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institutes of Health. A. D. P. holds a Canada Research Chair in the Genetics of Complex Diseases. S. B. B. was a recipient of a Canadian Institutes of Health Research (CIHR) Senior Investigator award (2002-7). L. M. is a recipient of a CIHR Research Scholarship. NR 53 TC 77 Z9 78 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2009 VL 29 IS 11 BP 1958 EP U609 DI 10.1161/ATVBAHA.109.192971 PG 26 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 509EE UT WOS:000270996300039 PM 19729612 ER PT J AU Musunuru, K Orho-Melander, M Caulfield, MP Li, SG Salameh, WA Reitz, RE Berglund, G Hedblad, B Engstrom, G Williams, PT Kathiresan, S Melander, O Krauss, RM AF Musunuru, Kiran Orho-Melander, Marju Caulfield, Michael P. Li, Shuguang Salameh, Wael A. Reitz, Richard E. Berglund, Goran Hedblad, Bo Engstrom, Gunnar Williams, Paul T. Kathiresan, Sekar Melander, Olle Krauss, Ronald M. TI Ion Mobility Analysis of Lipoprotein Subfractions Identifies Three Independent Axes of Cardiovascular Risk SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE lipids; lipoproteins; cardiovascular diseases; genetics ID LOW-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; LDL PARTICLE-SIZE; MAGNETIC-RESONANCE-SPECTROSCOPY; FAMILIAL COMBINED HYPERLIPIDEMIA; ARTERY-DISEASE; MYOCARDIAL-INFARCTION; GENETIC-DETERMINANTS; INTERVENTION TRIAL; METABOLIC SYNDROME AB Objective-Whereas epidemiological studies show that levels of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) predict incident cardiovascular disease (CVD), there is limited evidence relating lipoprotein subfractions and composite measures of subfractions to risk for CVD in prospective cohort studies. Methods and Results-We tested whether combinations of lipoprotein subfractions independently predict CVD in a prospective cohort of 4594 initially healthy men and women (the Malmo Diet and Cancer Study, mean follow-up 12.2 years, 377 incident cardiovascular events). Plasma lipoproteins and lipoprotein subfractions were measured at baseline with a novel high-resolution ion mobility technique. Principal component analysis (PCA) of subfraction concentrations identified 3 major independent (ie, zero correlation) components of CVD risk, one representing LDL-associated risk, a second representing HDL-associated protection, and the third representing a pattern of decreased large HDL, increased small/medium LDL, and increased triglycerides. The last corresponds to the previously described "atherogenic lipoprotein phenotype." Several genes that may underlie this phenotype-CETP, LIPC, GALNT2, MLXIPL, APOA1/A5, LPL-are suggested by SNPs associated with the combination of small/medium LDL and large HDL. Conclusion-PCA on lipoprotein subfractions yielded three independent components of CVD risk. Genetic analyses suggest these components represent independent mechanistic pathways for development of CVD. (Arterioscler Thromb Vasc Biol. 2009; 29:1975-1980.) C1 [Krauss, Ronald M.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. [Musunuru, Kiran; Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Musunuru, Kiran; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Musunuru, Kiran; Kathiresan, Sekar] Broad Inst MIT & Harvard, Cambridge, MA USA. [Orho-Melander, Marju; Berglund, Goran; Hedblad, Bo; Engstrom, Gunnar; Melander, Olle] Lund Univ, Malmo Univ Hosp, Malmo, Sweden. [Caulfield, Michael P.; Li, Shuguang; Salameh, Wael A.; Reitz, Richard E.] Quest Diagnost Nichols Inst, San Juan Capistrano, CA USA. [Williams, Paul T.] Ernest Orlando Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA USA. RP Krauss, RM (reprint author), Childrens Hosp Oakland, Res Inst, 5700 Martin Luther King Jr Way, Oakland, CA 94609 USA. EM rkrauss@chori.org OI Engstrom, Gunnar/0000-0002-8618-9152 FU United States National Institutes of Health (NIH) [U01HL069757]; Swedish Medical Research Council; Swedish Heart and Lung Foundation; Medical Faculty of Lund University; Malmo University Hospital; Albert Pahlsson Research Foundation; Crafoord foundation; Ernhold Lundstroms Research Foundation; Region Skane; Hulda and Conrad Mossfelt Foundation; King Gustaf V and Queen Victoria Foundation; Lennart Hanssons Memorial Fund; Doris Duke Charitable Foundation; Fannie E. Rippel Foundation; Donovan Family Foundation; Quest Diagnostics Inc FX K. M. is supported by a T32 grant in Cell and Molecular Training for Cardiovascular Biology from the United States National Institutes of Health (NIH). M.O.-M. and O.M. are supported by the Swedish Medical Research Council, the Swedish Heart and Lung Foundation, the Medical Faculty of Lund University, Malmo University Hospital, the Albert Pahlsson Research Foundation, the Crafoord foundation, the Ernhold Lundstroms Research Foundation, the Region Skane, the Hulda and Conrad Mossfelt Foundation, the King Gustaf V and Queen Victoria Foundation and the Lennart Hanssons Memorial Fund. S. K. is supported by a Doris Duke Charitable Foundation Clinical Scientist Development Award, a charitable gift from the Fannie E. Rippel Foundation, the Donovan Family Foundation, and a K23 career development award from the NIH. R. M. K. is supported by U01HL069757 from the NIH and has received research support from Quest Diagnostics Inc. For this study, ion mobility measurements of study participants were provided free of charge by Quest Diagnostics, which had no role in the analysis and interpretation of the data or in the preparation, review, or approval of the manuscript. NR 38 TC 76 Z9 78 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2009 VL 29 IS 11 BP 1975 EP U628 DI 10.1161/ATVBAHA.109.190405 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 509EE UT WOS:000270996300041 PM 19729614 ER PT J AU Elhassan, B Ozbaydar, M Diller, D Massimini, D Higgins, LD Warner, JJP AF Elhassan, Bassem Ozbaydar, Mehmet Diller, David Massimini, Daniel Higgins, Laurence D. Warner, Jon J. P. TI Open Versus Arthroscopic Acromioclavicular Joint Resection: A Retrospective Comparison Study SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article DE Acromioclavicular joint; Arthroscopic; Resection; Open; Comparison ID DISTAL CLAVICLE RESECTION; CONCOMITANT SUBACROMIAL DECOMPRESSION; CONSTANT SCORE; OSTEOLYSIS; SHOULDER; BURSAL AB Purpose: The purpose was to compare open and arthroscopic acrormoclavicular joint (ACJ) resection. Methods: We retrospectively reviewed 103 patients (105 shoulders) who underwent ACJ resection between 2000 and 2005. There were 56 women and 47 men with a mean age of 48 years. The mean duration of follow-up was 51 months (range, 15 to 91 months). Arthroscopic ACJ resection by use of a direct approach was performed in 81 shoulders (group A), and open ACJ resection was performed in 24 shoulders (group 13). Results were graded according to pain relief both subjectively and objectively with cross-body adduction testing and direct palpation of the ACJ, subjective shoulder value, Constant score, and improved function. Results: The Constant scores increased from 50 (range, 34 to 65) to 89 (range, 39 to 100) in group A (P < .0001) and from 46 (range, 22 to 63) to 87 (range, 43 to 100) in group B (P < .0001). There was no statistical difference in the postoperative normalized Constant score between group A and group B (P = .47), Pain with cross-body adduction testing and palpation of the ACJ improved in 76 shoulders (94%) in group A and 22 shoulders (92%) in group B. No patients had signs or symptoms of ACJ anteroposterior instability. Revision ACJ resection was performed in 5 patients (5 shoulders [6.2%]) in group A and I shoulder (4.2%) in group B (P = .37). The radiographs of the patients who underwent revision showed that 3 patients (3.7%) from group A had regrowth of the distal clavicle; in addition, 2 patients (2.5%) from group A and 1 patient (4.3%) from group B had incomplete distal clavicle excision. Conclusions: This study did not show a significant difference in the outcome between arthroscopic and open ACJ resection. Incomplete excision and regrowth of the distal clavicle are the most common causes of revision. Although only the arthroscopic group showed a small percentage of patients (3.7%) with regrowth of the distal clavicle, the number is too small to assume that this complication is the result of the arthroscopic technique only. Level of Evidence: Level IV, therapeutic case series. C1 [Elhassan, Bassem] Mayo Clin, Dept Orthoped, Rochester, MN USA. [Higgins, Laurence D.] Harvard Univ, Sports Med & Shoulder Serv, Sch Med, Boston, MA 02493 USA. [Warner, Jon J. P.] Harvard Univ, Dept Orthopaed Surg, Sch Med, Boston, MA 02493 USA. [Higgins, Laurence D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ozbaydar, Mehmet; Diller, David; Massimini, Daniel; Higgins, Laurence D.; Warner, Jon J. P.] Harvard Univ, Harvard Shoulder Serv, Boston, MA 02493 USA. RP Warner, JJP (reprint author), Harvard Univ, Harvard Shoulder Serv, Massachusetts Gen Hosp, Sch Med,Yawkey Ctr Outpatient Care, Suite 3G,55Fruit St, Boston, MA 02493 USA. EM jwarner@partners.org RI Ozbaydar, Mehmet/D-7391-2016 NR 28 TC 17 Z9 18 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 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD NOV PY 2009 VL 25 IS 11 BP 1224 EP 1232 DI 10.1016/j.arthro.2009.06.010 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 517NM UT WOS:000271621700010 PM 19896043 ER PT J AU Seo, JH Li, G Shetty, GM Kim, JH Bae, JH Jo, ML Kim, JS Lee, SJ Nha, KW AF Seo, Jeong-Hee Li, Guoan Shetty, Gautam M. Kim, Ji-Hoon Bae, Ji-Hoon Jo, Myoung-Lae Kim, Jung-Sung Lee, Sung-Jae Nha, Kyung-Wook TI Effect of Repair of Radial Tears at the Root of the Posterior Horn of the Medial Meniscus With the Pullout Suture Technique: A Biomechanical Study Using Porcine Knees SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article DE Medial meniscus; Posterior horn; Radial tear; Root tear; Contact area; Contact pressure; Pullout suture ID PRESSURE DISTRIBUTION; CONTACT AREA; MENISCECTOMY; CONSEQUENCES; JOINTS AB Purpose: Our purpose was to evaluate the result of radial tears at the root of the posterior horn of the medial meniscus (PHMM) in terms of tibiofemoral contact mechanics and the effectiveness of pullout sutures for such tears. Methods: Eleven mature pig knees each underwent 15 different testing conditions with an intact, simulated (incised) radial tear at the root of the PHMM and placement of pullout sutures in the radial tears of the medial meniscus at 5 different angles of flexion (0 degrees, 15 degrees, 30 degrees, 60 degrees, and 90 degrees) under a 1,500-N axial load. A K-Scan pressure sensor (Tekscan, Boston, MA) was used to measure medial tibiofemoral contact area and peak tibiofemoral contact pressure. Data were analyzed to assess the difference in medial contact area and tibiofemoral peak contact pressure among the 3 meniscal conditions at various degrees of knee flexion. Results: The mean contact area was significantly lower, and the peak tibiofemoral contact pressure was significantly high in knees with simulated radial tears at all angles of knee flexion compared with knees with intact menisci (P < .0001). The peak tibiofemoral contact pressure after the pullout suture technique was significantly high at 0 degrees and 15 degrees of flexion (P < .0001) compared with intact knee specimens. Failure of sutures occurred in 45% of the specimens at 0 degrees of flexion. Conclusions: Radial tears at the root of the PHMM in a porcine model significantly increased medial tibiofemoral contact pressure and decreased contact area. Although repair of tears of the PHMM with the pullout suture technique aids in significantly reducing tibiofemoral peak contact pressure between 30 degrees and 90 degrees, it remains significantly high at 0 degrees and 15 degrees of flexion. Clinical Relevance: Pullout sutures for radial tears at the root of the PHMM may lead to an increase in peak medial tibiofemoral contact pressure and may be prone to mechanical failure, especially during the stance (loading) phase of gait (mean, 15 degrees of flexion). C1 [Seo, Jeong-Hee; Shetty, Gautam M.; Kim, Ji-Hoon; Nha, Kyung-Wook] Inje Univ, Dept Orthopaed Surg, Ilsanpaik Hosp, Ilsan, South Korea. [Li, Guoan] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. [Li, Guoan] Harvard Univ, Sch Med, Boston, MA USA. [Bae, Ji-Hoon] Korea Univ, Dept Orthopaed Surg, Guro Hosp, Seoul, South Korea. [Seo, Jeong-Hee; Jo, Myoung-Lae; Lee, Sung-Jae] Inje Univ, Dept Biomed Engn, Gimhae, South Korea. [Kim, Jung-Sung] Corentec Co Ltd, Ctr Res & Dev, Cheonan, South Korea. [Kim, Jung-Sung] Yonsei Univ, Coll Med, Dept Med Engn, Seoul, South Korea. RP Nha, KW (reprint author), 2240 Daehwadong, Goyangsi 411706, Gyeonggido, South Korea. EM Kwnhamj@hotmail.com FU Ministry of Commerce, Industry and Energy South Korea [10025570] FX Supported by a grant from the Materials & Components Technology R&D Program funded by the Ministry of Commerce, Industry and Energy (10025570), South Korea, and by a 2007 Inje University research grant. NR 19 TC 25 Z9 26 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD NOV PY 2009 VL 25 IS 11 BP 1281 EP 1287 DI 10.1016/j.arthro.2009.05.014 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 517NM UT WOS:000271621700018 PM 19896051 ER PT J AU De Luca, G Gibson, CM Bellandi, F Noc, M Dudek, D Zeymer, U Arntz, HR Cutlip, D Maioli, M Zorman, S Gabriel, HM Emre, A Rakowski, T Gyongyosi, M Huber, K van't Hof, AWJ AF De Luca, Giuseppe Gibson, C. Michael Bellandi, Francesco Noc, Marko Dudek, Dariusz Zeymer, Uwe Arntz, Hans-Richard Cutlip, Donald Maioli, Mauro Zorman, Simona Gabriel, H. Mesquita Emre, Ayse Rakowski, Tomasz Gyongyosi, Mariann Huber, Kurt van't Hof, Arnoud W. J. TI Diabetes mellitus is associated with distal embolization, impaired myocardial perfusion, and higher mortality in patients with ST-segment elevation myocardial infarction treated with primary angioplasty and glycoprotein IIb-IIIa inhibitors SO ATHEROSCLEROSIS LA English DT Article DE Primary angioplasty; Distal embolization; Diabetes; Myocardial perfusion ID PERCUTANEOUS CORONARY INTERVENTION; NO-REFLOW PHENOMENON; THROMBOLYTIC THERAPY; RANDOMIZED-TRIALS; REPERFUSION; HYPERGLYCEMIA; GLUCOSE; ABCIXIMAB; VASODILATION; METAANALYSIS AB Background: It has been shown that, among patients with ST-segment elevation myocardial infarction (STEMI), diabetes is associated with a significantly higher mortality. The aim of the current study was to investigate the impact of diabetes on myocardial perfusion and mortality among STEMI patients treated with primary angioplasty and glycoprotein IIb-IIIa inhibitors. Methods: Our population is represented by a total of 1662 patients undergoing primary angioplasty for STEMI included in 11 randomized trials. Myocardial perfusion was evaluated by angiography (n = 1324) or postprocedural ECG ( n = 1371). 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 ( data available in 1181 patients). Results: Diabetes was observed in a total of 281 patients (16.9%). Diabetic patients were older, with a larger prevalence of female gender, hypertension, hypercholesterolemia, advanced killip class at presentation and multivessel disease. Diabetes was associated with impaired postprocedural TIMI 3 flow (82% vs 90%, p < 0.001), MBG 2-3 (60.1% vs 74.2%, p < 0.001), complete ST-segment resolution (43.2% vs 60%, p < 0.001) and more distal embolization (16.4% vs 10.1%, p < 0.0001). The association with impaired MBG and distal embolization was confirmed after correction for baseline confounding factors. Diabetes was associated with significantly impaired mortality (12.6% vs 3.9%, HR= 3.0 [1.84-4.89], p < 0.001), that persisted even after correction for baseline confounding factors (HR = 2.6 [1.52-4.45], p = 0.001). Conclusion: This study showed that, among patients with STEMI undergoing primary angioplasty on the top of glycoprotein IIb-IIIa inhibitors, diabetes mellitus is independently associated with impaired perfusion and distal embolization, that contribute to explain the higher mortality observed in these patients. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [De Luca, Giuseppe] Eastern Piedmont Univ, Maggiore Carita Hosp, Div Cardiol, Novara, Italy. [Gibson, C. Michael] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 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. [Dudek, Dariusz; Rakowski, Tomasz] Jagiellonian Univ, Inst Cardiol, Dept Cardiol 2, Krakow, Poland. [Zeymer, Uwe] Herzzentrum Ludwigshafen, Div Cardiol, Ludwigshafen, Germany. [Arntz, Hans-Richard] Charite, Med Klin 2, Berlin, Germany. [Cutlip, Donald] Beth Israel Deaconess Med Ctr, Intervent Cardiol Sect, Boston, MA 02215 USA. [Gabriel, H. Mesquita] Hosp Santa Maria, Div Cardiol, Lisbon, Portugal. [Emre, Ayse] Siyami Ersek Thorac & Cardiovasc Surg Ctr, Instabul, Turkey. [Gyongyosi, Mariann] Med Univ Vienna, Dept Cardiol, Vienna, Austria. [Huber, Kurt] Wilhelminen Hosp, 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 Carita Hosp, Div Cardiol, Novara, Italy. EM giuseppe.deluca@maggioreosp.novara.it NR 38 TC 59 Z9 61 U1 1 U2 3 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 NOV PY 2009 VL 207 IS 1 BP 181 EP 185 DI 10.1016/j.atherosclerosis.2009.03.042 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 528QE UT WOS:000272460700028 PM 19426981 ER PT J AU Cavusoglu, E Marmur, JD Chhabra, S Chopra, V Eng, C Jiang, XC AF Cavusoglu, Erdal Marmur, Jonathan D. Chhabra, Sandeep Chopra, Vineet Eng, Calvin Jiang, Xian-Cheng TI Relation of baseline plasma phospholipid transfer protein (PLTP) activity to left ventricular systolic dysfunction in patients referred for coronary angiography SO ATHEROSCLEROSIS LA English DT Article DE Phospholipid transfer protein; Inflammation; Left ventricular systolic dysfunction; Atherosclerosis ID CONGESTIVE-HEART-FAILURE; TYPE-2 DIABETES-MELLITUS; DENSITY-LIPOPROTEIN; PROGNOSTIC PREDICTOR; INSULIN-RESISTANCE; RISK-FACTOR; VITAMIN-E; DEFICIENCY; MICE; ATHEROSCLEROSIS AB Phospholipid transfer protein (PLTP) is an important modulator of phospholipid transfer and exchange among proteins. It also plays a role in inflammation and oxidative stress. Accordingly, PLTP has been implicated in the development of atherosclerosis. Left ventricular (LV) systolic dysfunction is common in patients with atherosclerosis, and both inflammation and oxidative stress have also been implicated in its development and progression. The goal of the present study was to examine the relation between plasma PLTP activity and LV systolic function. Baseline plasma PLTP activity was measured in 389 male patients referred for coronary angiography for a variety of indications. Detailed clinical, angiographic and laboratory characteristics were available for the patients. Compared to those patients with normal LV function ( defined as an ejection fraction of >= 55% on ventriculography), patients with any degree of LV dysfunction had elevated PLTP activity ( median PLTP 17.8 pmol/mu l/h versus 15.9 pmol/mu l/h, p = 0.0038). Using multivariate analysis, and adjusting for a variety of confounding variables known to affect both LV function and PLTP activity, PLTP activity was an independent predictor of the presence of any left ventricular systolic dysfunction in the entire population (OR 1.47, 95% CI 1.12-1.93, p = 0.0052). Furthermore, PLTP activity was an independent predictor of the presence of LV dysfunction in both patients with and without myocardial infarction on presentation ( OR 2.39, 95% CI 1.18-4.86, p = 0.0161 and OR 1.41, 95% CI 1.05-1.89, p = 0.0206, respectively). In conclusion, PLTP activity may represent a novel marker of LV systolic dysfunction in patients with known or suspected coronary artery disease. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Cavusoglu, Erdal; Marmur, Jonathan D.; Chhabra, Sandeep] Suny Downstate Med Ctr, Div Cardiol, Dept Med, Brooklyn, NY 11203 USA. [Cavusoglu, Erdal; Chopra, Vineet; Eng, Calvin] Bronx Vet Affairs Med Ctr, Div Cardiol, Dept Med, Bronx, NY USA. [Jiang, Xian-Cheng] Suny Downstate Med Ctr, Dept Anat & Cell Biol, Brooklyn, NY 11203 USA. RP Cavusoglu, E (reprint author), SUNY Hlth Sci Ctr, 450 Clarkson Ave,Box 1199, Brooklyn, NY 11203 USA. EM ECavusoglu@aol.com FU National Institutes of Health ( Bethesda, Maryland) [HL-69817] FX This study was supported in part by grant HL-69817 (XCJ) from the National Institutes of Health ( Bethesda, Maryland). NR 35 TC 11 Z9 15 U1 0 U2 0 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 NOV PY 2009 VL 207 IS 1 BP 261 EP 265 DI 10.1016/j.atherosclerosis.2009.04.011 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 528QE UT WOS:000272460700042 PM 19446293 ER PT J AU Waldman, ID Gizer, IR Singh, AL Harrington, KM Rowe, DC AF Waldman, I. D. Gizer, I. R. Singh, A. L. Harrington, K. M. Rowe, D. C. TI Between- and within-study heterogeneity in the association of attention deficit hyperactivity disorder with the 5HTTLPR SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 39th Annual Meeting of the Behavior-Genetics-Association CY JUN 17-20, 2009 CL Mineapolis, MN SP Behav Genet Assoc C1 [Waldman, I. D.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Gizer, I. R.] Univ N Carolina, Dept Human Genet, Chapel Hill, NC 27599 USA. [Singh, A. L.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. [Harrington, K. M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Rowe, D. C.] Univ Arizona, Late Program Genet & Cell Biol, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2009 VL 39 IS 6 BP 688 EP 688 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 522VL UT WOS:000272027300166 ER PT J AU Smith, RA Yuan, HS Weissleder, R Cantley, LC Josephson, L AF Smith, R. Adam Yuan, Hushan Weissleder, Ralph Cantley, Lewis C. Josephson, Lee TI A Wortmannin-Cetuximab as a Double Drug SO BIOCONJUGATE CHEMISTRY LA English DT Article ID GROWTH-FACTOR RECEPTOR; DEPENDENT CELLULAR CYTOTOXICITY; LUNG-CANCER; WILD-TYPE; CHEMOTHERAPY; COMBINATION; INHIBITION; THERAPY; PRODRUG; CELLS AB Double drugs are obtained when two pharmacologically active entities are covalently joined to improve potency. We conjugated the viridin Wm with a self-activating linkage to cetuximab and demonstrated the retention of immunoreactivity by the conjugate. Though cetuximab lacked a growth inhibitory activity against A549 cells, the Wm-cetuximab conjugate had an antiproliferative IC(50) of 155 nM in vitro. The chemistry of attaching a self-releasing Wm to clinically approved antibodies is general and, in selected instances, may yield antibody-based double drugs with improved efficacy. C1 [Smith, R. Adam; Yuan, Hushan; Weissleder, Ralph; Josephson, Lee] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Smith, R. Adam; Yuan, Hushan; Weissleder, Ralph; Josephson, Lee] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. [Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St, Charlestown, MA 02129 USA. EM ljosephson@mgh.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [P50 CA086355]; NIBIB NIH HHS [R01 EB004472]; NIGMS NIH HHS [R01 GM041890] NR 27 TC 2 Z9 2 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV PY 2009 VL 20 IS 11 BP 2185 EP 2189 DI 10.1021/bc900176a PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 520FP UT WOS:000271826600021 PM 19883074 ER PT J AU Koenigsberg, HW Fan, J Ochsner, KN Liu, X Guise, KG Pizzarello, S Dorantes, C Guerreri, S Tecuta, L Goodman, M New, A Siever, LJ AF Koenigsberg, Harold W. Fan, Jin Ochsner, Kevin N. Liu, Xun Guise, Kevin G. Pizzarello, Scott Dorantes, Christine Guerreri, Stephanie Tecuta, Lucia Goodman, Marianne New, Antonia Siever, Larry J. TI Neural Correlates of the Use of Psychological Distancing to Regulate Responses to Negative Social Cues: A Study of Patients with Borderline Personality Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Cognitive reappraisal; emotion; emotion regulation; fMRI; psychological distancing; social cognitive neuroscience ID EVENT-RELATED FMRI; ANTERIOR CINGULATE CORTEX; EMOTION REGULATION; PREFRONTAL CORTEX; VOLUNTARY SUPPRESSION; AFFECTIVE INSTABILITY; COGNITIVE CONTROL; PARIETAL CORTEX; FUNCTIONAL MRI; AMYGDALA AB Background: Emotional instability is a defining feature of borderline personality disorder (BPD); yet, little is understood about its underlying neural correlates. One possible contributing factor to emotional instability is a failure to adequately employ adaptive cognitive regulatory strategies such as psychological distancing. Methods: To determine whether there are differences in neural dynamics underlying this control strategy between BPD patients and healthy control (HC) subjects, blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging signals were acquired as 18 BPD and 16 HC subjects distanced from or simply looked at pictures depicting social interactions. Contrasts in signal between distance and look conditions were compared between groups. Results: Borderline personality disorder patients showed a different pattern of activation compared with HC subjects when looking at negative versus neutral pictures. When distancing versus looking at negative pictures, both groups showed decreased negative affect ratings and increased activation of the dorsolateral prefrontal cortex, areas near/along the intraparietal sulcus (IPS), ventrolateral prefrontal cortex, and posterior cingulate/precuneus regions. However, the BPD group showed less BOLD signal change in dorsal anterior cingulate cortex and IPS, less deactivation in the amygdala, and greater activation in the superior temporal sulcus and superior frontal gyrus. Conclusions: Borderline personality disorder and HC subjects display different neural dynamics while passively viewing social emotional stimuli. In addition, BPD patients do not engage the cognitive control regions to the extent that HCs do when employing a distancing strategy to regulate emotional reactions, which may be a factor contributing to the affective instability of BPD. C1 [Koenigsberg, Harold W.] Mt Sinai Sch Med, James J Peters VA Med Ctr, Mental Hlth Patient Care Ctr, Bronx, NY 10468 USA. [Koenigsberg, Harold W.; Fan, Jin; Liu, Xun; Guise, Kevin G.; Dorantes, Christine; Guerreri, Stephanie; Tecuta, Lucia; Goodman, Marianne; New, Antonia] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Ochsner, Kevin N.] Columbia Univ, Dept Psychol, New York, NY 10027 USA. [Pizzarello, Scott] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. RP Koenigsberg, HW (reprint author), Mt Sinai Sch Med, James J Peters VA Med Ctr, Mental Hlth Patient Care Ctr, 130 W Kingsbridge Rd,116A, Bronx, NY 10468 USA. EM HWarrenK@nyc.rr.com RI Fan, Jin/A-6716-2009; Frank, David/E-8213-2012; Liu, Xun/C-2400-2009; OI Fan, Jin/0000-0001-9630-8330; Liu, Xun/0000-0003-1366-8926; TECUTA, LUCIA/0000-0002-7984-3064 FU National Institute of Mental Health [RO1 MH077813]; HWK [MH076137]; National Center for Research Rasources, National institutes of Health for the Mount Sinai General Clinical Research Center [5MO1 RR00071] FX This work was supported in part by grants from, the National Institute of Mental Health (RO1 MH077813, Principal Investigator: HWK; MH076137. Principal Investigator: KNO) and from the National Center for Research Rasources, National institutes of Health for the Mount Sinai General Clinical Research Center (5MO1 RR00071). NR 76 TC 97 Z9 98 U1 4 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 2009 VL 66 IS 9 BP 854 EP 863 DI 10.1016/j.biopsych.2009.06.010 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 512BH UT WOS:000271216800007 PM 19651401 ER PT J AU Pidala, J Anasetti, C Kharfan-Dabaja, MA Cutler, C Sheldon, A Djulbegovic, B AF Pidala, Joseph Anasetti, Claudio Kharfan-Dabaja, Mohamed A. Cutler, Corey Sheldon, Andy Djulbegovic, Benjamin TI Decision Analysis of Peripheral Blood versus Bone Marrow Hematopoietic Stem Cells for Allogeneic Hematopoietic Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Peripheral blood mobilized stem cells; Bone marrow stem cells; Allogeneic hematopoietic cell transplantation; Decision analysis; Markov model ID COLONY-STIMULATING FACTOR; VERSUS-HOST-DISEASE; HLA-IDENTICAL SIBLINGS; HEMATOLOGICAL MALIGNANCIES; PROGENITOR CELLS; RANDOMIZED-TRIAL; APLASTIC-ANEMIA; CD3(+) CELLS; LOW-RISK; G-CSF AB Peripheral blood stem cells (PBSCs) and bone marrow (BM) hematopoietic stem cells represent therapeutic alternatives in allogeneic hematopoietic cell transplantation. Randomized controlled trials and an individual patient data meta-analysis (IPDMA) have demonstrated a decreased risk of disease relapse and an increased risk of acute and chronic graft-versus-host disease (aGVHD, cGVHD) in patients receiving PBSCs compared with those receiving BM stem cells. Decision modeling provides quantitative integration of the risks and benefits associated with these alternative treatments, incorporates survival discounts for lower quality of life in patients with aGVHD or cGVHD and post-transplantation relapse, and allows sensitivity analyses for all model assumptions. We have constructed an externally validated Markov model to represent and analyze the decision to use PBSC or BM, estimating post-transplantation state transition probabilities (eg, GVHD and relapse) and quality-of-life discounts from the IPDMA and relevant literature; importantly, this IPDMA synthesized data from primarily adult patients treated with myeloablative (MA) conditioning regimens with T cell-replete matched sibling donors. In this setting, the model demonstrates the superiority of PBSC over BM in both overall and quality-adjusted life expectancy, with a 7-month advantage for PBSC. Sensitivity analyses support this conclusion through a range of values for each variable supported by the IPDMA and quality-of-life discounts, as supported by the literature. However, BM is the optimal strategy in conditions in which the 1-year relapse probability is < 5%. PBSC is the optimal stem cell source in terms of both overall and quality-adjusted life expectancy, except in conditions with a very low relapse probability, in which BM provides optimal outcomes. Biol Blood Marrow Transplant 15: 1415-1421 (2009) (C) 2009 American Society for Blood and Marrow Transplantation C1 [Pidala, Joseph; Anasetti, Claudio; Kharfan-Dabaja, Mohamed A.; Djulbegovic, Benjamin] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Blood, Tampa, FL 33612 USA. [Pidala, Joseph; Anasetti, Claudio; Kharfan-Dabaja, Mohamed A.; Djulbegovic, Benjamin] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Marrow Transplantat, Tampa, FL 33612 USA. [Pidala, Joseph; Anasetti, Claudio; Kharfan-Dabaja, Mohamed A.; Djulbegovic, Benjamin] Univ S Florida, Dept Oncol Sci, Tampa, FL 33612 USA. [Cutler, Corey] Dana Farber Canc Inst, Dept Blood & Marrow Transplantat, Boston, MA 02115 USA. [Sheldon, Andy] TreeAge Software Inc, Williamstown, MA USA. RP Pidala, J (reprint author), MCC GME, H Lee Moffitt Canc Ctr, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM joseph.pidala@moffitt.org RI Djulbegovic, Benjamin/I-3661-2012 OI Djulbegovic, Benjamin/0000-0003-0671-1447 FU NCI NIH HHS [R01 CA133594] NR 41 TC 30 Z9 35 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2009 VL 15 IS 11 BP 1415 EP 1421 DI 10.1016/j.bbmt.2009.07.009 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 515UF UT WOS:000271497700009 PM 19822301 ER PT J AU Ulrickson, M Aldridge, J Kim, HT Hochberg, EP Hammerman, P Dube, C Attar, E Ballen, KK Dey, BR McAfee, SL Spitzer, TR Chen, YB AF Ulrickson, Matthew Aldridge, Julie Kim, Haesook T. Hochberg, Ephraim P. Hammerman, Peter Dube, Christine Attar, Eyal Ballen, Karen K. Dey, Bimalangshu R. McAfee, Steven L. Spitzer, Thomas R. Chen, Yi-Bin TI Busulfan and Cyclophosphamide (Bu/Cy) as a Preparative Regimen for Autologous Stem Cell Transplantation in Patients with Non-Hodgkin Lymphoma: A Single-Institution Experience SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Lymphoma; Autologous transplant; Busulfan ID BONE-MARROW-TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; CONDITIONING REGIMEN; MALIGNANT-LYMPHOMA; AGGRESSIVE LYMPHOMA; ETOPOSIDE; CARMUSTINE; RECOVERY; SURVIVAL; THIOTEPA AB High-dose chemotherapy with autologous stem cell transplantation (ASCT) has been established as a standard form of therapy for patients with non-Hodgkin lymphoma (NHL). While many high-dose chemotherapy combinations are used, no single regimen has proved superior over another. Here, we report our single center's experience in patients with NHL undergoing ASCT with the combination of busulfan and cyclophosphamide (Bu/Cy). This study is a retrospective analysis of 78 consecutive patients with NHL who underwent ASCT with Bu/Cy at Massachusetts General Hospital Cancer Center. Data were collected through review of electronic medical records. A total of 78 patients with NHL underwent ASCT with Bu/Cy preparative therapy between 1996 and 2006. Median follow-up for survivors was 5.0 years (range, 6 months to 12 years). Significant transplantation-associated complications included 9 documented bacterial infections, 4 cases of engraftment syndrome, 3 cases of hepatic veno-occlusive disease (VOID), 6 cases of cardiac complications, and 2 cases of pulmonary fibrosis. The 100-day treatment-related mortality (TRM) was 1%. At 3 years, progression-free survival (PFS) was 48% (95% confidence interval [CI] = 37% to 59%) and overall survival (OS) was 65% (95% CI = 53% to 74%). Our data indicate that in patients with NHL undergoing ASCT Bu/Cy has efficacy and toxicity comparable to that of other reported regimens. Biol Blood Marrow Transplant 15: 7447-1454 (2009) (C) 2009 American Society for Blood and Marrow Transplantation C1 [Chen, Yi-Bin] Massachusetts Gen Hosp, Dept Hematol Oncol, Div Bone Marrow Transplantat, Boston, MA 02114 USA. [Aldridge, Julie; Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Chen, YB (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Div Bone Marrow Transplantat, 55 Fruit St, Boston, MA 02114 USA. EM ychen6@partners.org FU Clinical Research of the Leukenna & Lymphoma Society FX Y.C. is a Special Fellow in Clinical Research of the Leukenna & Lymphoma Society. Author contributions: M.U. designed the research, collected data, performed research, analyzed data, and wrote the manuscript; J.A. analyzed data and reviewed the manuscript; H.T.K. analyzed data and reviewed the manuscript;, E.P.H. designed the research and reviewed the manuscript; P.H. collected data and reviewed the manuscript; C.D. maintained the clinical database and reviewed the manuscript;, E.A. provided clinical care and reviewed the manuscript; K.K.B. provided clinical care and reviewed the manuscript; B.R.D. provided clinical care and reviewed the manuscript;, S.L.M. provided clinical care and reviewed the manuscript; T.R.S. provided clinical care and reviewed the manuscript; Y.C. designed the research, performed research, collected data, analyzed data, and wrote the manuscript. NR 26 TC 16 Z9 16 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2009 VL 15 IS 11 BP 1447 EP 1454 DI 10.1016/j.bbmt.2009.07.014 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 515UF UT WOS:000271497700013 PM 19822305 ER PT J AU Fenske, TS Hari, PN Carreras, J Zhang, MJ Kamble, RT Bolwell, BJ Cairo, MS Champlin, RE Chen, YB Freytes, CO Gale, RP Hale, GA Ilhan, O Khoury, HJ Lister, J Maharaj, D Marks, DI Munker, R Pecora, AL Rowlings, PA Shea, TC Stiff, P Wiernik, PH Winter, JN Rizzo, JD van Besien, K Lazarus, HM Vose, JM AF Fenske, Timothy S. Hari, Parameswaran N. Carreras, Jeanette Zhang, Mei-Jie Kamble, Rammurti T. Bolwell, Brian J. Cairo, Mitchell S. Champlin, Richard E. Chen, Yi-Bin Freytes, Cesar O. Gale, Robert Peter Hale, Gregory A. Ilhan, Osman Khoury, H. Jean Lister, John Maharaj, Dipnarine Marks, David I. Munker, Reinhold Pecora, Andrew L. Rowlings, Philip A. Shea, Thomas C. Stiff, Patrick Wiernik, Peter H. Winter, Jane N. Rizzo, J. Douglas van Besien, Koen Lazarus, Hillard M. Vose, Julie M. TI Impact of Pre-transplant Rituximab on Survival after Autologous Hematopoietic Stem Cell Transplantation for Diffuse Large B Cell Lymphoma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Autologous hematopoietic stem cell transplantation; Lymphoma; Rituximab ID NON-HODGKINS-LYMPHOMA; R-CHOP; SALVAGE CHEMOTHERAPY; ELDERLY-PATIENTS; PLUS RITUXIMAB; THERAPY; DLBCL AB Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens to treat diffuse large B cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, however, many patients develop refractory or recurrent DLBCL and then undergo autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes after AuHCT Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n = 176; +R cohort) or was not (n = 818; -R cohort) administered with front-line or salvage therapy before AuHCT The +R cohort had superior progression-free survival (PFS; 50% vs 38%; P = .008) and overall survival (OS; 57% vs 45%; P = .006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Nonrelapse mortality (NRM) did not differ significantly between the 2 cohorts. In multivariate analysis, the +R cohort had improved PFS (relative risk of relapse/progression or death, 0.64; P < .001) and improved OS (relative risk of death, 0.74; P = .039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival after AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM. Biol Blood Marrow Transplant 15: 1455-1464 (2009) (C) 2009 American Society for Blood and Marrow Transplantation C1 [Fenske, Timothy S.] Med Coll Wisconsin, Div Neoplast Dis, Milwaukee, WI 53226 USA. [Hari, Parameswaran N.; Carreras, Jeanette; Zhang, Mei-Jie; Rizzo, J. Douglas] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Kamble, Rammurti T.] Baylor Coll Med, Houston, TX 77030 USA. [Bolwell, Brian J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Cairo, Mitchell S.] New York Presbyterian Hosp, New York, NY USA. [Champlin, Richard E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Chen, Yi-Bin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Gale, Robert Peter] Celgene Corp, Summit, NJ USA. [Hale, Gregory A.] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. [Ilhan, Osman] Ibni Sina Hosp, Ankara, Turkey. [Khoury, H. Jean] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Lister, John] Western Penn Hosp, Pittsburgh, PA 15224 USA. [Maharaj, Dipnarine] S Florida Bone Marrow Stem Cell Transplant Inst, Boynton Beach, FL USA. [Marks, David I.] United Bristol Healthcare, Bristol, Avon, England. [Munker, Reinhold] Louisiana State Univ, Med Ctr, Shreveport, LA USA. [Pecora, Andrew L.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Rowlings, Philip A.] Univ Newcastle, Calvary Mater Newcastle Hosp, Newcastle, NSW 2308, Australia. [Shea, Thomas C.] Univ N Carolina, Chapel Hill, NC USA. [Stiff, Patrick] Loyola Univ Hlth Syst, Maywood, IL USA. [Wiernik, Peter H.] Montefiore Med Ctr, North Div, Bronx, NY 10467 USA. [Wiernik, Peter H.] New York Med Coll, Bronx, NY USA. [Winter, Jane N.] NW Mem Hosp, Chicago, IL 60611 USA. [van Besien, Koen] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Vose, Julie M.] Univ Nebraska Med Ctr, Omaha, NE USA. RP Fenske, TS (reprint author), Med Coll Wisconsin, Div Neoplast Dis, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM tfenske@mcw.edu RI van Besien, Koen/G-4221-2012; OI van Besien, Koen/0000-0002-8164-6211; Hari, Parameswaran/0000-0002-8800-297X FU National Cancer Institute (NICT) [U24-CA76518]; National Heart, Lung and Blood Institute (NTHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U01HL069294]; NCI; Health Resources and Services Administration [HHSH234200637015C]; Office of Naval Research [N0001406-1-0704, N00014-08-1-0058]; AABB; Aetna; American Society for Blood and Marrow Transplantation; Amgen, Inc; Association of Medical Microbiology; Infectious Disease Canada; Astellas Pharma US, Inc; Baxter International, Inc; Bayer HealthCare Pharmaceuticals; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Canadian Blood and Marrow Transplant Group; Celgene Corp; CellGenix GmbH; Centers for Disease Control and Prevention; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals; Cylex, Inc; CytoTherm; DOR BloPharma, Inc; Dynal Biotech; Invitrogen Company; Enzon Pharmaceuticals, Inc; European Group for Blood and Marrow Transplantation; Gambro BCT, Inc; Gamida Cell, Ltd; Genzyme Corp; Histogenetics, Inc; HKS Medical Information Systems; Hospira, Inc; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewer, Co, Ltd; Merck Company; Medical College of Wisconsin; MGI Pharma, Inc; Michigan Community Blood Centers; Millennium Pharmaceuticals, Inc; Miller Pharmacal Group; Millinian USA, Inc; Miltenyi Biotec, Inc; National Marrow Donor Program; Nature Publishing Group; New York.Blood Center; Novartis Oncology; Oncology, Nursing Society; Osiris Therapeutics, Inc; Otsuka Pharmaceutical Development & Commercialization, Inc; Pall Life Sciences; PDL BioPharma, Inc; Pfizer Inc; Pharmion Corp; Saladax Biomedical, Inc; Schering Plough Corp; Society for Healthcare Epidemiology of America; StemCyte, Inc; StemSoft Soft-ware, Inc; Sysmex; Teva Pharmaceutical Industries; Marrow Foundation; THERAKOS, Inc; Vidacare Corp; Vion Pharmaceuticals, Inc; VitaCorLaboratories; ViroPharma, Inc; Wellpoint, Inc FX The CIBMR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NICT), the National Heart, Lung and Blood Institute (NTHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; Contract HHSH234200637015C from the Health Resources and Services Administration, Grants N0001406-1-0704 and N00014-08-1-0058 from the Office of Naval Research, and grant. from AABB; Aetna; American Society for Blood and Marrow Transplantation; Amgen, Inc, anonymous donation to the Medical College of Wisconsin; Association of Medical Microbiology, and Infectious Disease Canada; Astellas Pharma US, Inc; Baxter International, Inc; Bayer HealthCare Pharmaceuticals; BloodCenter of Wisconsin, Blue Cross and Blue Shield Association; Bone Marrow Foundation; Canadian Blood and Marrow Transplant Group; Celgene Corp; CellGenix GmbH; Centers for Disease Control and Prevention; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals; Cylex, Inc; CytoTherm; DOR BloPharma, Inc, Dynal Biotech, an Invitrogen Company; Enzon Pharmaceuticals, Inc; European Group for Blood and Marrow Transplantation;, Gambro BCT, Inc; Gamida Cell, Ltd; Genzyme Corp;, Histogenetics, Inc; HKS Medical Information Systems; Hospira, Inc; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewer, Co, Ltd; Merck & Company; Medical College of Wisconsin; MGI Pharma, Inc; Michigan Community Blood Centers; Millennium Pharmaceuticals, Inc; Miller Pharmacal Group; Millinian USA, Inc; Miltenyi Biotec, Inc; National Marrow Donor Program; Nature Publishing Group; New York.Blood Center; Novartis Oncology; Oncology, Nursing Society; Osiris Therapeutics, Inc; Otsuka Pharmaceutical Development & Commercialization, Inc; Pall Life Sciences; PDL BioPharma, Inc; Pfizer Inc;, Pharmion Corp; Saladax Biomedical, Inc; Schering Plough Corp; Society for Healthcare Epidemiology of America; StemCyte, Inc; StemSoft Soft-ware, Inc; Sysmex; Teva Pharmaceutical Industries; The Marrow Foundation; THERAKOS, Inc; Vidacare Corp; Vion Pharmaceuticals, Inc; VitaCorLaboratories; ViroPharma, Inc; and Wellpoint, Inc. NR 19 TC 31 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2009 VL 15 IS 11 BP 1455 EP 1464 DI 10.1016/j.bbmt.2009.07.017 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 515UF UT WOS:000271497700014 PM 19822306 ER PT J AU Weisdorf, DJ Nelson, G Lee, SJ Haagenson, M Spellman, S Antin, JH Bolwell, B Cahn, JY Cervantes, F Copelan, E Gale, R Gratwohl, A Khoury, HJ McCarthy, P Marks, DI Szer, J Woolfrey, A Cortes-Franco, J Horowitz, MM Arora, M AF Weisdorf, Daniel J. Nelson, Gene Lee, Stephanie J. Haagenson, Michael Spellman, Stephen Antin, Joseph H. Bolwell, Brian Cahn, Jean-Yves Cervantes, Francisco Copelan, Edward Gale, Robert Gratwohl, Alois Khoury, H. Jean McCarthy, Philip Marks, David I. Szer, Jeff Woolfrey, Ann Cortes-Franco, Jorge Horowitz, Mary M. Arora, Mukta CA Chronic Leukemia Working Comm TI Sibling versus Unrelated Donor Allogeneic Hematopoietic Cell Transplantation for Chronic Myelogenous Leukemia: Refined HLA Matching Reveals More Graft-versus-Host Disease but not Less Relapse SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Chronic myelogenous leukemia; HLA matching; Unrelated donor allotransplantation; Graft versus leukemia; Graft-versus-host disease ID BONE-MARROW-TRANSPLANTATION; CLASS-I; RECIPIENT; IMPACT AB Unrelated donor (URD) hematopoietic cell transplantation (HCT) can eradicate chronic myelogenous leukemia (CML). It has been postulated that greater donor-recipient histoincompatibility can augment the graft-versus-leukemia (GVL) effect. We previously reported similar, but not equivalent, outcomes of URD versus sibling donor HCT for CML using an older, less precise classification of HLA matching. Here, we used our recently refined HLA-matching classification, which is suitable for interpretation when complete allele-level typing is unavailable, to reanalyze outcomes of previous HCT for CML. We found that using our new matching criteria identifies substantially more frequent mismatching than older, less precise "6 of 6 antigen-matched" URD-HCT Under the new criteria, only 37% of those previously deemed "HLA-matched" were HLA well matched, and 44% were partially matched. Using our refined matching criteria confirms the greater risk of graft failure in partially matched or mismatched URD-recipient pairs compared with either sibling or well-matched URID-recipient pairs. Acute and chronic graft-versus-host disease (aGVHD, cGVHD) are significantly more frequent with all levels of recategorized URD HLA matching. Importantly, overall survival (CS) and leukemia-free survival (LFS) remain significantly worse after URD-HCT at any matching level. No augmented GVL effect accompanied URD HLA mismatch. Compared with sibling donor transplants, we observed only marginally increased (not statistically significant) risks of relapse in well-matched, partially matched, and mismatched URD-HCT These data confirm the applicability of revised HILA-matching scheme in analyzing retrospective data sets when fully informative, allele-level typing is unavailable. In this analysis, greater histoincompatibility can augment GVHD, but does not improve protection against relapse; thus the best donor remains the most closely matched donor. Biol Blood Marrow Transplant 15: 1475-1478 (2009) (C) 2009 American Society for Blood and Marrow Transplantation C1 [Weisdorf, Daniel J.; Arora, Mukta] Univ Minnesota, Minneapolis, MN 55455 USA. [Weisdorf, Daniel J.; Nelson, Gene; Lee, Stephanie J.; Haagenson, Michael; Spellman, Stephen; Horowitz, Mary M.; Arora, Mukta] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Lee, Stephanie J.; Woolfrey, Ann] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bolwell, Brian; Copelan, Edward] Cleveland Clin, Cleveland, OH 44106 USA. [Cahn, Jean-Yves] Besancon Univ Hosp, Besancon, France. [Cervantes, Francisco] Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain. [Gale, Robert] Ctr Adv Studies Leukemia, Los Angeles, CA USA. [Gratwohl, Alois] Univ Basel, Basel, Switzerland. [Khoury, H. Jean] Emory Clin, Winship Canc Inst, Atlanta, GA 30322 USA. [McCarthy, Philip] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Marks, David I.] United Bristol Healthcare Trust, Bristol, Avon, England. [Szer, Jeff] Royal Melbourne & Western Hosp, Parkville, Vic, Australia. [Cortes-Franco, Jorge] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Horowitz, Mary M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. RP Weisdorf, DJ (reprint author), Univ Minnesota, MMC 480,480 Delaware St SE, Minneapolis, MN 55455 USA. EM weisd001@umn.edu RI Cahn, Jean-Yves/M-6493-2014; OI Szer, Jeff/0000-0001-6783-2301 FU NCI NIH HHS [P01 CA111412, P01 CA111412-050001, U24 CA076518, U24-CA76518]; NHLBI NIH HHS [U01 HL069290, U01 HL069290-10, U01 HL069294]; PHS HHS [5U01H L069294, HHSH234200637015C] NR 8 TC 24 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2009 VL 15 IS 11 BP 1475 EP 1478 DI 10.1016/j.bbmt.2009.06.016 PG 4 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 515UF UT WOS:000271497700016 PM 19822308 ER PT J AU Medarova, Z AF Medarova, Z. TI NONINVASIVE IMAGING OF BREAST CANCER SO BIOTECHNOLOGY & BIOTECHNOLOGICAL EQUIPMENT LA English DT Review DE breast cancer; imaging; magnetic resonance imaging; cancer staging; muc-1 ID CARCINOMA IN-SITU; COMPARATIVE GENOMIC HYBRIDIZATION; LYMPH-NODE METASTASES; POSITRON-EMISSION-TOMOGRAPHY; MONOCLONAL-ANTIBODIES; TRANSFERRIN RECEPTOR; DUCTAL HYPERPLASIA; PROGNOSTIC-SIGNIFICANCE; TUMOR CHARACTERISTICS; PULMONARY METASTASES AB With the development of molecularly targeted cancer therapies, it is highly advantageous to be able to determine their efficacy, to improve overall patient survival, Non-invasive imaging techniques are currently available for visualizing different pathological conditions of the human body but their use for cancer monitoring is limited due to the lack of tumor-specific imaging probes. This review will attempt to summarize the current clinical diagnostic approaches for breast cancer detection, staging, and therapy assessment. In addition, I will present some novel concepts from the field of molecular imaging that form the basis of some of our research. We believe that this, general imaging strategy has the potential of significantly advancing our ability to diagnose breast cancer at the earliest stages of the pathology, before any overt clinical symptoms have developed as well as to better direct the development of molecularly-targeted individualized therapy protocols. C1 Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,MIT, Boston, MA 02115 USA. RP Medarova, Z (reprint author), Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,MIT, Boston, MA 02115 USA. EM zmedarova@partners.org NR 99 TC 2 Z9 2 U1 0 U2 2 PU DIAGNOSIS PRESS LTD PI SOFIA PA 67 DONDUKOV BLVD, 1504 SOFIA, BULGARIA SN 1310-2818 J9 BIOTECHNOL BIOTEC EQ JI Biotechnol. Biotechnol. Equip. PD NOV PY 2009 VL 23 IS 4 BP 1453 EP 1461 DI 10.2478/V10133-009-0001-Y PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 525GA UT WOS:000272201400011 ER PT J AU Roach, KL King, KR Uygun, BE Kohane, IS Yarmush, ML Toner, M AF Roach, Kenneth L. King, Kevin R. Uygun, Basak E. Kohane, Isaac S. Yarmush, Martin L. Toner, Mehmet TI High Throughput Single Cell Bioinformatics SO BIOTECHNOLOGY PROGRESS LA English DT Article DE cytometry; microfabrication; microwells; hepatocytes; mitochondria; membrane potential; free radicals ID GENE-EXPRESSION; NOISE; CYTOMETRY; PLATFORM; BIOLOGY; ARRAYS; CHIP AB Advances in systems biology and bioinformatics have highlighted that no cell population is truly, uniform and that stochastic behavior is an inherent property of many biological systems. As a result, bulk measurements can be misleading even when particular care has been taken to isolate a single cell type. and measurements averaged over multiple cell populations in a tissue can be as misleading as the average height at an elementary school. There is a growing need for experimental techniques that can provide a combination of single cell resolution, large cell populations, and the ability to track cells over multiple time points. In this article, a microwell array cytometry platform was developed to meet this need and investigate the heterogeneity and stochasticity of cell behavior on a single cell basis. The platform consisted of a microfabricated device with high-density, arrays of cell-sized microwells and custom software for automated image processing and data analysis. As a model experimental system, we used primary hepatocytes labeled with fluorescent probes sensitive to mitochondrial membrane potential and free radical generation. The cells were exposed to oxidative stress and the responses were dynamically monitored for each cell. The resulting data was then analyzed using bioinformatics techniques such as hierarchical and k-means clustering to visualize the data and identify interesting features. The results showed that clustering of the dynamic data not only enhanced comparisons between the treatment groups but also revealed a number of distinct response patterns within each treatment group. Heat-maps with hierarchical clustering also provided a data-rich complement to survival curves in a dose response experiment. The microwell array cytometry platform was shown to be powerful easy to use, and able to provide a detailed picture of the heterogeneity, present in cell responses to oxidative stress. We believe that our microwell array cytometry platform will have general utility for a wide range of questions related to cell population heterogeneity, biological stochasticity, and cell behavior under stress conditions. (C) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 25: 1772-1779, 2009 C1 [Roach, Kenneth L.; King, Kevin R.; Uygun, Basak E.; Yarmush, Martin L.; Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Shriners Hosp Children, Sch Med,BioMEMS Resource Ctr,Ctr Engn Med, Boston, MA 02115 USA. [Roach, Kenneth L.; King, Kevin R.; Kohane, Isaac S.; Yarmush, Martin L.; Toner, Mehmet] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Kohane, Isaac S.] Childrens Hosp, Informat Program, Boston, MA 02115 USA. RP Toner, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Shriners Hosp Children, Sch Med,BioMEMS Resource Ctr,Ctr Engn Med, Boston, MA 02115 USA. EM mtoner@hms.harvard.edu RI Kohane, Isaac Kohane/K-3716-2012; Uygun, Basak/I-1792-2012 OI Kohane, Isaac Kohane/0000-0003-2192-5160; Uygun, Basak/0000-0002-2600-7900 FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-14] NR 36 TC 22 Z9 23 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD NOV-DEC PY 2009 VL 25 IS 6 BP 1772 EP 1779 DI 10.1002/btpr.289 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 537ZA UT WOS:000273152000026 PM 19830811 ER PT J AU Mansour, HA Talkowski, ME Wood, J Chowdari, K McClain, L Prasad, K Montrose, D Fagiolini, A Friedman, ES Allen, MH Bowden, CL Calabrese, J El-Mallakh, RS Escamilla, M Faraone, SV Fossey, MD Gyulai, L Loftis, JM Hauser, P Ketter, TA Marangell, LB Miklowitz, DJ Nierenberg, AA Patel, J Sachs, GS Sklar, P Smoller, JW Laird, N Keshavan, M Thase, ME Axelson, D Birmaher, B Lewis, D Monk, T Frank, E Kupfer, DJ Devlin, B Nimgaonkar, VL AF Mansour, Hader A. Talkowski, Michael E. Wood, Joel Chowdari, KodavaliV McClain, Lora Prasad, Konasale Montrose, Debra Fagiolini, Andrea Friedman, Edward S. Allen, Michael H. Bowden, Charles L. Calabrese, Joseph El-Mallakh, Rif S. Escamilla, Michael Faraone, Stephen V. Fossey, Mark D. Gyulai, Laszlo Loftis, Jennifer M. Hauser, Peter Ketter, Terence A. Marangell, Lauren B. Miklowitz, David J. Nierenberg, Andrew A. Patel, Jayendra Sachs, Gary S. Sklar, Pamela Smoller, Jordan W. Laird, Nan Keshavan, Matcheri Thase, Michael E. Axelson, David Birmaher, Boris Lewis, David Monk, Tim Frank, Ellen Kupfer, David J. Devlin, Bernie Nimgaonkar, Vishwajit L. TI Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia SO BIPOLAR DISORDERS LA English DT Article DE association; bipolar disorder; circadian; gene; schizoaffective disorder; schizophrenia ID GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE-POLYMORPHISM; GLYCOGEN-SYNTHASE; MUTATIONAL ANALYSIS; SUGGESTIVE EVIDENCE; EUROPEAN-ANCESTRY; CANDIDATE GENES; CLOCK; LINKAGE; LITHIUM AB Objective: Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders. Methods: We assayed 276 publicly available 'tag' single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome-wide association studies (GWAS). Results: Using gene-based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL. Conclusions: Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results. C1 [Mansour, Hader A.; Talkowski, Michael E.; Wood, Joel; Chowdari, KodavaliV; McClain, Lora; Prasad, Konasale; Montrose, Debra; Friedman, Edward S.; Keshavan, Matcheri; Axelson, David; Birmaher, Boris; Lewis, David; Monk, Tim; Frank, Ellen; Kupfer, David J.; Devlin, Bernie; Nimgaonkar, Vishwajit L.] Univ Pittsburgh, Western Psychiat Inst & Clin, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Talkowski, Michael E.; Nimgaonkar, Vishwajit L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15213 USA. [Fagiolini, Andrea] Univ Siena, Sch Med, Dept Neurosci, I-53100 Siena, Italy. [Allen, Michael H.] Univ Colorado, Depress Ctr, Dept Psychiat, Denver, CO 80202 USA. [Bowden, Charles L.; Escamilla, Michael] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Calabrese, Joseph] Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, Dept Psychiat,Mood Disorders Program, Cleveland, OH 44106 USA. [El-Mallakh, Rif S.] Univ Louisville, Sch Med, Dept Psychiat & Behav Sci, Louisville, KY 40292 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat & Human Behav, Syracuse, NY USA. [Fossey, Mark D.; Hauser, Peter] Univ Oklahoma, Dept Psychiat, Tulsa, OK USA. [Gyulai, Laszlo] Univ Penn, Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. [Loftis, Jennifer M.; Hauser, Peter] Oregon Hlth & Sci Univ, Behav Hlth & Clin Neurosci Div, Portland VA Med Ctr, Portland, OR 97201 USA. [Loftis, Jennifer M.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Hauser, Peter] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Ketter, Terence A.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Bipolar Disorders Clin, Stanford, CA 94305 USA. [Marangell, Lauren B.] Eli Lilly & Co, US Med Div, Indianapolis, IN 46285 USA. [Miklowitz, David J.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. [Nierenberg, Andrew A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Clin Depress & Res Program, Boston, MA USA. [Patel, Jayendra] Univ Massachusetts, Sch Med, Schizophrenia Res Program, Bipolar Disorder Program, Worcester, MA USA. [Patel, Jayendra] Univ Massachusetts, Sch Med, Dept Psychiat, Ctr Psychopharmacol Res & Treatment, Worcester, MA 01655 USA. [Sachs, Gary S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Bipolar Clin & Res Program, Boston, MA USA. [Sklar, Pamela] Massachusetts Gen Hosp, Dept Psychiat, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat Genet Program Mood & Anxiety Disorders, Boston, MA 02114 USA. [Laird, Nan] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Thase, Michael E.] Univ Penn, Sch Med, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Nimgaonkar, VL (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Grad Sch Publ Hlth, Dept Psychiat & Human Genet,Sch Med, 3811 Ohara St,Room 441, Pittsburgh, PA 15213 USA. EM nimga+@pitt.edu RI Allen, Michael/A-8776-2011; Lewis, David/G-4053-2014; OI Lewis, David/0000-0002-3225-6778; FAGIOLINI, ANDREA/0000-0001-5827-0853; Prasad, Konasale/0000-0003-0245-1393; Faraone, Stephen/0000-0002-9217-3982 FU National Institutes of Health [MH63420, MH56242]; Mental Health Intervention Research Center [MH30915, MH45156]; NIMH [MH56242, R01 MH060952-06]; NIH/NCRR/GCRC [M01 RR00056]; Calabrese NIMH [P20 MH-66054]; [UL1 RR024153] FX We thank the research participants for their generous help. This research was supported in part by grants from the National Institutes of Health (MH63420, MH56242 to VLN, Mental Health Intervention Research Center, MH30915 to DJK and MH45156). Recruitment of some of the Pittsburgh controls was funded through NIMH grants (MH56242, R01 MH060952-06). This publication was also supported by funds received from the c UL1 RR024153 and NIH/NCRR/GCRC Grant M01 RR00056 and Calabrese NIMH P20 MH-66054. We thank Drs. Raymond Cho, Gordon Frankle, Gretchen Haas, and the clinical core staff of the Center for the Neuroscience of Mental Disorders (MH45156) for their assistance in diagnostic and psychopathological assessments of some of the controls analyzed here. NR 64 TC 82 Z9 83 U1 3 U2 10 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD NOV PY 2009 VL 11 IS 7 BP 701 EP 710 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 507BW UT WOS:000270826100003 PM 19839995 ER PT J AU Ostacher, MJ LeBeau, RT Perlis, RH Nierenberg, AA Lund, HG Moshier, SJ Sachs, GS Simon, NM AF Ostacher, Michael J. LeBeau, Richard T. Perlis, Roy H. Nierenberg, Andrew A. Lund, Hannah G. Moshier, Samantha J. Sachs, Gary S. Simon, Naomi M. TI Cigarette smoking is associated with suicidality in bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; impulsivity; nicotine; smoking; substance abuse; suicidality ID TREATMENT ENHANCEMENT PROGRAM; SUBSTANCE USE DISORDERS; CLINICAL PREDICTORS; MAJOR DEPRESSION; STEP-BD; IMPULSIVITY; AGGRESSION; BEHAVIOR; ACTS; COMORBIDITY AB Objectives: Cigarette smoking in individuals with bipolar disorder has been associated with suicidal behavior, although the precise relationship between the two remains unclear. Methods: In this prospective observational study of 116 individuals with bipolar disorder, we examined the association between smoking and suicidality as measured by Linehan's Suicide Behaviors Questionnaire (SBQ) and prospective suicide attempts over a nine-month period. Impulsivity was measured by the Barratt Impulsiveness Scale. Results: Smoking was associated with higher baseline SBQ scores in univariate and adjusted analyses, but was not significant after statistical adjustment for impulsivity in a regression model. A higher proportion of smokers at baseline made a suicide attempt during the follow-up period (5/31, 16.1%) compared to nonsmokers (3/85, 3.5%); p = 0.031, odds ratio = 5.25 (95% confidence interval: 1.2-23.5). Smoking at baseline also significantly predicted higher SBQ score at nine months. Conclusions: In this study, current cigarette smoking was a predictor of current and nine-month suicidal ideation and behavior in bipolar disorder, and it is likely that impulsivity accounts for some of this relationship. C1 [Ostacher, Michael J.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Ostacher, Michael J.; Perlis, Roy H.; Nierenberg, Andrew A.; Sachs, Gary S.; Simon, Naomi M.] Harvard Univ, Sch Med, Boston, MA USA. [Lund, Hannah G.] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. RP Ostacher, MJ (reprint author), Massachusetts Gen Hosp, Bipolar Clin & Res Program, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM mostacher@partners.org OI Ostacher, Michael/0000-0003-0353-7535 FU MGH Claflin Distinguished Scholar Award (NMS) [N01MH-8001]; National Institute of Mental Health (GSS); National Institute on Alcoholism and Alcohol Abuse (MJO) [K23AA016340-01A1] FX This study was supported by an MGH Claflin Distinguished Scholar Award (NMS), grant N01MH-8001 from the National Institute of Mental Health (GSS), and grant K23AA016340-01A1 from the National Institute on Alcoholism and Alcohol Abuse (MJO). NR 26 TC 34 Z9 34 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD NOV PY 2009 VL 11 IS 7 BP 766 EP 771 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 507BW UT WOS:000270826100010 PM 19840000 ER PT J AU Freytes, CO Lazarus, HM AF Freytes, C. O. Lazarus, H. M. TI Second hematopoietic SCT for lymphoma patients who relapse after autotransplantation: another autograft or switch to allograft? SO BONE MARROW TRANSPLANTATION LA English DT Review DE second transplants; lymphoma; relapse ID STEM-CELL TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; BONE-MARROW TRANSPLANTATION; MONOCLONAL-ANTIBODY THERAPY; PRIOR AUTOLOGOUS TRANSPLANT; HIGH-DOSE CHEMOTHERAPY; ALLOGENEIC TRANSPLANTATION; PROGRESSIVE DISEASE; FOLLICULAR LYMPHOMA; HEMATOLOGICAL MALIGNANCIES AB Although autologous hematopoietic SCT (auto-HSCT) is the only potentially curative treatment for lymphoma that has relapsed after conventional chemotherapy, the prognosis of patients with disease recurrence after auto-HSCT is poor. Some highly selected patients can benefit from second transplants. One-third with late recurrence after initial auto-HSCT may attain a prolonged remission after second auto-HSCT. Non-myeloablative or reduced-intensity conditioning (RIC) allogeneic hematopoietic SCT (allo-HSCT) has been used successfully after auto-HSCT failures, especially in subjects who have an HLA-compatible donor, chemosensitive disease and good performance status. Patients with chemosenstive disease recurrence who have completed at least 1 year after their first auto-HSCT should be considered for a second auto-HSCT. Patients who have chemoresistant disease are best served by participation in a well-designed clinical trial examining novel antitumor agents. Bone Marrow Transplantation (2009) 44, 559-569; doi:10.1038/bmt.2009.214; published online 24 August 2009 C1 [Freytes, C. O.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med Hematol & Med Oncol, BMTU 111, San Antonio, TX 78229 USA. [Freytes, C. O.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Lazarus, H. M.] Univ Hosp Case Med Ctr, Ireland Canc Ctr, Cleveland, OH USA. [Lazarus, H. M.] Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. RP Freytes, CO (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med Hematol & Med Oncol, BMTU 111, Mail Code 7880,7400 Merton Minter, San Antonio, TX 78229 USA. EM Freytes@uthscsa.edu NR 63 TC 6 Z9 8 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD NOV PY 2009 VL 44 IS 9 BP 559 EP 569 DI 10.1038/bmt.2009.214 PG 11 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 518AO UT WOS:000271661700001 PM 19701250 ER PT J AU Ballen, K AF Ballen, K. TI Introduction to Cord Blood Special Issue SO BONE MARROW TRANSPLANTATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Ballen, K (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. EM kballen@partners.org NR 0 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD NOV PY 2009 VL 44 IS 10 BP 619 EP 619 DI 10.1038/bmt.2009.279 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 524XL UT WOS:000272177600001 PM 19935808 ER PT J AU Cutler, C Ballen, K AF Cutler, C. Ballen, K. TI Reduced-intensity conditioning and umbilical cord blood transplantation in adults SO BONE MARROW TRANSPLANTATION LA English DT Review DE reduced-intensity conditioning; umbilical cord blood; adults ID BONE-MARROW; HEMATOLOGIC MALIGNANCIES; PREPARATIVE REGIMEN; UNRELATED DONORS; SUCCESSFUL ENGRAFTMENT; LUNG INJURY; RECIPIENTS; LEUKEMIA; FLUDARABINE; EXPERIENCE AB Reduced-intensity conditioning (RIC) preparative regimens are now widely used in umbilical cord blood (UCB) transplantation. Developed to reduce the rate of transplant-related morbidity and mortality as in adult stem cell donor transplantation, they are becoming more widely accepted. Results from RIC UCB series show a shortened time to engraftment, ranging from 12 to 24 days, with rates of TRM that generally do not exceed the rates seen with myeloablative UCB transplantation. There does not seem to be a convincing trend toward an increase in the rate of malignant relapse after RIC UCB transplantation, despite the lower intensity of the conditioning regimen. In this review, the results from several RIC UCB series are reviewed, comparisons with myeloablative UCB experiences are made and hypotheses regarding the engraftment potential of UCB after RIC regimens are discussed. In addition, a strategy for the optimal use of RIC regimens and UCB transplantation is presented. Bone Marrow Transplantation (2009) 44, 667-671; doi: 10.1038/bmt.2009.283; published online 5 October 2009 C1 [Cutler, C.] Harvard Univ, Dept Med Oncol, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ballen, K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Leukemia Program, Boston, MA 02115 USA. RP Cutler, C (reprint author), Harvard Univ, Dept Med Oncol, Sch Med, Dana Farber Canc Inst, 44 Binney St,D1B13, Boston, MA 02115 USA. EM corey_cutler@dfci.harvard.edu; kballen@partners.org NR 30 TC 13 Z9 14 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD NOV PY 2009 VL 44 IS 10 BP 667 EP 671 DI 10.1038/bmt.2009.283 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 524XL UT WOS:000272177600008 PM 19802028 ER PT J AU Thibert, RL Burns, JD Bhadelia, R Takeoka, M AF Thibert, Ronald L. Burns, Joseph D. Bhadelia, Rafeeque Takeoka, Masanori TI Reversible uncal herniation in a neonate with a large MCA infarct SO BRAIN & DEVELOPMENT LA English DT Article DE Neonate; Stroke; Uncal herniation ID INTRACRANIAL-PRESSURE; CEREBRAL INFARCTION; SPACE AB Uncal herniation due to a large cerebral infarct is well-described in adults, with high rates of morbidity and mortality. This phenomenon, however, has not been previously reported in neonates. We present a newborn male delivered via cesarean section with difficult extraction who presented with frequent seizures. He was found to have an acute left MCA territory infarct secondary to an M I occlusion detected on MRI/MRA. He became lethargic and developed a left uncal herniation on CT at 72 h of life. He was treated medically with osmolar agents and hemodynamic support, and had resolution of the herniation on CT at 120 h of life. At 19 months he had residual moderate right hemiparesis with only mild gait disturbance and mild speech delay. As seen in this case, uncal herniation, though rare, may occur in neonates. Also, the outcome for this neonate was much better than for typical adults with a similar disease course. (C) 2008 Elsevier B.V. All rights reserved. C1 [Takeoka, Masanori] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Thibert, Ronald L.] Massachusetts Gen Hosp, Pediat Epilepsy Program, Boston, MA 02114 USA. [Thibert, Ronald L.; Bhadelia, Rafeeque; Takeoka, Masanori] Harvard Univ, Sch Med, Boston, MA USA. [Burns, Joseph D.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Bhadelia, Rafeeque] Beth Israel Deaconess Med Ctr, Dept Neuroradiol, Boston, MA 02215 USA. [Thibert, Ronald L.; Burns, Joseph D.; Takeoka, Masanori] Floating Hosp Children, Div Pediat Neurol, Boston, MA USA. [Bhadelia, Rafeeque] Tufts Univ New England Med Ctr, Dept Neuroradiol, Boston, MA USA. RP Takeoka, M (reprint author), Childrens Hosp, Dept Neurol, Fegan 9,300 Longwood Ave, Boston, MA 02115 USA. EM Masanori.Takeoka@childrens.harvard.edu OI Burns, Joseph/0000-0003-4158-616X NR 10 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0387-7604 J9 BRAIN DEV-JPN JI Brain Dev. PD NOV PY 2009 VL 31 IS 10 BP 763 EP 765 DI 10.1016/j.braindev.2008.11.003 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 520CU UT WOS:000271818400009 PM 19097834 ER PT J AU Ghosh-Choudhury, T Mandal, CC Woodruff, K St Clair, P Fernandes, G Choudhury, GG Ghosh-Choudhury, N AF Ghosh-Choudhury, Triparna Mandal, Chandi C. Woodruff, Kathleen St Clair, Patricia Fernandes, Gabriel Choudhury, Goutam G. Ghosh-Choudhury, Nandini TI Fish oil targets PTEN to regulate NF kappa B for downregulation of anti-apoptotic genes in breast tumor growth SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Review DE PTEN; NF kappa B; DHA; EPA; Breast tumor growth; Apoptotic signal ID PROTEIN-KINASE B; PHOSPHATIDYLINOSITOL 3-KINASE/AKT PATHWAY; PROMOTES CELL-SURVIVAL; CANCER-CELLS; PHOSPHOINOSITIDE 3-KINASE; SIGNALING PATHWAY; PROSTATE-CANCER; BMP-2 GENE; OSTEOBLAST DIFFERENTIATION; TRANSCRIPTION FACTOR AB The molecular mechanism for the beneficial effect of fish oil on breast tumor growth is largely undefined. Using the xenograft model in nude mice, we for the first time report that the fish oil diet significantly increased the level of PTEN protein in the breast tumors. In addition, the fish oil diet attenuated the PI 3 kinase and Akt kinase activity in the tumors leading to significant inhibition of NF kappa B activation. Fish oil diet also prevented the expression of anti-apoptotic proteins Bcl-2 and Bcl-XL in the breast tumors with concomitant increase in caspase 3 activity. To extend these findings we tested the functional effects of DHA and EPA, the two active x-3 fatty acids of fish oil, on cultured MDA MB-231 cells. In agreement with our in vivo data, DHA and EPA treatment increased PTEN mRNA and protein expression and inhibited the phosphorylation of p65 subunit of NF kappa B in MDA MB-231 cells. Furthermore, DHA and EPA reduced expression of Bcl-2 and Bcl-XL. NF kappa B DNA binding activity and NF kappa B-dependent transcription of Bcl-2 and Bcl-XL genes were also prevented by DHA and EPA treatment. Finally, we showed that PTEN expression significantly inhibited NF kappa B-dependent transcription of Bcl-2 and Bcl-XL genes. Taken together, our data reveals a novel signaling pathway linking the fish oil diet to increased PTEN expression that attenuates the growth promoting signals and augments the apoptotic signals, resulting in breast tumor regression. C1 [Ghosh-Choudhury, Triparna; Mandal, Chandi C.; Woodruff, Kathleen; St Clair, Patricia; Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Choudhury, Goutam G.] Educ & Clin Ctr, San Antonio, TX USA. [Choudhury, Goutam G.; Ghosh-Choudhury, Nandini] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Ghosh-Choudhury, N (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. EM choudhury@uthscsa.edu FU NIH [RO1 AR52425, RO1 DK 50190, RO1 AG023648]; DOD Breast cancer Concept Award; Morrison Trust Fund; VA Merit Review grants; Juvenile Diabetes Research Foundation; Department of Veterans Affairs FX This work was supported by the NIH RO1 AR52425, DOD Breast cancer Concept Award, Morrison Trust Fund and VA Merit Review grants to NGC. GGC is supported by NIH RO1 DK 50190, VA Merit Review and Juvenile Diabetes Research Foundation Regular Research Grants. GGC is recipient of the Research Career Scientist Award from the Department of Veterans Affairs. GF is supported by NIH RO1 AG023648. NR 118 TC 45 Z9 46 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2009 VL 118 IS 1 BP 213 EP 228 DI 10.1007/s10549-008-0227-7 PG 16 WC Oncology SC Oncology GA 505YI UT WOS:000270737800023 PM 18953692 ER PT J AU Vogl, DT Stadtmauer, EA Richardson, PG Sonneveld, P Schuster, MW Irwin, D Facon, T Harousseau, JL Boral, A Neuwirth, R Anderson, KC AF Vogl, Dan T. Stadtmauer, Edward A. Richardson, Paul G. Sonneveld, Pieter Schuster, Michael W. Irwin, David Facon, Thierry Harousseau, Jean-Luc Boral, Anthony Neuwirth, Rachel Anderson, Kenneth C. TI Impact of prior therapies on the relative efficacy of bortezomib compared with dexamethasone in patients with relapsed/refractory multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE bortezomib; multiple myeloma; sequence; stem cell transplantation; thalidomide ID LENALIDOMIDE PLUS DEXAMETHASONE; CELL TRANSPLANTATION; RANDOMIZED-TRIAL; THALIDOMIDE; CHEMOTHERAPY; MELPHALAN AB This subgroup analysis of the phase III APEX (Assessment of Proteasome Inhibition for Extending Remissions) trial examined whether prior exposure to specific therapies affected the relative efficacy of bortezomib versus dexamethasone in relapsed/refractory myeloma. Time to progression and overall survival were superior with bortezomib in all subgroups, with no evidence of interaction between any prior therapies and assignment to study therapy. Patients with prior thalidomide exposure had worse outcomes overall, but neither prior thalidomide nor prior autologous stem cell transplantation affected the relative efficacy of bortezomib versus dexamethasone. These results confirm the superiority of bortezomib over dexamethasone, regardless of prior exposure to specific therapies (clinicaltrials. gov: NCT00048230). C1 [Vogl, Dan T.; Stadtmauer, Edward A.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sonneveld, Pieter] Univ Rotterdam Hosp, Rotterdam, Netherlands. [Schuster, Michael W.] New York Presbyterian Hosp, New York, NY USA. [Irwin, David] Alta Bates Canc Ctr, Berkeley, CA USA. [Facon, Thierry] Hop Claude Huriez, Lille, France. [Harousseau, Jean-Luc] Hop Hotel Dieu, Nantes, France. [Boral, Anthony; Neuwirth, Rachel] Millennium Pharmaceut Inc, Cambridge, MA USA. RP Vogl, DT (reprint author), Univ Penn, Abramson Canc Ctr, Perelman Ctr Room 2-189,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM Dan.Vogl@uphs.upenn.edu RI FACON, THIERRY/M-9736-2014; OI FACON, THIERRY/0000-0001-7705-8460; Vogl, Dan/0000-0002-2935-2566 NR 12 TC 20 Z9 21 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2009 VL 147 IS 4 BP 531 EP 534 DI 10.1111/j.1365-2141.2009.07875.x PG 4 WC Hematology SC Hematology GA 512IN UT WOS:000271240900012 PM 19725827 ER PT J AU Tammam, J Ware, C Efferson, C O'Neil, J Rao, S Qu, X Gorenstein, J Angagaw, M Kim, H Kenific, C Kunii, K Leach, KJ Nikov, G Zhao, J Dai, X Hardwick, J Scott, M Winter, C Bristow, L Elbi, C Reilly, JF Look, T Draetta, G Van der Ploeg, LHT Kohl, NE Strack, PR Majumder, PK AF Tammam, J. Ware, C. Efferson, C. O'Neil, J. Rao, S. Qu, X. Gorenstein, J. Angagaw, M. Kim, H. Kenific, C. Kunii, K. Leach, K. J. Nikov, G. Zhao, J. Dai, X. Hardwick, J. Scott, M. Winter, C. Bristow, L. Elbi, C. Reilly, J. F. Look, T. Draetta, G. Van der Ploeg, L. H. T. Kohl, N. E. Strack, P. R. Majumder, P. K. TI Down-regulation of the Notch pathway mediated by a gamma-secretase inhibitor induces anti-tumour effects in mouse models of T-cell leukaemia SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE gamma-secretase inhibitor; Notch; T-ALL; mitochondria; apoptosis ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; C-MYC; PROGNOSTIC-SIGNIFICANCE; TREATMENT RESPONSE; PROGENITOR CELLS; APOPTOSIS; MUTATIONS; ACTIVATION; EXPRESSION AB Background and purpose: gamma-Secretase inhibitors (GSIs) block NOTCH receptor cleavage and pathway activation and have been under clinical evaluation for the treatment of malignancies such as T-cell acute lymphoblastic leukaemia (T-ALL). The ability of GSIs to decrease T-ALL cell viability in vitro is a slow process requiring > 8 days, however, such treatment durations are not well tolerated in vivo. Here we study GSI's effect on tumour and normal cellular processes to optimize dosing regimens for anti-tumour efficacy. Experimental approach: Inhibition of the Notch pathway in mouse intestinal epithelium was used to evaluate the effect of GSIs and guide the design of dosing regimens for xenograft models. Serum A beta(40) and Notch target gene modulation in tumours were used to evaluate the degree and duration of target inhibition. Pharmacokinetic and pharmacodynamic correlations with biochemical, immunohistochemical and profiling data were used to demonstrate GSI mechanism of action in xenograft tumours. Key results: Three days of > 70% Notch pathway inhibition was sufficient to provide an anti-tumour effect and was well tolerated. GSI-induced conversion of mouse epithelial cells to a secretory lineage was time- and dose-dependent. Anti-tumour efficacy was associated with cell cycle arrest and apoptosis that was in part due to Notch-dependent regulation of mitochondrial homeostasis. Conclusions and implications: Intermittent but potent inhibition of Notch signalling is sufficient for anti-tumour efficacy in these T-ALL models. These findings provide support for the use of GSI in Notch-dependent malignancies and that clinical benefits may be derived from transient but potent inhibition of Notch. C1 [Tammam, J.; Efferson, C.; Kunii, K.; Scott, M.; Bristow, L.; Van der Ploeg, L. H. T.; Kohl, N. E.; Majumder, P. K.] Merck Res Labs, Dept Oncol Pharmacol, Boston, MA 02115 USA. [Ware, C.; Qu, X.; Reilly, J. F.] Merck Res Labs, Dept Pharmacol, Boston, MA 02115 USA. [Rao, S.; Gorenstein, J.; Kim, H.; Winter, C.; Elbi, C.; Draetta, G.; Van der Ploeg, L. H. T.; Majumder, P. K.] Merck Res Labs, Dept Canc Pathways Canc Biol & Therapeut, Boston, MA 02115 USA. [Angagaw, M.] Merck Res Labs, Dept Lab Anim Res, Boston, MA 02115 USA. [O'Neil, J.; Look, T.; Van der Ploeg, L. H. T.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kenific, C.; Van der Ploeg, L. H. T.] Merck Res Labs, Dept Neuropharmacol, Boston, MA 02115 USA. [Leach, K. J.; Nikov, G.; Zhao, J.] Merck Res Labs, Dept Drug Metab & Pharmacokinet, Boston, MA 02115 USA. [Dai, X.; Hardwick, J.] Merck Res Labs, West Point, PA USA. RP Majumder, PK (reprint author), Merck Res Labs, Dept Oncol Pharmacol, 33 Ave Louis Pasteur, Boston, MA 02115 USA. EM Pradip_Majumder@merck.com NR 53 TC 48 Z9 51 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD NOV PY 2009 VL 158 IS 5 BP 1183 EP 1195 DI 10.1111/j.1476-5381.2009.00389.x PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 509FW UT WOS:000271001400002 PM 19775282 ER PT J AU Pearson, KH AF Pearson, Kimberly H. TI Cognitive behavior therapy and eating disorders SO BRITISH JOURNAL OF PSYCHOLOGY LA English DT Book Review C1 [Pearson, Kimberly H.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Pearson, Kimberly H.] Massachusetts Gen Hosp, Eating Disorder Program, Boston, MA 02114 USA. RP Pearson, KH (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BRITISH PSYCHOLOGICAL SOC PI LEICESTER PA ST ANDREWS HOUSE, 48 PRINCESS RD EAST, LEICESTER LE1 7DR, LEICS, ENGLAND SN 0007-1269 J9 BRIT J PSYCHOL JI Br. J. Psychol. PD NOV PY 2009 VL 100 BP 804 EP 806 DI 10.1348/000712609X464380 PG 4 WC Psychology, Multidisciplinary SC Psychology GA 509PY UT WOS:000271031700013 ER PT J AU Horst, D Budczies, J Brabletz, T Kirchner, T Hlubek, F AF Horst, David Budczies, Jan Brabletz, Thomas Kirchner, Thomas Hlubek, Falk TI Invasion Associated Up-Regulation of Nuclear Factor kappa B Target Genes in Colorectal Cancer SO CANCER LA English DT Article DE nuclear factor kappa B; target genes; colorectal cancer; invasion; inflammation; up-regulation ID MESSENGER-RNA EXPRESSION; BETA-CATENIN EXPRESSION; TRANSCRIPTION FACTOR; INFLAMMATORY DISEASES; COLON-CARCINOMA; TENASCIN-C; MICROENVIRONMENT; TRANSFORMATION; ACTIVATION; TUMORS AB BACKGROUND: Colorectal cancer (CRC) displays intratumoral heterogeneity with less differentiated tumor cells at the invasive front (IF) than in the tumor center (TC). The authors previously observed that several genes were overexpressed at the IF of CRC with relations to inflammatory processes. Because nuclear factor kappa B (NF-kappa B), a dimeric transcription factor, is a major regulator of such processes, and because its target genes are involved in immune response, cell growth control, and cell survival, the expression of NF-kappa B target genes was investigated comparatively in CRC. METHODS: By using gene array profiling, NF-kappa B target gene expression was assessed in CRCs that expressed human mutL homolog 1 (hMLH1), hMSH2, and nuclear beta-catenin by comparing expression at the IF, in the TC, and in normal mucosa. In addition, 5 NF-kappa B target genes with high differential expression were validated by using immunohistochemistry. RESULTS: The expression of NF-kappa B target genes in the TC, at the IF, and in normal mucosa was distinct; whereas, specifically at the IF, most differentially expressed NF-kappa B targets were up-regulated. Moreover, the results indicated that the expression diverged between epithelial tumor cells and inflammatory stromal cells. CONCLUSIONS: Because the results demonstrated that inflammation and the activation of NF-kappa B signaling promoted CRC invasiveness, the current study provided further evidence that downstream targets of NF-kappa B signaling may be specifically relevant in invasion and progression of CRC. Finally, as has been suggested for colitis-associated cancer, the authors of this report concluded that the inhibition of NF-kappa B signaling also may be an additional option for the treatment of sporadic CRC. Cancer 2009;115:4946-58. (C) 2009 American Cancer Society. C1 [Horst, David; Kirchner, Thomas; Hlubek, Falk] Univ Munich, Inst Pathol, D-8000 Munich, Germany. [Budczies, Jan] Charite, Inst Pathol, D-13353 Berlin, Germany. [Brabletz, Thomas] Univ Freiburg, Comprehens Canc Ctr & Visceral Surg, Freiburg, Germany. RP Horst, D (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM DavidN_Horst@dfci.harvard.edu NR 46 TC 29 Z9 32 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2009 VL 115 IS 21 BP 4946 EP 4958 DI 10.1002/cncr.24564 PG 13 WC Oncology SC Oncology GA 511LY UT WOS:000271167900011 PM 19658179 ER PT J AU Carpenter, WR Godley, PA Clark, JA Talcott, JA Finnegan, T Mishel, M Bensen, J Rayford, W Su, LJ Fontham, ETH Mohler, JL AF Carpenter, William R. Godley, Paul A. Clark, Jack A. Talcott, James A. Finnegan, Timothy Mishel, Merle Bensen, Jeannette Rayford, Walter Su, L. Joseph Fontham, Elizabeth T. H. Mohler, James L. TI Racial Differences in Trust and Regular Source of Patient Care and the Implications for Prostate Cancer Screening Use SO CANCER LA English DT Article DE African American; Caucasian American; continuity of care; prostate cancer; screening; source of care; physician mistrust ID CLINICAL PREVENTIVE SERVICES; EMERGENCY-DEPARTMENT; ETHNIC DISPARITIES; AFRICAN-AMERICAN; UNITED-STATES; HEALTH; PHYSICIAN; MEDICINE; SATISFACTION; EXPERIENCE AB BACKGROUND: Nonmedical factors may modify the biological risk of prostate cancer (PCa) and contribute to the differential use of early detection; curative care; and, ultimately, greater racial disparities in PCa mortality. In this study, the authors examined patients' usual source of care, continuity of care, and mistrust of physicians and their association with racial differences in PCa screening. METHODS: Study nurses conducted in-home interviews of 1031 African-American men and Caucasian-American men aged >= 50 years in North Carolina and Louisiana within weeks of their PCa diagnosis. Medical records were abstracted, and the data were used to conduct bivariate and multivariate analyses. RESULTS: Compared with African Americans, Caucasian Americans exhibited higher physician trust scores and a greater likelihood of reporting a physician office as their usual source of care, seeing the same physician at regular medical encounters, and historically using any PCa screening. Seeing the same physician for regular care was associated with greater trust and screening use. Men who reported their usual source of care as a physician office, hospital clinic, or Veterans Administration facility were more likely to report prior PCa screening than other men. In multivariate regression analysis, seeing the same provider remained associated with prior screening use, whereas both race and trust lost their association with prior screening. CONCLUSIONS: The current results indicated that systems factors, including those that differ among different sources of care and those associated with the continuity of care, may provide tangible targets to address disparities in the use of PCa early detection, may attenuate racial differences in PCa screening use, and may contribute to reduced racial disparities in PCa mortality. Cancer 2009;115:5048-59. Published 2009 by the American Cancer Society*. C1 [Carpenter, William R.] Univ N Carolina, Dept Hlth Policy & Management, Sch Publ Hlth, Chapel Hill, NC 27599 USA. [Carpenter, William R.; Godley, Paul A.; Bensen, Jeannette; Mohler, James L.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Carpenter, William R.; Godley, Paul A.] Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC 27599 USA. [Carpenter, William R.] N Carolina Comprehens Canc Program, Raleigh, NC USA. [Godley, Paul A.; Finnegan, Timothy] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27599 USA. [Godley, Paul A.; Bensen, Jeannette] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Clark, Jack A.] Boston Univ, Sch Publ Hlth, Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, Boston, MA USA. [Talcott, James A.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Res,Med Sch, Boston, MA 02114 USA. [Mishel, Merle] Univ N Carolina, Sch Nursing, Chapel Hill, NC 27599 USA. [Rayford, Walter] Univ Tennessee, Dept Prevent Med, Sch Med, Memphis, TN USA. [Su, L. Joseph; Fontham, Elizabeth T. H.] Louisiana State Univ, Sch Publ Hlth, Hlth Sci Ctr, New Orleans, LA USA. [Mohler, James L.] Roswell Pk Canc Inst, Dept Urol Oncol, Buffalo, NY 14263 USA. [Mohler, James L.] SUNY Buffalo, Dept Urol, Buffalo, NY 14260 USA. RP Carpenter, WR (reprint author), Univ N Carolina, Dept Hlth Policy & Management, Sch Publ Hlth, 1102 McGavran Greenberg Hall,CB 7411, Chapel Hill, NC 27599 USA. EM wrc4@email.unc.edu RI Carpenter, William/E-5125-2013; OI Clark, Jack/0000-0002-7424-1670 FU Department of Defense [DAMD 17-03-2-0052]; National Cancer Institute [R25T CA 57726] FX The North Carolina-Louisiana Prostate Cancer Project is performed as a collaborative study supported by the Department of Defense contract DAMD 17-03-2-0052. Dr. Carpenter was supported by a training grant from the National Cancer Institute (R25T CA 57726). NR 52 TC 47 Z9 48 U1 2 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2009 VL 115 IS 21 BP 5048 EP 5059 DI 10.1002/cncr.24539 PG 12 WC Oncology SC Oncology GA 511LY UT WOS:000271167900021 PM 19637357 ER PT J AU Chen, LL Nolan, ME Silverstein, MJ Mihm, MC Sober, AJ Tanabe, KK Smith, BL Younger, J Michaelson, JS AF Chen, L. Leon Nolan, Matthew E. Silverstein, Melvin J. Mihm, Martin C., Jr. Sober, Arthur J. Tanabe, Kenneth K. Smith, Barbara L. Younger, Jerry Michaelson, James S. TI The Impact of Primary Tumor Size, Lymph Node Status, and Other Prognostic Factors on the Risk of Cancer Death SO CANCER LA English DT Article DE cancer death; risk; prediction; tumor size; lymph node status; prognostic factors; breast cancer; melanoma ID BREAST-CANCER; SURVIVAL AB BACKGROUND: Although many prognostic factors are associated with differences in cancer lethality, it may not be obvious whether a factor truly makes an independent contribution to lethality or simply is correlated with tumor size. There is currently no method for integrating tumor size, lymph node status, and other prognostic information from a patient into a single risk of death estimate. METHODS: The SizeOnly equation, which captures the relation between tumor size and risk of death, makes it possible to determine whether a prognostic factor truly makes an independent contribution to cancer lethally or merely is associated with tumor size (SizeAssessment method). The magnitude of each factor's lethal contribution can be quantified by a parameter, g, inserted into the SizeOnly equation (PrognosticMeasurement method). A series of linked equations (the Size+Nodes+PrognosticFactors [SNAP] method) combines information on tumor size, lymph node status, and other prognostic factors from a patient into a single estimate of the risk of death, RESULTS: Nine prognostic factors were identified that made marked, independent contributions to breast carcinoma lethality: grade; mucinous, medullary, tubular, and scirrhous adenocarcinoma; male sex; inflammatory disease; Paget disease; and lymph node status. In addition, it was determined that lymph node status made an independent contribution to melanoma lethality. The SNAP method was able to accurately estimate the risk of death and to finely stratify patients by risk. CONCLUSIONS: The methods described provide a new framework for identifying and quantifying those factors that contribute to cancer lethality and provide a basis for web-based calculators (available at: http://www.CancerMath.net accessed July 29, 2009) that accurately estimate the risk of death for each patient. Cancer 2009;115:5071-83. (C) 2009 American Cancer Society. C1 [Michaelson, James S.] Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Boston, MA 02114 USA. [Silverstein, Melvin J.] Hoag Mem Hosp, Breast Serv, Newport Beach, CA USA. [Mihm, Martin C., Jr.; Michaelson, James S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mihm, Martin C., Jr.; Michaelson, James S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Sober, Arthur J.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Sober, Arthur J.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Tanabe, Kenneth K.; Smith, Barbara L.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Younger, Jerry] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Younger, Jerry] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Michaelson, JS (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Yawkey Bldg 7,32 Fruit St, Boston, MA 02114 USA. EM michaelj@helix.mgh.harvard.edu FU Massachusetts General Hospital FX Supported by institutional funding to the Massachusetts General Hospital. NR 16 TC 12 Z9 12 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2009 VL 115 IS 21 BP 5071 EP 5083 DI 10.1002/cncr.24565 PG 13 WC Oncology SC Oncology GA 511LY UT WOS:000271167900023 PM 19658184 ER PT J AU Michaelson, JS Chen, LL Silverstein, MJ Cheongsiatmoy, JA Mihm, MC Sober, AJ Tanabe, KK Smith, BL Younger, J AF Michaelson, James S. Chen, L. Leon Silverstein, Melvin J. Cheongsiatmoy, Justin A. Mihm, Martin C., Jr. Sober, Arthur J. Tanabe, Kenneth K. Smith, Barbara L. Younger, Jerry TI Why Cancer at the Primary Site and in the Lymph Nodes Contributes to the Risk of Cancer Death SO CANCER LA English DT Article DE cancer death; risk; prediction; tumor size; lymph node status; breast cancer; melanoma; metastasis ID TUMOR SIZE; BREAST-CANCER; METASTASIS; CARCINOMA; GENES; PROGRESSION AB BACKGROUND: Cancer at both the primary site and in the lymph nodes is associated with lethality, although the mechanism by which lethality arises from each site has been poorly understood. For breast carcinoma, each positive lymph node contributes an approximately 6% risk of death, and each millimeter of primary tumor greatest dimension contributes approximately 1%; whereas, for melanoma, each positive lymph node contributes an approximately 23% risk, and each millimeter of tumor thickness contributes approximately 8%: This is described by a pair of linked equations, the Size+Nodes method. METHODS: A simple expression, the ProbabilityEstimation equation, which was derived from the authors' binary-biologic model of cancer metastasis, was used to calculate the probabilities of spread of cancer cells from data on tumor size, lymph node status, and death rate. RESULTS: In this report, the authors demonstrated, that when similar masses of cancer are compared, the chance of lethal spread of a cancer cell to the periphery is approximately the same whether the spread emerges from a lymph node or from the primary site. The greater the number of cells at the primary site (tumor size) or the greater the number of cells in the lymph nodes (number of positive lymph nodes), the greater is the aggregate chance that 1 or more cells has undergone a lethal event of spread, a process captured by the Size+Nodes equations. CONCLUSIONS: The lethal contributions of cancer at the primary site and lymph nodes can be explained by a simple mechanical process of the spread of cancer cells occurring with definable probabilities per cell. The presence of cancer in the lymph nodes does not indicate an intrinsic change in a malignancy but, rather, an increased mass of cancer from which spread can emerge. Cancer 2009;115:5084-94. (C) 2009 American Cancer Society. C1 [Michaelson, James S.] Massachusetts Gen Hosp, Div Surg Oncol, Dept Pathol, Boston, MA 02114 USA. [Michaelson, James S.; Chen, L. Leon; Cheongsiatmoy, Justin A.; Tanabe, Kenneth K.; Smith, Barbara L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Michaelson, James S.; Mihm, Martin C., Jr.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Silverstein, Melvin J.] Hoag Mem Hosp, Breast Serv, Newport Beach, CA USA. [Sober, Arthur J.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Sober, Arthur J.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Tanabe, Kenneth K.; Smith, Barbara L.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Younger, Jerry] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Younger, Jerry] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Michaelson, JS (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Dept Pathol, Yawkey Bldg 7,32 Fruit St, Boston, MA 02114 USA. EM michaelj@helix.mgh.harvard.edu FU Massachusetts General Hospital FX Supported by institutional funding of the Massachusetts General Hospital. NR 20 TC 11 Z9 11 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2009 VL 115 IS 21 BP 5084 EP 5094 DI 10.1002/cncr.24542 PG 11 WC Oncology SC Oncology GA 511LY UT WOS:000271167900024 PM 19670457 ER PT J AU Michaelson, JS Chen, LL Silverstein, MJ Mihm, MC Sober, AJ Tanabe, KK Smith, BL Younger, J AF Michaelson, James S. Chen, L. Leon Silverstein, Melvin J. Mihm, Martin C., Jr. Sober, Arthur J. Tanabe, Kenneth K. Smith, Barbara L. Younger, Jerry TI How Cancer at the Primary Site and in the Lymph Nodes Contributes to the Risk of Cancer Death SO CANCER LA English DT Article DE cancer death; risk; prediction; tumor size; lymph node status; breast cancer; melanoma ID RENAL-CELL CARCINOMA; BREAST-CANCER; TUMOR SIZE; SURVIVAL; MORPHOMETRY; VALIDATION; RECURRENCE; MELANOMA; IMPACT AB BACKGROUND: It has long been appreciated that tumor size, lymph node status, and patient survival are related qualities, although how to isolate their interactions has not been obvious, nor has it been obvious how to integrate tumor size and lymph node status into predictions of the risk of death for individual patients. METHODS: The authors describe a mathematical method, the binary-biological model of cancer metastasis, based on the spread of cancer cells, in which the equations capture the relations between tumor size, lymph node status, and cancer lethality. RESULTS: For melanoma, renal cell carcinoma, and breast carcinoma, the relation between tumor size and the risk of cancer death was captured by the SizeOnly equation. For melanoma and breast carcinoma, the relation between tumor size and the presence of cancer in the lymph nodes was captured by using the NodalSizeOnly equation. For lymph node-negative melanoma and breast carcinoma, the relation between tumor size and risk of death was captured by the PrimarySizeOnly equation. For breast carcinoma, the model indicated that each positive lymph node contributed similar to 6% extra risk of death, whereas each millimeter of greatest primary tumor dimension contributed similar to 1% risk of death. For melanoma, each positive lymph node contributed similar to 23% risk of death, whereas each millimeter of primary melanoma thickness contributed similar to 8% risk of death. This information was captured by a pair of linked equations, the Size+Nodes method. CONCLUSIONS: Both tumor size and the number of positive lymph nodes made independent contributions to the risk of cancer death, as estimated by using the Size+Nodes method. Cancer 2009;115:5095-107. (C) 2009 American Cancer Society. C1 [Michaelson, James S.] Massachusetts Gen Hosp, Div Surg Oncol, Dept Pathol, Boston, MA 02114 USA. [Michaelson, James S.; Chen, L. Leon; Tanabe, Kenneth K.; Smith, Barbara L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Michaelson, James S.; Mihm, Martin C., Jr.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Silverstein, Melvin J.] Hoag Mem Hosp, Breast Serv, Newport Beach, CA USA. [Sober, Arthur J.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Sober, Arthur J.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Tanabe, Kenneth K.; Smith, Barbara L.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Younger, Jerry] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Younger, Jerry] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Michaelson, JS (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Dept Pathol, Yawkey Bldg 7,32 Fruit St, Boston, MA 02114 USA. EM michaelj@helix.mgh.harvard.edu FU Massachusetts General Hospital FX Supported by institutional funding of the Massachusetts General Hospital. NR 20 TC 6 Z9 7 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2009 VL 115 IS 21 BP 5095 EP 5107 DI 10.1002/cncr.24592 PG 13 WC Oncology SC Oncology GA 511LY UT WOS:000271167900025 PM 19670458 ER PT J AU Ramos, AH Dutt, A Mermel, C Perner, S Cho, J Lafargue, CJ Johnson, LA Stiedl, AC Tanaka, KE Bass, AJ Barretina, J Weir, BA Beroukhim, R Thomas, RK Minna, JD Chirieac, LR Lindeman, NI Giordano, T Beer, DG Wagner, P Wistuba, II Rubin, MA Meyerson, M AF Ramos, Alex H. Dutt, Amit Mermel, Craig Perner, Sven Cho, Jeonghee Lafargue, Christopher J. Johnson, Laura A. Stiedl, Ann-Cathrin Tanaka, Kumiko E. Bass, Adam J. Barretina, Jordi Weir, Barbara A. Beroukhim, Rameen Thomas, Roman K. Minna, John D. Chirieac, Lucian R. Lindeman, Neal I. Giordano, Thomas Beer, David G. Wagner, Patrick Wistuba, Ignacio I. Rubin, Mark A. Meyerson, Matthew TI Amplification of chromosomal segment 4q12 in non-small cell lung cancer SO CANCER BIOLOGY & THERAPY LA English DT Article DE NSCLC; lung cancer; PDGFRA; KIT; sunitinib; imatinib; amplification; 4q12 ID GROWTH-FACTOR RECEPTOR; GASTROINTESTINAL STROMAL TUMORS; GLIOBLASTOMA-MULTIFORME; KINASE INHIBITORS; SOMATIC MUTATIONS; PDGFR-ALPHA; GENE; KIT; ADENOCARCINOMA; SUNITINIB AB In cancer, proto-oncogenes are often altered by genomic amplification. Here we report recurrent focal amplifications of chromosomal segment 4q12 overlapping the proto-oncogenes PDGFRA and KIT in non-small cell lung cancer (NSCSCLC). Single nucleotide polymorphism (SNP) array and fluorescent in situ hybridization (FISH) analysis indicate that 4q12 is amplified in 3-7% of lung adenocarcinomas and 8-10% of lung squamous cell carcinomas. In addition, we demonstrate that the NSCLC cell line NCI-H1703 exhibits focal amplification of PDGFRA and is dependent on PDGFR alpha activity for cell growth. Treatment of NCI-H1703 cells with PDGFRA-specific shRNAs or with the PDGFR alpha/KIT small molecule inhibitors imatinib or sunitinib leads to cell growth inhibition. However, these observations do not extend to NSCLC cell lines with lower-amplitude and broader gains of chromosome 4q. Together these observations implicate PDGFRA and KIT as potential oncogenes in NSCLC, but further study is needed to define the specific characteristics of those tumors that could respond to PDGFR alpha/KIT inhibitors. C1 [Ramos, Alex H.; Dutt, Amit; Mermel, Craig; Cho, Jeonghee; Johnson, Laura A.; Tanaka, Kumiko E.; Bass, Adam J.; Barretina, Jordi; Weir, Barbara A.; Beroukhim, Rameen; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ramos, Alex H.; Dutt, Amit; Mermel, Craig; Cho, Jeonghee; Johnson, Laura A.; Tanaka, Kumiko E.; Bass, Adam J.; Barretina, Jordi; Weir, Barbara A.; Beroukhim, Rameen; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Ramos, Alex H.; Dutt, Amit; Mermel, Craig; Johnson, Laura A.; Tanaka, Kumiko E.; Bass, Adam J.; Barretina, Jordi; Weir, Barbara A.; Beroukhim, Rameen; Meyerson, Matthew] Harvard & MIT, Broad Inst, Canc Program, Cambridge, MA USA. [Ramos, Alex H.; Mermel, Craig; Chirieac, Lucian R.; Lindeman, Neal I.; Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Perner, Sven; Stiedl, Ann-Cathrin] Univ Hosp Tubingen, Dept Pathol, Tubingen, Germany. [Lafargue, Christopher J.; Wagner, Patrick; Rubin, Mark A.] Cornell Univ, Dept Pathol, Weill Med Coll, New York, NY 10021 USA. [Thomas, Roman K.] Univ Cologne, Max Planck Inst Neurol Res, Klaus Joachim Zulch Labs, Max Planck Soc, Cologne, Germany. [Thomas, Roman K.] Univ Cologne, Fac Med, Cologne, Germany. [Thomas, Roman K.] Univ Cologne, Ctr Integrated Oncol, Cologne, Germany. [Thomas, Roman K.] Univ Cologne, Dept Internal Med, Cologne, Germany. [Minna, John D.] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Simmons Canc Ctr, Dallas, TX 75390 USA. [Minna, John D.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Minna, John D.] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA. [Chirieac, Lucian R.; Lindeman, Neal I.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Giordano, Thomas] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Beer, David G.] Univ Michigan, Dept Surg, Thorac Surg Sect, Ann Arbor, MI 48109 USA. [Wistuba, Ignacio I.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Wistuba, Ignacio I.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM Matthew_Meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; Dutt, Amit/I-1911-2013; OI Dutt, Amit/0000-0002-1119-4774; Rubin, Mark/0000-0002-8321-9950; Giordano, Thomas/0000-0003-0641-8873 FU Swiss National Science Foundation [PBZHB- 106297]; National Cancer Institute [5R01CA109038, 5P20CA90578] FX We thank Shantanu Banerji for critical reading of the manuscript and Christopher A. French for providing microscopy support. A. D. is supported by the Swiss National Science Foundation Fellowship # PBZHB- 106297. This work was supported by National Cancer Institute grants 5R01CA109038 and 5P20CA90578 (M. M.). NR 45 TC 49 Z9 51 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD NOV 1 PY 2009 VL 8 IS 21 BP 2042 EP 2050 DI 10.4161/cbt.8.21.9764 PG 9 WC Oncology SC Oncology GA 533BF UT WOS:000272796200013 PM 19755855 ER PT J AU Park, SM Park, CT Park, SY Bae, DS Nam, JH Cho, CH Lee, JM Earle, CC Yun, YH AF Park, Sang Min Park, Chong Taik Park, Sang Yoon Bae, Duk-Soo Nam, Joo Hyun Cho, Chi-Heum Lee, Jong Min Earle, Craig C. Yun, Young Ho TI Factors related to second cancer screening practice in disease-free cervical cancer survivors SO CANCER CAUSES & CONTROL LA English DT Article DE Cancer screening; Cervical cancer survivor; Second cancer ID RANDOMIZED CONTROLLED-TRIAL; BREAST-CANCER; PROSPECTIVE COHORT; COLORECTAL-CANCER; RISK; CARCINOMA; QUALITY; WOMEN; MALIGNANCY; INSURANCE AB Background Although cancer survivors are at increased risk for developing cancers at other sites, little is known about the current status of second cancer (cancers other than the index cancer) screening practices and related factors in cervical cancer survivors. Methods We enrolled 809 cervical cancer survivors aged >= 40 years who had been treated at six hospitals from 1983 to 2004. Subjects filled out a questionnaire that included the practices of second cancer screening (breast, stomach, and colorectum) and other sociodemographic variables. Results Among subjects, 38.9% had been recommended to receive screening for other cancers from health care providers, and 27.4% reported that they thought they had lower risk of other cancer than general population. Older (age >= 65 years) and poor (family income < 1,000$/month) subjects were less likely to have second cancer screening. Those to whom health care providers had recommended screening for other cancers (aOR = 2.14; 95% CI, 1.542.98), and those who had an appropriate perception of second cancer risk (aOR = 1.64; 95% CI, 1.11-2.43) were more likely to undergo breast cancer screening. Conclusion Lack of a recommendation for second cancer screening from health care providers and the misperception of second cancer risk might have negative impacts on the breast cancer screening behaviors in cervical cancer survivors. C1 [Park, Sang Min; Yun, Young Ho] Natl Canc Ctr, Div Canc Control, Goyang Si 411769, Gyeonggi Do, South Korea. [Park, Chong Taik] Pochon CHA Univ, Coll Med, Kangnam Cha Hosp, Dept Obstet & Gynecol, Seoul, South Korea. [Park, Sang Yoon] Natl Canc Ctr, Ctr Uterine Canc, Goyang, Gyeonggi, South Korea. [Bae, Duk-Soo] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Obstet & Gynecol, Seoul, South Korea. [Nam, Joo Hyun] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Obstet & Gynecol, Seoul, South Korea. [Cho, Chi-Heum] Keimyung Univ, Sch Med, Dept Obstet & Gynecol, Taegu, South Korea. [Lee, Jong Min] Kyung Hee Univ, EW Neo Med Ctr, Dept Obstet & Gynecol, Seoul, South Korea. [Earle, Craig C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Div Populat Sci, Boston, MA 02115 USA. RP Yun, YH (reprint author), Natl Canc Ctr, Div Canc Control, 809 Madu Dong, Goyang Si 411769, Gyeonggi Do, South Korea. EM lawyun08@ncc.re.kr RI Yun, Young Ho/J-5560-2012; Park, Sang Min/J-5484-2012 FU National Cancer Center [04101502, 07104221] FX This work was supported by National Cancer Center Grant No. 04101502 and National Cancer Center Grant No. 07104221. NR 29 TC 8 Z9 8 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2009 VL 20 IS 9 BP 1697 EP 1703 DI 10.1007/s10552-009-9421-0 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 511VF UT WOS:000271198400017 PM 19688183 ER PT J AU Menes, TS Kerlikowske, K Jaffer, S Seger, D Miglioretti, DL AF Menes, Tehillah S. Kerlikowske, Karla Jaffer, Shabnam Seger, Deborah Miglioretti, Diana L. TI Rates of Atypical Ductal Hyperplasia Have Declined with Less Use of Postmenopausal Hormone Treatment: Findings from the Breast Cancer Surveillance Consortium SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ESTROGEN PLUS PROGESTIN; SCREENING MAMMOGRAPHY; RISK-FACTORS; FOLLOW-UP; DISEASE; FREQUENCY; THERAPY; WOMEN; POPULATION; BIOPSIES AB Aim: To examine risk factors and rates of atypical ductal hyperplasia (ADH) with and without associated breast cancer over time and tumor characteristics of breast cancer with and without associated ADH in women previously screened with mammography. Methods: Data on screening mammograms done between 1996 and 2005 were collected from mammography registries that participate in the Breast Cancer Surveillance Consortium. Associations between age, family history of breast cancer, postmenopausal hormone treatment (HT), and final pathology result (ADH or cancer with or without ADH in the same breast) were examined. Rates of different outcomes were calculated per exam year. Tumor characteristics of cancers with and without associated ADH were compared. Results: A total of 2,453,483 screening mammograms were associated with 1,064 biopsies with ADH, 833 breast cancers with ADH, and 8,161 cancers with no ADH. Postmenopausal HT use decreased significantly from 35% to 11% during the study period. Rates of ADH decreased from a peak of 5.5/10,000 mammograms in 1999 to 2.4/10,000 in 2005. Rates of cancer with ADH decreased from a peak of 4.3/10,000 mammograms in 2003 to 3.3/10,000 in 2005. ADH and breast cancer were significantly associated with use of postmenopausal HT. Cancer associated with ADH was of lower grade and stage and more estrogen receptor positive than cancer with no ADH. Summary: Postmenopausal HT is associated with an increased risk of ADH with or without cancer. Rates of ADH have decreased over the past decade, which may be partially explained by the significant reduction in use of postmenopausal HT. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2822-8) C1 [Menes, Tehillah S.] Elmhurst Hosp Ctr, Dept Surg, Elmhurst, NY 11373 USA. [Menes, Tehillah S.] Mt Sinai Sch Med, New York, NY USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Med, San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94143 USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94143 USA. [Jaffer, Shabnam] Mt Sinai Med Ctr, Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA. [Miglioretti, Diana L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Menes, TS (reprint author), Elmhurst Hosp Ctr, Dept Surg, 79-01 Broadway, Elmhurst, NY 11373 USA. EM menest@nychhc.org FU National Cancer Institute [U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040] FX The National Cancer Institute-funded Breast Cancer Surveillance Consortium co-operative agreement (U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, and U01CA70040). NR 27 TC 11 Z9 11 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2009 VL 18 IS 11 BP 2822 EP 2828 DI 10.1158/1055-9965.EPI-09-0745 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 516SJ UT WOS:000271562600004 PM 19900937 ER PT J AU Pollitt, RA Geller, AC Brooks, DR Johnson, TM Park, ER Swetter, SM AF Pollitt, Ricardo A. Geller, Alan C. Brooks, Daniel R. Johnson, Timothy M. Park, Elyse R. Swetter, Susan M. TI Efficacy of Skin Self-Examination Practices for Early Melanoma Detection SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; INTERVENTION; 21ST-CENTURY; PHOTOGRAPHS; POPULATION; PREVENTION; TRIAL; CHECK; RISK AB Although skin self-examination (SSE) may increase rates of early melanoma detection, the efficacy of different SSE practices has not been thoroughly studied. We examined associations between SSE practices and tumor thickness in patients with recently diagnosed melanoma. Methods: 321 melanoma patients at three hospitals completed questionnaires on demographics and SSE practices. Patient-reported SSE was measured by routine examination of 13 specific body areas, frequency of mole examination, and use of a melanoma picture aid to assist with SSE. Histologic diagnoses and Breslow depth were confirmed by dermatopathologists. Regression analyses were used to calculate ratios of geometric mean tumor thickness and odds ratios for having thicker versus thinner tumors for different SSE behaviors. Results: Rates of SSE varied considerably by SSE item. Patients routinely examining at least some of their skin had thinner melanomas [adjusted geometric mean tumor ratio, 0.73; 95% confidence interval (95% CI), 0.50-0.94]. Frequency of mole examination did not predict tumor thickness. Using a melanoma picture as a SSE aid was strongly associated with reduced tumor thickness (adjusted ratio, 0.75; 95% Cl, 0.66-0.85 for ever versus never use). A composite measure of thoroughness of SSE was the best predictor of thickness (adjusted ratio, 0.58; 95% Cl, 0.36-0.75) for high versus low thoroughness. Conclusions: SSE was associated with decreased tumor thickness by most measures. However, the diverse rates of SSE practices and the distinct associations between these practices and melanoma thickness suggest a complexity in SSE that should be addressed in future studies. SSE should be evaluated by more than one measure. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3018-23) C1 [Pollitt, Ricardo A.; Swetter, Susan M.] Stanford Univ, Dept Dermatol, Pigmented Les & Melanoma Program, Sch Med, Stanford, CA 94305 USA. [Geller, Alan C.] Harvard Univ, Sch Publ Hlth, Div Publ Hlth Practice, Boston, MA 02115 USA. [Brooks, Daniel R.] Boston Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02215 USA. [Johnson, Timothy M.] Univ Michigan, Sch Med, Dept Dermatol, Ann Arbor, MI USA. [Johnson, Timothy M.] Univ Michigan, Sch Med, Dept Otolaryngol, Ann Arbor, MI USA. [Johnson, Timothy M.] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI USA. [Park, Elyse R.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Park, Elyse R.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Swetter, Susan M.] Vet Affairs Palo Alto Hlth Care Syst, Dermatol Serv, Palo Alto, CA USA. RP Swetter, SM (reprint author), Stanford Univ, Dept Dermatol, Med Ctr, 450 Broadway St,Pavil C,2nd Floor, Redwood City, CA 94063 USA. EM sswetter@stanford.edu OI Brooks, Daniel/0000-0001-6220-6889 FU Schering Plough FX Grant support: Schering Plough. The sponsor had no role in the design and conduct of the study, the collection, analysis, and interpretation of data, or the preparation, review, or approval of the article. NR 26 TC 36 Z9 36 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2009 VL 18 IS 11 BP 3018 EP 3023 DI 10.1158/1055-9965.EPI-09-0310 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 516SJ UT WOS:000271562600031 PM 19861521 ER PT J AU Fejerman, L Haiman, CA Reich, D Tandon, A Deo, RC John, EM Ingles, SA Ambrosone, CB Bovbjerg, DH Jandorf, LH Davis, W Ciupak, G Whittemore, AS Press, MF Ursin, G Bernstein, L Huntsman, S Henderson, BE Ziv, E Freedman, ML AF Fejerman, Laura Haiman, Christopher A. Reich, David Tandon, Arti Deo, Rahul C. John, Esther M. Ingles, Sue A. Ambrosone, Christine B. Bovbjerg, Dana Howard Jandorf, Lina H. Davis, Warren Ciupak, Gregory Whittemore, Alice S. Press, Michael F. Ursin, Giske Bernstein, Leslie Huntsman, Scott Henderson, Brian E. Ziv, Elad Freedman, Matthew L. TI An Admixture Scan in 1,484 African American Women with Breast Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; LINKAGE DISEQUILIBRIUM; RACIAL-DIFFERENCES; MULTIETHNIC POPULATION; CONFER SUSCEPTIBILITY; COMMON VARIANTS; LOS-ANGELES; RISK LOCUS; SURVIVAL; ESTROGEN AB African American women with breast cancer present more commonly with aggressive tumors that do not express the estrogen receptor (ER) and progesterone receptor (PR) compared with European American women. Whether this disparity is the result of inherited factors has not been established. We did an admixture-based genome-wide scan to search for risk alleles for breast cancer that are highly differentiated in frequency between African American and European American women, and may contribute to specific breast cancer phenotypes, such as ER-negative (ER-) disease. African American women with invasive breast cancer (n = 1,484) were pooled from six population-based studies and typed at similar to 1,500 ancestry-informative markers. We investigated global genetic ancestry and did a whole genome admixture scan searching for breast cancer-predisposing loci in association with disease phenotypes. We found a significant difference in ancestry between ER+PR+ and ER-PR- women, with higher European ancestry among ER+PR+ individuals, after controlling for possible confounders (odds ratios for a 0 to 1 change in European ancestry proportion, 2.84; 95% confidence interval, 1.13-7.14; P = 0.026). Women with localized tumors had higher European ancestry than women with non-localized tumors (odds ratios, 2.65; 95% confidence interval, 1.11-6.35; P = 0.029). No genome-wide statistically significant associations were observed between European or African ancestry at any specific locus and breast cancer, or in analyses stratified by ER/PR status, stage, or grade. In summary, in African American women, genetic ancestry is associated with ER/PR status and disease stage. However, we found little evidence that genetic ancestry at any one region contributes significantly to breast cancer risk or hormone receptor status. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3110-7) C1 [Fejerman, Laura; Huntsman, Scott; Ziv, Elad] Univ Calif San Francisco, Div Gen Internal Med, Dept Med, Inst Human Genet, San Francisco, CA 94143 USA. [Fejerman, Laura; Huntsman, Scott; Ziv, Elad] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Haiman, Christopher A.; Ingles, Sue A.; Ursin, Giske; Henderson, Brian E.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Reich, David; Tandon, Arti; Deo, Rahul C.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Deo, Rahul C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA. [Reich, David; Tandon, Arti; Freedman, Matthew L.] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Boston, MA USA. [John, Esther M.] No Calif Canc Ctr, Fremont, CA USA. [John, Esther M.; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Press, Michael F.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. [Ambrosone, Christine B.; Davis, Warren; Ciupak, Gregory] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Bovbjerg, Dana Howard] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Jandorf, Lina H.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA USA. [Ursin, Giske] Univ Oslo, Dept Nutr, Oslo, Norway. [Freedman, Matthew L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Freedman, Matthew L.] Dana Farber Harvard Canc Ctr, Boston, MA USA. RP Ziv, E (reprint author), Univ Calif San Francisco, Div Gen Internal Med, Dept Med, Inst Human Genet, Box 1732, San Francisco, CA 94143 USA. EM elad.ziv@ucsf.edu; freedman@broad.mit.edu OI Fejerman, Laura/0000-0003-3179-1151 FU Prevent Cancer Foundation; National Cancer Institute [CA63464, CA54281, R01 CA63446, R01 CA77305]; Komen Foundation Investigator-Initiated [KG080165]; Women's Circle of Health Study [NCI R01 CA100598, DAMD17-01-1-0334]; U.S. Army Medical Research Program [DAMD17-96-6071]; Richard and Susan Smith Family Foundation, Chestnut Hill, MA; National Institute of Child Health and Human Development [N01-HD-3-3175]; National Cancer Institute, NIH [RFA-CA-06-503]; Northern California Cancer Center [U01 CA69417] FX Grant support: Postdoctoral fellowship from the Prevent Cancer Foundation (L. Fejerman). The Multiethnic Cohort Study was supported by National Cancer Institute grants CA63464 and CA54281. Komen Foundation Investigator-Initiated grant KG080165 (E. Ziv). The Women's Circle of Health Study is supported by grants NCI R01 CA100598 and DAMD17-01-1-0334. The San Francisco Bay Area Breast Cancer Study was funded by grants from the National Cancer Institute (R01 CA63446 and R01 CA77305) and the U.S. Army Medical Research Program (DAMD17-96-6071; E.M. John). Richard and Susan Smith Family Foundation, Chestnut Hill, MA (M. Freedman). Burroughs Wellcome Career Development Award in the Biomedical Sciences (D. Reich). The Los Angeles Component of the Women's Contraceptive and Reproductive Experiences Study was supported by a contract from the National Institute of Child Health and Human Development (N01-HD-3-3175; L. Bernstein). The Breast Cancer Family Registry (BCFR) is funded by the National Cancer Institute, NIH under RFA-CA-06-503 and through cooperative agreements with members of the BCFR and Principal Investigators. The registry contributing data to this analysis was supported by U01 CA69417 (Northern California Cancer Center). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government or the BCFR. NR 47 TC 29 Z9 29 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2009 VL 18 IS 11 BP 3110 EP 3117 DI 10.1158/1055-9965.EPI-09-0464 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 516SJ UT WOS:000271562600045 PM 19843668 ER PT J AU Anderson, KC AF Anderson, Kenneth C. TI The Evolving Treatment Paradigm. in Multiple Myeloma SO CANCER JOURNAL LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Neoplasia, 44 Binney St,Mayer Bldg,Room 557, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu 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 1528-9117 J9 CANCER J JI Cancer J. PD NOV-DEC PY 2009 VL 15 IS 6 BP 456 EP 456 PG 1 WC Oncology SC Oncology GA 535EW UT WOS:000272951000002 PM 20010163 ER PT J AU Cirstea, D Vallet, S Raje, N AF Cirstea, Diana Vallet, Sonia Raje, Noopur TI Future Novel Single Agent and Combination Therapies SO CANCER JOURNAL LA English DT Review DE multiple myeloma; novel agents; combination therapy; bone marrow microenvironment ID MULTIPLE-MYELOMA CELLS; LENALIDOMIDE PLUS DEXAMETHASONE; HISTONE DEACETYLASE INHIBITOR; SUBEROYLANILIDE HYDROXAMIC ACID; ACTIVE PROTEASOME INHIBITOR; DEPENDENT KINASE INHIBITOR; HIGH-DOSE DEXAMETHASONE; IN-VIVO; SURVIVAL PATHWAYS; ANTICANCER AGENTS AB Although multiple myeloma (MM) remains an incurable bone marrow cancer, survival rates have dramatically improved over the past decade, most notably in the younger patient population. An understanding of MM biology and improvement in stem-cell transplantation, better supportive care, and novel therapies with higher efficacy and lower toxicity are all responsible for this improvement. Despite these trends, improvements among older patients remain modest, underscoring the need for innovative approaches. The availability of a rich pipeline of novel agents undergoing early-phase clinical trials in MM is an exciting and active area of research. Current novel agents targeting tumor and stromal compartments can be conceptualized as those that target membrane-bound receptors (insulin-like growth factor-1, vascular endothelial growth factor, CD40, etc.), intracellular signaling kinases (Janus kinase/signal transducers and activators of transcription, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin, mitogen-activated protein kinase pathways), cell cycle molecular machinery (cyclin-dependent kinases inhibitors), epigenetic abnormalities (DNA methyltransferase and histyone deacetylase), protein dynamics (heat-shock protein 90, ubiquitin-proteasome system), and tumor vasculature and microenvironment (angiogenesis, integrins). This review highlights some of these novel agents tested either alone or in combination for the treatment of MM. C1 [Vallet, Sonia; Raje, Noopur] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. [Cirstea, Diana; Raje, Noopur] Harvard Univ, Sch Med, Leebow Inst Myeloma Therapeut, Boston, MA 02114 USA. [Cirstea, Diana; Raje, Noopur] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02114 USA. RP Raje, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Canc Ctr, POB 216,55 Fruit St, Boston, MA 02114 USA. EM nraje@partners.org FU ASCO CDA; MMRF; LLS CDA FX Supported by ASCO CDA, MMRF, and LLS CDA (to N.R.). NR 95 TC 12 Z9 13 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD NOV-DEC PY 2009 VL 15 IS 6 BP 511 EP 518 PG 8 WC Oncology SC Oncology GA 535EW UT WOS:000272951000010 PM 20010171 ER PT J AU Xing, D Scangas, G Nitta, M He, L Xu, X Ioffe, YJM Aspuria, PJ Hedvat, CY Anderson, ML Oliva, E Karlan, BY Mohapatra, G Orsulic, S AF Xing, Deyin Scangas, George Nitta, Mai He, Lei Xu, Xuan Ioffe, Yevgeniya J. M. Aspuria, Paul-Joseph Hedvat, Cyrus Y. Anderson, Matthew L. Oliva, Esther Karlan, Beth Y. Mohapatra, Gayatry Orsulic, Sandra TI A Role for BRCA1 in Uterine Leiomyosarcoma SO CANCER RESEARCH LA English DT Article ID SMOOTH-MUSCLE TUMORS; IMMUNOHISTOCHEMICAL ANALYSIS; MOUSE MODEL; CELL-CYCLE; P53; EXPRESSION; LEIOMYOMAS; P16; RECEPTOR; MICE AB Uterine leiomyosarcoma (ULMS) is a rare gynecologic malignancy with a low survival rate. Currently, there is no effective treatment for ULMS. Infrequent occurrences of human WAS hamper the understanding of the initiation and progression of the disease, thereby limiting the ability to develop efficient therapies. To elucidate the roles of the p53 and BRCA1 tumor suppressor genes in gynecologic malignancies, we generated mice in which p53 and/or BRCA1 can be conditionally deleted using anti-Mullerian hormone type II receptor (Anthr2)-driven Cre recombinase. We showed that conditional deletion of p53 in mice results in the development of uterine tumors that resemble human ULMS and that concurrent deletion of p53 and BRCA1 significantly accelerates the progression of these tumors. This finding led to our hypothesis that BRCA1 may play a role in human ULMS development. Consistent with this hypothesis, we showed that the BRCA1 protein is absent in 29% of human ULMS and that BRCA1 promoter methylation is the likely mechanism of BRCA1 downregulation. These data indicate that the loss of BRCA1 function may be an important step in the progression of ULMS. Our findings provide a rationale for investigating therapies that target BRCA1 deficiency in ULMS. [Cancer Res 2009;69(21):8231-5] C1 [Xu, Xuan; Ioffe, Yevgeniya J. M.; Aspuria, Paul-Joseph; Karlan, Beth Y.; Orsulic, Sandra] Cedars Sinai Med Ctr, Womens Canc Res Inst, Los Angeles, CA 90048 USA. [Xing, Deyin; Scangas, George; Nitta, Mai; He, Lei; Mohapatra, Gayatry; Orsulic, Sandra] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Xing, Deyin; Scangas, George; Nitta, Mai; He, Lei; Mohapatra, Gayatry; Orsulic, Sandra] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Xing, Deyin; Scangas, George; Nitta, Mai; He, Lei; Oliva, Esther; Mohapatra, Gayatry; Orsulic, Sandra] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Oliva, Esther; Mohapatra, Gayatry; Orsulic, Sandra] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Hedvat, Cyrus Y.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Anderson, Matthew L.] Baylor Coll Med, Div Gynecol Oncol, Houston, TX 77030 USA. RP Orsulic, S (reprint author), Cedars Sinai Med Ctr, Womens Canc Res Inst, 8635 W 3rd St,Suite 290W, Los Angeles, CA 90048 USA. EM orsulics@cshs.org FU NIH [R01-CA103924]; Ovarian Cancer Research Fund; Liddy Shriver Sarcoma Initiative; LMSarcoma Direct Research Foundation; Sarcoma Foundation of America FX Received 7/8/09; revised 9/8/09; accepted 9/14/09; published OnlineFirst 10/20/09.; Grant support: NIH (R01-CA103924), Ovarian Cancer Research Fund, Liddy Shriver Sarcoma Initiative, LMSarcoma Direct Research Foundation, and the Sarcoma Foundation of America (S. Orsulic).; The costs of publication of this article were defrayed in part by the payment. of page charges. This article must. therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 17,34 solely to indicate this fact.; We thank Robert. Soslow (Memorial Sloan-Kettering Cancer Center, New York, NY), Gian Franco Zannoni (Universita Cattolica. Rome, Italy), Michele de Nictolis (Istituto di Anatomia e Istologia Patologica, Ancona Italy), Philip Branton (Inova Fairfax Hospital, Falls Church, VA), Christine Holschneider (Olive View Medical Center, Los Angeles, CA), and jenny Gross (Cedars-Sinai Medical Center) for contributing human specimens; Lejla Delic (Cedars-Sinai Medical Center) for help with IIIC; Richard Behringer (University of Texas, M.D. Anderson Cancer Center) for the Amhr2-Cre mice; members of the Women's Cancer Research Institute at Cedars-Sinai Medical Center for insightful suggestions; and Kristy J. Daniels for help in thepreparation of the manuscript. NR 20 TC 26 Z9 30 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2009 VL 69 IS 21 BP 8231 EP 8235 DI 10.1158/0008-5472.CAN-09-2543 PG 5 WC Oncology SC Oncology GA 514OA UT WOS:000271403000003 PM 19843854 ER PT J AU Hubbard, SA Friel, AM Kumar, B Zhang, L Rueda, BR Gargett, CE AF Hubbard, Sonya A. Friel, Anne M. Kumar, Beena Zhang, Ling Rueda, Bo R. Gargett, Caroline E. TI Evidence for Cancer Stem Cells in Human Endometrial Carcinoma SO CANCER RESEARCH LA English DT Article ID SIDE-POPULATION CELLS; BETA-CATENIN EXPRESSION; PROSPECTIVE IDENTIFICATION; E-CADHERIN; SCID MICE; IN-VITRO; TUMORS; CONTRIBUTE; SIGNATURE; LINE AB Emerging evidence indicates that the highly regenerative human endometrium harbors rare populations of epithelial progenitor cells. In tumors of other regenerative epithelial tissues, rare cancer stem cells (CSC) have been identified that may have originated from normal epithelial stem/progenitor cells. We hypothesized that CSC are responsible for epithelial neoplasia associated with endometrial carcinoma, the most common gynecologic malignancy in women. Stem cell characteristics of single cells isolated from endometrial carcinoma tissues from women ages 62 +/- 11.8 years (n = 34) were assessed. Twenty-five of 28 endometrial carcinoma samples contained a small population of clonogenic cells [0.24% (0-1.84%)], with no significant difference in cloning efficiency between the three grades of endometrial carcinoma or between endometrial carcinoma and normal endometrial epithelial samples. Isolated endometrial carcinoma cells transplanted under the kidney capsule of immunocompromised mice in serial dilution (2 x 10(6)-1 x 10(4) cells) generated tumors in 8 of 9 samples with morphologies similar to the parent tumors. These tumors recapitulated cytokeratin, vimentin, estrogen receptor-alpha, and progesterone receptor expression of the parent tumor, indicating that tumor-initiating cells likely differentiated into cells comprising the endometrial carcinoma tissue. Individual clones underwent serial clonal subculture 2.5 to 4 times, with a trend of increasing number of subclonings with increasing tumor grade, indicating increasing self-renewal with greater malignancy. Clonally derived endometrial carcinoma cells also expressed the self-renewal genes BMI-I, NANOG, and SOX-2. Isolated cells from primary tumors were serially transplanted 3 to 5 times in nonobese diabetic/severe combined immunodeficient mice, showing self-renewal in vivo. This evidence of cells with clonogenic, self-renewing, differentiating, and tumorigenic properties suggests that a CSC population may be responsible for production of endometrial carcinoma tumor cells. [Cancer Res 2009;69(21):8241-8] C1 [Gargett, Caroline E.] Monash Univ, Dept Obstet & Gynaecol, Monash Med Ctr, Clayton, Vic 3168, Australia. [Hubbard, Sonya A.; Gargett, Caroline E.] Monash Inst Med Res, Ctr Womens Hlth Res, Clayton, Vic, Australia. [Friel, Anne M.; Zhang, Ling; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Vincent Ctr Reprod Biol, Boston, MA USA. RP Gargett, CE (reprint author), Monash Univ, Dept Obstet & Gynaecol, Monash Med Ctr, 246 Clayton Rd, Clayton, Vic 3168, Australia. EM Caroline.Gargett@med.monash.edu.au OI Gargett, Caroline/0000-0002-3590-2077 FU Cancer Council Victoria [491079]; National Health and Medical Research Council [465121]; Australian Postgraduate Award; Advanced Medical Research Foundation; Harvard Stem Cell Institute; Victorian Government FX Grant support: Cancer Council Victoria grant 491079 and National Health and Medical Research Council R.D. Wright Career Development Award 465121 (C.E, Gargat); Australian Postgraduate Award (S.A. Hubbard); and Advanced Medical Research Foundation and Harvard Stem Cell Institute (B.R. Rueda). The endometrial cancer specimens used in this project were provided by the Victorian Cancer Biobank which is supported by the Victorian Government.; The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 48 TC 51 Z9 55 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2009 VL 69 IS 21 BP 8241 EP 8248 DI 10.1158/0008-5472.CAN-08-4808 PG 8 WC Oncology SC Oncology GA 514OA UT WOS:000271403000005 PM 19843861 ER PT J AU Sholl, LM Yeap, BY Iafrate, AJ Holmes-Tisch, AJ Chou, YP Wu, MT Goan, YG Su, L Benedettini, E Yu, J Loda, M Janne, PA Christiani, DC Chirieac, LR AF Sholl, Lynette M. Yeap, Beow Y. Iafrate, A. John Holmes-Tisch, Alison J. Chou, Yi-Ping Wu, Ming-Tsang Goan, Yih-Gang Su, Li Benedettini, Elisa Yu, Jian Loda, Massimo Jaenne, Pasi A. Christiani, David C. Chirieac, Lucian R. TI Lung Adenocarcinoma with EGFR Amplification Has Distinct Clinicopathologic and Molecular Features in Never-Smokers SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-RECEPTOR; IN-SITU-HYBRIDIZATION; GENE COPY NUMBER; GEFITINIB SENSITIVITY; MUTATIONS; CANCER; EXPRESSION; CARCINOMA; ERLOTINIB; RESPONSIVENESS AB In a subset of lung adenocarcinomas, the epidermal growth factor receptor (EGFR) is activated by kinase domain mutations and/or gene amplification, but the interaction between the two types of abnormalities is complex and unclear. For this study, we selected 99 consecutive never-smoking women of East Asian origin with lung adenocarcinomas that were characterized by histologic subtype. We analyzed EGFR mutations by PCR-capillary sequencing, EGFR copy number abnormalities by fluorescence and chromogenic in situ hybridization and quantitative PCR, and EGFR expression by immunohistochemistry with both specific antibodies against exon 19 deletion-mutated EGFR and total EGFR. We compared molecular and clinicopathologic features with disease-free survival. Lung adenocarcinomas with EGFR amplification had significantly more EGFR exon 19 deletion mutations than adenocarcinomas with disomy, and low and high polysomy (100% versus 54%, P = 0.009). EGFR amplification occurred invariably on the mutated and not the mild-type allele (median mutated/wild-type ratios 14.0 versus 0.33, P = 0.003), was associated with solid histology (P = 0.008), and advanced clinical stage (P = 0.009). EGFR amplification was focally distributed in lung cancer specimens, mostly in regions with solid histology. Patients with EGFR amplification had a significantly worse outcome in univariate analysis (median disease-free survival, 16 versus 31 months, P = 0.01) and when adjusted for stage (P = 0.027). Lung adenocarcinomas with EGFR amplification have a unique association with exon 19 deletion mutations and show distinct clinicopathologic features associated with a significantly worsened prognosis. in these cases, EGFR amplification is heterogeneously distributed, mostly in areas with a solid histology. [Cancer Res 2009;69(21):8341-8] C1 [Sholl, Lynette M.; Loda, Massimo; Chirieac, Lucian R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Christiani, David C.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Holmes-Tisch, Alison J.; Benedettini, Elisa; Loda, Massimo; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Chou, Yi-Ping] Kaohsiung Vet Gen Hosp, Dept Chest Surg, Kaohsiung, Taiwan. [Wu, Ming-Tsang; Goan, Yih-Gang] Kaohsiung Med Univ Hosp, Dept Family Med, Kaohsiung, Taiwan. [Wu, Ming-Tsang; Goan, Yih-Gang] Grad Inst Occupat Safety & Hlth, Kaohsiung, Taiwan. [Chou, Yi-Ping] Natl Yang Ming Univ, Taipei, Taiwan. [Yu, Jian] Cell Signaling Technol Inc, Danvers, MA USA. RP Chirieac, LR (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM lchirieac@partners.org RI Wu, Ming-Tsang/D-2385-2009 FU National Institutes of Health [CA074386, CA092824, ROI CA114465] FX Grant support: CA074386, CA092824, and ROI CA114465 From the National Institutes of Health.; The costs of publication of this article were defrayed in part. by the payment of page charges. This article most therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. We thank Laura Kwan and Brittany MacFarland for secretarial assistance, and Lilliam Z. Cruz for laboratory support. NR 33 TC 56 Z9 57 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2009 VL 69 IS 21 BP 8341 EP 8348 DI 10.1158/0008-5472.CAN-09-2477 PG 8 WC Oncology SC Oncology GA 514OA UT WOS:000271403000017 PM 19826035 ER PT J AU Kikuchi, H Pino, MS Zeng, M Shirasawa, S Chung, DC AF Kikuchi, Hirotoshi Pino, Maria S. Zeng, Min Shirasawa, Senji Chung, Daniel C. TI Oncogenic KRAS and BRAF Differentially Regulate Hypoxia-inducible Factor-1 alpha and-2 alpha in Colon Cancer SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TRANSCRIPTION FACTOR; FACTOR 1-ALPHA; CELL-LINES; EXPRESSION; RAS; MUTATIONS; TUMORIGENESIS; VEGF; ANGIOGENESIS AB KRAS and BRAF mutations are frequently observed in human colon cancers. These mutations occur in a mutually exclusive manner, and each is associated with distinctive biological features. We showed previously that K-ras can interact with hypoxia to activate multiple signaling pathways. Many hypoxic responses are mediated by hypoxia-inducible factor (HIF)-1 alpha and HIF-2 alpha, and we sought to define the roles of mutant KRAS and BRAF in the induction of HIF-1 alpha and HIF-2 alpha in colon cancer cells. Ectopic expression of mutant K-ras in Caco2 cells enhanced the hypoxic induction of only HIF-1 alpha, whereas mutant BRAF enhanced both HIF-1 alpha and HIF-2 alpha. Knockout or knockdown of mutant KRAS in DLD-1 and HCT116 cells impaired the hypoxic induction of only HIF-1 alpha. HIF-1 alpha mRNA levels were comparable in cells with and without a KRAS mutation. However, the rate of HIF-1 alpha protein synthesis was higher in cells with a KRAS mutation, and this was suppressed by the phosphoinositide 3-kinase inhibitor LY294002. In contrast, knockdown of mutant BRAF in HT29 cells suppressed both HIF-1 alpha and HIF-2 alpha. Although BRAF regulated mRNA levels of both HIF-1 alpha and HIF-2 alpha, knockdown of BRAF or treatment with the MEK inhibitor PD98059 impaired the translation of only HIF-2 alpha. Our data reveal that oncogenic KRAS and BRAF mutations differentially regulate the hypoxic induction of HIF-1 alpha and HIF-2 alpha in colon cancer, and this may potentially contribute to the phenotypic differences of KRAS and BRAF mutations in colon tumors. [Cancer Res 2009;69(21):8499-506] C1 [Kikuchi, Hirotoshi; Pino, Maria S.; Zeng, Min; Chung, Daniel C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Chung, Daniel C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Shirasawa, Senji] Fukuoka Univ, Dept Cell Biol, Fac Med, Fukuoka 81401, Japan. [Shirasawa, Senji] Fukuoka Univ, Dept Cell Biol, Fac Med, Fukuoka 81401, Japan. RP Chung, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, 50 Blossom St, Boston, MA 02114 USA. EM dchung@partners.org FU NIH [CA92594] FX NIH CA92594. NR 41 TC 53 Z9 55 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2009 VL 69 IS 21 BP 8499 EP 8506 DI 10.1158/0008-5472.CAN-09-2213 PG 8 WC Oncology SC Oncology GA 514OA UT WOS:000271403000035 PM 19843849 ER PT J AU Castorina, P Carco, D Guiot, C Deisboeck, TS AF Castorina, Paolo Carco, Daniela Guiot, Caterina Deisboeck, Thomas S. TI Tumor Growth Instability and Its Implications for Chemotherapy SO CANCER RESEARCH LA English DT Article ID NORTON-SIMON HYPOTHESIS; BREAST-CANCER; MODEL; RESISTANCE; THERAPY; SENSITIVITY; EXPRESSION; DESIGN AB Optimal delivery of chemotherapy intensity is dependent on host- and tumor-specific characteristics. In this article, the chemotherapy late intensity schedule is revised to account for tumor growth instability, where a small tumor cell fraction emerges that exhibits a higher proliferation rate than the parent strain. Modeling this instability as simplified two-population dynamics, we find that: (a) if this instability precedes the onset of treatment, the slope of the linear increase of the drug concentration for the standard "Norton-Simon late intensity schedule" changes and the initial value of the dose strongly depends on the ratio of the two tumor cell populations and on their distinct growth rates; and (b) if the instability trails the initial treatment, the effective chemotherapeutic drug concentration changes as well. Both cases point toward testable potential refinements of the Norton-Simon late intensity schedule. [Cancer Res 2009;69(21):8507-15] C1 [Castorina, Paolo] Univ Catania, Dipartimento Fis, I-95100 Catania, Italy. [Castorina, Paolo] Ist Nazl Fis Nucl, I-95129 Catania, Italy. [Castorina, Paolo] Ctr Siciliano Fis Nucl & Struct Mat, Catania, Italy. [Carco, Daniela] Ist Oncol Mediterraneo, Viagrande, Italy. [Guiot, Caterina] Univ Turin, Dipartimento Neurosci, Turin, Italy. [Guiot, Caterina] Univ Turin, CNISM, Turin, Italy. [Guiot, Caterina] Politecn Torino, Turin, Italy. [Deisboeck, Thomas S.] Massachusetts Gen Hosp, Harvard MIT HST, Athinoula A Martinos Ctr Biomed Imaging, Complex Biosyst Modeling Lab, Charlestown, MA USA. RP Castorina, P (reprint author), Univ Catania, Dipartimento Fis, Via Santa Sofia 64, I-95100 Catania, Italy. EM paolo.castorina@ct.infn.it RI guiot, caterina/C-6708-2009; OI guiot, caterina/0000-0001-8529-1625; Castorina, Paolo/0000-0002-5617-8102 FU NIH [CA 113004]; Harvard-MIT Athinoula A. Martinos Center for Biomedical Imaging; Department of Radiology at Massachusetts General Hospital; Regione Piemonte; University of Torino FX NIH grant CA 113004 (T.S. Deisboeck) and by the Harvard-MIT Athinoula A. Martinos Center for Biomedical Imaging and the Department of Radiology at Massachusetts General Hospital. C. Guiot was supported by Regione Piemonte (PSF 2007, 2008) and University of Torino (60% 2007, 2008). NR 25 TC 14 Z9 14 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2009 VL 69 IS 21 BP 8507 EP 8515 DI 10.1158/0008-5472.CAN-09-0653 PG 9 WC Oncology SC Oncology GA 514OA UT WOS:000271403000036 PM 19861540 ER PT J AU Sugimoto, M Ohno, T Graham, DY Yamaoka, Y AF Sugimoto, Mitsushige Ohno, Tomoyuki Graham, David Y. Yamaoka, Yoshio TI Gastric mucosal interleukin-17 and-18 mRNA expression in Helicobacter pylori-induced Mongolian gerbils SO CANCER SCIENCE LA English DT Article ID INTESTINAL METAPLASIA; INCREASED RISK; GENE POLYMORPHISMS; VIRULENCE FACTORS; JAPANESE SUBJECTS; IMMUNE-RESPONSE; PEPTIC-ULCER; CANCER RISK; INFECTION; INFLAMMATION AB Helicobacter pylori infection causes characteristic mucosal infiltration of inflammatory cells, resulting in the development of peptic ulcers and gastric cancer in approximately 10% of cases. Different clinical expressions of the infection may reflect different patterns of cytokine expression. Interleukin (IL)-1 ss, tumor necrosis factor (TNF)-alpha, IL-17, and IL-18 have been reported to be involved in H. pylori-induced gastric mucosal inflammation, but the details and relation to different patterns of inflammation remain unclear. Moreover, the proinflammatory virulence factor outer inflammatory protein (OipA) was reported to be associated with gastric mucosal inflammatory cytokine levels. To clarify these findings, Mongolian gerbils were infected for up to 12 months with wild-type H. pylori 7.13 or with isogenic oipA mutants for 3 months, and mucosal cytokines (IL-1 ss, IL-17, IL-18, and TNF-alpha) mRNA levels were then assessed using real-time RT-PCR. Antral mucosal IL-1 beta and IL-18 mRNA levels peaked 1 month after infection, whereas the peak of TNF-alpha mRNA was at 6-12 months; IL-17 levels peaked at 12 months. The inflammatory cell infiltration and mRNA levels of all cytokines studied were significantly lower in oipA mutants than in wild-type-infected gerbils. Mucosal IL-1 ss, IL-17, and TNF-alpha expression, but not that of IL-18, were significantly associated with the grade of inflammatory cell infiltration. The pattern of increased inflammatory cytokines differed relative to the phase of the infection and pattern of inflammation. OipA appears to play a role in IL-1 ss, IL-17, and TNF-alpha expression and the resulting inflammation. (Cancer Sci 2009). C1 [Sugimoto, Mitsushige; Ohno, Tomoyuki; Graham, David Y.; Yamaoka, Yoshio] Michael E DeBakey Vet Affairs Med Ctr, Dept Med Gastroenterol, Houston, TX USA. [Sugimoto, Mitsushige; Ohno, Tomoyuki; Graham, David Y.; Yamaoka, Yoshio] Baylor Coll Med, Houston, TX 77030 USA. [Yamaoka, Yoshio] Oita Univ, Fac Med, Dept Environm & Prevent Med, Oita 87011, Japan. RP Yamaoka, Y (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med Gastroenterol, Houston, TX USA. EM yyamaoka@bcm.tmc.edu FU NIH [DK62813] FX This material is based upon work supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs and by Public Health Service grant DK56338, which funds the Texas Medical Center Digestive Diseases Center. Dr Yamaoka is supported in part by a grant from the NIH (DK62813). The contents are solely the responsibility of die authors and do not necessarily represent the official views of the VA or NIH. NR 46 TC 41 Z9 43 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD NOV PY 2009 VL 100 IS 11 BP 2152 EP 2159 DI 10.1111/j.1349-7006.2009.01291.x PG 8 WC Oncology SC Oncology GA 505VV UT WOS:000270728200021 PM 19694753 ER PT J AU Zhu, YJ Hu, J Hu, YD Liu, WG AF Zhu, Yongjian Hu, Jue Hu, Yiduo Liu, Weiguo TI Targeting DNA repair pathways: A novel approach to reduce cancer therapeutic resistance SO CANCER TREATMENT REVIEWS LA English DT Review DE DNA repair; Cancer therapy; Chemotherapy and radiotherapy resistance; Small molecule inhibitors ID BASE EXCISION-REPAIR; DOUBLE-STRAND BREAKS; DEPENDENT PROTEIN-KINASE; PHASE-II TRIAL; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; HOMOLOGOUS RECOMBINATION; MOLECULAR-MECHANISMS; TOPOISOMERASE-II; MISMATCH REPAIR; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE AB Increased chemo-resistance and radio-resistance of cancer cells is a major obstacle in the treatment and management of malignant cancers. An important mechanism that underlies the development of such therapeutic resistance is that cancer cells recognize DNA lesions induced by DNA-damaging agents and by ionizing radiation, and repair these lesions by activating various DNA repair pathways. Therefore, Use of pharmacological agents that can inhibit certain DNA repair pathways in cancer cells has the potential for enhancing the targeted cytotoxicity of anticancer treatments and reversing the associated therapeutic resistance associated with DNA repair; such agents, offering a promising opportunity to achieve better therapeutic efficacy. Here we review the major DNA repair pathways and discuss recent advances in the development of novel inhibitors of DNA repair pathways; many of these agents are under preclinical/clinical investigation. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Zhu, Yongjian; Liu, Weiguo] Zhejiang Univ, Dept Neurosurg, Affiliated Hosp 2, Sch Med, Hangzhou 310009, Zhejiang, Peoples R China. [Hu, Jue] Zhejiang Med Coll, Dept Pharmacol, Hangzhou 310009, Zhejiang, Peoples R China. [Hu, Yiduo] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Hu, Yiduo] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Liu, WG (reprint author), Zhejiang Univ, Dept Neurosurg, Affiliated Hosp 2, Sch Med, Hangzhou 310009, Zhejiang, Peoples R China. EM yongjian_zhu@zju.edu.cn; hjmice@zjmc.net.cn; yiduo_hu@dfci.harvard.edu; neurosurgery@zju.edu.cn FU Zhejiang Provincial Administration of Traditional Chinese Medicine [2009CA044] FX We would like to thank Dr. Sonal Jhaveri for her comments on the manuscript. This work is supported in part by grant from the Zhejiang Provincial Administration of Traditional Chinese Medicine to J.H. (Grant 2009CA044). NR 89 TC 31 Z9 31 U1 1 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-7372 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD NOV PY 2009 VL 35 IS 7 BP 590 EP 596 DI 10.1016/j.ctrv.2009.06.005 PG 7 WC Oncology SC Oncology GA 523TV UT WOS:000272098400009 PM 19635647 ER PT J AU Sharma, SD Meeran, SM Katiyar, N Tisdale, GB Yusuf, N Xu, H Elmets, CA Katiyar, SK AF Sharma, Som D. Meeran, Syed M. Katiyar, Nandan Tisdale, George B. Yusuf, Nabiha Xu, Hui Elmets, Craig A. Katiyar, Santosh K. TI IL-12 deficiency suppresses 12-O-tetradecanoylphorbol-13-acetate-induced skin tumor development in 7,12-dimethylbenz(a)anthracene-initiated mouse skin through inhibition of inflammation SO CARCINOGENESIS LA English DT Article ID TEA POLYPHENOL (-)-EPIGALLOCATECHIN-3-GALLATE; NECROSIS-FACTOR-ALPHA; IFN-GAMMA PRODUCTION; SKH-1 HAIRLESS MICE; OXIDATIVE STRESS; CELL CARCINOMAS; HIGH-RISK; T-CELLS; IN-VIVO; INTERLEUKIN-12 AB Interleukin (IL)-12 deficiency exacerbates tumorigenesis in ultraviolet (UV) radiation-induced skin. Here, we assessed the effects of IL-12 deficiency on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion in 7,12-dimethylbenz(a)anthracene (DMBA)-initiated mouse skin. Using this two-stage chemical carcinogenesis protocol, we found that the development of DMBA/TPA-induced skin tumors was diminished in IL-12p40-knockout mice than in their wild-type counterparts. At the termination of the experiment (at 24 weeks), the skin tumor incidence and tumor multiplicity were significantly lower (P < 0.005) in interleukin-12-knockout (IL-12 KO) mice than in their wild-type counterparts, as was the malignant transformation of DMBA/TPA-induced papillomas to carcinomas (P < 0.01). Analysis of samples collected at the termination of the experiments for biomarkers of inflammation by immunohistochemical analysis, western blotting, enzyme-linked immunosorbent assay and real-time polymerase chain reaction revealed significantly lower levels of cyclooxygenase-2 (COX-2), prostaglandin (PG) E(2), proliferating cell nuclear antigen, cyclin D1 and the proinflammatory cytokines (tumor necrosis factor-alpha, IL-1 beta and IL-6) in the DMBA/TPA-treated tumors and tumor-uninvolved skin of IL-12 KO mice than the skin and tumors of DMBA/TPA-treated wild-type mice. Analysis of the skin 6 h after TPA treatment showed that the TPA-induced promotion of skin edema, inflammatory leukocyte infiltration, COX-2 expression and PGE(2) production was significantly lower in the skin of the IL-12-KO mice than their wild-type counterparts. These results indicate that DMBA/TPA-induced skin tumor development differs from UVB-induced skin tumor development in that endogenous IL-12 acts to inhibit UVB-induced skin tumor development and malignant progression of the skin tumors to carcinoma. In the case of DMBA/TPA-induced skin tumor development, the endogenous IL-12 modulates the tumor promoter stimulation of inflammatory responses. C1 [Sharma, Som D.; Meeran, Syed M.; Katiyar, Nandan; Tisdale, George B.; Yusuf, Nabiha; Xu, Hui; Elmets, Craig A.; Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Yusuf, Nabiha; Xu, Hui; Elmets, Craig A.; Katiyar, Santosh K.] Univ Alabama, UAB Skin Dis Res Ctr, Birmingham, AL 35294 USA. [Yusuf, Nabiha; Elmets, Craig A.; Katiyar, Santosh K.] Univ Alabama, UAB Comprehens Canc Ctr, Birmingham, AL 35294 USA. [Elmets, Craig A.; Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557, Birmingham, AL 35294 USA. EM skatiyar@uab.edu RI Xu, Hui/A-8167-2009 FU Veterans Administration Merit Review Award; National Institutes of Health [P30-AR050948, P30-CA013148] FX Veterans Administration Merit Review Award to S. K. K. and C. A. E.; National Institutes of Health (P30-AR050948, P30-CA013148). NR 42 TC 11 Z9 11 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2009 VL 30 IS 11 BP 1970 EP 1977 DI 10.1093/carcin/bgp228 PG 8 WC Oncology SC Oncology GA 524YB UT WOS:000272179200021 PM 19759192 ER PT J AU Joshi, SB Blum, AR Mansour, M Abbara, S AF Joshi, Subodh B. Blum, Andrew R. Mansour, Moussa Abbara, Suhny TI CT Applications in Electrophysiology SO CARDIOLOGY CLINICS LA English DT Article DE CT; Electrophysiology; Radiofrequency ablation; Cardiac resynchronization therapy; Cardiac imaging ID MULTIDETECTOR COMPUTED-TOMOGRAPHY; LEFT ATRIAL APPENDAGE; CARDIAC VENOUS SYSTEM; RIGHT-VENTRICULAR DYSPLASIA/CARDIOMYOPATHY; ELECTROANATOMIC MAPPING SYSTEM; PULMONARY VEIN ISOLATION; CHRONIC HEART-FAILURE; CATHETER ABLATION; MAGNETIC-RESONANCE; IMAGE INTEGRATION AB In recent years, extraordinary advances have been made in the management of cardiac arrhythmias. Increasingly complex procedures are being performed, and the breadth of conditions for which invasive arrhythmia therapy is indicated continues to grow. In addition to atrial and ventricular ablation procedures for treating arrhythmias, implantable defibrillators and biventricular pacemakers for cardiac resynchronization therapy have made electrophysiology an important part of heart failure management. C1 [Joshi, Subodh B.; Blum, Andrew R.; Abbara, Suhny] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR CT Program, Cardiovasc Imaging Sect, Boston, MA 02114 USA. [Mansour, Moussa] Massachusetts Gen Hosp, Cardiol Sect, Dept Radiol, Boston, MA 02114 USA. RP Abbara, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR CT Program, Cardiovasc Imaging Sect, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM sabbara@partners.org NR 62 TC 0 Z9 0 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 0733-8651 J9 CARDIOL CLIN JI Cardiol. Clin. PD NOV PY 2009 VL 27 IS 4 BP 619 EP + DI 10.1016/j.ccl.2009.06.012 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 507RZ UT WOS:000270873600010 PM 19766919 ER PT J AU Gould, D Patel, A Becker, G Connors, B Cardella, J Dawson, S Glaiberman, C Kessel, D Lee, M Lewandowski, W Phillips, R Reekers, J Sacks, D Sapoval, M Scerbo, M AF Gould, Derek Patel, Aalpen Becker, Gary Connors, Buddy Cardella, John Dawson, Steven Glaiberman, Craig Kessel, David Lee, Mick Lewandowski, William Phillips, Roger Reekers, Jim Sacks, David Sapoval, Marc Scerbo, Mark TI SIR/RSNA/CIRSE Joint Medical Simulation Task Force Strategic Plan: Executive Summary (vol 30, pg 551, 2007) SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Correction C1 [Gould, Derek] Royal Liverpool Univ Trust, Dept Radiol, Liverpool, Merseyside, England. [Patel, Aalpen] Univ Penn, Dept Radiol, Sch Med, Philadelphia, PA 19104 USA. [Becker, Gary] Univ Arizona, Coll Med, Dept Radiol, Tucson, AZ 85724 USA. [Connors, Buddy] Radiol Associates Sacramento, Sacramento, CA USA. [Cardella, John] Baystate Hlth Syst Tufts Univ, Sch Med, Dept Radiol, Springfield, MA 01199 USA. [Dawson, Steven] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Glaiberman, Craig] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Kessel, David] Leeds Teaching Hosp, Leeds, W Yorkshire, England. [Lee, Mick] Beaumont Hosp, Dept Radiol, Royal Coll Surg Ireland, Dublin 9, Ireland. [Lewandowski, William] William E Lewandowski Consulting, Daytona Beach, FL USA. [Phillips, Roger] Univ Hull, Dept Comp Sci, Kingston Upon Hull HU6 7RX, N Humberside, England. [Reekers, Jim] Univ Amsterdam, Acad Med Ctr, Dept Radiol, NL-1105 AZ Amsterdam, Netherlands. [Sacks, David] Reading Hosp Med Ctr, Dept Radiol, Reading, PA USA. [Sapoval, Marc] Hop Europeen G, Dept Radiol, Paris, France. [Scerbo, Mark] Old Dominion Univ, Dept Psychol, Norfolk, VA USA. RP Gould, D (reprint author), Royal Liverpool Univ Trust, Dept Radiol, Liverpool, Merseyside, England. EM dgould@liv.ac.uk NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD NOV PY 2009 VL 32 IS 6 BP 1320 EP 1320 DI 10.1007/s00270-009-9667-7 PG 1 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 515ON UT WOS:000271481800036 ER PT J AU Chen, CY Chai, H Wang, XW Lin, PH Yao, QZ AF Chen, Changyi Chai, Hong Wang, Xinwen Lin, Peter H. Yao, Qizhi TI Chlamydia heat shock protein 60 decreases expression of endothelial nitric oxide synthase in human and porcine coronary artery endothelial cells (vol 83, pg 768, 2009) SO CARDIOVASCULAR RESEARCH LA English DT Correction C1 [Chen, Changyi; Chai, Hong; Wang, Xinwen; Lin, Peter H.; Yao, Qizhi] Baylor Coll Med, Div Vasc Surg & Endovasc Therapy, Michael E DeBakey Dept Surg R413, Mol Surg Res Ctr, Houston, TX 77030 USA. [Chen, Changyi; Lin, Peter H.; Yao, Qizhi] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Chen, CY (reprint author), Baylor Coll Med, Div Vasc Surg & Endovasc Therapy, Michael E DeBakey Dept Surg R413, Mol Surg Res Ctr, 1 Baylor Plaza,Mail Stop BCM390, Houston, TX 77030 USA. EM jchen@bcm.tmc.edu RI Chai, Hong/H-5438-2011 NR 2 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD NOV 1 PY 2009 VL 84 IS 2 BP 336 EP 336 DI 10.1093/cvr/cvp316 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 514VD UT WOS:000271422900022 ER PT J AU Klein, AJ Chen, SJ Messenger, JC Hansgen, AR Plomondon, ME Carroll, JD Casserly, IP AF Klein, Andrew J. Chen, S. James Messenger, John C. Hansgen, Adam R. Plomondon, Mary E. Carroll, John D. Casserly, Ivan P. TI Quantitative Assessment of the Conformational Change in the Femoropopliteal Artery with Leg Movement SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE peripheral vascular disease; superficial femoral artery; popliteal artery ID SUPERFICIAL FEMORAL-ARTERY; SUBINTIMAL ANGIOPLASTY; STENT IMPLANTATION; NATURAL-HISTORY; NITINOL STENTS; KNEE FLEXION; DISEASE; LESIONS; TRIAL; LONG AB Background: The unique physical forces exerted on the femoropopliteal (FP) artery during movement have been implicated in the high rates of restenosis and stent fracture in this artery. Conformational changes in the FP artery during movement are important surrogates of these forces. This study sought to quantify the conformational change in the FP artery between the straight-leg (SL) and crossed-leg (CL) positions. Methods: Using paired angiographic images of overlapping segments of the FP artery in SL and CL positions from patients with peripheral arterial disease, 3-D models of individual segments were generated and subsequently fused to create a 3-D model of the entire FP artery in both leg positions. Based on these 3-D models, the following parameters in the SL and CL positions were quantitatively assessed for the superficial femoral artery (SFA), popliteal artery (PA), and FP artery (i.e., SFA and PA): length, curvature, torsion, twist angle, and development of new flexion angles =15 degrees. Results: In nine male patients with a mean age of 57 +/- 10.2 years, anglography was performed in 10 FP arteries, with successful generation of 3-D models for all vessels. Movement from the SL to the CL position for the SFA, PA, and FP artery was associated with (a) a mean shortening of 18.2 mm (P = 0.002), 32.2 mm (P < 0.001), and 50.3 mm (P < 0.001), respectively; (b) a mean increase in curvature of 0.04 cm(-1) (P = 0.012), 0.2 cm(-1) (P < 0.001), and 0.11 cm(-1) (P < 0.001), respectively; (c) and small absolute changes in mean torsion of 0.034 cm(-1) (P = 0.48), 0.006 cm(-1) (P < 0.001), and 0.057 cm(-1) (P < 0.001), respectively. The same leg movement was associated with a mean twist angle of 45.6 degrees +/- 27.9 degrees (range of 17.4 degrees-103.4 degrees) and 61.1 degrees +/- 31.9 degrees (range of 20.5 degrees-101.1 degrees) for the SFA and PA, respectively. Compared to the SL position, the CL position induced a single flexion point (FxP) =15 degrees in the SFA in two patients, and a mean of 2.4 FxPs =15 degrees (range 1-5) in the PA. Conclusions: Significant changes in length, curvature, and twist occur in the PA and significant but more modest changes in length and twist occur in the SFA during movement from the SL to the CL position. This data has important implications for endovascular therapies that are used to treat disease in the FP artery. (C) 2009 Wiley-Liss, Inc. C1 [Klein, Andrew J.; Chen, S. James; Messenger, John C.; Hansgen, Adam R.; Carroll, John D.; Casserly, Ivan P.] Univ Colorado Hosp, Aurora, CO USA. [Plomondon, Mary E.] Denver VA Med Ctr, Denver, CO USA. RP Casserly, IP (reprint author), Univ Colorado Denver, Anschutz Med Campus,Leprino Off Bldg,12401 E 17th, Aurora, CO 80045 USA. EM ivan.casserly@ucdenver.edu FU Boston Scientific FX Grant sponsor: Boston Scientific. NR 18 TC 39 Z9 41 U1 1 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD NOV 1 PY 2009 VL 74 IS 5 BP 787 EP 798 DI 10.1002/ccd.22124 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 515UD UT WOS:000271497500018 PM 19521998 ER PT J AU Blackiston, DJ McLaughlin, KA Levin, M AF Blackiston, Douglas J. McLaughlin, Kelly A. Levin, Michael TI Bioelectric controls of cell proliferation Ion channels, membrane voltage and the cell cycle SO CELL CYCLE LA English DT Review DE ion channel; ion pump; membrane voltage; electric potential; current; mitosis; growth control ID GATED POTASSIUM CHANNELS; EPIDERMAL-GROWTH-FACTOR; HUMAN PROSTATE-CANCER; X-RAY-MICROANALYSIS; HUMAN T-LYMPHOCYTES; EAG K+ CHANNELS; PERIPHERAL-BLOOD LYMPHOCYTES; LEFT-RIGHT AXIS; A-GO-GO; BREAST-CANCER AB All cells possess long-term, steady-state voltage gradients across the plasma membrane. These transmembrane potentials arise from the combined activity of numerous ion channels, pumps and gap junction complexes. Increasing data from molecular physiology now reveal that the role of changes in membrane voltage controls, and is in turn controlled by, progression through the cell cycle. We review recent functional data on the regulation of mitosis by bioelectric signals, and the function of membrane voltage and specific potassium, sodium and chloride ion channels in the proliferation of embryonic, somatic and neoplastic cells. Its unique properties place this powerful, well-conserved, but still poorly-understood signaling system at the center of the coordinated cellular interactions required for complex pattern formation. Moreover, disregulation of ion channel expression and function is increasingly observed to be not only a useful marker but likely a functional element in oncogenesis. New advances in genomics and the development of in vivo biophysical techniques suggest exciting opportunities for molecular medicine, bioengineering and regenerative approaches to human health. C1 [Blackiston, Douglas J.; McLaughlin, Kelly A.; Levin, Michael] Tufts Univ, Dept Biol, Dana Labs, Medford, MA 02155 USA. [Blackiston, Douglas J.; Levin, Michael] Tufts Univ, Ctr Regenerat & Dev Biol, Medford, MA 02155 USA. [Blackiston, Douglas J.] Forsyth Inst, Dept Regenerat & Dev Biol, Boston, MA USA. RP Levin, M (reprint author), Tufts Univ, Dept Biol, Dana Labs, Medford, MA 02155 USA. EM michael.levin@tufts.edu FU NIH [R01-GM077425, R01-EY018168, R01-GM078484]; Forsyth Institute [5T32DE007327-07]; NSF [IOS-0843355] FX This paper is dedicated to C. D. Cone, who was one of the first to study in detail the profound role of membrane voltage in proliferation control. We are grateful to the members of the Levin lab and the bioelectricity community for many useful discussions. We thank Dany Adams for the photos in Figure 4, and Ai-Sun Tseng for her comments on the manuscript. M. L. is supported by grants R01-GM077425, EY018168 and GM078484 from the NIH. D. B. is supported by Forsyth Institute's T32 grant 5T32DE007327-07. Kelly McLaughlin is supported by NSF grant IOS-0843355. NR 176 TC 47 Z9 49 U1 0 U2 23 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV 1 PY 2009 VL 8 IS 21 BP 3527 EP 3536 DI 10.4161/cc.8.21.9888 PG 10 WC Cell Biology SC Cell Biology GA 525LX UT WOS:000272218600024 PM 19823012 ER PT J AU Hotokezaka, Y van Leyen, K Lo, EH Beatrix, B Katayama, I Jin, G Nakamura, T AF Hotokezaka, Y. van Leyen, K. Lo, E. H. Beatrix, B. Katayama, I. Jin, G. Nakamura, T. TI alpha NAC depletion as an initiator of ER stress-induced apoptosis in hypoxia SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE nascent polypeptide-associated complex; apoptosis; ER stress; glycogen synthase kinase; hypoxia ID POLYPEPTIDE-ASSOCIATED COMPLEX; ENDOPLASMIC-RETICULUM STRESS; UBIQUITIN-PROTEASOME SYSTEM; NEURONAL CELL-DEATH; BETA-NAC; KINASE; BRAIN; PHOSPHORYLATION; IDENTIFICATION; ACTIVATION AB Accumulation of unfolded proteins triggers endoplasmic reticulum (ER) stress and is considered a part of the cellular responses to hypoxia. The nascent polypeptide-associated complex (NAC) participates in the proper maturation of newly synthesized proteins. However, thus far, there have been no comprehensive studies on NAC involvement in hypoxic stress. Here, we show that hypoxia activates glycogen synthase kinase-3 beta (GSK-3 beta) and that the activated GSK-3 beta destabilizes alpha NAC with the subsequent apoptosis of the cell. Hypoxia of various cell types and the mouse ischemic brain was associated with rapid downregulation of alpha NAC and ER stress responses involving PERK, ATF4, gamma-taxilin, elF2 alpha, Bip, and CHOP. Depletion of alpha NAC by RNA interference specifically activated ER stress responses and caused mitochondrial dysfunction, which resulted in apoptosis through caspase activation. Interestingly, we found that the hypoxic conditions activated GSK-3 beta, and that GSK-3 beta inhibition prevented alpha NAC protein downregulation in hypoxic cells and rescued the cells from apoptosis. In addition, alpha NAC overexpression increased the viability of hypoxic cells. Taken together, these results suggest that alpha NAC degradation triggers ER stress responses and initiates apoptotic processes in hypoxic cells, and that GSK-3 beta may participate upstream in this mechanism. Cell Death and Differentiation (2009) 16, 1505-1514; doi:10.1038/cdd.2009.90; published online 17 July 2009 C1 [Hotokezaka, Y.; Katayama, I.; Nakamura, T.] Nagasaki Univ, Sch Dent, Dept Radiol & Canc Biol, Nagasaki 8528588, Japan. [van Leyen, K.; Lo, E. H.; Jin, G.] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. [van Leyen, K.; Lo, E. H.; Jin, G.] Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. [van Leyen, K.; Lo, E. H.; Jin, G.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Beatrix, B.] Univ Munich, Dept Chem & Biochem, Gene Ctr, LMU, D-81377 Munich, Germany. RP Nakamura, T (reprint author), Nagasaki Univ, Sch Dent, Dept Radiol & Canc Biol, 1-7-1 Sakamoto, Nagasaki 8528588, Japan. EM taku@nagasaki-u.ac.jp RI van Leyen, Klaus/C-9126-2013 NR 46 TC 23 Z9 23 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD NOV PY 2009 VL 16 IS 11 BP 1505 EP 1514 DI 10.1038/cdd.2009.90 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 505GE UT WOS:000270679000009 PM 19609276 ER PT J AU Schon, K Quiroz, YT Hasselmo, ME Stern, CE AF Schon, Karin Quiroz, Yakeel T. Hasselmo, Michael E. Stern, Chantal E. TI Greater Working Memory Load Results in Greater Medial Temporal Activity at Retrieval SO CEREBRAL CORTEX LA English DT Review DE delayed match to sample; episodic memory; hippocampus; neuroimaging; subiculum ID SHORT-TERM-MEMORY; DORSOLATERAL PREFRONTAL CORTEX; MONKEY RETROSPLENIAL CORTEX; GRADED PERSISTENT ACTIVITY; LATERAL FRONTAL-CORTEX; EVENT-RELATED FMRI; ENTORHINAL CORTEX; EPISODIC MEMORY; RHESUS-MONKEY; MACAQUE MONKEY AB Most functional magnetic resonance imaging (fMRI) studies examining working memory (WM) load have focused on the prefrontal cortex (PFC) and have demonstrated increased prefrontal activity with increased load. Here we examined WM load effects in the medial temporal lobe (MTL) using an fMRI Sternberg task with novel complex visual scenes. Trials consisted of 3 sequential events: 1) sample presentation (encoding), 2) delay period (maintenance), and 3) probe period (retrieval). During sample encoding, subjects saw either 2 or 4 pictures consecutively. During retrieval, subjects indicated whether the probe picture matched one of the sample pictures. Results revealed that activity in the left anterior hippocampal formation, bilateral retrosplenial area, and left amygdala was greater at retrieval for trials with larger memory load, whereas activity in the PFC was greater at encoding for trials with larger memory load. There was no load effect during the delay. When encoding, maintenance, and retrieval periods were compared with fixation, activity was present in the hippocampal body/tail and fusiform gyrus bilaterally during encoding and retrieval, but not maintenance. Bilateral dorsolateral prefrontal activity was present during maintenance, but not during encoding or retrieval. The results support models of WM predicting that activity in the MTL should be modulated by WM load. C1 [Schon, Karin; Quiroz, Yakeel T.; Hasselmo, Michael E.; Stern, Chantal E.] Boston Univ, Ctr Memory & Brain, Boston, MA 02215 USA. [Schon, Karin; Quiroz, Yakeel T.; Hasselmo, Michael E.; Stern, Chantal E.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Schon, Karin; Quiroz, Yakeel T.; Hasselmo, Michael E.; Stern, Chantal E.] Boston Univ, Ctr Excellence Learing Educ Sci & Technol, Boston, MA 02215 USA. [Stern, Chantal E.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. RP Schon, K (reprint author), Boston Univ, Ctr Memory & Brain, 2 Cummington St,Suite 109, Boston, MA 02215 USA. EM kschon@bu.edu OI Schon, Karin/0000-0003-2963-8449; Hasselmo, Michael/0000-0002-9925-6377 FU National Science Foundation [SBE-0354278]; National Institutes of Health [P50 MH071702-01]; National Center for Research Resources [P41RR14075]; Mental Illness and Neuroscience Discovery Institute FX National Science Foundation grant (SBE-0354278); National Institutes of Health grants (P50 MH071702-01, National Center for Research Resources P41RR14075); Mental Illness and Neuroscience Discovery Institute. NR 111 TC 39 Z9 39 U1 2 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD NOV PY 2009 VL 19 IS 11 BP 2561 EP 2571 DI 10.1093/cercor/bhp006 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 505IJ UT WOS:000270685900006 PM 19224975 ER PT J AU Panizzon, MS Fennema-Notestine, C Eyler, LT Jernigan, TL Prom-Wormley, E Neale, M Jacobson, K Lyons, MJ Grant, MD Franz, CE Xian, H Tsuang, M Fischl, B Seidman, L Dale, A Kremen, WS AF Panizzon, Matthew S. Fennema-Notestine, Christine Eyler, Lisa T. Jernigan, Terry L. Prom-Wormley, Elizabeth Neale, Michael Jacobson, Kristen Lyons, Michael J. Grant, Michael D. Franz, Carol E. Xian, Hong Tsuang, Ming Fischl, Bruce Seidman, Larry Dale, Anders Kremen, William S. TI Distinct Genetic Influences on Cortical Surface Area and Cortical Thickness SO CEREBRAL CORTEX LA English DT Article DE cortical volume; genetic correlation; heritability; magnetic resonance imaging; twin study ID VIETNAM ERA TWIN; REGIONAL BRAIN VOLUMES; HUMAN CEREBRAL-CORTEX; SCHIZOPHRENIA; REGISTRY; METAANALYSIS; ZYGOSITY; AGE; INTELLIGENCE; ORGANIZATION AB Neuroimaging studies examining the effects of aging and neuropsychiatric disorders on the cerebral cortex have largely been based on measures of cortical volume. Given that cortical volume is a product of thickness and surface area, it is plausible that measures of volume capture at least 2 distinct sets of genetic influences. The present study aims to examine the genetic relationships between measures of cortical surface area and thickness. Participants were men in the Vietnam Era Twin Study of Aging (110 monozygotic pairs and 92 dizygotic pairs). Mean age was 55.8 years (range: 51-59). Bivariate twin analyses were utilized in order to estimate the heritability of cortical surface area and thickness, as well as their degree of genetic overlap. Total cortical surface area and average cortical thickness were both highly heritable (0.89 and 0.81, respectively) but were essentially unrelated genetically (genetic correlation = 0.08). This pattern was similar at the lobar and regional levels of analysis. These results demonstrate that cortical volume measures combine at least 2 distinct sources of genetic influences. We conclude that using volume in a genetically informative study, or as an endophenotype for a disorder, may confound the underlying genetic architecture of brain structure. C1 [Panizzon, Matthew S.; Fennema-Notestine, Christine; Eyler, Lisa T.; Jernigan, Terry L.; Franz, Carol E.; Tsuang, Ming; Dale, Anders; Kremen, William S.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Fennema-Notestine, Christine; Jernigan, Terry L.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Eyler, Lisa T.; Kremen, William S.] San Diego Vet Adm Hlth Care Syst, San Diego, CA 92161 USA. [Prom-Wormley, Elizabeth; Neale, Michael] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Sch Med, Richmond, VA 23219 USA. [Jacobson, Kristen] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. [Lyons, Michael J.; Grant, Michael D.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Xian, Hong] Washington Univ, Dept Psychiat, Sch Med, St Louis, MO 63130 USA. [Tsuang, Ming; Kremen, William S.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA. [Tsuang, Ming] Harvard Univ, Sch Med, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. [Fischl, Bruce] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. [Seidman, Larry] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Dale, Anders] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Tsuang, Ming] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Panizzon, MS (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr MC 0738, La Jolla, CA 92093 USA. EM mspanizz@ucsd.edu RI Jacobson, Kristen/D-2064-2009; Dale, Anders/A-5180-2010; Lyons, Michael/B-6119-2011; OI Prom-Wormley, Elizabeth/0000-0001-9230-9723; Lyons, Michael/0000-0001-6516-9219; Fennema-Notestine, Christine/0000-0002-6527-6361 FU National Institutes of Health/National Institute on Aging [U24 RR021382, R01 AG18386, RO1 AG18384, RO1 AG22381, RO1 AG 22982]; US Department of Veterans Affairs; VA Cooperative Studies Program; Department of Defense; National Personnel Records Center, National Archives, and Records Administration; Internal Revenue Service; National Opinion Research Center; National Research Council, National Academy of Sciences; Institute for Survey Research, Temple University; Schulman, Ronca, and Bucuvalas, Inc FX National Institutes of Health/National Institute on Aging Grants U24 RR021382, R01 AG18386, RO1 AG18384, RO1 AG22381, RO1 AG 22982; US Department of Veterans Affairs; VA Cooperative Studies Program; Department of Defense; National Personnel Records Center, National Archives, and Records Administration; Internal Revenue Service; National Opinion Research Center; National Research Council, National Academy of Sciences; Institute for Survey Research, Temple University; Schulman, Ronca, and Bucuvalas, Inc. NR 54 TC 371 Z9 374 U1 0 U2 22 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD NOV PY 2009 VL 19 IS 11 BP 2728 EP 2735 DI 10.1093/cercor/bhp026 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 505IJ UT WOS:000270685900022 PM 19299253 ER PT J AU Solis, J McCarty, D Levine, RA Handschumacher, MD Fernandez-Friera, L Chen-Tournoux, A Mont, L Vidal, B Singh, JP Brugada, J Picard, MH Sitges, M Hung, J AF Solis, Jorge McCarty, David Levine, Robert A. Handschumacher, Mark D. Fernandez-Friera, Leticia Chen-Tournoux, Annabel Mont, Luis Vidal, Barbara Singh, Jagmeet P. Brugada, Josep Picard, Michael H. Sitges, Marta Hung, Judy TI Mechanism of Decrease in Mitral Regurgitation After Cardiac Resynchronization Therapy Optimization of the Force-Balance Relationship SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE functional mitral regurgitation; 3D echocardiography; cardiac resynchronization therapy ID CHRONIC HEART-FAILURE; ORIFICE AREA; VENTRICULAR VOLUME; FLOW; INSIGHTS; ECHOCARDIOGRAPHY; DYSSYNCHRONY; VALIDATION; PREDICTORS; SIZE AB Background-Cardiac resynchronization therapy (CRT) has been shown to reduce functional mitral regurgitation (MR). It has been proposed that the mechanism of MR reduction relates to geometric change or, alternatively, changes in left ventricular (LV) contractile function. Normal mitral valve (MV) function relies on a balance between tethering and closing forces on the MV leaflets. Functional MR results from a derangement of this force-balance relationship, and CRT may be an important modulator of MV function by its ability to enhance the force-balance relationship on the MV. We hypothesized that CRT improves the comprehensive force balance acting on the valve, including favorable changes in both geometry and LV contractile function. Methods and Results-We examined the effect of CRT on 34 patients with functional MR before and after CRT (209 +/- 81 days). MR regurgitant volume, closing forces on MV (derived from Doppler transmitral pressure gradients), including dP/dt and a factor (closing pressure ratio) expressing how long the peak closing gradient is maintained over systole (closing pressure ratio = velocity time integral/MR peak velocity x mitral regurgitation time), and dyssynchrony by tissue Doppler were measured. End-diastolic volume, end-systolic volume, mitral valve annular area (MAA) and contraction (percent change in MAA from end-diastole to midsystole), leaflet closing area (leaflet area during valve closure), and tenting volume (volume under leaflets to annular plane) were measured by 3D echocardiography. After CRT, end-diastolic volume (253 +/- 111 versus 221 +/- 110 mL, P < 0.001) and end-systolic volume (206 +/- 97 versus 167 +/- 91 mL, P < 0.001) decreased and ejection fraction (19 +/- 6 versus 27 +/- 9%, P < 0.001) increased. MR regurgitant volume decreased from 35 +/- 17 to 23 +/- 14 mL (P < 0.001), MAA from 11.6 +/- 3.5 to 10.5 +/- 3.1 cm(2) (P < 0.001), leaflet closing area from 15.4 +/- 5 to 13.7 +/- 3.8 cm(2) (P < 0.001), and tenting volume from 5.7 +/- 2.6 to 4.6 +/- 2.2 mL (P < 0.001). Peak velocity (and therefore transmitral closing pressure) was more sustained throughout systole, as reflected by the increase in the closing pressure ratio (0.77 +/- 0.1 versus 0.84 +/- 0.1 before CRT versus after CRT, P = 0.01); dP/dt also improved after CRT. There was no change in dyssynchrony or MAA contraction. Conclusions-Reduction in MR after CRT is associated with favorable changes in MV geometry and closing forces on the MV. It does so by favorably affecting the force balance acting on the MV in 2 ways: reducing tethering through reversal of LV remodeling and increasing the systolic duration of peak transmitral closing pressures. (Circ Cardiovasc Imaging. 2009; 2: 444-450.) C1 [Hung, Judy] Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Mont, Luis; Vidal, Barbara; Brugada, Josep; Sitges, Marta] Univ Barcelona, Dept Cardiol, Thorax Clin Inst, Hosp Clin IDIBAPS,IDIBAPS Inst Invest Biomed Augu, E-08007 Barcelona, Spain. RP Hung, J (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Blake 256,55 Fruit St, Boston, MA 02114 USA. EM jhung@partners.org RI Fernandez Friera, Leticia /E-9931-2015; OI Fernandez Friera, Leticia /0000-0002-4237-2166; BRUGADA, JOSEP/0000-0002-5662-8302; Picard, Michael/0000-0002-9264-3243 FU National Institutes of Health/National Institute for Biomedical Imaging and Bioengineering [R21 EB005294]; American Society of Echocardiography Career Development Award; Spanish Society of Cardiology; St Jude Medical; Medtronic; Boston Scientific; Biotronix; Sorin; Philips Medical Systems FX Dr Singh is a consultant and recipient of research grants and speaking fees for the following companies: St Jude Medical, Medtronic, Boston Scientific, Biotronix, Sorin, and Philips Medical Systems. NR 34 TC 27 Z9 29 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD NOV PY 2009 VL 2 IS 6 BP 444 EP 450 DI 10.1161/CIRCIMAGING.108.823732 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 521BX UT WOS:000271895300004 PM 19920042 ER PT J AU Sosnovik, DE Garanger, E Aikawa, E Nahrendorf, M Figuiredo, JL Dai, GP Reynolds, F Rosenzweig, A Weissleder, R Josephson, L AF Sosnovik, David E. Garanger, Elisabeth Aikawa, Elena Nahrendorf, Matthias Figuiredo, Jose-Luiz Dai, Guangping Reynolds, Fred Rosenzweig, Anthony Weissleder, Ralph Josephson, Lee TI Molecular MRI of Cardiomyocyte Apoptosis With Simultaneous Delayed-Enhancement MRI Distinguishes Apoptotic and Necrotic Myocytes In Vivo Potential for Midmyocardial Salvage in Acute Ischemia SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE molecular imaging; MRI; apoptosis; myocardium; ischemia ID ACUTE MYOCARDIAL-INFARCTION; IRON-OXIDE PARTICLES; MAGNETIC-RESONANCE; CELL-DEATH; MICROVASCULAR OBSTRUCTION; CONTRAST AGENTS; FIELD-STRENGTH; ANNEXIN-V; INJURY; VISUALIZATION AB Background-A novel dual-contrast molecular MRI technique to image both cardiomyocyte apoptosis and necrosis in vivo within 4 to 6 hours of ischemia is presented. The technique uses the annexin-based nanoparticle AnxCLIO-Cy5.5 (apoptosis) and simultaneous delayed-enhancement imaging with a novel gadolinium chelate, Gd-DTPA-NBD (necrosis). Methods and Results-Mice with transient coronary ligation were injected intravenously at the onset of reperfusion with AnxCLIO-Cy5.5 (n = 7) or the control probe Inact_CLIO-Cy5.5 (n = 6). T2*-weighted MR images (9.4 T) were acquired within 4 to 6 hours of reperfusion. The contrast-to-noise ratio between injured and uninjured myocardium was measured. The mice were then injected with Gd-DTPA-NBD, and delayed-enhancement imaging was performed within 10 to 30 minutes. Uptake of AnxCLIO-Cy5.5 was most prominent in the midmyocardium and was significantly greater than that of Inact_CLIO-Cy5.5 (contrast-to-noise ratio, 8.82 +/- 1.5 versus 3.78 +/- 1.1; P < 0.05). Only 21 +/- 3% of the myocardium with accumulation of AnxCLIO-Cy5.5 showed delayed-enhancement of Gd-DTPA-NBD. Wall thickening was significantly reduced in segments with delayed enhancement and/or transmural accumulation of AnxCLIO-Cy5.5 (P < 0.001). Fluorescence microscopy of AnxCLIO-Cy5.5 and immunohistochemistry of Gd-DTPA-NBD confirmed the presence of large numbers of apoptotic but potentially viable cardiomyocytes (AnxCLIO-Cy5.5 positive, Gd-DTPA-NBD negative) in the midmyocardium. Conclusions-A novel technique to image cardiomyocyte apoptosis and necrosis in vivo within 4 to 6 hours of injury is presented and reveals large areas of apoptotic but viable myocardium in the midmyocardium. Strategies to salvage the numerous apoptotic but potentially viable cardiomyocytes in the midmyocardium in acute ischemia should be investigated. (Circ Cardiovasc Imaging. 2009; 2: 460-467.) C1 [Sosnovik, David E.; Garanger, Elisabeth; Aikawa, Elena; Nahrendorf, Matthias; Figuiredo, Jose-Luiz; Reynolds, Fred; Weissleder, Ralph; Josephson, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. [Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Sosnovik, David E.; Dai, Guangping] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA. [Nahrendorf, Matthias; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Rosenzweig, Anthony] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Cardiovasc Inst, Boston, MA 02215 USA. RP Sosnovik, DE (reprint author), 5416 CMIR,149 13th St, Charlestown, MA 02129 USA. EM sosnovik@nmr.mgh.harvard.edu FU National Institutes of Health [R01-HL093038, K08-HL079984, AHA 0835623D, HL-080731, HL-078641, CA-92782, CA-86355, R01EB004472] FX This study was supported in part by the following grants from the National Institutes of Health: R01-HL093038 and K08-HL079984 (D. E. S.), AHA 0835623D (M. N.), HL-080731, HL-078641, CA-92782, and CA-86355 (R. W.), and R01EB004472 (L. J.). NR 30 TC 49 Z9 53 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD NOV PY 2009 VL 2 IS 6 BP 460 EP 467 DI 10.1161/CIRCIMAGING.109.859678 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 521BX UT WOS:000271895300006 PM 19920044 ER PT J AU Sosnovik, DE Nahrendorf, M Panizzi, P Matsui, T Aikawa, E Dai, GP Li, L Reynolds, F Dorn, GW Weissleder, R Josephson, L Rosenzweig, A AF Sosnovik, David E. Nahrendorf, Matthias Panizzi, Peter Matsui, Takashi Aikawa, Elena Dai, Guangping Li, Ling Reynolds, Fred Dorn, Gerald W., II Weissleder, Ralph Josephson, Lee Rosenzweig, Anthony TI Molecular MRI Detects Low Levels of Cardiomyocyte Apoptosis in a Transgenic Model of Chronic Heart Failure SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE apoptosis; heart failure; MRI; molecular imaging; cardiomyocyte ID CARDIAC MYOCYTE APOPTOSIS; NONINVASIVE DETECTION; MEMBRANE PHOSPHATIDYLSERINE; MYOCARDIAL-INFARCTION; ANNEXIN A5; IN-VIVO; INHIBITION; ACTIVATION; DEATH; ATHEROSCLEROSIS AB Background-The ability to image cardiomyocyte (CM) apoptosis in heart failure could facilitate more accurate diagnostics and optimize targeted therapeutics. We thus aimed to develop a platform to image CM apoptosis quantitatively and specifically in heart failure in vivo. The myocardium in heart failure, however, is characterized by very low levels of CM apoptosis and normal vascular permeability, factors thought to preclude the use of molecular MRI. Methods and Results-Female mice with overexpression of Gaq were studied. Two weeks postpartum, these mice develop a cardiomyopathy characterized by low levels of CM apoptosis and minimal myocardial necrosis or inflammation. The mice were injected with the annexin-labeled nanoparticle (AnxCLIO-Cy5.5) or a control probe (CLIO-Cy5.5) and imaged in vivo at 9.4 T. Uptake of AnxCLIO-Cy5.5 occurred in isolated clusters, frequently in the subendocardium. Myocardial T2* was significantly lower (7.6 +/- 1.5 versus 16.8 +/- 2.7 ms, P < 0.05) in the mice injected with AnxCLIO-Cy5.5 versus CLIO-Cy5.5, consistent with the uptake of AnxCLIO-Cy5.5 by apoptotic CMs. A strong correlation (r(2) = 0.86, P < 0.05) was seen between in vivo T2* (AnxCLIO-Cy5.5 uptake) and myocardial caspase-3 activity. Conclusions-The ability of molecular MRI to image sparsely expressed targets in the myocardium is demonstrated in this study. Moreover, a novel platform for high-resolution and specific imaging of CM apoptosis in heart failure is established. In addition to providing novel insights into the pathogenesis of CM apoptosis, the developed platform could facilitate the development of novel antiapoptotic therapies in heart failure. (Circ Cardiovasc Imaging. 2009; 2: 468-475.) C1 [Sosnovik, David E.; Nahrendorf, Matthias; Panizzi, Peter; Aikawa, Elena; Reynolds, Fred; Weissleder, Ralph; Josephson, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. [Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Sosnovik, David E.; Dai, Guangping] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA. [Matsui, Takashi; Li, Ling; Rosenzweig, Anthony] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Cardiovasc Inst, Boston, MA 02215 USA. [Dorn, Gerald W., II] Washington Univ, Sch Med, Ctr Pharmacogenom, St Louis, MO USA. RP Sosnovik, DE (reprint author), 5416,149 13th St, Charlestown, MA 02129 USA. EM sosnovik@nmr.mgh.harvard.edu OI Panizzi, Peter/0000-0003-0141-8807 FU National Institutes of Health [R01 HL093038, K08 HL079984, R01EB004472, CA92782, CA86355, HL073363, HL077543, HL059521]; Leducq Network of Research Excellence Award FX This study was supported in part by the following grants from the National Institutes of Health: R01 HL093038 and K08 HL079984 (Dr Sosnovik); R01EB004472 (Dr Josephson); CA92782 and CA86355 (Dr Weissleder); and HL073363, HL077543, and HL059521 (Dr Rosenzweig); and a Leducq Network of Research Excellence Award (Dr Rosenzweig). NR 37 TC 30 Z9 31 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD NOV PY 2009 VL 2 IS 6 BP 468 EP 475 DI 10.1161/CIRCIMAGING.109.863779 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 521BX UT WOS:000271895300007 PM 19920045 ER PT J AU Bradley, SM Levy, WC Veenstra, DL AF Bradley, Steven M. Levy, Wayne C. Veenstra, David L. TI Cost-Consequences of Ultrafiltration for Acute Heart Failure A Decision Model Analysis SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE heart failure; ultrafiltration; diuretics; costs and cost analysis ID HEPARIN-INDUCED THROMBOCYTOPENIA; MOLECULAR-WEIGHT HEPARIN; CONTINUOUS VENOVENOUS HEMOFILTRATION; DISEASE MANAGEMENT PROGRAMS; BLOOD-STREAM INFECTIONS; UNFRACTIONATED HEPARIN; HOSPITALIZED-PATIENTS; READMISSION RATES; CONTROLLED-TRIAL; OLDER PATIENTS AB Background-Ultrafiltration for heart failure may reduce costs associated with acute heart failure by decreasing rehospitalization rates compared to intravenous diuretics. Methods and Results-We developed a decision-analytic model to explore the clinical outcomes and associated costs of ultrafiltration compared to intravenous diuretics for index and subsequent acute heart failure hospitalizations to 90 days from index hospitalization. We evaluated the model from societal, Medicare, and hospital payer perspectives. Base-case probabilities and costs were derived from the Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Congestive Heart Failure clinical trial, Medicare reimbursement schedules, and published data. From a societal perspective, treatment with ultrafiltration had an 86% probability of being more expensive than intravenous diuretics in probabilistic sensitivity analysis, with a base-case estimate of $13 469 per patient treated with ultrafiltration compared to $11 610 per patient treated with intravenous diuretics. Cost estimates were most influenced by length of index hospitalization, daily cost of rehospitalization, number of days rehospitalized, and number and cost of ultrafiltration filters. From a Medicare payer perspective, ultrafiltration had a >99% probability of being cost saving. From a hospital perspective, there was a 97% probability ultrafiltration was more expensive. Our model suggested similar 90-day mortality rates between treatment arms. Conclusion-Despite a reduction in rehospitalization rates, it is unlikely ultrafiltration results in cost savings from a societal perspective. The discordance in cost between societal, Medicare, and hospital perspectives underscores the importance of payer perspective in formulating strategies and reimbursement structures to reduce heart failure hospitalizations. (Circ Cardiovasc Qual Outcomes. 2009; 2: 566-573.) C1 [Bradley, Steven M.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Dept Vet Affairs, Seattle, WA 98101 USA. [Bradley, Steven M.; Levy, Wayne C.] Univ Washington, Dept Med, Div Cardiol, Seattle, WA USA. [Veenstra, David L.] Univ Washington, Dept Pharm, Pharmaceut Outcomes Res & Policy Program, Seattle, WA 98195 USA. RP Bradley, SM (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Dept Vet Affairs, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM Steve.Bradley@va.gov FU Department of Veterans Affairs; Veterans Health Administration; Office of Research and Development; Health Services Research and Development FX This material is based on work supported by the Department of Veterans Affairs, the Veterans Health Administration, the Office of Research and Development, and Health Services Research and Development. NR 47 TC 22 Z9 23 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD NOV PY 2009 VL 2 IS 6 BP 566 EP U99 DI 10.1161/CIRCOUTCOMES.109.853556 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575PD UT WOS:000276078500009 PM 20031894 ER PT J AU Rose, AJ Ozonoff, A Grant, RW Henault, LE Hylek, EM AF Rose, Adam J. Ozonoff, Al Grant, Richard W. Henault, Lori E. Hylek, Elaine M. TI Epidemiology of Subtherapeutic Anticoagulation in the United States SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE warfarin; thromboembolism; anticoagulants; quality of health care; medication therapy management ID INTERNATIONAL NORMALIZED RATIO; ATRIAL-FIBRILLATION; BLEEDING COMPLICATIONS; ORAL ANTICOAGULANT; WARFARIN THERAPY; RISK-FACTORS; EXCESSIVE ANTICOAGULATION; HEMORRHAGE; THROMBOEMBOLISM; OUTPATIENTS AB Background-Low international normalized ratio (INR; <= 1.5) increases risk for thromboembolism. However, little is known about the epidemiology of low INR. Methods and Results-We prospectively collected data from 47 community-based clinics located throughout the United States from 2000 to 2002. We examined risk factors for low INR (<= 1.5), reasons given in the medical record for low INR, and proportion of thromboembolic events that occurred during periods of low INR. Of the 4489 patients in our database, 1540 (34%) had at least 1 low INR. Compared with men, women had an increased incidence of low INR (adjusted incidence rate ratio, 1.44; P<0.001). Compared with patients anticoagulated for atrial fibrillation, patients anticoagulated for venous thromboembolism had an increased incidence of low INR (adjusted incidence rate ratio, 1.48; P<0.001). The 5 most common reasons for low INR were nonadherence (17%), interruptions for procedures (16%), recent dose reductions (15%), no reason apparent after questioning (15%), and second or greater consecutive low INR (13%). A total of 21.8% of thromboembolic events (95% CI, 12.2 to 35.4%) occurred during periods of low INR; 58% of these events were related to an interruption of warfarin therapy. Conclusions-In this cohort of patients receiving warfarin, more than 1 in 5 thromboembolic events occurred during a period of low INR. Women and patients anticoagulated for venous thromboembolism were particularly likely to experience low INR. Improving adherence, minimizing interruptions of therapy, and addressing low INR more promptly could reduce the risk of low INR. (Circ Cardiovasc Qual Outcomes. 2009;2:591-597.) C1 [Rose, Adam J.; Ozonoff, Al] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. [Rose, Adam J.; Henault, Lori E.; Hylek, Elaine M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Ozonoff, Al] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. [Grant, Richard W.] Massachusetts Gen Hosp, Dept Med, Clin Epidemiol Unit, Dept Med,Gen Med Div, Boston, MA 02114 USA. RP Rose, AJ (reprint author), Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd,Bldg 70, Bedford, MA 01730 USA. EM adamrose@bu.edu OI Ozonoff, Al/0000-0003-4233-5899; Grant, Richard/0000-0002-6164-8025 FU Bristol-Myers Squibb; makers of Coumadin brand warfarin; Department of Veterans Affairs Health Services Research and Development Service; NIDDK [K23 DK067452]; Boehringer Ingelheim; Bayer FX This study was funded by Bristol-Myers Squibb, the makers of Coumadin brand warfarin. Bristol-Myers Squibb had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, and approval of the manuscript. Dr Rose is supported by a career development award from the Department of Veterans Affairs Health Services Research and Development Service. Dr Grant is supported by an NIDDK career development award (K23 DK067452). The opinions expressed in this manuscript do not necessarily represent the views or policies of the Department of Veterans Affairs.; Dr Rose has received research funding from Boehringer Ingelheim to study warfarin utilization in the Veterans Affairs Health System. Dr Hylek has served as an advisor to Boehringer Ingelheim, Bristol-Myers Squibb, Sanofi-Aventis, and The Medicines Company and participated in a clinical symposium sponsored by Bayer and Bristol-Myers Squibb. NR 35 TC 30 Z9 31 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD NOV PY 2009 VL 2 IS 6 BP 591 EP 597 DI 10.1161/CIRCOUTCOMES.109.862763 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575PD UT WOS:000276078500012 PM 20031897 ER PT J AU Lewis, WR Ellrodt, AG Peterson, E Hernandez, AF LaBresh, KA Cannon, CP Pan, WQ Fonarow, GC AF Lewis, William R. Ellrodt, A. Gray Peterson, Eric Hernandez, Adrian F. LaBresh, Kenneth A. Cannon, Christopher P. Pan, Wenqin Fonarow, Gregg C. TI Trends in the Use of Evidence-Based Treatments for Coronary Artery Disease Among Women and the Elderly Findings From the Get With the Guidelines Quality-Improvement Program SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE quality control; coronary artery disease; age factors; sex ID ACUTE MYOCARDIAL-INFARCTION; LIPID-LOWERING THERAPY; RANDOMIZED TRIALS; OLDER PATIENTS; UNITED-STATES; CARE; MORTALITY; AGE AB Background-Significant disparities have been reported in the application of evidence-based guidelines in the treatment of coronary artery disease (CAD) in women and the elderly. We hypothesized that participation in a quality-improvement program could improve care for all patients and thus narrow treatment gaps over time. Methods and Results-Treatment of 237 225 patients hospitalized with CAD was evaluated in the Get With the Guidelines-CAD program from 2002 to 2007. Six quality measures were evaluated in eligible patients without contraindications: aspirin on admission and discharge, beta-blockers use at discharge, angiotensin-converting enzyme inhibitor or angiotensin receptor antagonist use, lipid-lowering medication use, and tobacco cessation counseling along with other care metrics. Over time, composite adherence on these 6 measures increased from 86.5% to 97.4% (+10.9%) in men and 84.8% to 96.2% (+11.4%) in women. There was a slight difference in composite adherence by sex that remained significant over time (P<0.0001), but this was confined to patients <75 years. Composite adherence in younger patients (<75 years) increased from 87.1% to 97.7% (+10.6%) and from 83.0% to 95.1% (+12.1%) in the elderly (>= 75 years) over time. Conclusions-Among hospitals participating in Get With the Guidelines-CAD, guideline adherence has improved substantially over time for both women and men and younger and older CAD patients, with only slight age and sex differences in some measures persisting. (Circ Cardiovasc Qual Outcomes. 2009;2:633-641.) C1 [Lewis, William R.] Case Western Reserve Univ, Clin Cardiol Heart & Vasc Ctr, Cleveland, OH 44109 USA. [Ellrodt, A. Gray] Berkshire Med Ctr, Pittsfield, MA USA. [Peterson, Eric; Hernandez, Adrian F.; Pan, Wenqin] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [LaBresh, Kenneth A.] Res Triangle Inst Int, Waltham, MA USA. [Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Lewis, WR (reprint author), Case Western Reserve Univ, Clin Cardiol Heart & Vasc Ctr, MetroHlth Campus,2500 MetroHlth Dr,Hamman 350, Cleveland, OH 44109 USA. EM wlewis@metrohealth.org RI LaBresh, Kenneth/A-6995-2017; Hernandez, Adrian F./A-7818-2016 OI LaBresh, Kenneth/0000-0001-9040-1956; Hernandez, Adrian F./0000-0003-3387-9616 FU American Heart Association; Schering Plough/Merck; BMS/Sanofi; Johnson Johnson/Scios; GlaxoSmithKline; Medtronic; Novartis; AstraZeneca; Accumetrics; Bristol-Myers Squibb/Sanofi; Merck; Merck/Schering Plough; Pfizer; Schering FX This study was funded by the American Heart Association.; Dr Lewis has received speaker honoraria from Reliant Pharmaceuticals and has served as a consultant for Medtronic. Dr Peterson has received research funding from Schering Plough/Merck and BMS/Sanofi. Dr Hernandez has received research funding and/or honoraria from Johnson & Johnson/Scios, GlaxoSmithKline, Medtronic, Novartis, and AstraZeneca. Dr LaBresh is an employee of Research Triangle Institute International. Dr Cannon has received research funding from Accumetrics, AstraZeneca, Bristol-Myers Squibb/Sanofi Partnership, GlaxoSmithKline, Merck, Merck/Schering Plough Partnership and has ownership interest in Automedics Medical Systems. Dr Fonarow has received research funding and honoraria from and served as a consultant for Medtronic, GlaxoSmithKline, and Novartis; has received other research support from Pfizer; and has served as a consultant for and received honoraria from BMS/Sanofi, Merck, and Schering. NR 21 TC 44 Z9 44 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD NOV PY 2009 VL 2 IS 6 BP 633 EP U191 DI 10.1161/CIRCOUTCOMES.108.824763 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575PD UT WOS:000276078500017 PM 20031902 ER PT J AU Spatz, ES Ross, JS AF Spatz, Erica S. Ross, Joseph S. TI Mis-SHAPEing Public Health Policy SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Editorial Material DE atherosclerosis; imaging; prevention; legislative mandates ID CARE; BENEFICIARIES; GUIDELINES; MEDICARE; SERVICES C1 [Spatz, Erica S.] Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06520 USA. [Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. [Ross, Joseph S.] James J Peters VA Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, Bronx, NY USA. [Ross, Joseph S.] James J Peters VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. RP Spatz, ES (reprint author), Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, IE 61,333 Cedar St, New Haven, CT 06520 USA. EM erica.spatz@yale.edu FU NIA NIH HHS [K08 AG032886, K08 AG032886-01] NR 15 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD NOV PY 2009 VL 2 IS 6 BP 681 EP 683 DI 10.1161/CIRCOUTCOMES.109.890715 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575PD UT WOS:000276078500024 PM 20031909 ER PT J AU Jensen, BC Swigart, PM De Marco, T Hoopes, C Simpson, PC AF Jensen, Brian C. Swigart, Philip M. De Marco, Teresa Hoopes, Charles Simpson, Paul C. TI alpha 1-Adrenergic Receptor Subtypes in Nonfailing and Failing Human Myocardium SO CIRCULATION-HEART FAILURE LA English DT Article DE receptors, adrenergic, alpha; receptors, adrenergic, beta; heart failure; myocardium ID SUSTAINED-RELEASE MOXONIDINE; ARTERIAL BLOOD-PRESSURE; ALPHA(1B)-ADRENERGIC RECEPTOR; HEART-FAILURE; ALPHA(1)-ADRENERGIC RECEPTORS; DILATED CARDIOMYOPATHY; CARDIAC-HYPERTROPHY; TRANSGENIC MICE; ADRENERGIC-RECEPTORS; GENE-EXPRESSION AB Background-alpha 1-adrenergic receptors (alpha 1-ARs) play adaptive roles in the heart and protect against the development of heart failure. The 3 alpha 1-AR subtypes, alpha 1A, alpha 1B, and alpha 1D, have distinct physiological roles in mouse heart, but very little is known about alpha 1 subtypes in human heart. Here, we test the hypothesis that the alpha 1A and alpha 1B subtypes are present in human myocardium, similar to the mouse, and are not downregulated in heart failure. Methods and Results-Hearts from transplant recipients and unused donors were failing (n = 12; mean ejection fraction, 24%) or nonfailing (n = 9; mean ejection fraction, 59%) and similar in age (approximate to 44 years) and sex (approximate to 70% male). We measured the alpha 1-AR subtypes in multiple regions of both ventricles by quantitative real-time reverse-transcription polymerase chain reaction and radioligand binding. All 3 alpha 1-AR subtype mRNAs were present, and alpha 1A mRNA was most abundant (approximate to 65% of total alpha 1-AR mRNA). However, only alpha 1A and alpha 1B binding were present, and the alpha 1B was most abundant (60% of total). In failing hearts, alpha 1A and alpha 1B binding was not downregulated, in contrast with beta 1-ARs. Conclusions-Our data show for the first time that the alpha 1A and alpha 1B subtypes are both present in human myocardium, but alpha 1D binding is not, and the alpha 1 subtypes are not downregulated in heart failure. Because alpha 1 subtypes in the human heart are similar to those in the mouse, where adaptive and protective effects of alpha 1 subtypes are most convincing, it might become feasible to treat heart failure with a drug targeting the alpha 1A and/or alpha 1B. (Circ Heart Fail. 2009; 2: 654-663.) C1 [Jensen, Brian C.; Swigart, Philip M.; Simpson, Paul C.] San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA USA. [Jensen, Brian C.; Swigart, Philip M.; Simpson, Paul C.] San Francisco VA Med Ctr, Res Serv, San Francisco, CA USA. [Jensen, Brian C.; De Marco, Teresa; Simpson, Paul C.] Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA. [Simpson, Paul C.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Hoopes, Charles] Univ Calif San Francisco, Div Cardiothorac Surg, San Francisco, CA 94143 USA. RP Simpson, PC (reprint author), VA Med Ctr 111C8, 4150 Clement St, San Francisco, CA 94121 USA. EM paul.simpson@ucsf.edu FU Department of Veterans Affairs; National Institutes of Health; GlaxoSmithKline Research and Education Foundation; UCSF Foundation FX This study was supported by the Department of Veterans Affairs and the National Institutes of Health (P.C.S.), a Young Investigators Award from the GlaxoSmithKline Research and Education Foundation for Cardiovascular Disease (to B.C.J.), and the UCSF Foundation for Cardiac Research (B.C.J.). NR 50 TC 29 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD NOV PY 2009 VL 2 IS 6 BP 654 EP 663 DI 10.1161/CIRCHEARTFAILURE.108.846212 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 521BD UT WOS:000271893100017 PM 19919991 ER PT J AU Salloum, ML Eberlin, KR Sethna, N Hamdan, US AF Salloum, Mariah L. Eberlin, Kyle R. Sethna, Navil Hamdan, Usama S. TI Combined Use of Infraorbital and External Nasal Nerve Blocks for Effective Perioperative Pain Control During and After Cleft Lip Repair SO CLEFT PALATE-CRANIOFACIAL JOURNAL LA English DT Article DE cleft lip repair; external nasal block; infraorbital block ID CHILDREN; MALFORMATIONS; INFANTS; PALATE AB Perioperative analgesia in patients undergoing cleft lip and palate repair is complicated by the risk of postoperative airway obstruction. We describe a technique of combined infraorbital and external nasal nerve blocks to reduce the need for opioid analgesia. Using this technique, we have successfully performed cleft lip repair under local anesthesia alone, without general anesthesia or intravenous sedation, in adolescents and adults. In children, this technique can reduce the need for postoperative opioids. We describe this novel analgesic approach to decrease opioid requirements and minimize perioperative risk. C1 [Salloum, Mariah L.] Tufts Med Ctr, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. [Eberlin, Kyle R.] Massachusetts Gen Hosp, Harvard Plast Surg Training Program, Boston, MA 02114 USA. [Sethna, Navil] Childrens Hosp Boston, Pain Treatment Serv, Boston, MA USA. [Sethna, Navil; Hamdan, Usama S.] Harvard Univ, Sch Med, Boston, MA USA. [Hamdan, Usama S.] Tufts Univ, Sch Med, Medford, MA 02155 USA. [Hamdan, Usama S.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Hamdan, US (reprint author), 28 Martingale Lane, Westwood, MA 02090 USA. EM uh@hamdan.us NR 24 TC 4 Z9 4 U1 0 U2 2 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1055-6656 J9 CLEFT PALATE-CRAN J JI Cleft Palate-Craniofac. J. PD NOV PY 2009 VL 46 IS 6 BP 629 EP 635 DI 10.1597/08-142.1 PG 7 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 522JA UT WOS:000271992500010 PM 19860508 ER PT J AU Schlesinger, N Hassett, AL Neustadter, L Schumacher, HR AF Schlesinger, N. Hassett, A. L. Neustadter, L. Schumacher, H. R., Jr. TI Does acute synovitis (pseudogout) occur in patients with chronic pyrophosphate arthropathy (pseudo-osteoarthritis)? SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE Pseudogout; pyrophosphate arthropathy ID DIHYDRATE CRYSTAL DEPOSITION; OSTEO-ARTHRITIS; CALCIUM; KNEE; CHONDROCALCINOSIS; DISEASE; PREVALENCE; JOINTS; SIZE AB Objective Pyrophosphate arthropathy has been linked to diverse clinical subtypes. The two most common are: acute synovitis (pseudogout) and chronic pyrophosphate arthropathy ("pseudo-osteoarthritis"). We have conducted a study to examine whether these are overlapping syndromes. Methods We reviewed all synovial fluid (SF) analyses performed in our laboratory from January 1988 to May 1997 to determine if patterns of SF leukocyte counts and Alizarin red stains in patients with repeated samples suggest that some patients were prone to acute attacks and some to chronic pyrophosphate arthropathy and whether acute attacks superimposed on chronic symptoms were common. Joint x-rays were screened for osteoarthritis (OA) and chondrocalcinosis. Results We identified 67 patients who had Calcium pyrophosphate dehydrate (CPPD) in their SF and had more than one SF examined (185 SF). We divided the patients into 2 groups. Group A (n=25) had at least one SF leukocyte count > than 2000 per mm(3) and group B (n=42) had SF leukocyte counts always < than 2000 per mm'. Chondrocalcinosis detected on x-ray was more common in group A versus group B, 48% versus 19% (p<0.05, Fisher's exact test). OA was mild (grades 0-1) in 39% of group A versus 12.5% of group B patients, but the difference between groups was not significant. CPPD crystals were not detected in 13.5% SFs previously having CPPD crystals. Alizarin red staining for suspected hydroxyapatite was more often 2+ to 3+ in group B (31.6%) compared to group A (15.5%; p<0.05, Fisher's exact test). Conclusion Acute synovitis and chronic pyrophosphate arthropathy are often two distinctive syndromes with some patients never having inflammatory attacks. Acute synovitis is more common in patients with chondrocalcinosis while chronic pyrophosphate arthropathy is associated with increased alizarin red staining and a trend suggestive of increased severity of OA. C1 [Schlesinger, N.; Hassett, A. L.] UMDNJ, Robert Wood Johnson Med Sch, Div Rheumatol, Dept Med, New Brunswick, NJ 08903 USA. [Neustadter, L.] S Jersey Healthcare Reg Med Ctr, Vineland, NJ USA. [Schumacher, H. R., Jr.] Univ Penn, Sch Med, Div Rheumatol, Philadelphia, PA 19104 USA. [Schumacher, H. R., Jr.] Vet Affairs Med Ctr, Director Arthrit Immunol Ctr, Philadelphia, PA USA. RP Schlesinger, N (reprint author), UMDNJ, Robert Wood Johnson Med Sch, Div Rheumatol, Dept Med, MEB 468,POB 19, New Brunswick, NJ 08903 USA. EM schlesna@umdnj.edu NR 30 TC 4 Z9 5 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD NOV-DEC PY 2009 VL 27 IS 6 BP 940 EP 944 PG 5 WC Rheumatology SC Rheumatology GA 552CO UT WOS:000274264700008 PM 20149309 ER PT J AU Sheikh, A Bhuiyan, MS Khanam, F Chowdhury, F Saha, A Ahmed, D Jamil, KMA LaRocque, RC Harris, JB Ahmad, MM Charles, R Brooks, WA Calderwood, SB Cravioto, A Ryan, ET Qadri, F AF Sheikh, Alaullah Bhuiyan, M. Saruar Khanam, Farhana Chowdhury, Fahima Saha, Amit Ahmed, Dilruba Jamil, K. M. A. LaRocque, Regina C. Harris, Jason B. Ahmad, Mian Mashhud Charles, Richelle Brooks, W. Abdullah Calderwood, Stephen B. Cravioto, Alejandro Ryan, Edward T. Qadri, Firdausi TI Salmonella enterica Serovar Typhi-Specific Immunoglobulin A Antibody Responses in Plasma and Antibody in Lymphocyte Supernatant Specimens in Bangladeshi Patients with Suspected Typhoid Fever SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID ENTEROTOXIGENIC ESCHERICHIA-COLI; INTESTINAL IMMUNE-RESPONSES; VIBRIO-CHOLERAE O1; BONE-MARROW; WIDAL TEST; SECRETING CELLS; STOOL SAMPLES; B-CELLS; VACCINE; BLOOD AB Many currently available diagnostic tests for typhoid fever lack sensitivity and/or specificity, especially in areas of the world where the disease is endemic. In order to identify a diagnostic test that better correlates with typhoid fever, we evaluated immune responses to Salmonella enterica serovar Typhi (serovar Typhi) in individuals with suspected typhoid fever in Dhaka, Bangladesh. We enrolled 112 individuals with suspected typhoid fever, cultured day 0 blood for serovar Typhi organisms, and performed Widal assays on days 0, 5, and 20. We harvested peripheral blood lymphocytes and analyzed antibody levels in supernatants collected on days 0, 5, and 20 (using an antibody-in-lymphocyte-supernatant [ALS] assay), as well as in plasma on these days. We measured ALS reactivity to a serovar Typhi membrane preparation (MP), a formalin-inactivated whole-cell preparation, and serovar Typhi lipopolysaccharide. We measured responses in healthy Bangladeshi, as well as in Bangladeshi febrile patients with confirmed dengue fever or leptospirosis. We categorized suspected typhoid fever individuals into different groups (groups I to V) based on blood culture results, Widal titer, and clinical features. Responses to MP antigen in the immunoglobulin A isotype were detectable at the time of presentation in the plasma of 81% of patients. The ALS assay, however, tested positive in all patients with documented or highly suspicious typhoid, suggesting that such a response could be the basis of improved diagnostic point-of-care- assay for serovar Typhi infection. It can be important for use in epidemiological studies, as well as in difficult cases involving fevers of unknown origin. C1 [Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Div Sci Lab, Immunol Unit, Dhaka 1000, Bangladesh. [Chowdhury, Fahima; LaRocque, Regina C.; Harris, Jason B.; Charles, Richelle; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Ahmad, Mian Mashhud] Dhaka Med Coll Hosp, Dhaka, Bangladesh. [Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol, Boston, MA USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Mol Ctr, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Qadri, F (reprint author), Int Ctr Diarrhoeal Dis Res, Div Sci Lab, Immunol Unit, GPO Box 128, Dhaka 1000, Bangladesh. EM fqadri@icddrb.org FU National Institutes of Health [AI072599, AI058935]; Fogarty International Center [TW05572, TW007409, TW07144]; Howard Hughes Medical Institute FX This study was supported by the ICDDR, B and grants from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (AI072599 [E. T. R.] and AI058935 [R. C. C. and S. B. C.]), a Training Grant in Vaccine Development from the Fogarty International Center (TW05572 [A. S., M. S. B., and F. Q.]), and Career Development Awards (K01) from the Fogarty International Center (TW007409 [J. B. H.] and TW07144 [R. C. L.]), and a Physician-Scientist Early Career Award from the Howard Hughes Medical Institute (R. C. L.). NR 39 TC 22 Z9 22 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD NOV PY 2009 VL 16 IS 11 BP 1587 EP 1594 DI 10.1128/CVI.00311-09 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 514DE UT WOS:000271373700008 PM 19741090 ER PT J AU Graham, DY AF Graham, David Y. TI Endoscopic Ulcers Are Neither Meaningful Nor Validated as a Surrogate for Clinically Significant Upper Gastrointestinal Harm SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ANTI-INFLAMMATORY AGENTS; CORONARY HEART-DISEASE; DOUBLE-BLIND; BLOOD-PRESSURE; END-POINTS; COMPLICATIONS; ASPIRIN; RISK; MISOPROSTOL C1 [Graham, David Y.] Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX USA. [Graham, David Y.] Baylor Coll Med, Houston, TX 77030 USA. RP Graham, DY (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX USA. FU NCI NIH HHS [R01 CA116845]; NIDDK NIH HHS [P30 DK056338, P30 DK056338-07, DK56338] NR 35 TC 15 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD NOV PY 2009 VL 7 IS 11 BP 1147 EP 1150 DI 10.1016/j.cgh.2009.06.006 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 519GM UT WOS:000271753000006 PM 19559818 ER PT J AU Chan, MY Cohen, H Spiegel, BMR AF Chan, Michael Y. Cohen, Hartley Spiegel, Brennan M. R. TI Fewer Polyps Detected by Colonoscopy as the Day Progresses at a Veteran's Administration Teaching Hospital SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID COLORECTAL-CANCER; ADENOMA DETECTION; TECHNICAL PERFORMANCE; SCREENING COLONOSCOPY; SLEEP-DEPRIVATION; COLONIC NEOPLASIA; ENDOSCOPY; QUALITY; RATES; POLYPECTOMY AB BACKGROUND & AIMS: One objective of colonoscopy is to identify and remove polyps-this process requires attention to detail and prolonged concentration. Providers are predisposed to cognitive errors because the procedure is often performed repetitively throughout the day. We measured the adjusted relationship between colonoscopy start time and polyp yield. METHODS: We performed a prospective Study of 477 patients that received screening, Surveillance, or diagnostic colonoscopies at a Veteran's Administration (VA) reaching hospital. The primary outcome measure was polyp yield. We collected data on colonoscopy start times, which were analyzed both as a dichotomous time period ("early-morning case" vs "later case") and as a continuous variable (start time). We identified significant risk factors using univariate analysis and performed Poisson multivariable regression to measure the independent effect of colonoscopy start time on polyp yield. We evaluated evidence of decreasing polyp yield as the day progressed throughout pre-specified time intervals. RESULTS: In univariate analysis, early-morning cases yielded 27% more polyps per patient than later cases (95% confidence interval, 11%-45%; P < .001). The total numbers of, hyperplastic and adenomatous polyps found decreased hour-by-hour as the day progressed. Multivariable analysis demonstrated that early-morning cases yielded 20% more polyps per patient than later cases (95% confidence interval, 5%-38%; P = .007). CONCLUSIONS: At a VA medical center, more polyps were detected in patients that received colonoscopies early in the morning compared with later in the day. Moreover, adenoma detection reduced as the day progressed. Providers might be most adept at detecting polyps at the beginning of the day; further validation in other practice settings is required. C1 [Cohen, Hartley; Spiegel, Brennan M. R.] VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA USA. [Chan, Michael Y.; Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [Spiegel, Brennan M. R.] CURE Digest Dis Res Ctr, Los Angeles, CA USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ, Los Angeles, CA USA. RP Spiegel, BMR (reprint author), 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU Veteran's Affairs Health Services Research and Development (HSR&D) Career Development Transition Award [RCD 03-179-2] FX Dr Spiegel is supported by a Veteran's Affairs Health Services Research and Development (HSR&D) Career Development Transition Award (RCD 03-179-2). NR 28 TC 41 Z9 42 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD NOV PY 2009 VL 7 IS 11 BP 1217 EP 1223 DI 10.1016/j.cgh.2009.07.013 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 519GM UT WOS:000271753000019 PM 19631284 ER PT J AU Khalid, A AF Khalid, Asif TI Differentiating Neoplastic From Benign Lesions of the Pancreas: Translational Techniques SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article CT 5th Joint Meeting of the Japanese-Society-of-Gastroenterology/American-Gastroenterological-Associ ation CY MAY 07-08, 2009 CL Sapporo, JAPAN SP Japanese Soc Gastroenterol, Amer Gastroenterol Assoc ID FINE-NEEDLE-ASPIRATION; PAPILLARY-MUCINOUS TUMORS; CYSTIC NEOPLASMS; BRUSH CYTOLOGY; TELOMERASE ACTIVITY; DIAGNOSTIC-ACCURACY; MOLECULAR ANALYSIS; MALIGNANCY; STRICTURES; ADENOCARCINOMA AB There has been substantial recent progress in our ability to image and sample the pancreas leading to the improved recognition of benign and premalignant conditions of the pancreas such as autoimmune pancreatitis (AIP) and mucinous lesions (mucinous cystic neoplasms [MCN] and intraductal papillary mucinous neoplasms [IPMN]), respectively. Clinically relevant and difficult situations that continue to be faced in this context include differentiating MCN and IPMN from nonmucinous pancreatic cysts, the early detection of malignant degeneration in MCN and IPMN, and accurate differentiation between pancreatic cancer and inflammatory masses, especially Alp. These challenges arise primarily due to the less than perfect sensitivity for malignancy utilizing cytological samples obtained via EUS and ERCP. Aspirates from pancreatic cysts are often paucicellular further limiting the accuracy of cytology. One approach to improve the diagnostic yield from these very small samples is through the use of molecular techniques. Because the development of pancreatic cancer and malignant degeneration in MCN and IPMN is associated with well studied genetic insults including oncogene activation (eg, k-ras), tumor suppressor gene losses (eg, p53, p16, and DPC4), and genome maintenance gene mutations (eg, BRCA2 and telomerase), detecting these molecular abnormalities may aid in improving our diagnostic accuracy. A number of studies have shown the utility of testing clinical samples from pancreatic lesions and bile duct strictures for these molecular markers of malignancy to differentiate between cancer and inflammation. The information from these studies will be discussed with emphasis on how to use this information in clinical practice. C1 [Khalid, Asif] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. [Khalid, Asif] VA Pittsburgh Hlth Care Syst, Dept Med, Pittsburgh, PA USA. RP Khalid, A (reprint author), Univ Pittsburgh, Med Ctr, M2,C Wing,PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM khalida@upmc.edu NR 35 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD NOV PY 2009 VL 7 IS 11 BP S55 EP S58 DI 10.1016/j.cgh.2009.07.033 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 519GN UT WOS:000271753100012 PM 19896100 ER PT J AU Pandol, S Edderkaoui, M Gukovsky, I Lugea, A Gukovskaya, A AF Pandol, Stephen Edderkaoui, Mouad Gukovsky, Ilya Lugea, Aurelia Gukovskaya, Anna TI Desmoplasia of Pancreatic Ductal Adenocarcinoma SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article CT 5th Joint Meeting of the Japanese-Society-of-Gastroenterology/American-Gastroenterological-Associ ation CY MAY 07-08, 2009 CL Sapporo, JAPAN SP Japanese Soc Gastroenterol, Amer Gastroenterol Assoc ID CANCER CELL-SURVIVAL; STELLATE CELLS; NADPH OXIDASE; EXTRACELLULAR-MATRIX; TUMOR PROGRESSION; MICROENVIRONMENT; PROLIFERATION; EXPRESSION; PHENOTYPE; CARCINOMA AB Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and is characterized by remarkable desmoplasia. The desmoplasia is composed of extracellular matrix (ECM) proteins, myofibroblastic pancreatic stellate cells, and immune cells associated with a multitude of cytokines, growth factors, and ECM metabolizing enzymes. The mechanisms of participation of this complex matrix process in carcinogenesis are only starting to be appreciated. Recent studies showed key roles for stellate cells in the production of ECM proteins as well as cytokines and growth factors that promote the growth of the cancer cells all present in the desmoplastic parts of PDAC. In addition, interactions of ECM proteins and desmoplastic secreted growth factors with the cancer cells of PDAC activate intracellular signals including reactive oxygen species that act to make the cancer cells resistant to dying. These findings suggest that the desmoplasia of PDAC is a key factor in regulating carcinogenesis of PDAC as well as responses to therapies. A better understanding of the biology of desmoplasia in the mechanism of PDAC will likely provide significant opportunities for better treatments for this devastating cancer. C1 [Pandol, Stephen] VA Greater Los Angeles Hlth Care Syst, Pancreat Res Grp, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Pandol, S (reprint author), VA Greater Los Angeles Hlth Care Syst, Pancreat Res Grp, Dept Med, Bldg 258,Room 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM stephen.pandol@va.gov FU NCCIH NIH HHS [P01AT003960, P01 AT003960]; NCI NIH HHS [R01 CA119025, R01CA119025]; NIAAA NIH HHS [P50 AA011999, P60 AA11999, R03 AA016008, R21AA016840] NR 32 TC 56 Z9 57 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD NOV PY 2009 VL 7 IS 11 BP S44 EP S47 DI 10.1016/j.cgh.2009.07.039 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 519GN UT WOS:000271753100010 PM 19896098 ER PT J AU Levine, BS Kleeman, CR Felsenfeld, AJ AF Levine, Barton S. Kleeman, Charles R. Felsenfeld, Arnold J. TI The Journey From Vitamin D-Resistant Rickets to the Regulation of Renal Phosphate Transport SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID FIBROBLAST GROWTH FACTOR-23; X-LINKED HYPOPHOSPHATEMIA; MATRIX EXTRACELLULAR PHOSPHOGLYCOPROTEIN; CHRONIC KIDNEY-DISEASE; 25-HYDROXYVITAMIN D-1-ALPHA-HYDROXYLASE ACTIVITY; SERUM PARATHYROID-HORMONE; HYP MOUSE PHENOTYPE; KLOTHO MUTANT MICE; D METABOLISM; SECONDARY HYPERPARATHYROIDISM AB In 1937, Fuller Albright first described two rare genetic disorders: Vitamin D resistant rickets and polyostotic fibrous dysplasia, now respectively known as X-linked hypophosphatemic rickets (XLH) and the McCune-Albright syndrome. Albright carefully characterized and meticulously analyzed one patient, W.M., with vitamin D-resistant rickets. Albright subsequently reported additional carefully performed balance studies on W.M. In this review, which evaluates the journey from the initial description of vitamin D-resistant rickets (XLH) to the regulation of renal phosphate transport, we (1) trace the timeline of important discoveries in unraveling the pathophysiology of XLH, (2) cite the recognized abnormalities in mineral metabolism in XLH, (3) evaluate factors that may affect parathyroid hormone values in XLH, (4) assess the potential interactions between the phosphate-regulating gene with homology to endopeptidase on the X chromosome and fibroblast growth factor 23 (FGF23) and their resultant effects on renal phosphate transport and vitamin D metabolism, (5) analyze the complex interplay between FGF23 and the factors that regulate FGF23, and (6) discuss the genetic and acquired disorders of hypophosphatemia and hyperphosphatemia in which FGF23 plays a role. Although Albright could not measure parathyroid hormone, he concluded on the basis of his studies that showed calcemic resistance to parathyroid extract in W.M. that hyperparathyroidism was present. Using a conceptual approach, we suggest that a defect in the skeletal response to parathyroid hormone contributes to hyperparathyroidism in XLH. Finally, at the end of the review, abnormalities in renal phosphate transport that are sometimes found in patients with polyostotic fibrous dysplasia are discussed. Clin J Am Soc Nephrol 4: 1866-1877, 2009. doi: 10.2215/CJN.03000509 C1 VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Felsenfeld, AJ (reprint author), W Los Angeles VA Med Ctr, Nephrol Sect 111L, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arnold.felsenfeld@va.gov NR 109 TC 9 Z9 11 U1 0 U2 8 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV PY 2009 VL 4 IS 11 BP 1866 EP 1877 DI 10.2215/CJN.03000509 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 517PN UT WOS:000271628400025 PM 19808223 ER PT J AU Oreskovic, NM Winickoff, JP Kuhlthau, KA Romm, D Perrin, JM AF Oreskovic, Nicolas M. Winickoff, Jonathan P. Kuhlthau, Karen A. Romm, Diane Perrin, James M. TI Obesity and the Built Environment Among Massachusetts Children SO CLINICAL PEDIATRICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies/Academic-Pediatric-Association/Society-for- Pediatric-Research National Conference CY MAY 02-06, 2008 CL Honolulu, HI SP Pediat Acad Soc, Acad Pediat Assoc, Soc Pediat Res DE obesity; pediatric; built environment; geographic information systems (GIS) ID FAST-FOOD RESTAURANTS; BODY-MASS INDEX; PHYSICAL-ACTIVITY; UNITED-STATES; URBAN SPRAWL; OVERWEIGHT; WEIGHT; SCHOOL; ASSOCIATION; PREVALENCE AB Background: The built environment may influence weight status. Method: Using cross-sectional data for children aged 2 to 18 years, the authors linked clinical and spatial data using geographic information systems and analyzed for associations between body mass index (BMI) and density of and distance to nearest built environment variable (schools, sidewalks, subway stations, bicycle trails, open space, and fast-food restaurants) using bivariate and multilevel analyses. Results: The study sampled 21 008 children; 54% were white, 26% Hispanic, 37% overweight, and 20% obese. In bivariate analysis, distance to nearest fast-food restaurant was inversely associated with 13141, whereas density of fast-food restaurants was positively associated with BMI. Distance to school and subway station, amount of open space, and density of subway stations were inversely associated with BMI. Controlling for sociodemographic factors, only living near a greater density of subway stations was inversely associated with overweight (odds ratio, 0.87; 95% confidence interval, 0.81-0.94) and obesity (odds ratio. 0.90; 95% confidence interval, 0.82-0.99). Conclusion: Distance to nearest subway station is associated with BMI among Massachusetts children. C1 [Oreskovic, Nicolas M.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Dept Internal Med, Boston, MA 02114 USA. [Oreskovic, Nicolas M.; Winickoff, Jonathan P.; Perrin, James M.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Dept Pediat, Boston, MA 02114 USA. RP Oreskovic, NM (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Dept Internal Med, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM nicolas.oreskovic@gmail.com OI Oreskovic, Nicolas/0000-0001-8702-8636 FU AHRQ HHS [T32 HS000063-13] NR 39 TC 44 Z9 44 U1 2 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD NOV PY 2009 VL 48 IS 9 BP 904 EP 912 DI 10.1177/0009922809336073 PG 9 WC Pediatrics SC Pediatrics GA 506ZC UT WOS:000270817400003 PM 19487763 ER PT J AU Sattelmair, JR Pertman, JH Forman, DE AF Sattelmair, Jacob R. Pertman, Jeremy H. Forman, Daniel E. TI Effects of Physical Activity on Cardiovascular and Noncardiovascular Outcomes in Older Adults SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Aging; Cardiovascular; Elderly; Exercise; Physical activity ID RANDOMIZED CONTROLLED-TRIAL; CORONARY-HEART-DISEASE; QUALITY-OF-LIFE; DEPENDENT DIABETES-MELLITUS; IMPAIRED GLUCOSE-TOLERANCE; BODY-MASS INDEX; OXIDATIVE STRESS BIOMARKERS; LEUKOCYTE TELOMERE LENGTH; HOME-BASED EXERCISE; GROWTH-FACTOR-I AB Aging is associated with a cascade of morphologic and physiologic changes that naturally predispose older adults to progressive weakening, functional decline, morbidity. disability, poor quality of life, and increased mortality Physical activity moderates such insidious aging patterns and is a vital preventive and therapeutic strategy to optimize health throughout the aging process. Regular exercise provides many physiologic benefits, reduces risk of disease outcomes, and triggers important psychological gains Advanced age presents distinctive obstacles to maintaining a physically active lifestyle Individualized exercise strategies and regimens make it possible, however, for every elderly adult to benefit from physical activity C1 [Forman, Daniel E.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Sattelmair, Jacob R.; Pertman, Jeremy H.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Forman, Daniel E.] VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA 02130 USA. RP Forman, DE (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. NR 177 TC 35 Z9 39 U1 2 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD NOV PY 2009 VL 25 IS 4 BP 677 EP + DI 10.1016/j.cger.2009.07.004 PG 28 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 596JD UT WOS:000277680200008 PM 19944267 ER PT J AU Cusi, K AF Cusi, Kenneth TI Role of Insulin Resistance and Lipotoxicity in Non-Alcoholic Steatohepatitis SO CLINICS IN LIVER DISEASE LA English DT Article DE Insulin resistance; Lipotoxicity; NAFLD; NASH; Type 2 diabetes mellitus ID FATTY LIVER-DISEASE; PLASMA ADIPONECTIN CONCENTRATIONS; INDUCED HEPATIC LIPOTOXICITY; TYPE-2 DIABETIC-PATIENTS; HUMAN SKELETAL-MUSCLE; BODY-MASS INDEX; FACTOR-KAPPA-B; GLUCOSE-TOLERANCE; ADIPOSE-TISSUE; RESONANCE-SPECTROSCOPY AB It is well established that the development of NAFLD and NASH are closely linked to an excess flow of free fatty acids (FFA) arising from dysfunctional/insulin resistant adipose tissue causing ectopic fat deposition in many organs. In the liver, when chronic lipid supply surpasses the metabolic ability to adapt it will induce hepatocellular damage as FFA are redirected into harmful pathways of non-oxidative metabolism with intracellular accumulation of toxic lipid-derived metabolites. Multiple mechanisms have been implicated including mitochondrial dysfunction, endoplasmic reticulum stress, and activation of multiple inflammatory pathways. Understanding the role of insulin resistance and lipotoxicity in NASH as part of a broader metabolic disorder is likely to assist practitioners in the successful management of these challenging patients. C1 [Cusi, Kenneth] Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, San Antonio, TX 78284 USA. [Cusi, Kenneth] Audie L Murphy Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Cusi, K (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, Room 3-390S,7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM cusi@uthscsa.edu NR 99 TC 66 Z9 73 U1 1 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1089-3261 J9 CLIN LIVER DIS JI Clin. Liver Dis. PD NOV PY 2009 VL 13 IS 4 BP 545 EP + DI 10.1016/j.cld.2009.07.009 PG 20 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 514JJ UT WOS:000271390100004 PM 19818304 ER PT J AU Chou, JCY AF Chou, James C. -Y TI MIXED EPISODES WITH PSYCHOTIC FEATURES SO CNS SPECTRUMS LA English DT Article ID BIPOLAR-I DISORDER; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; SUICIDAL IDEATION; ACUTE MANIA; DEPRESSION; LITHIUM; DIVALPROEX; OLANZAPINE; QUETIAPINE C1 [Chou, James C. -Y] Mt Sinai Sch Med, New York, NY USA. [Chou, James C. -Y] James J Peters VA Med Ctr, Bronx, NY USA. RP Chou, JCY (reprint author), Mt Sinai Sch Med, New York, NY USA. FU AstraZeneca; Bristol-Myers Squibb; Eli Lilly; GlaxoSmithKline; Janssen; Pfizer FX Dr. Chou has received honoraria from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, and Pfizer. NR 16 TC 0 Z9 0 U1 0 U2 1 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD NOV PY 2009 VL 14 IS 11 SU 11 BP 6 EP 8 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 540TW UT WOS:000273363500002 PM 20173694 ER PT J AU Nierenberg, AA AF Nierenberg, Andrew A. TI Failure to Integrate Brain and Mind (or Blaming Descartes to Understand a Very Modern Dilemma about Explanatory Models, Psychiatric Treatment, and Underfunding of Clinical Care and Research) SO CNS SPECTRUMS LA English DT Editorial Material ID MENTAL-DISORDERS; GLOBAL BURDEN C1 [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 9 TC 0 Z9 0 U1 0 U2 1 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD NOV PY 2009 VL 14 IS 11 BP 599 EP 600 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 529HV UT WOS:000272507600001 PM 20173684 ER PT J AU Mendez, MF AF Mendez, Mario F. TI The Neurobiology of Moral Behavior: Review and Neuropsychiatric Implications SO CNS SPECTRUMS LA English DT Review ID VENTROMEDIAL PREFRONTAL CORTEX; FRONTOTEMPORAL LOBAR DEGENERATION; ANTISOCIAL PERSONALITY-DISORDER; POSITRON-EMISSION-TOMOGRAPHY; MIRROR NEURON SYSTEM; SOCIAL COGNITION; DECISION-MAKING; ORBITOFRONTAL CORTEX; ACQUIRED SOCIOPATHY; FRONTAL-CORTEX AB Morality may be innate to the human brain. This review examines the neurobiological evidence from research involving functional magnetic resonance imaging of normal subjects, developmental sociopathy, acquired sociopathy from brain lesions, and frontotemporal dementia. These studies indicate a "neuromoral" network for responding to moral dilemmas centered in the ventromedial prefrontal cortex and its connections, particularly on the right. The neurobiological evidence indicates the existence of automatic "prosocial" mechanisms for identification with others that are part of the mora brain. Patients with disorders involving this moral network have attenuated emotional reactions to the possibility of harming others and may perform sociopathic acts. The existence of this neuromoral system has major clinical implications for the management of patients with dysmoral behavior from brain disorders and for forensic neuropsychiatry. CNS Spectr. 2009;14(11):608-620 C1 [Mendez, Mario F.] VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF, Los Angeles, CA 90073 USA. [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@UCLA.edu FU [R01AG03449902] FX This work was supported by grant # R01AG03449902. NR 169 TC 38 Z9 38 U1 5 U2 32 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD NOV PY 2009 VL 14 IS 11 BP 608 EP 620 PG 13 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 529HV UT WOS:000272507600003 PM 20173686 ER PT J AU Marques, L AF Marques, Luana TI Interviewing Clients Across Cultures SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Book Review C1 [Marques, Luana] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Marques, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Simches Res Bldg,2nd Floor,185 Cambridge St, Boston, MA 02114 USA. EM lmarques@partners.org NR 4 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 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD NOV PY 2009 VL 16 IS 4 BP 480 EP 481 PG 2 WC Psychology, Clinical SC Psychology GA 521BJ UT WOS:000271893800013 ER PT J AU Morland, LA Greene, CJ Rosen, C Mauldin, PD Frueh, BC AF Morland, Leslie A. Greene, Carolyn J. Rosen, Craig Mauldin, Patrick D. Frueh, B. Christopher TI Issues in the design of a randomized noninferiority clinical trial of telemental health psychotherapy for rural combat veterans with PTSD SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Posttraumatic stress disorder (PTSD); Rural; Military veterans; Telemedicine; Noninferiority trial ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-PROCESSING THERAPY; QUALITY-OF-LIFE; URBAN DISPARITIES; EXPOSURE THERAPY; TELEPSYCHIATRY; VALIDATION; INVENTORY; VICTIMS; SERVICE AB This methodological article provides a description of the design, methods, and rationale of the first prospective, noninferiority designed randomized clinical trial evaluating the clinical and cost implications of delivering an evidence-based cognitive-behavioral group intervention specifically treating posttraumatic stress disorder (PTSD) with a trauma-focused intervention via video teleconferencing (VTC). PTSD is a prevalent mental health problem found among returning Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) military populations. These returning military personnel often live in rural areas and therefore have limited access to care and specialized psychological treatments. In the field of mental health, telemental health (TMH) technology has introduced a potential solution to the persistent problem of access to care in remote areas. This study is enrolling approximately 126 returning veterans with Current combat-related PTSD who are receiving services through the Veteran Administration (VA) mental health care clinics on 4 Hawaiian Islands. Cognitive Processing Therapy (CPT), an empirically supported manualized treatment for PTSD, is being delivered across 9 cohorts. Participants are assigned to either the experimental VTC condition or the in-person control condition. Assessments measuring clinical, process, and cost outcomes are being conducted at baseline, mid-treatment, post-treatment, and 3 and 6 months post-treatment. The study employs a noninferiority design to determine if the group treatment delivered via VTC is as good as the traditional in-person modality. In addition, a cost analysis will be performed in order to compare the cost of the 2 modalities. Novel aspects of this trial and specific challenges are discussed. (C) 2009 Published by Elsevier Inc. C1 [Morland, Leslie A.] Natl Ctr PTSD, Pacific Isl Div, Dept Vet Affairs Pacific Isl Healthcare Syst, Honolulu, HI 96819 USA. [Greene, Carolyn J.; Rosen, Craig] Natl Ctr PTSD, Disseminat & Training Div, Dept Vet Affairs Palo Alto Healthcare Syst, Palo Alto, CA USA. [Greene, Carolyn J.; Rosen, Craig] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Mauldin, Patrick D.] S Carolina Coll Pharm, Dept Clin Pharm & Outcome Sci, Charleston, SC USA. [Mauldin, Patrick D.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Frueh, B. Christopher] Menninger Clin, Houston, TX USA. [Frueh, B. Christopher] Baylor Coll Med, Houston, TX 77030 USA. RP Morland, LA (reprint author), Natl Ctr PTSD, Pacific Isl Div, Dept Vet Affairs Pacific Isl Healthcare Syst, 3375 Koapaka St, Honolulu, HI 96819 USA. EM Leslie.Morland@va.gova FU Department of Defense [PT074516]; Office of Research and Development, Medical Research Service, Department of Veterans Affairs FX This work is partially supported by Grant PT074516 from the Department of Defense. This work is also supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs. All views and opinions expressed herein are those of the authors and do not necessarily reflect those of our respective institutions or the Department of Veterans Affairs. NR 67 TC 24 Z9 24 U1 3 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD NOV PY 2009 VL 30 IS 6 BP 513 EP 522 DI 10.1016/j.cct.2009.06.006 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 523YM UT WOS:000272111000003 PM 19576299 ER PT J AU Hahn, JO Reisner, AT Asada, HH AF Hahn, Jin-Oh Reisner, Andrew T. Asada, H. Harry TI Modeling and 2-sensor blind identification of human cardiovascular system SO CONTROL ENGINEERING PRACTICE LA English DT Article DE Cardiovascular system; Blind system identification; Two-channel Wiener system; Cardiovascular health monitoring; Aortic blood pressure ID AORTIC PRESSURE; WAVE-FORM; DERIVATION AB This paper presents modeling and blind identification of human cardiovascular system. In contrast to the population-based methods widespread in current practice, the proposed method does not require any a priori knowledge of the cardiovascular system. This paper develops a human cardiovascular system model, analyzes its identifiability, and identifies the model using two diametric blood pressure measurements. The aortic blood pressure reconstructed using the identified model can eliminate the use of invasive aortic blood pressure measurement for cardiovascular monitoring. Results based on the data from a realistic human cardiovascular system simulator demonstrate the validity of the proposed model and identification method. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Hahn, Jin-Oh; Asada, H. Harry] MIT, Dept Mech Engn, Arbeloff Lab Informat Syst & Technol, Cambridge, MA 02139 USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Hahn, JO (reprint author), MIT, Dept Mech Engn, Arbeloff Lab Informat Syst & Technol, 77 Massachusetts Ave 3-351, Cambridge, MA 02139 USA. EM jinoh.hahn@alum.mit.edu FU Sharp Corporation FX This research was supported in part by the Sharp Corporation. We also appreciate Professor Roger D. Kamm and Dr. Xinshu Xiao at Massachusetts Institute of Technology for their kind assistance and suggestions in the use of the human CV system simulator. NR 22 TC 7 Z9 7 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0967-0661 J9 CONTROL ENG PRACT JI Control Eng. Practice PD NOV PY 2009 VL 17 IS 11 BP 1318 EP 1328 DI 10.1016/j.conengprac.2009.06.006 PG 11 WC Automation & Control Systems; Engineering, Electrical & Electronic SC Automation & Control Systems; Engineering GA 509TS UT WOS:000271041900008 ER PT J AU Renaud, B Santin, A Coma, E Camus, N Van Pelt, D Hayon, J Gurgui, M Roupie, E Herve, J Fine, MJ Brun-Buisson, C Labarere, J AF Renaud, Bertrand Santin, Aline Coma, Eva Camus, Nicolas Van Pelt, Dave Hayon, Jan Gurgui, Merce Roupie, Eric Herve, Jerome Fine, Michael J. Brun-Buisson, Christian Labarere, Jose TI Association between timing of intensive care unit admission and outcomes for emergency department patients with community-acquired pneumonia SO CRITICAL CARE MEDICINE LA English DT Article DE pneumonia; community-acquired infection; emergency department; intensive care; severity of illness index; time to admission ID SYSTEMIC INFLAMMATORY RESPONSE; QUALITY-OF-LIFE; SEVERE SEPSIS; SEPTIC SHOCK; PREDICTION RULE; SEVERITY-INDEX; GUIDELINES; MANAGEMENT; DECISION; MULTICENTER AB Objective: To compare the 28-day mortality and hospital length of stay of patients with community-acquired pneumonia who were transferred to an intensive care unit on the same day of emergency department presentation (direct-transfer patients) with those subsequently transferred within 3 days of presentation (delayed-transfer patients). Design: Secondary analysis of the original data from two North American and two European prospective, multicenter, cohort studies of adult patients with community-acquired pneumonia. Patients: In all, 453 non-institutionalized patients transferred within 3 days of emergency department presentation to an intensive care unit were included in the analysis. Supplementary analysis was restricted to patients without an obvious indication for immediate transfer to an intensive care unit. Interventions: None. Measurements and Main Results: The sample consisted of 138 delayed-transfer and 315 direct-transfer patients, among whom 150 (33.1%) were considered to have an obvious indication for immediate intensive care unit admission. After adjusting for the quintile of propensity score, delayed intensive care unit transfer was associated with an increased odds ratio for 28-day mortality (2.07; 95% confidence interval, 1.12-3.85) and a decreased odds ratio for discharge from hospital for survivors (0.53; 95% confidence interval, 0.39-0.71). In a propensity-matched analysis, delayed-transfer patients had a higher 28-day mortality rate (23.4% vs. 11.7%; p = 0.02) and a longer median hospital length of stay (13 days vs. 7 days; p <.001) than direct-transfer patients. Similar results were found after excluding the 150 patients with an obvious indication for immediate intensive care unit admission. Conclusions: Our findings suggest that some patients without major criteria for severe community-acquired pneumonia, according to the recent Infectious Diseases Society of America/American Thoracic Society consensus guideline, may benefit from direct transfer to the intensive care unit. Further studies are needed to prospectively identify patients who may benefit from direct intensive care unit admission despite a lack of major severity criteria for community-acquired pneumonia based on the current guidelines. (Crit Care Med 2009; 37:2867-2874) C1 [Renaud, Bertrand; Santin, Aline; Camus, Nicolas; Hayon, Jan] Grp Hosp Henri Mondor Albert Chenevier, AP HP, Dept Emergency Med, Creteil, France. [Coma, Eva] Hosp Duran & Reynals, Serv Atencio Continuada USAC, Inst Catala Oncol, Barcelona, Spain. [Camus, Nicolas; Brun-Buisson, Christian] Univ Paris 12, Fac Med, Creteil, France. [Van Pelt, Dave] Med Ctr, Dept Crit Care & Pulm Consultants, Aurora, CO USA. [Hayon, Jan] Ctr Hosp Intercommunal Poissy St Germain, Dept Crit Care Med, St Germain En Laye, France. [Gurgui, Merce] Hosp Santa Creu & Sant Pau, Dept Emergency Med, Barcelona, Spain. [Roupie, Eric] Hop Cote Nacre, CHU Caen, Dept Emergency Med, Caen, France. [Roupie, Eric] Univ Caen Basse Normandie, Fac Med, Caen, France. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Fine, Michael J.] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Labarere, Jose] CHU Grenoble, Qual Care Unit, F-38043 Grenoble, France. RP Renaud, B (reprint author), Grp Hosp Henri Mondor Albert Chenevier, AP HP, Dept Emergency Med, Creteil, France. EM bertrand.renaud@hmn.aphp.fr RI Labarere, Jose/N-1688-2014; OI Labarere, Jose/0000-0001-7621-6586 FU Departement de la Formation Continue des Medecins de I'Assistance Publique des Hopitaux de Paris; ARMUR; AQUARE; GIaxoSmithKline France; Direction de la Recherche Clinique d'lle de France [AOM 89-145] FX Dr. Renaud has received grants from GIaxoSmithKline. Dr. Labarere was supported by a grant from the Egide Foundation, Paris, France (Programme Lavoisier) and from the Direction de la Recherche Clinique at Grenoble University Hospital. The remaining authors have not disclosed any potential conflicts of interest. NR 36 TC 68 Z9 69 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2009 VL 37 IS 11 BP 2867 EP 2874 DI 10.1097/CCM.0b013e3181b02dbb PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 517IP UT WOS:000271607000001 PM 19770748 ER PT J AU Martin, PI Naeser, MA Ho, M Treglia, E Kaplan, E Baker, EH Pascual-Leone, A AF Martin, Paula I. Naeser, Margaret A. Ho, Michael Treglia, Ethan Kaplan, Elina Baker, Errol H. Pascual-Leone, Alvaro TI Research With Transcranial Magnetic Stimulation in the Treatment of Aphasia SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review ID NONFLUENT APHASIA; POSTSTROKE APHASIA; RIGHT-HEMISPHERE; PREMOTOR CORTEX; FUNCTIONAL MRI; SPEECH-PERCEPTION; LANGUAGE FUNCTION; BRAIN PLASTICITY; FRONTAL-CORTEX; WORD RETRIEVAL AB Repetitive transcranial magnetic stimulation (rTMS) has been used to improve language behavior, including naming, in stroke patients with chronic, nonfluent aphasia. Part 1 of this article reviews functional imaging studies related to language recovery in aphasia. Part 2 reviews the rationale for using rTMS to treat nonfluent aphasia (based on functional imaging) and presents our current rTMS protocol. We present language results from our rTMS studies as well as imaging results from overt naming functional MRI scans obtained before and after a series of rTMS treatments. Part 3 presents results from a pilot study in which rTMS treatments were followed immediately by constraint-induced language therapy. Part 4 reviews our diffusion tensor imaging study examining the possible connectivity of the arcuate fasciculus to different parts of Broca's area (pars triangularis, pars opercularis) and to the ventral premotor cortex. The potential role of mirror neurons in the right pars opercularis and ventral premotor cortex in aphasia recovery is discussed. C1 [Martin, Paula I.] VA Boston Healthcare Syst, Aphasia Res Ctr 12A, Boston, MA 02130 USA. RP Martin, PI (reprint author), VA Boston Healthcare Syst, Aphasia Res Ctr 12A, 150 S Huntington Ave, Boston, MA 02130 USA. EM paulak@bu.edu FU National Institutes of Health (NIH) [RO1 DC05672]; Medical Research Service, Department of Veterans Affairs; NIH [RRO18875]; HarvardThorndike General Clinical Research Center [MO1 RR01032]; NIDCD [P30 DC05207] FX This research is supported by National Institutes of Health (NIH) grant # RO1 DC05672 from the National Institute on Deafness and Other Communication Disorders (NIDCD) and a grant from the Medical Research Service, Department of Veterans Affairs (to Dr. Naeser); a K24 NIH award (RRO18875; to Dr. Pascual-Leone) and the HarvardThorndike General Clinical Research Center (NCRR MO1 RR01032); and a P30 DC05207 NIDCD grant to the Harold Goodglass Boston University Aphasia Research Center. NR 55 TC 55 Z9 58 U1 2 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD NOV PY 2009 VL 9 IS 6 BP 451 EP 458 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 505XZ UT WOS:000270736600006 PM 19818232 ER PT J AU Heath, RJ Xavier, RJ AF Heath, Robert J. Xavier, Ramnik J. TI Autophagy, immunity and human disease SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE adaptive immunity; autophagy; Crohn's disease; innate immunity ID GENOME-WIDE ASSOCIATION; CROHNS-DISEASE; SUSCEPTIBILITY LOCI; TUMOR-SUPPRESSOR; GENE ATG5; BECLIN 1; COMPLEX; LC3; MACROPHAGES; ATG16L1 AB Purpose of review To give an overview of autophagy and its effects on innate and adaptive immunity and touch on some of the roles of autophagy in disease. Recent findings Precise regulation of autophagy is necessary to maintain metabolic equilibrium, immune homeostasis, delineate cell fate and influence host cell responses to cytosolic pathogens. A growing number of studies have implicated that inactivation of autophagy-selective responses contributes to inflammatory disorders, neurodegeneration and cancer, but the precise steps at which disease-associated autophagy-related (ATG) genes affect autophagy pathways is unknown at present. Summary In eukaryotic cells autophagy is constitutively active at low levels, whereas significant up-regulation occurs in response to a multitude of stresses. Autophagy has achieved notoriety as a perturbed biological process in many disease states and an exponential increase of studies attribute roles for autophagy in innate and adaptive immunity. Understanding how individual disease-associated ATG genes function will lead to a better understanding of and potentially novel therapies for treating the diseases in which they are involved. C1 [Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol,Richard B Simches Re, Boston, MA 02114 USA. [Heath, Robert J.; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Ctr Inflammatory Bowel Dis, Boston, MA 02114 USA. [Xavier, Ramnik J.] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Xavier, RJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol,Richard B Simches Re, 185 Cambridge St,7th Floor, Boston, MA 02114 USA. EM Xavier@molbiol.mgh.harvard.edu FU NIH [A1062773, DK83756, DK043351] FX R.J.X. and R.J.H. are supported by the following grants from the NIH: A1062773, DK83756, DK043351. NR 59 TC 21 Z9 22 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 2009 VL 25 IS 6 BP 512 EP 520 DI 10.1097/MOG.0b013e32833104f1 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 516SR UT WOS:000271563500004 PM 19826372 ER PT J AU Lin, NH Kuritzkes, DR AF Lin, Nina H. Kuritzkes, Daniel R. TI Tropism testing in the clinical management of HIV-1 infection SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE CCR5; CXCR4; genotypic assay; phenotypic assay; viral tropism AB Purpose of review A variety of methods are available to determine HIV-1 co-receptor usage, commonly referred to as viral tropism. This article reviews recent data on phenotypic and genotypic assays of HIV-1 tropism. Recent findings Tropism assays are used to determine co-receptor usage of HIV-1 in patients who may be candidates for treatment with CCR5 antagonists. Phenotypic assays are used most often in the clinical trials of CCR5 antagonists, and are considered the 'gold standard' for comparison with other methods of tropism testing. Enhancements have allowed detection of a lower threshold of minor CXCR4-using species. When compared with phenotypic assays, genotypic methods have poor sensitivity but good specificity at detecting CXCR4-using HIV-1. Preliminary results from a recent comparative study suggest that some genotypic methods may perform as well as phenotypic tests in predicting virologic response to CCR5 antagonists. Several studies show that tropism testing may provide useful prognostic information regarding the risk of disease progression. Summary Understanding the characteristic of different tropism assays is important for their clinical use. Although phenotypic testing currently is favored, genotypic assays may be a suitable alternative in appropriate settings. C1 [Lin, Nina H.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Lin, Nina H.; Kuritzkes, Daniel R.] Harvard Univ, Sch Med, Boston, MA USA. [Kuritzkes, Daniel R.] Brigham & Womens Hosp, Sect Retroviral Therapeut, Boston, MA 02115 USA. RP Kuritzkes, DR (reprint author), Brigham & Womens Hosp, Sect Retroviral Therapeut, 65 Landsdowne St,Rm 449, Cambridge, MA 02139 USA. EM dkuritzkes@partners.org FU NIH [K24 RR016482, R37 AI055357, U01 AI068636]; Harvard Institute for Global Health, Bristol-Myers Squibb; American Society for Tropical Medicine and Hygiene FX NIH grants K24 RR016482, R37 AI055357, and U01 AI068636 (to D.R.K) and fellowship support from the Harvard Institute for Global Health, Bristol-Myers Squibb, and the American Society for Tropical Medicine and Hygiene (to N.H.L). NR 46 TC 19 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD NOV PY 2009 VL 4 IS 6 BP 481 EP 487 DI 10.1097/COH.0b013e328331b929 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V19PD UT WOS:000208083400004 PM 20048714 ER PT J AU Herbstman, BJ Pincus, HA AF Herbstman, Benjamin J. Pincus, Harold A. TI Measuring mental healthcare quality in the United States: a review of initiatives SO CURRENT OPINION IN PSYCHIATRY LA English DT Review DE indicators; measures; mental health; quality; United States ID PERFORMANCE AB Purpose of review This review article aims to present a systematic overview of the current initiatives assessing mental and/or substance use (M/SU) healthcare quality in the United States. Recent findings The study found 36 initiatives incorporating M/SU indicators with efforts from the federal and state government, health plans, nongovernmental and professional organizations. Summary Although there has been much activity in recent years in the development of M/SU indicators, efforts have lacked coordination, have focused on limited areas of clinical activity, and have not been clearly linked to quality improvement activity. The study recommends that the United States government forms an entity to better coordinate efforts and address these concerns. Clinicians and provider organizations should also increase the use of already developed M/SU indicators to improve quality of care delivered. C1 [Herbstman, Benjamin J.] Harvard Univ, Sch Med, Boston, MA USA. [Herbstman, Benjamin J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Herbstman, Benjamin J.] McLean Hosp, Belmont, MA 02178 USA. [Pincus, Harold A.] Columbia Univ, Dept Psychiat, New York, NY USA. [Pincus, Harold A.] Columbia Univ, Irving Inst Clin & Translat Res, New York, NY USA. [Pincus, Harold A.] New York Presbyterian Hosp, New York, NY USA. [Pincus, Harold A.] RAND, Pittsburgh, PA USA. RP Pincus, HA (reprint author), 1051 Riverside Dr,Room 5813,Unit Box 09, New York, NY 10032 USA. EM pincush@pi.cpmc.columbia.edu FU Center for Mental Health Services, Substance Abuse and Mental Health Services Administration; U.S. Department of Health and Human Services, Irving Institute for Clinical and Translational Research at Columbia University [UL1 RR024156]; University of Pittsburgh [UL1 RR024153]; National Center for Research Resources (NCRR); National Institutes of Health (NIH); Mental Heath Therapeutics CERT at Rutgers; Agency for Healthcare Research and Quality (AHRQ) [5 U18 HS016097] FX Funding for this work was received by the Center for Mental Health Services, Substance Abuse and Mental Health Services Administration, U.S. Department of Health and Human Services, Irving Institute for Clinical and Translational Research at Columbia University (UL1 RR024156) and University of Pittsburgh (UL1 RR024153) both from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), Mental Heath Therapeutics CERT at Rutgers, the State University of New Jersey funded by the Agency for Healthcare Research and Quality (AHRQ) (5 U18 HS016097). NR 18 TC 10 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD NOV PY 2009 VL 22 IS 6 BP 623 EP 630 DI 10.1097/YCO.0b013e3283318ece PG 8 WC Psychiatry SC Psychiatry GA 513CW UT WOS:000271301000021 PM 19745741 ER PT J AU Hulspas, R Dombkowski, D Preffer, F Douglas, D Kildew-Shah, B Gilbert, J AF Hulspas, Ruud Dombkowski, David Preffer, Frederic Douglas, Derick Kildew-Shah, Brian Gilbert, John TI Flow Cytometry and the Stability of Phycoerythrin-Tandem Dye Conjugates SO CYTOMETRY PART A LA English DT Article DE degradation; fluorochrome; stability; T-regulatory cells; CD4/CD8; clinical; flow cytometry; compensation ID ENERGY-TRANSFER; FLUORESCENCE COMPENSATION; QUALITY-CONTROL; IMMUNOFLUORESCENCE; STANDARDS AB Routine clinical flow cytometric procedures demand rigorous, simple, and reproducible procedures for spectral compensation. The current, often laborious, spectral compensation procedures are the result of variability in instrument settings, instrument performance, and variability in reagents. In particular, the use of tandem dye conjugates necessitates elaborate spectral compensation procedures that need to be applied frequently. Manufacturer, lot number, and handling procedures are considered the key aspects affecting the fluorescence characteristics of tandem dyes. A better understanding of how specific conditions affect the variability in emission spectra of tandem dyes can lead to a considerable increase in reliability of measurements and a potential simplification of setup procedures for routine, clinical flow cytometry. We investigated the effect of light exposure, handling, and storage conditions on the fluorescence characteristics of some common phycoerythrin tandem fluorochromes. in general, PE-Cy5 showed the lowest degradation rates, whereas PE-Cy7 showed the highest. During storage, long-term degradation rates were lowest for reagents packaged using an extra light protective approach. Under these conditions, a degradation rate of 0.9%/month of a PE-Cy7 conjugate decreased to 0.3%/month. As degradation rates were minimized, we studied the effect of slow degradation of a set of tandem dye conjugates on compensation matrix values over several months. Finally, we explored the effect of slow degradation on flow cytometric analysis using the same compensation settings for extended periods for an analysis template with preset regions and gating strategies. (C) 2009 International Society for Advancement of Cytometry C1 [Hulspas, Ruud; Gilbert, John] Cytonome Inc, Boston, MA USA. [Dombkowski, David; Preffer, Frederic] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Douglas, Derick; Kildew-Shah, Brian] Sperotech Inc, Lake Forest, IL USA. RP Hulspas, R (reprint author), Cytonome ST LLC, 27 Drydock Ave, Boston, MA 02210 USA. EM rhulspas@cytonomest.com NR 20 TC 18 Z9 18 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD NOV PY 2009 VL 75A IS 11 BP 966 EP 972 DI 10.1002/cyto.a.20799 PG 7 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 515UN UT WOS:000271498500011 PM 19777547 ER PT J AU Cannizzo, E Bellio, E Ferry, JA Hasserjian, RP Sohani, AR Dorn, ME Sadowski, C Bucci, JJ Petrini, M Carulli, G Preffer, F AF Cannizzo, Elisa Bellio, Emanuele Ferry, Judith A. Hasserjian, Robert P. Sohani, Aliyah R. Dorn, Michelle E. Sadowski, Craig Bucci, Janessa J. Petrini, Mario Carulli, Giovanni Preffer, Frederic TI MULTIPARAMETER IMMUNOPHENOTYPING BY FLOW CYTOMETRY IN MULTIPLE MYELOMA: DEFINING RANGES OF NORMAL EXPRESSION AND THEIR DIAGNOSTIC UTILITY SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 24th Annual Meeting of the Clinical-Cytometry-Society CY OCT 16-18, 2009 CL Jacksonville, FL SP Clin Cytometry Soc C1 [Cannizzo, Elisa; Ferry, Judith A.; Hasserjian, Robert P.; Sohani, Aliyah R.; Dorn, Michelle E.; Sadowski, Craig; Bucci, Janessa J.; Preffer, Frederic] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Cannizzo, Elisa; Ferry, Judith A.; Hasserjian, Robert P.; Sohani, Aliyah R.; Dorn, Michelle E.; Sadowski, Craig; Bucci, Janessa J.; Preffer, Frederic] Harvard Univ, Sch Med, Boston, MA USA. [Cannizzo, Elisa; Bellio, Emanuele; Petrini, Mario; Carulli, Giovanni] Univ Pisa, Sect Hematol, Dept Oncol Transplants & Adv Med, Pisa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2009 VL 76B IS 6 BP 397 EP 397 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 508UK UT WOS:000270962200013 ER PT J AU Cannizzo, E Bellio, E Sohani, AR Hasserjian, RP Ferry, JA Dorn, ME Sadowski, C Bucci, JJ Petrini, M Carulli, G Preffer, F AF Cannizzo, Elisa Bellio, Emanuele Sohani, Aliyah R. Hasserjian, Robert P. Ferry, Judith A. Dorn, Michelle E. Sadowski, Craig Bucci, Janessa J. Petrini, Mario Carulli, Giovanni Preffer, Frederic TI THE DIAGNOSTIC ROLE OF MULTIPARAMETER IMMUNOPHENOTYPING BY FLOW CYTOMETRY IN MULTIPLE MYELOMA: A NEW MODEL SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 24th Annual Meeting of the Clinical-Cytometry-Society CY OCT 16-18, 2009 CL Jacksonville, FL SP Clin Cytometry Soc C1 [Cannizzo, Elisa; Sohani, Aliyah R.; Hasserjian, Robert P.; Ferry, Judith A.; Dorn, Michelle E.; Sadowski, Craig; Bucci, Janessa J.; Preffer, Frederic] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Cannizzo, Elisa; Sohani, Aliyah R.; Hasserjian, Robert P.; Ferry, Judith A.; Dorn, Michelle E.; Sadowski, Craig; Bucci, Janessa J.; Preffer, Frederic] Harvard Univ, Sch Med, Boston, MA USA. [Cannizzo, Elisa; Bellio, Emanuele; Petrini, Mario; Carulli, Giovanni] Dept Oncol Transplants & Adv Med, Sect Hematol, Pisa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2009 VL 76B IS 6 BP 397 EP 397 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 508UK UT WOS:000270962200012 ER PT J AU Mehta, NK Chang, VW AF Mehta, Neil K. Chang, Virginia W. TI MORTALITY ATTRIBUTABLE TO OBESITY AMONG MIDDLE-AGED ADULTS IN THE UNITED STATES SO DEMOGRAPHY LA English DT Article ID BODY-MASS-INDEX; ALL-CAUSE MORTALITY; WAIST-HIP RATIO; US ADULTS; HEALTH RESEARCH; EXCESS DEATHS; CONFIDENCE-INTERVALS; SOCIOECONOMIC-STATUS; PROSPECTIVE COHORT; CIGARETTE-SMOKING AB Obesity is considered a major cause of premature mortality and a potential threat to the long-standing secular decline in mortality in the United States. We measure relative and attributable risks associated with obesity among middle-aged adults using data from the Health and Retirement Study (1992-2004). Although class II/III obesity (BMI >= 35.0 kg/m(2)) increases mortality by 40% in females and 62% in males compared with normal BMI (BMI = 18.5-24.9), class I obesity (BMI = 30.0-34.9) and being overweight (BM] = 25.0-29.9) are not associated with excess mortality. With respect to attributable mortality, class II/III obesity (BMI >= 35.0) is responsible for approximately 4% of deaths among females and 3% of deaths among males. Obesity is often compared with cigarette smoking as a major source of avoidable mortality. Smoking-attributable mortality is much larger in this cohort: about 36% in females and 50% in males. Results are robust to confounding by preexisting diseases, multiple dimensions of socioeconomic status (SES), smoking, and other correlates. These findings challenge the viewpoint that obesity will stem the long-term secular decline in U.S. mortality C1 [Mehta, Neil K.] Univ Michigan, Robert Wood Johnson Fdn Hlth & Soc, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Chang, Virginia W.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Chang, Virginia W.] Univ Penn, Dept Sociol, Philadelphia, PA 19104 USA. [Chang, Virginia W.] Univ Penn, Ctr Populat Studies, Philadelphia, PA 19104 USA. [Chang, Virginia W.] Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Mehta, NK (reprint author), Univ Michigan, Robert Wood Johnson Fdn Hlth & Soc, Sch Publ Hlth, 3628 SPH Tower,1415 Washington Hts, Ann Arbor, MI 48109 USA. EM nkmehta@umich.edu FU NIA NIH HHS [T32 AG000177]; NICHD NIH HHS [K12 HD043459, K12HD043459] NR 81 TC 49 Z9 49 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0070-3370 EI 1533-7790 J9 DEMOGRAPHY JI Demography PD NOV PY 2009 VL 46 IS 4 BP 851 EP 872 PG 22 WC Demography SC Demography GA 526SE UT WOS:000272312800010 PM 20084832 ER PT J AU Smoller, JW Block, SR Young, MM AF Smoller, Jordan W. Block, Stefanie R. Young, Mirella M. TI GENETICS OF ANXIETY DISORDERS: THE COMPLEX ROAD FROM DSM TO DNA SO DEPRESSION AND ANXIETY LA English DT Review DE genetics; anxiety; genomewide association study; heritability ID OBSESSIVE-COMPULSIVE DISORDER; GENOME-WIDE ASSOCIATION; SEROTONIN TRANSPORTER GENOTYPE; POSTTRAUMATIC-STRESS-DISORDER; HURRICANE-EXPOSED ADULTS; PANIC DISORDER; SOCIAL PHOBIA; BEHAVIORAL-INHIBITION; GENERALIZED ANXIETY; LINKAGE SCAN AB Anxiety disorders are among the most common psychiatric disorders, affecting one in four individuals over a lifetime. Although our understanding of the etiology of these disorders is incomplete, familial and genetic factors are established risk factors. However, identifying the specific casual genes has been difficult. Within the past several years, advances in molecular and statistical genetic methods have made the genetic dissection of complex disorders a feasible project. Here we provide an overview of these developments, with a focus on their implications for genetic studies of anxiety disorders. Although the genetic and phenotypic complexity of the anxiety disorders present formidable challenges, advances in neuroimaging and experimental animal models of anxiety and fear offer important opportunities for discovery. Real progress in identifying the genetic basis of anxiety disorders will require integrative approaches that make use of these biologic tools as well as larger-scale genomic studies. If successful, such efforts may yield novel and more effective approaches for the prevention and treatment of these common and costly disorders. Depression and Anxiety 26:965-975, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Smoller, Jordan W.; Block, Stefanie R.; Young, Mirella M.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat Genet Program Mood & Anxiety Disorders, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Psychiat Genet Program Mood & Anxiety Disorders, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM jsmoller@hms.harvard.edu NR 113 TC 39 Z9 41 U1 6 U2 35 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD NOV PY 2009 VL 26 IS 11 BP 965 EP 975 DI 10.1002/da.20623 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 515DV UT WOS:000271447900002 PM 19885930 ER PT J AU Simon, NM Herlands, NN Marks, EH Mancini, C Letamendi, A Li, ZH Pollack, MH Van Ameringen, M Stein, MB AF Simon, Naomi M. Herlands, Nannette N. Marks, Elizabeth H. Mancini, Catherine Letamendi, Andrea Li, Zhonghe Pollack, Mark H. Van Ameringen, Michael Stein, Murray B. TI CHILDHOOD MALTREATMENT LINKED TO GREATER SYMPTOM SEVERITY AND POORER QUALITY OF LIFE AND FUNCTION IN SOCIAL ANXIETY DISORDER SO DEPRESSION AND ANXIETY LA English DT Article DE social anxiety disorder; social phobia; anxiety; child abuse; abuse ID NATIONAL COMORBIDITY SURVEY; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; SEXUAL-ABUSE; DSM-IV; PSYCHOMETRIC PROPERTIES; PHOBIA; RISK; PSYCHOPATHOLOGY; SCALE; QUESTIONNAIRE AB Background: There is a paucity of data examining the prevalence and impact of childhood maltreatment in patients presenting with a primary diagnosis of social anxiety disorder (SAD). We thus examined the presence of a broad spectrum of childhood maltreatment, including physical, sexual, and emotional abuse and neglect, in treatment-seeking individuals with the generalized subtype of SAD (GSAD). We hypothesized that a history of childhood maltreatment would be associated with greater SAD symptom severity and poorer associated function. Methods: One hundred and three participants with a primary diagnosis of GSAD (mean age 37+/-14, 70% male) completed the well-validated, self-related Childhood Trauma Questionnaire (CTQ), as well as measures of SAD symptom severity and quality of life. Results: Fully 70% (n = 72) of the GSAD sample met severity criteria for at least one type of childhood abuse or neglect as measured by the CTQ subscales using previously established thresholds CTQ total score adjusted for age and gender was associated with greater SAD severity, and poorer quality of life, Junction, and resilience. Further, the number of types of maltreatment present had an additive effect, with specific associations for emotional abuse and neglect with SAD severity. Conclusions: Despite the we of validated assessments, our findings are limited by the retrospective and subjective nature of self-report measures used to assess childhood maltreatment. Nonetheless, these data suggest a high rate of childhood maltreatment in individuals seeking treatment for GSAD, and the association of maltreatment with greater disorder severity suggests that screening is clinically prudent. Depression and Anxiety 26:1027-1032, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Simon, Naomi M.; Herlands, Nannette N.; Marks, Elizabeth H.; Li, Zhonghe; Pollack, Mark H.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Mancini, Catherine; Van Ameringen, Michael] McMaster Univ, Med Ctr, Hamilton, ON, Canada. [Letamendi, Andrea; Stein, Murray B.] Univ Calif San Diego, Anxiety & Traumat Stress Disorders Program, San Diego, CA 92103 USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Simches Res Bldg,2nd Floor,185 Cambridge St, Boston, MA 02114 USA. EM nsimon@partners.org FU NIMH NIH HHS [5R01MH070919, R01 MH070919, R01 MH070919-05] NR 29 TC 44 Z9 45 U1 2 U2 17 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD NOV PY 2009 VL 26 IS 11 BP 1027 EP 1032 DI 10.1002/da.20604 PG 6 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 515DV UT WOS:000271447900010 PM 19750554 ER PT J AU Alquier, T Peyot, ML Latour, MG Kebede, M Sorensen, CM Gesta, S Kahn, CR Smith, RD Jetton, TL Metz, TO Prentki, M Poitout, V AF Alquier, Thierry Peyot, Marie-Line Latour, Martin G. Kebede, Melkam Sorensen, Christina M. Gesta, Stephane Kahn, C. Ronald Smith, Richard D. Jetton, Thomas L. Metz, Thomas O. Prentki, Marc Poitout, Vincent TI Deletion of GPR40 Impairs Glucose-Induced Insulin Secretion In Vivo in Mice Without Affecting Intracellular Fuel Metabolism in Islets SO DIABETES LA English DT Article ID PROTEIN-COUPLED RECEPTOR; FATTY-ACID STIMULATION; PANCREATIC BETA-CELLS; RAT ISLETS; EXPRESSION; PHOSPHOLIPASE-A(2); MODULATION; ACTIVATION; STARVATION; CALCIUM AB OBJECTIVE-The G-protein-coupled receptor GPR40 mediates fatty acid potentiation of glucose-stimulated insulin secretion, but its contribution to insulin secretion in vivo and mechanisms of action remain uncertain. This study was aimed to ascertain whether GPR40 controls insulin secretion in vivo and modulates intracellular fuel metabolism in islets. RESEARCH DESIGN AND METHODS-Insulin secretion and sensitivity were assessed in GPR40 knockout mice and their wild-type littermates by hyperglycemic clamps and hyperinsulinemic euglycemic clamps, respectively. Transcriptomic analysis, metabolic studies, and lipid profiling were used to ascertain whether GPR40 modulates intracellular fuel metabolism in islets. RESULTS-Both glucose- and arginine-stimulated insulin secretion in vivo were decreased by similar to 60% in GPR40 knockout fasted and fed mice, without changes in insulin sensitivity. Neither gene expression profiles nor intracellular metabolism of glucose and palmitate in isolated islets were affected by GPR40 deletion. Lipid profiling of isolated islets revealed that the increase in triglyceride and decrease in lyso-phosphatidylethanolamine species in response to palmitate in vitro was similar in wild-type and knockout islets. In contrast, the increase in intracellular inositol phosphate levels observed in wild-type islets in response to fatty acids in vitro was absent in knockout islets. CONCLUSIONS-These results indicate that deletion of GPR40 impairs insulin secretion in vivo not only in response to fatty acids but also to glucose and arginine, without altering intracellular fuel metabolism in islets, via a mechanism that may involve the generation of inositol phosphates downstream of GPR40 activation. Diabetes 58:2607-2615, 2009 C1 [Alquier, Thierry; Peyot, Marie-Line; Latour, Martin G.; Kebede, Melkam; Prentki, Marc; Poitout, Vincent] Univ Montreal, Montreal Univ Hosp, Res Ctr, Montreal Diabet Res Ctr, Montreal, PQ, Canada. [Alquier, Thierry; Kebede, Melkam; Poitout, Vincent] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Sorensen, Christina M.; Smith, Richard D.; Metz, Thomas O.] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. [Gesta, Stephane; Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA 02215 USA. [Gesta, Stephane; Kahn, C. Ronald] Harvard Univ, Sch Med, Boston, MA USA. [Jetton, Thomas L.] Univ Vermont, Coll Med, Div Endocrinol Diabet & Metab, Burlington, VT USA. [Prentki, Marc] Univ Montreal, Dept Nutr, Montreal, PQ H3C 3J7, Canada. RP Poitout, V (reprint author), Univ Montreal, Montreal Univ Hosp, Res Ctr, Montreal Diabet Res Ctr, Montreal, PQ, Canada. EM vincent.poitout@umontreal.ca OI Alquier, Thierry/0000-0001-8171-802X; Poitout, Vincent/0000-0002-6555-5053; Metz, Tom/0000-0001-6049-3968 FU National Institutes of Health [R21-DK070598, R01-DK068329, R33-DK070146]; Canadian Institutes of Health Research [MOP 177381]; Canadian Diabetes Association; DOE [DE-AC06-76LO-1830] FX This work was supported by National Institutes of Health Grants R21-DK070598 to V.P., R01-DK068329 to T.L.J., and R33-DK070146 to R.D.S. and T.O.M. and the Canadian Institutes of Health Research (MOP 177381 to V.P.). T.A. was supported by a postdoctoral fellowship from the Canadian Diabetes Association. V.P. holds the Canada Research Chair in Diabetes and Pancreatic P-Cell Function. M.P. holds the Canada Research Chair in Diabetes and Metabolism. The Pacific Northwest National Laboratory (PNNL) is operated by Battelle Memorial Institute for the DOE under contract no. DE-AC06-76LO-1830. NR 39 TC 67 Z9 68 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2009 VL 58 IS 11 BP 2607 EP 2615 DI 10.2337/db09-0362 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 515RQ UT WOS:000271490900022 PM 19720802 ER PT J AU Pezzolesi, MG Katavetin, P Kure, M Poznik, GD Skupien, J Mychaleckyj, JC Rich, SS Warram, JH Krolewski, AS AF Pezzolesi, Marcus G. Katavetin, Pisut Kure, Masahiko Poznik, G. David Skupien, Jan Mychaleckyj, Josyf C. Rich, Stephen S. Warram, James H. Krolewski, Andrzej S. TI Confirmation of Genetic Associations at ELMO1 in the GoKinD Collection Supports Its Role as a Susceptibility Gene in Diabetic Nephropathy SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; AFRICAN-AMERICANS; SCAN; COMPLICATIONS; POPULATION; VARIANTS; MELLITUS; DISEASE AB OBJECTIVE-To examine the association between single nucleotide polymorphisms (SNPs) in the engulftnent and cell motility 1 (ELMO1) gene, a locus previously shown to be associated with diabetic nephropathy in two ethnically distinct type 2 diabetic populations, and the risk of nephropathy in type 1 diabetes. RESEARCH DESIGN AND METHODS-Genotypic data from a genome-wide association scan (GWAS) of the Genetics of Kidneys in Diabetes (GoKinD) study collection were analyzed for associations across the ELMO1 locus. In total, genetic associations were assessed using 118 SNPs and 1,705 individuals of European ancestry with type 1 diabetes (885 normoalbuminuric control subjects and 820 advanced diabetic nephropathy case subjects). RESULTS-The strongest associations in ELMO1 occurred at rs11769038 (odds ratio [OR] 1.24; P = 1.7 X 10(-3)) and rs1882080 (OR 1.23; P = 3.2 X 10(-3)) located in intron 16. Two additional SNPs, located in introns 18 and 20, respectively, were also associated with diabetic nephropathy. No evidence of association for variants previously reported in type 2 diabetes was observed in our collection. CONCLUSIONS-Using GWAS data from the GoKinD collection, we comprehensively examined evidence of association across the ELMO1 locus. Our investigation marks the third report of associations in ELMO1 with diabetic nephropathy, further establishing its role in the susceptibility of this disease. There is evidence of allelic heterogeneity, contributed by the diverse genetic backgrounds of the different ethnic groups examined. Further investigation of SNPs at this locus is necessary to fully understand the commonality of these associations and the mechanism(s) underlying their role in diabetic nephropathy. Diabetes 58:2698-2702, 2009 C1 [Pezzolesi, Marcus G.; Katavetin, Pisut; Kure, Masahiko; Poznik, G. David; Skupien, Jan; Warram, James H.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. [Pezzolesi, Marcus G.; Katavetin, Pisut; Kure, Masahiko; Poznik, G. David; Skupien, Jan; Warram, James H.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Mychaleckyj, Josyf C.; Rich, Stephen S.] Univ Virginia, Sch Med, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA. RP Krolewski, AS (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. EM andrzej.krolewski@joslin.harvard.edu FU National Institutes of Health (NIH) [DK77532]; Foundation for NIH (FNIH) [06GAIN0]; Joslin Diabetes Center's NIH [DK007260-31]; Juvenile Diabetes Research Foundation [3-2009-397] FX No potential conflicts of interest relevant to this article were reported. NR 23 TC 56 Z9 56 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2009 VL 58 IS 11 BP 2698 EP 2702 DI 10.2337/db09-0641 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 515RQ UT WOS:000271490900032 PM 19651817 ER PT J AU Li, RL O'Sullivan, MJ Robinson, J Safford, MM Curb, D Johnson, KC AF Li, Rongling O'Sullivan, Mary J. Robinson, Jennifer Safford, Monika M. Curb, David Johnson, Karen C. TI Family history of myocardial infarction predicts incident coronary heart disease in postmenopausal women with diabetes: the Women's Health Initiative Observational Study SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article DE family history; CHD; diabetes; women's health ID CARDIOVASCULAR RISK-FACTORS; ATHEROSCLEROSIS RISK; PARENTAL HISTORY; ARTERY DISEASE; MENOPAUSE; AGE; EPIDEMIOLOGY; FRAMINGHAM; COHORT AB Background Diabetes is a risk factor for coronary heart disease (CHD) but CHD does not occur in all diabetic individuals. The goal of this study was to assess the relationship between family history of myocardial infarction (MI) and incident CHD in diabetic postmenopausal women. Methods We conducted a prospective cohort study among 2642 diabetic postmenopausal women without CHD at baseline in the Women's Health Initiative Observational Study. Family history was defined as a proband report of MI in first-degree relatives. Incident CHD was defined as non-fatal MI, coronary revascularization, or CHD death. Results During 7.3 (+/- 1.8) years of follow-up, 14.3% of the participants had incident CHD. The risk of incident CHD was 50% higher (HR = 1.50, 95% Cl: 1.20-1.87, p = 0.0003) in those with a family history of an MI in at least one first-degree relative, and 79% higher (HR = 1.79, 95% Cl: 1.36-2.35, P < 0.0001) if two or more first-degree relatives had an MI, compared to participants without a family history, after adjustment for covariates. The CHD risk increased with elevated systolic blood pressure (SBP) (HR = 1.01, 95% Cl: 1.003-1.02, p = 0.001) but decreased with elevated diastolic BP (HR = 0.98, 95% Cl: 0.97-0-999, p = 0.005) and with two or more episodes per week of physical activity (HR = 0.70, 95% Cl: 0.52-0.93, p = 0.02). Conclusions The results suggest that a family history of MI predicts CHD in diabetic postmenopausal women. Close attention should be paid to BP control and physical activity in these women. Copyright (C) 2009 John Wiley & Sons Ltd,. C1 [Li, Rongling; Johnson, Karen C.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [O'Sullivan, Mary J.] Univ Miami, Miller Sch Med, Dept Obstet & Gynecol, Miami, FL 33136 USA. [Robinson, Jennifer] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Safford, Monika M.] Univ Alabama, Birmingham, AL USA. [Safford, Monika M.] Birmingham VA Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA. [Curb, David] Pacific Hlth Res Inst, Honolulu, HI USA. RP Li, RL (reprint author), NHGRI, OPG, NIH, 5635 Fishers Lane,Suite 4076,MSC 9305, Bethesda, MD 20892 USA. EM lir2@mail.nih.gov FU National Heart, Lung, and Blood Institute, NIH [NO1-WH-3-2100, NO1-WH-3-2101, NO1-WH-3-2102, NO1-WH-3-2105, NO1-WH-3-2106, NO1-WH-3-2108, NO1-WH-3-2109, NO1-WH-3-2110, NO1-WH-3-2111, NO1-WH-3-2112, NO1-WH-3-2113, NO1-WH-3-2115, NO1-WH-3-2118, NO1-WH-3-2119, NO1-WH-3-2120, NO1-WH-3-2122, NO1-WH-4-2107, NO1-WH-4-2108] FX We acknowledge all WHI-OS participants and NIH for making the funds available for the study. The WHI program is funded by NIH Contracts: NO1-WH-3-2100, NO1-WH-3-2101, NO1-WH-3-2102, NO1-WH-3-2105, NO1-WH-3-2106, NO1-WH-3-2108, NO1-WH-3-2109, NO1-WH-3-2110, NO1-WH-3-2111, NO1-WH-3-2112, NO1-WH-3-2113, NO1-WH-3-2115, NO1-WH-3-2118, NO1-WH-3-2119, NO1-WH-3-2120, NO1-WH-3-2122, NO1-WH-4-2107, NO1-WH-4-2108, NO1-WH-4-2109, NO1-WH-4-2110, NO1-WH-4-2111, NO1-WH-4-2112, NO1-WH-4-2113, NO1-WH-4-2114, NO1-WH-4-2115, NO1-WH-4-2116, NO1-WH-4-2117, NO1-WH-4-2118, NO1-WH-4-2119, NO1-WH-4-2120, NO1-WH-4-2121, NO1-WH-4-2122, NO1-WH-4-2123, NO1-WH-4-2124, NO1-WH-4-2125, NO1-WH-4-2126, NO1-WH-4-2129, NO1-WH-4-2130, NO1-WH-4-2131, and NO1-WH-4-2132 from the National Heart, Lung, and Blood Institute, NIH. NR 26 TC 1 Z9 2 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD NOV PY 2009 VL 25 IS 8 BP 725 EP 732 DI 10.1002/dmrr.1010 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 522RP UT WOS:000272016300005 PM 19780066 ER PT J AU Liew, CW Holman, A Kulkarni, RN AF Liew, C. W. Holman, A. Kulkarni, R. N. TI The roles of telomeres and telomerase in beta-cell regeneration SO DIABETES OBESITY & METABOLISM LA English DT Article DE beta-cells; diabetes; telomere; islets; ageing ID PANCREATIC-ISLET CELLS; INSULIN-RESISTANCE; DIABETES-MELLITUS; MAMMALIAN TELOMERES; MOUSE TELOMERASE; UNITED-STATES; BLOOD-CELLS; DNA-DAMAGE; DYSFUNCTION; GROWTH AB Telomerase is a specialized reverse transcriptase that is responsible for extending and preserving the end of the chromosomes (telomeres). Telomerase plays a key role in regulating the lifespan of mammalian cells and is involved in critical aspects of cellular ageing processes. In this review, we will briefly summarize our current understanding of the functions of telomeres, telomerase and their regulation. Considering that compensatory islet hyperplasia and beta-cell regeneration play important roles in the prevention and/or delay of the onset of overt diabetes, we will also examine current literature regarding the effects of diabetes on telomere shortening and provide insights from our own studies on the role of telomerase in beta-cell regeneration. C1 [Kulkarni, R. N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. EM Rohit.Kulkarni@joslin.harvard.edu FU NIH [RO1 DK 67536, RO1 DK 68721, 1RL9EB008539-01] FX We thank the organizers of the International Group on Insulin Secretion (IGIS) for the opportunity to share these data, and Lindsay Huse for excellent assistance with preparation of the manuscript. This work was supported in part by RO1 DK 67536 (R. N. K.) and RO1 DK 68721 (R. N. K.). An NIH training grant (1RL9EB008539-01) (SysCODE) supported C. W. L. NR 75 TC 11 Z9 11 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD NOV PY 2009 VL 11 BP 21 EP 29 DI 10.1111/j.1463-1326.2009.01103.x PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 504JS UT WOS:000270613000004 PM 19817785 ER PT J AU Weir, GC Marselli, L Marchetti, P Katsuta, H Jung, MH Bonner-Weir, S AF Weir, G. C. Marselli, L. Marchetti, P. Katsuta, H. Jung, M. H. Bonner-Weir, S. TI Towards better understanding of the contributions of overwork and glucotoxicity to the beta-cell inadequacy of type 2 diabetes SO DIABETES OBESITY & METABOLISM LA English DT Article DE beta-cell; endoplasmic reticulum (ER) stress; glucotoxicity; insulin secretion; laser capture microdissection; type 2 diabetes ID ENDOPLASMIC-RETICULUM STRESS; CHRONIC HYPERGLYCEMIA; INSULIN-SECRETION; GENE-EXPRESSION; PARTIAL-PANCREATECTOMY; GLUCOSE-TOLERANCE; ISLETS; RAT; REGENERATION; DYSFUNCTION AB Type 2 diabetes (T2D) is characterized by reduction of beta-cell mass and dysfunctional insulin secretion. Understanding beta-cell phenotype changes as T2D progresses should help explain these abnormalities. The normal phenotype should differ from the state of overwork when beta-cells compensate for insulin resistance to keep glucose levels normal. When only mild hyperglycaemia develops, beta-cells are subjected to glucotoxicity. As hyperglycaemia becomes more severe, so does glucotoxicity. beta-Cells in all four of these situations should have separate phenotypes. When assessing phenotype with gene expression, isolated islets have artefacts resulting from the trauma of isolation and hypoxia of islet cores. An advantage comes from laser capture microdissection (LCM), which obtains beta-cell-rich tissue from pancreatic frozen sections. Valuable data can be obtained from animal models, but the real goal is human beta-cells. Our experience with LCM and gene arrays on frozen pancreatic sections from cadaver donors with T2D and controls is described. Although valuable data was obtained, we predict that the approach of taking fresh samples at the time of surgery is an even greater opportunity to markedly advance our understanding of how beta-cell phenotype evolves as T2D develops and progresses. C1 [Weir, G. C.; Marselli, L.; Katsuta, H.; Jung, M. H.; Bonner-Weir, S.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. [Marchetti, P.] Univ Pisa, Dept Endocrinol & Metab, Metab Unit, Pisa, Italy. RP Weir, GC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu RI Marchetti, Piero/J-7439-2013 OI Marchetti, Piero/0000-0003-4907-0635 FU American Diabetes Association; Juvenile Diabetes Research Foundation; National Institutes of Health [DK66056, P30 DK36836] FX This study was supported by grants from the American Diabetes Association, the Juvenile Diabetes Research Foundation, the National Institutes of Health (DK66056, P30 DK36836) including the Advanced Microscopy Core of the Joslin Diabetes and Endocrinology Research Center (DERC), the Diabetes Research and Wellness Foundation and an important group of private donors. NR 35 TC 50 Z9 50 U1 0 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD NOV PY 2009 VL 11 BP 82 EP 90 DI 10.1111/j.1463-1326.2009.01113.x PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 504JS UT WOS:000270613000010 PM 19817791 ER PT J AU Markowitz, JT Lowe, MR Volkening, LK Laffel, LMB AF Markowitz, J. T. Lowe, M. R. Volkening, L. K. Laffel, L. M. B. TI Self-reported history of overweight and its relationship to disordered eating in adolescent girls with Type 1 diabetes SO DIABETIC MEDICINE LA English DT Article DE adolescence; obesity; type 1 diabetes ID QUESTIONNAIRE EDE-Q; DIETARY RESTRAINT; WOMEN; YOUNG; PREVALENCE; MELLITUS; BEHAVIOR; FEMALES; WEIGHT; NORMS AB Aims Increased body weight and disordered eating attitudes/behaviours are common in adolescent girls with Type 1 diabetes (T1D). Disordered eating increases risks for diabetes-related complications. This study aimed to identify a rapid screening approach for disordered eating attitudes and behaviours in adolescent girls with T1D and to examine the relationship between disordered eating and body weight in this population. Methods Ninety adolescent girls, aged 12-19 years, provided a self-assessment of weight status. Participants also completed questionnaires to assess attitudes/behaviours toward food and eating, appetitive responsiveness to the food environment, disinhibition in eating and weight history. Results Forty-three per cent of participants reported a history of overweight. Compared with participants who reported never being overweight, those who reported ever being overweight were significantly older, scored significantly higher on all measures of disordered eating attitudes/behaviours (P < 0.009) and were 4.8 times more likely to be currently overweight or obese (P < 0.001). Glycated haemoglobin (HbA(1c)) was similar between those who did and did not report ever being overweight. Conclusions Because of the ill-health effects of disordered eating and the higher rate of overweight in adolescent girls with T1D, effective screening tools are warranted. The single question 'Have you ever been overweight?' may be sufficient as a first question to screen for those at high risk for disordered eating attitudes/behaviours and to provide early intervention and prevention. C1 [Markowitz, J. T.; Volkening, L. K.; Laffel, L. M. B.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. [Markowitz, J. T.; Volkening, L. K.; Laffel, L. M. B.] Joslin Diabet Ctr, Genet & Epidemiol Sect, Boston, MA 02215 USA. [Lowe, M. R.] Drexel Univ, Dept Psychol, Philadelphia, PA 19104 USA. RP Markowitz, JT (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM jessica.markowitz@joslin.harvard.edu FU NIH [T32 DK007260]; Katherine Adler Astrove Youth Education Fund; Maria Griffin Drury Pediatric Fund FX The authors would like to thank Evan Forman PhD, Pamela Geller PhD, Terri Lipman PhD and Nancy Silverman PhD for their support. In addition, we would like to thank Yelena Chernyak MS and Graham Thomas MS for their help with data collection and analysis. This study was supported in part by NIH Training Grant No. T32 DK007260, the Charles H. Hood Foundation, the Katherine Adler Astrove Youth Education Fund and the Maria Griffin Drury Pediatric Fund. NR 37 TC 5 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD NOV PY 2009 VL 26 IS 11 BP 1165 EP 1171 DI 10.1111/j.1464-5491.2009.02844.x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 515ST UT WOS:000271493900013 PM 19929996 ER PT J AU Grant, RW Hivert, M Pandiscio, JC Florez, JC Nathan, DM Meigs, JB AF Grant, R. W. Hivert, M. Pandiscio, J. C. Florez, J. C. Nathan, D. M. Meigs, J. B. TI The clinical application of genetic testing in type 2 diabetes: a patient and physician survey SO DIABETOLOGIA LA English DT Article DE Diabetes prediction; Genetic risk; Genetic testing; Medication adherence; Patient motivation; Type 2 diabetes ID GENOME-WIDE ASSOCIATION; LIFE-STYLE MODIFICATION; PREVENTION PROGRAM; RISK-FACTORS; VARIANT; ADULTS AB Aims/hypothesis Advances in type 2 diabetes genetics have raised hopes that genetic testing will improve disease prediction, prevention and treatment. Little is known about current physician and patient views regarding type 2 diabetes genetic testing. We hypothesised that physician and patient views would differ regarding the impact of genetic testing on motivation and adherence. Methods We surveyed a nationally representative sample of US primary care physicians and endocrinologists (n=304), a random sample of non-diabetic primary care patients (n=152) and patients enrolled in a diabetes pharmacogenetics study (n=89). Results Physicians and patients favoured genetic testing for diabetes risk prediction (79% of physicians vs 80% of nondiabetic patients would be somewhat/very likely to order/request testing, p=0.7). More patients than physicians (71% vs 23%, p<0.01) indicated that a 'high risk' result would be very likely to improve motivation to adopt preventive lifestyle changes. Patients favoured genetic testing to guide therapy (78% of patients vs 48% of physicians very likely to request/recommend testing, p<0.01) and reported that genetic testing would make them 'much more motivated' to adhere to medications (72% vs 18% of physicians, p<0.01). Many physicians (39%) would be somewhat/very likely to order genetic testing before published evidence of clinical efficacy. Conclusions/interpretation Despite the paucity of current data, physicians and patients reported high expectations that genetic testing would improve patient motivation to adopt key behaviours for the prevention or control of type 2 diabetes. This suggests the testable hypothesis that 'genetic' risk information might have greater value to motivate behaviour change compared with standard risk information. C1 [Grant, R. W.; Hivert, M.; Pandiscio, J. C.; Meigs, J. B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Florez, J. C.; Nathan, D. M.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Grant, R. W.; Florez, J. C.; Nathan, D. M.; Meigs, J. B.] Harvard Univ, Sch Med, Boston, MA USA. [Florez, J. C.] Broad Inst Harvard & MIT, Cambridge, MA USA. RP Grant, RW (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM Rgrant@partners.org OI Grant, Richard/0000-0002-6164-8025 FU National Institutes of Health [NIDDK K23 DK067452]; Charlton Family Fund FX R. W. Grant is supported by a National Institutes of Health career development award (NIDDK K23 DK067452). This study was funded in part by the Charlton Family Fund. NR 24 TC 47 Z9 47 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD NOV PY 2009 VL 52 IS 11 BP 2299 EP 2305 DI 10.1007/s00125-009-1512-7 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 504XE UT WOS:000270650600007 PM 19727660 ER PT J AU Kaunitz, JD AF Kaunitz, Jonathan D. TI GRG Update: DDW 2009 and Upcoming GRG-Sponsored Meetings SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material C1 [Kaunitz, Jonathan D.] W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD NOV PY 2009 VL 54 IS 11 BP 2301 EP 2302 DI 10.1007/s10620-009-0987-x PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 507FI UT WOS:000270836900001 ER PT J AU Puli, SR Reddy, JBK Bechtold, ML Antillon, MR Brugge, WR AF Puli, Srinivas R. Reddy, Jyotsna B. K. Bechtold, Matthew L. Antillon, Mainor R. Brugge, William R. TI EUS-Guided Celiac Plexus Neurolysis for Pain due to Chronic Pancreatitis or Pancreatic Cancer Pain: A Meta-Analysis and Systematic Review SO DIGESTIVE DISEASES AND SCIENCES LA English DT Review DE Endoscopic ultrasound; Celiac plexus neurolysis; Pancreatic cancer; Chronic pancreatitis; Meta-analysis; Systematic review ID PROSPECTIVE RANDOMIZED-TRIAL; SHOCK-WAVE LITHOTRIPSY; ENDOSCOPIC ULTRASOUND; ABDOMINAL-PAIN; CLINICAL-TRIALS; BLOCK; RESECTION; DRAINAGE; THERAPY; QUALITY AB The objective of this study was to evaluate the efficacy of EUS-guided CPN for pain relief in patients with chronic pancreatitis and pancreatic cancer. An initial search identified 1,439 reference articles, of which 130 relevant articles were selected and reviewed. Data was extracted from 8 studies (N = 283) for EUS-guided CPN for pain due to pancreatic cancer and nine studies for chronic pancreatitis (N = 376) which met the inclusion criteria. With EUS-guided CPN, the pooled proportion of patients with pancreatic cancer that showed pain relief was 80.12% (95% CI = 74.47-85.22). In patients with pain due to chronic pancreatitis, EUS-guided CPN provided pain relief in 59.45% (95% CI = 54.51-64.30). In conclusion, EUS-guided CPN offers a safe alternative technique for pain relief in patients with chronic pancreatitis or pancreatic cancer. In patients with pain due to chronic pancreatitis, better techniques or injected materials are needed to improve the response. C1 [Puli, Srinivas R.; Reddy, Jyotsna B. K.; Bechtold, Matthew L.; Antillon, Mainor R.] Univ Missouri, Div Gastroenterol & Hepatol, Clin Support & Educ CE443, Columbia, MO 65212 USA. [Brugge, William R.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. RP Puli, SR (reprint author), Univ Missouri, Div Gastroenterol & Hepatol, Clin Support & Educ CE443, 5 Hosp Dr,DC043-00, Columbia, MO 65212 USA. EM pulis@missouri.edu NR 54 TC 94 Z9 103 U1 1 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD NOV PY 2009 VL 54 IS 11 BP 2330 EP 2337 DI 10.1007/s10620-008-0651-x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 507FI UT WOS:000270836900006 PM 19137428 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Demographic Characteristics of Hospitalized IBD Patients SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Environmental risk factors; Epidemiology of IBD; Geographic variation; Hospital statistics; Socio-economic status; Time trends ID INFLAMMATORY-BOWEL-DISEASE; EPIDEMIOLOGY; AMERICANS; MORTALITY; VOLUME AB The Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project (HCUP) was used to study the recent demographic characteristics of patients with Crohn's disease (CD) or ulcerative colitis (UC). HCUP data of the period 1997-2006 were extracted. The data were stratified by the categories pertaining to patient demographics, such as age-group, sex, race, insurance type, income group, residence in metropolitan area and region of the United States, as well as categories pertaining to hospital characteristics, such as type of ownership, teaching status, location, and bed-size. The distributions of inpatients among different categories were compared between CD or UC and all other diagnoses, using odds ratios and their 95% confidence intervals for comparison. The data revealed a slight female predominance in CD (1.08, 1.09-1.09) and a slight male predominance in UC (1.15, 1.14-1.15). Compared to patients with other diagnoses, patients with inflammatory bowel disease tended to be white (CD: 2.47, 2.45-2.50; UC: 2.13, 2.10-2.15), more affluent (CD: 1.44, 1.43-1.45; UC: 1.59, 1.58-1.61), live in metropolitan areas (CD: 1.09, 1.08-1.10; UC: 1.26, 1.25-1.27) and in the Northeast of the United States (CD: 1.27, 1.27-1.28; UC: 1.44, 1.43-1.45). These patterns confirm previously described characteristics of patients with inflammatory bowel disease and show that such characteristics still apply to present patient populations. C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, P3 GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 22 TC 13 Z9 13 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD NOV PY 2009 VL 54 IS 11 BP 2449 EP 2455 DI 10.1007/s10620-009-0973-3 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 507FI UT WOS:000270836900023 PM 19760158 ER PT J AU Nentwich, L Ulrich, AS AF Nentwich, Lauren Ulrich, Andrew S. TI High-Risk Chief Complaints II: Disorders of the Head and Neck SO EMERGENCY MEDICINE CLINICS OF NORTH AMERICA LA English DT Article DE Headache; Seizure; Acute neurologic deficits; Throat pain; Neck pain; Ocular emergencies; Difficult airway ID SPONTANEOUS INTRACEREBRAL HEMORRHAGE; PEDIATRIC EMERGENCY-DEPARTMENT; DIFFICULT TRACHEAL INTUBATION; TISSUE-PLASMINOGEN ACTIVATOR; IMPOSSIBLE MASK VENTILATION; ASSOCIATION STROKE COUNCIL; TRANSIENT ISCHEMIC ATTACK; HEALTH-CARE PROFESSIONALS; OF-NEUROLOGY AFFIRMS; C-SPINE RULE AB Of the many different complaints of patients presenting to the emergency department, some of the most difficult to diagnose and manage involve pathology of the head and neck. Often diagnoses of conditions affecting this part of the body are elusive, and occasionally, even once the diagnosis has been made, the management of these disorders remains challenging. This article addresses some of the high-risk chief complaints of the head and neck regarding diagnosis and management. These complaints include headache, seizure, acute focal neurologic deficits, throat and neck pain, ocular emergencies, and the difficult airway. C1 [Nentwich, Lauren] Massachusetts Gen Hosp, Ctr Stroke Res, Dept Neurol, Boston, MA 02114 USA. [Ulrich, Andrew S.] Boston Univ, Sch Med, Boston Med Ctr, Dept Emergency Med, Boston, MA 02118 USA. RP Nentwich, L (reprint author), Massachusetts Gen Hosp, Ctr Stroke Res, Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM lnentwich@partners.org NR 99 TC 3 Z9 3 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 0733-8627 EI 1558-0539 J9 EMERG MED CLIN N AM JI Emerg. Med. Clin. N. Am. PD NOV PY 2009 VL 27 IS 4 BP 713 EP + DI 10.1016/j.emc.2009.08.002 PG 35 WC Emergency Medicine SC Emergency Medicine GA 602LK UT WOS:000278140500014 PM 19932402 ER PT J AU Manini, AF Ilgen, J Noble, VE Bamberg, F Koenig, W Bohan, JS Hoffmann, U AF Manini, A. F. Ilgen, J. Noble, V. E. Bamberg, F. Koenig, W. Bohan, J. S. Hoffmann, U. TI Derivation and validation of a sensitive IMA cutpoint to predict cardiac events in patients with chest pain SO EMERGENCY MEDICINE JOURNAL LA English DT Article ID ISCHEMIA-MODIFIED ALBUMIN; ACUTE CORONARY SYNDROMES; EMERGENCY-DEPARTMENT; MYOCARDIAL-INFARCTION; BINDING ASSAY; LIMITATIONS; TROPONIN; RULE AB Objectives: In patients with acute chest pain, we derived a cutpoint for ischaemia-modified albumin (IMA) and prospectively validated this cutpoint to predict 30-day major adverse cardiac events (MACEs). Methods: We prospectively recruited a derivation cohort (18-month period) to establish a serum IMA cutpoint targeting 80% sensitivity. This was followed by a prospective validation cohort study of emergency department patients with acute chest pain at two university hospitals over a 3-month period. A MACE was defined as myocardial infarction, revascularisation or death at 30-day follow-up. Results: In the derivation cohort of 151 patients, the IMA cutpoint that achieved 80% sensitivity for MACEs was 75 KU/litre. The sensitivity was prospectively validated in 171 patients consecutively enrolled, of whom 106 underwent multiple-biomarker analysis (19.8% MACE rate, 81% sensitivity of IMA). Furthermore, IMA by itself (81%, p<0.01) and in combination with initial highly sensitive cardiac troponin T (hsTnT) (90%, p<0.001) had significantly higher sensitivity than initial hsTnT (29%) for prediction of MACEs. Conclusions: We prospectively validated the sensitive IMA cutpoint of 75 KU/litre with 80% sensitivity for MACEs in patients with acute chest pain. Our data suggest that IMA alone and in combination with initial hsTnT are more sensitive than the initial hsTnT for MACEs. C1 [Manini, A. F.] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA. [Ilgen, J.] Harvard Univ, Sch Med, Harvard Affiliated Emergency Med Residency, Boston, MA USA. [Noble, V. E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Bamberg, F.; Hoffmann, U.] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Koenig, W.] Univ Ulm, Div Cardiol, Ulm, Germany. [Bohan, J. S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. RP Manini, AF (reprint author), Mt Sinai Sch Med, Dept Emergency Med, 1 Gustrave L Levy Pl,Box 1620, New York, NY 10029 USA. EM alex.manini@mountsinai.org FU Dade Behring; Massachusetts General Hospital Departmental Award; National Institutes of Health [HL080053] FX Cardiac Diagnostics Grant from Dade Behring ( to JSB), Massachusetts General Hospital Departmental Award ( to AFM) and in part by the National Institutes of Health (HL080053 to UH). NR 19 TC 4 Z9 5 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1472-0205 J9 EMERG MED J JI Emerg. Med. J. PD NOV PY 2009 VL 26 IS 11 BP 791 EP 796 DI 10.1136/emj.2008.068130 PG 6 WC Emergency Medicine SC Emergency Medicine GA 509NB UT WOS:000271023600010 PM 19850803 ER PT J AU Peluso, JJ Gawkowska, A Liu, XF Shioda, T Pru, JK AF Peluso, John J. Gawkowska, Anna Liu, Xiufang Shioda, Toshi Pru, James K. TI Progesterone Receptor Membrane Component-1 Regulates the Development and Cisplatin Sensitivity of Human Ovarian Tumors in Athymic Nude Mice SO ENDOCRINOLOGY LA English DT Article ID CANCER-CELLS; MOLECULAR-MECHANISMS; BINDING-PROTEIN; EXPRESSION; MODELS; XENOGRAFTS; RESISTANCE; INHIBITION; VIABILITY; APOPTOSIS AB To determine whether progesterone receptor membrane component 1 (PGRMC1) regulates the development and cisplatin (CDDP)-sensitivity of human ovarian tumors, PGRMC1 was depleted from a human ovarian cancer cell line, dsRed-SKOV-3 cells, using a short hairpin RNA knockdown approach. Compared with parental dsRed-SKOV-3 cells, the PGRMC1-deplete cells grew slower in vitro and did not show progesterone's (P4) antiapoptotic effect. In fact, P4 induced apoptosis in PGRMC1-deplete cells in a dose-dependent manner. When transplanted into the peritoneum of athymic nude mice, parental dsRed-SKOV-3 cells developed numerous tumors, which were classified as either typical or oxyphilic clear cell tumors. CDDP increased the percentage of apoptotic nuclei in typical clear cell tumors and P4 attenuated CDDP-induced apoptosis. In contrast, the percentage of apoptotic nuclei in oxyphilic clear cell tumors was low (<= 1%) and was not significantly affected by CDDP and/or P4. Compared with tumors derived from parental dsRed SKOV-3 cells, PGRMC1-deplete tumors: 1) developed in fewer mice, 2) formed less frequently, 3) appeared smaller, and 4) resulted in fewer oxyphilic clear cell tumors. These PGRMC1-deplete tumors were not responsive to CDDP's apoptotic effects. The failure to respond to CDDP could be due to their poorly developed microvasculature system as judged by percentage of CD31-stained endothelial cells and/or their increased expression of ATP-binding cassette transporters, which are involved in drug resistance. Taken together, these findings indicate that PGRMC1 plays an essential role in the development and CDDP sensitivity of human ovarian tumors. (Endocrinology 150: 4846-4854, 2009) C1 [Peluso, John J.; Gawkowska, Anna; Liu, Xiufang] Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT 06030 USA. [Peluso, John J.] Univ Connecticut, Ctr Hlth, Dept Obstet & Gynecol, Farmington, CT 06030 USA. [Shioda, Toshi] Harvard Univ, Dept Tumor Biol, Mol Profiling Lab, Massachusetts Gen Hosp Ctr Canc Res,Med Sch, Charlestown, MA 02129 USA. [Pru, James K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Peluso, JJ (reprint author), Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT 06030 USA. EM peluso@nso2.uchc.edu FU Connecticut Department of Public Health Biomedical Research [BCH-2007-0918]; Vincent Memorial Research Funds FX Disclosure Summary: The authors have nothing to disclose. NR 35 TC 29 Z9 29 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2009 VL 150 IS 11 BP 4846 EP 4854 DI 10.1210/en.2009-0730 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 509ID UT WOS:000271007700004 PM 19797399 ER PT J AU Hill, JW Xu, Y Preitner, F Fukuda, M Cho, YR Luo, J Balthasar, N Coppari, R Cantley, LC Kahn, BB Zhao, JJ Elmquist, JK AF Hill, Jennifer W. Xu, Yong Preitner, Frederic Fukuda, Makota Cho, You-Ree Luo, Ji Balthasar, Nina Coppari, Roberto Cantley, Lewis C. Kahn, Barbara B. Zhao, Jean J. Elmquist, Joel K. TI Phosphatidyl Inositol 3-Kinase Signaling in Hypothalamic Proopiomelanocortin Neurons Contributes to the Regulation of Glucose Homeostasis SO ENDOCRINOLOGY LA English DT Article ID INCREASED INSULIN SENSITIVITY; GLUCOCORTICOID-RECEPTOR ANTAGONISM; POMC-EXPRESSING CELLS; PHOSPHOINOSITIDE 3-KINASE; MICE LACKING; BODY-WEIGHT; ENERGY HOMEOSTASIS; P85-ALPHA SUBUNIT; ARCUATE NUCLEUS; FOOD-INTAKE AB Recent studies demonstrated a role for hypothalamic insulin and leptin action in the regulation of glucose homeostasis. This regulation involves proopiomelanocortin (POMC) neurons because suppression of phosphatidyl inositol 3-kinase (PI3K) signaling in these neurons blunts the acute effects of insulin and leptin on POMC neuronal activity. In the current study, we investigated whether disruption of PI3K signaling in POMC neurons alters normal glucose homeostasis using mouse models designed to both increase and decrease PI3K-mediated signaling in these neurons. We found that deleting p85 alpha alone induced resistance to diet-induced obesity. In contrast, deletion of the p110 alpha catalytic subunit of PI3K led to increased weight gain and adipose tissue along with reduced energy expenditure. Independent of these effects, increased PI3K activity in POMC neurons improved insulin sensitivity, whereas decreased PI3K signaling resulted in impaired glucose regulation. These studies show that activity of the PI3K pathway in POMC neurons is involved in not only normal energy regulation but also glucose homeostasis. (Endocrinology 150: 4874-4882, 2009) C1 [Elmquist, Joel K.] Univ Texas SW Med Ctr Dallas, Div Hypothalam Res, Dept Internal Med, Touchstone Ctr Diabet Res, Dallas, TX 75390 USA. [Cho, You-Ree] Univ Texas SW Med Ctr Dallas, Dept Internal Med & Pharmacol, Dept Internal Med & Cell Biol, Touchstone Ctr Diabet Res, Dallas, TX 75390 USA. [Preitner, Frederic] Univ Lausanne, Cardiomet Mouse Metab Facil, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland. [Luo, Ji] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA. [Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02215 USA. [Zhao, Jean J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Luo, Ji] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. [Kahn, Barbara B.] Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. [Zhao, Jean J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Balthasar, Nina] Univ Bristol, Div Physiol, Bristol BS8 1TD, Avon, England. RP Elmquist, JK (reprint author), Univ Texas SW Med Ctr Dallas, Div Hypothalam Res, Dept Internal Med, Touchstone Ctr Diabet Res, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM jean_zhao@dfci.harvard.edu; joel.elmquist@utsouthwestern.edu RI Fukuda, Makoto/C-9745-2009; Coppari, Roberto/B-4799-2014; Cantley, Lewis/D-1800-2014; Fukuda, Makoto/I-7915-2014 OI Fukuda, Makoto/0000-0003-0112-9925; Cantley, Lewis/0000-0002-1298-7653; Fukuda, Makoto/0000-0003-0112-9925 FU University of Texas Southwestern Medical Center at Dallas [PL1 DK081182-01]; National Institutes of Health [1F32DK066972, K99HD056491, K99DK085330, PO1 DK56116, DK53301, GM41890, R01 DK53301-07S2, R01 CA134502-01]; V Foundation; Canadian Institute of Health Research; American Diabetes Association Smith Family Foundation; Takeda Pharmaceutical Co., Ltd., Japan FX Disclosure Summary: The authors have nothing to declare. NR 62 TC 45 Z9 48 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2009 VL 150 IS 11 BP 4874 EP 4882 DI 10.1210/en.2009-0454 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 509ID UT WOS:000271007700007 PM 19819947 ER PT J AU Lessard, SJ Rivas, DA Chen, ZP van Denderen, BJ Watt, MJ Koch, LG Britton, SL Kemp, BE Hawley, JA AF Lessard, Sarah J. Rivas, Donato A. Chen, Zhi-Ping van denderen, Bryce J. Watt, Matthew J. Koch, Lauren G. Britton, Steven L. Kemp, Bruce E. Hawley, John A. TI Impaired Skeletal Muscle beta-Adrenergic Activation and Lipolysis Are Associated with Whole-Body Insulin Resistance in Rats Bred for Low Intrinsic Exercise Capacity SO ENDOCRINOLOGY LA English DT Article ID HORMONE-SENSITIVE LIPASE; ORPHAN NUCLEAR RECEPTORS; FATTY-ACID OXIDATION; PROTEIN-KINASE; ARTIFICIAL SELECTION; AS160 PHOSPHORYLATION; UNCOUPLING PROTEIN-3; ENDURANCE EXERCISE; GLUCOSE-TOLERANCE; LIPID-CONTENT AB Rats selectively bred for high endurance running capacity (HCR) have higher insulin sensitivity and improved metabolic health compared with those bred for low endurance capacity (LCR). We investigated several skeletal muscle characteristics, in vitro and in vivo, that could contribute to the metabolic phenotypes observed in sedentary LCR and HCR rats. After 16 generations of selective breeding, HCR had approximately 400% higher running capacity (P < 0.001), improved insulin sensitivity (P < 0.001), and lower fasting plasma glucose and triglycerides (P < 0.05) compared with LCR. Skeletal muscle ceramide and diacylglycerol content, basal AMP-activated protein kinase (AMPK) activity, and basal lipolysis were similar between LCR and HCR. However, the stimulation of lipolysis in response to 10 mu M isoproterenol was 70% higher in HCR (P = 0.004). Impaired isoproterenol sensitivity in LCR was associated with lower basal triacylglycerol lipase activity, Ser660 phosphorylation of HSL, and beta 2-adrenergic receptor protein content in skeletal muscle. Expression of the orphan nuclear receptor Nur77, which is induced by beta-adrenergic signaling and is associated with insulin sensitivity, was lower in LCR (P < 0.05). Muscle protein content of Nur77 target genes, including uncoupling protein 3, fatty acid translocase/CD36, and the AMPK gamma 3 subunit were also lower in LCR (P < 0.05). Our investigation associates whole-body insulin resistance with impaired beta-adrenergic response and reduced expression of genes that are critical regulators of glucose and lipid metabolism in skeletal muscle. We identify impaired beta-adrenergic signal transduction as a potential mechanism for impaired metabolic health after artificial selection for low intrinsic exercise capacity. (Endocrinology 150: 4883-4891, 2009) C1 [Lessard, Sarah J.; Rivas, Donato A.; Hawley, John A.] Royal Melbourne Inst Technol, Sch Med Sci, Bundoora, Vic 3083, Australia. [Chen, Zhi-Ping; van denderen, Bryce J.; Kemp, Bruce E.] Univ Melbourne, St Vincents Inst, Fitzroy, Vic 3065, Australia. [Watt, Matthew J.] Monash Univ, Dept Physiol, Clayton, Vic 3800, Australia. [Koch, Lauren G.; Britton, Steven L.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Lessard, SJ (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM sarah.lessard@joslin.harvard.edu RI Koch, Lauren/D-1258-2010; Watt, Matthew/B-2089-2014; Kemp, Bruce/L-2633-2014 OI Kemp, Bruce/0000-0001-6735-5082 FU National Center for Research Resources [R24 RR17718]; National Institutes of Health; U.S. Public Health Service; Australian Research Council FX Disclosure Summary: The authors have nothing to disclose. NR 56 TC 28 Z9 29 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2009 VL 150 IS 11 BP 4883 EP 4891 DI 10.1210/en.2009-0158 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 509ID UT WOS:000271007700008 PM 19819977 ER PT J AU Stengel, A Goebel, M Wang, LX Rivier, J Kobelt, P Monnikes, H Lambrecht, NWG Tache, Y AF Stengel, Andreas Goebel, Miriam Wang, Lixin Rivier, Jean Kobelt, Peter Moennikes, Hubert Lambrecht, Nils W. G. Tache, Yvette TI Central Nesfatin-1 Reduces Dark-Phase Food Intake and Gastric Emptying in Rats: Differential Role of Corticotropin-Releasing Factor(2) Receptor SO ENDOCRINOLOGY LA English DT Article ID CAUDAL BRAIN-STEM; BODY-WEIGHT; CRF; CHOLECYSTOKININ; NUCLEUS; NEURONS; LEPTIN; IMMUNOREACTIVITY; HYPOTHALAMUS; INHIBITION AB Nesfatin-1, derived from nucleobindin2, is expressed in the hypothalamus and reported in one study to reduce food intake (FI) in rats. To characterize the central anorexigenic action of nesfatin-1 and whether gastric emptying (GE) is altered, we injected nesfatin-1 into the lateral brain ventricle (intracerebroventricular, icv) or fourth ventricle (4v) in chronically cannulated rats or into the cisterna magna (intracisternal, ic) under short anesthesia and compared with ip injection. Nesfatin-1 (0.05 mu g/rat, icv) decreased 2-3 h and 3-6 h dark-phase FI by 87 and 45%, respectively, whereas ;ip administration (2 mu g/rat) had no effect. The corticotropin-releasing factor (CRF)(1)/CRF2 antagonist astressin-B or the CRF2 antagonist astressin(2)-B abolished icv nesfatin-1's anorexigenic action, whereas an astressin(2)-B analog, devoid of CRF-receptor binding affinity, did not. Nesfatin-1 icv induced a dose-dependent reduction of GE by 26 and 43% that was not modified by icv astressin(2)-B. Nesfatin-1 into the 4v (0.05 mu g/rat) or ic (0.5 mu g/rat) decreased cumulative dark-phase FI by 29 and 60% at 1 h and by 41 and 37% between 3 and 5 h, respectively. This effect was neither altered by ic astressin(2)-B nor associated with changes in GE. Cholecystokinin (ip) induced Fos expression in 43% of nesfatin-1 neurons in the paraventricular hypothalamic nucleus and 24% of those in the nucleus tractus solitarius. These data indicate that nesfatin-1 acts centrally to reduce dark phase FI through CRF2-receptor-dependent pathways after forebrain injection and CRF2-receptor-independent pathways after hindbrain injection. Activation of nesfatin-1 neurons by cholecystokinin at sites regulating food intake may suggest a role in gut peptide satiation effect. (Endocrinology 150: 4911-4919, 2009) C1 [Stengel, Andreas; Goebel, Miriam; Wang, Lixin; Lambrecht, Nils W. G.; Tache, Yvette] Univ Calif Los Angeles, Vet Adm Greater Los Angeles Healthcare Syst, Dept Med, Ctr Neurobiol Stress,Digest Dis Div,CURE, Los Angeles, CA 90073 USA. [Rivier, Jean] Salk Inst Biol Studies, Peptide Biol Labs, La Jolla, CA 92037 USA. [Kobelt, Peter] Charite, Clin Psychosomat Med, D-10117 Berlin, Germany. [Moennikes, Hubert] Martin Luther Hosp, Dept Med, D-14193 Berlin, Germany. [Moennikes, Hubert] Martin Luther Hosp, Inst Neurogastroenterol, D-14193 Berlin, Germany. RP Tache, Y (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Ctr Neurovisceral Sci & Womens Hlth CURE, Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu OI Lambrecht, Nils/0000-0002-1275-1384 FU German Research Foundation [STE 1765/1-1, GO1718/1-1]; Veterans Administration Research Career Scientist Award; Veterans Administration Merit Award [NIHDK 33061]; Center Grant [DK-41301]; [DK PO1-26741] FX We thank Mrs. Honghui Liang for her excellent technical support, and we thank Ms. Eugenia Hu for reviewing the manuscript.; Address all correspondence and requests for reprints to: Yvette Tache, Ph.D., Center for Neurovisceral Sciences and Women's Health CURE, Building 115, Room 117, Veterans Administration Greater Los Angeles Healthcare System, 11301 Wilshire Boulevard, Los Angeles, California 90073. E-mail: ytache@mednet.ucla.edu.; This work was supported by German Research Foundation Grants STE 1765/1-1 (A.S.), GO1718/1-1 (M.G.), Veterans Administration Research Career Scientist Award, Veterans Administration Merit Award, NIHDK 33061, Center Grant DK-41301 (Animal Core) (Y.T.), and DK PO1-26741 (J.R.).; Disclosure Summary: A.S., M.G., L.W., P.K., H.M., N.W. G.L., and Y.T. have nothing to disclose. J.R. is Founder of Sentia Medical Sciences, Inc. No conflicts of interest exist. NR 49 TC 138 Z9 154 U1 0 U2 7 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2009 VL 150 IS 11 BP 4911 EP 4919 DI 10.1210/en.2009-0578 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 509ID UT WOS:000271007700011 PM 19797401 ER PT J AU Mandal, CC Choudhury, GG Ghosh-Choudhury, N AF Mandal, Chandi C. Choudhury, Goutam Ghosh Ghosh-Choudhury, Nandini TI Phosphatidylinositol 3 Kinase/Akt Signal Relay Cooperates with Smad in Bone Morphogenetic Protein-2-Induced Colony Stimulating Factor-1 (CSF-1) Expression and Osteoclast Differentiation SO ENDOCRINOLOGY LA English DT Article ID TUMOR-SUPPRESSOR PTEN; INDUCED DNA-SYNTHESIS; TGF-BETA RECEPTOR; KAPPA-B LIGAND; OSTEOBLAST DIFFERENTIATION; MESANGIAL CELLS; PROTEIN-KINASE; C2C12 CELLS; BMP-2 GENE; C-FOS AB Murine spleen cells produce mature osteoclasts when cocultured with osteoblastic cells. Colony-stimulating factor (CSF)-1 is the growth factor required for differentiating the monocyte-macrophage precursor cells into preosteoclasts. Bone morphogenic protein (BMP) signaling in osteoblasts regulates bone mass in mice, suggesting a role of BMP in osteoclastogenesis along with osteoblast activity. The intracellular signal transduction cross talk regulating the osteoblastic production of CSF-1 as a mechanism of BMP-induced osteoclastogenesis is described in this report. We have recently described the involvement of Smad 1/5 in BMP-2-induced CSF-1 expression and osteoclast formation. In this study, using the pharmacological inhibitors and the adenovirus (Ad) vectors expressing dominant-negative (DN) phosphatidylinositol 3 kinase (PI3K), the PI3K-signaling inhibitor, phosphatase and tensin homolog deleted in chromosome 10 (PTEN) or DN Akt kinase in the in vitro coculture assay, we show an essential role of the lipid kinase cascade in BMP-2-mediated multinucleated osteoclast formation and CSF-1 mRNA expression, transcription, and secretion. Inhibition of PI3K/Akt signaling blocked the binding of Smads 1/5 to the CSF-1 BMP-responsive element present in the CSF-1 promoter, resulting in attenuation of Smad-dependent CSF-1 transcription. Furthermore, PI3K inhibition and DN Akt prevented association of the transcriptional coactivator, CREB (cAMP response element binding protein) binding protein (CBP), with Smads 1/5. Together, these data for the first time demonstrate that PI3K-dependent Akt activation regulates BMP-2-induced CSF-1 expression and provides a mechanism for osteoblastic cell-assisted osteoclast differentiation. (Endocrinology 150: 4989-4998, 2009) C1 [Mandal, Chandi C.; Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Choudhury, Goutam Ghosh; Ghosh-Choudhury, Nandini] S Texas Vet Hlth Care Syst, Dept Vet Affairs Res, San Antonio, TX USA. [Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Ghosh-Choudhury, N (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM choudhury@uthscsa.edu FU National Institutes of Health (NIH) [RO1AR52425, RO1 DK50190]; Department of Veterans Affairs (VA) Research Service Merit Review; VA Merit Review; Juvenile Diabetes Research Foundation [1-2008-185] FX Disclosure Summary: The authors have nothing to disclose. NR 52 TC 25 Z9 28 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2009 VL 150 IS 11 BP 4989 EP 4998 DI 10.1210/en.2009-0026 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 509ID UT WOS:000271007700019 PM 19819979 ER PT J AU Stengel, A Keire, D Goebel, M Evilevitch, L Wiggins, B Tache, Y Reeve, JR AF Stengel, Andreas Keire, David Goebel, Miriam Evilevitch, Lena Wiggins, Brian Tache, Yvette Reeve, Joseph R., Jr. TI The RAPID Method for Blood Processing Yields New Insight in Plasma Concentrations and Molecular Forms of Circulating Gut Peptides SO ENDOCRINOLOGY LA English DT Article ID PANCREATIC-SECRETION; ENZYME-SECRETION; DESACYL GHRELIN; RATS; CHOLECYSTOKININ; DEGRADATION; HORMONE; CCK-58; FOOD; STABILITY AB The correct identification of circulating molecular forms and measurement of peptide levels in blood entails that the endocrine peptide being studied is stable and recovered in good yields during blood processing. However, it is not clear whether this is achieved in studies using standard blood processing. Therefore, we compared peptide concentration and form of 12 (125)I-labeled peptides using the standard procedure (EDTA-blood on ice) and a new method employing Reduced temperatures, Acidification, Protease inhibition, Isotopic exogenous controls, and Dilution (RAPID). During standard processing there was at least 80% loss for calcitonin-gene-related peptide and cholecystokinin-58 (CCK-58) and more than 35% loss for amylin, insulin, peptide YY forms (PYY((1-36)) and PYY((3-36))), and somatostatin-28. In contrast, the RAPID method significantly improved the recovery for 11 of 12 peptides (P < 0.05) and eliminated the breakdown of endocrine peptides occurring after standard processing as reflected in radically changed molecular forms for CCK-58, gastrin-releasing peptide, somatostatin-28, and ghrelin. For endogenous ghrelin, this led to an acyl/total ghrelin ratio of 1: 5 instead of 1: 19 by the standard method. These results show that the RAPID method enables accurate assessment of circulating gut peptide concentrations and forms such as CCK-58, acylated ghrelin, and somatostatin-28. Therefore, the RAPID method represents an efficacious means to detect circulating variations in peptide concentrations and form relevant to the understanding of physiological function of endocrine peptides. (Endocrinology 150: 5113-5118, 2009) C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Reeve, Joseph R., Jr.] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. RP Reeve, JR (reprint author), Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM JReeve@mednet.ucla.edu FU German Research Foundation [STE 1765/1-1, GO 1718/1-1]; National Institutes of Health Center [DK-41301, RO1 DK 33850, DK 56805]; Veterans Administration Research Services FX Disclosure Summary: The authors have nothing to disclose. NR 30 TC 56 Z9 57 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2009 VL 150 IS 11 BP 5113 EP 5118 DI 10.1210/en.2009-0697 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 509ID UT WOS:000271007700032 PM 19819958 ER PT J AU Fassan, M Castoro, C Saenz, AJ Cagol, M Ninfo, V Rugge, M AF Fassan, M. Castoro, C. Saenz, A. J. Cagol, M. Ninfo, V. Rugge, M. TI Inflammatory myofibroblastic tumor as adverse outcome of eosinophilic esophagitis SO ENDOSCOPY LA English DT Editorial Material C1 [Rugge, M.] Univ Padua, Cattedra Anat Patol 2, Dept Med Diagnost Sci & Special Therapies, Pathol Unit,Ist Oncol Veneto IRCCS, I-35121 Padua, Italy. [Castoro, C.] IOV IRCCS, Surg Unit, Padua, Italy. [Cagol, M.] Univ Padua, Dept Med & Surg Sci, Surg Unit, I-35121 Padua, Italy. [Saenz, A. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. RP Rugge, M (reprint author), Univ Padua, Cattedra Anat Patol 2, Dept Med Diagnost Sci & Special Therapies, Pathol Unit,Ist Oncol Veneto IRCCS, Via Aristide Gabelli 61, I-35121 Padua, Italy. EM massimo.rugge@unipd.it RI Fassan, Matteo/F-5152-2012; Rugge, Massimo/K-7525-2016; Castoro, Carlo/L-1046-2016 OI Fassan, Matteo/0000-0001-6515-5482; Castoro, Carlo/0000-0001-9601-9336 NR 5 TC 1 Z9 1 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD NOV PY 2009 VL 41 SU 2 BP E95 EP E96 DI 10.1055/s-2008-1077646 PG 2 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA V15DW UT WOS:000207783700059 PM 19396747 ER PT J AU Hartnick, CJ Zurakowski, D Haver, K AF Hartnick, Christopher J. Zurakowski, David Haver, Kenan TI Validation of a pediatric cough questionnaire SO ENT-EAR NOSE & THROAT JOURNAL LA English DT Article ID QUALITY-OF-LIFE; PERSISTENT COUGH; CHILDREN; FREQUENCY; SPECTRUM; THERAPY; SYMPTOM AB We conducted a study to determine if a five-item pediatric cough questionnaire (PCQ) is a valid and reliable means of measuring cough-specific quality of life in children. The five questions, which are answered by the child's parent or caregiver, cover cough frequency (Q1), sleep disturbance of the child (Q2), sleep disturbance of the parent (Q3), cough severity (Q4), and the degree of bothersomeness to the child (Q5). Each of the five items was scored on a 6-point Likert scale. The PCQ was administered three times. The first occurred when the parent telephoned to schedule an appointment for the child at a pediatric pulmonology outpatient clinic for a chief complaint of cough. The second PCQ was administered within 2 weeks of the first but before any treatment had been instituted so that test-retest reliability could be assessed. Each child was then diagnosed and treated in accordance with standard care practices. The third PCQ was administered 3 weeks after the second to determine if it would accurately reflect the parent's perception of how the child's cough had changed following treatment. Also, at the second and third encounters, parents were asked to provide their global assessment of whether their child's cough had improved, worsened, or stayed the same since the previous encounter. The parents of 120 children (70 boys and 50 girls; mean age: 6.8 yr) completed all three PCQs. Test-retest reliability was established (p < 0.001) for each of the five PCQ questions by Spearman correlation analysis (Q1: r = 0.5; Q2: r = 0.38; Q3: r = 0.42; Q4: r = 0.53; Q5: r = 0.5). Other statistical analyses confirmed the PCQ's internal consistency, discriminant validity, and convergent validity. Based on our findings, we conclude that the PCQ is a valid and reliable instrument with which to follow children with chronic cough longitudinally. C1 [Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Zurakowski, David] Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Haver, Kenan] Massachusetts Gen Hosp Children, Div Pediat Pulm Med, Boston, MA 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 23 TC 3 Z9 3 U1 0 U2 0 PU VENDOME GROUP LLC PI NEW YORK PA 149 FIFTH AVE, 10TH FLOOR, NEW YORK, NY 10010 USA SN 0145-5613 J9 ENT-EAR NOSE THROAT JI ENT-Ear Nose Throat J. PD NOV PY 2009 VL 88 IS 11 BP 1213 EP 1217 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 551JY UT WOS:000274205400008 PM 19924664 ER PT J AU Hart, JE Yanosky, JD Puett, RC Ryan, L Dockery, DW Smith, TJ Garshick, E Laden, F AF Hart, Jaime E. Yanosky, Jeff D. Puett, Robin C. Ryan, Louise Dockery, Douglas W. Smith, Thomas J. Garshick, Eric Laden, Francine TI Spatial Modeling of PM10 and NO2 in the Continental United States, 1985-2000 SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE GIS; nitrogen dioxide; outdoor air pollution; particulate matter ID PARTICULATE AIR-POLLUTION; LAND-USE REGRESSION; LONG-TERM EXPOSURE; RESPIRATORY SYMPTOMS; TRAFFIC EXPOSURE; TRUCKING INDUSTRY; LUNG-CANCER; MORTALITY; COHORT; ADULTS AB BACKGROUND: Epidemiologic studies of air pollution have demonstrated a link between long-term air pollution exposures and mortality. However, many have been limited to city-specific average pollution measures or spatial or land-use regression exposure models in small geographic areas. OBJECTIVES: Our objective was to develop nationwide models of annual exposure to particulate matter < 10 mu m in diameter (PM10) and nitrogen dioxide during 1985-2000. METHODS: We used generalized additive models (GAMS) to predict annual levels of the pollutants using smooth spatial surfaces of available monitoring data and geographic information system-derived covariates. Model performance was determined using a cross-validation (CV) procedure with 10% of the data. We also compared the results of these models with a commonly used spatial interpolation, inverse distance weighting. RESULTS: For PM10, distance to road, elevation, proportion of low-intensity residential, high-intensity residential, and industrial, commercial, or transportation land use within 1 km were all statistically significant predictors of measured PM10 (model R-2 = 0.49, CV R-2 = 0.55). Distance to road, population density, elevation, land use, and distance to and emissions of the nearest nitrogen oxides-emitting power plant were all statistically significant predictors of measured NO2 (model R-2 = 0.88, CV R-2 = 0.90). The GAMS performed better overall than the inverse distance models, with higher CV R-2 and higher precision. CONCLUSIONS: These models provide reasonably accurate and unbiased estimates of annual exposures for PM10 and NO2. This approach provides the spatial and temporal variability necessary to describe exposure in studies assessing the health effects of chronic air pollution. C1 [Hart, Jaime E.; Yanosky, Jeff D.; Puett, Robin C.; Dockery, Douglas W.; Smith, Thomas J.; Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. [Hart, Jaime E.; Garshick, Eric; Laden, Francine] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hart, Jaime E.; Garshick, Eric; Laden, Francine] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Hart, Jaime E.; Dockery, Douglas W.; Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Puett, Robin C.] Univ S Carolina, S Carolina Canc Prevent & Control Program, Columbia, SC 29208 USA. [Puett, Robin C.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Environm Hlth Sci, Columbia, SC 29208 USA. [Puett, Robin C.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. [Ryan, Louise] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Garshick, Eric] VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA. RP Hart, JE (reprint author), 181 Longwood Ave, Boston, MA 02115 USA. EM Jaime.hart@channing.harvard.edu RI Smith, Thomas/A-9640-2010; Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU National Institutes of Health/National Cancer Institute [R01 CA90792]; National Institute of Environmental Health Sciences (NIEHS) Center [ES00002]; NIEHS [T32 ES007069-29] FX This study was supported by grant R01 CA90792 from the National Institutes of Health/National Cancer Institute, National Institute of Environmental Health Sciences (NIEHS) Center grant ES00002, and NIEHS T32 ES007069-29 (J.E.H.). NR 57 TC 31 Z9 31 U1 1 U2 24 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2009 VL 117 IS 11 BP 1690 EP 1696 DI 10.1289/ehp.0900840 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 514MQ UT WOS:000271399300023 PM 20049118 ER PT J AU Myrskyla, M Chang, VW AF Myrskylae, Mikko Chang, Virginia W. TI Weight Change, Initial BMI, and Mortality Among Middle- and Older-aged Adults SO EPIDEMIOLOGY LA English DT Article ID BODY-MASS INDEX; LONG-TERM MORTALITY; ALL-CAUSE MORTALITY; US ADULTS; PROSPECTIVE COHORT; ELDERLY-MEN; LOSE WEIGHT; FOLLOW-UP; OVERWEIGHT; OBESITY AB Background: It is not known how the relationship between weight change and mortality is influenced by initial body mass index (BMI) or the magnitude of weight change. Methods: We use the nationally representative Health and Retirement Study (n = 13,104; follow-up 1992-2006) and Cox regression analysis to estimate relative mortality risks for 2-year weight change by initial BMI among 50- to-70-year-old Americans. We defined small weight loss or gain as a change of 1-2.9 BMI units and large weight loss or gain as a change of 3-5 BMI units. Results: Large and small weight losses were associated with excess mortality for all initial BMI levels below 32 kg/m(2) (eg, hazard ratio [HR] for large weight loss from BMI of 30 = 1.61 [95% confidence interval = 1.31-1.98]; HR for small : weight loss from BMI of 30 = 1.19 [1.06-1.28]). Large weight gains were associated with excess mortality only at high BMIs (eg, HR for large weight gain from BMI of 35 = 1.33 (1.00-1.77]). Small weight gains were not associated with excess mortality for any initial BMI level. The weight loss-mortality association was robust to adjustments for health status and to sensitivity analyses considering unobserved confounders. Conclusions: Weight loss is associated with excess mortality among normal, overweight, and mildly obese middle- and older-aged adults. The excess risk increases for larger losses and lower initial BMI. These results suggest that the potential benefits of a lower BMI may be offset by the negative effects associated with weight loss. Weight gain may be associated with excess mortality only among obese people with an initial BMI over 35. C1 [Myrskylae, Mikko] Max Planck Inst Demog Res, D-18057 Rostock, Germany. [Chang, Virginia W.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Chang, Virginia W.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Chang, Virginia W.] Univ Penn, Dept Sociol, Philadelphia, PA 19104 USA. [Chang, Virginia W.] Univ Penn, Ctr Populat Studies, Philadelphia, PA 19104 USA. RP Myrskyla, M (reprint author), Max Planck Inst Demog Res, Konrad Zuse Str 1, D-18057 Rostock, Germany. EM myrskyla@demogr.mpg.de FU National Institute of Child Health and Human Development [K12-HD043459] FX Supported by National Institute of Child Health and Human Development, K12-HD043459 (to VW.C.). NR 40 TC 42 Z9 43 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 BP 840 EP 848 DI 10.1097/EDE.0b013e3181b5f520 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SD UT WOS:000270874000010 PM 19806061 ER PT J AU Bind, MA Zanobetti, A Schwartz, J Suh, H Vokonas, P AF Bind, Marie-Abele Zanobetti, Antonella Schwartz, Joel Suh, Helen Vokonas, Pantel TI Traffic-Related Pollutants and Inflammatory Markers in an Elderly Cohort: Veterans Administration Normative Aging Study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Bind, Marie-Abele; Zanobetti, Antonella; Schwartz, Joel; Suh, Helen] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Harvard Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. [Vokonas, Pantel] VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA USA. [Vokonas, Pantel] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S144 EP S145 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874101078 ER PT J AU Hart, J Laden, F Garshick, E AF Hart, Jaime Laden, Francine Garshick, Eric TI Biomakers of Inflammation and Short-Term Fine Particulate Exposures SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Hart, Jaime; Laden, Francine; Garshick, Eric] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Hart, Jaime; Laden, Francine] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Hart, Jaime; Laden, Francine] Harvard Univ, Sch Med, Boston, MA USA. [Garshick, Eric] VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S131 EP S132 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874101035 ER PT J AU Hoffmann, B Luttmann-Gibson, H Cohen, A Suh, H Coull, B Schwartz, J Hamdy, O Foley, C Stone, P Horton, E Gold, D AF Hoffmann, Barbara Luttmann-Gibson, Heike Cohen, Allison Suh, Helen Coull, Brent Schwartz, Joel Hamdy, Osama Foley, Chris Stone, Peter Horton, Edward Gold, Diane TI Short-Term Fine Particulate Matter Air Pollution and Vascular Reactivity in Diabetic Patients SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Hoffmann, Barbara; Suh, Helen; Coull, Brent; Schwartz, Joel; Foley, Chris; Gold, Diane] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Hoffmann, Barbara; Luttmann-Gibson, Heike] Univ Duisburg Essen, Essen, Germany. [Cohen, Allison; Hamdy, Osama; Horton, Edward] Joslin Diabet Ctr, Boston, MA 02215 USA. [Stone, Peter] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gold, Diane] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S70 EP S71 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874100180 ER PT J AU Luttmann-Gibson, H Hoffmann, B Cohen, A Coull, B de Souza, C Horton, E Schwartz, J Suh, H Gold, D AF Luttmann-Gibson, Heike Hoffmann, Barbara Cohen, Allison Coull, Brent de Souza, Celine Horton, Edward Schwartz, Joel Suh, Helen Gold, Diane TI Short-Term Effects of Air Pollution on Exhaled Nitric Oxide in Diabetic Patients SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Luttmann-Gibson, Heike; Hoffmann, Barbara; de Souza, Celine; Schwartz, Joel; Suh, Helen; Gold, Diane] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hoffmann, Barbara] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany. [Cohen, Allison; Horton, Edward] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Coull, Brent] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Gold, Diane] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S144 EP S144 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874101077 ER PT J AU Park, SK Schwartz, J Wright, R Spiro, A Vokonas, P Hu, H AF Park, Sung Kyun Schwartz, Joel Wright, Robert Spiro, Avron, III Vokonas, Pantel Hu, Howard TI Atherosclerosis-Related Genes, Low-Level Lead Exposure and Age-Related Hearing Loss: The Normative Aging Study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Park, Sung Kyun; Hu, Howard] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Schwartz, Joel; Wright, Robert] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Spiro, Avron, III; Vokonas, Pantel] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Spiro, Avron, III; Vokonas, Pantel] VA Boston Healthcare Syst, VA Normat Aging Study, 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S211 EP S211 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874101291 ER PT J AU Maheshwari, A Cash, S AF Maheshwari, Atul Cash, S. TI THE BURST SUPPRESSION PATTERN OF SECONDARY GENERALIZED SEIZURES SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Maheshwari, Atul; Cash, S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 25 EP 25 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500046 ER PT J AU Frost, JD Lee, CL Hrachovy, RA Swann, JW AF Frost, James D. Lee, C. L. Hrachovy, R. A. Swann, J. W. TI HIGH FREQUENCY EEG ACTIVITY ASSOCIATED WITH ICTAL EVENTS IN THE TTX MODEL OF INFANTILE SPASMS SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Lee, C. L.; Swann, J. W.] Baylor Coll Med, Cain Fdn Labs, Houston, TX 77030 USA. [Hrachovy, R. A.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 28 EP 29 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500052 ER PT J AU Kinirons, P Cash, S Cole, A AF Kinirons, Peter Cash, S. Cole, A. TI RISK FACTORS FOR DRUG-RESISTANT IGE - A CLINICAL AND ELECTROPHYSIOLOGICAL STUDY SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Kinirons, Peter; Cash, S.; Cole, A.] 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 62 EP 63 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500128 ER PT J AU Valle, AC Rodrigues, NE Lima, MC Chamma, MT Jorge, MS Neto, AR Silva, DF Fregni, F AF Valle, A. C. Rodrigues, N. E. Lima, Moises C. Chamma, M. T. Jorge, M. S. Neto, A. R. Silva, D. F. Fregni, F. TI IDIOPATHIC GENERALIZED EPILEPSY IN ADULT CHARACTERIZED BY TYPICAL ABSENCE SEIZURES VIDEO-EEG STUDIES SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Valle, A. C.; Rodrigues, N. E.; Lima, Moises C.; Chamma, M. T.] FMUSP, Sao Paulo, Brazil. [Rodrigues, N. E.; Jorge, M. S.; Neto, A. R.; Silva, D. F.] Beneficencia Portuguesa, Sao Paulo, Brazil. [Fregni, F.] BIDMC, Boston, MA 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 67 EP 67 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500139 ER PT J AU Pugh, MJV Copeland, LA VanCott, AC Mortensen, E Zeber, J Wang, C Cramer, JA AF Pugh, Mary Jo V. Copeland, L. A. VanCott, A. C. Mortensen, E. Zeber, J. Wang, C. Cramer, J. A. TI SUICIDALITY AND NEW AED EXPOSURE IN OLDER PATIENTS: IS THE FDA WARNING APPROPRIATE FOR ALL DRUGS IN ALL POPULATIONS? SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Pugh, Mary Jo V.; Copeland, L. A.; Mortensen, E.; Zeber, J.; Wang, C.] S Texas Vet Hlth Care Syst, VERDICT11C6, San Antonio, TX USA. [VanCott, A. C.] Pittsburgh VA Hlth Care Syst, Pittsburgh, PA USA. [Cramer, J. A.] Yale Univ, Sch Med, New Haven, CT 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 109 EP 109 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500222 ER PT J AU Van Cott, AC Pugh, MJV AF Van Cott, A. C. Pugh, Mary Jo V. TI TRENDS IN ANTIEPILEPTIC DRUG PRESCRIBING FOR OLDER PATIENTS WITH NEW-ONSET EPILEPSY: 2004-2006 SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Pugh, Mary Jo V.] S Texas Vet Hlth Care Syst, VERDICT 11C6, San Antonio, TX USA. [Van Cott, A. C.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Van Cott, A. C.] Univ Pittsburgh, Pittsburgh, PA USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 112 EP 112 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500227 ER PT J AU Pouliot, WA Staley, KJ Dudek, FE AF Pouliot, Wendy A. Staley, K. J. Dudek, F. E. TI THE EFFECTS OF THE CANNABINOID-RECEPTOR ANTAGONIST, SR141716A, ON THE DEVELOPMENT OF SPONTANEOUS RECURRENT SEIZURES AFTER KAINATE-INDUCED STATUS EPILEPTICUS SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Pouliot, Wendy A.; Dudek, F. E.] Univ Utah, Salt Lake City, UT USA. [Staley, K. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 119 EP 119 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500242 ER PT J AU Chu-Shore, C Gallagher, A Costello, D Montenegro, M Major, P Thiele, EA AF Chu-Shore, Catherine Gallagher, A. Costello, D. Montenegro, M. Major, P. Thiele, E. A. TI CO-REGISTRATION OF CYST-LIKE TUBERS AND EPILEPTIFORM ACTIVITY IN TUBEROUS SCLEROSIS COMPLEX SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 168 EP 168 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500352 ER PT J AU Salinsky, MC AF Salinsky, Martin C. TI PSYCHOGENIC NON-EPILEPTIC SEIZURES AT A VETERANS ADMINISTRATION MEDICAL CENTER SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Salinsky, Martin C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Salinsky, Martin C.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 195 EP 195 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500413 ER PT J AU Gonzalez-Heydrich, J Luna, LM Rao, S McClendon, J Rotella, P Waber, D Boyer, K Whitney, J Faraone, SV Guild, D Hamoda, H Biederman, J AF Gonzalez-Heydrich, Joseph Luna, L. M. Rao, S. McClendon, J. Rotella, P. Waber, D. Boyer, K. Whitney, J. Faraone, S. V. Guild, D. Hamoda, H. Biederman, J. TI ELEVATED ADHD RATES IN MOTHERS OF CHILDREN WITH COMORBID ADHD AND EPILEPSY SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Gonzalez-Heydrich, Joseph; Luna, L. M.; Rao, S.; McClendon, J.; Rotella, P.; Waber, D.; Boyer, K.; Whitney, J.; Guild, D.; Hamoda, H.] Harvard Univ, Sch Med, Dept Psychiat, Childrens Hosp, Boston, MA 02115 USA. [Biederman, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychopharmacol Unit, Boston, MA USA. [Faraone, S. V.] SUNY Upstate Med Univ, Syracuse, NY 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 236 EP 236 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500506 ER PT J AU Paolini, J Chu-Shore, C Macdonald, C Bruno, P Thibert, R Thiele, E AF Paolini, Jan Chu-Shore, C. Macdonald, C. Bruno, P. Thibert, R. Thiele, E. TI ADVERSE EVENTS ASSOCIATED WITH ANTICONVULSANT DRUG FORMULATION SUBSTITUTION IN PEDIATRIC AND ADULT EPILEPSY PATIENTS SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Paolini, Jan; Chu-Shore, C.; Macdonald, C.; Bruno, P.; Thibert, R.; Thiele, E.] Mass Gen Hosp, 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 259 EP 260 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500560 ER PT J AU Leeman, BA Macklin, EA Schomer, DL O'Connor, MG AF Leeman, Beth A. Macklin, E. A. Schomer, D. L. O'Connor, M. G. TI TRANSIENT NEWS EVENTS TEST: FEASIBILITY IN ASSESSMENT OF POST-TEMPORAL LOBECTOMY REMOTE MEMORY DEFICITS SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Leeman, Beth A.; Schomer, D. L.; O'Connor, M. G.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Macklin, E. A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Leeman, Beth A.; Macklin, E. A.; Schomer, D. L.; O'Connor, M. G.] Harvard Univ, Sch Med, Boston, MA USA. RI Macklin, Eric/E-2955-2013 OI Macklin, Eric/0000-0003-1618-3502 NR 1 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 266 EP 267 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500575 ER PT J AU Van Cott, AC Pramuka, M AF Van Cott, Anne C. Pramuka, M. TI SURVEY OF INTERNET AND COMPUTER USE IN VETERANS WITH EPILEPSY SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Van Cott, Anne C.] VA Pittsburgh Healthcare Syst, Div Neurol, Pittsburgh, PA USA. [Van Cott, Anne C.; Pramuka, M.] Univ Pittsburgh, Pittsburgh, PA 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 274 EP 275 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500590 ER PT J AU Staley, KJ Coulter, D Cossart, R White, J AF Staley, Kevin J. Coulter, Douglas Cossart, Rosa White, John TI IMAGING SYNCHRONY WITH ACTIVITY-DEPENDENT DYES: THE NUTS AND BOLTS SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Staley, Kevin J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Staley, Kevin J.] Harvard Univ, Sch Med, Boston, MA USA. [Coulter, Douglas] Univ Penn, Philadelphia, PA 19104 USA. [White, John] Univ Utah, Salt Lake City, UT USA. [Cossart, Rosa] INSERM, U29, Luminy, France. RI Cossart, Rosa/E-7674-2014 OI Cossart, Rosa/0000-0003-2111-6638 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 310 EP 310 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500677 ER PT J AU Dyhrfjeld-Johnsen, J Swiercz, W Sabolek, H Berdichevsky, Y Staley, K AF Dyhrfjeld-Johnsen, Jonas Swiercz, W. Sabolek, H. Berdichevsky, Y. Staley, K. TI INTERICTAL SPIKES APPEAR DURING THE LATENT PERIOD IN A MODEL OF EPILEPTOGENESIS BASED ON ORGANOTYPIC HIPPOCAMPAL SLICE CULTURES SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Berdichevsky, Y.] Massachusetts Gen Hosp, Ctr Engn Med, Charlestown, MA USA. [Dyhrfjeld-Johnsen, Jonas; Swiercz, W.; Sabolek, H.; Berdichevsky, Y.; Staley, K.] Harvard Univ, Sch Med, 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 348 EP 348 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500771 ER PT J AU Berdichevsky, Y Swiercz, W Yarmush, ML Staley, KJ AF Berdichevsky, Yevgeny Swiercz, W. Yarmush, M. L. Staley, K. J. TI PARTIAL VOLTAGE-GATED SODIUM CHANNEL INACTIVATION RESULTS IN SEIZURES IN ORGANOTYPIC CULTURE MODEL OF EPILEPSY SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Berdichevsky, Yevgeny; Yarmush, M. L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Swiercz, W.; Staley, K. J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Berdichevsky, Yevgeny; Swiercz, W.; Yarmush, M. L.; Staley, K. J.] Harvard Univ, Sch Med, Boston, MA 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 356 EP 356 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500792 ER PT J AU Thibert, RL Thiele, E AF Thibert, Ronald L. Thiele, E. TI SEIZURES IN INDIVIDUALS WITH CHROMOSOME 15Q DUPLICATIONS SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Thibert, Ronald L.; Thiele, E.] 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 400 EP 401 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500898 ER PT J AU Bruno, PL Venna, P Hirshberg, J Paolini, J Thibert, R Thiele, E AF Bruno, Patricia L. Venna, P. Hirshberg, J. Paolini, J. Thibert, R. Thiele, E. TI CLINICAL EXPERIENCE WITH RUFINAMIDE (BANZEL) IN PATIENTS WITH INTRACTABLE EPILEPSY SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Bruno, Patricia L.; Venna, P.; Hirshberg, J.; Paolini, J.; Thibert, R.; Thiele, E.] Massachusetts Gen Hosp, Pediat Epilepsy Program, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 424 EP 424 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500949 ER PT J AU Camposano, SE Dabora, S Paolini, J Thiele, EA AF Camposano, S. E. Dabora, S. Paolini, J. Thiele, E. A. TI SIROLIMUS TREATMENT AND ITS EFFECT ON SEIZURES IN TSC: A CASE SERIES SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Camposano, S. E.; Paolini, J.; Thiele, E. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dabora, S.] Brigham & Womens Hosp, Translat Med Div, Boston, MA 02115 USA. [Dabora, S.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 424 EP 424 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500950 ER PT J AU Kilbride, R Costello, D AF Kilbride, Ronan Costello, D. TI PREDICTORS OF SURVIVAL IN PROLONGED REFRACTORY STATUS EPILEPTICUS (PRSE) SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Kilbride, Ronan; Costello, D.] 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 426 EP 426 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500956 ER PT J AU Gallagher, A Chu-Shore, CJ Roche-Labarbe, N Surova, A Franceschini, MA Thibert, RL Cash, SS Thiele, EA Grant, PE AF Gallagher, Anne Chu-Shore, C. J. Roche-Labarbe, N. Surova, A. Franceschini, M. A. Thibert, R. L. Cash, S. S. Thiele, E. A. Grant, P. E. TI PRE AND POST-ANTICONVULSIVE TREATMENT CHANGES IN INTERICTAL CEREBRAL OXYGENATION AND NEURONAL ACTIVITY IN INFANTS WITH INFANTILE SPASMS SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Gallagher, Anne; Chu-Shore, C. J.; Thibert, R. L.; Cash, S. S.; Thiele, E. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gallagher, Anne; Chu-Shore, C. J.; Roche-Labarbe, N.; Franceschini, M. A.; Thibert, R. L.; Cash, S. S.; Thiele, E. A.; Grant, P. E.] Harvard Univ, Sch Med, Boston, MA USA. [Roche-Labarbe, N.; Surova, A.; Franceschini, M. A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA USA. [Grant, P. E.] Childrens Hosp Boston, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA USA. RI Roche-Labarbe, Nadege/N-9101-2015 OI Roche-Labarbe, Nadege/0000-0002-5010-0400 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 435 EP 435 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500975 ER PT J AU Nakagawa, JA Whittemore, VH Cinkosky, M Sparagana, S Thiele, E Brown, C Frost, M McClintock, W Bebin, EM Kohrman, M Northrup, H Wu, JY Levisohn, P Koh, S Gupta, A Ashwal, S Duchowny, M Miller, IO LaJoie, J Jansen, A AF Nakagawa, Jo Anne Whittemore, V. H. Cinkosky, M. Sparagana, S. Thiele, E. Brown, C. Frost, M. McClintock, W. Bebin, E. M. Kohrman, M. Northrup, H. Wu, J. Y. Levisohn, P. Koh, S. Gupta, A. Ashwal, S. Duchowny, M. Miller, I. O. LaJoie, J. Jansen, A. TI THE TUBEROUS SCLEROSIS COMPLEX NATURAL HISTORY DATABASE PROJECT SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Nakagawa, Jo Anne; Whittemore, V. H.] Tuberous Sclerosis Alliance, Silver Spring, MD USA. [Cinkosky, M.] Tesuji Inc, Denver, CO USA. [Sparagana, S.] Texas Scottish Rite Hosp Children, Dallas, TX USA. [Thiele, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brown, C.] Childrens Hosp Oakland, Oakland, CA USA. [Frost, M.] Minnesota Epilepsy Grp PA, St Paul, MN USA. [McClintock, W.] Childrens Natl Med Ctr, Fairfax, VA USA. [Bebin, E. M.] Univ Alabama, Birmingham, AL USA. [Kohrman, M.] Univ Chicago, Chicago, IL 60637 USA. [Northrup, H.] Univ Texas Hlth Sci Ctr, Houston, TX USA. [Wu, J. Y.] Univ Calif Los Angeles, Los Angeles, CA USA. [Levisohn, P.; Koh, S.] Univ Colorado, Denver, CO 80202 USA. [Gupta, A.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Ashwal, S.] Loma Linda Univ, Med Ctr, Loma Linda, CA USA. [Duchowny, M.; Miller, I. O.] Miami Childrens Hosp, New York, NY USA. [LaJoie, J.] NYU, New York, NY USA. [Jansen, A.] UZ Brussel Hosp, Brussels, Belgium. RI Jansen, Anna/P-3121-2014 OI Jansen, Anna/0000-0002-3835-2824 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 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 457 EP 458 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550501027 ER PT J AU Thibert, RL Conant, KD Braun, EK Bruno, P Said, RR Nespeca, MP Thiele, EA AF Thibert, Ronald L. Conant, Kerry D. Braun, Eileen K. Bruno, Patricia Said, Rana R. Nespeca, Mark P. Thiele, Elizabeth A. TI Epilepsy in Angelman syndrome: A questionnaire-based assessment of the natural history and current treatment options SO EPILEPSIA LA English DT Article DE Epilepsy; Angelman syndrome; Chromosome 15; Antiepileptic medications ID EEG PATTERNS; DELETION; PHENOTYPES; DIAGNOSIS; EVOLUTION; 15Q11-13; CRITERIA; CHILDREN; THERAPY AB Purpose: Angelman syndrome (AS) commonly presents with epilepsy (>80%). The goal of this study was to examine the natural history and various treatments of epilepsy in AS in a large population. Methods: A detailed electronic survey containing comprehensive questions regarding epilepsy in AS was conducted through the Angelman Syndrome Foundation. Results: There were responses from 461 family members of individuals with AS, of whom 86% had epilepsy (60% with multiple seizure types), the most common being atonic, generalized tonic-clonic, absence, and complex partial. Partial-onset seizures only were reported in 11% of those with epilepsy. Epilepsy was most common among those with maternal deletions and unknown subtypes, with catastrophic epilepsies present in only these two subtypes. These epilepsies were refractory to medication, with only 15% responding to the first antiepileptic drug (AED). The most commonly prescribed AED were valproic acid and clonazepam, but lamotrigine and levetiracetam appeared to have similar efficacy and tolerability. Discussion: This is the largest study to date assessing epilepsy in AS. Although epilepsy in AS is considered a generalized epilepsy, there was a high prevalence of partial seizures. There are few previous data regarding the use of newer AED in AS, and the results of this study suggest that these newer agents, specifically levetiracetam and lamotrigine, may have efficacy similar to that of valproic acid and clonazepam, and that they appear to have similar or better side-effect profiles. Non-pharmacologic therapies such as dietary therapy and vagus nerve stimulation (VNS) also suggest favorable efficacy and tolerability, although further studies are needed. C1 [Thibert, Ronald L.; Conant, Kerry D.; Bruno, Patricia; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Pediat Epilepsy Program, Dept Neurol, Boston, MA 02114 USA. [Braun, Eileen K.] Angelman Syndrome Fdn, Aurora, IL USA. [Said, Rana R.] Univ Texas SW Med Ctr Dallas, Div Pediat Neurol, Dept Pediat, Childrens Med Ctr, Dallas, TX 75390 USA. [Nespeca, Mark P.] UCSD, Dept Neurosci, Div Neurol, Rady Childrens Hosp, San Diego, CA USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Pediat Epilepsy Program, Dept Neurol, 175 Cambridge St 340, Boston, MA 02114 USA. EM ethiele@partners.org FU Angelman Syndrome Foundation FX This study was supported by the Angelman Syndrome Foundation. NR 37 TC 33 Z9 38 U1 2 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 IS 11 BP 2369 EP 2376 DI 10.1111/j.1528-1167.2009.02108.x PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 509ZH UT WOS:000271057300006 PM 19453717 ER PT J AU Conant, KD Thibert, RL Thiele, EA AF Conant, Kerry D. Thibert, Ronald L. Thiele, Elizabeth A. TI Epilepsy and the sleep-wake patterns found in Angelman syndrome SO EPILEPSIA LA English DT Article DE Epilepsy; Angelman syndrome; Sleep patterns; Behavioral Evaluation of Disorders of Sleep ID INDIVIDUALS AB Sleep disturbances and epilepsy are common in Angelman syndrome (AS). This study examines seizure variables and sleep in a large AS cohort. Sleep disturbances and epilepsy were assessed in 290 individuals with AS using two questionnaires, including the Behavioral Evaluation of Disorders of Sleep (BEDS). Sensitivity to the sleeping environment, decreased nightly hours of sleep, and a difficulty initiating sleep were significantly correlated with the presence of epilepsy, particularly focal seizures. Use of multiple anticonvulsant drugs was shown to affect sleep. No significant associations were present between molecular sub-types of AS and individual sleep factors. Sleep problems appeared to be associated with epilepsy in individuals with AS, especially with focal and absence seizures and multiple seizure types. Results were consistent with those of prior studies assessing sleep in AS. Severity of epilepsy and use of anticonvulsant drugs may be related to a higher degree of sleep disturbance in this population. C1 [Conant, Kerry D.; Thibert, Ronald L.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Pediat Epilepsy Program, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Pediat Epilepsy Program, 175 Cambridge St Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org FU Angelman Syndrome Foundation (ASF) FX This study was supported by the Angelman Syndrome Foundation (ASF). NR 11 TC 26 Z9 26 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 IS 11 BP 2497 EP 2500 DI 10.1111/j.1528-1167.2009.02109.x PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 509ZH UT WOS:000271057300020 PM 19453716 ER PT J AU Fuchs, BB Mylonakis, E AF Fuchs, Beth Burgwyn Mylonakis, Eleftherios TI Our Paths Might Cross: the Role of the Fungal Cell Wall Integrity Pathway in Stress Response and Cross Talk with Other Stress Response Pathways SO EUKARYOTIC CELL LA English DT Review ID PROTEIN-KINASE-C; YEAST SACCHAROMYCES-CEREVISIAE; GTP-BINDING PROTEIN; SIGNAL-TRANSDUCTION PATHWAY; ACTIVATED MAP KINASE; CRYPTOCOCCUS-NEOFORMANS; CANDIDA-ALBICANS; OXIDATIVE-STRESS; GENE ENCODES; FISSION YEAST AB Fungi occupy diverse environments and are subjected to many extreme conditions. Among the stressful conditions faced by fungi are pH changes, osmotic changes, thermal changes, oxide radicals, nutrient deprivation, and exposure to chemicals. These adversities can be found either in the environment or in animal and human hosts. The cell wall integrity (CWI) pathway provides a means to fortify and repair damages to the cell wall in order to withstand stressful environments. The CWI pathway in comprised of cell wall stress sensors that lead to activation of a mitogen-activated protein kinase (MAPK) cascade. Signaling through the MAPK cascade leads to expression of transcription factors that facilitate biosynthesis of cell wall components and actin organization. Given the relatively limited number of components of the CWI pathway and the very diverse stimuli, there must be a means of expanding the pathway. To manage the diverse stress conditions, the CWI pathway cross talks with other pathways or proteins, and these cross talk events enhance the signaling capabilities of the CWI pathway. Lateral influences that facilitate maintaining the cell wall under stress conditions are TOR signaling, calcineurin signaling, the high-osmolarity glycerol pathway, the cyclic AMP-protein kinase A pathway, and additional proteins. In this article, we highlight several of the cross talk events that have been described for Saccharomyces cerevisiae and several other fungi. C1 [Fuchs, Beth Burgwyn; Mylonakis, Eleftherios] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM emylonakis@partners.org FU National Institutes of Health [R01 AI075286, R21 AI079569] FX We acknowledge three anonymous reviewers for helpful feedback and comments. NR 83 TC 83 Z9 84 U1 2 U2 29 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD NOV PY 2009 VL 8 IS 11 BP 1616 EP 1625 DI 10.1128/EC.00193-09 PG 10 WC Microbiology; Mycology SC Microbiology; Mycology GA 514BO UT WOS:000271368700001 PM 19717745 ER PT J AU Pukkila-Worley, R Peleg, AY Tampakakis, E Mylonakis, E AF Pukkila-Worley, Read Peleg, Anton Y. Tampakakis, Emmanouil Mylonakis, Eleftherios TI Candida albicans Hyphal Formation and Virulence Assessed Using a Caenorhabditis elegans Infection Model SO EUKARYOTIC CELL LA English DT Article ID HOST-PATHOGEN INTERACTIONS; ANTIFUNGAL DRUG-RESISTANCE; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTION FACTOR; FILAMENTOUS GROWTH; INNATE IMMUNITY; AMPHOTERICIN-B; PH RESPONSES; YEAST; IDENTIFICATION AB Candida albicans colonizes the human gastrointestinal tract and can cause life-threatening systemic infection in susceptible hosts. We study here C. albicans virulence determinants using the nematode Caenorhabditis elegans in a pathogenesis system that models candidiasis. The yeast form of C. albicans is ingested into the C. elegans digestive tract. In liquid media, the yeast cells then undergo morphological change to form hyphae, which results in aggressive tissue destruction and death of the nematode. Several lines of evidence demonstrate that hyphal formation is critical for C. albicans pathogenesis in C. elegans. First, two yeast species unable to form hyphae (Debaryomyces hansenii and Candida lusitaniae) were less virulent than C. albicans in the C. elegans assay. Second, three C. albicans mutant strains compromised in their ability to form hyphae (efg1 Delta/efg1 Delta, flo8 Delta/flo8 Delta, and cph1 Delta/cph1 Delta efg1 Delta/efg1 Delta) were dramatically attenuated for virulence. Third, the conditional tet-NRG1 strain, which enables the external manipulation of morphogenesis in vivo, was more virulent toward C. elegans when the assay was conducted under conditions that permit hyphal growth. Finally, we demonstrate the utility of the C. elegans assay in a screen for C. albicans virulence determinants, which identified several genes important for both hyphal formation in vivo and the killing of C. elegans, including the recently described CAS5 and ADA2 genes. These studies in a C. elegans-C. albicans infection model provide insights into the virulence mechanisms of an important human pathogen. C1 [Pukkila-Worley, Read; Peleg, Anton Y.; Tampakakis, Emmanouil; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Peleg, Anton Y.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Pukkila-Worley, Read; Peleg, Anton Y.; Mylonakis, Eleftherios] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM emylonakis@partners.org OI Peleg, Anton/0000-0002-2296-2126 FU Cancer Research Institute; University of Queensland Postgraduate Scholarship; National Institutes of Health [R01 AI075286]; Astellas Pharma, Inc.; Pfizer, Inc. FX E. M. received research support from Astellas Pharma, Inc., and is a member of the Speaker's Bureau for Pfizer, Inc. A. Y. P. has served as an advisor for Abbot Molecular, Inc. The other authors report no potential conflicts of interest. NR 52 TC 67 Z9 77 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD NOV PY 2009 VL 8 IS 11 BP 1750 EP 1758 DI 10.1128/EC.00163-09 PG 9 WC Microbiology; Mycology SC Microbiology; Mycology GA 514BO UT WOS:000271368700013 PM 19666778 ER PT J AU Matter, CM Stuber, M Nahrendorf, M AF Matter, Christian M. Stuber, Matthias Nahrendorf, Matthias TI Imaging of the unstable plaque: how far have we got? SO EUROPEAN HEART JOURNAL LA English DT Review DE Atherosclerosis; Molecular imaging; Vulnerable plaque ID CORONARY-ARTERY-DISEASE; MAGNETIC-RESONANCE ANGIOGRAPHY; ACUTE MYOCARDIAL-INFARCTION; ULTRASMALL SUPERPARAMAGNETIC PARTICLES; OPTICAL COHERENCE TOMOGRAPHY; POSITRON-EMISSION-TOMOGRAPHY; WATER SUPPRESSION IRON; IN-VIVO; INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUES AB Rupture of unstable plaques may lead to myocardial infarction or stroke and is the leading cause of morbidity and mortality in western countries. Thus, there is a clear need for identifying these vulnerable plaques before the rupture occurs. Atherosclerotic plaques are a challenging imaging target as they are small and move rapidly, especially in the coronary tree. Many of the currently available imaging tools for clinical use still provide minimal information about the biological characteristics of plaques, because they are limited with respect to spatial and temporal resolution. Moreover, many of these imaging tools are invasive. The new generation of imaging modalities such as magnetic resonance imaging, nuclear imaging such as positron emission tomography and single photon emission computed tomography, computed tomography, fluorescence imaging, intravascular ultrasound, and optical coherence tomography offer opportunities to overcome some of these limitations. This review discusses the potential of these techniques for imaging the unstable plaque. C1 [Matter, Christian M.] Univ Zurich, Inst Physiol, Zurich Ctr Integrat Human Physiol, CH-8057 Zurich, Switzerland. [Matter, Christian M.] Univ Zurich Hosp, Ctr Cardiovasc, CH-8091 Zurich, Switzerland. [Stuber, Matthias] Johns Hopkins Univ, Div Magnet Resonance Res, Dept Radiol, Sch Med, Baltimore, MD 21287 USA. [Stuber, Matthias] CHU Vaudois, Dept Radiol, CH-1011 Lausanne, Switzerland. [Stuber, Matthias] Univ Lausanne, CH-1011 Lausanne, Switzerland. [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Matter, CM (reprint author), Univ Zurich, Inst Physiol, Zurich Ctr Integrat Human Physiol, CH-8057 Zurich, Switzerland. EM cmatter@physiol.uzh.ch RI Stuber, Matthias/B-2949-2010; Centre d'imagerie Biomedicale, CIBM/B-5740-2012 OI Stuber, Matthias/0000-0001-9843-2028; FU Swiss National Science Foundation [31-114094/1]; AHA [0835623D]; NIH [R01HL095629-01, R01HL096576-01, R01-HL084186, R01-HL61912]; Donald W. Reynolds Foundation; MERCATOR Foundation Switzerland; Cardiovascular Research Foundation Zurich FX This work was supported by grants from the Swiss National Science Foundation 31-114094/1 (C. M. M.), the URPP 'Integrative Human Physiology' at the University of Zurich (C. M. M.), AHA SDG 0835623D (M. N.), and in part by the NIH grants R01HL095629-01 (M. N.), R01HL096576-01 (M. N.), R01-HL084186 (M. S.), R01-HL61912 (M. S.), and the Donald W. Reynolds Foundation (M. S.). Further support was provided by unrestricted grants from the MERCATOR Foundation Switzerland and a strategic alliance with Pfizer, Inc. New York. Funding to pay the Open Access publication charges for this article was provided by Cardiovascular Research Foundation Zurich. NR 76 TC 56 Z9 61 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD NOV PY 2009 VL 30 IS 21 BP 2566 EP 2574 DI 10.1093/eurheartj/ehp419 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 516WE UT WOS:000271573200009 PM 19833636 ER PT J AU Raut, CP Nucci, MR Wang, Q Manola, J Bertagnolli, MM Demetri, GD Morgan, JA Muto, MG Fletcher, CDM George, S AF Raut, Chandrajit P. Nucci, Marisa R. Wang, Qian Manola, Judith Bertagnolli, Monica M. Demetri, George D. Morgan, Jeffrey A. Muto, Michael G. Fletcher, Christopher D. M. George, Suzanne TI Predictive value of FIGO and AJCC staging systems in patients with uterine leiomyosarcoma SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Uterine sarcoma; Leiomyosarcoma; AJCC; FIGO; Staging system; Uterine leiomyosarcoma; Predictive value ID PROGNOSTIC-FACTORS; SARCOMAS; SURVIVAL; UTERUS; IMPACT; P53 AB Background: Cancer staging systems aim to identify patient cohorts with different outcomes based on clinically relevant prognostic factors. Uterine leiomyosarcoma (ULMS) is classified using the FIGO staging system developed for epithelial malignancies; other sarcomas use the AJCC staging system. Neither has been validated in ULMS. We critically evaluated both systems to determine if either identified patient groups with distinct outcomes. Methods: We staged 230 ULMS patients by the FIGO and AJCC systems. Progression-free survival (PFS) and overall survival (OS) rates were calculated; statistical pairwise comparisons were performed. Results: The number of stages I and III patients varied by staging system. There were few stage II patients by either system. Using the FIGO system, PFS was better in stage I patients versus stage III or IV patients, and OS was better in stage I patients versus stage IV patients. Using the AJCC system, PFS and OS were better in stage I patients (low grade) versus stage II, III or IV patients, and OS was better in stage III patients versus stage IV patients. Prognosis of patients with serosal involvement (FIGO IV) was similar to that of patients with metastases (FIGO IV). Conclusion: Neither system classifies ULMS patients into four clinically meaningful, non-overlapping stages predictive of PFS and OS. This analysis highlights the relevance of certain factors (low grade, serosal involvement) and rarity of others (FIGO stage II, cervical invasion). Once identified, prognostic factors relevant to this malignancy should be incorporated into a new staging system in an effort to identify appropriate cohorts for different treatments. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Raut, Chandrajit P.; Bertagnolli, Monica M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Surg, Boston, MA 02115 USA. [Nucci, Marisa R.; Fletcher, Christopher D. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Pathol, Boston, MA 02115 USA. [Wang, Qian; Manola, Judith] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Biostat, Boston, MA 02115 USA. [Demetri, George D.; Morgan, Jeffrey A.; George, Suzanne] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Med Oncol, Boston, MA 02115 USA. [Muto, Michael G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Gynecol Oncol, Boston, MA 02115 USA. RP Raut, CP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM craut@partners.org NR 20 TC 23 Z9 24 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2009 VL 45 IS 16 BP 2818 EP 2824 DI 10.1016/j.ejca.2009.06.030 PG 7 WC Oncology SC Oncology GA 526JL UT WOS:000272284200017 PM 19647426 ER PT J AU Illigens, BM Yamada, A Anosova, N Dong, VM Sayegh, MH Benichou, G AF Illigens, Ben M. Yamada, Akira Anosova, Natalie Dong, Victor M. Sayegh, Mohamed H. Benichou, Gilles TI Dual effects of the alloresponse by Th1 and Th2 cells on acute and chronic rejection of allotransplants SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Chronic graft rejection; Heart transplantation; Skin graft; T-cell allorecognition; Th1/Th2 cells ID PERSISTENT ALLOPEPTIDE REACTIVITY; CARDIAC ALLOGRAFT VASCULOPATHY; HLA-DR PEPTIDES; CD8(+) T-CELLS; INDIRECT RECOGNITION; IN-VIVO; INDIRECT ALLORECOGNITION; GRAFT-REJECTION; MHC PEPTIDES; TRANSPLANT RECIPIENTS AB The contribution of direct and indirect alloresponses by CD4(+) Th1 and Th2 cells in acute and chronic rejection of allogeneic transplants remains unclear. in the present study, we addressed this question using a transplant model in a single MHC class I-disparate donor-recipient mouse combination. BALB/c-dm2 (dm2) mutant mice do not express MHC class I L(d) molecules and reject acutely L(d+) skin grafts from BALB/c mice. In contrast, BALB/c hearts placed in dm2 mice are permanently accepted in the absence of chronic allograft vasculopathy. in this model, CD4(+) T cells are activated following recognition of a donor MHC class I determinant, L(d) 61-80, presented by MHC Class II A(d) molecules on donor and recipient APC. Pre-transplantation of recipients with L(d) 61-80 peptide emulsified in complete Freund's adjuvant induced a Th1 response, which accelerated the rejection of skin allografts, but it had no effect on cardiac transplants. In contrast, induction of a Th2 response to the same peptide abrogated the CD8(+) cytotoxic T cells response and markedly delayed the rejection of skin allografts while it induced de novo chronic rejection of heart transplants. This shows that Th2 cells activated via indirect allorecognition can exert dual effects on acute and chronic rejection of allogeneic transplants. C1 [Illigens, Ben M.; Anosova, Natalie; Benichou, Gilles] Harvard Univ, Massachusetts Gen Hosp, Transplantat Unit, Cellular & Mol Immunol Lab,Dept Surg,Sch Med, Boston, MA 02114 USA. [Yamada, Akira; Dong, Victor M.; Sayegh, Mohamed H.] Harvard Univ, Brigham & Womens Hosp, Transplantat Res Ctr, Sch Med, Boston, MA 02114 USA. [Yamada, Akira; Dong, Victor M.; Sayegh, Mohamed H.] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02114 USA. RP Benichou, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Transplantat Unit, Cellular & Mol Immunol Lab,Dept Surg,Sch Med, 55 Fruit St,Thier 807, Boston, MA 02114 USA. EM gbenichou@partners.org FU NIH [KO2AI53103, R01 HD050484] FX We would like to thank Ms. Karla Stenger, Colleen Doherty and Sarah Connolly for their assistance in the preparation of the manuscript. We also thank Drs. G. Tocco, A. Alessandrini and H. Winn for helpful discussions. This work was supported by grants from the NIH (KO2AI53103 and R01 HD050484) to G. B. NR 59 TC 18 Z9 20 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 2009 VL 39 IS 11 BP 3000 EP 3009 DI 10.1002/eji.200838980 PG 10 WC Immunology SC Immunology GA 524EH UT WOS:000272126100009 PM 19658090 ER PT J AU Iosifescu, DV Greenwald, S Devlin, P Mischoulon, D Denninger, JW Alpert, JE Fava, M AF Iosifescu, Dan V. Greenwald, Scott Devlin, Philip Mischoulon, David Denninger, John W. Alpert, Jonathan E. Fava, Maurizio TI Frontal EEG predictors of treatment outcome in major depressive disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Major depressive disorder; Antidepressants; Treatment response; Quantitative electroencephalography (QEEG) ID BRAIN ELECTRICAL TOMOGRAPHY; TREATMENT RESPONSE; ANTIDEPRESSANT TREATMENT; ASYMMETRY; SYMPTOMS; NONRESPONDERS; ONSET AB Objective: To investigate the rote of frontal EEG as predictor of clinical response to SSRIs or venlafaxine in major depressive disorder (MDD). Method: 82 subjects (age 35.9 +/- 13.0; 47.6% female) meeting DSM-IV criteria for MDD entered an 8-week prospective treatment with SSRIs or venlafaxine. At baseline and week 1 we recorded serial, 4-channel EEGs (F7-Fpz, F8-Fpz, A1-Fpz, A2-Fpz). We evaluated prospectively the relative theta power as predictor of treatment outcome. We also developed an Antidepressant Treatment Response (ATR) index using EEG parameters assessed at baseline and week 1. Results: 45 subjects (54.9%) responded to treatment (HAM-D-17 reduction 50%). At baseline, frontal relative theta power (i.e., 4-8 Hz power/2-20 Hz power) was significantly (p=0.017) tower (21%) in treatment responders than in non-responders (24%). Baseline relative theta power predicted treatment response with 63% accuracy [64% sensitivity, 62% specificity, 66% area under the receiver operator curve (AUROC) (p=0.014)]. Relative theta power at week 1 predicted treatment response with 60% accuracy [62% sensitivity, 57% specificity, 61% AUROC (p=0.089)]. ATR predicted response with 70% accuracy [82% sensitivity, 54% specificity, 72% AURCC (p=0.001)]. Conclusion: Using automated analysis of frontal EEG collected during the first week of antidepressant treatment it may be possible to facilitate prediction of SSRI or venlafaxine efficacy in MDD. (C) 2009 Elsevier B.V. and ECNR All rights reserved. C1 [Iosifescu, Dan V.; Mischoulon, David; Denninger, John W.; Alpert, Jonathan E.; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Iosifescu, Dan V.; Mischoulon, David; Denninger, John W.; Alpert, Jonathan E.; Fava, Maurizio] Harvard Univ, Sch Med, Boston, MA USA. [Greenwald, Scott; Devlin, Philip] Aspect Med Syst Inc, Norwood, MA USA. RP Iosifescu, DV (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM diosifescu@partners.org OI Alpert, Jonathan/0000-0002-4332-908X FU Aspect Medical Systems FX This study was supported by a grant from Aspect Medical Systems. Aspect Medical Systems had no further rote in the study design or data collection. Dr. Greenwald and Mr. Devlin who are employees of Aspect Medical Systems have contributed to the analysis of the EEG data and are authors of this manuscript. NR 28 TC 47 Z9 48 U1 3 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD NOV PY 2009 VL 19 IS 11 BP 772 EP 777 DI 10.1016/j.euroneuro.2009.06.001 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 511FX UT WOS:000271150400002 PM 19574030 ER PT J AU Kassarjian, A Llopis, E Schwartz, RB Bencardino, JT AF Kassarjian, Ara Llopis, Eva Schwartz, Richard B. Bencardino, Jenny T. TI Obturator externus bursa: prevalence of communication with the hip joint and associated intra-articular findings in 200 consecutive hip MR arthrograms SO EUROPEAN RADIOLOGY LA English DT Article DE Hip; MRI; Arthrogram; Anatomy; Obturator externus; Bursa ID FEMOROACETABULAR IMPINGEMENT; DIAGNOSIS AB The purpose of the study was to demonstrate the prevalence of communication between the hip joint and the obturator externus bursa on hip MR arthrography. Following institutional review board approval, 200 hip MR arthrograms in 196 subjects were independently reviewed by two musculoskeletal radiologists. Discrepancies were resolved by adjudication. The presence or absence of communication between the hip joint and the obturator externus bursa was recorded. Associated lesions involving the acetabular labrum and articular cartilage were recorded. The obturator externus bursa was shown to communicate with the hip joint in 11 of the 200 (5.5%) hip MR arthrograms. Of these, six were in men and five were in women. The age range was 15-63 years with a mean age of 34 years. All 11 patients had labral tears. Eight of the 11 had cartilage lesions. The obturator externus bursa can be seen to communicate with the hip joint in 5.5% of hip MR arthrograms. Associated labral and cartilage lesions are common. C1 [Kassarjian, Ara] Corades SL, Majadahonda Madrid 28220, Spain. [Kassarjian, Ara] Massachusetts Gen Hosp, Div Musculoksleletal Radiol, Boston, MA 02114 USA. [Llopis, Eva] Hosp Ribera, Dept Radiol, Valencia 46600, Spain. [Schwartz, Richard B.] Longwood MRI Specialists, Brookline, MA 02446 USA. [Bencardino, Jenny T.] NYU, Dept Radiol, New York, NY 10016 USA. RP Kassarjian, A (reprint author), Corades SL, Calle Galeon 2, Majadahonda Madrid 28220, Spain. EM Kassarjian@mac.com NR 7 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD NOV PY 2009 VL 19 IS 11 BP 2779 EP 2782 DI 10.1007/s00330-009-1476-5 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 507FS UT WOS:000270838000026 PM 19504101 ER PT J AU Smith, MR AF Smith, Matthew R. TI RANK Ligand-targeted Therapy: A Novel Approach to Prevent Bone Loss and Fractures in Men with Prostate Cancer SO EUROPEAN UROLOGY SUPPLEMENTS LA English DT Article CT 24th Congress of the Annual European-Association-of-Urology CY MAR 17-21, 2009 CL Stockholm, SWEDEN SP European Assoc Urol DE Bone; Bone metastases; Breast cancer; Denosumab; Prostate cancer; RANK; RANK Ligand ID ANDROGEN-DEPRIVATION THERAPY; CONTROLLED-TRIAL; ZOLEDRONIC ACID; DENOSUMAB; RISK; BISPHOSPHONATES; WOMEN AB Context: The importance of bone loss associated with both prostate cancer (PCa) and its treatment is being increasingly recognised, and new options to manage this complication are in development. Objective: To assess the impact of androgen-deprivation therapy (ADT) on bone and to outline recently reported and ongoing phase 3 studies of agents designed to prevent bone loss and fractures in men with PCa. Evidence acquisition: This article is based on a presentation at an Amgen-sponsored satellite symposium held at the European Association of Urology Congress in Stockholm, Sweden, in March 2009. Evidence synthesis: ADT for PCa is associated with bone loss and an increased fracture risk. Several bisphosphonates have been shown to improve bone mineral density (BMD) during ADT, but their effects on treatment-related fractures are unknown. Denosumab, a fully human monoclonal antibody to RANK Ligand, is being investigated for the management of bone loss associated with PCa. The results of a phase 3 randomised, placebo-controlled trial of denosumab to prevent bone loss and fractures during ADT in men with PCa have recently been reported. Compared with placebo, denosumab (60 mg subcutaneously every 6 mo) significantly reduced the incidence of new vertebral fractures by 62% after 3 yr. Denosumab also increased BMD significantly at various skeletal sites, including the spine, hip, and wrist. Conclusions: ADT decreases BMD and increases fracture risk in men with PCa. A recent phase 3 study has demonstrated that denosumab increases BMD and significantly reduces the risk of new vertebral fractures in men with PCa. Two ongoing phase 3 studies are evaluating denosumab for the prevention and treatment of bone metastases in men with castration-resistant prostate cancer. (C) 2009 European Association of Urology. Published by Elsevier B. V. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu NR 22 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9056 J9 EUR UROL SUPPL JI Eur. Urol. Suppl. PD NOV PY 2009 VL 8 IS 11 BP 834 EP 838 DI 10.1016/j.eursup.2009.08.006 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 512ZF UT WOS:000271290500004 ER PT J AU Noda, K Nakao, S Zandi, S Engelstadter, V Mashima, Y Hafezi-Moghadam, A AF Noda, Kousuke Nakao, Shintaro Zandi, Souska Engelstaedter, Verena Mashima, Yukihiko Hafezi-Moghadam, Ali TI Vascular adhesion protein-1 regulates leukocyte transmigration rate in the retina during diabetes SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE diabetic retinopathy; leukocyte recruitment; adhesion molecules; semicarbazide-sensitive amine oxidase ID IN-VIVO; AMINE OXIDASES; P-SELECTIN; STREPTOZOTOCIN; LEUKOSTASIS; RETINOPATHY; EXPRESSION; MOLECULE-1; CELLS; PERMEABILITY AB Vascular adhesion protein-1 (VAP-1) is an endothelial adhesion molecule that possesses semicarbazide-sensitive amine oxidase (SSAO) activity and is involved in leukocyte recruitment. Leukocyte adhesion to retinal vessels is a predominant feature of experimentally induced diabetic retinopathy (DR). However, the role of VAP-1 in this process is unknown. Diabetes was induced by i.p. injection of Streptozotocin in Long-Evans rats. The specific inhibitor of VAP-1, UV-002, was administered by daily i.p. injections. The expression of VAP-1 mRNA in the retinal extracts of normal and diabetic animals was measured by real-time quantitative polymerase chain reaction (PCR). Firm leukocyte adhesion was quantified in retinal flatmounts after intravascular staining with concanavalin A (ConA). Leukocyte transmigration rate was quantified by in vivo acridine orange leukocyte staining (AOLS). In diabetic rats, the rate of leukocyte transmigration into the retinal tissues of live animals was significantly increased, as determined by AOLS. When diabetic animals were treated with daily injections of the VAP-1 inhibitor (0.3 mg/kg), leukocyte transmigration rate was significantly reduced (P < 0.05). However, firm adhesion of leukocytes in diabetic animals treated with the inhibitor did not differ significantly from vehicle-treated diabetic controls. This work provides evidence for an important role of VAP-1 in the recruitment of leukocyte to the retina in experimental DR. Our results reveal the critical contribution of VAP-1 to leukocyte transmigration, with little impact on firm leukocyte adhesion in the retinas of diabetic animals. VAP-1 inhibition might be beneficial in the treatment of DR. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Noda, Kousuke; Nakao, Shintaro; Zandi, Souska; Engelstaedter, Verena; Hafezi-Moghadam, Ali] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Noda, Kousuke; Nakao, Shintaro; Zandi, Souska; Engelstaedter, Verena; Hafezi-Moghadam, Ali] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Mashima, Yukihiko] R Tech Ueno Ltd, Tokyo, Japan. RP Hafezi-Moghadam, A (reprint author), Angiogenesis Lab, 325 Cambridge St,3rd Floor, Boston, MA 02114 USA. EM ahm@meei.harvard.edu OI Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU NIH [AI050775, HL086933]; R-TECH-UENO, Bausch & Lomb Fellowships; Japan Eye Bank Association; NEI core [EY14104]; Massachusetts Lions Eye Research Fund Inc.; Edward F. Knight AMD Fund; Research to Prevent Blindness; American Health Assistance Foundation FX We thank Alexander Schering for compiling the 3D confocal images. This work was supported by NIH grants AI050775 (AHM) and HL086933 (Alan Cross, University of Maryland), research funds from R-TECH-UENO, Bausch & Lomb Fellowships (K.N. and S.N.), a Fellowship Award from the Japan Eye Bank Association (K.N. and S.N.). and NEI core grant EY14104. We are indebted to the Massachusetts Lions Eye Research Fund Inc. for generous funds provided for laboratory equipment used in this project. We would like to thank Marion W. and Edward F. Knight AMD Fund, Research to Prevent Blindness, and American Health Assistance Foundation for their support. NR 41 TC 27 Z9 31 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD NOV PY 2009 VL 89 IS 5 BP 774 EP 781 DI 10.1016/j.exer.2009.07.010 PG 8 WC Ophthalmology SC Ophthalmology GA 507KA UT WOS:000270850800021 PM 19635478 ER PT J AU Yan, BP Kiernan, TJ Gonzales-Cruz, I Lam, YY AF Yan, Bryan P. Kiernan, Thomas J. Gonzales-Cruz, Ignacio Lam, Yat-Yin TI Left atrial appendage-occluding devices for stroke prevention in patients with nonvalvular atrial fibrillation SO EXPERT REVIEW OF MEDICAL DEVICES LA English DT Review DE atrial fibrillation; left atrial appendage; oral anticoagulation; stroke ID HIGH-RISK PATIENTS; TRANSCATHETER OCCLUSION; CARDIAC-SURGERY; EXPERIENCE; REDUCTION; OBLITERATION; LIGATION; SYSTEM; TRIALS; PLAATO AB Atrial fibrillation is associated with a fivefold increased risk for stroke, mostly secondary to thromboembolic events. Anticoagulation with a vitamin K antagonist is the standard medical therapy for these patients but is difficult to maintain within the therapeutic range and requires frequent monitoring and dose adjustments. Approximately 90% of thromboembolism occurs in the left atrial appendage (LAA) in patients with nonvalvular atrial fibrillation. Occlusion of flow into the LAA may prevent thrombus formation in the appendage and, hence, reduction of stroke. Recently, several percutaneous transcatheter techniques of LAA exclusion using the Percutaneous Left Atrial Appendage Transcatheter Occlusion device, the WATCHMAN(R) device, and AMPLATZER(R) septal occluder and cardiac plug have been employed, with encouraging results. Occlusion of the LAA may be an alternative to vitamin K antagonist therapy for selected patients. C1 [Yan, Bryan P.; Lam, Yat-Yin] Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. [Yan, Bryan P.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Kiernan, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Gonzales-Cruz, Ignacio] Univ Hosp Salamanca, Div Cardiol, Salamanca, Spain. RP Yan, BP (reprint author), Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. EM bryan.yan@cuhk.edu.hk RI Hossain, Sarah /C-7332-2009; 2009, Secribsal/A-1266-2012; Yan, Bryan/P-5928-2015 OI Hossain, Sarah /0000-0003-1355-0979; NR 41 TC 4 Z9 4 U1 0 U2 2 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1743-4440 EI 1745-2422 J9 EXPERT REV MED DEVIC JI Expert Rev. Med. Devices PD NOV PY 2009 VL 6 IS 6 BP 611 EP 620 DI 10.1586/ERD.09.45 PG 10 WC Engineering, Biomedical SC Engineering GA 528HC UT WOS:000272432600010 PM 19911873 ER PT J AU Xu, DS Sharma, C Hemler, ME AF Xu, Daosong Sharma, Chandan Hemler, Martin E. TI Tetraspanin12 regulates ADAM10-dependent cleavage of amyloid precursor protein SO FASEB JOURNAL LA English DT Article DE Alzheimer's disease; alpha-secretase; pericellular proteolysis ID ALPHA-SECRETASE ADAM10; ALZHEIMERS-DISEASE; DISINTEGRIN-LIKE; TM4SF PROTEINS; CELL-MIGRATION; GROWTH-FACTOR; INTEGRIN; COMPLEXES; PALMITOYLATION; ASSOCIATION AB Using mass spectrometry, we identified ADAM10 (a membrane-associated metalloproteinase) as a partner for TSPAN12, a tetraspanin protein. TSPAN12-ADAM10 interaction was confirmed by reciprocal coimmunoprecipitation in multiple tumor cell lines. TSPAN12, to a greater extent than other tetraspanins (CD81, CD151, CD9, and CD82), associated with ADAM10 but not with ADAM17. Overexpression of TSPAN12 enhanced ADAM10-dependent shedding of amyloid precursor protein (APP) in MCF7 (breast cancer) and SH-SY5Y (neuroblastoma) cell lines. Conversely, siRNA ablation of endogenous TSPAN12 markedly diminished APP proteolysis in both cell lines. Furthermore, TSPAN12 overexpression enhanced ADAM10 prodomain maturation, whereas TSPAN12 ablation diminished ADAM10 maturation. A palmitoylation-deficient TSPAN12 mutant failed to associate with ADAM10, inhibited ADAM10-dependent proteolysis of APP, and inhibited ADAM10 maturation, most likely by interfering with endogenous wild-type TSPAN12. In conclusion, TSPAN12 serves as a novel and robust partner for ADAM10 and promotes ADAM10 maturation, thereby facilitating ADAM10-dependent proteolysis of APP. This novel mode of regulating APP cleavage is of relevance to Alzheimer's disease therapy.-Xu, D., Sharma, C., Hemler, M. E. Tetraspanin12 regulates ADAM10-dependent cleavage of amyloid precursor protein. FASEB J. 23, 3674-3681 (2009). www.fasebj.org C1 [Hemler, Martin E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM martin_hemler@dfci.harvard.edu FU National Institutes of Health [GM38903, CA102034] FX This work was supported by National Institutes of Health grants GM38903 and CA102034 to M. E. H. NR 50 TC 77 Z9 81 U1 1 U2 7 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 2009 VL 23 IS 11 BP 3674 EP 3681 DI 10.1096/fj.09-133462 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 512TC UT WOS:000271272500005 PM 19587294 ER PT J AU Huttunen, HJ Peach, C Bhattacharyya, R Barren, C Pettingell, W Hutter-Paier, B Windisch, M Berezovska, O Kovacs, DM AF Huttunen, Henri J. Peach, Camilla Bhattacharyya, Raja Barren, Cory Pettingell, Warren Hutter-Paier, Birgit Windisch, Manfred Berezovska, Oksana Kovacs, Dora M. TI Inhibition of acyl-coenzyme A: cholesterol acyl transferase modulates amyloid precursor protein trafficking in the early secretory pathway SO FASEB JOURNAL LA English DT Article DE Alzheimer's disease; cholesterol; endoplasmic reticulum; lipid; protein maturation ID ALZHEIMERS-DISEASE; ENDOPLASMIC-RETICULUM; BETA-PEPTIDE; QUALITY CONTROL; APP; CLEAVAGE; METABOLISM; GENERATION; CELLS; MODEL AB Amyloid beta-peptide (A beta) has a central role in the pathogenesis of Alzheimer's disease (AD). Cellular cholesterol homeostasis regulates endoproteolytic generation of A beta from the amyloid precursor protein (APP). Previous studies have identified acylcoenzyme A: cholesterol acyltransferase (ACAT), an enzyme that regulates subcellular cholesterol distribution, as a potential therapeutic target for AD. Inhibition of ACAT activity decreases A beta generation in cell-and animal-based models of AD through an unknown mechanism. Here we show that ACAT inhibition retains a fraction of APP molecules in the early secretory pathway, limiting the availability of APP for secretase-mediated proteolytic processing. ACAT inhibitors delayed the trafficking of immature APP molecules from the endoplasmic reticulum (ER) as shown by metabolic labeling and live-cell imaging. This resulted in partial ER retention of APP and enhanced ER-associated degradation of APP by the proteasome, without activation of the unfolded protein response pathway. The ratio of mature APP to immature APP was reduced in brains of mice treated with ACAT inhibitors, and strongly correlated with reduced brain APP-C99 and cerebrospinal fluid A beta levels in individual animals. Our results identify a novel ACAT-dependent mechanism that regulates secretory trafficking of APP, likely contributing to decreased A beta generation in vivo.-Huttunen, H. J., Peach, C., Bhattacharyya, R., Barren, C., Pettingell, W., Hutter-Paier, B., Windisch, M., Berezovska, O., Kovacs, D. M. Inhibition of acyl-coenzyme A: cholesterol acyl transferase modulates amyloid precursor protein trafficking in the early secretory pathway. FASEB J. 23, 3819-3828 (2009). www.fasebj.org C1 [Huttunen, Henri J.; Peach, Camilla; Bhattacharyya, Raja; Barren, Cory; Pettingell, Warren; Kovacs, Dora M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurobiol Dis Lab,Genet & Aging Res Unit, Charlestown, MA 02129 USA. [Huttunen, Henri J.; Peach, Camilla; Bhattacharyya, Raja; Barren, Cory; Pettingell, Warren; Berezovska, Oksana; Kovacs, Dora M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Huttunen, Henri J.; Peach, Camilla; Bhattacharyya, Raja; Barren, Cory; Pettingell, Warren; Hutter-Paier, Birgit; Windisch, Manfred; Berezovska, Oksana; Kovacs, Dora M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Hutter-Paier, Birgit; Windisch, Manfred] Inst Expt Pharmacol, JSW Res Forsch Lab, Graz, Austria. RP Kovacs, DM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurobiol Dis Lab,Genet & Aging Res Unit, 114 16th St, Charlestown, MA 02129 USA. EM dora_kovacs@hms.harvard.edu OI Huttunen, Henri/0000-0002-9867-4438 FU Cure Alzheimer's Fund; U.S. National Institutes of Health [R01 NS45860]; Helsingin Sanomat Centennial Foundation; Maud Kuistila Foundation [CI-1011, CP-113,818] FX This study was supported by grants from the Cure Alzheimer's Fund (D. M. K.), the U.S. National Institutes of Health (R01 NS45860; D. M. K.), the Helsingin Sanomat Centennial Foundation (H.J.H.), and the Maud Kuistila Foundation (H.J.H.). CI-1011 and CP-113,818 were kind gifts from Lit-Fui Lau and James Harwood (Pfizer, Groton, CT, USA), respectively. NR 50 TC 29 Z9 30 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 2009 VL 23 IS 11 BP 3819 EP 3828 DI 10.1096/fj.09-134999 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 512TC UT WOS:000271272500018 PM 19625658 ER PT J AU Brooks, TC Burlingame, M Burk, M Tortorice, K Dong, D Glassman, PA Lynch, JA Good, CB Rickman, HS Claborn, M Appleman, D Jones, W Shaverd, L AF Brooks, Traci C. Burlingame, Mark Burk, Muriel Tortorice, Kathy Dong, Diane Glassman, Peter A. Lynch, Jennie A. Good, Chester B. Rickman, Holly S. Claborn, Melanie Appleman, Duva Jones, William Shaverd, Lanita TI Travoprost A prostaglandin analogue for the treatment of glaucoma SO FORMULARY LA English DT Article ID OPEN-ANGLE GLAUCOMA; LATANOPROST AB In August 2003, the US Department of Veterans Affairs (VA) awarded a contract for prostaglandin ophthalmic agents with travoprost as the agent of choice. Although there was no national mandate to switch patients from existing therapy, many VA facilities had agreements from their local ophthalmology and optometry departments to conduct a therapeutic interchange of patients from existing prostaglandins (eg, latanoprost) to travoprost. The primary purpose of this report is to describe the experience of conversion to travoprost after this contract. Medical records of converted patients were evaluated for change in intraocular pressure (IOP), change in visual field, adverse events, and whether or not a change back to the original therapy or alternative therapy was required. Of 578 patients evaluated, most (84%) had been using latanoprost before the conversion. After conversion, mean IOP was significantly reduced by 1.64 +/- 4.95 mm Hg (P<.0001). Of 188 patients with documented visual field assessment, 89.9% had no change or improvement in visual field after conversion. Adverse events occurred in 44 (7.6%) patients, with hyperemia occurring in 13 (2.2%) patients. Discontinuation of travoprost was attributed to an adverse event in 29 (5.0%) patients and attributed to ineffectiveness in 17 (2.9%) patients. Adverse drug event rates were significantly less than those reported in the literature. Travoprost was effective and well tolerated in most patients after therapeutic interchange. This evaluation provides additional information regarding outcomes associated with the therapeutic interchange. (Formulary. 2009; 44:322-328.) C1 [Brooks, Traci C.] Womack Army Med Ctr, Ft Bragg, NC USA. [Brooks, Traci C.; Burlingame, Mark] N Florida S Georgia Vet Hlth Syst, Gainesville, FL USA. [Burk, Muriel; Dong, Diane] VA Ctr Medicat Safety, VACO PBM Serv, Hines, IL USA. [Tortorice, Kathy] VACO Pharm Benefits Management Serv, Hines, IL USA. [Glassman, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Lynch, Jennie A.] VISN 2 VA Healthcare Network Upstate New York, Syracuse, NY USA. [Good, Chester B.] Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Good, Chester B.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. [Rickman, Holly S.; Shaverd, Lanita] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. [Claborn, Melanie] Univ Arkansas Med Sci, Vet Healthcare Syst Ozarks, Fayetteville, AR USA. [Appleman, Duva] Univ Calif, No Calif Vet Healthcare Syst, Davis Mather, CA USA. [Jones, William] SW Consolidated Mail Outpatient Pharm, Tucson, AZ USA. [Jones, William] VACO PBM Serv, Tucson, AZ USA. RP Brooks, TC (reprint author), Womack Army Med Ctr, Ft Bragg, NC USA. NR 8 TC 4 Z9 4 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS INC PI WOODLAND HILLS PA 6200 CANOGA AVE, 2ND FLR, WOODLAND HILLS, CA 91367 USA SN 1082-801X J9 FORMULARY JI Formulary PD NOV PY 2009 VL 44 IS 11 BP 322 EP 328 PG 9 GA 521PK UT WOS:000271934000001 ER PT J AU Bass, AJ Meyerson, M AF Bass, Adam J. Meyerson, Matthew TI Genome-Wide Association Study in Esophageal Squamous Cell Carcinoma SO GASTROENTEROLOGY LA English DT Editorial Material ID CANCER SUSCEPTIBILITY LOCUS; COLORECTAL-CANCER; GENETIC POLYMORPHISMS; CHROMOSOME 8Q24; RISK; ALCOHOL; SCAN; CONSUMPTION; MUTATIONS; RS6983267 C1 [Bass, Adam J.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bass, Adam J.; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Bass, Adam J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Bass, Adam J.; Meyerson, Matthew] Broad Inst, Cambridge, MA USA. RP Bass, AJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM adam_bass@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 NR 21 TC 5 Z9 5 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2009 VL 137 IS 5 BP 1573 EP 1576 DI 10.1053/j.gastro.2009.09.026 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 515VJ UT WOS:000271500700011 PM 19789091 ER PT J AU Nosho, K Kure, S Irahara, N Shima, K Baba, Y Spiegelman, D Meyerhardt, JA Giovannucci, EL Fuchs, CS Ogino, S AF Nosho, Katsuhiko Kure, Shoko Irahara, Natsumi Shima, Kaori Baba, Yoshifumi Spiegelman, Donna Meyerhardt, Jeffrey A. Giovannucci, Edward L. Fuchs, Charles S. Ogino, Shuji TI A Prospective Cohort Study Shows Unique Epigenetic, Genetic, and Prognostic Features of Synchronous Colorectal Cancers SO GASTROENTEROLOGY LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; POPULATION-BASED SAMPLE; MICROSATELLITE INSTABILITY; DNA METHYLATION; LINE-1 HYPOMETHYLATION; MOLECULAR-FEATURES; COLON CANCERS; BRAF MUTATION; CIMP-LOW; EXPRESSION AB BACKGROUND & AIMS: Synchronous colorectal neoplasias (2 or more primary carcinomas identified in the same patient) are caused by common generic and environmental factors and can be used to study the field effect. Synchronous colon cancers have not been compared with control solitary cancers in a prospective study. METHODS: We analyzed data collected from 47 patients with synchronous colorectal cancers and 2021 solitary colorectal cancers (controls) in 2 prospective cohort studies. Tumors samples were analyzed for methylation in LINE-1 and 16 CpG islands (CACNA1G, CDKN2A [p16], CRABP1, IGF2, MLH1, NEUROG1, RUNX3, SOCS1, CHFR, HIC1, IGFBP3, MGMT, MINT1, MINT31, p14 [ARF], and WRN); microsatellite instability (MSI); the CpG island methylator phenotype (CIMP); 18q loss of heterozygosity; KRAS, BRAF, and PIK3CA mutations; and expression of beta-catenin, p53, p21, p27, cyclin D1, fatty acid synthase, and cyclooxygenase-2. RESULTS: Compared with patients with solitary colorectal cancer, synchronous colorectal cancer patients had reduced overall survival time (log-rank, P = .0048; hazard ratio [HR], 1.71; 95% confidence interval [CI]: 1.17-2.50; P = .0053; multivariate HR, 1.47; 9S% CI: 1.00-2.17; P = .049). Compared with solitary rumors, synchronous tumors more frequently contained BRAF mutations (P = .0041), CIMP-high (P = .013), and MSI-high (P = .037). Methylation levels of LINE-1 (Spearman r = 0.82; P = .0072) and CpG island methylation (P < .0001) correlated between synchronous cancer pairs from the same individuals. CONCLUSIONS: Synchronous colorectal cancers had more frequent mutations in BRAF, were more frequently CIMP- and MSI-high, and had a worse prognosis than solitary colorectal cancers. Similar epigenomic and epigenetic events were frequently observed within a synchronous cancer pair, suggesting the presence of a field defect. C1 [Ogino, Shuji] Harvard Univ, Sch Med, Ctr Mol Oncol Pathol, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. [Spiegelman, Donna; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Spiegelman, Donna; 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 Nutr, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Ctr Mol Oncol Pathol, Dana Farber Canc Inst,Dept Med Oncol, 44 Binney St,Room JF-215C, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [K07 CA122826-02, K07 CA122826, K07 CA122826-01A1, K07 CA122826-03, P01 CA055075, P01 CA055075-15, P01 CA087969, P01 CA087969-10, P01 CA55075, P01 CA87969, P50 CA127003, P50 CA127003-03] NR 50 TC 73 Z9 75 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2009 VL 137 IS 5 BP 1609 EP 1620 DI 10.1053/j.gastro.2009.08.002 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 515VJ UT WOS:000271500700018 PM 19686742 ER PT J AU Stoffel, E Mukherjee, B Raymond, VM Tayob, N Kastrinos, F Sparr, J Wang, F Bandipalliam, P Syngal, S Gruber, SB AF Stoffel, Elena Mukherjee, Bhramar Raymond, Victoria M. Tayob, Nabihah Kastrinos, Fay Sparr, Jennifer Wang, Fei Bandipalliam, Prathap Syngal, Sapna Gruber, Stephen B. TI Calculation of Risk of Colorectal and Endometrial Cancer Among Patients With Lynch Syndrome SO GASTROENTEROLOGY LA English DT Article ID MSH2 MUTATION CARRIERS; FAMILY-HISTORY; HNPCC; GENE; ASCERTAINMENT; INDIVIDUALS; ACCURACY; ONSET; MLH1 AB BACKGROUND & AIMS: Lynch syndrome is the most common hereditary colorectal cancer (CRC) syndrome. Some previous estimates of lifetime risk for CRC and endometrial cancer (EC) did not control for ascertainment and were susceptible to bias toward overestimated risk. METHODS: We studied 147 families with mismatch repair gene mutations (55 MLH1, 81 MSH2, and 11 MSH6) identified at 2 US cancer genetics clinics. Age-specific cumulative risks (penetrance) and hazard ratio (HR) estimates of CRC and EC risks were calculated and compared with the general population using modified segregation analysis. The likelihood for each pedigree was conditioned on the proband and first-degree relatives affected with CRC to reduce ascertainment bias and overestimation of penetrance. RESULTS: We analyzed 628 cases of CRC, diagnosed at the median ages of 42 and 47 years for men and women, respectively. The cumulative risk of CRC was 66.08% (95% confidence interval [CI], 59.47%-76.17%) for men and 42.71% (95% CI, 36.57%-52.83%) for women, with overall HRs of 148.4 and 51.1, respectively. CRC risk was highest for males with mutations in MLH1. There were 155 cases of EC, diagnosed at a median age of 47.5 years. The cumulative risk of EC was 39.39% (95% CI, 30.78%-46.94%) with an overall FIR of 39.0 (95% CI, 30.4-50.2). For women, the cumulative risk of CRC or EC was 73.42% (95% CI, 63.76%-80.54%). CONCLUSIONS: Lifetime risks of CRC and EC in mismatch repair gene mutation carriers are high even after adjusting for ascertainment. These estimates are valuable for patients and providers; specialized cancer surveillance is necessary. C1 [Gruber, Stephen B.] Univ Michigan, Sch Publ Hlth, Div Epidemiol & Human Genet, Dept Epidemiol & Human Genet, Ann Arbor, MI 48105 USA. [Gruber, Stephen B.] Univ Michigan, Sch Med, Dept Epidemiol & Human Genet, Ann Arbor, MI 48105 USA. [Raymond, Victoria M.; Gruber, Stephen B.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48105 USA. [Mukherjee, Bhramar; Tayob, Nabihah; Wang, Fei] Univ Michigan, Sch Med, Dept Biostat, Ann Arbor, MI 48105 USA. [Mukherjee, Bhramar; Tayob, Nabihah; Wang, Fei] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48105 USA. [Stoffel, Elena; Sparr, Jennifer; Bandipalliam, Prathap; Syngal, Sapna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Stoffel, Elena; Kastrinos, Fay; Syngal, Sapna] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Gruber, SB (reprint author), Univ Michigan, Sch Publ Hlth, Div Epidemiol & Human Genet, Dept Epidemiol & Human Genet, 1524 BSRB, Ann Arbor, MI 48105 USA. EM sgruber@med.umich.edu FU National Cancer Institute [R01 CA81488, K07 CA 120448-01-A2, K24 CA 113433, R03 CA130045]; University of Michigan's Cancer Center [5 P30 CA46592] FX This work was supported in part by the National Cancer Institute (R01 CA81488 to S.B.G., K07 CA 120448-01-A2 to E.S., and K24 CA 113433 to S.S., R03 CA130045 to B.M.), the University of Michigan's Cancer Center Support Grant (5 P30 CA46592). NR 24 TC 152 Z9 158 U1 1 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2009 VL 137 IS 5 BP 1621 EP 1627 DI 10.1053/j.gastro.2009.07.039 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 515VJ UT WOS:000271500700019 PM 19622357 ER PT J AU Friedman, LS Brandt, LJ Elta, GH Fitz, JG Gores, GJ Katz, PO Kuemmerle, JF Pardi, DS Vargo, JJ Stolar, MH AF Friedman, Lawrence S. Brandt, Lawrence J. Elta, Grace H. Fitz, J. Gregory Gores, Gregory J. Katz, Philip O. Kuemmerle, John F. Pardi, Darrell S. Vargo, John J. Stolar, Michael H. TI Report of the Multisociety Task Force on GI Training SO GASTROENTEROLOGY LA English DT Article C1 [Friedman, Lawrence S.] Tufts Univ, Sch Med, Harvard Univ, Newton Wellesley Hosp,Massachusetts Gen Hosp, Medford, MA 02155 USA. [Brandt, Lawrence J.] Albert Einstein Coll Med, Montefiore Med Ctr, Bronx, NY USA. [Elta, Grace H.] Univ Michigan, Ann Arbor, MI 48109 USA. [Gores, Gregory J.; Pardi, Darrell S.] Mayo Clin, Coll Med Rochester, Rochester, MN USA. [Katz, Philip O.] Thomas Jefferson Univ, Albert Einstein Med Ctr, Philadelphia, PA USA. [Kuemmerle, John F.] Virginia Commonwealth Univ, Coll Med, Richmond, VA 23284 USA. [Kuemmerle, John F.] Cleveland Clin Fdn, Inst Digest Dis, Cleveland Clin Lerner Coll Med, Cleveland, OH USA. RP Friedman, LS (reprint author), Tufts Univ, Sch Med, Harvard Univ, Newton Wellesley Hosp,Massachusetts Gen Hosp, Medford, MA 02155 USA. NR 0 TC 8 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2009 VL 137 IS 5 BP 1839 EP 1843 DI 10.1053/j.gastro.2009.07.003 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 515VJ UT WOS:000271500700041 PM 19854349 ER PT J AU Friedman, LS Brandt, LJ Elta, GH Fitz, JG Gores, GJ Katz, PO Kuemmerle, JF Pardi, DS Vargo, JJ Stolar, MH AF Friedman, Lawrence S. Brandt, Lawrence J. Elta, Grace H. Fitz, J. Gregory Gores, Gregory J. Katz, Philip O. Kuemmerle, John F. Pardi, Darrell S. Vargo, John J. Stolar, Michael H. CA Multisoc Task Force GI Training TI Report of the Multisociety Task Force on GI Training SO GASTROINTESTINAL ENDOSCOPY LA English DT Article C1 [Friedman, Lawrence S.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Brandt, Lawrence J.] Albert Einstein Coll Med, Montefiore Med Ctr, Bronx, NY 10461 USA. [Elta, Grace H.] Univ Michigan, Ann Arbor, MI 48109 USA. [Gores, Gregory J.; Pardi, Darrell S.] Mayo Clin, Coll Med, Rochester, MN USA. [Katz, Philip O.] Thomas Jefferson Univ, Albert Einstein Med Ctr, Philadelphia, PA 19107 USA. [Kuemmerle, John F.] Virginia Commonwealth Univ, Med Coll Virginia Campus, Richmond, VA 23284 USA. [Vargo, John J.] Cleveland Clin Fdn, Cleveland, OH USA. [Vargo, John J.] Cleveland Clin, Lerner Coll Med, Inst Digest Dis, Cleveland, OH 44106 USA. [Friedman, Lawrence S.] Tufts Univ, Sch Med, Medford, MA 02155 USA. [Friedman, Lawrence S.] Newton Wellesley Hosp, Newton, MA USA. [Friedman, Lawrence S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Friedman, LS (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. OI Vargo, John/0000-0001-7638-5283 NR 0 TC 7 Z9 7 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD NOV PY 2009 VL 70 IS 5 BP 823 EP 827 DI 10.1016/j.gie.2009.08.018 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 521BK UT WOS:000271893900001 ER PT J AU Jensen, DM Machicado, GA AF Jensen, Dennis M. Machicado, Gustavo A. TI Hemoclipping of chronic canine ulcers: a randomized, prospective study of initial deployment success, clip retention rates, and ulcer healing SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID HEATER PROBE THERMOCOAGULATION; BLEEDING PEPTIC-ULCERS; ENDOSCOPIC HEMOCLIP; GASTRIC-ULCERS; HIGH-RISK; HEMOSTASIS; INJECTION; HEMORRHAGE; TRIAL AB Background: Several different hemoclips are marketed for endoscopic hemostasis of nonvariceal upper GI (UGI) bleeding. No previous reports have compared Success rates of clip deployment onto bases of chronic gastric ulcers (GUs), clip retention rates, or their influence on ulcer healing. Objectives: For the treatment of chronic GUs, to compare 3 different hemoclips with multipolar electrocoagulation (MPEC) and control. Design: Randomized, controlled study Subjects: Seven adult dogs with prehepatic portal hypertension had GUs created by rubber band ligation. Animals received oral proton pump inhibitors daily and underwent weekly endoscopies to quantitate clip retention and ulcer healing. Interventions: One week after banding, 10 chronic ulcers were randomized in pairs to control (no endoscopic treatment), MPEC, or different hemoclips (QuickClip2 [QC], TriClip [TC], or Resolution Clip [RC]). Main Outcome Measurements: Times and success of hemoclip deployment, clip retention rates, and ulcer healing rates on weekly endoscopies. Results: Success rates of clip deployment were 100% for the RC, 93.1% for the TC, and 83.3% for the QC. Clip retention rates were significantly higher with the RC than the QC or TC at I to 3 weeks. Retained clips did not delay GU healing compared with MPEC or control. Conclusions: Hemoclipping time was similar with all 3 clips; the RC was retained significantly longer than the QC or TC, hemoclips did not delay ulcer healing compared with control or MPEC, and all 3 hemoclips were safe and no complications Such as bleeding and weight loss were noted. (Gastrointest Endosc 2009;70:969-75.) C1 [Jensen, Dennis M.] VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Hemostasis Res Grp, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Jensen, DM (reprint author), VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Hemostasis Res Grp, Bldg 115,Room 318,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU Boston Scientific Corp; Olympus America Inc; Pentax Corp; NIH [K24 DK02650] FX The following anthors received research support for this from Boston Scientific Corp and Olympus America Inc (for the bemoclips, partial funding for the animals, technical support, and supplies) and Pentax Corp (for the endoscope): D. M. Jensen, G. A. Machicado. Supported by a NIH grant (K24 DK02650) to D. M. Jensen. NR 22 TC 18 Z9 18 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD NOV PY 2009 VL 70 IS 5 BP 969 EP 975 DI 10.1016/j.gie.2009.04.052 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 521BK UT WOS:000271893900022 PM 19640519 ER PT J AU Boudreaux, ED Allen, MH Claassen, C Currier, GW Bertman, L Glick, R Park, J Feifel, D Camargo, CA AF Boudreaux, Edwin D. Allen, Michael H. Claassen, Cindy Currier, Glenn W. Bertman, Louise Glick, Rachel Park, Jennifer Feifel, David Camargo, Carlos A., Jr. CA PERC TI The Psychiatric Emergency Research Collaboration-01: methods and results SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Psychiatric emergency; Emergency medicine; Psychiatry ID SUBSTANCE USE; DEPARTMENT VISITS; INJURY; ROOM AB Objective: To describe the Psychiatric Emergency Research Collaboration (PERC), the methods used to create a structured chart review tool and the results of our multicenter study. Method: Members of the PERC Steering Committee created a structured chart review tool designed to provide a comprehensive picture of the assessment and management of psychiatric emergency patients. Ten primary indicators were chosen based on the Steering Committee's professional experience, the published literature and existing consensus panel guidelines. Eight emergency departments completed data abstraction of 50 randomly selected emergency psychiatric patients, with seven providing data from two independent raters. Inter-rater reliability (Kappas) and descriptive statistics were computed. Results: Four hundred patient charts were abstracted. Initial concordance between raters was variable, with some sites achieving high agreement and others not. Reconciliation of discordant ratings through re-review of the original source documentation was necessary for four of the sites. Two hundred eighty-five (71%) subjects had some forth of laboratory test performed, including 212 (53%) who had urine toxicology screening and 163 (41%) who had blood alcohol levels drawn. Agitation was present in 220 (52%), with 98 (25%) receiving a medication to reduce agitation and 22 (6%) being physically restrained. Self-harm ideation was present in 226 (55%), while other-harm ideation was present in 82 (20%). One hundred seventy-nine (45%) were admitted to an inpatient or observation unit. Conclusion: Creating a common standard for documenting, abstracting and reporting on the nature and management of psychiatric emergencies is feasible across a wide range of health care institutions. (C) 2009 Elsevier Inc. All rights reserved. C1 [Boudreaux, Edwin D.] Cooper Univ Hosp, Camden, NJ 08103 USA. [Boudreaux, Edwin D.] UMDNJ RWJMS, Camden, NJ 08103 USA. [Allen, Michael H.] Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. [Claassen, Cindy] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Currier, Glenn W.] Univ Rochester, Med Ctr, Dept Psychiat & Emergency Med, Rochester, NY 14642 USA. [Currier, Glenn W.] Canandaigua VAMC, Ctr Excellence VISN2, Canandaigua, NY USA. [Bertman, Louise] Calif Pacific Med Ctr, San Francisco, CA USA. [Glick, Rachel] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. [Park, Jennifer] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Feifel, David] Univ Calif San Diego, San Diego Med Ctr, Dept Psychiat, San Diego, CA 92103 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Boudreaux, ED (reprint author), Cooper Univ Hosp, 1 Cooper Plaza, Camden, NJ 08103 USA. EM edwin.boudreaux@umassmed.edu RI Allen, Michael/A-8776-2011; OI Boudreaux, Edwin/0000-0002-3223-6371 FU NIMH NIH HHS [K23 MH064517, K23 MH064517-05] NR 22 TC 13 Z9 13 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2009 VL 31 IS 6 BP 515 EP 522 DI 10.1016/j.genhosppsych.2009.04.009 PG 8 WC Psychiatry SC Psychiatry GA 523IN UT WOS:000272066300004 PM 19892209 ER PT J AU Lamprecht, R Dracheva, S Assoun, S LeDoux, JE AF Lamprecht, R. Dracheva, S. Assoun, S. LeDoux, J. E. TI Fear conditioning induces distinct patterns of gene expression in lateral amygdala SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Fear conditioning; gene expression; lateral amygdala; memory; microarray ID LONG-TERM POTENTIATION; VISININ-LIKE PROTEIN-2; SYNAPTIC PLASTICITY; MESSENGER-RNA; MEMORY CONSOLIDATION; CA(V)2.1 CHANNELS; MEMBRANE-PROTEIN; GROWTH CONE; RECEPTOR; HIPPOCAMPUS AB The lateral nucleus of the amygdala (LA) has been implicated in the formation of long-term associative memory (LTM) of stimuli associated with danger through fear conditioning. The current study aims to detect genes that are expressed in LA following associative fear conditioning. Using oligonucleotide microarrays, we monitored gene expression in rats subjected to paired training where a tone co-terminates with a footshock, or unpaired training where the tone and footshock are presented in a non-overlapping manner. The paired protocol consistently leads to auditory fear conditioning memory formation, whereas the unpaired protocol does not. When the paired group was compared with the unpaired group 5 h after training, the expression of genes coding for the limbic system-associated membrane protein (Lsamp), kinesin heavy chain member 2 (Kif2), N-ethylmaleimide-sensitive fusion protein (NSF) and Hippocalcin-like 4 protein (Hpcal4) was higher in the paired group. These genes encode proteins that regulate neuronal axonal morphology (Lsamp, Kif2), presynaptic vesicle cycling and release (Hpcal4 and NSF), and AMPA receptor maintenance in synapses (NSF). Quantitative real-time PCR (qPCR) showed that Kif2 and Lsamp are expressed hours following fear conditioning but minutes after unpaired training. Hpcal4 is induced by paired stimulation only 5 h after the training. These results show that fear conditioning induces a unique temporal activation of molecular pathways involved in regulating synaptic transmission and axonal morphology in LA, which is different from non-associative stimulation. C1 [Lamprecht, R.] Univ Haifa, Dept Neurobiol & Ethol, Fac Sci & Sci Educ, IL-31905 Haifa, Israel. [Lamprecht, R.; LeDoux, J. E.] Univ Haifa, Dept Biol, Fac Sci & Sci Educ, IL-31905 Haifa, Israel. [Dracheva, S.] Bronx Vet Affairs Med Ctr, Bronx, NY USA. [Dracheva, S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Assoun, S.] Univ Paris 06, Paris, France. [LeDoux, J. E.] NYU, Ctr Neural Sci, New York, NY USA. RP Lamprecht, R (reprint author), Univ Haifa, Dept Neurobiol & Ethol, Fac Sci & Sci Educ, IL-31905 Haifa, Israel. EM rlamp@research.haifa.ac.il FU National Institute of Health [P50 MH058911, R01 MH046516]; National Science Foundation [IBN-0131433]; VISN3 Mental Illness Research and Education Clinical Center FX This research was supported by grants to J. E. L. (National Institute of Health Grants P50 MH058911, R01 MH046516 and National Science Foundation Grant IBN-0131433) and to S. D. (VISN3 Mental Illness Research and Education Clinical Center). Wethank the Memorial Sloan-Kettering Cancer Center Genomics Core laboratory for microarray assay and analysis. NR 60 TC 20 Z9 20 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD NOV PY 2009 VL 8 IS 8 BP 735 EP 743 DI 10.1111/j.1601-183X.2009.00515.x PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 517QY UT WOS:000271633300001 PM 19689454 ER PT J AU Leussis, MP Frayne, ML Saito, M Berry, EM Aldinger, KA Rockwel, GN Hammer, RP Baskin-Hill, AE Singer, JB Nadeau, JH Sklar, P Petryshen, TL AF Leussis, M. P. Frayne, M. L. Saito, M. Berry, E. M. Aldinger, K. A. Rockwel, G. N. Hammer, R. P., Jr. Baskin-Hill, A. E. Singer, J. B. Nadeau, J. H. Sklar, P. Petryshen, T. L. TI Genomic survey of prepulse inhibition in mouse chromosome substitution strains SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Behavior; cognition; linkage; mouse genetics; psychiatric disorders; psychopathology; quantitative trait locus; sensorimotor gating; startle ID QUANTITATIVE TRAIT LOCI; ACOUSTIC STARTLE RESPONSE; OBSESSIVE-COMPULSIVE DISORDER; SCHIZOTYPAL PERSONALITY-DISORDER; SENSORIMOTOR GATING DEFICITS; BIPOLAR DISORDER; GENE-EXPRESSION; NEUROBIOLOGICAL MEASURES; COGNITIVE DEFICITS; COMPLEX TRAITS AB Prepulse inhibition (PPI) is a measure of sensorimotor gating, a pre-attentional inhibitory brain mechanism that filters extraneous stimuli. Prepulse inhibition is correlated with measures of cognition and executive functioning, and is considered an endophenotype of schizophrenia and other psychiatric illnesses in which patients show PPI impairments. As a first step toward identifying genes that regulate PPI, we performed a quantitative trait locus (QTL) screen of PPI phenotypes in a panel of mouse chromosome substitution strains (CSSs). We identified five CSSs with altered PPI compared with the host C57BL/6J strain: CSS-4 exhibited decreased PPI, whereas CSS-10, -11, -16 and -Y exhibited higher PPI compared with C57BL/6J. These data indicate that A/J chromosomes 4, 10, 11, 16 and Y harbor at least one QTL region that modulates PPI in these CSSs. Quantitative trait loci for the acoustic startle response were identified on seven chromosomes. Like PPI, habituation of the startle response is also disrupted in schizophrenia, and in the present study CSS-7 and -8 exhibited deficits in startle habituation. Linkage analysis of an F(2) intercross identified a highly significant QTL for PPI on chromosome 11 between positions 101.5 and 114.4 Mb (peak LOD = 4.54). Future studies will map the specific genes contributing to these QTLs using congenic strains and other genomic approaches. Identification of genes that modulate PPI will provide insight into the neural mechanisms underlying sensorimotor gating, as well as the psychopathology of disorders characterized by gating deficits. C1 [Leussis, M. P.; Saito, M.; Berry, E. M.; Sklar, P.; Petryshen, T. L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Leussis, M. P.; Sklar, P.; Petryshen, T. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Leussis, M. P.; Sklar, P.; Petryshen, T. L.] Harvard Univ, Sch Med, Boston, MA USA. [Leussis, M. P.; Frayne, M. L.; Saito, M.; Berry, E. M.; Aldinger, K. A.; Rockwel, G. N.; Sklar, P.; Petryshen, T. L.] Broad Inst Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Leussis, M. P.; Frayne, M. L.; Saito, M.; Berry, E. M.; Aldinger, K. A.; Rockwel, G. N.; Sklar, P.; Petryshen, T. L.] MIT, Cambridge, MA 02139 USA. [Hammer, R. P., Jr.] Univ Arizona, Dept Basic Med Sci, Coll Med, Phoenix, AZ USA. [Hammer, R. P., Jr.] Univ Arizona, Dept Pharmacol, Coll Med, Phoenix, AZ USA. [Baskin-Hill, A. E.; Nadeau, J. H.] Case Western Reserve Univ, Sch Med, Dept Genet, Cleveland, OH 44106 USA. [Singer, J. B.] Novartis Inst Biomed Res, Cambridge, MA USA. RP Petryshen, TL (reprint author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM petryshen@chgr.mgh.harvard.edu FU National Institutes of Health [R21 MH071673, RR12305]; USPHS [R01 MH0703930]; Stanley Medical Research Institute; National Alliance for Research on Schizophrenia and Depression; Canadian Institutes of Health Research Postdoctoral Fellowship FX This research was supported in whole or in part by National Institutes of Health grants R21 MH071673 (PS) and RR12305 (JHN and AEBH), USPHS Award R01 MH0703930 (RPH), the Stanley Medical Research Institute (TLP), Young Investigator Awards from the National Alliance for Research on Schizophrenia and Depression (TLP), and a Canadian Institutes of Health Research Postdoctoral Fellowship (TLP). The authors wish to thank Dr. Mark Daly and Andrew Kirby for analytical assistance and Skye Waggoner for technical assistance. NR 77 TC 9 Z9 9 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD NOV PY 2009 VL 8 IS 8 BP 806 EP 816 DI 10.1111/j.1601-183X.2009.00526.x PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 517QY UT WOS:000271633300008 PM 19694817 ER PT J AU Zhang, Y Levin, M AF Zhang, Ying Levin, Michael TI Left-Right Asymmetry in the Chick Embryo Requires Core Planar Cell Polarity Protein Vangl2 SO GENESIS LA English DT Article DE left-right asymmetry; planar cell polarity; embryogenesis; Vangl2; chick ID LEFT-RIGHT AXIS; PRIMITIVE STREAK; EARLY STEP; SIGNALING PATHWAY; CILIARY PROTEINS; TISSUE POLARITY; FROG EMBRYOS; HENSENS NODE; STRABISMUS; MORPHOGENESIS AB Consistent left-right patterning is a fascinating and biomedically important problem. In the chick embryo, it is not known how cells determine their position (left or right) relative to the primitive streak, which is required for subsequent asymmetric gene expression cascades. We show that the subcellular localization of Vangl2, a core planar cell polarity (PCP) protein, is consistently polarized, giving cells in the blastoderm a vector pointing toward the primitive streak. Moreover, morpholino-mediated loss-of-function of Vangl2 by electroporation into chicks at very early stages randomizes the normally left-sided expression of Sonic hedgehog. Strikingly, Vangl2 morpholinos also induce a desynchronization of asymmetric gene expression within the left and right domains of Hensen's node. These data reveal the existence of polarized planar cell polarity protein localization in gastrulating chick and demonstrate that the PCP pathway is functionally required for normal asymmetry in the chick upstream of Sonic hedgehog. These data suggest a new and widely applicable class of models for the spread and coordination of left-right patterning information in the embryonic blastoderm. genesis 47:719-728,2009. (C) 2009 Wiley-Liss, Inc. C1 [Zhang, Ying; Levin, Michael] Forsyth Inst, Ctr Regenerat & Dev Biol, Boston, MA USA. [Levin, Michael] Tufts Univ, Dept Biol, Medford, MA 02155 USA. [Levin, Michael] Tufts Univ, Tufts Ctr Regenerat & Dev Biol, Medford, MA 02155 USA. RP Levin, M (reprint author), Tufts Univ, Ctr Regenerat & Dev Biol, 200 Boston Ave, Medford, MA 02155 USA. EM michael.levin@tufts.edu RI Zhang, Ying/Q-6956-2016 OI Zhang, Ying/0000-0002-8045-3821 FU American Heart Association; NIH FX Contract grant sponsors: American Heart Association and the NIH NR 71 TC 26 Z9 26 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-954X J9 GENESIS JI Genesis PD NOV PY 2009 VL 47 IS 11 BP 719 EP 728 DI 10.1002/dvg.20551 PG 10 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 525KS UT WOS:000272215400001 PM 19621439 ER PT J AU Little, J Higgins, JPT Ioannidis, JPA Moher, D Gagnon, F von Elm, E Khoury, MJ Cohen, B Davey-Smith, G Grimshaw, J Scheet, P Gwinn, M Williamson, RE Zou, GY Hutchings, K Johnson, CY Tait, V Wiens, M Golding, J van Duijn, C McLaughlin, J Paterson, A Wells, G Fortier, I Freedman, M Zecevic, M King, R Infante-Rivard, C Stewart, A Birkett, N AF Little, Julian Higgins, Julian P. T. Ioannidis, John P. A. Moher, David Gagnon, France von Elm, Erik Khoury, Muin J. Cohen, Barbara Davey-Smith, George Grimshaw, Jeremy Scheet, Paul Gwinn, Marta Williamson, Robin E. Zou, Guang Yong Hutchings, Kim Johnson, Candice Y. Tait, Valerie Wiens, Miriam Golding, Jean van Duijn, Cornelia McLaughlin, John Paterson, Andrew Wells, George Fortier, Isabel Freedman, Matthew Zecevic, Maja King, Richard Infante-Rivard, Claire Stewart, Alex Birkett, Nick TI STrengthening the REporting of Genetic Association Studies (STREGA)-An Extension of the STROBE Statement SO GENETIC EPIDEMIOLOGY LA English DT Review DE gene-disease associations; genetics; gene-environment interaction; systematic review; meta-analysis; reporting recommendations; epidemiology; genome-wide association ID GENOME-WIDE ASSOCIATION; HARDY-WEINBERG EQUILIBRIUM; SINGLE-NUCLEOTIDE POLYMORPHISMS; POPULATION STRATIFICATION; RANDOMIZED-TRIALS; DISEASE ASSOCIATIONS; GENOTYPING ERRORS; COMPLEX DISEASES; PROSTATE-CANCER; LINKAGE-DISEQUILIBRIUM AB Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the STrengthening the Reporting of OBservational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis. Genet. Epidemiol. 33:581-598, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Little, Julian; Moher, David; Hutchings, Kim; Johnson, Candice Y.; Tait, Valerie; Wiens, Miriam; Birkett, Nick] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON K1H 8M5, Canada. [Higgins, Julian P. T.] MRC, Biostat Unit, Cambridge CB2 2BW, England. [Ioannidis, John P. A.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. [Ioannidis, John P. A.] Tufts Univ, Sch Med, Ctr Genet Epidemiol & Modeling, Boston, MA 02111 USA. [Gagnon, France] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [von Elm, Erik] Univ Bern, Inst Social & Prevent Med, Bern, Switzerland. [von Elm, Erik] Univ Med Ctr, Dept Med Biometry & Med Informat, German Cochrane Ctr, Freiburg, Germany. [Khoury, Muin J.; Gwinn, Marta] Ctr Dis Control & Prevent, Natl Off Publ Hlth Genom, Atlanta, GA USA. [Cohen, Barbara] Publ Lib Sci, San Francisco, CA USA. [Davey-Smith, George] Univ Bristol, MRC, Ctr Causal Anal Translat Epidemiol, Dept Social Med, Bristol, Avon, England. [Grimshaw, Jeremy] Univ Ottawa, Ottawa Hlth Res Inst, Clin Epidemiol Program, Dept Med, Ottawa, ON K1H 8M5, Canada. [Scheet, Paul] Univ Texas Houston, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Zou, Guang Yong] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada. [Zou, Guang Yong] Robarts Res Inst, London, ON N6A 5C1, Canada. [McLaughlin, John] Canc Care Ontario, Toronto, ON, Canada. [McLaughlin, John] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [Paterson, Andrew] Hosp Sick Children, Toronto, ON, Canada. [Wells, George] Univ Ottawa, Cardiovasc Res Methods Ctr, Inst Heart, Ottawa, ON K1H 8M5, Canada. [Fortier, Isabel] McGill Univ, Genome Quebec & P3G Observ, Montreal, PQ, Canada. [Fortier, Isabel] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Freedman, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Infante-Rivard, Claire] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Fac Med, Montreal, PQ, Canada. RP Little, J (reprint author), Univ Ottawa, Dept Epidemiol & Community Med, 451 Smyth Rd, Ottawa, ON K1H 8M5, Canada. EM jlittle@uottawa.ca RI Ioannidis, John/G-9836-2011; Higgins, Julian/H-4008-2011; Stewart, Alexandre/A-5677-2011; Grimshaw, Jeremy/D-8726-2013; McLaughlin, John/E-4577-2013; Zou, Guangyong/K-6408-2013; Paterson, Andrew/A-4088-2011; OI Moher , David /0000-0003-2434-4206; Higgins, Julian/0000-0002-8323-2514; Paterson, Andrew/0000-0002-9169-118X; von Elm, Erik/0000-0002-7412-0406; Stewart, Alexandre/0000-0003-2673-9164; Grimshaw, Jeremy/0000-0001-8015-8243; Golding, Jean/0000-0003-2826-3307 FU Canadian Institutes of Health Research NR 154 TC 45 Z9 48 U1 3 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2009 VL 33 IS 7 BP 581 EP 598 DI 10.1002/gepi.20410 PG 18 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 514PB UT WOS:000271406100003 PM 19278015 ER PT J AU Dupuis, J Shi, JX Manning, AK Benjamin, EJ Meigs, JB Cupples, LA Siegmund, D AF Dupuis, Josee Shi, Jianxin Manning, Alisa K. Benjamin, Emelia J. Meigs, James B. Cupples, L. Adrienne Siegmund, David TI Mapping Quantitative Traits in Unselected Families: Algorithms and Examples SO GENETIC EPIDEMIOLOGY LA English DT Article DE genetic linkage; quantitative trait locus; score test; extended pedigrees; variance component analysis ID BY-SEX INTERACTION; BODY-MASS INDEX; LINKAGE ANALYSIS; VARIANCE-COMPONENTS; GENERAL PEDIGREES; GENETIC-LINKAGE; BLOOD-PRESSURE; HEART-DISEASE; LOCI; REGRESSION AB Linkage analysis has been widely used to identify from family data genetic variants influencing quantitative traits. Common approaches have both strengths and limitations. Likelihood ratio tests typically computed in variance component analysis can accommodate large families but are highly sensitive to departure from normality assumptions. Regression-based approaches are more robust but their use has primarily been restricted to nuclear families. In this paper, we develop methods for mapping quantitative traits in moderately large pedigrees. Our methods are based on the score statistic, which in contrast to the likelihood ratio statistic can use nonparametric estimators of variability to achieve robustness of the false-positive rate against departures from the hypothesized phenotypic model. Because the score statistic is easier to calculate than the likelihood ratio statistic, our basic mapping methods utilize relatively simple computer code that performs statistical analysis on output from any program that computes estimates of identity by descent. This simplicity also permits development and evaluation of methods to deal with multivariate and ordinal phenotypes, and with gene-gene and gene-environment interaction. We demonstrate our methods on simulated data and on fasting insulin, a quantitative trait measured in the Framingham Heart Study. Genet. Epidemiol. 33:617-627, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, BUMC, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Evans Mem Dept Med,Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Shi, Jianxin] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Benjamin, Emelia J.] NHLBIs Framingham Heart Study, Framingham, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Siegmund, David] Stanford Univ, Dept Stat, Stanford, CA 94305 USA. RP Dupuis, J (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, BUMC, 801 Mass Ave,3rd Floor, Boston, MA 02118 USA. EM dupuis@bu.edu OI Cupples, L. Adrienne/0000-0003-0273-7965; Dupuis, Josee/0000-0003-2871-3603; Benjamin, Emelia/0000-0003-4076-2336 FU National Institute of Health [R01 HG000848, R21 DK65732, K24 DK080140]; American Diabetes Association Career Development [RO1 HL076784, 1R01 AG028321, RO1 HL064753]; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; Boston University Linux Cluster for Genetic Analysis (LinGA); NIH NCRR [1S10RR163736-01A1] FX Supported by the National Institute of Health R01 HG000848 (D.S.; J.D.), R21 DK65732, K24 DK080140 (J.B.M.), an American Diabetes Association Career Development Award (J.B.M.), RO1 HL076784 (E.J.B.), 1801 AG028321 (E.J.B.), RO1 HL064753 (E.J.B.), the National Heart, Lung, and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195), and the Boston University Linux Cluster for Genetic Analysis (LinGA) funded by the NIH NCRR Shared Instrumentation grant (1S10RR163736-01A1). NR 46 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2009 VL 33 IS 7 BP 617 EP 627 DI 10.1002/gepi.20413 PG 11 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 514PB UT WOS:000271406100006 PM 19278016 ER PT J AU Boros, J Donaldson, IJ O'Donnell, A Odrowaz, ZA Zeef, L Lupien, M Meyer, CA Liu, XS Brown, M Sharrocks, AD AF Boros, Joanna Donaldson, Ian J. O'Donnell, Amanda Odrowaz, Zaneta A. Zeef, Leo Lupien, Mathieu Meyer, Clifford A. Liu, X. Shirley Brown, Myles Sharrocks, Andrew D. TI Elucidation of the ELK1 target gene network reveals a role in the coordinate regulation of core components of the gene regulation machinery SO GENOME RESEARCH LA English DT Article ID TRANSCRIPTION FACTORS ELK-1; TERNARY COMPLEX FACTORS; SERUM RESPONSE FACTOR; RNA-POLYMERASE-II; EXPRESSION; PROMOTER; FAMILY; SAP-1; CHIP; SRF AB Transcription factors play an important role in orchestrating the activation of specific networks of genes through targeting their proximal promoter and distal enhancer regions. However, it is unclear how the specificity of downstream responses is maintained by individual members of transcription-factor families and, in most cases, what their target repertoire is. We have used ChIP-chip analysis to identify the target genes of the ETS-domain transcription factor ELK1. Two distinct modes of ELK1 target gene selection are identified; the first involves redundant promoter binding with other ETS-domain family members; the second occurs through combinatorial binding with a second transcription factor SRF, which specifies a unique group of target genes. One of the most prominent groups of genes forming the ELK1 target network includes classes involved in core gene expression control, namely, components of the basal transcriptional machinery, the spliceosome and the ribosome. Amongst the set of genes encoding the basal transcription machinery components, are a functionally linked subset of GTFs and TAFs. Our study, therefore, reveals an unsuspected level of coordinate regulation of components of the core gene expression control machinery and also identifies two different modes of promoter targeting through binding with a second transcription factor or redundant binding with other ETS-domain family members. C1 [Boros, Joanna; Donaldson, Ian J.; O'Donnell, Amanda; Odrowaz, Zaneta A.; Zeef, Leo; Sharrocks, Andrew D.] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England. [Lupien, Mathieu; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. [Lupien, Mathieu; Brown, Myles] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Lupien, Mathieu; Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Meyer, Clifford A.; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Meyer, Clifford A.; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Sharrocks, AD (reprint author), Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England. EM a.d.sharrocks@manchester.ac.uk RI Sharrocks, Andrew/J-6756-2013; OI Brown, Myles/0000-0002-8213-1658; O'Donnell, Amanda/0000-0003-3655-6126 FU Wellcome Trust; AICR; Cancer Research UK and a Royal Society-Wolfson award FX We thank Anne Clancy, Karren Palmer, and Leanne Wardleworth for excellent technical assistance; Andy Hayes in the core microarray facility; Casey Bergman and Stefan Roberts and members of our laboratory for comments on the manuscript and stimulating discussions; Richard Treisman for reagents; Andrew Smith ( Cold Spring Harbor Laboratory) for help, advice, and access to DME2; and Takashi Kondo and Takeshi Hori for access to anisomycin microarray cluster analysis gene lists. This work was supported by grants from the Wellcome Trust, the AICR, Cancer Research UK and a Royal Society-Wolfson award to A. D. S. NR 34 TC 59 Z9 59 U1 0 U2 6 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD NOV PY 2009 VL 19 IS 11 BP 1963 EP 1973 DI 10.1101/gr.093047.109 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 514WK UT WOS:000271426600005 PM 19687146 ER PT J AU Longas, MO Mrabat, H Hales, C Garg, H AF Longas, Maria O. Mrabat, Hicham Hales, Charles Garg, Hari TI N-Desulfonation of Low Molecular Weight 3-O-Acylated Heparin Decreases Its Growth Inhibition of Pulmonary Artery Smooth Muscle Cells SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2009 CL San Diego, CA SP Soc* Glycobiol C1 [Longas, Maria O.] Purdue Univ Calumet, Hammond, IN USA. [Mrabat, Hicham; Hales, Charles; Garg, Hari] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2009 VL 19 IS 11 MA 124 BP 1324 EP 1324 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505PX UT WOS:000270707700135 ER PT J AU Jacobson, BC Chan, AT Giovannucci, EL Fuchs, CS AF Jacobson, B. C. Chan, A. T. Giovannucci, E. L. Fuchs, C. S. TI Body mass index and Barrett's oesophagus in women SO GUT LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; GASTRIC CARDIA; ABDOMINAL OBESITY; RISK-FACTORS; INCREASING INCIDENCE; PROSPECTIVE COHORT; UNITED-STATES; FOLLOW-UP; ADENOCARCINOMA; ASSOCIATION AB Objective: Excess body mass is associated with symptoms of gastro-oesophageal reflux disease, and cross-sectional studies suggest an association between body mass index (BMI) and Barrett's oesophagus. The present study sought prospectively to examine the influence of BMI and other anthropomorphic measures on the risk for Barrett's oesophagus among women. Methods: This was a prospective study of 15 861 women who participated in the Nurses' Health Study, without a history of cancer, who underwent upper gastrointestinal endoscopy for any reason between 1986 and 2004. The main outcome measures were 261 cases of pathologically confirmed specialised intestinal metaplasia within the oesophagus (Barrett's oesophagus). Self-reported data on weight were collected from biennial questionnaires. Self-reported height was collected in 1976, and self-reported waist and hip circumferences were collected in 1986. Results: Compared with women with a BMI of 20-24.9 kg/m(2), women with a BMI of 25-29.9 had a multivariate OR for Barrett's oesophagus of 0.92 (95% CI 0.66 to 1.27), women with a BMI >= 30 had a multivariate OR of 1.52 (95% CI 1.02 to 2.28) and women with a BMI,20 had a multivariate OR of 0.92 (95% CI 0.65 to 1.31). Results were similar when controlling for symptoms of gastro-oesophageal reflux, and among the entire Nurses' Health Study cohort (n = 93 609) regardless of a history of endoscopy. In contrast, waist-to-hip ratio, waist circumference and height did not appear to be associated with Barrett's oesophagus. Conclusions: Obese, but not overweight, women appear to be at increased risk for Barrett's oesophagus. C1 [Jacobson, B. C.] Boston Med Ctr, Dept Med, Gastroenterol Sect, Boston, MA USA. [Chan, A. T.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Giovannucci, E. L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, E. L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Fuchs, C. S.] Dana Farber & Harvard Canc Ctr, Canc Epidemiol Program, Boston, MA USA. RP Jacobson, BC (reprint author), Boston Univ, Med Ctr, 88 E Concord St,Room 7721, Boston, MA 02118 USA. EM brian.jacobson@bmc.org OI Jacobson, Brian/0000-0001-7064-2357 FU National Cancer Institute [CA087969, CA107412]; National Institutes of Diabetes and Digestive and Kidney Diseases [DK070706]; Damon Runyon Cancer Research Foundation Clinical Investigator Award FX This work was supported by the National Cancer Institute (CA087969; CA107412 to ATC) and the National Institutes of Diabetes and Digestive and Kidney Diseases (DK070706 to BCJ). ATC is a recipient of the Damon Runyon Cancer Research Foundation Clinical Investigator Award. The sponsors had no role in the design and conduct of the study; collection, management, analyses and interpretation of the data; or preparation, review or approval of the manuscript. NR 68 TC 29 Z9 29 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD NOV PY 2009 VL 58 IS 11 BP 1460 EP 1466 DI 10.1136/gut.2008.174508 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 507JG UT WOS:000270848700008 PM 19336423 ER PT J AU Zinner, DE Bolcic-Jankovic, D Clarridge, B Blumenthal, D Campbell, EG AF Zinner, Darren E. Bolcic-Jankovic, Dragana Clarridge, Brian Blumenthal, David Campbell, Eric G. TI Participation Of Academic Scientists In Relationships With Industry SO HEALTH AFFAIRS LA English DT Article ID CONFLICTS-OF-INTEREST; NATIONAL-SURVEY; BIOMEDICAL-RESEARCH; UNIVERSITY; POLICIES; FACULTY AB Relationships between academic researchers and industry have received considerable attention in the past twenty years. However, current data on the prevalence, magnitude, and trends in such relationships are rare. In a mailed survey of 3,080 academic life science researchers conducted in 2007, we found that 52.8 percent have some form of relationship with industry. Life science faculty with industry research support were more productive than faculty without such support on virtually every measure. However, we also found a significant decrease in industry support of university research, which could have major consequences for the academic life science research sector. [Health Aff (Millwood). 2009; 28(6): 1814-25] C1 [Zinner, Darren E.] Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA 02254 USA. [Blumenthal, David] Massachusetts Gen Hosp Partners Healthcare, Inst Hlth Policy, Boston, MA USA. RP Zinner, DE (reprint author), Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA 02254 USA. EM ecampbell@partners.org FU National Human Genome Research Institute of the National Institutes of Health [1R01GM074915-01]; Brandeis University's Health Industry Forum FX This research was supported by the National Human Genome Research Institute of the National Institutes of Health (Grant no. 1R01GM074915-01, EricG. Campbell, principal investigator). Darren Zinner is partially supported by Brandeis University's Health Industry Forum, an independent policy consortium of major health care insurers, delivery systems, and biopharmacuetical and medical device firms. However, the research for this paper was conducted before he became part of the group. The authors acknowledge the contributions of Sandra Feibelmann, Steffanie Bristol, and Sowmya Rao of the Institute for Health Policy at Massachusetts General Hospital. The views expressed herein do not necessarily represent the views of the U.S. Department of Health and Human Services. NR 21 TC 31 Z9 31 U1 0 U2 2 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2009 VL 28 IS 6 BP 1814 EP 1825 DI 10.1377/hlthaff.28.6.1814 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 517NR UT WOS:000271622300026 PM 19887423 ER PT J AU Blumenthal, D AF Blumenthal, David TI PERSPECTIVE Portrait Of A Policy And Political Entrepreneur SO HEALTH AFFAIRS LA English DT Article C1 [Blumenthal, David] Massachusetts Gen Hosp Partners HealthCare Syst, Boston, MA USA. [Blumenthal, David] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Blumenthal, David] Harvard Univ, Interfac Program Hlth Syst Improvement, Cambridge, MA 02138 USA. EM David.Blumenthal@hhs.gov NR 0 TC 1 Z9 1 U1 0 U2 3 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2009 VL 28 IS 6 BP W1037 EP W1039 DI 10.1377/hlthaff.28.6.w1037 PG 3 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 517NR UT WOS:000271622300049 PM 19762356 ER PT J AU Jha, AK DesRoches, CM Shields, AE Miralles, PD Zheng, J Rosenbaum, S Campbell, EG AF Jha, Ashish K. DesRoches, Catherine M. Shields, Alexandra E. Miralles, Paola D. Zheng, Jie Rosenbaum, Sara Campbell, Eric G. TI Evidence Of An Emerging Digital Divide Among Hospitals That Care For The Poor SO HEALTH AFFAIRS LA English DT Article ID ELECTRONIC HEALTH RECORDS; INFORMATION-TECHNOLOGY; AMBULATORY-CARE; NATIONAL-SURVEY; UNITED-STATES; COSTS; BENEFITS; QUALITY; PHYSICIANS; EFFICIENCY AB Some hospitals that disproportionately care for poor patients are falling behind in adopting electronic health records (EHRs). Data from a national survey indicate early evidence of an emerging digital divide: U. S. hospitals that provide care to large numbers of poor patients also had minimal use of EHRs. These same hospitals lagged others in quality performance as well, but those with EHR systems seemed to have eliminated the quality gap. These findings suggest that adopting EHRs should be a major policy goal of health reform measures targeting hospitals that serve large populations of poor patients. [Health Aff (Millwood). 2009; 28(6): w1160-70 (published online 26 October 2009; 10.1377/hlthaff.28.6.w1160)] C1 [Jha, Ashish K.; Zheng, Jie] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [DesRoches, Catherine M.; Campbell, Eric G.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Rosenbaum, Sara] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM ajha@hsph.harvard.edu FU Office of the National Coordinator for Health Information Technology in the U.S. Department of Health and Human Services; Robert Wood Johnson Foundation FX This work was supported by the Office of the National Coordinator for Health Information Technology in the U.S. Department of Health and Human Services and by the Robert Wood Johnson Foundation. Ashish Jha provides consulting support for UpToDate Inc. The authors report no other potential conflicts of interest relevant to this work. NR 23 TC 41 Z9 42 U1 1 U2 5 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2009 VL 28 IS 6 BP W1160 EP W1170 DI 10.1377/hlthaff.28.6.w1160 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 517NR UT WOS:000271622300062 PM 19858142 ER PT J AU Pizer, SD Frakt, AB Iezzoni, LI AF Pizer, Steven D. Frakt, Austin B. Iezzoni, Lisa I. TI Uninsured Adults With Chronic Conditions Or Disabilities: Gaps In Public Insurance Programs SO HEALTH AFFAIRS LA English DT Article ID HEALTH-INSURANCE; US ADULTS; COVERAGE; ACCESS; CARE; PROSPECTS; RISK AB Among nonelderly U. S. adults (ages 25-61), uninsurance rates increased from 13.7 percent in 2000 to 16.0 percent in 2005. Despite the existence of public insurance programs, rates remained high for low-income people reporting serious health conditions (25 percent across years) or disabilities (15 percent). Residents of southern states had even higher rates (32 percent with health conditions, 22 percent with disabilities). Those who did not belong to a federally mandated Medicaid eligibility category were about twice as likely as others to be uninsured overall, and uninsurance among this group increased more rapidly over time. These regional and categorical differences reflect gaps in current policy that pose challenges for incremental health reform. [Health Aff (Millwood). 2009; 28(6): w1141-50 (published online 20 October 2009; 10.1377/hlthaffairs.28.6.w1141)] C1 [Pizer, Steven D.; Frakt, Austin B.] US Dept Vet Affairs, Boston, MA USA. [Iezzoni, Lisa I.] Harvard Univ, Sch Med, Inst Hlth Policy, Boston, MA USA. [Iezzoni, Lisa I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pizer, SD (reprint author), US Dept Vet Affairs, Boston, MA USA. EM Pizer@bu.edu FU Agency for Healthcare Research and Quality (AHRQ) [R01 HS01594-1-01]; Health Services Research and Development Service of the U.S. Department of Veterans Affairs [IIR 06-238] FX Preliminary results from this research were presented at the Academy Health Annual Research Meeting, 29 June 2009, in Chicago, Illinois. The authors gratefully acknowledge financial support from the Agency for Healthcare Research and Quality (AHRQ) (R01 HS01594-1-01) and from the Health Services Research and Development Service of the U.S. Department of Veterans Affairs (VA) (IIR 06-238). They thank Mari-Lynn Drainoni as well as the editors and two anonymous reviewers for helpful comments on previous drafts. The opinions expressed in this paper are those of the authors and do not necessarily reflect the official positions of AHRQ, the VA, Boston University, or Harvard University. NR 19 TC 7 Z9 7 U1 0 U2 3 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2009 VL 28 IS 6 BP W1141 EP W1150 DI 10.1377/hlthaff.28.6.w1141 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 517NR UT WOS:000271622300060 PM 19843552 ER PT J AU Melcher, JR Levine, RA Bergevin, C Norris, B AF Melcher, Jennifer R. Levine, Robert A. Bergevin, Christopher Norris, Barbara TI The auditory midbrain of people with tinnitus: Abnormal sound-evoked activity revisited SO HEARING RESEARCH LA English DT Article DE Hyperacusis; Midbrain; Phantom sensation; fMRI; Neuroimaging ID HUMAN BRAIN-STEM; FMRI ACTIVATION; PSYCHOMETRIC PROPERTIES; LATERALIZED TINNITUS; INFERIOR COLLICULUS; NOISE EXPOSURE; ACOUSTIC NOISE; SCANNER NOISE; LOUDNESS; PLASTICITY AB Sound-evoked fMRI activation of the inferior colliculi (IC) was compared between tinnitus and non-tinnitus subjects matched in threshold (normal), age, depression, and anxiety. Subjects were stimulated with broadband sound in an "on/off" fMRI paradigm with and without on-going sound from the scanner coolant pump. (1) With pump sounds off. the tinnitus; group showed greater stimulus-evoked activation of the IC than the non-tinnitus group, suggesting abnormal gain within the auditory pathway of tinnitus subjects. (2) Having pump sounds on reduced activation in the tinnitus, but not the non-tinnitus; group. This result suggests response saturation in tinnitus subjects, possibly occurring because abnormal gain increased response amplitude to an upper limit. (3) In contrast to Melcher et al. (2000), the ratio of activation between right and left IC did not differ significantly between tinnitus and non-tinnitus subjects or in a manner dependent on tinnitus laterality. However, new data from subjects imaged previously by Melcher et al. suggest a possible tinnitus subgroup with abnormally asymmetric function of the IC. The present and previous data together suggest elevated responses to sound in the IC are common among those with tinnitus and normal thresholds, while abnormally asymmetric activation is not, even among those with lateralized tinnitus. (C) 2009 Elsevier B.V. All rights reserved. C1 [Melcher, Jennifer R.; Levine, Robert A.; Bergevin, Christopher; Norris, Barbara] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Melcher, Jennifer R.; Bergevin, Christopher] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. [Melcher, Jennifer R.; Levine, Robert A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Levine, Robert A.] Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Melcher, JR (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM jennifer_melcher@meei.harvard.edu FU Tinnitus Research Consortium; American Tinnitus Association; Royal National Institute for Deaf People; Tinnitus Research Initiative; Jack and Shelley Blais; Kenneth Griffin; NIH/NIDCD [P30DC005209]; National Center for Research Resources [P41RR14075]; Mental Illness and Neuroscience Discovery (MIND) Institute FX We thank Irina Sigalovsky for her assistance in performing some of the experiments and Inge Knudson, Jianwen Gu and Christopher Shera for their comments on an earlier version of this manuscript. Support was provided by the Tinnitus Research Consortium, American Tinnitus Association, Royal National Institute for Deaf People, Tinnitus Research Initiative, Jack and Shelley Blais, Kenneth Griffin, and NIH/NIDCD P30DC005209. Partial support was also provided by the National Center for Research Resources (P41RR14075) and the Mental Illness and Neuroscience Discovery (MIND) Institute. NR 47 TC 54 Z9 56 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD NOV PY 2009 VL 257 IS 1-2 BP 63 EP 74 DI 10.1016/j.heares.2009.08.005 PG 12 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 511QB UT WOS:000271180200007 PM 19699287 ER PT J AU Friedman, LS Brandt, LJ Elta, GH Fitz, JG Gores, GJ Katz, PO Kuemmerle, JF Pardi, DS Vargo, JJ Stolar, MH AF Friedman, Lawrence S. Brandt, Lawrence J. Elta, Grace H. Fitz, J. Gregory Gores, Gregory J. Katz, Philip O. Kuemmerle, John F. Pardi, Darrell S. Vargo, John J. Stolar, Michael H. CA Task Force TI Report of the Multisociety Task Force on GI Training SO HEPATOLOGY LA English DT Article C1 [Friedman, Lawrence S.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Friedman, Lawrence S.] Tufts Univ, Sch Med, Medford, MA 02155 USA. [Friedman, Lawrence S.] Newton Wellesley Hosp, Newton, MA USA. [Friedman, Lawrence S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brandt, Lawrence J.] Montefiore Med Ctr, New York, NY USA. [Brandt, Lawrence J.] Albert Einstein Coll Med, Bronx, NY USA. [Elta, Grace H.] Univ Michigan, Ann Arbor, MI 48109 USA. [Fitz, J. Gregory] Univ Texas SW Med Sch, Dallas, TX USA. [Gores, Gregory J.; Pardi, Darrell S.] Mayo Clin, Coll Med Rochester, Rochester, MN USA. [Katz, Philip O.] Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. [Katz, Philip O.] Thomas Jefferson Univ, Philadelphia, PA USA. [Kuemmerle, John F.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Vargo, John J.] Cleveland Clin, Lerner Coll Med, Cleveland, OH USA. [Vargo, John J.] Cleveland Clin Fdn, Cleveland, OH USA. RP Friedman, LS (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2009 VL 50 IS 5 BP 1325 EP 1329 DI 10.1002/hep.23257 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 516TK UT WOS:000271565600001 ER PT J AU Freedman, ND Everhart, JE Lindsay, KL Ghany, MG Curto, TM Shiffman, ML Lee, WM Lok, AS Di Bisceglie, AM Bonkovsky, HL Hoefs, JC Dienstag, JL Morishima, C Abnet, CC Sinha, R AF Freedman, Neal D. Everhart, James E. Lindsay, Karen L. Ghany, Marc G. Curto, Teresa M. Shiffman, Mitchell L. Lee, William M. Lok, Anna S. Di Bisceglie, Adrian M. Bonkovsky, Herbert L. Hoefs, John C. Dienstag, Jules L. Morishima, Chihiro Abnet, Christian C. Sinha, Rashmi CA HALT-C Trial Grp TI Coffee Intake Is Associated with Lower Rates of Liver Disease Progression in Chronic Hepatitis C SO HEPATOLOGY LA English DT Article ID ALANINE AMINOTRANSFERASE ACTIVITY; GAMMA-GLUTAMYL-TRANSFERASE; TEA CONSUMPTION; HEPATOCELLULAR-CARCINOMA; UNITED-STATES; RISK; CAFFEINE; INHIBITION; CIRRHOSIS; PEGINTERFERON AB Higher coffee consumption has been associated inversely with the incidence of chronic liver disease in population studies. We examined the relationship of coffee consumption with liver disease progression in individuals with advanced hepatitis C-related liver disease. Baseline coffee and tea intake were assessed in 766 participants of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial who had hepatitis C-related bridging fibrosis or cirrhosis on liver biopsy and failed to achieve a sustained virological response to peginterferon plus ribavirin treatment. Participants were followed for 3.8 years for clinical outcomes and, for those without cirrhosis, a 2-point increase in Ishak fibrosis score on protocol biopsies. At baseline, higher coffee consumption was associated with less severe steatosis on biopsy, lower serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, alpha-fetoprotein, insulin, and homeostatic model assessment (HOMA2) score, and higher albumin (P < 0.05 for all). Two hundred thirty patients had outcomes. Outcome rates declined with increasing coffee intake: 11.1/100 person-years for none, 12.1 for less than 1 cup/day, 8.2 for 1 to fewer than 3 cups/day, and 6.3 for 3 or more cups/day (P-trend = 0.0011). Relative risks (95% confidence intervals) were 1.11 (0.76-1.61) for less than I cup/day; 0.70 (0.48-1.02) for I to fewer than 3 cups/day; and 0.47 (0.27-0.85) for 3 or more cups/day (P-trend = 0.0003) versus not drinking. Risk estimates did not vary by treatment assignment or cirrhosis status at baseline. Tea intake was not associated with outcomes. Conclusion: In a large prospective study of participants with advanced hepatitis C-related liver disease, regular coffee consumption was associated with lower rates of disease progression. (HEPATOLOGY 2009;50:1360-1369.) C1 [Freedman, Neal D.; Abnet, Christian C.; Sinha, Rashmi] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Everhart, James E.] NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Lindsay, Karen L.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA. [Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Curto, Teresa M.] New England Res Inst, Watertown, MA 02172 USA. [Shiffman, Mitchell L.] Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Lok, Anna S.] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA. [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. [Hoefs, John C.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Morishima, Chihiro] Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA. RP Freedman, ND (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS-320,MSC 7232, Rockville, MD 20852 USA. EM freedmanne@mail.nih.gov RI Abnet, Christian/C-4111-2015; Sinha, Rashmi/G-7446-2015; Freedman, Neal/B-9741-2015; OI Abnet, Christian/0000-0002-3008-7843; Sinha, Rashmi/0000-0002-2466-7462; Freedman, Neal/0000-0003-0074-1098; Yang, Shuman/0000-0002-9638-0890 FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Center for Minority Health and Health Disparities; General Clinical Research Center; National Center for Research Resources, National Institutes of Health FX Supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Additional support was provided by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, the National Center for Minority Health and Health Disparities and by General Clinical Research Center grants from the National Center for Research Resources, National Institutes of Health. This research was also supported in part by the Intramural Research Program of the National Cancer Institute. Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement with the National Institutes of Health. The funding organizations bad no role in the design and conduct of the study; the collection, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. NR 42 TC 78 Z9 81 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2009 VL 50 IS 5 BP 1360 EP 1369 DI 10.1002/hep.23162 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 516TK UT WOS:000271565600008 PM 19676128 ER PT J AU Kim, DI Manoach, DS Mathalon, DH Turner, JA Mannell, M Brown, GG Ford, JM Gollub, RL White, T Wible, C Belger, A Bockholt, HJ Clark, VP Lauriello, J O'Leary, D Mueller, BA Lim, KO Andreasen, N Potkin, SG Calhoun, VD AF Kim, Dae Il Manoach, Dara S. Mathalon, Daniel H. Turner, Jessica A. Mannell, Maggie Brown, Greg G. Ford, Judith M. Gollub, Randy L. White, Tonya Wible, Cynthia Belger, Aysenil Bockholt, H. Jeremy Clark, Vince P. Lauriello, John O'Leary, Daniel Mueller, Bryon A. Lim, Kelvin O. Andreasen, Nancy Potkin, Steve G. Calhoun, Vince D. TI Dysregulation of Working Memory and Default-Mode Networks in Schizophrenia Using Independent Component Analysis, an fBIRN and MCIC Study SO HUMAN BRAIN MAPPING LA English DT Article DE ICA; schizophrenia; working memory; functional connectivity; fBIRN; MCIC; auditory oddball; Sternberg ID DORSOLATERAL PREFRONTAL CORTEX; TASK-INDUCED DEACTIVATION; RESTING-STATE NETWORKS; FUNCTIONAL MRI DATA; COGNITIVE CONTROL; BLIND SEPARATION; MENTAL-DISORDERS; CORTICAL REGIONS; TIME-SERIES; HUMAN BRAIN AB Deficits in working memory (WM) are a consistent neurocognitive marker for schizophrenia. Previous studies have suggested that WM is the product of coordinated activity in distributed functionally connected brain regions. Independent component analysis (ICA) is a data-driven approach that can identify temporally coherent networks that underlie fMRI activity. We applied ICA to an fMRI dataset for 115 patients with chronic schizophrenia and 130 healthy controls by performing the Sternberg Item Recognition Paradigm. Here, we describe the first results using ICA to identify differences in the function of WM networks in schizophrenia compared to controls. ICA revealed six networks that showed significant differences between patients with schizophrenia and healthy controls. Four of these networks were negatively task-correlated and showed deactivation across the posterior cingulate, precuneus, medial prefrontal cortex, anterior cingulate, inferior parietal lobules, and parahippocampus. These networks comprise brain regions known as the default-mode network (DMN), a well-characterized set of regions shown to be active during internal modes of cognition and implicated in schizophrenia. Two networks were positively task-correlated, with one network engaging WM regions such as bilateral DLPFC and inferior parietal lobules while the other network engaged primarily the cerebellum Our results Suggest that DLPFC dysfunction in schizophrenia might be lateralized to the left and intrinsically tied to other regions such as the inferior parietal lobule and cingulate gyrus. Furthermore, we found that DMN dysfunction in schizophrenia exists across multiple subnetworks of the DMN and that these subnetworks are individually relevant to the pathophysiology of schizophrenia. In summary, this large multsite study identified multiple temporally coherent networks, which are aberrant in schizophrenia versus healthy controls and suggests that both task-correlated and task-anticorrelated networks may serve as potential biomarkers. Himi Brain Mapp 30:3795-3811, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Kim, Dae Il; Mannell, Maggie; Bockholt, H. Jeremy; Clark, Vince P.; Calhoun, Vince D.] Mind Res Network, Albuquerque, NM 87131 USA. [Manoach, Dara S.; Gollub, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Neuroimaging Div, Charlestown, MA USA. [Manoach, Dara S.; Gollub, Randy L.] Harvard Univ, Sch Med, Athinoula Martinos Ctr Biomed Imaging, Boston, MA USA. [Mathalon, Daniel H.; Ford, Judith M.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Turner, Jessica A.; Potkin, Steve G.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Brown, Greg G.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [White, Tonya; Mueller, Bryon A.; Lim, Kelvin O.] Univ Minnesota, Dept Psychiat, Med Ctr, Minneapolis, MN 55455 USA. [Wible, Cynthia] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Belger, Aysenil] Duke Univ, Med Ctr, Brain Imaging & Anal Ctr, Durham, NC USA. [Clark, Vince P.; Lauriello, John] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [O'Leary, Daniel; Andreasen, Nancy] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Clark, Vince P.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Belger, Aysenil] Univ N Carolina, Chapel Hill, NC USA. RP Kim, DI (reprint author), Mind Res Network, 1101 Yale Blvd NE, Albuquerque, NM 87131 USA. EM dkim@mm.org; vcalhoun@unm.edu RI Clark, Vincent/B-3343-2010; Potkin, Steven/A-2021-2013; Calhoun, Vince/H-7146-2013; Turner, Jessica/H-7282-2015; OI Clark, Vincent/0000-0002-9151-2102; Calhoun, Vince/0000-0001-9058-0747; Turner, Jessica/0000-0003-0076-8434; Mathalon, Daniel/0000-0001-6090-4974; Gollub, Randy L./0000-0002-9434-4044; Potkin, Steven/0000-0003-1028-1013; Belger, Aysenil/0000-0003-2687-1966 FU National Institutes of Health [1 R01 EB 000840]; NCRR [U24-RR021992]; DOE [DE-FG02-99ER62764] FX National Institutes of Health; Contract grant number: 1 R01 EB 000840; Contract grant sponsor: NCRR; Contract grant number: U24-RR021992; Contract grant sponsor: DOE; Contract grant number: DE-FG02-99ER62764. NR 63 TC 128 Z9 128 U1 4 U2 14 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD NOV PY 2009 VL 30 IS 11 BP 3795 EP 3811 DI 10.1002/hbm.20807 PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 516TH UT WOS:000271565300028 PM 19434601 ER PT J AU Oh, JS Kubicki, M Rosenberger, G Bouix, S Levitt, JJ McCarley, RW Westin, CF Shenton, ME AF Oh, Jungsu S. Kubicki, Marek Rosenberger, Gudrun Bouix, Sylvain Levitt, James J. McCarley, Robert W. Westin, Carl-Fredrik Shenton, Martha E. TI Thalamo-Frontal White Matter Alterations in Chronic Schizophrenia: A Quantitative Diffusion Tractography Study SO HUMAN BRAIN MAPPING LA English DT Article DE diffusion tensor imaging (DTI); Brodmann area (BA); internal capsule (IC); parameterization; chronic schizophrenia ID ASSOCIATION FIBER PATHWAYS; HUMAN BRAIN; COORDINATE SYSTEM; CORPUS-CALLOSUM; WORKING-MEMORY; TENSOR MRI; CORTEX; INTEGRITY; ABNORMALITIES; CONNECTIONS AB Diffusion tensor imaging (DTI) and fiber tractography are useful tools for reconstructing white matter tracts (WMT) in the brain. Previous tractography studies have sought to segment reconstructed WMT into anatomical structures using several approaches, but quantification has been limited to extracting mean values of diffusion indices. Delineating WMT in schizophrenia is of particular interest because schizophrenia has been hypothesized to be a disorder of disrupted connectivity, especially between frontal and temporal regions of the brain. In this study, we aim to differentiate diffusion properties of thalamo-frontal pathways in schizophrenia from normal controls. We present a quantitative group comparison method, which combines the strengths of both tractography-based and voxel-based studies. Our algorithm extracts white matter pathways using whole brain tractography. Functionally relevant bundles are selected and parsed from the resulting set of tracts, using an internal capsule (IC) region of interest (ROI) as "source", and different Brodmann area (BA) ROIs as "targets". The resulting bundles are then longitudinally parameterized so that diffusion properties can be measured and compared along the WMT. Using this processing pipeline, we were able to find altered diffusion properties in male patients with chronic schizophrenia in terms of fractional anisotropy (FA) decreases and mean diffusivity (MD) increases in precise and functionally relevant locations. These findings suggest that our method can enhance the regional and functional specificity of DTI group studies, thus improving our understanding of brain function. Hum Brain Mapp 30:3812-3825, 2009. (C) 2009 Wiley-Liss. Inc. C1 [Oh, Jungsu S.; Kubicki, Marek; Rosenberger, Gudrun; Bouix, Sylvain; Levitt, James J.; Shenton, Martha E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat,Psychiat Neuroimaging Lab, Boston, MA 02215 USA. [Oh, Jungsu S.] Seoul Natl Univ, Brain Korea Div Human Life Sci 21, Seoul, South Korea. [Kubicki, Marek; Levitt, James J.; McCarley, Robert W.; Shenton, Martha E.] VA Boston Healthcare Syst, Clin Neurosci Div, Neurosci Lab, Brockton, MA USA. [Rosenberger, Gudrun] Med Univ Innsbruck, Dept Gen Psychiat, Innsbruck, Austria. [Westin, Carl-Fredrik] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,Lab Math Imaging, Boston, MA 02215 USA. [Shenton, Martha E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,MRI Div,Surg Planning Lab, Boston, MA 02215 USA. RP Shenton, ME (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat,Psychiat Neuroimaging Lab, 1249 Boylston St, Boston, MA 02215 USA. EM shenton@bwh.harvard.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Bouix, Sylvain/0000-0003-1326-6054; Oh, Jungsu/0000-0002-1925-8103 FU Korea Research Foundation; Korean Government [MOEHRD KRF2006-352-D00220]; Second Stage Brain Korea 21 Project in 2008 (Division of Human Life Science), National Institute of Health [K05 MH070047, R01 MH 50740, P50 MH080272-01]; National Alliance for Medical Image Computing; NIH Roadmap for Medical Research Award [U54 EB005149]; Department of Veterans Affairs Merit Awards; VA Schizophrenia Center FX Contract grant sponsors: Korea Research Foundation by the Korean Government; Contract grant number: MOEHRD KRF2006-352-D00220; Contract grant sponsors: Second Stage Brain Korea 21 Project in 2008 (Division of Human Life Science), National Institute of Health; Contract grant numbers: K05 MH070047, R01 MH 50740, P50 MH080272-01; Contract grant sponsor: National Alliance for Medical Image Computing, and NIH Roadmap for Medical Research Award; Contract grant number: U54 EB005149; Contract grant sponsors: Department of Veterans Affairs Merit Awards; VA Schizophrenia Center. NR 67 TC 53 Z9 54 U1 2 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD NOV PY 2009 VL 30 IS 11 BP 3812 EP 3825 DI 10.1002/hbm.20809 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 516TH UT WOS:000271565300029 PM 19449328 ER PT J AU Saran, N Lyszkiewicz, M Pommerencke, J Witzlau, K Vakilzadeh, R von Boehmer, H Krueger, A AF Saran, Namita Lyszkiewicz, Marcin Pommerencke, Jens Witzlau, Katrin Vakilzadeh, Ramin von Boehmer, Harald Krueger, Andreas TI Multiple extra-thymic precursors contribute to T cell development with different kinetics SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT Combined Meeting of the 17th European-Society-of-Gene-and-Cell-Therapy/16th German-Society-for-Gene-Therapy/4th German-Society-for-Stem-Cell-Research CY NOV 21-25, 2009 CL Hannover, GERMANY SP Int Soc Cellular Therapy, European Branch, European Soc Gene & Cell Therapy, German Soc Gene Therapy, German Soc Stem Cell Res, BD Biosci, Biotech GmbH, Genethon, Cellectis, EUFETS, Lonza, Oxford BioMedica, Peprotech, Plasmidfactory, Regenx Biosci, Rentschler, Sartorius Stedim, StemCell Technologies C1 [Saran, Namita; Lyszkiewicz, Marcin; Pommerencke, Jens; Witzlau, Katrin; Vakilzadeh, Ramin; Krueger, Andreas] Hannover Med Sch, Hannover, Germany. [von Boehmer, Harald] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM krueger.andreas@mh-hannover.de RI Krueger, Andreas/B-9427-2009 OI Krueger, Andreas/0000-0001-7873-7334 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 2009 VL 20 IS 11 BP 1466 EP 1466 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 515BJ UT WOS:000271441000336 ER PT J AU Dirice, E Sanlioglu, A Kahraman, S Ozturk, S Balci, M Omer, A Griffith, T Sanlioglu, S AF Dirice, Ercument Sanlioglu, Ahter Kahraman, Sevim Ozturk, Saffet Balci, Mustafa Omer, Abdulkadir Griffith, Thomas Sanlioglu, Salih TI Adenovirus mediated TRAIL gene therapy approach provides sustained insulin expression in STZ-induced diabetic rats SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT Combined Meeting of the 17th European-Society-of-Gene-and-Cell-Therapy/16th German-Society-for-Gene-Therapy/4th German-Society-for-Stem-Cell-Research CY NOV 21-25, 2009 CL Hannover, GERMANY SP Int Soc Cellular Therapy, European Branch, European Soc Gene & Cell Therapy, German Soc Gene Therapy, German Soc Stem Cell Res, BD Biosci, Biotech GmbH, Genethon, Cellectis, EUFETS, Lonza, Oxford BioMedica, Peprotech, Plasmidfactory, Regenx Biosci, Rentschler, Sartorius Stedim, StemCell Technologies ID PROSTATE CARCINOMA-CELLS; APOPTOSIS; SIRNA C1 [Ozturk, Saffet] Akdeniz Univ, Fac Med, Dept Histol & Embryol, Antalya, Turkey. [Balci, Mustafa] Akdeniz Univ, Fac Med, Div Endocrinol & Metab Dis, Antalya, Turkey. [Omer, Abdulkadir] Harvard Univ, Sch Med, Joslin Diabet Ctr, Cambridge, MA 02138 USA. [Griffith, Thomas] Univ Iowa, Dept Urol, Iowa City, IA 52242 USA. [Griffith, Thomas] Univ Iowa, Dept Urol, Iowa City, IA 52242 USA. EM sanlioglu@akdeniz.edu.tr RI Ozturk, Saffet/C-1239-2016; Sanlioglu, Salih/F-9305-2016 NR 4 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 2009 VL 20 IS 11 BP 1471 EP 1472 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 515BJ UT WOS:000271441000351 ER PT J AU Kahraman, S Hapil, FZ Aydin, C Bisgin, A Dirice, E Griffith, TS Sanlioglu, AD Sanlioglu, S AF Kahraman, Sevim Hapil, Fatma Zehra Aydin, Cigdem Bisgin, Atil Dirice, Ercument Griffith, Thomas S. Sanlioglu, Ahter Dilsad Sanlioglu, Salih TI Tracing of the fate of allogeneic islet grafts via CCD camera SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT Combined Meeting of the 17th European-Society-of-Gene-and-Cell-Therapy/16th German-Society-for-Gene-Therapy/4th German-Society-for-Stem-Cell-Research CY NOV 21-25, 2009 CL Hannover, GERMANY SP Int Soc Cellular Therapy, European Branch, European Soc Gene & Cell Therapy, German Soc Gene Therapy, German Soc Stem Cell Res, BD Biosci, Biotech GmbH, Genethon, Cellectis, EUFETS, Lonza, Oxford BioMedica, Peprotech, Plasmidfactory, Regenx Biosci, Rentschler, Sartorius Stedim, StemCell Technologies C1 [Kahraman, Sevim; Hapil, Fatma Zehra; Aydin, Cigdem; Bisgin, Atil; Sanlioglu, Ahter Dilsad; Sanlioglu, Salih] Akdeniz Univ, Fac Med, Human Gene Therapy Div Med Genet, Antalya, Turkey. [Dirice, Ercument] Harvard Univ, Sch Med, Joslin Diabet Ctr, Cambridge, MA 02138 USA. [Griffith, Thomas S.] Univ Iowa, Dept Urol, Iowa City, IA 52242 USA. EM sanlioglu@akdeniz.edu.tr RI Sanlioglu, Salih/F-9305-2016 NR 2 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 2009 VL 20 IS 11 BP 1479 EP 1479 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 515BJ UT WOS:000271441000371 ER PT J AU Kahraman, S Hapil, FZ Ertosun, MG Dirice, E Sanlioglu, AD Sanlioglu, S AF Kahraman, Sevim Hapil, Fatma Zehra Ertosun, Mustafa Gokhan Dirice, Ercument Sanlioglu, Ahter Dilsad Sanlioglu, Salih TI In vivo fluorescence imaging as a method to assess pancreatic islet xenograft failure SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT Combined Meeting of the 17th European-Society-of-Gene-and-Cell-Therapy/16th German-Society-for-Gene-Therapy/4th German-Society-for-Stem-Cell-Research CY NOV 21-25, 2009 CL Hannover, GERMANY SP Int Soc Cellular Therapy, European Branch, European Soc Gene & Cell Therapy, German Soc Gene Therapy, German Soc Stem Cell Res, BD Biosci, Biotech GmbH, Genethon, Cellectis, EUFETS, Lonza, Oxford BioMedica, Peprotech, Plasmidfactory, Regenx Biosci, Rentschler, Sartorius Stedim, StemCell Technologies C1 [Kahraman, Sevim; Hapil, Fatma Zehra; Ertosun, Mustafa Gokhan; Sanlioglu, Ahter Dilsad; Sanlioglu, Salih] Akdeniz Univ, Fac Med, Human Gene Therapy Div Med Genet, Antalya, Turkey. [Dirice, Ercument] Harvard Univ, Sch Med, Joslin Diabet Ctr, Cambridge, MA 02138 USA. EM sanlioglu@akdeniz.edu.tr RI Sanlioglu, Salih/F-9305-2016 NR 2 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 2009 VL 20 IS 11 BP 1479 EP 1479 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 515BJ UT WOS:000271441000370 ER PT J AU Kahraman, S Dirice, E Sanlioglu, A Yoldas, B Bagci, H Erkilic, M Griffith, T Sanlioglu, S AF Kahraman, Sevim Dirice, Ercument Sanlioglu, Ahter Yoldas, Burcak Bagci, Huseyin Erkilic, Metin Griffith, Thomas Sanlioglu, Salih TI Monitoring of systemic delivery of adenovirus mediated EGFP transgene expression in mice using fluorescence imaging SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT Combined Meeting of the 17th European-Society-of-Gene-and-Cell-Therapy/16th German-Society-for-Gene-Therapy/4th German-Society-for-Stem-Cell-Research CY NOV 21-25, 2009 CL Hannover, GERMANY SP Int Soc Cellular Therapy, European Branch, European Soc Gene & Cell Therapy, German Soc Gene Therapy, German Soc Stem Cell Res, BD Biosci, Biotech GmbH, Genethon, Cellectis, EUFETS, Lonza, Oxford BioMedica, Peprotech, Plasmidfactory, Regenx Biosci, Rentschler, Sartorius Stedim, StemCell Technologies C1 [Kahraman, Sevim; Sanlioglu, Ahter; Yoldas, Burcak; Bagci, Huseyin; Sanlioglu, Salih] Akdeniz Univ, Fac Med, Human Gene Therapy Unit, Antalya, Turkey. [Dirice, Ercument] Harvard Univ, Sch Med, Joslin Diabet Ctr, Cambridge, MA 02138 USA. [Erkilic, Metin] Akdeniz Univ, Dept Nucl Med, Fac Med, Antalya, Turkey. [Griffith, Thomas] Univ Iowa, Dept Urol, Iowa City, IA 52242 USA. EM sanlioglu@akdeniz.edu.tr RI yoldas, burcak/C-3522-2016; Erkilic, Metin/C-8748-2016; Sanlioglu, Salih/F-9305-2016 NR 3 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 2009 VL 20 IS 11 BP 1507 EP 1507 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 515BJ UT WOS:000271441000447 ER PT J AU Eijgelsheim, M Newton-Cheh, C Aarnoudse, ALHJ van Noord, C Witteman, JCM Hofman, A Uitterlinden, AG Stricker, BHC AF Eijgelsheim, Mark Newton-Cheh, Christopher Aarnoudse, Adrianus L. H. J. van Noord, Charlotte Witteman, Jacqueline C. M. Hofman, Albert Uitterlinden, Andre G. Stricker, Bruno H. C. TI Genetic variation in NOS1AP is associated with sudden cardiac death: evidence from the Rotterdam Study SO HUMAN MOLECULAR GENETICS LA English DT Article ID QT-INTERVAL DURATION; GENOME-WIDE ASSOCIATION; ANALYSIS SYSTEM MEANS; MYOCARDIAL-INFARCTION; GENERAL-POPULATION; REGULATOR NOS1AP; COMMON VARIANTS; FAMILY-HISTORY; HEART-FAILURE; RISK AB Common variation within the nitric oxide-1 synthase activator protein (NOS1AP) locus is strongly related to QT interval, a sudden cardiac death (SCD) risk factor. A recent report describes common variation in NOS1AP associated with SCD in a US population of European ancestry. The objective of the current study was to obtain additional evidence by investigating the association between NOS1AP variants and SCD in the prospective population-based Rotterdam Study. The study population consisted of 5974 European ancestry subjects, aged 55 years and older, genotyped on Illumina arrays. SCD was defined according to European Society of Cardiology guidelines. Smoking, body mass index, diabetes mellitus, hypertension, heart failure and myocardial infarction were used as covariates in Cox proportional hazard models. Results were combined with reported evidence using inverse-variance weighted meta-analysis. Two hundred and eight (109 witnessed) cases of SCD occurred during a mean follow-up of 10.4 years. Within the Rotterdam Study alone, no significant associations were observed. Upon pooling of results with existing data, we observed strengthening of existing evidence for rs16847549 (US data HR = 1.31, P = 0.0024; Rotterdam Study HR = 1.18, P = 0.16; joint HR = 1.26, P = 0.0011). When the case definition in the Rotterdam Study was restricted to witnessed SCD, association of rs16847549 with SCD became stronger (joint P = 0.00019) and additionally the association between rs12567209 and SCD gained significance (US data HR = 0.57, P = 0.0035; Rotterdam Study HR = 0.69, P = 0.23; joint HR = 0.60, P = 0.0018). In conclusion, this study provided additional evidence for association between genetic variation within NOS1AP and SCD. The mechanism by which this effect is exerted remains to be elucidated. C1 [Eijgelsheim, Mark; Aarnoudse, Adrianus L. H. J.; van Noord, Charlotte; Witteman, Jacqueline C. M.; Hofman, Albert; Uitterlinden, Andre G.; Stricker, Bruno H. C.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Uitterlinden, Andre G.; Stricker, Bruno H. C.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA. [van Noord, Charlotte] Dutch Med Evaluat Board, NL-2500 BE The Hague, Netherlands. [Witteman, Jacqueline C. M.; Hofman, Albert; Uitterlinden, Andre G.; Stricker, Bruno H. C.] Netherlands Genom Initiat, Netherlands Consortium Healthy Ageing, Rotterdam, Netherlands. [Stricker, Bruno H. C.] Inspectorate Hlth Care, NL-2500 BC The Hague, Netherlands. RP Stricker, BHC (reprint author), Erasmus MC, Dept Epidemiol, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM b.stricker@erasmusmc.nl FU National Genomic Initiative/Netherlands Organization for Scientific Research [050.060.810]; Netherlands Organization for Scientific Research [175.010.2005.011]; Netherlands Heart Foundation [2007B221]; NIH [HL080025]; Doris Duke Charitable Foundation Clinical Scientist Development Award; Burroughs Wellcome Fund Career Award for Medical Scientists FX This work was supported by the National Genomic Initiative/Netherlands Organization for Scientific Research [050.060.810]; the Netherlands Organization for Scientific Research [175.010.2005.011]; the Netherlands Heart Foundation [2007B221 to M. E.]; NIH [HL080025 to C.N.-C.]; the Doris Duke Charitable Foundation Clinical Scientist Development Award [to C.N.-C.]; and the Burroughs Wellcome Fund Career Award for Medical Scientists [to C.N.-C.]. NR 34 TC 38 Z9 39 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 1 PY 2009 VL 18 IS 21 BP 4213 EP 4218 DI 10.1093/hmg/ddp356 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 505QD UT WOS:000270708300019 PM 19643915 ER PT J AU Li, J Milbury, CA Li, C Makrigiorgos, GM AF Li, Jin Milbury, Coren A. Li, Cheng Makrigiorgos, G. Mike TI Two-Round Coamplification at Lower Denaturation Temperature-PCR (COLD-PCR)-Based Sanger Sequencing Identifies a Novel Spectrum of Low-Level Mutations in Lung Adenocarcinoma SO HUMAN MUTATION LA English DT Article DE lung cancer; TP53; low-level mutation; intratumor heterogeneity; COLD-PCR ID P53 MUTATIONS; CELL CARCINOMA; COLD-PCR; CANCER; DNA; ABNORMALITIES; SURVIVAL; SAMPLES; ASSAY; CURVE AB Reliable identification of cancer-related mutations in TP53 is often problematic, as these mutations can be randomly distributed throughout numerous codons and their relative abundance in clinical samples can fall below the sensitivity limits of conventional sequencing. To ensure the highest sensitivity in mutation detection, we adapted the recently described coamplification at lower denaturation temperature-PCR (COLD-PCR) method to employ two consecutive rounds of COLD-PCR followed by Sanger sequencing. Using this highly sensitive approach we screened 48 nonmicrodissected lung adenocarcinoma samples for TP53 mutations. Twenty-four missense/frameshift TP53 mutations throughout exons 5 to 8 were identified in 23 out of 48 (48%) lung adenocarcinoma samples examined, including eight low-level mutations at an abundance of similar to 1 to 17%, most of which would have been missed using conventional methodologies. The identified alterations include two rare lung adenocarcinoma mutations, one of which is a "disruptive" mutation currently undocumented in the lung cancer mutation databases. A sample harboring a low-level mutation (similar to 2% abundance) con, currently with a clonal mutation (80% abundance) revealed intratumoral TP53 mutation heterogeneity. The ability to identify and sequence low-level mutations in the absence of elaborate microdissection, via COLD-PCR-based Sanger sequencing, provides a platform for accurate mutation profiling in clinical specimens and the use of TP53 as a prognostic/predictive biomarker, evaluation of cancer risk, recurrence, and further under standing of cancer biology. Hum Mutat 30:1583-1590, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Li, Jin; Milbury, Coren A.; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Div DNA Repair & Genome Stabil,Dept Radiat Oncol, Boston, MA USA. [Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Div Med Phys & Biophys,Dept Radiat Oncol, Boston, MA USA. [Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Li, Cheng] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Brigham & Womens Hosp, Dana Farber Brigham & Womens Canc Ctr, Level L2,75 Francis St, Boston, MA 02115 USA. EM mmakrigiorgos@partners.org FU JCRT Foundation; NIH [5 T32 CA09078, CA-138280, CA-111994] FX J.L. was supported by the JCRT Foundation and C.M. was supported by NIH training grant 5 T32 CA09078. This work was supported in part by NIH grants CA-138280 and CA-111994. NR 41 TC 33 Z9 36 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD NOV PY 2009 VL 30 IS 11 BP 1583 EP 1590 DI 10.1002/humu.21112 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 516XL UT WOS:000271576600011 PM 19760750 ER PT J AU Glasser, SP Basile, JN Lackland, DT AF Glasser, Stephen P. Basile, Jan N. Lackland, Daniel T. TI Does Prehypertension Represent an Increased Risk for Incident Hypertension and Adverse Cardiovascular Outcome? SO HYPERTENSION LA English DT Editorial Material ID BLOOD-PRESSURE; FOLLOW-UP; MORTALITY; COHORT; ADULTS; HEALTH C1 [Glasser, Stephen P.] Univ Alabama, Div Prevent Med, Birmingham, AL 35205 USA. [Basile, Jan N.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Lackland, Daniel T.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Glasser, SP (reprint author), Univ Alabama, Div Prevent Med, 1717 11th Ave S MT 638, Birmingham, AL 35205 USA. EM sglasser@uab.edu OI Glasser, Stephen/0000-0001-9620-6406 FU NHLBI NIH HHS [K30 HL004104] NR 13 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 2009 VL 54 IS 5 BP 954 EP 955 DI 10.1161/HYPERTENSIONAHA.109.138545 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 509CW UT WOS:000270992100004 PM 19720951 ER PT J AU Granado, NS Smith, TC Swanson, GM Harris, RB Shahar, E Smith, B Boyko, EJ Wells, TS Ryan, MAK AF Granado, Nisara S. Smith, Tyler C. Swanson, G. Marie Harris, Robin B. Shahar, Eyal Smith, Besa Boyko, Edward J. Wells, Timothy S. Ryan, Margaret A. K. CA Millennium Cohort Study Team TI Newly Reported Hypertension After Military Combat Deployment in a Large Population-Based Study SO HYPERTENSION LA English DT Article DE hypertension; incidence; stressful events; cohort studies; military personnel ID AMERICAN-HEART-ASSOCIATION; BLOOD-PRESSURE CONTROL; GULF-WAR VETERANS; BODY-MASS INDEX; MILLENNIUM COHORT; CARDIOVASCULAR-DISEASE; RESISTANCE EXERCISE; US MILITARY; ARTERIAL STIFFNESS; CIGARETTE-SMOKING AB High-stress situations, such as combat deployments, are a potential risk factor for hypertension. Although stress is postulated to increase blood pressure, the underlying role of stress on hypertension is not well established. We sought to determine the relations between combat deployment-induced stress and hypertension. The Millennium Cohort baseline questionnaire (2001-2003) was completed by 77 047 US active-duty and Reserve/National Guard members. Follow-up was completed by 55 021 responders approximate to 3 years later (2004-2006). Multivariable logistic regression was used to estimate the 3-year risk of newly reported hypertension, adjusting for general and mental health, demographics, and occupational and behavioral characteristics. After applying exclusion criteria, our analyses included 36 061 service members. Subanalyses of deployers included 8829 participants. Newly reported hypertension was identified in 6.9% of the cohort between baseline and follow-up, many of whom had deployed on military operations in support of the conflicts in Iraq and Afghanistan. After adjusting, deployers who experienced no combat exposures were less likely to report hypertension than nondeployers (odds ratio: 0.77; 95% CI: 0.67 to 0.89). Among deployers, those reporting multiple combat exposures were 1.33 times more likely to report hypertension compared with noncombat deployers (95% CI: 1.07 to 1.65). Although military deployers, in general, had a lower incidence of hypertension than nondeployers, deployment with multiple stressful combat exposures appeared to be a unique risk factor for newly reported hypertension. (Hypertension. 2009; 54: 966-973.) C1 [Granado, Nisara S.; Smith, Tyler C.; Smith, Besa] USN, Hlth Res Ctr, Dept Def Ctr Deployment Hlth Res, San Diego, CA 92106 USA. [Swanson, G. Marie] Indiana Univ, Sch Med, Dept Publ Hlth, Indianapolis, IN USA. [Harris, Robin B.; Shahar, Eyal] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Smith, Tyler C.] USAF, Res Lab, Dayton, OH USA. [Ryan, Margaret A. K.] USN, Hosp Camp Pendleton, Dept Occupat Hlth, Camp Pendleton, CA USA. RP Granado, NS (reprint author), USN, Hlth Res Ctr, Dept Def Ctr Deployment Hlth Res, 140 Sylvester Rd, San Diego, CA 92106 USA. EM nisara.granado@med.navy.mil FU Military Operational Medicine Research Program; United States Army Medical Research and Material Command FX The Millennium Cohort Study is funded through the Military Operational Medicine Research Program, United States Army Medical Research and Material Command (Fort Detrick, MD). NR 43 TC 36 Z9 37 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 2009 VL 54 IS 5 BP 966 EP 973 DI 10.1161/HYPERTENSIONAHA.109.132555 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 509CW UT WOS:000270992100010 PM 19752293 ER PT J AU Decaluwe, K Nimmegeers, S Thoonen, R Buys, E Brouckaert, P Van de Voorde, J AF Decaluwe, K. Nimmegeers, S. Thoonen, R. Buys, E. Brouckaert, P. Van de Voorde, J. TI IN VITRO AND IN VIVO STUDIES ON THE IMPORTANCE OF THE SOLUBLE GUANYLYL CYCLASE ALPHA 1 SUBUNIT IN PENILE ERECTION SO HYPERTENSION LA English DT Meeting Abstract CT 14th Annual Meeting of the European-Council-for-Cardiovascular-Research CY OCT 09-11, 2009 CL Nice, FRANCE SP European Council Cardiovasc Res C1 [Decaluwe, K.; Nimmegeers, S.; Van de Voorde, J.] Univ Ghent, Dept Pharmacol, B-9000 Ghent, Belgium. [Thoonen, R.; Brouckaert, P.] VIB, Dept Mol Biomed Res, Ghent, Belgium. [Buys, E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Anesthesia Ctr Crit Care Res,Dept Anesthesia & Cr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 2009 VL 54 IS 5 BP 1181 EP 1181 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 509CW UT WOS:000270992100121 ER PT J AU Patel, S Lorincz, K Hughes, R Huggins, N Growdon, J Standaert, D Akay, M Dy, J Welsh, M Bonato, P AF Patel, Shyamal Lorincz, Konrad Hughes, Richard Huggins, Nancy Growdon, John Standaert, David Akay, Metin Dy, Jennifer Welsh, Matt Bonato, Paolo TI Monitoring Motor Fluctuations in Patients With Parkinson's Disease Using Wearable Sensors SO IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE LA English DT Article DE Body sensor networks; Parkinson's disease; support vector machines (SVMs); wearable sensors ID LEVODOPA-INDUCED DYSKINESIAS; NEURAL-NETWORKS; 2 PARTS AB This paper presents the results of a pilot study to assess the feasibility of using accelerometer data to estimate the severity of symptoms and motor complications in patients with Parkinson's disease. A support vector machine (SVM) classifier was implemented to estimate the severity of tremor, bradykinesia and dyskinesia from accelerometer data features. SVM-based estimates were compared with clinical scores derived via visual inspection of video recordings taken while patients performed a series of standardized motor tasks. The analysis of the video recordings was performed by clinicians trained in the use of scales for the assessment of the severity of Parkinsonian symptoms and motor complications. Results derived from the accelerometer time series were analyzed to assess the effect on the estimation of clinical scores of the duration of the window utilized to derive segments (to eventually compute data features) from the accelerometer data, the use of different SVM kernels and misclassification cost values, and the use of data features derived from different motor tasks. Results were also analyzed to assess which combinations of data features carried enough information to reliably assess the severity of symptoms and motor complications. Combinations of data features were compared taking into consideration the computational cost associated with estimating each data feature on the nodes of a body sensor network and the effect of using such data features on the reliability of SVM-based estimates of the severity of Parkinsonian symptoms and motor complications. C1 [Patel, Shyamal; Hughes, Richard; Bonato, Paolo] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA 02114 USA. [Lorincz, Konrad; Welsh, Matt] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Huggins, Nancy; Growdon, John] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Movement Disorders Unit, Boston, MA 02114 USA. [Standaert, David] Univ Alabama, Birmingham, AL 35294 USA. [Akay, Metin] Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85287 USA. [Dy, Jennifer] Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. [Bonato, Paolo] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Patel, S (reprint author), Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA 02114 USA. EM spatel19@partners.org; konrad@eecs.harvard.edu; rhughes1@partners.org; huggins.nancy@gmail.com; growdon@helix.mgh.harvard.edu; dstandaert@uab.edu; metin.akay@asu.edu; jdy.ece@gmail.com; mdw@eecs.harvard.edu; pbonato@partners.org RI Patel, Shyamal/K-3176-2012; OI Standaert, David/0000-0003-2921-8348 FU National Institute of Neurological Disorders and Stroke [R21NS045401-02]; National Science Foundation [CNS-0546338]; Michael J. Fox Foundation for Parkinson's Research FX This work was supported in part by the National Institute of Neurological Disorders and Stroke under Grant R21NS045401-02, by the National Science Foundation under Grant CNS-0546338, by the Michael J. Fox Foundation for Parkinson's Research, and by gifts from Intel Corporation, Siemens, Microsoft, and Sun Microsystems. NR 24 TC 149 Z9 151 U1 2 U2 24 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1089-7771 J9 IEEE T INF TECHNOL B JI IEEE T. Inf. Technol. Biomed. PD NOV PY 2009 VL 13 IS 6 BP 864 EP 873 DI 10.1109/TITB.2009.2033471 PG 10 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Mathematical & Computational Biology; Medical Informatics GA 515OI UT WOS:000271481300002 PM 19846382 ER PT J AU Sharma, G Rege, K Budil, DE Yarmush, M Mavroidis, C AF Sharma, Gaurav Rege, Kaushal Budil, David E. Yarmush, Martin Mavroidis, Constantinos TI Biological Force Measurement in a Protein-Based Nanoactuator SO IEEE TRANSACTIONS ON NANOTECHNOLOGY LA English DT Article DE Biomolecular devices; coiled-coil protein; force measurement; nanotechnology ID MOLECULAR-DYNAMICS SIMULATIONS; SINGLE KINESIN MOLECULES; FREE-ENERGY CALCULATION; LEUCINE-ZIPPER; DNA; ALGORITHMS; GENERATION; KINETICS; SYSTEMS AB The mechanical force exerted by a nanoactuator due to pH actuation is discussed from a statistical mechanics and free energy of conformational change viewpoint. We use molecular dynamics to show that the nanoactuator, based on the coiled-coil leucine zipper portion of a yeast transcriptional activator protein, can generate mechanical forces of the order of 20-40 pN upon pH modulation. The forces are generated due to the electrostatic repulsions at low pH between His-tag handles and other charged residues engineered into the protein sequence. The biological force output of the nanoactuator is comparable to that generated by adenosine triphosphate (ATP)-based molecular motors such as myosin and kinesin even though the nanoactuator is smaller in size to these molecular motors. The force calculation technique can readily be applied to other biomolecular systems and has implications in the area of bionanotechnology and in particular to study and characterize the properties of novel protein and DNA-based nanodevices. C1 [Sharma, Gaurav; Mavroidis, Constantinos] Northeastern Univ, Mech & Ind Engn Dept, Boston, MA 02115 USA. [Rege, Kaushal] Massachusetts Gen Hosp, Boston, MA 02115 USA. [Budil, David E.] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Yarmush, Martin] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. RP Sharma, G (reprint author), Burnham Inst Med Res, La Jolla, CA 92037 USA. EM gsharma@burnham.org; kaushal.rege@asu.edu; d.budil@neu.edu; ireis@sbi.org; mavro@coe.neu.edu RI Budil, David/A-9931-2012 OI Budil, David/0000-0003-2384-7928 NR 46 TC 1 Z9 1 U1 0 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1536-125X J9 IEEE T NANOTECHNOL JI IEEE Trans. Nanotechnol. PD NOV PY 2009 VL 8 IS 6 BP 684 EP 691 DI 10.1109/TNANO.2009.2023517 PG 8 WC Engineering, Electrical & Electronic; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Engineering; Science & Technology - Other Topics; Materials Science; Physics GA 523BW UT WOS:000272047300004 ER PT J AU Weil, AA Arifuzzaman, M Bhuiyan, TR LaRocque, RC Harris, AM Kendall, EA Hossain, A Tarique, AA Sheikh, A Chowdhury, F Khan, AI Murshed, F Parker, KC Banerjee, KK Ryan, ET Harris, JB Qadri, F Calderwood, SB AF Weil, Ana A. Arifuzzaman, Mohammad Bhuiyan, Taufiqur R. LaRocque, Regina C. Harris, Aaron M. Kendall, Emily A. Hossain, Azim Tarique, Abdullah A. Sheikh, Alaullah Chowdhury, Fahima Khan, Ashraful I. Murshed, Farhan Parker, Kenneth C. Banerjee, Kalyan K. Ryan, Edward T. Harris, Jason B. Qadri, Firdausi Calderwood, Stephen B. TI Memory T-Cell Responses to Vibrio cholerae O1 Infection SO INFECTION AND IMMUNITY LA English DT Article ID RURAL EAST PAKISTAN; VACCINE CVD 103-HGR; FIELD-TRIAL AREA; BIOTYPE-EL-TOR; INFLAMMATORY MEDIATORS; COAGGLUTINATION TEST; SEROLOGICAL SURVEY; IMMUNE-RESPONSES; ENDEMIC CHOLERA; SYNONYM BENGAL AB Vibrio cholerae O1 can cause diarrheal disease that may be life-threatening without treatment. Natural infection results in long-lasting protective immunity, but the role of T cells in this immune response has not been well characterized. In contrast, robust B-cell responses to V. cholerae infection have been observed. In particular, memory B-cell responses to T-cell-dependent antigens persist for at least 1 year, whereas responses to lipopolysaccharide, a T-cell-independent antigen, wane more rapidly after infection. We hypothesize that protective immunity is mediated by anamnestic responses of memory B cells in the gut-associated lymphoid tissue, and T-cell responses may be required to generate and maintain durable memory B-cell responses. In this study, we examined B- and T-cell responses in patients with severe V. cholerae infection. Using the flow cytometric assay of the specific cell-mediated immune response in activated whole blood, we measured antigen-specific T-cell responses using V. cholerae antigens, including the toxin-coregulated pilus (TcpA), a V. cholerae membrane preparation, and the V. cholerae cytolysin/hemolysin (VCC) protein. Our results show that memory T-cell responses develop by day 7 after infection, a time prior to and concurrent with the development of B- cell responses. This suggests that T-cell responses to V. cholerae antigens may be important for the generation and stability of memory B- cell responses. The T-cell proliferative response to VCC was of a higher magnitude than responses observed to other V. cholerae antigens. C1 [LaRocque, Regina C.; Murshed, Farhan; Ryan, Edward T.; Harris, Jason B.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Weil, Ana A.; Arifuzzaman, Mohammad; Bhuiyan, Taufiqur R.; Harris, Aaron M.; Kendall, Emily A.; Hossain, Azim; Tarique, Abdullah A.; Sheikh, Alaullah; Chowdhury, Fahima; Khan, Ashraful I.; Qadri, Firdausi] Int Ctr Diarrheal Dis Res, Dhaka, Bangladesh. [LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Parker, Kenneth C.] Virgin Instruments, Sudbury, MA USA. [Banerjee, Kalyan K.] Natl Inst Cholera & Enter Dis, Div Biochem, Kolkata, India. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Calderwood, SB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM scalderwood@partners.org RI Tarique, Abdullah/M-2860-2013; OI Tarique, Abdullah/0000-0003-3782-345X; Parker, Kenneth/0000-0002-6282-2478; Kendall, Emily/0000-0002-0083-422X FU Centre for Health and Population Research [U01 AI058935, RO3 AI063079, U01 AI077883]; International Research Scientist Development Award [KO1 TW07144]; Howard Hughes Medical Institute Physician Scientist Early Career Award; Fogarty International Center Global Infectious Disease Research Training Program Award in Vaccine Development [D43 TW05572]; Fogarty International Center at the National Institutes of Health [D43 TW005572, R24 TW007988]; Swedish Agency for International Development and Corp. (SIDA/ SAREC) FX This research was supported by the ICDDR, B Centre for Health and Population Research and by the following grants: U01 AI058935 (S. B. C.), RO3 AI063079 (F. Q.), U01 AI077883 (E. T. R.), International Research Scientist Development Award KO1 TW07144 (R. C. L.), Howard Hughes Medical Institute Physician Scientist Early Career Award (R. C. L.), International Research Scientist Development Award KO1 TW07409 (J. B. H.), and a Fogarty International Center Global Infectious Disease Research Training Program Award in Vaccine Development D43 TW05572 (M. A., A. A. T., and A. S.). A. A. W., A. M. H., E. A. K., F. C., and A. I. K. are recipients of a Fogarty International Clinical Research Scholars award from the Fogarty International Center at the National Institutes of Health (D43 TW005572 and R24 TW007988). F. M. is a recipient of a Harvard Initiative for Global Health SURF Award. F. Q. and T. R. B. are recipients of funds from the Swedish Agency for International Development and Corp. (SIDA/ SAREC).; We are grateful for the participation of patients and the work of the field staff at the ICDDR, B. We also thank Mohammad Rasheduzzaman at the ICDDR, B and Richelle Charles at Massachusetts General Hospital for laboratory and technical assistance. NR 50 TC 23 Z9 23 U1 2 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2009 VL 77 IS 11 BP 5090 EP 5096 DI 10.1128/IAI.00793-09 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 507WH UT WOS:000270885800043 PM 19703973 ER PT J AU Smith, RM Conn, AKT AF Smith, R. Malcolm Conn, Alasdair K. T. TI Prehospital care - Scoop and run or stay and play? SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Prehospital Care; "Scoop and run"; "Stay and play" ID TRAUMATIC BRAIN-INJURY; LIFE-SUPPORT; HEAD-INJURY; INTUBATION AB Improved training and expertise has enabled emergency medical personnel to provide advanced levels of care at the scene of trauma. While this could be expected to improve the outcome from major injury, current data does not support this. Indeed, prehospital interventions beyond the BLS level have not been shown to be effective and in many cases have proven to be detrimental to patient outcome. It is better to "scoop and run" than "stay and play". Current data relates to the urban environment where transport times to trauma centres are short and where it appears better to simply rapidly transport the patient to hospital than attempt major interventions at the scene. There may be more need for advanced techniques in the rural environment or where transport times are prolonged and certainly a need for more studies into subsets of patients who may benefit from interventions in the field. C1 [Smith, R. Malcolm] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Trauma Serv, Boston, MA 02114 USA. RP Smith, RM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Trauma Serv, 55 Fruit St,WACC 5-525, Boston, MA 02114 USA. EM rmsmith@partners.org NR 9 TC 24 Z9 26 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 J9 INJURY JI Injury-Int. J. Care Inj. PD NOV PY 2009 VL 40 BP S23 EP S26 DI 10.1016/j.injury.2009.10.033 PG 4 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA 534YI UT WOS:000272933100004 PM 19895949 ER PT J AU Montgomery, SA Fava, M Padmanabhan, SK Guico-Pabia, CJ Tourian, KA AF Montgomery, Stuart A. Fava, Maurizio Padmanabhan, Sudharshan K. Guico-Pabia, Christine J. Tourian, Karen A. TI Discontinuation symptoms and taper/poststudy-emergent adverse events with desvenlafaxine treatment for major depressive disorder SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE Discontinuation-Emergent Signs and Symptoms; discontinuation symptoms; major depressive disorder; selective serotonin reuptake inhibitors; serotonin-norepinephrine reuptake inhibitors; taper/poststudy-emergent adverse events ID PLACEBO-CONTROLLED TRIAL; SEROTONIN REUPTAKE INHIBITORS; DOUBLE-BLIND; ANTIDEPRESSANT DISCONTINUATION; ABRUPT DISCONTINUATION; VENLAFAXINE XR; 100 MG/DAY; EFFICACY; SAFETY; WITHDRAWAL AB The objective of this study was to assess discontinuation symptoms with desvenlafaxine (administered as desvenlafaxine succinate) treatment for major depressive disorder. Data were analyzed from nine 8-week, double-blind (DB), placebo-controlled studies of desvenlafaxine (50, 100, 200, or 400 mg/day; placebo, n = 319; desvenlafaxine, n = 578) and a relapse-prevention study [12-week, open-label (OL) 200 or 400 mg/day desvenlafaxine (n = 373); 6-month 1313 placebo (n = 73) or desvenlafaxine (n = 118)]. Rates of taper/poststudy-emergent adverse events were summarized. Discontinuation-Emergent Signs and Symptoms (DESS) checklist scores were analyzed in treatment completers at the end of OL and DB treatment. The most common (>= 5%) taper/poststudy-emergent adverse events among desvenlafaxine patients were dizziness, nausea, headache, irritability, diarrhea, anxiety, abnormal dreams, fatigue, and hyperhidrosis. In the short-term studies, the highest DESS scores observed for desvenlafaxine groups occurred at first assessment after discontinuation of all active treatment (1.9-5.7). Desvenlafaxine 50- and 100-mg/day groups had significantly increased scores versus placebo (P values <= 0.028). DESS scores increased significantly for patients discontinuing 12-week, OL desvenlafaxine 200 and 400 mg/day doses compared with those continuing desvenlafaxine (P values <= 0.022). After the 6-month DB phase, DESS scores increased significantly compared with placebo for patients discontinuing 400 mg/day only (P = 0.029). In conclusion, cessation of desvenlafaxine use is associated with discontinuation symptoms after both short-term and long-term treatment. Int Clin Psychopharmacol 24:296-305 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Montgomery, Stuart A.] Univ London Imperial Coll Sci Technol & Med, Sch Med, London, England. [Fava, Maurizio] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Padmanabhan, Sudharshan K.; Guico-Pabia, Christine J.; Tourian, Karen A.] Wyeth Res, Collegeville, PA USA. RP Montgomery, SA (reprint author), POB 8751, London W13 8WH, England. EM Stuart@samontgomery.co.uk FU Wyeth Research, Collegeville, P.A. FX Medical writing support for the preparation of this article was provided by Kathleen Dorries, PhD, of Advogent, and this assistance was funded by Wyeth Research, Collegeville, P.A. NR 42 TC 7 Z9 7 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD NOV PY 2009 VL 24 IS 6 BP 296 EP 305 DI 10.1097/YIC.0b013e32832fbb5a PG 10 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 516RP UT WOS:000271560400003 PM 19779354 ER PT J AU Dougherty, DD Jameson, M Deckersbach, T Loh, R Thompson-Hollands, J Jenike, M Keuthen, NJ AF Dougherty, Darin D. Jameson, Mariko Deckersbach, Thilo Loh, Rebecca Thompson-Hollands, Johanna Jenike, Michael Keuthen, Nancy J. TI Open-label study of high (30 mg) and moderate (20 mg) dose escitalopram for the treatment of obsessive-compulsive disorder SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE compulsions; escitalopram; obsessions; obsessive-compulsive disorder; selective serotonin reuptake inhibitors ID DEPRESSION; INVENTORY; PLACEBO; SCALE AB This study sought to investigate the efficacy of escitalopram at different dosages for the treatment of obsessive-compulsive disorder (OCD). Thirty individuals were enrolled in a 16-week, open-label trial of escitalopram and randomly assigned to the 20 or 30 mg study arm. Study measures assessing OCD symptoms, anxiety, depression, and quality of life were administered at baseline and weeks 2, 4, 8, 12, and 16. For the 23 study completers, pretreatment and posttreatment analyses revealed significant improvements (P<0.05) on clinician-rated and self-rated measures of OCD symptoms, quality of life, anxiety, and depression. Approximately half of the sample (n=12) satisfied full medication response criteria and less than one-quarter (n=5) were partial medication responders. Intention-to-treat analyses showed similar improvements (P<0.05) on all study measures. At study completion, a superior responder rate and more improvement on the Yale-Brown Obsessive Compulsive Scale (P<0.05) was reported for those in the 30 versus 20 mg study arm. The difference between the two groups, however, disappeared when initial differences in baseline depression and anxiety scores were used as analysis covariates. These results suggest that the 30 mg (vs. 20 mg) dose of escitalopram may provide a superior reduction in OCD symptoms for those sufferers with comorbid depression and/or anxiety. Int Clin Psychopharmacol 24:306-311 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Dougherty, Darin D.; Jameson, Mariko; Deckersbach, Thilo; Thompson-Hollands, Johanna; Jenike, Michael; Keuthen, Nancy J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Loh, Rebecca] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Dougherty, DD (reprint author), MGH E, Massachusetts Gen Hosp, OCD Clin, Neurotherapeut Div, Fl 2,149 13th St, Charlestown, MA 02129 USA. EM ddougherty@partners.org FU Forest Laboratories Inc. FX This study was supported by a research grant from Forest Laboratories Inc. NR 17 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD NOV PY 2009 VL 24 IS 6 BP 306 EP 311 DI 10.1097/YIC.0b013e32833119d8 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 516RP UT WOS:000271560400004 PM 19730388 ER PT J AU Calil, C Liberato, FL Pereira, AC Meneghim, MD Goodson, JM Groppo, FC AF Calil, C. Liberato, F. L. Pereira, A. C. de Castro Meneghim, M. Goodson, J. M. Groppo, F. C. TI The relationship between volatile sulphur compounds, tongue coating and periodontal disease SO INTERNATIONAL JOURNAL OF DENTAL HYGIENE LA English DT Article DE halitosis; periodontal disease; tongue coating AB The purpose of the present study was to observe the casual levels of volatile sulphur compounds (VSC) in volunteers with different clinical scores of tongue coating, periodontal pockets depth and Gingival Bleeding Index. Seventy-two subjects who attended for the first time at the dental clinic of the University were randomly selected for intra-oral and periodontal examinations. Systemic and dental histories were also obtained. The subjects were unaware of all procedures. The level of VSC was assessed by using a portable sulphide monitor (Halimeter (R); Interscan Co., Chatsworth, CA, USA). High tongue coating levels were related with more VSC counts (multivariate anova, P = 0.01). No statistically significant relation (multiple linear regression, P > 0.05) was observed among the VSC levels considering age, bleeding and periodontal pockets sites (depth > 4 mm). We concluded that the tongue coating was one of the main factors influencing the VSC levels. C1 [Calil, C.; Groppo, F. C.] Univ Estadual Campinas, Dept Physiol Sci, Piracicaba Dent Sch, BR-13414903 Piracicaba, SP, Brazil. [Calil, C.] Univ Sao Paulo, Discipline Periodont, Dept Stomatol, Sch Dent, Sao Paulo, Brazil. [Liberato, F. L.; Pereira, A. C.; de Castro Meneghim, M.] Univ Estadual Campinas, Dept Social & Prevent Dent, Piracicaba Dent Sch, BR-13414903 Piracicaba, SP, Brazil. [Goodson, J. M.] Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Groppo, FC (reprint author), Univ Estadual Campinas, Dept Physiol Sci, Piracicaba Dent Sch, CP 52, BR-13414903 Piracicaba, SP, Brazil. EM fcgroppo@fop.unicamp.br RI Groppo, Francisco/C-3516-2012; Meneghim, Marcelo/D-8940-2012 OI Groppo, Francisco/0000-0002-8513-773X; NR 29 TC 13 Z9 13 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1601-5029 J9 INT J DENT HYG JI Int. J. Dent. Hyg. PD NOV PY 2009 VL 7 IS 4 BP 251 EP 255 DI 10.1111/j.1601-5037.2009.00366.x PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V16UT UT WOS:000207895200004 PM 19832911 ER PT J AU Kimball, AB Wu, Y AF Kimball, Alexa Boer Wu, Ying TI Cardiovascular disease and classic cardiovascular risk factors in patients with psoriasis SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Review ID C-REACTIVE PROTEIN; CORONARY-ARTERY-DISEASE; IMPAIRED GLUCOSE-TOLERANCE; OCCLUSIVE VASCULAR-DISEASE; BETA-CELL DYSFUNCTION; MIDDLE-AGED MEN; MYOCARDIAL-INFARCTION; INSULIN-RESISTANCE; ALCOHOL-CONSUMPTION; METABOLIC SYNDROME C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Centocor Inc, Res & Dev, Malvern, PA 19355 USA. RP Kimball, AB (reprint author), Harvard Univ, Sch Med, CURTIS, Massachusetts Gen Hosp, 50 Staniford St 246, Boston, MA 02114 USA. EM harvardskinstudies@partners.org FU Centocor, Inc FX Editorial support for the writing of the manuscript was provided by Jason McDonough, phd, and was funded by Centocor, Inc. The authors were not compensated and retained full editorial control.Dr Kimball is a consultant/investigator for Centocor, Abbott, and Amgen. Dr Wu is an employee of Centocor. NR 84 TC 15 Z9 15 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD NOV PY 2009 VL 48 IS 11 BP 1147 EP 1156 PG 10 WC Dermatology SC Dermatology GA 509WK UT WOS:000271049800001 PM 20064165 ER PT J AU Becker, AE Eddy, KT Perloe, A AF Becker, Anne E. Eddy, Kamryn T. Perloe, Alexandra TI Clarifying Criteria for Cognitive Signs and Symptoms for Eating Disorders in DSM-V SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Review DE diagnostic criteria; anorexia nervosa; bulimia nervosa; clinical inference; refusal ID ANOREXIA-NERVOSA; GASTROINTESTINAL PRACTICE; CLINICAL JUDGMENT; SELF-REPORT; BODY-IMAGE; HONG-KONG; CULTURE; ADOLESCENCE; ILLNESS; STIGMATIZATION AB Objective: This article reviews literature relevant to challenges in clinical ascertainment of cognitively-based diagnostic criteria of anorexia nervosa (AN) and bulimia nervosa (BN) to examine whether revision might enhance their clinical utility. Method: We performed a systematic literature search to identify publications relevant to clinical evaluation of cognitive symptoms of AN and BN. Results: The literature supports several reasons that individuals with an eating disorder may not endorse cognitive symptoms, despite their presence. These include limited insight, minimization, or denial, as well as intentional concealment related to perceived stigma, social desirability, or investment in maintaining behavioral symptoms. We also identified reasons that the word "refusal" in AN criterion A may render its application problematic. Discussion: We conclude that specific guidance for ascertainment of cognitive signs for AN and BN in the absence of patient disclosure or endorsement, longitudinal evaluation, and/or collateral data may improve clinical utility of these diagnostic criteria. (C) 2009 American Psychiatric Association. C1 [Becker, Anne E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Eddy, Kamryn T.] Massachusetts Gen Hosp, Dept Psychiat, Harris Ctr Educ & Advocacy Eating Disorders, Boston, MA 02114 USA. RP Becker, AE (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, 641 Huntington Ave, Boston, MA 02115 USA. EM anne_becker@hms.harvard.edu NR 74 TC 37 Z9 38 U1 2 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 EI 1098-108X J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD NOV PY 2009 VL 42 IS 7 BP 611 EP 619 DI 10.1002/eat.20723 PG 9 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 518QO UT WOS:000271708400006 PM 19650082 ER PT J AU Becker, AE Thomas, JJ Pike, KM AF Becker, Anne E. Thomas, Jennifer J. Pike, Kathleen M. TI Should Non-Fat-Phobic Anorexia Nervosa Be Included in DSM-V? SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Review DE anorexia nervosa; fat phobia; non-fal-phobic AN; low drive for thinness AN ID EATING-DISORDER INVENTORY; ENVIRONMENTAL RISK-FACTORS; HONG-KONG; CHINESE PATIENTS; SELF-STARVATION; ATTITUDES TEST; WEIGHT PHOBIA; BODY-IMAGE; BULIMIA-NERVOSA; UNDUE INFLUENCE AB Objective: Cross-cultural data suggest that rationales for food refusal vary in anorexia nervosa (AN), and a variant, termed non-fat-phobic AN (NFP-AN), has been described. This review evaluates whether data support modification of the requirement for intense fear of weight gain to meet AN criterion B in DSM-V. Method: We performed a systematic search of the Medline and Psychinfo literature and evaluated the relevant publications by Robins and Guze's (Am J Psychiatry 126, 983-987, 1970) criteria as a standard for diagnostic validity. We also performed a meta-analysis comparing the severity of eating pathology in AN to (a) NFP-AN and (b) AN with low drive for thinness (low-DT-AN). Results: A modest literature indicates that NFP-AN has wide geographic distribution and occurs in both Western and non-Western populations alongside cases of typical AN. Aggregating across eligible studies, patients with NFP-AN or low-DT-AN score at least 2/3 of a standard deviation lower on measures of eating pathology than patients with conventional AN. Transcultural comparison of drive for thinness suggests significantly lower norms in non-Western cultures. Discussion: NFP-AN occurs with wide distribution. Further research is necessary on the course and outcomes of NFP-AN to characterize its congruence with, or distinction from, conventional AN. We discuss several options for including a description of NFP-AN in DSM-V. (C) 2009 American Psychiatric Association. C1 [Becker, Anne E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Becker, Anne E.; Thomas, Jennifer J.] Massachusetts Gen Hosp, Dept Psychiat, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. [Thomas, Jennifer J.] McLean Hosp, Klarman Eating Disorders Ctr, Belmont, MA 02178 USA. [Pike, Kathleen M.] Temple Univ Japan, Coll Liberal Arts, Tokyo, Japan. RP Becker, AE (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, 641 Huntington Ave, Boston, MA 02115 USA. EM anne_becker@hms.harvard.edu NR 74 TC 54 Z9 56 U1 3 U2 15 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD NOV PY 2009 VL 42 IS 7 BP 620 EP 635 DI 10.1002/eat.20727 PG 16 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 518QO UT WOS:000271708400007 PM 19655370 ER PT J AU Viswanathan, AN Cormack, R Rawal, B Lee, H AF Viswanathan, Akila N. Cormack, Robert Rawal, Bhupendra Lee, Hang TI Increasing Brachytherapy Dose Predicts Survival for Interstitial and Tandem-Based Radiation for Stage IIIB Cervical Cancer SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Cervical cancer; Brachytherapy; Interstitial; Tandem; Stage IIIB ID GYNECOLOGICAL MALIGNANCIES; CARCINOMA; INTRACAVITARY; IRRADIATION; THERAPY; TEMPLATE; PATTERNS; TRIAL AB Purpose: To evaluate factors affecting survival and toxicity in patients with stage IIIB cervical cancer treated with external-beam radiotherapy and low-dose-rate brachytherapy. Materials and Methods: Seventy patients with stage IIIB cervical cancer treated between 1980 and 2000 were identified. A total of 51 patients had a tandem placed; 19 had interstitial brachytherapy only with no tandem placed. Univariate and multivariate analyses assessed factors potentially associated with survival and long-term complications. Results: Kaplan-Meier estimates for overall survival (OS) for the entire population at 2, 3, and 4 years were 43%, 29%, and 27%, respectively. Overall survival differed significantly between those treated with a tandem versus those treated without (log rank P < 0.0001). Significant predictors of OS on univariate Cox regression were presence of a tandem (hazards ratio [HR], 0.31; P = 0.0001) and cumulative dose to point A (HR, 0.95; P = 0.0001). Multivariate regression showed that the presence of a tandem was the only significant predictor of OS (HR, 0.46; P = 0.04). There were no significant predictors of complications. Conclusions: The dose to point A of approximately 85 Gy as associated with tandem use was a significant predictor of survival in patients with stage IIIB cervical carcinoma, indicating the significance of the central location of the high dose provided by the tandem. Patients selected for interstitial brachytherapy alone must receive sufficient dose, and a tandem should be placed whenever feasible for all patients with an intact uterus treated for locally advanced cervical cancer. C1 [Viswanathan, Akila N.; Cormack, Robert] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Viswanathan, Akila N.; Cormack, Robert] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rawal, Bhupendra; Lee, Hang] Massachusetts Gen Hosp, Dept Biostat Sci, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu OI Cormack, Robert/0000-0001-5553-9984 NR 24 TC 15 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD NOV PY 2009 VL 19 IS 8 BP 1402 EP 1406 DI 10.1111/IGC.0b013e3181b62e73 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 522YJ UT WOS:000272035900020 PM 20009897 ER PT J AU Seemayer, TA Arseneau, J Young, RH AF Seemayer, Thomas A. Arseneau, Jocelyne Young, Robert H. TI History of Gynecological Pathology XXIII. Jean-Paul Andre Latour, MD, CM SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Biographical-Item DE History of gynecological pathology; Jean-Paul Andre Latour C1 [Arseneau, Jocelyne] McGill Univ, Dept Pathol, Fac Med, Montreal, PQ H3A 2B4, Canada. [Seemayer, Thomas A.] Univ Nebraska, Med Ctr, Omaha, NE USA. [Arseneau, Jocelyne] Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada. [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. RP Arseneau, J (reprint author), McGill Univ, Dept Pathol, Fac Med, Lyman Duff Med Sci Bldg,3775 Univ Ave, Montreal, PQ H3A 2B4, Canada. EM jocelyne.arseneau@mcgill.ca 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 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD NOV PY 2009 VL 28 IS 6 BP 505 EP 513 DI 10.1097/PGP.0b013e3181a9ea34 PG 9 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 512JP UT WOS:000271244700001 PM 19851196 ER PT J AU Kawakami, T Urakami, S Hirata, H Tanaka, Y Nakajima, K Enokida, H Shiina, H Ogishima, T Tokizane, T Kawamoto, K Miura, K Ishii, N Dahiya, R AF Kawakami, T. Urakami, S. Hirata, H. Tanaka, Y. Nakajima, K. Enokida, H. Shiina, H. Ogishima, T. Tokizane, T. Kawamoto, K. Miura, K. Ishii, N. Dahiya, R. TI Superoxide dismutase analog (Tempol: 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine 1-oxyl) treatment restores erectile function in diabetes-induced impotence SO INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH LA English DT Article DE oxidative stress; nitric oxide; superoxide; diabetes; erectile dysfunction ID NITRIC-OXIDE; ENDOTHELIAL DYSFUNCTION; ANTIOXIDANT THERAPY; PENILE CRURA; RATS; STREPTOZOTOCIN; APOPTOSIS; COMPLICATIONS; EXPRESSION; DAMAGE AB We hypothesized that the administration of the superoxide dismutase (SOD) mimetic Tempol (4-hydroxy-2, 2, 6, 6-tetramethylpiperidine 1-oxyl) may reverse diabetes-induced erectile dysfunction. To test this hypothesis, reactive oxygen species-related genes (SOD1, SOD2, GP x 1, CAT, NOS2, NOS3) were tested, erectile functional studies and immunohistochemical analysis were carried out in diabetic rats treated with or without Tempol. Thirty Sprague-Dawley (3-4months old) rats were divided into three groups (n = 10 each), 20 with diabetes (diabetic control and Tempol treatment) and 10 healthy controls. At 12 weeks after the induction of diabetes by streptozotocin and Tempol treatment, all groups underwent in vivo cavernous nerve stimulation. Rat crura were harvested and the expression of antioxidative defense enzymes were examined by semi-quantitative reverse transcriptase PCR (RT-PCR). To confirm the RT-PCR results, we carried out immunohistochemistry (IHC) for catalase (CAT) and iNOS (NOS2). Nitration of tyrosine groups in proteins was also examined by IHC. Mean intracavernous pressure in the diabetic group was significantly lower than in the healthy controls (P < 0.001) and was reversed by Tempol treatment (P < 0.0108). NOS2 protein expression was significantly increased in diabetic animals compared with healthy controls and Tempol restored NOS2 protein level. Nitrotyrosine was also higher in diabetic animals and although Tempol treatment decreased its formation, it remained higher than that found in healthy controls. This study suggests that Tempol treatment increased erectile function through modulating oxidative stress-related genes in diabetic rats. This is the first report about the relationship between diabetes-induced erectile dysfunction and oxidative stress, and antioxidative therapy using the superoxide dismutase mimetic, Tempol, to restore erectile function. International Journal of Impotence Research (2009) 21, 348-355; doi:10.1038/ijir.2009.28; published online 25 June 2009 C1 [Kawakami, T.; Urakami, S.; Hirata, H.; Tanaka, Y.; Enokida, H.; Shiina, H.; Ogishima, T.; Tokizane, T.; Kawamoto, K.; Dahiya, R.] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA USA. [Kawakami, T.; Urakami, S.; Hirata, H.; Tanaka, Y.; Enokida, H.; Shiina, H.; Ogishima, T.; Tokizane, T.; Kawamoto, K.; Dahiya, R.] Univ Calif San Francisco, San Francisco, CA 94121 USA. [Kawakami, T.; Nakajima, K.; Miura, K.; Ishii, N.] Toho Univ, Fac Med, Dept Urol, Tokyo, Japan. RP Dahiya, R (reprint author), Vet Affairs Med Ctr, Dept Urol, Urol Res Ctr 112F, 4150 Clement St, San Francisco, CA 94121 USA. EM rdahiya@urology.ucsf.edu FU NIH [RO1DK075524, T32DK007790] FX We thank Dr Roger Erickson for his support and assistance with the preparation of the paper. This study was supported by Grants RO1DK075524, T32DK007790 from the NIH. NR 29 TC 9 Z9 12 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0955-9930 J9 INT J IMPOT RES JI Int. J. Impot. Res. PD NOV-DEC PY 2009 VL 21 IS 6 BP 348 EP 355 DI 10.1038/ijir.2009.28 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 517OV UT WOS:000271626400004 PM 19554009 ER PT J AU Salama, JK Haddad, RI Kies, MS Busse, PM Dong, L Brizel, DM Eisbruch, A Tishler, RB Trotti, AM Garden, AS AF Salama, Joseph K. Haddad, Robert I. Kies, Merril S. Busse, Paul M. Dong, Lei Brizel, David M. Eisbruch, Avraham Tishler, Roy B. Trotti, Andy M. Garden, Adam S. TI CLINICAL PRACTICE GUIDANCE FOR RADIOTHERAPY PLANNING AFTER INDUCTION CHEMOTHERAPY IN LOCOREGIONALLY ADVANCED HEAD-AND-NECK CANCER SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Induction chemotherapy; Intensity-modulated radiotherapy; Radiotherapy planning; Head-and-neck cancer ID INTENSITY-MODULATED RADIOTHERAPY; LOCALLY ADVANCED HEAD; SQUAMOUS-CELL CARCINOMA; STAGE NASOPHARYNGEAL CARCINOMA; RADIATION-THERAPY; CONCURRENT CHEMORADIOTHERAPY; SALIVARY FUNCTION; EXPERIENCE; FLUOROURACIL; IRRADIATION AB Purpose: The use of induction chemotherapy (IC) for locoregionally advanced head-and-neck cancer is increasing. The response to IC often causes significant alterations in tumor volume and location and shifts in normal anatomy. Proper determination of the radiotherapy (RT) targets after IC becomes challenging, especially with the use of conformal and precision RT techniques. Therefore, a consensus conference was convened to discuss issues related to RT planning and coordination of care for patients receiving IC. Methods and Materials: Ten participants with special expertise in the various aspects of integration of IC and RT for the treatment of locoregionally advanced head-and-neck cancer, including radiation oncologists, medical oncologists, and a medical physicist, participated. The individual members were assigned topics for focused, didactic presentations. Discussion was encouraged after each presentation, and recommendations were formulated. Results: Recommendations and guidelines emerged that emphasize up-front evaluation by all members of the head-and-neck management team, high-quality baseline and postinduction planning scans with the patient in the treatment position, the use of preinduction target volumes, and the use of full-dose RT, even in the face of a complete response. Conclusion: A multidisciplinary approach is strongly encouraged. Although these recommendations were provided primarily for patients treated with IC, many of these same principles apply to concurrent chemoradiotherapy without IC. A rapid response during RT is quite common, requiring the development of two or more plans in a sizeable fraction of patients, and suggesting the need for similar guidance in the rapidly evolving area of adaptive RT. (C) 2009 Elsevier Inc. C1 [Salama, Joseph K.] Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. [Haddad, Robert I.; Tishler, Roy B.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kies, Merril S.; Dong, Lei; Garden, Adam S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Busse, Paul M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brizel, David M.] Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA. [Eisbruch, Avraham] Univ Michigan, Ann Arbor, MI 48109 USA. [Trotti, Andy M.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. RP Salama, JK (reprint author), Univ Chicago, Dept Radiat & Cellular Oncol, 5758 S Maryland Ave,MC 9006, Chicago, IL 60637 USA. EM jsalama@radonc.uchicago.edu OI Dong, Lei/0000-0003-2623-3198 NR 53 TC 36 Z9 42 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2009 VL 75 IS 3 BP 725 EP 733 DI 10.1016/j.ijrobp.2008.11.059 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 503WR UT WOS:000270573100013 PM 19362781 ER PT J AU Lee, LJ Sadow, CA Russell, A Viswanathan, AN AF Lee, Larissa J. Sadow, Cheryl A. Russell, Anthony Viswanathan, Akila N. TI CORRELATION OF POINT B AND LYMPH NODE DOSE IN 3D-PLANNED HIGH-DOSE-RATE CERVICAL CANCER BRACHYTHERAPY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE HDR brachytherapy; cervical cancer; pelvic lymph nodes; point B ID PELVIC RADIOTHERAPY; RADIATION-THERAPY; UTERINE CERVIX; CARCINOMA; RECOMMENDATIONS; GUIDELINES; VOLUME; DELINEATION; TERMS AB Purpose: To compare high dose rate (HDR) point B to pelvic lymph node dose using three-dimensional-planned brachytherapy for cervical cancer. Methods and Materials: Patients with FIGO Stage IB-IIIB cervical cancer received 70 tandem HDR applications using CT-based treatment planning. The obturator, external, and internal iliac lymph nodes (LN) were contoured. Per fraction (PF) and combined fraction (CF) right (R), left (L), and bilateral (Bil) nodal doses were analyzed. Point B dose was compared with LN dose-volume histogram (DVH) parameters by paired t test and Pearson correlation coefficients. Results: Mean PF and CF doses to point B were R 1.40 Gy +/- 0.14 (CF: 7 Gy), L 1.43 +/- 0.15 (CF: 7.15 Gy), and Bil 1.41 +/- 0.15 (CF: 7.05 Gy). The correlation coefficients between point B and the D100, D90, D50, D2cc, D1cc, and D0.1cc LN were all less than 0.7. Only the D2cc to the obturator and the D0.1cc to the external iliac nodes were not significantly different from the point B dose. Significant differences between R and L nodal DVHs were seen, likely related to tandem deviation from irregular tumor anatomy. Conclusions: With HDR brachytherapy for cervical cancer, per fraction nodal dose approximates a dose equivalent to teletherapy. Point B is a poor surrogate for dose to specific nodal groups. Three-dimensional defined nodal contours during brachytherapy provide a more accurate reflection of delivered dose and should be part of comprehensive planning of the total dose to the pelvic nodes, particularly when there is evidence of pathologic involvement. (C) 2009 Elsevier Inc. C1 [Viswanathan, Akila N.] Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. [Lee, Larissa J.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Sadow, Cheryl A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Russell, Anthony] Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Viswanathan, AN (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst,Sch Med, 75 Francis St L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu OI Viswanathan, Akila/0000-0002-2003-0392 FU NCI NIH HHS [K07 CA117979, K07 CA117979-02, K07 CA117979-01, K07 CA117979-04, K07 CA117979-03] NR 16 TC 13 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2009 VL 75 IS 3 BP 803 EP 809 DI 10.1016/j.ijrobp.2008.11.052 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 503WR UT WOS:000270573100024 PM 19286328 ER PT J AU Rosenstein, BS Held, KD Rockwell, S Williams, JP Zeman, EM AF Rosenstein, Barry S. Held, Kathryn D. Rockwell, Sara Williams, Jacqueline P. Zeman, Elainie M. TI AMERICAN SOCIETY FOR RADIATION ONCOLOGY (ASTRO) SURVEY OF RADIATION BIOLOGY EDUCATORS IN US AND CANADIAN RADIATION ONCOLOGY RESIDENCY PROGRAMS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Radiation biology; Teaching; Radiation oncology residents ID RADIOBIOLOGY; CONSENSUS AB Purpose: To obtain, in a survey-based study, detailed information on the faculty currently responsible for teaching radiation biology courses to radiation oncology residents in the United States and Canada. Methods and Materials: In March-December 2007 a survey questionnaire was sent to faculty having primary responsibility for teaching radiation biology to residents in 93 radiation oncology residency programs in the United States and Canada. Results: The responses to this survey document the aging of the faculty who have primary responsibility for teaching radiation biology to radiation oncology residents. The survey found a dramatic decline with time in the percentage of educators whose graduate training was in radiation biology. A significant number of the educators responsible for teaching radiation biology were not fully acquainted with the radiation sciences, either through training or practical application. In addition, many were unfamiliar with some of the organizations setting policies and requirements for resident education. Freely available tools, such as the American Society for Radiation Oncology (ASTRO) Radiation and Cancer Biology Practice Examination and Study Guides, were widely used by residents and educators. Consolidation of resident courses or use of a national radiation biology review course was viewed as unlikely by most programs. Conclusions: A high priority should be given to the development of comprehensive teaching tools to assist those individuals who have responsibility for teaching radiation biology courses but who do not have an extensive background in critical areas of radiobiology related to radiation oncology. These findings also suggest a need for new graduate programs in radiobiology. (C) 2009 Elsevier Inc. C1 [Rosenstein, Barry S.] Mt Sinai Sch Med, Dept Radiat Oncol, New York, NY 10029 USA. [Rosenstein, Barry S.] NYU, Sch Med, Dept Radiat Oncol, New York, NY USA. [Held, Kathryn D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Rockwell, Sara] Yale Univ, Sch Med, Yale Comprehens Canc Ctr, Dept Radiat Therapy, New Haven, CT USA. [Rockwell, Sara] Yale Univ, Sch Med, Dept Pharmacol, Yale Comprehens Canc Ctr, New Haven, CT 06510 USA. [Williams, Jacqueline P.] Univ Rochester, James P Wilmot Canc Ctr, Dept Radiat Oncol, Rochester, NY USA. [Zeman, Elainie M.] Univ N Carolina, Sch Med, Dept Radiat Oncol, Chapel Hill, NC 27599 USA. RP Rosenstein, BS (reprint author), Mt Sinai Sch Med, Dept Radiat Oncol, 1 Gustave Levy Pl, New York, NY 10029 USA. EM bany.rosenstein@mssm.edu RI Rockwell, Sara/B-8458-2009 FU National Institutes of Health/National Institute of Allergy and Infectious Diseases [5U19 AI067733-03] FX Supported in part by Education Core Grant 5U19 AI067733-03 from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (to J.W.). NR 11 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2009 VL 75 IS 3 BP 896 EP 905 DI 10.1016/j.ijrobp.2009.05.009 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 503WR UT WOS:000270573100036 PM 19733012 ER PT J AU Ooi, YH Oh, DJ Rhee, DJ AF Ooi, Yen Hoong Oh, Dong-Jin Rhee, Douglas J. TI Effect of Bimatoprost, Latanoprost, and Unoprostone on Matrix Metalloproteinases and Their Inhibitors in Human Ciliary Body Smooth Muscle Cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPEN-ANGLE GLAUCOMA; ELEVATED INTRAOCULAR-PRESSURE; RANDOMIZED CLINICAL-TRIAL; FP PROSTAGLANDIN RECEPTOR; NORMAL-TENSION GLAUCOMA; OCULAR HYPERTENSION; TISSUE INHIBITORS; TRABECULAR MESHWORK; LOWERING EFFICACY; AQUEOUS-HUMOR AB PURPOSE. Matrix metalloproteinase (MMP)-mediated turnover of extracellular matrix (ECM) affects outflow resistance in the uveoscleral pathway. The balance of MMPs and tissue inhibitors of metalloproteinases (TIMPs) governs the rate of ECM turnover in many tissues. The hypothesis was that a differential effect on MMPs and TIMPs in ciliary body smooth muscle (CBSM) cells would relate to the relative intraocular pressure-lowering effectiveness of the prostaglandin analogues (PGAs) bimatoprost, latanoprost, and unoprostone. METHODS. Human CBSM cells isolated from donor corneoscleral rims were incubated for 24 hours with control (0.015% ethanol in DMEM) or the free acid forms of bimatoprost (0.01 or 0.1 mu g/mL), latanoprost (0.03 or 0.3 mu g/mL), or unoprostone (0.145 or 1.45 mu g/mL). Western blot analysis determined the relative protein concentrations of MMP-1, -2, -3, -9, and -24 as well as TIMP-1 through -4. Zymography measured the relative activity levels of MMP-1, -2, -3, and -9. RESULTS. All PGAs increased MMP-1, -3, and -9. Bimatoprost and latanoprost did not change MMP-2. Unoprostone decreased MMP-2 (21% +/- 3%). On zymography, MMP-1 and -2 did not change. Bimatoprost and latanoprost increased MMP-9 activity by 75% +/- 27% and 75% +/- 24%, respectively. MMP-3 activity was not detected on zymography. All PGAs increased TIMP-3, but only unoprostone increased TIMPs1 and -4 by 100% +/- 20% and 61% +/- 11%, respectively. TIMP-2 was unchanged by bimatoprost and latanoprost, but decreased by unoprostone (35% +/- 8%). CONCLUSIONS. Decreased MMP-2 with concurrent increases of TIMP-1 and -4 by unoprostone may explain the lower clinical efficacy of unoprostone. The MMP/TIMP balance relates to the observed intraocular pressure-lowering effectiveness in clinical studies with PGAs. (Invest Ophthalmol Vis Sci. 2009;50:5259-5265) DOI:10.1167/iovs.08-3356 C1 [Ooi, Yen Hoong; Oh, Dong-Jin; Rhee, Douglas J.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM dougrhee@aol.com FU Allergan; American Glaucoma Society Clinician-Scientist Fellowship; Massachusetts Lions Eye Research Foundation; Pfizer Ophthalmics; [EY 14104] FX Supported by Allergan, American Glaucoma Society Clinician-Scientist Fellowship, Massachusetts Lions Eye Research Foundation, Pfizer Ophthalmics, and EY 14104 (MEEI Vision-Core Grant). NR 74 TC 13 Z9 13 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2009 VL 50 IS 11 BP 5259 EP 5265 DI 10.1167/iovs.08-3356 PG 7 WC Ophthalmology SC Ophthalmology GA 514XH UT WOS:000271429200032 PM 19443729 ER PT J AU Vymazal, J Spuentrup, E Cardenas-Molina, G Wiethoff, AJ Hartmann, MG Caravan, P Parsons, EC AF Vymazal, Josef Spuentrup, Elmar Cardenas-Molina, Gerardo Wiethoff, Andrea J. Hartmann, Michael G. Caravan, Peter Parsons, Edward C., Jr. TI Thrombus Imaging With Fibrin-Specific Gadolinium-Based MR Contrast Agent EP-2104R Results of a Phase II Clinical Study of Feasibility SO INVESTIGATIVE RADIOLOGY LA English DT Article DE contrast media; fibrin; magnetic resonance imaging; thrombosis; thrombus ID STATE FREE PRECESSION; DEEP VENOUS THROMBOSIS; MAGNETIC-RESONANCE; PULMONARY-EMBOLISM; COMPUTED-TOMOGRAPHY; CORONARY-THROMBOSIS; INITIAL-EXPERIENCE; VEIN THROMBOSIS; THORACIC AORTA; SWINE MODEL AB Purpose: To determine the feasibility of detecting thrombi using a fibrin-specific gadolinium-based magnetic resonance imaging contrast agent, EP-2104R. Methods: Subjects with confirmed thrombus in the venous system (n = 14), or in the heart, or arterial system (n = 38) were enrolled. Patients were imaged before and at various times following a 4 mu mol/kg intravenous bolus injection of EP-2104R: < 1 hour (N = 16), 2 to 6 hours (N = 36), and/or 20 to 36 hours (N = 33). Images were assessed by investigators at each site and by a single reader not affiliated with the sites to determine whether thrombi were visible, not visible, or further enhanced with EP-2104R. A subset of data was analyzed quantitatively by measuring a signal intensity relative to background tissue. Results: Overall, 29 thrombi were visible before contrast administration, 3 of 14 in the venous system, and 26 of 38 in the arteries and heart. Thrombi generally enhanced in signal after EP-2104R injection, and an additional 7 were visualized. After contrast, 4 of 14 thrombi were visible in the venous system, and 32 of 38 in the arteries and heart. Thrombi were more conspicuous when imaged at 2 to 6 hours post EP-2104R compared with within I hour, because of lower blood background. Quantitatively, the post: pre signal intensity ratio was 1.90 at 2 to 6 hours post injection (standard deviation = 1.08, N = 20, P < 0.001); and 2.04 (standard deviation = 1.29, N = 19, P < 0.0025) for the 20 to 36 hours time point. There were no serious adverse events considered related to study drug. Conclusion: EP-2104R enhanced magnetic resonance imaging detects thrombi not readily visible in precontrast screening and gives additional enhancement of thrombi that are visible in precontrast imaging. C1 [Vymazal, Josef] Hosp Homolce, Dept Radiodiagnost, Prague, Czech Republic. [Spuentrup, Elmar] Univ Cologne, Dept Radiol, Cologne, Germany. [Cardenas-Molina, Gerardo] Hosp & Clin OCA, Monterrey, NL, Mexico. [Wiethoff, Andrea J.] Philips Healthcare, Best, Netherlands. [Hartmann, Michael G.] VP Diagnost Inc, Seattle, WA USA. [Caravan, Peter] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Parsons, Edward C., Jr.] EPIX Pharmaceut Inc, Lexington, MA USA. RP Parsons, EC (reprint author), 30 Wheatland St, Burlington, MA 01803 USA. EM edward.parsons@aya.yale.edu FU EPIX Pharmaceuticals, Inc FX Supported by EPIX Pharmaceuticals, Inc. NR 30 TC 70 Z9 74 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD NOV PY 2009 VL 44 IS 11 BP 697 EP 704 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 515SN UT WOS:000271493300002 PM 19809344 ER PT J AU Rukstalis, JM Habener, JF AF Rukstalis, J. Michael Habener, Joel F. TI Neurogenin3 A master regulator of pancreatic islet differentiation and regeneration SO ISLETS LA English DT Review DE beta-cells; stem/progenitor cells; pancreas regeneration; diabetes; islets; ducts AB The basic helix-loop-helix transcription factor neurogenin-3 (Ngn3, Neurog3) is critical for the development of the endocrine cells of the islets. Either disrupted or forced expression of Ngn3 early in mouse pancreas development abrogates the formation of islets. The successive waves of Ngn3 expression that occur during the primary and secondary transitions of endocrine cell development temporally determine the four distinct endocrine cell lineages, alpha, beta, PP and delta cells that express glucagon, insulin, pancreatic polypeptide and somatostatin, respectively. During islet regeneration after injury of the adult mouse pancreas, such as by duct ligation or streptozotocin, Ngn3 is activated in duct-associated stem/progenitor cells that transform into alpha and/or beta-cells (Xu et al., Collombat et al.). The important role of Ngn3 as a master regulator of endocrine pancreas development directs attention to finding therapeutic approaches to enhance Ngn3 expression in diabetes as a means to increase beta-cell mass and functions. C1 [Rukstalis, J. Michael; Habener, Joel F.] Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. EM jhabener@partners.org FU USPHS FX We thank William Hillmann for helpful contributions in the laboratory. Supported in part by a USPHS Research Career Development Award to J.M.R. NR 80 TC 48 Z9 51 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1938-2014 J9 ISLETS JI Islets PD NOV-DEC PY 2009 VL 1 IS 3 BP 177 EP 184 DI 10.4161/isl.1.3.9877 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V16WV UT WOS:000207900600002 PM 21099270 ER PT J AU Kawamori, D Kulkarni, RN AF Kawamori, Dan Kulkarni, Rohit N. TI Insulin modulation of glucagon secretion The role of insulin and other factors in the regulation of glucagon secretion SO ISLETS LA English DT Article DE glucagon; insulin; insulin receptor; hypoglycemia; somatostatin C1 [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Dept Cellular & Mol Physiol, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Dept Cellular & Mol Physiol, Joslin Diabet Ctr, Boston, MA 02115 USA. EM Rohit.Kulkarni@joslin.harvard.edu NR 35 TC 12 Z9 13 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1938-2014 J9 ISLETS JI Islets PD NOV-DEC PY 2009 VL 1 IS 3 BP 276 EP 279 DI 10.4161/isl.1.3.9967 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V16WV UT WOS:000207900600017 PM 21099284 ER PT J AU Lehman, SJ Schlett, CL Bamberg, F Lee, H Donnelly, P Shturman, L Kriegel, MF Brady, TJ Hoffmann, U AF Lehman, Sam J. Schlett, Christopher L. Bamberg, Fabian Lee, Hang Donnelly, Patrick Shturman, Leon Kriegel, Matthias F. Brady, Thomas J. Hoffmann, Udo TI Assessment of Coronary Plaque Progression in Coronary Computed Tomography Angiography Using a Semiquantitative Score SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE atherosclerosis; computed tomography; coronary artery disease; risk factors; progression ID RANDOMIZED CONTROLLED-TRIAL; INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUE; ARTERY CALCIFICATION; CARDIOVASCULAR RISK; LEFT MAIN; DISEASE; ASSOCIATION; REGRESSION; ACCURACY AB OBJECTIVES We sought to describe the progression of coronary atherosclerotic plaque over time by computed tomography (CT) angiography stratified by plaque composition and its association with cardiovascular risk profiles. BACKGROUND Data on the progression of atherosclerosis stratified by plaque composition with the use of noninvasive assessment by CT are limited and hampered by high measurement variability. METHODS This analysis included patients who presented with acute chest pain to the emergency department but initially showed no evidence of acute coronary syndromes. All patients underwent contrast-enhanced 64-slice CT at baseline and after 2 years with the use of a similar protocol. CT datasets were coregistered and assessed for the presence of calcified and noncalcified plaque at 1 mm cross sections of the proximal 40 mm of each major coronary artery. Plaque progression over time and its association with risk factors were determined. Measurement reproducibility and correlation to plaque volume was performed in a subset of patients. RESULTS We included 69 patients (mean age 55 +/- 12 years, 59% male patients) and compared 8,311 coregistered cross sections at baseline and follow-up. At baseline, any plaque, calcified plaque, and noncalcified were detected in 12.5%, 10.1%, and 2.4% of cross sections per patient, respectively. There was significant progression in the mean number of cross sections containing any plaque (16.5 +/- 25.3 vs. 18.6 +/- 25.5, p = 0.01) and noncalcified plaque (3.1 +/- 5.8 vs. 4.4 +/- 7.0, p = 0.04) but not calcified plaque (13.3 +/- 23.1 vs. 14.2 +/- 22.0, p = 0.2). In longitudinal regression analysis, the presence of baseline plaque, number of cardiovascular risk factors, and smoking were independently associated with plaque progression after adjustment for age, sex, and follow-up time interval. The semiquantitative score based on cross sections correlated closely with plaque volume progression (r = 0.75, p < 0.0001) and demonstrated an excellent intraobserver and interobserver agreement (kappa = 0.95 and kappa = 0.93, respectively). CONCLUSIONS Coronary plaque burden of patients with acute chest pain significantly increases during the course of 2 years. Progression over time is dependent on plaque composition and cardiovascular risk profile. Larger studies are needed to confirm these results and to determine the effect of medical treatment on progression. (J Am Coll Cardiol Img 2009; 2: 1262-70) (C) 2009 by the American College of Cardiology Foundation C1 [Bamberg, Fabian; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, 165 Charles River Plaza,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org FU NIH [RO1 HL080053, T32HL076136]; Siemens Medical Solutions; General Electric Healthcare; National Heart Foundation of Australia; Royal Australian and New Zealand College of Physicians; German Federal Ministry of Education and Research; Foundation of German Business, Berlin Germany FX This work was supported by the NIH (RO1 HL080053) and in part supported by Siemens Medical Solutions and General Electric Healthcare. Dr. Lehman was supported by grants from the National Heart Foundation of Australia and the Royal Australian and New Zealand College of Physicians, Dr. Schlett in part by grants from the German Federal Ministry of Education and Research and the Foundation of German Business, Berlin Germany, and Dr. Shturman in part by the National Institutes of Health grant T32HL076136. Drs. Lehman and Schlett contributed equally to this work. NR 27 TC 39 Z9 40 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD NOV PY 2009 VL 2 IS 11 BP 1262 EP 1270 DI 10.1016/j.jcmg.2009.07.007 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 725OX UT WOS:000287656200003 PM 19909929 ER PT J AU Weiser, SD Fernandes, KA Brandson, EK Lima, VD Anema, A Bangsberg, DR Montaner, JS Hogg, RS AF Weiser, Sheri D. Fernandes, Kimberly A. Brandson, Eirikka K. Lima, Viviane D. Anema, Aranka Bangsberg, David R. Montaner, Julio S. Hogg, Robert S. TI The Association Between Food Insecurity and Mortality Among HIV-Infected Individuals on HAART SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE food insecurity; HIV/AIDS; mortality; Vancouver ID ACTIVE ANTIRETROVIRAL THERAPY; INJECTION-DRUG USERS; IMMUNODEFICIENCY-VIRUS-INFECTION; CHRONIC ENERGY DEFICIENCY; BODY-MASS INDEX; CD4 CELL COUNT; DISEASE PROGRESSION; MENTAL-HEALTH; WEIGHT-LOSS; EPIDEMIOLOGY RESEARCH AB Background: Food insecurity is increasingly recognized as a barrier to optimal treatment outcomes, but there is little data on this issue. We assessed associations between food insecurity and mortality among HIV-infected antiretroviral therapy-treated individuals in Vancouver, British Columbia, and whether body max index (BMI) modified associations. Methods: Individuals were recruited from the British Columbia HIV/AIDS drug treatment program in 1998 and 1999 and were followed until June 2007 for outcomes. Food insecurity was measured with the Radimer/Cornell questionnaire. Cox proportional hazard models were used to determine associations between food insecurity, BMI, and nonaccidental deaths when controlling for confounders. Results: Among 1119 participants, 536 (48%) were categorized as food insecure and 160 (14%) were categorized as underweight (BMI < 18.5). After a median follow-up time of 8.2 years, 153 individuals (14%) had died from nonaccidental deaths. After controlling for adherence, CD4 counts, and socioeconomic variables, people who were food insecure and underweight were nearly 2 times more likely to die (adjusted hazard ratio = 1.94, 95% confidence interval = 1.10 to 3.40) compared with people who were not food insecure or underweight. There was also a trend toward increased risk of mortality among people who were food insecure and not underweight (adjusted hazard ratio = 1.40, 95% confidence interval = 0.91 to 2.05). In contrast, people who were underweight but food secure were not more likely to die. Conclusions: Food insecurity is a risk factor for mortality among antiretroviral therapy-treated individuals in British Columbia, particularly among individuals who are underweight. Innovative approaches to address food insecurity should be incorporated into HIV treatment programs. C1 [Weiser, Sheri D.] Univ Calif San Francisco, Posit Hlth Program, Dept Med, San Francisco Gen Hosp, San Francisco, CA 94143 USA. [Weiser, Sheri D.] Univ Calif San Francisco, Dept Med, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. [Fernandes, Kimberly A.; Brandson, Eirikka K.; Lima, Viviane D.; Anema, Aranka; Montaner, Julio S.; Hogg, Robert S.] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Lima, Viviane D.; Montaner, Julio S.] Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, Canada. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Harvard Initiat Global Hlth, Ctr Global Hlth,Ragon Inst,Sch Med, Boston, MA USA. [Hogg, Robert S.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. RP Weiser, SD (reprint author), Univ Calif San Francisco, Posit Hlth Program, POB 0874, San Francisco, CA 94143 USA. EM sheri.weiser@ucsf.edu RI Hogg, Robert/B-2783-2012; OI Hogg, Robert/0000-0003-3463-5488 FU Canadian Institute of Health Research; NIMH [79713-01]; Hellman Family Foundation FX Supported by funding from the Canadian Institute of Health Research. Dr. Sheri D. Weiser received additional funding from NIMH 79713-01 and the Hellman Family Foundation. NR 68 TC 79 Z9 81 U1 3 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2009 VL 52 IS 3 BP 342 EP 349 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 511WR UT WOS:000271202900007 PM 19675463 ER PT J AU Allen, JD Fantasia, HC Fontenot, H Flaherty, S Santana, J AF Allen, Jennifer D. Fantasia, Heidi Collins Fontenot, Holly Flaherty, Stephen Santana, Jeans TI College Men's Knowledge, Attitudes, and Beliefs about the Human Papillomavirus Infection and Vaccine SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Human papillomavirus; HPV; College health; Men's health ID BURDEN AB Men enrolled in an urban university participated in focus groups (k = 6; n = 45) to explore knowledge about human papillomavirus and attitudes toward prophylactic vaccine. Results suggest that regardless of whether vaccines become available to men, educational efforts should include them, as men tend to have many misconceptions and do not perceive themselves to be vulnerable. (C) 2009 Society for Adolescent Medicine. All rights reserved. C1 [Allen, Jennifer D.; Fantasia, Heidi Collins; Fontenot, Holly; Santana, Jeans] Boston Coll, William Connell Sch Nursing, Chestnut Hill, MA 02167 USA. [Allen, Jennifer D.; Flaherty, Stephen] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Allen, JD (reprint author), Boston Coll, William Connell Sch Nursing, 140 Commonwealth Ave, Boston, MA 02167 USA. EM Jennifer.allen.5@bc.edu RI Allen, Jennifer/M-2113-2015 NR 10 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD NOV PY 2009 VL 45 IS 5 BP 535 EP 537 DI 10.1016/j.jadohealth.2009.05.014 PG 3 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 513HR UT WOS:000271313800017 PM 19837363 ER PT J AU Soutullo, CA Escamilla-Canales, I Wozniak, J Gamazo-Garran, P Figueroa-Quintana, A Biederman, J AF Soutullo, Cesar A. Escamilla-Canales, Inmaculada Wozniak, Janet Gamazo-Garran, Pilar Figueroa-Quintana, Ana Biederman, Joseph TI Pediatric bipolar disorder in a Spanish sample: Features before and at the time of diagnosis SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Mania; Bipolar; Children; Adolescents; Phenomenology; Europe ID AGE-CHILDREN-PRESENT; K-SADS-PL; PREPUBERTAL CHILDREN; AFFECTIVE-ILLNESS; MOOD DISORDERS; MANIA SYMPTOMS; ADOLESCENTS; PHENOMENOLOGY; ONSET; ADHD AB Introduction: Bipolar disorder (BD) often starts in childhood or adolescence. Diagnostic delay is common and may have a negative impact on treatment response and outcome. Objectives: To describe the clinical characteristics and symptoms of children with BD prior to their diagnosis and at the time of diagnosis in a sample in Spain. Methods: We retrospectively reviewed the medical records of all children and adolescents (N = 38) with a DSM-IV diagnosis of BD evaluated in the Child & Adolescent Psychiatry Unit, University of Navarra, over a 6-year period. We collected the DSM-lV symptoms of BD prior and at the time of diagnosis using the K-SADS-PL interview template. Results: BID was diagnosed in close to 4% of clinic patients. Thirty (79%) were boys and 8 (21%) were girls; 17 (44.7%) had BD-1, 2 (5.3%) BD-2, and 19 (49.9%) BD-NOS. Median age at diagnosis was 13.9 (10.6; 15.9). Delay of diagnosis was 1.5 (0.7;3.4) years. Symptoms of BD were similar to those reported in U.S. samples with high rates of severe irritability (94.6%) and psychiatric comorbidity: 92.1% of the BD children had at least one comorbid disorder and 18.4% had three comorbidities, most frequently ADHD (21%) and substance abuse (18.4%). Conclusions: Clinical findings in this Spanish sample of children with BD closely resembles those described in U.S. clinics. Diagnostic delay, as in the U.S., and frequent misdiagnosis may explain low prevalence estimates found outside the U.S. (C) 2009 Elsevier B.V. All rights reserved. C1 [Soutullo, Cesar A.; Figueroa-Quintana, Ana] Univ Navarra, Child & Adolescent Psychiat Unit, Dept Psychiat & Med Psychol, Clin Univ, Pamplona 31008, Spain. [Escamilla-Canales, Inmaculada; Gamazo-Garran, Pilar] Univ Navarra, Child & Adolescent Psychiat Unit, Dept Psychiat & Med Psychol, Clin Univ, Madrid, Spain. [Wozniak, Janet; Biederman, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Res Unit, Boston, MA USA. RP Soutullo, CA (reprint author), Univ Navarra, Child & Adolescent Psychiat Unit, Dept Psychiat & Med Psychol, Clin Univ, Apartado 4209, Pamplona 31008, Spain. EM csoutullo@unav.es FU Alicia Koplowitz Foundation FX The authors thank the Alicia Koplowitz Foundation for a Teaching Grant that made possible a rotation of one of the authors (Dra. Inmaculada Escamilla-Canales) at the MCH Pediatric Psycho pharmacology Unit, Harvard University, Boston, MA, USA. NR 55 TC 16 Z9 19 U1 4 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD NOV PY 2009 VL 118 IS 1-3 BP 39 EP 47 DI 10.1016/j.jad.2009.02.010 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 506CI UT WOS:000270750500005 PM 19285348 ER PT J AU Yong, PL Werner, RM AF Yong, Pierre L. Werner, Rachel M. TI Process quality measures and asthma exacerbations in the Medicaid population SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Asthma; quality of care; Healthcare Effectiveness Data and Information Set; Medicaid ID PLAN EMPLOYER DATA; INHALED CORTICOSTEROIDS; OF-CARE; ADMINISTRATIVE DATA; PERSISTENT ASTHMA; INFORMATION SET; RISK; VALIDATION; PREVENTION; OUTCOMES AB Background: Asthma quality assessment often focuses on controller medication use, yet claims-based studies find conflicting associations between this care process and clinical outcomes. Objective: We sought to compare the association between 3 controller-based quality measures and asthma exacerbations to gain better understanding of how processes of care are related to clinical outcomes. Methods: Identifying a cohort of Medicaid beneficiaries with persistent asthma by using Healthcare Effectiveness Data and Information Set (HEDIS) criteria for asthma in 2001-2002 in California and New York, we assessed 3 asthma quality metrics in 2002: (1) the current HEDIS measure of at least I controller medication filling; (2) at least 4 controller medication prescription fillings; and (3) a controller-to-total asthma medication ratio of at least 0.5. We calculated the odds of having an asthma exacerbation in 2003 as a function of performance on each quality metric, adjusting for race, sex, age, and prior outpatient and acute care use for asthma. Results: Of 90,909 subjects with persistent asthma in California (48.1%) and New York (51.9%), those who obtained at least I or at least 4 controller medications had increased likelihood of poor outcomes (adjusted odds ratios, 1.80 [95% CI, 1.73-1.87] and 1.44 [95% CI 1.40-1.48], respectively). Beneficiaries meeting the controller-to-total asthma medication ratio measure were 23.0% less likely to have exacerbations (adjusted odds ratio, 0.77 [95% CI, 0.75-0.80]). Conclusions: A higher controller medication ratio indicated a lower likelihood of asthma exacerbations, whereas assessing the number of controller medication-dispensing events was associated with a higher odds of exacerbation. (J Allergy Clin Immunol 2009;124:961-6.) C1 [Yong, Pierre L.] Univ Penn, Robert Wood Johnson Clin Scholars Program, Sch Med, Philadelphia, PA 19106 USA. [Yong, Pierre L.; Werner, Rachel M.] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. [Yong, Pierre L.] Hosp Univ Penn, Dept Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA. [Yong, Pierre L.; Werner, Rachel M.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19106 USA. [Yong, Pierre L.] Univ Penn, Ctr Publ Hlth Initiat, Philadelphia, PA 19106 USA. RP Yong, PL (reprint author), Univ Penn, Robert Wood Johnson Clin Scholars Program, Sch Med, 1303A Blockley Hall,423 Guardian Dr, Philadelphia, PA 19106 USA. EM pyong@nas.edu FU Philadelphia Veterans Affairs Medical Center; Robert Wood Johnson Clinical Scholars; Veterans Affairs HSR&D Career Development; Clinical and Translational Science [UL1-RR024134] FX P. L. Y. is supported by a training grant from the Philadelphia Veterans Affairs Medical Center and the Robert Wood Johnson Clinical Scholars Program. R. M. W is supported in part by a Veterans Affairs HSR&D Career Development Award. The study was supported by pilot grant funding from the Leonard Davis Institute of Health Economics and resources supported by the Clinical and Translational Science Awards (UL1-RR024134). NR 26 TC 20 Z9 20 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2009 VL 124 IS 5 BP 961 EP 966 DI 10.1016/j.jaci.2009.07.027 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 523XI UT WOS:000272108000013 PM 19748660 ER PT J AU Patel, NC Chinen, J Rosenblatt, HM Hanson, IC Krance, RA Paul, ME Abramson, SL Noroski, LM Davis, CM Seeborg, FO Foster, SB Leung, KS Brown, BS Ritz, J Shearer, WT AF Patel, Niraj C. Chinen, Javier Rosenblatt, Howard M. Hanson, I. Celine Krance, Robert A. Paul, Mary E. Abramson, Stuart L. Noroski, Lenora M. Davis, Carla M. Seeborg, Filiz O. Foster, Samuel B. Leung, Kathryn S. Brown, Betty S. Ritz, Jerome Shearer, William T. TI Outcomes of patients with severe combined immunodeficiency treated with hematopoietic stem cell transplantation with and without preconditioning SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Hematopoietic stem cell transplantation; graft-versus-host disease; severe combined immunodeficiency; immune reconstitution; primary immunodeficiency; conditioning ID BONE-MARROW-TRANSPLANTATION; IMMUNE RECONSTITUTION; SINGLE-CENTER; DEFICIENCY; BMT AB Background: The effect of pretransplantation conditioning on the long-term outcomes of patients receiving hematopoietic stem cell transplantation for severe combined immunodeficiency (SCID) has not been completely determined. Objective: We sought to assess the outcomes of 23 mostly conditioned patients with SCID and compare their outcomes with those of 25 previously reported nonconditioned patients with SCID who underwent transplantation. Methods: In the present study we reviewed the medical records of these 23 consecutive, mostly conditioned patients with SCID who underwent transplantation between 1998 and 2007. Results: Eighteen patients (median age at transplantation, 10 months; range, 0.8-108 months) received haploidentical mismatched related donor, matched unrelated donor, or mismatched unrelated donor transplants, 17 of whom received pretransplantation conditioning (with I not conditioned); 13 (72%) patients engrafted with donor cells and survive at a median of 3.8 years (range, 1.8-9.8 year); 5 (38%) of 13 patients require intravenous immunoglobulin; and 6 of 6 age-eligible children attend school. Of 5 recipients (median age at transplantation, 7 months; range, 2-23 months) of matched related donor transplants, all 5 engrafted and survive at a median of 7.5 years (range, 1.5-9.5 year), I recipient requires intravenous immunoglobulin, and 3 of 3 age-eligible children attend school. Gene mutations were known in 16 cases: mutation in the common gamma chain of the IL-2 receptor (IL2RG) in 7 patients, mutation in the alpha chain of the IL-7 receptor (IL7RA) in 4 patients, mutation in the recombinase-activating gene (RAG1) in 2 patients, adenosine deaminase deficiency (ADA) in 2 patients, and adenylate kinase 2 (AK2) in I patient. Early outcomes and quality of life of the previous nonconditioned versus the present conditioned cohorts were not statistically different, but longer-term follow-up is necessary for confirmation. Conclusions: Hematopoietic stem cell transplantation in patients with SCED results in engraftment, long-term survival, and a good quality of life for the majority of patients with or without pretransplantation conditioning. (J Allergy Clin Immunol 2009;124:1062-9.) C1 [Patel, Niraj C.; Chinen, Javier; Hanson, I. Celine; Paul, Mary E.; Abramson, Stuart L.; Noroski, Lenora M.; Davis, Carla M.; Seeborg, Filiz O.; Foster, Samuel B.; Brown, Betty S.; Shearer, William T.] Texas Childrens Hosp, Dept Pediat, Sect Allergy & Immunol, Baylor Coll Med, Houston, TX 77039 USA. [Rosenblatt, Howard M.] Dell Childrens Med Ctr Cent Texas, Austin, TX USA. [Krance, Robert A.; Leung, Kathryn S.] Texas Childrens Hosp, Sect Hematol & Oncol, Baylor Coll Med, Houston, TX 77039 USA. [Ritz, Jerome] Harvard Univ, Sch Med, Div Hematol Malignancies, Boston, MA USA. [Ritz, Jerome] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ritz, Jerome] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA USA. RP Shearer, WT (reprint author), Texas Childrens Hosp, Dept Pediat, Sect Allergy & Immunol, Baylor Coll Med, 6621 Fannin,FC 330-01, Houston, TX 77039 USA. EM wtsheare@texaschildrenshospital.org FU Pfizer; Astella; Novartis; CSL Behring; Food Allergy and Anaphylaxis Network FX R. A. Krance has received research support from Pfizer and Astella. S. L. Abramson has received research support from Novartis and CSL Behring. C. M. Davis has received research support from the Food Allergy and Anaphylaxis Network. NR 17 TC 26 Z9 27 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2009 VL 124 IS 5 BP 1062 EP 1069 DI 10.1016/j.jaci.2009.08.041 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 523XI UT WOS:000272108000029 PM 19895994 ER PT J AU Leissner, KB Mahmood, FU AF Leissner, Kay B. Mahmood, Feroze U. TI Physiology and pathophysiology at high altitude: considerations for the anesthesiologist SO JOURNAL OF ANESTHESIA LA English DT Review DE High altitude; High altitude illness; Hypoxia; Hypoxic pulmonary vasoconstriction ID ACUTE MOUNTAIN-SICKNESS; HYPOXIC PULMONARY VASOCONSTRICTION; OPERATION EVEREST-II; INHALED NITRIC-OXIDE; PATENT FORAMEN OVALE; SEA-LEVEL; MODERATE ALTITUDE; CEREBRAL EDEMA; VENTILATORY RESPONSE; SIMULATED ALTITUDE AB Millions of people live in, work in, and travel to areas of high altitude (HA). Skiers, trekkers, and mountaineers reach altitudes of 2500 m to more than 8000 m for recreation, and sudden ascents to high altitude without the benefits of acclimatization are increasingly common. HA significantly affects the human body, especially the cardiovascular and pulmonary systems, because of oxygen deprivation due to decreased ambient barometric pressure. Rapid ascents may lead to high-altitude diseases that sometimes have fatal consequences. Other factors, such as severe cold, dehydration, high winds, and intense solar radiation, increase the morbidity of patients at HA. Anesthesiologists working in or visiting areas of higher elevations should become familiar with the human physiology, altered pharmacology, and disease pattern of HA. C1 [Leissner, Kay B.] VA Boston Healthcare Syst, Dept Anesthesia, Boston, MA USA. [Leissner, Kay B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Mahmood, Feroze U.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Anesthesia, Sch Med, Boston, MA 02215 USA. RP Leissner, KB (reprint author), VA Boston Healthcare Serv, Anesthesiol Serv, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. RI Mahmood, Feroze/B-1383-2008 OI Mahmood, Feroze/0000-0002-7071-0476 NR 114 TC 12 Z9 13 U1 2 U2 18 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 0913-8668 J9 J ANESTH JI J. Anesth. PD NOV PY 2009 VL 23 IS 4 BP 543 EP 553 DI 10.1007/s00540-009-0787-7 PG 11 WC Anesthesiology SC Anesthesiology GA 521QP UT WOS:000271938000013 PM 19921365 ER PT J AU Kellogg, DL Zhao, JL Wu, YB AF Kellogg, Dean L., Jr. Zhao, Joan L. Wu, Yubo TI Roles of nitric oxide synthase isoforms in cutaneous vasodilation induced by local warming of the skin and whole body heat stress in humans SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE skin; nitric oxide; nitric oxide synthase 1; nitric oxide synthase 3; microdialysis ID HUMAN CARDIOVASCULAR ADJUSTMENTS; FEMALE REPRODUCTIVE HORMONES; BLOOD-FLOW; REFLEX CONTROL; SELECTIVE-INHIBITION; ACTIVE VASODILATION; CONTROL MECHANISMS; CORE TEMPERATURE; L-ARGININE; IN-VIVO AB Kellogg DL, Jr, Zhao JL, Wu Y. Roles of nitric oxide synthase isoforms in cutaneous vasodilation induced by local warming of the skin and whole body heat stress in humans. J Appl Physiol 107: 1438-1444, 2009. First published September 10, 2009; doi: 10.1152/japplphysiol.00690.2009.Nitric oxide (NO) participates in the cutaneous vasodilation caused by increased local skin temperature (Tloc) and whole body heat stress in humans. In forearm skin, endothelial NO synthase (eNOS) participates in vasodilation due to elevated Tloc and neuronal NO synthase (nNOS) participates in vasodilation due to heat stress. To explore the relative roles and interactions of these isoforms, we examined the effects of a relatively specific eNOS inhibitor, N(omega)-amino-L-arginine (LNAA), and a specific nNOS inhibitor, N(omega)-propyl-L-arginine (NPLA), both separately and in combination, on skin blood flow (SkBF) responses to increased Tloc and heat stress in two protocols. In each protocol, SkBF was monitored by laser-Doppler flowmetry (LDF) and mean arterial pressure (MAP) by Finapres. Cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP). Intradermal microdialysis was used to treat one site with 5 mM LNAA, another with 5 mM NPLA, a third with combined 5 mM LNAA and 5 mM NPLA (Mix), and a fourth site with Ringer only. In protocol 1, Tloc was controlled with combined LDF/local heating units. Tloc was increased from 34 degrees C to 41.5 degrees C to cause local vasodilation. In protocol 2, after a period of normothermia, whole body heat stress was induced (water-perfused suits). At the end of each protocol, all sites were perfused with 58 mM nitroprusside to effect maximal vasodilation for data normalization. In protocol 1, at Tloc = 34 degrees C, CVC did not differ between sites (P > 0.05). LNAA and Mix attenuated CVC increases at Tloc = 41.5 degrees C to similar extents (P < 0.05, LNAA or Mix vs. untreated or NPLA). In protocol 2, in normothermia, CVC did not differ between sites (P > 0.05). During heat stress, NPLA and Mix attenuated CVC increases to similar extents, but no significant attenuation occurred with LNAA (P > 0.05, NPLA or Mix vs. untreated or LNAA). In forearm skin, eNOS mediates the vasodilator response to increased Tloc and nNOS mediates the vasodilator response to heat stress. The two isoforms do not appear to interact during either response. C1 [Kellogg, Dean L., Jr.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Hosp Div, Geriatr Res Educ & Clin Ctr, Dept Vet Affairs, San Antonio, TX USA. RP Kellogg, DL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Geriatr & Gerontol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kelloggd@uthscsa.edu FU National Heart, Lung, and Blood Institute [HL-065599] FX This work was supported in part by National Heart, Lung, and Blood Institute Grant HL-065599. NR 60 TC 61 Z9 64 U1 3 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 2009 VL 107 IS 5 BP 1438 EP 1444 DI 10.1152/japplphysiol.00690.2009 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 515KO UT WOS:000271468900011 PM 19745188 ER PT J AU Mayhew, DL Kim, JS Cross, JM Ferrando, AA Bamman, MM AF Mayhew, David L. Kim, Jeong-su Cross, James M. Ferrando, Arny A. Bamman, Marcas M. TI Translational signaling responses preceding resistance training-mediated myofiber hypertrophy in young and old humans SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE translation initiation; protein synthesis; muscle fiber; aging ID MUSCLE PROTEIN-SYNTHESIS; HUMAN SKELETAL-MUSCLE; EXERCISE-INDUCED INCREASE; P70 S6 KINASE; CLUSTER-ANALYSIS; MIXED MUSCLE; MYONUCLEAR ADDITION; GENE-EXPRESSION; MEN; PHOSPHORYLATION AB Mayhew DL, Kim J-S, Cross JM, Ferrando AA, Bamman MM. Translational signaling responses preceding resistance training-mediated myofiber hypertrophy in young and old humans. J Appl Physiol 107: 1655-1662, 2009. First published July 9, 2009; doi:10.1152/japplphysiol.91234.2008.-While skeletal muscle protein accretion during resistance training (RT)-mediated myofiber hypertrophy is thought to result from upregulated translation initiation signaling, this concept is based on responses to a single bout of unaccustomed resistance exercise (RE) with no measure of hypertrophy across RT. Further, aging appears to affect acute responses to RE, but whether age differences in responsiveness persist during RT leading to impaired RT adaptation is unclear. We therefore tested whether muscle protein fractional synthesis rate (FSR) and Akt/mammalian target of rapamycin (mTOR) signaling in response to unaccustomed RE differed in old vs. young adults, and whether age differences in acute responsiveness were associated with differences in muscle hypertrophy after 16 wk of RT. Fifteen old and 21 young adult subjects completed the 16-wk study. The phosphorylation states of Akt, S6K1, ribosomal protein S6 (RPS6), eukaryotic initiation factor 4E (eIF4E) binding protein (4EBP1), eIF4E, and eIF4G were all elevated (23-199%) 24 h after a bout of unaccustomed RE. A concomitant 62% increase in FSR was found in a subset (6 old, 8 young). Age x time interaction was found only for RPS6 phosphorylation (+335% in old subjects only), while there was an interaction trend (P = 0.084) for FSR (+96% in young subjects only). After 16 wk of RT, gains in muscle mass, type II myofiber size, and voluntary strength were similar in young and old subjects. In conclusion, at the level of translational signaling, we found no evidence of impaired responsiveness among older adults, and for the first time, we show that changes in translational signaling after unaccustomed RE were associated with substantial muscle protein accretion (hypertrophy) during continued RT. C1 [Bamman, Marcas M.] Univ Alabama, Dept Physiol & Biophys, Core Muscle Res Lab, Birmingham, AL 35294 USA. [Cross, James M.] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. [Mayhew, David L.] Univ Alabama, Med Scientist Training Program, Birmingham, AL 35294 USA. [Mayhew, David L.; Kim, Jeong-su; Bamman, Marcas M.] Birmingham Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Birmingham, AL USA. [Ferrando, Arny A.] Univ Arkansas Med Sci, Ctr Translat Res Aging & Longev, Little Rock, AR 72205 USA. [Ferrando, Arny A.] Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA. RP Bamman, MM (reprint author), Univ Alabama, Dept Physiol & Biophys, Core Muscle Res Lab, 966 McCallum Basic Hlth Sci Bldg,1530 3rd Ave S, Birmingham, AL 35294 USA. EM mbamman@uab.edu RI Ferrando, Adolfo /Q-7026-2016 FU National Institute on Aging [R01-AG-017896, F30-AG-031623]; Veterans Affairs Merit Grant; General Clinical Research Center [M01-RR-00032] FX Funding for this work was provided by National Institute on Aging Grants R01-AG-017896 (M. M. Bamman) and F30-AG-031623 (D. L. Mayhew), a Veterans Affairs Merit Grant (M. M. Bamman), and General Clinical Research Center Grant M01-RR-00032. NR 47 TC 86 Z9 88 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 2009 VL 107 IS 5 BP 1655 EP 1662 DI 10.1152/japplphysiol.91234.2008 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 515KO UT WOS:000271468900036 PM 19589955 ER PT J AU Sillanpaa, J Nallapareddy, SR Qin, X Singh, KV Muzny, DM Kovar, CL Nazareth, LV Gibbs, RA Ferraro, MJ Steckelberg, JM Weinstock, GM Murray, BE AF Sillanpaa, Jouko Nallapareddy, Sreedhar R. Qin, Xiang Singh, Kavindra V. Muzny, Donna M. Kovar, Christie L. Nazareth, Lynne V. Gibbs, Richard A. Ferraro, Mary J. Steckelberg, James M. Weinstock, George M. Murray, Barbara E. TI A Collagen-Binding Adhesin, Acb, and Ten Other Putative MSCRAMM and Pilus Family Proteins of Streptococcus gallolyticus subsp gallolyticus (Streptococcus bovis Group, Biotype I) SO JOURNAL OF BACTERIOLOGY LA English DT Article ID EXTRACELLULAR-MATRIX PROTEINS; URINARY-TRACT-INFECTION; GROUP-A STREPTOCOCCI; ENTEROCOCCUS-FAECALIS; STAPHYLOCOCCUS-AUREUS; BIOFILM FORMATION; ANTIGEN-I/II; CELL-WALL; SURFACE-PROTEINS; HUG MODEL AB Members of the Streptococcus bovis group are important causes of endocarditis. However, factors associated with their pathogenicity, such as adhesins, remain uncharacterized. We recently demonstrated that endocarditis-derived Streptococcus gallolyticus subsp. gallolyticus isolates frequently adhere to extracellular matrix (ECM) proteins. Here, we generated a draft genome sequence of an ECM protein-adherent S. gallolyticus subsp. gallolyticus strain and found, by genome-wide analyses, 11 predicted LPXTG-type cell wall-anchored proteins with characteristics of MSCRAMMs, including a modular architecture of domains predicted to adopt immunoglobulin (Ig)-like folding. A recombinant segment of one of these, Acb, showed high-affinity binding to immobilized collagen, and cell surface expression of Acb correlated with the presence of acb and collagen adherence of isolates. Three of the 11 proteins have similarities to major pilus subunits and are organized in separate clusters, each including a second Ig-fold-containing MSCRAMM and a class C sortase, suggesting that the sequenced strain encodes three distinct types of pili. Reverse transcription-PCR demonstrated that all three genes of one cluster, acb-sbs7-srtC1, are cotranscribed, consistent with pilus operons of other gram-positive bacteria. Further analysis detected expression of all 11 genes in cells grown to mid to late exponential growth phases. Wide distribution of 9 of the 11 genes was observed among S. gallolyticus subsp. gallolyticus isolates with fewer genes present in other S. bovis group species/subspecies. The high prevalence of genes encoding putative MSCRAMMs and pili, including a collagen-binding MSCRAMM, among S. gallolyticus subsp. gallolyticus isolates may play an important role in the predominance of this subspecies in S. bovis endocarditis. C1 [Sillanpaa, Jouko; Nallapareddy, Sreedhar R.; Singh, Kavindra V.; Murray, Barbara E.] Univ Texas Houston, Sch Med, Dept Internal Med, Div Infect Dis, Houston, TX 77030 USA. [Sillanpaa, Jouko; Nallapareddy, Sreedhar R.; Singh, Kavindra V.; Murray, Barbara E.] Univ Texas Houston, Sch Med, Ctr Study Emerging & Reemerging Pathogens, Houston, TX 77030 USA. [Murray, Barbara E.] Univ Texas Houston, Sch Med, Dept Microbiol & Mol Genet, Houston, TX 77030 USA. [Qin, Xiang; Muzny, Donna M.; Kovar, Christie L.; Nazareth, Lynne V.; Gibbs, Richard A.; Weinstock, George M.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Ferraro, Mary J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Steckelberg, James M.] Mayo Clin, Coll Med, Dept Internal Med, Div Infect Dis, Rochester, MN 55905 USA. RP Murray, BE (reprint author), Univ Texas Houston, Sch Med, Dept Internal Med, Div Infect Dis, 6431 Fannin St,MSB 2-112, Houston, TX 77030 USA. EM bem.asst@uth.tmc.edu RI Weinstock, George/C-6314-2013 OI Weinstock, George/0000-0002-2997-4592 FU J. Ralph Meadows Professorship in the Department of Internal Medicine, University of Texas Medical School FX This work was supported by the J. Ralph Meadows Professorship in the Department of Internal Medicine, University of Texas Medical School, to Barbara E. Murray. NR 73 TC 40 Z9 40 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2009 VL 191 IS 21 BP 6643 EP 6653 DI 10.1128/JB.00909-09 PG 11 WC Microbiology SC Microbiology GA 505UQ UT WOS:000270723700017 PM 19717590 ER PT J AU George, PM Saigal, R Lawlor, MW Moore, MJ Lavan, DA Marini, RP Selig, M Makhni, M Burdick, JA Langer, R Kohane, DS AF George, Paul M. Saigal, Rajiv Lawlor, Michael W. Moore, Michael J. LaVan, David A. Marini, Robert P. Selig, Martin Makhni, Melvin Burdick, Jason A. Langer, Robert Kohane, Daniel S. TI Three-dimensional conductive constructs for nerve regeneration SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE biocompatibility; electroactive polymer; nerve guide; nerve regeneration; polypyrrole ID NEURITE OUTGROWTH; AXON REGENERATION; DRUG-DELIVERY; GROWTH-FACTOR; POLYMER; BIOCOMPATIBILITY; STIMULATION; COMPOSITE; SCAFFOLDS; BEHAVIOR AB The unique electrochemical properties of conductive polymers can be utilized to form stand-alone polymeric tubes and arrays of tubes that are suitable for guides to promote peripheral nerve regeneration. Noncomposite, polypyrrole (PPy) tubes ranging in inner diameter from 25 mu m to 1.6 mm as well as multichannel tubes were fabricated by electrodeposition. While oxidation of the pyrrole monomer causes growth of the film, brief Subsequent reduction allowed mechanical dissociation from the electrode mold, creating a stand-alone, conductive PPy tube. Conductive polymer nerve guides made in this manner were placed in transected rat sciatic nerves and shown to support nerve regeneration over an 8-week time period. (C) 2008 Wiley Periodicals, Inc. J Biomed Mater Res 91A: 519-527, 2009 C1 [Kohane, Daniel S.] Harvard Univ, Sch Med, Childrens Hosp,Lab Biomat & Drug Delivery, Div Crit Care Med,Dept Anesthesiol, Boston, MA 02115 USA. [George, Paul M.; Saigal, Rajiv] MIT, Div Hlth Sci & Technol, Cambridge, MA 02142 USA. [Lawlor, Michael W.; Selig, Martin] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lawlor, Michael W.; Makhni, Melvin; Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02142 USA. [Moore, Michael J.] Tulane Univ, Dept Biomed Engn, New Orleans, LA 70118 USA. [LaVan, David A.] Yale Univ, Dept Mech Engn, New Haven, CT 06511 USA. [Marini, Robert P.] MIT, Div Comparat Med, Cambridge, MA 02142 USA. [Burdick, Jason A.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. RP Kohane, DS (reprint author), Harvard Univ, Sch Med, Childrens Hosp,Lab Biomat & Drug Delivery, Div Crit Care Med,Dept Anesthesiol, Boston, MA 02115 USA. EM daniel.kohane@childrens.harvard.edu RI Moore, Michael/E-9107-2011; LaVan, David/C-3943-2012 OI Moore, Michael/0000-0002-7853-5756; LaVan, David/0000-0002-1952-0028 FU NIH [GM073626, DE13023] FX Contract grant sponsor: NIH; contract grant numbers: GM073626, DE13023 NR 20 TC 19 Z9 20 U1 1 U2 22 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1549-3296 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD NOV PY 2009 VL 91A IS 2 BP 519 EP 527 DI 10.1002/jbm.a.32226 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 506BA UT WOS:000270746200022 PM 18985787 ER PT J AU Sheth, RA Josephson, L Mahmood, U AF Sheth, Rahul A. Josephson, Lee Mahmood, Umar TI Evaluation and clinically relevant applications of a fluorescent imaging analog to fluorodeoxyglucose positron emission tomography SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE optical molecular imaging; fluorescence biomarkers; FDG-PET; minimally invasive imaging; metabolic imaging; fluorescence endoscopy; quantitative imaging; intraoperative imaging ID GLUCOSE-UPTAKE; IN-VIVO; DEOXYGLUCOSE ANALOG; CELLS; 2-NBDG; MICE; SINGLE; PROBE; MODEL AB A fluorescent analog to 2-deoxy-2 [(18)F] fluoro-D-glucose position emission tomography (FDG-PET) would allow for the introduction of metabolic imaging into intraoperative and minimally invasive settings. We present through in vitro and in vivo experimentation an evaluation of 2-(N-(7-nitrobenz-2-oxa-1,3-diazol- 4-yl)amino)-2-deoxyglucose (2-NBDG), a fluorescently labeled glucose molecule, as a molecular beacon of glucose utilization. The competitive inhibition of 2-NBDG uptake by excess free glucose is directly compared against FDG uptake inhibition in cultured cells. 2-NBDG uptake in the brain of a mouse experiencing a generalized seizure is measured, as well as in subcutaneously implanted tumors in mice during fed and fasting states. Localization of 2-NBDG into malignant tissues is studied by laser scanning microscopy. The clinical relevance of 2-NBDG imaging is examined by performing fluorescence colonoscopy, and by correlating preoperative FDG-PET with intraoperative fluorescence imaging. 2-NBDG exhibits a similar uptake inhibition to FDG by excess glucose in the growth media. Uptake is significantly increased in the brain of an animal experiencing seizures versus control, and in subcutaneous tumors after the animals are kept nil per os (NPO) for 24 h versus ad libidum feeding. The clinical utility of 2-NBDG is confirmed by the demonstration of very high target-to-background ratios in minimally invasive and intraoperative imaging of malignant lesions. We present an optical analog of FDGPET to extend the applicability of metabolic imaging to minimally invasive and intraoperative settings. (C) 2009 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3259364] C1 [Sheth, Rahul A.; Josephson, Lee; Mahmood, Umar] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA 02114 USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, 55 Fruit St,White 427, Boston, MA 02114 USA. EM umahmood@mgh.harvard.edu FU NIH [P50CA127003, R01-EB001872] FX The authors wish to express their appreciation to Brett Marinelli for his assistance with the PET/CT imaging, and to Shena Hembrador for her assistance with the FDG cell uptake experiments. This research was supported in part by the Susan G. Komen for the Cure Foundation, as well as NIH grants P50CA127003 and R01-EB001872. NR 21 TC 23 Z9 24 U1 0 U2 4 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV-DEC PY 2009 VL 14 IS 6 AR 064014 DI 10.1117/1.3259364 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 552DO UT WOS:000274267900021 PM 20059252 ER PT J AU Lo Celso, C Wu, JW Lin, CP AF Lo Celso, Cristina Wu, Juwell W. Lin, Charles P. TI In vivo imaging of hematopoietic stem cells and their microenvironment SO JOURNAL OF BIOPHOTONICS LA English DT Review DE hematopoietic stem cell transplantation; in vivo imaging; intravital microscopy; cell tracking ID BONE-MARROW NICHES; PROGENITOR CELLS; PENETRATING PEPTIDES; MYELOID-LEUKEMIA; DENDRITIC CELLS; B-CELLS; QUIESCENCE; REPAIR; TISSUE; MICE AB In this review we provide a description of the basic concepts and paradigms currently constituting the foundations of adult stem cell biology, and discuss the role that live imaging techniques have in the development of the field. We focus on live imaging of hematopoietic stein cells (HSCs) as the basic biology and clinical applications of HSCs have historically been at the forefront of the stem cell field, and HSC are the first mammalian tissue stem cells to be visualized in vivo using advanced light microscopy techniques. We outline the current technical challenges that remain to be overcome before stein cells and their niche can be more fully characterized using the live imaging technology. [GRAPHICS] . hi vivo imaging of HSCs (white) 1 day after injection into an irradiated recipient, showing a single cell on the left and a cluster of 4 cells on the right that have undergone cell division. Blue, bone; green, osteoblasts; red, vasculature. Bar = 50 mu m. (C) 2009 by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim C1 [Lo Celso, Cristina; Lin, Charles P.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Lo Celso, Cristina] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Wu, Juwell W.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02145 USA. [Wu, Juwell W.; Lin, Charles P.] Massachusetts Gen Hosp, Adv Microscopy Program, Ctr Syst Biol, Boston, MA 02114 USA. [Wu, Juwell W.; Lin, Charles P.] Massachusetts Gen Hosp, Adv Microscopy Program, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Lin, CP (reprint author), Harvard Stem Cell Inst, 42 Church St, Cambridge, MA 02138 USA. EM lin@helix.mgh.harvard.edu OI Lo Celso, Cristina/0000-0002-1163-4207 FU EMBO; HFSP; Wellman Center; National Institutes of Health; Harvard Stem Cell Institute; M.O FX Cristina Lo Celso was funded by EMBO and HFSP. Juwell Wu was supported by Wellman Center for Photomedicine Graduate Student Fellowship. The project was funded by the National Institutes of Health, the Harvard Stem Cell Institute (to CPL) and by a personal anonymous donation to NIGH from M.O. NR 72 TC 27 Z9 27 U1 0 U2 11 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1864-063X J9 J BIOPHOTONICS JI J. Biophotonics PD NOV PY 2009 VL 2 IS 11 BP 619 EP 631 DI 10.1002/jbio.200910072 PG 13 WC Biochemical Research Methods; Biophysics; Optics SC Biochemistry & Molecular Biology; Biophysics; Optics GA 524EN UT WOS:000272126700007 PM 19847800 ER EF