FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Januzzi, JL Rehman, S Mueller, T van Kimmenade, RRJ Lloyd-Jones, DM AF Januzzi, James L., Jr. Rehman, Shafiq Mueller, Thomas van Kimmenade, Roland R. J. Lloyd-Jones, Donald M. TI Importance of Biomarkers for Long-Term Mortality Prediction in Acutely Dyspneic Patients SO CLINICAL CHEMISTRY LA English DT Article ID BRAIN NATRIURETIC PEPTIDE; OBSTRUCTIVE PULMONARY-DISEASE; COMMUNITY-ACQUIRED PNEUMONIA; GLOBAL CARDIOVASCULAR RISK; EMERGENCY-DEPARTMENT PRIDE; ACUTE CORONARY SYNDROMES; ACUTE HEART-FAILURE; C-REACTIVE PROTEIN; 1-YEAR MORTALITY; MYOCARDIAL-INFARCTION AB BACKGROUND: Although numerous biomarkers may be prognostically meaningful in patients with acute dyspnea, few comparative analyses have addressed possible associations between a wide range of candidate biomarkers and clinical variables. METHODS: Vital status was obtained for 517 acutely dyspneic patients at 4 years after emergency department presentation. A wide array of biomarkers was measured in this cohort, including natriuretic peptides, necrosis markers, inflammatory markers, hematologic markers, and renal markers. We performed statistical evaluation by using minimization of the Bayesian information criterion to evaluate predictors of 4-year mortality. Cox proportional hazards analysis was used to confirm results from the Bayesian information criterion. A final risk model was derived, and this model was then validated by applying it to patients from a separate cohort of acutely dyspneic patients. RESULTS: By 4 years, there were 186 deaths (36%). In addition to several clinical variables, several biomarkers were significant predictors of death, including log-transformed concentrations of hemoglobin (hazard ratio = 0.77; P < 0.001), soluble ST2 (hazard ratio = 1.38; P < 0.001), and amino-terminal pro-B-type natriuretic peptide (hazard ratio = 1.19; P < 0.001). Risk models that used these significant variables were accurate in predicting 4-year mortality in both the training and validation sets. CONCLUSIONS: When added to traditional clinical variables, selected biomarkers added significant value for long-term prognostication in acute dyspnea. (C) 2010 American Association for Clinical Chemistry C1 [Januzzi, James L., Jr.; Rehman, Shafiq; van Kimmenade, Roland R. J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Mueller, Thomas] Konventhosp Barmherzige Brueder, Dept Lab Med, Linz, Austria. [van Kimmenade, Roland R. J.] Univ Hosp Maastricht, Dept Cardiol, Maastricht, Netherlands. [Lloyd-Jones, Donald M.] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. [Lloyd-Jones, Donald M.] Northwestern Univ, Dept Med, Bluhm Cardiovasc Inst, Chicago, IL 60611 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM JJanuzzi@partners.org RI Lloyd-Jones, Donald/C-5899-2009; Kimmenade, R.R.J./L-4432-2015 FU Roche Diagnostics; Siemens; Critical Diagnostics; Balson Scholarship Fund; Dennis and Marilyn Barry Fellowship in Cardiovascular Medicine; Interuniversity Cardiology Institute of the Netherlands FX J.L. Januzzi, Roche Diagnostics, Siemens, Critical Diagnostics, and the Balson Scholarship Fund; S. Rehman, the Dennis and Marilyn Barry Fellowship in Cardiovascular Medicine; R.R.J. van Kimmenade, Interuniversity Cardiology Institute of the Netherlands. NR 38 TC 23 Z9 27 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD DEC PY 2010 VL 56 IS 12 BP 1814 EP 1821 DI 10.1373/clinchem.2010.146506 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 687EI UT WOS:000284759700010 PM 20921266 ER PT J AU Cramer, DW O'Rourke, DJ Vitonis, AF Matulonis, UA DiJohn-son, DA Sluss, PM Crum, CP Liu, BCS AF Cramer, Daniel W. O'Rourke, Dennis J. Vitonis, Allison F. Matulonis, Ursula A. DiJohn-son, Daniel A. Sluss, Patrick M. Crum, Christopher P. Liu, Brian C. -S. TI CA125 Immune Complexes in Ovarian Cancer Patients with Low CA125 Concentrations SO CLINICAL CHEMISTRY LA English DT Article ID SERUM CA-125 LEVELS; MUCIN; ANTIBODY; CARCINOMA; SURVIVAL; ANTIGEN; EPITOPE; CELL AB BACKGROUND: About 20% of women with ovarian cancer have low concentrations of serum cancer antigen 125 (CA125), and this important tumor marker cannot be used to monitor their disease. The measured concentration for mucin 1 (MUC1), or CA15-3, another tumor marker, can be lowered in breast and ovarian cancer patients when circulating immune complexes (CICs) containing antibodies bound to the free antigen are present. Because CA125 and MUC1 are related members of the mucin family, we sought to determine whether CICs might also exist for CA125 and interfere with its clinical assay. METHODS: We developed an antigen capture-based assay to determine the presence of CICs for CA125. We spotted mouse antibodies to CA125 onto nanoparticle slides, incubated them with patient serum, and added Cy5-tagged goat antihuman IgG antibodies. Fluorescence intensities were read and normalized to the intensities for glutathione S-transferase A1 as a control. RESULTS: Assay results for 23 ovarian cancer cases with high CA125 concentrations, 43 cases with low CA125 concentrations, and 19 controls (mean CA125 concentrations, 2706, 23, and 11 kilounits/L, respectively) revealed mean fluorescence intensities for CA125 CIC of 2.30, 2.72, and 1.99 intensity units (iu), respectively. A generalized linear model adjusted for batch and age showed higher CA125 CIC fluorescence intensities in low-CA125 cases than in high-CA125 cases (P = 0.03) and controls (P = 0.0005). Four ovarian cancer patients who had recurrent disease and always had low CA125 values had a mean CA125 CIC value of 3.06 iu (95% CI, 2.34-4.01 iu). CONCLUSIONS: These preliminary results suggest the existence of CICs involving CA125, which may help explain some ovarian cancer cases with low CA125 concentrations. C1 [Cramer, Daniel W.; Vitonis, Allison F.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [O'Rourke, Dennis J.; DiJohn-son, Daniel A.; Liu, Brian C. -S.] Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. [Matulonis, Ursula A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sluss, Patrick M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Crum, Christopher P.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Cramer, DW (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, 221 Longwood Ave, Boston, MA 02115 USA. EM dcramer@partners.org FU National Cancer Institute [P50 CA105009, R01 CA54419, 5U01 CA86381] FX D. W. Cramer, National Cancer Institute grants P50 CA105009 (Ovarian Cancer SPORE), R01 CA54419, and 5U01 CA86381 (Early Detection Research Network). NR 16 TC 7 Z9 7 U1 1 U2 3 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD DEC PY 2010 VL 56 IS 12 BP 1889 EP 1892 DI 10.1373/clinchem.2010.153122 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 687EI UT WOS:000284759700019 PM 20943848 ER PT J AU Valassi, E Biller, BMK Klibanski, A Swearingen, B AF Valassi, Elena Biller, Beverly M. K. Klibanski, Anne Swearingen, Brooke TI Clinical features of nonpituitary sellar lesions in a large surgical series SO CLINICAL ENDOCRINOLOGY LA English DT Article ID RATHKES CLEFT CYSTS; TRANSSPHENOIDAL SURGERY; PITUITARY SURGERY; PATHOLOGICAL FEATURES; METASTATIC TUMORS; CRANIOPHARYNGIOMA; HYPONATREMIA; EXPERIENCE; PREDICTORS; ADENOMAS AB P>Context Pituitary adenomas are the most common lesions in the sellar region, but other pathologies need to be considered in the differential diagnosis. Objective To assess the prevalence of unusual sellar masses in a large series of patients and identify clinicopathological factors that may aid the pre-operative diagnosis. Design Retrospective case series. Patients We analysed the records of 1469 transsphenoidal procedures performed between 1998 and 2009. One hundred sixteen cases (7 center dot 9%) were not pituitary adenomas. Measurements Final pathological diagnosis. Results One hundred sixteen patients (45 men, 71 women; mean age (+/- SD): 45 +/- 17 years) with nonadenomatous lesions were divided into four major aetiological groups: cystic lesions (CYS) (53%); benign neoplasms (BEN) (22%); malignancies (MAL) (16%) and inflammatory lesions (INF) (9%). Rathke's cysts, the most common lesions, represented 42% of all cases. Twenty-five per cent of malignant lesions were metastases, and some of the MAL (e.g., fibrosarcoma, lung metastasis) had a radiographical appearance suggestive of a pituitary adenoma. The most common presenting symptoms were visual field impairment (51%) and headache (34%). Pre-operative pituitary dysfunction was present in 58% of cases, with hyperprolactinaemia (35%), hypogonadism (23%) and hypocortisolism (23%) found most frequently. Postoperative resolution of headache and visual symptoms occurred in 63% and 65% of patients, respectively. Hyperprolactinaemia resolved in 77% of cases. Conclusions A substantial minority of sellar masses are not pituitary adenomas. While they frequently present with the symptoms, hormone abnormalities and radiographical appearance typical of pituitary tumours, the possibility of a nonadenomatous lesion needs to be considered in the differential diagnosis. C1 [Swearingen, Brooke] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Valassi, Elena; Biller, Beverly M. K.; Klibanski, Anne; Swearingen, Brooke] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Swearingen, B (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St, Boston, MA 02114 USA. EM BSwearingen@partners.org FU [ULI RR0257801] FX This work was supported in part by the following grant: ULI RR0257801. We appreciate statistical advice provided by Douglas Hayden of the Biostatistics Center, Massachusetts General Hospital and Harvard Medical School. NR 31 TC 13 Z9 14 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD DEC PY 2010 VL 73 IS 6 BP 798 EP 807 DI 10.1111/j.1365-2265.2010.03881.x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 681ND UT WOS:000284321700015 PM 20874772 ER PT J AU Lee, RJ Saylor, PJ Smith, MR AF Lee, Richard J. Saylor, Philip J. Smith, Matthew R. TI Contemporary Therapeutic Approaches Targeting Bone Complications in Prostate Cancer SO CLINICAL GENITOURINARY CANCER LA English DT Review DE Bisphosphonate; Denosumab; Osteoclast; RANKL; Toremifene; Zoledronic acid ID ANDROGEN-DEPRIVATION THERAPY; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; ORAL SODIUM CLODRONATE; ADVANCED MULTIPLE-MYELOMA; LONG-TERM EFFICACY; ZOLEDRONIC ACID; BREAST-CANCER; DOUBLE-BLIND; SKELETAL COMPLICATIONS AB Skeletal complications are major causes of morbidity in patients with prostate cancer. Despite the osteoblastic appearance of prostate cancer bone metastases, elevated serum and urinary markers of bone resorption are indicative of high osteoclast activity. Increased osteoclast activity is independently associated with subsequent skeletal complications, disease progression, and death. Osteoclast-targeted therapies aim to reduce the risk for disease-related skeletal complications, bone metastases, and treatment-related fractures. This review focuses on recent advances in osteoclast-targeted therapies in the treatment and prevention of bone complications in prostate cancer. Osteoclast-targeted therapies have been extensively studied in men with prostate cancer. The potent bisphosphonate zoledronic acid significantly decreased the risk of skeletal complications in men with castration-resistant prostate cancer and bone metastases, and is Federal Drug Administration approved for this indication. Denosumab is a human monoclonal antibody that inhibits receptor activator of nuclear factor-kappa B (RANK) ligand, a critical mediator of osteoclast differentiation, activation, and survival. Data from recent phase III clinic trials demonstrate the emerging role for denosumab in the treatment of prostate cancer bone metastases and prevention of fractures associated with androgen deprivation therapy. C1 [Lee, Richard J.; Saylor, Philip J.; Smith, Matthew R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Oncol,Canc Ctr, Boston, MA 02114 USA. RP Lee, RJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Oncol,Canc Ctr, 55 Fruit Sr,Yawkey 7E, Boston, MA 02114 USA. EM rjlee@partners.org FU NCI NIH HHS [K24 CA121990, K24 CA121990-05] NR 63 TC 13 Z9 15 U1 1 U2 3 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD DEC PY 2010 VL 8 IS 1 BP 29 EP 36 DI 10.3816/CGC.2010.n.005 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 700KV UT WOS:000285738600005 PM 21208853 ER PT J AU Gerding, DN Johnson, S AF Gerding, Dale N. Johnson, Stuart TI Management of Clostridium difficile Infection: Thinking Inside and Outside the Box SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID BOVINE IMMUNOGLOBULIN CONCENTRATE; RANDOMIZED CONTROLLED-TRIAL; TOXIN-BINDING POLYMER; INTRAVENOUS IMMUNOGLOBULIN; PSEUDOMEMBRANOUS COLITIS; MONOCLONAL-ANTIBODIES; METRONIDAZOLE THERAPY; FUSIDIC ACID; C-DIFFICILE; DIARRHEA AB Treatment of Clostridium difficile infection (CDI) has relied on 2 antimicrobial agents, metronidazole and vancomycin, since the recognition of this disease entity. While effective, these "inside the box" approaches to CDI management have the disadvantage of further microbial disruption of the host indigenous microflora. "Outside the box" therapies use non-antimicrobial approaches to management and are theoretically less prone to causing recurrent CDI episodes. Recent advances in understanding of "inside the box" approaches include appreciation of the decreased efficacy of metronidazole overall and the superior efficacy of vancomycin for treatment of severe CDI, as well as a new agent under development, fidaxomicin, which appears to be equal in efficacy to vancomycin but with less risk of subsequent CDI recurrences. Several "outside the box" approaches have also entered clinical development, including use of monoclonal antibodies, active vaccination, luminal toxin binders, and nontoxigenic C. difficile. These reports provide optimism that more-effective management of CDI is forthcoming. C1 [Gerding, Dale N.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Johnson, Stuart] Loyola Univ, Chicago Stritch Sch Med, Maywood, IL 60153 USA. RP Gerding, DN (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, 5000 S 5th Ave,POB 5000, Hines, IL 60141 USA. EM dale.gerding2@va.gov FU US Department of Veterans Affairs Research Service; Merck; ViroPharma; Optimer; Cepheid; Sanofi-Pasteur; GOJO FX US Department of Veterans Affairs Research Service (to D.N.G. and S.J.).; D.N.G. has served as a consultant for Astellas, Viropharma, Optimer, Cepheid, Merck, TheraDoc, Cubist, Actelion, and Medicines Co.; he holds research grants from Merck, ViroPharma, Optimer, Cepheid, Sanofi-Pasteur, and GOJO; and he holds patents for treatment of CDI licensed to ViroPharma. S.J. has served as a consultant for Astellas, Bio-K+, Viropharma, and Optimer. NR 74 TC 44 Z9 46 U1 3 U2 7 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 DEC 1 PY 2010 VL 51 IS 11 BP 1306 EP 1313 DI 10.1086/657116 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 675RZ UT WOS:000283850200015 PM 20979491 ER PT J AU Johansen, KL AF Johansen, Kirsten L. TI Association of Body Composition with Survival Among Patients on Hemodialysis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID DIALYSIS; MORTALITY; SIZE; WEIGHT; MASS C1 San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 111J,4150 Clement St, San Francisco, CA 94121 USA. EM kirsten.johansen@ucsf.edu NR 9 TC 1 Z9 1 U1 0 U2 0 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 DEC PY 2010 VL 5 IS 12 BP 2144 EP 2145 DI 10.2215/CJN.07950910 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 691LA UT WOS:000285080100003 PM 20947784 ER PT J AU Taylor, EN Stampfer, MJ Mount, DB Curhan, GC AF Taylor, Eric N. Stampfer, Meir J. Mount, David B. Curhan, Gary C. TI DASH-Style Diet and 24-Hour Urine Composition SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; KIDNEY-STONES; RISK-FACTORS; DIABETES-MELLITUS; OXALATE EXCRETION; PHYSICAL-ACTIVITY; CALCIUM INTAKE; WOMEN; DISEASE; HEALTH AB Background and objectives: We previously observed associations between a Dietary Approaches to Stop Hypertension (DASH)-style diet and large reductions in kidney stone risk. This study examined associations between a DASH-style diet and 24-hour excretions of urinary lithogenic factors. Design, setting, participants, & measurements: We studied 3426 participants with and without nephrolithiasis in the Health Professionals Follow-up Study (HPFS) and the Nurses' Health Studies (NHS) I and II. A dietary DASH score was based on seven components: high intake of fruits, vegetables, nuts and legumes, dairy products, and whole grains and low intake of sweetened beverages and red and processed meats. We used analysis of covariance to adjust for age, stone history, body size, and other factors. Results: Comparing participants in the highest to lowest quintiles of DASH score, multivariate-adjusted urinary calcium excretion was 3% greater in HPFS (P trend 0.12), 10% greater in NHS I (P trend <0.01), and 12% greater in NHS II (P trend 0.05). Urinary oxalate was 4% to 18% greater (P trend all <= 0.03), urinary citrate was 11% to 16% greater (P trend all <0.01), and urinary volume was 16% to 32% greater (P trend all <0.001). Higher DASH score was associated with higher urine potassium, magnesium, phosphate, and pH, and lower relative supersaturations (RSS) of calcium oxalate (women only) and uric acid. Conclusions: A DASH-style diet may reduce stone risk by increasing urinary citrate and volume. The small associations between higher DASH score and lower RSS suggest unidentified stone inhibitors in dairy products and/or plants. Clin J Am Soc Nephrol 5: 2315-2322, 2010. doi: 10.2215/CJN.04420510 C1 [Taylor, Eric N.] Maine Med Ctr, Div Nephrol & Transplantat, Portland, ME 04102 USA. [Taylor, Eric N.; Stampfer, Meir J.; Curhan, Gary C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02115 USA. [Mount, David B.; Curhan, Gary C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Renal Div, Boston, MA 02115 USA. [Stampfer, Meir J.; Curhan, Gary C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mount, David B.] VA Boston Healthcare Syst, Boston, MA USA. RP Taylor, EN (reprint author), Maine Med Ctr, Div Nephrol & Transplantat, 22 Bramhall St, Portland, ME 04102 USA. EM entaylor@partners.org FU National Institutes of Health [DK59583, DK70756, CA87969, CA55075, CA50385] FX We thank the study participants. Results from this study were presented orally at the 2009 annual meeting of the ROCK. (Research on Calculous Kinetics) society in Chaska, MN and in poster form at the Renal Week meeting of the American Society of Nephrology; October 27 through November 1, 2009 in San Diego, CA. This research was supported by grants DK59583, DK70756, CA87969, CA55075, and CA50385 from the National Institutes of Health. NR 30 TC 36 Z9 37 U1 0 U2 9 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 DEC PY 2010 VL 5 IS 12 BP 2315 EP 2322 DI 10.2215/CJN.04420510 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 691LA UT WOS:000285080100025 PM 20847091 ER PT J AU Evans, RW Applegate, WH Briscoe, DM Cohen, DJ Rorick, CC Murphy, BT Madsen, JC AF Evans, Roger W. Applegate, William H. Briscoe, David M. Cohen, David J. Rorick, Christopher C. Murphy, Barbara T. Madsen, Joren C. TI Cost-Related Immunosuppressive Medication Nonadherence Among Kidney Transplant Recipients SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID QUALITY-OF-LIFE; STAGE RENAL-DISEASE; ORGAN-TRANSPLANTATION; CYCLOSPORINE; DIALYSIS; MEDICINE; COVERAGE; CHILDREN AB Background and objectives: Immunosuppressive medications are essential in preventing kidney transplant rejection. Continuous insurance coverage for outpatient immunosuppressive medications remains a major issue. The objective of this study was to establish the prevalence and consequences of cost-related immunosuppressive medication nonadherence. Design, setting, participants, & measurements: A descriptive survey of all U.S. kidney transplant programs (n = 254) was conducted. The response rate for the survey exceeded 99%. The main outcome measures included the following: transplant recipient concerns related to medication costs, ability to pay for medications, medication nonadherence and its consequences, and failure of transplant centers to place patients on the transplant waiting list. Results: Continuous insurance coverage for outpatient immunosuppressive drugs is a problem having potentially grave consequences for the majority of kidney transplant recipients. More than 70% of kidney transplant programs report that their patients have an extremely or very serious problem paying for their medications. About 47% of the programs indicate that more than 40% of their patients are having difficulty paying for their immunosuppressive medications. In turn, 68% of the programs report deaths and graft losses attributable to cost-related immunosuppressive medication nonadherence. Some of the problems identified here are more significant for adult than pediatric patients. Conclusions: The prevalence and consequences of cost-related immunosuppressive medication nonadherence among kidney transplant recipients have now been documented. The results presented here should serve as the necessary impetus for the development of health care policies supporting Medicare coverage of immunosuppressive medications for the life of the transplanted kidney. Clin J Am Soc Nephrol 5: 2323-2328, 2010. doi: 10.2215/CJN.04220510 C1 [Evans, Roger W.] United Network Recruitment Transplantat Professio, Rochester, MN 55902 USA. [Applegate, William H.; Rorick, Christopher C.] Bryan Cave Strategies, Washington, DC USA. [Briscoe, David M.] Childrens Hosp, Boston, MA 02115 USA. [Cohen, David J.] Columbia Univ, Med Ctr, New York, NY USA. [Murphy, Barbara T.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Madsen, Joren C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Evans, RW (reprint author), United Network Recruitment Transplantat Professio, 2251 Baihly Hills Dr SW, Rochester, MN 55902 USA. EM Evans.Roger@Charter.net FU NIDDK NIH HHS [T32 DK007726] NR 35 TC 29 Z9 30 U1 1 U2 5 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 DEC PY 2010 VL 5 IS 12 BP 2323 EP 2328 DI 10.2215/CJN.04220510 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 691LA UT WOS:000285080100026 PM 20847093 ER PT J AU Reece, DE Vesole, DH Shrestha, S Zhang, MJ Perez, WS Dispenzieri, A Milone, GA Abidi, M Atkins, H Bashey, A Bredeson, CN Boza, WB Freytes, CO Gale, RP Gajewski, JL Gibson, J Hale, GA Kumar, S Kyle, RA Lazarus, HM McCarthy, PL Paylovsky, S Roy, V Weisdorf, DJ Wiernik, PH Hari, PN AF Reece, Donna E. Vesole, David H. Shrestha, Smriti Zhang, Mei-Jie Perez, Waleska S. Dispenzieri, Angela Milone, Gustavo A. Abidi, Muneer Atkins, Harold Bashey, Asad Bredeson, Christopher N. Bujan Boza, Willem Freytes, Cesar O. Gale, Robert Peter Gajewski, James L. Gibson, John Hale, Gregory A. Kumar, Shaji Kyle, Robert A. Lazarus, Hillard M. McCarthy, Philip L. Paylovsky, Santiago Roy, Vivek Weisdorf, Daniel J. Wiernik, Peter H. Hari, Parameswaran N. TI Outcome of Patients With IgD and IgM Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Retrospective CIBMTR Study SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Article DE Autotransplantations; IgA; IgG; Immunoglobulin isotype ID HIGH-DOSE CHEMOTHERAPY; THERAPY AB Introduction: Immunoglobulin D (IgD) and IgM multiple myeloma represent uncommon immunoglobulin isotypes, accounting for 2% and 0.5% of cases, respectively. Limited information is available regarding the prognosis of these isotypes, but they have been considered to have a more aggressive course than the more common immunoglobulin G (IgG) and IgA isotypes. In particular, the outcome after autologous hematopoietic stem cell transplantation (auto-HOT) has not been well defined. Patients and Methods: Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified 36 patients with IgD and 11 patients with IgM myeloma among 3578 myeloma patients who received intensive therapy and auto-HOT over a 10-year period. Results: The progression-free and overall survival probabilities at 3 years were 38% (95% CI, 21%-56%) and 69% (95% CI, 51%-84%) for IgD myeloma, and 47% (95% CI, 17%-78%) and 68% (95% CI, 36%-93%), respectively, for IgM disease. Although formal statistical analysis was limited by the small sample size, these results were comparable to those for IgG and IgA patients autografted during the same time period. Transplantation-related mortality and disease relapse/progression of myeloma were also similar for all isotypes. Conclusion: This analysis demonstrates comparable outcomes in all immunoglobulin isotypes. Therefore, auto-HOT should be offered to eligible patients with IgD and IgM myeloma. C1 [Reece, Donna E.] Princess Margaret Hosp, Toronto, ON M5G 2M9, Canada. [Vesole, David H.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Shrestha, Smriti; Zhang, Mei-Jie; Perez, Waleska S.; Hari, Parameswaran N.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Dispenzieri, Angela; Kumar, Shaji; Kyle, Robert A.] Mayo Clin, Rochester, MN USA. [Milone, Gustavo A.; Paylovsky, Santiago] Fundaleu, Buenos Aires, DF, Argentina. [Abidi, Muneer] Wayne State Univ Hosp, Karmanos Canc Inst, Detroit, MI USA. [Atkins, Harold] Ottawa Gen Hosp, Ottawa, ON K1H 8L6, Canada. [Bashey, Asad] Blood & Marrow Transplant Grp GA, Atlanta, GA USA. [Bredeson, Christopher N.] Froedtert Mem Lutheran Hosp, Milwaukee, WI USA. [Bujan Boza, Willem] Hosp Mexico, San Jose, Costa Rica. [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. [Gajewski, James L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Gibson, John] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia. [Hale, Gregory A.] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Roy, Vivek] Mayo Clin, Jacksonville, FL 32224 USA. [Weisdorf, Daniel J.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Wiernik, Peter H.] New York Med Coll, New York, NY USA. RP Reece, DE (reprint author), Princess Margaret Hosp, 610 Univ Ave,Ste 5-207, Toronto, ON M5G 2M9, Canada. EM donna.reece@uhn.on.ca RI Kumar, Shaji/A-9853-2008; OI Kumar, Shaji/0000-0001-5392-9284; Abidi, Muneer/0000-0002-9936-6031; Hari, Parameswaran/0000-0002-8800-297X; Dispenzieri, Angela/0000-0001-8780-9512 FU National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and Blood Institute (NHLBI) [5U01HL069294]; National Institute of Allergy and Infectious Diseases (NIAID); Health Resources and Services Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; AABB; Aetna; American Society for Blood and Marrow Transplantation; Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US, Inc.; Baxter International, Inc.; Bayer HealthCare Pharmaceuticals; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Buchanan Family Foundation; Canadian Blood and Marrow Transplant Group; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Centers for Disease Control and Prevention; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals; Cylex Inc.; CytoTherm; DOR BioPharma, Inc.; Dynal Biotech; Eisai, Inc.; Enzon Pharmaceuticals, Inc.; European Group for Blood and Marrow Transplantation; Gamida Cell, Ltd.; GE Healthcare; Genentech, Inc.; Genzyme Corporation; Histogenerics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery Co., Ltd.; The Leukemia & Lymphoma Society; Merck Company; The Medical College of Wisconsin; MGI Pharrna, Inc.; Michigan Community Blood Centers; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman 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 America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer Inc; Saladax Biomedical, Inc.; Schering Corporation; Society for Healthcare Epidemiology of America; Soligenix, Inc.; StemCyte, Inc.; StemSoft Software, Inc.; Sysmex America, Inc.; THERAKOS, Inc.; Thermogenesis Corporation; Vidacare Corporation; Vion Pharmaceuticals, Inc.; ViraCor Laboratories; ViroPharma, Inc.; Wellpoint, Inc.; Merck Co., Inc.; American Cancer Society; V Foundation for Cancer Research; Cephalon, Inc.; Novartis Pharmaceuticals Corporation FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); 2 Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from AABB; Aetna; American Society for Blood and Marrow Transplantation; Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US, Inc.; Baxter International, Inc.; Bayer HealthCare Pharmaceuticals; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Buchanan Family Foundation; Canadian Blood and Marrow Transplant Group; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Centers for Disease Control and Prevention; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals; Cylex Inc.; CytoTherm; DOR BioPharma, Inc.; Dynal Biotech, an Invitrogen Company; Eisai, Inc.; Enzon Pharmaceuticals, Inc.; European Group for Blood and Marrow Transplantation; Gamida Cell, Ltd.; GE Healthcare; Genentech, Inc.; Genzyme Corporation; Histogenerics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery Co., Ltd.; The Leukemia & Lymphoma Society; Merck & Company; The Medical College of Wisconsin; MGI Pharrna, Inc.; Michigan Community Blood Centers; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman 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 America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer Inc; Saladax Biomedical, Inc.; Schering Corporation; Society for Healthcare Epidemiology of America; Soligenix, Inc.; StemCyte, Inc.; StemSoft Software, Inc.; Sysmex America, Inc.; THERAKOS, Inc.; Thermogenesis Corporation; Vidacare Corporation; Vion Pharmaceuticals, Inc.; ViraCor Laboratories; ViroPharma, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, or any other agency of the U.S. Government.; Angela Dispenzieri has received research funding and honoraria from Celgene Corporation. Muneer Abidi has received research funding from Merck & Co., Inc.; has served as a concultant or been on an advisory/research panel for Millennium Pharmaceuticals, inc.; and has served as a member of a Speaker's Bureau for Genzyme Corporation and Millennium Pharmaceuticals, Inc. Gregory A. Hale has received research/grant funding from that American Cancer Society and the V Foundation for Cancer Research. Shaji Kumar has received research funding/clinical trial support from Celgene Corporation, Cephalon, Inc., Genzyme Corporation, Millennium Pharmaceuticals, Inc., and Novartis Pharmaceuticals Corporation; and has served as a consultant or been on an advisory/research panel for Merck & Co., Inc. Peter H. Wiernik has recieved research funding from and served on a Speaker's Bureau for Celgene Corporation, and has served as a consultant or been on an advisory/research panel for Celgene Corporation, Novartis Pharmaceuticals Corporation, and Pfizer Inc. The remaining authors have no relevant relationships to disclose. NR 17 TC 7 Z9 11 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD DEC PY 2010 VL 10 IS 6 BP 458 EP 463 DI 10.3816/CLML.2010.n.078 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 690RV UT WOS:000285024300006 PM 21156462 ER PT J AU Gautschi, OP Schlett, CL Fournier, JY Cadosch, D AF Gautschi, Oliver P. Schlett, Christopher L. Fournier, Jean-Yves Cadosch, Dieter TI Laboratory confirmed polymethyl-methacrylate (Palacos (R))-hypersensitivity after cranioplasty SO CLINICAL NEUROLOGY AND NEUROSURGERY LA English DT Article DE Bone cement; Acrylic resins; Polymethyl-methacrylate; Allergic reaction; Delayed-type hypersensitivity reaction; Cranioplasty ID ALLERGY AB Polymethyl-methacrylate (PMMA) as part of bone cement is a widely used material in the context of orthopaedic implants and also in cranioplasty Although PMMA is characterised by excellent biocompatibility with low intrinsic toxicity and inflammatory activation a minor portion of patients develop allergic reactions We present the case of a 39-year-old woman with an increasing headache and a corresponding erythema over the parieto-occipital cranioplasty which was performed 42 days prior using a PMMA compound A patch test specific for bone cement components confirmed the diagnosis of a PMMA delayed-type hypersensitivity reaction The prevalence of allergic reactions to bone cement components are known to vary from between 06% and 1 6% however no adequate, pre-interventional diagnostic tool is currently available Therefore physicians are required to consider this differential diagnosis even after an extremely delayed onset of symptoms This case describes the first ever-reported case in the literature of hypersensitivity to bone cement cranioplasty (C) 2010 Elsevier B V All rights reserved C1 [Gautschi, Oliver P.; Fournier, Jean-Yves] Cantonal Hosp St Gallen, Dept Neurosurg, CH-9000 St Gallen, Switzerland. [Schlett, Christopher L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac CT MR PET Imaging Program, Boston, MA USA. [Cadosch, Dieter] Univ Western Australia, Sch Anat & Human Biol, Crawley, WA, Australia. RP Gautschi, OP (reprint author), Cantonal Hosp St Gallen, Dept Neurosurg, Rorschacher Str 95, CH-9000 St Gallen, Switzerland. NR 3 TC 8 Z9 8 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0303-8467 J9 CLIN NEUROL NEUROSUR JI Clin. Neurol. Neurosurg. PD DEC PY 2010 VL 112 IS 10 BP 915 EP 916 DI 10.1016/j.clineuro.2010.07.013 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 689GV UT WOS:000284916500016 PM 20719430 ER PT J AU Isler, JR Martien, KM Grieve, PG Stark, RI Herbert, MR AF Isler, J. R. Martien, K. M. Grieve, P. G. Stark, R. I. Herbert, M. R. TI Reduced functional connectivity in visual evoked potentials in children with autism spectrum disorder SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Autism; Coherence; EEG; Power; Synchrony; Connectivity ID OSCILLATORY RESPONSES; NEURONAL OSCILLATIONS; TOP-DOWN; EEG; SYNCHRONIZATION; COHERENCE; INDIVIDUALS; STIMULUS; CORTEX; UNDERCONNECTIVITY AB Objective: An analysis of EEG synchrony between homologous early visual areas tested the hypothesis that interhemispheric functional connectivity during visual stimulation is reduced in children with autism compared to controls. Methods: EEG power and coherence within and between two homologous regions of the occipital cortex were measured during long latency flash visual evoked potentials. Measures were compared between two groups of children (5.5-8.5 years), one with autism spectrum disorders and the other with typical development. Results: In and below the theta band, interhemispheric synchrony was reduced in autistic subjects compared to typical controls by as much as 50%. Above the theta band interhemispheric synchrony in autistic children became indistinguishable from what would occur for uncorrelated cortical activity. Interhemispheric synchrony in autistic subjects was decreased in spite of bilaterally increased power. Wavelet power showed autistic children had a more rapid initial response to stimulation, a slower recovery, and more modulation at longer latencies. Conclusions: Results suggest that the sensory cortices of autistic children are hypersensitive to stimulation with concurrent diminished functional connectivity between hemispheres. Significance: Simultaneously increased intrahemispheric power and decreased interhemispheric synchronization of elemental visual information suggests either that power increases cause poor interhemispheric connectivity or that processes, such as thalamocortical regulation, impact power and coherence independently. (C) 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Isler, J. R.] Columbia Univ, Coll Phys & Surg, Dept Pediat, New York, NY 10032 USA. [Martien, K. M.] Massachusetts Gen Hosp, Dept Pediat, LADDERS Clin, Lurie Family Autism Ctr, Boston, MA 02114 USA. [Herbert, M. R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Martien, K. M.; Herbert, M. R.] Massachusetts Gen Hosp, TRANSCEND Res Program, Boston, MA 02114 USA. RP Isler, JR (reprint author), Columbia Univ, Coll Phys & Surg, Dept Pediat, P&S 3-440,630 W 168th St, New York, NY 10032 USA. EM jri2101@columbia.edu FU National Institutes of Health [NINDS 5K25NS052230]; Nancy Lurie Marks Family Foundation; National Alliance for Autism Research; Commonwealth Fund FX This work was supported by the National Institutes of Health [Grant No. NINDS 5K25NS052230], Cure Autism Now/Autism Speaks, the Nancy Lurie Marks Family Foundation, the National Alliance for Autism Research, and The Commonwealth Fund. The authors thank Professor Jerome Kagan of Harvard University, Dr. Charles Schroeder of Columbia University and the Nathan Kline Institute, and Dr. Michael Meyers and Dr. Amanda Tarullo of Columbia University for helpful comments. NR 49 TC 38 Z9 38 U1 4 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD DEC PY 2010 VL 121 IS 12 BP 2035 EP 2043 DI 10.1016/j.clinph.2010.05.004 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 672OV UT WOS:000283596800010 PM 20605520 ER PT J AU Nunez, F Vranceanu, AM Ring, D AF Nunez, Fiesky Vranceanu, Ana-Maria Ring, David TI Determinants of Pain in Patients with Carpal Tunnel Syndrome SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID CHRONIC MUSCULOSKELETAL PAIN; PRIMARY-CARE; CATASTROPHIZING SCALE; DEPRESSION; VALIDATION; ANXIETY AB Background Carpal tunnel syndrome causes numbness, weakness, and atrophy. Pain without numbness is not characteristic of this disease. Questions/purposes We tested the hypothesis that among patients with carpal tunnel syndrome confirmed by electrophysiologic testing, pain catastrophizing and/or depression would be good predictors of pain intensity at the time of diagnosis, whereas nerve conduction velocity would not. Patients and Methods Fifty-four patients completed a measure of tendency to misinterpret pain, a measure of depressive symptoms, anxiety about pain, self-efficacy in response to pain, and a five-point Likert measure of pain intensity. One-tailed Spearman correlation was performed to find a correlation between pain and continuous variables. One-way ANOVA was performed to assess differences between categorical variables. For each group, all variables with significant correlations with pain intensity were included in a multiple linear regression analysis. Results Sex, age, and electrophysiologic measures did not correlate with pain intensity. All measures of illness behavior correlated with pain intensity and were entered in a multiple linear regression model; only misinterpretation of nociception and depression were significantly associated and accounted for 39% of the variation in pain intensity. Conclusions Illness behavior (specifically depression and misinterpretation of nociception) predicts pain intensity in patients with carpal tunnel syndrome. C1 [Nunez, Fiesky; Vranceanu, Ana-Maria; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU American Orthopedics Foundation FX One or more of the authors (DR) received an unrestricted fund from the American Orthopedics Foundation. NR 20 TC 19 Z9 19 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2010 VL 468 IS 12 BP 3328 EP 3332 DI 10.1007/s11999-010-1551-x PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 735TJ UT WOS:000288440700026 PM 20811788 ER PT J AU Chang, MH Kish, TD Fung, HB AF Chang, Mei H. Kish, Troy D. Fung, Horatio B. TI Telavancin: A Lipoglycopeptide Antimicrobial for the Treatment of Complicated Skin and Skin Structure Infections Caused by Gram-Positive Bacteria in Adults SO CLINICAL THERAPEUTICS LA English DT Article DE telavancin; lipoglycopeptide; glycopeptides; complicated skin and skin structure infection ID RESISTANT STAPHYLOCOCCUS-AUREUS; IN-VITRO ACTIVITY; SOFT-TISSUE INFECTIONS; METHICILLIN-RESISTANT; VANCOMYCIN-INTERMEDIATE; HEALTHY-SUBJECTS; UNITED-STATES; MURINE MODEL; INTRAVENOUS TELAVANCIN; DOSE PHARMACOKINETICS AB Background: Telavancin, a lipoglycopeptide antibiotic, is a semisynthetic derivative of vancomycin. It was approved by the US Food and Drug Administration (FDA) in 2009 for the treatment of complicated skin and skin structure infections (cSSSIs) caused by gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Objective: This article summarizes the pharmacology, in vitro and in vivo activity, pharmacokinetic properties, and clinical efficacy and tolerability of telavancin. Methods: Relevant information was identified through a search of MEDLINE (1966 August 2010), Iowa Drug Information Service (1966 August 2010), International Pharmaceutical Abstracts (1970 August 2010), and Google Scholar using the terms telavancin, lipoglycopeptide, and TD-6424. Abstracts and posters from scientific meetings, as well as documents submitted by the manufacturer of telavancin to the FDA as part of the approval process, were consulted. In vivo and in vitro experimental and clinical studies and review articles that provided information on the activity, mechanism of action, pharmacologic and pharmacokinetic properties, clinical efficacy, and tolerability of telavancin were reviewed. Results: In vitro, telavancin has potent activity against S aureus, including methicillin-resistant strains; Streptococcus pneumoniae; and vancomycin-susceptible enterococci with MICs generally <1 mu g/mL. Telavancin appears to have a dual mechanism of action, inhibiting cell wall formation and disrupting the cell membrane. In Phase III studies (ATLAS 1 and ATLAS 2), telavancin was found to be noninferior to vancomycin, with clinical cure rates of 88.3% and 87.1%, respectively, in clinically evaluable patients in the treatment of cSSSIs (difference, 1.2%; 95% CI, -2.1 to 4.6; P = NS). The effectiveness of telavancin in the treatment of hospital-acquired pneumonia was assessed in 2 Phase III studies (ATTAIN 1 and ATTAIN 2). Preliminary findings were that the effectiveness of telavancin was not significantly different from that of vancomycin, with cure rates of 82.7% and 80.9% in the clinically evaluable population, respectively (difference, 1.8%; 95% CI, -4.1 to 7.7; P = NS). The most commonly (>10%) reported adverse events included taste disturbances, nausea, headache, vomiting, foamy urine, constipation, and insomnia. Conclusion: In clinical trials, the effectiveness of telavancin was not significantly different from that of vancomycin in the treatment of cSSSIs, and telavancin was generally well tolerated. (Clin Ther. 2010;32: 2160-2185) (C) 2010 Elsevier HS Journals, Inc. C1 [Chang, Mei H.; Fung, Horatio B.] James J Peters Vet Affairs Med Ctr, Serv Pharm, Bronx, NY 10468 USA. [Kish, Troy D.] Long Isl Univ, Arnold & Marie Schwartz Coll Pharm & Hlth Sci, Brooklyn, NY USA. RP Chang, MH (reprint author), James J Peters Vet Affairs Med Ctr, Pharm Serv 119, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Mei.Chang2@va.gov NR 102 TC 12 Z9 14 U1 0 U2 8 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD DEC PY 2010 VL 32 IS 13 BP 2160 EP 2185 DI 10.1016/j.clinthera.2010.12.005 PG 26 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 713DK UT WOS:000286715000003 PM 21316534 ER PT J AU Ziakas, PD Kourbeti, IS Voulgarelis, M Mylonakis, E AF Ziakas, Panayiotis D. Kourbeti, Irene S. Voulgarelis, Michael Mylonakis, Eleftherios TI Effectiveness of Systemic Antifungal Prophylaxis in Patients With Neutropenia After Chemotherapy: A Meta-Analysis of Randomized Controlled Trials SO CLINICAL THERAPEUTICS LA English DT Review DE antifungal prophylaxis; chemotherapy; meta-analysis; neutropenia ID MARROW TRANSPLANT RECIPIENTS; PLACEBO-CONTROLLED TRIAL; INVASIVE FUNGAL-INFECTIONS; LIPOSOMAL AMPHOTERICIN-B; STEM-CELL TRANSPLANTS; DOUBLE-BLIND; FLUCONAZOLE PROPHYLAXIS; CANCER-PATIENTS; HEMATOLOGIC MALIGNANCIES; ACUTE-LEUKEMIA AB Background: Invasive fungal infections are responsible for substantial morbidity and mortality among patients with neutropenia after chemotherapy. Objective: This meta-analysis was conducted to estimate the effect of systemic antifungal prophylaxis on the frequency of invasive fungal infections in patients with neutropenia and the mortality associated with these infections. Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through September 15, 2010, for English-language publications of randomized controlled trials that compared systemic antifungal prophylaxis with placebo or no treatment in patients with neutropenia. Studies involving nonsystemic antifungal agents, direct comparisons of antifungal agents, and empirical, preemptive, or salvage treatment were excluded. Data were extracted according to European Organization for Research and Treatment of Cancer definitions of proven, possible, or probable fungal infections. Effect measures were reported as odds ratios (ORs) for fungal infection and mortality. Outcomes were pooled using random-effects meta-analysis. Study quality was assessed based on the study setting (single center or multicenter), institutional review board approval/informed consent, randomization, description of allocation concealment, double blinding, and reporting of dropouts. Results: Twenty-six trials including a total of 3979 patients were included in the meta-analysis. Antifungal prophylaxis was associated with significant reductions in proven fungal infections (OR = 0.43; 95% CI, 0.31-0.60; number needed to treat [NNT] = 20) and mortality attributed to fungal infections (OR = 0.49; 95% CI, 0.30-0.80; NNT = 53). Overall mortality was not affected by antifungal prophylaxis (OR = 0.92; 95% CI, 0.74-1.14). Antifungal prophylaxis was associated with a reduction in risk for proven Candida infections (OR = 0.28; 95% CI, 0.20-0.38), but not for aspergillosis or zygomycosis. Antifungal prophylaxis was also associated with a decreased need for antifungal therapy (OR = 0.64; 95% CI, 0.48-0.86). In an explanatory subgroup analysis of major outcomes, only recipients of a hematopoietic stem cell transplant (HSCT) had a significant likelihood of benefiting from antifungal prophylaxis in terms of reductions in risk for proven infections (OR = 0.27; 95% CI, 0.16-0.44) and mortality attributed to infections (OR = 0.41; 95% CI, 0.21-0.81). A metaregression analysis indicated that a multicenter (vs single-center) design and a double-blind (vs unblinded) design were significant moderators of the effect of antifungal prophylaxis on overall mortality and proven systemic fungal infections, respectively. Conclusions: Systemic antifungal prophylaxis was associated with a reduction in proven fungal infections and mortality attributed to these infections in patients with neutropenia after chemotherapy. In the setting of HSCT, antifungal prophylaxis was associated with reductions in both proven infections and mortality attributed to infections. There was no significant association between antifungal prophylaxis and overall mortality. (Clin Ther. 2010;32:2316-2336) (C) 2010 Elsevier HS Journals, Inc. C1 [Ziakas, Panayiotis D.; Voulgarelis, Michael] Univ Athens, Sch Med, Dept Pathophysiol, Athens 11527, Greece. [Kourbeti, Irene S.] Chalkida Gen Hosp, Dept Internal Med, Chalkida, Greece. [Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Mylonakis, Eleftherios] Harvard Univ, Sch Med, Boston, MA USA. RP Ziakas, PD (reprint author), Univ Athens, Sch Med, Dept Pathophysiol, M Asias 75 Goudi, Athens 11527, Greece. EM zpanos@otenet.gr FU Astellas Pharma US, Inc. FX Dr. Mylonakis has received research support from Astellas Pharma US, Inc., and has served on the speakers' bureau of Pfizer Inc. The authors have indicated that they have no other conflicts of interest with regard to the content of this article. NR 75 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD DEC PY 2010 VL 32 IS 14 BP 2316 EP 2336 DI 10.1016/j.clinthera.2011.01.009 PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 738LE UT WOS:000288640500004 PM 21353103 ER PT J AU Deo, RC MacRae, CA AF Deo, Rahul C. MacRae, Calum A. TI Clinical Screening and Genetic Testing SO CLINICS IN LABORATORY MEDICINE LA English DT Article DE Genetic screening; Penetrance; Mendelian disorders; Genetic architecture ID RIGHT-VENTRICULAR DYSPLASIA/CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY; DILATED CARDIOMYOPATHY; PLAKOPHILIN-2 MUTATIONS; ATRIOVENTRICULAR-BLOCK; SUDDEN-DEATH; PREVALENCE; FAMILIES; DISEASE AB Clinical screening is most effective in diseases in which the disease is in its earliest form and may not have symptoms or signs but can be readily diagnosed with an inexpensive, noninvasive test. This article discusses the general principles of genetic disease architecture that can guide screening and diagnostic approaches for all of the cardiomyopathies and inherited diseases. It addresses how the genetic architecture of the trait guides, and how clinical characteristics of the disease influence, a clinical screening approach. C1 [MacRae, Calum A.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Deo, Rahul C.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP MacRae, CA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM camacrae@bics.bwh.harvard.edu FU NHLBI NIH HHS [R01 HL075431] NR 38 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD DEC PY 2010 VL 30 IS 4 BP 775 EP + DI 10.1016/j.cll.2010.07.003 PG 11 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 658ZH UT WOS:000282534100002 PM 20832651 ER PT J AU Kalia, SK Kalia, LV McLean, PJ AF Kalia, S. K. Kalia, L. V. McLean, P. J. TI Molecular Chaperones as Rational Drug Targets for Parkinson's Disease Therapeutics SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE Bcl-2 associated athanogene (BAG) family; C-terminal Hsp70 interacting protein (CHIP); chaperones; co-chaperones; heat shock protein (Hsp); Hsp90 inhibitors; neurodegeneration; Parkinson's disease ID HEAT-SHOCK PROTEINS; ALPHA-SYNUCLEIN AGGREGATION; AMYOTROPHIC-LATERAL-SCLEROSIS; STRESS-INDUCED APOPTOSIS; BULBAR MUSCULAR-ATROPHY; E3 UBIQUITIN LIGASE; MOUSE MODEL; ANDROGEN RECEPTOR; HSP90 INHIBITOR; QUALITY-CONTROL AB Parkinson's disease is a neurodegenerative movement disorder that is caused, in part, by the loss of dopaminergic neurons within the substantia nigra pars compacta of the basal ganglia. The presence of intracellular protein aggregates, known as Lewy bodies and Lewy neurites, within the surviving nigral neurons is the defining neuropathological feature of the disease. Accordingly, the identification of specific genes mutated in families with Parkinson's disease and of genetic susceptibility variants for idiopathic Parkinson's disease has implicated abnormalities in proteostasis, or the handling and elimination of misfolded proteins, in the pathogenesis of this neurodegenerative disorder. Protein folding and the refolding of misfolded proteins are regulated by a network of interactive molecules, known as the chaperone system, which is composed of molecular chaperones and co-chaperones. The chaperone system is intimately associated with the ubiquitin-proteasome system and the autophagy-lysosomal pathway which are responsible for elimination of misfolded proteins and protein quality control. In addition to their role in proteostasis, some chaperone molecules are involved in the regulation of cell death pathways. Here we review the role of the molecular chaperones Hsp70 and Hsp90, and the co-chaperones Hsp40, BAG family members such as BAG5, CHIP and Hip in modulating neuronal death with a focus on dopaminergic neurodegeneration in Parkinson's disease. We also review current progress in preclinical studies aimed at targetting the chaperone system to prevent neurodegeneration. Finally, we discuss potential future chaperone-based therapeutics for the symptomatic treatment and possible disease modification of Parkinson's disease. C1 [Kalia, S. K.; Kalia, L. V.; McLean, P. J.] Harvard Univ, Sch Med, MassGen Inst Neurodegenerat Dis, Massachusetts Gen Hosp,Dept Neurol, Charlestown, MA 02129 USA. [Kalia, S. K.] Univ Toronto, Dept Surg, Div Neurosurg, Toronto, ON, Canada. [Kalia, L. V.] Univ Toronto, Dept Med, Div Neurol, Toronto, ON, Canada. RP McLean, PJ (reprint author), Harvard Univ, Sch Med, MassGen Inst Neurodegenerat Dis, Massachusetts Gen Hosp,Dept Neurol, 114 16th St, Charlestown, MA 02129 USA. EM pmclean@partners.org FU NIH/NINDS [NS063963]; Michael J. Fox Foundation FX PJM is supported by NIH/NINDS NS063963 and research grants from the Michael J. Fox Foundation. NR 171 TC 46 Z9 48 U1 1 U2 20 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PD DEC PY 2010 VL 9 IS 6 BP 741 EP 753 PG 13 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 685HZ UT WOS:000284621100009 PM 20942788 ER PT J AU Blazhenkova, O Kozhevnikov, M AF Blazhenkova, Olesya Kozhevnikov, Maria TI Visual-object ability: A new dimension of non-verbal intelligence SO COGNITION LA English DT Article DE Visual imagery; Intelligence; Visual-object ability; Visual spatial ability ID SPATIAL MENTAL-IMAGERY; GENERAL INTELLIGENCE; COGNITIVE-ABILITIES; SEX-DIFFERENCES; WORKING-MEMORY; P-FIT; VISUALIZATION; TASK; METAANALYSIS; ACHIEVEMENT AB The goal of the current research was to introduce a new component of intelligence: visual-object intelligence, that reflects one's ability to process information about visual appearances of objects and their pictorial properties (e.g., shape, color and texture) as well as to demonstrate that it is distinct from visual spatial intelligence, which reflects one's ability to process information about spatial relations and manipulate objects in space. Study 1 investigated the relationship between performance on various measures of visual-object and visual spatial abilities, and areas of specialization (visual art, science and humanities). Study 2 examined qualitative differences in approaches to interpreting visual abstract information between visual artists, scientists and humanities/social science professionals. Study 3 investigated qualitative differences in visual-object versus visual spatial processing by examining how members of different professions generate, transform, inspect, and manipulate visual images. The results of the three studies demonstrated that visual-object ability satisfies the requirements of an independent component of intelligence: (1) it uniquely relates to specialization in visual art; (2) it supports processing of abstract visual-object information; and (3) it has unique quantitative and qualitative characteristics, distinct from those of visual spatial processing. (C) 2010 Elsevier B.V. All rights reserved. C1 [Kozhevnikov, Maria] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Blazhenkova, Olesya] Natl Univ Singapore, Dept Psychol, Singapore 117548, Singapore. RP Kozhevnikov, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM mkozhevn@nmr.mgh.harvard.edu RI Blazhenkova, Olesya/H-8367-2016 OI Blazhenkova, Olesya/0000-0002-9513-7258 NR 97 TC 26 Z9 27 U1 3 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0010-0277 J9 COGNITION JI Cognition PD DEC PY 2010 VL 117 IS 3 BP 276 EP 301 DI 10.1016/j.cognition.2010.08.021 PG 26 WC Psychology, Experimental SC Psychology GA 687AP UT WOS:000284746300003 PM 20887982 ER PT J AU Mendez, MF Kremen, SA Tsai, PH Shapira, JS AF Mendez, Mario F. Kremen, Sarah A. Tsai, Po-Heng Shapira, Jill S. TI Interhemispheric Differences in Knowledge of Animals Among Patients With Semantic Dementia SO COGNITIVE AND BEHAVIORAL NEUROLOGY LA English DT Article DE semantic dementia; animate-inanimate; prosopagnosia ID HERPES-SIMPLEX ENCEPHALITIS; FRONTOTEMPORAL LOBAR DEGENERATION; SENSORY QUALITY CATEGORIES; LIVING THINGS; ALZHEIMERS-DISEASE; TEMPORAL LOBECTOMY; RECOGNITION DISORDERS; NAMING DEFICIT; NEURAL BASIS; BRAIN AB Objective: To investigate interhemispheric differences on naming and fluency tasks for living versus nonliving things among patients with semantic dementia (SD). Background: In SD, left-temporal involvement impairs language and word comprehension, and right-temporal involvement impairs facial recognition. There may be other interhemispheric differences, particularly in the animate-inanimate dichotomy. Method: On the basis of magnetic resonance imaging (MRI) ratings of anterior temporal atrophy, 36 patients who met criteria for SD were divided into 21 with left-predominant and 11 with right-predominant involvement (4 others were too symmetric for analysis). The left and right-predominant groups were compared on naming, fluency, and facial recognition tests. Results: Consistent with greater language impairment, the left-predominant patients had worse naming, especially inanimate and letter fluency, than the right-predominant patients. In contrast, difference in scores suggested selective impairment of animal naming, animal name fluency, and semantic knowledge for animate items among the right-predominant patients. Proportionally more right than left-predominant patients misnamed animal items and faces. Conclusions: These findings support interhemispheric differences in animal knowledge. Whereas left-predominant SD equally affects animate and inanimate words from language involvement, right-predominant SD, with greater sparing of language, continues to impair other semantic aspects of animals. The right anterior temporal region seems to make a unique contribution to knowledge of living things. C1 [Mendez, Mario F.] VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit, Los Angeles, CA 90073 USA. [Mendez, Mario F.; Kremen, Sarah A.; Tsai, Po-Heng; Shapira, Jill S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Mendez, Mario F.; Kremen, Sarah A.; Tsai, Po-Heng; Shapira, Jill S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, 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 [R01AG034499-02] FX This study was supported by grant # R01AG034499-02. NR 73 TC 6 Z9 6 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1543-3633 J9 COGN BEHAV NEUROL JI Cogn. Behav. Neurol. PD DEC PY 2010 VL 23 IS 4 BP 240 EP 246 DI 10.1097/WNN.0b013e3181f22448 PG 7 WC Behavioral Sciences; Clinical Neurology SC Behavioral Sciences; Neurosciences & Neurology GA 692OC UT WOS:000285161100005 PM 21042206 ER PT J AU Condeelis, J Weissleder, R AF Condeelis, John Weissleder, Ralph TI In Vivo Imaging in Cancer SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID RED FLUORESCENT PROTEIN; OPTICAL PARAMETRIC OSCILLATOR; POSITRON-EMISSION-TOMOGRAPHY; DISK CONFOCAL MICROSCOPY; ENHANCED CELL MOTILITY; PRIMARY MAMMARY-TUMORS; BREAST-CANCER; NUDE-MOUSE; MULTIPHOTON MICROSCOPY; INTRAVITAL MICROSCOPY AB Imaging has become an indispensable tool in the study of cancer biology and in clinical prognosis and treatment. The rapid advances in high resolution fluorescent imaging at single cell level and MR/PET/CT image registration, combined with new molecular probes of cell types and metabolic states, will allow the physical scales imaged by each to be bridged. This holds the promise of translation of basic science insights at the single cell level to clinical application. In this article, we describe the recent advances in imaging at the macro-and micro-scale and how these advances are synergistic with new imaging agents, reporters, and labeling schemes. Examples of new insights derived from the different scales of imaging and relevant probes are discussed in the context of cancer progression and metastasis. C1 [Condeelis, John] Yeshiva Univ Albert Einstein Coll Med, Gruss Lipper Biophoton Ctr, Program Microenvironm & Metastasis, Bronx, NY 10461 USA. [Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA. RP Condeelis, J (reprint author), Yeshiva Univ Albert Einstein Coll Med, Gruss Lipper Biophoton Ctr, Program Microenvironm & Metastasis, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM condeeli@aecom.yu.edu FU [CA100324]; [CA113395]; [CA126511]; [CA92782]; [EB004626]; [CA119349]; [CA86355]; [CA126515] FX The authors wish to thank Bojana Gligorijevic, David Entenberg, Jeffrey Wyckoff, and Mikael Pittet for contributions of text and figures to this review. The work described herein was supported by CA100324, CA113395, and CA126511 (J.C.), and CA92782, EB004626, CA119349, CA86355, and CA126515 (R.W.). Ralph Weissleder has an equity stake and is a consultant to VisEn, a manufacturer of fluorescent imaging probes and systems. The authors report no other conflicts of interest relevant to this publication. NR 120 TC 69 Z9 72 U1 0 U2 26 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD DEC PY 2010 VL 2 IS 12 AR a003848 DI 10.1101/cshperspect.a003848 PG 22 WC Cell Biology SC Cell Biology GA 688RB UT WOS:000284868600008 PM 20861158 ER PT J AU Al-Mutawa, SA Shyama, M Al-Duwairi, Y Soparkar, P AF Al-Mutawa, S. A. Shyama, M. Al-Duwairi, Y. Soparkar, P. TI Dental caries experience of Kuwaiti kindergarten schoolchildren SO COMMUNITY DENTAL HEALTH LA English DT Article DE Dental caries; kindergarten schoolchildren; Kuwait ID PRESCHOOL-CHILDREN AB Objective The aim of the present study was to determine the caries free proportions, caries experience and restorative care received in Kuwaiti kindergarten schoolchildren. Methods A national epidemiologic survey of the 4- and 5-year-old kindergarten schoolchildren (n = 1,277) was conducted in the five governorates of Kuwait. Five trained and calibrated dentists examined the children. Dental caries was scored using WHO diagnostic criteria. Results The percentage of 4- and 5-year-old children with dft = 0 was 32% and 24% respectively. The corresponding mean dft/dfs for 4- and 5-year-olds were 3.7/6.9 and 4.8/9.6. The decayed score was the major component in the mean scores. There was a significant difference in caries experience by governorate, but no difference by gender. The restorative index for 4- and 5-year-olds was 9.4% and 14.1% respectively. Conclusions Caries levels are lower or similar to those in neighbouring and other Middle East countries. A high percentage of carious maxillary incisors indicate an early childhood caries pattern in these children. An extensive prevention programmme in preschool and kindergarten children is now in place. C1 [Soparkar, P.] Forsyth Inst, Boston, MA USA. RP Shyama, M (reprint author), POB 1952, Salmiya 22020, Kuwait. EM mshyama@yahoo.com NR 20 TC 4 Z9 4 U1 0 U2 0 PU F D I WORLD DENTAL PRESS LTD PI LOWESTOFT PA 5 BATTERY GREEN RD, LOWESTOFT NR32 1 DE, SUFFOLK, ENGLAND SN 0265-539X J9 COMMUNITY DENT HLTH JI Community Dent. Health PD DEC PY 2010 VL 27 IS 4 BP 213 EP 217 DI 10.1922/CDH_2520-Shyama05 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 698YJ UT WOS:000285630800005 PM 21473355 ER PT J AU Liu, HH Maida, CA Spolsky, VW Shen, J Li, H Zhou, XM Marcus, M AF Liu, Honghu Maida, Carl A. Spolsky, Vladimir W. Shen, Jie Li, Helen Zhou, Xiaomeng Marcus, Marvin TI Calibration of self-reported oral health to clinically determined standards SO COMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY LA English DT Article DE bootstrap; calibration; cross-validation; nomogram; oral health ID QUALITY-OF-LIFE; GENERAL HEALTH; PERIODONTAL HEALTH; DENTAL CONDITIONS; INDEX; IMPACT; VALIDITY; POPULATION; DENTISTS; DISEASE AB Objective: Self-report of oral health is an inexpensive approach to assessing an individual's oral health status, but it is heavily influenced by personal views and usually differs from that of clinically determined oral health status. To assist researchers and clinicians in estimating oral health self-report, we summarize clinically determined oral health measures that can objectively measure oral health and evaluate the discrepancies between self-reported and clinically determined oral health status. We test hypotheses of trends across covariates, thereby creating optimal calibration models and tools that can adjust self-reported oral health to clinically determined standards. Methods: Using National Health and Nutrition Examination Survey (NHANES) data, we examined the discrepancy between self-reported and clinically determined oral health. We evaluated the relationship between the degree of this discrepancy and possible factors contributing to this discrepancy, such as patient characteristics and general health condition. We used a regression approach to develop calibration models for self-reported oral health. Results: The relationship between self-reported and clinically determined oral health is complex. Generally, there is a discrepancy between the two that can best be calibrated by a model that includes general health condition, number of times a person has received health care, gender, age, education, and income. Conclusion: The model we developed can be used to calibrate and adjust self-reported oral health status to that of clinically determined standards and for oral health screening of large populations in federal, state, and local programs, enabling great savings in resources used in dental care. C1 [Liu, Honghu; Maida, Carl A.; Spolsky, Vladimir W.; Marcus, Marvin] Univ Calif Los Angeles, Div Publ Hlth & Community Dent, Sch Dent, Los Angeles, CA 90095 USA. [Zhou, Xiaomeng] Univ Calif Los Angeles, Dept Stat, Sch Publ Hlth, Los Angeles, CA 90095 USA. [Li, Helen] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Liu, HH (reprint author), Univ Calif Los Angeles, Div Publ Hlth & Community Dent, Sch Dent, 10833 Le Conte Ave,Room 63-037A CHS,Box 951668, Los Angeles, CA 90095 USA. EM hhliu@ucla.edu FU National Institute of Dental and Craniofacial Research (NIDCR) [R03DE018767] FX This research was supported by the National Institute of Dental and Craniofacial Research (NIDCR) grant R03DE018767. NR 43 TC 17 Z9 18 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0301-5661 J9 COMMUNITY DENT ORAL JI Community Dentist. Oral Epidemiol. PD DEC PY 2010 VL 38 IS 6 BP 527 EP 539 DI 10.1111/j.1600-0528.2010.00562.x PG 13 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 676WC UT WOS:000283948400006 PM 21054482 ER PT J AU Niv, N Shatkin, JP Hamilton, AB Unutzer, J Klap, R Young, AS AF Niv, Noosha Shatkin, Jess P. Hamilton, Alison B. Unuetzer, Juergen Klap, Ruth Young, Alexander S. TI The Use of Herbal Medications and Dietary Supplements by People with Mental Illness SO COMMUNITY MENTAL HEALTH JOURNAL LA English DT Article DE Complementary and alternative medicine; Herbal medication; Dietary supplement; Mental illness ID ALTERNATIVE MEDICINE USE; ST-JOHNS-WORT; UNITED-STATES; PSYCHIATRIC OUTPATIENTS; ANXIETY DISORDERS; NATIONAL-SURVEY; DEPRESSION; COMPLEMENTARY; HEALTH; THERAPIES AB This study examined the relationship between herbal medication and dietary supplement (HMDS) use and mental health characteristics. Data are drawn from a national household survey of the United States' civilian, non-institutionalized population (N = 9,585). Psychiatric medication and HMDS use, psychiatric diagnoses and treatment needs, utilization and satisfaction were assessed. Compared to non-users, HMDS users were more likely to perceive themselves as having mental health needs, to have received mental health and primary care treatment, and to be dissatisfied with their overall healthcare. Psychiatric medication use was not related to HMDS use, and in multivariate analyses, HMDS use was associated with perceived mental health needs. Differences in use of specific HMDS between those with and without a psychiatric disorder were also examined. The use of HMDS warrants particular attention in persons with perceived mental health problems as these individuals may be turning to HMDS use for treatment of their symptoms. C1 [Niv, Noosha] MIRECC, W Los Angeles VA, Los Angeles, CA 90073 USA. [Niv, Noosha; Hamilton, Alison B.; Young, Alexander S.] Desert Pacific Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs, Los Angeles, CA USA. [Niv, Noosha; Hamilton, Alison B.; Young, Alexander S.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Shatkin, Jess P.] NYU, Sch Med, New York, NY USA. [Unuetzer, Juergen] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. [Klap, Ruth] Univ Calif Los Angeles, Hlth Serv Res Ctr, Los Angeles, CA USA. RP Niv, N (reprint author), MIRECC, W Los Angeles VA, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM noosha23@yahoo.com RI Young, Alexander/A-1523-2009; OI Young, Alexander/0000-0002-9367-9213; Shatkin, Jess/0000-0002-4372-1583 FU NIMH NIH HHS [P30 MH068639, MH 082760, MH 068639, P30 MH082760] NR 38 TC 4 Z9 4 U1 7 U2 15 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0010-3853 J9 COMMUNITY MENT HLT J JI Community Ment. Health J. PD DEC PY 2010 VL 46 IS 6 BP 563 EP 569 DI 10.1007/s10597-009-9235-2 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 672NH UT WOS:000283591600005 PM 19688594 ER PT J AU Sun, A Murray, SS Simon, RJ Jawien, J Behnam, K Miller, TA Brochmann, EJ AF Sun, Argus Murray, Samuel S. Simon, Robert J. Jawien, Janusz Behnam, Keyvan Miller, Timothy A. Brochmann, Elsa J. TI Alanine-scanning mutations of the BMP-binding domain of recombinant secretory bovine spp24 affect cytokine binding SO CONNECTIVE TISSUE RESEARCH LA English DT Article DE secreted phosphoprotein 24; bone morphogenetic protein; surface plasmon resonance; bone and bones ID II RECEPTOR; PROTEIN; SEQUENCE; PEPTIDE AB Secreted phosphoprotein 24 kDa (spp24) is a bone morphogenetic protein (BMP)/transforming growth factor-beta cytokine-binding protein. The spp24 BMP-2-binding/transforming growth factor receptor II homology-1 (TRH1) domain is a highly conserved N-to-C terminally disulfide-bonded 19-amino acid residue loop similar to those in fetuin and the BMP receptor II. TRH1 domains exhibit a characteristic BTB or beta-pleated sheet/turn/beta-pleated sheet secondary structure. Our objective was to identify amino acid residues in the spp24 TRH1 domain that bind BMP-2, starting with the nine invariant mammalian residues. Alanine scanning (substitution of Ala for a native residue) was conducted for Cys(110), Arg(111), Ser(112), Thr(113), Val(114), Ser(117), Val(121), Val(124), and Cys(128) of recombinant bovine spp24 (residues 24-203). Binding to rhBMP-2 was assessed by surface plasmon resonance, and the equilibrium binding constants were calculated assuming 1:1 binding between spp24 or its mutants and rhBMP-2, so that affinity = K(D) = k(d)/k(a). Replacing Arg(111) (a positively charged basic residue), polar residues Thr(113) and Ser(117), and the nonpolar Cys(128) with Ala had little effect on BMP-2 binding. Replacing Val(114) or Val(121) with Ala increased binding affinity, whereas replacing Cys(110), Ser(112), Val(124), or both Cys(110) and Cys(128) with Ala decreased it. The kinetics of spp24 binding to BMP-2 can be manipulated by replacing invariant TRH1 residues. Decreasing the relative degree of hydrophobicity in the beta-pleated sheet secondary structural motif of the TRH1 domain by replacing key Val residues with Ala increased the affinity for BMP-2 whereas altering the composition of the alpha-helical turn did not. Thus, the beta-pleated sheets play a greater role in BMP-2 binding than the alpha-helical turn. C1 [Sun, Argus; Simon, Robert J.; Jawien, Janusz; Behnam, Keyvan] VA Greater Los Angeles Hlth Care Syst, Res Serv, Sepulveda, CA 91343 USA. [Sun, Argus; Murray, Samuel S.] Univ Calif Los Angeles, Interdept Program Biomed Engn, Los Angeles, CA USA. [Murray, Samuel S.; Brochmann, Elsa J.] VA Greater Los Angeles Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Sepulveda, CA 91343 USA. [Murray, Samuel S.; Brochmann, Elsa J.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Behnam, Keyvan] Lanx Inc, Broomfield, CO USA. [Miller, Timothy A.] W Los Angeles Med Ctr, VA Greater Los Angeles, Surg Serv, Los Angeles, CA USA. [Miller, Timothy A.] Univ Calif Los Angeles, Dept Surg, Div Plast Surg, Los Angeles, CA 90024 USA. RP Murray, SS (reprint author), VA Greater Los Angeles Hlth Care Syst, Geriatr Res Educ & Clin Ctr 11E, 16111 Plummer St, Sepulveda, CA 91343 USA. EM Samuel.Murray@va.gov FU Department of Veterans Affairs and Lanx, Inc. FX This research was supported by the Department of Veterans Affairs and Lanx, Inc. NR 14 TC 4 Z9 4 U1 1 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PD DEC PY 2010 VL 51 IS 6 BP 445 EP 451 DI 10.3109/03008201003615734 PG 7 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA 686DQ UT WOS:000284677400004 PM 20615094 ER PT J AU Hodgins, HS Adair, KC AF Hodgins, Holley S. Adair, Kathryn C. TI Attentional processes and meditation SO CONSCIOUSNESS AND COGNITION LA English DT Article DE Attention; Meditation; Change blindness; Selective attention; Perspective-shifting; Visual concentration; Sustained inattentional blindness ID SUSTAINED INATTENTIONAL BLINDNESS; GEOGRAPHICAL-SLANT PERCEPTION; SEE; BRAIN AB Visual attentional processing was examined in adult meditators and non-meditators on behavioral measures of change blindness, concentration, perspective-shifting, selective attention, and sustained inattentional blindness. Results showed that meditators (1) noticed more changes in flickering scenes and noticed them more quickly, (2) counted more accurately in a challenging concentration task, (3) identified a greater number of alternative perspectives in multiple perspectives images, and (4) showed less interference from invalid cues in a visual selective attention task, but (5) did not differ on a measure of sustained inattentional blindness. Together, results show that regular meditation is associated with more accurate, efficient, and flexible visual attentional processing across diverse tasks that have high face validity outside of the laboratory. Furthermore, effects were assessed in a context separate from actual meditation practice, suggesting that meditators' better visual attention is not just immediate, but extends to contexts separate from meditation practice. (C) 2010 Elsevier Inc. All rights reserved. C1 [Hodgins, Holley S.] Skidmore Coll, Saratoga Springs, NY 12866 USA. [Adair, Kathryn C.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. RP Hodgins, HS (reprint author), Skidmore Coll, Saratoga Springs, NY 12866 USA. EM hhodgins@skidmore.edu NR 36 TC 49 Z9 49 U1 7 U2 34 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8100 J9 CONSCIOUS COGN JI Conscious. Cogn. PD DEC PY 2010 VL 19 IS 4 BP 872 EP 878 DI 10.1016/j.concog.2010.04.002 PG 7 WC Psychology, Experimental SC Psychology GA 684AQ UT WOS:000284519800003 PM 20430650 ER PT J AU Dransfield, MT Huang, F Nath, H Singh, SP Bailey, WC Washko, GR AF Dransfield, Mark T. Huang, Frank Nath, Hrudaya Singh, Satinder P. Bailey, William C. Washko, George R. TI CT Emphysema Predicts Thoracic Aortic Calcification in Smokers with and Without COPD SO COPD-JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; CORONARY-ARTERY-DISEASE; RISK-FACTORS; COMPUTED-TOMOGRAPHY; SYSTEMIC INFLAMMATION; AIRWAY DIMENSIONS; LUNG-FUNCTION; STIFFNESS; ASSOCIATION; MORTALITY AB COPD patients are at increased risk for cardiovascular morbidity and mortality independent of smoking habits. Recent studies suggest CT emphysema is an independent predictor of cardiovascular risk as evidenced by its association with arterial stiffness and impaired endothelial function. We examined the relationship between demographics, lung function, CT emphysema and airway wall thickness and thoracic aortic calcification, another marker of cardiovascular risk, in the National Lung Screening Trial. We hypothesized that CT emphysema would be independently associated with thoracic aortic calcification. Two hundred forty current and former smokers were enrolled. After CT examination, we recorded subjects' demographics and they performed spirometry. Subjects were classified into COPD and non-COPD subgroups. CT emphysema was quantified as a percentage of lung volume and measurements of the right upper lobe airway were performed using standard methods and expressed as wall area (%). Total calcification scores for the thoracic aorta were computed using TeraRecon image analysis. Univariate and multivariate analyses were performed to determine the associations between calcium score and subject characteristics. Subjects with COPD were older, more often male, heavier smokers and had more CT emphysema and greater aortic calcification than those without COPD. Calcium score was associated with age, pack-years, CT emphysema, wall area%, and lung function on univariate testing but only with age and CT emphysema on multivariate analysis. We conclude that CT emphysema is independently associated with thoracic calcification and thus may be used to assess cardiovascular risk in smokers with and without COPD. C1 [Dransfield, Mark T.; Bailey, William C.] Univ Alabama, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA. [Huang, Frank] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Nath, Hrudaya; Singh, Satinder P.] Univ Alabama, Dept Radiol, Birmingham, AL USA. [Dransfield, Mark T.] Birmingham VA Med Ctr, Birmingham, AL USA. [Washko, George R.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. RP Dransfield, MT (reprint author), 422 THT 1900 Univ Blvd, Birmingham, AL 35294 USA. EM mdransfield99@msn.com; franco8305@gmail.com; hnath@uab.edu; ssingh.hospo11.hos1@uabmc.edu; wcbailey@uab.edu; gwashko@partners.org NR 41 TC 16 Z9 16 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1541-2555 J9 COPD JI COPD-J. Chronic Obstr. Pulm. Dis. PD DEC PY 2010 VL 7 IS 6 BP 404 EP 410 DI 10.3109/15412555.2010.528085 PG 7 WC Respiratory System SC Respiratory System GA 696QW UT WOS:000285457500004 PM 21166628 ER PT J AU Ferrell, BR Virani, R Paice, JA Malloy, P Dahlin, C AF Ferrell, Betty R. Virani, Rose Paice, Judith A. Malloy, Pam Dahlin, Constance TI Statewide Efforts to Improve Palliative Care in Critical Care Settings SO CRITICAL CARE NURSE LA English DT Article ID OF-LIFE CARE; CONSORTIUM TRAINING-PROGRAM; NURSING-EDUCATION; INTENSIVE-CARE; END; PAIN; ILL; BEHAVIORS; UNIT C1 [Ferrell, Betty R.; Virani, Rose] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Paice, Judith A.] Northwestern Univ, Feinberg Sch Med, Canc Pain Program, Chicago, IL 60611 USA. [Malloy, Pam] Amer Assoc Coll Nursing, Special Projects, Washington, DC USA. [Dahlin, Constance] Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. RP Ferrell, BR (reprint author), City Hope Natl Med Ctr, Dept Populat Sci Bldg 173, Div Nursing Res & Educ, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM bferrell@coh.org OI Paice, Judith/0000-0001-7534-1756 NR 27 TC 3 Z9 3 U1 0 U2 3 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 0279-5442 J9 CRIT CARE NURSE JI Crit. Care Nurse PD DEC PY 2010 VL 30 IS 6 BP 40 EP 45 DI 10.4037/ccn2010248 PG 6 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA 688BN UT WOS:000284824200008 PM 21123231 ER PT J AU Doria, A AF Doria, Alessandro TI Genetics of Diabetes Complications SO CURRENT DIABETES REPORTS LA English DT Article DE Diabetic nephropathy; Diabetic retinopathy; Coronary artery disease; Atherosclerosis; Polymorphisms; Candidate genes; Genome-wide association studies ID CORONARY-ARTERY-DISEASE; GENOME-WIDE ASSOCIATION; ENDOTHELIAL GROWTH-FACTOR; ALDOSE REDUCTASE GENE; CARDIOVASCULAR RISK; GLYCEMIC CONTROL; NEPHROPATHY; LOCUS; SUSCEPTIBILITY; RETINOPATHY AB A large body of evidence indicates that the risk for developing chronic diabetic complications is under the control of genetic factors. Previous studies using a candidate gene approach have uncovered a number of genetic loci that may shape this risk, such as the VEGF gene for retinopathy, the ELMO1 gene for nephropathy, and the ADIPOQ gene for coronary artery disease. Recently, a new window has opened on identifying these genes through genome-wide association studies. Such systematic approach has already led to the identification of a major locus for coronary artery disease on 9p21 as well three potential genes for nephropathy on 7p, 11p, and 13q. Further insights are expected from a broader application of this strategy. It is anticipated that the identification of these genes will provide novel insights on the etiology of diabetic complications, with crucial implications for the development of new drugs to prevent the adverse effects of diabetes. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. RP Doria, A (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM alessandro.doria@joslin.harvard.edu FU National Institutes of Health [HL73168, HL71981, DK36836] FX Results of the author's work described in this article were supported by National Institutes of Health grants HL73168, HL71981, and DK36836. NR 57 TC 21 Z9 25 U1 1 U2 4 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD DEC PY 2010 VL 10 IS 6 BP 467 EP 475 DI 10.1007/s11892-010-0147-x PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 736LC UT WOS:000288495200008 PM 20835900 ER PT J AU Zvolensky, MJ Vujanovic, AA Bernstein, A Leyro, T AF Zvolensky, Michael J. Vujanovic, Anka A. Bernstein, Amit Leyro, Teresa TI Distress Tolerance: Theory, Measurement, and Relations to Psychopathology SO CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE LA English DT Article DE distress tolerance; psychopathology; vulnerability; mechanism; assessment ID INTOLERANCE; UNCERTAINTY; SCALE AB In this article we present the theoretical and empirical bases of distress tolerance research. Although distress tolerance offers a promising lens through which to better understand various psychological symptoms and disorders, further theoretical development and empirical inquiry is needed to promote our understanding of the construct. Overall, a number of questions regarding its theoretical conceptualization and measurement, associations with related constructs and psychopathology, and role(s) in therapeutic change and intervention remain unanswered. Directions for future research are discussed to stimulate further empirical study on this theoretically and clinically promising topic. C1 [Zvolensky, Michael J.; Leyro, Teresa] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA. [Vujanovic, Anka A.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA. [Vujanovic, Anka A.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Bernstein, Amit] Univ Haifa, Dept Psychol, IL-31999 Haifa, Israel. RP Zvolensky, MJ (reprint author), Univ Vermont, Dept Psychol, 2 Colchester Ave, Burlington, VT 05405 USA. EM michael.zvolensky@uvm.edu NR 17 TC 52 Z9 54 U1 3 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0963-7214 J9 CURR DIR PSYCHOL SCI JI Curr. Dir. Psychol. PD DEC PY 2010 VL 19 IS 6 BP 406 EP 410 DI 10.1177/0963721410388642 PG 5 WC Psychology, Multidisciplinary SC Psychology GA 735OJ UT WOS:000288426500013 ER PT J AU Atlas, SA AF Atlas, Steven A. TI Aldosterone to Renin Ratio as a Predictor of Diuretic Response SO CURRENT HYPERTENSION REPORTS LA English DT Editorial Material DE Hypertension; Treatment; Therapy; Screening; Aldosteronism; Mineralocorticoid receptor antagonist; Thiazide ID ESSENTIAL HYPERTENSION; BLOOD-PRESSURE; SPIRONOLACTONE; VOLUME C1 James J Peters VA Med Ctr, Bronx, NY 10468 USA. RP Atlas, SA (reprint author), James J Peters VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM steven.atlas@va.gov NR 11 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1522-6417 EI 1534-3111 J9 CURR HYPERTENS REP JI Curr. Hypertens. Rep. PD DEC PY 2010 VL 12 IS 6 BP 395 EP 398 DI 10.1007/s11906-010-0156-9 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 680XV UT WOS:000284271700001 PM 21046491 ER PT J AU Wu, EQ Guerin, A Yu, AP Bollu, VK Guo, A Griffin, JD AF Wu, Eric Q. Guerin, Annie Yu, Andrew P. Bollu, Vamsi K. Guo, Amy Griffin, James D. TI Retrospective real-world comparison of medical visits, costs, and adherence between nilotinib and dasatinib in chronic myeloid leukemia SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE Adherence; Chronic myeloid leukemia; Cost; Tyrosine kinase inhibitor; Utilization ID CHRONIC MYELOGENOUS LEUKEMIA; IMATINIB-RESISTANT; TREATMENT OPTIONS; FAILURE; INTERRUPTIONS; INHIBITION; DATABASES; RESPONSES; THERAPY AB Objective: To compare healthcare resource utilization, costs, and treatment adherence associated with dasatinib versus nilotinib treatment as second-line therapies in chronic myeloid leukemia (CML) patients. Methods: Two large retrospective claims databases (01/1999-06/2009) were combined to identify CML patients (ICD-9 code 205.1x) who received one or more prescriptions of dasatinib or nilotinib. Studied patients had continuous enrollment >= 1 month prior to and after the index date, defined as the first prescription for dasatinib or nilotinib. Patients were followed for up to 6 months from the index date to the earliest of the termination of healthcare plan enrollment or end of data availability. Patients with bone marrow or stem cell transplant during the study period were excluded. Poisson regression models were used to compare healthcare resource utilization between the two groups. Results were reported as incidence rate ratios (IRR). Healthcare cost differences were estimated for each cost component using generalized linear models or two-part models. Treatment adherence was measured by the proportion of days covered (PDC) and compared using generalized linear models. Multivariate regressions were used to control for potential confounding factors. Results: A total of 521 CML patients receiving second-line tyrosine kinase inhibitors (TKI) (452 dasatinib and 69 nilotinib) were studied. During the study period, dasatinib patients were estimated to have more than twice as many inpatient days (IRR = 2.44; p<0.001) and nearly double the number of inpatient admissions (IRR = 1.99; p = 0.047) compared to nilotinib patients. Over the follow-up period, dasatinib patients incurred $8828 more in total medical service costs (p<0.001); cost differences were mainly driven by an adjusted inpatient cost difference of $8520 (p = 0.003). Dasatinib patients were less adherent, with a PDC value approximately 13% lower compared to nilotinib patients (p = 0.009). Conclusions: Among CML patients treated with second-line TKIs, nilotinib patients were more adherent and experienced lower healthcare resource utilization, resulting in medical service cost savings compared to dasatinib patients. C1 [Wu, Eric Q.; Guerin, Annie; Yu, Andrew P.] Anal Grp Inc, Boston, MA 02199 USA. [Griffin, James D.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wu, EQ (reprint author), Anal Grp Inc, 111 Huntington Ave,10th Floor, Boston, MA 02199 USA. EM ewu@analysisgroup.com FU Novartis Pharmaceuticals Corporation; Novartis; Analysis Group, Inc. FX This research was sponsored by Novartis Pharmaceuticals Corporation, which manufactures imatinib and nilotinib.; E.Q.W., A.P.Y. and A. Guerin have disclosed that they are employees of Analysis Group, Inc., which has received consultancy fees from Novartis. V. B. and A. Guo have disclosed that they are Novartis employees. J.D.G. has disclosed that he is an employee of the Dana Farber Cancer Institute which has received consultancy fees from Analysis Group, Inc. NR 30 TC 27 Z9 27 U1 1 U2 6 PU LIBRAPHARM/INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4 LQ, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD DEC PY 2010 VL 26 IS 12 BP 2861 EP 2869 DI 10.1185/03007995.2010.533648 PG 9 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 680GI UT WOS:000284220000018 PM 21062136 ER PT J AU Goldman, ID Chattopadhyay, S Zhao, RB Moran, R AF Goldman, I. David Chattopadhyay, Shrikanta Zhao, Rongbao Moran, Richard TI The antifolates: Evolution, new agents in the clinic, and how targeting delivery via specific membrane transporters is driving the development of a next generation of folate analogs SO CURRENT OPINION IN INVESTIGATIONAL DRUGS LA English DT Review DE Aminopterin; antifolate; folate; folate receptor; methotrexate; PCFT; pemetrexed; pralatrexate; proton-coupled folate transporter; reduced folate carrier; RFC; SLC19A1; SLC46A1 ID CELL LUNG-CANCER; PHASE-II TRIAL; THYMIDYLATE SYNTHASE INHIBITOR; MALIGNANT PLEURAL MESOTHELIOMA; L1210 LEUKEMIA-CELLS; METASTATIC BREAST-CANCER; MAMMALIAN FOLYLPOLYGLUTAMATE SYNTHETASE; ADJUVANT CHEMOENDOCRINE THERAPY; ADVANCED COLORECTAL-CANCER; HUMAN-TUMOR XENOGRAFTS AB More than 50 years after the introduction of the dihydrofolate reductase inhibitor, methotrexate, new antifolates have emerged and have been incorporated into the chemotherapeutic armamentarium. These include pralatrexate, with the same target as methotrexate, but with enhanced properties, and pemetrexed, with different enzyme targets and properties. Current synthetic efforts are focused on developing antifolates that are selectively delivered to cancer cells, but not to normal proliferating cells, exploiting the different properties of folate transporters. In another novel approach, drugs structurally and mechanistically unrelated to folates are linked to and use folic acid as a carrier to be endocytosed by folate receptors and then released to inhibit their cellular targets. This review describes the evolution and current status of antifolate pharmacology and prospects for the development of the next generation of folate analogs. C1 [Goldman, I. David; Zhao, Rongbao] Albert Einstein Coll Med, Ctr Canc, Dept Med, Bronx, NY 10803 USA. [Goldman, I. David; Zhao, Rongbao] Albert Einstein Coll Med, Ctr Canc, Dept Mol Pharmacol, Bronx, NY 10803 USA. [Chattopadhyay, Shrikanta] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Moran, Richard] Virginia Commonwealth Univ, Dept Pharmacol, Richmond, VA 23298 USA. [Moran, Richard] Virginia Commonwealth Univ, Med Coll Virginia, Massey Canc Ctr, Richmond, VA 23298 USA. RP Goldman, ID (reprint author), Albert Einstein Coll Med, Ctr Canc, Dept Med, Chanin 2,1300 Morris Pk Ave, Bronx, NY 10803 USA. EM i.david.goldman@einstein.yu.edu NR 161 TC 28 Z9 28 U1 2 U2 16 PU THOMSON REUTERS (SCIENTIFIC) LTD PI LONDON PA 77 HATTON GARDEN, LONDON, EC1N 8JS, ENGLAND SN 1472-4472 J9 CURR OPIN INVEST DR JI Curr. Opin. Investig. Drugs PD DEC PY 2010 VL 11 IS 12 BP 1409 EP 1423 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 692NT UT WOS:000285160200009 PM 21154123 ER PT J AU Rodig, SJ Shapiro, GI AF Rodig, Scott J. Shapiro, Geoffrey I. TI Crizotinib, a small-molecule dual inhibitor of the c-Met and ALK receptor tyrosine kinases SO CURRENT OPINION IN INVESTIGATIONAL DRUGS LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; CELL LUNG-CANCER; ANAPLASTIC LYMPHOMA KINASE; INFLAMMATORY MYOFIBROBLASTIC TUMOR; FACTOR SCATTER FACTOR; EML4-ALK FUSION GENE; CLINICAL-FEATURES; ACTIVATING MUTATIONS; MONOCLONAL-ANTIBODY; THERAPEUTIC TARGET AB Crizotinib (PF-02341066), under development by Pfizer, is an orally bioavailable, ATP-competitive, small-molecule inhibitor of the receptor tyrosine kinases (RTKs) c-Met (also known as hepatocyte growth factor receptor) and anaplastic lymphoma kinase (ALK), for the potential treatment of cancers dependent on these oncogenic kinases for growth and survival. Since the first published characterizations of crizotinib only a few years ago, the drug has been extensively validated as a highly specific inhibitor of c-Met and ALK among > 120 different RTKs surveyed. In preclinical tumor xenograft studies, crizotinib inhibited the growth and survival of cell lines dependent upon c-Met or ALK enzymatic activity. Crizotinib has been particularly effective against anaplastic large cell lymphoma and non-small cell lung cancer (NSCLC) cell lines that harbor ALK translocations resulting in expression of oncogenic ALK fusion proteins. During early-stage clinical testing, crizotinib was well tolerated and produced dramatic antitumor activity in patients with ALK-rearranged NSCLC. At the time of publication, an ongoing phase III clinical trial is comparing crizotinib with standard second-line chemotherapy in previously treated patients with NSCLC harboring ALK rearrangement, and a phase III trial comparing crizotinib with standard chemotherapy in the first-line setting in non-squamous lung cancer is planned. Thus, in the future, crizotinib is expected to become a highly used therapeutic for the treatment of ALK-rearranged tumors. C1 [Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Shapiro, Geoffrey I.] Dana Farber Canc Inst, Early Drug Dev Ctr, Dept Med Oncol, Boston, MA 02215 USA. RP Rodig, SJ (reprint author), Brigham & Womens Hosp, Dept Pathol, Amory 3,75 Francis St, Boston, MA 02115 USA. EM srodig@partners.org NR 101 TC 62 Z9 65 U1 2 U2 16 PU THOMSON REUTERS (SCIENTIFIC) LTD PI LONDON PA 77 HATTON GARDEN, LONDON, EC1N 8JS, ENGLAND SN 1472-4472 J9 CURR OPIN INVEST DR JI Curr. Opin. Investig. Drugs PD DEC PY 2010 VL 11 IS 12 BP 1477 EP 1490 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 692NT UT WOS:000285160200015 PM 21154129 ER PT J AU Adler, JT Sippel, RS Chen, H AF Adler, Joel T. Sippel, Rebecca S. Chen, Herbert TI New Trends in Parathyroid Surgery SO CURRENT PROBLEMS IN SURGERY LA English DT Review ID ASYMPTOMATIC PRIMARY HYPERPARATHYROIDISM; MINIMALLY INVASIVE PARATHYROIDECTOMY; RECURRENT LARYNGEAL NERVE; QUALITY-OF-LIFE; 3RD INTERNATIONAL WORKSHOP; ENDOCRINE NEOPLASIA TYPE-1; CALCIUM-SENSING RECEPTOR; FAMILIAL ISOLATED HYPERPARATHYROIDISM; IMPROVES NEUROCOGNITIVE DEFICITS; VIDEO-ASSISTED PARATHYROIDECTOMY C1 [Adler, Joel T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chen, Herbert] Univ Wisconsin, Dept Surg, Madison, WI USA. RP Adler, JT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Adler, Joel/0000-0001-8190-3444 NR 212 TC 24 Z9 26 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0011-3840 J9 CURR PROB SURG JI Curr. Probl. Surg. PD DEC PY 2010 VL 47 IS 12 BP 958 EP + DI 10.1067/j.cpsurg.2010.08.002 PG 61 WC Surgery SC Surgery GA 686UM UT WOS:000284721700001 PM 21044730 ER PT J AU Lu, WD Rosenthal, DS AF Lu, Weidong Rosenthal, David S. TI Recent Advances in Oncology Acupuncture and Safety Considerations in Practice SO CURRENT TREATMENT OPTIONS IN ONCOLOGY LA English DT Editorial Material ID CONTROLLED-TRIAL; CANCER-PATIENTS; BREAST-CANCER; SYMPTOMS; THERAPY; XEROSTOMIA; MANAGEMENT AB Oncology acupuncture is a new and emerging field of research. Recent advances from published clinical trials have added evidence to support the use of acupuncture for symptom management in cancer patients. Recent new developments include (1) pain and dysfunction after neck dissection; (2) radiation-induced xerostomia in head and neck cancer; (3) aromatase inhibitor-associated arthralgia in breast cancer; (4) hot flashes in breast cancer and prostate cancer; and (5) chemotherapyinduced neutropenia in ovarian cancer. Some interventions are becoming a non-pharmaceutical option for cancer patients, while others still require further validation and confirmation. Meanwhile, owing to the rapid development of the field and increased demands from cancer patients, safety issues concerning oncology acupuncture practice have become imperative. Patients with cancer may be at higher risk developing adverse reactions from acupuncture. Practical strategies for enhancing safety measures are discussed and recommended. C1 [Lu, Weidong; Rosenthal, David S.] Dana Farber Canc Inst, Leonard P Zakim Ctr Integrat Therapies, Boston, MA 02115 USA. RP Lu, WD (reprint author), Dana Farber Canc Inst, Leonard P Zakim Ctr Integrat Therapies, SW560,44 Binney St, Boston, MA 02115 USA. EM Weidong_lu@dfci.harvard.edu RI Lu, Weidong/C-3844-2008 OI Lu, Weidong/0000-0003-2838-6307 FU NCCIH NIH HHS [K01 AT004415-01, K01 AT004415, 5K01AT004415] NR 17 TC 13 Z9 16 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1527-2729 J9 CURR TREAT OPTION ON JI Curr. Treat. Options Oncol. PD DEC PY 2010 VL 11 IS 3-4 BP 141 EP 146 DI 10.1007/s11864-010-0126-0 PG 6 WC Oncology SC Oncology GA 691SJ UT WOS:000285100800011 PM 21103962 ER PT J AU Peckham, AD McHugh, RK Otto, MW AF Peckham, Andrew D. McHugh, R. Kathryn Otto, Michael W. TI A META-ANALYSIS OF THE MAGNITUDE OF BIASED ATTENTION IN DEPRESSION SO DEPRESSION AND ANXIETY LA English DT Review DE depression; attention; cognition; reaction time; Stroop test; meta-analysis ID GENERALIZED ANXIETY DISORDER; NEGATIVE INFORMATION; CONSTRUCT ACCESSIBILITY; EMOTIONAL DISORDERS; CLINICAL DEPRESSION; SELECTIVE ATTENTION; STROOP TASK; MOOD; INDIVIDUALS; MEMORY AB In this quantitative review, we examined the magnitude of attentional biases to negative stimuli in depression. Results from 29 empirical studies examining emotional Stroop or dot probe results in depressed participants (clinical depression, nonclinical dysphoria, and subjects undergoing depressive mood induction) were examined. Studies using the emotional Stroop task yielded marginally significant evidence of a difference between depressed and nondepressed samples, whereas those using the dot probe task showed significant differences between groups (d = 0.52). We found no evidence for significant moderation of these effects by age, sex, type of depressed sample, year of publication, stimulus presentation duration, or type of stimuli (verbal or nonverbal), although statistical power for these tests was limited. These results support the existence of biased attention to negative information in depression. Depression and Anxiety 27:1135-1142, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Peckham, Andrew D.; McHugh, R. Kathryn; Otto, Michael W.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Peckham, AD (reprint author), Massachusetts Gen Hosp, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM adpeckham@partners.org OI McHugh, R. Kathryn/0000-0002-3011-8697 NR 56 TC 110 Z9 114 U1 17 U2 117 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD DEC PY 2010 VL 27 IS 12 BP 1135 EP 1142 DI 10.1002/da.20755 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 687LR UT WOS:000284780500004 PM 21049527 ER PT J AU Ibrahimi, OA Jih, MH Aluma-Tenorio, MS Goldberg, LH Kimyai-Asadi, A AF Ibrahimi, Omar A. Jih, Ming H. Aluma-Tenorio, Maria S. Goldberg, Leonard H. Kimyai-Asadi, Arash TI Repair of Scalp Defects Using an H-Plasty Type of Bilateral Advancement Flap SO DERMATOLOGIC SURGERY LA English DT Article ID REDUCTION; DESIGN AB BACKGROUND Defects of the scalp often pose a reconstructive challenge in dermatologic surgery. OBJECTIVE We report our experience with the H-plasty type of bilateral advancement flap for the closure of small to medium-sized scalp defects that cannot be closed primarily. METHODS In this case series study, 69 scalp defects 1.5 to 3.0 cm in diameter that could not be closed primarily were repaired using the H-plasty type of bilateral advancement flap. RESULTS Sixty-nine 1.5- to 3.0-cm-diameter scalp defects resulting from Mohs micrographic surgery that could not be closed primarily were identified over the 2-year study period. All 69 defects were closed entirely with the bilateral advancement flap, and there were no significant complications. CONCLUSIONS The H-plasty type of bilateral advancement flap allows appropriately selected scalp defects that might not be readily closed primarily to be repaired easily using local skin, providing an attractive alternative to other flap techniques, skin grafting, and healing via secondary intention. The limitations of this study are that the results are based on a retrospective single-surgeon experience and that there was no long-term follow-up scheduled to evaluate the final cosmetic outcome of the repair. The authors have indicated no significant interest with commercial supporters. C1 [Ibrahimi, Omar A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. [Jih, Ming H.; Goldberg, Leonard H.; Kimyai-Asadi, Arash] DermSurgery Associates, Houston, TX USA. [Aluma-Tenorio, Maria S.] Fdn Colombiana Cancerol, Clin Vida, Aurora Ctr Especializado Cirugia Canc Piel, Medellin, Colombia. RP Kimyai-Asadi, A (reprint author), 7515 Main,Suite 290, Houston, TX 77030 USA. EM akimyai@yahoo.com NR 13 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD DEC PY 2010 VL 36 IS 12 BP 1993 EP 1997 DI 10.1111/j.1524-4725.2010.01806.x PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA 688YF UT WOS:000284892100014 PM 21070462 ER PT J AU White, PJ Arita, M Taguchi, R Kang, JX Marette, A AF White, Phillip J. Arita, Makoto Taguchi, Ryo Kang, Jing X. Marette, Andre TI Transgenic Restoration of Long-Chain n-3 Fatty Acids in Insulin Target Tissues Improves Resolution Capacity and Alleviates Obesity-Linked Inflammation and Insulin Resistance in High-Fat-Fed Mice SO DIABETES LA English DT Article ID NITRIC-OXIDE SYNTHASE; ADIPOSE-TISSUE; LIPID MEDIATORS; OMEGA-3-FATTY-ACIDS; RECEPTOR; SENSITIVITY; MUSCLE; RISK; DIET AB OBJECTIVE The catabasis of inflammation is an active process directed by n-3 derived pro-resolving lipid mediators. We aimed to determine whether high-fat (HF) diet-induced n-3 deficiency compromises the resolution capacity of obese mice and thereby contributes to obesity-linked inflammation and insulin resistance. RESEARCH DESIGN AND METHODS We used transgenic expression of the fat-1 n-3 fatty acid desaturase from C. elegans to endogenously restore n-3 fatty acids in HF-fed mice. After 8 weeks on HF or chow diets, wild-type and fat-1 transgenic mice were subjected to insulin and glucose tolerance tests and a resolution assay was performed. Metabolic tissues were then harvested for biochemical analyses. RESULTS We report that the n-3 docosanoid resolution mediator protectin D1 is lacking in muscle and adipose tissue of HF-fed wild-type mice. Accordingly, HF-fed wild-type mice have an impaired capacity to resolve an acute inflammatory response and display elevated adipose macrophage accrual and chemokine/cytokine expression. This is associated with insulin resistance and higher activation of iNOS and JNK in muscle and liver. These defects are reversed in HF-fed fat-1 mice, in which the biosynthesis of this important n-3 docosanoid resolution mediator is improved. Importantly, transgenic restoration of n-3 fatty acids prevented obesity-linked inflammation and insulin resistance in HF-fed mice without altering food intake, weight gain, or adiposity. CONCLUSIONS We conclude that inefficient biosynthesis of n-3 resolution mediators in muscle and adipose tissue contributes to the maintenance of chronic inflammation in obesity and that these novel lipids offer exciting potential for the treatment of insulin resistance and diabetes. Diabetes 59:3066-3073, 2010 C1 [White, Phillip J.; Marette, Andre] CHUQ Res Ctr, Quebec Heart & Lung Inst, Fac Med, Dept Med, Quebec City, PQ, Canada. [White, Phillip J.; Marette, Andre] Univ Laval, INAF, Quebec City, PQ, Canada. [Arita, Makoto] Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Hlth Chem, Tokyo, Japan. [Taguchi, Ryo] Univ Tokyo, Grad Sch Med, Dept Metabolome, Tokyo, Japan. [Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA. RP Marette, A (reprint author), CHUQ Res Ctr, Quebec Heart & Lung Inst, Fac Med, Dept Med, Quebec City, PQ, Canada. EM andre.marette@crchul.ulaval.ca RI Marette, Andre/E-9342-2013; OI White, Phillip/0000-0002-0957-425X FU Canadian Diabetes Association; Canadian Institutes of Health Research (CIHR); National Institutes of Health [R01-CA-113605]; Fonds de la Recherche en Sante du Quebec FX This work was supported by grants from the Canadian Diabetes Association and from the Canadian Institutes of Health Research (CIHR) to A.M. and by National Institutes of Health funding (R01-CA-113605) to J.X.K. A.M. is the holder of a CIHR/Pfizer research Chair in the pathogenesis of insulin resistance and cardiovascular diseases. P.J.W. is the recipient of a Ph.D. studentship from the Fonds de la Recherche en Sante du Quebec. No other potential conflicts of interest relevant to this article were reported. NR 29 TC 71 Z9 75 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD DEC PY 2010 VL 59 IS 12 BP 3066 EP 3073 DI 10.2337/db10-0054 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 703ON UT WOS:000285988200012 PM 20841610 ER PT J AU Al-Jebawi, AF AF Al-Jebawi, Ahmed F. TI Remission of diabetes mellitus type 2 with severe hyperglycemia after Exenatide treatment SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Exenatide; GLP-1; Incretin; Diabetes; Remission; Cure ID ROUX-EN-Y; GASTRIC BYPASS; HORMONES; SURGERY; OBESITY AB A 54-year-old obese woman with poorly controlled type 2 diabetes was put on the maximum allowed doses of Metformin, Glimepiride and Rosiglitazone. When Exenatide was added, she lost 33 kg. She remained euglycemic for at least 7 months after the sequential discontinuation of Exenatide and the other oral agents. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Al-Jebawi, Ahmed F.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Al-Jebawi, Ahmed F.] Hlth Author, Joslin Diabet Ctr, Phys Training Program, Dubai, U Arab Emirates. RP Al-Jebawi, AF (reprint author), POB 235580, Dubai, U Arab Emirates. EM aaljebaw@iupui.edu NR 12 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD DEC PY 2010 VL 90 IS 3 BP E88 EP E90 DI 10.1016/j.diabres.2010.09.018 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 698XU UT WOS:000285629300013 PM 21030101 ER PT J AU Reubi, JC Perren, A Rehmann, R Waser, B Christ, E Callery, M Goldfine, AB Patti, ME AF Reubi, J. C. Perren, A. Rehmann, R. Waser, B. Christ, E. Callery, M. Goldfine, A. B. Patti, M. E. TI Glucagon-like peptide-1 (GLP-1) receptors are not overexpressed in pancreatic islets from patients with severe hyperinsulinaemic hypoglycaemia following gastric bypass SO DIABETOLOGIA LA English DT Article DE Exendin; Gastric bypass; GLP-1 receptors; Hyperinsulinaemic hypoglycaemia; Nesidioblastosis; Pancreatic islets ID HUMAN TUMORS; SURGERY; HYPERPLASIA; EXPRESSION AB Aims/hypothesis Glucagon-like peptide-1 (GLP-1) receptors are highly overexpressed in benign insulinomas, permitting in vivo tumour visualisation with GLP-1 receptor scanning. The present study sought to evaluate the GLP-1 receptor status in vitro in other pancreatic disorders leading to hyperinsulinaemic hypoglycaemia, specifically after gastric bypass surgery. Methods Fresh frozen pancreatic tissue samples (n=7) from six gastric bypass surgery patients suffering from hyperinsulinaemic hypoglycaemia were evaluated for GLP-1 receptor content using in vitro receptor autoradiography, and compared with normal pancreas and with pancreatic insulinoma tissues. Results GLP-1 receptor analysis of the pancreatic tissues, which histopathologically were compatible with nesidioblastosis and originated from post-bypass hypoglycaemic patients, revealed a mean density value of GLP-1 receptors in the islets of 1,483 +/- 183 dpm/mg tissue. Pharmacological characterisation indicated the presence of specific GLP-1 receptors. The density of islet GLP-1 receptor in post-gastric bypass patients did not differ from that of normal pancreas (1,563 +/- 104 dpm/mg tissue, n=10). Receptor density in pancreatic acini was low in post-bypass and control conditions. In contrast, benign insulinomas showed a high density of GLP-1 receptors, with a mean value of 8,302 +/- 1,073 dpm/mg tissue (n=6). Conclusions/interpretation In contrast to insulinoma, hyperinsulinaemic hypoglycaemia after gastric bypass surgery is not accompanied by overexpression of GLP-1 receptor in individual islets. Thus, patients with post-gastric bypass hyperinsulinaemic hypoglycaemia are not candidates for GLP-1 receptor imaging in vivo using radiolabelled exendin. These GLP-1 receptor data support the notion that the islet pathobiology of post-gastric bypass hypoglycaemia is distinctly different from that of benign insulinomas. C1 [Reubi, J. C.; Perren, A.; Rehmann, R.; Waser, B.] Univ Bern, Inst Pathol, Div Cell Biol & Expt Canc Res, CH-3010 Bern, Switzerland. [Christ, E.] Univ Hosp Bern, Div Endocrinol, CH-3010 Bern, Switzerland. [Christ, E.] Univ Hosp Bern, Div Clin Nutr, CH-3010 Bern, Switzerland. [Christ, E.] Univ Hosp Bern, Div Diabetol, CH-3010 Bern, Switzerland. [Callery, M.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Goldfine, A. B.; Patti, M. E.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Callery, M.; Goldfine, A. B.; Patti, M. E.] Harvard Univ, Sch Med, Boston, MA USA. RP Reubi, JC (reprint author), Univ Bern, Inst Pathol, Div Cell Biol & Expt Canc Res, POB 62,Murtenstr 31, CH-3010 Bern, Switzerland. EM reubi@pathology.unibe.ch RI Christ, Emanuel/F-1196-2015; OI Christ, Emanuel/0000-0002-5604-4606; Perren, Aurel/0000-0002-6819-6092 FU Juvenile Diabetes Research Foundation; American Society for Metabolic and Bariatric Surgery FX This study was supported by the Juvenile Diabetes Research Foundation and the American Society for Metabolic and Bariatric Surgery. NR 12 TC 25 Z9 25 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD DEC PY 2010 VL 53 IS 12 BP 2641 EP 2645 DI 10.1007/s00125-010-1901-y PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683WV UT WOS:000284509900023 PM 20835917 ER PT J AU Nguyen, DM Schwartz, J Richardson, P El-Serag, HB AF Nguyen, Dang M. Schwartz, Jim Richardson, Peter El-Serag, Hashem B. TI Oral Bisphosphonate Prescriptions and the Risk of Esophageal Adenocarcinoma in Patients with Barrett's Esophagus SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Bisphosphonates; Barrett's esophagus; Esophageal adenocarcinoma; Veterans; Prescriptions; PPI ID ALENDRONATE; PREVALENCE; SAFETY AB Recent case reports suggested a link between oral bisphosphonate use and esophageal cancer. We therefore examined the association between these medications and the risk of esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). This was a nested, matched case-control study. Cases with incident EAC at least 6 months following BE index date were matched by incidence density sampling to controls with BE without EAC. Patients with BE were found in the national Department of Veterans Affairs computerized databases, and each filled prescriptions for oral bisphosphonates between BE diagnosis and EAC diagnosis (or corresponding dates in controls). Incidence density ratios were calculated using conditional logistic regression models. In a cohort of 11,823 patients with BE, we compared 116 cases and 696 controls. Most were men (97%). Most cases and controls had at least one filled proton pump inhibitor (PPI) prescription (95 vs. 94%, P = 0.5). Filled bisphosphonate prescriptions were very uncommon (1.7 vs. 1.9%) and were not associated with EAC; the incidence density ratio was 0.92 (95% CI, 0.21-4.15). In patients with BE, oral bisphosphonates were not associated with an increased risk of EAC. C1 [El-Serag, Hashem B.] Michael E DeBakey Vet Affairs Med Ctr 152, Houston, TX 77030 USA. [Nguyen, Dang M.; Schwartz, Jim; Richardson, Peter; El-Serag, Hashem B.] Baylor Coll Med, Houston, TX 77030 USA. [Richardson, Peter; El-Serag, Hashem B.] Houston Dept Vet Affairs Med, Houston, TX USA. RP El-Serag, HB (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu FU NIH [K24DK07 8154-03]; Texas Gulf Coast Digestive Diseases Center [NIH P50 DK56338] FX Dr. El-Serag is supported by NIH K24DK07 8154-03 and The Texas Gulf Coast Digestive Diseases Center (NIH P50 DK56338). NR 12 TC 22 Z9 22 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD DEC PY 2010 VL 55 IS 12 BP 3404 EP 3407 DI 10.1007/s10620-010-1198-1 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 678IB UT WOS:000284066200015 PM 20397052 ER PT J AU Nunn, D AF Nunn, Danny TI Preliminary Case Series Report of Incidence of Aspiration After Bilateral Lung Transplant SO DYSPHAGIA LA English DT Meeting Abstract C1 [Nunn, Danny] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD DEC PY 2010 VL 25 IS 4 BP 394 EP 395 PG 2 WC Otorhinolaryngology SC Otorhinolaryngology GA 685QD UT WOS:000284642300142 ER PT J AU Noebels, JL Avoli, M Rogawski, M Olsen, R Delgado-Escueta, AV AF Noebels, Jeffrey L. Avoli, Massimo Rogawski, Michael Olsen, Richard Delgado-Escueta, Antonio V. TI "Jasper's Basic Mechanisms of the Epilepsies" Workshop SO EPILEPSIA LA English DT Editorial Material DE Antiepileptic therapies; Brain development; Classification; Epileptogenesis; Genetics; Epilepsy; Neuronal excitability; Seizures AB P>In 1969, H.H. Jasper, A.A. Ward, and A. Pope and the Public Health Service Advisory Committee on the Epilepsies of the National Institutes of Health (NIH) published the first edition on Basic Mechanisms of the Epilepsies (BME). Since then, basic and clinical researchers in epilepsy have gathered together each decade to assess where epilepsy research has been, what it has accomplished, and where it should go. In 1999, the third edition of BME was named in honor of H.H. Jasper. Projected for publication in 2011, the fourth edition of Jasper's BME will (1) synthesize the role of interactions between neurons, synapses, and glia in the initiation, spread, and arrest of seizures; (2) examine the molecular, cellular, and network plasticity mechanisms that subserve excitability, seizure susceptibility, and ultimately epileptogenesis; (3) provide a framework for expanding the genome of rare mendelian epilepsies and understanding the complex heredity responsible for common epilepsies; (4) explore cellular mechanisms of the two main groups of presently known Mendelian epilepsy genes, namely ion channelopathies and developmental epilepsy genes; and (5) for the first time, describe the current efforts to translate the discoveries in epilepsy disease mechanisms into molecular and cellular therapeutic strategies in order to repair and cure the epilepsies. For an expanded treatment of this topic see Jasper's Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, eds) published by Oxford University Press (available on the National Library of Medicine Bookshelf [NCBI] at http://www.ncbi.nlm.nih.gov/books). C1 [Noebels, Jeffrey L.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Avoli, Massimo] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. [Rogawski, Michael] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. [Olsen, Richard; Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, Los Angeles, CA USA. [Delgado-Escueta, Antonio V.] VA GLAHS W Los Angeles, Los Angeles, CA USA. RP Noebels, JL (reprint author), Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. EM jnoebels@bcm.edu RI Rogawski, Michael/B-6353-2009; OI Rogawski, Michael/0000-0002-3296-8193; Delgado-Escueta, Antonio V./0000-0002-1581-6999; Noebels, Jeffrey /0000-0002-2887-0839 FU NINDS NIH HHS [R01 NS029709, R01 NS029709-19S1, R13 NS063608] NR 7 TC 5 Z9 8 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 DEC PY 2010 VL 51 SU 5 BP 1 EP 5 DI 10.1111/j.1528-1167.2010.02792.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 695QV UT WOS:000285388600001 PM 21208201 ER PT J AU Dudek, FE Staley, KJ AF Dudek, F. Edward Staley, Kevin J. TI Circuit mechanisms of acquired epileptogenesis SO EPILEPSIA LA English DT Article DE Animal model; Epilepsy; Excitatory circuits; Inhibitory interneurons; Latent period; Perinatal stroke; Spontaneous seizures; Temporal lobe epilepsy; Video-EEG telemetry AB P>The time course of development of spontaneous recurrent seizures is a sigmoid function of time after status epilepticus or perinatal stroke, which reflects underlying mechanisms of epileptogenesis. The increase in recurrent excitation after axon sprouting, along with death of specific gamma gamma-aminobutyric acid (GABA)ergic interneurons, may contribute to this temporal pattern of epileptogenesis. For an expanded treatment of this topic see Jasper's Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, eds) published by Oxford University Press (available on the National Library of Medicine Bookshelf [NCBI] at http://www.ncbi.nlm.nih.gov/books). C1 [Dudek, F. Edward] Univ Utah, Sch Med, Dept Physiol, Salt Lake City, UT 84108 USA. [Staley, Kevin J.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Dudek, FE (reprint author), Univ Utah, Sch Med, Dept Physiol, Salt Lake City, UT 84108 USA. EM ed.dudek@hsc.utah.edu NR 3 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 DEC PY 2010 VL 51 SU 5 BP 38 EP 38 DI 10.1111/j.1528-1167.2010.02824.x PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 695QV UT WOS:000285388600033 ER PT J AU Ferraro, TN Serratosa, JM Pal, DK Rouleau, GA Buono, RJ AF Ferraro, Thomas N. Serratosa, Jose M. Pal, Deb K. Rouleau, Guy A. Buono, Russell J. TI Strategies for studying the epilepsy genome SO EPILEPSIA LA English DT Article DE Association studies; Copy number variations; DNA sequencing; Genome-wide association; Linkage analysis; Seizures; Single nucleotide polymorphism (SNP); Susceptibility loci ID ASSOCIATION AB P>Most human epilepsies are multifactorial, resulting from combined effects of genes and environment. The large number of genes whose variation and/or mutation influences the development and progression of epilepsy are only now beginning to be identified. Advanced methods of genetic analysis promise to facilitate understanding of pathogenesis and establishment of new effective treatments. For an expanded treatment of this topic see Jasper's Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, eds) published by Oxford University Press (available on the National Library of Medicine Bookshelf [NCBI] at http://www.ncbi.nlm.nih.gov/books). C1 [Ferraro, Thomas N.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Ferraro, Thomas N.] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA. [Serratosa, Jose M.] Univ Autonoma Madrid, Unidad Epilepsia, Serv Neurol, Fdn Jimenez Diaz, Madrid, Spain. [Pal, Deb K.] Columbia Univ, Dept Neurol, New York, NY USA. [Rouleau, Guy A.] Univ Montreal, Fac Med, Montreal, PQ H3C 3J7, Canada. [Buono, Russell J.] Dept Vet Affairs Med Ctr, Res Serv, Philadelphia, PA 19104 USA. RP Ferraro, TN (reprint author), Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. EM Tnf@mail.med.upenn.edu RI Pal, Deb/F-3318-2011 NR 4 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 DEC PY 2010 VL 51 SU 5 BP 58 EP 58 DI 10.1111/j.1528-1167.2010.02844.x PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 695QV UT WOS:000285388600053 ER PT J AU Kahle, KT Staley, KJ AF Kahle, Kristopher T. Staley, Kevin J. TI A treatment paradigm for neonatal seizures based on the ontogeny of neuronal chloride/cation cotransporter expression in the human cortex SO EPILEPSIA LA English DT Article DE Bumetanide; Chloride concentration; Epilepsy; GABA(A) receptors; NKCC1; Neonatal seizures; Reversal potential AB P>Neonatal seizures are a common problem inadequately treated with standard gamma-aminobutyric acid (GABA)ergic anticonvulsants. Understanding how the ontogeny of neuronal cation/chloride cotransporter expression renders GABAergic signaling excitatory in the neonatal brain has helped explain the increased seizure propensity and poor efficacy of GABAergic anticonvulsants in newborns, and is the rational underlying the polypharmaceutical approach to treating neonatal seizures with bumetanide and phenobarbital. For an expanded treatment of this topic see Jasper's basic mechanisms of the epilepsies. 4th ed. (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, eds) published by Oxford University Press (available on the National Library of Medicine Bookshelf [NCBI] at http://www.ncbi.nlm.nih.gov/books). C1 [Staley, Kevin J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02144 USA. [Kahle, Kristopher T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02144 USA. RP Staley, KJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02144 USA. EM kstaley@partners.org NR 3 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 DEC PY 2010 VL 51 SU 5 BP 89 EP 89 DI 10.1111/j.1528-1167.2010.02875.x PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 695QV UT WOS:000285388600084 ER PT J AU Hausmann, LRM Kressin, NR Hanusa, BH Ibrahim, SA AF Hausmann, Leslie R. M. Kressin, Nancy R. Hanusa, Barbara H. Ibrahim, Said A. TI PERCEIVED RACIAL DISCRIMINATION IN HEALTH CARE AND ITS ASSOCIATION WITH PATIENTS' HEALTHCARE EXPERIENCES: DOES THE MEASURE MATTER? SO ETHNICITY & DISEASE LA English DT Article DE Perceived Discrimination; Quality of Care; Healthcare Utilization; Diabetes ID SELF-REPORTED DISCRIMINATION; AFRICAN-AMERICANS; COMMUNITY SAMPLE; NEW-HAMPSHIRE; DISPARITIES; ADULTS; PERSPECTIVES; PERCEPTIONS; DEPRESSION; SERVICES AB Objectives: Examine whether three measures of perceived racial discrimination in health care detect similar rates of discrimination and show similar associations with patients' health-care experiences. Design: Cross-sectional observational study involving telephone surveys and medical record reviews. Setting: Veterans Affairs Pittsburgh Healthcare System Participants: 50 White and 50 African American veterans with diabetes Main Outcome Measures: Three types of measures of perceived racial discrimination in health care were compared: single-item and multi-item measures assessing personal experiences of discrimination in healthcare settings, and a measure assessing general racism in the healthcare system. Associations of each measure with patient-reported problems with their medical care and receipt of recommended preventive screenings were also explored. Results: More African American than White veterans reported perceived discrimination on all measures (personal discrimination, single-item: 42% vs 6%, P<.001; personal discrimination, multi-item: 42% vs 18%, P=.01; general racism: 74% vs 40%, P=.001). In the total sample, discrimination was more likely to be reported on the general racism measure than on the single-item (OR=36.53, 95% CI=7.95-167.89) or multi-item measures (OR=20.28, 95% CI=5.12-80.34) of personal discrimination. The multi-item measure of personal discrimination (OR=3.96, 95% CI=1.29-12.18) and general racism measure (OR=3.61, 95% CI=1.34-9.71) were significantly associated with patient-reported problems with their care. Receipt of recommended screenings was not associated with any of the discrimination measures. Conclusions: Different measures of perceived racial discrimination in healthcare settings yield different rates of discrimination and show variable associations with patients' perceptions of care. (Ethn Dis. 2010;20:40-47) C1 [Hausmann, Leslie R. M.; Hanusa, Barbara H.; Ibrahim, Said A.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Hlth Serv Res & Dev Serv, Pittsburgh, PA 15206 USA. [Kressin, Nancy R.] Vet Affairs Boston Healthcare Syst, Hlth Serv Res & Dev Serv, Boston, MA USA. [Kressin, Nancy R.] Bedford Vet Affairs Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Kressin, Nancy R.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02215 USA. [Hanusa, Barbara H.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. [Ibrahim, Said A.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. RP Hausmann, LRM (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Hlth Serv Res & Dev Serv, 7180 Highland Dr 151 C-H, Pittsburgh, PA 15206 USA. EM leslie.hausmann@gmail.com FU Veterans Affairs Pittsburgh Healthcare System in Pittsburgh, PA; Center for Health Equity Research and Promotion Pilot Research Program [LIP 72-035]; VA Health Services Research and Development Career Development [RCD 06-287, ER 02801]; Harold Amos Robert Wood Johnson; National Institutes of Musculoskeletal and Skin Disorders [1K24AR055259-01]; Research Career Scientist; Department of Veterans Affairs; Health Services Research Development [RCS 02-066-1] FX This material is the result of work supported by resources and the use of facilities at the Veterans Affairs Pittsburgh Healthcare System in Pittsburgh, PA. The authors take full responsibility for the contents of this paper, which do not represent the views of the Department of Veterans Affairs or the United States Government. The study was funded by the Center for Health Equity Research and Promotion Pilot Research Program (LIP 72-035). Dr. Hausmann was also supported by VA Health Services Research and Development Career Development Awards (RCD 06-287 & ER 02801). Dr. Ibrahim is the recipient of a VA Health Services Research Career Development Award and the Harold Amos Robert Wood Johnson Scholar Award. Dr. Ibrahim was also supported by a K24 Award (1K24AR055259-01) from the National Institutes of Musculoskeletal and Skin Disorders. Dr. Kressin was supported by a Research Career Scientist award, Department of Veterans Affairs, Health Services Research & Development (RCS 02-066-1). The authors thank Amie Cantle and Elizabeth Flatley for their assistance with data collection. The authors have no conflicts of interest to disclose. NR 36 TC 25 Z9 25 U1 3 U2 13 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD WIN PY 2010 VL 20 IS 1 BP 40 EP 47 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 549NJ UT WOS:000274057600009 PM 20178181 ER PT J AU Ajijola, OA Macklin, EA Moore, SA McCarty, D Bischoff, KE Heist, EK Picard, M Ruskin, JN Dec, GW Singh, JP AF Ajijola, Olujimi A. Macklin, Eric A. Moore, Stephanie A. McCarty, David Bischoff, Kara E. Heist, Edwin Kevin Picard, Michael Ruskin, Jeremy N. Dec, George William Singh, Jagmeet P. TI Inpatient vs. elective outpatient cardiac resynchronization therapy device implantation and long-term clinical outcome SO EUROPACE LA English DT Article DE Cardiac resynchronization therapy; Heart failure; Pacing; Clinical outcomes ID HEART-FAILURE PATIENTS; MORTALITY; ECHOCARDIOGRAPHY; DYSSYNCHRONY; PREDICTORS; MORBIDITY AB It remains unclear whether cardiac resynchronization therapy (CRT) device implantation during inpatient (IP) hospitalization affords the same benefit as elective outpatient (OP) implantation. We hypothesized that IPs undergoing CRT device implantation during acute hospitalization may have worse outcomes compared with elective OP implantation. We retrospectively separated patients undergoing CRT implants at Massachusetts General Hospital into OP (n= 196) and IP (n = 105) cohorts. Long-term outcomes, measured as heart failure (HF) hospitalization, all-cause mortality, ventricular assist device placement, or heart transplant over a 2-year follow-up period, were estimated by the Kaplan-Meier method. Propensity scores were generated to balance the baseline co-morbidities between IP and OP. Baseline age, gender, left ventricular ejection fraction, and aetiology of cardiomyopathy were comparable between OP and IP (66.8 +/- 11.8 vs. 67.5 +/- 13.4 years, 78 vs. 84% males, 24 vs. 23%, and 39 vs. 50% ischaemic, P = NS). Inpatients had greater burden of diabetes mellitus (40 vs. 27%, P = 0.028), renal insufficiency (47 vs. 25%, P < 0.001), and right ventricular dysfunction (54 vs. 39%, P = 0.026) compared with OPs. At 2-year follow-up, IP implant was associated with greater risk of HF hospitalization (HR 1.6, 95% CI 1.03-2.48, P = 0.038) compared with elective OP implants. After propensity score adjustment, there was no statistically significant difference in HF hospitalization between the IP and OP groups (HR 1.031, 95% CI 0.61-1.78, P = 0.91). Compared with OP CRT implants, IPs are at increased risk for recurrent HF hospitalization; however, the increased risk is attributable to greater co-morbidities in the IP population. C1 [Ajijola, Olujimi A.; Bischoff, Kara E.; Heist, Edwin Kevin; Ruskin, Jeremy N.; Dec, George William; Singh, Jagmeet P.] Harvard Univ, Cardiac Arrhythmia Serv, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Macklin, Eric A.] Harvard Univ, Ctr Biostat, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Moore, Stephanie A.] Harvard Univ, Heart Failure Serv, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [McCarty, David; Picard, Michael] Harvard Univ, Echocardiog Serv, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Cardiac Arrhythmia Serv, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM jsingh@partners.org RI Macklin, Eric/E-2955-2013; OI Macklin, Eric/0000-0003-1618-3502; Picard, Michael/0000-0002-9264-3243 FU Medtronic, Inc.; St Jude Medical; Boston Scientific; Biotronik FX J.P.S receives research grants and is a consultant to Medtronic, Inc., St Jude Medical, Boston Scientific, and Biotronik. J.N.R is a consultant to Medtronic, Inc. He delivers speech annually for Boston Scientific and St Jude Medical. E.K.H. is a consultant to Biotronik, Boston Scientific, Medtronic, Sorin, and St Jude Medical. NR 13 TC 6 Z9 6 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 J9 EUROPACE JI Europace PD DEC PY 2010 VL 12 IS 12 BP 1745 EP 1749 DI 10.1093/europace/euq319 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 682WE UT WOS:000284432900016 PM 20852289 ER PT J AU Guo, LS Zhou, X Li, YH Cai, J Wei, DM Shi, LA Yang, G Armoundas, AA Yang, XC AF Guo, Lei-Sheng Zhou, Xu Li, Yan-Hui Cai, Jun Wei, Dong-Mei Shi, Liang Yang, Gang Armoundas, Antonis A. Yang, Xin-Chun TI Alcohol ablation at the posterior papillary muscle prevents ventricular fibrillation in swine without affecting mitral valve function SO EUROPACE LA English DT Article DE Chemical ablation; Ventricular fibrillation; Posterior papillary muscle; Swine ID HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY; SUDDEN CARDIAC DEATH; OPEN-CHEST DOGS; CATHETER ABLATION; MAINTENANCE; TACHYCARDIA; MECHANISMS; PURKINJE; REENTRY; HEART AB Radiofrequency ablation at the posterior papillary muscle (PM) significantly reduced ventricular fibrillation (VF) inducibility in rabbits and dogs, suggesting that PM may be involved in the generation of VF. However, the effect of ablation at the PM on VF inducibility remains unknown in normal intact swine hearts because in this species radiofrequency energy delivered at PM provoked incessant VF. Twelve anesthetized swine underwent median sternotomy. Under the ultrasonographic guidance, chemical ablation was performed via injection of dehydrated alcohol into the base of the posterior PM (group PM, n = 6) or anterior wall (control group, n = 6) in the left ventricle. Ventricular fibrillation inducibility and mitral valve function were measured pre- and post-ablation. Hearts were explanted and the ablated myocardium was stained with haematoxylin and eosin. Ventricular fibrillation inducibility was significantly decreased from 100 +/- 0% pre-ablation to 11.9 +/- 7.8% post-ablation in group PM (P = 0.001), whereas it was not statistically different in the control group (100 +/- 0 vs. 92.9 +/- 7.1%, pre-ablation vs. post-ablation). Haemorrhage and cellular necrosis was observed in the centre of ablated myocardium and no significant mitral regurgitation was observed following ablation at the posterior PM. Alcohol ablation of the left posterior PM reduced VF inducibility in normal intact swine hearts, with no significant mitral regurgitation. This suggests that the posterior PM may be involved in the generation of VF, and the recurrence of VF may be prevented by chemical ablation at the posterior PM. C1 [Guo, Lei-Sheng; Zhou, Xu; Li, Yan-Hui; Cai, Jun; Shi, Liang; Yang, Gang; Yang, Xin-Chun] Capital Med Univ, Chaoyang Hosp, Dept Cardiol, Beijing 100020, Peoples R China. [Wei, Dong-Mei] Capital Med Univ, Dept Echog, Chaoyang Hosp, Beijing 100020, Peoples R China. [Armoundas, Antonis A.] Harvard Univ, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. [Guo, Lei-Sheng] Henan Prov Peoples Hosp, Dept Cardiol, Zhengzhou 450003, Peoples R China. RP Yang, XC (reprint author), Capital Med Univ, Chaoyang Hosp, Dept Cardiol, Beijing 100020, Peoples R China. EM x_cyang@yahoo.com.cn FU National Natural Science Foundation of China [30770875]; American Heart Association [0635127N]; NIH [1R21AG035128, 1RO1HL103961]; Cardiovascular Research Society FX This work was supported by grant number 30770875 from National Natural Science Foundation of China (X.-C.Y.), by an American Heart Association Scientist Development Grant #0635127N (A.A.A.), by NIH grants 1R21AG035128 and 1RO1HL103961 (A.A.A.) and by the Cardiovascular Research Society (A.A.A.). NR 25 TC 1 Z9 1 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 EI 1532-2092 J9 EUROPACE JI Europace PD DEC PY 2010 VL 12 IS 12 BP 1781 EP 1786 DI 10.1093/europace/euq337 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 682WE UT WOS:000284432900024 PM 20858694 ER PT J AU Geyer, JR Stewart, CF Kocak, M Broniscer, A Phillips, P Douglas, JG Blaney, SM Packer, RJ Gururangan, S Banerjee, A Kieran, MW Kun, LE Gilbertson, RJ Boyett, JM AF Geyer, J. Russell Stewart, Clinton F. Kocak, Mehmet Broniscer, Alberto Phillips, Peter Douglas, James G. Blaney, Susan M. Packer, Roger J. Gururangan, Sri Banerjee, Anu Kieran, Mark W. Kun, Larry E. Gilbertson, Richard J. Boyett, James M. TI A phase I and biology study of gefitinib and radiation in children with newly diagnosed brain stem gliomas or supratentorial malignant gliomas SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Epidermal growth factor receptor; Gefitinib; Radiotherapy; Brain stem neoplasms; Supratentorial neoplasms; Glioma ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; GENE AMPLIFICATION; STEREOTACTIC BIOPSY; PONTINE GLIOMAS; SOLID TUMORS; CANCER GROUP; TRIAL; EXPRESSION; ZD1839 AB Purpose: To estimate the maximum-tolerated dose (MTD); study the pharmacology of escalating doses of gefitinib combined with radiation therapy in patients <= 21 years with newly diagnosed intrinsic brainstem gliomas (BSG) and incompletely resected supratentorial malignant gliomas (STMG); and to investigate epidermal growth factor receptor (EGFR) amplification and expression in STMG. Patients and methods: Three strata were identified: stratum 1A - BSG; stratum IB - incompletely resected STMG not receiving enzyme-inducing anticonvulsant drugs (EIACD); and stratum II - incompletely resected STMG receiving EIACD. Dose escalation using a modified 3 + 3 cohort design was performed in strata IA and II. The initial gefitinib dosage was 100 mg/m(2)/d commencing with radiation therapy and the dose-finding period extended until 2 weeks post-radiation. Pharmacokinetics (PK) and biology studies were performed in consenting patients. Results: Of the 23 eligible patients, 20 were evaluable for dose-finding. MTDs for strata IA and II were not established as accrual was halted due to four patients experiencing symptomatic intratumoral haemorrhage (ITH); two during and two post dose-finding. ITH was observed in 0 of 11 patients treated at 100 mg/m(2)/d, 1 of 10 at 250 mg/m(2)/d and 3 of 12 at 375 mg/m(2)/d. Subsequently a second patient at 250 mg/m(2)/d experienced ITH. PK analysis showed that the median gefitinib systemic exposure increased with dosage (p = 0.04). EGFR was over-expressed in 5 of 11 STMG and amplified in 4 (36%) samples. Conclusion: This trial provides clear evidence of EGFR amplification in a significant proportion of paediatric STMG and 250 mg/m(2)/d was selected for the phase II trial. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Boyett, James M.] St Jude Childrens Hosp, Dept Biostat, Memphis, TN 38105 USA. [Geyer, J. Russell; Douglas, James G.] Seattle Childrens Hosp, Seattle, WA USA. [Kocak, Mehmet; Boyett, James M.] Pediat Brain Rimor Consortium, Operat & Biostat Ctr, Memphis, TN USA. [Phillips, Peter] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Blaney, Susan M.] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Packer, Roger J.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Gururangan, Sri] Duke Univ, Med Ctr, Durham, NC USA. [Banerjee, Anu] Univ San Francisco, San Francisco, CA 94117 USA. [Kieran, Mark W.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Boyett, JM (reprint author), St Jude Childrens Hosp, Dept Biostat, 262 Danny Thomas Pl,Mail Stop 768, Memphis, TN 38105 USA. EM james.boyett@stjude.org OI Broniscer, Alberto/0000-0001-9646-0463; Kocak, Mehmet/0000-0002-3386-1734; Kieran, Mark/0000-0003-2184-7692 FU Astrazeneca FX Dr. Stewart received research funding from Astrazeneca for the conduct of the pharmacokinetic studies. Dr. Gururangan disclosed a consultant or advisory role with Boehringer Ingelheim Pharma. No other conflicts of interest have been declared. NR 34 TC 24 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 DEC PY 2010 VL 46 IS 18 BP 3287 EP 3293 DI 10.1016/j.ejca.2010.07.005 PG 7 WC Oncology SC Oncology GA 701IY UT WOS:000285812800028 PM 20708924 ER PT J AU Danilov, AV Danilova, OV Brown, JR Rabinowitz, A Klein, AK Huber, BT AF Danilov, Alexey V. Danilova, Olga V. Brown, Jennifer R. Rabinowitz, Arthur Klein, Andreas K. Huber, Brigitte T. TI Dipeptidyl peptidase 2 apoptosis assay determines the B-cell activation stage and predicts prognosis in chronic lymphocytic leukemia SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID GENE MUTATION STATUS; CD38 EXPRESSION; PROLINE DIPEPTIDASE; INHIBITOR P27(KIP1); TYROSINE KINASE; ZAP-70; PROGRESSION; QUIESCENCE; SURVIVAL; PATHWAY AB Objective Dipeptidyl peptidase 2 (DPP2/DPP7) is a regulator of quiescence as inhibition of DPP2 results in apoptosis of resting, but not activated lymphocytes The purpose of the present study was to investigate the prognostic value of DPP2 inhibition and the role of DPP2 in cell cycle in chronic lymphocytic leukemia (CLL) Materials and Methods We screened 152 peripheral blood samples from patients with CLL in an apoptosis assay with AX8819, a DPP2-specific inhibitor The apoptotic response was correlated with B-cell receptor signaling and cell cycle and molecular prognostic factors Results We categorized CLL Into two prognostic subgroups Inhibition of DPP2 induced apoptosis in 60% of CLL while 40% were resistant to apoptosis Resistance to apoptosis correlated with unmutated IgV(H) and increased ZAP-70 expression and was associated with unfavorable clinical outcomes Sensitive CLL B cells expressed high p27, low c-Myc protein levels and decreased Syk phosphorylation, indicative of a resting phenotype DPP2 inhibition in those cells resulted in apoptosis accompanied by enhanced phosphorylation of Syk, degradation of p27 and p130, and upregulation of c-Myc, indicative of activation and inappropriate cell cycle entry Resistant CLL demonstrated baseline low p27 and high c-Myc protein levels and increased pSyk, indicative of an activated phenotype Inhibition of heat shock protein 90 in this subset of CLL partially reversed apoptosis resistance Conclusions The DPP2 apoptosis assay provides a reliable prognostic factor in CLL CLL B cells sensitive to DPP2 inhibition are in true Go, while resistant CLL B-cells are partially activated DPP2 inhibition alone or with concomitant inhibition of heat shock protein 90 warrants investigation as a therapeutic modality in CLL (C) 2010 ISEH - Society for Hematology and Stem Cells Published by Elsevier Inc C1 [Danilova, Olga V.; Huber, Brigitte T.] Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. [Danilov, Alexey V.; Klein, Andreas K.] Tufts Med Ctr, Boston, MA USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rabinowitz, Arthur] Lahey Clin Fdn, Burlington, MA USA. RP Huber, BT (reprint author), Tufts Univ, Sch Med, Dept Pathol, 150 Harrison Ave, Boston, MA 02111 USA. FU BTH [DPP2 RO1A143469 OVD]; National Institutes of Health [K23 CA115682, PO1-CA081534] FX We would like to thank the CLL Research Consortium Tissue Bank for determination of IgVH and ZAP-70 on the DFCI CLL samples Supported by BTH - DPP2 RO1A143469 OVD - BD Biosciences Research Grant J R B was supported in part by National Institutes of Health grants K23 CA115682 and PO1-CA081534 for the CLL Research Consortium NR 41 TC 6 Z9 6 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD DEC PY 2010 VL 38 IS 12 BP 1167 EP 1177 DI 10.1016/j.exphem.2010.08.008 PG 11 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 689ZC UT WOS:000284968600006 PM 20817072 ER PT J AU Rodriguez, N Goldstein, DP Berkowitz, RS AF Rodriguez, Noah Goldstein, Donald P. Berkowitz, Ross S. TI Treating gestational trophoblastic disease SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE complete mole; gestational trophoblastic disease; gestational trophoblastic neoplasia; molar pregnancy ID HUMAN CHORIONIC-GONADOTROPIN; CENTRAL-NERVOUS-SYSTEM; COMPLETE HYDATIDIFORM MOLE; GYNECOLOGIC-ONCOLOGY-GROUP; QUALITY-OF-LIFE; BONE-MARROW-TRANSPLANTATION; UNDETECTABLE HCG LEVELS; HIGH-DOSE CHEMOTHERAPY; LOW-RISK; BRAIN METASTASES AB Importance of the field: Gestational trophoblastic disease is one of the few human malignancies that is curable, even in advanced stages of the disease. However, appropriate management and follow-up are essential components in curing this disease. Areas covered in this review: Observational, retrospective and prospective studies evaluating the efficacy of medical and surgical management of gestational trophoblastic disease were analyzed to provide a comprehensive review of current and new treatment modalities. We searched PubMed, Medline and the Library of Congress from January 1965 to January 2010. What the reader will gain: The reader will obtain information on how to classify gestational trophoblastic neoplasia (GTN) into low-and high-risk groups, as well as learn the medical and surgical management of low-and high-risk GTN and recurrent GTN. The effectiveness of treatment regimens and subsequent fertility is also reviewed. Take home message: GTN is highly responsive to chemotherapy. However, surgery is an important adjunct in select cases. Even in advanced-stage or recurrent disease, cure can be achieved and fertility preserved. C1 [Rodriguez, Noah; Goldstein, Donald P.; Berkowitz, Ross S.] Harvard Univ, Sch Med, Dana Farber Canc Inst,New England Trophoblast Dis, Brigham & Womens Hosp,Dept Obstet & Gynecol, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,New England Trophoblast Dis, Brigham & Womens Hosp,Dept Obstet & Gynecol, 44 Binney St, Boston, MA 02115 USA. EM rberkowitz@partners.org NR 120 TC 6 Z9 11 U1 2 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD DEC PY 2010 VL 11 IS 18 BP 3027 EP 3039 DI 10.1517/14656566.2010.512288 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 681KZ UT WOS:000284315200009 PM 20958110 ER PT J AU Siddiqui, MM Feldman, AS AF Siddiqui, Mohummad Minhaj Feldman, Adam S. TI Advances in the evaluation and management of lymph node involvement in urothelial carcinoma of the bladder SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Editorial Material DE bladder cancer imaging; bladder cancer staging; lymphotrophic nanoparticle; ultrasmall particles of iron oxide; urothelial carcinoma MRI ID TRANSITIONAL-CELL CARCINOMA; RADICAL CYSTECTOMY; URINARY-BLADDER; SURGICAL FACTORS; PROSTATE-CANCER; UROPLAKIN-II; LYMPHADENECTOMY; METASTASES; CT; PROGNOSIS C1 [Siddiqui, Mohummad Minhaj; Feldman, Adam S.] Massachusetts Gen Hosp, Boston, MA 02459 USA. RP Feldman, AS (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 7E, Boston, MA 02459 USA. EM afeldman@partners.org OI Siddiqui, Mohummad/0000-0002-4484-6820 NR 32 TC 0 Z9 0 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD DEC PY 2010 VL 10 IS 12 BP 1855 EP 1859 DI 10.1586/ERA.10.151 PG 5 WC Oncology SC Oncology GA 708HS UT WOS:000286353500001 PM 21110750 ER PT J AU Sher, L Mindes, J Novakovic, V AF Sher, Leo Mindes, Janet Novakovic, Vladan TI Transcranial magnetic stimulation and the treatment of suicidality SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Editorial Material DE brain stimulation; depression; suicide; transcranial magnetic stimulation ID OBSESSIVE-COMPULSIVE DISORDER; PREFRONTAL CORTEX; CONTROLLED-TRIAL; BEHAVIOR; DEPRESSION; NEUROBIOLOGY; STRATEGIES; EFFICACY; SAFETY; RTMS C1 [Sher, Leo; Novakovic, Vladan] James J Peters Vet Adm, Med Ctr, Mt Sinai Sch Med, Dept Psychiat, Bronx, NY 10468 USA. [Mindes, Janet] Columbia Univ, Ctr Bioeth, New York, NY USA. RP Sher, L (reprint author), James J Peters Vet Adm, Med Ctr, Mt Sinai Sch Med, Dept Psychiat, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM drleosher@gmail.com NR 36 TC 1 Z9 1 U1 1 U2 1 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD DEC PY 2010 VL 10 IS 12 BP 1781 EP 1784 DI 10.1586/ERN.10.166 PG 4 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 694SO UT WOS:000285319500003 PM 21091308 ER PT J AU Freedy, JR Steenkamp, MM Magruder, KM Yeager, DE Zoller, JS Hueston, WJ Carek, PJ AF Freedy, John R. Steenkamp, Maria M. Magruder, Kathryn M. Yeager, Derik E. Zoller, James S. Hueston, William J. Carek, Peter J. TI Post-traumatic stress disorder screening test performance in civilian primary care SO FAMILY PRACTICE LA English DT Article DE Civilian primary care; PTSD; screening ID MENTAL-HEALTH PROBLEMS; ADMINISTERED PTSD SCALE; PSYCHOMETRIC PROPERTIES; PSYCHIATRIC-DISORDERS; PC-PTSD; DEPRESSION; PREVALENCE; CHECKLIST; VETERANS; TRAUMA AB Methods. This was a cross-sectional cohort study of adults attending a family medicine residency training clinic in the southeastern USA. Four hundred and eleven participants completed a structured telephone interview that followed an index clinic visit. Screening tests included: PTSD Symptom Checklist-Civilian Version (17 items), SPAN (four items), Breslau's scale (seven items) and Primary Care PTSD screen (PC-PTSD) (four items). A modified Clinician-Administered PTSD Scale was used to determine past month PTSD for comparison. Receiver operating characteristic analysis based on area under the curve (AUC) was used to assess diagnostic efficiency (> 0.80 desired). Cut-off scores were selected to yield optimal sensitivity and specificity (> 80%). Results. Past month PTSD was substantial (women = 35.8% and men = 20.0%; P < 0.01). AUC values were PTSD Symptom Checklist (PCL) (0.897), SPAN (0.806), Breslau's scale (0.886) and PC-PTSD (0.885). Optimal cut-scores yielded the following sensitivities and specificities: PCL (80.0% and 80.7%; cut-off = 43), SPAN (75.9% and 71.6%; cut-off = 3), Breslau's scale (84.5% and 76.4%; cut-off = 4) and PC-PTSD (85.1% and 82.0%; cut-off = 3). Overall and gender-specific screening test performances were explored. Conclusions. Results confirm: (i) PTSD was common, especially among women; (ii) all four PTSD screening tests were diagnostically adequate; (iii) Two of four PTSD screening tests showed adequate sensitivity and specificity (> 80%) and (iv) The PC-PTSD screening test (four items) appeared to be the best single screening test. There are few studies to establish the utility of PTSD screening tests within civilian primary care. C1 [Freedy, John R.; Hueston, William J.; Carek, Peter J.] Med Univ S Carolina, Dept Family Med, Charleston, SC 29425 USA. [Steenkamp, Maria M.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Magruder, Kathryn M.; Yeager, Derik E.] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC 29401 USA. [Magruder, Kathryn M.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Zoller, James S.] Med Univ S Carolina, Dept Hlth Adm & Policy, Charleston, SC 29425 USA. RP Freedy, JR (reprint author), Med Univ S Carolina, Dept Family Med, 295 Calhoun St, Charleston, SC 29425 USA. EM freedyjr@musc.edu FU Office of Research and Sponsored Programs at the Medical University of South Carolina in Charleston (JRF) FX Funding: Office of Research and Sponsored Programs at the Medical University of South Carolina in Charleston (JRF). NR 69 TC 35 Z9 35 U1 3 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0263-2136 EI 1460-2229 J9 FAM PRACT JI Fam. Pr. PD DEC PY 2010 VL 27 IS 6 BP 615 EP 624 DI 10.1093/fampra/cmq049 PG 10 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 682WA UT WOS:000284432500005 PM 20622049 ER PT J AU Gu, AH Ji, GX Zhu, PF Zhou, Y Fu, GB Xia, YK Song, L Wang, SL Wang, XR AF Gu, Aihua Ji, Guixiang Zhu, Pengfei Zhou, Yong Fu, Guangbo Xia, Yankai Song, Ling Wang, Shoulin Wang, Xinru TI Nucleotide excision repair polymorphisms, polycyclic aromatic hydrocarbon exposure, and their effects on sperm deoxyribonucleic acid damage and male factor infertility SO FERTILITY AND STERILITY LA English DT Article DE Polycyclic aromatic hydrocarbons (PAHs); nucleotide excision repair (NER); xeroderma pigmentosum group A gene (XPA); polymorphism; gene-environment interaction; sperm DNA damage ID OXIDATIVE DNA-DAMAGE; BREAST-CANCER RISK; ENVIRONMENTAL-POLLUTION; CIGARETTE-SMOKING; ADDUCTS; GENES; CAPACITY; POPULATION; ERCC1; PAHS AB Objective: To evaluate the effects of polycyclic aromatic hydrocarbon (PAH) exposure and four functional genetic polymorphisms in the nucleotide excision repair pathway, alone or combined, on sperm DNA integrity and male fertility. Design: Retrospective case-only and case-control study. Setting: One university and three centers of clinical reproductive medicine in the Jiangsu Province of China. Patient(s): Six hundred twenty infertile men and 273 controls were recruited for the study. Intervention(s): None. Main Outcome Measure(s): Exposure to PAHs was detected as urinary 1-hydroxypyrene level. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism, and sperm DNA damage was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay with use of flow cytometry. Result(s): Increased sperm DNA damage was found to be associated significantly with increased urinary concentrations of 1-hydroxypyrene. We also observed that the xeroderma pigmentosum group A (XPA)-4 G/A polymorphism was associated with sperm DNA damage. Subjects homozygous for XPA-4 AA had significantly more sperm DNA damage compared with subjects for XPA-4 GG. Moreover, on the basis of a case-control study, a significant interaction was found between XPA-4 G/A polymorphism and PAH exposures on the sperm DNA damage risk (odds ratio = 2.86, 95% confidence interval = 1.77-4.61). Conclusion(s): We provide the first evidence for potential gene-environment interactions between nucleotide excision repair polymorphisms and PAH exposure on the sperm DNA damage and male factor infertility in men with no occupational exposure to PAHs. (Fertil Steril (R) 2010;94:2620-5. (C) 2010 by American Society for Reproductive Medicine.) C1 [Gu, Aihua; Ji, Guixiang; Zhu, Pengfei; Xia, Yankai; Song, Ling; Wang, Shoulin; Wang, Xinru] Nanjing Med Univ, Inst Toxicol, Key Lab Reprod Med, Nanjing 210029, Peoples R China. [Zhou, Yong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Fu, Guangbo] Nanjing Med Univ, Dept Urol, Huai An Affiliated Hosp 1, Huaian, Peoples R China. RP Wang, XR (reprint author), Nanjing Med Univ, Inst Toxicol, Key Lab Reprod Med, Nanjing 210029, Peoples R China. EM xrwang@njmu.edu.cn FU National Basic Research Program of China [2009CB941703]; National Science Foundation of China [30901210]; National Natural Science of China [30930079]; Natural Science Foundation of Jiangsu Province [BK2009422]; Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT) [IRT0631]; Natural Science Foundation of the Jiangsu Higher Education Institutions of China [09KJB330002]; Ministry of Education of China [20093234120001] FX Supported by the National Basic Research Program of China (973 Program, 2009CB941703); the National Science Foundation of China (grant 30901210); the State Key Program of National Natural Science of China (grant 30930079); the Natural Science Foundation of Jiangsu Province (grant BK2009422); the Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT), IRT0631; the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (grant 09KJB330002); and the Doctoral Fund of Ministry of Education of China (grant 20093234120001). NR 39 TC 2 Z9 2 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD DEC PY 2010 VL 94 IS 7 BP 2620 EP U154 DI 10.1016/j.fertnstert.2010.04.059 PG 11 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 684TV UT WOS:000284573700028 PM 20557883 ER PT J AU Oberley-Deegan, RE Rebits, BW Weaver, MR Tollefson, AK Bai, XY McGibney, M Ovrutsky, AR Chan, ED Crapo, JD AF Oberley-Deegan, Rebecca E. Rebits, Brittany W. Weaver, Michael R. Tollefson, Angela K. Bai, Xiyuan McGibney, Mischa Ovrutsky, Alida R. Chan, Edward D. Crapo, James D. TI An oxidative environment promotes growth of Mycobacterium abscessus SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Mycobacterium abscessus; Oxidation; Antioxidants; MnTE 2 PyP; N acetyl1 cysteine; IHP 1; Alveolar macrophages; Smoking; Free radicals ID SUPEROXIDE-DISMUTASE; GLUTATHIONE-PEROXIDASE; HUMAN MACROPHAGES; TUBERCULOSIS; DISEASE; CELLS AB Mycobacterium abscessus infections particularly those causing chronic lung diseases are becoming more prevalent worldwide M abscessus infections are difficult to treat because of antibiotic resistance Thus new treatment options are urgently needed M abscessus is an intracellular pathogen that primarily infects macrophages and fibroblasts Because this bacterium has only recently been identified as a separate species very little is known about M abscessus-host interactions and how M abscessus growth is regulated Oxidative stress has long been shown to inhibit the growth of bacterial organisms However some intracellular bacteria such as Mycobacterium tuberculosis grow well in oxidizing environments In this study we show that M abscessus infection causes the host cell environment to become more oxidizing Furthermore we show that a more oxidizing environment leads to enhanced growth of M abscessus inside macrophages In the presence of antioxidants MnTE-2 PyP (chemical name manganese(II) mesa tetrakis (N-methylpyridinium 2 yl) por phyrin) or N acetyl-1-cysteine M abscessus growth is inhibited These results lead us to postulate that antioxidants may aid in the treatment of M abscessus infections (C) 2010 Elsevier Inc All rights reserved C1 [Oberley-Deegan, Rebecca E.; Rebits, Brittany W.; Weaver, Michael R.; Tollefson, Angela K.; Bai, Xiyuan; McGibney, Mischa; Ovrutsky, Alida R.; Chan, Edward D.; Crapo, James D.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Bai, Xiyuan; McGibney, Mischa; Ovrutsky, Alida R.; Chan, Edward D.] Denver VA Med Ctr, Dept Med, Denver, CO 80220 USA. RP Oberley-Deegan, RE (reprint author), Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. RI Oberley-Deegan, Rebecca/E-4176-2013 OI Oberley-Deegan, Rebecca/0000-0002-0391-142X FU NIH [RO1-HL66112]; Potts Foundation; Monfort Foundation; Department of Defense FX This research was funded by NIH-RO1-HL66112 a Potts Foundation Award the Monfort Foundation and the Department of Defense The authors thank Dr Christine Weydert for her helpful suggestions NR 24 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC 1 PY 2010 VL 49 IS 11 BP 1666 EP 1673 DI 10.1016/j.freeradbiomed.2010.08.026 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 684MW UT WOS:000284555000007 PM 20807564 ER PT J AU Baba, Y Nosho, K Shima, K Huttenhower, C Tanaka, N Hazra, A Giovannucci, EL Fuchs, CS Ogino, S AF Baba, Yoshifumi Nosho, Katsuhiko Shima, Kaori Huttenhower, Curtis Tanaka, Noriko Hazra, Aditi Giovannucci, Edward L. Fuchs, Charles S. Ogino, Shuji TI Hypomethylation of the IGF2 DMR in Colorectal Tumors, Detected by Bisulfite Pyrosequencing, Is Associated With Poor Prognosis SO GASTROENTEROLOGY LA English DT Article DE Epigenetics; Clinical Outcome; Therapeutic Target; Imprinting Control Region ID ISLAND METHYLATOR PHENOTYPE; GROWTH-FACTOR-II; POPULATION-BASED SAMPLE; COLON-CANCER; MICROSATELLITE INSTABILITY; DNA METHYLATION; LINE-1 HYPOMETHYLATION; EXPRESSION PROFILE; BRAF MUTATION; RISK AB BACKGROUND & AIMS: The insulin-like growth factor 2 (IGF2) gene is normally imprinted. Constitutive loss of imprinting (LOI) of IGF2 has been associated with increased risks of colon cancer and adenoma, indicating its role in carcinogenesis. The conventional LOI assay relies on a germline polymorphism to distinguish between 2 allelic expression patterns but results in many uninformative cases. IGF2 LOI correlates with hypomethylation at the differentially methylated region (DMR)-0. An assay for methylation of the DMR0 could overcome the limitations of the conventional IGF2 LOI assay. METHODS: We measured methylation at the IGF2 DMR0 using a bisulfite-pyrosequencing assay with 1178 paraffin-embedded colorectal cancer tissue samples from 2 prospective cohort studies. A Cox proportional hazard model was used to calculate mortality hazard ratio (HR); calculations were adjusted for microsatellite instability; the CpG island methylator phenotype; LINE-1 methylation; and KRAS, BRAF, and PIK3CA mutations. RESULTS: Methylation at the IGF2 DMR0 was successfully measured in 1105 (94%) of 1178 samples. Colorectal tumors had significantly less methylation at the DMR0 compared with matched, normal colonic mucosa (P <.0001; N = 51). Among 1033 patients eligible for survival analysis, hypomethylation of the IGF2 DMR0 was significantly associated with higher overall mortality (log-rank P =.0006; univariate HR, 1.41; 95% confidence interval, 1.16 -1.71; P =.0006; multivariate HR, 1.33; 95% confidence interval, 1.08 -1.63; P =.0066). CONCLUSIONS: A bisulfite-pyrosequencing assay to measure methylation of the IGF2 DMR0 is robust and applicable to paraffin-embedded tissue. IGF2 DMR0 hypomethylation in colorectal tumor samples is associated with shorter survival time, so it might be developed as a prognostic biomarker. C1 [Ogino, Shuji] Harvard Univ, Sch Med, Ctr Mol Oncol Pathol,Dept Pathol, Dana Farber Canc Inst,Brigham & Womens Hosp, Boston, MA 02115 USA. [Baba, Yoshifumi; Nosho, Katsuhiko; Shima, Kaori; Tanaka, Noriko; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Huttenhower, Curtis; Tanaka, Noriko] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Hazra, Aditi; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Ctr Mol Oncol Pathol,Dept Pathol, Dana Farber Canc Inst,Brigham & Womens Hosp, 44 Binney St,Room JF-215C, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu OI Huttenhower, Curtis/0000-0002-1110-0096 FU US National Institutes of Health [P01 CA87969, P01 CA55075, P50 CA127003, K07 CA122826, R01 CA151993]; Bennett Family Fund for Targeted Therapies Research; Entertainment Industry Foundation through the National Colorectal Cancer Research Alliance; Uehara Memorial Foundation; Japan Society for the Promotion of Science FX This work was supported by the US National Institutes of Health (P01 CA87969 to S.H., P01 CA55075 to W.W., P50 CA127003 to C.S.F., K07 CA122826 to S.O., and R01 CA151993 to S.O.); the Bennett Family Fund for Targeted Therapies Research; and the Entertainment Industry Foundation through the National Colorectal Cancer Research Alliance. Y.B. was supported by a fellowship grant from the Uehara Memorial Foundation, and K.N. was supported by a fellowship grant from the Japan Society for the Promotion of Science. NR 53 TC 38 Z9 39 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2010 VL 139 IS 6 BP 1855 EP 1864 DI 10.1053/j.gastro.2010.07.050 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 688IS UT WOS:000284843600023 PM 20682317 ER PT J AU Sonnenberg, A Lash, RH Genta, RM AF Sonnenberg, Amnon Lash, Richard H. Genta, Robert M. TI A National Study of Helicobactor pylori Infection in Gastric Biopsy Specimens SO GASTROENTEROLOGY LA English DT Article DE Epidemiology of Gastritis; Barrett's Esophagus; Gastrointestinal Microbes; Stomach Cancer ID GASTROESOPHAGEAL-REFLUX DISEASE; BARRETTS-ESOPHAGUS; SYDNEY SYSTEM; INTESTINAL METAPLASIA; UNITED-STATES; RISK-FACTORS; EPIDEMIOLOGY; METAANALYSIS; PREVALENCE AB BACKGROUND & AIMS: We investigated whether infection with Helicobacter pylori and signs of chronic active gastritis and intestinal metaplasia in gastric biopsy samples were inversely associated with Barrett's metaplasia. METHODS: We studied gastric biopsy samples from 78,985 unique patients. Histologic findings were correlated with sociodemographic patient characteristics using multivariate logistic regression to calculate odds ratios and 95% confidence intervals. RESULTS: H pylori infection, chronic active gastritis, and intestinal metaplasia had similar epidemiologic patterns. The presence of each, based on histology analyses, was significantly associated with that of the others. They were also characterized by similar geographic distributions within the United States. All 3 disorders were more common among men and among Medicaid patients (compared with those with other insurance) and were inversely associated with Barrett's metaplasia (less frequent in patients with Barrett's metaplasia). CONCLUSIONS: H pylori infection and associated disorders, such as chronic active gastritis and intestinal metaplasia, are inversely associated with Barrett's metaplasia. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Lash, Richard H.; Genta, Robert M.] Caris Life Sci, Irving, TX USA. [Genta, Robert M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Genta, Robert M.] Dallas VA Med Ctr, Dallas, TX USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr P3 GI, 3710 SW,US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu FU Takeda Pharmaceuticals FX The authors disclose the following: Amnon Sonnenberg is supported by a grant from Takeda Pharmaceuticals. Richard H. Lash and Robert M. Genta are employed by Caris Life Sciences, Irving, Texas. Richard H. Lash is an officer and Richard H. Lash and Robert M. Genta are shareholders of Caris Life Sciences. The remaining authors disclose no conflicts. NR 19 TC 70 Z9 73 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2010 VL 139 IS 6 BP 1894 EP U157 DI 10.1053/j.gastro.2010.08.018 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 688IS UT WOS:000284843600027 PM 20727889 ER PT J AU Chaniotou, Z Giannogonas, P Theoharis, S Teli, T Gay, J Savidge, T Koutmani, Y Brugni, J Kokkotou, E Pothoulakis, C Karalis, KP AF Chaniotou, Zoi Giannogonas, Panagiotis Theoharis, Stamatis Teli, Thalia Gay, Jerome Savidge, Tor Koutmani, Yassemi Brugni, James Kokkotou, Efi Pothoulakis, Charalabos Karalis, Katia P. TI Corticotropin-Releasing Factor Regulates TLR4 Expression in the Colon and Protects Mice From Colitis SO GASTROENTEROLOGY LA English DT Article DE CRF; DSS-Colitis; TLR4; Intestinal Inflammation ID INFLAMMATORY-BOWEL-DISEASE; TOLL-LIKE RECEPTOR-4; ULCERATIVE-COLITIS; INTESTINAL INFLAMMATION; GENE-EXPRESSION; INNATE IMMUNITY; HORMONE; DEFICIENCY; ACTIVATION; MECHANISMS AB BACKGROUND & AIMS: Defects in the colonic innate immune response have been associated with inflammatory bowel disease (IBD). Corticotropin-releasing hormone (CRH, or corticotropin-releasing factor [CRF]) is a neuropeptide that mediates the stress response in humans, is an immunomodulatory factor with proinflammatory effects, and regulates transcription of Toll-like receptors (TLR)-2 and TLR4. We investigated the role of CRF in an innate immunity-dependent mouse model of IBD. METHODS: Crh(-/-) and wild-type (Crh(+/+)) mice, which are glucocorticoid insufficient, were given dextran sodium sulfate in their drinking water to induce colitis; in some experiments, mice were also given glucocorticoids. Phenotypes of mice were compared; tissues were analyzed by histology and for expression of immune mediators. RESULTS: Crh(-/-) mice had more colonic inflammation than Crh(+/+) mice, characterized by reduced numbers of crypts and severe epithelial damage and ulcerations. Colonic tissue levels of the proinflammatory factors interleukin-12 and prostaglandin E-2 were increased in the Crh(-/-) mice. Colons of Crh(-/-) mice expressed lower levels of Tlr4 than wild-type mice before, but not after, colitis was induced. Administration of glucocorticoid at low levels did not prevent Crh(-/-) mice from developing severe colitis. Crh(-/-) mice were unable to recover from acute colitis, as indicated by their increased death rate. CONCLUSIONS: Mice deficient in CRF down-regulate TLR4 and are more susceptible to dextran sodium sulfate-induced colitis. CRF has anti-inflammatory effects in innate immunity-dependent colitis and its recovery phase; these are independent of glucocorticoid administration. CRF might therefore be developed as a therapeutic target for patients with IBD. C1 [Chaniotou, Zoi; Giannogonas, Panagiotis; Teli, Thalia; Koutmani, Yassemi; Karalis, Katia P.] Acad Athens, Biomed Res Fdn, Ctr Basic Res, Dev Biol Sect, Athens, Greece. [Theoharis, Stamatis] Univ Athens, Sch Med, Dept Forens Med, GR-11527 Athens, Greece. [Gay, Jerome; Karalis, Katia P.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Savidge, Tor] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Brugni, James; Pothoulakis, Charalabos] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Ctr Inflammatory Bowel Dis, Los Angeles, CA 90095 USA. [Kokkotou, Efi] Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. RP Karalis, KP (reprint author), 4 Soranou Efessiou Papagou, Athens 12527, Greece. EM kkarali@bioacademy.gr NR 60 TC 15 Z9 17 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2010 VL 139 IS 6 BP 2083 EP 2092 DI 10.1053/j.gastro.2010.08.024 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 688IS UT WOS:000284843600046 PM 20732324 ER PT J AU Spiegel, BMR AF Spiegel, Brennan M. R. TI How and when to prepare for the GI board examination SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material C1 Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr,VA Ctr Outcomes Res & Edu, Los Angeles, CA 90095 USA. RP Spiegel, BMR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr,VA Ctr Outcomes Res & Edu, Los Angeles, CA 90095 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD DEC PY 2010 VL 72 IS 6 BP 1250 EP 1252 DI 10.1016/j.gie.2010.10.022 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 694SJ UT WOS:000285319000020 PM 21111875 ER PT J AU Antonescu, CR Zhang, L Chang, NE Pawel, BR Travis, W Katabi, N Edelman, M Rosenberg, AE Nielsen, GP Dal Cin, P Fletcher, CDM AF Antonescu, Cristina R. Zhang, Lei Chang, Ning-En Pawel, Bruce R. Travis, William Katabi, Nora Edelman, Morris Rosenberg, Andrew E. Nielsen, G. Petur Dal Cin, Paola Fletcher, Christopher D. M. TI EWSR1-POU5F1 Fusion in Soft Tissue Myoepithelial Tumors. A Molecular Analysis of Sixty-Six Cases, Including Soft Tissue, Bone, and Visceral Lesions, Showing Common Involvement of the EWSR1 gene SO GENES CHROMOSOMES & CANCER LA English DT Article ID IN-SITU HYBRIDIZATION; MUCOEPIDERMOID CARCINOMA; SALIVARY-GLANDS; CHORDOMA; EXPRESSION; ADENOMAS; DEFINES; POU5F1 AB The diagnosis of myoepithelial (ME) tumors outside salivary glands remains challenging, especially in unusual clinical presentations, such as bone or visceral locations. A few reports have indicated EWSR1 gene rearrangement in soft tissue ME tumors, and, in one case each, the fusion partner was identified as either PBX1 or ZNF444. However, larger studies to investigate whether these genetic abnormalities are recurrent or restricted to tumors in soft tissue locations are lacking. Sixty-six ME tumors mainly from soft tissue (71%), but also from skin, bone, and visceral locations, characterized by classic morphological features and supporting immunoprofile were studied. Gene rearrangements in EWSR1, FUS, PBX1, and ZNF444 were investigated by fluorescence in situ hybridization. EWSR1 gene rearrangement was detected in 45% of the cases. A EWSR1-POU5F1 fusion was identified in a pediatric soft tissue tumor by 3'Rapid Amplification of cDNA Ends (RACE) and subsequently confirmed in four additional soft tissue tumors in children and young adults. An EWSR1-PBX1 fusion was seen in five cases, whereas EWSR1-ZNF444 and FUS gene rearrangement was noted in one pulmonary tumor each. In conclusion, EWSR1 gene rearrangement is a common event in ME tumors arising outside salivary glands, irrespective of anatomical location. EWSR1-negative tumors were more often benign, superficially located, and showed ductal differentiation, suggesting the possibility of genetically distinct groups. A subset of soft tissue ME tumors with clear cell morphology harbor an EWSR1-POU5F1 fusion, which can be used as a molecular diagnostic test in difficult cases. These findings do not support a pathogenetic relationship between soft tissue ME tumors and their salivary gland counterparts. (C) 2010 Wiley-Liss, Inc. C1 [Antonescu, Cristina R.; Zhang, Lei; Chang, Ning-En; Travis, William; Katabi, Nora] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Pawel, Bruce R.] Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA. [Edelman, Morris] Long Isl Jewish Med Ctr, Dept Pathol, New Hyde Pk, NY USA. [Rosenberg, Andrew E.; Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Dal Cin, Paola; Fletcher, Christopher D. M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Antonescu, CR (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. EM antonesc@mskcc.org; cfleteher@partners.org FU [P01CA47179] FX Supported by: P01CA47179 (C. R. Antoneseu). NR 23 TC 155 Z9 159 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD DEC PY 2010 VL 49 IS 12 BP 1114 EP 1124 DI 10.1002/gcc.20819 PG 11 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 670CH UT WOS:000283398000005 PM 20815032 ER PT J AU Smolen, GA Zhang, JM Zubrowski, MJ Edelman, EJ Luo, BA Yu, M Ng, LW Scherber, CM Schott, BJ Ramaswamy, S Irimia, D Root, DE Haber, DA AF Smolen, Gromoslaw A. Zhang, Jianmin Zubrowski, Matthew J. Edelman, Elena J. Luo, Biao Yu, Min Ng, Lydia W. Scherber, Cally M. Schott, Benjamin J. Ramaswamy, Sridhar Irimia, Daniel Root, David E. Haber, Daniel A. TI A genome-wide RNAi screen identifies multiple RSK-dependent regulators of cell migration SO GENES & DEVELOPMENT LA English DT Article DE EMT; MCF10A; RNAi; RSK; cell migration; high throughput ID EPITHELIAL-MESENCHYMAL TRANSITION; RIBOSOMAL S6 KINASE; BREAST-CANCER; ESSENTIAL GENES; PROTEIN-KINASE; METASTASIS; EXPRESSION; REVEALS; PATHWAY; DISEASE AB To define the functional pathways regulating epithelial cell migration, we performed a genome-wide RNAi screen using 55,000 pooled lentiviral shRNAs targeting similar to 11,000 genes, selecting for transduced cells with increased motility. A stringent validation protocol generated a set of 31 genes representing diverse pathways whose knockdown dramatically enhances cellular migration. Some of these pathways share features of epithelial-to-mesenchymal transition (EMT), and together they implicate key regulators of transcription, cellular signaling, and metabolism, as well as novel modulators of cellular trafficking, such as DLG5. In delineating downstream pathways mediating these migration phenotypes, we observed universal activation of ERKs and a profound dependence on their RSK effectors. Pharmacological inhibition of RSK dramatically suppresses epithelial cell migration induced by knockdown of all 31 genes, suggesting that convergence of diverse migratory pathways on this kinase may provide a therapeutic opportunity in disorders of cell migration, including cancer metastasis. C1 [Smolen, Gromoslaw A.; Zhang, Jianmin; Zubrowski, Matthew J.; Edelman, Elena J.; Yu, Min; Ng, Lydia W.; Schott, Benjamin J.; Ramaswamy, Sridhar; Haber, Daniel A.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Charlestown, MA 02129 USA. [Luo, Biao; Ramaswamy, Sridhar; Root, David E.] Broad Inst, Cambridge, MA 02142 USA. [Scherber, Cally M.; Irimia, Daniel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, BioMEMS Resource Ctr,Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. [Haber, Daniel A.] Harvard Univ, Howard Hughes Med Inst, Sch Med, Boston, MA 02114 USA. RP Haber, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu OI Irimia, Daniel/0000-0001-7347-2082 FU March of Dimes Foundation [5-FY09-73]; Charles H. Hood Foundation; NIH [CA09361-27, CA129933]; Howard Hughes Medical Institute; DF/HCC SPORE in Breast Cancer [2P50 CA89393-09]; DOD Center of Excellence in Breast Cancer [BC05-COE W81XH-06-2-0033]; Harvard Medical School; AID for Cancer Research; [R21CA135601] FX We thank John Doench for critical reading of this manuscript. This work was supported by March of Dimes Foundation (#5-FY09-73) and Charles H. Hood Foundation (to G.A.S); NIH T32 Training Grant CA09361-27 (to J.Z.); Howard Hughes Medical Institute and NIH CA129933 (to D.A.H), and 2P50 CA89393-09 (DF/HCC SPORE in Breast Cancer) and BC05-COE W81XH-06-2-0033 (DOD Center of Excellence in Breast Cancer) (to S.R.); fellowships from Office of Enrichment Programs at Harvard Medical School and AID for Cancer Research (to L.W.N.); and R21CA135601 (to D.I.). NR 46 TC 49 Z9 51 U1 0 U2 9 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC 1 PY 2010 VL 24 IS 23 BP 2654 EP 2665 DI 10.1101/gad.1989110 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 688FS UT WOS:000284835800009 PM 21062900 ER PT J AU Pattaro, C Del Greco, F Luchner, A Pichler, I Winkler, T Hicks, AA Fuchsberger, C Franke, A Melville, SA Peters, A Wichmann, HE Schreiber, S Heid, IM Krawczak, M Minelli, C Wiedermann, CJ Pramstaller, PP AF Pattaro, Cristian Del Greco M, Fabiola Luchner, Andreas Pichler, Irene Winkler, Thomas Hicks, Andrew A. Fuchsberger, Christian Franke, Andre Melville, Scott A. Peters, Annette Wichmann, H-Erich Schreiber, Stefan Heid, Iris M. Krawczak, Michael Minelli, Cosetta Wiedermann, Christian J. Pramstaller, Peter P. TI Genome-Wide Association Study (GWAS) and Fine Mapping of NT-proBNP Level: Novel Loci and Novel Variants in the MTHFR-CLCN6-NPPA-NPPB Gene Cluster SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 19th Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 10-12, 2010 CL Boston, MA SP Int Genet Epidemiol Soc C1 [Pattaro, Cristian; Del Greco M, Fabiola; Pichler, Irene; Hicks, Andrew A.; Fuchsberger, Christian; Minelli, Cosetta; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Inst Med Genet, Bolzano, Italy. [Luchner, Andreas] Klinikum Univ Regensburg, Klin & Poliklin Innere Med 2, Regensburg, Germany. [Winkler, Thomas; Heid, Iris M.] Univ Regensburg, Dept Epidemiol & Prevent Med, Med Ctr, Regensburg, Germany. [Franke, Andre] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany. [Melville, Scott A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Peters, Annette; Wichmann, H-Erich] Inst Epidemiol, Helmholtz Zentrum Munchen, D-85764 Neuherberg, Germany. [Schreiber, Stefan] Univ Kiel, Inst Clin Mol Biol & Popgen Biobank, Kiel, Germany. [Krawczak, Michael] Univ Kiel, Inst Med Informat & Stat & Popgen Biobank, Kiel, Germany. [Wiedermann, Christian J.] Cent Hosp Bolzano, Dept Internal Med, Bolzano, Italy. RI Schreiber, Stefan/B-6748-2008; Fuchsberger, Christian/C-9646-2010; Krawczak, Michael/A-8964-2010; Pramstaller, Peter/C-2357-2008; Peters, Annette/A-6117-2011; Hicks, Andrew/E-9518-2017 OI Schreiber, Stefan/0000-0003-2254-7771; Krawczak, Michael/0000-0003-2603-1502; Hicks, Andrew/0000-0001-6320-0411 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD DEC PY 2010 VL 34 IS 8 MA 211 BP 975 EP 976 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 686TR UT WOS:000284719100217 ER PT J AU Wu, ZJ Meyer, CA Choudhury, S Shipitsin, M Maruyama, R Bessarabova, M Nikolskaya, T Sukumar, S Schwartzman, A Liu, JS Polyak, K Liu, XS AF Wu, Zhenhua Jeremy Meyer, Clifford A. Choudhury, Sibgat Shipitsin, Michail Maruyama, Reo Bessarabova, Marina Nikolskaya, Tatiana Sukumar, Saraswati Schwartzman, Armin Liu, Jun S. Polyak, Kornelia Liu, X. Shirley TI Gene expression profiling of human breast tissue samples using SAGE-Seq SO GENOME RESEARCH LA English DT Article ID DIFFERENTIAL EXPRESSION; SERIAL ANALYSIS; GENOME; CANCER; CELLS; TRANSCRIPTOMES; MICROARRAY; DISCOVERY; PATTERNS; DESIGN AB We present a powerful application of ultra high-throughput sequencing, SAGE-Seq, for the accurate quantification of normal and neoplastic mammary epithelial cell transcriptomes. We develop data analysis pipelines that allow the mapping of sense and antisense strands of mitochondrial and RefSeq genes, the normalization between libraries, and the identification of differentially expressed genes. We find that the diversity of cancer transcriptomes is significantly higher than that of normal cells. Our analysis indicates that transcript discovery plateaus at 10 million reads/sample, and suggests a minimum desired sequencing depth around five million reads. Comparison of SAGE-Seq and traditional SAGE on normal and cancerous breast tissues reveals higher sensitivity of SAGE-Seq to detect less-abundant genes, including those encoding for known breast cancer-related transcription factors and G protein-coupled receptors (GPCRs). SAGE-Seq is able to identify genes and pathways abnormally activated in breast cancer that traditional SAGE failed to call. SAGE-Seq is a powerful method for the identification of biomarkers and therapeutic targets in human disease. C1 [Liu, Jun S.] Harvard Univ, Dept Stat, Sci Ctr 715, Cambridge, MA 02138 USA. [Wu, Zhenhua Jeremy; Meyer, Clifford A.; Schwartzman, Armin; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Wu, Zhenhua Jeremy; Meyer, Clifford A.; Schwartzman, Armin; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Choudhury, Sibgat; Shipitsin, Michail; Maruyama, Reo; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Choudhury, Sibgat; Shipitsin, Michail; Maruyama, Reo; Polyak, Kornelia] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Choudhury, Sibgat; Shipitsin, Michail; Maruyama, Reo; Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Bessarabova, Marina; Nikolskaya, Tatiana] Russian Acad Sci, Vavilov Inst Gen Genet, Moscow 119331, Russia. [Sukumar, Saraswati] Johns Hopkins Oncol Ctr, Baltimore, MD 21231 USA. RP Liu, JS (reprint author), Harvard Univ, Dept Stat, Sci Ctr 715, Cambridge, MA 02138 USA. EM kornelia_polyak@dfci.harvard.edu; xsliu@jimmy.harvard.edu RI Nikolskaya, Tatiana/M-5008-2013; OI Schwartzman, Armin/0000-0001-5335-1611 FU NIH [R01 1HG004069]; NCI [P50 CA89393 CA, R01 CA116235-04S1]; AVON Foundation; Terri Brodeur Breast Cancer Research Foundation; Susan G. Komen Foundation [PDF0707996] FX We thank Andrea Richardson (Brigham and Women's Hospital) for her help with the acquisition of breast tumor samples; Haiyan Huang, Li Cai, Molin Wang, and David Harrington for valuable discussions; Love Nickerson for English proofreading. This work was supported by the Friends of Dana-Farber Women's Cancer Program (X.S.L.), NIH R01 1HG004069 (X.S.L.), NCI P50 CA89393 CA and R01 CA116235-04S1 (K.P.), the AVON Foundation (K.P.), Terri Brodeur Breast Cancer Research Foundation (S.C.), and the Susan G. Komen Foundation PDF0707996 (M.S., R.M.). NR 38 TC 25 Z9 26 U1 0 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD DEC PY 2010 VL 20 IS 12 BP 1730 EP 1739 DI 10.1101/gr.108217.110 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 688FK UT WOS:000284835000012 PM 21045080 ER PT J AU Kim, H Capezuti, E Kovner, C Zhao, ZL Boockvar, K AF Kim, Hongsoo Capezuti, Elizabeth Kovner, Christine Zhao, Zhonglin Boockvar, Kenneth TI Prevalence and Predictors of Adverse Events in Older Surgical Patients: Impact of the Present on Admission Indicator SO GERONTOLOGIST LA English DT Article DE Geriatric patient safety; Present on admission conditions; Chronic conditions; Surgery; Hospitals ID MULTIPLE CHRONIC CONDITIONS; LENGTH-OF-STAY; ADMINISTRATIVE DATA; POSTOPERATIVE MORTALITY; SAFETY INDICATORS; ELDERLY-PATIENTS; RISK-FACTORS; SURGERY; MORBIDITY; CARE AB Purpose of the Study: To examine the effects of the present on admission (POA) indicator on the prevalence of and factors associated with postsurgical adverse events in older patients. Design and Methods: This is a secondary data analysis of 82,898 surgical patients aged 65 years or older in 252 acute care hospitals in California in 2004. Four adverse events were counted using the Agency for Healthcare Research and Quality's Patient Safety Indicator (PSI) definitions with and without using the POA indicator. We also examined the effects of the POA indicator on the relationships between patient- and hospital-level factors and adverse events, using generalized linear mixed models. Results: The use of the POA indicator resulted in a marked reduction in the estimated rates of all 4 adverse event rates. Adjustment for POA conditions also influenced factors associated with adverse events. Compared with those with newly occurring adverse events only, admissions with only POA conditions were more likely to be admitted through the emergency department, be unplanned, and belong to patients with one or more preceding admissions or those with multiple admissions within the same year. Implications: Adverse event rates estimated from discharge abstracts using PSI methodology could be overstated when the POA indicator was not used. The POA indicator could influence predictors of adverse events. Studies on geriatric safety and outcomes using large administrative data sets should consider using the POA indicator. Further studies are needed on how to determine POA conditions. C1 [Kim, Hongsoo] Seoul Natl Univ, Grad Sch Publ Hlth, Seoul 151742, South Korea. [Kim, Hongsoo] Seoul Natl Univ, Inst Hlth & Environm, Seoul 151742, South Korea. [Capezuti, Elizabeth; Kovner, Christine] NYU, Coll Nursing, New York, NY 10003 USA. [Zhao, Zhonglin] NYU, Coll Dent, New York, NY 10003 USA. [Boockvar, Kenneth] James J Peters VA Med Ctr, Bronx, NY USA. [Boockvar, Kenneth] Mt Sinai Sch Med, New York, NY USA. [Boockvar, Kenneth] Jewish Home Lifecare, New York, NY USA. RP Kim, H (reprint author), Seoul Natl Univ, Grad Sch Publ Hlth, 599 Kwanak Ro, Seoul 151742, South Korea. EM hk65@snu.ac.kr OI Capezuti, Elizabeth/0000-0002-7450-6368; Boockvar, Kenneth/0000-0003-1165-5558; kovner, christine/0000-0001-7983-1066 NR 44 TC 5 Z9 5 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD DEC PY 2010 VL 50 IS 6 BP 810 EP 820 DI 10.1093/geront/gnq045 PG 11 WC Gerontology SC Geriatrics & Gerontology GA 682VM UT WOS:000284431100009 PM 20566833 ER PT J AU Cramer, DW Vitonis, AF Welch, WR Terry, KL Goodman, A Rueda, BR Berkowitz, RS AF Cramer, Daniel W. Vitonis, Allison F. Welch, William R. Terry, Kathryn L. Goodman, Annekathryn Rueda, Bo R. Berkowitz, Ross S. TI Correlates of the preoperative level of CA125 at presentation of ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; CA 125; BMI; Parity ID SERUM CA-125 LEVELS; POSTMENOPAUSAL WOMEN; CARCINOMA; RISK; SURVIVAL; ASCITES; BENIGN AB Objective. CA125 at presentation of ovarian cancer carries important prognostic significance; but, other than tumor characteristics, little is known about factors that influence CA125 levels. We examined the effect of epidemiologic variables and tumor features on CA125 at diagnosis and their effects on survival. Methods. CA125 levels before treatment, tumor features, and questionnaire data from 805 women with ovarian cancer receiving care at Partners Hospitals were recorded. CA125 values were log-normalized and generalized linear, logistic, or Cox proportional hazards models used to identify predictors of CA125 and influence on survival in the subset of women with invasive, nonmucinous tumors. Results. The importance of histology, grade, stage, laterality, and presence of ascites on CA125 level was confirmed. For nonmucinous invasive cancers, Jewish ethnicity, parity, prior breast cancer, and family history of breast or ovarian cancer predicted higher CA125, and greater body mass index (BMI), recurrent yeast infections, colitis, and appendectomy predicted lower CA125. A quadratic model best described the relationship between CA125 and age with lower levels in youngest and oldest women. In multivariate modeling, stage, ascites, and prior breast cancer were the strongest predictors of high CA125 and appendectomy and yeast infections strongest predictors of low CA125. A model with these variables plus CA125 revealed high CA125 remains a predictor of poorer survival. Conclusions. Ovarian tumor features and presence of ascites are key determinants of CA125 at diagnosis, but epidemiologic features such as BMI, parity, prior breast cancer, and history of inflammatory conditions of the genitourinary or gastrointestinal tracts may also play a role. (C) 2010 Elsevier Inc. All rights reserved. C1 [Cramer, Daniel W.; Welch, William R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Goodman, Annekathryn] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Cramer, DW (reprint author), Brigham & Womens Hosp, Dept Pathol, 221 Longwood Ave, Boston, MA 02115 USA. EM dcramer@partners.org; avitonis@partners.org; wrwelch@partners.org; kterry@partners.org; agoodman@partners.org; brueda@partners.org FU National Cancer Institute, Early Detection Research Network [P50 CA105009, R01 CA54419, 5U01 CA86381] FX This work was supported by the following National Cancer Institute grants to DWC: Ovarian Cancer SPORE (P50 CA105009), R01 CA54419, 5U01 CA86381 from the Early Detection Research Network, and a donation from Elizabeth Bennett to whom this work is dedicated. NR 30 TC 12 Z9 12 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2010 VL 119 IS 3 BP 462 EP 468 DI 10.1016/j.ygyno.2010.08.028 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 684NO UT WOS:000284556800012 PM 20850174 ER PT J AU Rodig, SJ Kutok, JL Paterson, JC Nitta, H Zhang, WJ Chapuy, B Tumwine, LK Montes-Moreno, S Agostinelli, C Johnson, NA Ben-Neriah, S Farinha, P Shipp, MA Piris, MA Grogan, TM Pileri, SA Gascoyne, RD Marafioti, T AF Rodig, Scott J. Kutok, Jeffery L. Paterson, Jennifer C. Nitta, Hiroaki Zhang, Wenjun Chapuy, Bjoern Tumwine, Lynette K. Montes-Moreno, Santiago Agostinelli, Claudio Johnson, Nathalie A. Ben-Neriah, Susana Farinha, Pedro Shipp, Margaret A. Piris, Miguel A. Grogan, Thomas M. Pileri, Stefano A. Gascoyne, Randy D. Marafioti, Teresa TI The pre-B-cell receptor associated protein VpreB3 is a useful diagnostic marker for identifying c-MYC translocated lymphomas SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE VpreB3; pre-BCR; immunohistochemistry; lymphoma; Burkitt lymphoma; diffuse large B-cell lymphoma; c-Myc ID BURKITTS-LYMPHOMA; MOLECULAR DIAGNOSIS; EXPRESSION; REPERTOIRE; CHILDREN; SUBSET; CHAINS AB Background During B-cell development, precursor B cells transiently express the pre-B-cell receptor composed of mu heavy chain complexed with VpreB and lambda 5 surrogate light chain polypeptides. Recent profiling studies unexpectedly revealed abundant transcripts of one member of the VpreB family, VpreB3, in a subset of mature B cells and Burkitt lymphoma. Design and Methods Here we used a novel antibody to investigate the normal expression pattern of VpreB3 protein in human hematopoietic and lymphoid tissues, and to determine whether VpreB3 could serve as a useful diagnostic biomarker for select B-cell lymphomas. Results We found that VpreB3 protein is normally expressed by precursor B cells in bone marrow and by a subset of normal germinal center B cells in secondary lymphoid organs. Among lymphoid malignancies, we found an association between VpreB3 expression and B-cell tumors with c-MYC abnormalities. VpreB3 was highly expressed in all cases of Burkitt lymphoma, whether of endemic or sporadic origin (44/44 cases, 100%), all cases of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (5/5 cases, 100%), and the majority of diffuse large B-cell lymphomas harboring a c-MYC translocation (15/18 cases, 83%). The expression of VpreB3 in diffuse large B-cell lymphomas without a c-MYC translocation was associated with c-MYC polysomy in 25/75 cases (33%) but only rarely observed in diffuse large B-cell lymphomas lacking a c-MYC abnormality (9/98 cases, 9%). Conclusions We conclude that for B-cell tumors with features suggesting a possible c-MYC translocation, such as intermediate to large cell size and high proliferation rate, the presence of VpreB3 should prompt subsequent confirmatory genetic testing, whereas the absence of VpreB3 is virtually always associated with wild-type c-MYC alleles. C1 [Paterson, Jennifer C.; Marafioti, Teresa] Univ Coll Hosp, Dept Histopathol, London WC1E 6JJ, England. [Rodig, Scott J.; Kutok, Jeffery L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Nitta, Hiroaki; Zhang, Wenjun; Grogan, Thomas M.] Ventana Med Syst, Roche Diagnost, Tucson, AZ USA. [Chapuy, Bjoern; Shipp, Margaret A.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Tumwine, Lynette K.] Makerere Univ, Dept Pathol, Kampala, Uganda. [Montes-Moreno, Santiago; Piris, Miguel A.] Spanish Natl Canc Ctr CNIO, Mol Pathol Programme, Madrid, Spain. [Agostinelli, Claudio; Pileri, Stefano A.] Univ Bologna, Sch Med, Dept Haematol & Clin Oncol L&A Seragnoli, Bologna, Italy. [Johnson, Nathalie A.; Ben-Neriah, Susana; Farinha, Pedro; Gascoyne, Randy D.] British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada. [Grogan, Thomas M.] Univ Arizona, Dept Pathol, Tucson, AZ USA. RP Marafioti, T (reprint author), Univ Coll Hosp, Dept Histopathol, 21 Univ St, London WC1E 6JJ, England. EM teresa@marafioti.org.uk RI Piris, Miguel/B-7067-2008; OI Piris, Miguel/0000-0001-5839-3634; Montes-Moreno, Santiago/0000-0002-3565-8262; Farinha, Pedro/0000-0001-9364-9391 FU Leukaemia Research [N. 0382] FX this work was supported by a Project Grant (N. 0382) from Leukaemia Research. NR 36 TC 5 Z9 7 U1 0 U2 2 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD DEC PY 2010 VL 95 IS 12 BP 2056 EP 2062 DI 10.3324/haematol.2010.025767 PG 7 WC Hematology SC Hematology GA 698DJ UT WOS:000285571400011 PM 20823132 ER PT J AU Hsu, J Fung, V Huang, J Price, M Brand, R Hui, RT Fireman, B Dow, WH Bertko, J Newhouse, JP AF Hsu, John Fung, Vicki Huang, Jie Price, Mary Brand, Richard Hui, Rita Fireman, Bruce Dow, William H. Bertko, John Newhouse, Joseph P. TI Fixing Flaws In Medicare Drug Coverage That Prompt Insurers To Avoid Low-Income Patients SO HEALTH AFFAIRS LA English DT Article ID RISK ADJUSTMENT; PART-D; SELECTION; BENEFIT; SAFETY; HEALTH AB Since 2006 numerous insurers have stopped serving the low-income segment of the Medicare Part D program, forcing millions of beneficiaries to change prescription drug plans. Using data from participating plans, we found that Medicare payments do not sufficiently reimburse insurers for the relatively high medication use among this population, creating perverse incentives for plans to avoid this part of the Part D market. Plans can accomplish this by increasing their premiums for all beneficiaries to an amount above regional benchmarks. We demonstrate that improving the accuracy of Medicare's risk and subsidy adjustments could mitigate these perverse incentives. C1 [Hsu, John] Massachusetts Gen Hosp, Clin Econ & Policy Anal Program, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Fung, Vicki; Huang, Jie; Price, Mary; Fireman, Bruce] Kaiser Permanente, Div Res, Oakland, CA USA. [Brand, Richard] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Hui, Rita] Kaiser Permanente Pharm Outcomes Res Grp, Oakland, CA USA. [Dow, William H.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Bertko, John] LMI Ctr Hlth Reform, Mclean, VA USA. [Newhouse, Joseph P.] Harvard Univ, Boston, MA 02115 USA. RP Hsu, J (reprint author), Massachusetts Gen Hosp, Clin Econ & Policy Anal Program, Mongan Inst Hlth Policy, Boston, MA 02114 USA. EM jhsu2000@gmail.com OI Dow, William/0000-0002-4080-1668 FU Medicare Payment Advisory Committee (MedPAC); National Institute on Aging [R01 AG029316]; Alfred P. Sloan Foundation FX The Medicare Payment Advisory Committee (MedPAC), National Institute on Aging (R01 AG029316), and Alfred P. Sloan Foundation provided funding for this study. Neither the funding agencies nor any of the private plans providing data influenced the decision to submit the manuscript for publication. Similarly, the statements in the article are those of the authors and do not necessarily reflect the positions of any of the funding agencies, plans, or institutions with which the authors are affiliated. Vicki Fung, Jie Huang, Mary Price, Bruce Fireman, and Rita Hui work for organizations that are part of Kaiser Permanente, which sells Medicare Advantage Part D policies. Will Dow provides econometric research consultation for an organization that is part of Kaiser Permanente. John Bertko is a MedPAC commissioner. Joseph Newhouse is a director of, and holds equity in, Aetna, which also sells Part D policies. [Published online October 28, 2010.] NR 23 TC 9 Z9 9 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 DEC PY 2010 VL 29 IS 12 BP 2335 EP 2342 DI 10.1377/hlthaff.2009.0323 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 690PF UT WOS:000285016000027 PM 21030394 ER PT J AU Colin-Ramirez, E Castillo-Martinez, L Orea-Tejeda, A Vergara-Castaneda, A Keirns-Davis, C Villa-Romero, A AF Colin-Ramirez, E. Castillo-Martinez, L. Orea-Tejeda, A. Vergara-Castaneda, A. Keirns-Davis, C. Villa-Romero, A. TI Outcomes of a school-based intervention (RESCATE) to improve physical activity patterns in Mexican children aged 8-10 years SO HEALTH EDUCATION RESEARCH LA English DT Article ID CARDIOVASCULAR RISK-FACTORS; AMERICAN-HEART-ASSOCIATION; DEVELOPING-COUNTRIES; PRESCHOOL-CHILDREN; CONTROLLED-TRIAL; OBESITY; ADOLESCENTS; HEALTH; PREVENTION; SCHOOLCHILDREN AB The aim of this study was to evaluate the impact of an intervention program on the patterns of physical activity in 8- to 10-year-old Mexican children from lower socioeconomic status. This study performed a randomized controlled field trial in 498 children aged 8-10 years from 10 public schools of low socioeconomic status in Mexico City. Schools were randomly assigned to intervention (n = 5) or control (n = 5) groups and followed up during 12 months. Physical and sedentary activities were assessed at the beginning of the program and after 6 and 12 months. At the end of follow-up, there was a significant increase in the performance of moderate physical activity (MPA) among children in intervention group who had not performed MPA at baseline any day of the week (40%, P = 0.04) but not in the control group (8%, P = not significant). The intervention group also showed a significant reduction in the proportion of children who spent more than 3 hours a day playing video games (from 23 to 13%, P = 0.01), while control group did not show significant changes. Given these findings, we conclude that intervention was able to modify positively physical activity and reduce time spent on such sedentary activities as video games among those at highest risk studied children. C1 [Colin-Ramirez, E.; Castillo-Martinez, L.; Orea-Tejeda, A.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Heart Failure Clin, Mexico City 14000, DF, Mexico. [Vergara-Castaneda, A.] Asociac Mexicana Prevenc Insuficiencia Cardiaca, Mexico City 03100, DF, Mexico. [Keirns-Davis, C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Villa-Romero, A.] Univ Nacl Autonoma Mexico, Dept Publ Hlth, Mexico City 04510, DF, Mexico. RP Castillo-Martinez, L (reprint author), Providencia 1218-A 402 Col Valle, Mexico City 03100, DF, Mexico. EM caml1225@yahoo.com RI Castillo-Martinez, Lilia/H-3750-2013 NR 38 TC 13 Z9 16 U1 2 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD DEC PY 2010 VL 25 IS 6 BP 1042 EP 1049 DI 10.1093/her/cyq056 PG 8 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 679MC UT WOS:000284164500012 PM 20884847 ER PT J AU Mulley, AG AF Mulley, Albert G., Jr. TI Patient-centred diagnosis SO HEALTH EXPECTATIONS LA English DT Book Review C1 [Mulley, Albert G., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Mulley, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM amulley@partners.org 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 1369-6513 J9 HEALTH EXPECT JI Health Expect. PD DEC PY 2010 VL 13 IS 4 BP 441 EP 442 DI 10.1111/j.1369-7625.2010.00606.x PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 677IA UT WOS:000283981100012 ER PT J AU Aarnisalo, AA Green, KM O'Malley, J Makary, C Adams, J Merchant, SN Evans, JE AF Aarnisalo, Antti A. Green, Karin M. O'Malley, Jennifer Makary, Chadi Adams, Joe Merchant, Saumil N. Evans, James E. TI A method for MSE differential proteomic analysis of archival formalin-fixed celloidin-embedded human inner ear tissue SO HEARING RESEARCH LA English DT Article ID TEMPORAL BONES; CANCER-TISSUE; LC-MS/MS AB Proteomic analysis of cadaveric formalin-fixed, celloidin-embedded (FFCE) temporal bone tissue has the potential to provide new insights into inner ear disorders. We have developed a liquid chromatography -mass spectrometry (LC-MS) method for tissue sections embedded with celloidin. Q-TOF (Quadrupole-time of flight mass spectrometry) MSE (mass spectrometry where E represents collision energy) and Identity(ETM) were used in conjunction with nano-UPLC (capillary ultrahigh pressure liquid chromatography) for robust identification and quantification of a large number of proteins. Formalin-fixed paraffin-embedded (FFPE) mouse liver sections were used to evaluate formalin de-cross-linking by five different methods. Unfixed fresh mouse liver tissue was used as a control. Five different methods for preparation of FFPE tissue for MS analysis were compared, as well as four methods for celloidin removal with FFCE mouse liver tissue. The methods judged best were applied to FFCE 20 mu m sections of mouse inner ear samples, and FFCE 20 mu m human inner ear and human otic capsule bone sections. Three of the five-tissue extraction methods worked equally in detecting peptides and proteins from FFPE mouse liver tissue. The modified Liquid Tissue kit protocol was chosen for further studies. Four different celloidin removal methods were compared and the acetone removal method was chosen for further analysis. These two methods were applied to the analysis of FFCE inner ear and otic capsule sections. Proteins from all major cellular components were detected in the FFCE archival human temporal bone sections. This newly developed technique enables the use of FFCE tissues for proteomic studies. (C) 2010 Elsevier B.V. All rights reserved. C1 [Aarnisalo, Antti A.; O'Malley, Jennifer; Makary, Chadi; Adams, Joe; Merchant, Saumil N.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Aarnisalo, Antti A.; Green, Karin M.; Evans, James E.] Univ Massachusetts, Sch Med, Worcester, MA USA. RP Aarnisalo, AA (reprint author), Univ Helsinki, Helsinki Univ Cent Hosp, Dept Otorhinolaryngol, POB 220, Helsinki 00029, Finland. EM antti.aarnisalo@hus.fi FU NIH [U24 DC008559]; Sigrid Juselius Foundation; Academy of Finland FX Supported in part by NIH grant U24 DC008559, Sigrid Juselius Foundation (A.A.A) and Academy of Finland (A.A.A.). NR 19 TC 8 Z9 8 U1 0 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 DEC 1 PY 2010 VL 270 IS 1-2 BP 15 EP 20 DI 10.1016/j.heares.2010.08.003 PG 6 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 707MH UT WOS:000286290200004 PM 20708670 ER PT J AU Singh, JP Ptaszek, LM Verma, A AF Singh, Jagmeet P. Ptaszek, Leon M. Verma, Atul TI Elusive atrial substrate: Complex fractionated atrial electrograms and beyond SO HEART RHYTHM LA English DT Review DE Atrial fibrillation; Catheter ablation; Complex fractionated atrial electrogram ID PULMONARY VEIN ISOLATION; POSTERIOR LEFT ATRIUM; CATHETER ABLATION; ANTRUM ISOLATION; FIBRILLATION; PERSISTENT; HUMANS; EFFICACY; SITES; HEART AB Most practitioners of atrial fibrillation (AF) ablation have attempted to move beyond pulmonary vein isolation into the realm of physiology-driven ablation for patients with persistent AF. This new strategy involves a combination of a common anatomic approach (with isolation of the pulmonary veins) and an individualized strategy tailored to the electrophysiologic characteristics of the atrial substrate present in each patient. In this review, we summarize the current reasoning and controversies related to this new approach. In addition, we attempt to unravel some of the complexities of targeting these patient-specific atrial electrical signals. C1 [Singh, Jagmeet P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv,Heart Ctr, Boston, MA 02115 USA. [Singh, Jagmeet P.; Ptaszek, Leon M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv,Heart Ctr, Boston, MA 02115 USA. EM jsingh@partners.org FU Boston Scientific Corp.; Biotronik; Medtronic, Inc.; Guidant Corp.; St. Jude Medical; Sorin Group FX Dr. Singh received research grants from St. Jude Medical, Medtronic, Inc., Boston Scientific Corp., and Biotronik; served on advisory boards or as a consultant for Boston Scientific Corp., St. Jude Medical, and Medtronic; and received honoraria or speaker fees from Medtronic, Inc., Biotronik, Guidant Corp., St. Jude Medical, and Sorin Group. Dr. Verma received research grants and consulting and speaker fees from St. Jude Medical. NR 30 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD DEC PY 2010 VL 7 IS 12 BP 1886 EP 1890 DI 10.1016/j.hrthm.2010.08.027 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 688TD UT WOS:000284875500036 PM 20817015 ER PT J AU Bauer, KA AF Bauer, Kenneth A. TI Duration of Anticoagulation: Applying the Guidelines and Beyond SO HEMATOLOGY-AMERICAN SOCIETY HEMATOLOGY EDUCATION PROGRAM LA English DT Article AB Despite an improved understanding of the risk factors underlying venous thromboembolism (VTE), extensive clinical investigation, and detailed clinical guidelines, the decision to extend anticoagulation indefinitely for an individual patient with VTE is often problematic. Patients with VTE in association with major surgery, trauma, immobilization, or pregnancy are at relatively low risk of recurrence and generally do not require more than 3 to 6 months of anticoagulant therapy. For patients with a first unprovoked, or idiopathic, episode of VTE, an individualized approach should be taken in deciding on the duration of anticoagulation based on the patient's recurrence and bleeding risk, as well as their personal preference. Although the presence of genetic thrombophilic disorders (factor V Leiden and prothrombin G20210A gene mutations; deficiencies of antithrombin, protein C, and protein S) predispose patients to a first episode of VTE, there is inconsistent data on whether testing for these defects changes patient outcomes or should alter their management. In patients with a single unprovoked VTE, measurement of D-dimer several weeks following the completion of anticoagulant therapy appears useful in stratifying patients with a first unprovoked episode of VTE with regard to recurrence risk. Through a series of clinical vignettes, the utility of the laboratory in risk-stratifying patients with respect to recurrence risk will be discussed, along with decision making regarding the duration of anticoagulation. The potential impact of having a nonremovable inferior vena caval filter will also be addressed. C1 [Bauer, Kenneth A.] VA Boston Healthcare Syst, Hematol Sect, Boston, MA USA. [Bauer, Kenneth A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Bauer, Kenneth A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Bauer, KA (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. EM kbauer@bidmc.harvard.edu NR 41 TC 3 Z9 3 U1 2 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2010 BP 210 EP 215 DI 10.1182/asheducation-2010.1.210 PG 6 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA V29PF UT WOS:000208759600034 ER PT J AU Cutler, C AF Cutler, Corey TI Allogeneic Hematopoietic Stem-Cell Transplantation for Myelodysplastic Syndrome SO HEMATOLOGY-AMERICAN SOCIETY HEMATOLOGY EDUCATION PROGRAM LA English DT Article AB Transplantation is the only known cure for myelodysplastic syndrome (MDS). While some comparative analyses have demonstrated early transplantation to be the preferred strategy for all MDS patients, many of these analyses are biased. Using newly identified prognostic factors and models, a rational approach to transplantation can be undertaken. Factors such as transfusion dependency, cytogenetics, medical comorbidity, and World Health Organization (WHO) histologic subtype should all be considered when deciding on the role of transplantation for the MDS patient. Unresolved issues in transplantation include the impact of pre-transplant tumor debulking with traditional chemotherapeutic agents or the new DNA hypomethylating agents, and the optimal timing of reduced-intensity conditioning transplantation for older patients or for those with medical comorbidities. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cutler, C (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,D1B13, Boston, MA 02115 USA. EM corey_cutler@dfci.harvard.edu NR 25 TC 10 Z9 11 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2010 BP 325 EP 329 DI 10.1182/asheducation-2010.1.325 PG 5 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA V29PF UT WOS:000208759600052 ER PT J AU Neufeld, EJ AF Neufeld, Ellis J. TI Update on Iron Chelators in Thalassemia SO HEMATOLOGY-AMERICAN SOCIETY HEMATOLOGY EDUCATION PROGRAM LA English DT Article AB Over the past four decades, there have been dramatic improvements in survival for patients with thalassemia major due in large measure to improved iron chelators. Two chelators are approved for use in the United States and Canada, parenteral deferoxamine and oral deferasirox. Three are available in much of the rest of the world, where oral deferiprone is also approved (in the United States, deferiprone is only available in studies, for emergency use, or on a "compassionate-use" basis). Many trials and worldwide clinical experience demonstrate that each of the three drugs can chelate and remove iron, and thereby prevent or improve transfusional hemosiderosis in thalassemia patients. However, the chelators differ strikingly in side-effect profile, cost, tolerability and ease of adherence, and (to some degree) efficacy for any specific patient. The entire field of chelator clinical trials suffers from the fact that each drug (as monotherapy or in combination) has not been tested directly against all of the other possibilities. Acknowledging the challenges of assessing chelators with diverse properties and imperfect comparative data, the purpose of this review is to summarize the last 4 years of studies that have improved our understanding of the applications and limitations of iron chelators in various settings for thalassemia patients, and to point out areas for much-needed future research. C1 [Neufeld, Ellis J.] Childrens Hosp Boston, Dana Farber Canc Inst, Boston, MA 02115 USA. [Neufeld, Ellis J.] Harvard Univ, Sch Med, Boston, MA USA. RP Neufeld, EJ (reprint author), Childrens Hosp Boston, Div Hematol, 300 Longwood Ave,Karp 08210, Boston, MA 02115 USA. EM ellis.neufeld@chboston.org FU Novartis; Ferrokin FX Conflict-of-interest disclosure: The author has received research funding from Novartis and Ferrokin. NR 38 TC 21 Z9 23 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2010 BP 451 EP 455 DI 10.1182/asheducation-2010.1.451 PG 5 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA V29PF UT WOS:000208759600072 ER PT J AU Rosovsky, R Lee, AYY AF Rosovsky, Rachel Lee, Agnes Y. Y. TI Evidence-Based Mini-Review: Should All Patients with Idiopathic Venous Thromboembolic Events Be Screened Extensively for Occult Malignancy? SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Article C1 [Rosovsky, Rachel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosovsky, Rachel] Harvard Univ, Sch Med, Boston, MA USA. [Lee, Agnes Y. Y.] Univ British Columbia, Vancouver Gen Hosp, Vancouver Coastal Hlth, Vancouver, BC V5Z 1M9, Canada. RP Lee, AYY (reprint author), Diamond Hlth Care Ctr, 2775 Laurel St,10th Floor, Vancouver, BC V5Z 1M9, Canada. EM alee14@bccancer.bc.ca NR 19 TC 5 Z9 6 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2010 BP 150 EP 152 DI 10.1182/asheducation-2010.1.150 PG 3 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA V29PF UT WOS:000208759600023 ER PT J AU Sankaran, VG Nathan, DG AF Sankaran, Vijay G. Nathan, David G. TI Thalassemia: An Overview of 50 Years of Clinical Research SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Thalassemia; Hemoglobin; Erythrocyte; Transfusion ID SICKLE-CELL-ANEMIA; BETA-GLOBIN GENE; FETAL-HEMOGLOBIN PRODUCTION; HEMATOPOIETIC STEM-CELLS; GENOME-WIDE ASSOCIATION; ZINC-FINGER NUCLEASES; PRENATAL-DIAGNOSIS; IRON OVERLOAD; MESSENGER-RNA; DNA POLYMORPHISMS AB The thalassemias are attributable to the defective production of the alpha- and beta-globin polypeptides of hemoglobin Significant discoveries have illuminated the pathophysiology and enhanced the prevention and treatment of the thalassemias and this article reviews many of the advances that have occurred in the past 50 years However the application of new approaches to the treatment of these disorders has been slow particularly in the developing world where the diseases are common but there is definite progress This article emphasizes how the increasing knowledge of cellular and molecular biology are facilitating the development of more effective therapies for these patients C1 [Sankaran, Vijay G.; Nathan, David G.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sankaran, Vijay G.; Nathan, David G.] Childrens Hosp Boston, Boston, MA 02115 USA. [Sankaran, Vijay G.; Nathan, David G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sankaran, Vijay G.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Nathan, DG (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 137 TC 18 Z9 22 U1 0 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 2010 VL 24 IS 6 BP 1005 EP + DI 10.1016/j.hoc.2010.08.009 PG 17 WC Oncology; Hematology SC Oncology; Hematology GA 694AS UT WOS:000285267900002 PM 21075277 ER PT J AU Chung, RT Poordad, FF Hassanein, T Zhou, XL Lentz, E Prabhakar, A Di Bisceglie, AM AF Chung, Raymond T. Poordad, Fred F. Hassanein, Tarek Zhou, Xiaolei Lentz, Ellen Prabhakar, Avinash Di Bisceglie, Adrian M. TI Association of Host Pharmacodynamic Effects with Virologic Response to Pegylated Interferon alfa-2a/Ribavirin in Chronic Hepatitis C SO HEPATOLOGY LA English DT Article ID 40KD PLUS RIBAVIRIN; PEGINTERFERON ALPHA-2A; COMBINATION THERAPY; AMERICAN PATIENTS; VIRUS GENOTYPE-1; WEIGHT-LOSS; ANEMIA; IMPACT; RETREATMENT; INFECTION AB Patients receiving therapy for chronic hepatitis C virus (HCV) infection frequently experience cytopenias and weight loss We retrospectively assessed the pharmacodynamic effects of pegylated interferon (PEG-IFN) alfa-2a and ribavirin by evaluating the relationship between changes in hematologic parameters, body weight, and virologic response Patients with HCV genotypes 1, 4, 5, or 6 receiving 24 or 48 weeks of PEG-IFN alfa-2a and ribavirin therapy were pooled from four phase 3/4 trials Maximum decreases in hemoglobin level, neutrophil count, platelet count, and weight during therapy were assessed according to virologic response category (sustained virologic response [SVR], relapse, breakthrough, and nonresponder) and race/ethnicity Of 1,778 patients analyzed, more than half were male, non-Hispanic Caucasian, and infected with HCV genotype 1, had a baseline HCV RNA >800,000, and had alanine aminotransferase levels <= 3 x the upper limit of normal Virologic responders (SVR, relapse, and breakthrough) experienced greater maximum decreases from baseline in hemoglobin level, neutrophil count, platelet count, and weight compared with nonresponders, however, no clear trend was observed between SVR, relapse, and breakthrough After adjusting for drug exposure and treatment duration, only decreases in neutrophil count remained associated with virologic response Significantly greater declines in neutrophil (P < 0 0001) and platelet (P < 0 005) count were observed at weeks 4, 12, and 24 of therapy in virologic responders compared with nonresponders This difference between responders and nonresponders was also observed among racial/ethnic groups, although statistical significance was not consistent across all groups Conclusion This post hoc analysis of HCV patients treated with PEG-IFN alfa-2a and ribavirin shows that maximum decreases from baseline in hematologic parameters and weight loss were associated with virologic response However, after adjusting for drug exposure and accounting for duration of therapy, only neutropenia was independently associated with virologic response (HEPATOLOGY 2010,52 1906-1914) C1 [Chung, Raymond T.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. [Poordad, Fred F.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Hassanein, Tarek] Univ Calif San Diego, San Diego, CA 92103 USA. [Zhou, Xiaolei] RTI Hlth Solut, Res Triangle Pk, NC USA. [Lentz, Ellen; Prabhakar, Avinash] Genentech Inc, San Francisco, CA 94080 USA. [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, St Louis, MO USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, GI Unit, Warren 1007, Boston, MA 02114 USA. FU Genentech Inc; Roche; Genentech FX Supported by Genentech Inc; Potential conflict of interest Dr Hassanein is on the speakers bureau of and receives grants from Roche Dr Zhou is employed by RTI Health Solutions and receives funding from Roche and Genentech Dr Poordad consults advises is on the speakers bureau of and receives grants from Roche and Genentech Drs Prabhakar and Lentz are employed by Genentech NR 29 TC 8 Z9 8 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 DEC PY 2010 VL 52 IS 6 BP 1906 EP 1914 DI 10.1002/hep.23947 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 690RP UT WOS:000285023700007 PM 21064034 ER PT J AU Lee, JS Padmanabhan, A Shin, J Zhu, SZ Guo, F Kanki, JP Epstein, JA Look, AT AF Lee, Jeong-Soo Padmanabhan, Arun Shin, Jimann Zhu, Shizhen Guo, Feng Kanki, John P. Epstein, Jonathan A. Look, A. Thomas TI Oligodendrocyte progenitor cell numbers and migration are regulated by the zebrafish orthologs of the NF1 tumor suppressor gene SO HUMAN MOLECULAR GENETICS LA English DT Article ID NEUROFIBROMATOSIS TYPE-1; SCHWANN-CELLS; SPINAL-CORD; IN-VIVO; PROLIFERATION; GLIOMA; BRAIN; GAP; DIFFERENTIATION; HETEROZYGOSITY AB Neurofibromatosis type 1 is the most commonly inherited human cancer predisposition syndrome. Neurofibromin (NF1) gene mutations lead to increased risk of neurofibromas, schwannomas, low grade, pilocytic optic pathway gliomas, as well as malignant peripheral nerve sheath tumors and glioblastomas. Despite the evidence for NF1 tumor suppressor function in glial cell tumors, the mechanisms underlying transformation remain poorly understood. In this report, we used morpholinos to knockdown the two nf1 orthologs in zebrafish and show that oligodendrocyte progenitor cell (OPC) numbers are increased in the developing spinal cord, whereas neurons are unaffected. The increased OPC numbers in nf1 morphants resulted from increased proliferation, as detected by increased BrdU labeling, whereas TUNEL staining for apoptotic cells was unaffected. This phenotype could be rescued by the forced expression of the GTPase-activating protein (GAP)-related domain of human NF1. In addition, the in vivo analysis of OPC migration following nf1 loss using time-lapse microscopy demonstrated that olig2-EGFP 1 OPCs exhibit enhanced cell migration within the developing spinal cord. OPCs pause intermittently as they migrate, and in nf1 knockdown animals, they covered greater distances due to a decrease in average pause duration, rather than an increase in velocity while in motion. Interestingly, nf1 knockdown also leads to an increase in ERK signaling, principally in the neurons of the spinal cord. Together, these results show that negative regulation of the Ras pathway through the GAP activity of NF1 limits OPC proliferation and motility during development, providing insight into the oncogenic mechanisms through which NF1 loss contributes to human glial tumors. C1 [Lee, Jeong-Soo; Shin, Jimann; Zhu, Shizhen; Guo, Feng; Kanki, John P.; Look, A. Thomas] Harvard Univ, Dana Farber Canc Inst, Dept Pediat Oncol, Sch Med, Boston, MA 02115 USA. [Padmanabhan, Arun; Epstein, Jonathan A.] Univ Penn, Dept Cell & Dev Biol, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA. [Padmanabhan, Arun; Epstein, Jonathan A.] Univ Penn, Inst Regenerat Med, Philadelphia, PA 19104 USA. [Look, A. Thomas] Harvard Univ, Div Hematol Oncol, Dept Pediat, Childrens Hosp Boston,Med Sch, Boston, MA 02115 USA. RP Look, AT (reprint author), Harvard Univ, Dana Farber Canc Inst, Dept Pediat Oncol, Sch Med, Mayer Bldg,Room 630,44 Binney St, Boston, MA 02115 USA. EM epsteinj@mail.med.upenn.edu; thomas_look@dfci.harvard.edu FU Department of Defense [NF050175]; Children's Tumor Foundation; Sarnoff Cardiovascular Research Foundation FX This work was supported by the Department of Defense (NF050175 to J.A.E. and A. T. L.). J.S.L. was supported by a Young Investigator Award (Children's Tumor Foundation) and A. P. by a fellowship from the Sarnoff Cardiovascular Research Foundation. NR 41 TC 22 Z9 22 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 DEC 1 PY 2010 VL 19 IS 23 BP 4643 EP 4653 DI 10.1093/hmg/ddq395 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 676QV UT WOS:000283930200009 PM 20858602 ER PT J AU Kostis, WJ Thijs, L Richart, T Kostis, JB Staessen, JA AF Kostis, William J. Thijs, Lutgarde Richart, Tom Kostis, John B. Staessen, Jan A. TI Persistence of Mortality Reduction After the End of Randomized Therapy in Clinical Trials of Blood Pressure-Lowering Medications SO HYPERTENSION LA English DT Article DE ACEIs; blood pressure-lowering medications; beta-blockers; diuretics; clinical trials; mortality; legacy effect ID ACUTE MYOCARDIAL-INFARCTION; ISOLATED SYSTOLIC HYPERTENSION; CONGESTIVE-HEART-FAILURE; LONG-TERM MORTALITY; ANTIHYPERTENSIVE DRUG-TREATMENT; VENTRICULAR EJECTION FRACTIONS; ENZYME-INHIBITOR TRANDOLAPRIL; FACTOR INTERVENTION TRIAL; FOLLOW-UP; ORAL CAPTOPRIL AB Long-term follow-up of clinical trials of blood pressure-lowering medications has suggested a continuation of event reduction after study completion. We evaluated the persistence of mortality benefit of these agents after the end of clinical trials, when all of the patients were advised to take the same open-label therapy. We performed a meta-analysis of randomized clinical trials using blood pressure-lowering medications, used in patients with hypertension, myocardial infarction, or left ventricular systolic dysfunction, (n = 18; 132 854 patients; 11 988 deaths) when a second report describing results after the end of the trial was available. During the randomized (first) phase, 80% (interquartile range: 75% to 83%) of the patients randomized to receive active therapy actually received it compared with 16% (interquartile range: 7% to 22%) of those randomized to control. In this phase, mortality was lower in the intervention group (odds ratio: 0.84 [95% CI: 0.79 to 0.90]; P <0.0001). Mortality was also lower during the open-label follow-up (second) phase (odds ratio: 0.85 [95% CI: 0.79 to 0.91]; P <0.0001), when all of the patients were advised to take the same therapy, and rates of receiving active therapy were similar in the 2 groups (59% [interquartile range: 46% to 77%], among those originally randomized to active, and 43% [interquartile range: 20% to 68%], in the control). Several sensitivity analyses indicated stability of the effects. In studies of antihypertensive medications, a decrease in overall mortality persists after the end of trial phase, when most patients in both the intervention and control groups receive active therapy. These analyses imply that earlier intervention would result in better clinical outcomes. (Hypertension. 2010; 56:1060-1068.). Online Data Supplement C1 [Kostis, William J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Thijs, Lutgarde; Richart, Tom; Staessen, Jan A.] Univ Leuven, Div Hypertens & Cardiac Rehabil, Dept Cardiovasc Dis, Louvain, Belgium. [Kostis, John B.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, New Brunswick, NJ 08903 USA. RP Kostis, WJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB-800, Boston, MA 02114 USA. EM wkostis@partners.org RI Staessen, Jan/A-1065-2011 OI Staessen, Jan/0000-0002-3026-1637 NR 47 TC 22 Z9 25 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 DEC PY 2010 VL 56 IS 6 BP 1060 EP U105 DI 10.1161/HYPERTENSIONAHA.110.160291 PG 22 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 681KA UT WOS:000284309800022 PM 20975031 ER PT J AU Robinson, ES Khankin, EV Choueiri, TK Dhawan, MS Rogers, MJ Karumanchi, SA Humphreys, BD AF Robinson, Emily S. Khankin, Eliyahu V. Choueiri, Toni K. Dhawan, Mallika S. Rogers, Miranda J. Karumanchi, S. Ananth Humphreys, Benjamin D. TI Suppression of the Nitric Oxide Pathway in Metastatic Renal Cell Carcinoma Patients Receiving Vascular Endothelial Growth Factor-Signaling Inhibitors SO HYPERTENSION LA English DT Article DE hypertension; albuminuria; angiogenesis inhibitors; NO; VEGF AB Therapies that target the vascular endothelial growth factor (VEGF) pathway cause hypertension, but the mechanism remains unknown. This cross-sectional study tested the hypothesis that VEGF inhibition causes hypertension by suppressing VEGF-mediated vasodilatory pathways. Urine was collected from 80 patients with metastatic renal cell carcinoma from 2002 to 2009, 40 at baseline and 40 while on VEGF inhibitors. Measured urinary biomarkers include albumin, metabolites of the nitric oxide (NO) pathway and its downstream effector cGMP, and prostaglandin pathway biomarkers prostaglandin E2, 6-keto prostaglandin F1 alpha, and cAMP, all normalized to urinary creatinine. The mean age in both groups was 61.8 years, 76% were men, and urinary albumin was higher in patients receiving VEGF inhibitors (median: 18.4 versus 4.6 mg/g; P=0.009). cGMP/creatinine was suppressed in patients on VEGF inhibitors (0.28 versus 0.39 pmol/mu g; P=0.01), with a trend toward suppression of nitrate/creatinine (0.46 versus 0.62 mu mol/mg; P=0.09). Both comparisons were strengthened when patients on bevacizumab were excluded, and only those receiving small molecule tyrosine kinase inhibitors were analyzed (cGMP/creatinine: P=0.003; nitrate/creatinine: P=0.01). Prostaglandin E2, 6-keto prostaglandin F1 alpha, and cAMP did not differ between groups. These results suggest that hypertension induced by VEGF inhibitors is mediated by suppression of NO production. Prospective studies are needed to explore whether these biomarkers may be useful predictors of efficacy in patients receiving VEGF-targeted therapies. (Hypertension. 2010;56:1131-1136.) C1 [Robinson, Emily S.; Dhawan, Mallika S.; Humphreys, Benjamin D.] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. [Khankin, Eliyahu V.; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. [Choueiri, Toni K.; Rogers, Miranda J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Karumanchi, S. Ananth] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Humphreys, BD (reprint author), Harvard Inst Med, Room 554,4 Blackfan Circle, Boston, MA 02115 USA. EM bhumphreys@partners.org RI Khankin, Eli/M-7648-2013 FU Harvard Catalyst; National Institutes of Health [DK073628, DK084316, and UL1 RR 025758-02]; National Kidney Foundation FX This work was supported by a pilot grant from Harvard Catalyst, as well as National Institutes of Health grants DK073628, DK084316, and UL1 RR 025758-02, with financial contributions from participating institutions (to B.D.H.) and a grant from the National Kidney Foundation (to E.S.R.). NR 0 TC 47 Z9 49 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD DEC PY 2010 VL 56 IS 6 BP 1131 EP 1136 DI 10.1161/HYPERTENSIONAHA.110.160481 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 681KA UT WOS:000284309800032 PM 20956731 ER PT J AU Xie, HH Zhou, SA Chen, DD Channon, KM Su, DF Chen, AF AF Xie, He-Hui Zhou, Shuang Chen, Dan-Dan Channon, Keith M. Su, Ding-Feng Chen, Alex F. TI GTP Cyclohydrolase I/BH4 Pathway Protects EPCs via Suppressing Oxidative Stress and Thrombospondin-1 in Salt-Sensitive Hypertension SO HYPERTENSION LA English DT Article DE endothelial progenitor cell; GTP cyclohydrolase; tetrahydrobiopterin; thrombospondin-1; nitric oxide synthase ID ENDOTHELIAL PROGENITOR CELLS; LOW-RENIN HYPERTENSION; NITRIC-OXIDE SYNTHASE; I OVEREXPRESSION; ANGIOGENESIS; MOBILIZATION; SENESCENCE; ARTERY; RISK AB Endothelial progenitor cells (EPCs) are both reduced and dysfunctional in hypertension that correlates inversely with its mortality, but the mechanisms are poorly understood. Endothelial nitric oxide synthase (eNOS) critically regulates EPC mobilization and function but is uncoupled in salt-sensitive hypertension because of the reduced cofactor tetrahydrobiopterin (BH4). We tested the hypothesis that GTP cyclohydrolase I (GTPCH I), the rate-limiting enzyme of BH4 de novo synthesis, protects EPCs and its function in deoxycorticosterone acetate (DOCA)-salt mice. EPCs were isolated from peripheral blood and bone marrow of wild-type (WT), WT DOCA-salt, endothelial-specific GTPCH transgenic (Tg-GCH), GTPCH transgenic DOCA-salt, and BH4-deficient hph-1 mice. In WT DOCA-salt and hph-1 mice, EPCs were significantly decreased with impaired angiogenesis and adhesion, which were restored in Tg-GCH DOCA-salt mice. Superoxide (O-2(-)) and nitric oxide (NO) levels in EPCs were elevated and reduced, respectively, in WT DOCA-salt and hph-1 mice; both were rescued in Tg-GCH DOCA-salt mice. eNOS(-/-)/GCH(+/-) hybrid mice demonstrated that GTPCH preserved the circulating EPC number, reduced intracellular O-2 in EPCs, and ameliorated EPC dysfunction independent of eNOS in DOCA-salt hypertension. Secreted thrombospondin-1 (TSP-1; a potent angiogenesis inhibitor) from EPCs was elevated in WT DOCA-salt and hph-1 but not DOCA-salt Tg-GCH mice. In vitro treatment with BH4, polyethylene glycol-superoxide dismutase (PEG-SOD), or Nomega-nitro-L-arginine (L-NNA) significantly augmented NO and reduced TSP-1 and O-2(-) levels from EPCs of WT DOCA-salt mice. These results demonstrated, for the first time, that the GTPCH/BH4 pathway critically regulates EPC number and function in DOCA-salt hypertensive mice, at least in part, via suppressing TSP-1 expression and oxidative stress. (Hypertension. 2010;56:1137-1144.) . Online Data Supplement C1 [Chen, Alex F.] Univ Pittsburgh, Sch Med, Dept Surg, VA Vasc Surg Res,Vasc Med Inst, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, McGowan Inst Regenerat Med, Pittsburgh, PA 15213 USA. [Xie, He-Hui; Su, Ding-Feng; Chen, Alex F.] Second Mil Med Univ, Dept Pharmacol, Shanghai 200433, Peoples R China. [Zhou, Shuang] Second Mil Med Univ, Dept Acupuncture & Moxibust, Shanghai 200433, Peoples R China. [Chen, Dan-Dan; Chen, Alex F.] Vet Affairs Pittsburgh Healthcare Syst, Surg Res, Pittsburgh, PA USA. [Channon, Keith M.] Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX1 2JD, England. RP Chen, AF (reprint author), Univ Pittsburgh, Sch Med, Dept Surg, VA Vasc Surg Res,Vasc Med Inst, W1148 Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15213 USA. EM dfsu2008@gmail.com; chena5@upmc.edu FU National Institute of General Medical Science/National Institutes of Health [R01GM077352]; American Heart Association [0855601G, 0720114Z]; Natural Sciences Foundation of China (NSFC) [30728021, 30700307, 30971158] FX This work was supported by National Institute of General Medical Science/National Institutes of Health grant R01GM077352, American Heart Association Grant 0855601G, International Collaborative grant 30728021 from the Natural Sciences Foundation of China (NSFC) (to A.F.C.), and NSFC grants 30700307 and 30971158 (to H.-H.X.). D.D.C. is the recipient of an American Heart Association postdoctoral fellowship award (0720114Z). NR 25 TC 23 Z9 26 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD DEC PY 2010 VL 56 IS 6 BP 1137 EP U274 DI 10.1161/HYPERTENSIONAHA.110.160622 PG 20 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 681KA UT WOS:000284309800033 PM 21059996 ER PT J AU Martin, MP Borecki, IB Zhang, ZY Nguyen, L Ma, DD Gao, XJ Qi, Y Carrington, M Rader, JS AF Martin, Maureen P. Borecki, Ingrid B. Zhang, Zhengyan Nguyen, Loan Ma, Duanduan Gao, Xiaojiang Qi, Ying Carrington, Mary Rader, Janet S. TI HLA-Cw group 1 ligands for KIR increase susceptibility to invasive cervical cancer SO IMMUNOGENETICS LA English DT Article DE Cervical neoplasia; HPV; HLA; KIR ID ANTIGEN CLASS-I; HUMAN-PAPILLOMAVIRUS INFECTION; POPULATION STRATIFICATION; NEOPLASIA; ASSOCIATION; DISEASE; ALLELES; RISK; POLYMORPHISMS; EXPRESSION AB Inherited genetic polymorphisms within immune response genes have been shown to associate with risk of invasive cervical cancer (ICC) and its immediate precursor, cervical intraepithelial neoplasia grade 3. Here, we used the transmission/disequilibrium test to detect disease-liability alleles and investigate haplotype transmission of KIR and HLA class I polymorphisms in a large family-based population of women with cervical cancer and their biological parents (359 trios). The effect of distinct human papillomavirus types was also explored. HLA-Cw group 1 (HLA-Cw alleles with asparagine at position 80), which serves as ligand for certain killer immunoglobulin-like receptors (KIR), was significantly overtransmitted in women with ICC (P = 0.04), and particularly in the subgroup of women infected with high risk HPV16 or 18 subtypes (P = 0.008). These data support the involvement of the HLA-C locus in modulating the risk of cervical neoplasia perhaps through its function as ligands for KIR, but functional studies are essential to confirm this hypothesis. C1 [Martin, Maureen P.; Gao, Xiaojiang; Qi, Ying; Carrington, Mary] NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. [Zhang, Zhengyan; Nguyen, Loan; Rader, Janet S.] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA. [Carrington, Mary] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA. [Carrington, Mary] Harvard Univ, Boston, MA 02114 USA. [Borecki, Ingrid B.; Ma, Duanduan; Rader, Janet S.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. RP Rader, JS (reprint author), Med Coll Wisconsin, Dept Obstet & Gynecol, Milwaukee, WI 53226 USA. EM jrader@mcw.edu FU National Cancer Institute [5R01CA094141, 5R01CA095713]; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX This work was supported by National Cancer Institute grants 5R01CA094141 and 5R01CA095713. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 33 TC 18 Z9 19 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD DEC PY 2010 VL 62 IS 11-12 BP 761 EP 765 DI 10.1007/s00251-010-0477-5 PG 5 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 678YW UT WOS:000284120700006 PM 20857097 ER PT J AU de Jong, A Pena-Cruz, V Cheng, TY Clark, RA Moody, B AF de Jong, A. Pena-Cruz, V. Cheng, T. -Y. Clark, R. A. Moody, B. TI CD1a autoreactive cells are normal part of the human T cell repertoire SO IMMUNOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Society-for-Immunology CY DEC 06-10, 2010 CL Liverpool, ENGLAND SP British Soc Immunol C1 [de Jong, A.; Cheng, T. -Y.; Moody, B.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Pena-Cruz, V.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Clark, R. A.] Brigham & Womens Hosp, Dept Dermatol, 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 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 2010 VL 131 SU 1 BP 28 EP 28 PG 1 WC Immunology SC Immunology GA 689XL UT WOS:000284964100074 ER PT J AU Johnson, EE Sandgren, A Cherayil, BJ Murray, M Wessling-Resnick, M AF Johnson, Erin E. Sandgren, Andreas Cherayil, Bobby J. Murray, Megan Wessling-Resnick, Marianne TI Role of Ferroportin in Macrophage-Mediated Immunity SO INFECTION AND IMMUNITY LA English DT Article ID MYCOBACTERIUM-TUBERCULOSIS; NITRIC-OXIDE; IRON HOMEOSTASIS; HEREDITARY HEMOCHROMATOSIS; SALMONELLA-TYPHIMURIUM; INTRACELLULAR GROWTH; HEPCIDIN EXPRESSION; MURINE MACROPHAGES; PEPTIDE HEPCIDIN; TNF-ALPHA AB Perturbations in iron metabolism have been shown to dramatically impact host response to infection. The most common inherited iron overload disorder results from defects in the HFE gene product, a major histocompatibility complex class I-like protein that interacts with transferrin receptors. HFE-associated hemochromatosis is characterized by abnormally high levels of the iron efflux protein ferroportin. In this study, J774 murine macrophages overexpressing ferroportin were used to investigate the influence of iron metabolism on the release of nitric oxide (NO) in response to infection. Overexpression of ferroportin significantly impaired intracellular Mycobacterium tuberculosis growth during early stages of infection. When challenged with lipopolysaccharide (LPS) or M. tuberculosis infection, control macrophages increased NO synthesis, but macrophages overexpressing ferroportin had significantly impaired NO production in response to LPS or M. tuberculosis. Increased NO synthesis in control cells was accompanied by increased iNOS mRNA and protein, while upregulation of iNOS protein was markedly reduced when J744 cells overexpressing ferroportin were challenged with LPS or M. tuberculosis, thus limiting the bactericidal activity of these macrophages. The proinflammatory cytokine gamma interferon reversed the inhibitory effect of ferroportin overexpression on NO production. These results suggest a novel role for ferroportin in attenuating macrophage-mediated immune responses. C1 [Johnson, Erin E.; Wessling-Resnick, Marianne] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Sandgren, Andreas; Murray, Megan] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Cherayil, Bobby J.] Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. RP Wessling-Resnick, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM wessling@hsph.harvard.edu FU NIH [T90 DK070078, T32 ES007155, R21 AI068077, R21 AI06519, R01 ES014638, R01 DK064750] FX This study was supported by grants from the NIH to E.E.J. (T90 DK070078 and T32 ES007155), M. M. (R21 AI068077). B.J.C. (R21 AI06519), and M.W.-R. (R01 ES014638 and R01 DK064750). A. S. conducted studies as a research fellow at HSPH. NR 56 TC 25 Z9 27 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2010 VL 78 IS 12 BP 5099 EP 5106 DI 10.1128/IAI.00498-10 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 680DW UT WOS:000284213600013 PM 20837712 ER PT J AU Marre, ML Darcy, CT Yinh, J Akira, S Uematsu, S Steere, AC Hu, LT AF Marre, Meghan L. Darcy, Courtney T. Yinh, Janeth Akira, Shizuo Uematsu, Satoshi Steere, Allen C. Hu, Linden T. TI Role of Adrenomedullin in Lyme Disease SO INFECTION AND IMMUNITY LA English DT Article ID ACTIVATED PROTEIN-KINASE; NECROSIS-FACTOR-ALPHA; MACROPHAGE CELL-LINE; TOLL-LIKE RECEPTOR-2; BORRELIA-BURGDORFERI; BINDING PROTEIN-1; EPITHELIAL-CELLS; SYNOVIAL-FLUID; MESSENGER-RNA; MATRIX METALLOPROTEINASES AB Borrelia burgdorferi stimulates a strong inflammatory response during infection of a mammalian host. To understand the mechanisms of immune regulation employed by the host to control this inflammatory response, we focused our studies on adrenomedullin, a peptide produced in response to bacterial stimuli that exhibits antimicrobial activity and regulates inflammatory responses by modulating the expression of inflammatory cytokines. Specifically, we investigated the effect of B. burgdorferi on the expression of adrenomedullin as well as the ability of adrenomedullin to dampen host inflammatory responses to the spirochete. The concentration of adrenomedullin in the synovial fluid of untreated Lyme arthritis patients was elevated compared with that in control osteoarthritis patient samples. In addition, coculture with B. burgdorferi significantly increased the expression of adrenomedullin in RAW264.7 macrophages through MyD88-, phosphatidylinositol 3-kinase (PI3-K)-, and p38-dependent signaling cascades. Furthermore, the addition of exogenous adrenomedullin to B. burgdorferi-stimulated RAW264.7 macrophages resulted in a significant decrease in the induction of proinflammatory cytokines. Taken together, these results suggest that B. burgdorferi increases the production of adrenomedullin, which in turn negatively regulates the B. burgdorferi-stimulated inflammatory response. C1 [Darcy, Courtney T.; Hu, Linden T.] Tufts Univ, Div Geog Med & Infect Dis, Sch Med, Tufts Med Ctr, Boston, MA 02111 USA. [Marre, Meghan L.] Tufts Univ, Grad Program Immunol, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA. [Yinh, Janeth] Tufts Univ, Div Rheumatol, Tufts Med Ctr, Sch Med, Boston, MA 02111 USA. [Akira, Shizuo; Uematsu, Satoshi] Osaka Univ, Dept Host Def, Microbial Dis Res Inst, Osaka, Japan. [Steere, Allen C.] Harvard Univ, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Sch Med,Div Rheumatol Allergy & Immunol, Boston, MA 02111 USA. RP Hu, LT (reprint author), Tufts Univ, Div Geog Med & Infect Dis, Sch Med, Tufts Med Ctr, 800 Washington St,Box 41, Boston, MA 02111 USA. EM lhu@tuftsmedicalcenter.org RI Akira, Shizuo/C-3134-2009; Hu, Linden/L-6314-2016 OI Hu, Linden/0000-0003-1659-5558 FU National Institutes of Health [R56AI80846, R01-AI-50043, T32 AI07077] FX This work was supported by the National Institutes of Health (R56AI80846 and R01-AI-50043 to L. T. H. and T32 AI07077 to M.L.M.). NR 59 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2010 VL 78 IS 12 BP 5307 EP 5313 DI 10.1128/IAI.00630-10 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 680DW UT WOS:000284213600033 PM 20921145 ER PT J AU Hyle, EP Ferraro, MJ Silver, M Lee, H Hooper, DC AF Hyle, E. P. Ferraro, M. J. Silver, M. Lee, H. Hooper, D. C. TI Ertapenem-Resistant Enterobacteriaceae: Risk Factors for Acquisition and Outcomes SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID KLEBSIELLA-PNEUMONIAE CARBAPENEMASE; OUTER-MEMBRANE PROTEIN; ESCHERICHIA-COLI; BETA-LACTAMASE; NEW-YORK; HOSPITALIZED-PATIENTS; KPC CARBAPENEMASE; EMERGENCE; INFECTION; IMIPENEM AB BACKGROUND AND OBJECTIVE. Carbapenem resistance among Enterobacteriaceae is of concern because of increasing prevalence and limited therapeutic options. Limited research has been focused on understanding ertapenem resistance as a more sensitive marker for resistance to other carbapenems. We sought to determine risk factors for acquisition of ertapenem-resistant, meropenem-susceptible, or intermediate Enterobacteriaceae and to assess associated patient outcomes. DESIGN. Retrospective case-control study among adult hospitalized inpatients. SETTING. A 902-bed quaternary care urban hospital. RESULTS. Sixty-two cases of ertapenem-resistant Enterobacteriaceae were identified from March 14, 2006, through October 31, 2007, and 62 unmatched control patients were randomly selected from other inpatients with cultures positive for ertapenem-susceptible Enterobacteriaceae. Thirty-seven (60%) of case patient isolates were Enterobacter cloacae, 20 (32%) were Klebsiella pneumoniae, and 5 (8%) were other species of Enterobacteriaceae. Risk factors for ertapenem-resistant Enterobacteriaceae infection included intensive care unit stay (odds ratio [OR], 4.6 [95% confidence interval {CI}, 2.0-10.3]), vancomycin-resistant Enterococcus colonization (OR, 7.1 [95% CI, 2.4-21.4]), prior central venous catheter use (OR, 10.0 [95% CI, 3.0-33.1]), prior receipt of mechanical ventilation (OR, 5.8 [95% CI, 2.1-16.2]), exposure to any antibiotic during the 30 days prior to a positive culture result (OR, 18.5 [95% CI, 4.9-69.9]), use of a beta-lactam during the 30 days prior to a positive culture result (OR, 6.9 [95% CI, 3.0-16.0], and use of a carbapenem during the 30 days prior to a positive culture result (OR, 18.2 [95% CI, 2.6-130.0]). For the 62 case patients, 30-day outcomes from the time of positive culture result were 24 discharges (39%), 10 deaths (16%), and 28 continued hospitalizations (44%). The final end point of the hospitalization was discharge for 44 patients (71%) and death for 18 patients (29%). CONCLUSIONS. Ertapenem-resistant Enterobacteriaceae are important nosocomial pathogens. Multiple mechanisms of resistance may be in operation. Additional study of ertapenem resistance is needed. C1 [Hyle, E. P.; Hooper, D. C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Ferraro, M. J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Silver, M.; Lee, H.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org NR 38 TC 18 Z9 18 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD DEC PY 2010 VL 31 IS 12 BP 1242 EP 1249 DI 10.1086/657138 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 675PJ UT WOS:000283842300006 PM 21029005 ER PT J AU Gradus, JL Qin, P Lincoln, AK Miller, M Lawler, E Sorensen, HT Lash, TL AF Gradus, Jaimie L. Qin, Ping Lincoln, Alisa K. Miller, Matthew Lawler, Elizabeth Sorensen, Henrik Toft Lash, Timothy L. TI Inflammatory Bowel Disease and Completed Suicide in Danish Adults SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Crohn's disease; ulcerative colitis; inflammatory bowel diseases; suicide ID POPULATION-BASED COHORT; QUALITY-OF-LIFE; ULCERATIVE-COLITIS; CROHNS-DISEASE; MORTALITY; REGISTER; DENMARK; RISK AB Background: The risk of suicide is increased among people with inflammatory bowel disease (IBD); however, most of the evidence regarding this association comes from studies of all-cause mortality, with small numbers of people who have committed suicide, or from clinical case reports. The current study examined the association between the two forms of IBD: Crohn's disease (CD) and ulcerative colitis (UC), and completed suicide in a population-based sample. Methods: Data for this nested case control study were obtained from the Danish national healthcare and social registries. We included 27,053 cases who completed suicide between January 1, 1981, and December 31, 2006. Controls were selected from the general population and matched to cases on gender, date of birth, and calendar time (n = 551,060). Results: There was an increased rate of suicide among participants with both CD (odds ratio [OR] = 1.6, 95% confidence interval [CI]: 1.1, 2.3) and UC (OR = 1.9, 95% CI: 1.4, 2.4), when adjusting for the matched factors and identified confounders. Conclusions: The current study suggests that physicians treating IBD patients should be vigilant about expressions of suicidal ideation or signs and symptoms of self-harm. C1 [Gradus, Jaimie L.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, Boston, MA 02130 USA. [Gradus, Jaimie L.; Sorensen, Henrik Toft; Lash, Timothy L.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Qin, Ping] Aarhus Univ, Ctr Registry Based Res, Aarhus, Denmark. [Lincoln, Alisa K.] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA. [Lincoln, Alisa K.] Northeastern Univ, Dept Sociol, Boston, MA 02115 USA. [Miller, Matthew] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Cambridge, MA 02138 USA. [Lawler, Elizabeth] Harvard Univ, Dept Med, Cambridge, MA 02138 USA. [Sorensen, Henrik Toft; Lash, Timothy L.] Aarhus Univ Hosp, Dept Clin Epidemiol, DK-8000 Aarhus, Denmark. RP Gradus, JL (reprint author), VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, 150 S Huntington Ave 116B-3, Boston, MA 02130 USA. EM Jaimie.Gradus@va.gov OI Gradus, Jaimie/0000-0003-1459-5327 FU The Broad Foundation FX Funded by a grant from the Broad Medical Research Program of The Broad Foundation. NR 20 TC 11 Z9 11 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD DEC PY 2010 VL 16 IS 12 BP 2158 EP 2161 DI 10.1002/ibd.21298 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 688NL UT WOS:000284856600022 PM 20848460 ER PT J AU Agarwal, R Gao, GD DesRoches, C Jha, AK AF Agarwal, Ritu Gao, Guodong (Gordon) DesRoches, Catherine Jha, Ashish K. TI The Digital Transformation of Healthcare: Current Status and the Road Ahead SO INFORMATION SYSTEMS RESEARCH LA English DT Article DE health information technology; health-care transformation; electronic health records; meaningful use ID PHYSICIAN ORDER ENTRY; ELECTRONIC MEDICAL-RECORDS; INFORMATION-TECHNOLOGY; US HOSPITALS; PRIVACY PROTECTION; AMBULATORY-CARE; NATIONAL-SURVEY; UNITED-STATES; SYSTEMS; ADOPTION AB As the United States expends extraordinary efforts toward the digitization of its health-care system, and as policy makers across the globe look to information technology (IT) as a means of making health-care systems safer, more affordable, and more accessible, a rare and remarkable opportunity has emerged for the information systems research community to leverage its in-depth knowledge to both advance theory and influence practice and policy. Although health IT (HIT) has tremendous potential to improve quality and reduce costs in healthcare, significant challenges need to be overcome to fully realize this potential. In this commentary, we survey the landscape of existing studies on HIT to provide an overview of the current status of HIT research. We then identify three major areas that warrant further research: (1) HIT design, implementation, and meaningful use; (2) measurement and quantification of HIT payoff and impact; and (3) extending the traditional realm of HIT. We discuss specific research questions in each domain and suggest appropriate methods to approach them. We encourage information systems scholars to become active participants in the global discourse on health-care transformation through IT. C1 [Agarwal, Ritu; Gao, Guodong (Gordon)] Univ Maryland, Ctr Hlth Informat & Decis Syst, Robert H Smith Sch Business, College Pk, MD 20742 USA. [DesRoches, Catherine] Harvard Univ, Sch Med, Boston, MA 02114 USA. [DesRoches, Catherine] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Jha, Ashish K.] Harvard Univ, Sch Publ Hlth & Vet Hlth Adm, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Agarwal, R (reprint author), Univ Maryland, Ctr Hlth Informat & Decis Syst, Robert H Smith Sch Business, College Pk, MD 20742 USA. EM ragarwal@rhsmith.umd.edu; ggao@rhsmith.umd.edu; cdesroches@partners.org; ajha@hsph.harvard.edu RI Wang, Charles/B-5565-2011 OI Wang, Charles/0000-0001-9331-8437 NR 95 TC 88 Z9 88 U1 31 U2 113 PU INFORMS PI HANOVER PA 7240 PARKWAY DR, STE 310, HANOVER, MD 21076-1344 USA SN 1047-7047 J9 INFORM SYST RES JI Inf. Syst. Res. PD DEC PY 2010 VL 21 IS 4 BP 796 EP 809 DI 10.1287/isre.1100.0327 PG 14 WC Information Science & Library Science; Management SC Information Science & Library Science; Business & Economics GA 695OZ UT WOS:000285383200012 ER PT J AU Hamade, AK Misra, V Rabold, R Tankersley, CG AF Hamade, Ali K. Misra, Vikas Rabold, Richard Tankersley, Clarke G. TI Age-related changes in cardiac and respiratory adaptation to acute ozone and carbon black exposures: Interstrain variation in mice SO INHALATION TOXICOLOGY LA English DT Article ID HEART-RATE-VARIABILITY; PARTICULATE MATTER; AIR-POLLUTION; LUNG-FUNCTION; ANTIOXIDANT SUPPLEMENTATION; INDUCED INFLAMMATION; SINUS ARRHYTHMIA; OXIDATIVE STRESS; YOUNG-ADULTS; TIME-COURSE AB Context: Epidemiological studies show positive associations between increased ambient air pollutant levels and adverse cardiopulmonary effects. These studies suggest that the elderly and those with certain genetic polymorphisms are susceptible to adverse air pollution-associated health events. Hypothesis/objective: We hypothesize that physiological responses to air pollutants vary with age and are genetically influenced. Materials and methods: To test this hypothesis, we exposed mice from three inbred strains (C57BL/6J, B6; C3H/HeJ, HeJ; C3H/HeOuJ, OuJ) to ozone (O-3) and carbon black (CB) at two ages, (5 months, 12 months), for 3 consecutive days, to either filtered air (FA), CB particles, or O-3 and CB sequentially (O3CB) (CB, 550 mu g/m(3); O-3, 600 ppb). Heart rate (HR), HR variability (HRV), breathing, and core temperature (Tco) responses were analyzed. Results: We observed time-dependent physiological changes in response to O3CB exposure in each strain, relative to FA exposure for both age groups. Each mouse strain showed distinct adaptation profiles to repeated acute exposures to O-3. In younger mice, several time-dependent effects (decreased HR and increased HRV) were prominent in HeJ and OuJ mice but not B6 mice. We also observed variability in adaptation in older mice. However, responses in older mice were generally attenuated when compared to the younger mice. In addition, cardiac-respiratory interactions were affected with CB and O3CB exposures albeit with patterns differing by age or exposure. Discussion/conclusion: Our results suggest that age considerably attenuates physiological responses to O-3 and O3CB exposures. Age-related physiological changes such as increased oxidative stress in mouse tissue may be involved in this attenuation. C1 [Hamade, Ali K.] Gradient Corp, Cambridge, MA 02138 USA. [Misra, Vikas] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rabold, Richard; Tankersley, Clarke G.] Johns Hopkins Univ, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. RP Tankersley, CG (reprint author), 615 N Wolfe St, Baltimore, MD 21205 USA. EM ctankers@jhsph.edu FU National Institute of Aging [AG-21057] FX This work was supported by AG-21057 (National Institute of Aging). NR 43 TC 9 Z9 9 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PD DEC PY 2010 VL 22 SU 2 BP 84 EP 94 DI 10.3109/08958378.2010.503974 PG 11 WC Toxicology SC Toxicology GA 693AP UT WOS:000285197300010 PM 20883109 ER PT J AU Jubran, A Lawm, G Duffner, L Collins, E Lanuza, D Hoffman, L Tobin, M AF Jubran, Amal Lawm, Gerald Duffner, Lisa A. Collins, Eileen G. Lanuza, Dorothy M. Hoffman, Leslie A. Tobin, Martin J. TI Post-traumatic stress disorder after weaning from prolonged mechanical ventilation SO INTENSIVE CARE MEDICINE LA English DT Article DE Mechanical ventilation; Post-traumatic stress disorder; Anxiety ID ACUTE RESPIRATORY-DISTRESS; GENERAL INTENSIVE-CARE; QUALITY-OF-LIFE; CRITICAL ILLNESS; ICU TREATMENT; SURVIVORS; SYMPTOMS; TRIAL; HEALTH; SAMPLE AB Weaning from prolonged mechanical ventilation may be associated with mental discomfort. It is not known whether such discomfort is linked with the development of post-traumatic stress disorder (PTSD). Accordingly, we investigated whether PTSD occurs in patients after weaning from prolonged ventilation. We also determined whether administering a questionnaire would identify patients at risk for developing PTSD. A prospective longitudinal study of patients transferred to a long-term acute-care hospital for weaning from prolonged ventilation was undertaken: 72 patients were studied 1 week after weaning, and 41 patients were studied again 3 months later. An experienced psychologist conducted a structured clinical interview 3 months after weaning to establish a diagnosis of PTSD. To assess for the presence of PTSD-related symptoms, the post-traumatic stress syndrome (PTSS-10) questionnaire was administered 1 week after weaning and 3 months later. The psychologist diagnosed PTSD in 12% of patients 3 months after ventilator weaning. Patients who developed PTSD were more likely to have a previous history of psychiatric disorders (P < 0.02). A PTSS-10 score > 20 one week after weaning reliably identified patients who were diagnosed with PTSD 3 months later: sensitivity 1.0; specificity 0.76; area under the receiver-operating characteristic curve 0.91. PTSD was diagnosed in 12% of patients who were weaned from prolonged ventilation. A PTSS-10 score > 20 one week after weaning identified patients diagnosed with PTSD 3 months later. This finding suggests that a simple questionnaire administered before hospital discharge can identify patients at risk for developing PTSD. C1 [Jubran, Amal; Tobin, Martin J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. [Lawm, Gerald; Duffner, Lisa A.] RML Specialty Hosp, Hinsdale, IL USA. [Collins, Eileen G.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Jubran, Amal; Tobin, Martin J.] Loyola Univ Chicago, Stritch Sch Med, Maywood, IL USA. [Collins, Eileen G.] Univ Illinois, Coll Nursing, Chicago, IL USA. [Lanuza, Dorothy M.] Univ Wisconsin, Sch Nursing, Madison, WI USA. [Hoffman, Leslie A.] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. RP Jubran, A (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. EM ajubran@lumc.edu; mtobin2@lumc.edu FU National Institute of Health [RO1 NR008782]; Veterans Administration Research Service FX This paper was supported by funding from the National Institute of Health (RO1 NR008782) and a Merit Review grant from the Veterans Administration Research Service. No financial or other potential conflicts of interest exist NR 40 TC 38 Z9 38 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD DEC PY 2010 VL 36 IS 12 BP 2030 EP 2037 DI 10.1007/s00134-010-1972-8 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 680ZK UT WOS:000284275800007 PM 20661726 ER PT J AU Pitts, R Fisher, D Sulemanji, D Kratohvil, J Jiang, YD Kacmarek, R AF Pitts, Renee Fisher, Daniel Sulemanji, Demet Kratohvil, Joseph Jiang, Yandong Kacmarek, Robert TI Variables affecting leakage past endotracheal tube cuffs: a bench study SO INTENSIVE CARE MEDICINE LA English DT Article DE Endotracheal tube; Aspiration; Ventilator associated pneumonia; Cuff pressure; PEEP; Ventilator bundles ID VENTILATOR-ASSOCIATED PNEUMONIA; INTENSIVE-CARE-UNIT; EXPIRATORY PRESSURE; PREVENT LEAKAGE; ASPIRATION; FLUID; VOLUME; MODEL AB Leakage of oral secretions past endotracheal tubes (ETT) has been implicated in ventilator associated pneumonia. The aim of this bench study was to compare the ability of current generation ETT cuffs to prevent fluid leakage and to determine the specific mechanical ventilator settings that affect movement of fluid across an inflated ETT cuff. Using a 2.3-cm internal diameter (ID) tracheal model and simulated ventilatory support, we evaluated the impact of cuff pressure (20 and 30 cmH(2)O), positive end-expiratory pressure/continuous positive airway pressure (PEEP/CPAP, 0-15 cmH(2)O), peak inspiratory pressure (PIP, 15-45 cmH(2)O), and mode of ventilation (volume control, volume assist/control, pressure control, pressure assist/control, and CPAP) on leakage of fluid past the ETT cuffs of 16 ETTs. The tracheal model was configured in the vertical position with 35 ml of vitaminwater(A (R)) on top of the inflated ETT cuff and mechanically ventilated. Fluid leakage past the cuff was determined by calculating the volume change in the tracheal model after each 30-min ventilation period. Initially five 8.0-mm-ID ETTs of each manufacturer type were evaluated at baseline ventilator settings. Tubes allowing a consistent leak within two SD of the mean leakage for the five tubes were numbered in consecutive order. A single tube from this group was then randomly selected for detailed evaluation. Cuff leakage varied among ETT types (p < 0.0001); median leak volume 6.0 ml (0.6-15.1) across all tubes under all conditions. Cuff leakage was inversely related to PEEP level, cuff pressure, and PIP except when PEEP was set at 15 cmH(2)O (all p < 0.0001). In addition, cuff leak varied among modes (p = 0.035). Cuff leakage varies greatly among ETT types and is affected by cuff pressure, PEEP, PIP, and mode. C1 [Pitts, Renee; Sulemanji, Demet; Jiang, Yandong; Kacmarek, Robert] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Pitts, Renee; Fisher, Daniel; Sulemanji, Demet; Kratohvil, Joseph; Jiang, Yandong; Kacmarek, Robert] Harvard Univ, Sch Med, Boston, MA USA. [Pitts, Renee] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Fisher, Daniel; Kratohvil, Joseph] Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. RP Kacmarek, R (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Ellison 401, Boston, MA 02114 USA. EM rkacmarek@partners.org FU Covidien, Carlsbad, CA, USA; Hamilton; General Electric; Newport; Drager; Covidien FX The authors would like to thank Edward Bittner MD, PhD for his gracious assistance with the statistical analysis. This project was funded by a gift from Covidien, Carlsbad, CA, USA. Robert M Kacmarek has received research grants from Covidien, Hamilton, General Electric, Newport, and Drager; honorarium for lecturing from Covidien, Hamilton, and Maquet; and is a consultant for Newport and KCI. NR 23 TC 27 Z9 30 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD DEC PY 2010 VL 36 IS 12 BP 2066 EP 2073 DI 10.1007/s00134-010-2048-5 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 680ZK UT WOS:000284275800012 PM 20852839 ER PT J AU Mailloux, AW Clark, AMA Young, MRI AF Mailloux, Adam W. Clark, Anna-Maria A. Young, M. Rita I. TI NK depletion results in increased CCL22 secretion and Treg levels in Lewis Lung Carcinoma via the accumulation of CCL22-secreting CD11b(+)CD11c(+) cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE natural killer cells; regulatory T-cells; chemokines; cancer; immune suppression ID REGULATORY T-CELLS; FOSTERS IMMUNE PRIVILEGE; TUMOR MICROENVIRONMENT; CANCER; RECRUITMENT; MICE; EXPRESSION; CHEMOKINES; INDUCTION; PROMOTION AB Tumor-induced immune suppression involves the accumulation of suppressive infiltrates in the tumor microenvironment such as regulatory T-cells (Tregs). Previous studies demonstrated that NK-dependant increases in CCL22 secretion selectively recruit Tregs toward murine lungs bearing Lewis Lung Carcinoma (LLC). To extend the in vitro studies, the present studies utilized in vivo depletion of NK cells to ascertain the contribution of NK-derived CCL22 toward total CCL22 and subsequent Treg levels in both normal and LLC-bearing lungs. However, NK depletion had the unexpected effect of increasing both CCL22 secretion and Treg levels in the lungs of NK-depleted LLC-bearing mice. This was concurrent with an increase in tumor burden. Flow cytometry and a series of both immunomagnetic and FACS isolations were used to identify the CCL22-producing cellular fractions in LLC-bearing lungs. A novel CD11b(+)CD11c(+) cell population was identified that accumulates in large numbers in NK-depleted LLC-bearing lung tissue. These CD11b(+)CD11c(+) cells secreted large amounts of CCL22 that may overcompensate for the loss of NK-derived CCL22 in the lungs of NK-depleted LLC-bearing mice. Taken together, these data suggest that NK cells play both a positive and negative role in the regulation of CCL22 secretion and, in turn, the recruitment of Tregs toward LLC-bearing lungs. C1 [Clark, Anna-Maria A.; Young, M. Rita I.] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC 29401 USA. [Mailloux, Adam W.] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Young, M. Rita I.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Young, M. Rita I.] Med Univ S Carolina, Dept Otolaryngol, Charleston, SC 29425 USA. RP Young, MRI (reprint author), Ralph H Johnson VA Med Ctr, Res Serv, 151,109 Bee St, Charleston, SC 29401 USA. EM rita.young@va.gov FU Medical Research Service of the Veteran's Affairs; National Institute of Health [R01CA8566, 1R01CA128837, R01DE018168] FX Grant sponsor: Medical Research Service of the Veteran's Affairs, Grant sponsor: National Institute of Health; Grant numbers: R01CA8566, 1R01CA128837, R01DE018168 (MRIY) NR 27 TC 9 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 1 PY 2010 VL 127 IS 11 BP 2598 EP 2611 DI 10.1002/ijc.25281 PG 14 WC Oncology SC Oncology GA 672TJ UT WOS:000283609500011 PM 20198623 ER PT J AU Janeway, KA Zhu, MJ Barretina, J Perez-Atayde, A Demetri, GD Fletcher, JA AF Janeway, Katherine A. Zhu, Mei-Jun Barretina, Jordi Perez-Atayde, Antonio Demetri, George D. Fletcher, Jonathan A. TI Strong expression of IGF1R in pediatric gastrointestinal stromal tumors without IGF1R genomic amplification SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE gastrointestinal stromal tumor; insulin like growth factor 1 receptor; pediatric ID GROWTH-FACTOR RECEPTOR; FACTOR-I RECEPTOR; THERAPEUTIC TARGET; WILD-TYPE; INSULIN; GIST; FIBROBLASTS; MECHANISMS; TRANSFORMATION; PROGRESSION AB Wildtype (WT) gastrointestinal stromal tumors (GISTs), lacking mutations in KIT or PDGFRA represent 85% of GISTs in pediatric patients. Treatment options for pediatric WT GIST are limited Recently of a limited number of pediatric and adult WT GISTs and more in depth study of a single pediatric WT GIST implicated the insulin like growth factor 1 receptor (IGF1R) as a potential therapeutic target in pediatric WT GIST. We performed immunoblotting, SNP and FISH studies to determine the extent of expression, biochemical activation and genomic amplification of IGF1R in a larger number of pediatric WT GISTs. Pediatric WT GISTs expressed IGF1R strongly, whereas typical adult KIT mutant GISTs did not IGF1R gene amplification was not detected in pediatric WT GISTs, and some KIT Mutant GISTs had IGF1R gene deletion due to monosomy, 15. Despite the absence of apparent genomic activation mechanisms accounting for overexpression,Clinical study of IGF1R-directed therapies in pediatric WT GIST is warranted. C1 [Zhu, Mei-Jun; Fletcher, Jonathan A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Demetri, George D.] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA 02115 USA. [Perez-Atayde, Antonio] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Barretina, Jordi] Broad Inst, Canc Program, Cambridge, MA 02142 USA. [Janeway, Katherine A.] Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. RP Janeway, KA (reprint author), 44 Binney St,Dana 3, Boston, MA 02115 USA. EM katherine_janeway@dfci.harvard.edu FU National Institutes of Health [1P50CA127003-02]; Clinical Investigator Training Program (CITP); GIST; Virginia and Daniel K. Ludwig Trust for Cancer Research; Life Raft Group FX Grant sponsor: The National Institutes of Health; Grant number: 1P50CA127003-02; Grant sponsors: Clinical Investigator Training Program (CITP), The GIST Cancer Research Fund, The Virginia and Daniel K. Ludwig Trust for Cancer Research, The Life Raft Group NR 26 TC 45 Z9 46 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD DEC 1 PY 2010 VL 127 IS 11 BP 2718 EP 2722 DI 10.1002/ijc.25247 PG 5 WC Oncology SC Oncology GA 672TJ UT WOS:000283609500024 PM 20162573 ER PT J AU Lodato, S Tomassy, GS De Leonibus, E Arlotta, P de la Prida, LM Studer, M AF Lodato, S. Tomassy, G. Srubek De Leonibus, E. Arlotta, P. Menendez de la Prida, L. Studer, M. TI Loss of coup-tfi results in increased generation of PV-expressing interneurons and resistance to epileptic seizures SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Meeting Abstract CT 18th Biennial Meeting of the International-Society-for-Developmental-Neuroscience CY JUN 06-09, 2010 CL Estoril, PORTUGAL SP Int Soc Dev Neurosci DE Resistance to epilepsy; Cortical interneurons; Caudal ganglionic eminence; Nuclear receptor; COUP-TFI C1 [Lodato, S.; Tomassy, G. Srubek; Arlotta, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Menendez de la Prida, L.] Inst Cajal, Madrid, Spain. [Studer, M.] INSERM, U636, F-75654 Paris 13, France. RI Studer, Michele/P-4580-2016 OI Studer, Michele/0000-0001-7105-2957 NR 0 TC 0 Z9 0 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD DEC PY 2010 VL 28 IS 8 SI SI BP 693 EP 693 DI 10.1016/j.ijdevneu.2010.07.150 PG 1 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 689YS UT WOS:000284967600147 ER PT J AU Gradus, JL Qin, P Lincoln, AK Miller, M Lawler, E Sorensen, HT Lash, TL AF Gradus, Jaimie L. Qin, Ping Lincoln, Alisa K. Miller, Matthew Lawler, Elizabeth Sorensen, Henrik Toft Lash, Timothy L. TI Acute stress reaction and completed suicide SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Suicide; case-control studies; stress disorders; traumatic; acute ID REGISTER AB Background Acute stress reaction is a diagnosis given immediately following the experience of an exceptional mental or physical stressor. To the best of our knowledge, no study has examined the association between acute stress reaction diagnosis and suicide. The current study examined this association in a population-based sample. In addition, we examined comorbid psychiatric diagnoses as modifiers of this association. Methods Data for the current study were obtained from the nationwide Danish health and administrative registries, which include data for all 5.4 million residents of Denmark. All suicides between 1 January 1994 and 31 December 2006 were included and controls were selected from a sample of all Danish residents. Using this nested case-control design, we examined 9612 suicide cases and 199 306 controls matched to cases with respect to gender, date of birth and time. Results In total, 95 cases (0.99%) and 165 controls (0.08%) had a diagnosis of acute stress reaction. Those diagnosed with acute stress reaction had 10 times the rate of completed suicide compared with those without this diagnosis, adjusting for the control to case matching, depression and marital status (95% confidence interval 7.7-14). Additionally, persons with acute stress reaction and depression, or acute stress reaction and substance abuse, had a greater rate of suicide than expected based on their independent effects. Conclusions Acute stress reaction is a risk factor for completed suicide. C1 [Gradus, Jaimie L.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02118 USA. [Gradus, Jaimie L.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Gradus, Jaimie L.; Sorensen, Henrik Toft; Lash, Timothy L.] Boston Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA USA. [Qin, Ping] Aarhus Univ, Natl Ctr Register Based Res, Aarhus, Denmark. [Lincoln, Alisa K.] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA. [Lincoln, Alisa K.] Northeastern Univ, Dept Sociol, Boston, MA 02115 USA. [Miller, Matthew] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Lawler, Elizabeth] Harvard Univ, Dept Med, Boston, MA USA. [Sorensen, Henrik Toft; Lash, Timothy L.] Aarhus Univ Hosp, Dept Clin Epidemiol, DK-8000 Aarhus, Denmark. RP Gradus, JL (reprint author), 150 S Huntington Ave,116B-3, Boston, MA 02130 USA. EM jaimie.gradus@va.gov OI Gradus, Jaimie/0000-0003-1459-5327 NR 15 TC 14 Z9 14 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 2010 VL 39 IS 6 BP 1478 EP 1484 DI 10.1093/ije/dyq112 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 689TQ UT WOS:000284952700013 PM 20624822 ER PT J AU Sullivan, BT Cherry, JA Sakamoto, H Henkes, LE Townson, DH Rueda, BR AF Sullivan, Brian T. Cherry, Jessica A. Sakamoto, Hideo Henkes, Luiz E. Townson, David H. Rueda, Bo R. TI Cytokeratin 18 Expression Inhibits Cytokine-Induced Death of Cervical Cancer Cells SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Cervix; Apoptosis; Cytokeratin; Cytokines ID INTERMEDIATE-FILAMENTS; TUMOR PROGRESSION; APOPTOSIS; RESISTANCE; CARCINOMA; KERATINS AB Objectives: In cervical cancer, increased cytokeratin 18 (CK18) filament expression is associated with disease progression. However, it may also provide resistance to cytokine-induced apoptosis. The present study tested whether CK18 expression influences susceptibility to cytokine-induced apoptosis. Methods: The cervical cancer cell lines C-4II (high CK18 expression), ME-180 (low CK18 expression), and 2 subtypes of HeLa cells containing or lacking CK18 expression (CK18(+) and CK18(-) cells, respectively) were exposed to vehicle (control), Fas ligand (FasL) (50 ng/mL), or tumor necrosis factor alpha (TNF-alpha; 10 ng/mL) without/with cycloheximide (CHX; 2.5 mu g/mL) to test the hypothesis that diminished CK18 expression increases susceptibility to cytokine-induced apoptosis. Results: Flow cytometric analysis of cell death via TUNEL staining revealed that cytokine-induced apoptosis was 2-fold greater in ME-180 cells than C-4II cells in response to FasL+CHX or TNF-alpha+CHX (P < 0.05). Similarly, there was a higher incidence of FasL-induced apoptosis in CK18(-) HeLa cells (23% and 91% apoptotic for FasL and FasL+CHX, respectively) than CK18(+) HeLa cells (1% and 11%, respectively; P < 0.05). Surprisingly, TNF-alpha had no effect on either CK18(+) or CK18(-) HeLa cells (P < 0.05). Caspase 3 activity was greater in CK18(-) HeLa cells than in CK18(+) HeLa cells at 8 and 18 hours after FasL treatment (P < 0.05), an effect abrogated by the caspase 8 inhibitor IETD-fmk (P < 0.05). Conclusions: Cervical cancer cells with diminished CK18 expression are more susceptible to cytokine-induced apoptosis, particularly in response to FasL treatment. These observations suggest that relative CK18 expression is an important factor when considering therapeutic strategies to enhance immune cell-mediated death of cervical cancer cells. C1 [Sullivan, Brian T.; Sakamoto, Hideo; Henkes, Luiz E.; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, MGH Dept Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Sullivan, Brian T.; Cherry, Jessica A.; Townson, David H.] Univ New Hampshire, Dept Mol Cellular & Biomed Sci, Durham, NH 03824 USA. [Sakamoto, Hideo; Henkes, Luiz E.; Rueda, Bo R.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Rueda, BR (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, MGH Dept Vincent Obstet & Gynecol, THR 901A,55 Fruit St, Boston, MA 02114 USA. EM dave.townson@unh.edu; brueda@partners.org FU USDA [2007-35203-18074]; Advanced Medical Research Foundation; Vincent Memorial Research Funds FX This study was supported by USDA 2007-35203-18074 (to D. H. T.), Advanced Medical Research Foundation (to B. R. R.), and Vincent Memorial Research Funds (to B.R.R.). NR 19 TC 7 Z9 7 U1 0 U2 3 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 DEC PY 2010 VL 20 IS 9 BP 1474 EP 1481 DI 10.1111/IGC.0b013e3181fc3a03 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 688BG UT WOS:000284822900007 PM 21119362 ER PT J AU Yasuda, H Soejima, K Watanabe, H Kawada, I Nakachi, I Yoda, S Nakayama, S Satomi, R Ikemura, S Terai, H Sato, T Suzuki, S Matsuzaki, Y Naoki, K Ishizaka, A AF Yasuda, Hiroyuki Soejima, Kenzo Watanabe, Hideo Kawada, Ichiro Nakachi, Ichiro Yoda, Satoshi Nakayama, Sohei Satomi, Ryosuke Ikemura, Shinnosuke Terai, Hideki Sato, Takashi Suzuki, Sadafumi Matsuzaki, Yumi Naoki, Katsuhiko Ishizaka, Akitoshi TI Distinct epigenetic regulation of tumor suppressor genes in putative cancer stem cells of solid tumors SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE epigenetics; cancer stem cells; DNA methylation ID IN-VITRO PROPAGATION; DNA METHYLATION; DEVELOPMENTAL REGULATORS; POLYCOMB COMPLEXES; INITIATING CELLS; HYPERMETHYLATION; DIFFERENTIATION; IDENTIFICATION; POPULATION; CARCINOMA AB Epigenetic gene regulation plays essential roles in differentiation of embryonic and tissue stem cells In these benign undifferentiated cells, some polycomb targeted genes are kept in a state of DNA hypomethylation and they have a distinct chromatin signature termed bivalent chromatin structure to maintain their plasticity We hypothesized that cancer stem cells (CSC), the malignant counterpart of these cells, are also under the control of epigenetics like benign stem cells We compared the DNA methylation and chromatin structure in 10 tumor suppressor genes between CSC and differentiated cancer cells of MCF7 and Huh7 cells We found that the level of DNA methylation was indeed significantly lower in CSC, while surprisingly, the bivalent chromatin structure was more ubiquitously seen in differentiated cancer cells compared to CSC However, repressive marks of chromatin structure, namely H3K27me3 and EZH2, were significantly lower in CSC As a consequence, CSC remained in a higher transcriptionally active chromatin state compared to differentiated cancer cells We found that the differentiation of CSCs is also epigenetically regulated These findings could help towards a comprehensive understanding of CSC, and also Improve the development of eradicative therapies against human malignancies C1 [Yasuda, Hiroyuki; Soejima, Kenzo; Kawada, Ichiro; Nakachi, Ichiro; Yoda, Satoshi; Nakayama, Sohei; Satomi, Ryosuke; Ikemura, Shinnosuke; Terai, Hideki; Sato, Takashi; Naoki, Katsuhiko; Ishizaka, Akitoshi] Keio Univ, Dept Pulm Med, Sch Med, Shinjuku Ku, Tokyo 1608582, Japan. [Suzuki, Sadafumi; Matsuzaki, Yumi] Keio Univ, Dept Physiol, Sch Med, Shinjuku Ku, Tokyo 1608582, Japan. [Watanabe, Hideo] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Soejima, K (reprint author), Keio Univ, Dept Pulm Med, Sch Med, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan. FU Ministry of Education, Culture, Sports, Science, and Technology of Japan FX We wish to thank Ms M Shibuya and Ms M Yamamoto for their excellent technical assistance with the molecular analyses This study was supported in part by Grants-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science, and Technology of Japan to KS The authors declare that they have no competing interests NR 42 TC 9 Z9 10 U1 0 U2 0 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD DEC PY 2010 VL 37 IS 6 BP 1537 EP 1546 DI 10.3892/ijo_0000087 PG 10 WC Oncology SC Oncology GA 689JA UT WOS:000284922700020 PM 21042723 ER PT J AU Susarla, SM Thomas, RJ Abramson, ZR Kaban, LB AF Susarla, S. M. Thomas, R. J. Abramson, Z. R. Kaban, L. B. TI Biomechanics of the upper airway: Changing concepts in the pathogenesis of obstructive sleep apnea SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Review DE obstructive sleep apnea; airway dynamics; maxillomandibular advancement; orthognathic surgery ID MAXILLOMANDIBULAR ADVANCEMENT SURGERY; PHARYNGEAL MOTOR CONTROL; CARDIOVASCULAR OUTCOMES; VENTILATORY STABILITY; BODY-COMPOSITION; PRESSURE CHANGES; METABOLIC-RATE; GENIOGLOSSUS; COMPLEX; WEIGHT AB Obstructive sleep apnea (OSA) is a disorder characterized by repetitive, episodic collapse of the pharyngeal airway. Over the last two decades, understanding of the pathophysiology of sleep disordered breathing, which includes OSA, has improved. Once thought to be predominately related to anatomic constriction of the maxillomandibular complex, central nervous system regulation of breathing is now recognized as a significant contributor to the pathogenesis of OSA. Ventilator control, the central response to chemoreceptor phenomena, has important implications for oral and maxillofacial surgeons who treat OSA, particularly for patients who appear refractory to treatment with maxillomandibular advancement (MMA). The purpose of this article is to review the biomechanics of the upper airway as it relates to the pathophysiology of OSA, to discuss emerging concepts of ventilator control mechanisms in normal sleep versus sleep-disordered breathing and to discuss the concept of complex sleep apnea, a new category of sleep disordered breathing with both obstructive and central features. C1 [Susarla, S. M.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, WACC230, Boston, MA 02114 USA. [Susarla, S. M.; Abramson, Z. R.; Kaban, L. B.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Thomas, R. J.] Beth Israel Deaconess Med Ctr, Dept Med, Div Pulm Crit Care & Sleep, Boston, MA 02215 USA. [Thomas, R. J.] Harvard Univ, Sch Med, Boston, MA USA. RP Susarla, SM (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, WACC230, Boston, MA 02114 USA. EM ssusarla1@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 FU Oral and Maxillofacial Surgery Foundation; AO/Synthes Research Fellowship in Pediatric Maxillofacial Surgery; Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Center for Applied Clinical Investigation and Education and Research Fund; National Heart, Lung and Blood Institute, National Institutes of Health [1RC1HL099749-01] FX This study was supported by the Oral and Maxillofacial Surgery Foundation Fellowship in Clinical Investigation (SMS), the AO/Synthes Research Fellowship in Pediatric Maxillofacial Surgery (ZRA), the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Center for Applied Clinical Investigation and Education and Research Fund (SMS, ZRA) and the National Heart, Lung and Blood Institute, National Institutes of Health (grant #1RC1HL099749-01, RJT). NR 98 TC 24 Z9 25 U1 2 U2 11 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0901-5027 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD DEC PY 2010 VL 39 IS 12 BP 1149 EP 1159 DI 10.1016/j.ijom.2010.09.007 PG 11 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 701LT UT WOS:000285820100001 PM 21030210 ER PT J AU Ottmani, SE Murray, MB Jeon, CY Baker, MA Kapur, A Lonnroth, K Harries, AD AF Ottmani, S-E. Murray, M. B. Jeon, C. Y. Baker, M. A. Kapur, A. Loennroth, K. Harries, A. D. TI Consultation meeting on tuberculosis and diabetes mellitus: meeting summary and recommendations SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE diabetes mellitus; tuberculosis; meeting report; screening; treatment outcomes AB The steadily growing epidemic of diabetes mellitus (DM) poses a threat for global tuberculosis (TB) control. Previous studies have identified an important association between DM and TB. However, these studies have limitations: very few were carried out in low-income countries, and none in Africa, raising uncertainty about the strength of the DM-TB association in these settings, and many critical questions remain unanswered. As a result of these questions and uncertainties, the International Union Against Tuberculosis and Lung Disease (The Union), the World Diabetes Foundation and the World Health Organization Stop TB Department undertook a SUMMARY series of consultations as of January 2009. A systematic review and meta-analysis was undertaken by the Department of Epidemiology, Harvard School of Public Health between May and August 2009, and a consultation meeting involving the experts who reviewed the report took place at The Union Headquarters in Paris on 6 and 7 November 2009. This paper constitutes a summary report of the findings, the research gaps and prioritised areas of research, and the recommendations from that meeting. C1 [Ottmani, S-E.; Loennroth, K.] WHO, Stop TB Dept, CH-1211 Geneva, Switzerland. [Murray, M. B.; Jeon, C. Y.; Baker, M. A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Murray, M. B.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Baker, M. A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Kapur, A.] World Diabet Fdn, Lyngby, Denmark. [Harries, A. D.] Int Union TB & Lung Dis, Paris, France. [Harries, A. D.] London Sch Hyg & Trop Med, London WC1, England. RP Harries, AD (reprint author), Vears Lane, Winchester SO21 1TQ, Hants, England. EM adharries@theunion.org RI Lonnroth, Knut/L-2339-2014 OI Lonnroth, Knut/0000-0001-5054-8240 FU World Diabetes Foundation, Lyngby, Denmark FX The consultation meeting was supported through an unrestricted educational grant from the World Diabetes Foundation, Lyngby, Denmark. NR 7 TC 17 Z9 17 U1 0 U2 2 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD DEC PY 2010 VL 14 IS 12 BP 1513 EP 1517 PG 5 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 694FL UT WOS:000285280300006 PM 21180207 ER PT J AU Li, HK Hubbard, LD Danis, RP Florez-Arango, JF Esquivel, A Krupinski, EA AF Li, Helen K. Hubbard, Larry D. Danis, Ronald P. Florez-Arango, Jose F. Esquivel, Adol Krupinski, Elizabeth A. TI Comparison of Multiple Stereoscopic and Monoscopic Digital Image Formats to Film for Diabetic Macular Edema Evaluation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2009 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol ID FUNDUS PHOTOGRAPHY; SLIDE FILM; RETINOPATHY; TELEOPHTHALMOLOGY; DIAGNOSIS AB PURPOSE. To assess agreement between evaluations of monoscopic and stereoscopic digital images versus stereo film photographs in diabetic macular edema (DME). METHODS. A 152-eye group of digital monoscopic macular images (seven-field sets and wide-angle mosaics) were compared with digital stereoscopic images (uncompressed and compressed seven-field sets) and stereo 35-mm film photos (Early Treatment Diabetic Retinopathy Study protocol) for the presence of hard exudates (HE), retinal thickening (RT), clinically significant macular edema (CSME), and RT at the center of the macular (RTCM). RESULTS. Agreement, according to the kappa statistic, was almost perfect in identifying HE and RT between all digital formats and stereo film (HE, kappa = 0.81-0.87; RT, kappa = 0.87-0.92). Distribution in all digital formats was not significantly different from that in film (Bhapkar test: HE, P = 0.20-0.40; RT, P = 0.06-1.0). CSME and RTCM grading differences were either significant or trended toward significance. The readers detected CSME and RTCM in film images more often than in digital formats. In identifying DME features, agreement between evaluations of monoscopic digital formats and film was similar to that between stereo digital formats and film, and the performance of uncompressed images versus film was similar to that of compressed images versus film. Repeatability between readers was similar in evaluations of film and all digital formats. Repeatability in identifying RTCM was lower than that of other DME components in film and all digital formats. CONCLUSIONS. Stereoscopic digital formats are equivalent to monoscopic for DME evaluation, but digital photography is not as sensitive as film in detecting CSME and RTCM. (Invest Ophthalmol Vis Sci. 2010;51:6753-6761) DOI:10.1167/iovs.10-5504 C1 [Li, Helen K.; Florez-Arango, Jose F.] Univ Texas Hlth Sci Ctr, Sch Biomed Informat, Houston, TX USA. [Li, Helen K.] Thomas Jefferson Univ, Dept Ophthalmol, Philadelphia, PA 19107 USA. [Hubbard, Larry D.; Danis, Ronald P.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Florez-Arango, Jose F.] Univ Antioquia, Medellin, Colombia. [Esquivel, Adol] Houston Vet Affairs Med Ctr, Houston, TX USA. [Esquivel, Adol] Baylor Coll Med, Houston, TX 77030 USA. [Krupinski, Elizabeth A.] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. RP Li, HK (reprint author), 1400 Hermann Dr, Houston, TX 77004 USA. EM hlimed@mac.com OI Florez-Arango, Jose F/0000-0001-9083-0195 NR 25 TC 7 Z9 7 U1 0 U2 2 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 DEC PY 2010 VL 51 IS 12 BP 6753 EP 6761 DI 10.1167/iovs.10-5504 PG 9 WC Ophthalmology SC Ophthalmology GA 688GJ UT WOS:000284837500086 PM 20574011 ER PT J AU Rao, RC Tchedre, KT Malik, MTA Coleman, N Fang, YA Marquez, VE Chen, DF AF Rao, Rajesh C. Tchedre, Kissaou T. Malik, Muhammad Taimur A. Coleman, Natasha Fang, Yuan Marquez, Victor E. Chen, Dong Feng TI Dynamic Patterns of Histone Lysine Methylation in the Developing Retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID NEURAL STEM-CELLS; GANGLION-CELLS; METHYLTRANSFERASE G9A; EARLY EMBRYOGENESIS; AXON REGENERATION; GENE-EXPRESSION; NERVOUS-SYSTEM; PROTEIN EZH2; CANCER-CELLS; DIFFERENTIATION AB PURPOSE. Histone lysine methylation (HKM) is an important epigenetic mechanism that establishes cell-specific gene expression and functions in development. However, epigenetic control of retinal development is poorly understood. To study the roles of HKM in retinogenesis, the authors examined the dynamic changes of three HKM modifications and of two of their regulators, the histone methyltransferases (HMTases) Ezh2 and G9a, in the mouse retina. METHODS. Retinal sections and lysates from embryonic day 16 through adult were processed for immunohistochemistry and immunoblotting using antibodies against various marks and HMTases. To further analyze the biological functions of HKM, the effects of small molecule inhibitors of HMTases were examined in vitro. RESULTS. Methylation marks of trimethyl lysine 4 and 27 on histone H3 (H3K4me3 and H3K27me3) were detected primarily in differentiated retinal neurons in the embryonic and adult retina. In contrast, dimethyl lysine 9 on histone H3 (H3K9me2) was noted in early differentiating retinal ganglion cells but was lost after birth. The HMTases controlling H3K27me3, H3K9me2, Ezh2, and G9a were enriched in the inner embryonic retina during the period of active retinogenesis. Using the chemical inhibitors of Ezh2 and G9a, the authors reveal a role for HKM in regulating retinal neuron survival. CONCLUSIONS. HKM is a dynamic and spatiotemporally regulated process in the developing retina. Epigenetic regulation of gene transcription by Ezh2- and G9a-mediated HKM plays crucial roles in retinal neuron survival and may represent novel epigenetic targets to enhance viability in retinal neurodegenerative diseases such as glaucoma. (Invest Ophthalmol Vis Sci. 2010;51:6784-6792) DOI:10.1167/iovs.09-4730 C1 [Chen, Dong Feng] Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA 02114 USA. [Rao, Rajesh C.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Fang, Yuan] Fudan Univ, Eye & ENT Hosp, Shanghai 200433, Peoples R China. [Marquez, Victor E.] NCI, Med Chem Lab, NIH, Frederick, MD 21701 USA. RP Chen, DF (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, 20 Staniford St, Boston, MA 02114 USA. EM dongfeng.chen@schepens.harvard.edu OI Rao, Rajesh/0000-0002-5776-8366 FU National Institutes of Health (NIH)/National Eye Institute (NEI) [R01EY017641]; NIH/National Institute on Drug Abuse [R21DA024803]; Department of Defense [W81XWH-04-2-0008, W23RYX-9104-N603]; Department of Veterans Affairs [1I01RX000110-01]; American Health Foundation (DFC); NIH/National Cancer Institute Center for Cancer Research (VEM); NIH/NEI [P30EY003790] FX Supported by National Institutes of Health (NIH)/National Eye Institute (NEI)Grant R01EY017641, NIH/National Institute on Drug Abuse Grant R21DA024803, Department of Defense Grants W81XWH-04-2-0008 and W23RYX-9104-N603, Department of Veterans Affairs Grant 1I01RX000110-01, and the American Health Foundation (DFC); the Intramural Research Program of the NIH/National Cancer Institute Center for Cancer Research (VEM); NIH/NEI Grant P30EY003790; and a core grant to Schepens Eye Research Institute. NR 66 TC 15 Z9 20 U1 0 U2 2 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 DEC PY 2010 VL 51 IS 12 BP 6784 EP 6792 DI 10.1167/iovs.09-4730 PG 9 WC Ophthalmology SC Ophthalmology GA 688GJ UT WOS:000284837500090 PM 20671280 ER PT J AU Sheetz, MJ Davis, MD Aiello, LP Milton, RC Danis, RP Zhi, X Girach, A Jimenez, MC Vignati, L AF Sheetz, Matthew J. Davis, Matthew D. Aiello, Lloyd P. Milton, Roy C. Danis, Ronald P. Zhi, Xin Girach, Aniz Jimenez, Maria C. Vignati, Louis CA PKC-DRS2 Study Grp TI Author Response: Effect of Ruboxistaurin on the Visual Acuity Decline Associated with Long-standing Diabetic Macular Edema SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Letter C1 [Sheetz, Matthew J.; Zhi, Xin; Girach, Aniz; Jimenez, Maria C.; Vignati, Louis] Lilly Res Labs, Indianapolis, IN USA. [Davis, Matthew D.; Danis, Ronald P.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Aiello, Lloyd P.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02115 USA. [Aiello, Lloyd P.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Milton, Roy C.] EMMES Corp, Rockville, MD USA. RP Sheetz, MJ (reprint author), Lilly Res Labs, Indianapolis, IN USA. NR 2 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2010 VL 51 IS 12 BP 6890 EP 6891 DI 10.1167/iovs.09-4285 PG 2 WC Ophthalmology SC Ophthalmology GA 688GJ UT WOS:000284837500104 ER PT J AU Henrich, TJ Tsibris, AMN Lewine, NRP Konstantinidis, I Leopold, KE Sagar, M Kuritzkes, DR AF Henrich, Timothy J. Tsibris, Athe M. N. Lewine, Nicolas R. P. Konstantinidis, Ioannis Leopold, Kay E. Sagar, Manish Kuritzkes, Daniel R. TI Evolution of CCR5 Antagonist Resistance in an HIV-1 Subtype C Clinical Isolate SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE antiviral therapy; CCR5 antagonists; HIV-1; HIV-1 resistance; maraviroc; TAK-779; vicriviroc ID HUMAN-IMMUNODEFICIENCY-VIRUS; SMALL-MOLECULE; HIV-1-INFECTED PATIENTS; REVERSE-TRANSCRIPTASE; MONOCLONAL-ANTIBODY; ANTIVIRAL ACTIVITY; ENTRY INHIBITORS; TYPE-1 GP120; V3 REGION; VICRIVIROC AB Objectives: We previously reported vicriviroc (VCV) resistance in an HIV-infected subject and used deep sequencing and clonal analyses to track the evolution of V3 sequence forms over 28 weeks of therapy. Here, we test the contribution of gp120 mutations to CCR5 antagonist resistance and investigate why certain minority V3 variants emerged as the dominant species under drug pressure. Methods: Nineteen site-directed HIV-1 mutants were generated that contained gp120 VCV resistance mutations. Viral sensitivities to VCV, maraviroc, TAK-779, and HGS004 were determined. Results: Three patterns of susceptibilities were observed as follows: sigmoid inhibition curves with 50% inhibitory concentration similar to pretreatment virus [07J-week 0 (W0)], single mutants with decreased 50% inhibitory concentrations compared with 07J-W0, and mutants that contained >= 5 of 7 VCV resistance mutations with flattened inhibition curves and decreased or negative percent maximal inhibition. Substitutions such as S306P, which sensitized virus to CCR5 antagonists when present as single mutations, were not detected in the baseline virus population but were necessary for maximal resistance when incorporated into V3 backbones that included preexisting VCV resistance mutations. Conclusions: CCR5 antagonist resistance was reproduced only when a majority of V3 mutations were present. Minority V3 loop variants may serve as a scaffold upon which additional mutations lead to complete VCV resistance. C1 [Henrich, Timothy J.; Sagar, Manish; Kuritzkes, Daniel R.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Henrich, Timothy J.; Tsibris, Athe M. N.; Sagar, Manish; Kuritzkes, Daniel R.] Harvard Univ, Sch Med, Boston, MA USA. [Tsibris, Athe M. N.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Lewine, Nicolas R. P.; Konstantinidis, Ioannis; Leopold, Kay E.] Harvard Univ, Cambridge, MA 02138 USA. RP Kuritzkes, DR (reprint author), Brigham & Womens Hosp, Sect Retroviral Therapeut, 65 Landsdowne St,Room 435, Cambridge, MA 02139 USA. EM dkuritzkes@partners.org OI Sagar, Manish/0000-0001-9803-6594 FU National Research Service Award [(T32) AI07387-19]; National Institutes of Health [K08 AI081547, R37 AI553537, K24 RR016482]; Harvard University Center for AIDS Research [P30 AI060354] FX Supported by a National Research Service Award (T32) AI07387-19 (to T.J.H.), by National Institutes of Health grants K08 AI081547 (to A.M.N.T.), R37 AI553537, K24 RR016482 (to D.R.K.), and the Harvard University Center for AIDS Research (P30 AI060354). NR 42 TC 18 Z9 18 U1 0 U2 0 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 DEC 1 PY 2010 VL 55 IS 4 BP 420 EP 427 DI 10.1097/QAI.0b013e3181f25574 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 675RR UT WOS:000283849100005 PM 20856130 ER PT J AU Boulware, DR Meya, DB Bergemann, TL Williams, D Vlasova-St Louis, IA Rhein, J Staddon, J Kambugu, A Janoff, EN Bohjanen, PR AF Boulware, David R. Meya, David B. Bergemann, Tracy L. Williams, Darlisha Vlasova-St. Louis, Irina A. Rhein, Josh Staddon, Jack Kambugu, Andrew Janoff, Edward N. Bohjanen, Paul R. TI Antiretroviral Therapy Down-Regulates Innate Antiviral Response Genes in Patients With AIDS in Sub-Saharan Africa SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE adult; gene expression profiling/BL; HAART; HIV; AIDS; oligonucleotide array sequence analysis ID IMMUNODEFICIENCY-VIRUS TYPE-1; BLOOD MONONUCLEAR-CELLS; E3 UBIQUITIN LIGASE; HIV-1 INFECTION; LYMPHATIC TISSUE; PROTEIN ISG15; EXPRESSION; RNA; REPLICATION; TRIM5-ALPHA AB Objective: HIV pathogenesis is characterized by destructive imbalances between virus-mediated immune damage, antiviral immune responses, and immune activation. We characterized the effects of successful antiretroviral therapy (ART) to identify the breadth and patterns of HIV-associated gene expression. Methods: In a prospective observational, longitudinal cohort study of 10 ART-naive Ugandans with AIDS (median 30 CD4(+)/mL), we measured mRNA gene profiles in peripheral blood using Affymetrix U133_Plus2.0 microarrays at 0, 2, 4, 8, and 24 weeks after ART initiation. Results: We identified 160 mRNA transcripts that were consistently down-regulated and 48 that were up-regulated after ART at each point over 24 weeks based on linear regression modeling (adjusted P < 0.05), Of these 208 transcripts, approximately half represent heretofore unrecognized ART-responsive genes and one-third have no known function. The down-regulated genes with known function encoded mediators of innate antiviral responses, including antiviral restriction factors, pattern recognition receptors, and interferon response proteins, and mediators of immune activation, cellular proliferation, and apoptosis. Conclusions: By using ART to block the viral stimulus, we identified transcripts involved in innate antiviral immunity, including antiviral restriction factors and pattern recognition receptors, that were not previously known to be induced by HIV infection. C1 [Bohjanen, Paul R.] Univ Minnesota, Ctr Infect Dis & Microbiol Translat Res, McGuire Translat Res Facil, Minneapolis, MN 55455 USA. [Boulware, David R.; Williams, Darlisha; Rhein, Josh; Staddon, Jack; Bohjanen, Paul R.] Univ Minnesota, Dept Med, Div Infect Dis & Int Med, Minneapolis, MN 55455 USA. [Meya, David B.; Kambugu, Andrew] Makerere Univ, Infect Dis Inst, Kampala, Uganda. [Bergemann, Tracy L.] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. [Williams, Darlisha; Vlasova-St. Louis, Irina A.; Staddon, Jack; Bohjanen, Paul R.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA. [Janoff, Edward N.] Univ Colorado, Denver Sch Med, Denver Vet Affairs Med Ctr,Div Infect Dis, Mucosal & Vaccine Res Program Colorado MAVRC, Denver, CO 80202 USA. RP Bohjanen, PR (reprint author), Univ Minnesota, Ctr Infect Dis & Microbiol Translat Res, McGuire Translat Res Facil, Room 3-214,2001 6th St SE, Minneapolis, MN 55455 USA. EM bohja001@umn.edu RI Boulware, David/B-5516-2011; Boulware, David/I-4533-2013; Bohjanen, Paul/B-2329-2015; OI Bohjanen, Paul/0000-0002-2772-3597; Bergemann, Tracy/0000-0003-3902-2605; Meya, David/0000-0002-4138-240X; Boulware, David/0000-0002-4715-0060 FU University of Minnesota Center for Infectious Diseases and Microbiology Translational Research; Tibotec REACH Initiative; National Institutes of Health [R03AI078750 PRB, T32AI055433, L30AI066779, K23AI073192: DRB, R01HD059527 ENJ]; Accordia Global Health Foundation; Minnesota Medical Foundation; Gilead Infectious Disease Scholarship Program; Mucosal and Vaccine Research Program Colorado; Veterans Affairs Research Service FX Supported in part by the University of Minnesota Center for Infectious Diseases and Microbiology Translational Research (P.R.B.) and Academic Health Center (P.R.B., D.B.M.), Tibotec REACH Initiative (P.R.B., D.R.B., D.B.M., A.K.), National Institutes of Health (R03AI078750 PRB; T32AI055433; L30AI066779; K23AI073192: DRB; R01HD059527 ENJ), Accordia Global Health Foundation (A.K., D.B.M.), Minnesota Medical Foundation through its grants program and through the Robert and Mabel Bohjanen Immune Reconstitution Research Fund (P.R.B., D.R.B., D.B.M.), Gilead Infectious Disease Scholarship Program (D.B.M.), the Mucosal and Vaccine Research Program Colorado (E.N.J.) and the Veterans Affairs Research Service (E.N.J.). NR 61 TC 9 Z9 9 U1 0 U2 1 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 DEC 1 PY 2010 VL 55 IS 4 BP 428 EP 438 DI 10.1097/QAI.0b013e3181ef4963 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 675RR UT WOS:000283849100006 PM 20838227 ER PT J AU Lima, VD Bangsberg, DR Harrigan, PR Deeks, SG Yip, B Hogg, RS Montaner, JSG AF Lima, Viviane D. Bangsberg, David R. Harrigan, P. Richard Deeks, Steven G. Yip, Benita Hogg, Robert S. Montaner, Julio S. G. TI Risk of Viral Failure Declines With Duration of Suppression on Highly Active Antiretroviral Therapy Irrespective of Adherence Level SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE adherence; HAART; virologic failure; viral rebound; resistance; long-term suppression ID HIV-INFECTED PATIENTS; DRUG-RESISTANCE; IN-VIVO; ZIDOVUDINE; VIRUS; MONOTHERAPY; LAMIVUDINE; DYNAMICS; REGIMENS; CELLS AB Objective: To model the effect of adherence and duration of viral suppression on the risk of viral rebound. Methods: Viral rebound was defined as the first of at least two consecutive viral loads greater than 400 copies/mL after initial viral suppression. The main exposures were adherence, presence of antiretroviral class resistance before rebound or censoring date, and the percentage of follow-up time with viral suppression. Results: A total of 274 (N = 1305 [21%]) individuals experienced viral rebound. Median time of suppression before rebound was 2 years. Viral rebound was less likely to occur among those with longer duration of continuous viral suppression (odds ratio, 0.37; 95% confidence interval, 0.32 to 0.42). Among individuals with moderate levels of adherence (80% to less than 95%), the probability of virologic failure was 0.85 after being suppressed for 12 months and it was 0.08 after 72 months being suppressed (P < 0.01). Individuals with drug resistance were at a higher risk of viral rebound. Conclusions: The risk of viral rebound decreased with longer duration of viral suppression within each of adherence strata studied. Although perfect adherence remains an important goal of therapy to prevent disease progression, individuals with long-term viral suppression may be able to miss more doses without experiencing viral rebound. C1 [Lima, Viviane D.; Harrigan, P. Richard; Yip, Benita; Hogg, Robert S.; Montaner, Julio S. G.] St Pauls Hosp, BC Ctr Excellence HIV AIDS, Vancouver, BC V6Z 1Y6, Canada. [Lima, Viviane D.; Harrigan, P. Richard; Montaner, Julio S. G.] Univ British Columbia, Dept Med, Fac Med, Div AIDS, Vancouver, BC, Canada. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Initiat Global Hlth, Boston, MA USA. [Deeks, Steven G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hogg, Robert S.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. RP Lima, VD (reprint author), St Pauls Hosp, BC Ctr Excellence HIV AIDS, Room 608,1081 Burrard St, Vancouver, BC V6Z 1Y6, Canada. EM vlima@cfenet.ubc.ca RI Hogg, Robert/B-2783-2012; OI Hogg, Robert/0000-0003-3463-5488 FU Canadian Institutes of Health Research; Michael Smith Foundation for Health Research; NIAAA [K-24 015287]; Mark and Lisa Schwartz Family Foundation FX This work was supported by the Canadian Institutes of Health Research and Michael Smith Foundation for Health Research through Fellowship Awards to V.D.L. D.R.B. received support from NIAAA K-24 015287 and the Mark and Lisa Schwartz Family Foundation. NR 23 TC 72 Z9 72 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 1 PY 2010 VL 55 IS 4 BP 460 EP 465 DI 10.1097/QAI.0b013e3181f2ac87 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 675RR UT WOS:000283849100010 PM 20838225 ER PT J AU Hayes, JH Ollendorf, DA Pearson, SD Barry, MJ Kantoff, PW Stewart, ST Bhatnagar, V Sweeney, CJ Stahl, JE McMahon, PM AF Hayes, Julia H. Ollendorf, Daniel A. Pearson, Steven D. Barry, Michael J. Kantoff, Philip W. Stewart, Susan T. Bhatnagar, Vibha Sweeney, Christopher J. Stahl, James E. McMahon, Pamela M. TI Active Surveillance Compared With Initial Treatment for Men With Low-Risk Prostate Cancer A Decision Analysis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID EXTERNAL-BEAM RADIATION; QUALITY-OF-LIFE; RADICAL PROSTATECTOMY; PROTON RADIOTHERAPY; SECONDARY-CANCER; SCREENING TRIAL; HEALTH STATES; PATIENT AGE; THERAPY; MANAGEMENT AB Context In the United States, 192 000 men were diagnosed as having prostate cancer in 2009, the majority with low-risk, clinically localized disease. Treatment of these cancers is associated with substantial morbidity. Active surveillance is an alternative to initial treatment, but long-term outcomes and effect on quality of life have not been well characterized. Objective To examine the quality-of-life benefits and risks of active surveillance compared with initial treatment for men with low-risk, clinically localized prostate cancer. Design and Setting Decision analysis using a simulation model was performed: men were treated at diagnosis with brachytherapy, intensity-modulated radiation therapy (IMRT), or radical prostatectomy or followed up by active surveillance (a strategy of close monitoring of newly diagnosed patients with serial prostate-specific antigen measurements, digital rectal examinations, and biopsies, with treatment at disease progression or patient choice). Probabilities and utilities were derived from previous studies and literature review. In the base case, the relative risk of prostate cancer-specific death for initial treatment vs active surveillance was assumed to be 0.83. Men incurred short-and long-term adverse effects of treatment. Patients Hypothetical cohorts of 65-year-old men newly diagnosed as having clinically localized, low-risk prostate cancer (prostate-specific antigen level <10 ng/mL, stage <= T2a disease, and Gleason score <= 6). Main Outcome Measure Quality-adjusted life expectancy (QALE). Results Active surveillance was associated with the greatest QALE (11.07 quality-adjusted life-years [QALYs]), followed by brachytherapy (10.57 QALYs), IMRT (10.51 QALYs), and radical prostatectomy (10.23 QALYs). Active surveillance remained associated with the highest QALE even if the relative risk of prostate cancer-specific death for initial treatment vs active surveillance was as low as 0.6. However, the QALE gains and the optimal strategy were highly dependent on individual preferences for living under active surveillance and for having been treated. Conclusions Under a wide range of assumptions, for a 65-year-old man, active surveillance is a reasonable approach to low-risk prostate cancer based on QALE compared with initial treatment. However, individual preferences play a central role in the decision whether to treat or to pursue active surveillance. JAMA. 2010;304(21):2373-2380 www.jama.com C1 [Hayes, Julia H.; Kantoff, Philip W.; Sweeney, Christopher J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Hayes, Julia H.; Stahl, James E.; McMahon, Pamela M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02115 USA. [Ollendorf, Daniel A.; Pearson, Steven D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Clin & Econ Review, Boston, MA 02115 USA. [Barry, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02115 USA. [Stewart, Susan T.] Harvard Univ, Interfac Program Hlth Syst Improvement, Cambridge, MA 02138 USA. [Stewart, Susan T.] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Bhatnagar, Vibha] Vet Affairs San Diego Hlth Care Syst, Ctr Patient Oriented Care, Hlth Serv Res & Dev, San Diego, CA USA. [Bhatnagar, Vibha] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. RP Hayes, JH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dana 1230,44 Binney St, Boston, MA 02115 USA. EM julia_hayes@dfci.harvard.edu FU Foundation for Informed Medical Decision Making; National Cancer Institute at the National Institutes of Health [R25 CA92203-08]; Department of Defense [W81XWH-09-1-0512]; Prostate Cancer Foundation; Blue Shield of California Foundation FX Dr Barry receives salary support as president of the Foundation for Informed Medical Decision Making, a not-for-profit private foundation. The foundation develops content for patient education programs, including a program on prostate cancer treatment. The foundation has an arrangement with a for-profit company, Health Dialog, to coproduce these programs. The programs are used as part of the decision support and disease management services Health Dialog provides to consumers through health care organizations and employers.; This work was supported in part by grant R25 CA92203-08 from the National Cancer Institute at the National Institutes of Health, by grant W81XWH-09-1-0512 from the Department of Defense, by a Young Investigators Award to Dr Hayes from the Prostate Cancer Foundation, and in part by funding to the Institute for Clinical and Economic Review from the Blue Shield of California Foundation. NR 62 TC 131 Z9 136 U1 1 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 1 PY 2010 VL 304 IS 21 BP 2373 EP 2380 DI 10.1001/jama.2010.1720 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 687FH UT WOS:000284763900018 PM 21119084 ER PT J AU Pitman, RK AF Pitman, Roger K. TI A Recent VA Rules Change and the Traumatic Event Requirement in PTSD SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Pitman, Roger K.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pitman, Roger K.] Harvard Univ, Sch Med, Boston, MA USA. RP Pitman, RK (reprint author), MGH E, Massachusetts Gen Hosp, 120 2nd Ave, Charlestown, MA 02129 USA. EM roger_pitman@hms.harvard.edu NR 8 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 1 PY 2010 VL 304 IS 21 BP 2409 EP 2410 DI 10.1001/jama.2010.1739 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 687FH UT WOS:000284763900024 PM 21119089 ER PT J AU Gupta, SR Suhler, EB Rosenbaum, JT AF Gupta, Seema R. Suhler, Eric B. Rosenbaum, James T. TI Intravenous Methylprednisolone Can Cause an Acute, Vision-Threatening Rise in Intraocular Pressure SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article ID PULSE THERAPY; ARTHRITIS; GLAUCOMA; UVEITIS; DISEASE C1 [Gupta, Seema R.; Suhler, Eric B.; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Casey Eye Inst, Portland, OR 97201 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med & Cell Biol, Portland, OR 97201 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. RP Gupta, SR (reprint author), 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM seema_r_gupta@yahoo.com FU Research to Prevent Blindness to Casey Eye Institute; Stan and Madelle Rosenfeld Family Trust; William and Mary Bauman Foundation; William C. Kuzell Foundation; Department of Veterans Affairs FX Funding for this study was received from unrestricted grant from the Research to Prevent Blindness to Casey Eye Institute, Stan and Madelle Rosenfeld Family Trust, William and Mary Bauman Foundation, William C. Kuzell Foundation, and the Department of Veterans Affairs. NR 11 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD DEC PY 2010 VL 16 IS 8 BP 397 EP 398 DI 10.1097/RHU.0b013e3181ffdd4f PG 2 WC Rheumatology SC Rheumatology GA 688CQ UT WOS:000284827800011 PM 21085011 ER PT J AU Chang, L El-Dairi, MA Frempong, TA Burner, EL Bhatti, MT Young, TL Leigh, F AF Chang, Lan El-Dairi, Mays A. Frempong, Tamiesha A. Burner, Erica L. Bhatti, M. Tariq Young, Terri L. Leigh, Fawn TI Optical coherence tomography in the evaluation of neurofibromatosis type-1 subjects with optic pathway gliomas SO JOURNAL OF AAPOS LA English DT Article ID VISUAL-EVOKED POTENTIALS; NATURAL-HISTORY; CHILDREN; TUMORS; NERVE; REPRODUCIBILITY; THICKNESS; DIAGNOSIS; EYES AB PURPOSE Neurofibromatosis type 1 (NF1) is the most common neurocutaneous disorder, with an approximate incidence of 1 in 3,500. Optic pathway gliomas (OPGs) develop in 15% of individuals with NF1, commonly in childhood. OPGs are difficult to detect via a clinical inspection in children, often requiring magnetic resonance imaging (MRI). Given the significant visual risks associated with OPGs in NF1, there is a need for improved noninvasive techniques to diagnose OPGs in children; therefore, we studied optical coherence tomography (OCT) as a potential tool to assess optic nerve and retinal nerve fiber layer (RNFL) abnormalities. This prospective study was designed to evaluate OCT detection of RNFL loss from optic atrophy attributable to OPGs in a cohort of pediatric patients with NF1. METHODS With the use of Stratus OCT, directed testing with the Fast Macular Thickness and Fast RNFL Thickness protocol scans were performed on 9 subjects with NF1 and known OPGs, 6 subjects with NF1 without OPGs, and 15 controls. RESULTS NF1 subjects with OPGs had thinner Was and macula when compared with age-matched controls and to NF1 subjects without OPGs. After applying the equivalence equation, the average RNFL thickness and macular volume in NF1 subjects without OPGs was equivalent to controls. CONCLUSIONS Our study suggests that OCT can be used to detect RNFL thinning secondary to OPGs in NF1 subjects. This objective tool shows promise as a useful adjunct to routine clinical ophthalmologic evaluation in children with NF1. (J AAPOS 2010;14:511-517) C1 [Chang, Lan; El-Dairi, Mays A.; Frempong, Tamiesha A.; Burner, Erica L.; Bhatti, M. Tariq; Young, Terri L.] Duke Eye Ctr, Durham, NC USA. [Frempong, Tamiesha A.] Mt Sinai Hosp, Dept Ophthalmol, New York, NY 10029 USA. [Bhatti, M. Tariq; Young, Terri L.; Leigh, Fawn] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. [Young, Terri L.; Leigh, Fawn] Duke Univ, Sch Med, Dept Pediat, Durham, NC 27706 USA. [Leigh, Fawn] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Leigh, F (reprint author), Neurofibromatosis Program, 185 Cambridge St,Floor 5,Room 5248, Boston, MA 02114 USA. EM fleigh@partners.org NR 32 TC 32 Z9 32 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-8531 J9 J AAPOS JI J. AAPOS PD DEC PY 2010 VL 14 IS 6 BP 511 EP 517 DI 10.1016/j.jaapos.2010.08.014 PG 7 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 699OY UT WOS:000285673900011 PM 21168074 ER PT J AU Kim, JW AF Kim, Joon Woo TI Aspiration of Fentanyl Patch SO JOURNAL OF ADDICTION MEDICINE LA English DT Editorial Material ID ABUSE C1 [Kim, Joon Woo] James J Peters VA Med Ctr, Bronx, NY USA. RP Kim, JW (reprint author), 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM joon.kim3@va.gov NR 11 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-0620 J9 J ADDICT MED JI J. Addict. Med. PD DEC PY 2010 VL 4 IS 4 BP 244 EP 245 DI 10.1097/ADM.0b013e3181c1df64 PG 2 WC Substance Abuse SC Substance Abuse GA 683RD UT WOS:000284492000010 PM 21769044 ER PT J AU Correa, R Akiskal, H Gilmer, W Nierenberg, AA Trivedi, M Zisook, S AF Correa, R. Akiskal, H. Gilmer, W. Nierenberg, A. A. Trivedi, M. Zisook, S. TI Is unrecognized bipolar disorder a frequent contributor to apparent treatment resistant depression? SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Review DE Treatment resistant depression (TRD); Bipolar disorder (BD); Antidepressants (AD); Major depressive disorder (MDD) ID MONOAMINE-OXIDASE INHIBITORS; STAR-ASTERISK-D; DOUBLE-BLIND; MAJOR DEPRESSION; ANTIDEPRESSANT TREATMENT; MOOD STABILIZERS; PRIVATE-PRACTICE; II-DISORDER; SWITCH; MANIA AB Background: There is widespread clinical belief that unrecognized bipolar disorder (BD) is a frequent contributor to apparent treatment resistant depression (TRD). This review attempts to assess the degree to which prevailing empirical data supports that view. Methods: All English-language articles published between January 1998 and January 2008 that focused on adults with major depressive disorder (MDD) and BD bearing on the question "Is unrecognized BD a frequent contributor to apparent TRD in patients initially diagnosed with MDD?" were reviewed. Results: 196 articles were reviewed; the preponderance of the data suggested: 1) TRD populations demonstrate high rates of hidden bipolar disorder, 2) there is not sufficient evidence to unequivocally support or reject the hypothesis that patients who relapse despite continued antidepressant treatment are likely to have bipolar spectrum disorder, 3) patients initially diagnosed with MDD do not demonstrate high rates of switching to mania or hypomania when treated with antidepressants and 4) in patients diagnosed with BD, antidepressants are not robustly effective and are poorly tolerated. Limitations: The main limitation of this review is that none of the individual studies were designed to test our primary hypothesis. Conclusions: This review provides at least moderate support to the hypothesis that BD is a contributor to apparent TRD. Thus, clinicians treating MDD are urged to search for "soft" signs of bipolarity and to be prepared to alter diagnosis and treatment strategies accordingly. Published by Elsevier B.V. C1 [Correa, R.; Akiskal, H.; Zisook, S.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Akiskal, H.; Zisook, S.] San Diego VA Healthcare Serv, San Diego, CA USA. [Gilmer, W.] Northwestern Univ, Feinberg Sch Med, Evanston, IL 60208 USA. [Nierenberg, A. A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bipolar Clin, Cambridge, MA 02138 USA. [Nierenberg, A. A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Res Program, Cambridge, MA 02138 USA. [Trivedi, M.] Univ Texas SW Emd Ctr Dallas, Dallas, TX USA. RP Zisook, S (reprint author), VA Med Ctr, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM szisook@ucsd.edu FU Chilean Ministry of Planning (MIDEPLAN) FX Dr Rodrigo Correa was supported by a Presidential Award from the Chilean Ministry of Planning (MIDEPLAN). When the work was completed, Dr Correa was a Visiting Scholar at the University of California, San Diego. His current affiliation of R. Correa: Universidad Mayor, Santiago, Chile. NR 59 TC 40 Z9 40 U1 2 U2 4 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 DEC PY 2010 VL 127 IS 1-3 BP 10 EP 18 DI 10.1016/j.jad.2010.06.036 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 692AJ UT WOS:000285123600002 PM 20655113 ER PT J AU Federman, AD Penrod, JD Livote, E Hebert, P Keyhani, S Doucette, J Siu, AL AF Federman, Alex D. Penrod, Joan D. Livote, Elayne Hebert, Paul Keyhani, Salomeh Doucette, John Siu, Albert L. TI Development of and Recovery From Difficulty With Activities of Daily Living: An Analysis of National Data SO JOURNAL OF AGING AND HEALTH LA English DT Article DE aging; activities of daily living; physical impairment; incident disability; recovery; antipsychotic medications ID SYSTEM-ACTIVE MEDICATIONS; DISABLED OLDER PERSONS; COGNITIVE IMPAIRMENT; MOBILITY DISABILITY; COMMUNITY; WOMEN; RISK; POPULATIONS; ASSOCIATION; DECLINE AB Background: National-level data are needed on predictors of mild physical impairment among older adults to assist policy makers with resource allocation. Method: We analyzed data on adults above age 64 from the Medicare Current Beneficiary Survey (MCBS) with no activity of daily living (ADL) difficulties at baseline (n = 14,226). Five ADLs were measured annually and recovery was defined as regaining complete ADL function at follow-up. Results: The strongest correlates of ADL difficulty were use of antipsychotic medications (adjusted odds ratio [AOR] = 1.93, 95% confidence interval [CI] = 1.44 to 2.58), instrumental ADL difficulty (AOR = 1.90, 95% CI = 1.74 to 2.07), and fair-poor general health (AOR = 1.59, 95% CI = 1.42 to 1.78). Only the number of incident ADL difficulties was associated with recovery (AOR = 0.02, 95% CI = 0.01 to 0.02). Conclusion: Identifying factors associated with development of mild physical impairment could help direct patients toward preventive care programs to preempt decline in physical function. C1 [Federman, Alex D.] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY 10029 USA. [Penrod, Joan D.; Livote, Elayne; Keyhani, Salomeh; Siu, Albert L.] Bronx Vet Affairs Med Ctr, Bronx, NY USA. [Hebert, Paul] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 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 NIA NIH HHS [1K23AG028955-01, K24 AG00918] NR 28 TC 6 Z9 6 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 J9 J AGING HEALTH JI J. Aging Health PD DEC PY 2010 VL 22 IS 8 BP 1081 EP 1098 DI 10.1177/0898264310375986 PG 18 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA 674GM UT WOS:000283724700002 PM 20660637 ER PT J AU Boyce, JA Assa'ad, A Burks, AW Jones, SM Sampson, HA Wood, RA Plaut, M Cooper, SF Fenton, MJ Arshad, SH Bahna, SL Beck, LA Byrd-Bredbenner, C Camargo, CA Eichenfield, L Furuta, GT Hanifin, JM Jones, C Kraft, M Levy, BD Lieberman, P Luccioli, S McCall, KM Schneider, LC Simon, RA Simons, FER Teach, SJ Yawn, BP Schwaninger, JM AF Boyce, Joshua A. Assa'ad, Amal Burks, A. Wesley Jones, Stacie M. Sampson, Hugh A. Wood, Robert A. Plaut, Marshall Cooper, Susan F. Fenton, Matthew J. Arshad, S. Hasan Bahna, Sami L. Beck, Lisa A. Byrd-Bredbenner, Carol Camargo, Carlos A., Jr. Eichenfield, Lawrence Furuta, Glenn T. Hanifin, Jon M. Jones, Carol Kraft, Monica Levy, Bruce D. Lieberman, Phil Luccioli, Stefano McCall, Kathleen M. Schneider, Lynda C. Simon, Ronald A. Simons, F. Estelle R. Teach, Stephen J. Yawn, Barbara P. Schwaninger, Julie M. TI Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article C1 [Plaut, Marshall; Cooper, Susan F.; Fenton, Matthew J.; Schwaninger, Julie M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Boyce, Joshua A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy,Dept Med, Boston, MA 02115 USA. [Assa'ad, Amal] Univ Cincinnati, Div Allergy & Immunol, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Burks, A. Wesley] Duke Univ, Med Ctr, Dept Pediat, Div Allergy & Immunol, Durham, NC 27710 USA. [Jones, Stacie M.] Univ Arkansas Med Sci, Div Allergy & Immunol, Dept Pediat, Arkansas Childrens Hosp, Little Rock, AR 72205 USA. [Sampson, Hugh A.] Mt Sinai Sch Med, Elliot & Roslyn Jaffe Food Allergy Inst, Div Allergy & Immunol, Dept Pediat, New York, NY USA. [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD USA. [Arshad, S. Hasan] Univ Southampton, Sch Med, Southampton, Hants, England. [Arshad, S. Hasan] St Marys Hosp, David Hide Asthma & Allergy Res Ctr, Newport, Wight, England. [Arshad, S. Hasan] Southampton Univ Hosp NHS Trust, Southampton, Hants, England. [Bahna, Sami L.] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, Allergy & Immunol Sect, Shreveport, LA 71105 USA. [Beck, Lisa A.] Univ Rochester, Dept Dermatol, Med Ctr, Rochester, NY 14627 USA. [Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Dept Med, Div Rheumatol Allergy & Immunol,Massachusetts Gen, Boston, MA USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Eichenfield, Lawrence] Rady Childrens Hosp, Div Pediat & Adolescent Dermatol, San Diego, CA USA. [Furuta, Glenn T.] Childrens Hosp Denver, Sect Pediat Gastroenterol Hepatol & Nutr, Digest Hlth Inst, Aurora, CO USA. [Furuta, Glenn T.] Univ Colorado, Dept Pediat, Denver Sch Med, Aurora, CO USA. [Furuta, Glenn T.] Natl Jewish Hlth, Dept Pediat, Denver, CO USA. [Hanifin, Jon M.] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA. [Jones, Carol] Allergy & Asthma Network Mothers Asthmat, Mclean, VA USA. [Kraft, Monica] Duke Univ, Med Ctr, Dept Med, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. [Levy, Bruce D.] Brigham & Womens Hosp, Partners Asthma Ctr, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Levy, Bruce D.] Harvard Univ, Sch Med, Boston, MA USA. [Lieberman, Phil] Univ Tennessee, Dept Med, Div Allergy & Immunol, Coll Med, Memphis, TN 38104 USA. [Luccioli, Stefano] US FDA, Off Food Addit Safety, College Pk, MD USA. [McCall, Kathleen M.] Childrens Hosp Orange Cty, Orange, CA USA. [Schneider, Lynda C.] Childrens Hosp Boston, Div Immunol, Boston, MA USA. [Simon, Ronald A.] Scripps Clin, Div Allergy Asthma & Immunol, San Diego, CA USA. [Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Pediat, Winnipeg, MB, Canada. [Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Child Hlth & Immunol, Winnipeg, MB, Canada. [Teach, Stephen J.] Childrens Natl Med Ctr, Div Emergency Med, Washington, DC 20010 USA. [Yawn, Barbara P.] Olmsted Med Ctr, Dept Res, Rochester, MN USA. [Yawn, Barbara P.] Univ Minnesota, Sch Med, Dept Family & Community Hlth, Minneapolis, MN 55455 USA. RP Fenton, MJ (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 6610 Rockledge Dr,Room 3105, Bethesda, MD 20892 USA. EM fentonm@niaid.nih.gov RI Byrd-Bredbenner, Carol/F-8064-2015 OI Byrd-Bredbenner, Carol/0000-0002-8010-3987 FU National Institutes of Health; GlaxoSmithKline; Food Allergy and Anaphylaxis Network, Gerber, Mead Johnson; Dyax Corp; Food Allergy and Anaphylaxis Network, Mead Johnson; National Peanut Board; Food Allergy Initiative; National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine); Phadia AB; Genentech; National Institutes of Health (National Institute of Allergy and Infectious Diseases); National Institute of Health Research, UK; American Academy of Allergy, Asthma, and Immunology; National Eczema Association; US Department of Agriculture; Canned Food Alliance; New Jersey Department of Health and Senior Services; Dey; Novartis; Astellas; Ferndale; Johnson Johnson; Sinclair; Stiefel; Therapeutics Inc.; American Gastrointestinal Association; ALZA; Astellas Pharma US, Inc; Asubio Pharmaceuticals, Inc; Centocor, Inc; Corgentech; Nucryst Pharmaceuticals; Seattle Genetics; Shionogi USA; Merck; Sepracor; Dey Laboratories; Schering-Plough; AstraZenica; TEVA; Pfizer; MEDA; Alcon; Intelliject; US Food and Drug Administration; AllerGen; Canadian Allergy; Asthma and Immunology Foundation/Anaphylaxis Canada; Canadian Institutes of Health Research; AstraZeneca Foundation; Aventis; Child Health Center Board; CNMC Research Advisory Council; National Association of Chain Drug Stores Foundation; National Institutes of Health (National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute); Novartis/Genentech; Robert Woods Johnson Foundation; US Centers for Disease Control and Prevention; US Public Health Service; Washington, DC, Department of Health FX J. A. Boyce has served on the Advisory Board of GlaxoSmithKline. He has served as a consultant and/or speaker for Altana, GlaxoSmithKline, and Merck. He has received funding/grant support from the National Institutes of Health.; A. Assa'ad holds, or is listed as an inventor on, US patent application #10/566903, entitled "Genetic markers of food allergy." She has served as a consultant for GlaxoSmithKline and as a speaker for the American College of Allergy, Asthma, and Immunology, the North East Allergy Society, the Virginia Allergy Society, the New England Allergy Society, and the American Academy of Pediatrics. Dr Assa'ad has received funding/grant support from GlaxoSmithKline.; A. W. Burks holds, or is listed as an inventor on, multiple US patents related to food allergy. He owns stock in Allertein and MastCell, Inc, and is a minority stockholder in Dannon Co Probiotics. He has served as a consultant for ActoGeniX NV, McNeil Nutritionals, Mead Johnson, and Novartis. He has served on the speaker's bureau for EpiPen/Dey, LP, and has served on the data monitoring committee for Genentech. He has served on an expert panel for Nutricia. Dr Burks has received funding/grant support from the Food Allergy and Anaphylaxis Network, Gerber, Mead Johnson, and the National Institutes of Health.; S. M. Jones has served as a speaker and grant reviewer and has served on the medical advisory committee for the Food Allergy and Anaphylaxis Network. She has received funding/grant support from Dyax Corp, the Food Allergy and Anaphylaxis Network, Mead Johnson, the National Peanut Board, and the National Institutes of Health.; H. A. Sampson holds, or is listed as an inventor on, multiple US patents related to food allergy. He owns stock in Allertein Therapeutics. He is the immediate past president of the American Academy of Allergy, Asthma, and Immunology. He has served as a consultant for Allertein Therapeutics, the American Academy of Allergy, Asthma, and Immunology, the Food Allergy Initiative, and Schering Plough. He has received funding/grant support for research projects from the Food Allergy Initiative, the National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine), and Phadia AB. He is a co-owner of Herbal Spring, LLC.; R. A. Wood has served as a speaker/advisory board member for GlaxoSmithKline, Merck, and Dey. He has received funding/grant support from Genentech and the National Institutes of Health (National Institute of Allergy and Infectious Diseases).; S. H. Arshad has received funding/grant support from the National Institutes of Health and the National Institute of Health Research, UK.; S. L. Bahna has received funding/grant support from Genentech.; L. A. Beck has received funding/grant support from the American Academy of Allergy, Asthma, and Immunology, the National Eczema Association, and the National Institutes of Health.; C. Byrd-Bredbenner owns stock in Johnson & Johnson. She has received funding/grant support from the US Department of Agriculture, the Canned Food Alliance, and the New Jersey Department of Health and Senior Services.; C. A. Camargo Jr has consulted for Dey and Novartis. He has received funding/grant support from a variety of government agencies and not-for-profit research foundations, as well as Dey and Novartis.; L. Eichenfield has received funding/grant support from a variety of not-for-profit foundations, as well as Astellas, Ferndale, Johnson & Johnson, Novartis, Sinclair, Stiefel, and Therapeutics Inc.; G. T. Furuta has served as a consultant and/or speaker to Ception Therapeutics and TAP. He has received funding/grant support from the American Gastrointestinal Association and the National Institutes of Health.; J. M. Hanifin has served as served as a consultant for ALZA, Anesiva, Inc, Barrier Therapeutics, Inc, Milliken & Company, Nordic Biotech, Novartis Pharmaceuticals Corporation, Shionogi USA, Taisho Pharmaceutical R&D, Inc, Teikoku Pharma USA, Inc, UCB, York Pharma, ZARS, Inc, and ZymoGenetics. He has served as an investigator or received research funding from ALZA, Astellas Pharma US, Inc, Asubio Pharmaceuticals, Inc, Centocor, Inc, Corgentech, Novartis, Nucryst Pharmaceuticals, Seattle Genetics, and Shionogi USA.; M. Kraft has served as a consultant and/or speaker for Astra-Zeneca, Genentech, GlaxoSmithKline, Merck, Novartis, and Sepracor. She has received funding/grant support from Genentech, GlaxoSmithKline, the National Institutes of Health and Novartis.; B. D. Levy holds, or is listed as an inventor on, US patent applications #20080064746 entitled "Lipoxins and aspirin-triggered lipoxins and their stable analogs in the treatment of asthma and inflammatory airway diseases" and #20080096961 entitled "Use of docosatrienes, resolvins and their stable analogs in the treatment of airway diseases and asthma." He owns stock in Resolvyx Pharmaceuticals. He has served as a consultant for Bayer Healthcare and Resolvyx Pharmaceuticals. Dr Levy has received funding/grant support from the National Institutes of Health.; P. Lieberman has served as a consultant and/or speaker to Dey Laboratories, Novartis, Schering-Plough, AstraZenica, Merck, TEVA, Pfizer, MEDA, Alcon, Genentech, Intelliject, and the Food Allergy and Anaphylaxis Network. He is past president of the American Academy of Allergy, Asthma, and Immunology.; L. C. Schneider has served as a consultant/clinical advisor for the Food Allergy Initiative. She has received funding/grant support from a variety of not-for-profit research foundations, as well as Novartis and the National Institutes of Health.; R. A. Simon has served as a speaker for Dey Laboratories, Genentech, GlaxoSmithKline, Merck, Novartis, and the US Food and Drug Administration.; F. E. R. Simons holds a patent on "Fast-disintegrating epinephrine tablets for sublingual administration." She is a past-president of the American Academy of Allergy, Asthma, and Immunology and of the Canadian Society of Allergy and Clinical Immunology. She is a member of the advisory boards of Dey, Intelliject, and ALK-Abello. She has received funding/grant support from AllerGen, the Canadian Allergy, Asthma and Immunology Foundation/Anaphylaxis Canada, and the Canadian Institutes of Health Research.; S. J. Teach has served as a speaker for AstraZeneca. He has received funding/grant support from the AstraZeneca Foundation, Aventis, the Child Health Center Board, the CNMC Research Advisory Council, the National Association of Chain Drug Stores Foundation, the National Institutes of Health (National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute), Novartis/Genentech, the Robert Woods Johnson Foundation, the US Centers for Disease Control and Prevention, the US Public Health Service, and the Washington, DC, Department of Health. NR 1 TC 399 Z9 409 U1 11 U2 36 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2010 VL 126 IS 6 BP 1105 EP 1118 DI 10.1016/j.jaci.2010.10.008 PG 14 WC Allergy; Immunology SC Allergy; Immunology GA 689RZ UT WOS:000284947800005 PM 21134568 ER PT J AU Ananworanich, J Apornpong, T Kosalaraksa, P Jaimulwong, T Hansudewechakul, R Pancharoen, C Bunupuradah, T Chandara, M Puthanakit, T Ngampiyasakul, C Wongsawat, J Kanjanavanit, S Luesomboon, W Klangsinsirikul, P Ngo-Giang-Huong, N Kerr, SJ Ubolyam, S Mengthaisong, T Gelman, RS Pattanapanyasat, K Saphonn, V Ruxrungtham, K Shearer, WT AF Ananworanich, Jintanat Apornpong, Tanakorn Kosalaraksa, Pope Jaimulwong, Tanyathip Hansudewechakul, Rawiwan Pancharoen, Chitsanu Bunupuradah, Torsak Chandara, Mom Puthanakit, Thanyawee Ngampiyasakul, Chaiwat Wongsawat, Jurai Kanjanavanit, Suparat Luesomboon, Wicharn Klangsinsirikul, Phennapha Ngo-Giang-Huong, Nicole Kerr, Stephen J. Ubolyam, Sasiwimol Mengthaisong, Tawan Gelman, Rebecca S. Pattanapanyasat, Kovit Saphonn, Vonthanak Ruxrungtham, Kiat Shearer, William T. CA PREDICT Study Grp TI Characteristics of lymphocyte subsets in HIV-infected, long-term nonprogressor, and healthy Asian children through 12 years of age SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE HIV; children; lymphocyte; monocyte; phenotyping; long-term nonprogressors; antiretroviral therapy; Asia; disease progression; pediatric AIDS ID ACTIVE ANTIRETROVIRAL THERAPY; CD4(+) T-CELLS; HIV-1-INFECTED CHILDREN; UNINFECTED CHILDREN; PREDICTORS; MARKERS; IMMUNODEFICIENCY; ACTIVATION; HAART; REPLICATION AB Background: There are limited data on the immune profiles of HIV-positive children compared with healthy controls, and no such data for Asian children. Objectives: To immunophenotype HIV-positive Asian children, including long-term nonprogressors (LTNPs), compared with age-matched healthy controls. Methods: We used flow cytometry to analyze 13 lymphocyte and monocyte subsets from 222 untreated, HIV-positive children with 15% to 24% CD4(+) T cells and no AIDS-related illnesses and 142 healthy children (controls). Data were compared among age categories. Profiles from LTNPs (n = 50), defined as children >= 8 years old with CD4(+) T-cell counts >= 350 cells/mm(3), were compared with data from age-matched non-LTNPs (n = 17) and controls (n = 53). Results: Compared with controls, HIV-positive children had lower values (cell count per mm(3) and percent distribution) for T(H) cells and higher values for cytotoxic T cells, with reductions in populations of naive T(H) and cytotoxic T cells, B cells, and natural killer (NK) cells. HIV-positive children had high values for activated T(H) and cytotoxic T cells. Compared with non-LTNPs, LTNPs had higher values of T(H) and cytotoxic T cells, naive and memory T-cell subsets, and B and NK cells. Surprisingly, counts of activated T(H) and cytotoxic T cells were also higher among LTNPs. LNTPs were more frequently male. Conclusion: Untreated, HIV-infected Asian children have immune profiles that differ from those of controls, characterized by low values for T(H) cells, naive T cells, B cells, and NK cells but high values for cytotoxic, activated T(H), and cytotoxic T cells. The higher values for activated T cells observed in LTNPs require confirmation in longitudinal studies. (J Allergy Clin Immunol 2010;126:1294-301.) C1 [Ananworanich, Jintanat; Apornpong, Tanakorn; Jaimulwong, Tanyathip; Bunupuradah, Torsak; Puthanakit, Thanyawee; Kerr, Stephen J.; Ubolyam, Sasiwimol; Mengthaisong, Tawan; Ruxrungtham, Kiat] HIV Netherlands Australia Thailand Res Collaborat, Thai Red Cross AIDS Res Ctr, Bangkok, Thailand. [Ananworanich, Jintanat] SE Asia Res Collaborat Hawaii, Bangkok, Thailand. [Ananworanich, Jintanat; Pancharoen, Chitsanu; Puthanakit, Thanyawee; Ruxrungtham, Kiat] Chulalongkorn Univ, Fac Med, Bangkok 10330, Thailand. [Kosalaraksa, Pope] Khon Kaen Univ, Khon Kaen, Thailand. [Hansudewechakul, Rawiwan] Chiangrai Prachanukroh Hosp, Chiang Rai, Thailand. [Chandara, Mom; Saphonn, Vonthanak] Natl Inst Publ Hlth, Phnom Penh, Cambodia. [Ngampiyasakul, Chaiwat] Prapokklao Hosp, Chanthaburi, Thailand. [Wongsawat, Jurai] Bamrasnaradura Infect Dis Inst, Nonthaburi, Thailand. [Kanjanavanit, Suparat] Nakornping Hosp, Chiang Mai, Thailand. [Luesomboon, Wicharn] Queen Savang Vadhana Mem Hosp, Chon Buri, Thailand. [Klangsinsirikul, Phennapha] Chiang Mai Univ, Fac Associated Med Sci, Chiang Mai, Thailand. [Ngo-Giang-Huong, Nicole] IRD U174 Program HIV Prevent & Treatment, Chiang Mai, Thailand. [Kerr, Stephen J.] Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. [Gelman, Rebecca S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gelman, Rebecca S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pattanapanyasat, Kovit] Mahidol Univ, Fac Med, Siriraj Hosp, Bangkok 10700, Thailand. [Saphonn, Vonthanak] Natl Ctr HIV AIDS Dermatol & STDs, Phnom Penh, Cambodia. [Shearer, William T.] Baylor Coll Med, Houston, TX 77030 USA. RP Ananworanich, J (reprint author), HIV NAT, Thai Red Cross AIDS Res Ctr, 104 Rajdumri Rd, Bangkok 10330, Thailand. EM jintanat.a@hivnat.org RI Kerr, Stephen/J-6126-2012; OI Kerr, Stephen/0000-0002-1919-4525 FU National Institute of Allergy and Infectious Diseases [U19 AI053741, 1R01AI075408-0]; Clinical trial.gov [NCT00234091]; Thai Research Council; Division of AIDS, National Institute of Allergy and Infectious Disease, NIH FX The PREDICT study was sponsored by the National Institute of Allergy and Infectious Diseases, grant no. U19 AI053741, Clinical trial.gov identification number NCT00234091. The lymphocyte subset study in HIV-positive children was sponsored by the National Institute of Allergy and Infectious Disease, grant no. 1R01AI075408-0. The Thai Research Council sponsored the study in healthy children. K.P. is a Thailand Research Fund-Senior Research Scholar. Antiretroviral therapy for PREDICT was provided by GlaxoSmithKline, Boehringer Ingelheim, Merck, Abbott, and Roche.; K. Ruxrungtham has received research support from the Division of AIDS, National Institute of Allergy and Infectious Disease, NIH. The rest of the authors have declared that they have no conflict of interest. NR 34 TC 10 Z9 10 U1 0 U2 3 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 DEC PY 2010 VL 126 IS 6 BP 1294 EP U352 DI 10.1016/j.jaci.2010.09.038 PG 18 WC Allergy; Immunology SC Allergy; Immunology GA 689RZ UT WOS:000284947800030 PM 21134574 ER PT J AU Kunisawa, T Nagashima, M Suzuki, A Takahata, O Iwasaki, H AF Kunisawa, Takayuki Nagashima, Michio Suzuki, Akihiro Takahata, Osamu Iwasaki, Hiroshi TI Accidental injection of remifentanil can cause a much more dangerous situation than the same dose of fentanyl SO JOURNAL OF ANESTHESIA LA English DT Letter ID PHARMACOKINETICS C1 [Kunisawa, Takayuki; Suzuki, Akihiro; Takahata, Osamu; Iwasaki, Hiroshi] Asahikawa Med Coll, Dept Anesthesiol & Crit Care Med, Asahikawa, Hokkaido 0788510, Japan. [Kunisawa, Takayuki] Asahikawa Med Coll Hosp, Surg Operat Dept, Asahikawa, Hokkaido, Japan. [Nagashima, Michio] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Nagashima, Michio] Harvard Univ, Sch Med, Boston, MA USA. RP Kunisawa, T (reprint author), Asahikawa Med Coll, Dept Anesthesiol & Crit Care Med, 2-1-1-1 Midorigaoka Higashi, Asahikawa, Hokkaido 0788510, Japan. EM taka.kunisawa@nifty.ne.jp NR 4 TC 2 Z9 2 U1 0 U2 0 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 DEC PY 2010 VL 24 IS 6 BP 970 EP 971 DI 10.1007/s00540-010-1008-0 PG 2 WC Anesthesiology SC Anesthesiology GA 692LD UT WOS:000285153400030 PM 20721610 ER PT J AU Siev, J Huppert, JD Chambless, DL AF Siev, Jedidiah Huppert, Jonathan D. Chambless, Dianne L. TI Obsessive-compulsive disorder is associated with less of a distinction between specific acts of omission and commission SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Obsessive-compulsive disorder; Omission bias; Cognitions; Thought-action fusion; Responsibility; Moral reasoning ID ANXIETY STRESS SCALES; PSYCHOMETRIC PROPERTIES; NONCLINICAL SAMPLE; OCI-R; VALIDATION; BELIEFS; VERSION; BIAS AB Individuals with obsessive-compulsive disorder (OCD) seem to judge harm caused actively and passively as morally equivalent. In contrast, people generally choose harm by omission over harm by commission, a propensity known as omission bias. Two studies examined the hypothesis that OCD is associated with less omission bias. In Study 1, with a student population, symptoms of OCD and related cognitions were negatively associated with omission bias about washing and checking scenarios targeting common OCD fears. In contrast, neither symptoms nor cognitions related to OCD were associated with general omission bias. In Study 2, individuals with self-reported OCD evinced less omission bias about washing and checking scenarios than did individuals without OCD. Again, general omission bias was not related to OCD. These results support the idea that individuals with elevated OCD symptoms distinguish less than others between acts of omission and commission for harm relevant to general OCD concerns. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Siev, Jedidiah] Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Siev, Jedidiah; Chambless, Dianne L.] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. [Huppert, Jonathan D.] Hebrew Univ Jerusalem, Dept Psychol, IL-93509 Jerusalem, Israel. RP Siev, J (reprint author), Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Sch Med, 185 Cambridge St,2nd Floor, Boston, MA 02114 USA. EM jsiev@partners.org; huppertj@mscc.huji.ac.il; chambless@psych.upenn.edu RI Chambless, Dianne/A-1065-2007; OI Huppert, Jonathan/0000-0002-0537-4701 NR 23 TC 4 Z9 4 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD DEC PY 2010 VL 24 IS 8 BP 893 EP 899 DI 10.1016/j.janxdis.2010.06.013 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 672YP UT WOS:000283624300012 PM 20637565 ER PT J AU Lovas, DA Barsky, AJ AF Lovas, David A. Barsky, Arthur J. TI Mindfulness-based cognitive therapy for hypochondriasis, or severe health anxiety: A pilot study SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Hypochondriasis; Health; Anxiety; Cognitive therapy; Mindfulness ID RANDOMIZED CONTROLLED-TRIAL; SOMATOSENSORY AMPLIFICATION; BEHAVIOR THERAPY; VALIDATION; DEPRESSION; MEDITATION; RUMINATION; INVENTORY; VALIDITY; SCALE AB In spite of the existence of evidence-based treatments for hypochondriasis, or severe health anxiety, recovery rates are low and morbidity is high. Therefore, more treatment options are needed for this prevalent condition. Mindfulness-based cognitive therapy (MBCT) interventions have been gaining research and clinical attention for the treatment of mood, and more recently anxiety disorders. A small, uncontrolled pilot study of an 8-week group MBCT intervention for hypochondriasis was conducted. Ten subjects (five females and five males) with a mean age of 35.6 (range = 25-59) recruited from an academic community health network met criteria and completed the study. There were significant improvements in measures of health anxiety, disease-related thoughts, somatic symptoms, and mindfulness at the end of treatment, and these benefits were sustained at 3-month follow-up. Participants evidenced high treatment satisfaction, with no drop-outs or adverse events. These findings provide the basis for a larger, more rigorous, controlled trial of this promising treatment approach. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Lovas, David A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Lovas, David A.; Barsky, Arthur J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Lovas, David A.] Cambridge Hlth Alliance, Cambridge, MA USA. RP Lovas, DA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM dlovas@partners.org NR 33 TC 30 Z9 30 U1 4 U2 31 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD DEC PY 2010 VL 24 IS 8 BP 931 EP 935 DI 10.1016/j.janxdis.2010.06.019 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 672YP UT WOS:000283624300018 PM 20650601 ER PT J AU Beal, MD Marchie, A Black, E Malchau, H Burke, D AF Beal, Matthew D. Marchie, Anthony Black, Eric Malchau, Henrik Burke, Dennis TI Treatment of a Well-Fixed Modular Fully Porous Coated Stem After Fracture Using a Custom Rescue Sleeve SO JOURNAL OF ARTHROPLASTY LA English DT Article DE stem fracture; full coat; extended trochanteric osteotomy; modular stem ID TOTAL HIP-ARTHROPLASTY; REVISION; COMPONENT AB We report a novel technique for the treatment of a fractured fully porous-coated modular stem The fracture of the stem occurred at the taper of the stem body junction In both cases the stem was well-fixed distally making the reconstruction difficult Previously authors have reported the use of an extended trochanteric osteotomy or multiple cortical windows for removal of this type of prosthesis The technique we describe uses a custom-made rescue sleeve that takes advantage of the distal ingrowth The rescue sleeve is fitted onto the existing stem obviating the need for an extended trochanteric osteotomy The rescue sleeve s geometry makes up for the loss in height and accepts the modular body components to give the surgeon the length options to optimize stability C1 [Beal, Matthew D.; Marchie, Anthony; Black, Eric; Malchau, Henrik; Burke, Dennis] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Malchau, Henrik] Harris Orthopaed Biomat & Biomech Lab, Boston, MA USA. RP Beal, MD (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Bldg 3B,55 Fruit St, Boston, MA 02114 USA. NR 9 TC 1 Z9 1 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD DEC PY 2010 VL 25 IS 8 BP 1301 EP 1303 DI 10.1016/j.arth.2010.05.024 PG 3 WC Orthopedics SC Orthopedics GA 687BT UT WOS:000284749500020 PM 20634037 ER PT J AU Hintermann, E Bayer, M Pfeilschifter, JM Luster, AD Christen, U AF Hintermann, Edith Bayer, Monika Pfeilschifter, Josef M. Luster, Andrew D. Christen, Urs TI CXCL10 promotes liver fibrosis by prevention of NK cell mediated hepatic stellate cell inactivation SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE Hepatic fibrosis; Inflammation; Cellular trafficking; Hepatitis; Chemokine ID INTERFERON-INDUCIBLE PROTEIN-10; PRIMARY BILIARY-CIRRHOSIS; ISLET-SPECIFIC EXPRESSION; CHEMOKINE RECEPTOR CXCR3; VIRUS-INFECTION; CONCANAVALIN-A; T-LYMPHOCYTES; IP-10; INJURY; GAMMA AB Chemokines such as CXCL10 promote hepatic inflammation in chronic or acute liver injury through recruitment of leukocytes to the liver parenchyma The CXCL10 receptor CXCR3 which is expressed on a subset of leukocytes plays an important part in Th1-dependent inflammatory responses Here we investigated the role of CXCL10 in chemically induced liver fibrosis We used carbon tetrachloride (CCI(4)) to trigger chronic liver damage in wildtype C57BL/6 and CXCL10-deficient mice Fibrosis severity was assessed by Sinus Red staining and intrahepatic leukocyte subsets were investigated by immunohistochemistry We have further analyzed hepatic stellate cell (HSC) distribution and activation and investigated the effect of CXCL10 on HSC motility and proliferation In order to demonstrate a possible therapeutic intervention strategy we have examined the anti-fibrotic potential of a neutralizing anti-CXCL10 antibody Upon CCI(4) administration CXCL10-deficient mice showed massively reduced liver fibrosis when compared to wildtype mice CXCL10-deficient mice had less B- and T lymphocyte and dendritic cell infiltrations within the liver and the number and activity of HSCs was reduced In contrast natural killer (NK) cells were more abundant in CXCL10-deficient mice and granzyme B expression was increased in areas with high numbers of NK cells Further detailed analysis revealed that HSCs express CXCR3 respond to CXCL10 and secrete CXCL10 when stimulated with IFN-gamma Blockade of CXCL10 with a neutralizing antibody exhibited a significant anti-fibrotic effect Our data suggest that CXCL10 is a pro-fibrotic factor which participates in a crosstalk between hepatocytes HSCs and Immune cells NK cells seem to play an important role in controlling HSC activity and fibrosis CXCL10 blockade may constitute a possible therapeutic intervention for hepatic fibrosis (c) 2010 Elsevier Ltd All rights reserved C1 [Hintermann, Edith; Bayer, Monika; Pfeilschifter, Josef M.; Christen, Urs] Goethe Univ Frankfurt, Pharmazentrum Frankfurt ZAFES, Frankfurt, Germany. [Luster, Andrew D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. RP Christen, U (reprint author), Klinikum Johann Wolfgang Goethe Univ, Pharmazentrum Frankfurt, Theodor Stern Kai 7, D-60590 Frankfurt, Germany. RI Christen, Urs/A-7338-2009 FU NIH [R21 DK071577, R01-CA069212]; German Research Foundation FX This work is supported by NIH grant R21 DK071577 and a grant of the German Research Foundation to U C and NIH grant R01-CA069212 to A D L. NR 59 TC 44 Z9 45 U1 2 U2 8 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD DEC PY 2010 VL 35 IS 4 BP 424 EP 435 DI 10.1016/j.jaut.2010.09.003 PG 12 WC Immunology SC Immunology GA 684RT UT WOS:000284567700017 PM 20932719 ER PT J AU Alberti-Segui, C Arndt, A Cugini, C Priyadarshini, R Davey, ME AF Alberti-Segui, Christine Arndt, Annette Cugini, Carla Priyadarshini, Richa Davey, Mary E. TI HU Protein Affects Transcription of Surface Polysaccharide Synthesis Genes in Porphyromonas gingivalis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID 6 CAPSULAR SEROTYPES; ESCHERICHIA-COLI; BIOFILM FORMATION; PERIODONTAL-DISEASE; BACILLUS-SUBTILIS; CRUCIFORM DNA; BACTERIA; VIRULENCE; LACKING; EXPRESSION AB K-antigen capsule synthesis is an important virulence determinant of the oral anaerobe Porphyromonas gingivalis. We previously reported that the locus required for synthesis of this surface polysaccharide in strain W83 (TIGR identification PG0106 to PG0120) is transcribed as a large (similar to 16.7-kb) polycistronic message. Through sequence analysis, we have now identified a 77-bp inverted repeat located upstream (206 bp) of the start codon of PG0106 that is capable of forming a large hairpin structure. Further sequence analysis just upstream and downstream of the capsule synthesis genes revealed the presence of two genes oriented in the same direction as the operon that are predicted to encode DNA binding proteins: PG0104, which is highly similar (57%) to DNA topoisomerase III, and PG0121, which has high similarity (72%) to DNA binding protein HU (beta-subunit). In this report, we show that these two genes, as well as the 77-bp inverted repeat region, are cotranscribed with the capsule synthesis genes, resulting in a large transcript that is similar to 19.4 kb (based on annotation). We also show that a PG0121 recombinant protein is a nonspecific DNA binding protein with strong affinity to the hairpin structure, in vitro, and that transcript levels of the capsule synthesis genes are downregulated in a PG0121 deletion mutant. Furthermore, we show that this decrease in transcript levels corresponds to a decrease in the amount of polysaccharide produced. Interestingly, expression analysis of another polysaccharide synthesis locus (PG1136 to PG1143) encoding genes involved in synthesis of a surface-associated phosphorylated branched mannan (APS) indicated that this locus is also downregulated in the PG0121 mutant. Altogether our data indicate that HU protein modulates expression of surface polysaccharides in P. gingivalis strain W83. C1 [Alberti-Segui, Christine; Arndt, Annette; Cugini, Carla; Priyadarshini, Richa; Davey, Mary E.] Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. [Davey, Mary E.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Davey, ME (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. EM mdavey@forsyth.org FU NIDCR [R21DE17168, R01DE1019117] FX This research was supported by grants R21DE17168 and R01DE1019117 (NIDCR) awarded to M.E.D. NR 58 TC 10 Z9 10 U1 1 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 DEC PY 2010 VL 192 IS 23 BP 6217 EP 6229 DI 10.1128/JB.00106-10 PG 13 WC Microbiology SC Microbiology GA 677LQ UT WOS:000283994300013 PM 20889748 ER PT J AU Bottonari, KA Safren, SA McQuaid, JR Hsiao, CB Roberts, JE AF Bottonari, Kathryn A. Safren, Steven A. McQuaid, John R. Hsiao, Chiu-Bin Roberts, John E. TI A longitudinal investigation of the impact of life stress on HIV treatment adherence SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE HIV/AIDS; Antiretrovirals; Treatment adherence; Depression; Life stress; Coping ID ACTIVE ANTIRETROVIRAL THERAPY; NEUROPSYCHIATRIC INTERVIEW MINI; SELF-REPORTED DISTRESS; MEDICATION ADHERENCE; PERCEIVED STRESS; SOCIAL SUPPORT; DSM-IV; DEPRESSIVE-DISORDERS; INFECTED INDIVIDUALS; POSITIVE PERSONS AB Suboptimal antiretroviral adherence is associated with poorer HIV outcomes. Psychosocial factors, including life stress, depression and coping, may influence adherence behavior. This prospective investigation sought to examine the impact of life stress (acute life events, chronic stress, and perceived stress), depression, and coping style on adherence to HIV treatment regimes over time. Participants were 87 treatment-seeking HIV-infected individuals recruited from an urban HIV clinic. They completed clinician-administered interviews and self-report questionnaires at baseline and 3-month follow-up. Acute life events and chronic stress prospectively predicted decreases in treatment adherence more strongly among individuals in a major depressive episode (n = 21) compared to non-depressed individuals (n = 66). Coping style did not appear to be the mechanism by which life stress influenced adherence among depressed HIV-infected individuals. These findings demonstrate that life stress has toxic effects for depressed individuals and suggest that treatment adherence interventions with depressed individuals could be enhanced via development of stress management skills. C1 [Bottonari, Kathryn A.] Charlie Norwood VA Med Ctr, Augusta, GA 30904 USA. [Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [McQuaid, John R.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Hsiao, Chiu-Bin] SUNY Buffalo, Dept Med, Buffalo, NY 14260 USA. [Roberts, John E.] SUNY Buffalo, Dept Psychol, Buffalo, NY 14260 USA. RP Bottonari, KA (reprint author), Charlie Norwood VA Med Ctr, 1 Freedom Way 261, Augusta, GA 30904 USA. EM Kathryn.Bottonari@va.gov FU NIMH NIH HHS [F31 MH072551, F31MH072551] NR 55 TC 15 Z9 16 U1 0 U2 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD DEC PY 2010 VL 33 IS 6 BP 486 EP 495 DI 10.1007/s10865-010-9273-9 PG 10 WC Psychology, Clinical SC Psychology GA 676WA UT WOS:000283948200007 PM 20577794 ER PT J AU Tokhtaeva, E Sachs, G Vagin, O AF Tokhtaeva, Elmira Sachs, George Vagin, Olga TI Diverse Pathways for Maturation of the Na,K-ATPase beta(1) and beta(2) Subunits in the Endoplasmic Reticulum of Madin-Darby Canine Kidney Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NA+-K+-ATPASE; ACTIVATED ADENOSINE-TRIPHOSPHATASE; UNFOLDED PROTEIN RESPONSE; N-GLYCOSYLATION SITES; XENOPUS-OOCYTES; QUALITY-CONTROL; INTRACELLULAR-TRANSPORT; FUNCTIONAL EXPRESSION; MOLECULAR-WEIGHT; ALPHA-SUBUNITS AB Proper folding of the Na,K-ATPase beta subunits followed by assembly with the alpha subunits is necessary for their export from the endoplasmic reticulum (ER). Here we examine roles of the ER lectin chaperone, calnexin, and non-lectin chaperone, BiP, in folding and quality control of the beta(1) and beta(2) subunits in Madin-Darby canine kidney cells. Short term prevention of glycan-calnexin interactions by castanospermine slightly increases ER retention of beta(1), suggesting minor involvement of calnexin in subunit folding. However, both prolonged incubation with castanospermine and removal of N-glycosylation sites do not affect the alpha(1)-assembly or trafficking of beta(1) but increase the amount of the beta(1)-bound BiP, showing that BiP can compensate for calnexin in assisting beta(1) folding. In contrast to beta(1), prevention of either N-glycosylation or glycan-calnexin interactions abolishes the alpha(1)-assembly and export of beta(2) from the ER despite increased beta(2)-BiP binding. Mutations in the alpha(1)-interacting regions of beta(1) and beta(2) subunits impair alpha(1) assembly but do not affect folding of the beta subunits tested by their sensitivity to trypsin. At the same time, these mutations increase the amount of beta-bound BiP but not of beta-bound calnexin and increase ER retention of both beta-isoforms. BiP, therefore, prevents the ER export of folded but alpha(1)-unassembled beta subunits. These alpha(1)-unassembled beta subunits are degraded faster than alpha(1)-bound beta subunits, preventing ER overload. In conclusion, folding of the beta(1) and beta(2) subunits is assisted predominantly by BiP and calnexin, respectively. Folded beta(1) and beta(2) either assemble with alpha(1) or bind BiP. The alpha(1)-bound beta subunits traffic to the Golgi, whereas BiP-bound beta subunits are retained and degraded in the ER. C1 Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. RP Vagin, O (reprint author), 11301 Wilshire Blvd,VAGLAHS W LA,Bldg 113,Rm 324, Los Angeles, CA 90073 USA. EM olgav@ucla.edu FU National Institutes of Health [DK077149, DK058333] FX This work was supported, in whole or in part, by National Institutes of Health Grants DK077149 and DK058333. NR 64 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC PY 2010 VL 285 IS 50 BP 39289 EP 39302 DI 10.1074/jbc.M110.172858 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 689PT UT WOS:000284941300057 PM 20937802 ER PT J AU Muratoglu, OK Wannomae, KK Rowell, SL Micheli, BR Malchau, H AF Muratoglu, Orhun K. Wannomae, Keith K. Rowell, Shannon L. Micheli, Brad R. Malchau, Henrik TI Ex Vivo Stability Loss of Irradiated and Melted Ultra-High Molecular Weight Polyethylene SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID CROSS-LINKED POLYETHYLENE; TOTAL HIP-ARTHROPLASTY; IN-VIVO; ACETABULAR COMPONENTS; CLINICAL-PERFORMANCE; GAMMA-STERILIZATION; FREE-RADICALS; UHMWPE; OXIDATION; WEAR AB Background Radiation crosslinking reduces wear of ultra-high molecular weight polyethylene (UHMWPE), and subsequent annealing or melting increases oxidative stability Little is known about the oxidative stability of polyethylene total joint components after in vivo service and subsequent shelf storage in air Methods We analyzed thirty-four surgically retrieved, radiation crosslinked acetabular liners to determine their oxidative stability after in vivo service (range, 0 5 to 84 0 months) Oxidation was determined at the time of explantation After shelf storage in air (range, 7 0 to 72 0 months), oxidation, crosslink density, and thermal properties were determined Oxidation of one control liner that was shelf-aged in air (for eighty four months) was also determined Results At the time of explantation, all components showed minimal oxidation, however, oxidation levels increased during shelf storage, with a concomitant decrease in crosslink density and increase in crystallinity Increasing oxidation, increasing crystallinity, and decreasing crosslink density correlated with the duration of ex vivo storage The shelf-aged control liner showed no detectable oxidation Conclusions The oxidation and loss of crosslink density of the irradiated and melted UHMWPE was surprising Two potential mechanisms that might alter the oxidative stability of UHMWPE in vivo are cyclic loading and absorption of lipids Both of these mechanisms can generate new free radicals in UHMWPE and can initiate and propagate its oxidation Clinical Relevance It is not known if the ex vivo instability reported here will occur in vivo in the long term and, therefore, further investigation of surgical explants is warranted C1 [Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, 55 Fruit St,GRJ-1206, Boston, MA 02114 USA. FU Zimmer, Inc FX In support of their research for or preparation of this work, one or more of the authors received in any one year, outside funding or grants in excess of $10,000 from Zimmer, Inc In addition, one or more of the authors or a member of his or her immediate family received, in any one year, payments or other benefits in excess of $10,000 or a commitment or agreement to provide such benefits from a commercial entity (Zimmer, Inc) NR 22 TC 38 Z9 38 U1 0 U2 5 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD DEC 1 PY 2010 VL 92A IS 17 BP 2809 EP 2816 DI 10.2106/JBJS.I.01017 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 691YK UT WOS:000285118500006 PM 21123611 ER PT J AU Chiao, EY Nambi, PV Naik, AD AF Chiao, Elizabeth Y. Nambi, Preethi V. Naik, Aanand D. TI The impact of diabetes process and outcome quality measures on overall survival in patients with co-morbid colorectal cancer SO JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE LA English DT Article DE Colorectal cancer; Diabetes mellitus; Survival; Quality of care; Outcomes ID COLON-CANCER; MELLITUS AB Purpose To evaluate the effect of prevalent diabetes mellitus (DM) and quality of diabetes process and outcome measures on overall survival in colorectal cancer (CRC) patients. Patient and Methods We conducted a retrospective cohort study among patients newly diagnosed with CRC. Kaplan-Meier analyses and Cox proportional hazard regression models were performed. Quality of diabetes process and outcomes measures in the year prior to CRC diagnosis were compared with those in the year after CRC diagnosis. Results Four hundred and seventy CRC patients were identified during the study period, including 122 (26%) patients with DM. Survival between diabetic and non-diabetic were not significantly different after stratifying by stage. In a multivariable model, only age (HR 1.04), stage 2 and 3 (HR 1.88), stage 4 (HR 4.26), and Deyo comorbidity score (HR 1.14) were significantly associated with increased risk of death. Overall, patients in this CRC cohort with DM had good to excellent diabetes quality of care in the year prior to diagnosis as evidenced by primary care and eye clinic visits, number of times diabetes intermediate outcomes were measured, and level of cholesterol (95.5 +/- 29.74) and hemoglobin A1c (7.2%+1.4) control. After CRC diagnosis, there was no significant change in these quality of care indices compared to the year prior. Conclusions Prevalent DM did not affect overall survival in this cohort of VA patients diagnosed with CRC. The quality of diabetes care prior to CRC diagnosis, which persisted after diagnosis, may have moderated the mortality effect of diabetes in this CRC cohort. C1 [Chiao, Elizabeth Y.] Michael E DeBakey VA Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. [Chiao, Elizabeth Y.; Nambi, Preethi V.; Naik, Aanand D.] Michael E DeBakey VA Med Ctr, Houston Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Chiao, Elizabeth Y.; Nambi, Preethi V.; Naik, Aanand D.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Chiao, EY (reprint author), Michael E DeBakey VA Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM echiao@bcm.edu FU Houston VA HSR&D Center of Excellence at the Michael E. DeBakey VA Medical Center [HFP90-020]; Baylor College of Medicine; National Cancer Institute [K23CA124318]; National Institute on Aging [5K23AG027144]; Doris Duke Charitable Foundation FX This work was supported in part by the Houston VA HSR&D Center of Excellence (HFP90-020) at the Michael E. DeBakey VA Medical Center and a pilot grant from the Dan L. Duncan Cancer Center-Prevention and Population Sciences Program at the Baylor College of Medicine. Dr. Chiao is also supported by a National Cancer Institute K23 grant (K23CA124318). Dr. Naik is also supported by a National Institute on Aging K23 grant (5K23AG027144) and a Doris Duke Charitable Foundation Clinical Scientist Development Award. No funding agencies had a role in the design and conduct of the study, analysis and interpretation of data, or preparation and approval of the manuscript. The views expressed herein are those of the authors and do not necessarily reflect those of the Department of Veterans Affairs or Baylor College of Medicine. NR 22 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1932-2259 J9 J CANCER SURVIV JI J. Cancer Surviv.-Res. Pract. PD DEC PY 2010 VL 4 IS 4 BP 381 EP 387 DI 10.1007/s11764-010-0141-y PG 7 WC Oncology; Social Sciences, Biomedical SC Oncology; Biomedical Social Sciences GA 788UB UT WOS:000292468800010 PM 20721633 ER PT J AU Monaco, F Landoni, G Biselli, C De Luca, M Frau, G Bignami, E Januzzi, JL Zangrillo, A AF Monaco, Fabrizio Landoni, Giovanni Biselli, Camilla De Luca, Monica Frau, Giovanna Bignami, Elena Januzzi, James L., Jr. Zangrillo, Alberto TI Predictors of Cardiac Troponin Release After Mitral Valve Surgery SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE anesthesia; cardiopulmonary bypass; myocardial injury; mitral valve ID BYPASS GRAFT-SURGERY; MYOCARDIAL-INFARCTION; EUROPEAN-SOCIETY; SHORT-TERM; MORTALITY; METAANALYSIS; COMMITTEE; INJURY; HEART; RISK AB Objectives: Although cardiac troponin I (cTnI) measurement is used extensively as a marker of perioperative myocardial injury, limited knowledge exists in noncoronary artery bypass graft surgery. Design: Observational study. Setting: Single-center intensive care unit. Intervention: None. Participants: One hundred eighty-five consecutive adult patients undergoing mitral valve surgery for predominant mitral regurgitation were enrolled and underwent measurement of cTnI at 24 hours after surgery. Measurements and Main Results: CTnI release after mitral valve surgery was significantly associated with an adverse outcome. The optimal cTnI value for predicting adverse outcomes was 14 ng/mL. Univariate preoperative predictors of cTnI release were prior use of diuretics (p = 0.04) or a rheumatic (p = 0.006), ischemic (p = 0.004), or myxomatous (p = 0.005) etiology to mitral disease, whereas intraoperative variables predictive of cTnI release were cross-clamp time (p = 0.005), cardiopulmonary bypass time (p < 0.001), need for mitral valve replacement (p = 0.024), number of electrical cardioversions (p = 0.03), patent foramen ovale closure (p = 0.03), tricuspid valve repair (p = 0.04), need for epinephrine/norepinephrine (p = 0.004) or intra-aortic balloon pump (p = 0.03) in the operating room; and, finally, the surgeon who performed the surgery (p = 0.014). There were no postoperative predictors of excessive cTnI release. In multivariate analysis, the only predictors of cTnI release were the cardiopulmonary bypass time (odds ratio, 1.42; confidence intervals, 1.019-1.064; p = 0.001) and the infusion of epinephrine/norepinephrine in the operating room (odds ratio, 4.002; confidence intervals, 1.238-12.929; p = 0.02). Conclusions: After mitral surgery, the need for epinephrine/norepinephrine perioperatively and the cardiopulmonary bypass time independently predict a cTnI release significantly related to an adverse outcome. (C) 2010 Elsevier Inc. All rights reserved. C1 [Monaco, Fabrizio; Landoni, Giovanni; Biselli, Camilla; De Luca, Monica; Frau, Giovanna; Bignami, Elena; Zangrillo, Alberto] Univ Vita Salute San Raffaele, Dept Anesthesia & Intens Care, I-20132 Milan, Italy. [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Landoni, G (reprint author), Univ Vita Salute San Raffaele, Dept Anesthesia & Intens Care, Via Olgettina 60, I-20132 Milan, Italy. EM Landoni.giovanni@hsr.it OI LANDONI, Giovanni/0000-0002-8594-5980 NR 24 TC 6 Z9 7 U1 2 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 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD DEC PY 2010 VL 24 IS 6 BP 931 EP 938 DI 10.1053/j.jvca.2010.06.029 PG 8 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 691YD UT WOS:000285117800005 PM 20832335 ER PT J AU Ficke, DJ Lee, J Chaney, MA Bas, H Vidal-Melo, MF Stone, ME AF Ficke, David J. Lee, Justin Chaney, Mark A. Bas, Heidi Vidal-Melo, Marcos F. Stone, Marc E. TI CASE 6-2010 Noncardiac Surgery in Patients With a Left Ventricular Assist Device SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE left ventricular assist devices; noncardiac surgery; mechanical assist devices ID INHALED NITRIC-OXIDE; END-ORGAN FUNCTION; CONTINUOUS-FLOW; HEART-FAILURE; SUPPORT; PULSATILE; THERAPY; IMPLANTATION; PROSTACYCLIN; MANAGEMENT C1 [Ficke, David J.; Lee, Justin; Chaney, Mark A.] Univ Chicago, Med Ctr, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA. [Bas, Heidi; Vidal-Melo, Marcos F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Stone, Marc E.] Mt Sinai Sch Med, New York, NY USA. RP Chaney, MA (reprint author), Univ Chicago, Med Ctr, Dept Anesthesia & Crit Care, 5841 S Maryland Ave,MC 4028, Chicago, IL 60637 USA. EM mchaney@dacc.uchicago.edu NR 31 TC 8 Z9 8 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 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD DEC PY 2010 VL 24 IS 6 BP 1002 EP 1009 DI 10.1053/j.jvca.2010.09.005 PG 8 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 691YD UT WOS:000285117800018 PM 21109156 ER PT J AU Kabra, R Heist, EK Barrett, CD Donaldson, D Blendea, D Beinart, R Koruth, J Singh, S Ruskin, J Mansour, M AF Kabra, Rajesh Heist, E. Kevin Barrett, Conor D. Donaldson, David Blendea, Dan Beinart, Roy Koruth, Jacob Singh, Sheldon Ruskin, Jeremy Mansour, Moussa TI Incidence and Electrophysiologic Properties of Dissociated Pulmonary Vein Activity Following Pulmonary Vein Isolation During Catheter Ablation of Atrial Fibrillation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; ablation; electrophysiology; pulmonary vein ID INITIATION; SUBSTRATE AB Methods and Results: This single center prospective study sought to assess the dissociated activity in the PVs following their isolation during AF ablation. In 100 consecutive patients (60 paroxysmal, 40 persistent) undergoing AF ablation, dissociated PV activity was recorded using a multielectrode mapping catheter following antral PV isolation. The dissociated PV activity was classified as (1) silent, (2) isolated ectopic beats, (3) ectopic rhythm, and (4) PV fibrillation. All the PVs were successfully isolated in all the patients. In 91 of 100 patients, there was dissociated activity in at least 1 isolated ipsilateral PV group. There was no significant difference in spontaneous PV activity between patients with paroxysmal and persistent AF (91.7% vs 90%, P = 1.0). Among the 200 isolated ipsilateral PV groups, 64 of 200 (32%) were silent, 86 of 200 (43%) demonstrated isolated ectopic beats, 41 of 200 (20.5%) had ectopic rhythms and 9 of 200 (4.5%) had PV fibrillation. The average cycle length of the PV ectopic rhythm was 2594 +/- 966 ms (range 1193-4750 ms). Conclusions: Following PV isolation, a majority of patients demonstrate dissociated activity in at least 1 PV. This finding was evident in patients with both paroxysmal and persistent AF. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1338-1343, December 2010). C1 [Mansour, Moussa] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Electrophysiol Lab,Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. RP Mansour, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Electrophysiol Lab,Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org FU Deane Institute for Integrative Research in Stroke and Atrial Fibrillation; Biosense Webster; St. Jude Medical; Boston Scientific; Medtronic; Biotronik FX This work was possible because of a grant from the Deane Institute for Integrative Research in Stroke and Atrial Fibrillation.; Dr. Mansour has received research grants from Biosense Webster and St. Jude Medical. Dr. Heist has received research grants from Boston Scientific, Medtronic, St. Jude Medical, and Biotronik and is a consultant to St. Jude Medical. Dr. Ruskin reports collaboration on research grants supported by Biosense Webster and St. Jude Medical; he serves as consultant to or on the advisory boards of sanofi-aventis, Biosense Webster, Medtronic, Pfizer, Astellas, and Sequel. Other authors: No disclosures. NR 16 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD DEC PY 2010 VL 21 IS 12 BP 1338 EP 1343 DI 10.1111/j.1540-8167.2010.01832.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 691ER UT WOS:000285063600008 PM 20586827 ER PT J AU Beinart, R Perna, F Danik, S Barrett, CD Heist, EK Ruskin, J Mansour, M AF Beinart, Roy Perna, Francesco Danik, Stephan Barrett, Conor D. Heist, E. Kevin Ruskin, Jeremy Mansour, Moussa TI Initial Experience With a Multielectrode Catheter Equipped With the Single-Axis Sensor Technology for High-Density Electroanatomical Mapping in a Swine Model SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE high-density mapping; electroanatomical mapping; activation mapping; multielectrode catheter; anatomical reconstruction; atrium; premature beats ID RIGHT-VENTRICULAR CARDIOMYOPATHY/DYSPLASIA; OUTFLOW TRACT TACHYCARDIA; FOCAL ATRIAL TACHYCARDIA; RADIOFREQUENCY ABLATION; ENDOMYOCARDIAL BIOPSY; FIBRILLATION; SUBSTRATE; ACCURACY; ARRHYTHMIAS; NAVIGATION AB Methods and Results: Anatomical reconstruction of cardiac chambers and the aorta, together with activation mapping of the right atrium during both sinus rhythm and pacing-induced premature atrial contractions (PACs), were performed in 5 swine using both a conventional mapping catheter and the novel multielectrode catheter equipped with SAS. The multielectrode mapping provided a detailed definition of cardiac anatomy while requiring shorter acquisition times. In addition, mapping of PACs origin was significantly faster using the multielectrode catheter. Conclusion: The novel multielectrode catheter equipped with the SAS technology can be used in combination with magnetic electroanatomical mapping systems to generate high-density anatomical reconstructions and activation maps. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1403-1407, December 2010). C1 [Mansour, Moussa] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Ctr Heart, Boston, MA 02114 USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Ctr Heart, GRB 109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org OI Perna, Francesco/0000-0002-9019-9492 FU St. Jude Medical; Biosense Webster FX E. K. Heist reports research grant from and consultant to St. Jude Medical. J. Ruskin reports collaboration on research grants supported by Biosense Webster and St. Jude Medical; he serves as consultant to or on the advisory boards of Sanofi-aventis, Biosense Webster, Medtronic, Pfizer, Astellas, and Sequel. M. Mansour reports research grant support from Biosense Webster and St. Jude Medical, and serves as consultant to or on the advisory boards of both companies. Other authors: No disclosures. NR 26 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD DEC PY 2010 VL 21 IS 12 BP 1403 EP 1407 DI 10.1111/j.1540-8167.2010.01829.x PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 691ER UT WOS:000285063600020 PM 20561103 ER PT J AU Tao, R Kim, SH Honbo, N Karliner, JS Alano, CC AF Tao, Rong Kim, Sun Hee Honbo, Norman Karliner, Joel S. Alano, Conrad C. TI Minocycline Protects Cardiac Myocytes Against Simulated Ischemia-Reperfusion Injury by Inhibiting Poly(ADP-ribose) Polymerase-1 SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE mitochondria; PARP-1; ischemia; ischemia/reperfusion; oxidative injury ID MITOCHONDRIAL PERMEABILITY TRANSITION; CELL-DEATH; CEREBRAL-ISCHEMIA; NAD(+) DEPLETION; CYTOCHROME-C; ACTIVATION; ASTROCYTES; NEURONS; SYNTHETASE; MICROGLIA AB There is an increase in reactive oxygen and nitrogen species in cardiomyocytes during myocardial ischemia/reperfusion injury. This leads to oxidative DNA damage and activation of nuclear repair enzymes such as poly(ADP-ribose) polymerase-1 (PARP-1). PARP-1 activation promotes DNA repair under normal conditions. However, excessive activation of PARP-1 leads to cell death. We report that PARP-1 enzymatic activity is directly inhibited by minocycline, and we propose that one mechanism of minocycline cardioprotection is the result of PARP-1 inhibition. Using cultured adult rat cardiac myocytes, we evaluated the mechanism of minocycline protection in which PARP-1 activation was induced by simulated ischemia/reperfusion injury using oxygen-glucose deprivation. We found an increase in reactive oxygen species production, PARP-1 activation, and PARP-1-mediated cell death after simulated ischemia/reperfusion. Cell death was significantly reduced by the PARP inhibitors 3, 4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (10 mu M) and PJ-34 (500 nM) or by minocycline (500 nM). Cellular NAD(+) depletion and poly(ADP-ribose) formation, which are biochemical markers of PARP-1 activation, were also blocked by minocycline. Finally, simulated ischemia/reperfusion led to induction of the mitochondrial permeability transition, which was prevented by minocycline. Therefore, we propose that the protective effect of minocycline on cardiac myocyte survival is the result of inhibition of PARP-1 activity. C1 [Tao, Rong; Honbo, Norman; Karliner, Joel S.; Alano, Conrad C.] San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA USA. [Tao, Rong] Jiao Tong Univ, Ruijin Hosp, Dept Cardiol, Shanghai 200030, Peoples R China. [Kim, Sun Hee; Alano, Conrad C.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Kim, Sun Hee; Alano, Conrad C.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Alano, CC (reprint author), VAMC, 4150 Clement St, San Francisco, CA 94121 USA. EM conrad.alano@ucsf.edu FU Department of Veterans Affairs; American Heart Association; National Institutes of Health [HL090606] FX This work was supported by a Merit Review grant from the Department of Veterans Affairs (CCA), American Heart Association grant (CCA), and a grant (HL090606) from the National Institutes of Health (JSK). NR 39 TC 20 Z9 24 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD DEC PY 2010 VL 56 IS 6 BP 659 EP 668 DI 10.1097/FJC.0b013e3181faeaf0 PG 10 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 692FI UT WOS:000285138000012 PM 20881608 ER PT J AU Naccarelli, GV Singh, BN AF Naccarelli, Gerald V. Singh, Bramah N. TI Treatment of Atrial Fibrillation in 2010 and Beyond SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Editorial Material ID PREVALENCE C1 [Naccarelli, Gerald V.] Penn State Univ, Coll Med, Inst Heart & Vasc, Hershey, PA 17033 USA. [Singh, Bramah N.] Vet Adm Greater Los Angeles Healthcare Syst, Div Cardiol, Los Angeles, CA USA. RP Naccarelli, GV (reprint author), Penn State Univ, Coll Med, Inst Heart & Vasc, Room H 1-511,500 Univ Dr, Hershey, PA 17033 USA. EM GNaccarelli@psu.edu NR 6 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1074-2484 J9 J CARDIOVASC PHARM T JI J. Cardiovasc. Pharmacol. Ther. PD DEC PY 2010 VL 15 IS 4 SU S BP 5 EP 5 DI 10.1177/1074248410390190 PG 1 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 684XG UT WOS:000284588000001 PM 21098414 ER PT J AU Singh, BN Cingolani, E AF Singh, Bramah N. Cingolani, Eugenio TI A New Agent for Atrial Fibrillation: Electrophysiological Properties of Dronedarone SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE amiodarone congeners; dronedarone; electrophysiological effect; repolarization; torsade de pointes ID LOW-DOSE AMIODARONE; SERIE DES BENZOFURANNES; MYOCARDIAL-INFARCTION; POINTES ARRHYTHMIAS; CARDIAC-MUSCLE; HEART-FAILURE; SINUS RHYTHM; EFFICACY; SOTALOL; TOXICITY AB Although originally synthesized as an antianginal compound, amiodarone has emerged as an effective antiarrhythmic for both supraventricular and ventricular arrhythmias. Over the decades, the properties, the effectiveness, the merits as well as the shortcomings of the compound have been well established. The major limitations of this agent are mainly due to the systemic side effects seen with prolonged therapy. Many of the toxic effects observed are primarily caused by the high iodine content present in the amiodarone molecule. Dronedarone, the first noniodinated amiodarone congener, has been developed largely to obtain the antiarrhythmic efficacy in the control of atrial fibrillation without the known adverse side effects of dronedarone. In this part of the supplement, the focus is the electrophysiological effects of dronedarone with the characterization in normal cardiac cells, in animal models of disease, as well as in human studies. C1 [Singh, Bramah N.; Cingolani, Eugenio] Vet Adm Greater Los Angeles Healthcare Syst, Div Cardiol, Los Angeles, CA 90073 USA. RP Singh, BN (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Div Cardiol, 11301 Wilshire Blvd,111E, Los Angeles, CA 90073 USA. EM bsingh@ucla.edu FU Cedars Sinai Medical Center FX The authors disclosed receipt of the following financial support for the research and/or authorship of this article: Dr Cingolani is a recipient of the Cedars Sinai Medical Center - Sports Spectacular Endowed Fellowship in Cardiology. NR 51 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1074-2484 EI 1940-4034 J9 J CARDIOVASC PHARM T JI J. Cardiovasc. Pharmacol. Ther. PD DEC PY 2010 VL 15 IS 4 SU S BP 6S EP 14S DI 10.1177/1074248410377618 PG 9 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 684XG UT WOS:000284588000002 PM 21098415 ER PT J AU Singh, BN AF Singh, Bramah N. TI Augmenting Maintenance of Sinus Rhythm in the Control of Atrial Fibrillation by Antiarrhythmic Drug Combinations SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE amiodarone congeners; dronedarone; combination of dual multiple; antiarrhythmic agents ID LEFT-VENTRICULAR DYSFUNCTION; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; RANDOMIZED-TRIAL; BETA-BLOCKERS; AMIODARONE; CARVEDILOL; DRONEDARONE; HEART; ARRHYTHMIAS AB In recent years, a major development in the treatment of atrial fibrillation (AF) is the use of catheter ablation, and a significant number of patients may benefit from this mode of therapy. On a global scale, it may not be feasible to deal with most patients solely on the basis of ablation. Therefore, it is likely that much of the therapy for AF will continue to rely on antiarrhythmic agents for maintaining sinus rhythm. For many years, amiodarone and sotalol have been the dominant antiarrhythmic agents, with amiodarone being the most effective antiarrhythmic in suppressing AF; however, amiodarone use is limited due to concerns of end-organ toxicity. Upstream therapies, such as statins, fish oil, angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers may also provide additive efficacy to these and other membrane-active antiarrhythmics. In recent years, a number of new agents are being developed and the first successful congener of amiodarone, dronedarone, has been shown to be effective in controlling AF and reducing cardiovascular hospitalization. This paper explores the possibility of augmenting the extent of controlling AF by combining multiple potent antiarrhythmic agents old and new. C1 Vet Adm Greater Los Angeles Healthcare Syst, Div Cardiol, Los Angeles, CA 90073 USA. RP Singh, BN (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Div Cardiol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM bsingh@ucla.edu NR 37 TC 3 Z9 3 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1074-2484 J9 J CARDIOVASC PHARM T JI J. Cardiovasc. Pharmacol. Ther. PD DEC PY 2010 VL 15 IS 4 SU S BP 31S EP 35S DI 10.1177/1074248410377617 PG 5 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 684XG UT WOS:000284588000006 PM 21098417 ER PT J AU Kim, WK Meliton, V Bourquard, N Hahn, TJ Parhami, F AF Kim, Woo-Kyun Meliton, Vicente Bourquard, Noam Hahn, Theodore J. Parhami, Farhad TI Hedgehog Signaling and Osteogenic Differentiation in Multipotent Bone Marrow Stromal Cells Are Inhibited by Oxidative Stress SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE OXIDATIVE STRESS; MESENCHYMAL STEM CELLS; HEDGEHOG; OSTEOGENESIS ID PLURIPOTENT MESENCHYMAL CELLS; OSTEOBLASTIC DIFFERENTIATION; PRIMARY CILIUM; FREE-RADICALS; STEM-CELLS; PATHWAY; MICE; OSTEOPOROSIS; EXPRESSION; MEMBRANE AB Oxidative stress may play a major role in age-related osteoporosis in part by inhibiting osteoblast generation from osteoprogenitors cells. In the present study, we hypothesized that oxidative stress may inhibit: the osteogenic differentiation of bone marrow stromal cells (MSC) in parr by inhibiting the Hedgehog (Hh) signaling pathway, which is essential for bone development and maintenance and induces osteogenic differentiation of osteoprogenitor cells. To test this hypothesis, we examined the effects of oxidative stress on Sonic Hh (Shh)-induced osteogenic differentiation and signaling in M2-10B4 (M2) MSC, C3H10T1/2 embryonic fibroblasts, and mouse primary MSC. Treatment of cells with H(2)O(2) inhibited Shh-induced osteogenic differentiation determined by the inhibition of Shh-induced expression of osteogenic differentiation markers alkaline phosphatase (ALP), osterix (OSX), anti bone sialoprotein (BSP). Similar effects were found when oxidative stress was induced by xanthine/xanthine oxidase (XXO) or minimally oxidized LDL (MM-LDL). H(2)O(2), XXO, and MM-LDL treatment inhibited Shh-induced expression of the Hh target genes Gli 1 and Patched 1 as well as Gli-dependent transcriptional activity in M2 cells. H(2)O(2) treatment also inhibited Hh signaling induced by the direct activation of Smoothened by purmorphamine (PM), but not by Gli 1 overexpression. This suggests that oxidative stress may inhibit Hh signaling upstream of Gli activation anti Gli-induced gene expression. These findings demonstrate for the first time that oxidative stress inhibits Hh signaling associated with osteogenic differentiation. Inhibition of Hit signaling-mediated osteogenic differentiation of osteoprogenitor cells may in part explain the inhibitory effects of oxidative stress on osteoblast development, differentiation, and maintenance in aging. J. Cell. Biochem. 111: 1199-1209, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Parhami, Farhad] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Hlth Sci, Dept Med, Los Angeles, CA 90095 USA. [Hahn, Theodore J.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. RP Parhami, F (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Hlth Sci, Dept Med, BH 307,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM fparhami@mednet.ucla.edu FU NIAMS; National Institutes of Health (NIH) [RO1AR050426]; National Institute of Aging [5P30AG028748] FX Grant sponsor: NIAMS; Grant sponsor: National Institutes of Health (NIH); Grant number: RO1AR050426; Grant sponsor: National Institute of Aging; Grant number: 5P30AG028748. NR 51 TC 30 Z9 36 U1 1 U2 12 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD DEC 1 PY 2010 VL 111 IS 5 BP 1199 EP 1209 DI 10.1002/jcb.22846 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 703YH UT WOS:000286017400015 PM 20717924 ER PT J AU Wilens, TE Lyne, A Youcha, S AF Wilens, Timothy E. Lyne, Andrew Youcha, Sharon TI A Study of the Coadministration of Guanfacine Extended Release and a Psychostimulant for the Treatment of Attention Deficit Hyperactivity Disorder: Design and Rationale SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 50th Annual National Institute of Mental Health (NIMH) New Clinical Drug Evaluation Unit (NCDEU) CY JUN 14-17, 2010 CL Boca Raton, FL C1 [Wilens, Timothy E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Lyne, Andrew] Shire Pharmaceut Dev Ltd, Basingstoke, Hants, England. [Youcha, Sharon] Shire Dev Inc, Wayne, PA USA. 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 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD DEC PY 2010 VL 20 IS 6 BP 530 EP 530 PG 1 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 699CE UT WOS:000285640700015 ER PT J AU Wang, CH Bonnemann, CG Rutkowski, A Sejersen, T Bellini, J Battista, V Florence, JM Schara, U Schuler, PM Wahbi, K Aloysius, A Bash, RO Beroud, C Bertini, E Bushby, K Cohn, RD Connolly, AM Deconinck, N Desguerre, I Eagle, M Estournet-Mathiaud, B Ferreiro, A Fujak, A Goemans, N Iannaccone, ST Jouinot, P Main, M Melacini, P Mueller-Felber, W Muntoni, F Nelson, LL Rahbek, J Quijano-Roy, S Sewry, C Storhaug, K Simonds, A Tseng, B Vajsar, J Vianello, A Zeller, R AF Wang, Ching H. Bonnemann, Carsten G. Rutkowski, Anne Sejersen, Thomas Bellini, Jonathan Battista, Vanessa Florence, Julaine M. Schara, Ulrike Schuler, Pamela M. Wahbi, Karim Aloysius, Annie Bash, Robert O. Beroud, Christophe Bertini, Enrico Bushby, Kate Cohn, Ronald D. Connolly, Anne M. Deconinck, Nicolas Desguerre, Isabelle Eagle, Michelle Estournet-Mathiaud, Brigitte Ferreiro, Ana Fujak, Albert Goemans, Nathalie Iannaccone, Susan T. Jouinot, Patricia Main, Marion Melacini, Paola Mueller-Felber, Wolfgang Muntoni, Francesco Nelson, Leslie L. Rahbek, Jes Quijano-Roy, Susana Sewry, Caroline Storhaug, Kari Simonds, Anita Tseng, Brian Vajsar, Jiri Vianello, Andrea Zeller, Reinhard TI Consensus Statement on Standard of Care for Congenital Muscular Dystrophies SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE standard of care; congenital muscular dystrophy ID RIGID SPINE SYNDROME; INTRAPULMONARY PERCUSSIVE VENTILATION; RESPIRATORY-TRACT INFECTIONS; LONG-TERM PROGNOSIS; QUALITY-OF-LIFE; LAMIN A/C GENE; NEUROMUSCULAR DISEASE; FUKUYAMA-TYPE; NONINVASIVE VENTILATION; ENDOTRACHEAL INTUBATION AB Congenital muscular dystrophies are a group of rare neuromuscular disorders with a wide spectrum of clinical phenotypes. Recent advances in understanding the molecular pathogenesis of congenital muscular dystrophy have enabled better diagnosis. However, medical care for patients with congenital muscular dystrophy remains very diverse. Advances in many areas of medical technology have not been adopted in clinical practice. The International Standard of Care Committee for Congenital Muscular Dystrophy was established to identify current care issues, review literature for evidence-based practice, and achieve consensus on care recommendations in 7 areas: diagnosis, neurology, pulmonology, orthopedics/rehabilitation, gastroenterology/ nutrition/speech/oral care, cardiology, and palliative care. To achieve consensus on the care recommendations, 2 separate online surveys were conducted to poll opinions from experts in the field and from congenital muscular dystrophy families. The final consensus was achieved in a 3-day workshop conducted in Brussels, Belgium, in November 2009. This consensus statement describes the care recommendations from this committee. C1 [Wang, Ching H.] Stanford Univ, Med Ctr, Dept Neurol & Neurol Sci, Sch Med, Stanford, CA 94305 USA. [Bonnemann, Carsten G.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Rutkowski, Anne] Cure CMD, Olathe, KS USA. [Sejersen, Thomas] Karolinska Inst, Stockholm, Sweden. [Battista, Vanessa] Boston Coll, Boston, MA USA. [Florence, Julaine M.; Connolly, Anne M.] Washington Univ, Sch Med, St Louis, MO USA. [Schara, Ulrike] Univ Essen Gesamthsch, Essen, Germany. [Schuler, Pamela M.] Univ Florida, Gainesville, FL USA. [Wahbi, Karim] Myol Inst, Paris, France. [Aloysius, Annie] Hammersmith Hosp, London, England. [Bash, Robert O.; Iannaccone, Susan T.; Nelson, Leslie L.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Beroud, Christophe] INSERM, Genet Mol Lab, U827, Montpellier, France. [Bertini, Enrico] Bambino Gesu Childrens Res Hosp, Rome, Italy. [Bushby, Kate; Eagle, Michelle] Univ Newcastle, Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England. [Cohn, Ronald D.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Deconinck, Nicolas] Hop Univ Enfants Reine Fabiola, Brussels, Belgium. [Desguerre, Isabelle] Hop St Vincent de Paul, F-75674 Paris, France. [Estournet-Mathiaud, Brigitte; Jouinot, Patricia; Quijano-Roy, Susana] Hop Raymond Poincare, Garches, France. [Ferreiro, Ana] Grp Hosp Pitie Salpetriere, Grp Myol, UMR 787, F-75634 Paris, France. [Fujak, Albert] Univ Erlangen Nurnberg, Erlangen, Germany. [Goemans, Nathalie; Main, Marion] Univ Leuven, Louvain, Belgium. [Melacini, Paola; Vianello, Andrea] Univ Padua, Padua, Italy. [Muntoni, Francesco; Sewry, Caroline] Dubowitz Neuromuscular Ctr, London, England. [Mueller-Felber, Wolfgang] Univ Munich, Munich, Germany. [Rahbek, Jes] Rehabiliterings Ctr Muskelsvind, Aarhus, Denmark. [Storhaug, Kari] Natl Resource Ctr Oral Hlth Rare Med Condit, Oslo, Norway. [Simonds, Anita] Royal Brompton Hosp, London SW3 6LY, England. [Tseng, Brian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Vajsar, Jiri; Zeller, Reinhard] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. RP Wang, CH (reprint author), Stanford Univ, Med Ctr, Dept Neurol & Neurol Sci, Sch Med, 300 Pasteur Dr,Room A343, Stanford, CA 94305 USA. EM wangch@stanford.edu RI Ferreiro, Ana/F-5371-2011; LABO, U827/A-8632-2008; BEROUD, Christophe/A-8381-2008; OI BEROUD, Christophe/0000-0003-2986-8738; Connolly, Anne/0000-0002-9193-2457; Bertini, Enrico/0000-0001-9276-4590; Sejersen, Thomas/0000-0001-5961-7097 FU CureCMD; TREAT-NMD; AFM-Association Francaise contre les Myopathies; Telethon Italy FX The authors disclosed receipt of the following financial support for the research and/or authorship of this article: This project is supported by grants from CureCMD (www.curecmd.com), TREAT-NMD (www.treat-nmd.edu), AFM-Association Francaise contre les Myopathies (www.afm-france.org), and Telethon Italy (www.telethon.it). NR 97 TC 61 Z9 64 U1 0 U2 16 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD DEC PY 2010 VL 25 IS 12 BP 1559 EP 1581 DI 10.1177/0883073810381924 PG 23 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 692IS UT WOS:000285147100021 PM 21078917 ER PT J AU Benz, EJ AF Benz, Edward J., Jr. TI Learning about genomics and disease from the anucleate human red blood cell SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID HEREDITARY SPHEROCYTOSIS; CHROMATIN INSULATORS; ERYTHROID-CELLS; GENE; ORGANIZATION; EXPRESSION; BOUNDARY; PROTEINS; ELEMENT; DOMAINS AB During the differentiation of an erythrocyte, the developing erythroblast shuts down expression of most of its genes but preserves high levels of expression of certain key genes, such as those encoding hemoglobin and critical membrane proteins. In this issue of the JCI, Gallagher et al. show that a specialized type of DNA sequence element known as an insulator protects the expression of ankyrin, a key membrane protein. In several kindreds, mutations in the insulator led to impaired ankyrin expression and congenital hemolytic anemia. This work provides important insights into ways in which epigenetic changes can alter gene expression and thereby lead to human disease. C1 Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. RP Benz, EJ (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Room 1628D,44 Binney St, Boston, MA 02115 USA. NR 20 TC 1 Z9 1 U1 1 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2010 VL 120 IS 12 BP 4204 EP 4206 DI 10.1172/JCI45433 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 690AD UT WOS:000284971400010 PM 21099106 ER PT J AU Marrotte, EJ Chen, DD Hakim, JS Chen, AF AF Marrotte, Eric J. Chen, Dan-Dan Hakim, Jeffrey S. Chen, Alex F. TI Manganese superoxide dismutase expression in endothelial progenitor cells accelerates wound healing in diabetic mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NITRIC-OXIDE SYNTHASE; OXIDATIVE STRESS; VASCULAR COMPLICATIONS; GENE-THERAPY; FOOT ULCERS; HYPERGLYCEMIA; ANGIOGENESIS; LEPTIN; GROWTH; NEOVASCULARIZATION AB Amputation as a result of impaired wound healing is a serious complication of diabetes. Inadequate angiogenesis contributes to poor wound healing in diabetic patients. Endothelial progenitor cells (EPCs) normally augment angiogenesis and wound repair but are functionally impaired in diabetics. Here we report that decreased expression of manganese superoxide dismutase (MnSOD) in EPCs contributes to impaired would healing in a mouse model of type 2 diabetes. A decreased frequency of circulating EPCs was detected in type 2 diabetic (db/db) mice, and when isolated, these cells exhibited decreased expression and activity of MnSOD. Wound healing and angiogenesis were markedly delayed in diabetic mice compared with normal controls. For cell therapy, topical transplantation of EPCs onto excisional wounds in diabetic mice demonstrated that diabetic EPCs were less effective than normal EPCs at accelerating wound closure. Transplantation of diabetic EPCs after MnSOD gene therapy restored their ability to mediate angiogenesis and wound repair. Conversely, siRNA-mediated knockdown of MnSOD in normal EPCs reduced their activity in diabetic wound healing assays. Increasing the number of transplanted diabetic EPCs also improved the rate of wound closure. Our findings demonstrate that cell therapy using diabetic EPCs after ex vivo MnSOD gene transfer accelerates their ability to heal wounds in a mouse model of type 2 diabetes. C1 [Chen, Alex F.] Univ Pittsburgh, Sch Med, McGowan Inst Regenerat Med, Dept Surg,Vasc Med Inst,VA Vasc Surg Res, Pittsburgh, PA 15213 USA. [Chen, Dan-Dan; Chen, Alex F.] Vet Affairs Pittsburgh Healthcare Syst, Vasc Surg Res, Pittsburgh, PA USA. [Chen, Alex F.] Second Mil Med Univ, Shanghai, Peoples R China. RP Chen, AF (reprint author), Univ Pittsburgh, Sch Med, McGowan Inst Regenerat Med, Dept Surg,Vasc Med Inst,VA Vasc Surg Res, W1148 Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15213 USA. OI Hakim, Jeffrey/0000-0002-2169-158X FU National Institute of General Medical Science, NIH [R01GM077352]; American Diabetes Association [7-08-RA 23]; Natural Sciences Foundation of China [30728021]; American Heart Association [0615519Z, 0720114Z] FX This work was funded by grant R01GM077352 from the National Institute of General Medical Science, NIH, grant 7-08-RA 23 from the American Diabetes Association, and International Collaborative grant 30728021 from the Natural Sciences Foundation of China (to A F Chen) E J Marrotte is a receipt of an American Heart Association predoctoral fellowship award (0615519Z), and D D Chen is a receipt of an American Heart Association postdoctoral fellowship award (0720114Z) NR 41 TC 81 Z9 91 U1 0 U2 10 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2010 VL 120 IS 12 BP 4207 EP 4219 DI 10.1172/JCI36858 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 690AD UT WOS:000284971400011 PM 21060152 ER PT J AU Burkhardt, R Toh, SA Lagor, WR Birkeland, A Levin, M Li, XY Robblee, M Fedorov, VD Yamamoto, M Satoh, T Akira, S Kathiresan, S Breslow, JL Rader, DJ AF Burkhardt, Ralph Toh, Sue-Anne Lagor, William R. Birkeland, Andrew Levin, Michael Li, Xiaoyu Robblee, Megan Fedorov, Victor D. Yamamoto, Masahiro Satoh, Takashi Akira, Shizuo Kathiresan, Sekar Breslow, Jan L. Rader, Daniel J. TI Trib1 is a lipid- and myocardial infarction-associated gene that regulates hepatic lipogenesis and VLDL production in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LOCI; TRIGLYCERIDE; POPULATION; DISEASE; CHOLESTEROL; HOMEOSTASIS; GLUCOSE; ALPHA; RISK AB Recent genome-wide association studies have identified a genetic locus at human chromosome 8q24 as having minor alleles associated with lower levels of plasma triglyceride (TG) and LDL cholesterol (LDL-C), higher levels of HDL-C, as well as decreased risk for myocardial infarction. This locus contains only one annotated gene, tribbles homolog 1 (TRIB1), which has not previously been implicated in lipoprotein metabolism. Here we demonstrate a role for Trib1 as a regulator of lipoprotein metabolism in mice. Hepatic-specific overexpression of Trib1 reduced levels of plasma TG and cholesterol by reducing VLDL production; conversely, Trib1-knockout mice showed elevated levels of plasma TG and cholesterol due to increased VLDL production. Hepatic Trib1 expression was inversely associated with the expression of key lipogenic genes and measures of lipogenesis. Thus, we provide functional evidence for what we believe to be a novel gene regulating hepatic lipogenesis and VLDL production in mice that influences plasma lipids and risk for myocardial infarction in humans. C1 [Burkhardt, Ralph; Birkeland, Andrew; Robblee, Megan; Fedorov, Victor D.; Breslow, Jan L.] Rockefeller Univ, Biochem Genet & Metab Lab, New York, NY 10065 USA. [Toh, Sue-Anne; Lagor, William R.; Levin, Michael; Li, Xiaoyu; Rader, Daniel J.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. [Toh, Sue-Anne; Rader, Daniel J.] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. [Toh, Sue-Anne] Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Yamamoto, Masahiro; Satoh, Takashi; Akira, Shizuo] Osaka Univ, WPI Immunol Frontier Res Ctr, Osaka, Japan. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Boston, MA USA. [Kathiresan, Sekar] Broad Inst, Cambridge, MA USA. [Rader, Daniel J.] Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. RP Breslow, JL (reprint author), Rockefeller Univ, Biochem Genet & Metab Lab, 1230 York Ave, New York, NY 10065 USA. RI Akira, Shizuo/C-3134-2009; Breslow, Jan/B-7544-2008; Burkhardt, Ralph/F-5221-2013 FU National Heart, Lung and Blood Institute; NIH [P01-HL059407, RC2-HL101864]; Bristol-Myers Squibb; Duetsche Forschungsgemeinschaft [BU2263/1-1]; NIH MSTP [GM07739]; American Heart Association [0315294T]; Institute for Translational Medicine and Therapeutics, University of Pennsylvania FX We thank Jeffrey Billheimer, Deborah Cromley, Edwige Eduoard, Hui Li, Dawn Marchadier, John Millar, Valeska Redon, Alanna Strong, Mao-Sen Sun, Aisha Wilson, and Sonja Stadler for assistance and suggestions We acknowledge the National Heart, Lung and Blood Institute Gene Therapy Resource Program for providing support for viral vector production as well as the vector core laboratory of the University of Pennsylvania for producing the vectors This work was supported in part by P01-HL059407 and RC2-HL101864 from the NIH and a "Freedom to Discover" Unrestricted Cardiovascular Research Grant from Bristol-Myers Squibb (to DJ Rader) R Burkhardt was supported by a fellowship of the Duetsche Forschungsgemeinschaft (BU2263/1-1), V D Fedorov by NIH MSTP grant GM07739, and S Toh by an American Heart Association fellowship (0315294T) and the Institute for Translational Medicine and Therapeutics, University of Pennsylvania NR 22 TC 72 Z9 73 U1 0 U2 15 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2010 VL 120 IS 12 BP 4410 EP 4414 DI 10.1172/JC144213 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 690AD UT WOS:000284971400026 PM 21084752 ER PT J AU Acharya, M Mukhopadhyay, S Paidassi, H Jamil, T Chow, C Kissler, S Stuart, LM Hynes, RO Lacy-Hulbert, A AF Acharya, Mridu Mukhopadhyay, Subhankar Paidassi, Helena Jamil, Tahseen Chow, Camille Kissler, Stephan Stuart, Lynda M. Hynes, Richard O. Lacy-Hulbert, Adam TI alpha v Integrin expression by DCs is required for Th17 cell differentiation and development of experimental autoimmune encephalomyelitis in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; REGULATORY T-CELLS; GROWTH-FACTOR-BETA; ULCERATIVE-COLITIS; CROHNS-DISEASE; INTESTINAL INFLAMMATION; HELPER-CELLS; TGF-BETA; LINEAGE AB Th17 cells are a distinct lineage of T helper cells that protect the body from bacterial and fungal infection. However, Th17 cells also contribute to inflammatory and autoimmune disorders such as multiple sclerosis. Th17 cell generation requires exposure of naive T cells to the cytokine TGF-beta in combination with proinflammatory cytokines. Here we show that differentiation of Th17 cells is also critically dependent on alpha v integrins. In mice, lack of integrin alpha v in the immune system resulted in loss of Th17 cells in the intestine and lymphoid tissues. It also led to protection from experimental autoimmune encephalomyelitis (EAE). Further analysis indicated that alpha v integrins on DCs activated latent TGF-beta during T cell stimulation and thereby promoted differentiation of Th17 cells. Furthermore, pharmacologic inhibition of alpha v integrins using cyclic RGD peptides blocked TGF-beta activation and Th17 cell generation in vitro and protected mice from EAE. These data demonstrate that activation of TGF-beta by alpha v-expressing myeloid cells may be a critical step in the generation of Th17 cells and suggest that alpha v integrins could be therapeutic targets in autoimmune disease. C1 [Acharya, Mridu; Mukhopadhyay, Subhankar; Paidassi, Helena; Jamil, Tahseen; Chow, Camille; Stuart, Lynda M.; Lacy-Hulbert, Adam] Massachusetts Gen Hosp, Program Dev Immunol, Dept Pediat, Boston, MA 02114 USA. [Acharya, Mridu; Mukhopadhyay, Subhankar; Paidassi, Helena; Jamil, Tahseen; Chow, Camille; Stuart, Lynda M.; Lacy-Hulbert, Adam] Harvard Univ, Sch Med, Boston, MA USA. [Mukhopadhyay, Subhankar] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. [Paidassi, Helena] Univ Edinburgh, Queens Med Res Inst, Edinburgh, Midlothian, Scotland. [Paidassi, Helena] Univ Edinburgh, MRC Ctr Inflammat Res, Edinburgh, Midlothian, Scotland. [Kissler, Stephan; Hynes, Richard O.] MIT, Koch Inst Integrated Canc Res, Cambridge, MA 02139 USA. [Hynes, Richard O.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Lacy-Hulbert, A (reprint author), Massachusetts Gen Hosp, Program Dev Immunol, Dept Pediat, GRJ1402,55 Fruit St, Boston, MA 02114 USA. RI Paidassi, Helena/M-5739-2014; OI , /0000-0003-3062-7800; Lacy-Hulbert, Adam/0000-0003-2162-0156 FU Hood Pediatric Research Foundation; Howard Hughes Medical Institute; Wellcome Trust; MRC [G0802069]; University of Edinburgh FX This work was supported by grants from the Hood Pediatric Research Foundation (to A Lacy-Hulbert) and the Howard Hughes Medical Institute (R.O Hynes) and by a Wellcome Trust Travelling Fellowship (to S Mukhopadhyay) Helena Paidassi was supported by MRC grant G0802069 to John Savill, University of Edinburgh, who we thank for support and helpful discussion NR 36 TC 40 Z9 42 U1 0 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2010 VL 120 IS 12 BP 4445 EP 4452 DI 10.1172/JCI43796 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 690AD UT WOS:000284971400030 PM 21099114 ER PT J AU McMahan, RH Golden-Mason, L Nishimura, MI McMahon, BJ Kemper, M Allen, TM Gretch, DR Rosen, HR AF McMahan, Rachel H. Golden-Mason, Lucy Nishimura, Michael I. McMahon, Brian J. Kemper, Michael Allen, Todd M. Gretch, David R. Rosen, Hugo R. TI Tim-3 expression on PD-1(+) HCV-specific human CTLs is associated with viral persistence, and its blockade restores hepatocyte-directed in vitro cytotoxicity SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HEPATITIS-C VIRUS; CD8(+) T-CELLS; HIV-1 INFECTION; RISK-FACTORS; EFFECTOR; LYMPHOCYTES; MEMORY; LIVER; EXHAUSTION; RESPONSES AB Having successfully developed mechanisms to evade immune clearance, hepatitis C virus (HCV) establishes persistent infection in approximately 75%-80% of patients. In these individuals, the function of HCV-specific CD8(+) T cells is impaired by ligation of inhibitory receptors, the repertoire of which has expanded considerably in the past few years. We hypothesized that the coexpression of the negative regulatory receptors T cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) and programmed death 1 (PD-1) in HCV infection would identify patients at risk of developing viral persistence during and after acute HCV infection. The frequency of PD-1(-)Tim-3(-) HCV-specific CTLs greatly outnumbered PD-1(+)Tim-3(+) CTLs in patients with acute resolving infection. Moreover, the population of PD-1(+)Tim-3(+) T cells was enriched for within the central memory T cell subset and within the liver. Blockade of either PD-1 or Tim-3 enhanced in vitro proliferation of HCV-specific CTLs to a similar extent, whereas cytotoxicity against a hepatocyte cell line that expressed cognate HCV epitopes was increased exclusively by Tim-3 blockade. These results indicate that the coexpression of these inhibitory molecules tracks with defective T cell responses and that anatomical differences might account for lack of immune control of persistent pathogens, which suggests their manipulation may represent a rational target for novel immunotherapeutic approaches. C1 [McMahan, Rachel H.; Golden-Mason, Lucy; Rosen, Hugo R.] Univ Colorado, Dept Med, Div Gastroenterol & Hepatol, Denver, CO USA. [Nishimura, Michael I.] Univ S Carolina, Ctr Canc, Dept Surg, Charleston, SC USA. [McMahon, Brian J.] Liver Dis & Hepatitis Program, ANTHC, Anchorage, AK USA. [McMahon, Brian J.] Ctr Dis Control & Prevent, Arctic Invest Program, Div Emerging Infect & Surveillance Serv, Natl Ctr Preparedness Detect & Control Infect Dis, Anchorage, AK USA. [Kemper, Michael; Allen, Todd M.] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Charlestown, MA USA. [Gretch, David R.] Univ Washington, Div Lab Med, Seattle, WA 98195 USA. [Rosen, Hugo R.] Natl Jewish Hlth, Denver, CO USA. [Rosen, Hugo R.] Denver VA Ctr, Denver, CO USA. RP Rosen, HR (reprint author), Univ Colorado Denver, GI & Hepatol Div, B-158,Acad Off Bldg 1,12631 E 17th Ave,Room 7614,, Aurora, CO 80045 USA. RI Allen, Todd/F-5473-2011 FU NIH [RO1 DK060590, U19 A 1066328, RO1 AI 066209] FX This research is supported by NIH grants RO1 DK060590 and U19 A 1066328 (HCV center grant) and VA Merit Review to H R. Rosen, and by NIH grant RO1 AI 066209 to D R Gretch We are grateful to the patients for their participation in the study, Steve Livingston and Lisa Townsend for helping coordinate specimen collection in Alaska, and Megan Brocato for specimen processing NR 49 TC 141 Z9 150 U1 0 U2 9 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2010 VL 120 IS 12 BP 4546 EP 4557 DI 10.1172/JCI43127 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 690AD UT WOS:000284971400038 PM 21084749 ER PT J AU Dyhrfjeld-Johnsen, J Berdichevsky, Y Swiercz, W Sabolek, H Staley, KJ AF Dyhrfjeld-Johnsen, J. Berdichevsky, Y. Swiercz, W. Sabolek, H. Staley, K. J. TI Interictal Spikes Precede Ictal Discharges in an Organotypic Hippocampal Slice Culture Model of Epileptogenesis SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Review DE Epileptogenesis; Growth medium; Interictal spikes; Ictal discharges; Organotypic hippocampal slices; Phenytoin ID INDUCED STATUS EPILEPTICUS; RAT HIPPOCAMPUS; NERVOUS-TISSUE; DENTATE GYRUS; BRAIN-INJURY; MOSSY FIBER; CA3 NETWORK; SYNAPSES; EPILEPSY; ORGANIZATION AB In organotypic hippocampal slice cultures, principal neurons form aberrant excitatory connections with other principal cells in response to slicing induced deafferentation, similar to mechanisms underlying epileptogenesis in posttraumatic epilepsy. To investigate the consequences of this synaptogenesis, the authors recorded field-potential activity from area CA3 during perfusion with the complete growth medium used during incubation. At 7 days in vitro, slice cultures only displayed multiunit activity. At 14 days in vitro, the majority displayed population bursts reminiscent of interictal-like spikes, but sustained synchronous activity was rare. Band-pass filtering of interictal discharges revealed fast ripple-like complexes, similar to in vivo recordings. Spontaneous ictal-like activity became progressively more prevalent with age: at 21 days in vitro, 50% of organotypic hippocampal slice cultures displayed long-lasting, ictal-like discharges that could be suppressed by phenytoin, whereas interictal activity was not suppressed. The fraction of cultures displaying ictal events continually increased with incubation time. Quantification of population spike activity throughout epileptogenesis using automatic detection and clustering algorithms confirmed the appearance of interictal-like activity before ictal-like discharges and also revealed high-frequency pathologic multiunit activity in slice cultures at 14 to 17 days in vitro. These experiments indicate that interictal-like spikes precede the appearance of ictal-like activity in a reduced in vitro preparation. Epileptiform activity in cultures resembled in vivo epilepsy, including sensitivity to anticonvulsants and steadily increasing seizure incidence over time, although seizure frequency and rate of epileptogenesis were higher in vitro. Organotypic hippocampal slice cultures comprise a useful model system for investigating mechanisms of epileptogenesis as well as developing antiepileptic and antiepileptogenic drugs. C1 [Dyhrfjeld-Johnsen, J.; Berdichevsky, Y.; Swiercz, W.; Sabolek, H.; Staley, K. J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Dyhrfjeld-Johnsen, J.; Swiercz, W.; Sabolek, H.; Staley, K. J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Berdichevsky, Y.] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. RP Staley, KJ (reprint author), MGH Neurol, CNY 114,Rm 2600,114 16th St, Charlestown, MA 02129 USA. EM kstaley@partners.org FU NIH [NS34360-12] FX Supported by the NIH grant NS34360-12 (to K. S.). NR 37 TC 43 Z9 43 U1 0 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD DEC PY 2010 VL 27 IS 6 BP 418 EP 424 DI 10.1097/WNP.0b013e3181fe0709 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 689PI UT WOS:000284939900009 PM 21076333 ER PT J AU Carvalho, CH Acioly, MA Batista, LM Wirtz, CR AF Carvalho, Carlos H. Acioly, Marcus A. Batista, Leonardo M. Wirtz, Christian Rainer TI Comment on: "Ependymal cyst in the conus medullaris" SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Letter C1 [Carvalho, Carlos H.; Wirtz, Christian Rainer] Univ Ulm, Univ Hosp, Dept Neurosurg, D-89312 Gunzburg, Germany. [Acioly, Marcus A.] Univ Estado Rio De Janeiro, Div Neurosurg, Dept Surg Specialties, Rio De Janeiro, Brazil. [Batista, Leonardo M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Stroke Res, Cambridge, MA 02138 USA. RP Carvalho, CH (reprint author), Univ Ulm, Univ Hosp, Dept Neurosurg, Ludwig Heilmeyerstr, D-89312 Gunzburg, Germany. EM ch_neurochirurgie@yahoo.com.br RI Acioly, Marcus /G-2724-2012; OI Wirtz, Christian Rainer/0000-0001-8358-1813 NR 3 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD DEC PY 2010 VL 17 IS 12 BP 1606 EP 1606 DI 10.1016/j.jocn.2010.08.006 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 682ZV UT WOS:000284442400036 PM 20888235 ER PT J AU Fidias, P Novello, S AF Fidias, Panos Novello, Silvia TI Strategies for Prolonged Therapy in Patients With Advanced Non-Small-Cell Lung Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID PHASE-III TRIAL; CHEMOTHERAPY-NAIVE PATIENTS; RANDOMIZED-TRIAL; 1ST-LINE CHEMOTHERAPY; SUPPORTIVE CARE; ERLOTINIB; MAINTENANCE; DOCETAXEL; CISPLATIN; CARBOPLATIN AB Purpose A key challenge in the treatment of advanced non-small-cell lung cancer (NSCLC) is improving outcomes for patients who have achieved at least stable disease after standard first-line therapy. Although current guidelines recommend a maximum of six cycles of first-line therapy, even in responding patients, recent trials have shown benefit with maintenance therapy. Methods We reviewed the English literature for randomized controlled trials on prolonged therapy for NSCLC conducted between January 1999 and January 2010. The search was supplemented by a review of abstracts presented at the American Society of Clinical Oncology annual meetings (2004 to 2010), the World Lung Cancer Conference (2007 to 2009), and the 2009 Joint European CanCer Organisation-European Society for Medical Oncology conference. Results Several alternative strategies for prolongation of chemotherapy have been tested: these can be broadly categorized as continuation (prolongation of the first-line regimen until disease progression, unacceptable toxicity, or administration of a predefined greater number of treatment cycles), switch-maintenance (administration of an active agent immediately after completion of the initial course of chemotherapy), and continuation-maintenance (ongoing administration of a lower intensity version of the first-line chemotherapy regimen). These approaches differ from traditional second line, which is defined as treatment administered after documented clinical progression subsequent to first-line therapy. Conclusion There are no data to support continuation chemotherapy in advanced NSCLC. Switch-maintenance trials with erlotinib and pemetrexed have demonstrated an improvement in overall survival. Thus far, continuation-maintenance has shown an improvement in progression-free survival, without an overall survival advantage. J Clin Oncol 28:5116-5123. (C) 2010 by American Society of Clinical Oncology C1 [Fidias, Panos] Massachusetts Gen Hosp, Ctr Thorac Canc, Boston, MA 02114 USA. Univ Turin, Turin, Italy. RP Fidias, P (reprint author), Massachusetts Gen Hosp, Ctr Thorac Canc, 55 Fruit St, Boston, MA 02114 USA. EM pfidias2@partners.org FU sanofi-aventis, US FX Editorial support was funded by sanofi-aventis, US. NR 45 TC 43 Z9 45 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2010 VL 28 IS 34 BP 5116 EP 5123 DI 10.1200/JCO.2010.30.7074 PG 8 WC Oncology SC Oncology GA 686JR UT WOS:000284693100025 PM 21041704 ER PT J AU Surman, CBH Monuteaux, MC Petty, CR Faraone, SV Spencer, TJ Chu, NF Biederman, J AF Surman, Craig B. H. Monuteaux, Michael C. Petty, Carter R. Faraone, Stephen V. Spencer, Thomas J. Chu, Nicole F. Biederman, Joseph TI Representativeness of Participants in a Clinical Trial for Attention-Deficit/Hyperactivity Disorder? Comparison With Adults From a Large Observational Study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; PSYCHIATRIC COMORBIDITY AB Background: Clinical trials have demonstrated that pharmacotherapies can safely treat attention-deficit/hyperactivity disorder (ADHD) in adulthood. Eligibility criteria in these trials may significantly limit their external validity by excluding a significant portion of adults with ADHD in the general population. In particular, exclusion criteria may frequently exclude individuals with comorbid mental health conditions, which are common in the adult ADHD population. Method: We addressed the representativeness of clinical trials by comparing 146 adult clinical trial participants with DSM-IV ADHD and a community sample composed of 124 adults with DSM-IV ADHD and 123 non-ADHD controls. Subjects were compared on socioeconomic status, Hollingshead occupational code, cognitive measures, lifetime psychopathology, and Global Assessment of Functioning (GAF) scale ratings. Results: Adults with ADHD in the community sample had higher rates of lifetime psychiatric comorbidity, lower GAF scores, and lower occupational codes than those in the clinical trial. The clinical trial eligibility criteria would have excluded 61% of community sample adults with ADHD. This excluded portion of the community sample had higher rates of lifetime psychiatric comorbidity and lower GAF scores than clinical trial participants. Conclusions: Adults with ADHD participating in the clinical trial had less evidence of functional impairment and endorsed less psychiatric comorbidity than the majority of community sample subjects with ADHD. This suggests that findings from clinical trials may have limited external validity for adults with ADHD in the general population, particularly for those adults with ADHD with the greatest burden of comorbid psychopathology. J Clin Psychiatry 2010;71(12):1612-1616 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 [Surman, Craig B. H.; Monuteaux, Michael C.; Petty, Carter R.; Spencer, Thomas J.; Chu, Nicole F.; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. RP Surman, CBH (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Ste 2000,185 Alewife Brook Pkwy, Cambridge, MA 02138 USA. EM csurman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU Abbott; Alza; Cephalon; Eli Lilly; ElMindA; Hilda and Preston Davis Foundation; McNeil; Merck; New River; National Institutes of Health (NIH) [R01MH57934, R29MH57511]; Organon; Pfizer; Shire; Takeda; Ortho-McNeil; NIH; Janssen; Novartis; GlaxoSmithKline; National Institute of Mental Health (NIMH); Bristol-Myers Squibb; AstraZeneca; Otsuka; National Institute of Child Health and Human Development; Fundacion Areces; Medice Pharmaceuticals; Spanish Child Psychiatry Association; Celltech; Esai; Forest; Gliatech; National Alliance for Research on Schizophrenia and Depression; National Institute on Drug Abuse; Noven; Neurosearch; Pharmacia; Prechter Foundation; Stanley Foundation; UCB Pharma; Wyeth FX Dr Surman has received research support from Abbott, Alza, Cephalon, Eli Lilly, ElMindA, the Hilda and Preston Davis Foundation, McNeil, Merck, New River, National Institutes of Health (NIH), Organon, Pfizer, Shire, and Takeda; has been a speaker for Janssen-Ortho, McNeil, Novartis, Shire, and Massachusetts General Hospital Academy/Reed Medical Education (which receives funding from multiple pharmaceutical companies); and has been a consultant/advisor for McNeil, Shire, and Takeda. Dr Faraone has, in the past year, received consulting fees and has been on advisory boards for Eli Lilly, Ortho-McNeil, and Shire; has received research support from Shire and the NIH; has, in previous years, received consulting fees from, has been on advisory boards for, or has been a speaker for Shire, McNeil, Janssen, Novartis, Pfizer, Ortho-McNeil, and Eli Lilly; and has, in previous years, received research support from Eli Lilly, Shire, Pfizer, and the NIH. Dr Spencer has received research support from, has been a speaker for, has been a member of the speaker's bureau for, has been an advisor for, or has been a member of the advisory board for Shire, Eli Lilly, GlaxoSmithKline, Janssen, McNeil, Novartis, Cephalon, Pfizer, and the National Institute of Mental Health (NIMH). Dr Biederman is currently receiving research support from Alza, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, McNeil, Merck, Organon, Otsuka, Shire, NIMH, and National Institute of Child Health and Human Development; received, in 2009, a speaker's fee from Fundacion Areces, Medice Pharmaceuticals, and the Spanish Child Psychiatry Association; and has, in previous years, received research support, consultation fees, or speaker's fees for/from Abbott, AstraZeneca, Celltech, Cephalon, Eli Lilly, Esai, Forest, GlaxoSmithKline, Gliatech, Janssen, McNeil, National Alliance for Research on Schizophrenia and Depression, National Institute on Drug Abuse, New River, Novartis, Noven, Neurosearch, Pfizer, Pharmacia, the Prechter Foundation, Shire, the Stanley Foundation, UCB Pharma, and Wyeth. Dr Monuteaux, Mr Petty, and Ms Chu report no conflicting interests.; Data analyzed in this work come from studies supported by grants from the NIH to Dr Faraone (R01MH57934) and to Dr Spencer (R29MH57511). Novartis supported a portion of the cost of active medication in the latter study. There were no other sponsors of this study. NR 15 TC 16 Z9 16 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2010 VL 71 IS 12 BP 1612 EP 1616 DI 10.4088/JCP.09m05344pur PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 707OO UT WOS:000286296100007 PM 20816030 ER PT J AU Marcus, DS Fotenos, AF Csernansky, JG Morris, JC Buckner, RL AF Marcus, Daniel S. Fotenos, Anthony F. Csernansky, John G. Morris, John C. Buckner, Randy L. TI Open Access Series of Imaging Studies: Longitudinal MRI Data in Nondemented and Demented Older Adults SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID EARLY ALZHEIMER-DISEASE; BRAIN VOLUME DECLINE; ATROPHY; VALIDATION; AD; PROGRESSION; BIOMARKERS; DIAGNOSIS; CORTEX; YOUNG AB The Open Access Series of Imaging Studies is a series of neuroimaging data sets that are publicly available for study and analysis. The present MRI data set consists of a longitudinal collection of 150 subjects aged 60 to 96 years all acquired on the same scanner using identical sequences. Each subject was scanned on two or more visits, separated by at least 1 year for a total of 373 imaging sessions. Subjects were characterized using the Clinical Dementia Rating (CDR) as either nondemented or with very mild to mild Alzheimer's disease. Seventy-two of the subjects were characterized as nondemented throughout the study. Sixty-four of the included subjects were characterized as demented at the time of their initial visits and remained so for subsequent scans, including 51 individuals with CDR 0.5 similar level of impairment to individuals elsewhere considered to have "mild cognitive impairment." Another 14 subjects were characterized as non-demented at the time of their initial visit (CDR 0) and were subsequently characterized as demented at a later visit (CDR > 0). The subjects were all right-handed and include bothmen (n = 62) and women (n = 88). For each scanning session, three or four individual T1-weighted MRI scans were obtained. Multiple within-session acquisitions provide extremely high contrast to noise, making the data amenable to a wide range of analytic approaches including automated computational analysis. Automated calculation of whole-brain volume is presented to demonstrate use of the data for measuring differences associated with normal aging and Alzheimer's disease. C1 [Marcus, Daniel S.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Csernansky, John G.] Northwestern Univ, Sch Med, Evanston, IL 60208 USA. [Buckner, Randy L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Buckner, Randy L.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Marcus, DS (reprint author), Washington Univ, Sch Med, Dept Radiol, Campus Box 8225,4525 Scott Ave, St Louis, MO 63110 USA. EM dmarcus@wustl.edu RI Morris, John/A-1686-2012 FU National Institutes of Health [P50 AG05681, P01 AG03991, R01 AG021910, P20 MH071616, RR14075, RR 16594, BIRN002]; Alzheimer's Association; James S. McDonnell Foundation; Mental Illness and Neuroscience Discovery Institute; Howard Hughes Medical Institute FX The authors thank the Washington University ADRC and the Conte Center for clinical assistance and participant recruitment; Elizabeth Grant for assistance with data preparation; Susan Larson, Amy Sanders, Laura Williams, Jamie Parker, and Glenn Foster for assistance with MRI data collection; Avi Snyder for development of analytic techniques; and Tim Olsen, Mohana Ramaratnam, Kevin Archie, and Mikhail Milchenko for development of database and Web tools. Anders Dale assisted with the original selection of imaging parameters. The acquisition of this data and the support for data analysis and management were provided by the National Institutes of Health grant nos. P50 AG05681, P01 AG03991, R01 AG021910, P20 MH071616, RR14075, RR 16594, and BIRN002; the Alzheimer's Association; the James S. McDonnell Foundation; the Mental Illness and Neuroscience Discovery Institute; and the Howard Hughes Medical Institute. NR 39 TC 62 Z9 63 U1 1 U2 6 PU M I T PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD DEC PY 2010 VL 22 IS 12 BP 2677 EP 2684 DI 10.1162/jocn.2009.21407 PG 8 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 641MB UT WOS:000281129400001 PM 19929323 ER PT J AU Kuperberg, GR Choi, A Cohn, N Paczynski, M Jackendoff, R AF Kuperberg, Gina R. Choi, Arim Cohn, Neil Paczynski, Martin Jackendoff, Ray TI Electrophysiological Correlates of Complement Coercion SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID EVENT-RELATED POTENTIALS; DEPTH-RECORDED POTENTIALS; LATENT SEMANTIC ANALYSIS; LEFT PREFRONTAL CORTEX; TIME-COURSE ANALYSIS; LANGUAGE COMPREHENSION; BRAIN POTENTIALS; EYE-MOVEMENTS; SENTENCE COMPREHENSION; THEMATIC RELATIONSHIPS AB This study examined the electrophysiological correlates of complement coercion. ERPs were measured as participants read and made acceptability judgments about plausible coerced sentences, plausible noncoerced sentences, and highly implausible animacy-violated sentences ("The journalist began/wrote/astonished the article before his coffee break"). Relative to noncoerced complement nouns, the coerced nouns evoked an N400 effect. This effect was not modulated by the number of possible activities implied by the coerced nouns (e.g., began reading the article; began writing the article) and did not differ either in magnitude or scalp distribution from the N400 effect evoked by the animacy-violated complement nouns. We suggest that the N400 modulation to both coerced and animacy-violated complement nouns reflected different types of mismatches between the semantic restrictions of the verb and the semantic properties of the incoming complement noun. This is consistent with models holding that a verb's semantic argument structure is represented and stored at a distinct level from its syntactic argument structure. Unlike the coerced complement noun, the animacy-violated nouns also evoked a robust P600 effect, which may have been triggered by the judgments of the highly implausible (syntactically determined) meanings of the animacy-violated propositions. No additional ERP effects were seen in the coerced sentences until the sentence-final word that, relative to sentence-final words in the noncoerced sentences, evoked a sustained anteriorly distributed positivity. We suggest that this effect reflected delayed attempts to retrieve the specific event(s) implied by coerced complement nouns. C1 [Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Kuperberg, Gina R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kuperberg, GR (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM kuperber@nmr.mgh.harvard.edu FU National Institute of Mental Health [RO1 MH02034]; National Alliance for Research in Schizophrenia and Depression (NARSAD); Sidney J. Baer Trust FX The authors thank Phillip Holcomb and Tali Ditman for their insightful comments on the project. They are also grateful to Abigail Swain for her assistance in collecting data. This work was funded by the National Institute of Mental Health (RO1 MH02034 to G. R. K.) and the National Alliance for Research in Schizophrenia and Depression (NARSAD) with the Sidney J. Baer Trust (G. R. K.). NR 96 TC 38 Z9 39 U1 1 U2 9 PU M I T PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD DEC PY 2010 VL 22 IS 12 BP 2685 EP 2701 DI 10.1162/jocn.2009.21333 PG 17 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 641MB UT WOS:000281129400002 PM 19702471 ER PT J AU Bangera, NB Schomer, DL Dehghani, N Ulbert, I Cash, S Papavasiliou, S Eisenberg, SR Dale, AM Halgren, E AF Bangera, Nitin B. Schomer, Donald L. Dehghani, Nima Ulbert, Istvan Cash, Sydney Papavasiliou, Steve Eisenberg, Solomon R. Dale, Anders M. Halgren, Eric TI Experimental validation of the influence of white matter anisotropy on the intracranial EEG forward solution SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE LA English DT Article DE Forward solution; White matter anisotropy; Intracranial EEG; Validation; FEM; Finite element model; Source localization ID LOCALIZATION ACCURACY; HUMAN BRAIN; HUMAN SKULL; ELECTRICAL-STIMULATION; TISSUE CONDUCTIVITY; IMPLANTED SOURCES; FIELD; MEG; POTENTIALS; RESISTANCE AB Forward solutions with different levels of complexity are employed for localization of current generators, which are responsible for the electric and magnetic fields measured from the human brain. The influence of brain anisotropy on the forward solution is poorly understood. The goal of this study is to validate an anisotropic model for the intracranial electric forward solution by comparing with the directly measured 'gold standard'. Dipolar sources are created at known locations in the brain and intracranial electroencephalogram (EEG) is recorded simultaneously. Isotropic models with increasing level of complexity are generated along with anisotropic models based on Diffusion tensor imaging (DTI). A Finite Element Method based forward solution is calculated and validated using the measured data. Major findings are (1) An anisotropic model with a linear scaling between the eigenvalues of the electrical conductivity tensor and water self-diffusion tensor in brain tissue is validated. The greatest improvement was obtained when the stimulation site is close to a region of high anisotropy. The model with a global anisotropic ratio of 10:1 between the eigenvalues (parallel: tangential to the fiber direction) has the worst performance of all the anisotropic models. (2) Inclusion of cerebrospinal fluid as well as brain anisotropy in the forward model is necessary for an accurate description of the electric field inside the skull. The results indicate that an anisotropic model based on the DTI can be constructed non-invasively and shows an improved performance when compared to the isotropic models for the calculation of the intracranial EEG forward solution. C1 [Bangera, Nitin B.; Eisenberg, Solomon R.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Bangera, Nitin B.; Dehghani, Nima; Dale, Anders M.; Halgren, Eric] Univ Calif San Diego, Dept Radiol, Multimodal Imaging Lab, La Jolla, CA 92093 USA. [Schomer, Donald L.; Papavasiliou, Steve] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Ulbert, Istvan] Hungarian Acad Sci, Inst Psychol, Budapest, Hungary. [Cash, Sydney] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Bangera, Nitin B.] Illinois MEG Ctr, Alexian Bros Ctr Brain Res, Elk Grove Village, IL 60007 USA. [Bangera, Nitin B.; Dehghani, Nima; Dale, Anders M.; Halgren, Eric] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Bangera, NB (reprint author), Illinois MEG Ctr, Alexian Bros Ctr Brain Res, 955 Beisner Rd, Elk Grove Village, IL 60007 USA. EM nitinb@bu.edu RI Ulbert, Istvan/F-2213-2010; OI Dehghani, Nima/0000-0003-2032-8903 FU NIH [NS44623, NS18741]; Trustees of Boston University FX The authors would like to first and foremost acknowledge the selfless co-operation of the patients who participated in this study. The authors would like to thank Lawrence Gruber, Frank Kampmann and the EEG technicians from the EEG laboratory at the Beth Israel Deaconess Medical Center for their assistance in set-up and collection of the data. In addition, the authors would like to thank the Scientific Computing and Visualization Center (http://scv.bu.edu) at Boston University for proving access to the FEM software used in our analysis. This study was financially supported by NIH grants NS44623/NS18741 and Trustees of Boston University. NR 36 TC 20 Z9 20 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5313 J9 J COMPUT NEUROSCI JI J. Comput. Neurosci. PD DEC PY 2010 VL 29 IS 3 BP 371 EP 387 DI 10.1007/s10827-009-0205-z PG 17 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA 679LM UT WOS:000284162900002 PM 20063051 ER PT J AU Doron-LaMarca, S Vogt, DS King, DW King, LA Saxe, GN AF Doron-LaMarca, Susan Vogt, Dawne S. King, Daniel W. King, Lynda A. Saxe, Glenn N. TI Pretrauma Problems, Prior Stressor Exposure, and Gender as Predictors of Change in Posttraumatic Stress Symptoms Among Physically Injured Children and Adolescents SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE posttraumatic stress symptoms; gender; life stressors; internalizing and externalizing problems ID HURRICANE-ANDREW; RISK-FACTORS; VIETNAM VETERANS; TRAUMATIC INJURY; DISORDER; MODEL; SAMPLE; AGE; SYMPTOMATOLOGY; METAANALYSIS AB Objective: This study addressed predictors of change in posttraumatic stress symptoms (PTSS) among youths who had experienced physical injuries. The influences of pretrauma internalizing and externalizing problems, prior stressor exposure, and gender were investigated. Additionally, gender was examined as 3 moderator of the associations between internalizing problems and PTSS, externalizing problems and PTSS, and prior stressor exposure and PTSS, Method: Participants were 157 children and adolescents (75% male; age M = 13.30 years, SD = 3.60; 44% Caucasian, 39% African American, 13% Hispanic, and 4% other) admitted to 2 hospitals for physical injuries. Youths and their parents completed measures of PTSS (Child Posttraumatic Stress Reaction Index), internalizing and externalizing problems (Child Behavior Checklist), and prior stressor exposure (Coddington Life Events Scale, Child) during the hospital stay; youths completed up to 3 additional PTSS assessments targeted at 3, 6, and 12 months postinjury. Results: Multilevel regression analyses revealed a significant average decline in PTSS over time (p < .05) that followed a curvilinear trajectory. Externalizing problems, prior stressor exposure, and female gender predicted higher initial PTSS levels (p < .05). Gender moderated the influence of internalizing problems, externalizing problems, and prior stressor exposure on decline in PTSS over time (p < .05). Patterns of recovery for those with high and low levels of each characteristic differed for girls and boys. Conclusions: Findings suggest targets for clinical consideration, both with respect to identifying subgroups of children and adolescents that may warrant early assessment and monitoring and timing of more directed PTSS treatment intervention. C1 [Doron-LaMarca, Susan; King, Daniel W.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA. [Doron-LaMarca, Susan; Vogt, Dawne S.; King, Daniel W.; King, Lynda A.] Boston Univ, Div Psychiat, Sch Med, Boston, MA 02215 USA. [Vogt, Dawne S.; King, Lynda A.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. [King, Daniel W.; King, Lynda A.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Saxe, Glenn N.] Harvard Univ, Ctr Behav Sci, Childrens Hosp, Sch Med, Cambridge, MA 02138 USA. [Saxe, Glenn N.] Harvard Univ, Dept Psychiat, Sch Med, Cambridge, MA 02138 USA. RP King, LA (reprint author), 31 Lothrop St, Beverly, MA 01915 USA. EM lking@bu.edu OI Saxe, Glenn/0000-0002-4756-1169 FU NIMH NIH HHS [R01MH57370, R01MH68626, R01MH063247, R03MH77907] NR 63 TC 6 Z9 6 U1 2 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 2010 VL 78 IS 6 BP 781 EP 793 DI 10.1037/a0021529 PG 13 WC Psychology, Clinical SC Psychology GA 687YN UT WOS:000284814500002 PM 21114341 ER PT J AU McKay, JR Van Horn, DHA Oslin, DW Lynch, KG Ivey, M Ward, K Drapkin, ML Becher, JR Coviello, DM AF McKay, James R. Van Horn, Deborah H. A. Oslin, David W. Lynch, Kevin G. Ivey, Megan Ward, Kathleen Drapkin, Michelle L. Becher, Julie R. Coviello, Donna M. TI A Randomized Trial of Extended Telephone-Based Continuing Care for Alcohol Dependence: Within-Treatment Substance Use Outcomes SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE comparative effectiveness study; alcohol dependence; continuing care; telephone counseling; monitoring and feedback ID RECOVERY MANAGEMENT CHECKUPS; ADDICTION SEVERITY INDEX; USE DISORDERS; COCAINE DEPENDENCE; DRINKING BEHAVIOR; CLINICAL-TRIALS; SELF-REPORTS; FOLLOW-UP; DRUG-USE; RELIABILITY AB Objective: The study tested whether adding up to 18 months of telephone continuing care, either as monitoring and feedback (TM) or longer contacts that included counseling (TMC), to intensive outpatient programs (IOPs) improved outcomes for alcohol-dependent patients. Method: Participants (N = 252) who completed 3 weeks of IOP were randomized to up to 36 sessions of TM (M = 11.5 sessions), TMC (M = 9.1 sessions), or IOP only (treatment as usual [TAU]). Quarterly assessment of alcohol use (79.9% assessed at 18 months) was corroborated with available collateral reports (N = 63 at 12 months). Participants with cocaine dependence (N = 199) also provided urine samples. Results: Main effects favored TMC over TAU on any alcohol use (odds ratio [OR] = 1.88, CI [1.13, 3.14]) and any heavy alcohol use (OR = 1.74, CI [1.03, 2.94]). TMC produced fewer days of alcohol use during Months 10-18 and heavy alcohol use during Months 13-18 than TAU (ds = 0.46-0.65). TMC also produced fewer days of any alcohol use and heavy alcohol use than TM during Months 4-6 (ds = 0.39 and 0.43). TM produced lower percent days alcohol use than TAU during Months 10-12 and 13-15 (ds = 0.41 and 0.39). There were no treatment effects on rates of cocaine-positive urines. Conclusions: Adding telephone continuing care to IOP improved alcohol use outcomes relative to IOP alone. Conversely, shorter calls that provided monitoring and feedback but no counseling generally did not improve outcomes over IOP. C1 [McKay, James R.] Univ Penn, Ctr Continuum Care Addict, Dept Psychiat, Philadelphia, PA 19104 USA. [McKay, James R.; Oslin, David W.; Drapkin, Michelle L.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP McKay, JR (reprint author), Univ Penn, Ctr Continuum Care Addict, Dept Psychiat, 3440 Market St,Suite 370, Philadelphia, PA 19104 USA. EM mckay_j@mail.trc.upenn.edu FU NIAAA NIH HHS [P01 AA016821-01A1, R01 AA014850-01, R01 AA14850, P01 AA016821, R01 AA014850]; NIDA NIH HHS [K02 DA000361, K02 DA000361-02] NR 42 TC 31 Z9 31 U1 1 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 2010 VL 78 IS 6 BP 912 EP 923 DI 10.1037/a0020700 PG 12 WC Psychology, Clinical SC Psychology GA 687YN UT WOS:000284814500012 PM 20873894 ER PT J AU Taft, CT O'Farrell, TJ Doron-LaMarca, S Panuzio, J Suvak, MK Gagnon, DR Murphy, CM AF Taft, Casey T. O'Farrell, Timothy J. Doron-LaMarca, Susan Panuzio, Jillian Suvak, Michael K. Gagnon, David R. Murphy, Christopher M. TI Longitudinal Risk Factors for Intimate Partner Violence Among Men in Treatment for Alcohol Use Disorders SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE partner violence; alcohol and drug use; antisocial personality; relationship adjustment; anger ID MARITAL VIOLENCE; AGGRESSION; SCALES; PARTICIPATION; DEPENDENCE; AGREEMENT; OUTCOMES; SAMPLE; ANGER AB Objective: This study examined static and time-varying risk factors for perpetration of intimate partner violence (IPV) among men in treatment for alcohol use disorders. Method: Participants were 178 men diagnosed with alcohol abuse or dependence and their partners. Most (85%) of the men were European American; their average age was 41.0 years. Participants completed measures assessing initial alcohol problem severity, baseline beliefs related to alcohol use, antisocial personality characteristics, alcohol and drug use, relationship adjustment, and IPV. Results: According to couples' reconciled reports, 42% of participants perpetrated IPV at baseline. Among this group, the IPV recurrence rate was 43% at 6-month follow-up and 36% at 12-month follow-up. For participants without IPV perpetration at baseline, new incidence of IPV was 15% and 7% at the 6-month and 12-month follow-up points, respectively. Fixed marker predictors of IPV rates included baseline alcohol problem severity variables, baseline beliefs related to alcohol use, and antisocial personality characteristics. Variable risk factor predictors included alcohol and drug use variables, relationship adjustment factors, and anger. Alcohol use variables and anger were associated with new incidents of IPV among those without reported IPV at baseline only. Conclusions: Findings suggest that assessing and monitoring IPV occurrence by both partners is important for men in treatment for alcohol use disorders. Results indicate vulnerability factors that may identify individuals at risk for IPV and provide targets for IPV prevention among those with alcohol use disorders. These findings can aid in the development of more comprehensive models that more precisely predict IPV. C1 [Taft, Casey T.; Doron-LaMarca, Susan; Suvak, Michael K.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Taft, Casey T.; Doron-LaMarca, Susan] Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02215 USA. [O'Farrell, Timothy J.] Harvard Univ, Families & Addict Program, Dept Psychiat, Sch Med, Cambridge, MA 02138 USA. [Panuzio, Jillian] Univ Nebraska, Dept Psychol, Lincoln, NE 68583 USA. [Gagnon, David R.] Massachusetts Vet Epidemiol Res & Informat Ctr, VA Cooperat Studies Program, Boston, MA USA. [Gagnon, David R.] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA. [Murphy, Christopher M.] Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst 116B 2, 150 S Huntington Ave, Boston, MA 02130 USA. EM casey.taft@va.gov OI Gagnon, David/0000-0002-6367-3179 NR 44 TC 27 Z9 27 U1 1 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 2010 VL 78 IS 6 BP 924 EP 935 DI 10.1037/a0021093 PG 12 WC Psychology, Clinical SC Psychology GA 687YN UT WOS:000284814500013 PM 20954758 ER PT J AU George, M Rand-Giovannetti, D Eakin, MN Borrelli, B Zettler, M Riekert, KA AF George, Maureen Rand-Giovannetti, Devin Eakin, Michelle N. Borrelli, Belinda Zettler, Melissa Riekert, Kristin A. TI Perceptions of barriers and facilitators Self-management decisions by older adolescents and adults with CF SO JOURNAL OF CYSTIC FIBROSIS LA English DT Article DE Sell management; Adherence; Quality of life; Feedback ID CYSTIC-FIBROSIS; TREATMENT ADHERENCE; CHILDREN AB Background Adherence to CF treatments is poor, which can lead to negative health outcomes The objective of our study was to qualitatively investigate the barriers and facilitators of self-management among older adolescents and adults with CF Methods Individual semi-structured interviews were conducted, audio-taped, transcribed verbatim and coded to identify common themes Results Twenty-five patients were interviewed Four broad themes were identified Bar tiers to Self-Management (e g, treatment burden (identified by 64% of patients) accidental or purposeful forgetting (60%), no perceived benefit (56%)) Facilitators of Self-Management (e g, CF clinic visits (76%), social support (68%) perceived benefit (68%)), Substitution of Alternative Approaches to Conventional Management (36%) and Planned Non-adherence (32%) Conclusions Older adolescents and adults with CF identified many barriers and facilitators of adherence that may be amenable to self-management counseling strategies particularly the use of health feedback (C) 2010 European Cystic Fibrosis Society Published by Elsevier B V All rights reserved C1 [Rand-Giovannetti, Devin; Eakin, Michelle N.; Riekert, Kristin A.] Johns Hopkins Univ, Johns Hopkins Adherence Res Ctr, Baltimore, MD 21224 USA. [George, Maureen] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Family & Community Hlth Div, Philadelphia, PA 19104 USA. [Borrelli, Belinda] Brown Med Sch, Ctr Behav & Prevent Med, Providence, RI 02903 USA. [Borrelli, Belinda] Miriam Hosp, Providence, RI 02903 USA. [Zettler, Melissa] Johns Hopkins Univ, Kennedy Krieger Inst, Baltimore, MD 21205 USA. RP Riekert, KA (reprint author), Johns Hopkins Univ, Johns Hopkins Adherence Res Ctr, 5501 Hopkins Bayview Circle 4B 74, Baltimore, MD 21224 USA. RI Hanghoj, Signe/E-2440-2012; OI Borrelli, Belinda/0000-0002-0859-796X FU National Heart Lung Blood Institute [HL87997] FX This research was supported by the National Heart Lung Blood Institute grant HL87997 The study sponsors had no role in the study design, collection, analysis, or interpretation of data, or in the writing of the manuscript or decision to submit for publication NR 23 TC 33 Z9 33 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-1993 J9 J CYST FIBROS JI J. Cyst. Fibros PD DEC PY 2010 VL 9 IS 6 BP 425 EP 432 DI 10.1016/j.jcf.2010.08.016 PG 8 WC Respiratory System SC Respiratory System GA 699ZI UT WOS:000285701500007 PM 20846910 ER PT J AU Tye, CE Sharma, R Smith, CE Bartlett, JD AF Tye, C. E. Sharma, R. Smith, C. E. Bartlett, J. D. TI Altered Ion-responsive Gene Expression in Mmp20 Null Mice SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE enamel; pH; MMP20; amelogenesis; mineralization ID RAT INCISOR ENAMEL; CYSTIC-FIBROSIS; AMELOGENESIS IMPERFECTA; ANION-EXCHANGER; MINERAL-CONTENT; PH; AE2; AMELOBLASTS; MATURATION; ACIDOSIS AB During enamel maturation, hydroxyapatite crystallites expand in volume, releasing protons that acidify the developing enamel. This acidity is neutralized by the buffering activity of carbonic anhydrases and ion transporters. Less hydroxyapatite forms in matrix metalloproteinase-20 null (Mmp20(-/-)) mouse incisors, because enamel thickness is reduced by approximately 50%. We therefore asked if ion regulation was altered in Mmp20(-/-) mouse enamel. Staining of wild-type and Mmp20(-/-) incisors with pH indicators demonstrated that wild-type mice had pronounced changes in enamel pH as development progressed. These pH changes were greatly attenuated in Mmp20(-/-) mice. Expression of 4 ion-regulatory genes (Atp2b4, Slc4a2, Car6, Cftr) was significantly decreased in enamel organs from Mmp20(-/-) mice. Notably, expression of secreted carbonic anhydrase ( Car6) was reduced to almost undetectable levels in the null enamel organ. In contrast, Odam and Klk4 expression was unaffected. We concluded that a feedback mechanism regulates ion-responsive gene expression during enamel development. C1 [Tye, C. E.; Sharma, R.; Bartlett, J. D.] Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst, Boston, MA 02115 USA. [Tye, C. E.; Sharma, R.; Bartlett, J. D.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Smith, C. E.] Univ Montreal, Fac Med Dent, Montreal, PQ H3C 3J7, Canada. [Smith, C. E.] McGill Univ, Fac Dent, Montreal, PQ, Canada. RP Bartlett, JD (reprint author), Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst, 188 Longwood Ave, Boston, MA 02115 USA. EM jbartlett@forsyth.org RI Sharma, Ramaswamy/F-8401-2012; Testes, Olga/E-8912-2013 FU National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA [DE016276] FX This investigation was supported by research grant DE016276 from the National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA. NR 34 TC 3 Z9 3 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2010 VL 89 IS 12 BP 1421 EP 1426 DI 10.1177/0022034510384625 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 684EG UT WOS:000284531100014 PM 20929715 ER PT J AU Cao, Z Sun, X Yeh, CK Sun, Y AF Cao, Z. Sun, X. Yeh, C. -K. Sun, Y. TI Rechargeable Infection-responsive Antifungal Denture Materials SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE antifungal denture; infection-responsive; rechargeable; Candida-associated denture stomatitis ID CANDIDA-ALBICANS; IN-VITRO; ACID PRODUCTION; SILVER-ZEOLITE; STOMATITIS; DELIVERY; GROWTH; BEHAVIOR AB Candida-associated denture stomatitis (CADS) is a significant clinical concern. We developed rechargeable infection-responsive antifungal denture materials for potentially managing the disease. Polymethacrylic acid (PMAA) was covalently bound onto diurethane dimethacrylate denture resins in the curing step. The PMAA resins bound cationic antifungal drugs such as miconazole and chlorhexidine digluconate (CG) through ionic interactions. The anticandidal activities of the drug-containing PMAA-resin discs were sustained for a prolonged period of time (weeks and months). Drug release was much faster at acidic conditions (pH 5) than at pH 7. Drugs bound to the denture materials could be "washed out" by treatment with EDTA, and the drug-depleted resins could be recharged with the same or a different class of anticandidal drugs. These results suggest clinical potential of the newly developed antifungal denture materials in the management of CADS and other infectious conditions. C1 [Cao, Z.; Sun, X.; Sun, Y.] Univ S Dakota, Biomed Engn Program, Sioux Falls, SD 57107 USA. [Yeh, C. -K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Dent Diagnost Sci, San Antonio, TX 78229 USA. [Yeh, C. -K.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Sun, Y (reprint author), Univ S Dakota, Biomed Engn Program, 4800 N Career Ave, Sioux Falls, SD 57107 USA. EM yuyu.sun@usd.edu FU NIH, NIDCR [R03DE018735] FX This study was sponsored by NIH, NIDCR (R03DE018735). NR 23 TC 15 Z9 15 U1 2 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2010 VL 89 IS 12 BP 1517 EP 1521 DI 10.1177/0022034510379604 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 684EG UT WOS:000284531100031 PM 20940361 ER PT J AU Kosaka, S Yasumoto, M Akilov, OE Hasan, T Kawana, S AF Kosaka, Sachiko Yasumoto, Minako Akilov, Oleg E. Hasan, Tayyaba Kawana, Seiji TI Comparative split-face study of 5-aminolevulinic acid photodynamic therapy with intense pulsed light for photorejuvenation of Asian skin SO JOURNAL OF DERMATOLOGY LA English DT Article DE 5-aminolevulinic acid photodynamic therapy; Asian; intense pulsed light; photoaging; rejuvenation AB Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) (ALA-PDT) using intense pulsed light (IPL) as a light source (IPL-ALA-PDT) has been used for photorejuvenation, but it is unclear if this protocol can be applied to darker skin types. We performed this study to assess our IPL-ALA-PDT protocol for photorejuvenation in Asian skin. To determine an appropriate dose, ALA ointment (0-20%) was applied to the upper arm of five healthy volunteers and the fluorescence intensity (FI) was measured using a spectrofluorometer. Non-linear regression analysis of FI 2 h after ALA application with global fitting gave a typical sigmoid dose-response curve with R(2) = 0.9705 and saturation after 5% ALA. The entire faces of 16 Japanese women with photodamage were then treated with IPL (500-670 and 870-1400 nm, 23-30 J/cm(2)) 2 h after application of 5% ALA to one side of the face. Three treatments were delivered at 4-week intervals with follow-up visits. Comparative analysis of photorejuvenation showed noticeable improvements on both sides of the face, although the reduction in the photoaging score from baseline did not differ significantly between the two sides in all subjects. Despite this finding, 75% of the patients felt that the IPL-ALA-PDT-treated side of the face showed greater improvement than the IPL-treated side. However, all IPL-ALA-PDT-treated sides showed adverse effects such as erythema and pain. Therefore, we conclude that the IPL-ALA-PDT protocol requires optimization for photorejuvenation in Asians. C1 [Kosaka, Sachiko] Nippon Med Sch, Dept Dermatol, Bunkyo Ku, Tokyo 1138603, Japan. [Akilov, Oleg E.; Hasan, Tayyaba] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, Boston, MA USA. RP Kosaka, S (reprint author), Nippon Med Sch, Dept Dermatol, Bunkyo Ku, 1-1-5 Sendagi, Tokyo 1138603, Japan. EM p-chan@nms.ac.jp NR 11 TC 14 Z9 14 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0385-2407 J9 J DERMATOL JI J. Dermatol. PD DEC PY 2010 VL 37 IS 12 BP 1005 EP 1010 DI 10.1111/j.1346-8138.2010.00946.x PG 6 WC Dermatology SC Dermatology GA 682BA UT WOS:000284370500001 PM 21083701 ER PT J AU Alkasab, TK Harris, MA Zalis, ME Dreyer, KJ Rosenthal, DI AF Alkasab, Tarik K. Harris, Mitchell A. Zalis, Michael E. Dreyer, Keith J. Rosenthal, Daniel I. TI A Case Tracking System with Electronic Medical Record Integration to Automate Outcome Tracking for Radiologists SO JOURNAL OF DIGITAL IMAGING LA English DT Article DE Web technology; databases; radiology teaching files; quality assurance; Electronic Medical Record (EMR); productivity; Radiology Information Systems (RIS); radiology workflow AB Radiologists make many diagnoses, but only sporadically get feedback on the subsequent clinical courses of their patients. We have created a web-based application that empowers radiologists to create and maintain personal databases of cases of interest. This tool integrates with existing information systems to minimize manual input such that radiologists can quickly flag cases for further follow-up without interrupting their clinical work. We have integrated this case-tracking system with an electronic medical record aggregation and search tool. As a result, radiologists can learn the outcomes of their patients with much less effort. We intend this tool to aid radiologists in their own personal quality improvement and to increase the efficiency of both teaching and research. We also hope to develop the system into a platform for systematic, continuous, quantitative monitoring of performance in radiology. C1 [Alkasab, Tarik K.; Harris, Mitchell A.; Zalis, Michael E.; Dreyer, Keith J.; Rosenthal, Daniel I.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Alkasab, Tarik K.; Harris, Mitchell A.; Zalis, Michael E.; Dreyer, Keith J.; Rosenthal, Daniel I.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Alkasab, TK (reprint author), Massachusetts Gen Hosp, Dept Radiol, FND 216,55 Fruit St, Boston, MA 02114 USA. EM talkasab@partners.org OI Alkasab, Tarik/0000-0002-4433-9482 FU RSNA Research and Education Foundation FX The authors express their thanks to Drs. Laura Avery, Matthew Cushing, and Vincent Flanders for serving as early test users. This work is supported by a Resident Research Grant to TKA from the RSNA Research and Education Foundation. NR 10 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD DEC PY 2010 VL 23 IS 6 BP 658 EP 665 DI 10.1007/s10278-009-9228-2 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 679LQ UT WOS:000284163300002 PM 19760294 ER PT J AU Zhong, Y Garcia, R Kaye, EK Cai, JW Kaufman, JS Trope, M Wilcosky, T Caplan, DJ AF Zhong, Yan Garcia, Raul Kaye, Elizabeth K. Cai, Jianwen Kaufman, Jay S. Trope, Martin Wilcosky, Tim Caplan, Daniel J. TI Association of Endodontic Involvement with Tooth Loss in the Veterans Affairs Dental Longitudinal Study SO JOURNAL OF ENDODONTICS LA English DT Article DE Apical radiolucency; endodontics; epidemiology; root canal therapy; survival analysis; tooth loss ID ROOT-CANAL TREATMENT; TREATED TEETH; FILLED TEETH; RISK-FACTORS; SURVIVAL; POPULATION; ADULTS AB Introduction: The effect of endodontic involvement on tooth loss has not been quantified, so the present study aimed to assess this relationship after controlling for other relevant risk factors for tooth loss. Methods: We analyzed data from 791 participants (18,798 teeth) in the Veterans Affairs Dental Longitudinal Study. Potential tooth-level and person-level covariates were fitted into marginal proportional hazards models, including both apical radiolucencies (AR) and root canal therapy (RCT) status as time-dependent variables. Survival curves were plotted for teeth according to their AR and RCT status. Results: Both current AR and RCT status were associated with increased risk of tooth loss (P < .01), after controlling for baseline levels of periodontal disease, caries, tooth type, number of proximal contacts, number of teeth, age, education, and smoking history. Root canal filled (RCF) teeth seemed to have better survival than non-RCF teeth among teeth with AR but worse survival than non-RCF teeth among teeth without AR. Conclusions: Endodontic involvement was associated with tooth loss, controlling for other potential risk factors. Additional prospective studies are needed to provide better evidence as to the impact of endodontic involvement on tooth loss. (J Endod 2010;36:1943-1949) C1 [Zhong, Yan] Univ N Carolina, Dept Oral Epidemiol, Chapel Hill, NC USA. [Garcia, Raul; Kaye, Elizabeth K.] VA Boston Healthcare Syst, Boston, MA USA. [Garcia, Raul; Kaye, Elizabeth K.] Boston Univ, Henry M Goldman Sch Dent Med, Boston, MA 02215 USA. [Cai, Jianwen] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Kaufman, Jay S.; Wilcosky, Tim] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [Trope, Martin] Univ N Carolina, Sch Dent, Dept Endodont, Chapel Hill, NC USA. [Caplan, Daniel J.] Univ Iowa, Coll Dent, Dept Prevent & Community Dent, Iowa City, IA 52242 USA. RP Zhong, Y (reprint author), 1441 Shoal Dr, San Mateo, CA 94404 USA. EM yanzhong06@gmail.com OI Garcia, Raul/0000-0003-2153-4629; Kaye, Elizabeth/0000-0001-7529-2501; Kaufman, Jay/0000-0003-1606-401X FU U.S. Department of Veterans Affairs; VA HSRD Service; National Institute of Dental and Craniofacial Research [K24-DE00419]; NIH [UL1 RR025747]; NIDCR [R01 DE013807, R03 DE017948, R03 DE016357] FX The authors thank Drs Jeffrey Hatter, Joel Chasm, Ryan Yamanaka, and John Stamm, without whose assistance this study would not have been possible. The VA Dental Longitudinal Study and the VA Normative Aging Study are components of the Massachusetts Veterans Epidemiology Research & Information Center, VA Boston Healthcare System, Boston, MA. The studies are supported by the VA Cooperative Studies Program/ERIC, U.S. Department of Veterans Affairs. Dr Garcia was the recipient of a Career Development Award in Health Services Research from VA HSR&D Service. He is supported by a VA Epidemiology Merit Review Award and by NIH grant K24-DE00419 from the National Institute of Dental and Craniofacial Research. Dr. Cai is supported by NIH grant UL1 RR025747. The study was also supported by NIDCR Grants R01 DE013807, R03 DE017948, and R03 DE016357. NR 35 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-2399 J9 J ENDODONT JI J. Endod. PD DEC PY 2010 VL 36 IS 12 BP 1943 EP 1949 DI 10.1016/j.joen.2010.08.051 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 692AR UT WOS:000285124400004 PM 21092810 ER PT J AU Carrasquillo, O Betancourt, J AF Carrasquillo, Olveen Betancourt, Joseph TI Massachusetts Health Disparities: Key Lessons for the Nation SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 [Carrasquillo, Olveen] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Betancourt, Joseph] Harvard Univ, Sch Med, Boston, MA USA. [Betancourt, Joseph] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA. RP Carrasquillo, O (reprint author), Univ Miami, Miller Sch Med, Clin Res Bldg,Room 968 Locater Code C223,1120 NW, Miami, FL 33136 USA. EM oc6@med.miami.edu NR 5 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2010 VL 25 IS 12 BP 1266 EP 1267 DI 10.1007/s11606-010-1535-2 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 690CN UT WOS:000284978700002 PM 20957446 ER PT J AU Tsuang, DW Jayadev, S Bird, TD AF Tsuang, Debby W. Jayadev, Suman Bird, Thomas D. TI Updates on the Genetics of Neurodegenerative Disorders SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Editorial Material DE genetics; neurodegeneration; dementia AB Since the publication in 1998 of the last special issue of JGPN on the genetics of dementia, we have witnessed the completion of the Human Genome Project and an exponential increase in the identification of causative genes in human diseases. This special issue revisits the 6 neurodegenerative disorders described in that issue, offering important updates to the genetic findings for these disorders that together comprise the most common causes of dementia among elderly people. It is critical for practicing neurologists, psychiatrists, and geriatricians to keep abreast of these advances as they will impact the clinical diagnosis and management of these disorders. The reviews in this issue have been written by an outstanding group of international experts who provide a clear and insightful update on the molecular genetic advances and genetic counseling principles for each disorder. C1 [Tsuang, Debby W.; Jayadev, Suman; Bird, Thomas D.] Univ Washington, Seattle, WA 98195 USA. [Tsuang, Debby W.; Bird, Thomas D.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Tsuang, DW (reprint author), Univ Washington, Seattle, WA 98195 USA. EM dwt1@u.washington.edu RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU NIA NIH HHS [P50 AG005136] NR 0 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD DEC PY 2010 VL 23 IS 4 BP 211 EP 212 DI 10.1177/0891988710383575 PG 2 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 674DL UT WOS:000283714000001 PM 20923756 ER PT J AU Bekris, LM Yu, CE Bird, TD Tsuang, DW AF Bekris, Lynn M. Yu, Chang-En Bird, Thomas D. Tsuang, Debby W. TI Genetics of Alzheimer Disease SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Review DE Alzheimer disease; genetics; neurodegeneration ID AMYLOID-PRECURSOR-PROTEIN; APOLIPOPROTEIN-E GENOTYPE; GAMMA-SECRETASE ACTIVITY; ELDERLY AFRICAN-AMERICANS; BETA-PROTEIN; TRANSGENIC MICE; MESSENGER-RNAS; EPSILON-4 ALLELE; SENILE PLAQUES; E POLYMORPHISM AB Alzheimer disease (AD) is the most common causes of neurodegenerative disorder in the elderly individuals. Clinically, patients initially present with short-term memory loss, subsequently followed by executive dysfunction, confusion, agitation, and behavioral disturbances. Three causative genes have been associated with autosomal dominant familial AD (APP, PSEN1, and PSEN2) and 1 genetic risk factor (APOE epsilon 4 allele). Identification of these genes has led to a number of animal models that have been useful to study the pathogenesis underlying AD. In this article, we provide an overview of the clinical and genetic features of AD. C1 [Tsuang, Debby W.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. [Bekris, Lynn M.; Yu, Chang-En] Univ Washington, Sch Med, Dept Med, Seattle, WA 98108 USA. [Bird, Thomas D.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98108 USA. RP Tsuang, DW (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, VAPSHCS 116,1660 S Columbian Way, Seattle, WA 98108 USA. EM dwt1@u.washington.edu RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU VA Puget Sound Health Care System, Seattle, Washington; U.S. Department of Veterans Affairs; Office of Research and Development; Biomedical Laboratory Research Program; NIH [T32 AG000258]; Mental Illness Research Education and Clinical Center; Geriatric Research Education and Clinical Center; The University of Washington Alzheimer's Disease Research Center [NIA AG005136] FX This material is the result of work supported by resources from the VA Puget Sound Health Care System, Seattle, Washington.; The author(s) disclosed receipt of the following financial support for the research and/or authorship of this article: supported in part by the U.S. Department of Veterans Affairs, Office of Research and Development, Biomedical Laboratory Research Program and NIH Training Grant: T32 AG000258; Mental Illness Research Education and Clinical Center; Geriatric Research Education and Clinical Center. The University of Washington Alzheimer's Disease Research Center, NIA AG005136. NR 177 TC 162 Z9 168 U1 9 U2 36 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD DEC PY 2010 VL 23 IS 4 BP 213 EP 227 DI 10.1177/0891988710383571 PG 15 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 674DL UT WOS:000283714000002 PM 21045163 ER PT J AU Bekris, LM Mata, IF Zabetian, CP AF Bekris, Lynn M. Mata, Ignacio F. Zabetian, Cyrus P. TI The Genetics of Parkinson Disease SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE genetics; neurodegeneration; Parkinson disease ID EARLY-ONSET PARKINSONISM; ALPHA-SYNUCLEIN GENE; RECESSIVE JUVENILE PARKINSONISM; AUTOSOMAL-DOMINANT PARKINSONISM; PROGRESSIVE SUPRANUCLEAR PALSY; PATHOGENIC DJ-1 MUTATIONS; GENOME-WIDE ASSOCIATION; LEWY BODY DISORDERS; MAPT H1 HAPLOTYPE; PINK1 MUTATIONS AB Parkinson disease (PD) is the second most common neurodegenerative disorder. In most instances, PD is thought to result from a complex interaction between multiple genetic and environmental factors, though rare monogenic forms of the disease do exist. Mutations in 6 genes (SNCA, LRRK2, PRKN, DJ1, PINK1, and ATP13A2) have conclusively been shown to cause familial parkinsonism. In addition, common variation in 3 genes (MAPT, LRRK2, and SNCA) and loss-of-function mutations in GBA have been well-validated as susceptibility factors for PD. The function of these genes and their contribution to PD pathogenesis remain to be fully elucidated. The prevalence, incidence, clinical manifestations, and genetic components of PD are discussed in this review. C1 [Bekris, Lynn M.; Mata, Ignacio F.; Zabetian, Cyrus P.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Bekris, Lynn M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Mata, Ignacio F.; Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. RP Bekris, LM (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM lbekris@u.washington.edu OI Fernandez Mata, Ignacio/0000-0003-1198-0633; Zabetian, Cyrus/0000-0002-7739-4306 FU Department of Veterans Affairs [1I01BX000531]; National Institutes of Health [P50 NS062684, R01 NS065070, T32 AG000258] FX The author(s) disclosed receipt of the following financial support for the research and/or authorship of this article: the Department of Veterans Affairs (1I01BX000531, Office and Research and Development, Biomedical Laboratory Research Program) and the National Institutes of Health (P50 NS062684, R01 NS065070 and T32 AG000258). NR 215 TC 123 Z9 136 U1 4 U2 15 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD DEC PY 2010 VL 23 IS 4 BP 228 EP 242 DI 10.1177/0891988710383572 PG 15 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 674DL UT WOS:000283714000003 PM 20938043 ER PT J AU Guitton, TG Zurakowski, D van Dijk, NC Ring, D AF Guitton, Thierry G. Zurakowski, David van Dijk, Niek C. Ring, David TI Incidence and Risk Factors for the Development of Radiographic Arthrosis After Traumatic Elbow Injuries SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Arthrosis; elbow; osteoarthritis; posttraumatic; predictors ID FRACTURE-DISLOCATIONS; RADIAL HEAD; ADULTS; OLECRANON; HUMERUS AB Purpose Radiographic arthrosis is a common sequela of elbow trauma Few studies have addressed risk factors for radiographic arthrosis after elbow injury, especially in the long term Data from multiple long-term follow-up studies of patients with surgically treated elbow fractures provided us with an opportunity to assess risk factors for long-term radiographic arthrosis after elbow injury Methods During a 5-year period, we obtained radiographs during a research-specific evaluation of 139 patients (81 men and 58 women) 10 or more years (median, 19 5 y, range, 10-34 y) after surgical treatment of an elbow fracture as part of multiple retrospective studies Radiographic arthrosis was graded according to the system of Broberg and Money Bivariate and multivariable analyses evaluated risk factors for radiographic arthrosis Results Of 139 patients, 75 had radiographic evidence of arthrosis at final evaluation and 32 had moderate or severe radiographic arthrosis Mechanism of injury, age, gender, follow-up time, occupation, and limb dominance were not associated with radiographic arthrosis Multiple logistic regression analysis identified the type of injury as the only independent predictor of moderate to severe radiographic arthrosis Patients with a bicolumnar fracture of the distal humerus, a capitellum/trochlear fracture, or an elbow fracture dislocation were 8 0, 7 3, and 5 2 times more likely (odds ratio), respectively, to develop radiographic evidence of moderate or severe radiographic arthrosis than the average patient in this cohort Conclusions Distal humerus fractures (both columnar and capitellum/trochlea) and elbow fracture dislocations are more likely than fractures of the olecranon and radial head to develop moderate or severe radiographic arthrosis m the long term (J Hand Surg 2010,35A 1976-1980 (C) 2010 Published by Elsevier Inc on behalf of the American Society for Surgery of the Hand) C1 [Ring, David] Harvard Univ, Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv,Med Sch, Boston, MA 02114 USA. Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv,Med Sch, Suite 2100,55 Fruit St, Boston, MA 02114 USA. OI Guitton, Thierry/0000-0002-2599-1985 FU Stryker Joint Active Systems; Biomet FX D R receives royalties from Hand Innovations Skeletal Dynamics and Wright Medical He is a paid consultant to Wright Medical Tornier Acumed and Skeletal Dynamics He received research specific grants from Stryker Joint Active Systems and Biomet and honoraria/travel from AO North America and AO International He has stock options in Illuminos Inc and Mimedex Inc NR 18 TC 12 Z9 13 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD DEC PY 2010 VL 35A IS 12 BP 1976 EP 1980 DI 10.1016/j.jhsa.2010.08.010 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 695LJ UT WOS:000285371300009 PM 20961703 ER PT J AU Ojwang, JO Adrianto, I Gray-McGuire, C Nath, SK Sun, C Kaufman, KM Harley, JB Rayan, GM AF Ojwang, Joshua O. Adrianto, Indra Gray-McGuire, Courtney Nath, Swapan K. Sun, Celi Kaufman, Kenneth M. Harley, John B. Rayan, Ghazi M. TI Genome-Wide Association Scan of Dupuytren's Disease SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Dupuytren's disease; Dupuytren's disease genetics; admixture mapping; SNP analysis ID GENETIC SUSCEPTIBILITY; CONTRACTURE; POPULATIONS; ADMIXTURE; LINKAGE AB Purpose Dupuytren's disease (DD) has a strong genetic component that is suggested by population studies and family clustering Genetic studies have yet to identify the gene(s) involved in DD The purpose of this study was to identify regions of the entire genome (chromosomes 1-23) associated with the disease by performing a genome-wide association scan on DD patients and controls Methods We isolated genomic DNA from saliva collected from 40 unrelated DD patients and 40 unaffected controls We conducted the genotyping using CytoSNP-Infinium HD Ultra genotyping assay on the Illumina platform Using both log regression and mapping by admixture linkage disequilibrium analysis methods, we analyzed the single nucleotide polymorphism genotyping data Results Single nucleotide polymorphism analysis revealed a significant association in regions for chromosomes 1, 3 through 6, 11, 16, 17, and 23 Mapping by admixture linkage disequilibrium analysis showed ancestry-associated regions in chromosomes 2, 6, 8, 11, 16, and 20, which may harbor DD susceptibility genes Both analysis methods revealed loci association in chromosomes 6, 11, and 16 Conclusions Our data suggest that chromosomes 6, 11, and 16 may contain the genes for DD and that multiple genes may be involved in DD Future genetic studies on DD should focus on these areas of the genome (J Hand Surg 2010,35A 2039-2045 (C) 2010 Published by Elsevier Inc on behalf of the American Society for Surgery of the Hand) C1 Univ Oklahoma, Dept Arthrit & Immunol, Oklahoma Med Res Fdn, Dept Orthoped Surg, Oklahoma City, OK USA. Univ Oklahoma, Hlth Sci Ctr, Dept Med, Div Hand Surg,Integris Baptists Med Ctr, Oklahoma City, OK USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Rayan, GM (reprint author), 3366 NW Expressway, Oklahoma City, OK 73112 USA. RI Sun, Celi/A-7563-2013; Adrianto, Indra/D-4214-2013 OI Adrianto, Indra/0000-0002-9973-3057 FU National Institutes of Health [N01 AR62277, P01 AI 083194, R37 AI 24717, R01 AR42460, P01 AR049084, P20-RR020143, R01 AI045050, P30 AR053483]; US Department of Veteran Affairs; Alliance for Lupus Research; Lupus Family Registry and Repository FX Supported in part by National Institutes of Health grants N01 AR62277 P01 AI 083194 R37 AI 24717 R01 AR42460 P01 AR049084 P20-RR020143 R01 AI045050 and P30 AR053483 the US Department of Veteran Affairs the Alliance for Lupus Research and the Lupus Family Registry and Repository NR 24 TC 10 Z9 10 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD DEC PY 2010 VL 35A IS 12 BP 2039 EP 2045 DI 10.1016/j.jhsa.2010.08.008 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 695LJ UT WOS:000285371300019 PM 20971583 ER PT J AU Peterson, SL Freeland, AE AF Peterson, Steven L. Freeland, Alan E. TI Scapholunate Stabilization With Dynamic Extensor Carpi Radialis Longus Tendon Transfer SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Review DE Scapholunate dissociation; tendon transfer ID DORSAL INTERCARPAL LIGAMENT; DISSOCIATION; INSTABILITY; WRIST; CAPSULODESIS; PATHOMECHANICS; REPAIR AB Dynamic extensor carpi radians longus tendon transfer to the distal pole of the scaphoid acts synchronously and synergistically with wrist motion to restore the slider crank mechanism of the scaphoid after scapholunate interosseous ligament (SLIL) injury The procedure is designed to simulate a hypothetical dorsal radioscaphoid ligament that more closely approximates the normal viscoelastic forces acting on the scaphoid throughout all phases of wrist motion than does the static checkrein effect and motion limitations of capsulodesis or tenodesis Extensor carpi radians longus transfer may be independently sufficient to support normal or near-normal scapholunate and midcarpal kinematics and prevent further injury propagation in patients with partial SLIL tears and dynamic scapholunate instability Extensor carpi radians longus transfer alone may improve carpal congruity in patients with static scapholunate instability, but SLIL and dorsal lunate ligament repair or reconstruction is essential for favorable durable outcomes Extensor carpi radians longus transfer offers a simple and reasonable alternative to capsulodesis or tenodesis to support these ligament repairs or reconstructions, does not require intercarpal fixation, and allows rehabilitation to proceed expeditiously at approximately 1 month after surgery (J Hand Surg 2010,35A 2093-2100 (C) 2010 Published by Elsevier Inc on behalf of the American Society for Surgery of the Hand) C1 [Peterson, Steven L.] Portland VA Med Ctr, Operat Care Div, Portland, OR 97201 USA. Univ Mississippi, Med Ctr, Dept Orthoped Surg & Rehabil, Jackson, MS 39216 USA. RP Peterson, SL (reprint author), Portland VA Med Ctr, Operat Care Div, 3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. NR 21 TC 4 Z9 4 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD DEC PY 2010 VL 35A IS 12 BP 2093 EP 2100 DI 10.1016/j.jhsa.2010.09.021 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 695LJ UT WOS:000285371300028 PM 21134618 ER PT J AU Wucherpfennig, KW AF Wucherpfennig, Kai W. TI The First Structures of T Cell Receptors Bound to Peptide-MHC SO JOURNAL OF IMMUNOLOGY LA English DT Editorial Material ID CLASS-II MOLECULE; ALPHA-BETA; SELF-PEPTIDE; COMPLEX; ANTIGEN; RECOGNITION; BINDING; HLA-A2; CRYSTALLIZATION; H-2K(B) C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, 44 Binney St,Room D1410, Boston, MA 02115 USA. EM Kai_Wucherpfennig@dfci.harvard.edu NR 26 TC 3 Z9 3 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2010 VL 185 IS 11 BP 6391 EP 6393 DI 10.4049/jimmunol.1090110 PG 3 WC Immunology SC Immunology GA 681KJ UT WOS:000284311500001 PM 21084667 ER PT J AU Albacker, LA Karisola, P Chang, YJ Umetsu, SE Zhou, MX Akbari, O Kobayashi, N Baumgarth, N Freeman, GJ Umetsu, DT DeKruyff, RH AF Albacker, Lee A. Karisola, Piia Chang, Ya-Jen Umetsu, Sarah E. Zhou, Meixia Akbari, Omid Kobayashi, Norimoto Baumgarth, Nicole Freeman, Gordon J. Umetsu, Dale T. DeKruyff, Rosemarie H. TI TIM-4, a Receptor for Phosphatidylserine, Controls Adaptive Immunity by Regulating the Removal of Antigen-Specific T Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDUCED AIRWAY HYPERREACTIVITY; APOPTOTIC CELLS; PERIPHERAL TOLERANCE; TRANSGENIC MICE; ACTIVATION; RESPONSES; FAMILY; PHAGOCYTOSIS; LIGAND; DIFFERENTIATION AB Adaptive immunity is characterized by the expansion of an Ag-specific T cell population following Ag exposure. The precise mechanisms, however, that control the expansion and subsequent contraction in the number of Ag-specific T cells are not fully understood. We show that T cell/transmembrane, Ig, and mucin (TIM)-4, a receptor for phosphatidylserine, a marker of apoptotic cells, regulates adaptive immunity in part by mediating the removal of Ag-specific T cells during the contraction phase of the response. During Ag immunization or during infection with influenza A virus, blockade of TIM-4 on APCs increased the expansion of Ag-specific T cells, resulting in an increase in secondary immune responses. Conversely, overexpression of TIM-4 on APCs in transgenic mice reduced the number of Ag-specific T cells that remained after immunization, resulting in reduced secondary T cell responses. There was no change in the total number of cell divisions that T cells completed, no change in the per cell proliferative capacity of the remaining Ag-specific T cells, and no increase in the development of Ag-specific regulatory T cells in TIM-4 transgenic mice. Thus, TIM-4-expressing cells regulate adaptive immunity by mediating the removal of phosphatidylserine-expressing apoptotic, Ag-specific T cells, thereby controlling the number of Ag-specific T cells that remain after the clearance of Ag or infection. The Journal of Immunology, 2010, 185: 6839-6849. C1 [DeKruyff, Rosemarie H.] Childrens Hosp Boston, Div Immunol, Karp Labs, Boston, MA 02115 USA. [Kobayashi, Norimoto; Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Albacker, Lee A.; Karisola, Piia; Chang, Ya-Jen; Zhou, Meixia; Akbari, Omid; Umetsu, Dale T.; DeKruyff, Rosemarie H.] Harvard Univ, Sch Med, Dept Pediat, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kobayashi, Norimoto; Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Umetsu, Sarah E.] Northwestern Univ, Feinberg Sch Med, Dept Microbiol Immunol, Chicago, IL 60611 USA. [Baumgarth, Nicole] Univ Calif Davis, Sch Vet Med, Dept Pathol, Davis, CA 95616 USA. [Baumgarth, Nicole] Univ Calif Davis, Sch Vet Med, Dept Microbiol, Davis, CA 95616 USA. [Baumgarth, Nicole] Univ Calif Davis, Sch Vet Med, Dept Immunol, Davis, CA 95616 USA. RP DeKruyff, RH (reprint author), Childrens Hosp Boston, Div Immunol, Karp Labs, Room 10126,1 Blackfan Circle, Boston, MA 02115 USA. EM rosemarie.dekruyff@childrens.harvard.edu FU National Institutes of Health [P01 AI054456, HL069507]; Academy of Finland [112860]; Division of Medical Sciences, Harvard University FX This work was supported by National Institutes of Health Grants P01 AI054456 (to D. T. U., G.J.F., and R. H. D.) and HL069507 (to R. H. D.), Academy of Finland Grant 112860 (to P. K.), and the Program on Immunology, Division of Medical Sciences, Harvard University (to L.A.A.). NR 55 TC 38 Z9 40 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2010 VL 185 IS 11 BP 6839 EP 6849 DI 10.4049/jimmunol.1001360 PG 11 WC Immunology SC Immunology GA 681KJ UT WOS:000284311500050 PM 21037090 ER PT J AU Zinzow, HM Resnick, HS Amstadter, AB McCauley, JL Ruggiero, KJ Kilpatrick, DG AF Zinzow, Heidi M. Resnick, Heidi S. Amstadter, Ananda B. McCauley, Jenna L. Ruggiero, Kenneth J. Kilpatrick, Dean G. TI Drug- or Alcohol-Facilitated, Incapacitated, and Forcible Rape in Relationship to Mental Health Among a National Sample of Women SO JOURNAL OF INTERPERSONAL VIOLENCE LA English DT Article DE rape; PTSD; depression; rape tactics; substance use ID POSTTRAUMATIC-STRESS-DISORDER; SEXUAL-ASSAULT; SYMPTOM SEVERITY; MODEL; EXPERIENCES; TRAUMA; IMPACT; PTSD; RISK AB Rape is a well-established risk factor for mental health disorders such as posttraumatic stress disorder (PTSD) and depression. However, most studies have focused on forcible rape tactics and have not distinguished these from tactics that involve drug or alcohol intoxication. The authors' aim was to examine correlates of PTSD and depression in a community sample of women, with particular emphasis on evaluating the unique effects of lifetime exposure to three specific rape tactics. A nationally representative sample of 3,001 noninstitutionalized, civilian, English-or Spanish-speaking women (aged 18-86 years) participated in a structured telephone interview by use of Computer-Assisted Telephone Interviewing (CATI) technology. Multivariable models showed that history of drug or alcohol-facilitated rape tactics (OR = 1.87, p<.05) and history of forcible rape tactics (OR = 3.46, p<.001) were associated with PTSD. History of forcible rape was associated with depression (OR = 3.65, p<.001). Forcible rape tactics were associated with a number of factors that may have contributed to their stronger association with mental health outcomes, including force, injury, lower income, revictimization history, and labeling the event as rape. The results underscore the importance of using a behaviorally specific assessment of rape history, as rape tactic and multiple rape history differentially predicted psychopathology outcomes. The association between drug-or alcohol-facilitated rape tactics and PTSD suggests that these are important rape tactics to include in assessments and future studies. C1 [Zinzow, Heidi M.] Clemson Univ, Dept Psychol, Clemson, SC 29634 USA. [Resnick, Heidi S.] Med Univ S Carolina, Natl Crime Victims Res & Treatment Ctr, Dept Psychiat, Charleston, SC USA. [Amstadter, Ananda B.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. [Ruggiero, Kenneth J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Zinzow, HM (reprint author), Clemson Univ, Dept Psychol, 418 Brackett Hall, Clemson, SC 29634 USA. EM hzinzow@clemson.edu FU NIMH NIH HHS [F32 MH083469, F32 MH083469-01, T32 MH018869, T32 MH018869-21] NR 25 TC 14 Z9 14 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0886-2605 J9 J INTERPERS VIOLENCE JI J. Interpers. Violence PD DEC PY 2010 VL 25 IS 12 BP 2217 EP 2236 DI 10.1177/0886260509354887 PG 20 WC Criminology & Penology; Family Studies; Psychology, Applied SC Criminology & Penology; Family Studies; Psychology GA 673IM UT WOS:000283652900004 PM 20100896 ER PT J AU Boonyaratanakornkit, JB Yue, LL Strachan, LR Scalapino, KJ LeBoit, PE Lu, Y Leong, SP Smith, JE Ghadially, R AF Boonyaratanakornkit, Jim B. Yue, Lili Strachan, Lauren R. Scalapino, Kenneth J. LeBoit, Philip E. Lu, Ying Leong, Stanley P. Smith, Janellen E. Ghadially, Ruby TI Selection of Tumorigenic Melanoma Cells Using ALDH SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID ALDEHYDE DEHYDROGENASE-ACTIVITY; CANCER STEM-CELL; ACUTE MYELOID-LEUKEMIA; IDENTIFICATION; SUBPOPULATION; GROWTH; TUMORS; CD133 AB Despite increasing knowledge regarding melanoma-initiating cells (MICs), questions persist regarding the number and phenotypic nature of cells with tumor-generating capability. Evidence for a phenotypically distinct human MIC has been found in NOD/SCID (non-obese diabetic/severe combined immunodeficiency) mice. However, a phenotypically distinct human MIC was not found in the NOD/SCIDIl2rg(-)/(-) (NSG) mouse model. The demonstration of a distinct population of human melanoma cells responsible for tumorigenesis and tumor cell self-renewal would provide an important target for new melanoma therapies. In this study, we show a 100-fold range in MIC frequency in human melanoma (1 in 18,000 to 1 in 1,851,000 cells) in the NOD/SCID mouse. In this model, human melanoma cells with high aldehyde dehydrogenase (ALDH) activity were enriched 16.8-fold in tumorigenic cells over unfractionated (UNF) cells, such that 1 in 21,000 cells was a MIC. In the NSG mouse, the ALDH expressing cell population was enriched 100-fold in tumorigenic cells over UNF cells, such that one in four cells was a MIC. Xenograft melanomas that developed from ALDH(+) cells displayed robust self-renewal, whereas those from ALDH(-) cells showed minimal self-renewal in vitro. Thus, ALDH(+) melanoma cells have enhanced tumorigenicity over ALDH(-) cells and superior self-renewal ability. C1 [Ghadially, Ruby] Univ Calif San Francisco, Vet Affairs Med Ctr, Inst Regenerat Med, Dept Dermatol, San Francisco, CA 94121 USA. [Scalapino, Kenneth J.] Univ Calif San Francisco, Dept Med, Div Rheumatol, San Francisco, CA 94121 USA. [Scalapino, Kenneth J.] San Francisco VA Med Ctr, San Francisco, CA USA. [LeBoit, Philip E.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94121 USA. [LeBoit, Philip E.] Univ Calif San Francisco, Dept Dermatopathol, San Francisco, CA 94121 USA. [LeBoit, Philip E.] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94121 USA. [Lu, Ying] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94121 USA. [Lu, Ying] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Leong, Stanley P.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94121 USA. [Smith, Janellen E.] Univ Calif Irvine, Dept Dermatol, Irvine, CA 92717 USA. RP Ghadially, R (reprint author), Univ Calif San Francisco, Vet Affairs Med Ctr, Inst Regenerat Med, Dept Dermatol, 4150 Clement St MC190, San Francisco, CA 94121 USA. EM ghadiallyr@derm.ucsf.edu FU NIH [AR01]; Department of Veterans Affairs; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX This work was supported by an NIH AR01 grant (RG), the Department of Veterans Affairs (RG), as well as gifts from D Gregory, JC McIntosh, and S Reeves. We thank C Largman, A Charruyer, HJ Lawrence, T Jenkins, M Florero, and L-C Liu for invaluable advice and support. We thank S Fong for his outstanding technical support. Dr Scalapino's work is supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. NR 23 TC 54 Z9 55 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2010 VL 130 IS 12 BP 2799 EP 2808 DI 10.1038/jid.2010.237 PG 10 WC Dermatology SC Dermatology GA 679GX UT WOS:000284151000018 PM 20739950 ER PT J AU Kinscherff, R AF Kinscherff, Robert TI Proposition: A Personality Disorder May Nullify Responsibility for a Criminal Act SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID BORDERLINE; PSYCHOPATHY; CHILDHOOD; ABNORMALITIES; EXPERIENCES; DYSFUNCTION; STRESS; ABUSE AB This article argues in support of the proposition that "A Personality Disorder May Nullify Responsibility for a Criminal Act." Building upon research in categorical and dimensional controversies in diagnosis, neurocognitive science and the behavioral genetics of mental disorders, and difficulties in differential diagnosis and co-morbidity with personality disorders, this article holds that a per se rule barring personality diagnosis as a basis for a defense of legal insanity is scientifically and conceptually indefensible. Rather, focus should be upon the severity and impact in specific cases of any legally relevant functional deficits arising from a mental disorder (including personality disorders). Failure to do so risks potentially misleading "battles of the experts" about a defendant's diagnosis in criminal responsibility defenses and improper usurpation of the role of the legal finder of fact as mental health expert witnesses are inserted as gatekeepers indefensibly based upon diagnosis. Implications for practice and public policy are considered, including a "modest proposal" for post-trial management of defendants found not guilty by reason of insanity on the basis of functional deficits arising from personality disorder. C1 [Kinscherff, Robert] Massachusetts Gen Hosp, Adult Forens Training Law & Psychiat Serv, Boston, MA 02114 USA. [Kinscherff, Robert] Boston Univ, Sch Law, Boston, MA 02215 USA. [Kinscherff, Robert] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. NR 41 TC 2 Z9 2 U1 2 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD WIN PY 2010 VL 38 IS 4 BP 745 EP 759 DI 10.1111/j.1748-720X.2010.00528.x PG 15 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 684YI UT WOS:000284590800004 PM 21105938 ER PT J AU Gros, DF Simms, LJ Acierno, R AF Gros, Daniel F. Simms, Leonard J. Acierno, Ron TI Specificity of Posttraumatic Stress Disorder Symptoms An Investigation of Comorbidity Between Posttraumatic Stress Disorder Symptoms and Depression in Treatment-Seeking Veterans SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE PTSD; factor structure; dysphoria; numbing; hybrid models of depression and anxiety ID BECK DEPRESSION INVENTORY; DSM-IV ANXIETY; MOOD DISORDERS; BEHAVIORAL ACTIVATION; MENTAL-DISORDERS; PTSD; CLASSIFICATION; VETERANS; FEATURES; PROPOSAL AB In response to high levels of comorbidity and symptom overlap between posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and other disorders, much attention has been devoted to the role of specific and nonspecific symptoms among the disorders. The present study investigated the overlapping symptoms of PTSD and MDD in treatment-seeking veterans. Exploratory factor analyses were used to identify latent factors of both self-reported and clinician-rated symptoms of PTSD and MDD. Results of exploratory factor analyses supported a 2-factor model representing symptoms of depression and PTSD; however, a subset of PTSD symptoms, characterized by emotional numbing and dysphoria, loaded onto the depression factor, rather than the PTSD factor. These nonspecific PTSD symptoms were predictive of comorbid MDD and increased depression symptomatology in patients with PTSD. Together, these findings demonstrate the importance of accounting for nonspecific symptoms in diagnosis and treatment of PTSD, highlighting a need for revisions to our current diagnostics. C1 [Gros, Daniel F.] Ralph H Johnson Vet Adm, Med Ctr, Mental Hlth Serv 116, Charleston, SC 29401 USA. [Gros, Daniel F.; Acierno, Ron] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Simms, Leonard J.] SUNY Buffalo, Dept Psychol, Buffalo, NY 14260 USA. RP Gros, DF (reprint author), Ralph H Johnson Vet Adm, Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu NR 36 TC 38 Z9 38 U1 13 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD DEC PY 2010 VL 198 IS 12 BP 885 EP 890 DI 10.1097/NMD.0b013e3181fe7410 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 690XI UT WOS:000285043000008 PM 21135640 ER PT J AU Flessner, CA Lochner, C Stein, DJ Woods, DW Franklin, ME Keuthen, NJ AF Flessner, Christopher A. Lochner, Christine Stein, Dan J. Woods, Douglas W. Franklin, Martin E. Keuthen, Nancy J. TI Age of Onset of Trichotillomania Symptoms Investigating Clinical Correlates SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Trichotillomania; hair-pulling; age of onset; phenomenology ID OBSESSIVE-COMPULSIVE DISORDER; EXPLORING DIFFERENCES; HAIR PULLERS; PHENOMENOLOGY; COMORBIDITY; CHILDHOOD; SEVERITY; STYLES; IMPACT; HABIT AB Pathological hair-pulling with onset in very early childhood is thought to represent a different disorder from that with later onset. We examined whether there are differences between adult hair-pullers with very early onset (VEO, i.e., <6 years), early onset (EO, i.e., 6 years to <18 years), and late onset (LO, i.e., >18 years) trichotillomania symptomatology. Participants with VEO (n = 76; 5%), EO (n = 1280; 80%), and LO (n = 248; 15%) symptoms of trichotillomania did not differ significantly from one another in terms of hair-pulling phenomenologies, comorbidity, functional impact, and perceived treatment response. However, hair-pulling sites varied across the groups; the VEO and EO groups were significantly more likely to pull eyelashes whereas the EO group was more likely to pull pubic hair. Study subjects had current hair-pulling, so biasing the sample to those with more enduring symptoms, despite differences in age of onset of initial pulling. The lack of significant differences found here does not support subtyping hair-pulling by age of onset in patients who present in adulthood. C1 [Lochner, Christine; Stein, Dan J.] Univ Stellenbosch, MRC Unit Anxiety & Stress Disorders, Dept Psychiat, ZA-7505 Tygerberg, South Africa. [Flessner, Christopher A.] Bradley Hasbro Childrens Res Ctr, Providence, RI USA. [Flessner, Christopher A.] Brown Univ, Warren Alpert Sch Med, Providence, RI 02912 USA. [Stein, Dan J.] Univ Cape Town, Dept Psychiat & Mental Hlth, ZA-7925 Cape Town, South Africa. [Woods, Douglas W.] Univ Wisconsin, Dept Psychol, Milwaukee, WI 53201 USA. [Franklin, Martin E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Keuthen, Nancy J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Lochner, C (reprint author), Univ Stellenbosch, MRC Unit Anxiety & Stress Disorders, Dept Psychiat, POB 19063, ZA-7505 Tygerberg, South Africa. EM cl2@sun.ac.za RI Citations, TLC SAB/C-4006-2011; Flessner, Christopher/K-1483-2015; Stein, Dan/A-1752-2008 OI Stein, Dan/0000-0001-7218-7810 FU Trichotillomania Learning Center FX Supported by Trichotillomania Learning Center. NR 33 TC 7 Z9 7 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD DEC PY 2010 VL 198 IS 12 BP 896 EP 900 DI 10.1097/NMD.0b013e3181fe7423 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 690XI UT WOS:000285043000010 PM 21135642 ER PT J AU Engdahl, B Leuthold, AC Tan, HRM Lewis, SM Winskowski, AM Dikel, TN Georgopoulos, AP AF Engdahl, B. Leuthold, A. C. Tan, H-R M. Lewis, S. M. Winskowski, A. M. Dikel, T. N. Georgopoulos, A. P. TI Post-traumatic stress disorder: a right temporal lobe syndrome? SO JOURNAL OF NEURAL ENGINEERING LA English DT Article ID COMORBIDITY SURVEY REPLICATION; DSM-IV DISORDERS; TIME-SERIES; BRAIN; MAGNETOENCEPHALOGRAPHY; PREVALENCE; MECHANISMS; SEVERITY; EPILEPSY; SIGNALS AB In a recent paper (Georgopoulos et al 2010 J Neural Eng 7 016011) we reported on the power of the magnetoencephalography (MEG)-based synchronous neural interactions (SNI) test to differentiate post-traumatic stress disorder (PTSD) subjects from healthy control subjects and to classify them with a high degree of accuracy Here we show that the main differences in cortical communication circuitry between these two groups lie in the miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas This lateralized temporal-posterior pattern of miscommunication was very similar but was attenuated in patients with PTSD in remission These findings are consistent with observations (Penfield 1958 Proc Natl Acad Sci USA 44 51-66, Penfield and Perot 1963 Brain 86 595-696, Gloor 1990 Brain 113 1673-94, Banceaud et al 1994 Brain 117 71-90 Fried 1997 J Neuropsycluatry Clin Neurosci 9 420-8) that electrical stimulation of the temporal cortex m awake human subjects mostly in the right hemisphere, can elicit the re-enactment and re-living of past experiences Based on these facts, we attribute our findings to the re-experiencing component of PTSD and hypothesize that it reflects an involuntarily persistent activation of interacting neural networks involved in experiential consolidation C1 [Engdahl, B.; Leuthold, A. C.; Tan, H-R M.; Lewis, S. M.; Winskowski, A. M.; Georgopoulos, A. P.] US Dept Vet Affairs, Brain Sci Ctr, Med Ctr, Minneapolis, MN 55417 USA. [Engdahl, B.; Winskowski, A. M.] US Dept Vet Affairs, Psychol Sect, Med Ctr, Minneapolis, MN 55417 USA. [Engdahl, B.] Univ Minnesota, Dept Psychol, Minneapolis, MN USA. [Leuthold, A. C.; Tan, H-R M.; Georgopoulos, A. P.] Univ Minnesota, Sch Med, Dept Neurosci, Minneapolis, MN 55455 USA. [Lewis, S. M.; Georgopoulos, A. P.] Univ Minnesota, Sch Med, Dept Neurol, Minneapolis, MN 55455 USA. [Dikel, T. N.] Counseling Associates, Gainesville, FL 32606 USA. [Georgopoulos, A. P.] Univ Minnesota, Sch Med, Dept Psychiat, Minneapolis, MN 55455 USA. [Georgopoulos, A. P.] Univ Minnesota, Ctr Cognit Sci, Minneapolis, MN 55455 USA. RP Georgopoulos, AP (reprint author), US Dept Vet Affairs, Brain Sci Ctr, Med Ctr, 11B, Minneapolis, MN 55417 USA. OI Engdahl, Brian/0000-0001-5436-457X; Tan, Heng-Ru May/0000-0003-2109-0781 FU United States Department of Veterans Affairs [VISN23] FX We thank Nancy Tabaka and Cynthia Marceau for their help in patient consent and various aspects of database entry This work was partially supported by a grant from the United States Department of Veterans Affairs VISN23 NR 34 TC 35 Z9 35 U1 2 U2 7 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD DEC PY 2010 VL 7 IS 6 AR 066005 DI 10.1088/1741-2560/7/6/066005 PG 8 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 694BS UT WOS:000285270600006 PM 20980718 ER PT J AU Giannakopoulou, D Armata, I Mitsacos, A Shashidharan, P Giompres, P AF Giannakopoulou, Dimitra Armata, Ioanna Mitsacos, Ada Shashidharan, Pullani Giompres, Panagiotis TI Modulation of the basal ganglia dopaminergic system in a transgenic mouse exhibiting dystonia-like features SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE Hyperkinesia; DYT1 dystonia; cDopamine transporter; D2 dopamine receptor; Basal ganglia; Movement disorder ID DYT1 DYSTONIA; IN-VIVO; MOVEMENT-DISORDERS; RECEPTOR SUBTYPES; TORSION DYSTONIA; RAT NEOSTRIATUM; D2 RECEPTORS; MICE; RELEASE; MODEL AB Dystonia is a movement disorder characterized by involuntary excessive muscle activity and abnormal postures. There are data supporting the hypothesis that basal ganglia dysfunction, and specifically dopaminergic system dysfunction, plays a role in dystonia. In the present study, we used hyperkinetic transgenic mice generated as a model of DYT1 dystonia and compared the basal ganglia dopaminergic system between transgenic mice exhibiting hyperkinesia (affected), transgenic mice not showing movement abnormalities (unaffected), and non-transgenic littermates. A decrease in the density of striatal D2 binding sites, measured by [(3)H]raclopride binding, and D2 mRNA expression in substantia nigra pars compacta (SNpc) was revealed in affected and unaffected transgenic mice when compared with non-transgenic. No difference in D1 receptor binding and DAT binding, measured by [(3)H]SCH23390 and [(3)H]WIN35428 binding, respectively, was found in striatum of transgenic animals. In SNpc, increased levels of DAT binding sites were observed in affected and unaffected animals compared to non-transgenic, whereas no change in DAT mRNA expression was found. Our results show selective neurochemical changes in the basal ganglia dopaminergic system, suggesting a possible involvement in the pathophysiology of dystonia-like motor hyperactivity. C1 [Giannakopoulou, Dimitra; Giompres, Panagiotis] Univ Patras, Lab Human & Anim Physiol, Dept Biol, Patras 26500, Greece. [Mitsacos, Ada] Univ Patras, Dept Physiol, Sch Med, Patras 26500, Greece. [Shashidharan, Pullani] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Armata, Ioanna] Massachusetts Gen Hosp, Mol Neurogenet Unit, Dept Neurol, Boston, MA 02114 USA. [Armata, Ioanna] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Armata, Ioanna] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. RP Giompres, P (reprint author), Univ Patras, Lab Human & Anim Physiol, Dept Biol, Patras 26500, Greece. EM giompres@upatras.gr FU NINDS, NIH [NS43038] FX D. Giannakopoulou was supported by the Polembros Shipping Limited and P. Shashidharan is supported by NINDS, NIH through grant number NS43038. NR 43 TC 4 Z9 4 U1 1 U2 1 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD DEC PY 2010 VL 117 IS 12 BP 1401 EP 1409 DI 10.1007/s00702-010-0521-5 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 693FC UT WOS:000285209000009 PM 21136125 ER PT J AU Dorne, H Zaidat, OO Fiorella, D Hirsch, J Prestigiacomo, C Albuquerque, F Tarr, RW AF Dorne, Howard Zaidat, Osama O. Fiorella, David Hirsch, Joshua Prestigiacomo, Charles Albuquerque, Felipe Tarr, Robert W. TI Chronic cerebrospinal venous insufficiency and the doubtful promise of an endovascular treatment for multiple sclerosis SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material C1 [Tarr, Robert W.] Univ Hosp, Case Med Ctr, Cleveland, OH 44102 USA. [Dorne, Howard] St Joseph Hosp Hlth Syst, Orange, CA USA. [Zaidat, Osama O.] Med Coll Wisconsin, Froedtert Hosp, Dept Neurol Neurosurg & Radiol, Milwaukee, WI 53226 USA. [Fiorella, David] Stony Brook Univ Med Ctr, Stony Brook, NY USA. [Hirsch, Joshua] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Prestigiacomo, Charles] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. [Albuquerque, Felipe] Barrow Neurol Inst, Phoenix, AZ 85013 USA. RP Tarr, RW (reprint author), Univ Hosp, Case Med Ctr, Cleveland, OH 44102 USA. EM robert.tarr@uhhospitals.org NR 19 TC 4 Z9 5 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD DEC PY 2010 VL 2 IS 4 BP 309 EP 311 DI 10.1136/jnis.2010.003947 PG 3 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 683HP UT WOS:000284466100002 PM 21990639 ER PT J AU Gomez, MA Byers, EJ Stingley, P Sheridan, RM Hirsch, JA AF Gomez, Max A. Byers, Ernest J. Stingley, Preston Sheridan, Robert M. Hirsch, Joshua A. TI Establishing operational stability-developing human infrastructure SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article AB Over the past year, Toyota has come under harsh scrutiny as a result of several recalls. These well publicized mishaps have not only done damage to Toyota's otherwise sterling reputation for quality but have also called into question the assertions from a phalanx of followers that Toyota's production system (generically referred to as TPS or Lean) is the best method by which to structure one's systems of operation. In this article, we discuss how Toyota, faced with the pressure to grow its business, did not appropriately cadence this growth with the continued development and maintenance of the process capabilities (vis a vis the development of human infrastructure) needed to adequately support that growth. We draw parallels between the pressure Toyota faced to grow its business and the pressure neurointerventional practices face to grow theirs, and offer a methodology to support that growth without sacrificing quality. C1 [Gomez, Max A.; Byers, Ernest J.; Stingley, Preston; Sheridan, Robert M.; Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02129 USA. RP Gomez, MA (reprint author), Massachusetts Gen Hosp, 175 Cambridge St,Suite 200, Boston, MA 02129 USA. EM mgomezii@partners.org NR 7 TC 1 Z9 1 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD DEC PY 2010 VL 2 IS 4 BP 379 EP 384 DI 10.1136/jnis.2010.002212 PG 6 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 683HP UT WOS:000284466100015 PM 21990652 ER PT J AU Nogueira, RG Kasper, E Walcott, BP Nahed, BV Redjal, N Coumans, JV Hirsch, JA AF Nogueira, Raul G. Kasper, Ekkehard Walcott, Brian P. Nahed, Brian V. Redjal, Navid Coumans, Jean-Valery Hirsch, Joshua A. TI Lateral sacral artery aneurysm of the lumbar spine: hemorrhage resulting in cauda equina syndrome SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article AB Objective To describe the effective treatment of a ruptured lateral sacral artery aneurysm presenting as a spinal epidural hematoma. Design Case report and literature review. Setting University teaching hospital, neurovascular center. Participant A man with a history of renal allograft who presented with sudden onset low back pain. Intervention The patient underwent emergent decompressive surgery, diagnostic angiogram and endovascular embolization. Main outcome measure Obliteration of aneurysm and restoration of neurological function. Results Surgery resulted in decompression of the cauda equina. The patient's aneurysm was endovascularly obliterated. There was complete restoration of neurological function. Conclusion Lateral sacral artery aneurysm formation and rupture is a rare cause of epidural hemorrhage and one described only in patients who have undergone renal transplantation. It may be caused by high flow from transpelvic collaterals between both internal iliac arteries. Treatment includes endovascular obliteration and may necessitate operative decompression in the setting of neurological compromise. C1 [Walcott, Brian P.; Nahed, Brian V.; Redjal, Navid; Coumans, Jean-Valery] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Nogueira, Raul G.; Kasper, Ekkehard; Walcott, Brian P.; Nahed, Brian V.; Redjal, Navid; Coumans, Jean-Valery; Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. [Nogueira, Raul G.; Hirsch, Joshua A.] Massachusetts Gen Hosp, Div Intervent Neuroradiol & Endovasc Neurosurg, Boston, MA 02114 USA. [Nogueira, Raul G.] Massachusetts Gen Hosp, Div Vasc & Crit Care Neurol, Boston, MA 02114 USA. [Kasper, Ekkehard] Beth Israel Deaconess Med Ctr, Dept Neurosurg, Boston, MA 02215 USA. RP Coumans, JV (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, WACC 021,15 Parkman St, Boston, MA 02114 USA. EM jcoumans@partners.org NR 7 TC 1 Z9 1 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD DEC PY 2010 VL 2 IS 4 BP 399 EP 401 DI 10.1136/jnis.2009.002154 PG 3 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 683HP UT WOS:000284466100019 PM 21990656 ER PT J AU Gu, JW Halpin, CF Nam, EC Levine, RA Melcher, JR AF Gu, Jianwen Wendy Halpin, Christopher F. Nam, Eui-Cheol Levine, Robert A. Melcher, Jennifer R. TI Tinnitus, Diminished Sound-Level Tolerance, and Elevated Auditory Activity in Humans With Clinically Normal Hearing Sensitivity SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID FMRI ACTIVATION; SELECTIVE ATTENTION; PSYCHOMETRIC PROPERTIES; INFERIOR COLLICULUS; HUMAN BRAIN; CORTEX; LOUDNESS; INVENTORY; NOISE; FIBROMYALGIA AB Gu JW, Halpin CF, Nam E-C, Levine RA, Melcher JR. Tinnitus, diminished sound-level tolerance, and elevated auditory activity in humans with clinically normal hearing sensitivity. J Neurophysiol 104: 3361-3370, 2010. First published September 29, 2010; doi:10.1152/jn.00226.2010. Phantom sensations and sensory hypersensitivity are disordered perceptions that characterize a variety of intractable conditions involving the somatosensory, visual, and auditory modalities. We report physiological correlates of two perceptual abnormalities in the auditory domain: tinnitus, the phantom perception of sound, and hyperacusis, a decreased tolerance of sound based on loudness. Here, subjects with and without tinnitus, all with clinically normal hearing thresholds, underwent 1) behavioral testing to assess sound-level tolerance and 2) functional MRI to measure sound-evoked activation of central auditory centers. Despite receiving identical sound stimulation levels, subjects with diminished sound-level tolerance (i.e., hyperacusis) showed elevated activation in the auditory midbrain, thalamus, and primary auditory cortex compared with subjects with normal tolerance. Primary auditory cortex, but not subcortical centers, showed elevated activation specifically related to tinnitus. The results directly link hyperacusis and tinnitus to hyperactivity within the central auditory system. We hypothesize that the tinnitus-related elevations in cortical activation may reflect undue attention drawn to the auditory domain, an interpretation consistent with the lack of tinnitus-related effects subcortically where activation is less potently modulated by attentional state. The data strengthen, at a mechanistic level, analogies drawn previously between tinnitus/hyperacusis and other, nonauditory disordered perceptions thought to arise from neural hyperactivity such as chronic neuropathic pain and photophobia. pain and photophobia. C1 [Gu, Jianwen Wendy; Nam, Eui-Cheol; Levine, Robert A.; Melcher, Jennifer R.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Gu, Jianwen Wendy; Halpin, Christopher F.; Melcher, Jennifer R.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA USA. [Halpin, Christopher F.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. [Halpin, Christopher F.; Levine, Robert A.; Melcher, Jennifer R.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Nam, Eui-Cheol] Kangwon Natl Univ Hosp, Dept Otolaryngol, Chunchon, South Korea. [Levine, Robert A.] Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Gu, JW (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM fwendie@alum.mit.edu FU American Tinnitus Association; Tinnitus Research Initiative; Jack and Shelley Blais; Kenneth Griffin; National Institute on Deafness and Other Communication Disorders [T32 DC-00038, P30 DC-005209]; National Center for Research Resources [P41RR14075]; Mental Illness and Neuroscience Discovery Institute FX This work was supported by the American Tinnitus Association, the Tinnitus Research Initiative, Jack and Shelley Blais, Kenneth Griffin, and National Institute on Deafness and Other Communication Disorders Grants T32 DC-00038 and P30 DC-005209. Partial support was also provided by National Center for Research Resources Grant P41RR14075 and the Mental Illness and Neuroscience Discovery Institute. NR 44 TC 101 Z9 104 U1 2 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 2010 VL 104 IS 6 BP 3361 EP 3370 DI 10.1152/jn.00226.2010 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 695SK UT WOS:000285392700040 PM 20881196 ER PT J AU Liachko, NF Guthrie, CR Kraemer, BC AF Liachko, Nicole F. Guthrie, Chris R. Kraemer, Brian C. TI Phosphorylation Promotes Neurotoxicity in a Caenorhabditis elegans Model of TDP-43 Proteinopathy SO JOURNAL OF NEUROSCIENCE LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; TAU-INDUCED NEUROTOXICITY; DNA-BINDING PROTEIN-43; TARDBP MUTATIONS; ALPHA-SYNUCLEIN; DISEASE; EXPRESSION; ALS; NEUROPATHOLOGY AB Neurodegenerative disorders characterized by neuronal and glial lesions containing aggregated pathological TDP-43 protein in the cytoplasm, nucleus, or neurites are collectively referred to as TDP-43 proteinopathies. Lesions containing aggregated TDP-43 protein are a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U). In addition, mutations in human TDP-43 cause ALS. We have developed a Caenorhabditis elegans model of TDP-43 proteinopathies to study the cellular, molecular, and genetic underpinnings of TDP-43-mediated neurotoxicity. Expression of normal human TDP-43 in all C. elegans neurons causes moderate motor defects, whereas ALS-mutant G290A, A315T, or M337V TDP-43 transgenes cause severe motor dysfunction. The model recapitulates some characteristic features of ALS and FTLD-U including age-induced decline in motor function, decreased life span, and degeneration of motor neurons accompanied by hyperphosphorylation, truncation, and ubiquitination of TDP-43 protein that accumulates in detergent-insoluble protein deposits. In C. elegans, TDP-43 neurotoxicity is independent of activity of the cell death caspase CED-3. Furthermore, phosphorylation of TDP-43 at serine residues 409/410 drives mutant TDP-43 toxicity. This model provides a tractable system for additional dissection of the cellular and molecular mechanisms underlying TDP-43 neuropathology. C1 [Liachko, Nicole F.; Guthrie, Chris R.; Kraemer, Brian C.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Kraemer, Brian C.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98104 USA. [Liachko, Nicole F.] Univ Washington, Dept Pathol, Seattle, WA 98104 USA. RP Kraemer, BC (reprint author), Seattle Vet Affairs Puget Sound Hlth Care Syst, S182,1660 S Columbian Way, Seattle, WA 98108 USA. EM kraemerb@u.washington.edu FU Department of Veterans Affairs; National Institute of Neurological Disorders and Stroke [R01 NS064131]; National Institute on Aging [AG 000057-31] FX This work was supported by a Department of Veterans Affairs Merit Review Grant (B.C.K.) and by National Institute of Neurological Disorders and Stroke Grant R01 NS064131 (B.C.K.). N.F.L. was supported by National Institute on Aging Training Grant AG 000057-31. We thank Dr. James H. Thomas for advice regarding C. elegans genetics and strains. We thank Drs. Gerard Schellenberg and Chang-En Yu for helpful discussion regarding human genetics and TDP-43. We thank the C. elegans Genetics Center for providing strains. We thank Elaine Loomis, Leo Anderson, and Tobin Martin for outstanding technical assistance. We thank Andrew Fire for providing C. elegans expression vectors, Yishi Jin for strain CZ1200, James Rand for plasmid RM#509p, and the Developmental Studies Hybridoma Bank (National Institute of Child Health and Human Development) for the beta-tubulin antibody E7. NR 59 TC 69 Z9 75 U1 3 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 1 PY 2010 VL 30 IS 48 BP 16208 EP 16219 DI 10.1523/JNEUROSCI.2911-10.2010 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 690JK UT WOS:000284999900015 PM 21123567 ER PT J AU Drzymalski, DM Oh, WK Werner, L Regan, MM Kantoff, P Tuli, S AF Drzymalski, Dan Michael Oh, William K. Werner, Lillian Regan, Meredith M. Kantoff, Philip Tuli, Sagun TI Predictors of survival in patients with prostate cancer and spinal metastasis SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Article DE prostate cancer; spinal metastasis; survival ID RADICAL PROSTATECTOMY; NATURAL-HISTORY; PROGRESSION; PROGNOSIS; DISEASE; SYSTEM AB Object. Prostate cancer is the second most common malignancy to cause death in men, with metastases to the spine being the most common site of metastatic burden. A retrospective observational study was performed to determine survival of patients in whom spinal metastasis from prostate cancer had been diagnosed. Methods. The patient population was obtained from the Prostate Clinical Research Information System (CRIS) at the Dana-Farber Cancer Institute. Patients were observed over a period of 19 years, between June 1990 and April 2009. Clinical covariates were studied in their relationship to overall survival, the primary outcome, by using the Kaplan-Meier method and Cox regression. Results. Of a total of 9010 patients in the Prostate CRIS database, 333 were identified as having developed spinal metastases. The median overall survival after diagnosis of spinal metastasis was 24 months (95% CI 21-28 months). The estimated 1-year overall survival was 73% (95% CI 67%-77%). In 85% of patients, at least I additional site of metastasis was documented. Among 28 patients who had no additional sites of metastases, the median survival was 55.9 months, whereas an increasing burden of disease was associated with shorter survival (p = 0.0001). The association was observed regardless of whether the metastatic burden was characterized as the presence of additional (nonspinal) bone metastasis, the presence of additional nonbone metastasis, or as the number of concomitant metastatic sites (all p = 0.0001). In multivariate analysis, a higher prostate-specific antigen level at the diagnosis of spinal metastasis, a longer duration between the diagnosis of prostate cancer and spinal metastasis, and the presence of additional metastasis at the time of diagnosis of spinal metastasis (all p = 0.0001) were independently associated with a shorter over all survival. Conclusions. The results of this study are important for oncologists, neurosurgeons, and primary care physicians who have patients with prostate cancer that metastasizes to the spine, because these results can be used to form a prognosis and guide the physician in making appropriate decisions regarding the patient's treatment. Future work should include building a predictive model that accurately determines survival in patients with metastatic disease, because this would guide the physician in devising the most appropriate treatment plan for each patient. (DOI:10.3171/2010.6.SPINE10167) C1 [Drzymalski, Dan Michael; Tuli, Sagun] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Oh, William K.] Mt Sinai Sch Med, New York, NY USA. [Drzymalski, Dan Michael; Oh, William K.; Regan, Meredith M.; Kantoff, Philip; Tuli, Sagun] Harvard Univ, Sch Med, Boston, MA USA. [Werner, Lillian; Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Oh, William K.; Kantoff, Philip] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Tuli, S (reprint author), Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA. EM stuli@partners.org RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 21 TC 7 Z9 7 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1547-5654 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD DEC PY 2010 VL 13 IS 6 BP 789 EP 794 DI 10.3171/2010.6.SPINE10167 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 684QS UT WOS:000284565000023 PM 21121759 ER PT J AU AlJaroudi, W Aggarwal, H Venkataraman, R Heo, J Iskandrian, AE Hage, FG AF AlJaroudi, Wael Aggarwal, Himanshu Venkataraman, Rajesh Heo, Jaekyeong Iskandrian, Ami E. Hage, Fadi G. TI Impact of left ventricular dyssynchrony by phase analysis on cardiovascular outcomes in patients with end-stage renal disease SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE Dyssynchrony; phase analysis; end-stage renal disease; left ventricular ejection fraction (LVEF); coronary artery disease (CAD) ID MYOCARDIAL-PERFUSION SPECT; MECHANICAL DYSSYNCHRONY; HEMODIALYSIS; DYSFUNCTION AB Cardiovascular disease is the leading cause of mortality in patients with end-stage renal disease (ESRD). While left ventricular (LV) perfusion pattern and ejection fraction (EF) are important determinant of outcome, the prognostic importance of LV dyssynchrony, which can also be assessed by gated SPECT myocardial perfusion imaging (MPI), has not been well studied in this population. The indices of LV mechanical dyssynchrony were measured by automated analysis of gated SPECT MPI in patients with ESRD who were evaluated for transplantation at our institution (2001-2004) and who had coronary angiography within 6 months of the evaluation. All-cause mortality data were prospectively collected and verified against the social security death index database. The study population consisted of 144 ESRD patients aged 53 +/- A 9 years. 35% were women and 63% had diabetes mellitus. The LVEF was 48 +/- A 12%. They were followed-up for 41 +/- A 28 months during which time 55 (38%) died prior to renal transplantation. An abnormal QRS duration was not predictive of worse outcomes (log-rank P = .9). The median phase bandwidth (BW) was 62A degrees (inter-quartile range 47-98A degrees) and standard deviation (SD) was 23A degrees (inter-quartile range 15-35A degrees). Patients with a BW above the median had worse survival (log-rank P = .017) and there was a trend toward worse survival in those with a SD above the median (log-rank P = .096). A 2-year mortality was higher in those with BW a parts per thousand yen 62A degrees in the entire cohort, and in the subsets of patients with normal LVEF (log-rank P = .001), coronary artery disease by angiography, increased LV mass index, QRS < 110 ms, and perfusion defect size < 20% of the LV. LV mechanical dyssynchrony by phase analysis is a predictor of mortality in patients with ESRD. It may have a role in risk-stratifying patients and should be incorporated in future studies using gated MPI. C1 [AlJaroudi, Wael; Aggarwal, Himanshu; Venkataraman, Rajesh; Heo, Jaekyeong; Iskandrian, Ami E.; Hage, Fadi G.] Univ Alabama, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Div Cardiol, Birmingham, AL USA. RP AlJaroudi, W (reprint author), Univ Alabama, Div Cardiovasc Dis, 318 LHRB,1900 Univ Blvd, Birmingham, AL 35294 USA. EM wjaroudi@hotmail.com OI Hage, Fadi/0000-0002-1397-4942 NR 22 TC 32 Z9 32 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD DEC PY 2010 VL 17 IS 6 BP 1058 EP 1064 DI 10.1007/s12350-010-9271-x PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 684KS UT WOS:000284549400015 PM 20658272 ER PT J AU Kinard, BE Dodson, TB AF Kinard, Brian E. Dodson, Thomas B. TI Most Patients With Asymptomatic, Disease-Free Third Molars Elect Extraction Over Retention as Their Preferred Treatment SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID 3RD-MOLAR SURGERY; REMOVAL; AGE AB Purpose: To answer the clinical question, "Among patients presenting for evaluation of their third molars (M3s), do those who choose M3 extraction, compared with those who choose M3 retention, differ in important demographic, clinical, anatomic, or radiographic ways?" Materials and Methods: The investigators implemented a retrospective cohort study and enrolled a sample composed of patients presenting for M3 evaluation. The primary predictor variable was the clinician's assessment of M3 status categorized as asymptomatic, disease free (Sx-/D-); asymptomatic, disease present (Sx-/D+); symptomatic, disease free (Sx+/D-); and symptomatic, disease present (Sx+/D+). The secondary predictor variable was treatment recommendation grouped as extraction, retention, or patient choice. The primary outcome variable was the subject's treatment decision: extract or retain M3s. Data analyses were performed using bivariate and multiple regression methods. Results: The study sample comprised 249 subjects (855 M3s) with a mean age of 27.3 +/- 10.4 (median = 25.0) years. Of the 855 M3s evaluated, 37.3% were Sx-/D-, 0.6% were Sx+/D-, 51.1% were Sx-/D+, and 11.0% were Sx+/D+. The treatment recommendations were retention (6.5%), extraction (55.7%), or patient choice (37.8%). Subjects chose M3 extraction 82.1% of the time. In the adjusted multiple logistic regression model, increasing age, presence of Sx-/D- M3s, and a treatment recommendation of M3 retention were factors statistically (P < .05) associated with subject treatment choice of M3 retention. Conclusion: When offered the choice of retention or extraction, most patients (60%) with asymptomatic, disease-free M3s elected for extraction. When M3 symptoms or disease were present, more than 95% of patients chose extraction as the preferred treatment. (C) 2010 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 68:2935-2942, 2010 C1 [Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, 55 Fruit St,Warren Bldg,Suite 1201, Boston, MA 02114 USA. EM tbdodson@partners.org FU Oral and Maxillofacial Surgery Foundation; Harvard Medical School Office of Enrichment; Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund; Center for Applied Clinical Investigation; Massachusetts General Physicians Organization FX This project was supported in part by the Oral and Maxillofacial Surgery Foundation Student Research Training Award (B.E.K.), Harvard Medical School Office of Enrichment Research Award (B.E.K.), Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund (B.E.K.), Center for Applied Clinical Investigation (T.B.D.), and Massachusetts General Physicians Organization (T.B.D.). NR 20 TC 10 Z9 10 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD DEC PY 2010 VL 68 IS 12 BP 2935 EP 2942 DI 10.1016/j.joms.2010.07.058 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 696GU UT WOS:000285430700002 PM 21095505 ER PT J AU Friedlander, AH Scully, C AF Friedlander, Arthur H. Scully, Crispian TI Diagonal Ear Lobe Crease and Atherosclerosis: A Review of the Medical Literature and Oral and Maxillofacial Implications SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Review ID CORONARY-ARTERY-DISEASE; EARLOBE CREASE; HEART-DISEASE; CARDIOVASCULAR-DISEASE; RISK-FACTORS; ALL-CAUSE; ASSOCIATION; THICKNESS; SIGN; MORTALITY AB Background: A significant number of individuals die from atherosclerotic disease of the coronary and carotid arteries without having classic risk factors and prodromal symptoms. A diagonal ear lobe crease (DELC) has been characterized in the medical literature as a marker that can identify high-risk patients having occult atherosclerosis. The oral and maxillofacial surgery literature, however, offers very little information on the subject. Materials and Methods: The authors conducted a MEDLINE search using the key terms "earlobe crease," "ear lobe crease," "atherosclerosis," "cardiovascular disease," and "cerebrovascular disease." They selected articles published in peer-review journals and gave preference to articles reporting randomized controlled trials. Results: A majority of clinical, angiographic, and postmortem reports support the premise that DELC is a valuable extravascular physical sign able to distinguish some patients at risk of succumbing to atherosclerosis of the coronary arteries. Of particular interest to oral and maxillofacial surgeons is the reported association between individuals with DELC and the development of morbid cardiovascular events associated with the administration of general anesthesia. More recently, reports using B-mode ultrasound have also linked DELC to atherosclerosis of the carotid artery, and another report has related DELC to the presence of calcified carotid artery atheromas on panoramic radiographs. A minority of studies have, however, failed to support the association between DELC and atherosclerosis. Conclusions: DELC is readily visible during presurgical/preanesthetic physical examination and, in conjunction with the patient's medical history, vital signs, and panoramic radiograph, may assist in risk assessment and the identification of individuals needing further evaluation. (C) 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved. J Oral Maxillofac Surg 68:3043-3050, 2010 C1 [Friedlander, Arthur H.] Ronald Reagan UCLA Med Ctr, Hosp Dent Serv, Los Angeles, CA USA. [Friedlander, Arthur H.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [Scully, Crispian] Univ Coll London EDI, Div Maxillofacial Diagnost Med & Surg Serv, London, England. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@med.va.gov NR 51 TC 9 Z9 10 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD DEC PY 2010 VL 68 IS 12 BP 3043 EP 3050 DI 10.1016/j.joms.2010.07.009 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 696GU UT WOS:000285430700018 PM 20970909 ER PT J AU Vo, N Seo, HY Robinson, A Sowa, G Bentley, D Taylor, L Studer, R Usas, A Huard, J Alber, S Watkins, SC Lee, J Coehlo, P Wang, D Loppini, M Robbins, PD Niedernhofer, LJ Kang, J AF Vo, Nam Seo, Hyoung-Yeon Robinson, Andria Sowa, Gwendolyn Bentley, Douglas Taylor, Lauren Studer, Rebecca Usas, Arvydas Huard, Johnny Alber, Sean Watkins, Simon C. Lee, Joon Coehlo, Paulo Wang, Dong Loppini, Mattia Robbins, Paul D. Niedernhofer, Laura J. Kang, James TI Accelerated Aging of Intervertebral Discs in a Mouse Model of Progeria SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE intervertebral disc degeneration aging; DNA repair proteoglycan; mouse models ID NOTOCHORDAL NUCLEUS PULPOSUS; VERTEBRAL END-PLATE; AGE-RELATED-CHANGES; HUMAN LUMBAR DISC; EXTRACELLULAR-MATRIX; SAND RAT; CHONDROITINASE ABC; GENOTOXIC STRESS; DNA-DAMAGE; DEGENERATION AB Intervertebral disc degeneration (IDD) is a common and debilitating disorder that results in reduced flexibility of the spine pain and reduced mobility Risk factors for IDD include age, genetic predisposition, injury and other environmental factors such as smoking Loss of proteoglycans (PGs) contributes to IDD with advancing age Currently there is a lack of a model for rapid investigation of disc aging and evaluation of therapeutic interventions Here we examined progression of disc aging in a murine model of a human progeroid syndrome caused by deficiency of the DNA repair endonuclease, ERCC1-XPF (Ercc1(-/Delta) mice) The ERCC1 deficient mice showed loss of disc height and degenerative structural changes in their vertebral bodies similar to those reported for old rodents Compared to their wild type littermates Ercc1(-/Delta) mice also exhibit other age related IDD characteristics including premature loss of disc PG reduced matrix PG synthesis and enhanced apoptosis and cell senescence Finally, the onset of age associated disc pathologies was further accelerated in Ercc1(-/Delta) mice following chronic treatment with the chemotherapeutic agent mechlorethamine These results demonstrate that Ercc1(-/Delta) mice represent an accurate and rapid model of disc aging and provide novel evidence that DNA damage negatively impacts PG synthesis (c) 2010 Orthopaedic Research Society Published by Wiley Periodicals Inc J Orthop Res 28 1600-1607, 2010 C1 [Vo, Nam; Seo, Hyoung-Yeon; Sowa, Gwendolyn; Bentley, Douglas; Taylor, Lauren; Studer, Rebecca; Lee, Joon; Coehlo, Paulo; Wang, Dong; Kang, James] Univ Pittsburgh, Ferguson Lab Orthopaed Res, Dept Orthopaed Surg, Sch Med, Pittsburgh, PA 15261 USA. [Seo, Hyoung-Yeon] Chonnam Natl Univ, Sch Med, Dept Orthopaed, Kwangju 501757, South Korea. [Robinson, Andria; Niedernhofer, Laura J.] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA 15213 USA. [Robinson, Andria] Univ Pittsburgh, Dept Human Genet, Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Sowa, Gwendolyn; Coehlo, Paulo] Univ Pittsburgh, Dept Phys Med & Rehabil, Sch Med, Pittsburgh, PA 15261 USA. [Studer, Rebecca] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Sch Med, Pittsburgh, PA 15261 USA. [Usas, Arvydas; Huard, Johnny] UPMC Stem Cell Res Ctr, Dept Orthopaed Surg, Pittsburgh, PA 15261 USA. [Alber, Sean; Watkins, Simon C.] Univ Pittsburgh, Ctr Biol Imaging, Sch Med, Pittsburgh, PA 15261 USA. [Watkins, Simon C.] Univ Pittsburgh, Dept Cell Biol, Sch Med, Pittsburgh, PA 15261 USA. [Wang, Dong] Beijing Haidian Hosp, Dept Orthopaed, Beijing 100080, Peoples R China. [Loppini, Mattia] Univ Rome, Dept Orthopaed & Trauma Surg, I-00185 Rome, Italy. [Robbins, Paul D.; Niedernhofer, Laura J.] Univ Pittsburgh, Dept Microbiol & Mol Genet, Sch Med, Pittsburgh, PA 15219 USA. RP Vo, N (reprint author), Univ Pittsburgh, Ferguson Lab Orthopaed Res, Dept Orthopaed Surg, Sch Med, Pittsburgh, PA 15261 USA. OI Loppini, Mattia/0000-0001-8569-0669 FU Pittsburgh Foundation; Orthopaedic Research and Education Foundation; NIEHS [ES016114]; Ellison Medical Foundation [AG NS 0303 05]; AOSpine North America Young Investigator Research Grant FX The contributions from the following individuals are gratefully acknowledged Studer R, Sowa G, Lee J, Robbins P, Niedern hofer L, and Kang J (experimental design, data interpretation, intellectual inputs, and manuscript preparation), Taylor L, Loppini M, Alber S, Watkins S (histology and immunohistology), Usas A, Huard J (radiography), Robison A, Hyoung Yeon S (breeding, MEC treatment, and dissection of mice), Coehlo P, Bentley D, Wang D (matrix gene expression and synthesis) The authors also thank Kevin Bell and Helga Georgescu for their technical assistance as well as Lou Duerring for her administrative assistance This work was supported in part by the Albert B Ferguson, Jr M D Orthopaedic Fund of the Pittsburgh Foundation, The Orthopaedic Research and Education Foundation Grant to Joon Lee, The AOSpine North America Young Investigator Research Grant to Nam Vo Laura Niedernhofer and Andria Robinson are supported by NIEHS (ES016114) and the Ellison Medical Foundation (AG NS 0303 05) NR 45 TC 26 Z9 29 U1 3 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD DEC PY 2010 VL 28 IS 12 BP 1600 EP 1607 DI 10.1002/jor.21153 PG 8 WC Orthopedics SC Orthopedics GA 677WT UT WOS:000284026000008 PM 20973062 ER PT J AU Tam, S Joyce, D Gerber, MR Tan, A AF Tam, Samantha Joyce, Donna Gerber, Megan R. Tan, Andre TI Head and Neck Injuries in Adult Victims of Intimate-Partner Violence SO JOURNAL OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 63rd Annual Meeting of the Canadian-Society-of-Otolaryngology-Head-and-Neck-Surgery CY MAY 10-12, 2009 CL Halifax, CANADA SP Canadian Soc Otolaryngol, Head & Neck Surg DE domestic violence; head and neck injury; intimate-partner violence; otolaryngology; physical injury; screening ID DOMESTIC VIOLENCE; MAXILLOFACIAL INJURIES; FACIAL INJURIES; PHYSICAL INJURY; CHILD-ABUSE; WOMEN; MARKERS; OTOLARYNGOLOGIST; PATTERNS; RISK AB Objective: To quantify head and neck injuries in known adult victims of intimate-partner violence (IPV). Design: Retrospective chart review. Setting: Sexual assault and domestic violence program in a southeastern Ontario hospital. Methods: All subjects over the age of 16 years consenting for evaluation by a domestic violence nurse from August 2004 until February 2009 were eligible for inclusion. Subjects for which no physical injury was documented were excluded. Data were extracted from body maps and surveys completed by a specially trained domestic violence nurse. Demographic data, mechanisms of injury, relationship to the assailant, and a history of IPV from the same assailant were collected from the survey. The type and anatomic location of the injury were collected from body maps. Injuries were categorized into six larger categories for analysis according to general anatomic area and multiplicity of areas involved. Main Outcome Measure: Anatomic location of the injury. Results: One hundred eight visits were eligible for inclusion in the study. Data on 657 injuries were recorded. The frequency of any head and neck injury was significantly greater than no head and neck injury (p < .001). In subjects experiencing multiple areas of injury, head and neck injuries were significantly more common than not (p < .001). In subjects experiencing only one area of injury, head and neck injuries were more common than lower extremity injuries alone (p = .003) and trunk injuries alone (p = .033) but not significantly more common than upper extremity injuries (p = .102). Conclusions: Head and neck injuries are more common than not in known adult victims of IPV. C1 [Tam, Samantha; Tan, Andre] Queens Univ, Dept Otolaryngol, Sch Med, Kingston, ON K7L 5G2, Canada. [Joyce, Donna] Kingston Gen Hosp, Sexual Assault Domest Violence Program, Kingston, ON K7L 2V7, Canada. [Gerber, Megan R.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. RP Tan, A (reprint author), Queens Univ, Dept Otolaryngol, Sch Med, 144 Brock St, Kingston, ON K7L 5G2, Canada. NR 30 TC 7 Z9 7 U1 0 U2 5 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1916-0216 J9 J OTOLARYNGOL-HEAD N JI J. Otolaryngol-Head Neck Surg. PD DEC PY 2010 VL 39 IS 6 BP 737 EP 743 DI 10.2310/7070.2010.090292 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 701PB UT WOS:000285831800020 PM 21144372 ER PT J AU Casarett, D Shreve, S Luhrs, C Lorenz, K Smith, D De Sousa, M Richardson, D AF Casarett, David Shreve, Scott Luhrs, Carol Lorenz, Karl Smith, Dawn De Sousa, Maysa Richardson, Diane TI Measuring Families' Perceptions of Care Across a Health Care System: Preliminary Experience with the Family Assessment of Treatment at End of Life Short Form (FATE-S) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE End-of-life care; quality improvement; measurement; veterans ID ILL HOSPITALIZED ADULTS; PALLIATIVE CARE; QUALITY MEASURE; HOSPICE CARE; DATA SET; DEATH; VETERANS; OUTCOMES; OLDER; DIE AB Context. Because the Family Evaluation of Treatment at End of Life (FATE) survey was too long for routine use in the Veterans Administration (VA) health care system to measure quality of care, a shorter instrument was developed. Objectives. To evaluate the short version of the FATE survey for use as a nationwide quality measure in the VA health care system. Methods. Fifty-one VA medical centers, including acute and long-term care, participated in this nationwide telephone survey. Family members of the patients were eligible if the patients died in a participating facility. One family member per patient was selected from medical records using predefined eligibility criteria and invited to participate. The survey consists of 14 items describing key aspects of the patient's care in his or her last month of life, one global rating, and two open-ended questions for additional comments. Results. Interviews were completed with 2827 family members. Overall, the survey showed excellent psychometric characteristics, with good homogeneity (e.g., Cronbach's alpha = 0.84) and strong evidence of discriminant validity. Two survey items have been targeted for quality improvement efforts in multisite collaboratives. Conclusion. Surveys of surrogates offer an important source of quality data that can be used to improve the quality of end-of-life care and promote accountability. J Pain Symptom Manage 2010;40:801-809. Published by Elsevier Inc. on behalf of U.S. Cancer Pain Relief Committee C1 [Casarett, David; Smith, Dawn; De Sousa, Maysa; Richardson, Diane] Dept Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Shreve, Scott] Dept Vet Affairs, Washington, DC USA. [Shreve, Scott] Penn State Univ, Coll Med, Hershey, PA USA. [Luhrs, Carol] New York Harbor HCS, Dept Vet Affairs Med Ctr, New York, NY USA. [Lorenz, Karl] Vet Adm Greater Los Angeles Healthcare Syst, Palliat Care, Los Angeles, CA USA. RP Casarett, D (reprint author), Dept Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM casarett@mail.med.upenn.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, HSRD FX This material is based on the work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, HSR&D. The authors declare no conflicts of interest. NR 26 TC 11 Z9 11 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD DEC PY 2010 VL 40 IS 6 BP 801 EP 809 DI 10.1016/j.jpainsymman.2010.03.019 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 704KO UT WOS:000286052100007 PM 20813493 ER PT J AU Dellon, EP Shores, MD Nelson, KI Wolfe, J Noah, TL Hanson, LC AF Dellon, Elisabeth P. Shores, Mitchell D. Nelson, Katherine I. Wolfe, Joanne Noah, Terry L. Hanson, Laura C. TI Caregiver Perspectives on Discussions About the Use of Intensive Treatments in Cystic Fibrosis SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Cystic fibrosis; patient preferences; communication; advance care planning ID OF-LIFE CARE; LUNG TRANSPLANTATION; RESPIRATORY-FAILURE; NONINVASIVE VENTILATION; MECHANICAL VENTILATION; END; SURVIVAL; ADULTS; CHILDREN AB Context. Intensive treatments intended to sustain life are often used for patients with advanced cystic fibrosis (CF). There are no guidelines for selecting patients whose survival and quality of life may be enhanced by such treatments or for communication with patients and caregivers about possible treatment outcomes. Objectives. We aimed to describe caregivers' perspectives on decision making for the use of intensive treatments for patients with advanced CF lung disease. Methods. We conducted semi-structured interviews with 36 caregivers of 36 patients who died of CF about treatment preference discussions and solicited recommendations for improving discussions. Results. Twenty (56%) patients received intensive treatments during the last week of life. Twenty-two (61%) caregivers reported ever having discussed intensive treatment preferences with a physician, and 17 (77%) of these discussions were initiated during an acute illness. Only 14 (39%) of all patients participated. Caregivers expressed less certainty about consistency of treatments with patient preferences when patients did not participate. Twenty-nine (81%) caregivers endorsed first discussing treatment preferences during a period of medical stability. Conclusions. Discussions about preferences for the use of intensive treatments for patients with CF often take place during episodes of acute illness and may be delayed until patients themselves are too ill to participate. Bereaved caregivers suggest first addressing intensive treatment preferences during a stable period so that patient preferences are understood and unwanted treatments are minimized. J Pain Symptom Manage 2010; 40: 821-828. (C) 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Dellon, Elisabeth P.; Shores, Mitchell D.; Noah, Terry L.] Univ N Carolina, Sch Med, Dept Pediat, Div Pulmonol, Chapel Hill, NC 27599 USA. [Hanson, Laura C.] Univ N Carolina, Sch Med, Div Geriatr Med, Chapel Hill, NC 27599 USA. [Hanson, Laura C.] Univ N Carolina, Sch Med, Palliat Care Program, Dept Med, Chapel Hill, NC 27599 USA. [Nelson, Katherine I.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC 27599 USA. [Wolfe, Joanne] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. RP Dellon, EP (reprint author), Univ N Carolina, Sch Med, Dept Pediat, Div Pulmonol, CB 7217,5119-B Bioinformat Bldg,130 Mason Farm Rd, Chapel Hill, NC 27599 USA. EM epdellon@med.unc.edu FU Cystic Fibrosis Foundation; Agency for Healthcare Research and Quality [U18HS10397-06] FX This work was supported by grants from the Cystic Fibrosis Foundation and the Agency for Healthcare Research and Quality (U18HS10397-06, PI: Alan Stiles). The funders were not involved in the conduct of the study or development of the submission. The authors declare no conflicts of interest. NR 30 TC 13 Z9 13 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD DEC PY 2010 VL 40 IS 6 BP 821 EP 828 DI 10.1016/j.jpainsymman.2010.03.021 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 704KO UT WOS:000286052100009 PM 20828981 ER PT J AU Dellon, EP Shores, MD Nelson, KI Wolfe, J Noah, TL Hanson, LC AF Dellon, Elisabeth P. Shores, Mitchell D. Nelson, Katherine I. Wolfe, Joanne Noah, Terry L. Hanson, Laura C. TI Family Caregiver Perspectives on Symptoms and Treatments for Patients Dying From Complications of Cystic Fibrosis SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Cystic fibrosis; symptom burden; symptom prevalence; palliative treatments ID PAIN MANAGEMENT; CARE; ADULTS; LIFE; END; CHILDREN; CANCER; INFORMATION; ILLNESS; DYSPNEA AB Context. Most patients with advanced cystic fibrosis (CF) die from respiratory failure and experience distressing symptoms as lung disease progresses. Little has been reported about symptom management and the continuation of disease-specific treatments near the end of life for patients with CF. Objective. We aimed to describe symptom prevalence, symptom management, and frequency of use of disease-specific treatments for patients dying from complications of CF. Methods. We conducted semistructured interviews about end-of-life care in CF with bereaved family caregivers and asked questions about symptoms and treatments. Results. Twenty-seven caregivers answered questions about symptoms and treatments. Caregivers reported that distressing symptoms were common during the last week of life, including dyspnea (100%), fatigue (96%), anorexia (85%), anxiety (74%), pain (67%), and cough (56%). Most caregivers felt that symptom control was "somewhat good.'' Many reported that medical providers "did the best they could'' to manage symptoms but four (15%) recalled no physician inquiry about symptoms. Caregivers expressed beliefs that symptoms could not be controlled and described concerns about side effects and potential for hastening death with the use of opioids and anxiolytics. Patients received numerous disease-specific treatments, and caregivers described many of them as uncomfortable but necessary. Conclusions. Distressing symptoms are common in dying CF patients, and disease-specific treatments also cause discomfort. Many family caregivers have low expectations for symptom control. This exploratory research can be used to inform clinical interventions to improve symptom management for patients with advanced CF. J Pain Symptom Manage 2010;40:829-837. (C) 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Dellon, Elisabeth P.; Shores, Mitchell D.; Noah, Terry L.] Univ N Carolina, Sch Med, Dept Pediat, Div Pulmonol, Chapel Hill, NC 27599 USA. [Hanson, Laura C.] Univ N Carolina, Sch Med, Div Geriatr Med, Chapel Hill, NC 27599 USA. [Hanson, Laura C.] Univ N Carolina, Sch Med, Palliat Care Program, Dept Med, Chapel Hill, NC 27599 USA. [Nelson, Katherine I.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC 27599 USA. [Wolfe, Joanne] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. RP Dellon, EP (reprint author), Univ N Carolina, Sch Med, Dept Pediat, Div Pulmonol, CB 7217,5119-B Bioinformat Bldg,130 Mason Farm Rd, Chapel Hill, NC 27599 USA. EM elisabeth_dellon@med.unc.edu FU Cystic Fibrosis Foundation; Agency for Healthcare Research and Quality [U18HS10 397-06] FX This work was supported by grants from the Cystic Fibrosis Foundation and the Agency for Healthcare Research and Quality (U18HS10 397-06, PI: Alan Stiles). The funders were not involved in the conduct of the study or development of the submission. The authors declare no conflicts of interest. NR 29 TC 12 Z9 13 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD DEC PY 2010 VL 40 IS 6 BP 829 EP 837 DI 10.1016/j.jpainsymman.2010.03.024 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 704KO UT WOS:000286052100010 PM 20850267 ER PT J AU Abernethy, AP Aziz, NM Basch, E Bull, J Cleeland, CS Currow, DC Fairclough, D Hanson, L Hauser, J Ko, D Lloyd, L Morrison, RS Otis-Green, S Pantilat, S Portenoy, RK Ritchie, C Rocker, G Wheeler, JL Zafar, SY Kutner, JS AF Abernethy, Amy P. Aziz, Noreen M. Basch, Ethan Bull, Janet Cleeland, Charles S. Currow, David C. Fairclough, Diane Hanson, Laura Hauser, Joshua Ko, Danielle Lloyd, Linda Morrison, R. Sean Otis-Green, Shirley Pantilat, Steve Portenoy, Russell K. Ritchie, Christine Rocker, Graeme Wheeler, Jane L. Zafar, S. Yousuf Kutner, Jean S. TI A Strategy To Advance the Evidence Base in Palliative Medicine: Formation of a Palliative Care Research Cooperative Group SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID CONTROLLED-TRIAL; CLINICAL-TRIALS; STATIN THERAPY; CANCER; POPULATION; ATORVASTATIN; PREVALENCE; PREVENTION; RISK; PAIN AB Background: Palliative medicine has made rapid progress in establishing its scientific and clinical legitimacy, yet the evidence base to support clinical practice remains deficient in both the quantity and quality of published studies. Historically, the conduct of research in palliative care populations has been impeded by multiple barriers including health care system fragmentation, small number and size of potential sites for recruitment, vulnerability of the population, perceptions of inappropriateness, ethical concerns, and gate-keeping. Methods: A group of experienced investigators with backgrounds in palliative care research convened to consider developing a research cooperative group as a mechanism for generating high-quality evidence on prioritized, clinically relevant topics in palliative care. Results: The resulting Palliative Care Research Cooperative (PCRC) agreed on a set of core principles: active, interdisciplinary membership; commitment to shared research purposes; heterogeneity of participating sites; development of research capacity in participating sites; standardization of methodologies, such as consenting and data collection/management; agile response to research requests from government, industry, and investigators; focus on translation; education and training of future palliative care researchers; actionable results that can inform clinical practice and policy. Consensus was achieved on a first collaborative study, a randomized clinical trial of statin discontinuation versus continuation in patients with a prognosis of less than 6 months who are taking statins for primary or secondary prevention. This article describes the formation of the PCRC, highlighting processes and decisions taken to optimize the cooperative group's success. C1 [Abernethy, Amy P.; Wheeler, Jane L.; Zafar, S. Yousuf] Duke Univ, Med Ctr, Div Med Oncol, Dept Med, Durham, NC 27710 USA. [Abernethy, Amy P.] Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA. [Aziz, Noreen M.] NINR, Div Extramural Activ, NIH, Bethesda, MD 20892 USA. [Basch, Ethan] Mem Sloan Kettering Canc Ctr, Hlth Outcomes Grp, New York, NY 10021 USA. [Bull, Janet] Four Seasons, Flat Rock, NC USA. [Cleeland, Charles S.] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, Div Internal Med, Houston, TX 77030 USA. [Currow, David C.] Flinders Univ S Australia, Dept Palliat & Support Serv, Div Med, Bedford Pk, SA 5042, Australia. [Currow, David C.] Repatriat Gen Hosp, So Adelaide Palliat Serv, Daw Pk, SA, Australia. [Fairclough, Diane] Colorado Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO USA. [Hanson, Laura] Univ N Carolina, Div Geriatr, Chapel Hill, NC USA. [Hauser, Joshua] Northwestern Univ, Palliat Care & Home Hosp Program, Feinberg Sch Med, Chicago, IL 60611 USA. [Ko, Danielle] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Lloyd, Linda] San Diego Hosp, San Diego, CA USA. [Lloyd, Linda] Inst Palliat Med, San Diego, CA USA. [Morrison, R. Sean] Mt Sinai Sch Med, New York, NY USA. [Otis-Green, Shirley] City Hope Natl Med Ctr, Div Nursing Res & Educ, Duarte, CA 91010 USA. [Pantilat, Steve] Univ Calif San Francisco, Dept Med, Palliat Care Program, Div Hosp Med, San Francisco, CA 94110 USA. [Portenoy, Russell K.] Beth Israel Deaconess Med Ctr, Dept Pain Med & Palliat Care, New York, NY 10003 USA. [Ritchie, Christine] Univ Alabama Birmingham, Birmingham Atlanta VA Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. [Ritchie, Christine] Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, Birmingham, AL USA. [Rocker, Graeme] Dalhousie Univ, Div Respirol, Halifax, NS, Canada. [Rocker, Graeme] Dalhousie Univ, Dept Med, Div Palliat Med, Halifax, NS, Canada. [Kutner, Jean S.] Univ Colorado, Dept Med, Div Gen Internal Med, Denver Sch Med, Denver, CO USA. RP Abernethy, AP (reprint author), Duke Univ, Med Ctr, Div Med Oncol, Dept Med, Box 3436, Durham, NC 27710 USA. EM amy.abernethy@duke.edu OI Zafar, S. Yousuf/0000-0002-9039-5258; Currow, David/0000-0003-1988-1250; Abernethy, Amy/0000-0001-6930-8722 FU Pfizer; Helsinn; Kanglaite; Eisai; Eli Lilly; Biovex; Amgen FX Amy Abernethy receives research funding from Pfizer, Helsinn, Kanglaite, Eisai, Eli Lilly, Biovex, and Amgen, and consulting funding (less than $10,000) from Helsinn and Pfizer. Janet Bull is on the speakers bureau for MEDI, Pfizer, and Wyeth, and the scientific advisory board for Pfizer and MEDI. No competing financial interests are disclosed by Ethan Basch, David Currow, Diane Fairclough, Joshua Hauser, Danielle Ko, Jean Kutner, Linda Lloyd, Shirley Otis-Green, Steve Pantilat, Christine Ritchie, Russell Portenoy, Jane Wheeler, and S. Yousuf Zafar. NR 39 TC 37 Z9 38 U1 0 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD DEC PY 2010 VL 13 IS 12 BP 1407 EP 1413 DI 10.1089/jpm.2010.0261 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 694KC UT WOS:000285295100004 PM 21105763 ER PT J AU Cohen, MJ McCannon, JB Edgman-Levitan, S Kormos, WA AF Cohen, Marya J. McCannon, Jessica B. Edgman-Levitan, Susan Kormos, William A. TI Exploring Attitudes toward Advance Care Directives in Two Diverse Settings SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE CARE; DECISION-MAKING; ETHNIC-DIFFERENCES; VIDEO IMAGES; END; PREFERENCES; BARRIERS; POPULATION; COMPLETION; AMERICAN AB Background: Advance care directives (ACD) are not used equally by different ethnic groups in the United States. Theories regarding this difference include lack of access to health care, mistrust of the health care system, absence of surrogate decision makers, and universal lack of knowledge on this topic. Few studies have investigated attitudes toward advance care planning for future end-of-life decision-making in the Latino and Cambodian communities. Methods: Six focus groups were conducted, including a total of 20 Latino and 19 Cambodian patients of two community health centers. Focus groups were audiotaped, transcribed, and qualitatively analyzed to identify major themes regarding attitudes toward advance directives and engaging in discussion about advance care planning. Results: Most patients did not have a health care proxy nor had discussed this topic with their doctor. Two broad themes were identified: integration of belief systems (including religion, suffering/destiny, and importance of quality of life) as well as process/preferences regarding decision-making (including family roles, provider roles, confusion/uncertainty regarding ACD, and openness to learning about ACD). Conclusions: In focus groups discussing end-of-life decision making among Latino and Cambodian patients, two main themes emerged: integration of belief systems and process/preferences regarding end-of-life care. In particular, efforts to improve completion of advance care directives in diverse populations should consider patients' emphasis on quality of life and destiny in end-of-life planning as well as the role of family consensus in decision-making. C1 [Cohen, Marya J.] Massachusetts Gen Hosp, Gen Med Unit, Div Gen Med, Boston, MA 02114 USA. [McCannon, Jessica B.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Edgman-Levitan, Susan; Kormos, William A.] Massachusetts Gen Hosp, John D Stoeckle Ctr Primary Care Innovat, Boston, MA 02114 USA. RP Cohen, MJ (reprint author), Massachusetts Gen Hosp, Gen Med Unit, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM mjcohen@partners.org FU Institutional National Research Service Award [T32HP10251-02]; Division of General Medicine, Massachusetts General Hospital; Harvard Medical School; John D. Stoeckle Center FX Dr. Marya Cohen was supported by an Institutional National Research Service Award #T32HP10251-02, and by the Division of General Medicine, Massachusetts General Hospital and the Harvard Medical School Fellowship in General Medicine and Primary Care. Additional support for transcribing focus groups was provided by the John D. Stoeckle Center's SIGP grant on Advance Care Directives. The funding organizations had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; nor in the preparation, review, or approval of the manuscript. NR 33 TC 10 Z9 10 U1 2 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD DEC PY 2010 VL 13 IS 12 BP 1427 EP 1432 DI 10.1089/jpm.2010.0200 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 694KC UT WOS:000285295100007 PM 21091225 ER PT J AU Jackson, V Arnold, RM AF Jackson, Vicki Arnold, Robert M. TI Using Grand Rounds as an Instrument of Culture Change SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material C1 [Jackson, Vicki] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jackson, V (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM VJackson@partners.org 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 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD DEC PY 2010 VL 13 IS 12 BP 1475 EP 1475 DI 10.1089/jpm.2010.9754 PG 1 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 694KC UT WOS:000285295100014 PM 21155642 ER PT J AU Nosho, K Baba, Y Tanaka, N Shima, K Hayashi, M Meyerhardt, JA Giovannucci, E Dranoff, G Fuchs, CS Ogino, S AF Nosho, Katsuhiko Baba, Yoshifumi Tanaka, Noriko Shima, Kaori Hayashi, Marika Meyerhardt, Jeffrey A. Giovannucci, Edward Dranoff, Glenn Fuchs, Charles S. Ogino, Shuji TI Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review SO JOURNAL OF PATHOLOGY LA English DT Article DE colon cancer; reaction; mismatch repair; epigenetics; immunology; therapeutic target; immunity ID ISLAND METHYLATOR PHENOTYPE; MICROSATELLITE INSTABILITY; COLON-CANCER; LINE-1 HYPOMETHYLATION; FRAMESHIFT MUTATIONS; PIK3CA MUTATION; POOR-PROGNOSIS; BRAF MUTATION; IMMUNE CELLS; SURVIVAL AB The abundance of tumour-infiltrating T-cells has been associated with microsatellite instability (MSI) and a favourable prognosis in colorectal cancer. However, numerous molecular alterations have been associated with clinical outcome, and potentially confounding the biological and prognostic significance of tumour-infiltrating T-cells. We utilized a database of clinically and molecularly-annotated colon and rectal carcinoma cases (N = 768; stage I-IV) in two prospective cohort studies (the Nurses' Health Study and the Health Professionals Follow-up Study) and quantified the densities of CD3(+), CD8(+), CD45RO(+) (PTPRC), and FOXP3(+) cells within neoplastic epithelial areas using an Ariol image analysis system and tissue microarray. We used Cox proportional hazard models to compute the mortality hazard ratio, adjusting for clinical and molecular features including KRAS, BRAF, and PIK3CA mutations, MSI, CIMP, and LINE-1 hypomethylation. The densities of CD8(+), CD45RO(+), and FOXP3(+) cells were significantly associated with patient survival in univariate analyses (p(trend) < 0.007). In the multivariate model, tumour-infiltrating CD45RO(+)-cell density, but not CD3(+), CD8(+) or FOXP3(+)-cell density, was significantly associated with survival (p = 0.0032). In multivariate linear regression analysis, MSI-high (p < 0.0001) and high-level tumour LINE-1 methylation (p = 0.0013) were independently associated with higher CD45RO(+)-cell density. The survival benefit associated with CD45RO(+) cells was independent of MSI and LINE-1 status. In conclusion, tumour-infiltrating CD45RO(+)-cell density is a prognostic biomarker associated with longer survival of colorectal cancer patients, independent of clinical, pathological, and molecular features. In addition, MSI-high and tumour LINE-1 methylation level are independent predictors of CD45RO(+)-cell density. Our data offer a possible mechanism by which MSI confers an improved clinical outcome and support efforts to augment the host immune response in the tumour microenvironment as a strategy of targeted immunotherapy. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Ogino, Shuji] Brigham & Womens Hosp, Ctr Mol Oncol Pathol, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Nosho, Katsuhiko; Baba, Yoshifumi; Tanaka, Noriko; Shima, Kaori; Hayashi, Marika; Meyerhardt, Jeffrey A.; Dranoff, Glenn; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Tanaka, Noriko] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Giovannucci, Edward; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. [Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. RP Ogino, S (reprint author), Brigham & Womens Hosp, Ctr Mol Oncol Pathol, Dana Farber Canc Inst, Dept Pathol, 44 Binney St,Room JF 215C, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU US National Institute of Health [P01 CA87969, P01 CA55075, K07 CA122826, R01 CA151993, P50 CA127003]; Bennett Family Fund for Targeted Therapies Research; Entertainment Industry Foundation through National Colorectal Cancer Research Alliance; Japan Society for Promotion of Science; Uehara Memorial Foundation FX We deeply thank the Nurses' Health Study and Health Professionals Follow-up Study cohort participants who generously agreed to provide us with biological specimens and information through responses to questionnaires, and hospitals and pathology departments throughout the US for providing us with tumour tissue materials. We thank the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY. This work was supported by US National Institute of Health [P01 CA87969 (to S Hankinson), P01 CA55075 (to W Willett), K07 CA122826 (to SO), R01 CA151993 (to SO), P50 CA127003 (GI SPORE to CSF), and a GI SPORE Developmental Project Award (to SO)]; the Bennett Family Fund for Targeted Therapies Research; and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. KN was supported by a fellowship grant from the Japan Society for Promotion of Science. YB was supported by a fellowship grant from the Uehara Memorial Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views NR 71 TC 178 Z9 186 U1 5 U2 36 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3417 J9 J PATHOL JI J. Pathol. PD DEC PY 2010 VL 222 IS 4 BP 350 EP 366 DI 10.1002/path.2774 PG 17 WC Oncology; Pathology SC Oncology; Pathology GA 680FY UT WOS:000284219000005 PM 20927778 ER PT J AU Smith, JT Curtis, TA Spencer, S Kasser, JR Mahan, ST AF Smith, Jeremy T. Curtis, Tracy A. Spencer, Samantha Kasser, James R. Mahan, Susan T. TI Complications of Talus Fractures in Children SO JOURNAL OF PEDIATRIC ORTHOPAEDICS LA English DT Article DE talus; fracture; children; avascular necrosis; complications; outcome ID AVASCULAR NECROSIS; FOLLOW-UP; NECK; INJURIES; ANLAGE; BODY AB Background: Pediatric talus fractures are rare with variable rates of posttraumatic complications reported in the literature. The purpose of this retrospective study was to evaluate posttraumatic complications in children after talus fracture and report injury characteristics. Methods: This study included 29 children with talus fractures sustained between 1999 and 2008 at an average age of 13.5 years (range, 1.2-17.8). Patient records and radiographs were reviewed to determine the mechanism of injury, fracture type, associated injuries, and treatment. Posttraumatic complications assessed were avascular necrosis, arthrosis, nonunion or delayed union, neurapraxia, infection or wound-healing problems, and the need for further unanticipated surgery. Clinical follow-up averaged 24 months (range, 6 mo-5 y). Results: Twenty-nine children sustained a major fracture of the talar body, neck, or head. Avascular necrosis occurred in 2 patients (7%), arthrosis in 5 (17%), delayed union in 1 (3%), neurapraxia in 2 (7%), infection in 0, and the need for further surgery in 3 (10%). Both high-energy mechanism and fracture displacement corresponded to a greater number of posttraumatic complications. The number and severity of talus fractures increased in older children. Conclusions: In this case series, posttraumatic complications after pediatric talus fractures occurred more frequently after a high-energy mechanism of injury or a displaced fracture. Talus fractures occurred more commonly and with more severity in older children. Level of Evidence: Level IV. Retrospective case series. C1 [Smith, Jeremy T.; Curtis, Tracy A.; Spencer, Samantha; Kasser, James R.; Mahan, Susan T.] Childrens Hosp, Dept Orthopaed, Boston, MA 02115 USA. RP Smith, JT (reprint author), Massachusetts Gen Hosp, Harvard Combined Orthopaed Residency Program, 55 Fruit St, Boston, MA 02114 USA. EM jsmith42@partners.org NR 29 TC 5 Z9 9 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-6798 J9 J PEDIATR ORTHOPED JI J. Pediatr. Orthop. PD DEC PY 2010 VL 30 IS 8 BP 779 EP 784 DI 10.1097/BPO.0b013e3181f73e6e PG 6 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA 684VO UT WOS:000284581500005 PM 21102201 ER PT J AU Fay, A Nguyen, J Waner, M AF Fay, Aaron Nguyen, John Waner, Milton TI Conceptual Approach to the Management of Infantile Hemangiomas SO JOURNAL OF PEDIATRICS LA English DT Article ID CAPILLARY ENDOTHELIAL-CELLS; SUBGLOTTIC HEMANGIOMA; FRACTIONAL PHOTOTHERMOLYSIS; CORTICOSTEROID INJECTION; PERIOCULAR HEMANGIOMAS; PROPRANOLOL; INFANCY; THERAPY; LASER; VINCRISTINE C1 [Fay, Aaron] Massachusetts Eye & Ear Infirm, Ophthalm Plast & Reconstruct Surg Div, Boston, MA 02114 USA. [Fay, Aaron] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Nguyen, John] W Virginia Univ, Dept Ophthalmol, Robert C Byrd Hlth Sci Ctr, Sch Med, Morgantown, WV 26506 USA. [Waner, Milton] St Lukes Roosevelt Hosp, Vasc Birthmark Inst New York, New York, NY USA. RP Fay, A (reprint author), Massachusetts Eye & Ear Infirm, Ophthalm Plast & Reconstruct Surg Div, 243 Charles St, Boston, MA 02114 USA. EM Aaron_Fay@meei.harvard.edu NR 51 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD DEC PY 2010 VL 157 IS 6 BP 881 EP + DI 10.1016/j.jpeds.2010.08.013 PG 13 WC Pediatrics SC Pediatrics GA 681JG UT WOS:000284307200006 PM 20884010 ER PT J AU Sasaki, H Suzuki, N AlShwaimi, E Xu, Y Battaglino, R Morse, L Stashenko, P AF Sasaki, H. Suzuki, N. AlShwaimi, E. Xu, Y. Battaglino, R. Morse, L. Stashenko, P. TI 18 beta-Glycyrrhetinic acid inhibits periodontitis via glucocorticoid-independent nuclear factor-kappa B inactivation in interleukin-10-deficient mice SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE 18 beta-glycyrrhetinic acid; periodontal disease; nuclear factor-kappa B; interleukin-10-deficient mouse ID 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-2; INFLAMMATORY ARTHRITIS; DESTRUCTIVE IMMUNITY; GENE-EXPRESSION; BONE LOSS; ACTIVATION; CELLS; LYMPHOCYTE; SUPPRESSION; METABOLISM AB Background and Objective: 18 beta-Glycyrrhetinic acid (GA) is a natural anti-inflammatory compound derived from licorice root extract (Glycyrrhiza glabra). The effect of GA on experimental periodontitis and its mechanism of action were determined in the present study. Material and Methods: Periodontitis was induced by oral infection with Porphyromonas gingivalis W83 in interleukin-10-deficient mice. The effect of GA, which was delivered by subcutaneous injections in either prophylactic or therapeutic regimens, on alveolar bone loss and gingival gene expressions was determined on day 42 after initial infection. The effect of GA on lipopolysaccharide (LPS)-stimulated macrophages, T cell proliferation and osteoclastogenesis was also examined in vitro. Results: 18 beta-Glycyrrhetinic acid administered either prophylactically or therapeutically resulted in a dramatic reduction of infection-induced bone loss in interleukin-10-deficient mice, which are highly disease susceptible. Although GA has been reported to exert its anti-inflammatory activity via downregulation of 11 beta-hydroxysteroid dehydrogenase-2 (HSD2), which converts active glucocorticoids to their inactive forms, GA did not reduce HSD2 gene expression in gingival tissue. Rather, in glucocorticoid-free conditions, GA potently inhibited LPS-stimulated proinflammatory cytokine production and RANKL-stimulated osteoclastogenesis, both of which are dependent on nuclear factor-kappa B. Furthermore, GA suppressed LPS- and RANKL-stimulated phosphorylation of nuclear factor-kappa B p105 in vitro. Conclusion: These findings indicate that GA inhibits periodontitis by inactivation of nuclear factor-kappa B in an interleukin-10- and glucocorticoid-independent fashion. C1 [Sasaki, H.; Battaglino, R.; Stashenko, P.] Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. [Suzuki, N.] Tokyo Med & Dent Univ, Grad Sch, Bunkyo Ku, Tokyo, Japan. [AlShwaimi, E.] King Faisal Univ, Endodont Div, Restorat Dent Sci Dept, Coll Dent, Dammam, Saudi Arabia. [Xu, Y.] Kunming Med Univ, Dept Med Microbiol & Immunol, Kunming, Yunnan, Peoples R China. [Morse, L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Morse, L.] Spaulding Rehabil Hosp, Boston, MA USA. RP Sasaki, H (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM hsasaki@forsyth.org RI AlShwaimi, Emad /F-4077-2012; battaglino, ricardo/D-2892-2015; Morse, Leslie/C-9442-2015 OI Morse, Leslie/0000-0002-7426-6341 FU National Institute of Dental and Craniofacial Research/National Institutes of Health [DE-15888, DE-09018] FX We thank Mina Milosavljevic, a scholar in the Forsyth Educational Outreach Program, for technical assistance with cell cultures and assays, and Mr Subbiah Yoganathan for animal husbandry. This work was supported in part by grants DE-15888 (to H.S.) and DE-09018 (to P.S.) from the National Institute of Dental and Craniofacial Research/National Institutes of Health. NR 34 TC 10 Z9 16 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD DEC PY 2010 VL 45 IS 6 BP 757 EP 763 DI 10.1111/j.1600-0765.2010.01296.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 669UK UT WOS:000283375500008 PM 20682015 ER PT J AU Ham, M Mizumori, M Watanabe, C Wang, JH Inoue, T Nakano, T Guth, PH Engel, E Kaunitz, JD Akiba, Y AF Ham, Maggie Mizumori, Misa Watanabe, Chikako Wang, Joon-Ho Inoue, Takuya Nakano, Takanari Guth, Paul H. Engel, Eli Kaunitz, Jonathan D. Akiba, Yasutada TI Endogenous Luminal Surface Adenosine Signaling Regulates Duodenal Bicarbonate Secretion in Rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; CHLORIDE SECRETION; CYCLIC-AMP; NUCLEOSIDE TRANSPORTERS; CARBONIC-ANHYDRASES; EXTRACELLULAR ATP; GENE-EXPRESSION; HCO3-SECRETION; RECEPTORS; PATHWAY AB Luminal ATP increases duodenal bicarbonate secretion (DBS) via brush border P2Y receptors. Because ATP is sequentially dephosphorylated to adenosine (ADO) and the brush border highly expresses adenosine deaminase (ADA), we hypothesized that luminal [ADO] regulators and sensors, including P1 receptors, ADA, and nucleoside transporters (NTs) regulate DBS. We measured DBS with pH and CO(2) electrodes, perfusing ADO +/- adenosine receptor agonists or antagonists or the cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTR(inh)-172 on DBS. Furthermore, we examined the effect of inhibitors of ADA or NT on DBS. Perfusion of AMP or ADO (0.1 mM) uniformly increased DBS, whereas inosine had no effect. The A(1/2) receptor agonist 5'-(N-ethylcarboxamido)adenosine (0.1 mM) increased DBS, whereas ADO-augmented DBS was inhibited by the potent A(2B) receptor antagonist N-(4-cyanophenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl) phenoxy]-acetamide (MRS1754) (10 mu M). Other selective adenosine receptor agonists or antagonists had no effect. The A(2B) receptor was immunolocalized to the brush border membrane of duodenal villi, whereas the A(2A) receptor was immunolocalized primarily to the vascular endothelium. Furthermore, ADO-induced DBS was enhanced by 2'-deoxycoformycin (1 mu M) and formycin B (0.1 mM), but not by S-(4-nitrobenzyl)-6-thioinosine (0.1 mM), and it was abolished by CFTR(inh)-172 pretreatment (1 mg/kg i.p). Moreover, ATP (0.1 mM)induced DBS was partially reduced by (1R,2S,4S,5S)-4-2-iodo-6-(methylamino)-9H-purin-9-yl]-2-(phosphonooxy) bicyclo[3.1.0] hexane-1-methanol dihydrogen phosphate ester tetraammonium salt (MRS2500) or 8-[4-[4-(4-chlorophenzyl) piperazide-1-sulfonyl) phenyl]]-1-propylxanthine (PSB603) and abolished by both, suggesting that ATP is sequentially degraded to ADO. Luminal ADO stimulates DBS via A(2B) receptors and CFTR. ATP release, ectophosphohydrolases, ADA, and concentrative NT may coordinately regulate luminal surface ADO concentration to modulate ADO-P1 receptor signaling in rat duodenum. C1 [Ham, Maggie; Mizumori, Misa; Watanabe, Chikako; Wang, Joon-Ho; Inoue, Takuya; Nakano, Takanari; Kaunitz, Jonathan D.; Akiba, Yasutada] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Engel, Eli] Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA USA. [Guth, Paul H.; Kaunitz, Jonathan D.; Akiba, Yasutada] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Kaunitz, Jonathan D.; Akiba, Yasutada] Brentwood Biomed Res Inst, Los Angeles, CA USA. RP Kaunitz, JD (reprint author), VA Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU Department of Veterans Affairs; National Institute of Health National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK54221, P30-DK0413] FX This work was supported by a Department of Veterans Affairs Merit Review Award (to J.D.K.); the National Institute of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant R01-DK54221] (to J.D.K.); and the animal core of the National Institute of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant P30-DK0413] (to J.E. Rozengurt). NR 45 TC 12 Z9 12 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2010 VL 335 IS 3 BP 607 EP 613 DI 10.1124/jpet.110.171520 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 681JS UT WOS:000284308800010 PM 20805305 ER PT J AU Busch, CJ Graveline, AR Jiramongkolchai, K Liu, H Sanchez, LS Bloch, KD AF Busch, C. J. Graveline, A. R. Jiramongkolchai, K. Liu, H. Sanchez, L. S. Bloch, K. D. TI PHOSPHODIESTERASE 3A EXPRESSION IS MODULATED BY NITRIC OXIDE IN RAT PULMONARY ARTERY SMOOTH MUSCLE CELLS SO JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article DE nitric oxide; cyclic guanosine monaphosphate; GSNO; phosphodiesterase 3A; soluble guanylate cyclase; vasodilation ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; POTENTIAL MECHANISM; GUANYLATE-CYCLASE; HYPERTENSION; ISOFORMS; HEART; INHIBITORS; LAMBS; PDE3A; IDENTIFICATION AB Phosphodiesterases (PDEs) limit vasodilation in response to a variety of signaling cascades by metabolizing the cyclic nucleotides cAMP and cGMP. The objective of this study was to test the hypothesis that NO regulates expression of PDE3A, a cGMP-inhibited PDE. Incubation of rat pulmonary artery smooth muscle cells (rPaSMCs) with the NO-donor compound 5-nitroso-glutathione (GSNO) increased PDE3A gene expression in a dose- and time-dependent manner. NO-donors increased PDE3A protein levels. Total and milrinone inhibitable cAMP PDE activity were increased 2.8+/-0.1- and 2.0+/-0.1-fold respectively in extracts of rPaSMCs exposed to GSNO. The effects of GSNO on PDE3A gene expression were mimicked by the soluble guanylate cyclase (sGC) activators YC-1 and BAY 41-2272 and blocked by the sGC inhibitor ODQ. Incubation of rPaSMC with interleukin-1 beta and tumor necrosis factor-alpha induced PDE3A gene expression, an effect which was inhibited by L-NIL, an antagonist of NO synthase 2, or ODQ. Actinomycin D, an inhibitor of RNA polymerase, blocked the GSNO-induced increase of PDE3A mRNA levels, whereas cycloheximide, an inhibitor of protein translation, did not. These observations suggest that NO modulates PDE3A gene expression via mechanisms dependent upon cGMP synthesis and gene transcription. Prolonged exposure to NO may alter the sensitivity of vascular smooth muscle to cGMP- or cAMP-dependent vasodilators, as well as PDE isoform-selective inhibitors. C1 [Busch, C. J.] Univ Heidelberg, Dept Anaesthesiol, D-69120 Heidelberg, Germany. [Busch, C. J.; Bloch, K. D.] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Sch Med, Charlestown, MA USA. [Busch, C. J.; Graveline, A. R.; Jiramongkolchai, K.; Liu, H.; Sanchez, L. S.; Bloch, K. D.] Harvard Univ, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Med,Sch Med, Charlestown, MA USA. RP Busch, CJ (reprint author), Univ Heidelberg, Dept Anaesthesiol, 110 Neuenheimer Feld St, D-69120 Heidelberg, Germany. EM Cornelius_Busch@med.uni-heidelberg.de FU National Institutes of Health [HL-74352]; INO Therapeutics, LLC FX This study was supported by a grant from the National Institutes of Health HL-74352 and a sponsored research agreement with INO Therapeutics, LLC (K. D. Bloch). We thank Dr. York Zausig for the helpful discussion of the manuscript. NR 40 TC 7 Z9 7 U1 0 U2 0 PU POLISH PHYSIOLOGICAL SOC PI GRZEGORZECKA PA JAGIELLONIAN UNIV SCHOOL MED, INST PHYSIOLOGY, 31-531 KRAKOW, 16 GRZEGORZECKA, POLAND SN 0867-5910 J9 J PHYSIOL PHARMACOL JI J. Physiol. Pharmacol. PD DEC PY 2010 VL 61 IS 6 BP 663 EP 669 PG 7 WC Physiology SC Physiology GA 708HV UT WOS:000286353800003 PM 21224496 ER PT J AU Hajdu, SD Vercler, CJ Tobias, AM AF Hajdu, Steven D. Vercler, Christian J. Tobias, Adam M. TI The barrel-suction method for silicone gel removal from ruptured breast implants SO JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY LA English DT Letter C1 [Hajdu, Steven D.; Vercler, Christian J.; Tobias, Adam M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Surg, Div Plast & Reconstruct Surg,Med Sch, Boston, MA 02215 USA. RP Hajdu, SD (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Surg, Div Plast & Reconstruct Surg,Med Sch, 110 Francis St,Suite 5A, Boston, MA 02215 USA. EM ATOBIAS@bidmc.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1748-6815 J9 J PLAST RECONSTR AES JI J. Plast. Reconstr. Aesthet. Surg. PD DEC PY 2010 VL 63 IS 12 BP 2197 EP 2198 DI 10.1016/j.bjps.2010.05.001 PG 3 WC Surgery SC Surgery GA 683HE UT WOS:000284463500067 PM 20570230 ER PT J AU Orenstein, IH Weinstein, BF Gelman, AS Fiks, S McCartney, JW AF Orenstein, Ira H. Weinstein, Bradley F. Gelman, Asher S. Fiks, Serge McCartney, John W. TI A TECHNIQUE FOR CONVERTING AN EXISTING DENTURE INTO A CAST METAL-REINFORCED IMPLANT-RETAINED OVERDENTURE SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article ID SUPPORTED OVERDENTURE; BASE AB Prosthesis fracture is a common complication associated with implant-retained overdentures A new overdenture can be strengthened by incorporating a cast metal reinforcement during processing The authors describe a technique for converting an existing conventional nonreinforced serviceable denture into an overdenture that includes a cast metal reinforcement and its attachments (J Prosthet Dent 2010,104 397-400) C1 [Orenstein, Ira H.] James J Peters VA Med Ctr, Dent Serv 160, Bronx, NY 10468 USA. [Orenstein, Ira H.] Columbia Univ, Coll Dent Med, New York, NY USA. [Weinstein, Bradley F.; Gelman, Asher S.] Mt Sinai Sch Med, New York, NY USA. [Fiks, Serge] Cent Dent Lab, Dept Vet Affairs, Removable Prosthet Div, Washington, DC USA. RP Orenstein, IH (reprint author), James J Peters VA Med Ctr, Dent Serv 160, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 22 TC 3 Z9 3 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD DEC PY 2010 VL 104 IS 6 BP 397 EP 400 DI 10.1016/S0022-3913(10)60175-8 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 702NP UT WOS:000285901700009 PM 21095403 ER PT J AU Zhou, F Cardoza, JD Ficarro, SB Adelmant, GO Lazaro, JB Marto, JA AF Zhou, Feng Cardoza, Job D. Ficarro, Scott B. Adelmant, Guillaume O. Lazaro, Jean-Bernard Marto, Jarrod A. TI Online Nanoflow RP-RP-MS Reveals Dynamics of Multicomponent Ku Complex in Response to DNA Damage SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE tandem affinity purification; RP-RP; reversed phase-reversed phase; LC-MS; LC-MS/MS; 2D-LC; two-dimensional separation; online fractionation; SCX-RP; mudpit; Orbitrap; Qstar; protein complex; DNA damage ID TANDEM AFFINITY PURIFICATION; MULTIDIMENSIONAL LIQUID-CHROMATOGRAPHY; LARGE-SCALE IDENTIFICATION; STRONG-CATION-EXCHANGE; EMBRYONIC STEM-CELLS; MASS-SPECTROMETRY; SHOTGUN PROTEOMICS; PROTEIN COMPLEXES; REVERSED-PHASE; YEAST PROTEOME AB Tandem affinity purification (TAP) coupled with mass spectrometry has become the technique of choice for characterization of multicomponent protein complexes While current TAP protocols routinely provide high yield and specificity for proteins expressed under physiologically relevant conditions, analytical figures of merit required for efficient and in-depth LC-MS analysis remain unresolved Here we implement a multidimensional chromatography platform based on two stages of reversed-phase (RP) separation operated at high and low pH respectively We compare performance metrics for RP-RP and SCX-RP for the analysis of complex peptide mixtures derived from cell lysate as well as protein complexes purified via TAP Our data reveal that RP-RP fractionation outperforms SCX-RP primarily due to increased peak capacity in the first dimension separation We integrate this system with miniaturized LC assemblies to achieve true online fractionation at low (<= 5 nL/min) effluent flow rates Stable isotope labeling is used to monitor the dynamics of the multicomponent Ku protein complex in response to DNA damage induced by gamma radiation C1 [Zhou, Feng; Cardoza, Job D.; Ficarro, Scott B.; Adelmant, Guillaume O.; Lazaro, Jean-Bernard; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Ficarro, Scott B.; Adelmant, Guillaume O.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Zhou, Feng; Cardoza, Job D.; Ficarro, Scott B.; Adelmant, Guillaume O.; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Lazaro, Jean-Bernard] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Marto, JA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St,Smith 1158A, Boston, MA 02115 USA. FU NHGRI NIH HHS [P50HG004233, P50 HG004233, P50 HG004233-04]; NINDS NIH HHS [P01 NS047572, P01 NS047572-06, P01NS047572] NR 70 TC 23 Z9 24 U1 2 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD DEC PY 2010 VL 9 IS 12 BP 6242 EP 6255 DI 10.1021/pr1004696 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 688NI UT WOS:000284856200014 PM 20873769 ER PT J AU Zhang, XY Xiu, MH Song, C Chen, DC Wu, GY Haile, CN Kosten, TA Kosten, TR AF Zhang, Xiang Yang Xiu, Mei Hong Song, Cai Chen, Da Chun Wu, Gui Ying Haile, Colin N. Kosten, Therese A. Kosten, Thomas R. TI Increased serum S100B in never-medicated and medicated schizophrenic patients SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Schizophrenia; S100B; Early psychosis; Antipsychotic treatment; Psychopathology ID NEURON-SPECIFIC ENOLASE; MYELIN BASIC-PROTEIN; CEREBROSPINAL-FLUID; MOOD DISORDERS; S-100B PROTEIN; PLASMA-LEVELS; WEIGHT-GAIN; ANTIPSYCHOTICS; DYSFUNCTION; PATHOLOGY AB S100B is a calcium-binding protein, which is produced primarily by glial cells. It modulates the proliferation and differentiation of neurons and glia by affecting protective and apoptotic mechanisms. Recently, several studies have shown increased serum S100B levels in patients with schizophrenia, suggesting that S100B might be relevant to the pathophysiology of schizophrenia. S100B levels were assessed using ELISA in the serum of 80 never-medicated early-stage and 82 medicated chronic schizophrenia patients and 97 healthy controls subjects. The psychopathology of schizophrenia was assessed by the Positive and Negative Syndrome Scale (PANSS). Our results showed significantly increased serum 51008 levels in both never-medicated and medicated patients compared to normal controls (both p < 0.0001). S100B in never-medicated patients was also markedly increased, compared with medicated patients (p < 0.0001). S100B changes observed were irrespective of neuroleptic medication. gender, age, and smoking. Increased S100B levels in the early stage of schizophrenia suggest that glial cell activation or structural damage may be part of a neurodegenerative process in schizophrenia. The lower S100B levels in chronic than early-stage patients further suggest that antipsychotic treatment may reduce this neurodegeneration. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Zhang, Xiang Yang] Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China. [Zhang, Xiang Yang; Xiu, Mei Hong; Chen, Da Chun] Beijing Hui Long Guan Hosp, Ctr Biol Psychiat, Beijing, Peoples R China. [Zhang, Xiang Yang; Wu, Gui Ying; Haile, Colin N.; Kosten, Therese A.; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Song, Cai] Univ Prince Edward Isl, Atlantic Vet Coll, Dept Biomed Sci, Charlottetown, PE C1A 4P3, Canada. RP Zhang, XY (reprint author), VA Med Ctr, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. EM xyzhang@bcm.edu; kosten@bcm.edu OI Haile, Colin/0000-0001-8293-7291 FU Beijing Municipal Natural Science Foundation [ID: 7072035]; Stanley Medical Research Institute [03T-459, 05T-726]; Department of Veterans Affairs; VISN 16; Mental Illness Research, Education and Clinical Center (MIRECC); United States National Institute of Health [K05-DA0454, P50-DA18827, U01-MH79639] FX This study was funded by the Beijing Municipal Natural Science Foundation (ID: 7072035), the Stanley Medical Research Institute (03T-459 and 05T-726), and the Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC), United States National Institute of Health K05-DA0454, P50-DA18827 and U01-MH79639. These sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 40 TC 19 Z9 22 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD DEC PY 2010 VL 44 IS 16 BP 1236 EP 1240 DI 10.1016/j.jpsychires.2010.04.023 PG 5 WC Psychiatry SC Psychiatry GA 703CP UT WOS:000285952000016 PM 20510426 ER PT J AU Langevin, JP De Salles, AAF Kosoyan, HP Krahl, SE AF Langevin, Jean-Philippe De Salles, Antonio A. F. Kosoyan, Hovsep P. Krahl, Scott E. TI Deep brain stimulation of the amygdala alleviates post-traumatic stress disorder symptoms in a rat model SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Deep brain stimulation; Amygdala; Post-traumatic stress disorder; Basolateral nucleus; Fear; Functional imaging ID COMORBIDITY SURVEY REPLICATION; MEDIAL PREFRONTAL CORTEX; DSM-IV DISORDERS; BLOOD-FLOW; PTSD; FEAR; PREVALENCE; EXPRESSION; VETERANS; LESIONS AB Post-traumatic stress disorder (PTSD) is an anxiety disorder triggered by a life-threatening event causing intense fear. Recently, functional neuroimaging studies have suggested that amygdala hyperactivity is responsible for the symptoms of PTSD. Deep brain stimulation (DBS) can functionally reduce the activity of a cerebral target by delivering an electrical signal through an electrode. We tested whether DBS of the amygdala could be used to treat PTSD symptoms. Rats traumatized by inescapable shocks, in the presence of an unfamiliar object, develop the tendency to bury the object when re-exposed to it several days later. This behavior mimics the symptoms of PTSD. 10 Sprague Dawley rats underwent the placement of an electrode in the right basolateral nucleus of the amygdala (BLn). The rats were then subjected to a session of inescapable shocks while being exposed to a conspicuous object (a ball). Five rats received DBS treatment while the other 5 rats did not. After 7 days of treatment, the rats were re-exposed to the ball and the time spent burying it under the bedding was recorded. Rats treated with BLn DBS spent on average 13 times less time burying the ball than the sham control rats. The treated rats also spent 18 times more time exploring the ball than the sham control rats. In conclusion, the behavior of treated rats in this PTSD model was nearly normalized. We argue that these results have direct implications for patients suffering from treatment-resistant PTSD by offering a new therapeutic strategy. Published by Elsevier Ltd. C1 [Langevin, Jean-Philippe] Univ Arizona, Div Neurosurg, Tucson, AZ 85724 USA. [Langevin, Jean-Philippe] So Arizona Vet Affairs Healthcare Syst, Neurosurg Serv, Tucson, AZ 85723 USA. [De Salles, Antonio A. F.; Krahl, Scott E.] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA 90095 USA. [Kosoyan, Hovsep P.; Krahl, Scott E.] Greater Los Angeles Vet Affairs Healthcare Syst, Res & Dev Serv, Los Angeles, CA 90073 USA. RP Langevin, JP (reprint author), Univ Arizona, Div Neurosurg, POB 245070,1501 N Campbell Ave,Room 4310, Tucson, AZ 85724 USA. EM jean-philippe.langevin@va.gov NR 26 TC 32 Z9 34 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD DEC PY 2010 VL 44 IS 16 BP 1241 EP 1245 DI 10.1016/j.jpsychires.2010.04.022 PG 5 WC Psychiatry SC Psychiatry GA 703CP UT WOS:000285952000017 PM 20537659 ER PT J AU Osman, A Gutierrez, PM Wong, JL Freedenthal, S Bagge, CL Smith, KD AF Osman, Augustine Gutierrez, Peter M. Wong, Jane L. Freedenthal, Stacey Bagge, Courtney L. Smith, Kimberly D. TI Development and Psychometric Evaluation of the Suicide Anger Expression Inventory-28 SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE Suicide; Anger expression; Factor analysis; Self-report; Psychometrics ID IDEATION PANSI INVENTORY; COGNITIVE VULNERABILITY; COLLEGE-STUDENTS; NEGATIVE AFFECT; YOUNG-ADULTS; SELF-REPORT; ADOLESCENTS; VALIDATION; RUMINATION; SCALE AB We conducted 4 studies to develop and cross-validate scores on a multidimensional self-report measure of suicide and anger expression, the Suicide Anger Expression Inventory-28 (SAEI-28) The SAEI-28 evaluates Suicide Rumination, Maladaptive Expression, Reactive Distress, and Adaptive Expression with 7 content specific items each Participants were between ages 14 and 47 years old Study 1 developed a pool of content relevant and representative items for the new inventory Study 2 explored potential domains of the SAEI-28 items, evaluating preliminary estimates of internal consistency reliability Study 3 examined specific structures of the SAEI-28 items and scale reliability Study 4 evaluated the fit of the oblique 4-factor model to 2 alternative solutions Support was found for estimates of internal consistency reliability for the scales Criterion-related validity and potential correlates for the SAEI-28 scales were also assessed C1 [Osman, Augustine; Smith, Kimberly D.] Univ Texas San Antonio, Dept Psychol, San Antonio, TX 78249 USA. [Gutierrez, Peter M.] MIRECC, Denver VA Med Ctr, Denver, CO USA. [Wong, Jane L.] Armstrong Atlantic State Univ, Savannah, GA USA. [Freedenthal, Stacey] Univ Denver, Denver, CO USA. [Bagge, Courtney L.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. RP Osman, A (reprint author), Univ Texas San Antonio, Dept Psychol, 1 UTSA Circle, San Antonio, TX 78249 USA. NR 85 TC 5 Z9 5 U1 4 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 EI 1573-3505 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD DEC PY 2010 VL 32 IS 4 BP 595 EP 608 DI 10.1007/s10862-010-9186-5 PG 14 WC Psychology, Clinical SC Psychology GA 681HU UT WOS:000284302800015 ER PT J AU Reddy, SM Anandarajah, AP Fisher, MC Mease, PJ Greenberg, JD Kremer, JM Reed, G Chen, R Messing, S Kaukeinen, K Ritchlin, CT AF Reddy, Soumya M. Anandarajah, Allen P. Fisher, Mark C. Mease, Philip J. Greenberg, Jeffrey D. Kremer, Joel M. Reed, George Chen, Rui Messing, Susan Kaukeinen, Kimberly Ritchlin, Christopher T. TI Comparative Analysis of Disease Activity Measures, Use of Biologic Agents, Body Mass Index, Radiographic Features, and Bone Density in Psoriatic Arthritis and Rheumatoid Arthritis Patients Followed in a Large U.S. Disease Registry SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE PSORIATIC ARTHRITIS; RHEUMATOID ARTHRITIS; RADIOGRAPHY; BONE DENSITY; DISEASE ACTIVITY ID MINERAL DENSITY; CLINICAL-TRIALS; GASTRIC BYPASS; REMISSION; OBESITY; RISK; INFLAMMATION; THERAPY; JOINT; DRUG AB Objective. To compare disease activity, radiographic features, and bone density in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) matched cohorts. Methods. Disease activity and radiographic data in the Consortium of Rheumatology Researchers of North America database from 2001 to 2008 were compared for 2481 patients with PsA and 17,107 patients with RA subsequently matched for age, gender, and disease duration. Radiographic outcomes included presence of erosions, and joint deformity. In addition, bone mineral density (BMD) scores for lumbar spine (L-spine) and femoral neck were compared using the same matching criteria plus weight and smoking status. Results. Tender (4.5 vs 3.4, p <0.001) and swollen (4.4 vs 2.9, p <0.012) joint counts, and modified Health Assessment Questionnaire scores were significantly higher (0.4 vs 0.3, p < 0.001) in patients with RA compared with patients with PsA. Patient general health and pain scores were also higher in patients with RA vs patients with PsA. Joint erosions (47.4% vs 37.6%, p = 0.020) and deformity (25.2% vs 21.6%, p = 0.021) were more prevalent in RA than PsA. In multivariate analysis, a reduced prevalence of erosions in PsA vs RA was noted (OR 0.609, p <0.001). After matching, T-scores for L-spine (-0.54 vs -0.36, p = 0.077) and femoral neck (-0.88 vs -0.93, p = 0.643) were similar in patients with RA and patients with PsA, although body weight was a major confounder. Conclusion. The level of disease activity and radiographic damage was significantly higher for RA vs PsA subjects, although the magnitude of differences was relatively small. BMD levels were comparable between cohorts. Outcomes in patients with PsA and patients with RA may be more similar than previously reported. (First Release Sept 15 2010; J Rheumatol 2010;37:2566-72; doi:3899/jrheum.100483) C1 [Reddy, Soumya M.; Greenberg, Jeffrey D.] NYU, Hosp Joint Dis, Sch Med, New York, NY 10003 USA. [Anandarajah, Allen P.; Chen, Rui; Messing, Susan; Kaukeinen, Kimberly; Ritchlin, Christopher T.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Fisher, Mark C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Mease, Philip J.] Seattle Rheumatol Associates, Seattle, WA USA. [Kremer, Joel M.] Albany Med Coll, Albany, NY 12208 USA. [Reed, George] Univ Massachusetts, Worcester, MA 01605 USA. RP Reddy, SM (reprint author), NYU, Hosp Joint Dis, Sch Med, New York, NY 10003 USA. EM Soumya.Reddy@nyumc.org RI Chen, Rui/A-5679-2012 FU CORRONA FX Funded by CORRONA. Drs. Kremer, Greenberg, and Reed serve as CORRONA president, Chief Scientific Officer, and research contractee through the University of Massachusetts, respectively. NR 31 TC 17 Z9 17 U1 0 U2 6 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD DEC PY 2010 VL 37 IS 12 BP 2566 EP 2572 DI 10.3899/jrheum.100483 PG 7 WC Rheumatology SC Rheumatology GA 694CM UT WOS:000285272600019 PM 20843908 ER PT J AU Dao, TK Chu, D Springer, J Hiatt, E Nguyen, Q AF Dao, Tam K. Chu, Danny Springer, Justin Hiatt, Emily Nguyen, Quang TI Depression and Geographic Status as Predictors for Coronary Artery Bypass Surgery Outcomes SO JOURNAL OF RURAL HEALTH LA English DT Article DE CABG; cardiovascular disease; mental health; rural; urban ID RANDOMIZED CONTROLLED-TRIAL; HEART-DISEASE; PRIMARY-CARE; ADMINISTRATIVE DATABASES; PSYCHIATRIC-DISORDERS; COMORBIDITY INDEX; GRAFT-SURGERY; RISK-FACTORS; MORTALITY; PSYCHOTHERAPY AB Purpose: To examine the relationships between depression, geographic status, and clinical outcomes following a coronary artery bypass grafting (CABG) surgery. Methods: Using the 2004 Nationwide Inpatient Sample database, we identified 63,061 discharge records of patients who underwent a primary CABG surgery (urban 57,247 and rural 5,814). We analyzed 7 demographic variables, 19 preoperative medical and psychiatric variables, and 2 outcome variables (ie, in-hospital mortality and length of stay). Logistic regression and multivariable regression analyses were used to assess urban-rural status and depression as independent predictors of in-hospital mortality and length of stay. Findings: Rural patients were more likely to have a comorbid depression diagnosis compared to urban patients (urban = 19.4%, rural = 21.4%, P < .001). After adjusting for confounding factors, having a comorbid depression diagnosis (B = 1.10, P < .001) and residing in a rural area (B = .986, P < .05) were associated with an increased length of in-hospital stay following CABG surgery. Furthermore, having a depression diagnosis (OR = 1.63, 95% CI = 1.45-2.21) and residing in a rural area (OR = 1.43, 95% CI = .896-1.45) were associated with an increased likelihood of in-hospital mortality. Conclusions: Rural patients were more likely than urban ones to have a depression diagnosis. Depression was a significant independent predictor of both in-hospital mortality and length of stay for patients receiving CABG surgery. Also, rural patients had increased lengths of in-hospital stay as well as in-hospital mortality rates compared to those who resided in urban areas. C1 [Dao, Tam K.] Univ Houston, Michael E DeBakey Vet Affairs Med Ctr, Dept Educ Psychol, Houston, TX 77030 USA. [Dao, Tam K.; Springer, Justin; Nguyen, Quang] Michael E DeBakey VA Med Ctr, Dept Surg, Houston, TX USA. [Dao, Tam K.; Chu, Danny; Springer, Justin; Nguyen, Quang] Baylor Coll Med, Houston, TX 77030 USA. [Dao, Tam K.; Springer, Justin; Nguyen, Quang] Univ Texas Houston, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Houston, TX 77225 USA. [Chu, Danny] Div Cardiothorac Surg, Houston, TX USA. RP Dao, TK (reprint author), Univ Houston, Michael E DeBakey Vet Affairs Med Ctr, Dept Educ Psychol, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM tam.dao@va.gov NR 36 TC 8 Z9 8 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0890-765X J9 J RURAL HEALTH JI J. Rural Health PD WIN PY 2010 VL 26 IS 1 BP 36 EP 43 DI 10.1111/j.1748-0361.2009.00263.x PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 540EJ UT WOS:000273313500006 PM 20105266 ER PT J AU Delaney, TF Duan, ZF Hornicek, FJ AF Delaney, Thomas F. Duan, Zhenfeng Hornicek, Francis J. TI Proteomic Profiling of Chordoma SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Editorial Material C1 [Delaney, Thomas F.] Massachusetts Gen Hosp, Dept Radiat Oncol, FH Burr Proton Therapy Ctr, Boston, MA 02114 USA. [Duan, Zhenfeng; Hornicek, Francis J.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Div Orthopaed Oncol, Boston, MA 02114 USA. RP Delaney, TF (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, FH Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. EM tdelaney@partners.org OI Duan, Zhenfeng/0000-0002-8543-083X NR 5 TC 2 Z9 3 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD DEC 1 PY 2010 VL 102 IS 7 BP 719 EP 719 DI 10.1002/jso.21766 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 694FV UT WOS:000285281300003 PM 21104921 ER PT J AU Thurber, GM Figueiredo, JL Weissleder, R AF Thurber, Greg M. Figueiredo, Jose-Luiz Weissleder, Ralph TI Detection Limits of Intraoperative Near Infrared Imaging for Tumor Resection SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE antibody targeting; antigen expression; fluorescence; surgery ID SOFT-TISSUE SARCOMA; COLORECTAL-CANCER; LOCAL RECURRENCE; MONOCLONAL-ANTIBODIES; CYTOREDUCTIVE SURGERY; CURATIVE RESECTION; PRECLINICAL MODEL; OVARIAN-CARCINOMA; RESIDUAL DISEASE; SURVIVAL AB Background and Objectives: The application of fluorescent molecular imaging to surgical oncology is a developing field with the potential to reduce morbidity and mortality. However, the detection thresholds and other requirements for successful intervention remain poorly understood. Here we modeled and experimentally validated depth and size of detection of tumor deposits, trade-offs in coverage and resolution of areas of interest, and required pharmacokinetics of probes based on differing levels of tumor target presentation. Methods: Three orthotopic tumor models were imaged by widefield epifluorescence and confocal microscopes, and the experimental results were compared with pharmacokinetic models and light scattering simulations to determine detection thresholds. Results: Widefield epifluorescence imaging can provide sufficient contrast to visualize tumor margins and detect tumor deposits 3-5 mm deep based on labeled monoclonal antibodies at low objective magnification. At higher magnification, surface tumor deposits at cellular resolution are detectable at TBR ratios achieved with highly expressed antigens. Conclusions: A widefield illumination system with the capability for macroscopic surveying and microscopic imaging provides the greatest utility for varying surgical goals. These results have implications for system and agent designs, which ultimately should aid complete resection in most surgical beds and provide real-time feedback to obtain clean margins. J. Surg. Oncol. 2010;102:758-764. (C) 2010 Wiley-Liss, Inc. C1 [Thurber, Greg M.; Figueiredo, Jose-Luiz; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. RP Weissleder, R (reprint author), Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu OI Thurber, Greg/0000-0001-7570-2080 FU [P50 CA86355]; [U24 CA092782]; [T32 CA079443] FX We would like to thank Joshua Dunham for help in creating the tumor phantoms, Rabi Upadhyay and Claudio Vinegoni for helpful discussion and review of the manuscript, and Yvonna Fisher-Jeffes for manuscript review. Grant support was provided in part by P50 CA86355, U24 CA092782, and T32 CA079443. NR 39 TC 18 Z9 18 U1 0 U2 14 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD DEC 1 PY 2010 VL 102 IS 7 BP 758 EP 764 DI 10.1002/jso.21735 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 694FV UT WOS:000285281300012 PM 20872807 ER PT J AU Fink, MP AF Fink, Mitchell P. TI The Therapeutic Potential of Pyruvate SO JOURNAL OF SURGICAL RESEARCH LA English DT Editorial Material ID ETHYL PYRUVATE; PROLIFERATING CELLS; HEART MITOCHONDRIA; AEROBIC GLYCOLYSIS; SODIUM PYRUVATE; ISCHEMIA; REPERFUSION; PROTECTION; TRANSIENT; RAT C1 VA Greater Los Angeles, Dept Surg MF 10H2, Los Angeles, CA 90073 USA. RP Fink, MP (reprint author), VA Greater Los Angeles, Dept Surg MF 10H2, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 22 TC 4 Z9 4 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD DEC PY 2010 VL 164 IS 2 BP 218 EP 220 DI 10.1016/j.jss.2010.01.046 PG 3 WC Surgery SC Surgery GA 690AO UT WOS:000284972600009 PM 20451918 ER PT J AU Ibrahim, OA Levins, PC AF Ibrahim, Omar A. Levins, Paul C. TI The Harvard program and the enduring legacy of Thomas B Fitzpatrick SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter C1 [Ibrahim, Omar A.; Levins, Paul C.] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ibrahim, OA (reprint author), Harvard Univ, Sch Med, Dept Dermatol, 55 Fruit Si BH 616, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD DEC PY 2010 VL 63 IS 6 BP 1099 EP 1100 DI 10.1016/j.jaad.2010.03.042 PG 2 WC Dermatology SC Dermatology GA 689YX UT WOS:000284968100023 PM 21093665 ER PT J AU Jensen, JD Dunnick, CA Arbuckle, HA Brice, S Freeman, SR High, W Howe, W Prado, R Prok, L Seitz, G Vance, K Gamble, RG Dellavalle, RP AF Jensen, James Daniel Dunnick, Cory A. Arbuckle, H. Alan Brice, Sylvia Freeman, Scott R. High, Whitney Howe, William Prado, Renata Prok, Lori Seitz, Gregory Vance, Karl Gamble, Ryan G. Dellavalle, Robert P. TI Dermatology information on the Internet An appraisal by dermatologists and dermatology residents SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter C1 [Jensen, James Daniel; Vance, Karl; Gamble, Ryan G.] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Dunnick, Cory A.; Arbuckle, H. Alan; Brice, Sylvia; Freeman, Scott R.; High, Whitney; Howe, William; Prado, Renata; Prok, Lori; Seitz, Gregory; Dellavalle, Robert P.] Univ Colorado Denver, Dept Dermatol, Aurora, CO USA. [Arbuckle, H. Alan; Dellavalle, Robert P.] Denver Vet Affairs Med Ctr, Aurora, CO USA. [Arbuckle, H. Alan; Prok, Lori] Childrens Hosp, Aurora, CO USA. RP Dellavalle, RP (reprint author), 1055 Clermont St,165, Denver, CO 80220 USA. RI Dellavalle, Robert/L-2020-2013 OI Dellavalle, Robert/0000-0001-8132-088X NR 5 TC 6 Z9 6 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD DEC PY 2010 VL 63 IS 6 BP 1101 EP 1103 DI 10.1016/j.jaad.2010.01.031 PG 3 WC Dermatology SC Dermatology GA 689YX UT WOS:000284968100025 PM 21093668 ER PT J AU DeFranco, MJ Higgins, LD Warner, JJP AF DeFranco, Michael J. Higgins, Laurence D. Warner, Jon J. P. TI Subscapularis Management in Open Shoulder Surgery SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Review ID LESSER TUBEROSITY OSTEOTOMY; ROTATOR CUFF REPAIR; BIOMECHANICAL EVALUATION; MUSCLE FUNCTION; ARTHROPLASTY; TENDON; REPLACEMENT; FOOTPRINT; INSERTION; STABILIZATION AB Management of the subscapularis in open shoulder surgery is a controversial topic Subscapularis tenotomy has been the traditional approach, but other techniques have recently been developed to preserve the integrity of the subscapularis tendon These include subscapularis peel, subscapularis split, and lesser tuberosity osteotomy The biologic healing and biomechanical properties associated With each surgical approach must be evaluated to determine the best option for each patient A strong, anatomic repair is required to achieve optimal clinical outcomes C1 [DeFranco, Michael J.] Lenox Hill Hosp, Shoulder Serv, Dept Orthopaed Surg, New York, NY 10021 USA. [Higgins, Laurence D.] Brigham & Womens Hosp, Harvard Shoulder Serv, Dept Orthopaed Surg, Boston, MA 02115 USA. [Warner, Jon J. P.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Harvard Shoulder Serv, Boston, MA 02114 USA. RP DeFranco, MJ (reprint author), Lenox Hill Hosp, Shoulder Serv, Dept Orthopaed Surg, New York, NY 10021 USA. FU Aircast Arthrex; Mitek Smith Nephew; ArthroCare FX Dr Higgins or an immediate family member has received royalties from Zimmer and is a member of a speakers' bureau or has made paid presentations on behalf of and serves as a paid consultant to or is an employee of Johnson & Johnson Dr Warner or an immediate family member has received royalties from Zimmer and has received research or institutional support from Aircast Arthrex, Mitek Smith & Nephew, and ArthroCare Neither Dr De Franco nor any immediate family member has received anything of value from or owns stock in a commercial company or institution related directly or indirectly to the subject of this article NR 45 TC 10 Z9 10 U1 0 U2 1 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD DEC PY 2010 VL 18 IS 12 BP 707 EP 717 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 690CV UT WOS:000284980700001 PM 21119137 ER PT J AU Marcaurelle, LA Comer, E Dandapani, S Duvall, JR Gerard, B Kesavan, S Lee, MD Liu, HB Lowe, JT Marie, JC Mulrooney, CA Pandya, BA Rowley, A Ryba, TD Suh, BC Wei, JQ Young, DW Akella, LB Ross, NT Zhang, YL Fass, DM Reis, SA Zhao, WN Haggarty, SJ Palmer, M Foley, MA AF Marcaurelle, Lisa A. Comer, Eamon Dandapani, Sivaraman Duvall, Jeremy R. Gerard, Baudouin Kesavan, Sarathy Lee, Maurice D. Liu, Haibo Lowe, Jason T. Marie, Jean-Charles Mulrooney, Carol A. Pandya, Bhaumik A. Rowley, Ann Ryba, Troy D. Suh, Byung-Chul Wei, Jingqiang Young, Damian W. Akella, Lakshmi B. Ross, Nathan T. Zhang, Yan-Ling Fass, Daniel M. Reis, Surya A. Zhao, Wen-Ning Haggarty, Stephen J. Palmer, Michelle Foley, Michael A. TI An Aldol-Based Build/Couple/Pair Strategy for the Synthesis of Medium- and Large-Sized Rings: Discovery of Macrocyclic Histone Deacetylase Inhibitors SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID CLOSING METATHESIS REACTION; RUTHENIUM-CATALYZED CYCLOADDITION; DIVERSITY-ORIENTED SYNTHESIS; AZIDE-ALKYNE CYCLOADDITION; FLUOROUS MIXTURE SYNTHESIS; SOLID-PHASE SYNTHESIS; NATURAL-PRODUCTS; SKELETAL DIVERSITY; SELECTIVE REDUCTIONS; OLEFIN METATHESIS AB An aldol-based build/couple/pair (B/C/P) strategy was applied to generate a collection of stereochemically and skeletally diverse small molecules. In the build phase, a series of asymmetric syn- and anti-aldol reactions were performed to produce four stereoisomers of a Boc-protected gamma-amino acid. In addition, both stereoisomers of O-PMB-protected alaninol were generated to provide a chiral amine coupling partner. In the couple step, eight stereoisomeric amides were synthesized by coupling the chiral acid and amine building blocks. The amides were subsequently reduced to generate the corresponding secondary amines. In the pair phase, three different reactions were employed to enable intramolecular ring-forming processes: nucleophilic aromatic substitution (S(N)Ar), Huisgen [3+2] cycloaddition, and ring-closing metathesis (RCM). Despite some stereochemical dependencies, the ring-forming reactions were optimized to proceed with good to excellent yields, providing a variety of skeletons ranging in size from 8-to 14-membered rings. Scaffolds resulting from the RCM pairing reaction were diversified on the solid phase to yield a 14 400-membered library of macrolactams. Screening of this library led to the discovery of a novel class of histone deacetylase inhibitors, which display mixed enzyme inhibition, and led to increased levels of acetylation in a primary mouse neuron culture. The development of stereo-structure/activity relationships was made possible by screening all 16 stereoisomers of the macrolactams produced through the aldol-based B/C/P strategy. C1 [Marcaurelle, Lisa A.; Zhang, Yan-Ling; Fass, Daniel M.; Reis, Surya A.; Zhao, Wen-Ning; Haggarty, Stephen J.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Fass, Daniel M.; Reis, Surya A.; Zhao, Wen-Ning; Haggarty, Stephen J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Marcaurelle, LA (reprint author), Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM lisa@broadinstitute.org OI Haggarty, Stephen J./0000-0002-7872-168X FU NIGMS-sponsored Center of Excellence in Chemical Methodology and Library Development (Broad Institute CMLD) [P50 GM069721]; NIH [1R01DA028301-01]; Stanley Medical Research Institute FX We thank Prof. Stuart Schreiber, Dr. Edward Holson, and Dr. Florence Wagner for helpful discussions, Dr. Stephen Johnston and Anita Vrcic for analytical support, and Dr. Peter Muller for X-ray crystallography. We thank the Chemical Biology Platform Informatics group for the development of the Stereo-Structure Attribute Relationship (SSAR) visualization tool where attribute value represents activity, purity, yield, or any measurement of interest. This work was funded in part by the NIGMS-sponsored Center of Excellence in Chemical Methodology and Library Development (Broad Institute CMLD; P50 GM069721). Financial support for D.M.F., S.A.R, W.-N.Z., and S.J.H. from the NIH (1R01DA028301-01) and Stanley Medical Research Institute is also gratefully acknowledged. NR 95 TC 126 Z9 127 U1 3 U2 39 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 DEC 1 PY 2010 VL 132 IS 47 BP 16962 EP 16976 DI 10.1021/ja105119r PG 15 WC Chemistry, Multidisciplinary SC Chemistry GA 690AM UT WOS:000284972400040 PM 21067169 ER PT J AU Patti, JA AF Patti, John A. TI Leadership and the ACR: A Road Map to Success SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Patti, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA. EM jpatti@partners.org NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD DEC PY 2010 VL 7 IS 12 BP 911 EP 911 DI 10.1016/j.jacr.2010.10.009 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V23SV UT WOS:000208363400001 PM 21129677 ER PT J AU Ingraham, AM Cohen, ME Bilimoria, KY Dimick, JB Richards, KE Raval, MV Fleisher, LA Hall, BL Ko, CY AF Ingraham, Angela M. Cohen, Mark E. Bilimoria, Karl Y. Dimick, Justin B. Richards, Karen E. Raval, Mehul V. Fleisher, Lee A. Hall, Bruce L. Ko, Clifford Y. TI Association of Surgical Care Improvement Project Infection-Related Process Measure Compliance with Risk-Adjusted Outcomes: Implications for Quality Measurement SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; PERFORMANCE-MEASURES; HOSPITAL QUALITY; CLINICAL-OUTCOMES; MORTALITY-RATES; SITE INFECTION; US HOSPITALS; OF-CARE; PROGRAM; SURGERY AB BACKGROUND: Facility-level process measure adherence is being publicly reported. However, the association between measure adherence and surgical outcomes is not well-established. Our objective was to determine the degree to which Surgical Care Improvement Project (SCIP) process measures are associated with American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) risk-adjusted outcomes. STUDY DESIGN: This cross-sectional study included hospitals participating in the ACS NSQIP and SCIP (n = 200). ACS NSQIP outcomes (30-day overall morbidity, serious morbidity, surgical site infections [SSI], and mortality) and adherence to SCIP SSI-related process measures (from the Hospital Compare database) were collected from January 1, 2008, through December 31, 2008. Hospital-level correlation coefficients between compliance with 4 process measures (ie, antibiotic administration within 1 hour before incision [SCIP-1]; appropriate antibiotic prophylaxis [SCIP-2]; antibiotic discontinuation within 24 hours after surgery [SCIP-3]; and appropriate hair removal [SCIP 6]) and 4 risk-adjusted outcomes were calculated. Regression analyses estimated the contribution of process measure adherence to risk-adjusted outcomes. RESULTS: Of 211 ACS NSQIP hospitals, 95% had data reported by Hospital Compare. Depending on the measure, hospital-level compliance ranged from 60% to 100%. Of the 16 correlations, 15 demonstrated nonsignificant associations with risk-adjusted outcomes. The exception was the relationship between SCIP-2 and SSI (p = 0.004). SCIP-1 demonstrated an intriguing but nonsignificant relationship with SSI (p = 0.08) and overall morbidity (p = 0.08). Although adherence to SCIP-2 was a significant predictor of risk-adjusted SSI (p < 0.0001) and overall morbidity (p < 0.0001), inclusion of compliance for SCIP-1 and SCIP-2 caused only slight improvement in model quality. CONCLUSIONS: Better adherence to infection-related process measures over the observed range was not significantly associated with better outcomes with one exception. Different measures of quality might be needed for surgical infection. (J Am Coll Surg 2010; 211: 705-714. (C) 2010 by the American College of Surgeons) C1 [Ingraham, Angela M.] Univ Cincinnati, Dept Surg, Coll Med, Cincinnati, OH 45267 USA. [Ingraham, Angela M.; Cohen, Mark E.; Richards, Karen E.; Raval, Mehul V.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Bilimoria, Karl Y.; Raval, Mehul V.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Dimick, Justin B.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Fleisher, Lee A.] Univ Penn Hlth Syst, Dept Anesthesia, Philadelphia, PA USA. [Hall, Bruce L.] John Cochran Vet Affairs Med Ctr, Dept Surg, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Hall, Bruce L.] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Hall, Bruce L.] Washington Univ, Ctr Hlth Policy, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Olin Business Sch, St Louis, MO USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Ingraham, AM (reprint author), Univ Cincinnati, Dept Surg, Coll Med, 231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM angieingraham@gmail.com OI Raval, Mehul/0000-0002-1527-2661 FU American College of Surgeons; John Gray Research Fellowship; Daniel F and Ada L Rice Foundation; Northwestern University; Center for Health Policy, Washington University St Louis FX Nothing to disclose. Drs Ingraham and Raval are supported by the Clinical Scholar in Residence Program at the American College of Surgeons. Dr Raval is supported by the John Gray Research Fellowship and the Daniel F and Ada L Rice Foundation. Dr Bilimoria is supported by a Priority Grant from Northwestern University. Dr Hall is supported by the Center for Health Policy, Washington University St Louis. NR 38 TC 93 Z9 94 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD DEC PY 2010 VL 211 IS 6 BP 705 EP 714 DI 10.1016/j.jamcollsurg.2010.09.006 PG 10 WC Surgery SC Surgery GA 697GE UT WOS:000285500200003 PM 21109157 ER PT J AU Raval, MV Cohen, ME Ingraham, AM Dimick, JB Osborne, NH Hamilton, BH Ko, CY Hall, BL AF Raval, Mehul V. Cohen, Mark E. Ingraham, Angela M. Dimick, Justin B. Osborne, Nicholas H. Hamilton, Barton H. Ko, Clifford Y. Hall, Bruce L. TI Improving American College of Surgeons National Surgical Quality Improvement Program Risk Adjustment: Incorporation of a Novel Procedure Risk Score SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID PRIVATE-SECTOR; PATIENT SAFETY; MORTALITY; CARE; MORBIDITY; HOSPITALS; IMPACT; NSQIP AB BACKGROUND: Risk-adjusted evaluation is a key component of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). The purpose of this study was to improve standard ACS NSQIP risk adjustment using a novel procedure risk score. STUDY DESIGN: Current Procedural Terminology codes (CPTs) represented in ACS NSQIP data were assigned to 136 procedure groups. Log odds predicted risk from preliminary logistic regression modeling generated a continuous risk score for each procedure group, used in subsequent modeling. Appropriate subsets of 271,368 patients in the 2008 ACS NSQIP were evaluated using logistic models for overall 30-day morbidity, 30-day mortality, and surgical site infection (SSI). Models were compared when including either work Relative Value Unit (RVU), RVU and the standard ACS NSQIP CPT range variable (CPT range), or RVU and the newly constructed CPT risk score (CPT risk), plus routine ACS NSQIP predictors. RESULTS: When comparing the CPT risk models with the CPT range models for morbidity in the overall general and vascular surgery dataset, CPT risk models provided better discrimination through higher c statistics at earlier steps (0.81 by step 3 vs 0.81 by step 46), more information through lower Akaike's information criterion (127,139 vs 130,019), and improved calibration through a smaller Hosmer-Lemeshow chi-square statistic (48.76 vs 116.79). Improved model characteristics of CPT risk over CPT range were most apparent for broader patient populations and outcomes. The CPT risk and standard CPT range models were moderately consistent in identification of outliers as well as assignment of hospitals to quality deciles (weighted kappa >= 0.870). CONCLUSIONS: Information from focused, clinically meaningful CPT procedure groups improves the risk estimation of ACS NSQIP models. (J Am Coll Surg 2010; 211: 715-723. (C) 2010 by the American College of Surgeons) C1 [Raval, Mehul V.; Cohen, Mark E.; Ingraham, Angela M.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Raval, Mehul V.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Ingraham, Angela M.] Univ Cincinnati, Coll Med, Dept Surg, Cincinnati, OH 45267 USA. [Dimick, Justin B.; Osborne, Nicholas H.] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI USA. [Hamilton, Barton H.; Hall, Bruce L.] Washington Univ, Olin Business Sch, John Cochran Vet Affairs Med Ctr, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Dept Surg, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Barnes Jewish Hosp, Ctr Hlth Policy, St Louis, MO USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Raval, MV (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM m-raval@md.northwestern.edu RI Hamilton, Barton/P-5187-2015; OI Raval, Mehul/0000-0002-1527-2661 FU John Gray Research Fellowship; Daniel F and Ada L Rice Foundation FX MVR and AMI participate in the American College of Surgeons Clinical Scholars in Residence Program. MVR is supported by the John Gray Research Fellowship and the Daniel F and Ada L Rice Foundation. NR 25 TC 47 Z9 48 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD DEC PY 2010 VL 211 IS 6 BP 715 EP 723 DI 10.1016/j.jamcollsurg.2010.07.021 PG 9 WC Surgery SC Surgery GA 697GE UT WOS:000285500200004 PM 20846884 ER PT J AU Konstantinidis, IT Dursun, A Zheng, H Wargo, JA Thayer, SP Fernandez-del Castillo, C Warshaw, AL Ferrone, CR AF Konstantinidis, Ioannis T. Dursun, Abdulmetin Zheng, Hui Wargo, Jennifer A. Thayer, Sarah P. Fernandez-del Castillo, Carlos Warshaw, Andrew L. Ferrone, Cristina R. TI Metastatic Tumors in the Pancreas in the Modern Era SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID RENAL-CELL CARCINOMA; OVARIAN-CANCER; RESECTION; SURVIVAL; SURGERY; RECURRENCE AB BACKGROUND: Tumors metastasizing to the pancreas are rare, and published series are limited by few patients treated for extended periods of time. Renal cell cancer (RCC) is the most common primary tumor metastasizing to the pancreas. Our aim was to describe the clinicopathologic characteristics and patient outcomes in a modern series of patients who underwent metastasectomy, with an emphasis on RCC. STUDY DESIGN: Retrospective review of all pancreatic resections between January 1993 and October 2009. RESULTS: We identified 40 patients with a median age of 62 years; 55% were female. Patients most commonly presented with abdominal pain (47.5%). Operations performed included 10 pancreaticoduodenectomies, 1 middle, 23 distal, 3 total pancreatectomies, and 3 enucleations. Primary cancers were RCC (n = 20), ovarian (n = 6), sarcoma (n = 3), colon (n = 3), melanoma (n = 2), and others (n = 6). Median survival for all patients after metastasectomy was 4.4 years. Median survival after metastasectomy for RCC was 8.7 years, and the 5-year actuarial survival was 61%. For RCCs, pancreas was the first site of an extrarenal recurrence in 85% and was synchronous with the primary in 5% of patients. There was no survival difference if the time interval to metastasis was shorter than the median (8.7 years), if tumor nodules were multiple or bigger than the median (3 cm), or if the pancreas was not the first site of metastases. CONCLUSIONS: An aggressive approach to lesions metastatic to the pancreas is often warranted if the patient can be rendered free of disease. Although patients with RCC can experience long-term survival after metastasectomy, survival is less favorable for other primary tumors. (J Am Coll Surg 2010; 211: 749-753. (C) 2010 by the American College of Surgeons) C1 [Konstantinidis, Ioannis T.; Dursun, Abdulmetin; Wargo, Jennifer A.; Thayer, Sarah P.; Fernandez-del Castillo, Carlos; Warshaw, Andrew L.; Ferrone, Cristina R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Ferrone, CR (reprint author), Wang Ambulatory Care Ctr 460, 15 Parkman St, Boston, MA 02114 USA. EM cferrone@partners.org FU NCI NIH HHS [P01 CA117969-04S1, P01 CA117969-04, P01 CA117969, P50 CA127003, P50 CA127003-05, P50 CA127003-04]; NIDDK NIH HHS [K08 DK071329-05, K08 DK071329-04, K08 DK071329] NR 18 TC 43 Z9 45 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD DEC PY 2010 VL 211 IS 6 BP 749 EP 753 DI 10.1016/j.jamcollsurg.2010.08.017 PG 5 WC Surgery SC Surgery GA 697GE UT WOS:000285500200009 PM 21109158 ER PT J AU Matula, SR Trivedi, AN Miake-Lye, I Glassman, PA Shekelle, P Asch, S AF Matula, Sierra R. Trivedi, Amal N. Miake-Lye, Isomi Glassman, Peter A. Shekelle, Paul Asch, Steven TI Comparisons of Quality of Surgical Care between the US Department of Veterans Affairs and the Private Sector SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Review ID UNIVERSITY MEDICAL-CENTERS; 30-DAY POSTOPERATIVE MORTALITY; PATIENT SAFETY; SURGERY; OPERATIONS; HOSPITALS; MORBIDITY; TRANSPLANTATION; IMPROVEMENT; RESECTION C1 [Matula, Sierra R.; Asch, Steven] Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90024 USA. [Matula, Sierra R.] Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Surg Outcomes & Qual, Los Angeles, CA USA. [Matula, Sierra R.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Trivedi, Amal N.] Brown Univ, Providence VA Med Ctr, Providence, RI 02912 USA. [Trivedi, Amal N.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Glassman, Peter A.; Shekelle, Paul; Asch, Steven] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Matula, SR (reprint author), Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, 911 Broxton Ave, Los Angeles, CA 90024 USA. EM smatula@mednet.ucla.edu FU VA Health Services Research and Development Evidence Synthesis Program, Los Angeles, CA; Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Health Services Research and Development (HSRD) Service; VA; Center on Systems, Outcomes and Quality in Chronic Disease and Rehabilitation, Research Enhancement [HSRD REA 08-263]; Robert Wood Johnson Clinical Scholars Program; Department of Veterans Affairs FX This research was supported by the VA Health Services Research and Development Evidence Synthesis Program, Los Angeles, CA (Miake-Lye, Glassman, Shekelle, and Asch), Career Development Award (CDA-2) from the Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Health Services Research and Development (HSR&D) Service to Dr Trivedi, Robert Wood Johnson Physician VA Faculty Scholar Award to Dr Trivedi, Center on Systems, Outcomes and Quality in Chronic Disease and Rehabilitation, Research Enhancement Award Program (HSR&D REA 08-263) (Dr Trivedi); and the Robert Wood Johnson Clinical Scholars Program (Dr Matula).; All authors are employed by and receive a salary from the Department of Veterans Affairs. NR 31 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD DEC PY 2010 VL 211 IS 6 BP 823 EP 832 DI 10.1016/j.jamcollsurg.2010.09.001 PG 10 WC Surgery SC Surgery GA 697GE UT WOS:000285500200019 PM 21109159 ER PT J AU Chodosh, J Miller-Martinez, D Aneshensel, CS Wight, RG Karlamangla, AS AF Chodosh, Joshua Miller-Martinez, Dana Aneshensel, Carol S. Wight, Richard G. Karlamangla, Arun S. TI Depressive Symptoms, Chronic Diseases, and Physical Disabilities as Predictors of Cognitive Functioning Trajectories in Older Americans SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE depression; cognitive decline; physical health; physical disabilities ID TYPE-2 DIABETES-MELLITUS; METHODOLOGICAL ISSUES; LONGITUDINAL FINDINGS; LATE-LIFE; DECLINE; AGE; POPULATION; DEMENTIA; ADULTS; HEALTH AB OBJECTIVES To determine the concurrent influence of depressive symptoms, medical conditions, and disabilities in activities of daily living (ADLs) on rates of decline in cognitive function of older Americans. DESIGN Prospective cohort. SETTING National population based. PARTICIPANTS A national sample of 6,476 adults born before 1924. MEASUREMENTS Differences in cognitive function trajectories were determined according to prevalence and incidence of depressive symptoms, chronic diseases, and ADL disabilities. Cognitive performance was tested five times between 1993 and 2002 using a multifaceted inventory examined as a global measure (range 0-35, standard deviation (SD) 6.0) and word recall (range 0-20, SD 3.8) analyzed separately. RESULTS Baseline prevalence of depressive symptoms, stroke, and ADL limitations were independently and strongly associated with lower baseline cognition scores but did not predict future cognitive decline. Each incident depressive symptom was independently associated with a 0.06-point lower (95% confidence interval (CI)=0.02-0.10) recall score, incident stroke with a 0.59-point lower total score (95% CI=0.20-0.98), each new basic ADL limitation with a 0.07-point lower recall score (95% CI=0.01-0.14) and a 0.16-point lower total score (95% CI=0.07-0.25), and each incident instrumental ADL limitation with a 0.20-point lower recall score (95% CI=0.10-0.30) and a 0.52-point lower total score (95% CI=0.37-0.67). CONCLUSION Prevalent and incident depressive symptoms, stroke, and ADL disabilities contribute independently to poorer cognitive functioning in older Americans but do not appear to influence rates of future cognitive decline. Prevention, early identification, and aggressive treatment of these conditions may ameliorate the burdens of cognitive impairment. C1 [Chodosh, Joshua] VA Greater Los Angeles Hlth Syst, Geriatr Res Educ & Clin Ctr, Hlth Serv Res & Dev Ctr Excellence, Los Angeles, CA 90073 USA. [Chodosh, Joshua; Miller-Martinez, Dana; Karlamangla, Arun S.] Univ Calif Los Angeles, Sch Med, Dept Med, Div Geriatr, Los Angeles, CA 90024 USA. [Aneshensel, Carol S.; Wight, Richard G.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Community Hlth Sci, Los Angeles, CA 90024 USA. RP Chodosh, J (reprint author), VA Greater Los Angeles Hlth Syst, Geriatr Res Educ & Clin Ctr, Hlth Serv Res & Dev Ctr Excellence, 11G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jchodosh@mednet.ucla.edu OI Chodosh, Joshua/0000-0001-7784-4306 FU National Institute on Aging [R01 AG022537]; National Institute on Aging Older Americans Independence Center at the University of California at Los Angeles [5P30 AG028748] FX This research was supported by a grant from the National Institute on Aging (R01 AG022537, Carol S. Aneshensel, PhD, Principal Investigator). Dr. Karlamangla was partially supported by the National Institute on Aging Older Americans Independence Center at the University of California at Los Angeles (5P30 AG028748). NR 40 TC 13 Z9 14 U1 2 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2010 VL 58 IS 12 BP 2350 EP 2357 DI 10.1111/j.1532-5415.2010.03171.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 692MI UT WOS:000285156500012 PM 21087219 ER PT J AU Singh, JA Lewallen, DG AF Singh, Jasvinder A. Lewallen, David G. TI Predictors of Activity Limitation and Dependence on Walking Aids After Primary Total Hip Arthroplasty SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE primary total hip arthroplasty; THA; predictors; activity limitation; function; walking aids ID REVISION TOTAL HIP; KNEE ARTHROPLASTY; FUNCTIONAL STATUS; UNITED-STATES; REPLACEMENT; PAIN; AGE; VALIDATION; MORBIDITY; QUESTIONNAIRE AB OBJECTIVES To study function outcomes and their predictors after primary total hip arthroplasty (THA). DESIGN Prospective cohort study. SETTING Mayo Clinic. PARTICIPANTS All patients who underwent primary THA at the Mayo Clinic between 1993 and 2005 and were alive at the time of follow-up. MEASUREMENTS Whether sex, age, body mass index (BMI), comorbidity, anxiety, and depression predict moderate to severe activity limitation (limitation in >= 3 activities) and complete dependence on waling aids 2 and 5 years after primary THA was examined. Multivariable logistic regression adjusted for operative diagnosis, American Society of Anesthesiologists score, implant type, and distance from medical center. RESULTS At 2 years, 30.3% of participants reported moderate to severe activity limitation; at 5 years, 35% of participants reported moderate to severe activity limitation. Significant predictors of moderate to severe activity limitations at 2-year follow-up were female sex (odds ratio (OR)=1.2, 95% confidence interval (CI)=1.1-1.4), aged 71 to 80 (OR=2.0, 95% CI=1.6-2.5), aged 80 and older (OR=4.5, 95% CI=3.4-6.0), depression (OR=2.1, 95% CI=1.6-2.7), and BMI greater than 30.0. At 5-year follow-up, significant predictors were aged 71 to 80 (OR=1.7, 95% CI=1.3-2.2), older than 80 (OR=4.3, 95% CI=2.8-6.6), depression (OR=2.3, 95% CI=1.6-3.4), and BMI greater than 30.0.Significant predictors of complete dependence on walking aids at 2 years were female sex (OR=2.0, 95% CI=1.4-2.7), aged 71 to 80 (OR=2.4, 95% CI=1.4-4.2), older than 80 (OR=11.4, 95% CI=6.0-21.9), higher Deyo-Charlson score (OR=1.5, 95% CI=(1.1-1.2) for 5-point increase, depression (OR=2.0, 95% CI=1.2-3.4), and BMI greater than 35.0. Each of these factors also significantly predicted complete dependence on walking at 5-year follow-up, with similar odds ratios, except that BMI of 30.0 to 34.9 was not significantly associated. CONCLUSION Higher BMI, depression, older age, and female sex predict activity limitation and complete dependence on walking aids 2 and 5 years after primary THA. C1 [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Hlth Sci Res, Rochester, MN USA. [Singh, Jasvinder A.; Lewallen, David G.] Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA. [Singh, Jasvinder A.] Vet Affairs Med Ctr, Med Serv, Rheumatol Sect, Minneapolis, MN 55417 USA. [Singh, Jasvinder A.] Univ Minnesota, Dept Med, Div Rheumatol, Minneapolis, MN 55455 USA. [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama, Birmingham, AL USA. RP Singh, JA (reprint author), Minneapolis VA Med Ctr, Rheumatol 111R,1 Vet Dr, Minneapolis, MN 55417 USA. EM jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU Zimmer; TAP; Savient; Abbott; Allergan; Wyeth; URL Pharmaceuticals; Novartis; National Institutes of Health [1 KL2 RR024151-01]; Department of Orthopedic Surgery, Mayo Clinic School of Medicine, Rochester, Minnesota; DePuy; Stryker FX David G. Lewallen has received royalties and speaker fees from Zimmer, has been a paid consultant to Zimmer, and has received institutional research funds from DePuy, Stryker, and Zimmer. Jasvinder A. Singh has received research grants, travel grants and speaker fees from TAP, Savient, Abbott, Allergan, and Wyeth and consultant fees from Savient, URL Pharmaceuticals, and Novartis. No funding was received for this study.; This study was supported by the National Institutes of Health Clinical and Translational Science Awards Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research) and the Department of Orthopedic Surgery, Mayo Clinic School of Medicine, Rochester, Minnesota, and the resources and the use of facilities at the Birmingham Veterans Affairs Medical Center, Alabama. NR 32 TC 31 Z9 32 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2010 VL 58 IS 12 BP 2387 EP 2393 DI 10.1111/j.1532-5415.2010.03182.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 692MI UT WOS:000285156500018 PM 21143444 ER PT J AU Labovitz, AJ Noble, VE Bierig, M Goldstein, SA Jones, R Kort, S Porter, TR Spencer, KT Tayal, VS Wei, K AF Labovitz, Arthur J. Noble, Vicki E. Bierig, Michelle Goldstein, Steven A. Jones, Robert Kort, Smadar Porter, Thomas R. Spencer, Kirk T. Tayal, Vivek S. Wei, Kevin TI Focused Cardiac Ultrasound in the Emergent Setting: A Consensus Statement of the American Society of Echocardiography and American College of Emergency Physicians SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Echocardiography; Emergency department; Focused cardiac ultrasound; Resuscitation ID INFERIOR VENA-CAVA; SUSPECTED PULMONARY-EMBOLISM; RIGHT ATRIAL PRESSURE; TRANSTHORACIC ECHOCARDIOGRAPHY; VENTRICULAR DYSFUNCTION; VALVULAR REGURGITATION; PORTABLE ULTRASOUND; PROGNOSTIC VALUE; ARREST PATIENTS; DIAGNOSIS AB The use of ultrasound has developed over the last 50 years into an indispensable first-line test for the cardiac evaluation of symptomatic patients. The technologic miniaturization and improvement in transducer technology, as well as the implementation of educational curriculum changes in residency training programs and specialty practice, have facilitated the integration of focused cardiac ultrasound into practice by specialties such as emergency medicine. In the emergency department, focused cardiac ultrasound has become a fundamental tool to expedite the diagnostic evaluation of the patient at the bedside and to initiate emergent treatment and triage decisions by the emergency physician. (J Am Soc Echocardiogr 2010;23:1225-30.) C1 [Labovitz, Arthur J.; Bierig, Michelle] St Louis Univ, Sch Med, St Louis, MO USA. [Noble, Vicki E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goldstein, Steven A.] Washington Hosp Ctr, Washington, DC 20010 USA. [Jones, Robert] Metrohlth Med Ctr, Cleveland, OH USA. [Kort, Smadar] SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA. [Porter, Thomas R.] Univ Nebraska Med Ctr, Omaha, NE USA. [Spencer, Kirk T.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Tayal, Vivek S.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Wei, Kevin] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Labovitz, AJ (reprint author), Amer Soc Echocardiog, 2100 Gateway Ctr Blvd,Suite 310, Morrisville, NC 27560 USA. EM ase@asecho.org FU Siemens Medical; Lantheus Medical Imaging; NuVox Pharma; Astellas Pharma, Inc; Philips Ultrasound; Zonare FX The following authors report a relationship with one or more commercial interests: Thomas R. Porter, MD, FASE, serves as a consultant for Lantheus Medical Imaging, receives research support from Siemens Medical, and receives grant support from Lantheus Medical Imaging, NuVox Pharma, and Astellas Pharma, Inc. Vivek S. Tayal, MD, FACEP, receives research support from Philips Ultrasound. Kevin Wei, MD, receives grant support from Zonare and Philips Ultrasound. All other authors reported no actual or potential conflicts of interest in relation to this document. NR 56 TC 177 Z9 183 U1 1 U2 12 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD DEC PY 2010 VL 23 IS 12 BP 1225 EP 1230 DI 10.1016/j.echo.2010.10.005 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 685JL UT WOS:000284624900002 PM 21111923 ER PT J AU O'Hare, AM Covinsky, KE AF O'Hare, Ann M. Covinsky, Kenneth E. TI Prediction Modeling to Assess the Prognostic Significance of a Biomarker Panel SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID CHRONIC KIDNEY-DISEASE; OLDER-ADULTS; OUTCOMES; STRATIFICATION; ALBUMINURIA; VALIDATION; MORTALITY; INDEX; CKD C1 [O'Hare, Ann M.] VA Puget Sound Healthcare Syst, Dept Med, Seattle, WA USA. [O'Hare, Ann M.] Univ Washington, Seattle, WA 98195 USA. [Covinsky, Kenneth E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Covinsky, Kenneth E.] VA Med Ctr, Dept Med, San Francisco, CA USA. RP O'Hare, AM (reprint author), VA Med Ctr, Div Nephrol, 1660 S Columbian Way, Seattle, WA 98109 USA. EM ann.ohare@va.gov FU NIA NIH HHS [K24 AG029812] NR 16 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2010 VL 21 IS 12 BP 2017 EP 2019 DI 10.1681/ASN.2010101078 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 697RJ UT WOS:000285533300005 PM 21088293 ER PT J AU Fox, CS Gona, P Larson, MG Selhub, J Tofler, G Hwang, SJ Meigs, JB Levy, D Wang, TJ Jacques, PF Benjamin, EJ Vasan, RS AF Fox, Caroline S. Gona, Philimon Larson, Martin G. Selhub, Jacob Tofler, Geoffrey Hwang, Shih-Jen Meigs, James B. Levy, Daniel Wang, Thomas J. Jacques, Paul F. Benjamin, Emelia J. Vasan, Ramachandran S. TI A Multi-Marker Approach to Predict Incident CKD and Microalbuminuria SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; RISK-ASSESSMENT STRATEGIES; BRAIN NATRIURETIC PEPTIDE; CORONARY-HEART-DISEASE; SERUM CYSTATIN-C; CARDIOVASCULAR OUTCOMES; RENAL-INSUFFICIENCY; VULNERABLE PATIENT; HYPERTENSIVE-RATS AB Traditional risk factors do not adequately identify individuals at risk for CKD. We related a multi-marker panel consisting of the following seven circulating biomarkers to the incidence of CKD and microalbuminuria (MA) in 2345 participants who attended the sixth Framingham Offspring Study examination (1995 to 1998): C-reactive protein, aldosterone, renin, B-type natriuretic peptide (BNP), plasminogen-activator inhibitor type 1, fibrinogen, and homocysteine. We defined CKD at follow-up (2005 to 2008) as estimated GFR (eGFR) <60 ml/min per 1.73 m(2); we defined MA as urine albumin-to-creatinine ratio >= 25 (women) or 17 (men) mg/g on spot urine samples. We identified a parsimonious set of markers related to outcomes adjusting for standard risk factors and baseline renal function, and we assessed their incremental predictive utility. During a mean 9.5-year follow-up, 213 participants developed CKD and 186 developed MA. In multivariable logistic regression models, the multi-marker panel was associated with incident CKD (P < 0.001) and MA (P = 0.003). Serum homocysteine and aldosterone both were significantly associated with CKD incidence, and log-transformed aldosterone, BNP, and homocysteine were significantly associated with incident MA. Biomarkers improved risk prediction as measured by improvements in the c-statistics for both CKD and MA and by a 7% increase in net risk reclassification. In conclusion, circulating homocysteine, aldosterone, and BNP provide incremental information regarding risk for incident CKD and MA beyond traditional risk factors. C1 [Fox, Caroline S.; Gona, Philimon; Larson, Martin G.; Hwang, Shih-Jen; Levy, Daniel; Benjamin, Emelia J.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Fox, Caroline S.; Hwang, Shih-Jen; Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA. [Selhub, Jacob; Jacques, Paul F.] Tufts Univ, USDA, Human Nutr Res Ctr, Boston, MA 02111 USA. [Tofler, Geoffrey] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Div Cardiol & Prevent Med, Boston, MA 02118 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195, 2-K24-HL04334, R01-HL-077477, R01-DK-080739, 1R01 AG028321] FX This study was supported by National Heart, Lung and Blood Institute's Framingham Heart Study (N01-HC-25195) Grants 2-K24-HL04334, R01-HL-077477, R01-DK-080739, and 1R01 AG028321. NR 44 TC 43 Z9 44 U1 0 U2 5 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2010 VL 21 IS 12 BP 2143 EP 2149 DI 10.1681/ASN.2010010085 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 697RJ UT WOS:000285533300020 PM 20966127 ER PT J AU Greer, BE Koh, WJ Abu-Rustum, NR Apte, SM Campos, SM Chan, J Cho, KR Copeland, L Crispens, MA DuPont, N Eifel, PJ Gaffney, DK Huh, WK Kapp, DS Lurain, JR Martin, L Morgan, MA Morgan, RJ Mutch, D Remmenga, SW Reynolds, RK Small, W Teng, N Valea, FA AF Greer, Benjamin E. Koh, Wui-Jin Abu-Rustum, Nadeem R. Apte, Sachin M. Campos, Susana M. Chan, John Cho, Kathleen R. Copeland, Larry Crispens, Marta Ann DuPont, Nefertiti Eifel, Patricia J. Gaffney, David K. Huh, Warner K. Kapp, Daniel S. Lurain, John R., III Martin, Lainie Morgan, Mark A. Morgan, Robert J., Jr. Mutch, David Remmenga, Steven W. Reynolds, R. Kevin Small, William, Jr. Teng, Nelson Valea, Fidel A. TI Cervical Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; cervical cancer; human papillomavirus; chemotherapy; radiation therapy; hysterectomy ID GYNECOLOGIC-ONCOLOGY-GROUP; SQUAMOUS-CELL-CARCINOMA; LAPAROSCOPIC RADICAL HYSTERECTOMY; PHASE-II TRIAL; PELVIC RADIATION-THERAPY; POSITRON-EMISSION-TOMOGRAPHY; 13 EUROPEAN COUNTRIES; LONG-TERM SURVIVAL; OF-THE-LITERATURE; UTERINE CERVIX C1 [Greer, Benjamin E.] Univ Washington, Seattle, WA 98195 USA. [Koh, Wui-Jin] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Abu-Rustum, Nadeem R.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Apte, Sachin M.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Campos, Susana M.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Chan, John] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Cho, Kathleen R.; Reynolds, R. Kevin] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Copeland, Larry] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Copeland, Larry] Solove Res Inst, Columbus, OH USA. [Crispens, Marta Ann] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [DuPont, Nefertiti] Roswell Pk Canc Inst, Buffalo, NY USA. [Eifel, Patricia J.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Gaffney, David K.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Huh, Warner K.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Kapp, Daniel S.] Stanford Comprehens Canc Ctr, Stanford, CA USA. [Lurain, John R., III; Small, William, Jr.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Martin, Lainie; Morgan, Mark A.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Morgan, Robert J., Jr.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Mutch, David] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Mutch, David] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Remmenga, Steven W.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Teng, Nelson] Stanford Comprehens Canc Ctr, Stanford, CA USA. [Valea, Fidel A.] Duke Comprehens Canc Ctr, Durham, NC USA. RP Greer, BE (reprint author), Univ Washington, Seattle, WA 98195 USA. NR 168 TC 26 Z9 29 U1 0 U2 5 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD DEC PY 2010 VL 8 IS 12 BP 1388 EP 1416 PG 29 WC Oncology SC Oncology GA 692DR UT WOS:000285132200007 PM 21147903 ER PT J AU Arya, M Williams, LT Stone, VE Behforouz, HL Viswanath, K Giordano, TP AF Arya, Monisha Williams, Lena Tionne Stone, Valerie E. Behforouz, Heidi Louise Viswanath, Kasisomayajula Giordano, Thomas Peter TI A Key Strategy for Reducing HIV in African American Communities: Promoting HIV Testing SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Editorial Material DE HIV/AIDS; African Americans ID PERSONS AWARE; HEALTH-CENTER; INFORMATION; PREVENTION; DISPARITIES; RISK; PREVALENCE; BEHAVIOR; UNAWARE; STATES C1 [Arya, Monisha; Williams, Lena Tionne] Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. [Arya, Monisha; Giordano, Thomas Peter] Michael E Debakey VA Med Ctr, Houston VA Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Stone, Valerie E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stone, Valerie E.; Behforouz, Heidi Louise] Harvard Univ, Sch Med, Boston, MA USA. [Stone, Valerie E.] Internal Med Associates, Boston, MA USA. [Behforouz, Heidi Louise] Brigham & Womens Hosp, Dept Med, Div Social Med & Hlth Inequal, Boston, MA 02115 USA. [Behforouz, Heidi Louise] Brigham Internal Med Associates, Boston, MA USA. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Arya, M (reprint author), Baylor Coll Med, Dept Med, Infect Dis Sect, 1 Baylor Plaza,Mailstop BCM 288, Houston, TX 77030 USA. EM monishaa@bcm.edu FU NIAID NIH HHS [P30 AI036211, P30AI060354, P30 AI060354] NR 33 TC 3 Z9 3 U1 3 U2 5 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD DEC PY 2010 VL 102 IS 12 BP 1264 EP 1266 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 699KK UT WOS:000285662100022 PM 21287912 ER PT J AU McQuinn, TC Deardorff, RL Mukherjee, R Taylor, AGB Graham, EM Atz, AM Forbus, GA DeSantis, SM Young, JB Stroud, RE Crawford, FA Bradley, SM Reeves, ST Spinale, FG AF McQuinn, Tim C. Deardorff, Rachael L. Mukherjee, Rupak Taylor, Anna Greta B. Graham, Eric M. Atz, Andrew M. Forbus, Geoffrey A. DeSantis, Stacia M. Young, Jennifer B. Stroud, Robert E. Crawford, Fred A. Bradley, Scott M. Reeves, Scott T. Spinale, Francis G. TI Circulating matrix metalloproteinase levels after ventricular septal defect repair in infants SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID SYSTEMIC INFLAMMATORY RESPONSE; CARDIOPULMONARY BYPASS; CARDIAC-SURGERY; HEART-DISEASE; IN-VIVO; CHILDREN; IMMUNITY; INHIBITION; ACTIVATION; APROTININ AB Background: Surgery for congenital heart disease initiates a complex inflammatory response that can influence the postoperative course. However, broad integration of the cytokine and proteolytic cascades (matrix metalloproteinases: MMPs), which may contribute to postoperative outcomes, has not been performed. Methods and Results: Using a low-volume (50-60 mu L), high-sensitivity, multiplex approach, we serially measured a panel of cytokines (interleukins 2, 4, 6, 8, and 10, tumor necrosis factor alpha, interleukin 1 beta, and granulocyte-macrophage colony stimulating factor) and matrix metalloproteinases (matrix metalloproteinases 2, 3, 7, 8, 9, 12, and 13) in patients (n = 9) preoperatively and after repair of ventricular septal defect. Results were correlated with outcomes such as inotropic requirement, oxygenation, and fluid balance. Serial changes in perioperative plasma levels of the cytokines and matrix metalloproteinases exhibited distinct temporal profiles. Plasma levels of interleukins 2, 8, and 10 and matrix metalloproteinase 9 peaked within 4 hours, whereas levels of matrix metalloproteinase 3 and 8 remained elevated at 24 and 48 hours after cross-clamp removal. Area-under-the-curve analysis of early cytokine levels were associated with major clinical variables, including inverse correlations between early interleukin 10 levels and cumulative inotrope requirement at 48 hours (r: 0.85; P < .005) and late matrix metalloproteinase 7 levels and cumulative fluid balance (r: -0.90; P < .001). Conclusions: The unique findings of this study were that serial profiling a large array of cytokines and proteolytic enzymes after surgery for congenital heart disease can provide insight into relationships between changes in bioactive molecules to early postoperative outcomes. Specific patterns of cytokine and matrix metalloproteinase release may hold significance as biomarkers for predicting and managing the postoperative course after surgery for congenital heart disease. (J Thorac Cardiovasc Surg 2010;140:1257-65) C1 [McQuinn, Tim C.; Mukherjee, Rupak; Graham, Eric M.; Atz, Andrew M.; Forbus, Geoffrey A.; Young, Jennifer B.] Med Univ S Carolina, Div Pediat Cardiol, Charleston, SC 29425 USA. [Deardorff, Rachael L.; Mukherjee, Rupak; Stroud, Robert E.; Crawford, Fred A.; Bradley, Scott M.; Spinale, Francis G.] Med Univ S Carolina, Dept Cardiothorac Surg, Charleston, SC 29425 USA. [Taylor, Anna Greta B.; Reeves, Scott T.] Med Univ S Carolina, Dept Anesthesia, Charleston, SC 29425 USA. [DeSantis, Stacia M.] Med Univ S Carolina, Dept Biostat & Epidemiol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), STRB Annex, 114 Doughty St, Charleston, SC 29425 USA. EM wilburnm@musc.edu FU National Institutes of Health [R01 HL059165, HL-057952, C06 RR015455]; VA Merit Award FX This work was supported in part by National Institutes of Health grants R01 HL059165, HL-057952 (F.G.S.) and a VA Merit Award (F.G.S.), and elements of the work were conducted in a facility constructed with support from NIH C06 RR015455. T.C.M. also received a grant from the National Institutes of Health. NR 24 TC 3 Z9 4 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD DEC PY 2010 VL 140 IS 6 BP 1257 EP 1265 DI 10.1016/j.jtcvs.2010.05.014 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 679GG UT WOS:000284149200009 PM 20561637 ER PT J AU Ou, SHI Bazhenova, L Camidge, DR Solomon, BJ Herman, J Kain, T Bang, YJ Kwak, EL Shaw, AT Salgia, R Maki, RG Clark, JW Wilner, KD Iafrate, AJ AF Ou, Sai-Hong Ignatius Bazhenova, Lyudmila Camidge, D. Ross Solomon, Benjamin J. Herman, June Kain, Tatiana Bang, Yung-Jue Kwak, Eunice L. Shaw, Alice T. Salgia, Ravi Maki, Robert G. Clark, Jeffrey W. Wilner, Keith D. Iafrate, A. John TI Rapid and Dramatic Radiographic and Clinical Response to an ALK Inhibitor (Crizotinib, PF02341066) in an ALK Translocation-Positive Patient with Non-small Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE 18-FDG PET/CT; Adenocarcinoma of the lung; ALK positive NSCLC; Crizotinib (PF02341066); ALK FISH testing; Anaplastic lymphoma kinase ID EML4-ALK C1 [Ou, Sai-Hong Ignatius] Univ Calif Irvine, Div Hematol Oncol, Dept Med, Chao Family Comprehens Canc Ctr,Med Ctr, Orange, CA 92868 USA. [Bazhenova, Lyudmila] Univ Calif San Diego, Med Ctr, Moores Canc Ctr, La Jolla, CA 92093 USA. [Camidge, D. Ross] Univ Colorado, Ctr Canc, Aurora, CO USA. [Solomon, Benjamin J.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Herman, June; Kain, Tatiana] Univ Calif Irvine, Div Mol Imaging, Dept Radiol Sci, Chao Family Comprehens Canc Ctr,Med Ctr, Orange, CA 92868 USA. [Bang, Yung-Jue] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. [Kwak, Eunice L.; Shaw, Alice T.; Clark, Jeffrey W.; Iafrate, A. John] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Salgia, Ravi] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Maki, Robert G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wilner, Keith D.] Pfizer Global Res & Dev, Dept Clin Res, La Jolla, CA USA. [Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Ou, SHI (reprint author), Univ Calif Irvine, Div Hematol Oncol, Dept Internal Med, Chao Family Comprehens Canc Ctr,Med Ctr, 101 City Dr,Bldg 56,RT 81,Rm 241, Orange, CA 92868 USA. EM Ignatius.ou@uci.edu RI Bang, Yung Jue/J-2759-2012 FU Pfizer, Inc.; Pfizer [A8081001] FX Disclosure: All institutions listed received funding from Pfizer, Inc. ELK, YJB, AJI received honorarium from Pfizer. AJI also received honorarium from Abbott Molecular Diagonstics. KW is an employee of Pfizer, Inc.; A8081001 is funded and sponsored by Pfizer. NR 7 TC 46 Z9 50 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD DEC PY 2010 VL 5 IS 12 BP 2044 EP 2046 DI 10.1097/JTO.0b013e318200f9ff PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 684VA UT WOS:000284579200029 PM 21102269 ER PT J AU Goldman, J Paschold, EH Webb, T Chen, L Kozcywas, M Lufkin, JM Vukovic, V Shapiro, GI Socinski, MA AF Goldman, J. Paschold, E. H. Webb, T. Chen, L. Kozcywas, M. Lufkin, J. M. Vukovic, V. Shapiro, G. I. Socinski, M. A. TI A Phase II Study Of The Hsp90 Inhibitor STA-9090 Administered To Patients With Advanced Non-small Cell Lung Cancer (NSCLC) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Goldman, J.] Premiere Oncol, Santa Monica, CA USA. [Paschold, E. H.] Piedmont Hematol Oncol Associates, PLLC, Winston Salem, NC USA. [Webb, T.] Genesis Canc Ctr, Hot Springs, AR USA. [Chen, L.] Nevada Canc Inst, Las Vegas, NV USA. [Kozcywas, M.] City Hope Natl Med Ctr, Duarte, CA USA. [Lufkin, J. M.; Vukovic, V.] Synta Pharmaceut, Lexington, MA USA. [Shapiro, G. I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Socinski, M. A.] Univ N Carolina, Chapel Hill, 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD DEC PY 2010 VL 5 IS 12 SU 7 BP S560 EP S560 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 690HQ UT WOS:000284994100152 ER PT J AU Lynch, TJ Neal, J Bondarenko, I Luft, A Serwatowski, P Barlesi, F Chacko, R Sebastian, M Cuillerot, J Reck, M AF Lynch, T. J. Neal, J. Bondarenko, I. Luft, A. Serwatowski, P. Barlesi, F. Chacko, R. Sebastian, M. Cuillerot, J. Reck, M. TI Overall Survival and Progression Free Survival Results for a Randomized Phase 2 Trial of Ipilimumab (IPI) and Paclitaxel/Carboplatin (P/C) in First-Line Stage IIIb/IV Non-small Cell Lung Cancer (NSCLC) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Lynch, T. J.] Smilow Canc Hosp, New Haven, CT USA. [Lynch, T. J.] Yale Canc Ctr, New Haven, CT USA. [Neal, J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Bondarenko, I.] Clin Hosp Dnipropetrovsk, Dnepropetrovsk, Ukraine. [Luft, A.] Leningrad Reg Clin Hosp, St Petersburg, Russia. [Serwatowski, P.] Oddzial Chemioterapii, Szczecin, Poland. [Barlesi, F.] Univ Aix Marseille 2, Assistance Publ Hop Marseille, Marseille, France. [Chacko, R.] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. [Sebastian, M.] Univ Med Mainz, Mainz, Germany. [Cuillerot, J.] Bristol Myers Squibb Co, Res & Dev, Wallingford, CT 06492 USA. [Reck, M.] Hosp Grosshansdorf, Grosshansdorf, 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD DEC PY 2010 VL 5 IS 12 SU 7 BP S515 EP S515 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 690HQ UT WOS:000284994100036 ER PT J AU Ou, SHI Salgia, R Clark, J Kwak, EL Camidge, DR Maki, R Bang, YJ Solomon, B Tan, WW Shapiro, GI AF Ou, Sai Hong Ignatius Salgia, Ravi Clark, Jeffrey Kwak, Eunice L. Camidge, David Ross Maki, Robert Bang, Yung-Jue Solomon, Ben Tan, Weiwei Shapiro, Geoffrey I. TI Comparison of Crizotimb (PF-02341066) Pharmacokinetics between Asian and Non-Asian Patients with Advanced Malignancies SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Ou, Sai Hong Ignatius] Univ Calif Irvine, Dept Med Hematol Oncol, Chao Family Comprehens Canc Ctr, Med Ctr, Irvine, CA 92717 USA. [Salgia, Ravi] Univ Chicago, Dept Med Hematol Oncol, Med Ctr, Chicago, IL 60637 USA. [Clark, Jeffrey; Kwak, Eunice L.] Massachusetts Gen Hosp, Dept Med Hematol Oncol, Boston, MA 02114 USA. [Camidge, David Ross] Univ Colorado, Dept Med Hematol Oncol, Anchultz Canc Ctr, Med Ctr, Boulder, CO 80309 USA. [Maki, Robert] Mem Sloan Kettering Canc Ctr, Dept Med Hematol Oncol, New York, NY USA. [Bang, Yung-Jue] Seoul Natl Univ, Dept Med Hematol Oncol, Med Ctr, Seoul 151, South Korea. [Solomon, Ben] Peter Maccallum Canc Ctr, Dept Med Hematol Oncol, Melbourne, Vic, Australia. [Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med Hematol Oncol, Boston, MA USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD DEC PY 2010 VL 5 IS 12 SU 5 BP S382 EP S382 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 690HO UT WOS:000284993900037 ER PT J AU Sbar, E Besse, B Felip, E Shaw, A Ahn, M Salvati, M Bhagavatheeswaran, P Soria, J AF Sbar, E. Besse, B. Felip, E. Shaw, A. Ahn, M. Salvati, M. Bhagavatheeswaran, P. Soria, J. TI A Double-Blind, Randomized, Parallel, Two-Arm Phase H Trial of BMS-690514 versus Erlotinib in Previous Chemotherapy-Treated Non-small Cell Lung Cancer (NSCLC) Patients: A Safety Review SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Sbar, E.; Salvati, M.; Bhagavatheeswaran, P.] Bristol Myers Squibb Co, Princeton, NJ USA. [Besse, B.; Soria, J.] Inst Gustave Roussy, Villejuif, France. [Felip, E.] Hosp Valle De Hebron, Barcelona, Spain. [Shaw, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ahn, M.] Sungkyunkwan Univ, Samsung Med Ctr, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD DEC PY 2010 VL 5 IS 12 SU 7 BP S538 EP S539 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 690HQ UT WOS:000284994100099 ER PT J AU Sbar, E Besse, B Felip, E Shaw, A Ahn, MJ Salvati, M Bhagavatheeswaran, P Soria, JC AF Sbar, Eric Besse, Benjamin Felip, Enriqueta Shaw, Alice Ahn, Myung-Ju Salvati, Mark Bhagavatheeswaran, Prabhu Soria, Jean-Charles TI A Double-Blind, Randomized, Parallel, Two-Arm Phase II Trial of BMS-690514 versus Erlotimb in Previous Chemotherapy-Treated Non-Small Cell Lung Cancer (NSCLC) Patients A Safety Review SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Besse, Benjamin; Soria, Jean-Charles] Inst Gustave Roussy, Dept Med, Paris, France. [Felip, Enriqueta] Hosp Vall D Hebron, Dept Med Oncol, Barcelona, Spain. [Shaw, Alice] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Ahn, Myung-Ju] Sungkyunkwan Univ, Dept Med, Samsung Med Ctr, Seoul, South Korea. [Sbar, Eric; Salvati, Mark; Bhagavatheeswaran, Prabhu] Bristol Myers Squibb Co, Dept Oncol, New York, NY 10154 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD DEC PY 2010 VL 5 IS 12 SU 5 BP S385 EP S385 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 690HO UT WOS:000284993900046 ER PT J AU Willers, H Kachnic, L Birkelbach, M Ferraiolo, N Gheorghiu, L Daly, B Ebright, M O'Hara, C Dahm-Daphi, J Settleman, J AF Willers, H. Kachnic, L. Birkelbach, M. Ferraiolo, N. Gheorghiu, L. Daly, B. Ebright, M. O'Hara, C. Dahm-Daphi, J. Settleman, J. TI Detection of Homologous Recombination Repair Defects in NSCLC SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Willers, H.; Ferraiolo, N.; Gheorghiu, L.; Settleman, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kachnic, L.; Daly, B.; Ebright, M.; O'Hara, C.] Boston Med Ctr, Boston, MA USA. [Birkelbach, M.; Dahm-Daphi, J.] Univ Hamburg, Hamburg, Germany. 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD DEC PY 2010 VL 5 IS 12 SU 7 BP S516 EP S516 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 690HQ UT WOS:000284994100038 ER PT J AU Yang, CH Shih, JY Su, WC Hsia, TC Sequist, LV Chang, GC Calvo, R Cong, XJ Shahidi, M Miller, VA AF Yang, Chih-Hsin Shih, Jin Yuan Su, Wu-Chou Hsia, Te-Chun Sequist, Lecia V. Chang, Gee-Chen Calvo, Roser Cong, Xiuyu Julie Shahidi, Mehdi Miller, Vincent A. TI A Phase II Study of Afatinib (BIBW 2992) in Patients with Adenocarcinoma of the Lung and Activating EGFR/HER1 Mutations (LUX-Lung 2) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Yang, Chih-Hsin; Shih, Jin Yuan] Natl Taiwan Univ Hosp, Dept Oncol, Taipei, Taiwan. [Su, Wu-Chou] Natl Cheng Kung Univ Hosp, Dept Internal Med, Tainan, Taiwan. [Hsia, Te-Chun] China Med Univ Hosp, Dept Internal Med, Taichung, Taiwan. [Sequist, Lecia V.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Chang, Gee-Chen] Taichung Vet Gen Hosp, Dept Internal Med, Taichung, Taiwan. [Miller, Vincent A.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD DEC PY 2010 VL 5 IS 12 SU 5 BP S376 EP S377 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 690HO UT WOS:000284993900020 ER PT J AU Cuker, A Arepally, G Crowther, MA Rice, L Datko, F Hook, K Propert, KJ Kuter, DJ Ortel, TL Konkle, BA Cines, DB AF Cuker, A. Arepally, G. Crowther, M. A. Rice, L. Datko, F. Hook, K. Propert, K. J. Kuter, D. J. Ortel, T. L. Konkle, B. A. Cines, D. B. TI The HIT Expert Probability (HEP) Score: a novel pre-test probability model for heparin-induced thrombocytopenia based on broad expert opinion SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE clinical prediction rule; clinical scoring model; diagnosis; heparin-induced thrombocytopenia ID PARTICLE GEL IMMUNOASSAY; MOLECULAR-WEIGHT HEPARIN; OPTICAL-DENSITY VALUES; CARDIOPULMONARY BYPASS; SKIN-LESIONS; 4TS SCORE; DIAGNOSIS; THROMBOSIS; METAANALYSIS; ANTIBODIES AB Background: The diagnosis of heparin-induced thrombocytopenia (HIT) is challenging. Over-diagnosis and over-treatment are common. Objectives: To develop a pre-test clinical scoring model for HIT based on broad expert opinion that may be useful in guiding clinical decisions regarding therapy. Patients/methods: A pre-test model, the HIT Expert Probability (HEP) Score, was constructed based on the opinions of 26 HIT experts. Fifty patients referred to a reference laboratory for HIT testing comprised the validation cohort. Two hematology trainees scored each patient using the HEP Score and a previously published clinical scoring system (4 T's). A panel of three independent experts adjudicated the 50 patients and rendered a diagnosis of HIT likely or unlikely. All subjects underwent HIT laboratory testing with a polyspecific HIT ELISA and serotonin release assay (SRA). Results: The HEP Score exhibited significantly greater interobserver agreement [intraclass correlation coefficient: 0.88 (95% CI 0.80-0.93) vs. 0.71 (0.54-0.83)], correlation with the results of HIT laboratory testing and concordance with the diagnosis of the expert panel (area under receiver-operating curve: 0.91 vs. 0.74, P = 0.017) than the 4 T's. The model was 100% sensitive and 60% specific for determining the presence of HIT as defined by the expert panel and would have allowed for a 41% reduction in the number of patients receiving a direct thrombin inhibitor (DTI). Conclusion: The HEP Score is the first pre-test clinical scoring model for HIT based on broad expert opinion, exhibited favorable operating characteristics and may permit clinicians to confidently reduce use of alternative anticoagulants. Prospective multicenter validation is warranted. C1 [Cuker, A.; Datko, F.; Hook, K.; Propert, K. J.; Cines, D. B.] Univ Penn, Philadelphia, PA 19104 USA. [Arepally, G.; Ortel, T. L.] Duke Univ, Durham, NC USA. [Crowther, M. A.] McMaster Univ, Hamilton, ON, Canada. [Rice, L.] Weill Cornell Med Coll, Houston, TX USA. [Kuter, D. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Konkle, B. A.] Puget Sound Blood Ctr, Seattle, WA 98104 USA. RP Cuker, A (reprint author), Hosp Univ Penn, Penn Comprehens Hemophilia & Thrombosis Program, 3 Dulles,3400 Spruce St, Philadelphia, PA 19104 USA. EM adam.cuker@uphs.upenn.edu FU University of Pennsylvania Institute of Translational Medicine and Therapeutics; Heart and Stroke Foundation of Ontario; [K12 HL087064-03]; [HL099973]; [HL081012] FX A. Cuker thanks the American Society of Hematology Clinical Research Training Institute for invaluable assistance with the design of this study. The authors also wish to thank the questionnaire respondents: C. Abrams (University of Pennsylvania), K. Bauer (Beth Israel Deaconess Medical Center), Y. Datta (University of Minnesota), T. Gernsheimer (Puget Sound Blood Center), C. Kempton (Emory University), N. Key (University of North Carolina), T. Kickler (Johns Hopkins University), R. Kruse-Jarres (Tulane University), D. Kuter (Massachusetts GeneralHospital), C. Leissinger (Tulane University), S. Lentz (University of Iowa), J. Lin (Brigham and Women's Hospital), M. Linenberger (Puget Sound Blood Center), K. McCrae (Case Western Reserve University), S. Moll (University of North Carolina), T. Ortel (Duke University), M. Ragni (University of Pittsburgh), M. Reding (University of Minnesota), R. Sarode (University of Texas Southwestern), A. Schmaier (Case Western Reserve University), S. Sood (University of Michigan), M. Streiff (Johns Hopkins University), N. Whitlatch (Duke University), E. Williams (University of Wisconsin) and J. Zwicker (Beth Israel Deaconess Medical Center). The present study was supported by K12 HL087064-03 and a grant from the University of Pennsylvania Institute of Translational Medicine and Therapeutics (to A. C.), a Career Investigator Award from the Heart and Stroke Foundation of Ontario (to M.A.C.) and HL099973 and HL081012 (to D.B.C.). NR 26 TC 93 Z9 95 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD DEC PY 2010 VL 8 IS 12 BP 2642 EP 2650 DI 10.1111/j.1538-7836.2010.04059.x PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 691WE UT WOS:000285110700007 PM 20854372 ER PT J AU Liebschutz, J Schwartz, S Hoyte, J Conoscenti, L Christian, AB Muhammad, L Harper, D James, T AF Liebschutz, Jane Schwartz, Sonia Hoyte, Joel Conoscenti, Lauren Christian, Anthony B., Sr. Muhammad, Leroy Harper, Derrick James, Thea TI A Chasm Between Injury and Care: Experiences of Black Male Victims of Violence SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE Black male; Community violence; Qualitative research ID STRESS-DISORDER PERSISTS; HEALTH-CARE; INTERVENTION PROGRAM; MAJOR TRAUMA; RISK-FACTORS; ADOLESCENTS; PREVENTION; SYSTEM; TRUST; YOUTH AB Background: Despite higher rates of stabbing and shooting violence among black men, healthcare systems have not demonstrated an efficacious response to these patients. This study describes challenges and promotive factors for engaging black male violence victims of violence with medical and mental healthcare. Methods: Black male victims of stabbings and shootings were recruited through fliers and word of mouth, and were interviewed individually (n = 12) or in pairs (n = 4) using a semistructured guide. A racially diverse multidisciplinary team analyzed the data using Grounded Theory methods. Results: Challenges to engagement with healthcare included the following: (1) Disconnect in the aftermath; e. g. participants reported not realizing they were seriously injured ("just a scratch" "poke"), were disoriented ("did not know where I was"), or were consumed with anger. (2) Institutional mistrust: blurred lines between healthcare and police, money-motivated care. (3) Foreshortened future: expectations they would die young. (4) Self-reliance: fix mental and substance abuse issues on their own. (5) Logistical issues: postinjury mental health symptoms, disability, and safety concerns created structural barriers to recovery and engagement with healthcare. Promotive factors included the following: (1) desire professionalism, open personality, and shared experience from clinicians; (2) turning points: injury or birth of a child serve as a "wake up call"; and (3) positive people, future-oriented friends and family. Conclusions: For black male violence victims, medical treatment did not address circumstances of and reactions to injury. Policies delineating boundaries between medical care and law enforcement and addressing postinjury mental health symptoms, disability, and safety concerns may improve the recovery process. C1 [Liebschutz, Jane; Schwartz, Sonia; Hoyte, Joel] Boston Univ, Sch Med, Clin Addict Res & Educ Unit, Boston Med Ctr, Boston, MA 02118 USA. [Liebschutz, Jane; Schwartz, Sonia; Hoyte, Joel] Boston Univ, Sch Publ Hlth, Clin Addict Res & Educ Unit, Boston Med Ctr, Boston, MA 02118 USA. [James, Thea] Boston Univ, Sch Publ Hlth, Gen Internal Med Sect, Boston Med Ctr, Boston, MA 02118 USA. [James, Thea] Boston Univ, Sch Publ Hlth, Dept Emergency Med, Boston Med Ctr, Boston, MA 02118 USA. [James, Thea] Boston Univ, Sch Med, Gen Internal Med Sect, Boston Med Ctr, Boston, MA 02118 USA. [James, Thea] Boston Univ, Sch Med, Dept Emergency Med, Boston Med Ctr, Boston, MA 02118 USA. [Conoscenti, Lauren] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Christian, Anthony B., Sr.; Muhammad, Leroy] Boston Med Ctr, Violence Intervent Advocacy Program, Boston, MA USA. [Harper, Derrick] Pyramid Builders Assoc, Boston, MA USA. RP Liebschutz, J (reprint author), Boston Univ, Sch Med, Clin Addict Res & Educ Unit, Boston Med Ctr, 801 Massachusetts Ave,2nd Floor, Boston, MA 02118 USA. EM Jane.Liebschutz@bmc.org OI James, Thea/0000-0001-5242-9245; Liebschutz, Jane/0000-0003-3492-1521 FU NIDA NIH HHS [K23 DA016665-05, K23 DA016665] NR 27 TC 5 Z9 5 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD DEC PY 2010 VL 69 IS 6 BP 1372 EP 1378 DI 10.1097/TA.0b013e3181e74fcf PG 7 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 695RT UT WOS:000285391000021 PM 20838259 ER PT J AU Karlin, BE Ruzek, JI Chard, KM Eftekhari, A Monson, CM Hembree, EA Resick, PA Foa, EB AF Karlin, Bradley E. Ruzek, Josef I. Chard, Kathleen M. Eftekhari, Afsoon Monson, Candice M. Hembree, Elizabeth A. Resick, Patricia A. Foa, Edna B. TI Dissemination of Evidence-Based Psychological Treatments for Posttraumatic Stress Disorder in the Veterans Health Administration SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID COGNITIVE-PROCESSING THERAPY; PROLONGED EXPOSURE THERAPY; PTSD; VICTIMS; TRIAL AB Unlike the post-Vietnam era, effective, specialized treatments for posttraumatic stress disorder (PTSD) now exist, although these treatments have not been widely available in clinical settings. The U. S. Department of Veterans Affairs (VA) is nationally disseminating 2 evidence-based psychotherapies for PTSD throughout the VA health care system. The VA has developed national initiatives to train mental health staff in the delivery of Cognitive Processing Therapy (CPT) and Prolonged Exposure therapy (PE) and has implemented a variety of strategies to promote local implementation. In this article, the authors examine VA's national CPT and PE training initiatives and report initial patient, therapist, and system-level program evaluation results. Key issues, lessons learned, and next steps for maximizing impact and sustainability are also addressed. C1 [Ruzek, Josef I.; Eftekhari, Afsoon] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Palo Alto, CA USA. [Chard, Kathleen M.] Cincinnati VA Med Ctr, Cincinnati, OH USA. [Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Monson, Candice M.] Ryerson Univ, Toronto, ON, Canada. [Hembree, Elizabeth A.; Foa, Edna B.] Univ Penn, Philadelphia, PA 19104 USA. RP Karlin, BE (reprint author), VA Cent Off, Off Mental Hlth Serv 116, 810 Vermont Ave NW, Washington, DC 20420 USA. EM Bradley.Karlin2@va.gov NR 31 TC 178 Z9 178 U1 3 U2 21 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2010 VL 23 IS 6 BP 663 EP 673 DI 10.1002/jts.20588 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 697NS UT WOS:000285520900002 PM 21171126 ER PT J AU Weiss, DS Brunet, A Best, SR Metzler, TJ Liberman, A Pole, N Fagan, JA Marmar, CR AF Weiss, Daniel S. Brunet, Alain Best, Suzanne R. Metzler, Thomas J. Liberman, Akiva Pole, Nnamdi Fagan, Jeffrey A. Marmar, Charles R. TI Frequency and Severity Approaches to Indexing Exposure to Trauma: The Critical Incident History Questionnaire for Police Officers SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; RISK-FACTORS; SYMPTOMS; PERSONNEL; METAANALYSIS; RELIABILITY; EXPERIENCES; PREDICTORS; DISTRESS; VETERANS AB The Critical Incident History Questionnaire indexes cumulative exposure to traumatic incidents in police by examining incident frequency and rated severity. In over 700 officers, event severity was negatively correlated (rs = -.61) with frequency of exposure. Cumulative exposure indices that varied emphasis on frequency and severity-using both nomothetic and idiographic methods-all showed satisfactory psychometric properties and similar correlates. All indices were only modestly related to posttraumatic stress disorder (PTSD) symptoms. Ratings of incident severity were not influenced by whether officers had ever experienced the incident. Because no index summarizing cumulative exposure to trauma had superior validity, our findings suggest that precision is not increased if frequency is weighted by severity. C1 [Weiss, Daniel S.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Brunet, Alain] McGill Univ, Dept Psychiat, Montreal, PQ H3A 2T5, Canada. [Metzler, Thomas J.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Liberman, Akiva] Urban Inst, Justice Policy Ctr, Washington, DC 20037 USA. [Pole, Nnamdi] Smith Coll, Dept Psychol, Northampton, MA 01063 USA. [Fagan, Jeffrey A.] Columbia Univ, Sch Law, New York, NY 10027 USA. [Marmar, Charles R.] NYU, Dept Psychiat, New York, NY 10003 USA. RP Weiss, DS (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. EM daniel.weiss@ucsf.edu FU NIMH NIH HHS [R01 MH056350] NR 35 TC 25 Z9 25 U1 3 U2 13 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2010 VL 23 IS 6 BP 734 EP 743 DI 10.1002/jts.20576 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 697NS UT WOS:000285520900010 PM 21171134 ER PT J AU Gutner, CA Pineles, SL Griffin, MG Bauer, MR Weierich, MR Resick, PA AF Gutner, Cassidy A. Pineles, Suzanne L. Griffin, Michael G. Bauer, Margaret R. Weierich, Mariann R. Resick, Patricia A. TI Physiological Predictors of Posttraumatic Stress Disorder SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID ADMINISTERED PTSD SCALE; PERITRAUMATIC DISSOCIATION; HEART-RATE; PSYCHOPHYSIOLOGY; VETERANS; IMAGERY; TRAUMA; WAR AB Studies have assessed relationships between posttraumatic stress disorder (PTSD) symptoms and physiological reactivity concurrently; fewer have assessed these relationships longitudinally. This study tests concurrent and prospective relationships between physiological reactivity (heart rate and skin conductance) to a monologue procedure and PTSD symptoms in female assault survivors, tested within 1 and 3 months posttrauma. After controlling for initial PTSD and peritraumatic dissociation, 3 measures of increased physiological reactivity to the trauma monologue at 1 month predicted 3-month PTSD reexperiencing severity. Additionally, increased heart rate following trauma and neutral monologues at 1 month was predictive of 3-month numbing symptoms. Implications for the prospective relationship between physiological reactivity to trauma cues and PTSD over time are discussed. C1 [Griffin, Michael G.] Univ Missouri St Louis, Dept Psychol, St Louis, MO USA. [Griffin, Michael G.] Univ Missouri St Louis, Ctr Trauma Recovery, St Louis, MO USA. [Weierich, Mariann R.] CUNY Hunter Coll, Dept Psychol, New York, NY 10021 USA. [Resick, Patricia A.] Boston Univ, Dept Psychol, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div,VA Boston Healthcare Syst, Boston, MA 02215 USA. [Resick, Patricia A.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Resick, PA (reprint author), VA Boston Healthcare Syst 116B3, Womens Hlth Sci Div, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM patricia.resick@va.gov FU NIMH NIH HHS [R01 MH046992-02, R01-MH6992, R01 MH046992] NR 19 TC 3 Z9 3 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2010 VL 23 IS 6 BP 775 EP 784 DI 10.1002/jts.20582 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 697NS UT WOS:000285520900015 PM 21171139 ER PT J AU Smith, MR Klotz, L Persson, BE Olesen, TK Wilde, AAM AF Smith, Matthew R. Klotz, Laurence Persson, Bo-Eric Olesen, Tine Kold Wilde, Arthur A. M. TI Cardiovascular Safety of Degarelix: Results From a 12-Month, Comparative, Randomized, Open Label, Parallel Group Phase III Trial in Patients With Prostate Cancer SO JOURNAL OF UROLOGY LA English DT Article DE adenocarcinoma; gonadotropin-releasing hormone; drug monitoring ID ANDROGEN-DEPRIVATION THERAPY; METABOLIC SYNDROME; QT INTERVAL; TESTOSTERONE; DISEASE; RISK AB Purpose: We assessed the cardiovascular safety profile of degarelix, a new gonadotropin-releasing hormone antagonist. Materials and Methods: This is the first report to our knowledge on cardiovascular safety data from a completed 1-year randomized controlled trial of leuprolide acetate vs degarelix. Outcomes considered in these analyses included the QT interval by central reading and analysis, and cardiovascular adverse events. On multivariate analyses relationships between selected baseline factors and cardiovascular events were evaluated. Results: There were no significant differences between treatment groups for mean change in Fridericia's correction of QT during the trial. Markedly abnormal Fridericia's correction of QT values (500 milliseconds or greater) were observed in only a small number of subjects by treatment group, that is 2 (less than 1%) in the pooled degarelix group and 2 (1%) in the leuprolide group. Supraventricular arrhythmias were the most common type of arrhythmias, affecting 2% of subjects in the pooled degarelix group and 4% in the leuprolide group. Other arrhythmias occurred in 1% or less of subjects by treatment group. The most frequently reported cardiac disorder was ischemic heart disease, which occurred in 4% of subjects treated with degarelix and 10% of those on leuprolide. Cox proportional hazard ratio estimates for selected baseline covariates showed a significantly increased risk of cardiovascular events by age (p = 0.0459) and systolic blood pressure (p = 0.0061). Conclusions: In men with prostate cancer degarelix and leuprolide have similar cardiovascular safety profiles. These observations suggest that the cardiovascular events associated with both agents result from hypogonadism rather than a direct drug effect. C1 [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Klotz, Laurence] Univ Toronto, Sunnybrook Hlth Sci Ctr, Div Urol, Toronto, ON, Canada. [Olesen, Tine Kold] Ferring Pharmaceut AS, Clin Res & Dev Urol, Copenhagen, Denmark. [Persson, Bo-Eric] Ferring Pharmaceut, St Prex, Switzerland. [Wilde, Arthur A. M.] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, Heart Failure Res Ctr, NL-1105 AZ Amsterdam, Netherlands. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 7038,55 Fruit St, Boston, MA 02114 USA. EM mrsmith@partners.org FU Ferring Pharmaceuticals A/S; Prostate Cancer Foundation; National Institutes of Health [5K24CA121990-03]; Ferring Pharmaceuticals FX Supported by Ferring Pharmaceuticals A/S.; Supported by the Prostate Cancer Foundation and the National Institutes of Health Grant 5K24CA121990-03.; Financial interest and/or other relationship with Ferring Pharmaceuticals. NR 20 TC 27 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2010 VL 184 IS 6 BP 2313 EP 2319 DI 10.1016/j.juro.2010.08.012 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 677ZY UT WOS:000284037900030 PM 20952020 ER PT J AU Desai, DG Liao, KS Cevallos, ME Trautner, BW AF Desai, Devak G. Liao, Kershena S. Cevallos, Manuel E. Trautner, Barbara W. TI Silver or Nitrofurazone Impregnation of Urinary Catheters Has a Minimal Effect on Uropathogen Adherence SO JOURNAL OF UROLOGY LA English DT Article DE ureter; urinary catheterization; anti-infective agents; Escherichia coli; Enterococcus faecalis ID CRYSTALLINE BACTERIAL BIOFILMS; TRACT-INFECTIONS; ASYMPTOMATIC BACTERIURIA; FOLEY CATHETERS; PREVENTION; GUIDELINES; CONSTRUCTION; ENCRUST; ADULTS; TRIAL AB Purpose: Bacterial adherence to the urinary catheter is an early step in biofilm formation and the pathogenesis of catheter associated urinary tract infection. We studied in vitro the effect of silver or nitrofurazone impregnation of urinary catheters on uropathogen ability to adhere to urinary catheters. Materials and Methods: We studied commercially available nitrofurazone-silicone, silicone only, silver-silicone-hydrogel, silicone-hydrogel, silver-latex-hydrogel and latex-hydrogel catheters. Catheters were incubated in sterile broth for 0, 3, 5, 7 and 10 days, respectively, before inoculation and overnight incubation with Escherichia coli or Enterococcus faecalis. Results: Adherence of E. coli and E. faecalis to nitrofurazone catheters was significantly decreased compared to that of silicone-only catheters when catheters were fresh. The anti-adherence effect of nitrofurazone on E. coli decreased with time but was still significant at 5 days. For E. faecalis the effect of nitrofurazone was lost by 3 days of pre-incubation. E. coli adherence was not significantly decreased on silver impregnated catheters compared to that on control catheters of the same base material. Silver was associated with a significant decrease in E. faecalis adherence to latex-hydrogel catheters but not to silicone-hydrogel catheters. The adherence of each species to silicone catheters with hydrogel was significantly lower than that to silicone-only control catheters. Conclusions: Silver impregnation had little effect on bacterial adherence in our model and nitrofurazone impregnation had a significant effect only for the first 5 days. Our results do not support a role for silver urinary catheters to prevent catheter associated urinary tract infection by decreasing bacterial adherence. C1 [Trautner, Barbara W.] Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. [Trautner, Barbara W.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Desai, Devak G.; Liao, Kershena S.; Cevallos, Manuel E.; Trautner, Barbara W.] Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. [Trautner, Barbara W.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Trautner, BW (reprint author), 1 Baylor Plaza,BCM 286,N1319, Houston, TX 77030 USA. EM trautner@bcm.edu FU Department of Veterans Affairs [B4623W]; National Institutes of Health [DK077313, HD058985]; Houston Center for Quality of Care and Utilization Studies [HFP90-020] FX Supported by Department of Veterans Affairs Rehabilitation Research and Development Service Career Development Award B4623W, National Institutes of Health Grants DK077313 and HD058985, and Houston Center for Quality of Care and Utilization Studies (Houston VA HSR & D Center of Excellence HFP90-020). NR 26 TC 30 Z9 33 U1 2 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2010 VL 184 IS 6 BP 2565 EP 2571 DI 10.1016/j.juro.2010.07.036 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 677ZY UT WOS:000284037900130 PM 21030042 ER PT J AU Oklu, R Walker, TG Wicky, S Hesketh, R AF Oklu, Rahmi Walker, Thomas G. Wicky, Stephan Hesketh, Robin TI Angiogenesis and Current Antiangiogenic Strategies for the Treatment of Cancer SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; REGULATES TUMOR ANGIOGENESIS; METASTATIC COLORECTAL-CANCER; TYROSINE KINASE INHIBITOR; FACTOR GENE-EXPRESSION; FACTOR MESSENGER-RNA; FACTOR-BETA; TGF-BETA; IN-VIVO; SPHINGOSINE 1-PHOSPHATE AB Angiogenesis is a complex process critical for embryonic development and for survival. It is also a critical player in many pathologic processes, most notably in neoplasia. The cell signaling pathways involved in angiogenesis have become key targets for drug design, with more than 2,500 clinical trials currently under way. This review summarizes the essential features of angiogenesis and discusses therapeutic strategies that have been applied to specific diseases known to be associated with perturbation of normal angiogenic control. C1 [Oklu, Rahmi; Walker, Thomas G.; Wicky, Stephan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent,Dept Radiol, Boston, MA 02114 USA. [Hesketh, Robin] Univ Cambridge, Dept Biochem, Sect Cardiovasc Biol, Cambridge CB2 1QW, England. RP Oklu, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent,Dept Radiol, 55 Fruit St,GRB2, Boston, MA 02114 USA. EM r6251@yahoo.com FU Medtronic (Minneapolis, Minnesota) FX T.G.W. is a paid consultant for the Scientific Advisory Panel of Medtronic (Minneapolis, Minnesota). None of the other authors have identified a conflict of interest. NR 129 TC 26 Z9 27 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD DEC PY 2010 VL 21 IS 12 BP 1791 EP 1805 DI 10.1016/j.jvir.2010.08.009 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 695LW UT WOS:000285372600001 PM 20980167 ER PT J AU Georgiades, CS Rodriguez, R Littrup, PJ Frangakis, CE Leveille, R Ahrar, K Atwell, TD Cadeddu, J Trimmer, C Durack, JC Hammers, HJ Meng, MV Raman, S Solomon, SB Zagoria, RJ McLennan, G LaBerge, JM Gervais, DA Kee, ST AF Georgiades, Christos S. Rodriguez, Ronald Littrup, Peter J. Frangakis, Constantine E. Leveille, Raymond Ahrar, Kamran Atwell, Thomas D. Cadeddu, Jeffrey Trimmer, Clayton Durack, Jeremy C. Hammers, Hans-Joerg Meng, Maxwell V. Raman, Steven Solomon, Stephen B. Zagoria, Ronald J. McLennan, Gordon LaBerge, Jeanne M. Gervais, Debra A. Kee, Stephen T. TI Development of a Research Agenda for Percutaneous Renal Tumor Ablation: Proceedings from a Multidisciplinary Research Consensus Panel SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Editorial Material ID RADIO-FREQUENCY ABLATION; NEPHRON-SPARING SURGERY; GUIDED RADIOFREQUENCY ABLATION; CONTRAST-ENHANCED SONOGRAPHY; CELL CARCINOMA; FOLLOW-UP; CLINICAL-EXPERIENCE; COMPUTED-TOMOGRAPHY; CRYOABLATION; CT C1 [Georgiades, Christos S.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21287 USA. [Georgiades, Christos S.] Johns Hopkins Univ, Dept Surg, Baltimore, MD 21287 USA. [Rodriguez, Ronald] Johns Hopkins Univ, Dept Urol, Baltimore, MD 21287 USA. [Hammers, Hans-Joerg] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21287 USA. [Frangakis, Constantine E.] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD 21287 USA. [Littrup, Peter J.] Wayne State Univ, Dept Urol, Detroit, MI USA. [Leveille, Raymond] Univ Miami, Dept Urol, Miami, FL USA. [Ahrar, Kamran] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. [Cadeddu, Jeffrey] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA. [Trimmer, Clayton] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA. [Atwell, Thomas D.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Durack, Jeremy C.; LaBerge, Jeanne M.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Meng, Maxwell V.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Raman, Steven; Kee, Stephen T.] Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA. [Solomon, Stephen B.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. [Zagoria, Ronald J.] Wake Forest Univ, Dept Radiol, Winston Salem, NC 27109 USA. [McLennan, Gordon] Cleveland Clin, Dept Radiol, Cleveland, OH 44106 USA. [Gervais, Debra A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Georgiades, CS (reprint author), Johns Hopkins Univ, Dept Radiol, 600 N Wolfe St,Blalock 544, Baltimore, MD 21287 USA. EM g_christos@hotmail.com OI Zagoria, Ronald/0000-0001-6926-4627; McLennan, Gordon/0000-0002-9173-0898 NR 70 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD DEC PY 2010 VL 21 IS 12 BP 1807 EP 1816 DI 10.1016/j.jvir.2010.10.002 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 695LW UT WOS:000285372600002 PM 21111363 ER PT J AU Ryland, EG Tang, YH Christie, CD Feeney, ME AF Ryland, Elizabeth G. Tang, Yanhua Christie, Celia D. Feeney, Margaret E. TI Sequence Evolution of HIV-1 following Mother-to-Child Transmission SO JOURNAL OF VIROLOGY LA English DT Article ID IN-VIVO; VIRUS; INFECTION; ESCAPE; REVERSION; MUTATIONS; RESPONSES; VARIANTS; REVEALS; POLYMORPHISMS AB The genetic heterogeneity of HIV-1 poses a major obstacle to vaccine development. Although most horizontally acquired HIV-1 infections are initiated by a single homogeneous virus, marked genetic diversification and evolution occur following transmission. The relative contribution of the antiviral immune response to intrahost viral evolution remains controversial, in part because the sequence of the transmitted virus and the array of T-cell epitopes targeted by both donor and recipient are seldom known. We directly compared predominant viral sequences derived from 52 mother-child transmission pairs following vertical infection and identified 1,475 sites of mother-infant amino acid divergence within Nef, Gag, and Pol. The cumulative number of mutations away from the consensus subtype B sequence increased linearly with time since transmission, whereas reversions toward the consensus sequence accumulated more slowly with increasing duration of infection. Comprehensive mapping of T-cell epitopes targeted by these mothers and infants revealed that 14% of nonsynonymous mutations away from the consensus sequence were located within regions targeted by the infant, whereas 24% of nonsynonymous mutations toward the consensus sequence were located in regions targeted by the mother. On the basis of analysis of optimal epitopes listed in the HIV Molecular Immunology Database, fewer than 10% of epitopes containing maternal escape mutations reverted to the consensus sequence following transmission to an infant lacking the restricting HLA allele. This surprisingly low reversion rate of mutated epitopes following transmission suggests that the fitness cost associated with many CD8 epitope mutations may be modest. C1 [Feeney, Margaret E.] Univ Calif San Francisco, Div Expt Med, San Francisco, CA 94110 USA. [Ryland, Elizabeth G.; Tang, Yanhua; Feeney, Margaret E.] Ragon Inst, Boston, MA USA. [Ryland, Elizabeth G.; Tang, Yanhua; Feeney, Margaret E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Christie, Celia D.] Univ W Indies, Jamaica Pediat Perinatal & Adolescent HIV AIDS Pr, Dept Obstet & Gynecol, Kingston 7, Jamaica. [Christie, Celia D.] Univ W Indies, Dept Pediat, Kingston 7, Jamaica. RP Feeney, ME (reprint author), Univ Calif San Francisco, Div Expt Med, Bldg 3,Rm 525A,1001 Potrero Ave, San Francisco, CA 94110 USA. EM margaret.feeney@ucsf.edu FU Elizabeth Glaser Pediatric AIDS Foundation; Jewelers for Children; Charles H. Hood Foundation; NIAID/NIH [R01-AI068497]; Jewelers for Children Elizabeth Glaser Scientist Award FX This work was supported by the Elizabeth Glaser Pediatric AIDS Foundation (M.E.F. and C.D.C.), Jewelers for Children, the Charles H. Hood Foundation (M. E. F.), and the NIAID/NIH (grant R01-AI068497 to M.E.F.). C.D.C. is a recipient of an International Leadership Award from the Elizabeth Glaser Pediatric AIDS Foundation. M.E.F. is the recipient of the Jewelers for Children Elizabeth Glaser Scientist Award. NR 24 TC 6 Z9 7 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2010 VL 84 IS 23 BP 12437 EP 12444 DI 10.1128/JVI.01617-10 PG 8 WC Virology SC Virology GA 675BT UT WOS:000283799500032 PM 20861265 ER PT J AU Mattocks, KM Skanderson, M Goulet, JL Brandt, C Womack, J Krebs, E Desai, R Justice, A Yano, E Haskell, S AF Mattocks, Kristin M. Skanderson, Melissa Goulet, Joseph L. Brandt, Cynthia Womack, Julie Krebs, Erin Desai, Rani Justice, Amy Yano, Elizabeth Haskell, Sally TI Pregnancy and Mental Health Among Women Veterans Returning from Iraq and Afghanistan SO JOURNAL OF WOMENS HEALTH LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; DEPRESSIVE SYMPTOMS; PSYCHIATRIC-DISORDERS; RISK-FACTORS; PSYCHOLOGICAL DISTRESS; MATERNAL DEPRESSION; ANXIETY DISORDERS; PRETERM DELIVERY; PRENATAL-CARE; POSTPARTUM AB Background: Veterans of Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) may experience significant stress during military service that can have lingering effects. Little is known about mental health problems or treatment among pregnant OEF/OIF women veterans. The aim of this study was to determine the prevalence of mental health problems among veterans who received pregnancy-related care in the Veterans Health Administration (VHA) system. Methods: Data from the Defense Manpower Data Center (DMDC) deployment roster of military discharges from October 1, 2001, through April 30, 2008, were used to assemble an administrative cohort of female OEF/OIF veterans enrolled in care at the VHA (n = 43,078). Pregnancy and mental health conditions were quantified according to ICD-9-CM codes and specifications. Mental healthcare use and prenatal care were assessed by analyzing VHA stop codes. Results: During the study period, 2966 (7%) women received at least one episode of pregnancy-related care, and 32% of veterans with a pregnancy and 21% without a pregnancy received one or more mental health diagnoses (p<0.0001). Veterans with a pregnancy were twice as likely to have a diagnosis of depression, anxiety, post-traumatic stress disorder (PTSD), bipolar disorder, or schizophrenia as those without a pregnancy. Conclusions: Women OEF/OIF veterans commonly experience mental health problems after military service. The burden of mental health conditions is higher among women with an identified instance of pregnancy than among those without. Because women do not receive pregnancy care at the VHA, however, little is known about ongoing concomitant prenatal and mental healthcare or about pregnancy outcomes among these women veterans. C1 [Mattocks, Kristin M.; Skanderson, Melissa; Goulet, Joseph L.; Womack, Julie; Desai, Rani; Justice, Amy; Haskell, Sally] VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Mattocks, Kristin M.; Skanderson, Melissa; Goulet, Joseph L.; Brandt, Cynthia; Justice, Amy; Haskell, Sally] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Brandt, Cynthia] Yale Univ, Sch Med, Yale Ctr Med Informat, New Haven, CT 06510 USA. [Krebs, Erin] Regenstrief Inst Inc, Roudebush VA Med Ctr, Ctr Implementing Evidence Based Practice, Indianapolis, IN USA. [Krebs, Erin] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. [Desai, Rani] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA. [Yano, Elizabeth] VA Greater Angeles Healthcare Syst, VA HSR&D Ctr Excellence Study Healthcare Provider, Sepulveda, CA USA. [Yano, Elizabeth] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RP Mattocks, KM (reprint author), VA Connecticut Healthcare Syst, 950 Campbell Ave,11 ACSLG, West Haven, CT 06516 USA. EM kristin.mattocks@va.gov OI Goulet, Joseph/0000-0002-0842-804X FU VA HSRD FX This work was funded by VA HSR&D Merit Award (Cynthia Brandt, p1). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. NR 59 TC 28 Z9 28 U1 3 U2 14 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD DEC PY 2010 VL 19 IS 12 BP 2159 EP 2166 DI 10.1089/jwh.2009.1892 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 685KF UT WOS:000284626900004 PM 21039234 ER PT J AU Johansen, KL Chertow, GM Kutner, NG Dalrymple, LS Grimes, BA Kaysen, GA AF Johansen, Kirsten L. Chertow, Glenn M. Kutner, Nancy G. Dalrymple, Lorien S. Grimes, Barbara A. Kaysen, George A. TI Low level of self-reported physical activity in ambulatory patients new to dialysis SO KIDNEY INTERNATIONAL LA English DT Article DE dialysis; end-stage renal disease (ESRD); Human Activity Profile (HAP); physical activity ID QUALITY-OF-LIFE; STAGE RENAL-DISEASE; HEMODIALYSIS-PATIENTS; HEALTH; MORTALITY; EXERCISE; SURVIVAL; DEPRESSION; MORBIDITY; OUTCOMES AB Physical inactivity contributes to the frailty and the decline in function that develops over time among patients with end-stage renal disease. We assessed physical activity among 1547 ambulatory patients new to dialysis in the United States Renal Data System Comprehensive Dialysis Study. We used a self-reporting Human Activity Profile that included Maximal and Adjusted Activity Scores and compared results to established norms by age and gender. Physical activity was found to be extremely low with scores for all age and gender categories below the 5th percentile of healthy individuals and 95% of patients had scores consonant with low fitness. Older age, female gender, diabetes, atherosclerotic disease, and a low level of education were associated with lower activity scores assessed by univariate and multivariable linear regression analysis. Higher serum albumin, creatinine, and lower body mass index, but not hemoglobin levels, were associated with greater physical activity. By multivariable analysis, patients on hemodialysis using a catheter reported lower levels of physical activity compared to those on peritoneal dialysis, hemodialysis using an arteriovenous fistula, or with a graft. Lower Maximal and Adjusted Activity Scores were associated with poor physical function and mental health. Hence, physical activity is distressingly low among patients new to dialysis. Thus, strategies to enhance activity in these patients should be explored. Kidney International (2010) 78, 1164-1170; doi: 10.1038/ki.2010.312; published online 1 September 2010 C1 [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. [Johansen, Kirsten L.; Grimes, Barbara A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Chertow, Glenn M.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Kutner, Nancy G.] Emory Univ, Sch Med, Dept Rehabil Med, Atlanta, GA USA. [Dalrymple, Lorien S.; Kaysen, George A.] Univ Calif Davis, Dept Med, Davis, CA 95616 USA. [Kaysen, George A.] Vet Affairs No Calif Hlth Care Syst, Med Serv, Mather, CA USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 111J 4150 Clement St, San Francisco, CA 94121 USA. EM Kirsten.johansen@ucsf.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [N01-DK-7-0005, N01-DK-7-5004] FX This work was supported through contracts N01-DK-7-0005 and N01-DK-7-5004 from the National Institute of Diabetes and Digestive and Kidney Diseases and was presented in oral form at the 42nd Annual Meeting and Scientific Exposition of the American Society of Nephrology in San Diego, CA. We acknowledge David Daughton for permission to include the Human Activity Profile in the CDS. NR 26 TC 46 Z9 50 U1 3 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2010 VL 78 IS 11 BP 1164 EP 1170 DI 10.1038/ki.2010.312 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 679PM UT WOS:000284173300015 PM 20811334 ER PT J AU Colvin, RB Hirohashi, T Farris, AB Minnei, F Collins, AB Smith, RN AF Colvin, Robert B. Hirohashi, Tsutomu Farris, Alton B. Minnei, Francesca Collins, A. Bernard Smith, R. Neal TI Emerging role of B cells in chronic allograft dysfunction SO KIDNEY INTERNATIONAL LA English DT Review DE chronic allograft nephropathy; C4d; HLA antibodies; renal allograft; transplant glomerulopathy ID ANTIBODY-MEDIATED REJECTION; KIDNEY-TRANSPLANT PATIENTS; RENAL-ALLOGRAFTS; PERITUBULAR CAPILLARIES; PATHOLOGICAL FEATURES; C4D DEPOSITION; ALLOANTIBODY; HLA; BIOPSIES; GLOMERULOPATHY AB B cells have many possible mechanisms by which they can affect allograft survival, including antigen presentation, cytokine production, immune regulation, and differentiation into alloantibody-producing plasma cells. This report reviews the last mechanism, which the authors regard as most critical for the long-term survival of allografts, namely, the promotion of chronic rejection by alloantibodies. Chronic humoral rejection characteristically arises late after transplantation and causes transplant glomerulopathy, multilamination of peritubular capillary basement membranes, and C4d deposition in PTCs and glomeruli. Circulating antidonor human leukocyte antigen class II antibodies are commonly detected and may precede the development of graft injury. Prognosis is poor, especially when recognized after graft dysfunction has developed. Improved detection and treatment are critically needed for this common cause of late graft loss. C1 [Colvin, Robert B.; Collins, A. Bernard; Smith, R. Neal] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Colvin, Robert B.; Hirohashi, Tsutomu; Collins, A. Bernard; Smith, R. Neal] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hirohashi, Tsutomu] Massachusetts Gen Hosp, Div Transplantat, Boston, MA 02114 USA. [Hirohashi, Tsutomu] Massachusetts Gen Hosp, Cardiac Surg Div, Boston, MA 02114 USA. [Farris, Alton B.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Minnei, Francesca] Osped Pediat Bambino Gesu, Dept Anat Patol, Rome, Italy. RP Colvin, RB (reprint author), Massachusetts Gen Hosp, Dept Pathol, Thier 831, Boston, MA 02114 USA. EM colvin@helix.mgh.harvard.edu FU National Institutes of Health; Roche Organ Transplant Research Foundation FX The studies reported from the authors' laboratory were supported by grants from the National Institutes of Health and the Roche Organ Transplant Research Foundation. NR 49 TC 14 Z9 14 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2010 VL 78 SU 119 BP S13 EP S17 DI 10.1038/ki.2010.436 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 687AB UT WOS:000284743000003 ER PT J AU Millington, TM Madsen, JC AF Millington, Timothy M. Madsen, Joren C. TI Innate immunity and cardiac allograft rejection SO KIDNEY INTERNATIONAL LA English DT Review DE complement; heart transplant; innate immunity; natural killer cells; Toll-like receptors ID NATURAL-KILLER-CELLS; ISCHEMIA-REPERFUSION INJURY; TOLL-LIKE RECEPTOR; ACUTE GRAFT-REJECTION; HEART-TRANSPLANTATION; NK CELLS; INFLAMMATORY RESPONSE; MYOCARDIAL-ISCHEMIA; COMPLEMENT; EXPRESSION AB The development of immunosuppressive drugs to control adaptive immune responses has led to the success of heart transplantation as a therapy for end-stage heart failure. However, these agents are largely ineffective in suppressing components of the innate immune system. This distinction has gained clinical significance as mounting evidence now indicates that innate immune responses have important roles in the acute and chronic rejection of cardiac allografts including cardiac allograft vasculopathy (CAV). Whereas clinical interest in natural killer (NK) cells was once largely confined to the field of bone marrow transplantation, recent findings suggest that these cells can also participate in the acute rejection of cardiac allografts and in the development of CAV. Stimulation of Toll-like receptors (TLRs), another important component of innate immunity, by endogenous ligands released in response to ischemia/reperfusion is now known to cause an inflammatory milieu favorable to graft rejection. Finally, new data indicate that activation of complement is linked to acute rejection and CAV. In summary, the conventional wisdom that the innate immune system is of little importance in whole-organ transplantation is no longer tenable. The addition of strategies that target TLRs, NK cells, and complement will be necessary to prevent CAV completely and to eventually achieve long-term tolerance to cardiac allografts. C1 [Millington, Timothy M.; Madsen, Joren C.] Harvard Univ, MGH Transplant Ctr, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Millington, Timothy M.; Madsen, Joren C.] Harvard Univ, Div Cardiac Surg, Massachusetts Gen Hosp, Sch Med,Dept Surg, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Harvard Univ, MGH Transplant Ctr, Sch Med, Massachusetts Gen Hosp, 55 Fruit St,Cox 654, Boston, MA 02114 USA. EM jcmadsen@partners.org FU National Heart, Lung, and Blood Institute [PO1HL018646, RO1HL093131]; National Institute of Allergy and Infectious Disease of the National Institutes of Health [U19AI066705]; Roche Organ Transplantation Research Foundation (ROTRF); International Society of Heart & Lung Transplantation (ISHLT) FX This work was supported in part by the National Heart, Lung, and Blood Institute (PO1HL018646, RO1HL093131) and the National Institute of Allergy and Infectious Disease (U19AI066705) of the National Institutes of Health and the Roche Organ Transplantation Research Foundation (ROTRF). TMM is the recipient of an International Society of Heart & Lung Transplantation (ISHLT) research fellowship. NR 34 TC 12 Z9 12 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2010 VL 78 SU 119 BP S18 EP S21 DI 10.1038/ki.2010.417 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 687AB UT WOS:000284743000004 ER PT J AU Kopans, DB AF Kopans, Daniel B. TI Screening for breast cancer among women in their 40s SO LANCET ONCOLOGY LA English DT Editorial Material ID MORTALITY; AGE C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 7 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD DEC PY 2010 VL 11 IS 12 BP 1108 EP 1109 DI 10.1016/S1470-2045(10)70272-2 PG 2 WC Oncology SC Oncology GA 694TJ UT WOS:000285321600002 PM 21126682 ER PT J AU Wilson, WH Connor, OAO Czuczman, MS LaCasce, AS Gerecitano, JF Leonard, JP Tulpule, A Dunleavy, K Xiong, H Chiu, YL Cui, Y Busman, T Elmore, SW Rosenberg, SH Krivoshik, AP Enschede, SH Humerickhouse, RA AF Wilson, Wyndham H. Connor, Owen A. O. Czuczman, Myron S. LaCasce, Ann S. Gerecitano, John F. Leonard, John P. Tulpule, Anil Dunleavy, Kieron Xiong, Hao Chiu, Yi Lin Cui, Yue Busman, Todd Elmore, Steven W. Rosenberg, Saul H. Krivoshik, Andrew P. Enschede, Sari H. Humerickhouse, Rod A. TI Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity SO LANCET ONCOLOGY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; PAN-BCL-2 FAMILY ANTAGONIST; B-CELL LYMPHOMA; INTERNATIONAL WORKSHOP; OBATOCLAX GX15-070; SOLID TUMORS; PROTEIN; APOPTOSIS; DEATH AB Background Proteins of the BCL 2 family regulate clonal selection and survival of lymphocytes, and are frequently overexpressed in lymphomas Navitoclax is a targeted high affinity small molecule that inhibits the anti apoptotic activity of BCL 2 and BCL XL We aimed to assess the safety and antitumour activity of navitoclax in patients with lymphoid tumours and establish the drug's pharmacokinetic and pharmacodynamic profiles Methods In this phase 1 dose escalation study patients (aged >= 18 years) with relapsed or refractory lymphoid malignancies were enrolled and treated at seven sites in the USA between November 2006 and November 2009 A modified Fibonacci 3+3 design was used to assign patients to receive oral navitoclax once daily by one of two dosing schedules intermittently for the first 14 days of a 21 day cycle (14/21) at doses of 10 20 40 80 110, 160, 225, 315 or 440 mg/day or continuously for 21 days of a 21 day cycle (21/21) at doses of 200, 275, 325 or 425 mg/day Study endpoints were safety, maximum tolerated dose, pharmacokinetic profile pharmacodynamic effects on platelets and T cells and antitumour activity This trial is registered with ClinicalTrials gov number NCT00406809 Findings 55 patients were enrolled (median age 59 years IQR 51-67), 38 to receive the 14/21 dosing schedule and 17 to receive the 21/21 dosing schedule Common toxic effects included grade 1 or 2 anaemia (41 patients) infection (39) diarrhoea (31) nausea (29) and fatigue (21) and grade 3 or 4 thrombocytopenia (29) lymphocytopenia (18) and neutropenia (18) On the Intermittent 14/21 schedule, dose limiting toxic effects were hospital admissions for bronchitis (one) and pleural effusion (one) grade 3 increase in aminotransferases (one) grade 4 thrombocytopenia (one), and grade 3 cardiac arrhythmia (one) To reduce platelet nadir associated with intermittent 14/21 dosing we assessed a 150 mg/day lead in dose followed by a continuous 21/21 dosing schedule On the 21/21 dosing schedule two patients did not complete the first cycle and were excluded from assessment of dose-limiting toxic effects dose-limiting toxic effects were grade 4 thrombocytopenia (one), grade 3 increase m aminotransferases (one) and grade 3 gastrointestinal bleeding (one) Navitoclax showed a pharmacodynamic effect on circulating platelets and T cells Clinical responses occurred across the range of doses and in several tumour types Ten of 46 patients with assessable disease had a partial response and these responders had median progression free survival of 455 days (IQR 40-218) Interpretation Navitoclax has a novel mechanism of peripheral thrombocytopenia and T cell lymphopenia attributable to high affinity inhibition of BCL XL and BCL 2 respectively On the basis of these findings a 150 mg 7 day lead in dose followed by a 325 mg dose administered on a continuous 21/21 dosing schedule was selected for phase 2 study C1 [Wilson, Wyndham H.] NCI, Lymphoma Therapeut Sect, Metab Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Connor, Owen A. O.] NYU Langone Med Ctr, NYU Canc Inst, New York, NY USA. [Czuczman, Myron S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [LaCasce, Ann S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gerecitano, John F.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Leonard, John P.] Cornell Univ, New York, NY 10021 USA. [Tulpule, Anil] Univ So Calif, Los Angeles, CA USA. [Xiong, Hao; Chiu, Yi Lin; Cui, Yue; Busman, Todd; Elmore, Steven W.; Rosenberg, Saul H.; Krivoshik, Andrew P.; Enschede, Sari H.; Humerickhouse, Rod A.] Abbott Labs, Abbott Pk, IL 60064 USA. RP Wilson, WH (reprint author), NCI, Lymphoma Therapeut Sect, Metab Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RI Jones, Jeffrey/E-9827-2013 FU Abbott Laboratories; Genentech; National Cancer Institute National Institutes of Health FX Abbott Laboratories Genentech and National Cancer Institute National Institutes of Health NR 38 TC 272 Z9 275 U1 4 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD DEC PY 2010 VL 11 IS 12 BP 1149 EP 1159 DI 10.1016/S1470.2045(10)70261.8 PG 11 WC Oncology SC Oncology GA 694TJ UT WOS:000285321600018 PM 21094089 ER PT J AU Abbott, MM Hasserjian, RP Emerick, KS AF Abbott, Megan M. Hasserjian, Robert P. Emerick, Kevin S. TI Marginal Zone B-Cell Lymphoma of the Infratemporal Fossa: A Rare Case and Review SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Combined Sections Meeting of The-Triological-Society CY FEB 04-07, 2010 CL Orlando, FL SP Triol Soc DE Infratemporal fossa; lymphoma; marginal zone; extranodal AB Although it represents the second most common neoplasm of the head and neck, lymphoma is generally not surgically managed and thus may be less familiar to otolaryngologists than other malignancies. However, otolaryngologists are often involved in the initial diagnosis, and should be aware of unusual presentations and the main lymphoma subtypes. We present a case of an extranodal marginal zone B-cell lymphoma, an indolent non-Hodgkin's lymphoma subtype. This type of lymphoma most commonly occurs in the stomach, but was found in the infratemporal fossa. This is the first report of an extranodal marginal zone B-cell lymphoma occurring in this location. C1 [Abbott, Megan M.; Hasserjian, Robert P.; Emerick, Kevin S.] Harvard Univ, Sch Med, Boston, MA USA. [Abbott, Megan M.; Emerick, Kevin S.] Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Emerick, KS (reprint author), 243 Charles St, Boston, MA 02114 USA. EM kevin_emerick@meei.harvard.edu NR 8 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2010 VL 120 IS 12 BP 2430 EP 2433 DI 10.1002/lary.20944 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 690WW UT WOS:000285041300014 PM 21046542 ER PT J AU Shargorodsky, J Whittemore, KR Lee, GS AF Shargorodsky, Josef Whittemore, Kenneth R. Lee, Gi Soo TI Bacterial Tracheitis: A Therapeutic Approach SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Combined Sections Meeting of The-Triological-Society CY FEB 04-07, 2010 CL Orlando, FL SP Triol Soc DE Tracheitis; croup; pediatric; airway ID EXPERIENCE; AIRWAY AB Objectives/Hypothesis: tracheitis is an acute, infectious, potentially life-threatening condition of the pediatric airway. Historically, patients have often required urgent invasive airway support, and have been treated with broad-spectrum antibiotics, often combined with direct laryngoscopy and bronchoscopy. Study Design: Retrospective chart review. Methods: Six patients between the ages of 10 months and 16 years were treated at Children & apos;s Hospital, Boston, Massachusetts, for bacterial tracheitis between January 2009 and March 2009. All patients underwent urgent direct laryngoscopy and bronchoscopy for debridement of mucopurulent debris and tissue culture. Broad-spectrum intravenous antibiotics were administered, and patients were kept on acute cardiopulmonary monitoring for 48 to 72 hours, after which time the airway was re-evaluated by direct laryngoscopy and bronchoscopy in five of the patients, and by fiberoptic nasolaryngoscopy in one patient. All of the patients were transitioned to oral antibiotic therapy for 10 to 14 days after discharge. Results: Following debridement, all of the patients did well with aggressive medical management. None of the patients required urgent intubation, although one patient was kept on ventilator support for 48 hours until disease resolution was confirmed. No patients required tracheotomy, and there were no cardiopulmonary arrests. The mean hospital length of stay was 4.8 days (range, 3-8 days). Conclusions: This study highlights the importance of early disease identification and urgent surgical intervention in the management of bacterial tracheitis. It also demonstrates an approach with the potential to improve patient outcomes from this dangerous condition. C1 [Shargorodsky, Josef] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Shargorodsky, Josef] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Whittemore, Kenneth R.; Lee, Gi Soo] Childrens Hosp, Dept Otolaryngol & Commun Enhancement, Boston, MA 02115 USA. RP Shargorodsky, J (reprint author), Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM josef_shargorodsky@meei.harvard.edu NR 14 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2010 VL 120 IS 12 BP 2498 EP 2501 DI 10.1002/lary.21105 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 690WW UT WOS:000285041300026 PM 21108480 ER PT J AU Chan, NPY Ho, SGY Yeung, CK Shek, SYN Chan, HH AF Chan, Nicola P. Y. Ho, Stephanie G. Y. Yeung, Chi K. Shek, Samantha Y. N. Chan, Henry H. TI The Use of Non-Ablative Fractional Resurfacing in Asian Acne Scar Patients SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE acne; Asian; fractional; laser; non-ablative; photothermolysis; post-inflammatory hyperpigmentation; scar ID LASER PHOTOTHERMOLYSIS; SKIN; COMPLICATIONS; EXPERIENCE AB Background and Objectives: Non-ablative fractional resurfacing (NA FR) has been shown to be effective for photorejuvenation and acne scarring. Previous studies indicated that density, more than pulse energy, was associated with post-inflammatory hyperpigmentation (PIH) in Asians. The objective of this retrospective study was to assess the efficacy and complications of eight passes of NAFR('full-NA FR') with the 1,550 nm erbium-doped fibre fractional laser (Fraxel SR laser system, Solta Medical, Hayward, CA) versus four passes ('mini-NAFR') with comparable pulse energy and treatment level as 'full-NA FR', but double the number of treatment sessions in Asian acne scar patients. Materials and Methods: Forty-seven Asian atrophic facial acne scar patients who received full-face full-NA FR or mini-NA FR treatments between December 2005 and February 2009 were included. All photographic images captured with the Canfield Visia CR system at baseline and follow-ups were assessed for clinical efficacy and complications by an independent, non-treating and blinded physician. Results: The total treatment densities for full-NA FR and mini-NA FR were 442.5 and 210.5 MTZ/cm(2), respectively. For full-NAFR, the PIH risk was 18.2% with cross-polarized images compared to 6.0% for mini-NA FR. This difference was statistically significant (P < 0.001). Improvement in skin texture, acne scarring, enlarged pores and overall pigmentation irregularity all reached statistical significance at last follow-up compared to baseline. There was no statistically significant difference in clinical efficacy between three full-NA FR and six mini-NA FR treatments. Conclusions: NA FR was effective and safe in Asians. By reducing the number of passes and the total treatment density, the risk of PIH could be reduced. Meanwhile, clinical efficacy could be maintained by increasing the total number of treatment sessions. Lasers Surg. Med. 42:710-715, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Chan, Henry H.] Univ Hong Kong, Dept Med, Div Dermatol, Dermatol & Laser Ctr, Hong Kong, Hong Kong, Peoples R China. [Chan, Henry H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Chan, HH (reprint author), Univ Hong Kong, Dept Med, Div Dermatol, Dermatol & Laser Ctr, 13th Floor,16 Ice House St, Hong Kong, Hong Kong, Peoples R China. EM hhlchan@hku.hk RI Yeung, Chi Keung/L-4795-2013; Chan, Henry Hin Lee/L-2267-2013 NR 30 TC 33 Z9 33 U1 1 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD DEC PY 2010 VL 42 IS 10 BP 710 EP 715 DI 10.1002/lsm..20976 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 709LS UT WOS:000286440100002 PM 21246574 ER PT J AU Weisberg, E Ray, A Barrett, R Nelson, E Christie, AL Porter, D Straub, C Zawel, L Daley, JF Lazo-Kallanian, S Stone, R Galinsky, I Frank, D Kung, AL Griffin, JD AF Weisberg, E. Ray, A. Barrett, R. Nelson, E. Christie, A. L. Porter, D. Straub, C. Zawel, L. Daley, J. F. Lazo-Kallanian, S. Stone, R. Galinsky, I. Frank, D. Kung, A. L. Griffin, J. D. TI Smac mimetics: implications for enhancement of targeted therapies in leukemia SO LEUKEMIA LA English DT Article DE CML; AML; IAP inhibitor; kinase inhibitor; residual disease; synergy AB Drug resistance is a growing concern with clinical use of tyrosine kinase inhibitors. Utilizing in vitro models of intrinsic drug resistance and stromal-mediated chemoresistance, as well as functional mouse models of progressive and residual disease, we attempted to develop a potential therapeutic approach designed to suppress leukemia recurrence following treatment with selective kinase inhibitors. The novel inhibitor of apoptosis (IAP), LCL161, was observed to potentiate the effects of tyrosine kinase inhibition against leukemic disease both in the absence and presence of a stromal protected environment. LCL161 enhanced the proapoptotic effects of nilotinib and PKC412, against leukemic disease in vitro and potentiated the activity of both kinase inhibitors against leukemic disease in vivo. In addition, LCL161 synergized in vivo with nilotinib to reduce leukemia burden significantly below the baseline level suppression exhibited by a moderate-to-high dose of nilotinib. Finally, LCL161 displayed antiproliferative effects against cells characterized by intrinsic resistance to tyrosine kinase inhibitors as a result of expression of point mutations in the protein targets of drug inhibition. These results support the idea of using IAP inhibitors in conjunction with targeted tyrosine kinase inhibition to override drug resistance and suppress or eradicate residual disease. Leukemia (2010) 24, 2100-2109; doi:10.1038/leu.2010.212; published online 16 September 2010 C1 [Weisberg, E.; Ray, A.; Barrett, R.; Nelson, E.; Daley, J. F.; Lazo-Kallanian, S.; Stone, R.; Galinsky, I.; Frank, D.; Griffin, J. D.] Dana Farber Canc Inst, Dept Med Oncol Hematol Neoplasia, Boston, MA 02115 USA. [Christie, A. L.; Kung, A. L.] Dana Farber Canc Inst, Lurie Family Imaging Ctr, CBIO, Boston, MA 02115 USA. [Porter, D.; Straub, C.; Zawel, L.] Novartis Pharma AG, Basel, Switzerland. [Kung, A. L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kung, A. L.] Childrens Hosp, Boston, MA 02115 USA. RP Weisberg, E (reprint author), Dana Farber Canc Inst, Dept Med Oncol Hematol Neoplasia, 44 Binney St, Boston, MA 02115 USA. EM Ellen_Weisberg@dfci.harvard.edu OI Kung, Andrew/0000-0002-9091-488X FU NIH [CA66996, CA36167, DK50654]; Leukemia and Lymphoma Society FX JDG is supported by NIH Grant CA66996, and a Specialized Center of Research Award from the Leukemia and Lymphoma Society. JDG is also supported by NIH Grants CA36167 and DK50654. NR 28 TC 42 Z9 44 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD DEC PY 2010 VL 24 IS 12 BP 2100 EP 2109 DI 10.1038/leu.2010.212 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 695OF UT WOS:000285380900015 PM 20844561 ER PT J AU Kotton, CN Hurtado, RM AF Kotton, Camille Nelson Hurtado, Rocio M. TI Not Just a Fluke: Expanding the Organ Supply SO LIVER TRANSPLANTATION LA English DT Editorial Material ID SOLID-ORGAN; TRANSPLANT RECIPIENTS; TRANSMISSION; CLONORCHIASIS; INFECTIONS; DONOR C1 [Kotton, Camille Nelson; Hurtado, Rocio M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. [Hurtado, Rocio M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Kotton, CN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St,Cox 5, Boston, MA 02114 USA. EM ckotton@partners.org NR 13 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD DEC PY 2010 VL 16 IS 12 BP 1343 EP 1344 DI 10.1002/lt.22178 PG 2 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 693IA UT WOS:000285216600002 PM 21117192 ER PT J AU Jameel, NM Thirunavukkarasu, C Murase, N Cascio, M Prelich, J Yang, ST Harvey, SAK Gandhi, CR AF Jameel, Noor Mohamed Thirunavukkarasu, Chinnasamy Murase, Noriko Cascio, Michael Prelich, John Yang, Shuting Harvey, Stephen A. K. Gandhi, Chandrashekhar R. TI Constitutive Release of Powerful Antioxidant-Scavenging Activity by Hepatic Stellate Cells: Protection of Hepatocytes From lschemia/Reperfusion Injury SO LIVER TRANSPLANTATION LA English DT Article ID SUPEROXIDE-INDUCED APOPTOSIS; PLATELET-ACTIVATING-FACTOR; GROWTH-FACTOR-BETA; REACTIVE OXYGEN; RETINOIC ACID; KUPFFER CELLS; CULTURED-HEPATOCYTES; EXTRACELLULAR-MATRIX; REPERFUSION INJURY; OXIDATIVE STRESS AB Within the liver, reactive oxygen species produced by infiltrating blood cells and Kupffer cells (resident macrophages) can injure hepatocytes. We hypothesized that hepatocyte survival is influenced by the relatively small juxtaposed population of hepatic stellate cells (HSCs). We used cultures of primary rat hepatocytes as targets for superoxide-induced damage, which was determined by crystal violet assay and lactate dehydrogenase release. An HSC-conditioned medium prevented the superoxide-induced death of hepatocytes, and the protective factor released by HSCs was a protein or proteins (apparent molecular weight > 100 kDa) resistant to heat (70 degrees C) and pH (4.5-8.5). The protein or proteins were partially purified on DE52 cellulose, and the active fraction contained no detectable levels of superoxide dismutase: after separation by Sephadex G-100 gel filtration, the antioxidant activity could be reconstituted by the combination of 2 protein peaks, and this reconstituted activity was protective both in vitro and against liver ischemia/reperfusion injury in intact rats. Mass spectrometry proteomic studies confirmed that this activity could not be attributed to any previously identified antioxidant protein. Thus, HSCs protect hepatocytes against oxidative damage through the production of a novel protein, the further purification of which may lead to the isolation of a powerful oxygen radical scavenger with clinical applications. Liver Transpl 16:14001409, 2010. (C) 2010 AASLD. C1 [Jameel, Noor Mohamed; Thirunavukkarasu, Chinnasamy; Murase, Noriko; Yang, Shuting; Gandhi, Chandrashekhar R.] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15213 USA. [Jameel, Noor Mohamed; Thirunavukkarasu, Chinnasamy; Murase, Noriko; Yang, Shuting; Gandhi, Chandrashekhar R.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. [Cascio, Michael] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA 15213 USA. [Harvey, Stephen A. K.] Univ Pittsburgh, Dept Ophthalmol, Pittsburgh, PA 15213 USA. [Prelich, John; Gandhi, Chandrashekhar R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Cascio, Michael] Duquesne Univ, Dept Chem & Biochem, Pittsburgh, PA 15219 USA. RP Gandhi, CR (reprint author), Univ Pittsburgh, Thomas E Starzl Transplantat Inst, E-1540 BST,200 Lothrop St, Pittsburgh, PA 15213 USA. EM gandhics@msx.upmc.edu FU National Institutes of Health [RO1-DK054411, PO1-AI081678] FX This study was supported by the National Institutes of Health (grants RO1-DK054411 and PO1-AI081678). NR 42 TC 4 Z9 5 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD DEC PY 2010 VL 16 IS 12 BP 1400 EP 1409 DI 10.1002/lt.22172 PG 10 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 693IA UT WOS:000285216600010 PM 21117250 ER PT J AU Andronesi, OC Ramadan, S Mountford, CE Sorensen, AG AF Andronesi, Ovidiu C. Ramadan, Saadallah Mountford, Carolyn E. Sorensen, A. Gregory TI Low-Power Adiabatic Sequences for In Vivo Localized Two-Dimensional Chemical Shift Correlated MR Spectroscopy SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE total correlated spectroscopy (TOCSY); correlated spectroscopy (COSY); gradient offset independent adiabatic (GOIA); in vivo 2D MRS ID MULTIDIMENSIONAL NMR-SPECTRA; SOLID-STATE NMR; HUMAN-BRAIN; MAGNETIC-RESONANCE; H-1-NMR SPECTRA; ROTATING-FRAME; HIGH-FIELD; HEAD COIL; Z-FILTERS; PULSES AB Novel low-power adiabatic sequences are demonstrated for in vivo localized two-dimensional correlated MR spectroscopy, such as correlated spectroscopy and total correlated spectroscopy. The design is based on three new elements for in vivo two-dimensional MRS: the use of gradient modulated constant adiabaticity GOIA-W(16,4) pulses for (i) localization (correlated spectroscopy and total correlated spectroscopy) and (ii) mixing (total correlated spectroscopy), and (iii) the use of longitudinal mixing (z-filter) for magnetization transfer during total correlated spectroscopy. GOIA-W(16,4) provides accurate signal localization, and more importantly, lowers the SAR for both total correlated spectroscopy mixing and localization. Longitudinal mixing improves considerably (fivefolds) the efficiency of total correlated spectroscopy transfer. These are markedly different from previous 1D editing total correlated spectroscopy sequences using spatially nonselective pulses and transverse mixing. Fully adiabatic (adiabatic mixing with adiabatic localization) and semiadiabatic (adiabatic mixing with nonadiabatic localization) methods for two-dimensional total correlated spectroscopy are compared. Results are presented for simulations, phantoms, and in vivo two-dimensional spectra from healthy volunteers and patients with brain tumors obtained on 3T clinical platforms equipped with standard hardware. To the best of our knowledge, this is the first demonstration of in vivo adiabatic two-dimensional total correlated spectroscopy and fully adiabatic two-dimensional correlated spectroscopy. It is expected that these methodological developments will advance the in vivo applicability of multi(spectrally)dimensional MRS to reliably identify metabolic biomarkers. Magn Reson Med 64:1542-1556, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Andronesi, Ovidiu C.; Sorensen, A. Gregory] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Dept Radiol, Boston, MA 02129 USA. [Andronesi, Ovidiu C.] Univ Babes Bolyai, Dept Clin Psychol, R-3400 Cluj Napoca, Romania. [Ramadan, Saadallah; Mountford, Carolyn E.] Harvard Univ, Dept Radiol, Ctr Clin Spect, Brigham & Womens Hosp,Med Sch, Boston, MA 02129 USA. RP Andronesi, OC (reprint author), Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Dept Radiol, 149 13th St,Suite 2301, Boston, MA 02129 USA. EM ovidiu@nmr.mgh.harvard.edu; sorensen@nmr.mgh.harvard.edu FU NIH [R01 1200-206456] FX Grant sponsor: NIH; Grant number: R01 1200-206456. NR 74 TC 14 Z9 14 U1 0 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD DEC PY 2010 VL 64 IS 6 BP 1542 EP 1556 DI 10.1002/mrm.22535 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 685WR UT WOS:000284659300002 PM 20890988 ER PT J AU Spanakis, EK Kourkoumpetis, TK Livanis, G Peleg, AY Mylonakis, E AF Spanakis, Elias K. Kourkoumpetis, Themistoklis K. Livanis, Grigorios Peleg, Anton Y. Mylonakis, Eleftherios TI Statin Therapy and Decreased Incidence of Positive Candida Cultures Among Patients With Type 2 Diabetes Mellitus Undergoing Gastrointestinal Surgery SO MAYO CLINIC PROCEEDINGS LA English DT Article ID SEPSIS; COLONIZATION; INFECTIONS; ALBICANS; DISEASE; IMPACT; COHORT; TRACT AB OBJECTIVE: To assess whether statin therapy decreases the incidence of cultures positive for Candlda species among high-risk hospitalized patients with type 2 diabetes mellitus (DM). PATIENTS AND METHODS: We performed a retrospective cohort study analyzing the records of all patients with type 2 DM who were admitted to Massachusetts General Hospital for lower gastrointestinal tract surgery between January 1, 2001, and May 1, 2008. We defined statln exposure as the filling of at least 1 prescription of statins during the 6 months before hospitalization or during the current hospital stay. The primary outcome was a culture positive for Candlda species during hospitalization. Clinical information on a wide range of covariates was collected. Logistic regression analysis was used to adjust for possible confounders. RESULTS: Of the 1019 patients who were eligible for the study, 493 (48%) were receiving statins. A total of 139 patients (14%) had at least 1 culture positive for Candlda species during hospitalization. An adjusted multivariate model based on a backward stepwise elimination procedure showed that statin therapy significantly decreased the incidence of cultures positive for Candlda species (odds ratio, 0.60; 95% confidence interval [CI], 0.38-0.96; P=.03) with a statistically significant prolonged time to event compared with no statin therapy (adjusted hazard ratio, 0.62; 95% CI, 0.440.88; P=.01). The benefit of statins was more prominent in patients with type 2 DM who had greater comorbidities (Charlson Comorbidity Index >= 2) (adjusted odds ratio, 0.47; 95% CI, 0.27-0.79; P=.01). CONCLUSION: Among patients with type 2 DM who underwent gastrointestinal surgery, use of statins correlated with a decreased incidence of cultures positive for Candlda species. Mayo Clin Proc. 2010;85(12):1073-1079 C1 [Spanakis, Elias K.; Kourkoumpetis, Themistoklis K.; Mylonakis, Eleftherios] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. [Spanakis, Elias K.] Caritas St Elizabeths Med Ctr, Dept Internal Med, Boston, MA USA. [Livanis, Grigorios] Northeastern Univ, Coll Business Adm, Boston, MA 02115 USA. [Peleg, Anton Y.] Alfred Hosp, Dept Infect Dis, Melbourne, Vic, Australia. [Peleg, Anton Y.] Monash Univ, Dept Microbiol, Melbourne, Vic 3004, Australia. [Peleg, Anton Y.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. RP Mylonakis, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St,Gray Jackson 5,Room GRJ-504, Boston, MA 02114 USA. EM espanakis@gmail.com; emylonakis@partners.org OI Peleg, Anton/0000-0002-2296-2126 FU Astellas Pharma US FX Dr Mylonakis has received research support from Astellas Pharma US and was a member of the speaker's bureau for Pfizer. Dr Peleg has acted as an advisor to Abbott Molecular and Ortho-McNeil-Janssen. None of the funders was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. NR 28 TC 11 Z9 11 U1 0 U2 2 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD DEC PY 2010 VL 85 IS 12 BP 1073 EP 1079 DI 10.4065/mcp.2010.0447 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 694HA UT WOS:000285284400002 PM 21123633 ER PT J AU Ruhnke, GW Coca-Perraillon, M Kitch, BT Cutler, DM AF Ruhnke, Gregory W. Coca-Perraillon, Marcelo Kitch, Barrett T. Cutler, David M. TI Trends in Mortality and Medical Spending in Patients Hospitalized for Community-Acquired Pneumonia 1993-2005 SO MEDICAL CARE LA English DT Article DE community-acquired pneumonia; mortality trend; hospitalization costs; improved productivity ID PNEUMOCOCCAL POLYSACCHARIDE VACCINE; CONGESTIVE-HEART-FAILURE; ELDERLY-PATIENTS; ANTIMICROBIAL THERAPY; SECULAR TRENDS; OUTCOMES; CARE; ADULTS; GUIDELINE; LENGTH AB Background: Community-acquired pneumonia (CAP) is the most common infectious cause of death in the United States. To understand the effect of efforts to improve quality and efficiency of care in CAP, we examined the trends in mortality and costs among hospitalized CAP patients. Methods: Using the National Inpatient Sample between 1993 and 2005, we studied 569,524 CAP admissions. The primary outcome was mortality at discharge. We used logistic regression to evaluate the mortality trend, adjusting for age, gender, and comorbidities. To account for the effect of early discharge practices, we also compared daily mortality rates and performed a Cox proportional hazards model. We used a generalized linear model to analyze trends in hospitalization costs, which were derived using cost-to-charge ratios. Results: Over time, length of stay declined, while more patients were discharged to other facilities. The frequency of many comorbidities increased. Age/gender-adjusted mortality decreased from 8.9% to 4.1% (P < 0.001). In multivariable analysis, the mortality risk declined through 2005 (odds ratio, 0.50; 95% confidence interval, 0.48-0.53), compared with the reference year 1993. The daily mortality rates demonstrated that most of the mortality reduction occurred early during hospitalization. After adjusting for early discharge practices, the risk of mortality still declined through 2005 (hazard ratio, 0.74; 95% confidence interval, 0.70-0.78). Median hospitalization costs exhibited a moderate reduction over time, mostly because of reduced length of stay. Conclusions: Mortality among patients hospitalized for CAP has declined. Lower in-hospital mortality at a reduced cost suggests that pneumonia is a case of improved productivity in health care. C1 [Ruhnke, Gregory W.] Univ Chicago, Med Ctr, Sect Hosp Med, Dept Internal Med, Chicago, IL 60637 USA. [Coca-Perraillon, Marcelo; Cutler, David M.] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Kitch, Barrett T.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Kitch, Barrett T.] N Shore Med Ctr, Div Crit Care Med, Salem, MA USA. [Cutler, David M.] Harvard Univ, Cambridge, MA 02138 USA. RP Ruhnke, GW (reprint author), Univ Chicago, Med Ctr, Sect Hosp Med, Dept Internal Med, 5841 S Maryland Ave,MC 5000, Chicago, IL 60637 USA. EM gruhnke@medicine.bsd.uchicago.edu FU Health Resources and Services Administration of the Department of Health and Human Services [T32HP11001]; Agency for Healthcare Research and Quality [F32 HS016948-01]; National Institute on Aging [P01 AG31098, P30 AG12810, P01 AG005842] FX This study was funded by grant number T32HP11001 from the Health Resources and Services Administration of the Department of Health and Human Services to support the Harvard Medical School Fellowship in General Medicine and Primary Care. It was also supported by grant F32 HS016948-01 from the Agency for Healthcare Research and Quality, as well as unrestricted grants P01 AG31098, P30 AG12810, and P01 AG005842 from the National Institute on Aging. The supporters had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 38 TC 21 Z9 23 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD DEC PY 2010 VL 48 IS 12 BP 1111 EP 1116 DI 10.1097/MLR.0b013e3181f38006 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 682DN UT WOS:000284380200010 PM 21063230 ER PT J AU Borzecki, AM Christiansen, CL Chew, P Loveland, S Rosen, AK AF Borzecki, Ann M. Christiansen, Cindy L. Chew, Priscilla Loveland, Susan Rosen, Amy K. TI Comparison of In-Hospital Versus 30-Day Mortality Assessments for Selected Medical Conditions SO MEDICAL CARE LA English DT Article DE hospital mortality; quality indicators; quality improvement ID COMORBIDITIES; LENGTH; STAY AB Background: In-hospital mortality measures such as the Agency for Healthcare Research and Quality (AHRQ) Inpatient Quality Indicators (IQIs) are easily derived using hospital discharge abstracts and publicly available software. However, hospital assessments based on a 30-day postadmission interval might be more accurate given potential differences in facility discharge practices. Objectives: To compare in-hospital and 30-day mortality rates for 6 medical conditions using the AHRQ IQI software. Methods: We used IQI software (v3.1) and 2004-2007 Veterans Health Administration (VA) discharge and Vital Status files to derive 4-year facility-level in-hospital and 30-day observed mortality rates and observed/expected ratios (O/Es) for admissions with a principal diagnosis of acute myocardial infarction, congestive heart failure, stroke, gastrointestinal hemorrhage, hip fracture, and pneumonia. We standardized software-calculated O/Es to the VA population and compared O/Es and outlier status across sites using correlation, observed agreement, and kappas. Results: Of 119 facilities, in-hospital versus 30-day mortality O/E correlations were generally high (median: r = 0.78; range: 0.31-0.86). Examining outlier status, observed agreement was high (median: 84.7%, 80.7%-89.1%). Kappas showed at least moderate agreement (k > 0.40) for all indicators except stroke and hip fracture (k <= 0.22). Across indicators, few sites changed from a high to nonoutlier or low outlier, or vice versa (median: 10, range: 7-13). Conclusions: The AHRQ IQI software can be easily adapted to generate 30-day mortality rates. Although 30-day mortality has better face validity as a hospital performance measure than in-hospital mortality, site assessments were similar despite the definition used. Thus, the measure selected for internal benchmarking should primarily depend on the healthcare system's data linkage capabilities. C1 [Borzecki, Ann M.; Christiansen, Cindy L.; Chew, Priscilla] Bedford VAMC, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Borzecki, Ann M.; Christiansen, Cindy L.; Loveland, Susan; Rosen, Amy K.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Borzecki, Ann M.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Loveland, Susan; Rosen, Amy K.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Rosen, Amy K.] Boston Univ, Sch Med, Dept Family Med, Boston, MA 02118 USA. RP Borzecki, AM (reprint author), Bedford VA Hosp 152, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd, Bedford, MA 01730 USA. EM amb@bu.edu OI Christiansen, Cindy/0000-0001-9951-480X FU Veterans Health Administration FX Supported by Veterans Health Administration. NR 24 TC 27 Z9 28 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD DEC PY 2010 VL 48 IS 12 BP 1117 EP 1121 DI 10.1097/MLR.0b013e3181ef9d53 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 682DN UT WOS:000284380200011 PM 20978451 ER PT J AU Ly, DP Lopez, L Isaac, T Jha, AK AF Ly, Dan P. Lopez, Lenny Isaac, Thomas Jha, Ashish K. TI How Do Black-Serving Hospitals Perform on Patient Safety Indicators? Implications for National Public Reporting and Pay-for-Performance SO MEDICAL CARE LA English DT Article DE disparities; quality; public reporting ID QUALITY; CARE; MORTALITY; RATES AB Background: There is increasing policy interest in public reporting and tying financial incentives to metrics of patient safety. How black-serving hospitals fare on these measures will have important implications for disparities in care. Objectives: To determine how black-serving hospitals perform on patient safety indicators (PSIs). Research Design: We used national Medicare data to calculate the performance of hospitals on 11 medical and surgical PSIs. We designated US hospitals in the top decile of proportion of hospitalized patients who are black as "black-serving." We calculated overall and race-specific rates and examined the relationship between being a black-serving hospital and PSI rates. Subjects: Medicare fee-for-service enrollees discharged from 4488 acute-care US hospitals. Results: Black-serving hospitals performed worse than other hospitals on 6 of 11 PSIs. For example, black-serving hospitals had nearly twice the rate of postoperative pulmonary embolism or deep venous thrombosis (19.4 vs. 11.5 per 1000 discharges, P < 0.001). Adjusting for hospital characteristics had moderate effects. In race-specific analyses, we found that both white and black patients generally had higher rates of potential safety events in black-serving hospitals than they did in non-black-serving hospitals. Conclusions: Hospitals that disproportionately care for black patients have higher rates of potential safety events among both black and white patients than other hospitals. Current efforts to penalize hospitals with high PSI rates will have a greater effect on hospitals that disproportionately care for black patients. C1 [Ly, Dan P.] Harvard Univ, John F Kennedy Sch Govt, Cambridge, MA 02138 USA. [Ly, Dan P.] Weill Cornell Med Coll, New York, NY USA. [Lopez, Lenny] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Isaac, Thomas] Beth Israel Deaconess Med Ctr, Dept Gen Med & Primary Care, Brookline, MA USA. [Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. [Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Ly, DP (reprint author), Harvard Univ, John F Kennedy Sch Govt, 10 Akron St,Unit 101, Cambridge, MA 02138 USA. EM dan_ly@hks11.harvard.edu NR 21 TC 29 Z9 29 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD DEC PY 2010 VL 48 IS 12 BP 1133 EP 1137 DI 10.1097/MLR.0b013e3181f81c7e PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 682DN UT WOS:000284380200014 PM 21063225 ER PT J AU Ding, AP Gu, JW Trofimov, AV Xu, XG AF Ding, Aiping Gu, Jianwei Trofimov, Alexei V. Xu, X. George TI Monte Carlo calculation of imaging doses from diagnostic multidetector CT and kilovoltage cone-beam CT as part of prostate cancer treatment plans SO MEDICAL PHYSICS LA English DT Article DE Monte Carlo; imaging dose; CT; DVH ID RADIATION-THERAPY; GUIDED RADIOTHERAPY; COMPUTED-TOMOGRAPHY; PATIENT; DISTRIBUTIONS; DOSIMETRY AB Purpose: To calculate imaging doses to the rectum, bladder, and femoral heads as part of a prostate cancer treatment plans, assuming an image guided radiation therapy (IGRT) procedure involving either the multidetector CT (MDCT) or kilovoltage cone-beam CT (kV CBCT). Methods: This study considered an IGRT treatment plan for a prostate carcinoma patient involving 50.4 Gy from 28 initial fractions and a boost of 28.8 Gy from 16 fractions. A total of 45 CT imaging procedures, each involving a MDCT or a kV CBCT scan procedure, were carefully modeled using the MCNPX code version 2.5.0. The MDCT scanner model is based on the GE LightSpeed 16-MDCT scanner and the kV CBCT scanner model is based on the Varian On-Board Imager using parameters reported by the CT manufacturers and literatures. A patient-specific treatment planning CT data set was used to construct the phantom for the dose calculation. The target, organs-at-risk (OARs), and background voxels in the CT data set were categorized into six tissue types according to CT numbers for Monte Carlo calculations. Results: For a total of 45 imaging procedures, it was found that the rectum received 78.4 and 76.7 cGy from MDCT and kV CBCT, respectively. The bladder received slightly greater doses of 82.4 and 77.9 cGy, while the femoral heads received much higher doses of 182.3 and 141.3 cGy from MDCT and kV CBCT, respectively. To investigate the impact of these imaging doses on treatment planning, OAR doses from MDCT or kV CBCT imaging procedures were added to the corresponding dose matrix reported by the original treatment plans to construct dose volume histograms. It was found that after the imaging dose is added, the rectum volumes irradiated to 75 and 70 Gy increased from 13.9% and 21.2%, respectively, in the original plan to 14.8% and 21.8%. The bladder volumes receiving 80 Gy increased to 4.6% from 4.1% in the original plan and the volume receiving 75 Gy increased to 7.9% from 7.5%. All values remained within the tolerance levels: V(70) <25%, V(75) <15% for rectum and V(75) <25%, V(80) <15% for bladder. The irradiation of femoral heads was also acceptable with no volume receiving >45 Gy. Conclusions: IGRT procedures can irradiate the OARs to an imaging dose level that is great enough to require careful evaluation and perhaps even adjustment of original treatment planning in order to still satisfy the dose constraints. This study only considered one patient CT because the CT x rays cover a relatively larger volume of the body and the dose distribution is considerably more uniform than those associated with the therapeutic beams. As a result, the dose to an organ from CT imaging doses does not vary much from one patient to the other for the same CT settings. One factor that would potentially affect such CT dose level is the size of the patient body. More studies are needed to develop accurate and convenient methods of accounting for the imaging doses as part of treatment planning. (C) 2010 American Association of Physicists in Medicine. [DOI: 10.1118/1.3512791] C1 [Ding, Aiping; Gu, Jianwei; Xu, X. George] Rensselaer Polytech Inst, Nucl Engn & Engn Phys Program, Troy, NY 12180 USA. [Trofimov, Alexei V.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Xu, XG (reprint author), Rensselaer Polytech Inst, Nucl Engn & Engn Phys Program, Troy, NY 12180 USA. EM xug2@rpi.edu RI DING, AIPING/E-8338-2011 FU National Cancer Institute [R01CA116743] FX The CT scanner modeling and Monte Carlo computing resources were made available from a project funded by the National Cancer Institute (Grant No. R01CA116743). Dr. Yi Wang from MGH assisted in analyzing imaging and treatment plans. Dr. Yong Hum Na from RPI provided 3D rendering of the patient CT phantom. Mr. Matt Mille and Mr. Bin Han of RPI were helpful in the Monte Carlo calculations. NR 19 TC 16 Z9 16 U1 0 U2 7 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 2010 VL 37 IS 12 BP 6199 EP 6204 DI 10.1118/1.3512791 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 701UR UT WOS:000285849400010 PM 21302776 ER PT J AU Ganda, OP AF Ganda, Om P. TI The Role of Bile Acid Sequestrants in the Management of Type 2 Diabetes Mellitus SO METABOLIC SYNDROME AND RELATED DISORDERS LA English DT Article ID BLOOD-GLUCOSE CONTROL; DISEASE RISK-FACTORS; CARDIOVASCULAR-DISEASE; PRIMARY HYPERCHOLESTEROLEMIA; MYOCARDIAL-INFARCTION; RETROSPECTIVE COHORT; STATIN THERAPY; LIFE-STYLE; FOLLOW-UP; METAANALYSIS AB The prevalence of type 2 diabetes (T2DM) and cardiovascular disease (CVD) continues to escalate globally. There is now abundant clinical trial evidence that the optimal treatment of CVD risk factors, with lifestyle changes aimed at weight loss in most patients, and pharmacologic management of dyslipidemia and hyperglycemia, can help mitigate the CVD burden. Yet more than 50% of patients are still not achieving glycosylated hemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDL-C) goals. Over the past 15 years, many novel and emerging drugs have made it possible to achieve optimal glycemic control, generally in combination therapy, without untoward effects of weight gain, hypoglycemia, and other adverse effects with traditional agents. Although the long-term efficacy and safety of some of the newer classes of agents are yet to be determined, bile acid sequestrants represent a unique long-standing class of agents. These drugs have the dual efficacy in glycemic control and LDL-C reduction, and an established record of long-term safety. Colesevelam HCl is the only drug approved for this dual indication and is an adjunct in the treatment of both hyperglycemia and hypercholesterolemia that frequently co-exist in adults with T2DM. C1 [Ganda, Om P.] Harvard Univ, Sch Med, Lipid Clin, Joslin Diabet Ctr, Boston, MA 02115 USA. [Ganda, Om P.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Ganda, OP (reprint author), Harvard Univ, Sch Med, Lipid Clin, Joslin Diabet Ctr, Boston, MA 02115 USA. EM om.ganda@joslin.harvard.edu FU DERC [P30 DK-36836] FX Supported, in part, by enrichment core of the DERC grant # P30 DK-36836. NR 41 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-4196 J9 METAB SYNDR RELAT D JI Metab. Syndr. Relat. Disord. PD DEC PY 2010 VL 8 SU 1 BP S15 EP S21 DI 10.1089/met.2010.0095 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 692XK UT WOS:000285189000004 PM 21034179 ER PT J AU Finley, EP Zeber, JE Pugh, MJV Cantu, G Copeland, LA Parchman, ML Noel, PH AF Finley, Erin P. Zeber, John E. Pugh, Mary Jo V. Cantu, Gabriela Copeland, Laurel A. Parchman, Michael L. Noel, Polly H. TI Postdeployment Health Care for Returning OEF/OIF Military Personnel and Their Social Networks: A Qualitative Approach SO MILITARY MEDICINE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; OPERATION IRAQI FREEDOM; MENTAL-HEALTH; VETERANS; CHILDREN; AFGHANISTAN; MANAGEMENT; FAMILIES; SOLDIERS; STARNET AB Little is known regarding the health care needs of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) deployed veterans seeking care outside of Veterans Affairs facilities. Responding to this gap, we conducted a mixed methods study of postdeployment health among veterans and members of their social networks in six community-based primary care clinics. A total of 347 patients completed a survey dealing with deployment to Iraq/Afghanistan (whether their own or that of a family member, friend, or coworker), and subsequent psychosocial and health problems. A subset of 52 participants responded to an open-ended question requesting additional information about experiences during and postdeployment. Content analysis of these responses revealed five overarching themes: connectedness, perceptions of conflict, consequences of deployment, health and treatment concerns, and respect and concern for service members/veterans. These data point to significant deployment-related disruptions in the well-being of service members and those in their broader social networks, with implications for defining service needs in community health settings. C1 [Finley, Erin P.; Zeber, John E.; Pugh, Mary Jo V.; Cantu, Gabriela; Copeland, Laurel A.; Parchman, Michael L.; Noel, Polly H.] VERDICT, Dept Vet Affairs, S Texas Vet Hlth Care Syst, Hlth Serv Res & Dev, San Antonio, TX 78229 USA. [Finley, Erin P.; Noel, Polly H.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Zeber, John E.; Copeland, Laurel A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Parchman, Michael L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. RP Finley, EP (reprint author), VERDICT, Dept Vet Affairs, S Texas Vet Hlth Care Syst, Hlth Serv Res & Dev, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. OI Copeland, Laurel/0000-0002-9478-0209; Finley, Erin/0000-0003-4497-7721 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development; Area Health Education Center at the University of Texas Health Science Center at San Antonio FX The study team expresses its appreciation to Brendan Nadeau, Paula Winkler, Raquel Romero, and the community clinics, providers, and patients who facilitated work on this project. This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development, along with funds provided by the Area Health Education Center at the University of Texas Health Science Center at San Antonio. NR 29 TC 6 Z9 6 U1 0 U2 6 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD DEC PY 2010 VL 175 IS 12 BP 953 EP 957 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 691KO UT WOS:000285078900007 PM 21265301 ER PT J AU Pellicano, R El-Serag, HB Rizzetto, M AF Pellicano, R. El-Serag, H. B. Rizzetto, M. TI Hepatocellular carcinoma at the cutting edge of science and practice SO MINERVA MEDICA LA English DT Editorial Material ID LIVER-TRANSPLANTATION; UNITED-STATES; HEPATITIS-B; SORAFENIB; SURVEILLANCE; THERAPY; CANCER C1 [Pellicano, R.; Rizzetto, M.] Molinette Hosp SGAS, Dept Gastroenterol & Hepatol, Turin, Italy. [El-Serag, H. B.] Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. [El-Serag, H. B.] Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX USA. [El-Serag, H. B.] Baylor Coll Med, Houston, TX 77030 USA. RP Pellicano, R (reprint author), Molinette Mauriziano Hosp, Dept Gastroenterol & Hepatol, Via Cavour 31, I-10123 Turin, Italy. EM rinaldo_pellican@hot-mail.com NR 20 TC 0 Z9 0 U1 0 U2 0 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0026-4806 J9 MINERVA MED JI Minerva Med. PD DEC PY 2010 VL 101 IS 6 BP 391 EP 393 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 711HR UT WOS:000286578300003 PM 21196898 ER PT J AU O'Malley, DP Duong, A Barry, TS Chen, S Hibbard, MK Ferry, JA Hasserjian, RP Thompson, MA Richardson, MS Jaffe, R Sidhu, JS Banks, PM AF O'Malley, Dennis P. Duong, Angie Barry, Todd S. Chen, Steve Hibbard, Michele K. Ferry, Judith A. Hasserjian, Robert P. Thompson, Mary A. Richardson, Mary S. Jaffe, Ronald Sidhu, Jagmohan S. Banks, Peter M. TI Co-occurrence of Langerhans cell histiocytosis and Rosai-Dorfman disease: possible relationship of two histiocytic disorders in rare cases SO MODERN PATHOLOGY LA English DT Article DE array comparative genomic hybridization; histiocyte; Langerhans cell histiocytosis; Rosai-Dorfman disease AB Rosai-Dorfman disease and Langerhans cell histiocytosis are both disorders of accessory immune cells. Two cases have been previously reported of concurrent Langerhans cell histiocytosis and Rosai-Dorfman disease. In this report, we characterize the findings and selected molecular studies in nine additional cases. Histology was reviewed. Immunohistochemical stains were performed on all cases in which slides or blocks were available. A combination of CD1a, S-100, CD3, CD20, langerin, CD68, CD163, CD21, CD35 and CD123 immunohistochemical stains were performed. High-resolution array comparative genomic hybridization was performed on six samples from five cases. In these cases, seven were female and two male, with an average age of 25 years (15 months-59 years). A majority of the cases were identified in lymph node. Areas of Langerhans cell histiocytosis had a typical appearance with the existence of bland 'coffee-bean' nuclei, clear cytoplasm and associated eosinophils. The immunophenotype was typical, including expression of CD1a, S100, CD68 and langerin. In areas of Rosai-Dorfman disease, there was emperipolesis seen in all cases. Cells were intermediate-large in size with large round nuclei and ample clear or pale cytoplasm. The lesional cells were positive for S100, CD68, CD163, without expression of langerin or CD1a. Array comparative genomic hybridization showed gains and/or losses in four of the six samples. One case showed no gains or losses and one additional case showed gains and losses in the Langerhans cell histiocytosis, while no abnormalities were discovered in the Rosai-Dorfman disease component. These findings are comparable to those seen in previous studies of Langerhans cell histiocytosis. We report the clinical and pathologic findings of the combination of Langerhans cell histiocytosis and Rosai-Dorfman disease. Furthermore, we suggest on the basis of evidence from our cases that, when simultaneous, the two entities may be pathophysiologically related. Modern Pathology (2010) 23, 1616-1623; doi:10.1038/modpathol.2010.157; published online 20 August 2010 C1 [O'Malley, Dennis P.; Barry, Todd S.; Chen, Steve; Hibbard, Michele K.] Clarient, Dept Pathol, Aliso Viejo, CA 92656 USA. [Duong, Angie; Richardson, Mary S.] Med Univ S Carolina, Dept Pathol, Charleston, SC 29425 USA. [Ferry, Judith A.; Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Thompson, Mary A.] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Jaffe, Ronald] Childrens Hosp Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. [Sidhu, Jagmohan S.] United Hlth Serv Hosp, Dept Pathol, Johnson City, NY USA. [Banks, Peter M.] Carolinas Med Ctr, Dept Pathol, Charlotte, NC 28203 USA. RP O'Malley, DP (reprint author), Clarient, Dept Pathol, 31 Columbia, Aliso Viejo, CA 92656 USA. EM domalley@clarientinc.com NR 9 TC 16 Z9 16 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD DEC PY 2010 VL 23 IS 12 BP 1616 EP 1623 DI 10.1038/modpathol.2010.157 PG 8 WC Pathology SC Pathology GA 688AX UT WOS:000284821600008 PM 20729813 ER PT J AU Kan, MC Oruganty-Das, A Cooper-Morgan, A Jin, GA Swanger, SA Bassell, GJ Florman, H van Leyen, K Richter, JD AF Kan, Ming-Chung Oruganty-Das, Aparna Cooper-Morgan, Amalene Jin, Guang Swanger, Sharon A. Bassell, Gary J. Florman, Harvey van Leyen, Klaus Richter, Joel D. TI CPEB4 Is a Cell Survival Protein Retained in the Nucleus upon Ischemia or Endoplasmic Reticulum Calcium Depletion SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID APOPTOSIS-INDUCING FACTOR; TRANSIENT CEREBRAL-ISCHEMIA; MESSENGER-RNA; CYTOPLASMIC POLYADENYLATION; TRANSLATIONAL CONTROL; SYNAPTIC PLASTICITY; CHANNEL FUNCTION; PLASMA-MEMBRANE; NEURONAL DEATH; KNOCKOUT MICE AB The RNA binding protein CPEB (cytoplasmic polyadenylation element binding) regulates cytoplasmic polyadenylation and translation in germ cells and the brain. In neurons, CPEB is detected at postsynaptic sites, as well as in the cell body. The related CPEB3 protein also regulates translation in neurons, albeit probably not through polyadenylation; it, as well as CPEB4, is present in dendrites and the cell body. Here, we show that treatment of neurons with ionotropic glutamate receptor agonists causes CPEB4 to accumulate in the nucleus. All CPEB proteins are nucleus-cytoplasm shuttling proteins that are retained in the nucleus in response to calcium-mediated signaling and alpha-calcium/calmodulin-dependent kinase protein II (CaMKII) activity. CPEB2, -3, and -4 have conserved nuclear export signals that are not present in CPEB. CPEB4 is necessary for cell survival and becomes nuclear in response to focal ischemia in vivo and when cultured neurons are deprived of oxygen and glucose. Further analysis indicates that nuclear accumulation of CPEB4 is controlled by the depletion of calcium from the ER, specifically, through the inositol-1,4,5-triphosphate (IP3) receptor, indicating a communication between these organelles in redistributing proteins between subcellular compartments. C1 [Kan, Ming-Chung; Oruganty-Das, Aparna; Cooper-Morgan, Amalene; Richter, Joel D.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. [Florman, Harvey] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01605 USA. [Jin, Guang; van Leyen, Klaus] Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA 02129 USA. [Swanger, Sharon A.; Bassell, Gary J.] Emory Univ, Sch Med, Dept Cell Biol, Atlanta, GA 30322 USA. [Swanger, Sharon A.; Bassell, Gary J.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. RP Richter, JD (reprint author), Univ Massachusetts, Sch Med, Program Mol Med, 373 Plantat St,Suite 204, Worcester, MA 01605 USA. EM joel.richter@umassmed.edu RI van Leyen, Klaus/C-9126-2013; OI Swanger, Sharon/0000-0003-0615-6244 FU NIH [GM46779, HD37267]; Diabetes and Endocrinology Research Center [DK32520]; [3 R01 GM046779-19S1] FX This work was supported by grants from the NIH (GM46779 and HD37267). A.C.-M. was supported by grant number 3 R01 GM046779-19S1. Core support from the Diabetes and Endocrinology Research Center Program Project (DK32520) is gratefully acknowledged. NR 54 TC 20 Z9 20 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2010 VL 30 IS 24 BP 5658 EP 5671 DI 10.1128/MCB.00716-10 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 682UU UT WOS:000284429300006 PM 20937770 ER PT J AU Susa, M Choy, E Liu, XZ Schwab, J Hornicek, FJ Mankin, H Duan, ZF AF Susa, Michiro Choy, Edwin Liu, Xianzhe Schwab, Joseph Hornicek, Francis J. Mankin, Henry Duan, Zhenfeng TI Cyclin G-Associated Kinase Is Necessary for Osteosarcoma Cell Proliferation and Receptor Trafficking SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID GROWTH-FACTOR RECEPTOR; CLATHRIN-COATED VESICLES; POTENTIAL THERAPEUTIC TARGET; ADVANCED SOLID TUMORS; FACTOR-I; PHASE-I; MEDIATED ENDOCYTOSIS; MULTIDRUG-RESISTANCE; MULTIPLE-MYELOMA; DRUG-RESISTANCE AB Osteosarcoma is the most frequent primary malignant bone tumor among the children. The advent of neoadjuvant chemotherapy significantly improved the prognosis of patients with osteosarcoma in the 1980s, but it has since plateaued in the past decades. Recently, one of the most researched areas in sarcoma treatment is tyrosine kinases. Here, we describe research on a serine/threonine kinase, cyclin G-associated kinase (GAK), which has not been reported in osteosarcoma previously. In this study, a lentiviral based human shRNA library was utilized to screen for kinases in KHOS and U-2OS osteosarcoma cells. The expression of GAK was examined in osteosarcoma and the effect on cell proliferation was analyzed by GAK siRNA knockdown. The level ofGAKexpression and its correlation to prognosis was analyzed in osteosarcoma tissue microarray. The effect of GAK depletion on insulin-like growth factor and epidermal growth factor receptor-mediated signal transduction was analyzed by Western blot. We observed that GAK was overexpressed in both osteosarcoma cell lines and tissue samples when compared with human osteoblasts. GAK knockdown by siRNA decreased cell proliferation in both drug-sensitive and multidrug-resistant osteosarcoma cell lines. Immunohistochemistry of osteosarcoma tissue microarray revealed that overexpression of GAK was associated with poor prognosis. Finally, knockdown of GAK resulted in alterations of receptor trafficking and several downstream proteins. In conclusion, our results suggest that osteosarcoma cell proliferation and survival are dependent on GAK. These findings may lead to the development of new therapeutic options for osteosarcoma. Mol Cancer Ther; 9(12); 3342- 50. (C) 2010 AACR. C1 [Susa, Michiro; Choy, Edwin; Liu, Xianzhe; Schwab, Joseph; Hornicek, Francis J.; Mankin, Henry; Duan, Zhenfeng] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, Boston, MA 02114 USA. [Susa, Michiro; Liu, Xianzhe; Schwab, Joseph; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, 55 Fruit St Jackson 1115, Boston, MA 02114 USA. EM zduan@partners.org RI Susa, Michiro/L-2291-2013; OI Choy, Edwin/0000-0001-9896-8084 FU Gaetagno and Wechsler funds; Kenneth Stanton Fund; National Cancer Institute [R01-CA119617]; Sarcoma Foundation of America; Jennifer Hunter Yates Sarcoma Foundation FX This project was supported by a grant from the Gaetagno and Wechsler funds. Support has also been provided by the Kenneth Stanton Fund. Z. Duan is supported, in part, by a grant from the National Cancer Institute (Nanotechnology Platform Partnership), R01-CA119617, and Sarcoma Foundation of America. E. Choy is supported by the Jennifer Hunter Yates Sarcoma Foundation. NR 42 TC 9 Z9 9 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2010 VL 9 IS 12 BP 3342 EP 3350 DI 10.1158/1535-7163.MCT-10-0637 PG 9 WC Oncology SC Oncology GA 694KL UT WOS:000285296300023 PM 20881269 ER PT J AU Gordon, V Bhadel, S Wunderlich, W Zhang, J Ficarro, SB Mollah, SA Shabanowitz, J Hunt, DF Xenarios, I Hahn, WC Conaway, M Carey, MF Gioeli, D AF Gordon, Vicki Bhadel, Shriti Wunderlich, Winfried Zhang, JoAnn Ficarro, Scott B. Mollah, Sahana A. Shabanowitz, Jeffrey Hunt, Donald F. Xenarios, Ioannis Hahn, William C. Conaway, Mark Carey, Michael F. Gioeli, Daniel TI CDK9 Regulates AR Promoter Selectivity and Cell Growth through Serine 81 Phosphorylation SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ANDROGEN RECEPTOR PHOSPHORYLATION; RNA-POLYMERASE-II; PROSTATE-CANCER PROGRESSION; P-TEFB; TYROSINE PHOSPHORYLATION; TRANSCRIPTION ELONGATION; IN-VIVO; GLUCOCORTICOID-RECEPTOR; MASS-SPECTROMETRY; RESPONSE ELEMENT AB Previously we determined that S81 is the highest stoichiometric phosphorylation on the androgen receptor (AR) in response to hormone. To explore the role of this phosphorylation on growth, we stably expressed wild-type and S81A mutant AR in LHS and LAPC4 cells. The cells with increased wild-type AR expression grow faster compared with parental cells and S81A mutant-expressing cells, indicating that loss of S81 phosphorylation limits cell growth. To explore how S81 regulates cell growth, we tested whether S81 phosphorylation regulates AR transcriptional activity. LHS cells stably expressing wild-type and S81A mutant AR showed differences in the regulation of endogenous AR target genes, suggesting that S81 phosphorylation regulates promoter selectivity. We next sought to identify the S81 kinase using ion trap mass spectrometry to analyze AR-associated proteins in immunoprecipitates from cells. We observed cyclin-dependent kinase (CDK)9 association with the AR. CDK9 phosphorylates the AR on S81 in vitro. Phosphorylation is specific to S81 because CDK9 did not phosphorylate the AR on other serine phosphorylation sites. Overexpression of CDK9 with its cognate cyclin, Cyclin T, increased S81 phosphorylation levels in cells. Small interfering RNA knockdown of CDK9 protein levels decreased hormone-induced S81 phosphorylation. Additionally, treatment of LNCaP cells with the CDK9 inhibitors, 5,6-dichloro-1-beta-D-ribo-furanosylbenzimidazole and Flavopiridol, reduced S81 phosphorylation further, suggesting that CDK9 regulates S81 phosphorylation. Pharmacological inhibition of CDK9 also resulted in decreased AR transcription in LNCaP cells. Collectively these results suggest that CDK9 phosphorylation of AR S81 is an important step in regulating AR transcriptional activity and prostate cancer cell growth. (Molecular Endocrinology 24: 2267-2280, 2010) C1 [Gordon, Vicki; Bhadel, Shriti; Gioeli, Daniel] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. [Ficarro, Scott B.; Mollah, Sahana A.; Shabanowitz, Jeffrey; Hunt, Donald F.] Univ Virginia, Dept Chem, Charlottesville, VA 22908 USA. [Hunt, Donald F.] Univ Virginia, Dept Pathol, Charlottesville, VA 22908 USA. [Conaway, Mark] Univ Virginia, Dept Hlth Evaluat Sci, Charlottesville, VA 22908 USA. [Zhang, JoAnn; Carey, Michael F.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Zhang, JoAnn; Carey, Michael F.] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA. [Xenarios, Ioannis] Univ Lausanne, Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland. [Hahn, William C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hahn, William C.] Dept Med Oncol, Boston, MA 02115 USA. RP Gioeli, D (reprint author), Univ Virginia, Dept Microbiol, Jordan Hall Room 2-16,Box 800734,1300 Jefferson P, Charlottesville, VA 22908 USA. RI Hunt, Donald/I-6936-2012; Wunderlich, Wilfried/E-2128-2015; OI Hunt, Donald/0000-0003-2815-6368; Wunderlich, Wilfried/0000-0003-4354-4801; Carey, Michael/0000-0003-3899-6280; Xenarios, Ioannis/0000-0002-3413-6841 FU National Institute of Health [R01 CA124706]; University of Virginia American Cancer Society; Prostate Cancer Foundation; National Institutes of Health [GM 37537] FX This work was supported by National Institute of Health Grant R01 CA124706 (to D.G.), University of Virginia American Cancer Society (to D.G.), Prostate Cancer Foundation (to M.C. and D.G.), and National Institutes of Health Grant GM 37537 (to D.F.H.). NR 52 TC 56 Z9 58 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 2010 VL 24 IS 12 BP 2267 EP 2280 DI 10.1210/me.2010-0238 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 684WF UT WOS:000284585200003 PM 20980437 ER PT J AU McCarthy, JR Bhaumik, J Karver, MR Erdem, SS Weissleder, R AF McCarthy, Jason R. Bhaumik, Jayeeta Karver, Mark R. Erdem, S. Sibel Weissleder, Ralph TI Targeted nanoagents for the detection of cancers SO MOLECULAR ONCOLOGY LA English DT Review DE Nanomedicine; Imaging; Affinity ligands ID IRON-OXIDE NANOPARTICLES; MULTIFUNCTIONAL MAGNETIC NANOPARTICLES; PLASMINOGEN-ACTIVATOR SYSTEM; MRI CONTRAST AGENTS; IN-VIVO; BREAST-CANCER; PROSTATE-CANCER; DRUG-DELIVERY; PERFLUOROCARBON NANOPARTICLES; MACROMOLECULAR THERAPEUTICS AB Nanotechnology has enabled a renaissance in the diagnosis of cancers. This is due, in part to the ability to develop agents bearing multiple functionalities, including those utilized for targeting, imaging, and therapy, allowing for the tailoring of the properties of the nanomaterials. Whereas many nanomaterials exhibit localization to diseased tissues via intrinsic targeting, the addition of targeting ligands, such as antibodies, peptides, aptamers, and small molecules, facilitates far more sensitive cancer detection. As such, this review focuses upon some of the most poignant examples of the utility of affinity ligand targeted nanoagents in the detection of cancer. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 [McCarthy, Jason R.] Harvard Univ, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McCarthy, JR (reprint author), Harvard Univ, Sch Med, Ctr Syst Biol, 185 Cambridge St,Suite 5-210, Boston, MA 02114 USA. EM jason_mccarthy@hms.harvard.edu FU NIH [R21HL093607, U01-HL080731] FX This work was supported in part by NIH grants R21HL093607 (JM) and U01-HL080731 (JM, RW) NR 95 TC 38 Z9 39 U1 4 U2 27 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1574-7891 J9 MOL ONCOL JI Mol. Oncol. PD DEC PY 2010 VL 4 IS 6 BP 511 EP 528 DI 10.1016/j.molonc.2010.08.003 PG 18 WC Oncology SC Oncology GA 692CO UT WOS:000285129300005 PM 20851695 ER PT J AU Rodriguez, AL Grier, MD Jones, CK Herman, EJ Kane, AS Smith, RL Williams, R Zhou, Y Marlo, JE Days, EL Blatt, TN Jadhav, S Menon, UN Vinson, PN Rook, JM Stauffer, SR Niswender, CM Lindsley, CW Weaver, CD Conn, PJ AF Rodriguez, Alice L. Grier, Mark D. Jones, Carrie K. Herman, Elizabeth J. Kane, Alexander S. Smith, Randy L. Williams, Richard Zhou, Ya Marlo, Joy E. Days, Emily L. Blatt, Tasha N. Jadhav, Satyawan Menon, Usha N. Vinson, Paige N. Rook, Jerri M. Stauffer, Shaun R. Niswender, Colleen M. Lindsley, Craig W. Weaver, C. David Conn, P. Jeffrey TI Discovery of Novel Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5 Reveals Chemical and Functional Diversity and In Vivo Activity in Rat Behavioral Models of Anxiolytic and Antipsychotic Activity SO MOLECULAR PHARMACOLOGY LA English DT Article ID MGLU5 RECEPTOR; LOCOMOTOR-ACTIVITY; BINDING-SITE; ANTAGONIST; POTENT; 2-METHYL-6-(PHENYLETHYNYL)PYRIDINE; PHARMACOLOGY; ANXIETY; FENOBAM; MPEP AB Modulators of metabotropic glutamate receptor subtype 5 (mGluR5) may provide novel treatments for multiple central nervous system (CNS) disorders, including anxiety and schizophrenia. Although compounds have been developed to better understand the physiological roles of mGluR5 and potential usefulness for the treatment of these disorders, there are limitations in the tools available, including poor selectivity, low potency, and limited solubility. To address these issues, we developed an innovative assay that allows simultaneous screening for mGluR5 agonists, antagonists, and potentiators. We identified multiple scaffolds that possess diverse modes of activity at mGluR5, including both positive and negative allosteric modulators (PAMs and NAMs, respectively). 3-Fluoro-5-(3-(pyridine-2-yl)-1,2,4-oxadiazol-5-yl) benzonitrile (VU0285683) was developed as a novel selective mGluR5 NAM with high affinity for the 2-methyl-6-(phenyl-ethynyl)-pyridine (MPEP) binding site. VU0285683 had anxiolytic-like activity in two rodent models for anxiety but did not potentiate phen-cyclidine-induced hyperlocomotor activity. (4-Hydroxypiperidin-1-yl)(4-phenylethynyl) phenyl) methanone (VU0092273) was identified as a novel mGluR5 PAM that also binds to the MPEP site. VU0092273 was chemically optimized to an orally active analog, N-cyclobutyl-6-((3-fluorophenyl) ethynyl) nicotinamide hydrochloride (VU0360172), which is selective for mGluR5. This novel mGluR5 PAM produced a dose-dependent reversal of amphetamine-induced hyperlocomotion, a rodent model predictive of antipsychotic activity. Discovery of structurally and functionally diverse allosteric modulators of mGluR5 that demonstrate in vivo efficacy in rodent models of anxiety and antipsychotic activity provide further support for the tremendous diversity of chemical scaffolds and modes of efficacy of mGluR5 ligands. In addition, these studies provide strong support for the hypothesis that multiple structurally distinct mGluR5 modulators have robust activity in animal models that predict efficacy in the treatment of CNS disorders. C1 [Conn, P. Jeffrey] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Jones, Carrie K.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN USA. [Lindsley, Craig W.] Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA. [Rodriguez, Alice L.; Jones, Carrie K.; Herman, Elizabeth J.; Kane, Alexander S.; Williams, Richard; Zhou, Ya; Marlo, Joy E.; Jadhav, Satyawan; Menon, Usha N.; Vinson, Paige N.; Rook, Jerri M.; Stauffer, Shaun R.; Niswender, Colleen M.; Lindsley, Craig W.; Weaver, C. David; Conn, P. Jeffrey] Vanderbilt Univ, Vanderbilt Program Drug Discovery, Nashville, TN 37232 USA. [Days, Emily L.; Blatt, Tasha N.; Weaver, C. David] Vanderbilt Univ, Vanderbilt Inst Chem Biol, Nashville, TN 37232 USA. RP Conn, PJ (reprint author), Vanderbilt Univ, Med Ctr, Dept Pharmacol, 1215D Light Hall,2215 Garland Ave, Nashville, TN 37232 USA. EM jeff.conn@vanderbilt.edu RI Conn, Peter/D-7848-2012; Zhou, Ya/F-1220-2013 FU National Institutes of Health National Institute of Neurological Disorders and Stroke [1F32-NS049865, R01-NS031373]; National Institutes of Health National Institute of Mental Health [R01-MH062646, R01-MH074953]; National Institutes of Health National Institute on Drug Abuse [1R01-DA023947-01]; Vanderbilt is a center in the National Institutes of Health FX This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grants 1F32-NS049865, R01-NS031373]; the National Institutes of Health National Institute of Mental Health [Grants R01-MH062646, R01-MH074953]; and the National Institutes of Health National Institute on Drug Abuse [Grant 1R01-DA023947-01]. Vanderbilt is a center in the National Institutes of Health-supported Molecular Libraries Screening Centers Network. NR 52 TC 104 Z9 106 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 2010 VL 78 IS 6 BP 1105 EP 1123 DI 10.1124/mol.110.067207 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 680WC UT WOS:000284267200014 PM 20923853 ER PT J AU Healy, BC Glanz, BI Stankiewicz, J Buckle, G Weiner, H Chitnis, T AF Healy, Brian C. Glanz, Bonnie I. Stankiewicz, James Buckle, Guy Weiner, Howard Chitnis, Tanuja TI A method for evaluating treatment switching criteria in multiple sclerosis SO MULTIPLE SCLEROSIS LA English DT Article DE disease-modifying therapies; multiple sclerosis; outcome measurement; relapsing-remitting; treatment switching ID PLACEBO-CONTROLLED TRIAL; RELAPSE RATE; DOUBLE-BLIND; MULTICENTER; DISABILITY; THERAPY; MODELS AB Background and Objective: We investigated a method to evaluate a treatment switching approach, namely treatment change after one multiple sclerosis (MS) relapse. Methods: Patients who experienced a relapse while on a first-line disease-modifying therapy, glatiramer acetate, were identified. Based on their subsequent course, patients were divided into two groups: those who changed treatment and those who did not. Patients were allowed to change to any other treatment. Subsequent annualized relapse rate and time to next relapse were compared in the two groups. Since patients were not randomized to treatment group, negative binomial and Cox regression models were used to control for several potential clinical confounders, including relapse severity, relapse duration, age, disease duration and presence of previous/combination therapy. In addition, an inverse probability of treatment weighting model was used to control for confounding. Several secondary analyses investigated patient subgroups. Results: Statistical modeling showed that there was no significant difference between groups in terms of relapse rate (rate ratio; 95% CI = 0.68; 0.35, 1.31) and time to next relapse (hazard ratio; 95% CI = 0.61; 0.30, 1.25). All secondary analyses confirmed these results. In addition, no significant difference in time to sustained progression on the Expanded Disability Status Scale was observed (p > 0.05). Our approach allowed investigation of the choice to change treatment after a relapse. Conclusions: Our results showed that a single relapse may not be sufficient to indicate treatment failure. Although clinical confounders were addressed in our modeling, unmeasured confounders, particularly the presence of magnetic resonance imaging activity, may have biased our conclusion. C1 [Healy, Brian C.; Glanz, Bonnie I.; Stankiewicz, James; Buckle, Guy; Weiner, Howard; Chitnis, Tanuja] Brigham & Womens Hosp, Dept Neurol, Partners Multiple Sclerosis Ctr, Boston, MA 02115 USA. [Healy, Brian C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Healy, BC (reprint author), Harvard Univ, Sch Med, Partners MS Ctr, 1 Brookline Pl,Suite 602, Brookline, MA 02445 USA. EM bchealy@partners.org FU Nancy Davis Foundation FX This research received funding from the Nancy Davis Foundation. NR 23 TC 10 Z9 10 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD DEC PY 2010 VL 16 IS 12 BP 1483 EP 1489 DI 10.1177/1352458510379245 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 687EW UT WOS:000284762800009 PM 20736245 ER PT J AU Lu, ZS Dai, TH Huang, LY Kurup, DB Tegos, GP Jahnke, A Wharton, T Hamblin, MR AF Lu, Zongshun Dai, Tianhong Huang, Liyi Kurup, Divya B. Tegos, George P. Jahnke, Ashee Wharton, Tim Hamblin, Michael R. TI Photodynamic therapy with a cationic functionalized fullerene rescues mice from fatal wound infections SO NANOMEDICINE LA English DT Article DE antimicrobial photodynamic therapy; buckminsterfullerene; mouse model; Proteus mirabilis; Pseudomonas aeruginosa; wound infection ID NONVIRAL GENE-DELIVERY; IN-VIVO; ESCHERICHIA-COLI; BACTERIA; WATER; PHTHALOCYANINE; INACTIVATION; RESISTANCE; MECHANISM; SURFACE AB Aims: Fullerenes are under intensive study for potential biomedical applications. We have previously reported that a C60 fullerene functionalized with three dimethylpyrrolidinium groups (BF6) is a highly active broad-spectrum antimicrobial photosensitizer in vitro when combined with white-light illumination. We asked whether this high degree of in vitro activity would translate into an in vivo therapeutic effect in two potentially lethal mouse models of infected wounds. Materials & methods: We used stable bioluminescent bacteria and a low light imaging system to follow the progress of the infection noninvasively in real time. An excisional wound on the mouse back was contaminated with one of two bioluminescent Gram-negative species, Proteus mirabilis (2.5 x 10(7) cells) and Pseudomonas aeruginosa (5 x 10(6) cells). A solution of BF6 was placed into the wound followed by delivery of up to 180 J/cm(2) of broadband white light (400-700 nm). Results: In both cases there was a light-dose-dependent reduction of bioluminescence from the wound not observed in control groups (light alone or BF6 alone). Fullerene-mediated photodynamic therapy of mice infected with P. mirabilis led to 82% survival compared with 8% survival without treatment (p < 0.001). Photodynamic therapy of mice infected with highly virulent P. aeruginosa did not lead to survival, but when photodynamic therapy was combined with a suboptimal dose of the antibiotic tobramycin (6 mg/kg for 1 day) there was a synergistic therapeutic effect with a survival of 60% compared with a survival of 20% with tobramycin alone (p < 0.01). Conclusion: These data suggest that cationic fullerenes have clinical potential as an antimicrobial photosensitizer for superficial infections where red light is not needed to penetrate tissue. C1 [Lu, Zongshun; Dai, Tianhong; Huang, Liyi; Kurup, Divya B.; Tegos, George P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Lu, Zongshun] Tianjin Med Univ, Gen Hosp, Tianjin, Peoples R China. [Dai, Tianhong; Huang, Liyi; Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Boston, MA USA. [Huang, Liyi] Guangxi Med Univ, Affiliated Coll & Hosp 1, Nanning, Peoples R China. [Tegos, George P.] Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA. [Jahnke, Ashee; Wharton, Tim] Lynntech Inc, College Stn, TX USA. [Jahnke, Ashee] Univ Toronto, Toronto, ON, Canada. [Wharton, Tim] Texas Biochem, College Stn, TX USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Tegos, George/C-8830-2011; OI Hamblin, Michael/0000-0001-6431-4605 FU NIH [R43AI68400, R01AI050875]; US Air Force [FA9550-04-1-0079]; Bullock Wellman Postdoctoral Fellowship; Massachusetts Technology Transfer Center FX At the time of writing, Tim Wharton and Ashlee Jahnke were employees of Lynntech Inc. Lynntech Inc. has licensed a patent on which Tim Wharton and Michael R Hamblin are inventors. This work was supported by the NIH (grants R43AI68400 to Lynntech Inc and R01AI050875 to Michael R Hamblin) and by the US Air Force Medical Free Electron Laser Program (FA9550-04-1-0079). Tianhong Dai was supported by the Bullock Wellman Postdoctoral Fellowship. George P Tegos was partly supported by a Massachusetts Technology Transfer Center Award. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. NR 38 TC 49 Z9 49 U1 2 U2 23 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 J9 NANOMEDICINE-UK JI Nanomedicine PD DEC PY 2010 VL 5 IS 10 BP 1525 EP 1533 DI 10.2217/NNM.10.98 PG 9 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA 710UE UT WOS:000286541700008 PM 21143031 ER PT J AU Galarneau, G Palmer, CD Sankaran, VG Orkin, SH Hirschhorn, JN Lettre, G AF Galarneau, Genevieve Palmer, Cameron D. Sankaran, Vijay G. Orkin, Stuart H. Hirschhorn, Joel N. Lettre, Guillaume TI Fine-mapping at three loci known to affect fetal hemoglobin levels explains additional genetic variation SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; BETA-THALASSEMIA; BCL11A; EXPRESSION; HBS1L-MYB; VARIANTS AB We used resequencing and genotyping in African Americans with sickle cell anemia (SCA) to characterize associations with fetal hemoglobin (HbF) levels at the BCL11A, HBS1L-MYB and beta-globin loci. Fine-mapping of HbF association signals at these loci confirmed seven SNPs with independent effects and increased the explained heritable variation in HbF levels from 38.6% to 49.5%. We also identified rare missense variants that causally implicate MYB in HbF production. C1 [Sankaran, Vijay G.; Orkin, Stuart H.] Childrens Hosp Boston, Div Hematol & Oncol, Boston, MA 02115 USA. [Galarneau, Genevieve; Lettre, Guillaume] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp Boston, Div Genet, Boston, MA USA. [Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp Boston, Div Endocrinol, Boston, MA USA. [Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp Boston, Program Genom, Boston, MA USA. [Palmer, Cameron D.; Hirschhorn, Joel N.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Sankaran, Vijay G.; Orkin, Stuart H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Lettre, Guillaume] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. RP Orkin, SH (reprint author), Childrens Hosp Boston, Div Hematol & Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu; joelh@broadinstitute.org; guillaume.lettre@mhi-humangenetics.org FU Fondation de l'Institut de Cardiologie de Montreal; Doris Duke Charitable Foundation; National Heart, Lung, and Blood Institute [N01-HV-48194] FX We thank all the individuals who participated in this study, and T. Nguyen and M. Beaudoin for DNA genotyping support. We thank S. Raychaudhuri for critical reading of the manuscript, G. Boucher for statistical advice and the CARe Sickle Cell Disease working group for providing the Cooperative Study of Sickle Cell Disease (CSSCD) principal components. This work was funded by the Fondation de l'Institut de Cardiologie de Montreal (to G.L.) and was supported by an Innovations in Clinical Research Award grant from the Doris Duke Charitable Foundation (to G.L. and J.N.H.). Resequencing services were provided by the University of Washington, Department of Genome Sciences, under US Federal Government contract number N01-HV-48194 from the National Heart, Lung, and Blood Institute. NR 15 TC 105 Z9 107 U1 4 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2010 VL 42 IS 12 BP 1049 EP 1051 DI 10.1038/ng.707 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 684UZ UT WOS:000284578800006 PM 21057501 ER PT J AU Sotoodehnia, N Isaacs, A de Bakker, PIW Dorr, M Newton-Cheh, C Nolte, IM van der Harst, P Muller, M Eijgelsheim, M Alonso, A Hicks, AA Padmanabhan, S Hayward, C Smith, AV Polasek, O Giovannone, S Fu, JY Magnani, JW Marciante, KD Pfeufer, A Gharib, SA Teumer, A Li, M Bis, JC Rivadeneira, F Aspelund, T Kottgen, A Johnson, T Rice, K Sie, MPS Wang, YA Klopp, N Fuchsberger, C Wild, SH Leach, IM Estrada, K Volker, U Wright, AF Asselbergs, FW Qu, JX Chakravarti, A Sinner, MF Kors, JA Petersmann, A Harris, TB Soliman, EZ Munroe, PB Psaty, BM Oostra, BA Cupples, LA Perz, S de Boer, RA Uitterlinden, AG Volzke, H Spector, TD Liu, FY Boerwinkle, E Dominiczak, AF Rotter, JI van Herpen, G Levy, D Wichmann, HE van Gilst, WH Witteman, JCM Kroemer, HK Kao, WHL Heckbert, SR Meitinger, T Hofman, A Campbell, H Folsom, AR van Veldhuisen, DJ Schwienbacher, C O'Donnell, CJ Volpato, CB Caulfield, MJ Connell, JM Launer, L Lu, XW Franke, L Fehrmann, RSN Meerman, GT Groen, HJM Weersma, RK van den Berg, LH Wijmenga, C Ophoff, RA Navis, G Rudan, I Snieder, H Wilson, JF Pramstaller, PP Siscovick, DS Wang, TJ Gudnason, V van Duijn, CM Felix, SB Fishman, GI Jamshidi, Y Stricker, BHC Samani, NJ Kaab, S Arking, DE AF Sotoodehnia, Nona Isaacs, Aaron de Bakker, Paul I. W. Doerr, Marcus Newton-Cheh, Christopher Nolte, Ilja M. van der Harst, Pim Mueller, Martina Eijgelsheim, Mark Alonso, Alvaro Hicks, Andrew A. Padmanabhan, Sandosh Hayward, Caroline Smith, Albert Vernon Polasek, Ozren Giovannone, Steven Fu, Jingyuan Magnani, Jared W. Marciante, Kristin D. Pfeufer, Arne Gharib, Sina A. Teumer, Alexander Li, Man Bis, Joshua C. Rivadeneira, Fernando Aspelund, Thor Koettgen, Anna Johnson, Toby Rice, Kenneth Sie, Mark P. S. Wang, Ying A. Klopp, Norman Fuchsberger, Christian Wild, Sarah H. Leach, Irene Mateo Estrada, Karol Voelker, Uwe Wright, Alan F. Asselbergs, Folkert W. Qu, Jiaxiang Chakravarti, Aravinda Sinner, Moritz F. Kors, Jan A. Petersmann, Astrid Harris, Tamara B. Soliman, Elsayed Z. Munroe, Patricia B. Psaty, Bruce M. Oostra, Ben A. Cupples, L. Adrienne Perz, Siegfried de Boer, Rudolf A. Uitterlinden, Andre G. Voelzke, Henry Spector, Timothy D. Liu, Fang-Yu Boerwinkle, Eric Dominiczak, Anna F. Rotter, Jerome I. van Herpen, Ge Levy, Daniel Wichmann, H-Erich van Gilst, Wiek H. Witteman, Jacqueline C. M. Kroemer, Heyo K. Kao, W. H. Linda Heckbert, Susan R. Meitinger, Thomas Hofman, Albert Campbell, Harry Folsom, Aaron R. van Veldhuisen, Dirk J. Schwienbacher, Christine O'Donnell, Christopher J. Volpato, Claudia Beu Caulfield, Mark J. Connell, John M. Launer, Lenore Lu, Xiaowen Franke, Lude Fehrmann, Rudolf S. N. Meerman, Gerard te Groen, Harry J. M. Weersma, Rinse K. van den Berg, Leonard H. Wijmenga, Cisca Ophoff, Roel A. Navis, Gerjan Rudan, Igor Snieder, Harold Wilson, James F. Pramstaller, Peter P. Siscovick, David S. Wang, Thomas J. Gudnason, Vilmundur van Duijn, Cornelia M. Felix, Stephan B. Fishman, Glenn I. Jamshidi, Yalda Stricker, Bruno H. Ch Samani, Nilesh J. Kaeaeb, Stefan Arking, Dan E. TI Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; QT INTERVAL DURATION; RICH REPEAT PROTEIN; HEART-RATE; TRANSCRIPTION FACTOR; GENE-EXPRESSION; PR INTERVAL; SYSTEM; DISEASE; ELECTROCARDIOGRAM AB The QRS interval, from the beginning of the Q wave to the end of the S wave on an electrocardiogram, reflects ventricular depolarization and conduction time and is a risk factor for mortality, sudden death and heart failure. We performed a genomewide association meta-analysis in 40,407 individuals of European descent from 14 studies, with further genotyping in 7,170 additional Europeans, and we identified 22 loci associated with QRS duration ( P < 5 x 10(-8)). These loci map in or near genes in pathways with established roles in ventricular conduction such as sodium channels, transcription factors and calcium-handling proteins, but also point to previously unidentified biologic processes, such as kinase inhibitors and genes related to tumorigenesis. We demonstrate that SCN10A, a candidate gene at the most significantly associated locus in this study, is expressed in the mouse ventricular conduction system, and treatment with a selective SCN10A blocker prolongs QRS duration. These findings extend our current knowledge of ventricular depolarization and conduction. C1 [Sotoodehnia, Nona] Univ Washington, Dept Med, Div Cardiol, Seattle, WA 98195 USA. [Sotoodehnia, Nona; Marciante, Kristin D.; Bis, Joshua C.; Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Isaacs, Aaron; Sie, Mark P. S.; van Duijn, Cornelia M.] Erasmus Med Ctr MC, Genet Epidemiol Unit, Dept Epidemiol, Rotterdam, Netherlands. [Isaacs, Aaron; Oostra, Ben A.; van Duijn, Cornelia M.] Ctr Med Syst Biol, Leiden, Netherlands. [de Bakker, Paul I. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet,Dept Med, Boston, MA 02115 USA. [de Bakker, Paul I. W.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [de Bakker, Paul I. W.] Univ Med Ctr, Dept Med Genet, Utrecht, Netherlands. [de Bakker, Paul I. W.] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Doerr, Marcus; Felix, Stephan B.] Ernst Moritz Arndt Univ Greifswald, Dept Internal Med B, Greifswald, Germany. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Newton-Cheh, Christopher; Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Newton-Cheh, Christopher; Magnani, Jared W.; Wang, Ying A.; Cupples, L. Adrienne; Levy, Daniel; O'Donnell, Christopher J.; Wang, Thomas J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Nolte, Ilja M.; Fu, Jingyuan; Asselbergs, Folkert W.; Lu, Xiaowen; Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Unit Genet Epidemiol & Bioinformat, Groningen, Netherlands. [van der Harst, Pim; Leach, Irene Mateo; Asselbergs, Folkert W.; de Boer, Rudolf A.; van Gilst, Wiek H.; van Veldhuisen, Dirk J.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Mueller, Martina] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Mueller, Martina; Sinner, Moritz F.] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany. [Mueller, Martina; Klopp, Norman; Wichmann, H-Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany. [Eijgelsheim, Mark; Rivadeneira, Fernando; Uitterlinden, Andre G.; Witteman, Jacqueline C. M.; Hofman, Albert; Stricker, Bruno H. Ch] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Alonso, Alvaro; Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Hicks, Andrew A.; Fuchsberger, Christian; Schwienbacher, Christine; Volpato, Claudia Beu; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Inst Med Genet, Bolzano, Italy. [Hicks, Andrew A.; Pfeufer, Arne; Fuchsberger, Christian; Schwienbacher, Christine; Volpato, Claudia Beu; Pramstaller, Peter P.] Univ Lubeck, Affiliated Inst, Lubeck, Germany. [Padmanabhan, Sandosh; Dominiczak, Anna F.] Univ Glasgow, Inst Cardiovasc & Med Sci, Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland. [Hayward, Caroline; Wright, Alan F.] MRC, Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Smith, Albert Vernon; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert Vernon; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Polasek, Ozren] Univ Zagreb, Sch Med, Andrija Stampar Sch Publ Hlth, Zagreb 41001, Croatia. [Giovannone, Steven; Qu, Jiaxiang; Liu, Fang-Yu; Fishman, Glenn I.] NYU, Sch Med, Leon H Charney Div Cardiol, New York, NY USA. [Fu, Jingyuan; Fehrmann, Rudolf S. N.; Meerman, Gerard te; Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 AB Groningen, Netherlands. [Magnani, Jared W.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Pfeufer, Arne; Meitinger, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany. [Pfeufer, Arne; Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-8000 Munich, Germany. [Gharib, Sina A.] Univ Washington, Dept Med, Ctr Lung Biol, Seattle, WA USA. [Teumer, Alexander; Voelker, Uwe] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany. [Li, Man; Koettgen, Anna; Kao, W. H. Linda] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Li, Man; Kao, W. H. Linda] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Rivadeneira, Fernando; Estrada, Karol] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Johnson, Toby; Munroe, Patricia B.; Caulfield, Mark J.] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, Clin Pharmacol & Barts & London Genome Ctr, London, England. [Johnson, Toby; Munroe, Patricia B.; Caulfield, Mark J.] Barts & London Natl Inst Hlth Res, Cardiovasc Biomed Res Unit, London, England. [Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Wang, Ying A.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Wild, Sarah H.; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands. [Chakravarti, Aravinda; Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Kors, Jan A.; van Herpen, Ge; Stricker, Bruno H. Ch] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands. [Petersmann, Astrid] Ernst Moritz Arndt Univ Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Harris, Tamara B.; Launer, Lenore] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Soliman, Elsayed Z.] Wake Forest Univ, Sch Med, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC 27109 USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.; Heckbert, Susan R.] Grp Hlth Cooperat Puget Sound, Gup Hlth Res Inst, Seattle, WA 98121 USA. [Oostra, Ben A.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. [Perz, Siegfried] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, Neuherberg, Germany. [Uitterlinden, Andre G.; Witteman, Jacqueline C. M.; Hofman, Albert; van Duijn, Cornelia M.; Stricker, Bruno H. Ch] NCHA, NGI, Rotterdam, Netherlands. [Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany. [Spector, Timothy D.; Snieder, Harold; Jamshidi, Yalda] St Thomas Hosp, Kings Coll London, Dept Twin Res, London, England. [Spector, Timothy D.; Snieder, Harold; Jamshidi, Yalda] St Thomas Hosp, Kings Coll London, Genet Epidemiol Unit, London, England. [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Inst Mol Med, Houston, TX USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Bethesda, MD 20892 USA. [Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. [Kroemer, Heyo K.] Ernst Moritz Arndt Univ Greifswald, Dept Pharmacol, Ctr Pharmacol & Expt Therapeut, Greifswald, Germany. [Schwienbacher, Christine] Univ Ferrara, Dept Expt & Diagnost Med, I-44100 Ferrara, Italy. [Connell, John M.] Univ Dundee, Ninewells Hosp & Med Sch, Dundee DD1 9SY, Scotland. [Franke, Lude] Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst Cell & Mol Sci, London, England. [Groen, Harry J. M.] Univ Groningen, Univ Med Ctr Groningen, Dept Pulmonol, NL-9700 AB Groningen, Netherlands. [Weersma, Rinse K.] Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, NL-9700 AB Groningen, Netherlands. [van den Berg, Leonard H.] Univ Utrecht, Dept Neurol, Rudolf Magnus Inst, Univ Med Ctr Utrecht, NL-3584 CX Utrecht, Netherlands. [Ophoff, Roel A.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Ophoff, Roel A.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA. [Navis, Gerjan] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, NL-9700 AB Groningen, Netherlands. [Rudan, Igor] Univ Split, Ctr Global Hlth, Sch Med, Split, Croatia. [Rudan, Igor] Gen Info Ltd, Zagreb, Croatia. [Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy. [Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. [Jamshidi, Yalda] St Georges Univ London, Div Clin Dev Sci, London, England. [Stricker, Bruno H. Ch] Inspectorate Hlth Care, The Hague, Netherlands. [Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Samani, Nilesh J.] Glenfield Gen Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester LE3 9QP, Leics, England. RP Sotoodehnia, N (reprint author), Univ Washington, Dept Med, Div Cardiol, Seattle, WA 98195 USA. EM nsotoo@u.washington.edu; skaab@med.lmu.de; arking@jhmi.edu RI Pfeufer, Arne/B-6634-2013; van Veldhuisen, Dirk Jan/E-8967-2014; Wijmenga, Cisca/D-2173-2009; Pramstaller, Peter/C-2357-2008; Gudnason, Vilmundur/K-6885-2015; Wilson, James F/A-5704-2009; Meitinger, Thomas/O-1318-2015; Rivadeneira, Fernando/O-5385-2015; Smith, Albert/K-5150-2015; Hayward, Caroline/M-8818-2016; Franke, Lude/P-7036-2016; Padmanabhan, Sandosh/S-3963-2016; Hicks, Andrew/E-9518-2017; van Gilst, Wiek/C-3828-2008; Aspelund, Thor/C-5983-2008; Kottgen, Anna/D-2920-2012; Kaab, Stefan/H-3915-2012; Rudan, Igor/I-1467-2012; Polasek, Ozren/B-6002-2011; Rice, Kenneth/A-4150-2013; de Bakker, Paul/B-8730-2009; Alonso, Alvaro/A-4917-2010; Soliman, Elsayed/D-8124-2011; Fehrmann, Rudolf/E-2551-2011; Fuchsberger, Christian/C-9646-2010; Aspelund, Thor/F-4826-2011 OI Cupples, L. Adrienne/0000-0003-0273-7965; Fuchsberger, Christian/0000-0002-5918-8947; Johnson, Toby/0000-0002-5998-3270; Padmanabhan, Sandosh/0000-0003-3869-5808; Jamshidi, Yalda/0000-0003-0151-6482; Wijmenga, Cisca/0000-0002-5635-1614; Gudnason, Vilmundur/0000-0001-5696-0084; Wilson, James F/0000-0001-5751-9178; Rivadeneira, Fernando/0000-0001-9435-9441; Smith, Albert/0000-0003-1942-5845; Hayward, Caroline/0000-0002-9405-9550; Franke, Lude/0000-0002-5159-8802; Hicks, Andrew/0000-0001-6320-0411; Aspelund, Thor/0000-0002-7998-5433; Rudan, Igor/0000-0001-6993-6884; Polasek, Ozren/0000-0002-5765-1862; Rice, Kenneth/0000-0001-5779-4495; de Bakker, Paul/0000-0001-7735-7858; Alonso, Alvaro/0000-0002-2225-8323; Soliman, Elsayed/0000-0001-5632-8150; Fehrmann, Rudolf/0000-0002-7516-315X; FU Biotechnology and Biological Sciences Research Council [G20234]; British Heart Foundation [06/094, PG/02/128, RG/07/005/23633, SP/08/005/25115]; Chief Scientist Office [, CZB/4/710]; Department of Health; Intramural NIH HHS; Medical Research Council [G0400874, G9521010, G9521010D, MC_U127561128]; NCRR NIH HHS [M01-RR00425, UL1RR025005]; NHGRI NIH HHS [U01HG004402]; NHLBI NIH HHS [HL80025, K23HL80025, L30 HL097675, N01 HC-15103, N01 HC-55222, N01-HC-25195, N01-HC-35129, N01-HC-45133, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01-HC-75150, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N02-HL-6-4278, R01 HL082727, R01 HL087652, R01 HL088456, R01 HL088456-04, R01HL086694, R01HL087641, R01HL59367, R01HL64757, U01 HL080295]; NIA NIH HHS [N01-AG-12100]; NIDDK NIH HHS [DK063491]; NINDS NIH HHS [NS058980]; PHS HHS [HHSN268200625226C]; Wellcome Trust [076113/B/04/Z] NR 66 TC 141 Z9 142 U1 1 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2010 VL 42 IS 12 BP 1068 EP U62 DI 10.1038/ng.716 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 684UZ UT WOS:000284578800009 PM 21076409 ER PT J AU Elks, CE Perry, JRB Sulem, P Chasman, DI Franceschini, N He, CY Lunetta, KL Visser, JA Byrne, EM Cousminer, DL Gudbjartsson, DF Esko, T Feenstra, B Hottenga, JJ Koller, DL Kutalik, Z Lin, P Mangino, M Marongiu, M McArdle, PF Smith, AV Stolk, L Van Wingerden, SH Zhao, JH Albrecht, E Corre, T Ingelsson, E Hayward, C Magnusson, PKE Smith, EN Ulivi, S Warrington, NM Zgaga, L Alavere, H Amin, N Aspelund, T Bandinelli, S Barroso, I Berenson, GS Bergmann, S Blackburn, H Boerwinkle, E Buring, JE Busonero, F Campbell, H Chanock, SJ Chen, W Cornelis, MC Couper, D Coviello, AD d'Adamo, P de Faire, U de Geus, EJC Deloukas, P Doring, A Smith, GD Easton, DF Eiriksdottir, G Emilsson, V Eriksson, J Ferrucci, L Folsom, AR Foroud, T Garcia, M Gasparini, P Geller, F Gieger, C Gudnason, V Hall, P Hankinson, SE Ferreli, L Heath, AC Hernandez, DG Hofman, A Hu, FB Illig, T Jarvelin, MR Johnson, AD Karasik, D Khaw, KT Kiel, DP Kilpelainen, TO Kolcic, I Kraft, P Launer, LJ Laven, JSE Li, SX Liu, JJ Levy, D Martin, NG McArdle, WL Melbye, M Mooser, V Murray, JC Murray, SS Nalls, MA Navarro, P Nelis, M Ness, AR Northstone, K Oostra, BA Peacock, M Palmer, LJ Palotie, A Pare, G Parker, AN Pedersen, NL Peltonen, L Pennell, CE Pharoah, P Polasek, O Plump, AS Pouta, A Porcu, E Rafnar, T Rice, JP Ring, SM Rivadeneira, F Rudan, I Sala, C Salomaa, V Sanna, S Schlessinger, D Schork, NJ Scuteri, A Segre, AV Shuldiner, AR Soranzo, N Sovio, U Srinivasan, SR Strachan, DP Tammesoo, ML Tikkanen, E Toniolo, D Tsui, K Tryggvadottir, L Tyrer, J Uda, M van Dam, RM van Meurs, JBJ Vollenweider, P Waeber, G Wareham, NJ Waterworth, DM Weedon, MN Wichmann, HE Willemsen, G Wilson, JF Wright, AF Young, L Zhai, GJ Zhuang, WV Bierut, LJ Boomsma, DI Boyd, HA Crisponi, L Demerath, EW van Duijn, CM Econs, MJ Harris, TB Hunter, DJ Loos, RJF Metspalu, A Montgomery, GW Ridker, PM Spector, TD Streeten, EA Stefansson, K Thorsteinsdottir, U Uitterlinden, AG Widen, E Murabito, JM Ong, KK Murray, A AF Elks, Cathy E. Perry, John R. B. Sulem, Patrick Chasman, Daniel I. Franceschini, Nora He, Chunyan Lunetta, Kathryn L. Visser, Jenny A. Byrne, Enda M. Cousminer, Diana L. Gudbjartsson, Daniel F. Esko, Tonu Feenstra, Bjarke Hottenga, Jouke-Jan Koller, Daniel L. Kutalik, Zoltan Lin, Peng Mangino, Massimo Marongiu, Mara McArdle, Patrick F. Smith, Albert V. Stolk, Lisette Van Wingerden, Sophie H. Zhao, Jing Hua Albrecht, Eva Corre, Tanguy Ingelsson, Erik Hayward, Caroline Magnusson, Patrik K. E. Smith, Erin N. Ulivi, Shelia Warrington, Nicole M. Zgaga, Lina Alavere, Helen Amin, Najaf Aspelund, Thor Bandinelli, Stefania Barroso, Ines Berenson, Gerald S. Bergmann, Sven Blackburn, Hannah Boerwinkle, Eric Buring, Julie E. Busonero, Fabio Campbell, Harry Chanock, Stephen J. Chen, Wei Cornelis, Marilyn C. Couper, David Coviello, Andrea D. d'Adamo, Pio de Faire, Ulf de Geus, Eco J. C. Deloukas, Panos Doering, Angela Smith, George Davey Easton, Douglas F. Eiriksdottir, Gudny Emilsson, Valur Eriksson, Johan Ferrucci, Luigi Folsom, Aaron R. Foroud, Tatiana Garcia, Melissa Gasparini, Paolo Geller, Frank Gieger, Christian Gudnason, Vilmundur Hall, Per Hankinson, Susan E. Ferreli, Liana Heath, Andrew C. Hernandez, Dena G. Hofman, Albert Hu, Frank B. Illig, Thomas Jaervelin, Marjo-Riitta Johnson, Andrew D. Karasik, David Khaw, Kay-Tee Kiel, Douglas P. Kilpelaeinen, Tuomas O. Kolcic, Ivana Kraft, Peter Launer, Lenore J. Laven, Joop S. E. Li, Shengxu Liu, Jianjun Levy, Daniel Martin, Nicholas G. McArdle, Wendy L. Melbye, Mads Mooser, Vincent Murray, Jeffrey C. Murray, Sarah S. Nalls, Michael A. Navarro, Pau Nelis, Mari Ness, Andrew R. Northstone, Kate Oostra, Ben A. Peacock, Munro Palmer, Lyle J. Palotie, Aarno Pare, Guillaume Parker, Alex N. Pedersen, Nancy L. Peltonen, Leena Pennell, Craig E. Pharoah, Paul Polasek, Ozren Plump, Andrew S. Pouta, Anneli Porcu, Eleonora Rafnar, Thorunn Rice, John P. Ring, Susan M. Rivadeneira, Fernando Rudan, Igor Sala, Cinzia Salomaa, Veikko Sanna, Serena Schlessinger, David Schork, Nicholas J. Scuteri, Angelo Segre, Ayellet V. Shuldiner, Alan R. Soranzo, Nicole Sovio, Ulla Srinivasan, Sathanur R. Strachan, David P. Tammesoo, Mar-Liis Tikkanen, Emmi Toniolo, Daniela Tsui, Kim Tryggvadottir, Laufey Tyrer, Jonathon Uda, Manuela van Dam, Rob M. van Meurs, Joyce B. J. Vollenweider, Peter Waeber, Gerard Wareham, Nicholas J. Waterworth, Dawn M. Weedon, Michael N. Wichmann, H. Erich Willemsen, Gonneke Wilson, James F. Wright, Alan F. Young, Lauren Zhai, Guangju Zhuang, Wei Vivian Bierut, Laura J. Boomsma, Dorret I. Boyd, Heather A. Crisponi, Laura Demerath, Ellen W. van Duijn, Cornelia M. Econs, Michael J. Harris, Tamara B. Hunter, David J. Loos, Ruth J. F. Metspalu, Andres Montgomery, Grant W. Ridker, Paul M. Spector, Tim D. Streeten, Elizabeth A. Stefansson, Kari Thorsteinsdottir, Unnur Uitterlinden, Andre G. Widen, Elisabeth Murabito, Joanne M. Ong, Ken K. Murray, Anna CA GIANT Consortium TI Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies SO NATURE GENETICS LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; ENERGY-BALANCE; SEQUENCE VARIANTS; INHIBIN-B; PUBERTY; WOMEN; GIRLS; GENE; EPIDEMIOLOGY; HERITABILITY AB To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 x 10(-60)) and 9q31.2 (P = 2.2 x 10(-33)), we identified 30 new menarche loci (all P < 5 x 10(-8)) and found suggestive evidence for a further 10 loci (P < 1.9 x 10(-6)). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing. C1 [Lunetta, Kathryn L.; Johnson, Andrew D.; Levy, Daniel; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Elks, Cathy E.; Zhao, Jing Hua; Kilpelaeinen, Tuomas O.; Li, Shengxu; Wareham, Nicholas J.; Loos, Ruth J. F.; Montgomery, Grant W.; Ong, Ken K.] Addenbrookes Hosp, Epidemiol Unit, MRC, Inst Metab Sci, Cambridge, England. [Perry, John R. B.; Weedon, Michael N.; Ridker, Paul M.; Murray, Anna] Univ Exeter, Peninsula Med Sch, Exeter EX4 4QJ, Devon, England. [Sulem, Patrick; Gudbjartsson, Daniel F.; Rafnar, Thorunn; Stefansson, Kari; Thorsteinsdottir, Unnur] deCODE Genet, Reykjavik, Iceland. [Chasman, Daniel I.; Buring, Julie E.; Pare, Guillaume; Ridker, Paul M.; Ong, Ken K.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Chasman, Daniel I.; Buring, Julie E.; Pare, Guillaume; Peltonen, Leena; Ridker, Paul M.] Harvard Univ, Sch Med, Boston, MA USA. [Elks, Cathy E.; Perry, John R. B.; Sulem, Patrick; Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [He, Chunyan] Indiana Univ, Sch Med, Dept Publ Hlth, Indiana, PA USA. [He, Chunyan] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indiana, PA USA. [Lunetta, Kathryn L.; Zhuang, Wei Vivian] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Visser, Jenny A.; Stolk, Lisette; Rivadeneira, Fernando; van Meurs, Joyce B. J.; Uitterlinden, Andre G.] Erasmus Med Ctr MC, Dept Internal Med, Rotterdam, Netherlands. [Byrne, Enda M.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Byrne, Enda M.] Univ Queensland, Brisbane, Qld, Australia. [Cousminer, Diana L.; Palotie, Aarno; Peltonen, Leena; Tikkanen, Emmi; Widen, Elisabeth] Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00014 Helsinki, Finland. [Esko, Tonu; Alavere, Helen; Nelis, Mari; Tammesoo, Mar-Liis; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Esko, Tonu; Nelis, Mari; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, Dept Biotechnol, EE-50090 Tartu, Estonia. [Esko, Tonu; Nelis, Mari; Metspalu, Andres] Estonian Bioctr, Genotyping Core Facil, Tartu, Estonia. [Feenstra, Bjarke; Geller, Frank; Melbye, Mads; Boyd, Heather A.] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Hottenga, Jouke-Jan; de Geus, Eco J. C.; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Koller, Daniel L.; Foroud, Tatiana] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Kutalik, Zoltan; Bergmann, Sven] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland. [Kutalik, Zoltan; Bergmann, Sven] Swiss Inst Bioinformat, Lausanne, Switzerland. [Lin, Peng; Rice, John P.; Bierut, Laura J.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Mangino, Massimo; Soranzo, Nicole; Zhai, Guangju; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Marongiu, Mara; Busonero, Fabio; Ferreli, Liana; Porcu, Eleonora; Sanna, Serena; Scuteri, Angelo; Uda, Manuela; Crisponi, Laura] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy. [McArdle, Patrick F.; Shuldiner, Alan R.; Streeten, Elizabeth A.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Smith, Albert V.; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert V.; Aspelund, Thor; Gudnason, Vilmundur; Econs, Michael J.] Univ Iceland, Reykjavik, Iceland. [Stolk, Lisette; Hofman, Albert; Rivadeneira, Fernando; van Meurs, Joyce B. J.; van Duijn, Cornelia M.; Uitterlinden, Andre G.] Netherlands Consortium Healthy Aging, Rotterdam, Netherlands. [Van Wingerden, Sophie H.; Amin, Najaf; Oostra, Ben A.; van Duijn, Cornelia M.] Erasmus Univ, Dept Epidemiol, Med Ctr, Genet Epidemiol Unit, Rotterdam, Netherlands. [Albrecht, Eva; Doering, Angela; Gieger, Christian; Illig, Thomas; Wichmann, H. Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany. [Corre, Tanguy; Sala, Cinzia; Toniolo, Daniela] Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy. [Ingelsson, Erik; Magnusson, Patrik K. E.; Hall, Per; Pedersen, Nancy L.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Hayward, Caroline; Navarro, Pau; Wright, Alan F.] Western Gen Hosp, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. [Smith, Erin N.; Murray, Sarah S.; Schork, Nicholas J.] Scripps Genom Med, La Jolla, CA USA. [Smith, Erin N.; Murray, Sarah S.; Schork, Nicholas J.] Scripps Translat Sci Inst, La Jolla, CA USA. [Smith, Erin N.; Murray, Sarah S.; Schork, Nicholas J.] Scripps Res Inst, La Jolla, CA 92037 USA. [Ulivi, Shelia; d'Adamo, Pio; Gasparini, Paolo] Univ Trieste, Dept Reprod Sci & Dev, Trieste, Italy. [Warrington, Nicole M.; Palmer, Lyle J.] Univ Western Australia, Ctr Genet Epidemiol & Biostat, Crawley, WA, Australia. [Zgaga, Lina; Campbell, Harry; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. [Barroso, Ines; Blackburn, Hannah; Deloukas, Panos; Palotie, Aarno; Peltonen, Leena; Soranzo, Nicole] Wellcome Trust Sanger Inst, Cambridge, England. [Berenson, Gerald S.; Chen, Wei; Srinivasan, Sathanur R.] Tulane Univ, New Orleans, LA 70118 USA. [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Buring, Julie E.; Hankinson, Susan E.; Hu, Frank B.; Kraft, Peter; Hunter, David J.; Ridker, Paul M.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chanock, Stephen J.; Hunter, David J.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Cornelis, Marilyn C.; Hu, Frank B.; Kraft, Peter; van Dam, Rob M.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Couper, David] Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. [Coviello, Andrea D.; Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med Prevent Med & Endocrinol, Boston, MA 02118 USA. [de Faire, Ulf] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Smith, George Davey] Univ Bristol, Dept Social Med, MRC Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England. [Easton, Douglas F.; Pharoah, Paul; Tyrer, Jonathon] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Easton, Douglas F.; Pharoah, Paul; Tyrer, Jonathon] Univ Cambridge, Dept Oncol, Strangeways Res Labs, Cambridge, England. [Emilsson, Valur] Merck & Co Inc, MPRI, Rahway, NJ 07065 USA. [Eriksson, Johan; Peltonen, Leena; Pouta, Anneli; Salomaa, Veikko; Tikkanen, Emmi] Natl Inst Hlth & Welf, Helsinki, Finland. [Eriksson, Johan] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Eriksson, Johan] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Eriksson, Johan] Folkhalsan Res Ctr, Helsinki, Finland. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. [Folsom, Aaron R.; Demerath, Ellen W.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Garcia, Melissa; Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Hankinson, Susan E.; Hu, Frank B.; Kraft, Peter; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Hankinson, Susan E.; Hu, Frank B.; Karasik, David; Kiel, Douglas P.; Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA USA. [Heath, Andrew C.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Hernandez, Dena G.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Jaervelin, Marjo-Riitta; Sovio, Ulla] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England. [Johnson, Andrew D.; Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Karasik, David; Kiel, Douglas P.] Harvard Univ, Hebrew Senior Life Inst Aging Res, Boston, MA 02115 USA. [Khaw, Kay-Tee] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England. [Kolcic, Ivana; Polasek, Ozren] Univ Zagreb, Sch Med, Zagreb 41001, Croatia. [Laven, Joop S. E.] Erasmus, MC, Dept Obstet & Gynaecol, Rotterdam, Netherlands. [Liu, Jianjun] Genome Inst Singapore, Singapore, Singapore. [Levy, Daniel] Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA. [Martin, Nicholas G.; Montgomery, Grant W.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [McArdle, Wendy L.; Northstone, Kate; Ring, Susan M.] Univ Bristol, Dept Social Med, ALSPAC, Bristol, Avon, England. [Mooser, Vincent; Waterworth, Dawn M.] GlaxoSmithKline, Div Genet, King Of Prussia, PA USA. [Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Nalls, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA. [Ness, Andrew R.] Univ Bristol, Dept Oral & Dent Sci, Bristol, Avon, England. [Oostra, Ben A.] Erasmus Univ, Dept Clin Genet, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Peacock, Munro; Econs, Michael J.] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. [Palotie, Aarno; Peltonen, Leena; Segre, Ayellet V.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Pare, Guillaume] McMaster Univ, Genet & Mol Epidemiol Lab, Hamilton, ON, Canada. [Parker, Alex N.; Tsui, Kim; Young, Lauren] Amgen Inc, Cambridge, MA USA. [Pennell, Craig E.] Univ Western Australia, Sch Womens & Infants Hlth, Crawley, WA, Australia. [Polasek, Ozren] Gen Info Ltd, Zagreb, Croatia. [Plump, Andrew S.] Merck Res Lab, Rahway, NJ USA. [Rudan, Igor] Univ Split, Croatian Ctr Global Hlth, Sch Med, Split, Croatia. [Schlessinger, David] NIA, Gerontol Res Ctr, Bethesda, MD 20892 USA. [Scuteri, Angelo] IRCCS, INRCA, Unita Operativa Geriatr, Rome, Italy. [Segre, Ayellet V.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA. [Strachan, David P.] Univ London, Div Community Hlth Sci, London, England. [Tryggvadottir, Laufey] Iceland Canc Registry, Reykjavik, Iceland. [van Dam, Rob M.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Epidemiol & Publ Hlth, Singapore 117595, Singapore. [van Dam, Rob M.] Natl Univ Singapore, Dept Med, Singapore 117595, Singapore. [Vollenweider, Peter; Waeber, Gerard] BH 10 Ctr Hosp Univ Vaudois CHUV, Dept Internal Med, Lausanne, Switzerland. [Wichmann, H. Erich] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Wichmann, H. Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. [Stefansson, Kari; Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Ong, Ken K.] Univ Cambridge, Dept Paediat, Cambridge, England. RP Murabito, JM (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA. EM murabito@bu.edu; ken.ong@mrc-epid.cam.ac.uk; anna.murray@pms.ac.uk RI Hayward, Caroline/M-8818-2016; Davey Smith, George/A-7407-2013; Magnusson, Patrik/C-4458-2017; Kolcic, Ivana/E-2713-2017; Byrne, Enda/J-6068-2014; Ness, Andy/M-7612-2013; d'Adamo, Adamo Pio/G-4064-2011; Lin, P/G-7702-2014; Palmer, Lyle/K-3196-2014; Warrington, Nicole/P-4868-2014; Gudnason, Vilmundur/K-6885-2015; Wilson, James F/A-5704-2009; de Geus, Eco/M-9318-2015; Montgomery, Grant/B-7148-2008; Rivadeneira, Fernando/O-5385-2015; Smith, Albert/K-5150-2015; mangino, massimo/F-5134-2011; Colaus, PsyColaus/K-6607-2013; van Dam, Rob/F-9674-2010; Northstone, Kate/A-8165-2011; Polasek, Ozren/B-6002-2011; Smith, Erin/E-5933-2011; Aspelund, Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; Visser, Jenny /F-8156-2011; Kilpelainen, Tuomas/F-8569-2012; Rudan, Igor/I-1467-2012; Deloukas, Panos/B-2922-2013; Johnson, Andrew/G-6520-2013; Ulivi, Sheila/H-3700-2013 OI Martin, Nicholas/0000-0003-4069-8020; Gieger, Christian/0000-0001-6986-9554; Kiel, Douglas/0000-0001-8474-0310; Karasik, David/0000-0002-8826-0530; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Eriksson, Johan/0000-0002-2516-2060; Bergmann, Sven/0000-0002-6785-9034; sanna, serena/0000-0002-3768-1749; Gudbjartsson, Daniel/0000-0002-5222-9857; Monsalve, Beatriz Elena/0000-0002-5994-866X; MARONGIU, MARA/0000-0002-7321-2384; Tryggvadottir, Laufey/0000-0001-8067-9030; Hayward, Caroline/0000-0002-9405-9550; Davey Smith, George/0000-0002-1407-8314; Kolcic, Ivana/0000-0001-7918-6052; Byrne, Enda/0000-0002-9491-7797; Murabito, Joanne/0000-0002-0192-7516; Lunetta, Kathryn/0000-0002-9268-810X; Soranzo, Nicole/0000-0003-1095-3852; Zgaga, Lina/0000-0003-4089-9703; Murray, Anna/0000-0002-2351-2522; Esko, Tonu/0000-0003-1982-6569; Ness, Andy/0000-0003-3548-9523; d'Adamo, Adamo Pio/0000-0001-9367-4909; Palmer, Lyle/0000-0002-1628-3055; Warrington, Nicole/0000-0003-4195-775X; Gudnason, Vilmundur/0000-0001-5696-0084; Wilson, James F/0000-0001-5751-9178; de Geus, Eco/0000-0001-6022-2666; Montgomery, Grant/0000-0002-4140-8139; Rivadeneira, Fernando/0000-0001-9435-9441; Smith, Albert/0000-0003-1942-5845; mangino, massimo/0000-0002-2167-7470; van Dam, Rob/0000-0002-7354-8734; Northstone, Kate/0000-0002-0602-1983; Polasek, Ozren/0000-0002-5765-1862; Aspelund, Thor/0000-0002-7998-5433; Rudan, Igor/0000-0001-6993-6884; Deloukas, Panos/0000-0001-9251-070X; Ulivi, Sheila/0000-0003-3606-835X FU Academy of Finland (Finnish Centre of Excellence in Complex Disease Genetics) [129680, 120315, 129287, 129494]; Affymetrix [N02-HL-6-4278]; Agency of Science, Technology and Research of Singapore (A*STAR); Althingi (the Icelandic Parliament); American Heart Association [0855082E]; Amgen; Augustinus Foundation; Australian National Health and Medical Research Council [241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498, 619667]; Australian Research Council [A7960034, A79801419, A79906588, DP0212016, DP0343921, DP0770096]; Baltimore Veterans Administration Medical Center Geriatrics Research; Canadian Institutes of Health Research [166067]; Cancer Research United Kingdom; Cariplo Foundation; Center for Disease Control and Prevention (USA), Centre for Medical Systems Biology (CMSB); Chief Scientist Office of the Scottish Government; Clinical Nutrition Research Unit of Maryland [P30 DK072488]; Danish National Research Foundation; Danish Pharmacists' Fund; Egmont Foundation; Erasmus Medical Center; Erasmus University; Estonian Government [SF0180142s08]; European Commision [212111 BBMRI, 205419 ECOGENE, 201413 ENGAGE, HEALTH-F2-2008-201865-GEFOS, HEALTH-F2-2008-35627, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550 HYPERGENES, 245536 OPENGENE, TREAT-OA, QLG2-CT-2002-01254, EU/QLRT-2001-01254, ERC-230374]; European Union [LSHG-CT-2006-018947, LSHM-CT-2003-503041]; European Regional Development Fund; Faculty of Biology and Medicine of Lausanne, Switzerland; Fondazione Compagnia di San Paolo Health Ministry, Framingham Heart Study [N01-HC-25195]; GENEVA Coordinating Center [U01HG004446]; German Federal Ministry of Education and Research; German National Genome Research Network [NGFN-2, 01GS0823]; Giorgi-Cavaglieri Foundation; GlaxoSmithKline; Health Fund of the Danish Health Insurance Societies; Helmholtz Zentrum Munchen-German Research Center for Environmental Health; Hjartavernd (the Icelandic Heart Association); Italian Ministry of Health [ICS110.1/RF97.71, RF-FSR-2007-647201]; Juvenile Diabetes Research Foundation International (JDRF); Leenaards Foundation; March of Dimes Birth Defects Foundation; Medical Research Council [G0000934, G0500539, G0701863]; National Cancer Institute [CA40356, CA98233, P01CA087969, P01CA055075, CA047988, CA63464, CA54281, CA136792, CA089392, CA104021]; Munich Center of Health Sciences (MC Health, LMUinnovativ); National Health and Medical Research Council of Australia [572613, 003209]; National Heart, Lung, and Blood Institute [HL043851, HL087679, HL69757, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, RC2 HL102419]; National Human Genome Research Institute (NHGRI); National Institute of Aging [263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002, AG-16592, R21AG032598]; National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute on Aging ((NIAMS/NIA) [R01 AR/AG 41398)]; National Institute of Child Health and Human Development [HD-061437]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01DK058845, U01 DK062418]; National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute of Allergy and Infectious Diseases (NIAID); National Institute on Drug Abuse (NIDA); National Institutes of Health [U01HG004446, AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, HHSN268200782096C, M01 RR-00750, MH66206, N01-AG-12100, N01-AG-1-2109, P01-AG-18397, R01-088119, R01-DA013423, RFAHG006033, U01DE018993, U01DE018903, U01HG004422, U01HL72515, U01 HL84756, U01HG004399, U01HG004402, U01HG004415, U01HG004423, U01HG004436, U01HG004438, U01HG004726, U01HG004728, U01HG004729, U01HG004735, U01HG004738, U01HG04424, U10AA008401, U54RR025204-01, UL1RR025005, UL1 RR025774, Z01CP010200, HHSN268200625226C]; National Institute for Health Research Cambridge Biomedical Research Centre; Netherlands Organization for Scientific Research [904-61-193, 575-25-006, 480-04-004, 56-464-14192, NWO 480-05-003, 175.010.2005.011, 911-03-012, 014-93-015]; Netherlands Genomic Initiative (NGI) [050-060-810]; National Institute on Aging (NIA); Laboratory of Neurogenetics; US National Institutes of Health Genes, Environment and Health Initiative; Republic of Croatia Ministry of Science, Education and Sports [108-1080315-0302]; Robert Dawson Evans Endowment; Royal Society, Royal Swedish Academy of Science; State of Bavaria, Germany; Susan G. Komen Breast Cancer Foundation; Swedish Foundation for Strategic Research (SSF); Swedish Heart-Lung Foundation; Swedish Ministry of Higher Education and Research; Swedish Research Council; Swedish Society of Medicine; Swiss National Science Foundation [33CSCO-122661, 3100AO-116323/1]; University of Bristol, University of Maryland General Clinical Research Center [M01 RR 16500]; Wellcome Trust [068545/Z/02, 076467/Z/05/Z, 077016/Z/05/Z, 89061/Z/09/Z, 079895]; Western Australian DNA Bank; Western Australian Genetic Epidemiology Resource FX Academy of Finland (Finnish Centre of Excellence in Complex Disease Genetics 129680, 120315, 129287, 129494); Affymetrix (N02-HL-6-4278); Agency of Science, Technology and Research of Singapore (A*STAR); Althingi (the Icelandic Parliament); American Heart Association (0855082E); Amgen; Augustinus Foundation; Australian National Health and Medical Research Council (241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498, 619667); Australian Research Council (A7960034, A79801419, A79906588, DP0212016, DP0343921, DP0770096); Baltimore Veterans Administration Medical Center Geriatrics Research; Canadian Institutes of Health Research (grant ID 166067); Cancer Research United Kingdom; the Cariplo Foundation; Center for Disease Control and Prevention (USA), Centre for Medical Systems Biology (CMSB); the Chief Scientist Office of the Scottish Government; Clinical Nutrition Research Unit of Maryland (P30 DK072488); Danish National Research Foundation; Danish Pharmacists' Fund; the Egmont Foundation; Erasmus Medical Center; Erasmus University; Estonian Government (SF0180142s08); the European Commision (212111 BBMRI, 205419 ECOGENE, 201413 ENGAGE, HEALTH-F2-2008-201865-GEFOS, HEALTH-F2-2008-35627, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550 HYPERGENES, 245536 OPENGENE, TREAT-OA, GenomEUtwin Project QLG2-CT-2002-01254, EU/QLRT-2001-01254; ERC-230374); European Union framework program 6 EUROSPAN project (LSHG-CT-2006-018947, LSHM-CT-2003-503041); European Regional Development Fund; Faculty of Biology and Medicine of Lausanne, Switzerland; Fondazione Compagnia di San Paolo Health Ministry, Framingham Heart Study (N01-HC-25195); GENEVA Coordinating Center (U01HG004446); German Federal Ministry of Education and Research; German National Genome Research Network (NGFN-2 and NGFNPlus: 01GS0823); Giorgi-Cavaglieri Foundation; GlaxoSmithKline; Health Fund of the Danish Health Insurance Societies; Helmholtz Zentrum Munchen-German Research Center for Environmental Health; Hjartavernd (the Icelandic Heart Association); Italian Ministry of Health (ICS110.1/RF97.71, RF-FSR-2007-647201); Juvenile Diabetes Research Foundation International (JDRF); Leenaards Foundation; March of Dimes Birth Defects Foundation; the Medical Research Council (G0000934, G0500539, G0701863); National Cancer Institute (CA40356, CA98233, P01CA087969, P01CA055075, CA047988, CA63464, CA54281, CA136792, CA089392, CA104021); Munich Center of Health Sciences (MC Health, LMUinnovativ); National Health and Medical Research Council of Australia (572613 and 003209); National Heart, Lung, and Blood Institute (HL043851, HL087679, HL69757, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, RC2 HL102419); National Human Genome Research Institute (NHGRI); National Institute of Aging (263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.; 1-AG-1-2111, N01-AG-5-0002, AG-16592, Genetics of Reproductive Life Period and Health Outcomes R21AG032598); National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute on Aging ((NIAMS/NIA) R01 AR/AG 41398); National Institute of Child Health and Human Development (HD-061437); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, R01DK058845, U01 DK062418); National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute of Allergy and Infectious Diseases (NIAID); National Institute on Drug Abuse (NIDA); National Institutes of Health (AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, HHS268200782096C, M01 RR-00750, MH66206, N01-AG-12100, N01-AG-1-2109, P01-AG-18397, R01-088119, R01-DA013423, RFAHG006033, U01DE018993, U01DE018903, U01HG004422, U01HG004446, U01HL72515, U01 HL84756, U01HG004399, U01HG004402, U01HG004415, U01HG004423, U01HG004436, U01HG004438, U01HG004402, U01HG004446, U01HG004726, U01HG004728, U01HG004729, U01HG004735, U01HG004738, U01HG04424, U10AA008401, U54RR025204-01, UL1RR025005, UL1 RR025774, Z01CP010200, HHSN268200625226C); the National Institute for Health Research Cambridge Biomedical Research Centre; Netherlands Organization for Scientific Research (904-61-193, 575-25-006, 480-04-004, 56-464-14192, NWO 480-05-003, 175.010.2005.011, 911-03-012, 014-93-015); Netherlands Genomic Initiative (NGI, 050-060-810), National Institute on Aging (NIA) Intramural Research Program; and Laboratory of Neurogenetics; US National Institutes of Health Genes, Environment and Health Initiative; Republic of Croatia Ministry of Science, Education and Sports (108-1080315-0302); Robert Dawson Evans Endowment; the Royal Society, Royal Swedish Academy of Science; State of Bavaria, Germany; Susan G. Komen Breast Cancer Foundation; Swedish Foundation for Strategic Research (SSF); Swedish Heart-Lung Foundation; Swedish Ministry of Higher Education and Research; Swedish Research Council; Swedish Society of Medicine; Swiss National Science Foundation (Ref: 33CSCO-122661, 3100AO-116323/1); the University of Bristol, University of Maryland General Clinical Research Center (M01 RR 16500); the Wellcome Trust (068545/Z/02, 076467/Z/05/Z, 077016/Z/05/Z, 89061/Z/09/Z, strategic award 079895); Western Australian DNA Bank; Western Australian Genetic Epidemiology Resource (see Supplementary Note for extended acknowledgments). NR 44 TC 218 Z9 222 U1 1 U2 39 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2010 VL 42 IS 12 BP 1077 EP U73 DI 10.1038/ng.714 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 684UZ UT WOS:000284578800010 PM 21102462 ER PT J AU Loewer, S Cabili, MN Guttman, M Loh, YH Thomas, K Park, IH Garber, M Curran, M Onder, T Agarwal, S Manos, PD Datta, S Lander, ES Schlaeger, TM Daley, GQ Rinn, JL AF Loewer, Sabine Cabili, Moran N. Guttman, Mitchell Loh, Yuin-Han Thomas, Kelly Park, In Hyun Garber, Manuel Curran, Matthew Onder, Tamer Agarwal, Suneet Manos, Philip D. Datta, Sumon Lander, Eric S. Schlaeger, Thorsten M. Daley, George Q. Rinn, John L. TI Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells SO NATURE GENETICS LA English DT Article ID HUMAN SOMATIC-CELLS; DEVELOPMENTAL REGULATORS; GENE-EXPRESSION; DEFINED FACTORS; IPS CELLS; CHROMATIN; FIBROBLASTS; GENERATION; POLYCOMB; TRANSCRIPTION AB The conversion of lineage-committed cells to induced pluripotent stem cells (iPSCs) by reprogramming is accompanied by a global remodeling of the epigenome(1-5), resulting in altered patterns of gene expression(2,6-9). Here we characterize the transcriptional reorganization of large intergenic non-coding RNAs (lincRNAs)(10,11) that occurs upon derivation of human iPSCs and identify numerous lincRNAs whose expression is linked to pluripotency. Among these, we defined ten lincRNAs whose expression was elevated in iPSCs compared with embryonic stem cells, suggesting that their activation may promote the emergence of iPSCs. Supporting this, our results indicate that these lincRNAs are direct targets of key pluripotency transcription factors. Using loss-of-function and gain-of-function approaches, we found that one such lincRNA (lincRNA-RoR) modulates reprogramming, thus providing a first demonstration for critical functions of lincRNAs in the derivation of pluripotent stem cells. C1 [Loewer, Sabine; Loh, Yuin-Han; Park, In Hyun; Curran, Matthew; Onder, Tamer; Agarwal, Suneet; Manos, Philip D.; Datta, Sumon; Schlaeger, Thorsten M.; Daley, George Q.] Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Div Pediat Hematol & Oncol, Stem Cell Transplantat Program, Boston, MA USA. [Loewer, Sabine; Loh, Yuin-Han; Park, In Hyun; Curran, Matthew; Onder, Tamer; Agarwal, Suneet; Manos, Philip D.; Datta, Sumon; Schlaeger, Thorsten M.; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Loewer, Sabine; Loh, Yuin-Han; Park, In Hyun; Onder, Tamer; Agarwal, Suneet; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Loewer, Sabine; Loh, Yuin-Han; Park, In Hyun; Curran, Matthew; Onder, Tamer; Agarwal, Suneet; Manos, Philip D.; Datta, Sumon; Schlaeger, Thorsten M.; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA USA. [Loewer, Sabine; Loh, Yuin-Han; Park, In Hyun; Onder, Tamer; Manos, Philip D.; Datta, Sumon; Schlaeger, Thorsten M.; Daley, George Q.] Childrens Hosp Boston, Stem Cell Program, Boston, MA USA. [Cabili, Moran N.; Guttman, Mitchell; Thomas, Kelly; Garber, Manuel; Lander, Eric S.; Rinn, John L.] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA USA. [Guttman, Mitchell; Lander, Eric S.] MIT, Dept Biol, Cambridge, MA USA. [Cabili, Moran N.; Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Thomas, Kelly; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Daley, George Q.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Rinn, John L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Boston, MA 02115 USA. [Rinn, John L.] Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Div Pediat Hematol & Oncol, Stem Cell Transplantat Program, Boston, MA USA. EM george.daley@childrens.harvard.edu RI Onder, Tamer /H-3330-2013; Loh, Yuin-Han/E-1096-2014 OI Onder, Tamer /0000-0002-2372-9158; Loh, Yuin-Han/0000-0002-4715-6454 FU Howard Hughes Medical Institute; NHLBI NIH HHS [1 RC2-HL102815, K08 HL089150, RC2 HL102815]; NIH HHS [1DP2OD00667-01, DP2 OD006670, DP2 OD006670-01] NR 35 TC 356 Z9 389 U1 9 U2 57 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2010 VL 42 IS 12 BP 1113 EP + DI 10.1038/ng.710 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 684UZ UT WOS:000284578800015 PM 21057500 ER PT J AU Franke, A McGovern, DPB Barrett, JC Wang, K Radford-Smith, GL Ahmad, T Lees, CW Balschun, T Lee, J Roberts, R Anderson, CA Bis, JC Bumpstead, S Ellinghaus, D Festen, EM Georges, M Green, T Haritunians, T Jostins, L Latiano, A Mathew, CG Montgomery, GW Prescott, NJ Raychaudhuri, S Rotter, JI Schumm, P Sharma, Y Simms, LA Taylor, KD Whiteman, D Wijmenga, C Baldassano, RN Barclay, M Bayless, TM Brand, S Buning, C Cohen, A Colombel, JF Cottone, M Stronati, L Denson, T De Vos, M D'Inca, R Dubinsky, M Edwards, C Florin, T Franchimont, D Gearry, R Glas, J Van Gossum, A Guthery, SL Halfvarson, J Verspaget, HW Hugot, JP Karban, A Laukens, D Lawrance, I Lemann, M Levine, A Libioulle, C Louis, E Mowat, C Newman, W Panes, J Phillips, A Proctor, DD Regueiro, M Russell, R Rutgeerts, P Sanderson, J Sans, M Seibold, F Steinhart, AH Stokkers, PCF Torkvist, L Kullak-Ublick, G Wilson, D Walters, T Targan, SR Brant, SR Rioux, JD D'Amato, M Weersma, RK Kugathasan, S Griffiths, AM Mansfield, JC Vermeire, S Duerr, RH Silverberg, MS Satsangi, J Schreiber, S Cho, JH Annese, V Hakonarson, H Daly, MJ Parkes, M AF Franke, Andre McGovern, Dermot P. B. Barrett, Jeffrey C. Wang, Kai Radford-Smith, Graham L. Ahmad, Tariq Lees, Charlie W. Balschun, Tobias Lee, James Roberts, Rebecca Anderson, Carl A. Bis, Joshua C. Bumpstead, Suzanne Ellinghaus, David Festen, Eleonora M. Georges, Michel Green, Todd Haritunians, Talin Jostins, Luke Latiano, Anna Mathew, Christopher G. Montgomery, Grant W. Prescott, Natalie J. Raychaudhuri, Soumya Rotter, Jerome I. Schumm, Philip Sharma, Yashoda Simms, Lisa A. Taylor, Kent D. Whiteman, David Wijmenga, Cisca Baldassano, Robert N. Barclay, Murray Bayless, Theodore M. Brand, Stephan Buening, Carsten Cohen, Albert Colombel, Jean-Frederick Cottone, Mario Stronati, Laura Denson, Ted De Vos, Martine D'Inca, Renata Dubinsky, Marla Edwards, Cathryn Florin, Tim Franchimont, Denis Gearry, Richard Glas, Juergen Van Gossum, Andre Guthery, Stephen L. Halfvarson, Jonas Verspaget, Hein W. Hugot, Jean-Pierre Karban, Amir Laukens, Debby Lawrance, Ian Lemann, Marc Levine, Arie Libioulle, Cecile Louis, Edouard Mowat, Craig Newman, William Panes, Julian Phillips, Anne Proctor, Deborah D. Regueiro, Miguel Russell, Richard Rutgeerts, Paul Sanderson, Jeremy Sans, Miquel Seibold, Frank Steinhart, A. Hillary Stokkers, Pieter C. F. Torkvist, Leif Kullak-Ublick, Gerd Wilson, David Walters, Thomas Targan, Stephan R. Brant, Steven R. Rioux, John D. D'Amato, Mauro Weersma, Rinse K. Kugathasan, Subra Griffiths, Anne M. Mansfield, John C. Vermeire, Severine Duerr, Richard H. Silverberg, Mark S. Satsangi, Jack Schreiber, Stefan Cho, Judy H. Annese, Vito Hakonarson, Hakon Daly, Mark J. Parkes, Miles TI Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci SO NATURE GENETICS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; SEQUENCE VARIANTS; COMMON VARIANTS; NEDD4 FAMILY; ASSOCIATION; GENE; IDENTIFICATION; RECEPTOR; PROTEIN; ACTIVATION AB We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 x 10(-8)). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease. C1 [Lee, James; Parkes, Miles] Univ Cambridge, Inflammatory Bowel Dis Res Grp, Cambridge, England. [Franke, Andre; Ellinghaus, David; Schreiber, Stefan] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany. [McGovern, Dermot P. B.; Targan, Stephan R.] Cedars Sinai Med Ctr, Inflammatory Bowel & Immunobiol Res Inst, Los Angeles, CA 90048 USA. [McGovern, Dermot P. B.; Haritunians, Talin; Rotter, Jerome I.; Taylor, Kent D.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Barrett, Jeffrey C.; Anderson, Carl A.; Bumpstead, Suzanne; Jostins, Luke] Wellcome Trust Sanger Inst, Cambridge, England. [Wang, Kai; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Radford-Smith, Graham L.; Simms, Lisa A.] Queensland Inst Med Res, Inflammatory Bowel Dis Res Grp, Brisbane, Qld 4006, Australia. [Ahmad, Tariq] Peninsula Coll Med & Dent, Exeter, Devon, England. [Lees, Charlie W.; Satsangi, Jack] Univ Edinburgh, Western Gen Hosp, Gastrointestinal Unit, Mol Med Ctr, Edinburgh, Midlothian, Scotland. [Balschun, Tobias] Univ Kiel, PopGen Biobank, Kiel, Germany. [Roberts, Rebecca; Barclay, Murray; Gearry, Richard] Univ Otago, Dept Med, Christchurch, New Zealand. [Bis, Joshua C.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Festen, Eleonora M.; Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands. [Georges, Michel] Univ Liege, Fac Vet Med, Dept Genet, Liege, Belgium. [Green, Todd; Raychaudhuri, Soumya; Daly, Mark J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Latiano, Anna; Annese, Vito] IRCCS CSS Hosp, Gastroenterol Unit, San Giovanni Rotondo, Italy. [Mathew, Christopher G.; Prescott, Natalie J.] Guys Hosp, Kings Coll London, Sch Med, Dept Med & Mol Genet, London SE1 9RT, England. [Schumm, Philip] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Sharma, Yashoda; Proctor, Deborah D.; Cho, Judy H.] Yale Univ, Dept Med, Sect Digest Dis, New Haven, CT 06520 USA. [Baldassano, Robert N.; Hakonarson, Hakon] Childrens Hosp Philadelphia, Dept Pediat, Ctr Pediat Inflammatory Bowel Dis, Philadelphia, PA 19104 USA. [Bayless, Theodore M.; Brant, Steven R.] Johns Hopkins Univ, Sch Med, Dept Med, Ctr Inflammatory Bowel Dis, Baltimore, MD 21205 USA. [Brand, Stephan; Glas, Juergen] Univ Munich, Dept Med 2, Univ Hosp Munich Grosshadern, Munich, Germany. [Buening, Carsten] Univ Med Berlin, Charite, Dept Gastroenterol, Berlin, Germany. [Cohen, Albert] Montreal Jewish Gen Hosp, Montreal, PQ, Canada. [Colombel, Jean-Frederick] Univ Lille, Registre Malad Inflammatoires Tube Digestif Nord, Lille, France. [Cottone, Mario] Cervello Hosp, Gastroenterol Unit, Palermo, Italy. [Stronati, Laura] Agenzia Nazl Nuove Tecnol Energia Sviluppo Econ S, Dept Biol Radiat & Human Hlth, Rome, Italy. [Denson, Ted] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [De Vos, Martine; Laukens, Debby] Ghent Univ Hosp, Dept Gastroenterol & Hepatol, B-9000 Ghent, Belgium. [D'Inca, Renata] Univ Hosp Padua, Div Gastroenterol, Padua, Italy. [Dubinsky, Marla] Cedars Sinai Med Ctr, Dept Pediat, Los Angeles, CA 90048 USA. [Edwards, Cathryn] Torbay Hosp, Torquay, Avon, England. [Florin, Tim] Mater Hlth Serv, Dept Gastroenterol, Brisbane, Qld, Australia. [Franchimont, Denis; Van Gossum, Andre] Univ Libre Brussels, Erasme Hosp, Dept Gastroenterol, B-1050 Brussels, Belgium. [Glas, Juergen] Univ Munich, Dept Prevent Dent & Periodontol, Munich, Germany. [Glas, Juergen] Rhein Westfal TH Aachen, Dept Human Genet, Aachen, Germany. [Guthery, Stephen L.] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA. [Halfvarson, Jonas] Orebro Univ Hosp, Dept Med, Orebro, Sweden. [Verspaget, Hein W.] Leiden Univ, Med Ctr, Dept Gastroenterol, Leiden, Netherlands. [Lemann, Marc] Univ Paris Diderot, GETAID Grp, Paris, France. [Karban, Amir] Technion Israel Inst Technol, Fac Med, Dept Gastroenterol, Haifa, Israel. [Lawrance, Ian] Univ Western Australia, Sch Med & Pharmacol, Fremantle, WA, Australia. [Levine, Arie] Tel Aviv Univ, Pediat Gastroenterol Unit, Wolfson Med Ctr, IL-69978 Tel Aviv, Israel. [Levine, Arie] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Libioulle, Cecile; Louis, Edouard] Univ Liege, Ctr Hosp Univ, Div Gastroenterol, Liege, Belgium. [Mowat, Craig; Phillips, Anne] Univ Dundee, Ninewells Hosp & Med Sch, Dept Med, Dundee DD1 9SY, Scotland. [Newman, William] Univ Manchester, Dept Med Genet, Manchester, Lancs, England. [Panes, Julian; Sans, Miquel] Hosp Clin Barcelona, Dept Gastroenterol, CIBER EHD, IDIBAPS, Barcelona, Spain. [Regueiro, Miguel; Duerr, Richard H.] Univ Pittsburgh, Sch Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Russell, Richard] Yorkhill Hosp, Dept Paediat Gastroenterol, Glasgow, Lanark, Scotland. [Rutgeerts, Paul; Vermeire, Severine] Univ Hosp Gasthuisberg, Div Gastroenterol, B-3000 Louvain, Belgium. [Sanderson, Jeremy] St Thomas Hosp, Dept Gastroenterol, Guys & St Thomas Natl Hlth Serv Fdn Trust, London, England. [Seibold, Frank] Univ Bern, Inselspital, Div Gastroenterol, CH-3010 Bern, Switzerland. [Steinhart, A. Hillary; Silverberg, Mark S.] Univ Toronto, Mt Sinai Hosp, Ctr Inflammatory Bowel Dis, Toronto, ON M5G 1X5, Canada. [Stokkers, Pieter C. F.] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol, NL-1105 AZ Amsterdam, Netherlands. [Torkvist, Leif] Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden. [Kullak-Ublick, Gerd] Univ Zurich Hosp, Div Clin Pharmacol & Toxicol, CH-8091 Zurich, Switzerland. [Wilson, David] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Walters, Thomas; Griffiths, Anne M.] Univ Toronto, Hosp Sick Children, Toronto, ON M5S 1A1, Canada. [Rioux, John D.] Univ Montreal, Montreal, PQ, Canada. [Rioux, John D.] Univ Montreal, Notre Dame Hosp, Res Ctr, Montreal Heart Inst, Montreal, PQ H2L 4M1, Canada. [D'Amato, Mauro] Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden. [Weersma, Rinse K.] Univ Med Ctr Groningen, Dept Gastroenterol, NL-9713 AV Groningen, Netherlands. [Kugathasan, Subra] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. [Mansfield, John C.] Univ Newcastle, Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England. [Duerr, Richard H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Schreiber, Stefan] Univ Kiel, Dept Gen Internal Med, Kiel, Germany. [Cho, Judy H.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Annese, Vito] Univ Hosp Careggi, Gastroenterol Unit, Florence, Italy. RP Parkes, M (reprint author), Univ Cambridge, Inflammatory Bowel Dis Res Grp, Cambridge, England. EM miles.parkes@addenbrookes.nhs.uk RI Wijmenga, Cisca/D-2173-2009; Rioux, John/A-9599-2015; Florin, Tim/F-1890-2010; Schreiber, Stefan/B-6748-2008; Montgomery, Grant/B-7148-2008; Prescott, Natalie/F-6490-2011; Hugot, Jean-Pierre/F-6594-2012; Mathew, Christopher/G-3434-2015; Whiteman, David/P-2728-2014; D'Amato, Mauro/F-2450-2010; Ellinghaus, David/G-4467-2012; Anderson, Carl/B-8327-2013; Silverberg, Mark/B-4183-2008; Latiano, Anna/R-1965-2016; Festen, Eleonora/S-3557-2016; Franke, Andre/B-2151-2010; OI Rioux, John/0000-0001-7560-8326; Schreiber, Stefan/0000-0003-2254-7771; Montgomery, Grant/0000-0002-4140-8139; Prescott, Natalie/0000-0002-5901-7371; Mathew, Christopher/0000-0003-4178-1838; Whiteman, David/0000-0003-2563-9559; D'Amato, Mauro/0000-0003-2743-5197; Anderson, Carl/0000-0003-1719-7009; Lee, James/0000-0001-5711-9385; Gearry, Richard/0000-0002-2298-5141; Halfvarson, Jonas/0000-0003-0122-7234; Newman, William/0000-0002-6382-4678; Latiano, Anna/0000-0003-3719-2061; Franke, Andre/0000-0003-1530-5811; Laukens, Debby/0000-0002-1984-5850; Duerr, Richard/0000-0001-6586-3905; Vermeire, Severine/0000-0001-9942-3019; Cottone, Mario/0000-0003-1523-7556; Panes, Julian/0000-0002-4971-6902; Wijmenga, Cisca/0000-0002-5635-1614; Barrett, Jeffrey/0000-0002-1152-370X FU Chief Scientist Office [CZB/4/540]; Medical Research Council [G0600329, G0800675, G0800759, ]; NCRR NIH HHS [M01 RR000425, M01-RR00425]; NHLBI NIH HHS [N01 HC-55222, N01 HC015103, N01 HC035129, N01 HC045133, N01-HC-75150, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01HC55222, N01HC75150, N01HC85079, N01HC85086, R01 HL087652, U01 HL080295]; NIAMS NIH HHS [K08 AR055688, K08 AR055688-01A1S1, K08 AR055688-03, K08 AR055688-04]; NIDDK NIH HHS [DK 063491, DK062413, DK062420, DK062422, DK062423, DK062429, DK062431, DK062432, DK064869, DK069513, DK084554, DK76984, K23 DK069513, P01 DK046763, P01-DK046763, P30 DK043351, P30 DK063491, R01 DK064869, R03 DK076984, R21 DK084554, U01 DK062413, U01 DK062420, U01 DK062422, U01 DK062423, U01 DK062429, U01 DK062431, U01 DK062432]; Wellcome Trust [089120, WT089120/Z/09/Z] NR 52 TC 1140 Z9 1154 U1 12 U2 118 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2010 VL 42 IS 12 BP 1118 EP + DI 10.1038/ng.717 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 684UZ UT WOS:000284578800016 PM 21102463 ER PT J AU de Jong, A Pena-Cruz, V Cheng, TY Clark, RA Van Rhijn, I Moody, DB AF de Jong, Annemieke Pena-Cruz, Victor Cheng, Tan-Yun Clark, Rachael A. Van Rhijn, Ildiko Moody, D. Branch TI CD1a-autoreactive T cells are a normal component of the human alpha beta T cell repertoire SO NATURE IMMUNOLOGY LA English DT Article ID CUTANEOUS LYMPHOCYTE ANTIGEN; ARYL-HYDROCARBON RECEPTOR; HUMAN LANGERHANS CELLS; NKT CELLS; SELF-GLYCOLIPIDS; PRESENTING CELLS; CD1D TETRAMERS; INTERLEUKIN 22; TH17 CELLS; HUMAN SKIN AB CD1 activates T cells, but the function and size of the possible human T cell repertoires that recognize each of the CD1 antigen-presenting molecules remain unknown. Using an experimental system that bypasses major histocompatibility complex (MHC) restriction and the requirement for defined antigens, we show that polyclonal T cells responded at higher rates to cells expressing CD1a than to those expressing CD1b, CD1c or CD1d. Unlike the repertoire of invariant natural killer T (NKT) cells, the CD1a-autoreactive repertoire contained diverse T cell antigen receptors (TCRs). Functionally, many CD1a-autoreactive T cells homed to skin, where they produced interleukin 22 (IL-22) in response to CD1a on Langerhans cells. The strong and frequent responses among genetically diverse donors define CD1a-autoreactive cells as a normal part of the human T cell repertoire and CD1a as a target of the T(H)22 subset of helper T cells. C1 [de Jong, Annemieke; Cheng, Tan-Yun; Van Rhijn, Ildiko; Moody, D. Branch] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Pena-Cruz, Victor] Dana Farber Canc Inst, Boston, MA 02115 USA. [Clark, Rachael A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Van Rhijn, Ildiko] Univ Utrecht, Fac Vet Med, Dept Immunol & Infect Dis, Utrecht, Netherlands. RP Moody, DB (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. EM bmoody@rics.bwh.harvard.edu OI de Jong, Annemieke/0000-0001-6707-6585 FU National Institute of Arthritis, Musculoskeletal and Skin Diseases [048632, AR056720]; National Institute of Allergy and Infectious Diseases [AI071155, AI054456, AI056299]; Damon Runyon Cancer Research Foundation; Burroughs Wellcome Fund; National Psoriasis Foundation FX We thank D.C. Barral, M. Brenner and M. Relloso (Harvard Medical School) and M. Sugita (Kyoto University) for CD1 plasmid constructs; J. Gumperz (University of Wisconsin) and M. Brigl (Harvard Medical School) for human NKT cell lines; G. Losyev for cell sorting; and K. Magalhaes, S. Huang, I.C. Ho and R. Grenningloh for technical advice. Supported by the National Institute of Arthritis, Musculoskeletal and Skin Diseases (048632 to D.B.M. and AR056720 to R.A.C.), the National Institute of Allergy and Infectious Diseases (AI071155 to D.B.M., and AI054456 and AI056299), the Damon Runyon Cancer Research Foundation (R.A.C.), the Burroughs Wellcome Fund (D.B.M.) and the National Psoriasis Foundation (A.d.J.). NR 58 TC 109 Z9 109 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2010 VL 11 IS 12 BP 1102 EP U98 DI 10.1038/ni.1956 PG 9 WC Immunology SC Immunology GA 680UX UT WOS:000284262200009 PM 21037579 ER PT J AU Paust, S Gill, HS Wang, BZ Flynn, MP Moseman, EA Senman, B Szczepanik, M Telenti, A Askenase, PW Compans, RW von Andrian, UH AF Paust, Silke Gill, Harvinder S. Wang, Bao-Zhong Flynn, Michael P. Moseman, E. Ashley Senman, Balimkiz Szczepanik, Marian Telenti, Amalio Askenase, Philip W. Compans, Richard W. von Andrian, Ulrich H. TI Critical role for the chemokine receptor CXCR6 in NK cell-mediated antigen-specific memory of haptens and viruses SO NATURE IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; GAMMA CHAIN; T-CELLS; LYMPHOID DEVELOPMENT; INFLUENZA INFECTION; ADAPTIVE IMMUNITY; DENDRITIC CELLS; HLA-B; EXPRESSION; MICE AB Hepatic natural killer (NK) cells mediate antigen-specific contact hypersensitivity (CHS) in mice deficient in T cells and B cells. We report here that hepatic NK cells, but not splenic or naive NK cells, also developed specific memory of vaccines containing antigens from influenza, vesicular stomatitis virus (VSV) or human immunodeficiency virus type 1 (HIV-1). Adoptive transfer of virus-sensitized NK cells into naive recipient mice enhanced the survival of the mice after lethal challenge with the sensitizing virus but not after lethal challenge with a different virus. NK cell memory of haptens and viruses depended on CXCR6, a chemokine receptor on hepatic NK cells that was required for the persistence of memory NK cells but not for antigen recognition. Thus, hepatic NK cells can develop adaptive immunity to structurally diverse antigens, an activity that requires NK cell-expressed CXCR6. C1 [Paust, Silke; Flynn, Michael P.; Moseman, E. Ashley; Senman, Balimkiz; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Paust, Silke; Telenti, Amalio] MGH & Harvard, MIT, Ragon Inst, Charlestown, MA USA. [Gill, Harvinder S.; Wang, Bao-Zhong; Compans, Richard W.] Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Gill, Harvinder S.; Wang, Bao-Zhong; Compans, Richard W.] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Gill, Harvinder S.] Texas Tech Univ, Dept Chem Engn, Lubbock, TX 79409 USA. [Szczepanik, Marian] Jagiellonian Univ, Coll Med, Dept Human Dev Biol, Krakow, Poland. [Telenti, Amalio] Univ Lausanne, Univ Hosp, Inst Microbiol, Lausanne, Switzerland. [Szczepanik, Marian; Askenase, Philip W.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [von Andrian, Ulrich H.] Immune Dis Inst, Boston, MA USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM uva@hms.harvard.edu RI von Andrian, Ulrich/A-5775-2008; Compans, Richard/I-4087-2013; Gill, Harvinder/D-8252-2014; OI Compans, Richard/0000-0003-2360-335X; Gill, Harvinder/0000-0003-0832-5291; Wang, Bao-Zhong/0000-0002-1561-4318 FU US National Institutes of Health [AI069259, AI072252, AI078897, HL56949, AR42689]; Ragon Institute; Cancer Research Institute; Ragon Institute of MIT, Harvard and MGH FX We thank G. Cheng and J.D. Sullivan for technical support and A. Wagers (Harvard Medical School) for Act(EGFP) mice. Supported by the US National Institutes of Health (AI069259, AI072252, AI078897, HL56949 and AR42689), the Ragon Institute (U.H.v.A.), the Cancer Research Institute (S.P.) and the Ragon Institute of MIT, Harvard and MGH (S.P.). NR 45 TC 246 Z9 252 U1 3 U2 23 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2010 VL 11 IS 12 BP 1127 EP U128 DI 10.1038/ni.1953 PG 10 WC Immunology SC Immunology GA 680UX UT WOS:000284262200012 PM 20972432 ER PT J AU El Khoury, J AF El Khoury, Joseph TI Neurodegeneration and the neuroimmune system SO NATURE MEDICINE LA English DT Letter ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; MICROGLIAL ACTIVATION; AMYLOID DEPOSITION; BETA; PET; ADJUVANT; FUTURE; MODELS; BRAIN C1 [El Khoury, Joseph] Massachusetts Gen Hosp, Lab Innate Immun & Neuroimmunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. [El Khoury, Joseph] Harvard Univ, Sch Med, Charlestown, MA USA. RP El Khoury, J (reprint author), Massachusetts Gen Hosp, Lab Innate Immun & Neuroimmunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. EM jelkhoury@partners.org NR 25 TC 8 Z9 8 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2010 VL 16 IS 12 BP 1369 EP 1370 DI 10.1038/nm1210-1369 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 690ZH UT WOS:000285048900014 PM 21135838 ER PT J AU Tanaka, H Kono, E Tran, CP Miyazaki, H Yamashiro, J Shimomura, T Fazli, L Wada, R Huang, JT Vessella, RL An, JB Horvath, S Gleave, M Rettig, MB Wainberg, ZA Reiter, RE AF Tanaka, Hiroshi Kono, Evelyn Tran, Chau P. Miyazaki, Hideyo Yamashiro, Joyce Shimomura, Tatsuya Fazli, Ladan Wada, Robert Huang, Jiaoti Vessella, Robert L. An, Jaibin Horvath, Steven Gleave, Martin Rettig, Matthew B. Wainberg, Zev A. Reiter, Robert E. TI Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance SO NATURE MEDICINE LA English DT Article ID MESENCHYMAL TRANSITION; ANDROGEN RECEPTOR; ANTITUMOR-ACTIVITY; STEM-CELLS; PROGRESSION; THERAPY; INDEPENDENCE; INCREASES; PATHWAY; BIOLOGY AB The transition from androgen-dependent to castration-resistant prostate cancer (CRPC) is a lethal event of uncertain molecular etiology. Comparing gene expression in isogenic androgen-dependent and CRPC xenografts, we found a reproducible increase in N-cadherin expression, which was also elevated in primary and metastatic tumors of individuals with CRPC. Ectopic expression of N-cadherin in nonmetastatic, androgen-dependent prostate cancer models caused castration resistance, invasion and metastasis. Monoclonal antibodies against the ectodomain of N-cadherin reduced proliferation, adhesion and invasion of prostate cancer cells in vitro. In vivo, these antibodies slowed the growth of multiple established CRPC xenografts, blocked local invasion and metastasis and, at higher doses, led to complete regression. N-cadherin-specific antibodies markedly delayed the time to emergence of castration resistance, markedly affected tumor histology and angiogenesis, and reduced both AKT serine-threonine kinase activity and serum interleukin-8 (IL-8) secretion. These data indicate that N-cadherin is a major cause of both prostate cancer metastasis and castration resistance. Therapeutic targeting of this factor with monoclonal antibodies may have considerable clinical benefit. (C) 2010 Nature America, Inc. All rights reserved. C1 [Tanaka, Hiroshi; Kono, Evelyn; Tran, Chau P.; Yamashiro, Joyce; Shimomura, Tatsuya; Wada, Robert; An, Jaibin; Rettig, Matthew B.; Reiter, Robert E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Tanaka, Hiroshi; Kono, Evelyn; Tran, Chau P.; Yamashiro, Joyce; Shimomura, Tatsuya; Huang, Jiaoti; Rettig, Matthew B.; Wainberg, Zev A.; Reiter, Robert E.] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Miyazaki, Hideyo] Univ Tokyo, Dept Urol, Tokyo, Japan. [Fazli, Ladan; Gleave, Martin] Univ British Columbia, Vancouver Prostate Ctr, Vancouver, BC V5Z 1M9, Canada. [Huang, Jiaoti] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. [Vessella, Robert L.] Univ Washington, Med Ctr, Dept Urol, Puget Sound Vet Hlth Care Adm, Seattle, WA 98195 USA. [An, Jaibin; Rettig, Matthew B.] Vet Affairs Greater Los Angeles Healthcare Syst W, Dept Med, Los Angeles, CA USA. [Horvath, Steven] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Horvath, Steven] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA. [Wainberg, Zev A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Reiter, Robert E.] Univ Calif Los Angeles, David Geffen Sch Med, Inst Mol Biol, Los Angeles, CA 90095 USA. RP Reiter, RE (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. EM rreiter@mednet.ucla.edu FU US National Cancer Institute Prostate Cancer SPORE at the University of California-Los Angeles [P50CA092131-09]; US Department of Defense [W81XWH-06-1-0324, W81XWH-09-1-0630, PC061456]; Takeda Pharmaceuticals; Jean Perkins Foundation; American Cancer Society [RSG-07-092-01-TBE] FX This work was supported in parts by the US National Cancer Institute Prostate Cancer SPORE at the University of California-Los Angeles (P50CA092131-09 to R. E. R.), US Department of Defense Prostate Cancer Research grants (W81XWH-06-1-0324 to Z.A.W., W81XWH-09-1-0630 to R. E. R. and M. B. R., PC061456 to J.H.), Takeda Pharmaceuticals, the Jean Perkins Foundation and the American Cancer Society (RSG-07-092-01-TBE to J.H.). We also thank S. and L. Resnick, the Prostate Cancer Foundation and the Luskin Foundation for generous support and J. Said and N. Doan for immunohistochemical assessments. LNCaP-CL1 cells were provided by C. L. Tso (University of California-Los Angeles). Plasmid p Delta VPR was provided by I. Chen (University of California-Los Angeles). NR 28 TC 128 Z9 134 U1 0 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2010 VL 16 IS 12 BP 1414 EP U96 DI 10.1038/nm.2236 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 690ZH UT WOS:000285048900035 PM 21057494 ER PT J AU Jagani, Z Mora-Blanco, EL Sansam, CG McKenna, ES Wilson, B Chen, DS Klekota, J Tamayo, P Nguyen, PTL Tolstorukov, M Park, PJ Cho, YJ Hsiao, K Buonamici, S Pomeroy, SL Mesirov, JP Ruffner, H Bouwmeester, T Luchansky, SJ Murtie, J Kelleher, JF Warmuth, M Sellers, WR Roberts, CWM Dorsch, M AF Jagani, Zainab Mora-Blanco, E. Lorena Sansam, Courtney G. McKenna, Elizabeth S. Wilson, Boris Chen, Dongshu Klekota, Justin Tamayo, Pablo Nguyen, Phuong T. L. Tolstorukov, Michael Park, Peter J. Cho, Yoon-Jae Hsiao, Kathy Buonamici, Silvia Pomeroy, Scott L. Mesirov, Jill P. Ruffner, Heinz Bouwmeester, Tewis Luchansky, Sarah J. Murtie, Joshua Kelleher, Joseph F. Warmuth, Markus Sellers, William R. Roberts, Charles W. M. Dorsch, Marion TI Loss of the tumor suppressor Snf5 leads to aberrant activation of the Hedgehog-Gli pathway SO NATURE MEDICINE LA English DT Article ID GENOMIC INSTABILITY; SWI/SNF COMPLEX; RHABDOID TUMORS; SONIC-HEDGEHOG; GENE; CANCER; MUTATIONS; EXPRESSION; CHROMATIN; MEDULLOBLASTOMA AB Aberrant activation of the Hedgehog (Hh) pathway can drive tumorigenesis(1). To investigate the mechanism by which glioma-associated oncogene family zinc finger-1 (GLI1), a crucial effector of Hh signaling(2), regulates Hh pathway activation, we searched for GLI1-interacting proteins. We report that the chromatin remodeling protein SNF5 (encoded by SMARCB1, hereafter called SNF5), which is inactivated in human malignant rhabdoid tumors (MRTs), interacts with GLI1. We show that Snf5 localizes to Gli1-regulated promoters and that loss of Snf5 leads to activation of the Hh-Gli pathway. Conversely, re-expression of SNF5 in MRT cells represses GLI1. Consistent with this, we show the presence of a Hh-Gli-activated gene expression profile in primary MRTs and show that GLI1 drives the growth of SNF5-deficient MRT cells in vitro and in vivo. Therefore, our studies reveal that SNF5 is a key mediator of Hh signaling and that aberrant activation of GLI1 is a previously undescribed targetable mechanism contributing to the growth of MRT cells. C1 [Mora-Blanco, E. Lorena; Sansam, Courtney G.; McKenna, Elizabeth S.; Wilson, Boris; Nguyen, Phuong T. L.; Roberts, Charles W. M.] Childrens Hosp Boston, Dept Pediat Oncol, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA USA. [Tamayo, Pablo; Cho, Yoon-Jae; Mesirov, Jill P.] Broad Inst Harvard, Cambridge, MA USA. [Tamayo, Pablo; Cho, Yoon-Jae; Mesirov, Jill P.] MIT, Cambridge, MA 02139 USA. [Tolstorukov, Michael; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA. [Cho, Yoon-Jae; Pomeroy, Scott L.] Childrens Hosp Boston, Dept Neurol, Boston, MA USA. [Ruffner, Heinz; Bouwmeester, Tewis] Novartis Inst BioMed Res, Basel, Switzerland. [Jagani, Zainab; Chen, Dongshu; Klekota, Justin; Hsiao, Kathy; Buonamici, Silvia; Luchansky, Sarah J.; Murtie, Joshua; Kelleher, Joseph F.; Warmuth, Markus; Sellers, William R.; Dorsch, Marion] Novartis Inst BioMed Res, Cambridge, MA USA. RP Dorsch, M (reprint author), Sanofi Aventis, Cambridge, MA USA. EM charles_roberts@dfci.harvard.edu; marion.dorsch@sanofi-aventis.com FU NCI NIH HHS [R01 CA113794, R01 CA121941] NR 39 TC 98 Z9 104 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2010 VL 16 IS 12 BP 1429 EP U112 DI 10.1038/nm.2251 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 690ZH UT WOS:000285048900037 PM 21076395 ER PT J AU McGregor, R Siegel, JM AF McGregor, Ronald Siegel, Jerome M. TI Illuminating the locus coeruleus: control of posture and arousal SO NATURE NEUROSCIENCE LA English DT Editorial Material ID IN-VIVO MICRODIALYSIS; RELEASE; NEURONS; PONTINE; CATAPLEXY; NUCLEUS; ATONIA; CELLS C1 [McGregor, Ronald; Siegel, Jerome M.] Vet Adm Greater Los Angeles Healthcare Syst, North Hills, CA USA. [McGregor, Ronald; Siegel, Jerome M.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [McGregor, Ronald; Siegel, Jerome M.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. RP McGregor, R (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, North Hills, CA USA. EM icelos@gmail.com; jsiegel@ucla.edu NR 15 TC 11 Z9 11 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 2010 VL 13 IS 12 BP 1448 EP 1449 DI 10.1038/nn1210-1448 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 684CW UT WOS:000284525800005 PM 21102568 ER PT J AU Goss, PE Chambers, AF AF Goss, Paul E. Chambers, Ann F. TI Does tumour dormancy offer a therapeutic target? SO NATURE REVIEWS CANCER LA English DT Review ID STAGE BREAST-CANCER; ADJUVANT TAMOXIFEN THERAPY; MINIMAL RESIDUAL DISEASE; MAMMARY-CARCINOMA CELLS; RANDOMIZED-TRIAL; BONE-MARROW; POSTMENOPAUSAL WOMEN; METASTATIC INEFFICIENCY; PREMENOPAUSAL WOMEN; ANGIOGENIC SWITCH AB The increasing number of cancer survivors is cause for celebration, but this expanding population has highlighted the problem of tumour dormancy, which can lead to relapse. As we start to understand more about the biology of dormant cancer cells, we can begin to address how best to treat this form of disease. Preclinical models and initial clinical trials, as exemplified in patients with breast cancer, are paving the way to address how best to treat long-term cancer survivors to minimize the risk of cancer recurrence. C1 [Chambers, Ann F.] Univ Western Ontario, London Reg Canc Program, London, ON N6A 4L6, Canada. [Chambers, Ann F.] Univ Western Ontario, Dept Oncol, London, ON N6A 4L6, Canada. [Goss, Paul E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Chambers, AF (reprint author), Univ Western Ontario, London Reg Canc Program, 790 Commissioners Rd E, London, ON N6A 4L6, Canada. EM ann.chambers@Lhsc.on.ca RI Chambers, Ann/L-6285-2015 OI Chambers, Ann/0000-0002-9509-5123 FU Avon Foundation for Women in New York, USA FX P.E.G. is supported by the Avon Foundation for Women in New York, USA. A.F.C. is Canada Research Chair in Oncology. NR 72 TC 128 Z9 133 U1 0 U2 23 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD DEC PY 2010 VL 10 IS 12 BP 871 EP 877 DI 10.1038/nrc2933 PG 7 WC Oncology SC Oncology GA 684TM UT WOS:000284572200013 PM 21048784 ER PT J AU Carey, L Winer, E Viale, G Cameron, D Gianni, L AF Carey, Lisa Winer, Eric Viale, Giuseppe Cameron, David Gianni, Luca TI Triple-negative breast cancer: disease entity or title of convenience? SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID EPITHELIAL-MESENCHYMAL TRANSITION; ESTROGEN-RECEPTOR STATUS; BASAL-LIKE PHENOTYPE; GENE-EXPRESSION PROFILES; POLY(ADP-RIBOSE) POLYMERASE; PROGESTERONE-RECEPTOR; PHASE-II; PROGNOSTIC-SIGNIFICANCE; ACTIVATING MUTATIONS; THERAPEUTIC STRATEGY AB This Review outlines the understanding and management of triple-negative breast cancer (TNBC). TNBC shares morphological and genetic abnormalities with basal-like breast cancer (BLBC), a subgroup of breast cancer defined by gene-expression profiling. However, TNBC and BLBC tumors are heterogeneous and overlap is incomplete. Breast cancers found in BRCA1 mutation carriers are also frequently triple negative and basal like. TNBC and BLBC occur most frequently in young women, especially African Americans, and tend to exhibit aggressive, metastatic behavior. These tumors respond to conventional chemotherapy but relapse more frequently than hormone receptor-positive, luminal subtypes and have a worse prognosis. New systemic therapies are urgently needed as most patients with TNBC and/or BLBC relapse with distant metastases, and hormonal therapies and HER2-targeted agents are ineffective in this group of tumors. Poly (ADP-ribose) polymerase inhibitors, angiogenesis inhibitors, EGFR-targeted agents, and src kinase and mTOR inhibitors are among the therapeutic agents being actively investigated in clinical trials in patients with TNBC and/or BRCA1-associated tumors. Increased understanding of the genetic abnormalities involved in the pathogenesis of TNBC, BLBC and BRCA1-associated tumors is opening up new therapeutic possibilities for these hard-to-treat breast cancers. C1 [Gianni, Luca] Fdn IRCCS Ist Nazl Tumori, I-20133 Milan, Italy. [Carey, Lisa] Univ N Carolina, Chapel Hill, NC 27599 USA. [Winer, Eric] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Viale, Giuseppe] Univ Milan, European Inst Oncol, I-20141 Milan, Italy. [Cameron, David] Edinburgh Univ Canc Ctr, Edinburgh EH4 2XU, Midlothian, Scotland. RP Gianni, L (reprint author), Fdn IRCCS Ist Nazl Tumori, Via Venezian 1, I-20133 Milan, Italy. EM luca.gianni@istitutotumori.mi.it NR 143 TC 256 Z9 262 U1 9 U2 60 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD DEC PY 2010 VL 7 IS 12 BP 683 EP 692 DI 10.1038/nrclinonc.2010.154 PG 10 WC Oncology SC Oncology GA 687DP UT WOS:000284756200006 PM 20877296 ER PT J AU Turley, SJ Fletcher, AL Elpek, KG AF Turley, Shannon J. Fletcher, Anne L. Elpek, Kutlu G. TI The stromal and haematopoietic antigen-presenting cells that reside in secondary lymphoid organs SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID CD8-ALPHA(+) DENDRITIC CELLS; FIBROBLASTIC RETICULAR CELLS; CD8(+) T-CELLS; HIGH ENDOTHELIAL VENULES; SPLENIC WHITE PULP; TOLERANCE IN-VIVO; STEADY-STATE; CROSS-PRESENTATION; PERIPHERAL TOLERANCE; SELF-ANTIGENS AB T cells encounter their cognate antigens in specialized compartments of secondary lymphoid organs (SLOs). There, dendritic cells (DCs) present self and non-self antigens to T cells, and promote immunity or tolerance depending on the availability of danger signals. Resident stromal cells orchestrate the interaction between T cells and DCs by recruiting them to T cell zones and guiding their migration within SLOs. Recent studies have shown that SLO-resident stromal cells also have a crucial role in tolerance induction in the periphery. In this Review, we discuss the roles of SLO-resident DCs and stromal cells in shaping T cell responses. C1 [Turley, Shannon J.; Fletcher, Anne L.; Elpek, Kutlu G.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Turley, Shannon J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Turley, SJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM shannon_turley@dfci.harvard.edu FU US National Institutes of Health [R01 DK074500, P01 AI045757]; American Association for Cancer Research; National Health Medical Research Council FX The authors thank D. Malhotra for thoughtful suggestions on the manuscript. We apologize to those authors who could not be cited here owing to space limitations. This work was supported by US National Institutes of Health grants R01 DK074500 and P01 AI045757 (to S.J.T.), the American Association for Cancer Research Centennial Postdoctoral Fellowship in Cancer Research (to K. G. E.) and a National Health Medical Research Council Postdoctoral Biomedical Training Fellowship (to A. L. F.). NR 137 TC 78 Z9 79 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD DEC PY 2010 VL 10 IS 12 BP 813 EP 825 DI 10.1038/nri2886 PG 13 WC Immunology SC Immunology GA 685CD UT WOS:000284601100008 PM 21088682 ER PT J AU Hochedlinger, K AF Hochedlinger, Konrad TI Journal club FROM MYOD1 TO IPS CELLS SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Editorial Material C1 [Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Howard Hughes Med Inst, Boston, MA 02114 USA. [Hochedlinger, Konrad] Harvard Stem Cell Inst, Ctr Regenerat Med, Boston, MA USA. [Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Boston, MA 02115 USA. [Hochedlinger, Konrad] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hochedlinger, K (reprint author), Massachusetts Gen Hosp, Ctr Canc, Howard Hughes Med Inst, Boston, MA 02114 USA. EM khochedlinger@helix.mgh.harvard.edu NR 0 TC 1 Z9 2 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD DEC PY 2010 VL 11 IS 12 DI 10.1038/nrm3018 PG 1 WC Cell Biology SC Cell Biology GA 684CT UT WOS:000284525500003 PM 21102604 ER PT J AU Kotton, CN AF Kotton, Camille N. TI Management of cytomegalovirus infection in solid organ transplantation SO NATURE REVIEWS NEPHROLOGY LA English DT Review ID GANCICLOVIR-RESISTANT CYTOMEGALOVIRUS; RENAL-ALLOGRAFT RECIPIENTS; STEM-CELL TRANSPLANTATION; AMPLICOR CMV MONITOR; LIVER-TRANSPLANT; PREEMPTIVE THERAPY; ORAL GANCICLOVIR; HIGH-RISK; LUNG TRANSPLANTATION; T-CELLS AB Cytomegalovirus (CMV) infections are among the most common infections that occur following solid organ transplantation. CMV disease ranges from asymptomatic viremia, to CMV syndrome, to tissue-invasive disease. As CMV prophylaxis, treatment, diagnostics, and overall awareness have improved, the general trend has been towards earlier diagnosis of CMV disease and more mild clinical presentations in solid organ transplant recipients. Major stumbling blocks remain in the areas of duration of prophylaxis for the individual recipient, in the identification of which patients might need secondary prophylaxis, in the treatment of resistant virus, and in the possible use of the adoptive transfer of CMV-specific T cells. Several guidelines have been published during the past few years regarding the management of CMV in solid organ transplant recipients. This Review covers CMV diagnostics, methods for the prevention of CMV infection, treatment of both regular and drug-resistant CMV, as well as future directions for CMV management and research. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Cox 5, Boston, MA 02114 USA. EM ckotton@partners.org NR 138 TC 47 Z9 49 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5061 J9 NAT REV NEPHROL JI Nat. Rev. Nephrol. PD DEC PY 2010 VL 6 IS 12 BP 711 EP 721 DI 10.1038/nrneph.2010.141 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 685JZ UT WOS:000284626300005 PM 20978468 ER PT J AU Peralta, CA Lin, F Shlipak, MG Siscovick, D Lewis, C Jacobs, DR Bibbins-Domingo, K AF Peralta, Carmen A. Lin, Feng Shlipak, Michael G. Siscovick, David Lewis, Cora Jacobs, David R., Jr. Bibbins-Domingo, Kirsten TI Race differences in prevalence of chronic kidney disease among young adults using creatinine-based glomerular filtration rate-estimating equations SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE chronic kidney disease; glomerular filtration rate; race ID STAGE RENAL-DISEASE; SERUM CREATININE; GFR; PERFORMANCE; HEALTH AB Background. Despite a higher incidence of end-stage renal disease (stage 5), blacks have been shown to have the same or lower prevalence of chronic kidney disease (CKD stages 3 and 4). Current creatinine-based glomerular filtration rate (GFR)-estimating equations may misclassify young, healthy blacks. Methods. Among 3501 young adults (mean age 45), we compared the prevalence of CKD in blacks and whites using the Modification of Diet in Renal Disease (MDRD) and the CKD Epidemiology Collaboration (CKD-EPI) equations. In addition, we used measured creatinine excretion rates to determine the actual excretion ratio for CARDIA (race coefficient 12%) and applied this to the CKD-EPI equation. We also studied the prevalence of CKD risk factors among black and white participants near the CKD threshold cut-off (eGFR CKD-EPI 60-80 mL/min/1.73 m(2)) to estimate the relative likelihood of misclassification in blacks and whites. Results. Using the MDRD equation, prevalence of CKD stages 4 and 5 was higher for blacks compared with whites (0.6% vs. 0.1%, P-value 0.05). In contrast, prevalence of eGFR <60 mL/min/1.73 m(2) was significantly higher for whites (3.6%) compared with blacks (1.9%), due to higher prevalence of stage 3 among whites. Prevalence of CKD was similar for blacks and whites using CKD-EPI equation (1.2%), but was higher among blacks when using the CARDIA-derived race coefficient (1.6% vs. 1.2%, P-value = 0.03). Among persons with eGFR by CKD-EPI of 60-80 mL/min/1.73 m(2), blacks had higher levels of albuminuria, uric acid, systolic blood pressure and higher diabetes prevalence. Conclusions. CKD classification among young blacks is very sensitive to the race coefficients. Despite whites having higher rates of CKD stage 3, blacks with eGFRs just above the CKD threshold had higher rates of CKD risk factors. Current equations used to define CKD may systematically miss a high-risk group of blacks at a time in the disease course when interventions are crucial. C1 [Peralta, Carmen A.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Peralta, Carmen A.; Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Lin, Feng; Shlipak, Michael G.; Bibbins-Domingo, Kirsten] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Siscovick, David] Univ Washington, Dept Med & Epidemiol, Seattle, WA 98195 USA. [Lewis, Cora] Univ Alabama, Div Prevent Med, Birmingham, AL USA. [Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. [Bibbins-Domingo, Kirsten] San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA 94110 USA. [Bibbins-Domingo, Kirsten] San Francisco Gen Hosp, UCSF Ctr Vulnerable Populat San Francisco, San Francisco, CA 94110 USA. RP Peralta, CA (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM Carmenalicia.peralta@ucsf.edu FU NIDDK [1K23DK082793-01] FX C.A.P. is funded by grant 1K23DK082793-01 from NIDDK. NR 15 TC 16 Z9 16 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD DEC PY 2010 VL 25 IS 12 BP 3934 EP 3939 DI 10.1093/ndt/gfq299 PG 7 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 685PK UT WOS:000284640400022 PM 20519233 ER PT J AU Gutierrez, OM Isakova, T Smith, K Epstein, M Patel, N Wolf, M AF Gutierrez, Orlando M. Isakova, Tamara Smith, Kelsey Epstein, Michael Patel, Neha Wolf, Myles TI Racial differences in postprandial mineral ion handling in health and in chronic kidney disease SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE calcium; ethnic differences; fibroblast growth factor 23; parathyroid hormone; phosphorus ID STAGE RENAL-DISEASE; D-ENDOCRINE SYSTEM; VITAMIN-D; UNITED-STATES; PARATHYROID-HORMONE; CALCIUM-ABSORPTION; AFRICAN-AMERICANS; WHITE WOMEN; METABOLISM; MORTALITY AB Background. Increased serum phosphate is associated with cardiovascular disease. Compared with whites, blacks have significantly higher serum phosphate and increased risk of hyperphosphataemia in health and chronic kidney disease (CKD). While population-based studies suggest that diminished urinary phosphorus excretion in blacks may explain these differences, few physiological studies explored the potential mechanisms. The aim of this study was to examine racial differences in postprandial urinary mineral ion excretion in health and in CKD. Methods. Twenty-eight healthy (18 white and 10 black) and 19 CKD (9 white and 10 black) subjects consumed a standardized meal; after which, blood and urine samples were collected for 4 h for measurement of phosphate, calcium, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). Results. Although serum phosphate did not differ by race, blacks had similar to 30% lower postprandial fractional excretion of phosphate than whites in health (P<0.001) and CKD (P=0.02). Similarly, blacks had similar to 35% lower fractional excretion of calcium in health (P=0.02) and CKD (P=0.3). Moreover, the postprandial response in serum calcium among CKD subjects differed by race (P=0.03), with serum calcium significantly decreasing in whites but not blacks. Conclusions. Blacks had lower fractional excretion of phosphate than whites despite similar levels of PTH and FGF23 in health and in CKD, suggesting racial variability in renal sensitivity to phosphaturic hormones. Furthermore, blacks defend postprandial serum calcium more effectively than whites in CKD. Further studies are needed to define the mechanisms underlying these observations and evaluate whether racial differences in mineral ion handling may contribute to disparities in CKD outcomes. C1 [Gutierrez, Orlando M.; Smith, Kelsey; Patel, Neha; Wolf, Myles] Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Dept Med, Miami, FL 33136 USA. [Isakova, Tamara; Epstein, Michael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Nephrol Div, Boston, MA USA. RP Gutierrez, OM (reprint author), Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Dept Med, Miami, FL 33136 USA. EM ogutierrez2@med.miami.edu FU American Kidney Fund Clinical Scientist in Nephrology Fellowship; National Institutes of Health [K30RR02229207, M01RR01066, K23DK081673, R01DK076116, R01DK081374] FX This study was supported by the American Kidney Fund Clinical Scientist in Nephrology Fellowship (to O.M.G. and T.I.), and grants K30RR02229207; M01RR01066 (Mallinckrodt General Clinical Research Program at the Massachusetts General Hospital); K23DK081673 (to O.M.G.); and R01DK076116 and R01DK081374 (to M.W.) from the National Institutes of Health. NR 35 TC 20 Z9 20 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD DEC PY 2010 VL 25 IS 12 BP 3970 EP 3977 DI 10.1093/ndt/gfq316 PG 8 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 685PK UT WOS:000284640400027 PM 20530498 ER PT J AU Garcia-Alloza, M Borrelli, LA Hyman, BT Bacskai, BJ AF Garcia-Alloza, Monica Borrelli, Laura A. Hyman, Bradley T. Bacskai, Brian J. TI Antioxidants have a rapid and long-lasting effect on neuritic abnormalities in APP:PS1 mice SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; Oxidative stress; alpha-Phenyl-N-tert-butyl nitrone (PBN); Ginkgo biloba extract (EGb 761); Trolox; Multiphoton microscopy (MPM); Neurite ID TRANSGENIC MOUSE MODEL; BILOBA EXTRACT EGB-761; ALZHEIMER-DISEASE MODEL; AMYLOID-BETA PLAQUES; GINKGO-BILOBA; OXIDATIVE STRESS; IN-VIVO; MULTIPHOTON MICROSCOPY; CACHE COUNTY; PROTEIN AB Senile plaques are a major pathological hallmark of Alzheimer's disease (AD). Compelling evidence suggests that senile plaques lead to structural alterations of neuronal processes and that local toxicity may be mediated by increased oxidative stress. Anti-oxidant therapy can alleviate the neuronal abnormalities in APP mice, but the time-course of this beneficial effect is unknown. We used multiphoton microscopy to assess in vivo the characteristics of antioxidant treatment on senile plaques and neurites in AD model mice (APPswe/PS1dE9). We observed that alpha-phenyl-N-tert-butyl nitrone (PBN), Ginkgo biloba extract (EGb 761) and Trolox had no effect on the size of existing senile plaques. However, all anti-oxidants had a straightening effect on curved neurites. This effect was detected as soon as 4 days after commencing the treatment, and was maintained after I month of daily treatment, with no further increase in the effect. The straightening of neurites persisted 15 days after stopping the treatment. These data indicate that neuronal plasticity is fast and still active in adult animals, and suggest that amelioration of the neuritic distortions associated with senile plaques with antioxidants is both rapid and long lasting. (C) 2008 Elsevier Inc. All rights reserved. C1 [Garcia-Alloza, Monica; Borrelli, Laura A.; Hyman, Bradley T.; Bacskai, Brian J.] Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, 114 16th St, Charlestown, MA 02129 USA. EM bbacskai@partners.org OI Garcia-Alloza, Monica/0000-0003-1610-4114 FU NIH [AG020570, EB000768, AG024688, AG08487]; IPSEN; AHA-Bugher Foundation FX This work was supported by NIH AG020570, EB000768, AG024688, IPSEN (BJB), NIH AG08487, and a fellowship from the AHA-Bugher Foundation fellowship (M.G.-A.). NR 63 TC 15 Z9 15 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD DEC PY 2010 VL 31 IS 12 BP 2058 EP 2068 DI 10.1016/j.neurobiolaging.2008.11.006 PG 11 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 677VE UT WOS:000284019500004 PM 19124175 ER PT J AU Wasterlain, CG Thompson, KW Suchomelova, L Niquet, J AF Wasterlain, Claude G. Thompson, Kerry W. Suchomelova, Lucie Niquet, Jerome TI Brain Energy Metabolism During Experimental Neonatal Seizures SO NEUROCHEMICAL RESEARCH LA English DT Article DE Epilepsy; Neonatal seizures; Energy metabolism; ATP; Brain development; Hypoglycemia ID NUCLEAR-MAGNETIC-RESONANCE; PROLONGED EPILEPTIC SEIZURES; INDUCED NEURONAL INJURY; IMMATURE RAT-BRAIN; FEBRILE SEIZURES; CEREBRAL METABOLISM; RECURRENT SEIZURES; COMBINED H-1; INVIVO P-31; DAMAGE AB During flurothyl seizures in 4-day-old rats, cortical concentration of ATP, phosphocreatine and glucose fell while lactate rose. Cortical energy use rate more than doubled, while glycolytic rate increased fivefold. Calculation of the cerebral metabolic balance during sustained seizures suggests that energy balance could be maintained in hyperglycemic animals, and would decline slowly in normoglycemia, but would be compromised by concurrent hypoglycemia, hyperthermia or hypoxia. These results suggest that the metabolic challenge imposed on the brain by this model of experimental neonatal seizures is milder than that seen at older ages, but can become critical when associated with other types of metabolic stress. C1 [Wasterlain, Claude G.; Thompson, Kerry W.; Suchomelova, Lucie; Niquet, Jerome] VA Greater Angeles Hlth Care Syst, Epilepsy Res Lab, W Los Angels, CA 90073 USA. [Thompson, Kerry W.] Occidental Coll, Dept Biol, Los Angeles, CA 90041 USA. [Wasterlain, Claude G.; Thompson, Kerry W.; Suchomelova, Lucie; Niquet, Jerome] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Wasterlain, Claude G.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. RP Wasterlain, CG (reprint author), VA Greater Angeles Hlth Care Syst, Epilepsy Res Lab, 11301 Wilshire Blvd, W Los Angels, CA 90073 USA. EM wasterla@ucla.edu FU VHA Research Service; NINDS [RO1-NS13515] FX Supported by VHA Research Service and by research grant RO1-NS13515 from NINDS. A large part of the credit for this work belongs to Dr. Thomas E. Duffy, who unfortunately died before its completion. We are indebted to Barbara Blackburn for preparation of the manuscript, and to Roger Baldwin for superb technical help. I (CGW) am particularly indebted to Dr Abel Lajtha for his support during my early days as a neurochemist. He was both a mentor and an inspiration, and was always available and generous with fresh ideas, new techniques and very wise advice. Abel and Claude Baxter welcomed me into the Society for Neurochemistry, which was a young and vibrant meeting place for all kinds of scientists. Abel was a strong leader, but his style was so kind and unassuming that I always felt like he was helping me to find my own way. There are only a few people whose influence on the world has been exclusively positive, and he is one of those elite few. I hope that he will continue to provide wisdom and inspiration to present and future neurochemists. NR 56 TC 12 Z9 14 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD DEC PY 2010 VL 35 IS 12 SI SI BP 2193 EP 2198 DI 10.1007/s11064-010-0339-4 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 695IX UT WOS:000285364900037 PM 21136154 ER PT J AU Reuter, M Rosas, HD Fischl, B AF Reuter, Martin Rosas, H. Diana Fischl, Bruce TI Highly accurate inverse consistent registration: A robust approach SO NEUROIMAGE LA English DT Article DE Image registration; Robust statistics; Inverse consistent alignment; Motion correction; Longitudinal analysis ID MEDICAL IMAGE REGISTRATION; SURFACE-BASED ANALYSIS; RIGID-BODY MOTION; GRAY-MATTER LOSS; CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; CORTICAL THICKNESS; BRAIN IMAGES; MRI; SCHIZOPHRENIA AB The registration of images is a task that is at the core of many applications in computer vision. In computational neuroimaging where the automated segmentation of brain structures is frequently used to quantify change, a highly accurate registration is necessary for motion correction of images taken in the same session, or across time in longitudinal studies where changes in the images can be expected. This paper, inspired by Nestares and Heeger (2000), presents a method based on robust statistics to register images in the presence of differences, such as jaw movement, differential MR distortions and true anatomical change. The approach we present guarantees inverse consistency (symmetry), can deal with different intensity scales and automatically estimates a sensitivity parameter to detect outlier regions in the images. The resulting registrations are highly accurate due to their ability to ignore outlier regions and show superior robustness with respect to noise, to intensity scaling and outliers when compared to state-of-the-art registration tools such as FLIRT (in FSL) or the coregistration tool in SPM. (C) 2010 Elsevier Inc. All rights reserved. C1 [Reuter, Martin; Rosas, H. Diana; Fischl, Bruce] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Reuter, Martin; Rosas, H. Diana; Fischl, Bruce] Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Reuter, Martin; Fischl, Bruce] MIT, Comp Sci Lab, Cambridge, MA 02139 USA. [Reuter, Martin; Fischl, Bruce] MIT, AI Lab, Cambridge, MA 02139 USA. RP Reuter, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM mreuter@nmr.mgh.harvard.ed RI Reuter, Martin/B-3456-2010 OI Reuter, Martin/0000-0002-2665-9693 FU National Center for Research Resources [P41-RR14075, BIRN002, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01 EB006758]; National Institute on Aging [R01 AG022381, U54 AG024904]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01, R01 NS042861, P01 NS058793]; Ellison Medical Foundation FX Support for this research was provided in part by the National Center for Research Resources (P41-RR14075, and the NCRR BIRN Morphometric Project BIRN002, U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (R01 EB006758), the National Institute on Aging (R01 AG022381, U54 AG024904), and the National Institute for Neurological Disorders and Stroke (R01 NS052585-01, R01 NS042861, P01 NS058793). Additional support was provided by The Autism 82 Dyslexia Project funded by the Ellison Medical Foundation. The authors would like to thank Dr. Greg Sorensen for kindly supplying the tumor sample data. NR 74 TC 237 Z9 237 U1 1 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2010 VL 53 IS 4 BP 1181 EP 1196 DI 10.1016/j.neuroimage.2010.07.020 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 654KB UT WOS:000282165800002 PM 20637289 ER PT J AU Wilcox, T Haslup, JA Boas, DA AF Wilcox, Teresa Haslup, Jennifer A. Boas, David A. TI Dissociation of processing of featural and spatiotemporal information in the infant cortex SO NEUROIMAGE LA English DT Article DE Near-infrared spectroscopy; Infants; Featural information; Spatiotemporal information; Cortical development ID INFERIOR TEMPORAL CORTEX; NEAR-INFRARED SPECTROSCOPY; OBJECT REPRESENTATIONS; INDIVIDUATE OBJECTS; OPTICAL TOPOGRAPHY; OCCLUSION EVENTS; VISUAL-CORTEX; AWAKE INFANTS; FROM-MOTION; RECOGNITION AB A great deal is known about the development of visual object processing capacities and the neural structures that mediate these capacities in the mature observer. In contrast, little is known about the neural structures that mediate these capacities in the infant or how these structures eventually give rise to mature processing. The present research used near-infrared spectroscopy to investigate neural activation in visual, temporal, and parietal cortex during object processing tasks. Infants aged 5-7 months viewed visual events that required processing of the featural (Experiment 1) or the spatiotemporal (Experiment 2) properties of objects. In Experiment 1, different patterns of neural were obtained in temporal cortex in response to shape than color information. In Experiment 2, different patterns of neural activation were obtained in parietal cortex in response to spatiotemporal (speed and path of motion) than featural (shape and color) information. These results suggest a dissociation of processing of featural and spatiotemporal information in the infant cortex and provide evidence for early functional specification of the human brain. The outcome of these studies informs brain-behavior models of cognitive development and lays the foundation for systematic investigation of the functional maturation of object processing systems in the infant brain. (C) 2010 Elsevier Inc. All rights reserved. C1 [Wilcox, Teresa; Haslup, Jennifer A.] Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. [Boas, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Wilcox, T (reprint author), Texas A&M Univ, Dept Psychol, 4235 TAMU, College Stn, TX 77843 USA. EM tgw@psyc.tamu.edu FU NSF [0518986, 0642996]; NIH [5R21HD048943, P41-RR14075] FX We thank Tracy Smith, Kayla Boone, Jennifer Norvell, and the staff of the Infant Cognition Lab at Texas A&M University for help with data collection and management, Lesley Wheeler for preparation of figures, and the infants and parents who so graciously participated in the research. This work was supported by NSF grants 0518986 and 0642996 to T.W., NIH grant 5R21HD048943 to T.W., and NIH grant P41-RR14075 to D.A.B. NR 48 TC 27 Z9 27 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2010 VL 53 IS 4 BP 1256 EP 1263 DI 10.1016/j.neuroimage.2010.06.064 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 654KB UT WOS:000282165800008 PM 20603218 ER PT J AU Andreano, JM Cahill, L AF Andreano, Joseph M. Cahill, Larry TI Menstrual cycle modulation of medial temporal activity evoked by negative emotion SO NEUROIMAGE LA English DT Article DE Progesterone; Emotion; fMRI; Amygdala; Hippocampus ID PLASMA-CORTICOSTERONE RESPONSES; PITUITARY-ADRENOCORTICAL AXIS; SEX-DIFFERENCES; ELECTRICAL-STIMULATION; GENDER-DIFFERENCES; AMYGDALA ACTIVITY; HORMONAL CYCLE; ADRENAL AXIS; ACUTE STRESS; LONG-TERM AB Previous studies have indicated phase-related differences in HPA activity and amygdala responsiveness in women, such that the response to negative emotional images is reduced during high-estrogen phases of the menstrual cycle. Other research has indicated an opposite effect of exogenous progesterone, increasing amygdala activity at some doses. However, no study to date has assessed the response of the brain's arousal circuitry to negative images during the luteal phase, when both progesterone and estrogen levels are elevated. To address this question, 17 naturally cycling women were each scanned during the early follicular and mid-luteal phases of the cycle, and response to IAPS images was assessed by fMRI. The results indicated significantly increased activity in hippocampus and amygdala during mid-luteal scans when compared to scans in the early follicular phase. These findings suggest that progesterone-mediated effects dominate during the luteal phase, and further suggest that estrogen and progesterone may play opposing roles in modulating the brain's arousal circuitry. (C) 2010 Elsevier Inc. All rights reserved. C1 [Andreano, Joseph M.; Cahill, Larry] Univ Calif Irvine, Ctr Neurobiol Learning & Memory, Dept Neurobiol & Behav, Irvine, CA 92717 USA. RP Andreano, JM (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA USA. EM andreano@nmr.mgh.harvard.edu FU NIMH NIH HHS [R01 MH057508-08, R01 MH057508] NR 46 TC 74 Z9 78 U1 0 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2010 VL 53 IS 4 BP 1286 EP 1293 DI 10.1016/j.neuroimage.2010.07.011 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 654KB UT WOS:000282165800012 PM 20637290 ER PT J AU Gollub, RL Turner, DA AF Gollub, Randy L. Turner, Dennis A. TI Neuroinformatics in Clinical and Translational Medicine-Novel Approaches SO NEUROINFORMATICS LA English DT Editorial Material ID DEMENTED OLDER-ADULTS; OPEN ACCESS SERIES; WORKING-MEMORY; MRI DATA; SCHIZOPHRENIA; DISEASE; DATABASE; FBIRN C1 [Gollub, Randy L.] Massachusetts Gen Hosp, Psychiat Neuroimaging Res Program, Charlestown, MA 02129 USA. [Turner, Dennis A.] Duke Univ, Med Ctr, Ctr Neuroengn, Durham, NC 27710 USA. [Gollub, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Gollub, Randy L.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. RP Gollub, RL (reprint author), Massachusetts Gen Hosp, Psychiat Neuroimaging Res Program, Bldg 120,Suite 100, Charlestown, MA 02129 USA. EM rgollub@partners.org OI Gollub, Randy L./0000-0002-9434-4044 NR 24 TC 1 Z9 1 U1 2 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 J9 NEUROINFORMATICS JI Neuroinformatics PD DEC PY 2010 VL 8 IS 4 SI SI BP 207 EP 212 DI 10.1007/s12021-010-9087-5 PG 6 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA 679XP UT WOS:000284194400001 PM 20924724 ER PT J AU Kim, DI Sui, J Rachakonda, S White, T Manoach, DS Clark, VP Ho, BC Schulz, SC Calhoun, VD AF Kim, Dae Il Sui, Jing Rachakonda, Srinivas White, Tonya Manoach, Dara S. Clark, V. P. Ho, Beng Choon Schulz, S. Charles Calhoun, Vince D. TI Identification of Imaging Biomarkers in Schizophrenia: A Coefficient-constrained Independent Component Analysis of the Mind Multi-site Schizophrenia Study SO NEUROINFORMATICS LA English DT Article DE Schizophrenia; Coefficient constrained independent component analysis; Independent component analysis; fMRI; Biomarkers; CCICA; Working memory; Auditory oddball; Sensorimotor ID WORKING-MEMORY PERFORMANCE; AUDITORY ODDBALL TASK; 1ST-EPISODE SCHIZOPHRENIA; FUNCTIONAL CONNECTIVITY; COGNITIVE DEFICITS; PREFRONTAL CORTEX; TIME-SERIES; FMRI; METAANALYSIS; DYSFUNCTION AB A number of recent studies have combined multiple experimental paradigms and modalities to find relevant biological markers for schizophrenia. In this study, we extracted fMRI features maps from the analysis of three experimental paradigms (auditory oddball, Sternberg item recognition, sensorimotor) for a large number (n=154) of patients with schizophrenia and matched healthy controls. We used the general linear model (GLM) and independent component analysis (ICA) to extract feature maps (i.e. ICA component maps and GLM contrast maps), which were then subjected to a coefficient-constrained independent component analysis (CCICA) to identify potential neurobilogical markers. A total of 29 different feature maps were extracted for each subject. Our results show a number of optimal feature combinations that reflect a set of brain regions that significantly discriminate between patients and controls in the spatial heterogeneity and amplitude of their feature signals. Spatial heterogeneity was seen in regions such as the superior/middle temporal and frontal gyri, bilateral parietal lobules, and regions of the thalamus. Most strikingly, an ICA feature representing a bilateral frontal pole network was consistently seen in the ten highest feature results when ranked on differences found in the amplitude of their feature signals. The implication of this frontal pole network and the spatial variability which spans regions comprising of bilateral frontal/temporal lobes and parietal lobules suggests that they might play a significant role in the pathophysiology of schizophrenia. C1 [Kim, Dae Il; Sui, Jing; Rachakonda, Srinivas; Clark, V. P.; Calhoun, Vince D.] Mind Res Network, Albuquerque, NM 87131 USA. [White, Tonya; Schulz, S. Charles] Univ Minnesota, Med Ctr, Dept Psychiat, Minneapolis, MN 55454 USA. [Manoach, Dara S.] Massachusetts Gen Hosp, Dept Psychiat, Neuroimaging Div, Charlestown, MA 02129 USA. [Clark, V. P.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect Engn, Albuquerque, NM 87131 USA. [Ho, Beng Choon] Univ Iowa, Coll Med, Dept Psychiat, Iowa City, IA 52242 USA. RP Kim, DI (reprint author), Mind Res Network, 1101 Yale Blvd NE, Albuquerque, NM 87131 USA. EM dkim@mrn.org; vcalhoun@unm.edu RI Ho, Beng-Choon/D-6959-2011; Clark, Vincent/B-3343-2010 OI Ho, Beng-Choon/0000-0003-3976-1555; Clark, Vincent/0000-0002-9151-2102 FU National Institutes of Health [1 RO1 EB 006841] FX This work was supported by the National Institutes of Health; Contract grant number: 1 RO1 EB 006841. We would like to personally thank Christopher Abbott for his insightful comments on this manuscript. NR 52 TC 18 Z9 18 U1 2 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 J9 NEUROINFORMATICS JI Neuroinformatics PD DEC PY 2010 VL 8 IS 4 SI SI BP 213 EP 229 DI 10.1007/s12021-010-9077-7 PG 17 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA 679XP UT WOS:000284194400002 PM 20607449 ER PT J AU Perlis, RH Ostacher, MJ Goldberg, JF Miklowitz, DJ Friedman, E Calabrese, J Thase, ME Sachs, GS AF Perlis, Roy H. Ostacher, Michael J. Goldberg, Joseph F. Miklowitz, David J. Friedman, Edward Calabrese, Joseph Thase, Michael E. Sachs, Gary S. TI Transition to Mania During Treatment of Bipolar Depression SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE bipolar disorder; mania; switch; antidepressant; adverse effect ID TREATMENT ENHANCEMENT PROGRAM; DISORDER STEP-BD; TREATMENT-EMERGENT MANIA; ANTIDEPRESSANT TREATMENT; SWITCH PROCESS; I DISORDER; FOLLOW-UP; COMBINATION; HYPOMANIA; RECOVERY AB Some individuals with bipolar disorder transition directly from major depressive episodes to manic, hypomanic, or mixed states during treatment, even in the absence of antidepressant treatment. Prevalence and risk factors associated with such transitions in clinical populations are not well established, and were examined in the Systematic Treatment Enhancement Program for Bipolar Disorder study, a longitudinal cohort study. Survival analysis was used to examine time to transition to mania, hypomania, or mixed state among 2166 bipolar I and II individuals in a major depressive episode. Cox regression was used to examine baseline clinical and sociodemographic features associated with hazard for such a direct transition. These features were also examined for interactive effects with antidepressant treatment. In total, 461/2166 subjects in a major depressive episode (21.3%) transitioned to a manic/hypomanic or mixed state before remission, including 289/1475 (19.6%) of those treated with antidepressants during the episode. Among the clinical features associated with greatest transition hazard were greater number of past depressive episodes, recent or lifetime rapid cycling, alcohol use disorder, previous suicide attempt, and history of switch while treated with antidepressants. Greater manic symptom severity was also associated with risk for manic transition among both antidepressant-treated and antidepressant-untreated individuals. Three features, history of suicide attempt, younger onset age, and bipolar subtype, exhibited differential effects between individuals treated with antidepressants and those who were not. These results indicate that certain clinical features may be associated with greater risk of transition from depression to manic or mixed states, but the majority of them are not specific to antidepressant-treated patients. Neuropsychopharmacology (2010) 35, 2545-2552; doi:10.1038/npp.2010.122; published online 8 September 2010 C1 [Perlis, Roy H.; Ostacher, Michael J.; Sachs, Gary S.] Massachusetts Gen Hosp, Bipolar Clin, Dept Psychiat, Boston, MA 02114 USA. [Perlis, Roy H.; Ostacher, Michael J.; Sachs, Gary S.] Massachusetts Gen Hosp, Res Program, Dept Psychiat, Boston, MA 02114 USA. [Perlis, Roy H.; Ostacher, Michael J.; Sachs, Gary S.] Harvard Univ, Sch Med, Boston, MA USA. [Goldberg, Joseph F.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Miklowitz, David J.] Univ Colorado, Dept Psychiat, Boulder, CO 80309 USA. [Friedman, Edward] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Calabrese, Joseph] Case Western Reserve Univ, Dept Psychiat, Cleveland, OH USA. [Thase, Michael E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Bipolar Clin, Dept Psychiat, 50 Staniford St,5th Floor, Boston, MA 02114 USA. EM rperlis@partners.org OI Ostacher, Michael/0000-0003-0353-7535 FU NIMH [R01MH086026]; National Institute of Mental Health (NIMH), National Institutes of Health [N01MH80001]; Eli Lilly; Elan/Eisai; AstraZeneca; Bristol-Myers Squibb; Pfizer; Bristol-Myers Squibb Company; GlaxoSmithkline; Janssen-Cilag; Merck; Abbott Laboratories; Bristol Myers Squibb/Otsuka; Ciba-Geigy; Janssen Pharmaceutica; Lilly Research Laboratories; MacArthur Foundation; National Alliance for Research in Schizophrenia and Affective Disorders; Novartis; Parke-Davis Pharmaceuticals; Robert Wood Johnson Pharmaceutical Research Institute; Sandoz Pharmaceuticals Corporation; Shire Labs; SmithKline Beecham Pharmaceuticals; Solvay/Wyeth; Stanley Medical Research Institute; Solvay; Tap Holdings; Teva Pharmaceuticals; UCB Pharma; Abbott; Janssen; Memory Pharmaceuticals; Repligen; Shire; Wyeth FX Dr Perlis is supported by NIMH R01MH086026. This project has been funded in whole or in part with Federal funds from the National Institute of Mental Health (NIMH), National Institutes of Health, under Contract N01MH80001. Any opinions, findings, and conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the NIMH. The authors thank Dr Katharina Trede for her translation of the 6th Edition of Kraepelin's text and assistance in tracing the emergence of the quotation that begins this article.; Dr Perlis has received research support from Eli Lilly, Elan/Eisai; Advisory/Consulting fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Pfizer; Speaking Fees or Honoraria from AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly, GlaxoSmithkline, Pfizer; and has Equity Holdings and Patents for Concordant Rater Systems.; Dr Goldberg has received speaking fees from AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Merck, and Pfizer. He has also been a scientific advisory board member or consultant to Eli Lilly.; Dr Calabrese has received funding from or is a consultant to the National Institutes of Mental Health, Abbott Laboratories, AstraZeneca, Bristol Myers Squibb/Otsuka, Ciba-Geigy, Merck, GlaxoSmithKline, Janssen Pharmaceutica, Lilly Research Laboratories, MacArthur Foundation, National Alliance for Research in Schizophrenia and Affective Disorders, Novartis, Parke-Davis Pharmaceuticals, Robert Wood Johnson Pharmaceutical Research Institute, Sandoz Pharmaceuticals Corporation, Shire Labs, SmithKline Beecham Pharmaceuticals, Solvay/Wyeth, Stanley Medical Research Institute, Solvay, Tap Holdings, Teva Pharmaceuticals, and UCB Pharma.; Dr Sachs has received research support from Abbott, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Memory Pharmaceuticals, NIMH, Novartis, Pfizer, Repligen, Shire, and Wyeth; he has served on the speakers bureaus of Abbott, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Memory Pharmaceuticals, Novartis, Pfizer, Sanofi-Aventis, and Wyeth; he has served as an advisory board member or consultant for Abbott, AstraZeneca, Bristol-Myers Squibb, Cephalon, CNS Response, Elan Pharmaceuticals, Eli Lilly, GlaxoSmithKline, Janssen, Memory Pharmaceuticals, Merck, Novartis, Organon, Pfizer, Repligen, Sanofi-Aventis, Shire, Sigma-Tau, Solvay, and Wyeth; and his spouse is a shareholder with Concordant Rater Systems. NR 30 TC 37 Z9 38 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2010 VL 35 IS 13 BP 2545 EP 2552 DI 10.1038/npp.2010.122 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 678TS UT WOS:000284104400007 PM 20827274 ER PT J AU Sollu, C Pars, K Cornu, TI Thibodeau-Beganny, S Maeder, ML Joung, JK Heilbronn, R Cathomen, T AF Soellue, Cem Pars, Kaweh Cornu, Tatjana I. Thibodeau-Beganny, Stacey Maeder, Morgan L. Joung, J. Keith Heilbronn, Regine Cathomen, Toni TI Autonomous zinc-finger nuclease pairs for targeted chromosomal deletion SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DOUBLE-STRAND BREAKS; HUMAN STEM-CELLS; GENE-THERAPY; RESTRICTION ENZYMES; MAJOR DETERMINANT; FORCE-FIELD; KNOCKOUT; CLEAVAGE; DOMAIN; INTEGRATION AB Zinc-finger nucleases (ZFNs) have been successfully used for rational genome engineering in a variety of cell types and organisms. ZFNs consist of a non-specific FokI endonuclease domain and a specific zinc-finger DNA-binding domain. Because the catalytic domain must dimerize to become active, two ZFN subunits are typically assembled at the cleavage site. The generation of obligate heterodimeric ZFNs was shown to significantly reduce ZFN-associated cytotoxicity in single-site genome editing strategies. To further expand the application range of ZFNs, we employed a combination of in silico protein modeling, in vitro cleavage assays, and in vivo recombination assays to identify autonomous ZFN pairs that lack cross-reactivity between each other. In the context of ZFNs designed to recognize two adjacent sites in the human HOXB13 locus, we demonstrate that two autonomous ZFN pairs can be directed simultaneously to two different sites to induce a chromosomal deletion in similar to 10% of alleles. Notably, the autonomous ZFN pair induced a targeted chromosomal deletion with the same efficacy as previously published obligate heterodimeric ZFNs but with significantly less toxicity. These results demonstrate that autonomous ZFNs will prove useful in targeted genome engineering approaches wherever an application requires the expression of two distinct ZFN pairs. C1 [Soellue, Cem; Pars, Kaweh; Cathomen, Toni] Hannover Med Sch, Dept Expt Hematol, D-3000 Hannover, Germany. [Soellue, Cem; Pars, Kaweh; Cornu, Tatjana I.; Heilbronn, Regine; Cathomen, Toni] Charite, Inst Virol, Berlin, Germany. [Thibodeau-Beganny, Stacey; Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA USA. [Thibodeau-Beganny, Stacey; Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Maeder, Morgan L.; Joung, J. Keith] Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA USA. [Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cathomen, T (reprint author), Hannover Med Sch, Dept Expt Hematol, D-3000 Hannover, Germany. EM cathomen.toni@mh-hannover.de RI Heilbronn, Regine/E-1349-2013; OI Cathomen, Toni/0000-0002-7757-4630 FU European Commission [ZNIP-037783, PERSIST-222878]; National Institutes of Health [R01GM069906, R01GM088040, R21HL091808]; Charite Medical School; Kind-Philipp-Stiftung fur Leukamieforschung; National Science Foundation FX European Commission's 6th and 7th Framework Programmes (ZNIP-037783, PERSIST-222878 to T.C.); The National Institutes of Health (R01GM069906, R01GM088040, R21HL091808 to J.K.J.); fellowships from Charite Medical School (to C.S.); 'Kind-Philipp-Stiftung fur Leukamieforschung' (to K.P.); the National Science Foundation (to M.L.M.), respectively. Funding for open access charge: European Commission's 7th Framework Programme, grant PERSIST-222878. NR 45 TC 59 Z9 62 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC PY 2010 VL 38 IS 22 BP 8269 EP 8276 DI 10.1093/nar/gkq720 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 696CU UT WOS:000285420300042 PM 20716517 ER PT J AU Fabrizio, KS Keltner, NL AF Fabrizio, Katherine S. Keltner, Norman L. TI Traumatic Brain Injury in Operation Enduring Freedom/Operation Iraqi Freedom: A Primer SO NURSING CLINICS OF NORTH AMERICA LA English DT Article DE Brain injury; Blast; Military; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; PSYCHIATRIC-DISORDERS; PART II; AFGHANISTAN; SOLDIERS; WAR; CONSEQUENCES; DEPRESSION; RECOVERY; LONG AB In greater numbers than in prior conflicts, service members deployed as part of Operation Enduring Freedom and Operation Iraqi Freedom have an increased risk of experiencing a traumatic brain injury (TBI). The basics of TBI are discussed, with particular attention paid to blast-related events, as this is a common mechanism of injury in this population. Particular attention is focused on the pharmacologic treatment of the sequlae of TBI and common comorbid conditions. C1 [Fabrizio, Katherine S.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. [Keltner, Norman L.] Univ Alabama, Sch Nursing, Birmingham, AL 35294 USA. RP Fabrizio, KS (reprint author), Birmingham Vet Affairs Med Ctr, Phys Med & Rehabil 117,700 S 19th St, Birmingham, AL 35233 USA. EM Katherine.Fabrizio@va.gov NR 39 TC 10 Z9 10 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0029-6465 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD DEC PY 2010 VL 45 IS 4 BP 569 EP + DI 10.1016/j.cnur.2010.06.003 PG 13 WC Nursing SC Nursing GA 683AI UT WOS:000284443700006 PM 20971337 ER PT J AU Cole, GM Ma, QL Frautschy, SA AF Cole, Greg M. Ma, Qiu-Lan Frautschy, Sally A. TI Dietary fatty acids and the aging brain SO NUTRITION REVIEWS LA English DT Review DE Alzheimer's disease; amyloid; dementia; docosahexaenoic acid (DHA); omega-3 fatty acid (n-3) ID MILD COGNITIVE IMPAIRMENT; RETINOID-X-RECEPTOR; DISEASE MOUSE MODEL; ALZHEIMERS-DISEASE; DOCOSAHEXAENOIC ACID; AMYLOID-BETA; DENDRITIC PATHOLOGY; MEDITERRANEAN DIET; SYNAPTIC PROTEINS; CONTROLLED-TRIAL AB Aging contributes to physiological decline and vulnerability to disease. In the brain, even with minimal neuronal loss, aging increases oxidative damage, inflammation, demyelination, impaired processing, and metabolic deficits, particularly during pathological brain aging. In this review, the possible role of docosahexaenoic acid (DHA) in the prevention of age-related disruption of brain function is discussed. High-fat diabetogenic diets, cholesterol, and the omega-6 fatty acid arachidonate and its prostaglandin metabolites have all been implicated in promoting the pathogenesis of Alzheimer's disease. Evidence presented here shows DHA acts to oppose this, exerting a plethora of pleiotropic activities to protect against the pathogenesis of Alzheimer's disease. C1 [Cole, Greg M.; Ma, Qiu-Lan; Frautschy, Sally A.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Cole, Greg M.; Frautschy, Sally A.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Cole, Greg M.; Ma, Qiu-Lan; Frautschy, Sally A.] Greater Los Angeles Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr, VA Med Ctr, North Hills, CA USA. RP Cole, GM (reprint author), Greater Los Angeles Healthcare Syst, GRECC Vet Affairs, Res 151,Bldg 7,Rm A101,16111 Plummer St, North Hills, CA 91343 USA. EM gmcole@ucla.edu FU National Center for Complementary and Alternative Medicine (NCCAM) [NIH R01 AT3008, NIA R01AG13471, VA MERIT, AG021975] FX Funding. This work was supported by National Center for Complementary and Alternative Medicine (NCCAM) NIH R01 AT3008, NIA R01AG13471, VA MERIT (SAF, GMC), AG021975 (SAF). NR 80 TC 33 Z9 33 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0029-6643 EI 1753-4887 J9 NUTR REV JI Nutr. Rev. PD DEC PY 2010 VL 68 IS 12 SU 2 BP S102 EP S111 DI 10.1111/j.1753-4887.2010.00345.x PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 684WZ UT WOS:000284587300007 PM 21091943 ER PT J AU Vredenburgh, JJ Cloughesy, T Samant, M Prados, M Wen, PY Mikkelsen, T Schiff, D Abrey, LE Yung, WKA Paleologos, N Nicholas, MK Jensen, R Das, A Friedman, HS AF Vredenburgh, James J. Cloughesy, Timothy Samant, Meghna Prados, Michael Wen, Patrick Y. Mikkelsen, Tom Schiff, David Abrey, Lauren E. Yung, W. K. Alfred Paleologos, Nina Nicholas, Martin K. Jensen, Randy Das, Asha Friedman, Henry S. TI Corticosteroid Use in Patients with Glioblastoma at First or Second Relapse Treated with Bevacizumab in the BRAIN Study SO ONCOLOGIST LA English DT Article DE Corticosteroid; Glioblastoma; Anti-VEGF; Antiangiogenic ID PHASE-II TRIAL; PLUS IRINOTECAN; RECURRENT GLIOBLASTOMA; MALIGNANT GLIOMA; EFFICACY; PATTERNS; TUMORS AB Background. Vascular endothelial growth factor inhibitors have corticosteroid-sparing effects in patients with high-grade gliomas. We assessed corticosteroid use in patients with recurrent glioblastoma treated with bevacizumab (BEV) in the BRAIN study (J Clin Oncol 2009; 27: 4733-4740). Methods. BRAIN was a phase II, multicenter, randomized, noncomparative trial of BEV alone (n = 85) or in combination with irinotecan (CPT-11) (n = 82) in adults with recurrent glioblastoma. Median corticosteroid dose for patients who used corticosteroids at baseline was summarized by treatment arm; the percentage of patients who had sustained (>= 50% corticosteroid dose reduction for >= 50% of time on study drug) or complete (discontinuation of corticosteroid for >= 25% of time on study drug) reduction in corticosteroid dose overall and by objective response and progression-free survival was calculated. The incidence of corticosteroidrelated adverse events was summarized. Results. In each treatment group, 50% of patients were using systemic corticosteroids at baseline. The majority of those experienced a reduction in dose while receiving BEV-based therapy. Thirteen (30.2%) BEV and 20 (46.5%) BEV + CPT-11 patients had a sustained reduction of corticosteroid dose; 7 (16.3%) BEV and 9 20.9%) BEV + CPT-11 patients had a complete reduction of corticosteroid dose. The majority of patients who had an objective response or progression-free survival >6 months experienced corticosteroid dose reduction. Approximately 64% of patients who used corticosteroids while receiving BEV-based therapy experienced infection. Conclusion. BEV may have corticosteroid-sparing effects in patients with recurrent glioblastoma. Corticosteroid reduction may positively affect patient health-related quality of life. Given the exploratory nature of the analyses in a noncomparative study, these results should be interpreted cautiously. The Oncologist 2010;15:1329-1334 C1 [Vredenburgh, James J.] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr Duke, Durham, NC 27710 USA. [Cloughesy, Timothy] Univ Calif Los Angeles, Los Angeles, CA USA. [Samant, Meghna; Das, Asha] Genentech Inc, San Francisco, CA USA. [Prados, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mikkelsen, Tom] Henry Ford Hosp, Detroit, MI 48202 USA. [Schiff, David] Univ Virginia, Charlottesville, VA USA. [Abrey, Lauren E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Yung, W. K. Alfred] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Paleologos, Nina] NorthShore Univ HealthSyst, Evanston, IL USA. [Nicholas, Martin K.] Univ Chicago, Chicago, IL 60637 USA. [Jensen, Randy] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. RP Vredenburgh, JJ (reprint author), Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr Duke, Box 3624, Durham, NC 27710 USA. EM vrede001@mc.duke.edu FU Roche Genentech; Genentech, Inc. FX James J. Vredenburgh: Consultant/advisory role: Genentech, Inc.; Honoraria: Genentech, Inc.; Timothy Cloughesy: Honoraria: Genentech, Inc. (advisory board); Expert testimony: Genentech (GBM ODAC meeting); Meghna Samant: Employment/leadership position: Genentech, Inc.; Michael Prados: None; Patrick Y. Wen: None; Tom Mikkelsen: Consultant/advisory role: Roche Genentech (advisory board); Honoraria: Roche Genentech (Speaker's Bureau); Research funding/contracted research: Roche Genentech (clinical trials support); David Schiff: Honoraria: Genentech, Inc.; Research funding/contracted research: Genentech, Inc.; Lauren E. Abrey: Consultant/advisory role: Genentech, Inc.; Research funding/contracted research: Genentech, Inc.; W. K. Alfred Yung: Consultant/advisory role: Genentech, Inc. (advisory board); Nina Paleologos: Consultant/advisory role: Genentech, Inc.; Honoraria: Genentech, Inc.; Martin K. Nicholas: Consultant/advisory role: Genentech, Inc. (advisory boards); Honoraria: Genentech, Inc.; Research funding/contracted research: Genentech, Inc. (funding a trial written by M.K.N. under their IST program); Randy Jensen: None; Asha Das: Employment/leadership position: Genentech, Inc.; Ownership interest: F. Hoffmann-La Roche Ltd. (stock); Henry S. Friedman: Consultant/advisory role: Genentech, Inc.; Honoraria: Genentech, Inc. NR 14 TC 34 Z9 34 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD DEC PY 2010 VL 15 IS 12 BP 1329 EP 1334 DI 10.1634/theoncologist.2010-0105 PG 6 WC Oncology SC Oncology GA 699SK UT WOS:000285682900011 PM 21147867 ER PT J AU Bunnell, CA Shulman, LN AF Bunnell, Craig A. Shulman, Lawrence N. TI Will We Be Able To Care For Cancer Patients In The Future? SO ONCOLOGY-NEW YORK LA English DT Article ID CELL LUNG-CANCER; PHYSICIAN WORKFORCE; COLORECTAL-CANCER; GEFITINIB; CARBOPLATIN; PACLITAXEL; COMBINATION; CETUXIMAB; SURVIVORS; TRIAL AB The number of cancer patients and cancer survivors continues to increase rapidly amid predictions of a shortfall in physicians to care for them. In addition, newer cancer therapies have become increasingly complex and resource-intensive, compounding the impending workforce shortage. Simultaneously, the growing understanding of the biologic heterogeneity of cancer and the development of pharmacogenomics have opened up the possibility of personalized approaches to cancer diagnosis and treatment. Such personalization has been promulgated as a means of decreasing the cost of drug development, improving the efficacy of treatments, and reducing treatment toxicity. Although there have been notable successes, the fulfillment of these promises has been inconsistent. Providing care for future cancer patients will require the development of innovative delivery models. Moreover, new approaches to clinical research design, to the assessment of therapeutic value, and to the approval of and reimbursement for diagnostics and treatments are needed. C1 [Bunnell, Craig A.; Shulman, Lawrence N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bunnell, Craig A.; Shulman, Lawrence N.] Harvard Univ, Sch Med, Boston, MA USA. RP Bunnell, CA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 25 TC 8 Z9 8 U1 1 U2 1 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD DEC PY 2010 VL 24 IS 14 BP 1343 EP 1348 PG 6 WC Oncology SC Oncology GA 800ED UT WOS:000293341700012 PM 21294481 ER PT J AU Goldstein, MA Schapira, L AF Goldstein, Michael A. Schapira, Lidia TI Where Expert Opinion Meets Public Resistance SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 [Goldstein, Michael A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Schapira, Lidia] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goldstein, MA (reprint author), Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD DEC PY 2010 VL 24 IS 14 BP 1350 EP 1351 PG 2 WC Oncology SC Oncology GA 800ED UT WOS:000293341700013 PM 21294482 ER PT J AU Smits, M Nilsson, J Mir, SE van der Stoop, PM Hulleman, E Niers, JM Hamer, PCDW Marquez, VE Cloos, J Krichevsky, AM Noske, DP Tannous, BA Wurdinger, T AF Smits, Michiel Nilsson, Jonas Mir, Shahryar E. van der Stoop, Petra M. Hulleman, Esther Niers, Johanna M. Hamer, Phillip C. de Witt Marquez, Victor E. Cloos, Jacqueline Krichevsky, Anna M. Noske, David P. Tannous, Bakhos A. Wurdinger, Thomas TI miR-101 is down-regulated in glioblastoma resulting in EZH2-induced proliferation, migration, and angiogenesis SO ONCOTARGET LA English DT Article DE cancer; microRNA; Policomb group; glioblastoma; angiogenesis ID HISTONE METHYLTRANSFERASE ACTIVITY; H3 LYSINE-27 METHYLATION; GROUP PROTEIN EZH2; MOUSE DEVELOPMENT; PROSTATE-CANCER; CELL FATE; IN-VIVO; POLYCOMB; EXPRESSION; GENE AB Background: Glioblastoma (GBM) is a malignant brain tumor with dismal prognosis. GBM patients have a median survival of less than 2 years. GBM is characterized by fast cell proliferation, infiltrative migration, and by the induction of angiogenesis. MicroRNAs and polycomb group (PcG) proteins have emerged as important regulators of gene expression. Methods: Here we determined that miR-101 is down-regulated in GBM, resulting in overexpression of the miR-101 target PcG protein EZH2, a histone methyltransferase affecting gene expression profiles in an epigenetic manner. Results: Inhibition of EZH2 in vitro by pre-miR-101, EZH2 siRNA, or small molecule DZNep, attenuated GBM cell growth, migration/invasion, and GBM-induced endothelial tubule formation. In addition, for each biological process we identified ontology-associated transcripts that significantly correlate with EZH2 expression. Inhibition of EZH2 in vivo by systemic DZNep administration in a U87-Fluc-mCherry GBM xenograft mouse imaging model resulted in reduced tumor growth. Conclusion: Our results indicate that EZH2 has a versatile function in GBM progression and that its overexpression is at least partly due to decreased miR-101 expression. Inhibition of EZH2 may be a potential therapeutic strategy to target GBM proliferation, migration, and angiogenesis.cancer, microRNA, Policomb group, glioblastoma, angiogenesis C1 [Smits, Michiel; Nilsson, Jonas; Mir, Shahryar E.; van der Stoop, Petra M.; Hulleman, Esther; Hamer, Phillip C. de Witt; Cloos, Jacqueline; Noske, David P.; Wurdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Neurosurg, Neurooncol Res Grp, Amsterdam, Netherlands. [Smits, Michiel; Nilsson, Jonas; Mir, Shahryar E.; van der Stoop, Petra M.; Hulleman, Esther; Hamer, Phillip C. de Witt; Cloos, Jacqueline; Noske, David P.; Wurdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Pediat Oncol Hematol, Neurooncol Res Grp, Amsterdam, Netherlands. [Niers, Johanna M.; Tannous, Bakhos A.; Wurdinger, Thomas] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. [Niers, Johanna M.; Tannous, Bakhos A.; Wurdinger, Thomas] Massachusetts Gen Hosp, Dept Radiol, Mol Neurogenet Unit, Boston, MA 02114 USA. [Niers, Johanna M.; Tannous, Bakhos A.; Wurdinger, Thomas] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Marquez, Victor E.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21701 USA. [Krichevsky, Anna M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Nilsson, J (reprint author), Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Neurosurg, Neurooncol Res Grp, Amsterdam, Netherlands. EM j.nilsson@vumc.nl; t.wurdinger@vumc.nl RI De Witt Hamer, Philip/E-7630-2013 OI De Witt Hamer, Philip/0000-0003-2988-8544 FU Dutch Cancer Foundation; Lion's Cancer Research Foundation; Umea University, Sweden; Stichting Translational Research CCA/VU University medical center; Swedish Research Counsil; NIH, National Cancer Institute, Center for Cancer Research FX We thank X. O. Breakefield for helpful discussions and P. Van der Valk and L. Wedekind for technical assistance. This work was supported by the Dutch Cancer Foundation (S. E. M.), Lion's Cancer Research Foundation, Umea University, Sweden; Stichting Translational Research CCA/VU University medical center; Swedish Research Counsil (R.J.A.N.). This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 45 TC 117 Z9 122 U1 1 U2 11 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD DEC PY 2010 VL 1 IS 8 BP 710 EP 720 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 802JQ UT WOS:000293506500003 PM 21321380 ER PT J AU Nucera, C Lawler, J Hodin, R Parangi, S AF Nucera, Carmelo Lawler, Jack Hodin, Richard Parangi, Sareh TI The BRAF(V600E) mutation: what is it really orchestrating in thyroid cancer? SO ONCOTARGET LA English DT Article DE BRAFV600E; thrombospondin-1; integrins; collagen; laminin; extracellular matrix; gene set enrichment analysis; thyroid cancer ID GENE-EXPRESSION PROFILES; RET/PTC REARRANGEMENTS; EXTRACELLULAR-MATRIX; BRAF MUTATION; CELL BIOLOGY; B-RAF; THROMBOSPONDIN-1; ACTIVATION; CARCINOMA; DEDIFFERENTIATION AB BRAF(V600E) is a constitutively active onco-kinase and is the most common genetic alteration in papillary thyroid carcinoma (PTC), and in anaplastic thyroid carcinoma as well, albeit at a lower frequency. The BRAF(V600E) mutation in some studies has been significantly associated with extra-thyroidal extension, metastases, recurrence, and mortality in patients with PTC. A recent genome-wide expression profiling approach (Gene Set Enrichment Analysis (GSEA)) and in vitro and in vivo functional studies revealed that BRAF(V600E) affects extracellular matrix composition (i.e. increased expression of some collagens and laminins) and promotes thyroid cancer migration and invasion. BRAF(V600E) through the phospho-MEK1/2 and phospho-ERK1/2 pathway may control a network of genes crucial in integrating and regulating the extracellular and intracellular signaling in thyroid cancer cells, which may be fundamental to trigger an abnormal cell differentiation/totipotency and shape/polarity, and contribute to tumor aggressiveness mechanisms (i.e. cell adhesion, migration, and invasion). Increasing our knowledge of BRAF(V600E)-modulated ECM genes and targeting the subset of genes essential for tumor aggressiveness will help establish a novel paradigm for treatment of thyroid cancers harboring BRAF(V600E). Furthermore, identifying downstream events from the BRAF(V600E)/ERK1/2 pathway will eventually identify novel biomarkers that can be used to correlate with disease outcome and overall survival. C1 [Nucera, Carmelo; Hodin, Richard; Parangi, Sareh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thyroid Canc Res Lab,Endocrine Surg Unit, Boston, MA 02467 USA. [Nucera, Carmelo; Lawler, Jack] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Canc Biol & Angiogenesis,Dept Pathol, Boston, MA 02215 USA. RP Parangi, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thyroid Canc Res Lab,Endocrine Surg Unit, Boston, MA 02467 USA. EM sparangi@partners.org FU NIH; MIUR, Italy FX Dr. Carmelo Nucera (M. D., Ph.D.) was a recipient of a doctorate Fellowship in Experimental Endocrinology and Metabolic Diseases (MIUR, Italy). Drs. Sareh Parangi (M. D.), Jack Lawler (PhD), and Richard A. Hodin (M. D.) were funded through the NIH Grants. NR 35 TC 32 Z9 32 U1 0 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD DEC PY 2010 VL 1 IS 8 BP 751 EP 756 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 802JQ UT WOS:000293506500008 PM 21321384 ER PT J AU Gower, EW Keay, LJ Oechsler, RA Iovieno, A Alfonso, EC Jones, DB Colby, K Tuli, SS Patel, SR Lee, SM Irvine, J Stulting, RD Mauger, TF Schein, OD AF Gower, Emily W. Keay, Lisa J. Oechsler, Rafael A. Iovieno, Alfonso Alfonso, Eduardo C. Jones, Dan B. Colby, Kathryn Tuli, Sonal S. Patel, Seema R. Lee, Salena M. Irvine, John Stulting, R. Doyle Mauger, Thomas F. Schein, Oliver D. TI Trends in Fungal Keratitis in the United States, 2001 to 2007 SO OPHTHALMOLOGY LA English DT Article ID SOFT CONTACT-LENSES; MICROBIAL KERATITIS; RISK-FACTORS; ULCERATIVE KERATITIS; SOUTH-INDIA; DAILY-WEAR; SPECTRUM; OUTBREAK; EYE; SINGAPORE AB Objective: Fungal keratitis is a serious ocular infection that is considered to be rare among contact lens wearers. The recent Fusarium keratitis outbreak raised questions regarding the background rate of Fusarium-related keratitis and other fungal keratitis in this population. Design: Retrospective, multicenter case series. Participants: Six hundred ninety-five cases of fungal keratitis cases who presented to 1 of 10 tertiary medical centers from 2001 to 2007. Methods: Ten tertiary care centers in the United States performed a retrospective review of culture-positive fungal keratitis cases at their centers between January 2001 and December 2007. Cases were identified using microbiology, pathology, and/or confocal microscopy records. Information was collected on contact lens status, method of diagnosis, and organism(s) identified. The quarterly number of cases by contact lens status was calculated and Poisson regression was used to evaluate presence of trends. The Johns Hopkins Medicine Institutional Review Board (IRB) and the IRBs at each participating center approved the research. Main Outcome Measures: Quarterly number of fungal keratitis cases and fungal species. Results: We identified 695 fungal keratitis cases; 283 involved the use of contact lenses. The quarterly number of Fusarium cases increased among contact lens wearers (CLWs) during the period that ReNu with MoistureLoc (Bausch & Lomb, Rochester, NY) was on the market, but returned to prior levels after withdrawal of the product from the market. The quarterly frequency of other filamentous fungi cases showed a statistically significant increase among CLWs comparing October 2004 through June 2006 with July 2006 through December 2007 with January 2001 through September 2004 (P<0.0001). Conclusions: The quarterly number of Fusarium fungal keratitis cases among CLWs returned to pre-Renu with Moistureloc levels after removal of the product from the market. However, the number of other filamentous fungal keratitis cases, although small, seems to have increased among refractive CLWs. Reasons for these apparent increases are unclear. C1 [Gower, Emily W.; Schein, Oliver D.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA. [Keay, Lisa J.] George Inst, Sydney, NSW, Australia. [Oechsler, Rafael A.; Alfonso, Eduardo C.] Univ Miami, Bascom Palmer Eye Inst, Miami, FL USA. [Iovieno, Alfonso] CIR Lab Ophthalmol, Rome, Italy. [Iovieno, Alfonso] GB Bietti Eye Fdn, Rome, Italy. [Jones, Dan B.] Baylor Coll Med, Cullen Eye Inst, Dept Ophthalmol, Houston, TX 77030 USA. [Colby, Kathryn] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Tuli, Sonal S.] Univ Florida, Dept Ophthalmol, Gainesville, FL USA. [Patel, Seema R.] Thomas Jefferson Univ, Jefferson Med Coll, Wills Eye Hosp, Philadelphia, PA 19107 USA. [Lee, Salena M.] Univ Calif San Francisco, FI Proctor Fdn, San Francisco, CA 94143 USA. [Irvine, John] Univ So Calif, Doheny Eye Inst, Los Angeles, CA USA. [Stulting, R. Doyle] Emory Univ, Emory Eye Ctr, Atlanta, GA 30322 USA. [Mauger, Thomas F.] Ohio State Univ, Havener Eye Inst, Columbus, OH 43210 USA. RP Gower, EW (reprint author), Johns Hopkins Sch Med, 600 N Wolfe St,116 Wilmer Bldg, Baltimore, MD 21287 USA. EM egower1@jhmi.edu RI Iovieno, Alfonso /B-2939-2011 FU Bausch Lomb Inc.; Bausch & Lomb, Incorporated.; Research to Prevent Blindness FX The authors have made the following disclosures: Eduardo Alfonso - Consultant - Bausch & Lomb, Inc. Oliver Schein - Consultant - Bausch & Lomb Inc. R. Doyle Stulting - Consultant - Allergan Incorporated and Alcon Laboratories Inc. Emily Gower - Grant support - Bausch & Lomb Inc. This project was funded by an unrestricted grant from Bausch & Lomb, Incorporated. Bausch & Lomb did not provide input into the content of this manuscript. Funded through an unrestricted grant from Bausch & Lomb Incorporated. B&L did not have input on the content of the manuscript or the analyses. Dr. Gower is a recipient of the Research to Prevent Blindness Althouse Special Scholars Award. NR 24 TC 36 Z9 38 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 2010 VL 117 IS 12 BP 2263 EP 2267 DI 10.1016/j.ophtha.2010.03.048 PG 5 WC Ophthalmology SC Ophthalmology GA 688SI UT WOS:000284872600005 PM 20591493 ER PT J AU Ng, E Ilsen, PF AF Ng, Eileen Ilsen, Pauline F. TI Orbital Metastases SO OPTOMETRY-JOURNAL OF THE AMERICAN OPTOMETRIC ASSOCIATION LA English DT Article DE Orbital metastasis; Radiation; Palliative therapy; Proptosis; Ptosis; Diplopia ID RENAL-CELL CARCINOMA; RADIATION-INDUCED MENINGIOMAS; BREAST-CARCINOMA; TUMORS; CANCER; EYE; MELANOMA; ADENOCARCINOMA; RETINOPATHY; MANAGEMENT AB BACKGROUND: Orbital metastasis, although uncommon, is a condition optometrists should consider in a patient presenting with proptosis, ptosis, diplopia, or a lid mass with a history of cancer. However, in as many as 19% of cases, patients have no prior or concurrent history of systemic cancer when presenting with ophthalmic symptoms. If suspecting an orbital metastasis, neuroimaging is important, as well as a referral to the patient's primary care provider, oncologist, and ophthalmologist. CASE REPORTS: Three patients with orbital metastasis are discussed. The first was a 55-year-old white man who initially presented with a left ptosis of unclear etiology. Magnetic resonance imaging of his orbits and an orbital biopsy found metastatic esophageal adenocarcinoma. Radiotherapy and chemotherapy were initiated, but the patient died shortly afterward. The second patient was a 49-year-old black man who also presented with a ptosis of the right upper eyelid. An area of the retina appeared elevated; ophthalmic B-scan and computed tomography of the orbits confirmed the presence of a mass, determined to be metastatic lung carcinoma to the right orbit. A course of radiotherapy was initiated, but the patient died 3 clays after completing therapy. The last case was a 77-year-old white man with a history of metastasis to the left orbit from non-Hodgkin's lymphoma. On examination, he had proptosis of the left eye, initially thought to be caused by a recurrence of the metastasis. However, a computed tomography scan showed a new meningioma in the same orbit, and treatment was started. The proptosis improved, and the patient continues to be followed up regularly. CONCLUSIONS: Any patient with proptosis and/or ptosis with a history of cancer should be evaluated for orbital metastasis. Optometrists should keep in mind that an orbital metastasis may represent the initial manifestation of undiagnosed systemic cancer. Prognosis can be poor, and thus treatment is sometimes palliative in nature, intending to slow the progression of the disease instead of providing a cure. Optometry 2010;81:647-657 C1 W Los Angeles Vet Affairs Healthcare Ctr, Los Angeles, CA USA. So Calif Coll Optometry, Los Angeles, CA USA. RP Ng, E (reprint author), W Los Angeles Vet Affairs Healthcare, Optometry, Bldg 304,Room 2-111,11031 Wilshire Blvd, Los Angeles, CA 90073 USA. EM eng510@gmail.com NR 53 TC 5 Z9 5 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-1839 J9 OPTOMETRY JI Optometry PD DEC PY 2010 VL 81 IS 12 BP 647 EP 657 DI 10.1016/j.optm.2010.07.026 PG 11 WC Ophthalmology SC Ophthalmology GA 778ML UT WOS:000291708300005 PM 21111373 ER PT J AU Singh, JA Ayub, S AF Singh, J. A. Ayub, S. TI Accuracy of VA databases for diagnoses of knee replacement and hip replacement SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Hip replacement; Knee replacement; Validity; Databases; Veterans Affairs ID HEALTH-CARE-SYSTEM; VETERANS; QUALITY AB Purpose: To examine the validity of International Classification of Diseases-Ninth Revision (ICD-9) and Current Procedural Terminology (CPT) codes for knee replacement and hip replacement in Veterans Affairs (VA) databases. Methods: From a cohort of veterans who received health care at Minneapolis VA Medical Center and/or affiliated medical facilities, we obtained four random samples of 50 patients each with: neither hip nor knee replacement code, knee replacement code only, hip replacement code only and both knee and hip replacement codes. The gold standard was documentation of knee or hip replacement surgery in patient medical records. Accuracy of ICD-9 or CPT code for knee and hip replacement was assessed by calculating sensitivity, specificity, positive and negative predictive values (PPV and NPV). Results: Of the 200 patients, medical records were available for 166:140 (70%) had complete medical records and 26 (13%) had incomplete medical records. Knee replacement codes were accurate with excellent PPV of 95%, sensitivity of 95%, specificity of 96% and NPV of 96%. Hip replacement codes were accurate with excellent PPV of 98%, sensitivity of 96%, specificity of 99% and NPV of 96%. Sensitivity analyses that included incomplete charts had little impact on these estimates. The procedure dates found in VA databases matched exactly with medical records in 96%. Conclusions: The ICD-9 and CPT codes for knee replacement and hip replacement in VA databases are valid. These codes may be used to identify cohorts of veterans with knee replacement and hip replacement for research studies. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. C1 [Singh, J. A.] Univ Alabama, Birmingham, AL 35294 USA. [Singh, J. A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Singh, J. A.] Mayo Clin, Sch Med, Dept Hlth Sci Res, Rochester, MN USA. [Singh, J. A.] Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA. [Singh, J. A.] VA Med Ctr, Minneapolis, MN USA. [Ayub, S.] Univ Minnesota, Div Rheumatol, Minneapolis, MN USA. RP Singh, JA (reprint author), Univ Alabama, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU Allergan; Takeda; Savient; Wyeth; Amgen; URL pharmaceuticals; NIH (Mayo Clinic Center for Clinical and Translational Research) [KL2 RR024151-01]; Birmingham VA Medical Center, Alabama, USA FX There are no financial conflicts related to this work. JAS has received speaker honoraria from Abbott; research and travel grants from Allergan, Takeda, Savient, Wyeth and Amgen; and consultant fees from Savient and URL pharmaceuticals. SA has no financial conflicts.; JAS's time was protected for research through a NIH CTSA Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research) grant. The funding source had no contributions to design or conduct of study, preparation of manuscript or decision to submit it for publication. This material is the result of work supported by the resources and the use of facilities at the Birmingham VA Medical Center, Alabama, USA. NR 14 TC 20 Z9 20 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD DEC PY 2010 VL 18 IS 12 BP 1639 EP 1642 DI 10.1016/j.joca.2010.10.003 PG 4 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 701IT UT WOS:000285812300012 PM 20950694 ER PT J AU Bumpous, JM Randolph, GW AF Bumpous, Jeffrey M. Randolph, Gregory W. TI The Expanding Utility of Office-Based Ultrasound for the Head and Neck Surgeon SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Ultrasound; Head and neck surgery; Office-based ultrasound ID DIFFERENTIATED THYROID-CARCINOMA; RADIOFREQUENCY ABLATION; PRIMARY HYPERPARATHYROIDISM; ULTRASONOGRAPHY; CONTROVERSIES; MANAGEMENT; NODULES AB This article presents basics of ultrasound technology for the office, evaluation technique, thyroid and parathyroid imaging, ultrasound for neck lymphatics, office-based head and neck ultrasound biopsy, and therapeutic applications of head and neck ultrasound. C1 [Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Bumpous, Jeffrey M.] Univ Louisville, Univ Surg Associates, Dept Surg, Louisville, KY 40202 USA. RP Randolph, GW (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Gregory_Randolph@meei.harvard.edu RI Bumpous, Jeffrey/B-8127-2013 NR 16 TC 9 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 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD DEC PY 2010 VL 43 IS 6 BP 1203 EP + DI 10.1016/j.otc.2010.08.009 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 683WD UT WOS:000284507400006 PM 21044736 ER PT J AU Cashman, EC AF Cashman, Emma C. TI Otolaryngology and Irish literature: An important medico-literary alliance COMMENTARY SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Editorial Material AB For a comparatively small island, Ireland has made a disproportionately large contribution to world literature in all its aspects. The literary lineage of those who pursue medicine and also write is long and well established. The Irish contribution to world literature in all its aspects is well documented. Less explored, however, is the prominent influence of Dublin-based otolaryngologists in the Irish literary movement at the turn of the last century. Here, we examine two such figures, Sir William Wilde and Oliver St. John Gogarty, and their pivotal roles both professionally and in establishing Ireland on the world's literary stage. During the early part of the 1800s, otology was perceived as a defunct subspecialty that could be adequately managed, without much expertise, in the primary care setting. It was through the efforts of William Wilde and others that otology gained clinical and scientific credence during the latter half of the 19th century. Copyright (C) 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Cashman, EC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 7 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD DEC PY 2010 VL 143 IS 6 BP 745 EP 748 DI 10.1016/j.otohns.2010.09.002 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 690BF UT WOS:000284974400003 PM 21109072 ER PT J AU Nazar, G Garmendia, ML Royer, M McDowell, JA Weymuller, EA Yueh, B AF Nazar, Gonzalo Garmendia, Maria Luisa Royer, Michel McDowell, Jennifer A. Weymuller, Ernest A., Jr. Yueh, Bevan TI Spanish validation of the University of Washington Quality of Life questionnaire for head and neck cancer patients SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID PERFORMANCE STATUS SCALE; OROPHARYNGEAL CANCER; UW-QOL; DOMAIN; LARYNGECTOMY; DISABILITY AB OBJECTIVE: The University of Washington Quality of Life (UW-QOL) questionnaire is one of the most widely used instruments to evaluate the quality of life of head and neck cancer patients. The aim of this study was to perform a Spanish translation and validation of the UW-QOL questionnaire. STUDY DESIGN: A cross-sectional study. SETTING: Three tertiary-care hospitals and a laryngectomee rehabilitation center. SUBJECTS AND METHODS: The translation and cultural adaptation of the questionnaire were performed following accepted international guidelines. The psychometric validation was performed on a consecutive series of patients treated for squamous cell carcinoma of the upper aerodigestive tract with no signs of relapse, recruited from May 2007 to December 2008. Eligible subjects were invited to complete the Spanish version of the UW-QOL questionnaire during routine clinical consultation, and complete it again within 15 days. Subjects also completed a validated Spanish version of the Goldberg Mental Health Survey and were evaluated by the use of the Karnofsky Index. RESULTS: A Spanish version of the questionnaire was developed in iterative fashion. In the psychometric validation process, a total of 76 patients were analyzed. Reliability was excellent, including both internal consistency (Cronbach's alpha of 0.84) and test-retest reliability (intraclass correlation coefficient between 0.91 and 0.97 with a confidence interval of 95%). Construct validity was supported by statistically significant relationships between the Karnofsky Index, the Goldberg Mental Health Survey, and the translated UW-QOL questionnaire. CONCLUSION: The Spanish version of the UW-QOL questionnaire appears to be culturally appropriate and psychometrically valid. Copyright (C) 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved. C1 [Nazar, Gonzalo] Clin Las Condes, Dept Otolaryngol, Santiago, Chile. [Garmendia, Maria Luisa] Univ Chile, Sch Publ Hlth, Santiago, Chile. [Royer, Michel] Univ Chile, Hosp Clin, Dept Otolaryngol, Santiago, Chile. [McDowell, Jennifer A.] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. [Weymuller, Ernest A., Jr.] Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Yueh, Bevan] Univ Minnesota, Dept Otolaryngol Head & Neck Surg, Minneapolis, MN USA. RP Nazar, G (reprint author), Clin Las Condes, Dept Otolaryngol, Lo Fontecilla 441, Santiago, Chile. RI Garmendia, Maria Luisa/H-7417-2013; OI Garmendia, Maria Luisa/0000-0002-0589-6091; Yueh, Bevan/0000-0003-1380-1053 FU Chilean Society of Otolaryngology, Head and Neck Surgery FX This study was financially supported by the Chilean Society of Otolaryngology, Head and Neck Surgery The funding organization had no influence in study design, data analysis or manuscript writing The Chilean Society of Otolaryngology only demands that the paper resulting from the funded research must be published in a medical journal NR 29 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 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD DEC PY 2010 VL 143 IS 6 BP 801 EP 807 DI 10.1016/j.otohns.2010.08.008 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 690BF UT WOS:000284974400012 PM 21109081 ER PT J AU McCall, AA Curtin, HD McKenna, MJ AF McCall, Andrew A. Curtin, Hugh D. McKenna, Michael J. TI Posterior Semicircular Canal Dehiscence Arising From Temporal Bone Fibrous Dysplasia SO OTOLOGY & NEUROTOLOGY LA English DT Editorial Material C1 [McCall, Andrew A.; McKenna, Michael J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [McCall, Andrew A.; Curtin, Hugh D.; McKenna, Michael J.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Curtin, Hugh D.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP McKenna, MJ (reprint author), 243 Charles St, Boston, MA 02114 USA. EM Michael_McKenna@meei.harvard.edu NR 5 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD DEC PY 2010 VL 31 IS 9 BP 1516 EP 1517 DI 10.1097/MAO.0b013e3181be6b12 PG 2 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 678VW UT WOS:000284111700030 PM 19816226 ER PT J AU Koruth, JS Heist, EK Milan, DJ AF Koruth, Jacob S. Heist, E. Kevin Milan, David J. TI Pacemaker Tachycardia with Changing Rates SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Editorial Material DE defibrillation-ICD; electrocardiogram C1 [Koruth, Jacob S.; Heist, E. Kevin; Milan, David J.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Koruth, JS (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA. EM js_koruth@yahoo.com 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 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD DEC PY 2010 VL 33 IS 12 BP 1552 EP 1553 DI 10.1111/j.1540-8159.2010.02816.x PG 2 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 690NZ UT WOS:000285012800024 PM 20561228 ER PT J AU Mankarious, LA Goudy, SL AF Mankarious, Leila A. Goudy, Steven L. TI Craniofacial and upper airway development SO PAEDIATRIC RESPIRATORY REVIEWS LA English DT Article DE Craniofacial abnormalities; Candidate gene defects; Clinical manifestations ID OBSTRUCTIVE SLEEP-APNEA; PIERRE-ROBIN-SEQUENCE; CLEFT-PALATE; ROBIN,PIERRE SEQUENCE; MICE; MORPHOGENESIS; EXPRESSION; TONGUE; MOUSE; FGF8 AB Development of the craniofacial and upper airway structures is a complex choreography of mesenchymal and epithelial tissues responding to soluble growth factors and transcription factors in a tightly regulated sequence. Interruption of the development process or mutation of required transcription or growth factors leads to congenital anomalies of the facial and airway structures. Oftentimes, these patients suffer life-long consequences, require multiple medical and surgical interventions, and have significant associated morbidity and mortality. Furthering our understanding of the basic developmental mechanisms of craniofacial and upper airway development will lead to improved diagnostic and treatment strategies to improve the care of these patients. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Mankarious, Leila A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Goudy, Steven L.] Vanderbilt Univ, Vanderbilt Childrens Hosp, Nashville, TN 37232 USA. RP Mankarious, LA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM Leila_mankarious@meei.harvard.edu; Steven.l.goudy@vanderbilt.edu FU [K08 NIDCR DE017953-01A2] FX Dr Goudy is currently supported by K08 NIDCR DE017953-01A2. NR 36 TC 2 Z9 3 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1526-0542 J9 PAEDIATR RESPIR REV JI Paediatr. Respir. Rev. PD DEC PY 2010 VL 11 IS 4 BP 193 EP 198 DI 10.1016/j.prrv.2010.06.003 PG 6 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 704AH UT WOS:000286023000002 PM 21109176 ER PT J AU Morasco, BJ Duckart, JP Carr, TP Deyo, RA Dobscha, SK AF Morasco, Benjamin J. Duckart, Jonathan P. Carr, Thomas P. Deyo, Richard A. Dobscha, Steven K. TI Clinical characteristics of veterans prescribed high doses of opioid medications for chronic non-cancer pain SO PAIN LA English DT Article DE Chronic pain; Opioids; Epidemiology; Quality of life; Pain/drug therapy ID PRIMARY-CARE PHYSICIANS; CHRONIC BACK-PAIN; ADMINISTRATIVE DATA; NONMALIGNANT PAIN; ATTITUDES; PRESCRIPTIONS; THERAPY; ASSOCIATION; MANAGEMENT; DISORDERS AB Little is known about patients prescribed high doses of opioids to treat chronic non-cancer pain, though these patients may be at higher risk for medication-related complications. We describe the prevalence of high-dose opioid use and associated demographic and clinical characteristics among veterans treated in a VA regional healthcare network. Veterans with chronic non-cancer pain prescribed high doses of opioids (>= 180 mg/day morphine equivalent; n = 478) for 90+ consecutive days were compared to two groups with chronic pain: Traditional-dose (5-179 mg/day; n = 500) or no opioid (n = 500). High-dose opioid use occurred in 2.4% of all chronic pain patients and in 8.2% of all chronic pain patients prescribed opioids long-term. The average dose in the high-dose group was 324.9 (SD = 285.1) mg/day. The only significant demographic difference among groups was race (p = 0.03) with black veterans less likely to receive high doses. High-dose patients were more likely to have four or more pain diagnoses and the highest rates of medical, psychiatric, and substance use disorders. After controlling for demographic factors and VA facility, neuropathy, low back pain, and nicotine dependence diagnoses were associated with increased likelihood of high-dose prescriptions. High-dose patients frequently did not receive care consistent with treatment guidelines: there was frequent use of short-acting opioids, urine drug screens were administered to only 25.7% of patients in the prior year, and 32.0% received concurrent benzodiazepine prescriptions, which may increase risk for overdose and death. Further study is needed to identify better predictors of high-dose usage, as well as the efficacy and safety of such dosing. Published by Elsevier B.V. on behalf of International Association for the Study of Pain. C1 [Morasco, Benjamin J.; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR 97201 USA. [Carr, Thomas P.] Oregon Hlth & Sci Univ, Div Gen Med & Geriatr, Dept Med, Primary Care Div,Portland VA Med Ctr, Portland, OR 97201 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97201 USA. [Duckart, Jonathan P.; Dobscha, Steven K.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Mental & Phys D, Portland, OR USA. RP Morasco, BJ (reprint author), Portland VA Med Ctr R&D99, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM benjamin.morasco@va.gov FU National Institute on Drug Abuse [K23DA023467]; VA Health Services Research and Development service; National Center for Research Resources, a component of the National Institutes of Health [Ul1RR024140]; NIH Roadmap for Medical Research FX This study was supported in part by award K23DA023467 from the National Institute on Drug Abuse to Dr. Morasco. Jonathan Duckart, MPS, was supported by a Research Enhancement Award Program grant from the VA Health Services Research and Development service. The authors appreciate assistance from Sharon Medley and for the support provided by the Oregon Clinical and Translational Research Institute, Grant number Ul1RR024140 from the National Center for Research Resources, a component of the National Institutes of Health and NIH Roadmap for Medical Research. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, National Institute on Drug Abuse, or the Department of Veterans Affairs. NR 55 TC 78 Z9 79 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC PY 2010 VL 151 IS 3 BP 625 EP 632 DI 10.1016/j.pain.2010.08.002 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 673KC UT WOS:000283657300014 PM 20801580 ER PT J AU Meiksin, R Chang, JC Bhargava, T Arnold, R Dado, D Frankel, R Rodriguez, KL Ling, B Zickmund, S AF Meiksin, Rebecca Chang, Judy C. Bhargava, Tina Arnold, Robert Dado, Diane Frankel, Richard Rodriguez, Keri L. Ling, Bruce Zickmund, Susan TI Now is the chance: Patient-provider communication about unplanned pregnancy during the first prenatal visit SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Patient-provider relationship; Communication; Prenatal care; Pregnancy; Unplanned ID UNINTENDED PREGNANCY; WOMEN; DEPRESSION; HEALTH AB Objective: Unplanned pregnancy is associated with psychosocial stress, post-partum depression, and future unplanned pregnancies. Our study describes how topics related to unplanned pregnancy were addressed with patients during the first prenatal visit. Methods: We audio-recorded and transcribed initial prenatal visits between 48 patients and 16 providers from a clinic serving racially diverse, lower-socio-economic patients. We conducted a fine-grained thematic analysis of cases in which the patient's pregnancy was unplanned. Results: Of the 48 patients, 35 (73%) had unplanned pregnancies. Twenty-nine visits for unplanned pregnancies (83%) included discussion of the patient's feelings about the pregnancy. Approximately half (51%) of the visits touched on partner or other types of social support. Six patients (17%) were offered referrals to counseling or social services. Only four visits (11%) touched on future birth control options. Conclusion: Most initial prenatal visits for unplanned pregnancies included discussion of patient feelings about the pregnancy. However, opportunities to discuss future birth control and for more in-depth follow-up regarding social support and psychological risks associated with unplanned pregnancy were typically missed. Practice implications: Obstetrics care providers should be cautious about making assumptions and should consider discussing pregnancy circumstances and psychosocial issues in more depth when treating patients facing unplanned pregnancy. Published by Elsevier Ireland Ltd. C1 [Meiksin, Rebecca] VA Puget Sound, Seattle, WA 98101 USA. [Meiksin, Rebecca] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Chang, Judy C.; Dado, Diane] Magee Womens Hosp, Pittsburgh, PA USA. [Bhargava, Tina] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Arnold, Robert; Rodriguez, Keri L.; Ling, Bruce; Zickmund, Susan] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Frankel, Richard] Indiana Univ Sch Med, Med & Regenstrief Inst, Bloomington, IN USA. [Rodriguez, Keri L.; Ling, Bruce; Zickmund, Susan] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Rodriguez, Keri L.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Meiksin, R (reprint author), VA Puget Sound, Metropolitan Pk W,Suite 1400,1100 Olive Way, Seattle, WA 98101 USA. EM Rebecca.Meiksin@va.gov FU Association of Professors of Gynecology and Obstetrics/Abbott Medical Education; Scaife Family Foundation; NIH/NICHD [5 K12HD43441-04 PI]; Agency for Healthcare Research and Quality [1 K08 HS13913-01A1]; Veterans Affairs Health Services Research Development FX Financial support came from an Association of Professors of Gynecology and Obstetrics/Abbott Medical Education Program Award, the Scaife Family Foundation, and a Building Interdisciplinary Research Careers in Women's Health Award (NIH/NICHD 5 K12HD43441-04 PI Roberts; Scholar Chang). The efforts of Dr. Chang were also supported by the Agency for Healthcare Research and Quality (1 K08 HS13913-01A1). The efforts of Drs. Rodriguez and Zickmund were respectively sponsored by the Veterans Affairs Health Services Research & Development Merit Review Entry Program (MREP) and Investigator-Initiative Merit Review Award Program. None of the sponsors of this study had any role in the study design; collection, analysis and interpretation of the data; writing of the report; or decision to submit the paper for publication. NR 25 TC 8 Z9 9 U1 2 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD DEC PY 2010 VL 81 IS 3 SI SI BP 462 EP 467 DI 10.1016/j.pec.2010.09.002 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 707OH UT WOS:000286295400023 PM 20884161 ER PT J AU Lee, CJ Gray, SW Lewis, N AF Lee, Chul-joo Gray, Stacy Wang Lewis, Nehama TI Internet use leads cancer patients to be active health care consumers SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE The Internet; Active participation; Patient education; eHealth; Medical decision making ID DECISION-MAKING; INFORMATION; PARTICIPATION; COMMUNICATION; KNOWLEDGE; IMPACT; BEHAVIOR; EXPLORATION; ENGAGEMENT; PHYSICIANS AB Objective: This study examines whether cancer patients' Internet use leads them to prefer a more active role in medical decision making and whether the effects of Internet use on active participation preferences vary according to patients' education levels. Methods: Randomly drawn sample (N = 2013) from the Pennsylvania Cancer Registry, comprised of breast, prostate, and colon cancer patients, completed mail surveys in the fall of 2006 (overall response rate = 64%). Of 2013 baseline respondents, 85% agreed to participate in follow-up survey (N = 1703). Of those who agreed, 76% (N = 1293) completed follow-up surveys in the fall of 2007. Results: Cancer patients' Internet use for health information at wave one led them to want to be more active participants in medical decision making at wave two (beta = .06, p < .05). This applied to all cancer patients regardless of their education levels. Conclusion: Higher levels of Internet use among cancer patients may lead patients to want to be more actively involved in medical decision making. Practice Implications: Considering the beneficial effects of patients' active participation in medical decision making, it will be worthwhile for health educators to recommend Internet use to cancer patients. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Lee, Chul-joo] Ohio State Univ, Sch Commun, Columbus, OH 43210 USA. [Gray, Stacy Wang] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lewis, Nehama] Florida Int Univ, Dept Psychol, Miami, FL 33199 USA. RP Lee, CJ (reprint author), Ohio State Univ, Sch Commun, 3062 Derby Hall,154 N Oval Mall, Columbus, OH 43210 USA. EM lee.4030@osu.edu FU National Cancer Institute [5P50CA095856-05] FX This paper was supported by Grant Number 5P50CA095856-05 from the National Cancer Institute. We acknowledge that the NCI does not bear any responsibility for the content reported in this paper. We are grateful to Katrina Armstrong, Angel Bourgoin, Taressa Fraze, Derek Freres, Robert C. Hornik, Bridget Kelly, Lourdes Martinez, Rebekah Nagler, Susana Ramirez, Anca Romantan, J. Sanford Schwartz, Aaron Smith-McLallen, and Norman Wong for their insightful comments on earlier drafts of the manuscript and/or contributions to instrument development, data collection, and coding, and to Robin Otto, Craig Edelman and personnel at the Pennsylvania Cancer Registry for collaboration on sample development. NR 46 TC 40 Z9 41 U1 1 U2 21 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD DEC PY 2010 VL 81 SU 1 BP S63 EP S69 DI 10.1016/j.pec.2010.09.004 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 707OK UT WOS:000286295700009 PM 20889279 ER PT J AU Nagler, RH Gray, SW Romantan, A Kelly, BJ DeMichele, A Armstrong, K Schwartz, JS Hornik, RC AF Nagler, Rebekah H. Gray, Stacy W. Romantan, Anca Kelly, Bridget J. DeMichele, Angela Armstrong, Katrina Schwartz, J. Sanford Hornik, Robert C. TI Differences in information seeking among breast, prostate, and colorectal cancer patients: Results from a population-based survey SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Information seeking; Information needs; Breast cancer; Prostate cancer; Colorectal cancer ID HEALTH INFORMATION; DECISION-MAKING; NEEDS; INTERNET; SUPPORT; BEHAVIOR; SERVICE; CARE; SURVIVORS; OUTCOMES AB Objective: There is much research describing cancer patients' information needs and their use of the Internet, print media, and other sources to fulfill these needs. Yet little is known about whether patients with different types of cancer vary in their information needs and seeking behaviors. This study used population-based data to address this question. Methods: A sample was randomly drawn from the list of patients with breast, prostate, or colorectal cancer reported to the Pennsylvania Cancer Registry in 2005. Patients completed a mail survey (N = 2010); respective response rates were 68%, 64%, and 61%. Results: Colorectal cancer patients reported consistently less information seeking than breast and prostate cancer patients. Multivariate analyses revealed that differences by cancer type were not explained by sex or other demographics, disease stage, or treatment received. These differences were most pronounced among patients with early stage cancer. Conclusion: Cancer patients have myriad information needs and use a range of sources to satisfy these needs, but there appear to be important differences in information engagement by cancer type. Practice implications: Understanding differences in information seeking among disease-specific populations may help guide future patient education and decision making across the care continuum. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Nagler, Rebekah H.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Nagler, Rebekah H.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Nagler, Rebekah H.; DeMichele, Angela; Armstrong, Katrina; Schwartz, J. Sanford; Hornik, Robert C.] Univ Penn, Annenberg Sch Commun, Ctr Excellence Canc Commun Res, Philadelphia, PA 19104 USA. [Gray, Stacy W.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Romantan, Anca] Univ Massachusetts, Dept Commun, Amherst, MA 01003 USA. [Kelly, Bridget J.] Res Triangle Inst, Washington, DC USA. [DeMichele, Angela] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Armstrong, Katrina; Schwartz, J. Sanford] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Armstrong, Katrina; Schwartz, J. Sanford] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Nagler, RH (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St,LW 601, Boston, MA 02115 USA. EM rebekah_nagler@dfci.harvard.edu OI Hornik, Robert/0000-0002-2148-8805 FU National Cancer Institute's Center of Excellence in Cancer Communication (CECCR) at the Annenberg School for Communication, University of Pennsylvania [P50-CA095856-05] FX The authors wish to acknowledge the funding support of the National Cancer Institute's Center of Excellence in Cancer Communication (CECCR) located at the Annenberg School for Communication, University of Pennsylvania (P50-CA095856-05). This publication's contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 55 TC 61 Z9 62 U1 6 U2 24 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD DEC PY 2010 VL 81 SU 1 BP S54 EP S62 DI 10.1016/j.pec.2010.09.010 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 707OK UT WOS:000286295700008 PM 20934297 ER PT J AU Ingerski, LM Laffel, L Drotar, D Repaske, D Hood, KK AF Ingerski, Lisa M. Laffel, Lori Drotar, Dennis Repaske, David Hood, Korey K. TI Correlates of glycemic control and quality of life outcomes in adolescents with type 1 diabetes SO PEDIATRIC DIABETES LA English DT Article DE adolescence; glycemic control; QOL; type 1 diabetes ID METABOLIC-CONTROL; FAMILY CONFLICT; DEPRESSIVE SYMPTOMS; CHILDREN; INSULIN; MANAGEMENT; MELLITUS; YOUTH; ASSOCIATION; ADHERENCE AB Background: A major focus of pediatric multidisciplinary diabetes care is promoting glycemic control (A1c) while ensuring high quality of life (QOL). The current study investigated factors associated with A1c and QOL using a methodology that considered these variables as simultaneous outcomes. Method: A total of 261 adolescents (aged 13-18) with type 1 diabetes completed measures of blood glucose monitoring (BGM) frequency, diabetes-specific QOL, negative affect, and depression. Caregivers completed measures of demographic and disease characteristics, depression, and family conflict. Results: A1c was negatively correlated with QOL (r = -0.18 to -0.29, p < 0.01) across all subscales. Based on clinical A1c goals and median QOL scores, adolescents fell into four glycemic control-QOL groups. Multinomial logistic regression determined correlates of group membership utilizing adolescents with suboptimal glycemic control-low QOL as the referent group. Adolescents with optimal glycemic control-high QOL reported increased BGM frequency (OR = 1.87), less negative affect (OR = 1.32), and were more likely to use CSII (OR = 5.41). Adolescents with optimal A1c-low QOL reported greater BGM frequency (OR = 1.91) and shorter disease duration (OR = 1.09). Adolescents with suboptimal glycemic control-high QOL reported greater BGM frequency (OR = 1.41), fewer depressive symptoms (OR = 1.13), and less negative affect (OR = 1.31). Conclusions: Results reveal disease, management, and psychosocial characteristics that differentiate glycemic control-QOL outcome groups and identify risk factors related to this relationship. Further appreciation of these characteristics may increase clinicians' understanding and attention to these important clinical outcomes and help tailor the most appropriate interventions (e.g., individual psychotherapy vs. family problem-solving interventions) to help adolescents achieve glycemic control without sacrificing QOL. C1 [Ingerski, Lisa M.; Drotar, Dennis; Hood, Korey K.] Cincinnati Childrens Hosp, Med Ctr, Ctr Treatment Adherence, Div Behav Med & Clin Psychol, Cincinnati, OH 45229 USA. [Laffel, Lori] Harvard Univ, Sch Med, Pediat Adolescent & Young Adult Sect, Genet & Epidemiol Sect,Joslin Diabet Ctr, Boston, MA USA. [Drotar, Dennis; Repaske, David; Hood, Korey K.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. [Repaske, David] Cincinnati Childrens Hosp, Med Ctr, Ctr Diabet, Div Endocrinol, Cincinnati, OH 45229 USA. RP Hood, KK (reprint author), Cincinnati Childrens Hosp, Med Ctr, Ctr Promot Treatment Adherence & Self Management, Div Behav Med & Clin Psychol, 3333 Burnet Ave,MLC 7039, Cincinnati, OH 45229 USA. EM Korey.Hood@cchmc.org RI Repaske, David/E-3939-2011 FU National Institute for Diabetes and Digestive and Kidney Diseases [K23 DK073340] FX Research supported by a grant from the National Institute for Diabetes and Digestive and Kidney Diseases (K23 DK073340) awarded to Dr Korey K Hood. NR 32 TC 19 Z9 19 U1 3 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1399-543X J9 PEDIATR DIABETES JI Pediatr. Diabetes PD DEC PY 2010 VL 11 IS 8 BP 563 EP 571 DI 10.1111/j.1399-5448.2010.00645.x PG 9 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 688NA UT WOS:000284854900009 PM 20149122 ER PT J AU Bhargava, P Parisi, M AF Bhargava, Puneet Parisi, Marguerite TI Infected thyroglossal duct cyst SO PEDIATRIC RADIOLOGY LA English DT Editorial Material C1 [Bhargava, Puneet] Univ Washington, Dept Radiol, Seattle, WA 98108 USA. [Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Parisi, Marguerite] Univ Washington, Dept Radiol, Seattle, WA 98105 USA. [Parisi, Marguerite] Seattle Childrens Hosp, Seattle, WA 98105 USA. RP Bhargava, P (reprint author), Univ Washington, Dept Radiol, Mailbox 358280,S-114 Radiol,1660 S Columbian Way, Seattle, WA 98108 USA. EM bhargp@u.washington.edu RI Bhargava, Puneet /F-1330-2011; OI Bhargava, Puneet/0000-0002-3849-9666 NR 2 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD DEC PY 2010 VL 40 SU 1 BP 84 EP 84 DI 10.1007/s00247-010-1563-4 PG 1 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 692KZ UT WOS:000285153000040 ER PT J AU Bhargava, P Phillips, G AF Bhargava, Puneet Phillips, Grace TI Giant gastric bezoar presenting as an acute abdominal emergency SO PEDIATRIC RADIOLOGY LA English DT Editorial Material C1 [Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Bhargava, Puneet; Phillips, Grace] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Phillips, Grace] Seattle Childrens Hosp, Div Computed Tomog, Seattle, WA USA. RP Bhargava, P (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-114 Radiol,Mail Stop 35828, Seattle, WA 98108 USA. EM bhargp@u.washington.edu RI Bhargava, Puneet /F-1330-2011; OI Bhargava, Puneet/0000-0002-3849-9666 NR 2 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD DEC PY 2010 VL 40 SU 1 BP 99 EP 99 DI 10.1007/s00247-009-1511-3 PG 1 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 692KZ UT WOS:000285153000049 ER PT J AU Sagar, P Shailam, R Nimkin, K AF Sagar, Pallavi Shailam, Randheer Nimkin, Katherine TI Avascular necrosis of the metacarpal head: a report of two cases and review of literature SO PEDIATRIC RADIOLOGY LA English DT Review DE Metacarpal head; Dieterich disease; Hand; Avascular necrosis; Children ID DIETERICHS-DISEASE; IDIOPATHIC OSTEONECROSIS; RENAL-TRANSPLANTATION; ASEPTIC NECROSIS; 3RD METACARPAL AB Avascular necrosis (AVN) of the metacarpal head is a rare condition that can go unrecognized on radiography and progress to degenerative arthritis. Few reports describe the association with trauma, steroid use and systemic lupus erythematosus (SLE). Optimal treatment for this condition has not been established and long-term prognosis is unknown. We present two cases of children with AVN of the fourth metacarpal head with a relatively recent history of indirect hand trauma. Both of our cases had radiographs and MRI of the hand. MRI was diagnostic in both cases; however, radiographs were reported as normal in the early stage in one case. AVN of the metacarpal head is rare but can occur in children. Pediatric radiologists should be aware of this uncommon clinical entity, especially in light of increased involvement of children in sporting activities. Active children with hand trauma and children treated with steroids for a variety of conditions are particularly at risk. C1 [Sagar, Pallavi; Shailam, Randheer; Nimkin, Katherine] Massachusetts Gen Hosp, Dept Radiol, Div Pediat Radiol, Boston, MA 02114 USA. RP Sagar, P (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Pediat Radiol, 34 Fruit St,Ellison 237, Boston, MA 02114 USA. EM psagar@partners.org NR 25 TC 3 Z9 3 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD DEC PY 2010 VL 40 IS 12 BP 1895 EP 1901 DI 10.1007/s00247-010-1763-y PG 7 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 682BX UT WOS:000284375300006 PM 20614113 ER PT J AU Sarvet, B Gold, J Bostic, JQ Masek, BJ Prince, JB Jeffers-Terry, M Moore, CF Molbert, B Straus, JH AF Sarvet, Barry Gold, Joseph Bostic, Jeff Q. Masek, Bruce J. Prince, Jefferson B. Jeffers-Terry, Mary Moore, Charles F. Molbert, Benjamin Straus, John H. TI Improving Access to Mental Health Care for Children: The Massachusetts Child Psychiatry Access Project SO PEDIATRICS LA English DT Article DE access to health care; child psychiatry; primary health care ID PEDIATRIC PRIMARY-CARE; SERVICE USE; UNMET NEED; MANAGEMENT; DISORDERS; IDENTIFICATION; ADOLESCENTS; DEPRESSION; SETTINGS; BARRIERS AB BACKGROUND: Inadequate access to care for mentally ill children and their families is a persistent problem in the United States. Although promotion of pediatric primary care clinicians (PCCs) in detection, management, and coordination of child mental health care is a strategy for improving access, limitations in training, time, and specialist availability represent substantial barriers. The Massachusetts Child Psychiatry Access Project (MCPAP), publicly funded with 6 regional consultation teams, provides Massachusetts PCCs with rapid access to child psychiatry expertise, education, and referral assistance. METHODS: Data collected from MCPAP teams measured participation and utilization over 3.5 years from July 1, 2005, to December 31, 2008. Data were analyzed for 35 335 encounters. PCC surveys assessed satisfaction and impact on access to care. RESULTS: The MCPAP enrolled 1341 PCCs in 353 practices covering 95% of the youth in Massachusetts. The MCPAP served 10 114 children. Practices varied in their utilization of the MCPAP, with a mean of 12 encounters per practice per quarter (range: 0-245). PCCs contacted the MCPAP for diagnostic questions (34%), identifying community resources (27%), and consultation regarding medication (27%). Provider surveys revealed improvement in ratings of access to child psychiatry. The rate of PCCs who reported that they are usually able to meet the needs of psychiatric patients increased from 8% to 63%. Consultations were reported to be helpful by 91% of PCCs. CONCLUSIONS: PCCs have used and value a statewide system that provides access to teams of psychiatric consultants. Access to child mental health care may be substantially improved through public health interventions that promote collaboration between PCCs and child mental health specialists. Pediatrics 2010;126:1191-1200 C1 [Sarvet, Barry] Tufts Univ, Div Child & Adolescent Psychiat, Sch Med, Baystate Med Ctr, Springfield, MA 01199 USA. [Gold, Joseph] Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. [Bostic, Jeff Q.; Masek, Bruce J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Child & Adolescent Psychiat, Boston, MA USA. [Prince, Jefferson B.] Harvard Univ, Div Child Psychiat, Mass Gen Hosp Children, N Shore Med Ctr,Med Sch, Salem, MA USA. [Jeffers-Terry, Mary] Univ Massachusetts, Sch Med, Div Child & Adolescent Psychiat, UMass Mem Med Ctr, Worcester, MA USA. [Moore, Charles F.] Tufts Univ, Sch Med, Div Child & Adolescent Psychiat, Tufts Med Ctr, Boston, MA 02111 USA. [Molbert, Benjamin] Harvard Univ, Sch Med, Div Child & Adolescent Psychiat, Brockton, MA 02401 USA. [Straus, John H.] ValueOptions Inc, Massachusetts Behav Hlth Partnership, Dept Med Affairs, Boston, MA USA. RP Sarvet, B (reprint author), Tufts Univ, Div Child & Adolescent Psychiat, Sch Med, Baystate Med Ctr, 3300 Main St,4th Floor, Springfield, MA 01199 USA. EM barry.sarvet@baystatehealth.org NR 29 TC 52 Z9 52 U1 1 U2 11 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 2010 VL 126 IS 6 BP 1191 EP 1200 DI 10.1542/peds.2009-1340 PG 10 WC Pediatrics SC Pediatrics GA 688EF UT WOS:000284831900046 PM 21059722 ER PT J AU Salomone, S Soydan, G Ip, PCT Hopson, KMP Waeber, C AF Salomone, Salvatore Soydan, Guray Ip, Peter Ching-Tze Hopson, Kristen M. Park Waeber, Christian TI Vessel-specific role of sphingosine kinase 1 in the vasoconstriction of isolated basilar arteries SO PHARMACOLOGICAL RESEARCH LA English DT Article DE Sphingosine kinase; Vasoconstriction; Basilar artery ID CEREBRAL-ARTERIES; ENDOTHELIAL-CELLS; SMOOTH-MUSCLE; RHO-KINASE; SPHINGOSINE-1-PHOSPHATE; 1-PHOSPHATE; RECEPTORS; FTY720; TONE; CONSTRICTION AB Sphingosine-1-phosphate (S1P) constricts cerebral arteries through S1P(3) receptor stimulation Because the activity of the key S1P-synthesizing enzyme sphingosine kinase (SPK) can be stimulated by agonists of various G protein-coupled receptors it is likely that S1P also acts as a second messenger for other vasoconstrictors We investigated the effect of SPK inhibitors and SPK gene deletion on the contractile responses of Isolated vessels to vasoactive agonists and KCl-induced depolarization Basilar and femoral arteries of rat mounted in a wire myograph were Incubated with dimethylsphingosine (DMS) 2-(p-hydroxyanilino)-4-(p-chlorophenyl) thiazole (Compound 2) or FTY720 and exposed to KCl 5-hydroxytryptamine (5-HT) SIP or phenylephrine (PE) Vasomotor responses in basilar artery were decreased by DMS Compound 2 and FTY720 while they were not affected in femoral artery Basilar arteries from SPK1(-/-) mice exhibited weaker vasoconstriction to both KCl and agonists (SIP and the prostanoid U46619) when compared to either wild type (WT) or SPK2(-/-) In contrast in mesenteric resistance arteries neither the contraction to KCl nor the maximum contraction to PE and S1P significantly differed among WT SPK1(-/-) and SPK2(-/-) Quantitative analysis of SPK mRNA (reverse transcription and real time polymerase chain reaction) in mouse arteries showed 40-80-fold higher SPK1 expression in cerebral arteries than in aorta or mesenteric arteries SPK1 critically modulates the reactivity of cerebral vasculature to vasoconstrictors S1P plays a specific role as modulator of cerebral blood flow potentially acting either directly outside vascular smooth muscle cells on S1P(3) receptors or indirectly after being generated inside the cell in response to vasoconstrictors (C) 2010 Elsevier Ltd All rights reserved C1 [Salomone, Salvatore; Soydan, Guray; Ip, Peter Ching-Tze; Hopson, Kristen M. Park; Waeber, Christian] Massachusetts Gen Hosp, Dept Radiol, Stroke & Neurovasc Lab Regulat, Charlestown, MA 02129 USA. RP Waeber, C (reprint author), Massachusetts Gen Hosp, Dept Radiol, Stroke & Neurovasc Lab Regulat, CNY149,Room 6403,149 13th St, Charlestown, MA 02129 USA. RI Waeber, Christian/A-8333-2009; OI Waeber, Christian/0000-0001-6078-0027; Salomone, Salvatore/0000-0001-5307-6103 FU National Institutes of Health [R01NS049263, P01NS055104, 5T32AG00277] FX This work was supported by grants from the National Institutes of Health [grant numbers R01NS049263, P01NS055104] to C W and [5T32AG00277] to K P NR 33 TC 9 Z9 9 U1 1 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-6618 J9 PHARMACOL RES JI Pharmacol. Res. PD DEC PY 2010 VL 62 IS 6 BP 465 EP 474 DI 10.1016/j.phrs.2010.09.002 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 689XZ UT WOS:000284965700002 PM 20850539 ER PT J AU Liu, JJ Fisher, DE AF Liu, Jue J. Fisher, David E. TI Lighting a path to pigmentation: mechanisms of MITF induction by UV SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Article DE microphthalmia-associated transcription factor; skin pigmentation; melanins ID TRANSCRIPTION FACTOR; MELANOCYTE DEVELOPMENT; ULTRAVIOLET-RADIATION; SKIN PIGMENTATION; STEM-CELLS; MICROPHTHALMIA; MUTATIONS; FAMILY; P53; SUMOYLATION AB P>While sunlight is important for life, ultraviolet radiation (UVR) can have harmful and mutagenic effects. This duality is particularly relevant to human skin, in which UVR both participates in evolutionarily important photochemical reactions yet may act as a potential carcinogen. UVR can upregulate production of melanin, the "tanning response" that serves a photoprotective function. This genetic program is centrally tuned by the transcription factor MITF, a master regulator of melanogenesis and melanocyte function. In this review, we discuss the myriad consequences of UV exposure for skin homeostasis, highlighting the diverse pathways activated by this ultraviolet radiation. C1 [Liu, Jue J.; Fisher, David E.] Harvard Univ, Sch Med, Dept Dermatol, Cutaneous Biol Res Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Cutaneous Biol Res Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM dfisher3@partners.org FU NIAMS NIH HHS [R01 AR043369] NR 27 TC 30 Z9 30 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD DEC PY 2010 VL 23 IS 6 BP 741 EP 745 DI 10.1111/j.1755-148X.2010.00775.x PG 5 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 664QQ UT WOS:000282977800007 PM 20973930 ER PT J AU Huang, GJ Smith, AL Gray, DHD Cosgrove, C Singer, BH Edwards, A Sim, S Parent, JM Johnsen, A Mott, R Mathis, D Klenerman, P Benoist, C Flint, J AF Huang, Guo-Jen Smith, Adrian L. Gray, Daniel H. D. Cosgrove, Cormac Singer, Benjamin H. Edwards, Andrew Sim, Stuart Parent, Jack M. Johnsen, Alyssa Mott, Richard Mathis, Diane Klenerman, Paul Benoist, Christophe Flint, Jonathan TI A Genetic and Functional Relationship between T Cells and Cellular Proliferation in the Adult Hippocampus SO PLOS BIOLOGY LA English DT Article ID NEURAL PROGENITOR CELLS; QUANTITATIVE TRAIT LOCI; COLLABORATIVE CROSS; COMPLEX TRAITS; DENTATE GYRUS; NEUROGENESIS; MICE; MOUSE; FOREBRAIN; ABLATION AB Neurogenesis continues through the adult life of mice in the subgranular zone of the dentate gyrus in the hippocampus, but its function remains unclear. Measuring cellular proliferation in the hippocampus of 719 outbred heterogeneous stock mice revealed a highly significant correlation with the proportions of CD8+ versus CD4+ T lymphocyte subsets. This correlation reflected shared genetic loci, with the exception of the H-2Ea locus that had a dominant influence on T cell subsets but no impact on neurogenesis. Analysis of knockouts and repopulation of TCR alpha-deficient mice by subsets of T cells confirmed the influence of T cells on adult neurogenesis, indicating that CD4+ T cells or subpopulations thereof mediate the effect. Our results reveal an organismal impact, broader than hitherto suspected, of the natural genetic variation that controls T cell development and homeostasis. C1 [Huang, Guo-Jen; Edwards, Andrew; Mott, Richard; Flint, Jonathan] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Smith, Adrian L.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England. [Gray, Daniel H. D.; Johnsen, Alyssa; Mathis, Diane; Benoist, Christophe] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA. [Gray, Daniel H. D.; Johnsen, Alyssa; Mathis, Diane; Benoist, Christophe] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Cosgrove, Cormac; Sim, Stuart; Klenerman, Paul] Univ Oxford, Nuffield Dept Med, Oxford, England. [Singer, Benjamin H.; Parent, Jack M.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. RP Huang, GJ (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. EM jf@well.ox.ac.uk RI Gray, Daniel/A-3293-2013; OI Gray, Daniel/0000-0002-8457-8242; Singer, Benjamin/0000-0002-4721-6920; Flint, Jonathan/0000-0002-9427-4429 FU Wellcome Trust; National Institutes of Health [R01 AR055271] FX This work was supported by a grant from the Wellcome Trust to JF and by grant R01 AR055271 from the National Institutes of Health to CB and DM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 14 Z9 14 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD DEC PY 2010 VL 8 IS 12 AR e1000561 DI 10.1371/journal.pbio.1000561 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 697GD UT WOS:000285500100009 PM 21179499 ER PT J AU Mendenhall, EM Koche, RP Truong, T Zhou, VW Issac, B Chi, AS Ku, M Bernstein, BE AF Mendenhall, Eric M. Koche, Richard P. Truong, Thanh Zhou, Vicky W. Issac, Biju Chi, Andrew S. Ku, Manching Bernstein, Bradley E. TI GC-Rich Sequence Elements Recruit PRC2 in Mammalian ES Cells SO PLOS GENETICS LA English DT Article ID EMBRYONIC STEM-CELLS; DNA METHYLATION; METHYLTRANSFERASE ACTIVITY; DEVELOPMENTAL REGULATORS; DROSOPHILA-MELANOGASTER; POLYCOMB TARGETS; SELF-RENEWAL; CHROMATIN; COMPLEX; PROTEIN AB Polycomb proteins are epigenetic regulators that localize to developmental loci in the early embryo where they mediate lineage-specific gene repression. In Drosophila, these repressors are recruited to sequence elements by DNA binding proteins associated with Polycomb repressive complex 2 (PRC2). However, the sequences that recruit PRC2 in mammalian cells have remained obscure. To address this, we integrated a series of engineered bacterial artificial chromosomes into embryonic stem (ES) cells and examined their chromatin. We found that a 44 kb region corresponding to the Zfpm2 locus initiates de novo recruitment of PRC2. We then pinpointed a CpG island within this locus as both necessary and sufficient for PRC2 recruitment. Based on this causal demonstration and prior genomic analyses, we hypothesized that large GC-rich elements depleted of activating transcription factor motifs mediate PRC2 recruitment in mammals. We validated this model in two ways. First, we showed that a constitutively active CpG island is able to recruit PRC2 after excision of a cluster of activating motifs. Second, we showed that two 1 kb sequence intervals from the Escherichia coli genome with GC-contents comparable to a mammalian CpG island are both capable of recruiting PRC2 when integrated into the ES cell genome. Our findings demonstrate a causal role for GC-rich sequences in PRC2 recruitment and implicate a specific subset of CpG islands depleted of activating motifs as instrumental for the initial localization of this key regulator in mammalian genomes. C1 [Mendenhall, Eric M.; Koche, Richard P.; Truong, Thanh; Zhou, Vicky W.; Issac, Biju; Chi, Andrew S.; Ku, Manching; Bernstein, Bradley E.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Mendenhall, Eric M.; Koche, Richard P.; Truong, Thanh; Zhou, Vicky W.; Issac, Biju; Chi, Andrew S.; Ku, Manching; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mendenhall, Eric M.; Koche, Richard P.; Truong, Thanh; Zhou, Vicky W.; Issac, Biju; Chi, Andrew S.; Ku, Manching; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA USA. [Mendenhall, Eric M.; Koche, Richard P.; Truong, Thanh; Zhou, Vicky W.; Issac, Biju; Chi, Andrew S.; Ku, Manching; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Mendenhall, Eric M.; Koche, Richard P.; Truong, Thanh; Zhou, Vicky W.; Issac, Biju; Chi, Andrew S.; Ku, Manching; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Mendenhall, Eric M.; Koche, Richard P.; Truong, Thanh; Zhou, Vicky W.; Issac, Biju; Chi, Andrew S.; Ku, Manching; Bernstein, Bradley E.] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA USA. [Koche, Richard P.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Chi, Andrew S.] Massachusetts Gen Hosp, Dept Neurol, Neuro Oncol Div, Boston, MA 02114 USA. RP Mendenhall, EM (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. EM Bernstein.Bradley@mgh.harvard.edu OI Mendenhall, Eric/0000-0002-7395-6295 FU National Cancer Institute; National Defense Science and Engineering; Croucher Foundation; Burroughs Wellcome Fund; Culpeper Foundation; Massachusetts General Hospital; Broad Institute FX EMM is supported by a Ruth Kirschstein-NRSA institutional training grant from the National Cancer Institute. VWZ is supported by a National Defense Science and Engineering Graduate Fellowship. ASC is supported by an NIH K12 institutional training grant from the National Cancer Institute. MK is supported by a Croucher Foundation fellowship. BEB is a Charles E. Culpeper Medical Scholar and an Early Career Scientist of the Howard Hughes Medical Institute. This research was supported by funds from the Burroughs Wellcome Fund, the Culpeper Foundation, Massachusetts General Hospital, and the Broad Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 57 TC 179 Z9 182 U1 3 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD DEC PY 2010 VL 6 IS 12 AR e1001244 DI 10.1371/journal.pgen.1001244 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 698FM UT WOS:000285578900022 PM 21170310 ER PT J AU Shah, M Bhoumik, A Goel, V Dewing, A Breitwieser, W Kluger, H Krajewski, S Krajewska, M DeHart, J Lau, E Kallenberg, DM Jeong, H Eroshkin, A Bennett, DC Chin, L Bosenberg, M Jones, N Ronai, ZA AF Shah, Meera Bhoumik, Anindita Goel, Vikas Dewing, Antimone Breitwieser, Wolfgang Kluger, Harriet Krajewski, Stan Krajewska, Maryla DeHart, Jason Lau, Eric Kallenberg, David M. Jeong, Hyeongnam Eroshkin, Alexey Bennett, Dorothy C. Chin, Lynda Bosenberg, Marcus Jones, Nic Ronai, Ze'ev A. TI A Role for ATF2 in Regulating MITF and Melanoma Development SO PLOS GENETICS LA English DT Article ID ACTIVATING TRANSCRIPTION FACTOR-2; SIGNAL-TRANSDUCTION PATHWAY; MALIGNANT-MELANOMA; TISSUE MICROARRAYS; CELL PROLIFERATION; EXPRESSION; SURVIVAL; INHIBITION; PROMOTER; BIOLOGY AB The transcription factor ATF2 has been shown to attenuate melanoma susceptibility to apoptosis and to promote its ability to form tumors in xenograft models. To directly assess ATF2's role in melanoma development, we crossed a mouse melanoma model (Nras(Q61K)::Ink4a(-/-)) with mice expressing a transcriptionally inactive form of ATF2 in melanocytes. In contrast to 7/21 of the Nras(Q61K)::Ink4a(-/)-mice, only 1/21 mice expressing mutant ATF2 in melanocytes developed melanoma. Gene expression profiling identified higher MITF expression in primary melanocytes expressing transcriptionally inactive ATF2. MITF downregulation by ATF2 was confirmed in the skin of Atf2(-/)-mice, in primary human melanocytes, and in 50% of human melanoma cell lines. Inhibition of MITF transcription by MITF was shown to be mediated by ATF2-JunB-dependent suppression of SOX10 transcription. Remarkably, oncogenic BRAF (V600E)-dependent focus formation of melanocytes on soft agar was inhibited by ATF2 knockdown and partially rescued upon shMITF co-expression. On melanoma tissue microarrays, a high nuclear ATF2 to MITF ratio in primary specimens was associated with metastatic disease and poor prognosis. Our findings establish the importance of transcriptionally active ATF2 in melanoma development through fine-tuning of MITF expression. C1 [Breitwieser, Wolfgang; Jones, Nic] Univ Manchester, Paterson Inst Canc Res, Manchester, Lancs, England. [Kluger, Harriet] Yale Univ, Dept Med, New Haven, CT 06520 USA. [Kallenberg, David M.; Bennett, Dorothy C.] Univ London, London, England. [Jeong, Hyeongnam; Chin, Lynda] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bosenberg, Marcus] Yale Univ, Dept Pathol, New Haven, CT USA. EM ronai@sanfordburnham.org RI Bennett, Dorothy/C-2418-2008; OI Bennett, Dorothy/0000-0002-3639-7527; Jones, Nic/0000-0002-7619-8151; RONAI, ZEEV/0000-0002-3859-0400 FU NCI [CA099961]; Wellcome Trust [078327] FX Support from NCI grant CA099961 (ZAR) and Wellcome Trust grant 078327 (DCB) are gratefully acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 65 TC 36 Z9 37 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD DEC PY 2010 VL 6 IS 12 AR e1001258 DI 10.1371/journal.pgen.1001258 PG 21 WC Genetics & Heredity SC Genetics & Heredity GA 698FM UT WOS:000285578900036 PM 21203491 ER PT J AU Boulware, DR Meya, DB Bergemann, TL Wiesner, DL Rhein, J Musubire, A Lee, SJ Kambugu, A Janoff, EN Bohjanen, PR AF Boulware, David R. Meya, David B. Bergemann, Tracy L. Wiesner, Darin L. Rhein, Joshua Musubire, Abdu Lee, Sarah J. Kambugu, Andrew Janoff, Edward N. Bohjanen, Paul R. TI Clinical Features and Serum Biomarkers in HIV Immune Reconstitution Inflammatory Syndrome after Cryptococcal Meningitis: A Prospective Cohort Study SO PLOS MEDICINE LA English DT Article ID COLONY-STIMULATING FACTOR; ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; ALLERGIC BRONCHOPULMONARY MYCOSIS; ENDOTHELIAL GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; CD4(+) T-CELLS; RESTORATION DISEASE; INFECTED PATIENTS; RISK-FACTORS AB Background: Although antiretroviral therapy (ART) improves survival in persons with cryptococcal meningitis (CM) and AIDS, ART frequently elicits HIV immune reconstitution inflammatory syndrome (IRIS), an exaggerated and frequently deadly inflammatory reaction that complicates recovery from immunodeficiency. The pathogenesis of IRIS is poorly understood and prediction of IRIS is not possible. Methods and Findings: We prospectively followed 101 ART-naive Ugandans with AIDS and recent CM for one year after initiating ART, and used Luminex multiplex assays to compare serum cytokine levels in participants who did or did not develop IRIS. IRIS occurred in 45% of participants with recent CM on ART, including 30% with central nervous system (CNS) manifestations. The median time to CM-IRIS was 8.8 wk on ART. Overall mortality on ART was 36% with IRIS and 21% without IRIS. CM-IRIS was independently associated with death (HR = 2.3, 95% CI 1.1-5.1, p = 0.04). Patients experiencing subsequent CM-IRIS had 4-fold higher median serum cryptococcal antigen (CRAG) levels pre-ART (p = 0.006). Higher pre-ART levels of interleukin (IL)-4 and IL-17 as well as lower tumor necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) predicted future IRIS in multivariate analyses (area under the curve [AUC] = 0.82). An algorithm based on seven pre-ART serum biomarkers was a robust tool for stratifying high (83%), moderate (48%), and low risk (23%) for IRIS in the cohort. After ART was initiated, increasing levels of C-reactive protein (CRP), D-dimer, IL-6, IL-7, IL-13, G-CSF, or IL-1RA were associated with increasing hazard of IRIS by time-to-event analysis (each p <= 0.001). At the time of IRIS onset, multiple proinflammatory cytokine responses were present, including CRP and IL-6. Mortality was predicted by pre-ART increasing IL-17, decreasing GM-CSF, and CRP level >32 mg/l (highest quartile). Pre-ART CRP level >32 mg/l alone was associated with future death (OR = 8.3, 95% CI 2.7-25.6, p<0.001). Conclusions: Pre-ART increases in Th-17 and Th-2 responses (e.g., IL-17, IL-4) and lack of proinflammatory cytokine responses (e.g., TNF-alpha, G-CSF, GM-CSF, VEGF) predispose individuals to subsequent IRIS, perhaps as biomarkers of immune dysfunction and poor initial clearance of CRAG. Although requiring validation, these biomarkers might be an objective tool to stratify the risk of CM-IRIS and death, and could be used clinically to guide when to start ART or use prophylactic interventions. C1 [Boulware, David R.; Meya, David B.; Rhein, Joshua; Lee, Sarah J.; Kambugu, Andrew; Bohjanen, Paul R.] Univ Minnesota, Dept Med, Div Infect Dis & Int Med, Minneapolis, MN 55455 USA. [Boulware, David R.; Wiesner, Darin L.; Rhein, Joshua; Bohjanen, Paul R.] Univ Minnesota, Ctr Infect Dis & Microbiol Translat Res, Minneapolis, MN 55455 USA. [Meya, David B.; Musubire, Abdu; Kambugu, Andrew] Makerere Univ, Infect Dis Inst, Kampala, Uganda. [Bergemann, Tracy L.] Univ Minnesota, Div Biostat, Sch Publ Hlth, Minneapolis, MN 55455 USA. [Janoff, Edward N.] Univ Colorado, Mucosal & Vaccine Res Program Colorado MAVRC, Div Infect Dis, Denver Sch Med,Denver Vet Affairs Med Ctr, Denver, CO 80202 USA. [Bohjanen, Paul R.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA. RP Boulware, DR (reprint author), Univ Minnesota, Dept Med, Div Infect Dis & Int Med, Box 736 UMHC, Minneapolis, MN 55455 USA. EM boulw001@umn.edu RI Boulware, David/B-5516-2011; Boulware, David/I-4533-2013; Bohjanen, Paul/B-2329-2015; OI Bohjanen, Paul/0000-0002-2772-3597; Meya, David/0000-0002-4138-240X; Bergemann, Tracy/0000-0003-3902-2605; Boulware, David/0000-0002-4715-0060 FU University of Minnesota Academic Health Center; NIH National Institute of Allergy and Infectious Diseases [T32AI055433-03, L30AI066779, K12RR023247-04, K23AI073192, R03AI078750]; Minnesota Medical Foundation; Tibotec REACH Initiative; University of Minnesota; Academic Alliance Foundation; Mucosal and Vaccine Research Program Colorado; Veterans Affairs Research Service FX This work was supported by the University of Minnesota Academic Health Center (PRB, DBM), NIH National Institute of Allergy and Infectious Diseases (DRB: T32AI055433-03; L30AI066779; K12RR023247-04; K23AI073192. PRB: R03AI078750), Minnesota Medical Foundation (PRB, DRB, DBM), Tibotec REACH Initiative (PRB, DRB, DBM), University of Minnesota Dean's Grant-in-Aid (DRB), Academic Alliance Foundation (AK, DBM), Mucosal and Vaccine Research Program Colorado (ENJ), and the Veterans Affairs Research Service (ENJ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 67 TC 103 Z9 103 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD DEC PY 2010 VL 7 IS 12 AR e1000384 DI 10.1371/journal.pmed.1000384 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 697GA UT WOS:000285499600010 PM 21253011 ER PT J AU Land, T Rigotti, NA Levy, DE Paskowsky, M Warner, D Kwass, JA Wetherell, L Keithly, L AF Land, Thomas Rigotti, Nancy A. Levy, Douglas E. Paskowsky, Mark Warner, Donna Kwass, Jo-Ann Wetherell, LeAnn Keithly, Lois TI A Longitudinal Study of Medicaid Coverage for Tobacco Dependence Treatments in Massachusetts and Associated Decreases in Hospitalizations for Cardiovascular Disease SO PLOS MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-HEART-DISEASE; SMOKING-CESSATION; UNITED-STATES; QUITTING SMOKING; HEALTH; RISK; MORTALITY; EXPOSURE; CHARGES AB Background: Insurance coverage of tobacco cessation medications increases their use and reduces smoking prevalence in a population. However, uncertainty about the impact of this coverage on health care utilization and costs is a barrier to the broader adoption of this policy, especially by publicly funded state Medicaid insurance programs. Whether a publicly funded tobacco cessation benefit leads to decreased medical claims for tobacco-related diseases has not been studied. We examined the experience of Massachusetts, whose Medicaid program adopted comprehensive coverage of tobacco cessation medications in July 2006. Over 75,000 Medicaid subscribers used the benefit in the first 2.5 years. On the basis of earlier secondary survey work, it was estimated that smoking prevalence declined among subscribers by 10% during this period. Methods and Findings: Using claims data, we compared the probability of hospitalization prior to use of the tobacco cessation pharmacotherapy benefit with the probability of hospitalization after benefit use among Massachusetts Medicaid beneficiaries, adjusting for demographics, comorbidities, seasonality, influenza cases, and the implementation of the statewide smoke-free air law using generalized estimating equations. Statistically significant annualized declines of 46% (95% confidence interval 2%-70%) and 49% (95% confidence interval 6%-72%) were observed in hospital admissions for acute myocardial infarction and other acute coronary heart disease diagnoses, respectively. There were no significant decreases in hospitalizations rates for respiratory diagnoses or seven other diagnostic groups evaluated. Conclusions: Among Massachusetts Medicaid subscribers, use of a comprehensive tobacco cessation pharmacotherapy benefit was associated with a significant decrease in claims for hospitalizations for acute myocardial infarction and acute coronary heart disease, but no significant change in hospital claims for other diagnoses. For low-income smokers, removing the barriers to the use of smoking cessation pharmacotherapy has the potential to decrease short-term utilization of hospital services. C1 [Land, Thomas; Paskowsky, Mark; Warner, Donna; Kwass, Jo-Ann; Keithly, Lois] Massachusetts Tobacco Cessat & Prevent Program, Boston, MA USA. [Rigotti, Nancy A.; Levy, Douglas E.] Massachusetts Gen Hosp, Dept Med, Tobacco Res & Treatment Ctr, Div Gen Med, Boston, MA 02114 USA. [Rigotti, Nancy A.; Levy, Douglas E.] Harvard Univ, Sch Med, Boston, MA USA. [Rigotti, Nancy A.; Levy, Douglas E.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Wetherell, LeAnn] Off Medicaid Commonwealth Massachusetts, Boston, MA USA. RP Land, T (reprint author), Massachusetts Tobacco Cessat & Prevent Program, Boston, MA USA. EM Thomas.Land@state.ma.us FU U.S. Centers for Disease Control and Prevention (CDC) [U58/CCU122821] FX The U.S. Centers for Disease Control and Prevention (CDC) has supported this work under the CDC Grant/Cooperative Agreement Number U58/CCU122821. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 25 TC 17 Z9 17 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD DEC PY 2010 VL 7 IS 12 AR e1000375 DI 10.1371/journal.pmed.1000375 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 697GA UT WOS:000285499600002 PM 21170313 ER PT J AU Walensky, RP Wood, R Ciaranello, AL Paltiel, AD Lorenzana, SB Anglaret, X Stoler, AW Freedberg, KA AF Walensky, Rochelle P. Wood, Robin Ciaranello, Andrea L. Paltiel, A. David Lorenzana, Sarah B. Anglaret, Xavier Stoler, Adam W. Freedberg, Kenneth A. CA CEPAC-Int Investigators TI Scaling Up the 2010 World Health Organization HIV Treatment Guidelines in Resource-Limited Settings: A Model-Based Analysis SO PLOS MEDICINE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; COTE-DIVOIRE; COST-EFFECTIVENESS; SOUTH-AFRICA; INFECTED ADULTS; RISK-FACTORS; VIRAL LOAD; IMPACT; PROPHYLAXIS; ZIDOVUDINE AB Background: The new 2010 World Health Organization (WHO) HIV treatment guidelines recommend earlier antiretroviral therapy (ART) initiation (CD4<350 cells/mu l instead of CD4<200 cells/mu l), multiple sequential ART regimens, and replacement of first-line stavudine with tenofovir. This paper considers what to do first in resource-limited settings where immediate implementation of all of the WHO recommendations is not feasible. Methods and Findings: We use a mathematical model and local input data to project clinical and economic outcomes in a South African HIV-infected cohort (mean age = 32.8 y, mean CD4 = 375/mu l). For the reference strategy, we assume that all patients initiate stavudine-based ART with WHO stage III/IV disease and receive one line of ART (stavudine/WHO/one-line). We rank-in survival, cost-effectiveness, and equity terms-all 12 possible combinations of the following: (1) stavudine replacement with tenofovir, (2) ART initiation (by WHO stage, CD4,200 cells/mu l, or CD4,350 cells/mu l), and (3) one or two regimens, or lines, of available ART. Projected life expectancy for the reference strategy is 99.0 mo. Considering each of the guideline components separately, 5-y survival is maximized with ART initiation at CD4,350 cells/mu l (stavudine/<350/mu l/one-line, 87% survival) compared with stavudine/WHO/two-lines (66%) and tenofovir/WHO/one-line (66%). The greatest life expectancies are achieved via the following stepwise programmatic additions: stavudine/<350/mu l/one-line (124.3 mo), stavudine/<350/mu l/two-lines (177.6 mo), and tenofovir/<350/mu l/two-lines (193.6 mo). Three program combinations are economically efficient: stavudine/<350/ml/one-line (cost-effectiveness ratio, US$610/years of life saved [YLS]), tenofovir/<350/mu l/one-line (US$1,140/YLS), and tenofovir/<350/mu l/two-lines (US$2,370/YLS). Conclusions: In settings where immediate implementation of all of the new WHO treatment guidelines is not feasible, ART initiation at CD4,350 cells/mu ml provides the greatest short-and long-term survival advantage and is highly cost-effective. C1 [Walensky, Rochelle P.; Ciaranello, Andrea L.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.; Lorenzana, Sarah B.; Stoler, Adam W.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Ctr AIDS Res, Harvard Inst Global Hlth, Cambridge, MA 02138 USA. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Wood, Robin] Univ Cape Town, Desmond Tutu HIV Ctr, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa. [Paltiel, A. David] Yale Univ, Sch Med, New Haven, CT USA. [Anglaret, Xavier] INSERM, Ctr Rech Epidemiol & Biostat, Unite 897, Bordeaux, France. [Anglaret, Xavier] Univ Victor Segalen Bordeaux 2, Bordeaux, France. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. EM rwalensky@partners.org RI Wood, Robin/G-8509-2011; Anglaret, Xavier/F-7333-2013; OI Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Allergy and Infectious Diseases [R01 AI058736, K24 AI062476, P30 AI060354, K01 AI078754]; National Institute on Drug Abuse [R01 DA015612]; Doris Duke Charitable Foundation FX This work was supported by the National Institute of Allergy and Infectious Diseases (R01 AI058736, K24 AI062476, P30 AI060354, K01 AI078754), National Institute on Drug Abuse (R01 DA015612), and the Doris Duke Charitable Foundation (Clinical Scientist Development Award). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of manuscript. NR 41 TC 50 Z9 50 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD DEC PY 2010 VL 7 IS 12 AR e1000382 DI 10.1371/journal.pmed.1000382 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 697GA UT WOS:000285499600008 PM 21209794 ER PT J AU Acka, CA Raso, G N'Goran, EK Tschannen, AB Bogoch, II Seraphin, E Tanner, M Obrist, B Utzinger, J AF Acka, Cinthia A. Raso, Giovanna N'Goran, Eliezer K. Tschannen, Andres B. Bogoch, Isaac I. Seraphin, Essane Tanner, Marcel Obrist, Brigit Utzinger, Juerg TI Parasitic Worms: Knowledge, Attitudes, and Practices in Western Cote d'Ivoire with Implications for Integrated Control SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID NEGLECTED TROPICAL DISEASES; SCHISTOSOMA-MANSONI INFECTION; TRANSMITTED HELMINTH INFECTIONS; SPATIAL RISK PREDICTION; HEALTH-EDUCATION; INTESTINAL HELMINTHS; UPPER EGYPT; RURAL AREA; SCHOOLCHILDREN; HOOKWORM AB Background: In the developing world where parasitic worm infections are pervasive, preventive chemotherapy is the key strategy for morbidity control. However, local knowledge, attitudes, and practices (KAP) of parasitic worms are poorly understood, although such information is required for prevention and sustainable control. Methods: We carried out KAP surveys in two rural communities of Cote d'Ivoire that were subjected to school-based and community-based research and control activities. We used qualitative and quantitative methods. The former included observations, in-depth interviews with key informants, and focus group discussions with school children and adults. Quantitative methods consisted of a structured questionnaire administered to household heads. Principal Findings: Access to clean water was lacking in both communities and only a quarter of the households had functioning latrines. There was a better understanding of soil-transmitted helminthiasis than intestinal schistosomiasis, but community-based rather than school-based interventions appeared to improve knowledge of schistosomiasis. In the villages with community-based interventions, three-quarters of household interviewees knew about intestinal schistosomiasis compared to 14% in the village where school-based interventions were implemented (P<0.001). Whereas two-thirds of respondents from the community-based intervention village indicated that the research and control project was the main source of information, only a quarter of the respondents cited the project as the main source. Conclusions/Significance: Preventive chemotherapy targeting school-aged children has limitations, as older population segments are neglected, and hence lack knowledge about how to prevent and control parasitic worm infections. Improved access to clean water and sanitation is necessary, along with health education to make a durable impact against helminth infections. C1 [Acka, Cinthia A.; Seraphin, Essane] Univ Cocody Abidjan, UFR Sci Sociales, Abidjan, Cote Ivoire. [Acka, Cinthia A.; Raso, Giovanna; N'Goran, Eliezer K.; Tschannen, Andres B.] Ctr Suisse Rech Sci Cote Ivoire, Dept Environm & Sante, Abidjan, Cote Ivoire. [Raso, Giovanna; Tanner, Marcel; Obrist, Brigit; Utzinger, Juerg] Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland. [Raso, Giovanna; Tanner, Marcel; Obrist, Brigit; Utzinger, Juerg] Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland. [N'Goran, Eliezer K.] Univ Cocody Abidjan, UFR Biosci, Abidjan, Cote Ivoire. [Bogoch, Isaac I.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Obrist, Brigit] Univ Basel, Inst Social Anthropol, Basel, Switzerland. RP Acka, CA (reprint author), Univ Cocody Abidjan, UFR Sci Sociales, Abidjan, Cote Ivoire. EM juerg.utzinger@unibas.ch FU Centre Suisse de Recherches Scientifiques en Cote d'Ivoire (CSRS); Swiss Agency for Development and Cooperation (SDC); Swiss Federal Commission; Swiss National Science Foundation [PBBSB-109011, PPOOB-102883, PPOOB-119129]; European Union [032203] FX This study was supported by the Centre Suisse de Recherches Scientifiques en Cote d'Ivoire (CSRS) and received financial support from the Swiss Agency for Development and Cooperation (SDC), through the project "Contribution du CSRS au processus de reconciliation en Cote d'Ivoire" in the frame of the "Programme d'appui de la SDC a la reconciliation en Cote d'Ivoire". C. A. Acka is grateful to the Swiss Federal Commission for Fellowships for Foreign Student (CFBEE) for financing a several-months stay at the Swiss Tropical and Public Health Institute for analysis and writing up the current manuscript. G. Raso (project no. PBBSB-109011) and J. Utzinger (project no. PPOOB-102883, PPOOB-119129) are grateful to the Swiss National Science Foundation for financial support. J. Utzinger also acknowledges support from the European Union (FP6 STREP CONTRAST project, contract no. 032203). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 62 TC 23 Z9 23 U1 1 U2 18 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1935-2727 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD DEC PY 2010 VL 4 IS 12 AR e910 DI 10.1371/journal.pntd.0000910 PG 14 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 697VI UT WOS:000285547000009 PM 21200423 ER PT J AU Sheikh, A Charles, RC Rollins, SM Harris, JB Bhuiyan, MS Khanam, F Bukka, A Kalsy, A Porwollik, S Brooks, WA LaRocque, RC Hohmann, EL Cravioto, A Logvinenko, T Calderwood, SB McClelland, M Graham, JE Qadri, F Ryan, ET AF Sheikh, Alaullah Charles, Richelle C. Rollins, Sean M. Harris, Jason B. Bhuiyan, Md. Saruar Khanam, Farhana Bukka, Archana Kalsy, Anuj Porwollik, Steffen Brooks, W. Abdullah LaRocque, Regina C. Hohmann, Elizabeth L. Cravioto, Alejandro Logvinenko, Tanya Calderwood, Stephen B. McClelland, Michael Graham, James E. Qadri, Firdausi Ryan, Edward T. TI Analysis of Salmonella enterica Serotype Paratyphi A Gene Expression in the Blood of Bacteremic Patients in Bangladesh SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID TRANSCRIBED SEQUENCES SCOTS; COMPLETE GENOME SEQUENCE; TYPHOID-FEVER PATIENTS; SEROVAR TYPHIMURIUM; SELECTIVE CAPTURE; ESCHERICHIA-COLI; DIFFERENTIAL REGULATION; ANTIMICROBIAL PEPTIDES; PATHOGENICITY ISLANDS; RESISTANT SALMONELLA AB Background: Salmonella enterica serotype Paratyphi A is a human-restricted cause of paratyphoid fever, accounting for up to a fifth of all cases of enteric fever in Asia. Methodology/Principal Findings: In this work, we applied an RNA analysis method, Selective Capture of Transcribed Sequences (SCOTS), and cDNA hybridization-microarray technology to identify S. Paratyphi A transcripts expressed by bacteria in the blood of three patients in Bangladesh. In total, we detected 1,798 S. Paratyphi A mRNAs expressed in the blood of infected humans (43.9% of the ORFeome). Of these, we identified 868 in at least two patients, and 315 in all three patients. S. Paratyphi A transcripts identified in at least two patients encode proteins involved in energy metabolism, nutrient and iron acquisition, vitamin biosynthesis, stress responses, oxidative stress resistance, and pathogenesis. A number of detected transcripts are expressed from PhoP and SlyA-regulated genes associated with intra-macrophage survival, genes contained within Salmonella Pathogenicity Islands (SPIs) 1-4, 6, 10, 13, and 16, as well as RpoS-regulated genes. The largest category of identified transcripts is that of encoding proteins with unknown function. When comparing levels of bacterial mRNA using in vivo samples collected from infected patients to samples from in vitro grown organisms, we found significant differences for 347, 391, and 456 S. Paratyphi A transcripts in each of three individual patients (approximately 9.7% of the ORFeome). Of these, expression of 194 transcripts (4.7% of ORFs) was concordant in two or more patients, and 41 in all patients. Genes encoding these transcripts are contained within SPI-1, 3, 6 and 10, PhoP-regulated genes, involved in energy metabolism, nutrient acquisition, drug resistance, or uncharacterized genes. Using quantitative RT-PCR, we confirmed increased gene expression in vivo for a subset of these genes. Conclusion/Significance: To our knowledge, we describe the first microarray-based transcriptional analysis of a pathogen in the blood of naturally infected humans. C1 [Sheikh, Alaullah; Bhuiyan, Md. Saruar; Khanam, Farhana; Brooks, W. Abdullah; Cravioto, Alejandro; Qadri, Firdausi] Bangladesh ICDDR B, Int Ctr Diarrhoeal Dis Res, Dhaka, Bangladesh. [Sheikh, Alaullah; Charles, Richelle C.; Rollins, Sean M.; Harris, Jason B.; Bhuiyan, Md. Saruar; Kalsy, Anuj; LaRocque, Regina C.; Hohmann, Elizabeth L.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Charles, Richelle C.; Harris, Jason B.; LaRocque, Regina C.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Bukka, Archana] Univ Louisville, Sch Med, Dept Microbiol & Immunol, Louisville, KY 40292 USA. [Porwollik, Steffen; McClelland, Michael] Vaccine Res Inst San Diego, San Diego, CA USA. [Logvinenko, Tanya] Tufts Med Ctr, ICRHPS, Div Biostat, Boston, MA USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sheikh, A (reprint author), Bangladesh ICDDR B, Int Ctr Diarrhoeal Dis Res, Dhaka, Bangladesh. EM alaullah@icddrb.org RI McClelland, Michael/A-8583-2011; OI Rollins, Sean/0000-0002-3724-1989; McClelland, Michael/0000-0003-1788-9347 FU ICDDR,B; National Institutes of Health; National Institute of Allergy & Infectious Diseases [AI072599, AI077883, AI058935, AI052237, AI073971, AI075093, AI083964, AI039557, AI077645, AI083646, BARD IS-4267-09, A148635]; Johns Hopkins Bloomberg School of Public Health; ICDDRB-US Centers for Disease Control and Prevention; Thrasher Research Fund; Fogarty International Center [TW05572, K01 TW007409, K01 TW07144]; American Recovery and Reinvestment Act (ARRA) FIC [TW05572-S1]; NIAID [K08 AI089721]; Howard Hughes Medical Institute FX This work was supported by the ICDDR,B (www.icddrb.org) and grants from the National Institutes of Health, including the National Institute of Allergy & Infectious Diseases (www.niaid.nih.gov - AI072599, AI077883 [ETR]; AI058935 [SBC]; AI052237, AI073971, AI075093, AI083964, AI039557, AI077645, AI083646, and BARD IS-4267-09 [MMCC]; A148635 [JEG]); the PneumoADIP Project of the Johns Hopkins Bloomberg School of Public Health (www.preventpneumo.org - WAB); a ICDDRB-US Centers for Disease Control and Prevention Cooperative Agreement (www.cdc.gov - WAB); ICDDR, B core funds (FQ, WAB); The Thrasher Research Fund (www.thrasherresearch.org - WAB); a Training Grant in Vaccine Development from the Fogarty International Center (www.fic.nih.gov - TW05572 [AS, MSB, FQ]); an American Recovery and Reinvestment Act (ARRA) FIC Post-doctoral Fellowship in Global Infectious Diseases (TW05572-S1 [RCC]); Career Development Awards from the Fogarty International Center (K01 TW007409 [JBH], K01 TW07144 [RCL]), and NIAID (K08 AI089721 [RCC]); and a Physician Scientist Early Career Award from the Howard Hughes Medical Institute (www.hhmi.org - RCL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 16 Z9 17 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1935-2727 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD DEC PY 2010 VL 4 IS 12 AR e908 DI 10.1371/journal.pntd.0000908 PG 10 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 697VI UT WOS:000285547000007 PM 21151879 ER PT J AU Li, QY Eklund, AC Juul, N Haibe-Kains, B Workman, CT Richardson, AL Szallasi, Z Swanton, C AF Li, Qiyuan Eklund, Aron C. Juul, Nicolai Haibe-Kains, Benjamin Workman, Christopher T. Richardson, Andrea L. Szallasi, Zoltan Swanton, Charles TI Minimising Immunohistochemical False Negative ER Classification Using a Complementary 23 Gene Expression Signature of ER Status SO PLOS ONE LA English DT Article ID PRIMARY BREAST-CANCER; ESTROGEN-RECEPTOR STATUS; HISTOLOGIC GRADE; RECURRENCE; PREDICT; CHEMOTHERAPY; RESISTANCE; PATTERNS; SUBTYPES; THERAPY AB Background: Expression of the oestrogen receptor (ER) in breast cancer predicts benefit from endocrine therapy. Minimising the frequency of false negative ER status classification is essential to identify all patients with ER positive breast cancers who should be offered endocrine therapies in order to improve clinical outcome. In routine oncological practice ER status is determined by semi-quantitative methods such as immunohistochemistry (IHC) or other immunoassays in which the ER expression level is compared to an empirical threshold[1,2]. The clinical relevance of gene expression-based ER subtypes as compared to IHC-based determination has not been systematically evaluated. Here we attempt to reduce the frequency of false negative ER status classification using two gene expression approaches and compare these methods to IHC based ER status in terms of predictive and prognostic concordance with clinical outcome. Methodology/Principal Findings: Firstly, ER status was discriminated by fitting the bimodal expression of ESR1 to a mixed Gaussian model. The discriminative power of ESR1 suggested bimodal expression as an efficient way to stratify breast cancer; therefore we identified a set of genes whose expression was both strongly bimodal, mimicking ESR expression status, and highly expressed in breast epithelial cell lines, to derive a 23-gene ER expression signature-based classifier. We assessed our classifiers in seven published breast cancer cohorts by comparing the gene expression-based ER status to IHC-based ER status as a predictor of clinical outcome in both untreated and tamoxifen treated cohorts. In untreated breast cancer cohorts, the 23 gene signature-based ER status provided significantly improved prognostic power compared to IHCbased ER status (P = 0.006). In tamoxifen-treated cohorts, the 23 gene ER expression signature predicted clinical outcome (HR = 2.20, P = 0.00035). These complementary ER signature-based strategies estimated that between 15.1% and 21.8% patients of IHC-based negative ER status would be classified with ER positive breast cancer. Conclusion/Significance: Expression-based ER status classification may complement IHC to minimise false negative ER status classification and optimise patient stratification for endocrine therapies. C1 [Li, Qiyuan; Eklund, Aron C.; Juul, Nicolai; Workman, Christopher T.; Szallasi, Zoltan] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Haibe-Kains, Benjamin] Harvard Univ, Ctr Canc Computat Biol, Dana Farber Canc Inst, Computat Biol & Funct Genom Lab,Sch Publ Hlth, Boston, MA 02115 USA. [Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Szallasi, Zoltan] Harvard Univ, Childrens Hosp, Harvard MIT Div Hlth Sci & Technol CHIP HST, Informat Program,Sch Med, Boston, MA 02115 USA. [Swanton, Charles] Canc Res UK London Res Inst, Translat Canc Therapeut Lab, London, England. [Swanton, Charles] Royal Marsden Hosp, Breast Unit, Sutton, Surrey, England. [Swanton, Charles] Royal Marsden Hosp, Drug Dev Unit, Sutton, Surrey, England. RP Li, QY (reprint author), Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. EM zszallasi@chip.org; Charles.swanton@cancer.org.uk RI Haibe-Kains, Benjamin/D-3702-2011; Workman, Christopher/K-1066-2015; OI Haibe-Kains, Benjamin/0000-0002-7684-0079; Workman, Christopher/0000-0002-2210-3743; Szallasi, Zoltan/0000-0001-5395-7509; Eklund, Aron Charles/0000-0003-0861-1001 FU Cancer Research UK; Medical Research Council; Inflammatory Breast Cancer UK; Danish Council for Independent Research, Medical Sciences (FSS); National Institute of Health [NCI SPORE P50 CA 89393, R21LM008823-01A1, 1R03LM009979-01]; Breast Cancer Research Foundation (BCRF); BioSim (NoE) [LSHB-CT-2004-005137] FX CS is a senior Medical Research Council clinical research fellow and is funded by Cancer Research UK, the Medical Research Council and Inflammatory Breast Cancer UK. ZS and ACE are funded by the Danish Council for Independent Research, Medical Sciences (FSS), the National Institute of Health (grants NCI SPORE P50 CA 89393, R21LM008823-01A1, 1R03LM009979-01) and by the Breast Cancer Research Foundation (BCRF). QL is funded by BioSim (NoE), FP6, LSHB-CT-2004-005137. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 12 Z9 12 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 1 PY 2010 VL 5 IS 12 AR e15031 DI 10.1371/journal.pone.0015031 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 688AU UT WOS:000284821300013 PM 21152022 ER PT J AU Hashmi, JT Huang, YY Osmani, BZ Sharma, SK Naeser, MA Hamblin, MR AF Hashmi, Javad T. Huang, Ying-Ying Osmani, Bushra Z. Sharma, Sulbha K. Naeser, Margaret A. Hamblin, Michael R. TI Role of Low-Level Laser Therapy in Neurorehabilitation SO PM&R LA English DT Article AB This year marks the 50th anniversary of the discovery of the laser. The development of lasers for medical use, which became known as low-level laser therapy (LLLT) or photobiomodulation, followed in 1967. In recent years, LLLT has become an increasingly mainstream modality, especially in the areas of physical medicine and rehabilitation. At first used mainly for wound healing and pain relief, the medical applications of LLLT have broadened to include diseases such as stroke, myocardial infarction, and degenerative or traumatic brain disorders. This review will cover the mechanisms of LLLT that operate both on a cellular and a tissue level. Mitochondria are thought to be the principal photoreceptors, and increased adenosine triphosphate, reactive oxygen species, intracellular calcium, and release of nitric oxide are the initial events. Activation of transcription factors then leads to expression of many protective, anti-apoptotic, antioxidant, and pro-proliferation gene products. Animal studies and human clinical trials of LLLT for indications with relevance to neurology, such as stroke, traumatic brain injury, degenerative brain disease, spinal cord injury, and peripheral nerve regeneration, will be covered. PM R 2010;2:S292-S305 C1 [Hashmi, Javad T.; Huang, Ying-Ying; Sharma, Sulbha K.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hashmi, Javad T.; Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [Osmani, Bushra Z.] Aga Khan Med Coll, Karachi, Pakistan. [Naeser, Margaret A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Naeser, Margaret A.] VA Boston Healthcare Syst, Boston, MA USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Huang, Ying-ying/G-3153-2011; OI Huang, Ying-ying/0000-0003-3066-6981; Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01AI050875]; Center for Integration of Medicine and Innovative Technology [DAMD17-02-2-0006]; CDMRP Program in TBI [W81XWH-09-1-0514]; Air Force Office of Scientific Research [FA9950-04-1-0079] FX Disclosure: research in the Hamblin laboratory supported by NIH grant R01AI050875, Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006), CDMRP Program in TBI (W81XWH-09-1-0514), and Air Force Office of Scientific Research (FA9950-04-1-0079) NR 85 TC 75 Z9 83 U1 4 U2 28 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD DEC PY 2010 VL 2 IS 12 SU 2 BP S292 EP S305 DI 10.1016/j.pmrj.2010.10.013 PG 14 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V24LT UT WOS:000208412600010 PM 21172691 ER PT J AU Zafonte, R AF Zafonte, Ross TI Neural Plasticity: Developing a Physiologic Approach to Neurologic Recovery Introduction SO PM&R LA English DT Editorial Material C1 Harvard Univ, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Sch Med,Massachussets Gen Hosp, Boston, MA 02114 USA. RP Zafonte, R (reprint author), Harvard Univ, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Sch Med,Massachussets Gen Hosp, 125 Nashua St, Boston, MA 02114 USA. EM rzafonte@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD DEC PY 2010 VL 2 IS 12 SU 2 BP S207 EP S207 DI 10.1016/j.pmrj.2010.10.011 PG 1 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V24LT UT WOS:000208412600001 PM 21172682 ER PT J AU Borsook, D George, E Kussman, B Becerra, L AF Borsook, David George, Edward Kussman, Barry Becerra, Lino TI Anesthesia and perioperative stress Consequences on neural networks and postoperative behaviors SO PROGRESS IN NEUROBIOLOGY LA English DT Review DE Functional imaging; Pain; Stress; Surgery; Awareness; Cytokines; Anesthetics ID NEAR-INFRARED SPECTROSCOPY; TOTAL INTRAVENOUS ANESTHESIA; RANDOMIZED CONTROLLED-TRIAL; MULTIPLE NOXIOUS STIMULI; DEVELOPING RAT-BRAIN; GENERAL-ANESTHESIA; BISPECTRAL INDEX; APOPTOTIC NEURODEGENERATION; INTRAOPERATIVE AWARENESS; HEALTHY-VOLUNTEERS AB Anesthesia is a state of drug-induced unconsciousness with suppression of sensory perception and consists of both hypnotic and analgesic components The anesthesiologist monitors the clinical response to noxious stimuli and adjusts drug dosage(s) to achieve an adequate depth of anesthesia with the aim of reducing operative stress Acute stress in the perioperative period has four major contributors anxiety pain the surgical stress response and the potential neurotoxicity of anesthetic agents Any or all of these may act deleteriously on multiple systems in the brain and have known significant effects on brain regions such as the hippocampus and the hypothalamic-pituitary-adrenal axis Perioperative stress on the nervous system and the resultant central nervous system (CNS) changes are likely to be causative for altered behaviors that are seen postoperatively including chronic pain posttraumatic stress disorder and learning difficulties Improving the ability of the anesthesiologist to control all four components of acute perioperative stress could potentially reduce the negative impact of surgery on the brain Currently there is no objective measurement for any of these stressors The development and application of objective measures for perioperative stressors is the first step towards controlling these risk factors and eliminating or reducing their serious postoperative consequences In this paper we review known and likely effects of perioperative stressors on brain systems and how they may play a significant role in altered postoperative behaviors We discuss the role of current (and developing) measures of brain function and their potential for monitoring perioperative stress with an emphasis on functional neuroimaging (C) 2010 Elsevier Ltd All rights reserved C1 [Borsook, David; Becerra, Lino] Childrens Hosp Boston, Dept Radiol, Boston, MA USA. [George, Edward] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. [Kussman, Barry] Childrens Hosp Boston, Dept Anesthesiol, Boston, MA USA. RP Borsook, D (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Radiol & Psychiat, 115 Mill St, Belmont, MA 02478 USA. FU L Herlands Philanthropic Fund for Pain Research; NINDS [K24 (NS064050)] FX This work was supported by the L Herlands Philanthropic Fund for Pain Research to DB and LB and K24 (NS064050) NINDS (DB) NR 195 TC 20 Z9 24 U1 4 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD DEC PY 2010 VL 92 IS 4 BP 601 EP 612 DI 10.1016/j.pneurobio.2010.08.006 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 699RC UT WOS:000285679500010 PM 20727935 ER PT J AU Askenazi, M Marto, JA Linial, M AF Askenazi, Manor Marto, Jarrod A. Linial, Michal TI The complete peptide dictionary - A meta-proteomics resource SO PROTEOMICS LA English DT Article DE Bioinformatics; MS proteomics; Peptides; RESTful interface; Web service ID MASS-SPECTROMETRY; BACTERIA AB Recent developments in MS based proteomics have increased the emphasis on peptides as a primary observable While peptides are identified by tandem mass spectra the link between peptide and protein remains implicit given the bottom up nature of the experiment in which proteins are enzymatically digested prior to sequencing It is therefore useful to provide a fast lookup from peptide to protein in order to systematically establish the broadest possible protein basis for the observed peptides Here we describe Pep2Pro a fast web service providing protein lookup by peptides covering the entire protein space comprising 10 million UniRef100 sequences We demonstrate the usefulness of the service by reanalyzing peptides from two recent meta proteomic data sets and identifying taxon specific peptides thereby implicating individual species as being present in these complex samples The Pep2Pro web service can be accessed at http //www pep2pro org C1 [Askenazi, Manor; Linial, Michal] Hebrew Univ Jerusalem, Dept Biol Chem, IL-91904 Jerusalem, Israel. [Askenazi, Manor; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Askenazi, Manor; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Askenazi, Manor; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Linial, M (reprint author), Hebrew Univ Jerusalem, Dept Biol Chem, IL-91904 Jerusalem, Israel. FU BSF [2007219]; EU FRVII Prospects consortium FX The authors thank members of the Linial Lab for valuable discussions and testing of the Pep2Pro web service This work was supported by the BSF grant number 2007219 and EU FRVII Prospects consortium NR 14 TC 9 Z9 9 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD DEC PY 2010 VL 10 IS 23 BP 4306 EP 4310 DI 10.1002/pmic.201000270 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 701VK UT WOS:000285851900016 PM 21082763 ER PT J AU Elder, GA Mitsis, EM Ahlers, ST Cristian, A AF Elder, Gregory A. Mitsis, Effie M. Ahlers, Stephen T. Cristian, Adrian TI Blast-induced Mild Traumatic Brain Injury SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Blast-related brain injury; Improvised explosive device; Posttraumatic stress disorder; Traumatic brain injury ID POSTTRAUMATIC-STRESS-DISORDER; CENTRAL-NERVOUS-SYSTEM; DIFFUSE AXONAL INJURY; ADULT-RAT BRAIN; PERSISTENT POSTCONCUSSIVE SYMPTOMS; TYMPANIC-MEMBRANE PERFORATION; LASTING IMPULSE NOISE; NON-PENETRATIVE BLAST; WHITE-MATTER INJURY; HEAD-INJURY AB Traumatic brain injury (TBI) has been a major cause of mortality and morbidity in the wars in Iraq and Afghanistan Blast exposure has been the most common cause of TBI, occurring through multiple mechanisms What is less clear is whether the primary blast wave causes brain damage through mechanisms that are distinct from those common in civilian TBI and whether multiple exposures to low-level blast can lead to long-term sequelae Complicating TBI in soldiers is the high prevalence of posttraumatic stress disorder At present the relationship is unclear Resolution of these issues will affect both treatment strategies and strategies for the protection of troops in the field C1 [Elder, Gregory A.] James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, Bronx, NY 10468 USA. [Elder, Gregory A.; Mitsis, Effie M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Elder, Gregory A.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Mitsis, Effie M.; Cristian, Adrian] James J Peters Vet Affairs Med Ctr, Rehabil Med Serv, Bronx, NY 10468 USA. [Ahlers, Stephen T.] Naval Med Res Ctr, Operat & Undersea Med Directorate, Silver Spring, MD 20910 USA. [Cristian, Adrian] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY 10029 USA. RP Elder, GA (reprint author), James J Peters Vet Affairs Med Ctr, Neurol Serv, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 105 TC 71 Z9 72 U1 1 U2 14 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 2010 VL 33 IS 4 BP 757 EP + DI 10.1016/j.psc.2010.08.001 PG 26 WC Psychiatry SC Psychiatry GA 694TA UT WOS:000285320700003 PM 21093677 ER PT J AU Riggio, S AF Riggio, Silvana TI Traumatic Brain Injury and Its Neurobehavioral Sequelae SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Traumatic brain injury; Postconcussive syndrome; Neuropsychiatric disorders; Frontal lobe seizures ID POSTTRAUMATIC-STRESS-DISORDER; HEAD-INJURY; CHRONIC PAIN; PSYCHIATRIC-DISORDERS; SYMPTOMS; FATIGUE; ASSOCIATION; PREVALENCE; CONCUSSION; DISABILITY AB The neurobehavioral sequelae (NBS) of traumatic brain injury (TBI) consist of a spectrum of somatic neurological and psychiatric symptoms The challenge for clinicians lies in understanding the interface of the various symptoms and how they interrelate with other entities Specifically, the challenge is differentiating post-TBI-related symptoms from pre-existing or de novo psychiatric neurological and/or systemic disorders A comprehensive evaluation and a multidisciplinary approach to evaluating patients are essential to be able to develop the differential diagnosis needed to design a management plan that maximizes recovery C1 [Riggio, Silvana] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Riggio, Silvana] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Riggio, Silvana] James J Peters VAMC, Dept Psychiat, Bronx, NY USA. RP Riggio, S (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. NR 46 TC 15 Z9 15 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 2010 VL 33 IS 4 BP 807 EP + DI 10.1016/j.psc.2010.08.004 PG 14 WC Psychiatry SC Psychiatry GA 694TA UT WOS:000285320700006 PM 21093680 ER PT J AU Pasinetti, GM Fivecoat, H Ho, L AF Pasinetti, Giulio Maria Fivecoat, Hayley Ho, Lap TI Personalized Medicine in Traumatic Brain Injury SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Postconscussive traumatic brain injury; MicroRNA; Biomarker; Personalized medicine ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; COGNITIVE REHABILITATION; BREAST-CANCER; TASK-FORCE; EXPRESSION; RISK; TAU; CHEMOTHERAPY; MECHANISMS AB Patients who have sustained a mild traumatic brain injury (TBI) from both civilian and military populations exhibit clinical symptoms of varying severity with minimal to profound impact on their daily functioning Although most patients make a full recovery, a subgroup of mild TBI patients develop cognitive somatic, and neurobehavioral sequelae that generally resolve over 3 to 6 months a smaller subgroup develop persisting symptoms The reason why a mild TBI results in varying clinical symptoms is currently unknown Based on evidence that microRNA species in peripheral blood mononuclear cells (PBMCs) may reflect molecular alterations in neurodegenerative disorders it can be hypothesized that at early preclinical phases of the disease PBMC may provide an ideal and clinically assessable window' into the brain Thus it is conceivable that changes in the expression profile of clinically accessible biological indices (biomarkers) such as microRNA in PBMC may reflect molecular alterations C1 [Pasinetti, Giulio Maria; Fivecoat, Hayley; Ho, Lap] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY 10468 USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. NR 40 TC 5 Z9 5 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 2010 VL 33 IS 4 BP 905 EP + DI 10.1016/j.psc.2010.09.003 PG 11 WC Psychiatry SC Psychiatry GA 694TA UT WOS:000285320700011 PM 21093685 ER PT J AU Goldstein, G Luther, JF Haas, GL Appelt, CJ Gordon, AJ AF Goldstein, Gerald Luther, James F. Haas, Gretchen L. Appelt, Cathleen J. Gordon, Adam J. TI Factor Structure and Risk Factors for the Health Status of Homeless Veterans SO PSYCHIATRIC QUARTERLY LA English DT Article DE Homeless; Health status; Comorbidity ID SERIOUS MENTAL-ILLNESS AB Homeless veterans have numerous health problems that have been previously characterized as falling into four major subgroups; addiction, psychosis, vascular disorders, and generalized medical and psychiatric illness. Comorbid conditions are common, often involving a combination of psychiatric and medical disorders. Using data from the same survey of homeless veterans that was used to establish these subgroups with cluster analysis, the present study examined the structure of these subgroup patterns through the use of factor analysis. This analysis yielded a five factor solution. They were named "Cardiac", Mood, Stress, Addiction, and Psychosis factors. Factor scores were computed and an odds ratio analysis was accomplished to determine the association between obtaining a high score on a given factor with a number of sociodemographic and homelessness related variables. It was concluded that health status of homeless veterans is a complex condition, but has a clear latent structure demonstrated by factor analysis. Scoring high or low on a particular factor is associated with numerous historical and sociodemographic considerations, notably age, ethnicity, and employment status. C1 [Goldstein, Gerald; Luther, James F.; Haas, Gretchen L.; Appelt, Cathleen J.; Gordon, Adam J.] Vet Affairs Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. [Goldstein, Gerald; Luther, James F.; Haas, Gretchen L.; Appelt, Cathleen J.; Gordon, Adam J.] Univ Pittsburgh, Pittsburgh, PA USA. [Gordon, Adam J.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. RP Goldstein, G (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. EM ggold@nb.net FU NIMH NIH HHS [T32 MH15169] NR 16 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-2720 J9 PSYCHIAT QUART JI Psychiatr. Q. PD DEC PY 2010 VL 81 IS 4 BP 311 EP 323 DI 10.1007/s11126-010-9140-4 PG 13 WC Psychiatry SC Psychiatry GA 666ED UT WOS:000283094300005 PM 20532627 ER PT J AU Denneson, LM Basham, C Dickinson, KC Crutchfield, MC Millet, L Shen, X Dobscha, SK AF Denneson, Lauren M. Basham, Chandra Dickinson, Kathryn C. Crutchfield, Megan C. Millet, Lisa Shen, Xun Dobscha, Steven K. TI Suicide Risk Assessment and Content of VA Health Care Contacts Before Suicide Completion by Veterans in Oregon SO PSYCHIATRIC SERVICES LA English DT Article ID MENTAL-HEALTH; DEPRESSION; POPULATION; STRATEGIES; MORTALITY; VALIDITY; SYSTEM; DEATH; IRAQ AB Objective: This study described health care contacts at a Department of Veterans Affairs (VA) medical center in Oregon in the year before death of veterans who completed suicide. Methods: Oregon Violent Death Reporting System (OVDRS) data and VA administrative data were linked to identify the 112 veterans who completed suicide in Oregon between 2000 and 2005 and who had contact with a single VA medical center in the year before death. Medical records were reviewed to collect data on clinician assessment of suicide risk and reasons for the last contact. Results: In the year before death, 54 veterans (48%) had one or more mental health contacts and 71 (63%) had one or more primary care contacts. The mean age was 57; common diagnoses included mood disorders (38%) and cardiovascular disease (38%). The median number of days between the last contact and date of death was 42 (range=0-358). Thirty-six last contacts (32%) were patient initiated for new or exacerbated medical concerns, and 76 (68%) were follow-ups for ongoing problems. Clinicians noted that 41 patients (37%) were experiencing emotional distress at the last contact. Thirteen of the 18 patients (72%) who were assessed for suicidal ideation at their last contact denied such thoughts. Conclusions: During their last contact, most veterans were seen for routine medical care and few endorsed thoughts of suicide. Results underscore challenges that clinicians face in identifying and caring for veterans at risk of suicide in health care settings. Additional research is indicated to identify better ways to facilitate communication of suicidal thoughts when they are present. (Psychiatric Services 61:1192-1197, 2010) C1 [Denneson, Lauren M.; Dickinson, Kathryn C.; Crutchfield, Megan C.; Dobscha, Steven K.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Phys & Mental D, Portland, OR 97207 USA. [Basham, Chandra] ZoomCare PC, Hillsboro, OR USA. [Millet, Lisa; Shen, Xun] Injury & Violence Prevent Program, Oregon Publ Hlth Div, Portland, OR USA. RP Denneson, LM (reprint author), Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Phys & Mental D, 3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM lauren.denneson@va.gov FU VA; Veterans Health Administration; VA Health Services [DHI-08-096] FX This article is based on work supported in part by the VA, the Veterans Health Administration, and VA Health Services Research and Development Service Project DHI-08-096. The views expressed are those of the authors and do not necessarily reflect the position or policy of the VA or the U.S. government. NR 23 TC 22 Z9 22 U1 3 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD DEC PY 2010 VL 61 IS 12 BP 1192 EP 1197 DI 10.1176/appi.ps.61.12.1192 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 688DE UT WOS:000284829200006 PM 21123402 ER PT J AU Hansen, RA Chen, SY Gaynes, BN Maciejewski, ML AF Hansen, Richard A. Chen, Shih-Yin Gaynes, Bradley N. Maciejewski, Matthew L. TI Relationship of Pharmaceutical Promotion to Antidepressant Switching and Adherence: A Retrospective Cohort Study SO PSYCHIATRIC SERVICES LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PRESCRIPTION DRUGS; PHARMACY RECORDS; CONSUMER; DEPRESSION; PHYSICIANS; VALIDATION; REQUESTS; THERAPY; IMPACT AB Objective: Patient nonadherence and early discontinuation of antidepressant treatment are common. Pharmaceutical promotion to consumers and physicians may influence this behavior. The objectives of this study were to explore whether promotional spending is related to early antidepressant switching, acute-phase adherence, and continuation-phase adherence. Methods: A retrospective cohort study was conducted with national promotional expenditure data merged with medical and prescription claims data from a large national health plan affiliated with i3 Innovus. Included were records for continuously insured adults with major depression who received a new prescription for an antidepressant: 5,010 were in the cohort assessed for switching, 4,457 were in the cohort assessed for acute-phase adherence, and 1,772 were in the cohort assessed for continuation-phase adherence. National promotional efforts were estimated by examining inflation-adjusted spending on direct-to-consumer advertising (DTCA) and physician detailing. Clinical guidelines were used to create proxies for aspects of treatment outcomes, including antidepressant switching and adherence in the acute phase and adherence in the continuation phase. Logistic regression models estimated the association between promotional variables and these outcomes. Results: Patients taking medications that were more highly promoted to physicians were less likely to switch medications (odds ratio [ OR]=.61) and were more likely to be adherent during the acute phase of treatment (OR=1.13). DTCA had little effect on switching or antidepressant adherence. Conclusions: Detailing to physicians was associated with lower rates of medication switching and had a positive relationship with patient adherence during early antidepressant treatment. This finding indicates that certain aspects of promotion may have beneficial effects on antidepressant use. (Psychiatric Services 61:1232-1238, 2010) C1 [Hansen, Richard A.] Univ N Carolina, Div Pharmaceut Outcomes & Policy, Chapel Hill, NC USA. [Gaynes, Bradley N.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Chen, Shih-Yin] United BioSource Corp, Ctr Hlth Econ & Sci Policy, Lexington, MA USA. [Maciejewski, Matthew L.] Duke Univ, US Dept Vet Affairs, Ctr Hlth Serv Res Primary Care, Med Ctr, Durham, NC USA. [Maciejewski, Matthew L.] Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27710 USA. RP Hansen, RA (reprint author), Auburn Univ, Harrison Sch Pharm, Dept Pharm Care Syst, 207 Dunstan Hall, Auburn, AL 26849 USA. EM rah0019@auburn.edu OI Gaynes, Bradley/0000-0002-8283-5030; Hansen, Richard/0000-0002-4578-6698 FU American Association of Colleges of Pharmacy; National Institutes of Health [K12RR023248]; Takeda Pharmaceuticals; GlaxoSmithKline; Bristol-Myers Squibb; M-3 Information; Novartis FX A portion of this work was funded by the new investigator program of the American Association of Colleges of Pharmacy. Dr. Hansen was supported by grant K12RR023248 from the National Institutes of Health at the time of this work. The authors thank Emily Brouwer, Pharm.D., for her contributions to data management; David Ridley, Ph.D., for his contribution to study design; and Julie Donohue, Ph.D., for her insightful comments on the manuscript.; Dr. Hansen has received consulting fees and research support from Takeda Pharmaceuticals and GlaxoSmithKline. Dr. Gaynes has received consulting fees and research support from Bristol-Myers Squibb, M-3 Information, and Novartis, and he has served as an advisor to Bristol-Myers Squibb. Dr. Maciejewski has received consulting fees from Takeda Pharmaceuticals. Dr. Chen reports no competing interests. NR 35 TC 6 Z9 7 U1 3 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD DEC PY 2010 VL 61 IS 12 BP 1232 EP 1238 DI 10.1176/appi.ps.61.12.1232 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 688DE UT WOS:000284829200012 PM 21123408 ER PT J AU Tolin, DF Steenkamp, MM Marx, BP Litz, BT AF Tolin, David F. Steenkamp, Maria M. Marx, Brian P. Litz, Brett T. TI Detecting Symptom Exaggeration in Combat Veterans Using the MMPI-2 Symptom Validity Scales: A Mixed Group Validation SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE MMPI-2; posttraumatic stress disorder; veterans; validity; symptom exaggeration ID POSTTRAUMATIC-STRESS-DISORDER; DISCRIMINANT FUNCTION INDEX; COMPENSATION-SEEKING; US VETERANS; PTSD; VIETNAM; PSYCHOPATHOLOGY; POPULATION; INVENTORY; AGREEMENT AB Although validity scales of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2; J. N. Butcher, W. G. Dahlstrom, J. R. Graham, A. Tellegen, & B. Kaemmer, 1989) have proven useful in the detection of symptom exaggeration in criterion-group validation (CGV) studies, usually comparing instructed feigners with known patient groups, the application of these scales has been problematic when assessing combat veterans undergoing posttraumatic stress disorder (PTSD) examinations. Mixed group validation (MGV) was employed to determine the efficacy of MMPI-2 exaggeration scales in compensation-seeking (CS) and noncompensation-seeking (NCS) veterans. Unlike CGV, MGV allows for a mix of exaggerating and nonexaggerating individuals in each group, does not require that the exaggeration versus nonexaggerating status of any individual be known, and can be adjusted for different base-rate estimates. MMPI-2 responses of 377 male veterans were examined according to CS versus NCS status. MGV was calculated using 4 sets of base-rate estimates drawn from the literature. The validity scales generally performed well (adequate sensitivity, specificity, and efficiency) under most base-rate estimations, and most produced cutoff scores that showed adequate detection of symptom exaggeration, regardless of base-rate assumptions. These results support the use of MMPI-2 validity scales for PTSD evaluations in veteran populations, even under varying base rates of symptom exaggeration. C1 [Tolin, David F.] Inst Living, Anxiety Disorders Ctr, Hartford, CT 06106 USA. [Tolin, David F.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Steenkamp, Maria M.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Litz, Brett T.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Litz, Brett T.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Tolin, DF (reprint author), Inst Living, Anxiety Disorders Ctr, 200 Retreat Ave, Hartford, CT 06106 USA. EM dtolin@harthosp.org NR 49 TC 14 Z9 14 U1 0 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD DEC PY 2010 VL 22 IS 4 BP 729 EP 736 DI 10.1037/a0020973 PG 8 WC Psychology, Clinical SC Psychology GA 693NR UT WOS:000285231300002 PM 21038968 ER PT J AU Phelan, CH Love, GD Ryff, CD Brown, RL Heidrich, SM AF Phelan, Cynthia H. Love, Gayle D. Ryff, Carol D. Brown, Roger L. Heidrich, Susan M. TI Psychosocial Predictors of Changing Sleep Patterns in Aging Women A Multiple Pathway Approach SO PSYCHOLOGY AND AGING LA English DT Article DE sleep older women; psychological well being; depression; health ID QUALITY-OF-LIFE; OLDER-ADULTS; COMPLAINTS; HEALTH; COMMUNITY; PREVALENCE; INSOMNIA; MODEL; INDEX; INTERLEUKIN-6 AB The authors of this investigation sought to examine changes in the sleep quality of older women over time and to determine whether dimensions of psychological well being health (subjective health and number of illnesses) and psychological distress (depression and anxiety) predict these changes A secondary analysis was conducted with a longitudinal sample of aging women (Kwan Love Ryff & Essex 2003) Of 518 community dwelling older women in the parent study, 115 women (baseline M age = 67 years SD = 7 18) with data at baseline, 8 years, and 10 years were used for this investigation Participants completed self administered questionnaires and participated in in home interviews and observations Growth curve modeling was used to examine the overall linear trajectories of sleep quality Growth mixture modeling was used to examine whether there were different patterns of change in sleep quality over time and to examine baseline predictors of each pattern Sleep quality declined over time but not for all women Two distinctly different sleep patterns emerged good but declining sleep quality and disrupted sleep quality Higher psychological well being (positive relations with others environmental mastery personal growth purpose in life and self acceptance) fewer Illnesses and lower depression scores at baseline predicted reduced odds for membership in the disrupted sleep group Future research is needed to examine whether interventions focused on maintaining or enhancing psychological well being could minimize later life declines in sleep quality C1 [Phelan, Cynthia H.] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI 53705 USA. [Love, Gayle D.; Ryff, Carol D.] Univ Wisconsin, Inst Aging, Madrid, Spain. [Brown, Roger L.; Heidrich, Susan M.] Univ Wisconsin, Sch Nursing, Madison, WI USA. RP Phelan, CH (reprint author), William S Middleton Mem Vet Adm Med Ctr, GRECC, 2500 Overlook Terrace, Madison, WI 53705 USA. FU NCRR NIH HHS [M01 RR003186-20, M01 RR03186, M01 RR003186]; NIA NIH HHS [R01-AG0879]; NIMH NIH HHS [P50 MH061083, P50 MH061083-01, P50 MH61083] NR 52 TC 19 Z9 20 U1 2 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD DEC PY 2010 VL 25 IS 4 BP 858 EP 866 DI 10.1037/a0019622 PG 9 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA 701IM UT WOS:000285811600012 PM 20731498 ER PT J AU Lozano, BE Stephens, RS AF Lozano, Brian E. Stephens, Robert S. TI Comparison of Participatively Set and Assigned Goals in the Reduction of Alcohol Use SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE goal setting; alcohol; college students; social cognitive theory ID COLLEGE-STUDENT DRINKERS; SELF-EFFICACY; CONSTRUCT-VALIDITY; TASK-PERFORMANCE; FOLLOW-UP; CONTROLLED DRINKING; SETTING PROCESS; COMMITMENT; ABSTINENCE; ACCEPTANCE AB The effects of setting goals on goal commitment, self-efficacy for goal achievement, and goal achievement in the context of an alcohol use intervention were examined using an experimental design in which participants were randomized to participatively set goals. assigned goals. and no goal conditions. One hundred and twenty-six heavy-drinking college students received a single cognitive-behavioral assessment/intervention session and completed measures of goal commitment. self-efficacy for goal achievement, and alcohol use. Results were consistent with, and expanded upon, previous research by demonstrating that having a goal for limiting alcohol consumption was predictive of lower quantity and frequency of alcohol use relative to not having a goal. Participation in goal setting yielded greater goal commitment and self-efficacy for goal achievement than assigned goals. but did not result in significantly greater reductions in alcohol use relative to assigned goals. Goal commitment and self-efficacy explained unique variance in the prediction of alcohol use at follow-up. Findings support the importance of goal setting in alcohol interventions and suggest areas for further research. C1 [Lozano, Brian E.] Ralph H Johnson VAMC, Mental Hlth Serv 116, Charleston, SC 29401 USA. [Stephens, Robert S.] Virginia Polytech Inst & State Univ, Dept Psychol, Blacksburg, VA 24061 USA. RP Lozano, BE (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM Brian.Lozano@va.gov NR 61 TC 11 Z9 11 U1 4 U2 8 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD DEC PY 2010 VL 24 IS 4 BP 581 EP 591 DI 10.1037/a0021444 PG 11 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 705WJ UT WOS:000286171100004 PM 21198221 ER PT J AU Charnas, JW Hilsenroth, MJ Zodan, J Blais, MA AF Charnas, Jocelyn W. Hilsenroth, Mark J. Zodan, Jennifer Blais, Mark A. TI SHOULD I STAY OR SHOULD I GO? PERSONALITY ASSESSMENT INVENTORY AND RORSCHACH INDICES OF EARLY WITHDRAWAL FROM PSYCHOTHERAPY SO PSYCHOTHERAPY LA English DT Article DE Personality Assessment Inventory (PAI); Rorschach; early withdrawal ID MENTAL-HEALTH TREATMENT; PSYCHOLOGICAL-ASSESSMENT; THERAPEUTIC ALLIANCE; COMPREHENSIVE SYSTEM; PREMATURE TERMINATION; TEMPORAL STABILITY; PATIENT PROGRESS; THERAPIST; DROPOUT; MMPI AB The Personality Assessment Inventory (PAI) and the Rorschach were used to investigate differences between patients who withdrew early from university-based outpatient psychodynamic psychotherapy and those who continued in treatment. The study employs two sets of analyses, one utilizing the complete sample (N = 101) and a second comprised of comparison pairs matched on the specific therapist delivering treatment (n = 36 for Rorschach; n = 38 for PAI). It was hypothesized that early withdrawers would score higher on the PAI Treatment Rejection Scale (RXR) and the PAI Treatment Process Index (TPI) than treatment continuers. It was also hypothesized that early treatment withdrawers will have better overall interpersonal relationships, less need for closeness and intimacy, less available psychological resources and more current stimulus demands, and lower levels of psychological/cognitive disturbance as measured by the Rorschach. In addition, differences between the two groups on PAI treatment and clinical scales and subscales were examined. Results indicated that PAI RXR differentiated between the two groups (p < .05) in the expected direction. Limited differences between withdrawers and continuers were found on the Rorschach and other PAI scales. Potential explanations for the findings as well as a discussion of clinical applicability are presented. C1 [Charnas, Jocelyn W.; Hilsenroth, Mark J.; Zodan, Jennifer] Adelphi Univ, Derner Inst Adv Psychol Studies, Garden City, NY 11530 USA. [Blais, Mark A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Blais, Mark A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Charnas, JW (reprint author), 610 Pk Ave, New York, NY 10065 USA. EM jocelyncharnas@gmail.com NR 81 TC 8 Z9 9 U1 0 U2 5 PU AMER PSYCHOLOGICAL ASSOC, DIV PSYCHOTHERAPY PI CORAL GABLES PA 1390 SOUTH DIXIE HIGHWAY, STE 2222, CORAL GABLES, FL 33146-2946 USA SN 0033-3204 J9 PSYCHOTHERAPY JI Psychotherapy PD DEC PY 2010 VL 47 IS 4 BP 484 EP 499 DI 10.1037/a0021180 PG 16 WC Psychology, Clinical SC Psychology GA 705WB UT WOS:000286170300005 PM 21198237 ER PT J AU Regenbogen, SE Hirose, M Imanaka, Y Oh, EH Fukuda, H Gawande, AA Takemura, T Yoshihara, H AF Regenbogen, S. E. Hirose, M. Imanaka, Y. Oh, E-H Fukuda, H. Gawande, A. A. Takemura, T. Yoshihara, H. TI A comparative analysis of incident reporting lag times in academic medical centres in Japan and the USA SO QUALITY & SAFETY IN HEALTH CARE LA English DT Article ID PATIENT SAFETY; SYSTEM; PHYSICIANS; ERRORS; ATTITUDES; HOSPITALS; BARRIERS; EVENTS AB Background Delays in reporting of medical errors may signal deficiencies in the performance of hospital-based incident reporting. We sought to understand the characteristics of hospitals, providers and patient injuries that affect such delays. Setting and Methods All incident reports filed between May 2004 and August 2005 at the Kyoto University Hospital (KUH) in Japan and the Brigham and Women's Hospital (BWH) in the USA were evaluated. Lag time between each event and the submission of an incident report were computed. Multivariable Poisson regression with overdispersion, to control for previously described confounding factors and identify independent predictors of delays, was used. Results Unadjusted lag times were significantly longer for physicians than other reporters (3.6 vs 1.8 days, p<0.0001), longer for major than minor events (4.1 vs 1.9 days, p=0.0006) and longer at KUH than at BWH (3.1 vs 1.0 days, p<0.0001). In multivariable analysis, lag times at KUH remained nearly three times longer than at BWH (incidence-rate ratio 2.95, 95% CI 2.84 to 3.06, p<0.0001). Conclusions Lag time provides a novel and useful metric for evaluating the performance of hospital-based incident reporting systems. Across two very different health systems, physicians reported far fewer events, with significant delays compared with other providers. Even after controlling for important confounding factors, lag times at KUH were nearly triple those at BWH, suggesting significant differences in the performance of their reporting systems, potentially attributable to either the ease of online reporting at BWH or to the greater attention to patient safety reporting in that hospital. C1 [Regenbogen, S. E.; Hirose, M.; Gawande, A. A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Regenbogen, S. E.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Hirose, M.] Kyoto Univ Hosp, Patient Safety Div, Sakyou Ku, Kyoto 606, Japan. [Hirose, M.; Imanaka, Y.; Oh, E-H; Fukuda, H.] Kyoto Univ, Dept Healthcare Econ & Qual Management, Sch Publ Hlth, Grad Sch Med,Sakyou Ku, Kyoto, Japan. [Oh, E-H] Hyupsung Univ, Dept Hlth Management, Hwaseong Si, Gyeonggi Do, South Korea. [Gawande, A. A.; Yoshihara, H.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Takemura, T.] Kyoto Univ Hosp, Dept Med Informat, Sakyou Ku, Kyoto 606, Japan. RP Hirose, M (reprint author), Shimane Univ Hosp, Ctr Educ Hosp Med, 89-1 Enya Chou, Izumo, Shimane 6938501, Japan. EM mhirose@med.shimane-u.ac.jp FU Agency for Healthcare Research and Quality [T32-HS000020]; Abe Fellowship Program; Japan Foundation Center for Global Partnership; American Council of Learned Societies FX Dr Regenbogen was supported by Kirschstein National Research Service Award T32-HS000020 from the Agency for Healthcare Research and Quality. Dr Hirose was supported in part by the Abe Fellowship Program, administered by the Social Science Research Council and the American Council of Learned Societies, in cooperation with and with funds provided by the Japan Foundation Center for Global Partnership. NR 20 TC 0 Z9 0 U1 2 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD DEC PY 2010 VL 19 IS 6 AR e10 DI 10.1136/qshc.2008.029215 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 705BL UT WOS:000286103300009 PM 20194219 ER PT J AU Kim, HJ Park, SH Pickhardt, PJ Yoon, SN Lee, SS Yee, J Kim, DH Kim, AY Kim, JC Yu, CS Ha, HK AF Kim, Hye Jin Park, Seong Ho Pickhardt, Perry J. Yoon, Sang Nam Lee, Seung Soo Yee, Judy Kim, David H. Kim, Ah Young Kim, Jin Cheon Yu, Chang Sik Ha, Hyun Kwon TI CT Colonography for Combined Colonic and Extracolonic Surveillance after Curative Resection of Colorectal Cancer SO RADIOLOGY LA English DT Article ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; FOLLOW-UP; ADVANCED NEOPLASIA; COLONOSCOPY; POPULATION; EXPERIENCE; RISK; FEASIBILITY; RECURRENCE; ADENOMAS AB Purpose: To determine the accuracy of contrast material-enhanced computed tomographic (CT) colonography for postoperative surveillance in colorectal cancer patients without clinical or laboratory evidence of disease recurrence. Materials and Methods: The Institutional Review Board approved this HIPAA-compliant study and waived informed consent. Between January 2006 and December 2007, 742 consecutive patients without clinical or laboratory evidence of recurrence following curative-intent colorectal cancer surgery underwent contrast-enhanced CT colonography. Of these, 548 patients who had subsequent colonoscopy and pathologic confirmation of colonic lesions (reference standard) were included in the colonic analysis. All 742 patients were included in the extracolonic analysis. Sensitivity and specificity of CT colonography for nonanastomotic colonic lesions at least 6 mm in size and anastomotic lesions of any size, including performance according to lesion histologic type, were determined. Diagnostic yields of contrast-enhanced CT colonography for colonic cancers and for extracolonic recurrences were obtained. Results: CT colonography depicted all six metachronous cancers and one anastomotic recurrence within the colon in six patients (0.8%; 95% confidence interval [CI]: 0.3%, 1.8%]), for per-patient and per-lesion sensitivities of 100% (95% CIs: 64.3%, 100% and 67.8%, 100%, respectively). All cancer lesions within the colon were amenable to additional curative treatment. CT colonography per-patient and per-lesion sensitivity was 81.8% (95% CI: 60.9%, 93.3%) and 80.8% (95% CI: 64.3%, 97.2%), respectively, for advanced neoplasia and 80.0% (95% CI: 68.6%, 88.1%) and 78.5% (95% CI: 68.3%, 88.7%), respectively, for all adenomatous lesions. Negative predictive values for adenocarcinoma, advanced neoplasia, and all adenomatous lesions were 100%, 99.1%, and 97.0%, respectively. CT colonography specificity was 93.1% (95% CI: 90.4%, 95.2%). Contrast-enhanced CT colonography enabled detection of extracolonic recurrences in an additional 11 patients (1.5%; 95% CI: 0.8%, 2.7%). Conclusion: Contrast-enhanced CT colonography is an accurate and practical surveillance tool following colorectal cancer surgery in patients without clinical or laboratory evidence of recurrence, allowing for simultaneous less-invasive evaluation of both colon and extracolonic organs. (C)RSNA, 2010 C1 [Kim, Hye Jin; Park, Seong Ho; Lee, Seung Soo; Kim, Ah Young; Ha, Hyun Kwon] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol, Seoul 138736, South Korea. [Kim, Hye Jin; Park, Seong Ho; Lee, Seung Soo; Kim, Ah Young; Ha, Hyun Kwon] Univ Ulsan, Coll Med, Asan Med Ctr, Res Inst Radiol, Seoul 138736, South Korea. [Yoon, Sang Nam; Kim, Jin Cheon; Yu, Chang Sik] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Surg, Seoul 138736, South Korea. [Pickhardt, Perry J.; Kim, David H.] Univ Wisconsin, Sch Med, Dept Radiol, Madison, WI USA. [Yee, Judy] Univ Calif San Francisco, San Francisco Vet Adm Med Ctr, Dept Radiol, San Francisco, CA 94143 USA. RP Park, SH (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol, Asanbyeongwon Gil 86, Seoul 138736, South Korea. EM seonghopark@paran.com OI Park, Seong Ho/0000-0002-1257-8315 FU NCI NIH HHS [R01 CA144835] NR 29 TC 27 Z9 29 U1 2 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2010 VL 257 IS 3 BP 697 EP 704 DI 10.1148/radiol.10100385 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 683IL UT WOS:000284469300014 PM 20876390 ER PT J AU Roelofs, E Persoon, L Qamhiyeh, S Verhaegen, F De Ruysscher, D Scholz, M Iancu, G Engelsman, M Rasch, C Zijp, L De Meerleer, G Coghe, M Langendijk, J Schilstra, C Pijls-Johannesma, M Lambin, P AF Roelofs, Erik Persoon, Lucas Qamhiyeh, Sima Verhaegen, Frank De Ruysscher, Dirk Scholz, Michael Iancu, Gheorghe Engelsman, Martijn Rasch, Coen Zijp, Lambert De Meerleer, Gert Coghe, Marc Langendijk, Johannes Schilstra, Cornelis Pijls-Johannesma, Madelon Lambin, Philippe TI Design of and technical challenges involved in a framework for multicentric radiotherapy treatment planning studies SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Treatment planning studies; In silico; Radiotherapy; Multicentric; Clinical trial; Quality assurance; Public repositories; Data pooling ID CELL LUNG-CANCER; COMPLICATION PROBABILITY-MODELS; HEALTH-CARE ENTERPRISE; SILICO CLINICAL-TRIAL; PET; FEASIBILITY; STANDARDS; PATHOLOGY; TUMOR AB This report introduces a framework for comparing radiotherapy treatment planning in multicentric in silico clinical trials. Quality assurance, data incompatibility, transfer and storage issues, and uniform analysis of results are discussed. The solutions that are given provide a useful guide for the set-up of future multicentric planning studies or public repositories of high quality data. (C) 2010 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 97 (2010) 567-571 C1 [Roelofs, Erik; Persoon, Lucas; Qamhiyeh, Sima; Verhaegen, Frank; De Ruysscher, Dirk; Pijls-Johannesma, Madelon; Lambin, Philippe] Maastricht Univ, Med Ctr, Dept Radiat Oncol MAASTRO, Maastricht, Netherlands. [Verhaegen, Frank] McGill Univ, Montreal, PQ, Canada. [Scholz, Michael; Iancu, Gheorghe] Gesell Schwerionenforsch mbH, Darmstadt, Germany. [Engelsman, Martijn] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Rasch, Coen; Zijp, Lambert] Netherlands Canc Inst, Amsterdam, Netherlands. [De Meerleer, Gert; Coghe, Marc] Ghent Univ Hosp, Ghent, Belgium. [Langendijk, Johannes; Schilstra, Cornelis] Univ Groningen, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands. RP Pijls-Johannesma, M (reprint author), Maastricht Univ, Med Ctr, Dept Radiat Oncol MAASTRO, Maastricht, Netherlands. EM madelon.pijls@maastro.nl OI schilstra, cornelis/0000-0002-1526-1743; Roelofs, Erik/0000-0003-2172-8669 NR 32 TC 20 Z9 20 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD DEC PY 2010 VL 97 IS 3 BP 567 EP 571 DI 10.1016/j.radonc.2010.08.009 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 693KE UT WOS:000285222200037 PM 20864198 ER PT J AU Bagarova, J Chowdhury, TA Kimura, M Kleene, KC AF Bagarova, Jana Chowdhury, Tamjid A. Kimura, Mine Kleene, Kenneth C. TI Identification of elements in the Smcp 5 ' and 3 ' UTR that repress translation and promote the formation of heavy inactive mRNPs in spermatids by analysis of mutations in transgenic mice SO REPRODUCTION LA English DT Article ID PROTAMINE-1 MESSENGER-RNA; OPEN READING FRAME; Y-BOX PROTEIN; IN-VITRO; POSTTRANSCRIPTIONAL CONTROL; PREMATURE TRANSLATION; TRANSITION PROTEIN-2; COMPARATIVE GENOMICS; SPERMATOGENIC CELLS; CONSERVED SEQUENCE AB The sperm mitochondria-associated cysteine-rich protein (Smcp) mRNA is transcribed in step 3 spermatids, and is stored in free mRNPs until translation begins similar to 6 days later in step 11. To identify sequences that control the timing of Smcp mRNA translation, mutations in both UTRs were analyzed in transgenic mice using green fluorescent protein (GFP), squashes of seminiferous tubules, and quantification of polysomal loading in adult and 21 dpp testes in sucrose and Nycodenz gradients. GFP fluorescence is first detected in step 9 spermatids in lines harboring a transgene containing the Gfp 5' UTR and Smcp 3' UTR. Unexpectedly, this mRNA is stored in large, inactive mRNPs in early spermatids that sediment with polysomes in sucrose gradients, but equilibrate with the density of free mRNPs in Nycodenz gradients. Randomization of the segment 6-38 nt upstream of the first Smcp poly(A) signal results in early detection of GFP, a small increase in polysomal loading in 21 dpp testis, inactivation of the formation of heavy mRNPs, and loss of binding of a Y-box protein. GFP is first detected in step 5 spermatids in a transgene containing the Smcp 5' UTR and Gfp 3' UTR. Mutations in the start codons in the upstream reading frames eliminate translational delay by the Smcp 5' UTR. Collectively, these findings demonstrate that Smcp mRNA translation is regulated by multiple elements in the 5' UTR and 3' UTR. In addition, differences in regulation between Smcp-Gfp mRNAs containing one Smcp UTR and the natural Smcp mRNA suggest that interactions between the Smcp 5' UTR and 3' UTR may be required for regulation of the Smcp mRNA. Reproduction (2010) 140 853-864 C1 [Chowdhury, Tamjid A.; Kleene, Kenneth C.] Univ Massachusetts, Dept Biol, Boston, MA 02125 USA. [Bagarova, Jana] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kimura, Mine] George Washington Univ, Dept Forens Sci, Washington, DC 20007 USA. RP Kleene, KC (reprint author), Univ Massachusetts, Dept Biol, Boston, MA 02125 USA. EM kenneth.kleene@umb.edu FU National Science Foundation [BCE-0348497, MCB-0642128] FX This research was supported by Grants BCE-0348497 and MCB-0642128 from the National Science Foundation. NR 42 TC 8 Z9 8 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1470-1626 J9 REPRODUCTION JI Reproduction PD DEC PY 2010 VL 140 IS 6 BP 853 EP 864 DI 10.1530/REP-10-0323 PG 12 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA 685JN UT WOS:000284625100006 PM 20876225 ER PT J AU Friel, AM Zhang, L Curley, MD Therrien, VA Sergent, PA Belden, SE Borger, DR Mohapatra, G Zukerberg, LR Foster, R Rueda, BR AF Friel, Anne M. Zhang, Ling Curley, Michael D. Therrien, Vanessa A. Sergent, Petra A. Belden, Sarah E. Borger, Darrell R. Mohapatra, Gayatry Zukerberg, Lawrence R. Foster, Rosemary Rueda, Bo R. TI Epigenetic regulation of CD133 and tumorigenicity of CD133 positive and negative endometrial cancer cells SO REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY LA English DT Article ID TUMOR INITIATING CELLS; HUMAN OVARIAN-CANCER; STEM-CELLS; SIDE-POPULATION; PROSPECTIVE IDENTIFICATION; HEMATOPOIETIC STEM; MOUSE ENDOMETRIUM; EXPRESSION; CARCINOGENESIS; DEFINES AB Background: Recent data provide significant evidence to support the hypothesis that there are sub-populations of cells within solid tumors that have an increased tumor initiating potential relative to the total tumor population. CD133, a cell surface marker expressed on primitive cells of neural, hematopoietic, endothelial and epithelial lineages has been identified as a marker for tumor initiating cells in solid tumors of the brain, colon, pancreas, ovary and endometrium. Our objectives were to assess the relative level of CD133 expressing cells in primary human endometrial tumors, confirm their tumorigenic potential, and determine whether CD133 expression was epigenetically modified. Methods: We assessed CD133 expression in primary human endometrial tumors by flow cytometry and analyzed the relative tumorigenicity of CD133+ and CD133- cells in an in vivo NOD/SCID mouse model. We assessed potential changes in CD133 expression over the course of serial transplantation by immunofluorescence and flow cytometry. We further examined CD133 promoter methylation and expression in normal endometrium and malignant tumors. Results: As determined by flow cytometric analysis, the percentage of CD133+ cells in primary human endometrial cancer samples ranged from 5.7% to 27.4%. In addition, we confirmed the tumor initiating potential of CD133+ and CD133(-) cell fractions in NOD/SCID mice. Interestingly, the percentage of CD133+ cells in human endometrial tumor xenografts, as evidenced by immunofluorescence, increased with serial transplantation although this trend was not consistently detected by flow cytometry. We also determined that the relative levels of CD133 increased in endometrial cancer cell lines following treatment with 5-aza-2'-deoxycytidine suggesting a role for methylation in the regulation of CD133. To support this finding, we demonstrated that regions of the CD133 promoter were hypomethylated in malignant endometrial tissue relative to benign control endometrial tissue. Lastly, we determined that methylation of the CD133 promoter decreases over serial transplantation of an endometrial tumor xenograft. Conclusions: These findings support the hypotheses that CD133 expression in endometrial cancer may be epigenetically regulated and that cell fractions enriched for CD133+ cells may well contribute to endometrial cancer tumorigenicity, pathology and recurrence. C1 [Friel, Anne M.; Zhang, Ling; Curley, Michael D.; Therrien, Vanessa A.; Sergent, Petra A.; Foster, Rosemary; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. [Friel, Anne M.; Curley, Michael D.; Foster, Rosemary; Rueda, Bo R.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Belden, Sarah E.; Borger, Darrell R.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. [Mohapatra, Gayatry; Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Dept Mol Pathol, Boston, MA 02114 USA. [Mohapatra, Gayatry; Zukerberg, Lawrence R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Rueda, Bo R.] Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Rueda, BR (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. EM brueda@partners.org OI Belden, Sarah/0000-0002-7132-5318 FU Advanced Medical Research Foundation; Vincent Memorial Research Fund; NCI [P50 CA098258]; Belkin Family FX This work was supported in part by the Advanced Medical Research Foundation (BRR), Vincent Memorial Research Fund (BRR), Belkin Family contribution (BRR) and a pilot proposal sponsored by NCI P50 CA098258 NR 41 TC 24 Z9 28 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1477-7827 J9 REPROD BIOL ENDOCRIN JI Reprod. Biol. Endocrinol. PD DEC 1 PY 2010 VL 8 AR 147 DI 10.1186/1477-7827-8-147 PG 13 WC Endocrinology & Metabolism; Reproductive Biology SC Endocrinology & Metabolism; Reproductive Biology GA 703KV UT WOS:000285977700001 PM 21122138 ER PT J AU Meeker, JD Ehrlich, S Toth, TL Wright, DL Calafat, AM Trisini, AT Ye, XY Hauser, R AF Meeker, John D. Ehrlich, Shelley Toth, Thomas L. Wright, Diane L. Calafat, Antonia M. Trisini, Ana T. Ye, Xiaoyun Hauser, Russ TI Semen quality and sperm DNA damage in relation to urinary bisphenol A among men from an infertility clinic SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE Biomarkers; Endocrine disruption; Environment; Epidemiology; Estrogenic; Exposure; Fertility; Male; Reproduction ID MICROARRAY ANALYSIS; HUMAN EXPOSURE; COMET ASSAY; MOUSE; SPERMATOGENESIS; METABOLITES; PARAMETERS; STRESS; CELLS; RATS AB Bisphenol A (BPA) impairs spermatogenesis in animals but human studies are lacking We measured urinary BPA concentrations semen quality and sperm DNA damage (comet assay) in 190 men recruited through an infertility clinic BPA was detected in 89% of samples with a median (interquartile range [IQR]) concentration of 1 3 (0 8-2 5) ng/mL Urinary BPA concentration was associated with slightly elevated though not statistically significant odds for below reference sperm concentration motility and morphology When modeled as continuous dependent variables an IQR increase in urinary BPA concentration was associated with declines in sperm concentration motility and morphology of 23% (95%CI -40% -0 3%) 7 5% (-17% +1 5%) and 13% (-26% -0 1%) respectively along with a 10% (0 03% 19%) increase in sperm DNA damage measured as the percentage of DNA in comet tail In conclusion urinary BPA may be associated with declined semen quality and increased sperm DNA damage but confirmatory studies are needed (C) 2010 Elsevier Inc All rights reserved C1 [Meeker, John D.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Ehrlich, Shelley; Trisini, Ana T.; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Toth, Thomas L.; Wright, Diane L.; Hauser, Russ] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. [Calafat, Antonia M.; Ye, Xiaoyun] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Meeker, JD (reprint author), Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, 6635 SPH Tower,109 S Observ St, Ann Arbor, MI 48109 USA. RI Ehrlich , Shelley/L-6991-2015; OI Meeker, John/0000-0001-8357-5085 FU National Institute of Environmental Health Sciences (NIEHS) National Institutes of Health (NIH) [ES009718, ES00002] FX Work supported by grants ES009718 and ES00002 from the National Institute of Environmental Health Sciences (NIEHS) National Institutes of Health (NIH) The authors gratefully acknowledge Amber Bishop Tao Jia and Jack Reidy (CDC Atlanta GA) for measuring the urinary concentrations of BPA NR 34 TC 120 Z9 126 U1 2 U2 37 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD DEC PY 2010 VL 30 IS 4 BP 532 EP 539 DI 10.1016/j.reprotox.2010.07.005 PG 8 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 690VI UT WOS:000285036300004 PM 20656017 ER PT J AU DiBlasi, RM Myers, TR Hess, DR AF DiBlasi, Robert M. Myers, Timothy R. Hess, Dean R. TI Evidence-Based Clinical Practice Guideline: Inhaled Nitric Oxide for Neonates With Acute Hypoxic Respiratory Failure SO RESPIRATORY CARE LA English DT Article DE inhaled nitric oxide; mechanical ventilation; neonate; persistent pulmonary hypertension of the newborn; hypoxemia ID PERSISTENT PULMONARY-HYPERTENSION; EXTRACORPOREAL MEMBRANE-OXYGENATION; CONGENITAL DIAPHRAGMATIC-HERNIA; HIGH-FREQUENCY VENTILATION; CONTROLLED MECHANICAL VENTILATION; RANDOMIZED CONTROLLED-TRIAL; TERM NEWBORN-INFANTS; NEAR-TERM; COST-EFFECTIVENESS; FOLLOW-UP AB Inhaled nitric oxide (INO) is a colorless, odorless gas that is also a potent pulmonary vasodilator. When given via the inhaled route it is a selective pulmonary vasodilator. INO is approved by the United States Food and Drug Administration (FDA) for the treatment of term and near-term neonates with hypoxemic respiratory failure associated with clinical or echocardiographic evidence of pulmonary arterial hypertension. A systematic review of the literature was conducted with the intention of making recommendations related to the clinical use of INO for its FDA-approved indication. Specifically, we wrote these evidence-based clinical practice guidelines to address the following questions: (1) What is the evidence for labeled use? (2) What are the specific indications for INO for neonates with acute hypoxemic respiratory failure? (3) Does the use of INO impact oxygenation, mortality, or utilization of extracorporeal membrane oxygenation (ECMO)? (4) Does INO affect long-term outcomes? (5) Is INO cost-effective therapy? (6) How is the appropriate dosing regimen and dose response to INO established? (7) How is the dose of INO titrated and weaned? (8) Which INO delivery system should be used? (9) How should INO be implemented with different respiratory support devices? (10) What adverse effects of INO should be monitored, and at what frequency? (11) What physiologic parameters should be monitored during INO? (12) Is scavenging of gases necessary to protect the caregivers? Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) scoring system, 22 recommendations are developed for the use of INO in newborns. C1 [DiBlasi, Robert M.] Seattle Childrens Hosp, Resp Care Dept, Seattle, WA 98101 USA. [DiBlasi, Robert M.] Seattle Childrens Res Inst, Ctr Dev Therapeutics, Seattle, WA 98101 USA. [Myers, Timothy R.] Case Western Reserve Univ, Womens & Childrens Resp & Procedural Serv, Cleveland, OH 44106 USA. [Myers, Timothy R.] Case Western Reserve Univ, Pediat Heart Ctr, Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. [Myers, Timothy R.] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. [Hess, Dean R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Resp Care Serv, Boston, MA USA. [Hess, Dean R.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP DiBlasi, RM (reprint author), Seattle Childrens Hosp, Resp Care Dept, 1900 9th Ave, Seattle, WA 98101 USA. EM robert.diblasi@seattlechildrens.org RI Myers, Timothy/D-9895-2017 FU American Respiratory Care Foundation through Ikaria FX Preparation of this clinical practice guideline was supported by the American Respiratory Care Foundation through an unrestricted grant from Ikaria. Ikaria was not involved in creating the questions, doing the literature search, writing the review, or drafting the recommendations. Full editorial control rests with the authors and the American Association for Respiratory Care Clinical Practice Guidelines Committee. NR 130 TC 12 Z9 12 U1 2 U2 9 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD DEC PY 2010 VL 55 IS 12 BP 1717 EP 1745 PG 29 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 705LK UT WOS:000286129700010 PM 21122181 ER PT J AU Semenas, E Nozari, A Wiklund, L AF Semenas, Egidijus Nozari, Ala Wiklund, Lars TI Sex differences in cardiac injury after severe haemorrhage and ventricular fibrillation in pigs SO RESUSCITATION LA English DT Article DE Cardiopulmonary resuscitation; Haemorrhage; Hypertonic saline; Sex ID MYOCARDIAL INFLAMMATORY RESPONSE; GENDER-DIFFERENCES; TRAUMA; ARREST; RESUSCITATION AB Aim of the study: Experimental studies have shown sex differences in haemodynamic response and outcome after trauma and haemorrhagic shock. We recently reported that female sex protects against cerebral injury after exsanguination cardiac arrest (CA), independent of sexual effects of hormones. The current study examines if female sex is also cardioprotective. Methods: In this study 21 sexually immature piglets (12 males and 9 females) were subjected to 5 min of haemorrhagic shock followed by 2 min of ventricular fibrillation and 8 min of cardiopulmonary resuscitation (CPR). Volume resuscitation was started during CPR with intravenous administration of 3 ml kg(-1) hypertonic saline-dextran (HSD) solution for 20 min. Sexually immature animals were used to differentiate innate sex differences from the effects of sexual hormones. Sex differences in haemodynamics, myocardial injury (troponin l), and short-term survival (3-h) were evaluated. Results: After resuscitation female animals had a higher blood pressure, lower heart rate, lower troponin I concentrations, and higher survival rate (100% and 63% in 3 h) despite comparable sex hormone levels. Conclusions: After resuscitation from haemorrhage and circulatory arrest, haemodynamic parameters are better preserved and myocardial injury is smaller in female piglets. This difference in outcome is independent of sexual hormones. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Semenas, Egidijus; Wiklund, Lars] Univ Uppsala Hosp, Dept Surg Sci Anesthesiol & Intens Care, Fac Med, S-75185 Uppsala, Sweden. [Nozari, Ala] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Sch Med, Boston, MA 02114 USA. RP Semenas, E (reprint author), Univ Uppsala Hosp, Dept Surg Sci Anesthesiol & Intens Care, Fac Med, S-75185 Uppsala, Sweden. EM egidijus.semenas@gmail.com FU Laerdal Foundation for Acute Medicine, Stavanger, Norway FX The research was supported, in part, by the Laerdal Foundation for Acute Medicine, Stavanger, Norway. The authors express their gratitude to Monica Nygren, Elisabeth Pettersson and Anders Nordgren, research assistants, for excellent assistance. NR 16 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-9572 J9 RESUSCITATION JI Resuscitation PD DEC PY 2010 VL 81 IS 12 BP 1718 EP 1722 DI 10.1016/j.resuscitation.2010.08.010 PG 5 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA 701JU UT WOS:000285815000023 PM 20817375 ER PT J AU Cortot, AB AF Cortot, A. B. TI EGFR inhibitors in non-small cell lung cancer: More than yesterday (but less than tomorrow) SO REVUE DE PNEUMOLOGIE CLINIQUE LA French DT Article DE Non Small Cell Lung Cancer; Molecular targeted agents; EGFR; Gefitinib; Erlotinib; Cetuximab ID PHASE-III TRIAL; PREVIOUSLY TREATED PATIENTS; RECEPTOR TYROSINE KINASE; 1ST-LINE TREATMENT; GEFITINIB; MUTATIONS; PLUS; CARBOPLATIN; PACLITAXEL; RESISTANCE AB Molecular targeted agents represent a major breakthrough in the treatment of non-small cell lung cancer. Among these agents, Epidermal Growth Factor Receptor (EGFR) inhibitors are probably the more important so far. Whether inhibition is obtained by targeting the tyrosine kinase of the receptor (gefitinib or erlotinib) or by using a monoclonal antibody (cetuximab), the place of these treatments will increase in the next years. This article details the role of EGFR in lung carcinogenesis and the main therapeutic approaches used to inhibit EGFR activity. The results of the major clinical trials evaluating these agents are also discussed". (C) 2010 Elsevier Masson SAS. All rights reserved. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. RP Cortot, AB (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 44 Binney St,D820, Boston, MA 02115 USA. EM alexis_cortot@dfci.harvard.edu NR 32 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0761-8417 EI 1776-2561 J9 REV PNEUMOL CLIN JI Rev. Pneumol. Clin. PD DEC PY 2010 VL 66 IS 6 BP 367 EP 374 DI 10.1016/j.pneumo.2010.07.017 PG 8 WC Respiratory System SC Respiratory System GA 704IJ UT WOS:000286044500008 PM 21167447 ER PT J AU Juillerat, P Pittet, V Mottet, C Felley, C Gonvers, JJ Vader, JP Burnand, B Froehlich, F Wolters, FL Stockbrugger, RW Michetti, P AF Juillerat, Pascal Pittet, Valerie Mottet, Christian Felley, Christian Gonvers, Jean-Jacques Vader, John-Paul Burnand, Bernard Froehlich, Florian Wolters, Frank L. Stockbrugger, Reinhold W. Michetti, Pierre CA EC-IBD Grp TI Appropriateness of early management of newly diagnosed Crohn's disease in a European population-based cohort SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Appropriateness; Crohn's disease; inflammatory bowel disease; RAND appropriateness method; therapy ID INFLAMMATORY-BOWEL-DISEASE; INCEPTION COHORT; EC-IBD; PREVALENCE; THERAPY; COUNTY; ADULTS; UPDATE; EPACT; NORTH AB Objective. The European Panel on the Appropriateness of Crohn's disease Therapy (EPACT) has developed appropriateness criteria. We have applied these criteria retrospectively to the population-based inception cohort of Crohn's disease (CD) patients of the European Collaborative Study Group on Inflammatory Bowel Disease (EC-IBD). Material and methods. A total of 426 diagnosed CD patients from 13 European centers were enrolled at the time of diagnosis (first flare, naive patients). We used the EPACT definitions to identify 247 patients with active luminal CD. We then assessed the appropriateness of the initial drug prescription according to the EPACT criteria. Results. Among the cohort patients 163 suffered from mild-to-moderate CD and 84 from severe CD. Among the mild-to-moderate disease group, 96 patients (59%) received an appropriate treatment, whereas for 66 patients (40%) the treatment was uncertain and in one case (1%) inappropriate. Among the severe disease group, 86% were treated medically and 14% required surgery. 59 (70%) were appropriately treated, whereas for one patient (1%) the procedure was considered uncertain and for 24 patients (29%) inappropriate. Conclusion. Initial treatment was appropriate in the majority of cases for non-complicated luminal CD. Inappropriate or uncertain treatment was given in a significant minority of patients, with an increased potential risk of adverse events. C1 [Juillerat, Pascal; Mottet, Christian; Felley, Christian; Gonvers, Jean-Jacques; Froehlich, Florian; Michetti, Pierre] CHU Vaudois, Dept Gastroenterol & Hepatol, CH-1011 Lausanne, Switzerland. [Juillerat, Pascal; Pittet, Valerie; Mottet, Christian; Felley, Christian; Gonvers, Jean-Jacques; Vader, John-Paul; Burnand, Bernard; Froehlich, Florian; Michetti, Pierre] Univ Lausanne, Lausanne, Switzerland. [Juillerat, Pascal; Pittet, Valerie; Vader, John-Paul; Burnand, Bernard] CHU Vaudois, Healthcare Evaluat Unit, Inst Social & Prevent Med IUMSP, CH-1011 Lausanne, Switzerland. [Froehlich, Florian] Univ Basel Hosp, Div Gastroenterol & Hepatol, CH-4031 Basel, Switzerland. [Wolters, Frank L.; Stockbrugger, Reinhold W.] Univ Hosp Maastricht, Dept Gastroenterol & Hepatol, Maastricht, Netherlands. RP Juillerat, P (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, MGH Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM pjuillerat@partners.org OI Bernklev, Tomm/0000-0002-9988-2271; Koutroubakis, Ioannis/0000-0002-2773-2709 FU Swiss National Science Foundation (SNF) [3347CO-108792/1, PBLAP3-124341]; European Commission [QLG4-CT-2000-01414] FX We gratefully acknowledge the contribution of all the gastroenterologists and investigators who are listed in the Appendix and Miss Susan Giddons for editorial assistance. This study was supported by the Swiss National Science Foundation (SNF): grants No 3347CO-108792/1 and No PBLAP3-124341. The IBDT2K follow-up study was supported by a grant from the European Commission (fifth framework) No QLG4-CT-2000-01414. NR 37 TC 3 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PD DEC PY 2010 VL 45 IS 12 BP 1449 EP 1456 DI 10.3109/00365521.2010.505660 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 680WR UT WOS:000284268700009 PM 20653489 ER PT J AU Wang, JJ Liu, EY Freudenreich, O Goff, D Henderson, DC Fan, XD AF Wang, JiJun Liu, Emily Y. Freudenreich, Oliver Goff, Donald Henderson, David C. Fan, Xiaoduo TI Phenotypic characteristics in metabolically obese but normal weight non-diabetic patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Metabolic problem; Insulin resistance; Lipoprotein ID NUCLEAR-MAGNETIC-RESONANCE; INSULIN-RESISTANCE ATHEROSCLEROSIS; NUTRITION EXAMINATION SURVEY; GLUCOSE-TOLERANCE; APOLIPOPROTEIN-B; NATIONAL-HEALTH; DISEASE; INTERVENTION; PREVALENCE; PREDICTION AB Background A unique group of individuals termed metabolically obese but normal weight (MONW) has been identified in the general population The present study examined phenotypic characteristics of MONW individuals in a sample of normal weight non-diabetic patients with schizophrenia Methods Outpatients 19 to 75 years old diagnosed with schizophrenia or schizoaffective disorder participated in a multi-center cross-sectional study Those with normal weight (body-mass-index (BMI)<25 kg/m(2)) were included in the present analysis Patients were further defined as MONW or metabolically nonobese based on a cut-off value of the homeostasis model assessment of insulin resistance (HOMA-IR = 1 86) Fasting blood samples were collected to determine levels of various metabolic parameters In addition lipoprotein subclass concentrations and sizes were analyzed using nuclear magnetic resonance (NMR) spectroscopy Results Seventeen MONW individuals and 17 metabolically nonobese individuals matched by BMI and gender were identified from a study sample of 206 patients with schizophrenia There were no significant differences between the two groups on anthropometnc measures (waist circumference and waist/hip ratio ps>0 3) However the MONW group had significantly higher levels of intermediate VLDL particle and Apolipoprotein B and significantly lower levels of large HDL particle compared with the metabolically nonobese group (p = 0 012 p = 0 036 and p = 0 041 respectively) Conclusion The MONW individuals in non-diabetic schizophrenia patients seem to have an unfavorable metabolic profile and significant atherogenecity Clinicians should be vigilant about the risk of cardiometabolic comorbidity even when the patient body weight is normal (C) 2010 Elsevier BV All rights reserved C1 [Wang, JiJun] Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Shanghai 200030, Peoples R China. [Liu, Emily Y.] Partners Community Healthcare Inc, Haverhill, MA USA. [Freudenreich, Oliver; Goff, Donald; Henderson, David C.; Fan, Xiaoduo] Massachusetts Gen Hosp, Dept Psychiat, Schizophrenia Program, Boston, MA 02114 USA. [Freudenreich, Oliver; Goff, Donald; Henderson, David C.; Fan, Xiaoduo] Harvard Univ, Sch Med, Boston, MA USA. RP Fan, XD (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. FU Eli Lilly and Company; National Natural Science Foundation of China [30770773]; National Scientific and Technological 863 Program of China [2007AA02Z420, 2008AA02Z412] FX The original study (F1D MC HGJX) was sponsored by Eli Lilly and Company Eli Lilly was responsible for the collection of the original study data For this study/paper Eli Lilly was not involved in analyzing or interpreting the data or deciding to submit the paper for publication This study was supported by the National Natural Science Foundation of China (30770773 Dr Wang) and the National Scientific and Technological 863 Program of China (2007AA02Z420 2008AA02Z412 Dr Wang) NR 26 TC 3 Z9 3 U1 3 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2010 VL 124 IS 1-3 BP 49 EP 53 DI 10.1016/j.schres.2010.09.013 PG 5 WC Psychiatry SC Psychiatry GA 694UE UT WOS:000285323700007 PM 20947306 ER PT J AU Demirtas-Tatlidede, A Freitas, C Cromer, JR Safar, L Ongur, D Stone, WS Seidman, LJ Schmahmann, JD Pascual-Leone, A AF Demirtas-Tatlidede, Ash Freitas, Catarina Cromer, Jennifer R. Safar, Laura Ongur, Dost Stone, William S. Seidman, Larry J. Schmahmann, Jeremy D. Pascual-Leone, Alvaro TI Safety and proof of principle study of cerebellar vermal theta burst stimulation in refractory schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Transcranial Magnetic Stimulation (TMS); Intermittent Theta Burst Stimulation (TBS); Vermis; Cerebellum; Schizophrenia; Safety ID TRANSCRANIAL MAGNETIC STIMULATION; POSITRON-EMISSION-TOMOGRAPHY; HUMAN MOTOR CORTEX; COGNITIVE DYSMETRIA; PREFRONTAL CORTEX; NEGATIVE SYMPTOMS; WHITE-MATTER; NEURONAL INTEGRITY; MENTAL SYMPTOMS; PSYCHOSIS AB Background Early invasive electrical stimulation studies suggested that enhancement of cerebellar vermal activity might prove valuable in symptomatic treatment of refractory neuropsychiatric diseases via modulation of emotion and affect This proof of principle study aimed to test this hypothesis using noninvasive brain stimulation and to explore the safety of this protocol in schizophrenia Methods Eight treatment-refractory patients with schizophrenia underwent ten sessions of inteimittent theta burst stimulation (TBS) to the cerebellar vermis using MRI-guided transcranial magnetic stimulation (TMS) Assessments included side effect questionnaires cardiovascular monitoring psychiatric evaluations and comprehensive neuropsychological testing before and after TBS and at one-week follow-up Results Overall TBS was tolerated well with mild side effects primarily comprising neck pain and headache No serious adverse events occurred Diastolic blood pressure (BP) showed mild decreases for five minutes post-TBS no significant changes were detected for systolic BP or pulse PANSS negative subscale showed significant improvements following TBS and during the follow-up Calgary Depression Scale and self-report visual analog scales for Happiness and Sadness pointed to significant mood elevation Neuropsychological testing revealed significantly fewer omissions in working memory and interference conditions of a Continuous Performance Test a longer spatial span and better delay organization on the Rey-Osteineth Complex Figure during follow-up No significant worsening in psychiatric or neuropsychological measures was detected Conclusions Theta burst stimulation of the cerebellar vermis is safe and well-tolerated while offering the potential to modulate affect emotion and cognition in schizophrenia Future randomized sham stimulation controlled studies are warranted to support the clinical efficacy of this technique (C) 2010 Elsevier BV All lights reserved C1 [Demirtas-Tatlidede, Ash; Freitas, Catarina; Pascual-Leone, Alvaro] Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Behav Neurol Unit, Dept Neurol, Boston, MA 02215 USA. [Demirtas-Tatlidede, Ash; Freitas, Catarina; Cromer, Jennifer R.; Safar, Laura; Ongur, Dost; Stone, William S.; Seidman, Larry J.; Schmahmann, Jeremy D.; Pascual-Leone, Alvaro] Harvard Univ, Sch Med, Boston, MA USA. [Ongur, Dost] McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. [Stone, William S.; Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Publ Psychiat Div, Massachusetts Mental Hlth Ctr, Boston, MA 02215 USA. [Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Dept Neurol, Ataxia Unit, Cognit Behav Neurol Unit, Boston, MA 02114 USA. RP Pascual-Leone, A (reprint author), Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Behav Neurol Unit, Dept Neurol, 330 Brookline Ave KS 158, Boston, MA 02215 USA. FU Harvard Clinical and Translational Science Center; National Center for Research Resources [UL1 RR025758]; National Institutes of Health [K24 RR018875]; Birmingham Foundation; Executive Committee on Research of the Massachusetts General Hospital; MINDlink foundation; Foundation for Science and Technology Portugal [SFRH/BPD/44126/2008] FX Funding for this study was provided in part by Harvard Clinical and Translational Science Center from the National Center for Research Resources (UL1 RR025758) and National Institutes of Health grant (K24 RR018875) to APL and by the Birmingham Foundation the Executive Committee on Research of the Massachusetts General Hospital and the MINDlink foundation to JDS CF was supported by the Foundation for Science and Technology Portugal (SFRH/BPD/44126/2008) The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health NR 101 TC 50 Z9 56 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2010 VL 124 IS 1-3 BP 91 EP 100 DI 10.1016/j.schres.2010.08.015 PG 10 WC Psychiatry SC Psychiatry GA 694UE UT WOS:000285323700014 PM 20817483 ER PT J AU Bespalova, IN Durner, M Ritter, BP Angelo, GW Rossy-Fullana, E Carrion-Baralt, J Schmeidler, J Silverman, JM AF Bespalova, Irina N. Durner, Martina Ritter, Benjamin P. Angelo, Gary W. Rossy-Fullana, Enrique Carrion-Baralt, Jose Schmeidler, James Silverman, Jeremy M. TI Non-synonymous variants in the AMACR gene are associated with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; 5p13; AMACR; Genetic association; Case control study ID METHYLACYL-COA-RACEMASE; 409 EUROPEAN-ANCESTRY; GENOME-WIDE SCAN; PROSTATE-CANCER; FATTY-ACIDS; REVEALS ALTERATIONS; GENDER-DIFFERENCES; EXPRESSION; LOCUS; RISK AB Background The AMACR gene is located in the schizophrenia susceptibility locus on chromosome 5p13 previously identified in a large Puerto Rican pedigree of Spanish origin The AMACR-encoded protein is an enzyme involved in the metabolism of branched chain fatty and bile acids The enzyme deficiency causes structural and functional brain changes and disturbances in fatty acid and oxidative phosphorylation pathways observed in individuals with schizophrenia Therefore AMACR is both a positional and functional candidate gene for susceptibility to schizophrenia Methods The study had a two step design we performed mutation analysis of the coding and flanking regions of AMACR in affected members of the pedigree and tested the detected sequence variants for association with schizophrenia in a Puerto Rican case-control sample (n = 383) of Spanish descent Results and conclusion We identified three missense variants segregating with the disorder in the family rs2278008 rs2287939 and rs10941112 Two of them rs2278008 and rs2287939 demonstrated significant differences in genotype (P = 4 x 10(-4) P = 4 x 10(-4)) and allele (P = 1 x10(-4) P = 9 5 x 10(-5)) frequencies in unrelated male patients compare to controls with the odds ratios (OR) 2 24 (95% Cl 1 48-3 40) and 225 (95% Cl 1 49-3 38) respectively The G-C-G haplotype of rs2278008-rs2287939 rs10941112 revealed the most significant association with schizophrenia (P = 425 x 10(-6) OR = 2 96 95% Cl 1 85-4 76) in male subjects There were no statistically significant differences in genotype allele and haplotype frequencies between female schizophrenia subjects and controls Our results suggest that AMACR may play a significant role in susceptibility to schizophrenia in male patients (C) 2010 Elsevier B V All rights reserved C1 [Bespalova, Irina N.; Durner, Martina; Ritter, Benjamin P.; Angelo, Gary W.; Schmeidler, James; Silverman, Jeremy M.] Mt Sinai Med Ctr, Dept Psychiat, New York, NY 10029 USA. [Bespalova, Irina N.; Durner, Martina; Ritter, Benjamin P.; Angelo, Gary W.; Silverman, Jeremy M.] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Rossy-Fullana, Enrique] San Juan Vet Affairs Med Ctr, San Juan, PR USA. [Carrion-Baralt, Jose] Univ Puerto Rico, San Juan, PR 00936 USA. RP Bespalova, IN (reprint author), Mt Sinai Med Ctr, Dept Psychiat, 1 Gustave Levy Pl,Box 1230, New York, NY 10029 USA. FU National Alliance for Research on Schizophrenia and Depression (NARSAD); National Institute of Mental Health (NIMH) [RO3MH082134 01, RO3MH082134]; Department of Veterans Affairs (VA); NINDC [R01NS37466] FX Funding for this study was provided by the National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award to INB the National Institute of Mental Health (NIMH) Award RO3MH082134 01 to INB and The Department of Veterans Affairs (VA) Merit Award to JMS The funding sources had no further role in study design in the collection analysis and interpretation of data; The authors thank all the subjects for their participation in the study and Mount Sinai Core Facility for sequencing our samples This study was supported by the NIMH Award RO3MH082134 (INB) the NARSAD Young Investigator Award (INB) the NINDC Award R01NS37466 (MD) and the Department of Veterans Affairs Merit Award (JMS) NR 73 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2010 VL 124 IS 1-3 BP 208 EP 215 DI 10.1016/j.schres.2010.08.040 PG 8 WC Psychiatry SC Psychiatry GA 694UE UT WOS:000285323700028 PM 20875727 ER PT J AU Desai, SP Januzzi, JL Pande, AN Pomerantsev, EV Resnic, FS Fossel, A Chibnik, LB Solomon, DH AF Desai, Sonali P. Januzzi, James L. Pande, Ashvin N. Pomerantsev, Eugene V. Resnic, Frederic S. Fossel, Anne Chibnik, Lori B. Solomon, Daniel H. TI Comparison of Symptoms, Treatment, and Outcomes of Coronary Artery Disease among Rheumatoid Arthritis and Matched Subjects Undergoing Percutaneous Coronary Intervention SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Review DE rheumatoid arthritis; coronary artery disease ID CONGESTIVE-HEART-FAILURE; CARDIOVASCULAR MORTALITY; RISK; COHORT; METAANALYSIS AB Objective: Rheumatoid arthritis (RA) is associated with an increased prevalence of coronary artery disease (CAD). We investigated the presenting symptoms of CAD, coronary anatomy (single versus multi-vessel CAD), and treatment among a group of subjects undergoing percutaneous coronary intervention (PCI) with angioplasty and/or stenting. Methods: We evaluated a retrospective cohort of 43 RA subjects and 43 matched non-RA subjects undergoing PCI at 2 academic referral centers. RA subjects were matched to non-RA subjects on age, gender, history of coronary artery bypass grafting, date of PCI, and interventional cardiologist. We compared cardiac risk factors, presentation, treatment, and outcomes. Results: The mean age of the study cohort was 71 +/- 10 years, and the distribution of traditional cardiac risk factors was similar in the subjects with RA compared with the matched non-RA subjects (all P values > 0.05). Seventy-four percent of subjects with RA compared with 67% of those without RA presented with an acute coronary syndrome before PCI (P = 0.48). All subjects in this cohort undergoing PCI had at least 1 stenosis in a major epicardial vessel and similar percentages of subjects with RA (44%) and without RA (40%) had multi-vessel CAD (P = 0.66). The administration of cardiac medications both at PCI and at hospital discharge was not different among subjects with RA compared with matched non-RA subjects. Conclusions: Among this cohort with significant CAD undergoing PCI, clinical characteristics, presentation, severity of CAD, treatment modalities, and outcomes were similar in subjects with RA and well-matched non-RA subjects. (C) 2010 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 40:215-221 C1 [Desai, Sonali P.; Fossel, Anne; Chibnik, Lori B.; Solomon, Daniel H.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Resnic, Frederic S.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. [Januzzi, James L.; Pomerantsev, Eugene V.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Pande, Ashvin N.] Boston Med Ctr, Div Cardiol, Boston, MA USA. RP Desai, SP (reprint author), Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, 75 Francis St,PBB B3, Boston, MA 02115 USA. EM sdesai5@partners.org FU NIH [T32 AR007530, AR 055989, AR 0477820]; American College of Rheumatology; Arthritis Foundation; AHRQ DECiDE Center FX Dr. Desai's efforts are supported by the NIH (T32 AR007530, Institutional Training Grant) and the American College of Rheumatology Research and Education Fund Physician Scientist Development Award. Dr. Solomon is supported by NIH Grants AR 055989 and AR 0477820, the Arthritis Foundation, and an AHRQ DECiDE Center Award. NR 20 TC 6 Z9 8 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 0049-0172 EI 1532-866X J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD DEC PY 2010 VL 40 IS 3 BP 215 EP 221 DI 10.1016/j.semarthrit.2010.04.002 PG 7 WC Rheumatology SC Rheumatology GA 694GL UT WOS:000285282900005 PM 20541791 ER PT J AU Ko, JM Velez, NF Tsao, H AF Ko, Justin M. Velez, Nicole F. Tsao, Hensin TI Pathways to Melanoma SO SEMINARS IN CUTANEOUS MEDICINE AND SURGERY LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; KIT PROTEIN EXPRESSION; BRAF-MUTANT MELANOMA; CLEAR-CELL SARCOMA; SITE-SPECIFIC RISK; MELANOCYTIC NEVI; UVEAL MELANOMA; SOLAR KERATOSES; NRAS MUTATIONS; HUMAN CANCERS AB Melanoma is one of the most aggressive and yet poorly understood of human malignancies. Advances in genomics has allowed a more nuanced understanding of the disease, moving beyond the traditional dysplastic nevus-to-melanoma model and identifying multiple divergent oncogenic pathways leading to melanoma. An understanding of the molecular mechanisms driving melanoma has opened the doors for the development of targeted therapeutic approaches. As we enter the era of personalized medicine, it will be critical for clinicians to both appreciate and be able to determine the molecular profile of their patients' melanoma because this profile will guide risk stratification, genetic counseling, and treatment customization. A review of the divergent pathways of melanoma development is presented here, with a particular emphasis on recently identified mutations, and their implications for patient care. Semin Cutan Med Surg 29:210-217 (C) 2010 Published by Elsevier Inc. C1 [Tsao, Hensin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. RP Tsao, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Dept Dermatol, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org FU Millennium Melanoma Fund FX This work was made possible by the generous donors to the MGH Millennium Melanoma Fund. NR 80 TC 15 Z9 18 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1085-5629 J9 SEMIN CUTAN MED SURG JI Semin. Cutan. Med. Surg. PD DEC PY 2010 VL 29 IS 4 BP 210 EP 217 DI 10.1016/j.sder.2010.10.004 PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA 721UB UT WOS:000287382200003 PM 21277534 ER PT J AU Kuballa, P Xavier, RJ AF Kuballa, Petric Xavier, Ramnik J. TI Failure and exploitation of autophagy in human pathologies-cellular integrity between inflammation, infection, and cell survival SO SEMINARS IN IMMUNOPATHOLOGY LA English DT Editorial Material ID DISEASE C1 [Kuballa, Petric; Xavier, Ramnik J.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Kuballa, Petric; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Kuballa, Petric; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. RP Xavier, RJ (reprint author), Broad Inst MIT & Harvard, Cambridge, MA USA. EM xavier@molbio.mgh.harvard.edu NR 6 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2297 J9 SEMIN IMMUNOPATHOL JI Semin. Immunopathol. PD DEC PY 2010 VL 32 IS 4 BP 319 EP 322 DI 10.1007/s00281-010-0229-5 PG 4 WC Immunology; Pathology SC Immunology; Pathology GA 692KN UT WOS:000285151800001 PM 21107575 ER PT J AU Ng, ACY AF Ng, Aylwin C. Y. TI Integrative systems biology and networks in autophagy SO SEMINARS IN IMMUNOPATHOLOGY LA English DT Review DE Autophagy; Systems biology; Network; Genomics; RNAi ID GENOME-WIDE ASSOCIATION; PROGRAMMED CELL-DEATH; SIGNALING PATHWAYS; CROHNS-DISEASE; GENE ATG16L1; DROSOPHILA; IMMUNITY; POLYGLUTAMINE; PATHOGENESIS; DISORDERS AB The growing recognition that autophagy has important roles in many biological pathways, physiological systems, and infection and disease states necessitates a multidimensional perspective and systems-wide understanding of how autophagy is triggered or modulated by diverse stimuli. To delineate the nonlinearity and combinatorial complexity of biological networks and signaling pathways impinging on autophagy requires an integrative framework that brings together diverse information from genome-scale data (genomics, transcriptomics, proteomics, interactomics, functional RNAi screens) to dynamic time-series analyses and biochemical assays across a variety of biological and clinical contexts. We outline recent applications of genome-wide approaches to studying autophagy and highlight how some of these could be integrated to derive sub-networks that are more functionally focused. Viewed from a network perspective, the extensive interconnectivity between pathway systems converging on autophagy provides the essential foundation from which to systematically elucidate the regulatory nuances and crosstalks that orchestrate autophagic processes in different pathophysiological contexts. C1 [Ng, Aylwin C. Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Ng, Aylwin C. Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Ng, Aylwin C. Y.] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Ng, ACY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Simches Res Ctr 7th Floor,185 Cambridge St, Boston, MA 02114 USA. EM ang@ccib.mgh.harvard.edu NR 49 TC 9 Z9 9 U1 1 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2297 J9 SEMIN IMMUNOPATHOL JI Semin. Immunopathol. PD DEC PY 2010 VL 32 IS 4 BP 355 EP 361 DI 10.1007/s00281-010-0225-9 PG 7 WC Immunology; Pathology SC Immunology; Pathology GA 692KN UT WOS:000285151800004 PM 20842363 ER PT J AU Bekpen, C Xavier, RJ Eichler, EE AF Bekpen, Cemaletin Xavier, Ramnik J. Eichler, Evan E. TI Human IRGM gene "to be or not to be" SO SEMINARS IN IMMUNOPATHOLOGY LA English DT Review DE Human IRGM gene; IRG gene family; Autophagy; Crohn's disease; Innate immunity; Genome-wide association studies; Evolution of IRGM; Death and resurrection of a gene ID CROHNS-DISEASE SUSCEPTIBILITY; GENOME-WIDE ASSOCIATION; IFN-GAMMA; ENDOGENOUS RETROVIRUS; TOXOPLASMA-GONDII; P47 GTPASES; INTRACELLULAR PATHOGENS; EVOLUTIONARY HISTORY; ULCERATIVE-COLITIS; RESISTANCE GTPASES AB The immunity-related GTPases (IRG proteins) are one of the strongest early resistance systems against intracellular pathogens. The IRG gene family contains 21 copies arranged as tandem gene clusters on two chromosomes in the C57BL/6 mouse genome but has been reduced to only two copies in humans: IRGC and IRGM. IRGC is not involved in immunity, but the human IRGM gene plays a role in autophagy-targeted destruction of Mycobacterium tuberculosis (BCG) and Salmonella typhimurium. Variant IRGM haplotypes have been associated with increased risk for Crohn's disease and correlated with differential expression of IRGM transcripts. This article reviews in detail the studies performed on human samples, in vitro, and in sequence analyses that provide evidence for the unusual evolutionary history of the IRGM locus and the important role of the IRGM gene in autophagy and Crohn's disease in response to pathogenesis. C1 [Xavier, Ramnik J.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Bekpen, Cemaletin; Eichler, Evan E.] Howard Hughes Med Inst, Seattle, WA USA. [Bekpen, Cemaletin; Eichler, Evan E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. RP Bekpen, C (reprint author), Bogazici Univ, Dept Mol Biol & Genet, TR-34342 Istanbul, Turkey. EM bekpen@u.washington.edu RI Bekpen, Cemalettin/J-4263-2012 NR 68 TC 16 Z9 19 U1 1 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2297 EI 1863-2300 J9 SEMIN IMMUNOPATHOL JI Semin. Immunopathol. PD DEC PY 2010 VL 32 IS 4 BP 437 EP 444 DI 10.1007/s00281-010-0224-x PG 8 WC Immunology; Pathology SC Immunology; Pathology GA 692KN UT WOS:000285151800011 PM 20737271 ER PT J AU Chu-Shore, CJ Thiele, EA AF Chu-Shore, Catherine J. Thiele, Elizabeth A. TI New Drugs for Pediatric Epilepsy SO SEMINARS IN PEDIATRIC NEUROLOGY LA English DT Review ID PARTIAL-ONSET SEIZURES; LENNOX-GASTAUT-SYNDROME; RANDOMIZED CONTROLLED-TRIAL; COMPLEX PARTIAL SEIZURES; PLACEBO-CONTROLLED TRIAL; ADD-ON THERAPY; MG/DAY BRIVARACETAM UCB-34714; TUBEROUS SCLEROSIS COMPLEX; KINGDOM INFANTILE SPASMS; DOUBLE-BLIND AB The last 2 decades have witnessed an unprecedented period of new antiepileptic drug (AED) development. Newer-generation AEDs have been developed with the intention of improving the ease of use, decreasing drug interactions, decreasing adverse side effects, and identifying drugs with unique mechanisms of action, some of which may bear relevance to potential neuroprotective activity. Drug trials have also been refined in some cases to evaluate AED efficacy in children and against distinct epilepsy syndromes. This progress provides many new treatment options for the child neurologist facing children with epilepsy but also introduces the burden of determining appropriate AED choices. Here we highlight 6 new antiepileptic medications recently approved or pending approval for use in the United States: lacosamide, rufinamide, vigabatrin, retigabine, brivaracetam, and clobazam. For each of these medications, we present information regarding the history of drug development, proposed mechanism(s) of action, pharmacokinetics and recommended dosing, evidence for clinical efficacy, tolerability, and when, available, any unique features that are relevant for the pediatric population. Semin Pediatr Neurol 17:214-223 (C) 2010 Published by Elsevier Inc. C1 [Chu-Shore, Catherine J.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Pediat Epilepsy Program, Dept Neurol, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Pediat Epilepsy Program, Dept Neurol, 175 Cambridge St,Suite 340,CPZS 3-340, Boston, MA 02114 USA. EM ethiele@partners.org NR 103 TC 20 Z9 21 U1 0 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 1071-9091 J9 SEMIN PEDIATR NEUROL JI Semin. Pediatr. Neurol. PD DEC PY 2010 VL 17 IS 4 BP 214 EP 223 DI 10.1016/j.spen.2010.10.003 PG 10 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 705OF UT WOS:000286145100003 PM 21183127 ER PT J AU Kwolek, CJ Blazick, E AF Kwolek, Christopher J. Blazick, Elizabeth TI Current Management of Traumatic Thoracic Aortic Injury SO SEMINARS IN VASCULAR SURGERY LA English DT Article ID ENDOVASCULAR STENT GRAFT; SURGERY-OF-TRAUMA; SPIRAL COMPUTED-TOMOGRAPHY; SOLE DIAGNOSTIC METHOD; AMERICAN-ASSOCIATION; OPERATIVE REPAIR; RUPTURE; EXPERIENCE; MULTICENTER; METAANALYSIS AB Traumatic aortic rupture is a devastating injury that is difficult to manage because of the need to approach aortic repair, often in concert with management of complex associated injuries to nonvascular organ systems. Traditional open repair, while effective in the long-term, is associated with a periprocedural mortality between 10% and 20%, along with a 5% risk of stroke and up to a 5% risk of spinal chord ischemia. The advent of endovascular stent graft repair has allowed single centers to cut periprocedural mortality in half and decrease the risk of major neurologic events to <2%. It is unlikely that a multicenter prospective randomized trial will ever be performed to evaluate these two procedures. However, several large meta-analyses have been published recently, along with a clinical practice guideline from the Society for Vascular Surgery. The purpose of this article is to review the trends and current concepts in the management of traumatic rupture of the thoracic aorta. Semin Vasc Surg 23:215-220 (C) 2011 Published by Elsevier Inc. C1 [Kwolek, Christopher J.; Blazick, Elizabeth] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg,Dept Surg, Boston, MA 02114 USA. RP Kwolek, CJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg,Dept Surg, 15 Parkman St,WAC-440, Boston, MA 02114 USA. EM ckwolek@partners.org NR 36 TC 7 Z9 10 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0895-7967 J9 SEMIN VASC SURG JI Semin. Vasc. Surg. PD DEC PY 2010 VL 23 IS 4 BP 215 EP 220 DI 10.1053/j.semvascsurg.2010.11.003 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 709AM UT WOS:000286407500004 PM 21194638 ER PT J AU Houbballah, R LaMuraglia, GM AF Houbballah, Rabih LaMuraglia, Glenn M. TI Clotting Problems: Diagnosis and Management of Underlying Coagulopathies SO SEMINARS IN VASCULAR SURGERY LA English DT Article ID HEPARIN-INDUCED THROMBOCYTOPENIA; THROMBOEMBOLIC COMPLICATIONS; THROMBOPHILIC DISORDERS; VENOUS THROMBOEMBOLISM; THROMBOTIC RISK; PROTEIN-C; DEFICIENCY; MALIGNANCY; HEREDITARY; FAILURE AB Vessel wall injury, stasis, and blood hypercoagulable state are major predisposing factors of thrombosis. Although, a procoagulable factor is found in half of patients with venous thromboembolism, relatively little is known about coagulopathies that predispose to arterial thromboembolism or unexplained arterial revascularization thrombosis. Those hypercoagulable states can be inherited or acquired and related to either an increase of a procoagulable factor or a decrease of an anticoagulation agent. However, most thrombotic episodes seem to occur with additive combination of acquired and inherited predisposing factors. Therefore, controversy exists as to which patients and family members to test for thrombophilia and which patients to treat with life-long anticoagulation. The aim of this review is to provide a practical overview with guidelines for detecting, and treatment of, the principal underlying coagulopathies that a vascular surgeon should be aware of in his/her practice and for the care of patients with vascular disease. Semin Vasc Surg 23:221-227 (C) 2011 Published by Elsevier Inc. C1 [Houbballah, Rabih; LaMuraglia, Glenn M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg Gen Surg Serv, Boston, MA 02114 USA. RP LaMuraglia, GM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg Gen Surg Serv, ACC440,15 Parkman St, Boston, MA 02114 USA. EM glamuraglia@partners.org NR 30 TC 4 Z9 5 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 0895-7967 J9 SEMIN VASC SURG JI Semin. Vasc. Surg. PD DEC PY 2010 VL 23 IS 4 BP 221 EP 227 DI 10.1053/j.semvascsurg.2010.11.001 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 709AM UT WOS:000286407500005 PM 21194639 ER PT J AU Hough, S AF Hough, Sigmund TI The Year That Was: 2010 SO SEXUALITY AND DISABILITY LA English DT Editorial Material C1 VA Boston Healthcare Syst, Spinal Cord Injury Serv SCI 128, W Roxbury, MA 02132 USA. RP Hough, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury Serv SCI 128, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM Sigmund_Hough@hms.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0146-1044 J9 SEX DISABIL JI Sex. Disabil. PD DEC PY 2010 VL 28 IS 4 BP 211 EP 211 DI 10.1007/s11195-010-9181-5 PG 1 WC Rehabilitation SC Rehabilitation GA 683WQ UT WOS:000284509400001 ER PT J AU Conhaim, RL Mangino, MJ Dovi, WF Watson, KE Warner, TF Harms, BA AF Conhaim, Robert L. Mangino, Martin J. Dovi, William F. Watson, Kal E. Warner, Thomas F. Harms, Bruce A. TI MICROTHROMBUS FORMATION MAY TRIGGER LUNG INJURY AFTER ACUTE BLOOD LOSS SO SHOCK LA English DT Article DE Acute lung injury; shock lung; acute respiratory distress syndrome; pulmonary microcirculation; microcirculatory thrombosis ID INTERALVEOLAR PERFUSION; RAT LUNGS; SEPSIS AB We showed previously that acute blood loss, without resuscitation, caused marked maldistribution of interalveolar perfusion. Because hemorrhage is a known risk factor for the development of lung injury, the goal of our present studies was to determine if there was a correlation between perfusion maldistribution and the subsequent development of lung injury after blood loss. Specifically, we wanted to know if the perfusion maldistribution might be due to microthrombus formation and/or leukocyte sequestration within the pulmonary microcirculation. We bled rats (30% blood loss) and harvested their lungs 45 min or 24 h later. Lungs were prepared for perfusion distribution analysis, Western blot analysis to measure whole-lung fibrinogen concentrations, and for immunohistochemistry to measure fibrin deposition and leukocyte deposition (CD16 fluorescence). Perfusion was significantly maldistributed at 45 min and 24 h (P < 0.05). At 45 min, whole-lung fibrinogen concentrations were less than half that in controls (P < 0.05), whereas numbers of fibrin microthrombi were 2.5-fold greater than control by 45 min (not statistically significant) and were 4.5-fold greater by 24 h (P = 0.01). Leukocyte deposition was two-fold greater than control by 45 min (not statistically significant) and was 4-fold greater by 24 h (P = 0.02). Fibrin-to-leukocyte nearest-neighbor distances remained unchanged (18.1 [SD, 1.1] mu m) even as the numbers of both increased with time after blood loss. Our results suggest that soluble fibrinogen polymerized to insoluble fibrin within minutes after acute blood loss, which caused perfusion maldistribution and attracted leukocytes. The development of lung injury after blood loss may be a consequence of leukocyte chemoattraction to fibrin microthrombi that seem to form within minutes after blood loss. C1 [Conhaim, Robert L.; Watson, Kal E.; Harms, Bruce A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA. [Conhaim, Robert L.; Dovi, William F.; Warner, Thomas F.; Harms, Bruce A.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Mangino, Martin J.] Virginia Commonwealth Univ, Dept Surg, Richmond, VA USA. RP Conhaim, RL (reprint author), H5-301 BX3236,600 Highland Ave, Madison, WI 53792 USA. EM conhaim@surgery.wisc.edu FU Department of Veterans Affairs FX This study was supported by a grant from the Department of Veterans Affairs. NR 17 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD DEC PY 2010 VL 34 IS 6 BP 601 EP 607 DI 10.1097/SHK.0b013e3181e46e2a PG 7 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 680LW UT WOS:000284234400009 PM 20442694 ER PT J AU Seelig, AD Jacobson, IG Smith, B Hooper, TI Boyko, EJ Gackstetter, GD Gehrman, P Macera, CA Smith, TC AF Seelig, Amber D. Jacobson, Isabel G. Smith, Besa Hooper, Tomoko I. Boyko, Edward J. Gackstetter, Gary D. Gehrman, Philip Macera, Carol A. Smith, Tyler C. CA Millennium Cohort Study Team TI Sleep Patterns Before, During, and After Deployment to Iraq and Afghanistan SO SLEEP LA English DT Article DE Sleep; deployment; Millennium Cohort; mental health; veterans ID POSTTRAUMATIC-STRESS-DISORDER; MILITARY DEPLOYMENT; MILLENNIUM COHORT; GENERAL-POPULATION; COMBAT DEPLOYMENT; DECISION-MAKING; YOUNG-ADULTS; DURATION; DEPRIVATION; HEALTH AB Study Objectives: To determine the associations between deployment in support of the wars in Iraq and Afghanistan and sleep quantity and quality. Design: Longitudinal cohort study Setting: The Millennium Cohort Study survey is administered via a secure website or US mail. Participants: Data were from 41,225 Millennium Cohort members who completed baseline (2001-2003) and follow-up (2004-2006) surveys. Participants were placed into 1 of 3 exposure groups based on their deployment status at follow-up: nondeployed, survey completed during deployment, or survey completed postdeployment. Interventions: N/A Measurements and Results: Study outcomes were self-reported sleep duration and trouble sleeping, defined as having trouble falling asleep or staying asleep. Adjusted mean sleep duration was significantly shorter among those in the deployed and postdeployment groups compared with those who did not deploy. Additionally, male gender and greater stress were significantly associated with shorter sleep duration. Personnel who completed their survey during deployment or postdeployment were significantly more likely to have trouble sleeping than those who had not deployed. Lower self-reported general health, female gender, and reporting of mental health symptoms at baseline were also significantly associated with increased odds of trouble sleeping. Conclusions: Deployment significantly influenced sleep quality and quantity in this population though effect size was mediated with statistical modeling that included mental health symptoms. Personnel reporting combat exposures or mental health symptoms had increased odds of trouble sleeping. These findings merit further research to increase understanding of temporal relationships between sleep and mental health outcomes occurring during and after deployment. C1 [Seelig, Amber D.; Jacobson, Isabel G.; Smith, Besa; Smith, Tyler C.] USN, Hlth Res Ctr, Dept Deployment Hlth Res, San Diego, CA 92106 USA. [Hooper, Tomoko I.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Gackstetter, Gary D.] Analyt Serv Inc ANSER, Arlington, VA USA. [Gehrman, Philip] Univ Penn, Dept Psychiat, Penn Sleep Ctr, Philadelphia, PA 19104 USA. [Seelig, Amber D.; Macera, Carol A.] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. RP Seelig, AD (reprint author), USN, Hlth Res Ctr, Dept Deployment Hlth Res, 140 Sylvester Rd, San Diego, CA 92106 USA. EM amber.seelig@med.navy.mil FU Henry M. Jackson Foundation FX In addition to the authors, the Millennium Cohort Study Team includes Melissa Bagnell, Lacy Farnell, Gia Gumbs, Nisara Granado, Jaime Horton, Kelly Jones, Molly Kelton, Cynthia LeardMann, Travis Leleu, Gordon Lynch, Jamie McGrew, Amanda Pietrucha, Teresa Powell, Donald Sandweiss, Beverly Sheppard, Katherine Snell, Steven Spiegel, Kari Welch, Martin White, James Whitmer, and Charlene Wong, from the Department of Deployment Health Research, Naval Health Research Center, San Diego, CA; Paul Amoroso, from the Madigan Army Medical Center, Tacoma, WA; Gregory Gray, from the College of Public Health and Health Professions, University of Florida, Gainesville, FL; James Riddle; Margaret Ryan from the Naval Hospital Camp Pendleton, Camp Pendleton, CA; and Timothy Wells from the US Air Force Research Laboratory, Wright-Patterson Air Force Base, OH.; The authors thank the Millennium Cohort Study participants, without whom these analyses would not be possible. We thank Scott Seggerman from the Management Information Division, US Defense Manpower Data Center, Monterey, CA; Michelle Stoia from the Naval Health Research Center; and all the professionals from the US Army Medical Research and Materiel Command, especially those from the Military Operational Medicine Research Program, Fort Detrick, MD. We appreciate the support of the Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, MD. NR 41 TC 64 Z9 64 U1 1 U2 11 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD DEC 1 PY 2010 VL 33 IS 12 BP 1615 EP 1622 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 686TZ UT WOS:000284719900006 PM 21120123 ER PT J AU Leger, D Partinen, M Hirshkowitz, M Chokroverty, S Hedner, J AF Leger, Damien Partinen, Markku Hirshkowitz, Max Chokroverty, Sudhansu Hedner, Jan CA EQUINOX Evaluation Daytime QUality TI Characteristics of insomnia in a primary care setting: EQUINOX survey of 5293 insomniacs from 10 countries SO SLEEP MEDICINE LA English DT Article DE Insomnia; Epidemiology; Difficulties initiating sleep; Difficulties maintaining sleep; Nocturnal awakenings; Non restorative sleep; Primary care ID GENERAL-POPULATION; SLEEP; PREVALENCE; ADULTS; COMPLAINTS AB Objective: To describe the characteristics of insomnia in primary care physicians' (PCPs') practices in 10 countries and to understand how the difficulty of maintaining sleep (DMS) was or was not associated with other insomnia symptoms such as difficulty initiating sleep (DIS), early morning awakenings (EMA) or nonrestorative sleep (NRS) in PCPs patients with insomnia. Methods: International, noninterventional, cross-sectional, observational survey conducted in a primary care setting in subjects complaining of sleep disturbances in 10 countries. A questionnaire based on DSM-IV and ICSD criteria was administered. Results: Thirteen thousand one hundred twenty-four subjects were enrolled by 647 physicians; 5293 of them (32.6%) had insomnia and were surveyed. The population was predominantly female (63.9%) with a mean age of 47.8 +/- 15.3 years; 39.9% of these patients have already been treated for sleep difficulties. Combination of all types of insomnia symptoms (DIS + DMS + EMA + NRS) was the most frequently reported combination (38.6% of the subjects), while the percentage of subjects presenting with only one type of insomnia symptom (DIS, DMS, EMA or NRS) was very low: 3%, 1.8%, 0.9% and 1.4% respectively. DMS was on average the most commonly reported insomnia symptom (80.2%). Multiple logistic regression showed that DMS, EMA and NRS symptoms were significantly linked with each other and also to other insomnia criteria (sleep satisfaction, sleep quality, sleep duration, number of hours of sleep, frequency of insomnia symptoms, wake up rested / unrested and non restorative sleep). Conclusions: Patients visiting PCPs with insomnia are likely to present with severe and poly-symptomatic insomnia. (C) 2010 Elsevier B.V. All rights reserved. C1 [Leger, Damien] Univ Paris 05, APHP, Ctr Sommeil & Vigilance, Hotel Dieu Paris, F-75004 Paris, France. [Partinen, Markku] Rinnekoti Res Ctr, Skogby Sleep Clin, Espoo, Finland. [Hirshkowitz, Max] VA Med Ctr, Sleep Disorders & Res Ctr, Houston, TX USA. [Chokroverty, Sudhansu] JFK Med Ctr, New Jersey Neurosci Inst, Edison, NJ USA. [Hedner, Jan] Sahlgrens Univ Hosp, Dept Resp Med & Allergol, Sleep Lab Unit, Gothenburg, Sweden. RP Leger, D (reprint author), Univ Paris 05, Pl Parvis Notre Dame, F-75181 Paris 04, France. EM damien.leger@htd.aphp.fr FU Sanofi Aventis FX This survey has been supported by Sanofi Aventis. All authors have been sponsored to design the protocol and review the data as a scientific advisory board. NR 29 TC 21 Z9 21 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 J9 SLEEP MED JI Sleep Med. PD DEC PY 2010 VL 11 IS 10 SI SI BP 987 EP 998 DI 10.1016/j.sleep.2010.04.019 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 704AD UT WOS:000286022600006 PM 21093363 ER PT J AU Leger, D Partinen, M Hirshkowitz, M Chokroverty, S Touchette, E Hedner, J AF Leger, Damien Partinen, Markku Hirshkowitz, Max Chokroverty, Sudhansu Touchette, Evelyne Hedner, Jan CA EQUINOX Evaluation Daytime QUality TI Daytime consequences of insomnia symptoms among outpatients in primary care practice: EQUINOX international survey SO SLEEP MEDICINE LA English DT Article DE Insomnia; Difficulty initiating sleep; Difficulty maintaining sleep; Early morning awakening; Non-restorative sleep; Daytime consequences; International survey ID QUALITY-OF-LIFE; GENERAL-POPULATION; PSYCHIATRIC-DISORDERS; SLEEP DISTURBANCES; PREVALENCE; ADULTS; MANAGEMENT; COMPLAINTS; IMPACT AB Objective: To assess the daytime consequences in outpatients suffering from different insomnia symptoms in primary care practice. Methods: An international cross-sectional survey was conducted in 5293 outpatients complaining of sleep disturbances in primary care practice. A sleep questionnaire addressing daytime consequences, insomnia symptoms, socio-demographic characteristics, and other sleep variables was administered by 647 physicians in 10 countries. Results: Overall, 20-33% of subjects reported "severe" daytime impairments associated with sleep disturbances. Approximately 45% of patients complaining of sleep disturbances in primary, care practice suffered from a combination of insomnia symptoms. Patients suffering from all insomnia symptoms reported the most severe daytime functioning impairments compared with patients suffering from initiation or maintenance insomnia only. Conversely, the majority of patients suffering from non-restorative sleep reported little daytime functioning impairments compared to the patients suffering from other combinations of insomnia symptoms. The strongest risk factor associated with "severe" daytime functioning impairments was sleep quality perception. Conclusions: Primary insomnia disturbs subjective daytime functioning. A report of combined insomnia symptoms reflected the most damaging insomnia subtype and had a negative impact on a wide range of daytime functioning consequences. (C) 2010 Elsevier B.V. All rights reserved. C1 [Leger, Damien; Touchette, Evelyne] Univ Paris 05, APHP, Ctr Sommeil & Vigilance, Hotel Dieu Paris, F-75181 Paris 04, France. [Partinen, Markku] Rinnekoti Res Ctr, Skogby Sleep Clin, Espoo, Finland. [Hirshkowitz, Max] VA Med Ctr, Sleep Disorders & Res Ctr, Houston, TX USA. [Chokroverty, Sudhansu] JFK Med Ctr, New Jersey Neurosci Inst, Edison, NJ USA. [Hedner, Jan] Sahlgrens Univ Hosp, Dept Resp Med & Allergol, Sleep Lab Unit, Gothenburg, Sweden. RP Leger, D (reprint author), Univ Paris 05, APHP, Ctr Sommeil & Vigilance, Hotel Dieu Paris, 1 Pl Parvis Notre Dame, F-75181 Paris 04, France. EM damien.leger@htd.aphp.fr RI Touchette, Evelyne/A-3592-2013 OI Touchette, Evelyne/0000-0002-0557-9352 FU Sanofi-Aventis FX This survey has been supported by Sanofi-Aventis. All authors have been sponsored to design the protocol and review the data as a scientific advisory board. NR 31 TC 11 Z9 14 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 J9 SLEEP MED JI Sleep Med. PD DEC PY 2010 VL 11 IS 10 SI SI BP 999 EP 1009 DI 10.1016/j.sleep.2010.04.018 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 704AD UT WOS:000286022600007 PM 20965779 ER PT J AU Perron, BE Bohnert, ASB Vaughn, MG Bauer, MS Kilbourne, AM AF Perron, Brian E. Bohnert, Amy S. B. Vaughn, Michael G. Bauer, Mark S. Kilbourne, Amy M. TI Profiles of disability among adults with bipolar spectrum disorders SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article DE Bipolar disorders; Disability; Classification strategies; Latent profile analysis ID LATENT CLASS ANALYSIS; PRIMARY-CARE; DEPRESSION SEVERITY; IMPAIRMENT; SYMPTOMS; SCALE; SCHIZOPHRENIA; COMORBIDITY; POPULATION; PATTERNS AB Heterogeneous groups of patients with a spectrum of service needs are commonplace in mental health settings. Although comprehensive assessments are available to measure variations in service needs, numerous challenges still exist when confronting this heterogeneity and many assessments used in clinic settings are lengthy and have not been demonstrated to be consistent over time. The purpose of this study was to identify subgroups of persons with bipolar spectrum disorders, who have similar disability profiles, and to the extent to which the subgrouping is stable over time. Participants were recruited from the Continuous Improvement for Veterans in Care-Mood Disorders. Eligible patients (N = 435) were those who received inpatient or outpatient treatment for bipolar disorder at a large urban VA mental health facility in Western Pennsylvania from July 2004 through July 2006. This was a naturalistic cohort study of patients with bipolar spectrum disorders. Baseline and 1-year follow-up data were collected using face-to-face interviews and recorded abstraction. The World Health Organization Disability Assessment Scale was the primary measure used to identify subgroups within this sample. Using a classification strategy called latent profile analysis, this study identified three unique subgroups that showed significant differences in various clinical measures at baseline and follow-up. The largest and most consistent subgroup differences were observed in the current bipolar symptomatology. The classification of functional status in the present study can aid clinicians in the identification of bipolar patients, with specific impairment profiles, who may need additional intervention. Future research is needed to understand whether specific interventions targeted at these subgroups can improve the quality of care for this high-need and at-risk population. C1 [Perron, Brian E.; Bohnert, Amy S. B.; Kilbourne, Amy M.] Univ Michigan, Ann Arbor, MI 48109 USA. [Vaughn, Michael G.] St Louis Univ, St Louis, MO 63103 USA. [Bauer, Mark S.] VA Boston Healthcare Syst, Boston, MA USA. [Bauer, Mark S.] Harvard Univ, Sch Med, Boston, MA USA. RP Perron, BE (reprint author), Univ Michigan, Ann Arbor, MI 48109 USA. EM beperron@umich.edu RI Bohnert, Amy/C-7313-2015 FU Department of Veterans Affairs; Veterans Health Administration; Health Services Research and Development Service [HR 02-283]; National Institute of Mental Health [MH 74509, MH 79994] FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (HR 02-283) and the National Institute of Mental Health (MH 74509; MH 79994). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 39 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0933-7954 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD DEC PY 2010 VL 45 IS 12 BP 1125 EP 1134 DI 10.1007/s00127-009-0153-y PG 10 WC Psychiatry SC Psychiatry GA 678WN UT WOS:000284113900003 PM 19851701 ER PT J AU Livingston, JD Boyd, JE AF Livingston, James D. Boyd, Jennifer E. TI Correlates and consequences of internalized stigma for people living with mental illness: A systematic review and meta-analysis SO SOCIAL SCIENCE & MEDICINE LA English DT Review DE Stigma; Mental illness; Meta-analysis; Systematic review ID QUALITY-OF-LIFE; SCHIZOPHRENIA SPECTRUM DISORDERS; MODIFIED LABELING THEORY; DEPRESSION SELF-STIGMA; PRIMARY-CARE PATIENTS; STRESS-COPING MODEL; PERCEIVED STIGMA; HEALTH-SERVICES; SOCIAL ANXIETY; PSYCHIATRIC OUTPATIENTS AB An expansive body of research has investigated the experiences and adverse consequences of internalized stigma for people with mental illness. This article provides a systematic review and meta-analysis of the extant research regarding the empirical relationship between internalized stigma and a range of sociodemographic, psychosocial, and psychiatric variables for people who live with mental illness. An exhaustive review of the research literature was performed on all articles published in English that assessed a statistical relationship between internalized stigma and at least one other variable for adults who live with mental illness. In total, 127 articles met the inclusion criteria for systematic review, of which, data from 45 articles were extracted for meta-analyses. None of the sociodemographic variables that were included in the study were consistently or strongly correlated with levels of internalized stigma. The review uncovered a striking and robust negative relationship between internalized stigma and a range of psychosocial variables (e.g., hope, self-esteem, and empowerment). Regarding psychiatric variables, internalized stigma was positively associated with psychiatric symptom severity and negatively associated with treatment adherence. The review draws attention to the lack of longitudinal research in this area of study which has inhibited the clinical relevance of findings related to internalized stigma. The study also highlights the need for greater attention on disentangling the true nature of the relationship between internalized stigma and other psychosocial variables. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Livingston, James D.] Prov Hlth Serv Author, BC Mental Hlth Serv, Forens Psychiat Serv Commiss, Port Coquitlam, BC V3C 5X9, Canada. [Livingston, James D.] Prov Hlth Serv Author, Addict Serv, Forens Psychiat Serv Commiss, Port Coquitlam, BC V3C 5X9, Canada. [Livingston, James D.] Simon Fraser Univ, Sch Criminol, Burnaby, BC V5A 1S6, Canada. [Boyd, Jennifer E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Boyd, Jennifer E.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Livingston, JD (reprint author), Prov Hlth Serv Author, BC Mental Hlth Serv, Forens Psychiat Serv Commiss, 70 Colony Farm Rd, Port Coquitlam, BC V3C 5X9, Canada. EM jlivingston@forensic.bc.ca NR 171 TC 283 Z9 296 U1 18 U2 125 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD DEC PY 2010 VL 71 IS 12 BP 2150 EP 2161 DI 10.1016/j.socscimed.2010.09.030 PG 12 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 702RN UT WOS:000285912300013 PM 21051128 ER PT J AU He, Y Zaslavsky, AM Landrum, MB Harrington, DP Catalano, P AF He, Y. Zaslavsky, A. M. Landrum, M. B. Harrington, D. P. Catalano, P. TI Multiple imputation in a large-scale complex survey: a practical guide SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Article ID FULLY CONDITIONAL SPECIFICATION; MODEL AB The Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium is a multisite, multimode, multiwave study of the quality and patterns of care delivered to population-based cohorts of newly diagnosed patients with lung and colorectal cancer. As is typical in observational studies, missing data are a serious concern for CanCORS, following complicated patterns that impose severe challenges to the consortium investigators. Despite the popularity of multiple imputation of missing data, its acceptance and application still lag in large-scale studies with complicated data sets such as CanCORS. We use sequential regression multiple imputation, implemented in public-available software, to deal with non-response in the CanCORS surveys and construct a centralised completed database that can be easily used by investigators from multiple sites. Our work illustrates the feasibility of multiple imputation in a large-scale multiobjective survey, showing its capacity to handle complex missing data. We present the implementation process in detail as an example for practitioners and discuss some of the challenging issues which need further research. C1 [He, Y.; Zaslavsky, A. M.; Landrum, M. B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Harrington, D. P.; Catalano, P.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP He, Y (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM he@hcp.med.harvard.edu FU NCI NIH HHS [U01 CA093344-05, U01 CA093344] NR 32 TC 65 Z9 65 U1 0 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0962-2802 EI 1477-0334 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PD DEC PY 2010 VL 19 IS 6 BP 653 EP 670 DI 10.1177/0962280208101273 PG 18 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 687EY UT WOS:000284763000005 PM 19654173 ER PT J AU Xu, HC Stamova, B Jickling, G Tian, YF Zhan, XH Ander, BP Liu, DZ Turner, R Rosand, J Goldstein, LB Furie, KL Verro, P Johnston, SC Sharp, FR DeCarli, CS AF Xu, Huichun Stamova, Boryana Jickling, Glen Tian, Yingfang Zhan, Xinhua Ander, Bradley P. Liu, Dazhi Turner, Renee Rosand, Jonathan Goldstein, Larry B. Furie, Karen L. Verro, Piero Johnston, S. Claiborne Sharp, Frank R. DeCarli, Charles S. TI Distinctive RNA Expression Profiles in Blood Associated With White Matter Hyperintensities in Brain SO STROKE LA English DT Article DE Alzheimer disease; blood; gene expression profiling; inflammation; ischemia; oxidative stress; white matter ID MILD COGNITIVE IMPAIRMENT; CENTRAL-NERVOUS-SYSTEM; TEMPORAL-LOBE ATROPHY; GENE-EXPRESSION; ALZHEIMERS-DISEASE; CARDIOVASCULAR HEALTH; ISCHEMIC-STROKE; LESIONS; MICROARRAY; BIOMARKERS AB Background and Purpose-White matter hyperintensities (WMH) are areas of high signal detected by T2 and fluid-attenuated inversion recovery sequences on brain MRI. Although associated with aging, cerebrovascular risk factors, and cognitive impairment, the pathogenesis of WMH remains unclear. Thus, RNA expression was assessed in the blood of individuals with and without extensive WMH to search for evidence of oxidative stress, inflammation, and other abnormalities described in WMH lesions in brain. Methods-Subjects included 20 with extensive WMH (WMH+), 45% of whom had Alzheimer disease, and 18 with minimal WMH (WMH-), 44% of whom had Alzheimer disease. All subjects were clinically evaluated and underwent quantitative MRI. Total RNA from whole blood was processed on human whole genome Affymetrix HU133 Plus 2.0 microarrays. RNA expression was analyzed using an analysis of covariance. Results-Two hundred forty-one genes were differentially regulated at +/- 1.2-fold difference (P<0.005) in subjects with WMH+ as compared to WMH-, regardless of cognitive status and 50 genes were differentially regulated with +/- 1.5-fold difference (P<0.005). Cluster and principal components analyses showed that the expression profiles for these genes distinguished WMH+ from WMH- subjects. Function analyses suggested that WMH-specific genes were associated with oxidative stress, inflammation, detoxification, and hormone signaling, and included genes associated with oligodendrocyte proliferation, axon repair, long-term potentiation, and neurotransmission. Conclusions-The unique RNA expression profile in blood associated with WMH is consistent with roles of systemic oxidative stress and inflammation, as well as other potential processes in the pathogenesis or consequences of WMH. (Stroke. 2010;41:2744-2749.) C1 [Xu, Huichun; DeCarli, Charles S.] Univ Calif Davis, Med Ctr, Dept Neurol, Imaging Dementia & Aging IDeA Lab, Sacramento, CA 95817 USA. [Xu, Huichun; Stamova, Boryana; Jickling, Glen; Tian, Yingfang; Zhan, Xinhua; Ander, Bradley P.; Liu, Dazhi; Turner, Renee; Verro, Piero; Sharp, Frank R.] Univ Calif Davis, Med Ctr, MIND Inst, Sacramento, CA 95817 USA. [DeCarli, Charles S.] Univ Calif Davis, Med Ctr, Alzheimers Dis Ctr, Sacramento, CA 95817 USA. [DeCarli, Charles S.] Univ Calif Davis, Med Ctr, Ctr Neurosci, Sacramento, CA 95817 USA. [Rosand, Jonathan; Furie, Karen L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Goldstein, Larry B.] Duke Univ, Dept Med Neurol, Durham, NC USA. [Goldstein, Larry B.] Durham VA Med Ctr, Durham, NC USA. [Xu, Huichun; Johnston, S. Claiborne] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Xu, HC (reprint author), Univ Calif Davis, Med Ctr, Dept Neurol, Imaging Dementia & Aging IDeA Lab, Sacramento, CA 95817 USA. EM huixu@ucdavis.edu RI Liu, DaZhi/B-6850-2011; Jickling, Glen/K-4002-2013; OI Turner, Renee/0000-0003-4278-8302; Jickling, Glen/0000-0003-3543-0820 FU NIH [P30 AG10129, R01 AG021028, RO1 NS056302]; American Heart Association Bugher Foundation Center for Stroke Prevention Research; NIH/NCRR [UL1 RR024131]; American Stroke Association Bugher Foundation Center for Stroke Prevention Research FX Supported by NIH P30 AG10129 (C.D.), R01 AG021028 (C.D.), RO1 NS056302 (F.R.S.), and the American Heart Association Bugher Foundation Center for Stroke Prevention Research (F.R.S., J.R., L.B.G., K.L.F.), NIH/NCRR UCSF-CTSI grant number UL1 RR024131. H.X., B.A., and Y.T. were supported by fellowship awards from American Stroke Association Bugher Foundation Center for Stroke Prevention Research. NR 28 TC 20 Z9 20 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 2010 VL 41 IS 12 BP 2744 EP 2749 DI 10.1161/STROKEAHA.110.591875 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 686GU UT WOS:000284685600011 PM 20966416 ER PT J AU Rost, NS Fitzpatrick, K Biffi, A Kanakis, A Devan, W Anderson, CD Cortellini, L Furie, KL Rosand, J AF Rost, Natalia S. Fitzpatrick, Kaitlin Biffi, Alessandro Kanakis, Allison Devan, William Anderson, Christopher D. Cortellini, Lynelle Furie, Karen L. Rosand, Jonathan TI White Matter Hyperintensity Burden and Susceptibility to Cerebral Ischemia SO STROKE LA English DT Article DE acute cerebral infarction; leukoaraiosis; risk factors; stroke; transient ischemic attack ID AMYLOID ANGIOPATHY; ELDERLY-PEOPLE; STROKE; ATTACK; LEUKOARAIOSIS; RISK; PREVENTION; SEVERITY; LESIONS; HEALTH AB Background and Purpose-White matter hyperintensity (WMH) burden increases risk of ischemic stroke; furthermore, it predicts infarct growth in acute cerebral ischemia. We hypothesized that WMH would be less severe in patients with TIA as compared to those with acute ischemic stroke and completed infarct. Methods-Cases (TIA, n=30) and controls (acute ischemic stroke, n=120) were selected from an ongoing longitudinal cohort study of patients with stroke and matched for age, gender, and race/ethnicity. All subjects had brain MRI within 48 hours of presentation to evaluate for evidence of acute cerebral ischemia. WMH burden on MRI was quantified using a validated computer-assisted program with high inter-rater reliability. Results-Median WMH volume in individuals with TIA was 3.7 cm(3) (interquartile range, 1.5-8.33 cm(3)) compared to 6.9 cm(3) (interquartile range, 3.1-11.9 cm(3)) in acute ischemic stroke (P<0.04). In multivariable analysis, the odds of completed infarct were higher (OR, 2.19; 95% CI, 1.27-3.77; P<0.005) in subjects with larger volumes of WMH. Conclusions-WMH burden was significantly less in subjects with TIA as opposed to those with ischemic stroke. These data provide further evidence to support a detrimental role of WMH burden on the capacity of cerebral tissue to survive acute ischemia. (Stroke. 2010;41:2807-2811.) C1 [Rost, Natalia S.; Fitzpatrick, Kaitlin; Biffi, Alessandro; Kanakis, Allison; Devan, William; Anderson, Christopher D.; Cortellini, Lynelle; Furie, Karen L.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. [Rost, Natalia S.; Biffi, Alessandro; Devan, William; Anderson, Christopher D.; Cortellini, Lynelle; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Rost, NS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM nrost@partners.org OI Anderson, Christopher/0000-0002-0053-2002 FU American Heart Association Bugher Foundation; Massachusetts General Hospital Deane Institute for Integrative Research in Atrial Fibrillation and Stroke; National Institute of Neurological Disorders and Stroke (NINDS) [5P50NS051343-04, 5R01NS059727, 5P50NS051343, R01NS063925, K23NS064052-01A] FX This study was supported by project grants from the American Heart Association Bugher Foundation, the Massachusetts General Hospital Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, and the National Institute of Neurological Disorders and Stroke (NINDS).; C.D.A. is supported by the American Heart Association Bugher Foundation. A.B. is supported by the American Heart Association Bugher Foundation. K.L.F. is supported by the National Institute of Neurological Disorders and Stroke (NINDS) (5P50NS051343-04). J.R. is supported by the National Institute of Neurological Disorders and Stroke (NINDS) (5R01NS059727, 5P50NS051343, R01NS063925) and the American Heart Association Bugher Foundation. N.S.R. is supported by the National Institute of Neurological Disorders and Stroke (NINDS) (K23NS064052-01A). NR 34 TC 10 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 2010 VL 41 IS 12 BP 2807 EP 2811 DI 10.1161/STROKEAHA.110.595355 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 686GU UT WOS:000284685600021 PM 20947843 ER PT J AU Pascual, B Prieto, E Arbizu, J Marti-Climent, J Olier, J Masdeu, JC AF Pascual, Belen Prieto, Elena Arbizu, Javier Marti-Climent, Josep Olier, Jorge Masdeu, Joseph C. TI Brain Glucose Metabolism in Vascular White Matter Disease With Dementia Differentiation From Alzheimer Disease SO STROKE LA English DT Article DE Alzheimer disease; brain metabolism; vascular dementia; white matter disease ID MILD COGNITIVE IMPAIRMENT; POSITRON-EMISSION-TOMOGRAPHY; CLINICAL-DIAGNOSIS; FDG-PET; LESIONS; LEUKOARAIOSIS; PREVALENCE; LACUNES; VOLUME AB Background and Purpose-The boundary between vascular dementia and Alzheimer disease (AD) continues to be unclear. Some posit that gradually progressive vascular dementia, as with small vessel disease, is simply vascular disease plus AD. Because AD presents a characteristic pattern on fluorodeoxyglucose positron emission tomography, we sought to determine whether the fluorodeoxyglucose pattern of vascular dementia resembled more AD or the pattern in nondemented patients with severe microvascular brain disease. Methods-Vascular disease patients were selected on the basis of confluent white matter lesions on both hemispheres. Among them, with a similar degree of vascular disease on MRI, neuropsychological testing separated groups with dementia and without dementia. Patients with AD and healthy controls were also studied. The 4 groups, with 12 subjects each, were matched by age, gender, and educational level. Fluorodeoxyglucose distribution was analyzed using both voxel-based and volume of interest methods. Results-The AD group had the characteristic pattern of bilaterally decreased metabolism in parieto-temporal association cortex and precuneus. By contrast, patients with vascular disease and dementia had a similar anatomic pattern to that of the vascular patients without dementia, but with greater metabolic abnormalities, particularly in the frontal lobes and deep nuclei. Conclusions-The anatomy of metabolic abnormalities in vascular disease with dementia suggests that, at least in some cases, dementia with vascular disease may be independent of AD. The metabolic abnormality involves the thalamus, caudate, and frontal lobe, a pattern concordant with the neuropsychological findings of impaired executive function characteristic of vascular dementia. (Stroke. 2010;41:2889-2893.) C1 [Pascual, Belen; Masdeu, Joseph C.] Univ Navarra, Ctr Appl Med Res, Div Neurosci, E-31080 Pamplona, Spain. [Pascual, Belen; Prieto, Elena; Arbizu, Javier; Marti-Climent, Josep; Masdeu, Joseph C.] CIBERNED, Pamplona, Spain. [Prieto, Elena; Arbizu, Javier; Olier, Jorge] Univ Navarra, Dept Nucl Med, E-31080 Pamplona, Spain. [Olier, Jorge] Hosp Navarra, Dept Radiol, Pamplona, Spain. RP Pascual, B (reprint author), Massachusetts Gen Hosp, Frontotemporal Dementia Unit, Dept Neurol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,149-2691, Charlestown, MA 02129 USA. EM belen@nmr.mgh.harvard.edu RI Prieto, Elena/N-2142-2014 OI Prieto, Elena/0000-0002-3609-1210 FU European Community [LSHB-CT-2005-512146]; "Union Temporal de Empresas (UTE): Centro de Investigacion Medica Aplicada," University of Navarra; Fundacion Mutua Madrilena; Government of Navarra; Spanish Ministry of Health FX This study was funded in part by the EC-FP6 project DiMI, LSHB-CT-2005-512146 of the European Community, by the "Union Temporal de Empresas (UTE): Centro de Investigacion Medica Aplicada," University of Navarra, by the "Fundacion Mutua Madrilena," by a grant from the Government of Navarra, and by the CIBER on Neurodegeneration of the Spanish Ministry of Health. NR 34 TC 13 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2010 VL 41 IS 12 BP 2889 EP 2893 DI 10.1161/STROKEAHA.110.591552 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 686GU UT WOS:000284685600034 PM 21051671 ER PT J AU Reeves, MJ Gargano, J Maier, KS Broderick, JP Frankel, M LaBresh, KA Moomaw, CJ Schwamm, L AF Reeves, Mathew J. Gargano, Julia Maier, Kimberly S. Broderick, Joseph P. Frankel, Michael LaBresh, Kenneth A. Moomaw, Charles J. Schwamm, Lee TI Patient-Level and Hospital-Level Determinants of the Quality of Acute Stroke Care A Multilevel Modeling Approach SO STROKE LA English DT Article DE health care; multilevel analysis; quality; registries ID ACUTE MYOCARDIAL-INFARCTION; TRANSIENT ISCHEMIC ATTACK; PERFORMANCE-MEASURES; HEALTH RESEARCH; OF-CARE; OUTCOMES; REGISTRY; STATEMENT; ADHERENCE; CENTERS AB Background and Purpose-Quality of care may be influenced by patient and hospital factors. Our goal was to use multilevel modeling to identify patient-level and hospital-level determinants of the quality of acute stroke care in a stroke registry. Methods-During 2001 to 2002, data were collected for 4897 ischemic stroke and TIA admissions at 96 hospitals from 4 prototypes of the Paul Coverdell National Acute Stroke Registry. Duration of data collection varied between prototypes (range, 2-6 months). Compliance with 8 performance measures (recombinant tissue plasminogen activator treatment, antithrombotics <24 hours, deep venous thrombosis prophylaxis, lipid testing, dysphagia screening, discharge antithrombotics, discharge anticoagulants, smoking cessation) was summarized in a composite opportunity score defined as the proportion of all needed care given. Multilevel linear regression analyses with hospital specified as a random effect were conducted. Results-The average hospital composite score was 0.627. Hospitals accounted for a significant amount of variability (intraclass correlation=0.18). Bed size was the only significant hospital-level variable; the mean composite score was 11% lower in small hospitals (<= 145 beds) compared with large hospitals (>= 500 beds). Significant patient-level variables included age, race, ambulatory status documentation, and neurologist involvement. However, these factors explained < 2.0% of the variability in care at the patient level. Conclusions-Multilevel modeling of registry data can help identify the relative importance of hospital-level and patient-level factors. Hospital-level factors accounted for 18% of total variation in the quality of care. Although the majority of variability in care occurred at the patient level, the model was able to explain only a small proportion. (Stroke. 2010;41:2924-2931.) C1 [Reeves, Mathew J.; Gargano, Julia] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Maier, Kimberly S.] Michigan State Univ, Coll Educ, E Lansing, MI 48824 USA. [Broderick, Joseph P.; Moomaw, Charles J.] Univ Cincinnati, Dept Neurol, Cincinnati, OH 45221 USA. [Frankel, Michael] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. [LaBresh, Kenneth A.] Massachusetts PRO, Waltham, MA USA. [Schwamm, Lee] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Reeves, MJ (reprint author), Michigan State Univ, Dept Epidemiol, B 601 W Fee Hall, E Lansing, MI 48824 USA. EM reevesm@msu.edu RI LaBresh, Kenneth/A-6995-2017; OI LaBresh, Kenneth/0000-0001-9040-1956; Schwamm, Lee/0000-0003-0592-9145 FU U.S. Centers for Disease Control and Prevention (CDC) FX The Paul Coverdell National Acute Stroke Registry was funded by a cooperative agreement from the U.S. Centers for Disease Control and Prevention (CDC). NR 27 TC 18 Z9 18 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 2010 VL 41 IS 12 BP 2924 EP 2931 DI 10.1161/STROKEAHA.110.598664 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 686GU UT WOS:000284685600040 PM 20966407 ER PT J AU Anderson, CD Biffi, A Greenberg, SM Rosand, J AF Anderson, Christopher D. Biffi, Alessandro Greenberg, Steven M. Rosand, Jonathan TI Personalized Approaches to Clopidogrel Therapy Are We There Yet? SO STROKE LA English DT Review DE antiplatelet; genetics; stroke; review ID OF-FUNCTION POLYMORPHISM; PROTON PUMP INHIBITORS; CARDIOVASCULAR EVENTS; ANTIPLATELET THERAPY; HEALTHY-SUBJECTS; RISK; PRASUGREL; DRUGS; PANTOPRAZOLE; ASSOCIATION AB Clopidogrel is one of the most commonly prescribed medications worldwide. Recent advisories from the US Food and Drug Administration have drawn attention to the possibility of personalized decision-making for people who are candidates for clopidogrel. As is the case with antihypertensives, statins, and warfarin, common genetic sequence variants can influence clopidogrel metabolism and its effect on platelet activity. These genetic variants have, in multiple studies, been associated with adverse clinical outcomes. Concurrent medication use also influences how the body handles clopidogrel. Proton pump inhibitors, widely prescribed in conjunction with clopidogrel, may blunt its effectiveness. We address implications for bedside decision-making in light of accumulated data and current Food and Drug Administration advisories and conclude that genetic testing for CYP2C19 genotype and limitation of proton pump inhibitor interactions do not yet appear to offer an opportunity to optimize treatment given the current state of knowledge. (Stroke. 2010;41:2997-3002.) C1 [Anderson, Christopher D.; Biffi, Alessandro; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Stroke Serv, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Anderson, Christopher D.; Biffi, Alessandro; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Hemorrhag Stroke Res Program, Boston, MA 02114 USA. [Anderson, Christopher D.; Biffi, Alessandro; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Stroke Serv, Div Neurocrit Care & Emergency Neurol, 185 Cambridge St,CPZN-6818, Boston, MA 02114 USA. EM jrosand@partners.org OI Anderson, Christopher/0000-0002-0053-2002 FU Bugher Foundation Centers for Stroke Prevention Research/American Stroke Association; National Institutes of Neurologic Disorders and Stroke [R01 NS059727]; Massachusetts General Hospital Deane Institute FX This work was supported by the Bugher Foundation Centers for Stroke Prevention Research/American Stroke Association, National Institutes of Neurologic Disorders and Stroke (grant No. R01 NS059727), and Massachusetts General Hospital Deane Institute for the Integrative Study of Atrial Fibrillation and Stroke. NR 29 TC 16 Z9 19 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 2010 VL 41 IS 12 BP 2997 EP 3002 DI 10.1161/STROKEAHA.110.594069 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 686GU UT WOS:000284685600054 PM 21030701 ER PT J AU Goldfarb, M Gondek, S Hodin, R Parangi, S AF Goldfarb, Melanie Gondek, Stephen Hodin, Richard Parangi, Sareh TI Resident/fellow assistance in the operating room for endocrine surgery in the era of fellowships SO SURGERY LA English DT Article ID THYROID-SURGERY; SURGICAL CARE; UNITED-STATES; EXPERIENCE; RESIDENCY; PATTERNS; DISEASES; QUALITY; FUTURE; RISK AB Background. Historically, a high percentage of endocrine surgical procedures are performed by general surgeons in nonteaching environments. With the institution of accredited fellowships, we sought to determine whether that dynamic is changing. Materials and Methods. The American College of Surgeons National Surgeons Quality Improvement Program was queried for all thyroid, parathyroid, and adrenal operations performed during 2005-2008. Resident assistance was classified as none, junior (postgraduate years 1-3), senior (postgraduate years 4 and 5) or fellow (>= postgraduate year 6). Data were also examined for associations between resident/fellow assistance and surgical outcomes. Results. In all, 24.7% of endocrine operations (7,140/29,161) were performed by an attending surgeon operating alone (17.1% adrenals, 27.4% thyroids, and 20.6% parathyroids). Fellows assisted in 6.6% of operations (18.3% adrenals, 4.7% thyroids, and 8.2% parathyroids; 2006: 586 operations, 2007: 629 operations, and 2008: 720 operations). Comparing attending surgeons operating alone with those assisted by residents/fellows, they had shorter operative times (P < .001), longer surgical duration of stay (parathyroid: 1.73 days, thyroid: 1.80 days, P < .001), and a higher prevalence of obese, diabetic, or octogenarian patients. However, no significant difference was found, in the rates of wound infections, medical complications, return to the operating room, or overall morbidity. Conclusion. Even with the increase in endocrine surgery fellowships, almost one fourth of all endocrine operations are still performed by attending surgeons operating alone. Although operations assisted by residents/fellows took longer and patients had a greater duration of stay, there were no significant differences in measured outcomes. (Surgery 2010;148:1065-72.) C1 [Parangi, Sareh] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Thyroid Canc Res Lab, Div Gen & Gastrointestinal Surg,Endocrine Surg Un, Boston, MA 02115 USA. [Goldfarb, Melanie; Gondek, Stephen] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Parangi, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Thyroid Canc Res Lab, Div Gen & Gastrointestinal Surg,Endocrine Surg Un, Wang ACC 460,15 Parkman St, Boston, MA 02115 USA. EM sparangi@partners.org NR 21 TC 6 Z9 6 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2010 VL 148 IS 6 BP 1065 EP 1071 DI 10.1016/j.surg.2010.09.010 PG 7 WC Surgery SC Surgery GA 704XM UT WOS:000286088900004 PM 21134534 ER PT J AU Randolph, GW AF Randolph, Gregory W. TI Papillary cancer nodal surgery and the advisability of prophylactic central neck dissection: Primum, non nocere SO SURGERY LA English DT Article ID DIFFERENTIATED THYROID-CARCINOMA; CENTRAL COMPARTMENT; CLINICAL-SIGNIFICANCE; PROGNOSTIC-FACTORS; METASTASIS; MANAGEMENT; RECURRENCE; SURVIVAL; MICROCARCINOMA; MALIGNANCY C1 [Randolph, Gregory W.] Harvard Univ, Sch Med,Dept Surg, Massachusetts Gen Hosp,Div Surg Oncol,Endocrine S, Dept Otol & Laryngol,Massachusetts Eye & Ear Infi, Boston, MA 02114 USA. RP Randolph, GW (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM gregory_randolph@meei.harvard.edu NR 39 TC 4 Z9 4 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2010 VL 148 IS 6 BP 1108 EP 1112 DI 10.1016/j.surg.2010.09.035 PG 5 WC Surgery SC Surgery GA 704XM UT WOS:000286088900014 PM 21134540 ER PT J AU Lubitz, CC Hunter, GJ Hamberg, LM Parangi, S Ruan, D Gawande, A Gaz, RD Randolph, GW Moore, FD Hodin, RA Stephen, AE AF Lubitz, Carrie C. Hunter, George J. Hamberg, Leena M. Parangi, Sareh Ruan, Daniel Gawande, Atul Gaz, Randall D. Randolph, Gregory W. Moore, Francis D., Jr. Hodin, Richard A. Stephen, Antonia E. TI Accuracy of 4-dimensional computed tomography in poorly localized patients with primary hyperparathyroidism SO SURGERY LA English DT Article ID MINIMALLY INVASIVE PARATHYROIDECTOMY; SURGERY; MANAGEMENT; NECK AB Background. Four-dimensional computed tomography (4D-CT) utilizes multiplanar images and, perfusion characteristics to identify abnormal parathyroid glands. We assessed the role of 4D-CT in patients with inconclusive preoperative ultrasound and sestamibi localization studies. Methods. Adult patients with primary hyperparathyroidism with negative or discordant standard imaging who underwent both localization with 4D-CT and operative intervention for curative intent were included. Patient characteristics, 4D-CT scan results compared with operative findings, and curative proportion were assessed. Results. Of the 60 patients, 4D-CT accurately lateralized 73% and localized 60% of abnormal glands found at operation. Single candidate lesions (46/60) were confirmed at operation in 70%. When multiple lesions were identified on 4D-CT (14/60), accuracy dropped to 29% (P = .03). The accuracy of 4D-CT was not different between primary and reoperative cases (P =. 79). Of the 8 patients with multigland disease diagnosed perioperatively, 5 had multiple candidate lesions noted on 4D-CT In 94% (48/51) of patients, a > 50% drop in intraoperative parathormone (IOPTH) level was achieved after resection and 87% (48/55) had long-term cure with a median follow-up of 221 days. Conclusion. 4D-CT identifies the more than half of abnormal parathyroids missed by traditional imaging and should be considered in cases with negative or discordant sestamibi and ultrasound. Bilateral exploration is warranted when multiple candidate lesions are reported on 4D-CT Multigland disease remains a challenging entity. (Surgery 2010;148:1129-38.) C1 [Lubitz, Carrie C.] Massachusetts Gen Hosp, Wang Ambulatory Care Ctr 460, Div Gen Surg, Dept Surg, Boston, MA 02114 USA. [Lubitz, Carrie C.; Hunter, George J.; Hamberg, Leena M.; Parangi, Sareh; Gaz, Randall D.; Randolph, Gregory W.; Hodin, Richard A.; Stephen, Antonia E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ruan, Daniel; Gawande, Atul; Moore, Francis D., Jr.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Lubitz, CC (reprint author), Massachusetts Gen Hosp, Wang Ambulatory Care Ctr 460, Div Gen Surg, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. EM clubitz@partners.org OI Gawande, Atul/0000-0002-1824-9176 NR 27 TC 34 Z9 34 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2010 VL 148 IS 6 BP 1129 EP 1137 DI 10.1016/j.surg.2010.09.002 PG 9 WC Surgery SC Surgery GA 704XM UT WOS:000286088900019 PM 21134543 ER PT J AU Nehs, MA Nagarkatti, S Nucera, C Hodin, RA Parangi, S AF Nehs, Matthew A. Nagarkatti, Sushruta Nucera, Carmelo Hodin, Richard A. Parangi, Sareh TI Thyroidectomy with neoadjuvant PLX4720 extends survival and decreases tumor burden in an orthotopic mouse model of anaplastic thyroid cancer SO SURGERY LA English DT Article ID CARCINOMA; BRAF; INHIBITORS; RAF; KINASE; CELLS AB Background. B-Raf(V600E) is a frequent mutation in anaplastic thyroid cancers and is a novel therapeutic target. We hypothesized that PLX4720 (an inhibitor of B-Raf(V600E)) and thyroidectomy would extend survival and would decrease tumor burden in a mouse model. Methods. Orthotopic anaplastic thyroid tumors were induced in severe combined immunodeficient mice. Mice were treated with PLX4720 or vehicle after 7 days of tumor growth, and thyroidectomy or sham surgery was performed at day 14. The neck space was re-explored, and tumor volume was measured at day 35. Mice were sacrificed when they lost >25% of their initial weight. Results. All 5 mice that received the vehicle developed cachexia, had invasive tumors (average 61 mm(3)) and were sacrificed by day 35. All 6 mice receiving PLX4720 + sham had small tumors (average 1.3 mm(3)) and maintained their weight. Three out of 6 mice receiving PLX4720+thyroidectomy had no evidence of tumor at 35 days; the other 3 mice had small tumors (average 1.4 mm(3)) and showed no signs of metastatic disease. All mice treated with PLX4720 were alive and well-appearing at 50 days. Conclusion. Thyroidectomy with neoadjuvant PLX4720 could be an effective therapeutic strategy for early anaplastic thyroid cancers that harbor the B-Raf(V600E) mutation and are refractory to conventional therapeutic modalities. (Surgery 2010;148:1154-62.) C1 [Nehs, Matthew A.; Nagarkatti, Sushruta; Nucera, Carmelo; Hodin, Richard A.; Parangi, Sareh] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Endocrine Surg,Thyroid Canc Res Lab, Boston, MA 02115 USA. RP Parangi, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Endocrine Surg,Thyroid Canc Res Lab, Wang ACC 460,15 Parkman St, Boston, MA 02115 USA. EM sparangi@partners.org FU NIH [5T32 DK007754-10] FX Supported by the NIH T32 Grant #5T32 DK007754-10. NR 16 TC 22 Z9 22 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2010 VL 148 IS 6 BP 1154 EP 1162 DI 10.1016/j.surg.2010.09.001 PG 9 WC Surgery SC Surgery GA 704XM UT WOS:000286088900025 PM 21134546 ER PT J AU Liu, YW Zhou, A Zhao, SP Huber, WE Li, QH AF Liu, Yingwang Zhou, An Zhao, Shuiping Huber, Wade E. Li, Qiaohua TI Quadruple Atrioventricular Nodal Pathways Involved in Orthodromic Atrioventricular Reentrant Tachycardia SO TEXAS HEART INSTITUTE JOURNAL LA English DT Article DE Atrioventricular node/physiopathology; cardiac electrophysiology; catheter ablation; diagnosis; differential; electrocardiography; tachycardia; atrioventricular, reentry/complications/diagnosis/epidemiology/physiopathology/therapy; tachycardia, supraventricular/diagnosis; treatment outcome ID ATRIAL-FIBRILLATION AB Supra ventricular tachycardia can be caused by multiple atrioventricular nodal pathways or atrioventricular accessory pathways. Herein, we report the case of a patient who was diagnosed with an orthodromic atrioventricular reentrant tachycardia that was caused by an unusual combination of quadruple atrioventricular nodal pathways and an atrioventricular accessory pathway Radiofrequency catheter ablation of the accessory pathway successfully eliminated the arrhythmias and the patient's symptoms. Careful analysis of complete electrophysiologic studies can help in the diagnosis of such rare clinical presentations. (Tex Heart Inst J 2010;37(6):706-9) C1 [Liu, Yingwang; Zhao, Shuiping; Li, Qiaohua] Cent S Univ, Dept Cardiol, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China. [Zhou, An] Cent S Univ, Dept Nephrol, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China. [Huber, Wade E.] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. RP Li, QH (reprint author), Cent S Univ, Dept Cardiol, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China. EM li_qiaohua@sina.com NR 6 TC 0 Z9 0 U1 0 U2 0 PU TEXAS HEART INST PI HOUSTON PA PO BOX 20345, HOUSTON, TX 77225-0345 USA SN 0730-2347 J9 TEX HEART I J JI Tex. Heart Inst. J. PD DEC PY 2010 VL 37 IS 6 BP 706 EP 709 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 691YI UT WOS:000285118300026 PM 21224952 ER PT J AU Sparrow, D Aloia, M DeMolles, DA Gottlieb, DJ AF Sparrow, David Aloia, Mark DeMolles, Deborah A. Gottlieb, Daniel J. TI A telemedicine intervention to improve adherence to continuous positive airway pressure: a randomised controlled trial SO THORAX LA English DT Article ID OBSTRUCTIVE SLEEP-APNEA; NASAL CPAP; APNOEA/HYPOPNOEA SYNDROME; APNEA/HYPOPNEA SYNDROME; PATIENT COMPLIANCE; HYPERTENSION; ASSOCIATION; THERAPY; ADULTS; POPULATION AB Background Continuous positive airway pressure (CPAP) is the most widely prescribed treatment for obstructive sleep apnoea syndrome (OSAS). Although it has been shown to improve the symptoms of OSAS, many patients have difficulty adhering to this treatment. The purpose of this study was to investigate the effectiveness of an automated telemedicine intervention to improve adherence to CPAP. Methods A randomised clinical trial was undertaken in 250 patients being started on CPAP therapy for OSAS. Patients were randomly assigned to use a theory-driven interactive voice response system designed to improve CPAP adherence (telephone-linked communications for CPAP (TLC-CPAP), n = 124) or to an attention placebo control (n = 126) for 12 months. TLC-CPAP monitors patients' self-reported behaviour and CPAP-related symptoms and provides feedback and counselling through a structured dialogue to enhance motivation to use CPAP. A Sleep Symptoms Checklist, the Functional Outcomes of Sleep Questionnaire, the Center for Epidemiological Studies Depression Scale and the Psychomotor Vigilance Task were administered at study entry and at 6-month and 12-month follow-up. Hours of CPAP usage at effective mask pressure were measured by the CPAP device stored in its memory and retrieved at each visit. Results Median observed CPAP use in patients randomised to TLC-CPAP was approximately 1 h/night higher than in the control subjects at 6 months and 2 h/night higher at 12 months. Using generalised estimating equation modelling, the intervention had a significant effect on CPAP adherence. For secondary analysis, the effect of CPAP adherence on the secondary outcomes was analysed. CPAP adherence was significantly associated with a greater reduction in sleep apnoea symptoms and depressive symptoms and a greater improvement in functional status. No significant association was observed between CPAP adherence and reaction time. Conclusions The TLC-CPAP intervention resulted in improved CPAP adherence, which was associated with improved functional status and fewer depressive symptoms. C1 [Sparrow, David; DeMolles, Deborah A.; Gottlieb, Daniel J.] VA Boston Healthcare Syst, Boston, MA USA. [Sparrow, David; Gottlieb, Daniel J.] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. [Aloia, Mark] Natl Jewish Hlth, Denver, CO USA. RP Sparrow, D (reprint author), VA Boston Healthcare Syst 151N, 150 S Huntington Ave, Boston, MA 02130 USA. EM david.sparrow@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service FX Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 42 TC 47 Z9 47 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD DEC PY 2010 VL 65 IS 12 BP 1061 EP 1066 DI 10.1136/thx.2009.133215 PG 6 WC Respiratory System SC Respiratory System GA 681WQ UT WOS:000284354800008 PM 20880872 ER PT J AU Perrier, ND Randolph, GW Inabnet, WB Marple, BF vanHeerden, J Kuppersmith, RB AF Perrier, Nancy D. Randolph, Gregory W. Inabnet, William B., III Marple, Bradley F. vanHeerden, Jon Kuppersmith, Ronald B. TI Robotic Thyroidectomy: A Framework for New Technology Assessment and Safe Implementation SO THYROID LA English DT Article ID SURGERY AB Robotic thyroidectomy is a new approach to thyroid surgery that offers the benefit of eliminating the anterior neck incision utilized in traditional approaches. Although no level I evidence exists to strongly support a robotic approach to thyroid surgery, initial non-randomized reports of robotic surgical approaches, in a variety of surgical specialty areas such as cardiothoracic, urologic, gynecologic and head and neck surgery suggest possible advantages of robot assisted techniques. These include platform and instrument stability, tremor reduction, articulating end effectors, three-dimensional, magnified imaging, and improved surgeon ergonomics. Potential negatives associated with robotic surgery include its expense, the lack of haptic feedback, instrument limitations, and the implicit learning curve. Robotic thyroidectomy introduces new potential risks, not typically associated with thyroid surgery. These risks are related to a new approach to the surrounding anatomy and are also associated with the learning curve. The introduction of new technology to any surgery mandates a rational framework for initial assessment and safe implementation. A New Technology Task Force was convened to draft guiding principles which may serve as a framework for the safe implementation of emerging technologies in thyroid surgery. This document suggests initial minimum steps that surgeons should consider during initial implementation of robotic thyroidectomy. C1 [Kuppersmith, Ronald B.] Texas ENT & Allergy, College Stn, TX 77845 USA. [Perrier, Nancy D.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Randolph, Gregory W.] Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Inabnet, William B., III] Mt Sinai Med Ctr, Dept Surg, New York, NY 10029 USA. [Marple, Bradley F.] Univ Texas Dallas, SW Med Ctr, Dept Otolaryngol, Dallas, TX USA. [vanHeerden, Jon] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. RP Kuppersmith, RB (reprint author), Texas ENT & Allergy, 1730 Birmingham Dr, College Stn, TX 77845 USA. EM rbk@texasentandallergy.com NR 15 TC 54 Z9 54 U1 1 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD DEC PY 2010 VL 20 IS 12 BP 1327 EP 1332 DI 10.1089/thy.2010.1666 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 687CJ UT WOS:000284751500001 PM 21114381 ER PT J AU Jonklaas, J Cooper, DS Ain, KB Bigos, T Brierley, JD Haugen, BR Ladenson, PW Magner, J Ross, DS Skarulis, MC Steward, DL Maxon, HR Sherman, SI AF Jonklaas, Jacqueline Cooper, David S. Ain, Kenneth B. Bigos, Thomas Brierley, James D. Haugen, Bryan R. Ladenson, Paul W. Magner, James Ross, Douglas S. Skarulis, Monica C. Steward, David L. Maxon, Harry R. Sherman, Steven I. CA NTCTCSG TI Radioiodine Therapy in Patients with Stage I Differentiated Thyroid Cancer SO THYROID LA English DT Letter ID CARCINOMA C1 [Jonklaas, Jacqueline] Georgetown Univ, Med Ctr, Div Endocrinol & Metab, Washington, DC 20007 USA. [Cooper, David S.; Ladenson, Paul W.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Ain, Kenneth B.] Univ Kentucky, Med Ctr, Lexington, KY USA. [Bigos, Thomas] Maine Med Ctr, Portland, ME 04102 USA. [Brierley, James D.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Haugen, Bryan R.] Univ Colorado, Denver, CO 80202 USA. [Haugen, Bryan R.] Hlth Sci Ctr, Aurora, CO USA. [Magner, James] Genzyme Corp, Cambridge, MA USA. [Ross, Douglas S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Skarulis, Monica C.] NIH, Bethesda, MD 20892 USA. [Steward, David L.; Maxon, Harry R.] Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. [Sherman, Steven I.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Jonklaas, J (reprint author), Georgetown Univ, Med Ctr, Div Endocrinol & Metab, Suite 230,Bldg D,4000 Reservoir Rd NW, Washington, DC 20007 USA. EM jj@bc.georgetown.edu OI Ain, Kenneth/0000-0002-2668-934X; Sherman, Steven/0000-0002-3079-5153 NR 5 TC 27 Z9 27 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD DEC PY 2010 VL 20 IS 12 BP 1423 EP 1424 DI 10.1089/thy.2010.0308 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 687CJ UT WOS:000284751500015 PM 21054207 ER PT J AU Smith, MW Chen, S Siroka, AM Hamlett-Berry, K AF Smith, Mark W. Chen, Shuo Siroka, Andrew M. Hamlett-Berry, Kim TI Using policy to increase prescribing of smoking cessation medications in the VA healthcare system SO TOBACCO CONTROL LA English DT Article ID TOBACCO-DEPENDENCE TREATMENT; SUSTAINED-RELEASE BUPROPION; NICOTINE PATCH; SERVICES; LESSONS AB Background Since 2002 the US Veterans Affairs (VA) healthcare system has initiated national policies and programmes to reduce smoking among its patients and to increase evidence-based treatment for smoking. Objective To document changes in dispensing rates of cessation-related medications in VA from 2004 to 2008. Design Retrospective analysis of VA administrative data. Results Prescription fills for nicotine replacement therapy (NAT), and for bupropion among NAT users, each grew more than 60% in four years. The increase stemmed primarily from treating more people rather than from filling more prescriptions per person. Conclusion The results provide strong support for the efficacy of these policies and illustrate how healthcare systems can successfully employ multiple strategies to increase evidence-based smoking-cessation treatment. C1 [Smith, Mark W.; Chen, Shuo; Siroka, Andrew M.] Vet Affairs Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, Menlo Pk, CA USA. [Smith, Mark W.] Stanford Med Sch, Ctr Primary Care & Outcomes Res, Stanford, CA USA. [Hamlett-Berry, Kim] US Dept Vet Affairs, Publ Hlth Strateg Hlth Care Grp, Off Publ Hlth Policy & Prevent, Washington, DC USA. RP Smith, MW (reprint author), VA Palo Alto Hlth Care Syst 650 617 2630, Hlth Econ Resource Ctr, 795 Willow Rd,152 MPD, Menlo Pk, CA 94025 USA. EM mark.smith9@va.gov RI Smith, Mark/G-1522-2012 OI Smith, Mark/0000-0002-4582-9088 FU Clinical Science Research and Development Service, US Department of Veterans Affairs [519] FX Funding was provided by the Cooperative Studies Program of the Clinical Science Research and Development Service, US Department of Veterans Affairs (CSP #519). The views expressed here are those of the authors and riot necessarily those of the US Department of Veterans Affairs. NR 27 TC 8 Z9 8 U1 1 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD DEC PY 2010 VL 19 IS 6 BP 507 EP 511 DI 10.1136/tc.2009.035147 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 681WI UT WOS:000284353800020 PM 20870742 ER PT J AU Morgan, KL Estevez, AO Mueller, CL Cacho-Valadez, B Miranda-Vizuete, A Szewczyk, NJ Estevez, M AF Morgan, Kathleen L. Estevez, Annette O. Mueller, Catherine L. Cacho-Valadez, Briseida Miranda-Vizuete, Antonio Szewczyk, Nathaniel J. Estevez, Miguel TI The Glutaredoxin GLRX-21 Functions to Prevent Selenium-Induced Oxidative Stress in Caenorhabditis elegans SO TOXICOLOGICAL SCIENCES LA English DT Article DE selenium; antioxidant; toxicity; glutaredoxin; glutathione; glrx-21 ID AMYOTROPHIC-LATERAL-SCLEROSIS; THIOREDOXIN REDUCTASE; REDUCED GLUTATHIONE; CANCER PREVENTION; SODIUM SELENITE; AQUATIC BIRDS; DNA-DAMAGE; CELL-DEATH; C-ELEGANS; TOXICITY AB Selenium is an essential micronutrient that functions as an antioxidant. Yet, at higher concentrations, selenium is pro-oxidant and toxic. In extreme cases, exposures to excess selenium can lead to death or selenosis, a syndrome characterized by teeth, hair and nail loss, and nervous system alterations. Recent interest in selenium as an anti- tumorigenic agent has reemphasized the need to understand the mechanisms underlying the cellular consequences of increased selenium exposure. We show here, that in the nematode, Caenorhabditis elegans, selenium has a concentration range in which it functions as an antioxidant, but beyond this range it exhibits a dose- and time-dependent lethality. Oxidation-induced fluorescence emitted by the dye, carboxy-H(2)DCFDA, indicative of reactive oxygen species formation was significantly higher in animals after a brief exposure to 5mM sodium selenite. Longer-term exposures lead to a progressive selenium-induced motility impairment that could be partially prevented by coincident exposure to the cellular antioxidant-reduced glutathione. The C elegans glrx-21 gene belongs to the family of glutaredoxins (glutathione-dependent oxidoreductases) and the glrx-21(tm2921) allele is a null mutation that renders animals hypersensitive for the selenium-induced motility impairment, but not lethality. In addition, the lethality of animals with the tm2921 mutation exposed to selenium was unaffected by the addition of reduced glutathione, suggesting that GLRX-21 is required for glutathione to moderate this selenium-induced lethality. Our findings provide the first description of selenium-induced toxicity in C elegans and support its use as a model for elucidating the mechanisms of selenium toxicity. C1 [Morgan, Kathleen L.; Estevez, Miguel] Vet Affairs Pittsburgh Healthcare Syst, Res & Dev 151U, Dept Neurol, Pittsburgh, PA 15240 USA. [Morgan, Kathleen L.; Estevez, Annette O.; Mueller, Catherine L.; Estevez, Miguel] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Cacho-Valadez, Briseida; Miranda-Vizuete, Antonio] Univ Pablo de Olavide, CSIC, CABD, Seville 41013, Spain. [Cacho-Valadez, Briseida; Miranda-Vizuete, Antonio] Univ Pablo de Olavide, Dept Fisiol Anat & Biol Celular, Seville 41013, Spain. [Miranda-Vizuete, Antonio] Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Inst Biomed Sevilla, Seville 41013, Spain. [Szewczyk, Nathaniel J.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. RP Estevez, M (reprint author), Univ Arizona, Dept Neurol, 1501 N Campbell Ave, Tucson, AZ 85724 USA. EM estevezm@email.arizona.edu RI Miranda-Vizuete, Antonio/D-6927-2012; IBIS, FISIOLOGIA/O-9485-2015; OI Miranda-Vizuete, Antonio/0000-0002-6856-5396; Szewczyk, Nathaniel/0000-0003-4425-9746 FU Office of Research and Development, Department of Veterans Affairs; National Institutes of Environmental Health Sciences [R21-ES012305]; Arthritis and Musculoskeletal and Skin Diseases [R01-AR054342]; Instituto de Salud Carlos III [PI050065, PI080557]; Fondo Social Europeo, FEDER; Junta de Andalucia, Spain [P07-CVI-02697, P08-CVI-03629]; CONACYT, Mexico FX This work was supported by a Career Development Award (M. E.) provided through the Office of Research and Development, Department of Veterans Affairs, the National Institutes of Environmental Health Sciences (R21-ES012305 to A. E. and M. E.) and Arthritis and Musculoskeletal and Skin Diseases (R01-AR054342 to N.J.S.), the Instituto de Salud Carlos III (Projects PI050065 and PI080557, co-financed with the Fondo Social Europeo, FEDER) and Junta de Andalucia (Projects P07-CVI-02697 and P08-CVI-03629), Spain (A. M.-V.) and a predoctoral fellowship from CONACYT, Mexico (B.C.-V.). NR 90 TC 20 Z9 24 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2010 VL 118 IS 2 BP 530 EP 543 DI 10.1093/toxsci/kfq273 PG 14 WC Toxicology SC Toxicology GA 682WB UT WOS:000284432600019 PM 20833709 ER PT J AU Patterson, HC Sturtevant, O Schott, D Alyea, EP Onderdonk, AB Kao, GS AF Patterson, H. C. Sturtevant, O. Schott, D. Alyea, E. P., III Onderdonk, A. B. Kao, G. S. TI Isolation of non-typhoidal Salmonella from a haematopoietic progenitor cell product SO TRANSFUSION MEDICINE LA English DT Article C1 [Patterson, H. C.; Onderdonk, A. B.; Kao, G. S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Sturtevant, O.; Schott, D.; Kao, G. S.] Dana Farber Canc Inst, Cell Manipulat Core Facil, Boston, MA 02115 USA. RP Patterson, HC (reprint author), 75 Francis St, Boston, MA 02115 USA. EM ckunst@partners.org NR 10 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0958-7578 J9 TRANSFUSION MED JI Transfus. Med. PD DEC PY 2010 VL 20 IS 6 BP 424 EP 425 DI 10.1111/j.1365-3148.2010.01031.x PG 2 WC Hematology SC Hematology GA 667BP UT WOS:000283167900010 PM 20735761 ER PT J AU De Gasperi, R Sosa, MAG Naumowicz, Z Hof, PR Notterpek, L Davis, KL Buxbaum, JD Elder, GA AF De Gasperi, Rita Sosa, Miguel A. Gama Naumowicz, Zuzanna Hof, Patrick R. Notterpek, Lucia Davis, Kenneth L. Buxbaum, Joseph D. Elder, Gregory A. TI PERIPHERAL MYELIN PROTEIN-22 IS EXPRESSED IN CNS MYELIN SO TRANSLATIONAL NEUROSCIENCE LA English DT Article DE Myelin; Peripheral myelin protein-22; Schizophrenia AB Myelin abnormalities exist in schizophrenia leading to the hypothesis that oligodendrocyte dysfunction plays a role in the pathophysiology of the disease. The expression of the mRNA for the peripheral myelin protein-22 (PMP-22) is decreased in schizophrenia and recent genetic evidence suggests a link between PMP-22 and schizophrenia. While PMP-22 mRNA is found in both rodent and human brain it has been generally thought that no protein expression occurs. Here we show that PMP-22 protein is present in myelin isolated from adult mouse and human brain. These results suggest that PMP-22 protein likely plays a role in the maintenance and function of central nervous system (CNS) myelin and provide an explanation for why altered PMP-22 expression may be pathophysiologically relevant in a CNS disorder such as schizophrenia. C1 [De Gasperi, Rita; Elder, Gregory A.] James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, Bronx, NY 10468 USA. [De Gasperi, Rita; Sosa, Miguel A. Gama; Naumowicz, Zuzanna; Davis, Kenneth L.; Buxbaum, Joseph D.; Elder, Gregory A.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Hof, Patrick R.; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Hof, Patrick R.] Mt Sinai Sch Med, Dept Geriatr & Palliat Care, New York, NY 10029 USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Elder, Gregory A.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Notterpek, Lucia] Univ Florida, Coll Med, McKnight Brain Inst, Dept Neurosci, Gainesville, FL 32610 USA. RP De Gasperi, R (reprint author), James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, Bronx, NY 10468 USA. EM gregory.elder@mssm.edu OI Buxbaum, Joseph/0000-0001-8898-8313 FU Mount Sinai Silvio Conte Neuroscience Center (NIH) [P50 MH36692] FX This research was supported by the Mount Sinai Silvio Conte Neuroscience Center (NIH grant P50 MH36692). We thank Dr. Vahram Haroutunian for providing frozen samples of postmortem human brain. NR 21 TC 5 Z9 5 U1 0 U2 3 PU VERSITA PI WARSAW PA SOLIPSKA 14A-1, 02-482 WARSAW, POLAND SN 2081-3856 J9 TRANSL NEUROSCI JI Transl. Neurosci. PD DEC PY 2010 VL 1 IS 4 BP 282 EP 285 DI 10.2478/v10134-010-0038-3 PG 4 WC Neurosciences SC Neurosciences & Neurology GA V20QA UT WOS:000208153300004 PM 21572910 ER PT J AU Qazi, A Pal, J Maitah, M Fulciniti, M Pelluru, D Nanjappa, P Lee, S Batchu, RB Prasad, M Bryant, CS Rajput, S Gryaznov, S Beer, DG Weaver, DW Munshi, NC Goyal, RK Shammas, MA AF Qazi, Aamer Pal, Jagannath Maitah, Ma'in Fulciniti, Mariateresa Pelluru, Dheeraj Nanjappa, Puru Lee, Saem Batchu, Ramesh B. Prasad, Madhu Bryant, Christopher S. Rajput, Samiyah Gryaznov, Sergei Beer, David G. Weaver, Donald W. Munshi, Nikhil C. Goyal, Raj K. Shammas, Masood A. TI Anticancer Activity of a Broccoli Derivative, Sulforaphane, in Barrett Adenocarcinoma: Potential Use in Chemoprevention and as Adjuvant in Chemotherapy SO TRANSLATIONAL ONCOLOGY LA English DT Article ID CELL-CYCLE ARREST; PROSTATE-CANCER CELLS; NATURALLY-OCCURRING ISOTHIOCYANATE; CASPASE-MEDIATED APOPTOSIS; INHIBITS TUMOR-GROWTH; PHENETHYL ISOTHIOCYANATE; HISTONE DEACETYLASE; EPITHELIAL-CELLS; G(2)/M ARREST; UP-REGULATION AB INTRODUCTION: The incidence of Barrett esophageal adenocarcinoma (BEAC) has been increasing at an alarming rate in western countries. In this study, we have evaluated the therapeutic potential of sulforaphane (SFN), an antioxidant derived from broccoli, in BEAC. METHODS: BEAC cells were treated with SFN, alone or in combination with chemotherapeutic, paclitaxel, or telomerase-inhibiting agents (MST-312, GRN163L), and live cell number determined at various time points. The effect on drug resistance/chemosensitivity was evaluated by rhodamine efflux assay. Apoptosis was detected by annexin V labeling and Western blot analysis of poly(ADP-ribose) polymerase cleavage. Effects on genes implicated in cell cycle and apoptosis were determined by Western blot analyses. To evaluate the efficacy in vivo, BEAC cells were injected subcutaneously in severe combined immuno-deficient mice, and after the appearance of palpable tumors, mice were treated with SFN. RESULTS: SFN induced both time-and dose-dependent decline in cell survival, cell cycle arrest, and apoptosis. The treatment with SFN also suppressed the expression of multidrug resistance protein, reduced drug efflux, and increased anticancer activity of other antiproliferative agents including paclitaxel. A significant reduction in tumor volume was also observed by SFN in a subcutaneous tumor model of BEAC. Anticancer activity could be attributed to the induction of caspase 8 and p21 and down-regulation of hsp90, a molecular chaperon required for activity of several proliferation-associated proteins. CONCLUSIONS: These data indicate that a natural product with antioxidant properties from broccoli has great potential to be used in chemoprevention and treatment of BEAC. C1 [Pal, Jagannath; Fulciniti, Mariateresa; Pelluru, Dheeraj; Nanjappa, Puru; Rajput, Samiyah; Munshi, Nikhil C.; Shammas, Masood A.] Harvard Dana Farber Canc Inst, Boston, MA USA. [Qazi, Aamer; Maitah, Ma'in; Batchu, Ramesh B.; Prasad, Madhu; Bryant, Christopher S.; Weaver, Donald W.] Wayne State Univ, Dept Surg, Detroit, MI USA. [Qazi, Aamer; Maitah, Ma'in; Batchu, Ramesh B.; Prasad, Madhu; Bryant, Christopher S.; Weaver, Donald W.] Karmanos Canc Inst, Detroit, MI USA. [Pal, Jagannath; Fulciniti, Mariateresa; Pelluru, Dheeraj; Nanjappa, Puru; Lee, Saem; Munshi, Nikhil C.; Goyal, Raj K.; Shammas, Masood A.] Harvard Univ, Sch Med, Boston, MA USA. [Pal, Jagannath; Fulciniti, Mariateresa; Pelluru, Dheeraj; Nanjappa, Puru; Lee, Saem; Munshi, Nikhil C.; Goyal, Raj K.; Shammas, Masood A.] VA Boston Healthcare Syst, Boston, MA USA. [Gryaznov, Sergei] Geron Corp, Menlo Pk, CA USA. [Beer, David G.] Univ Michigan, Ann Arbor, MI 48109 USA. [Qazi, Aamer; Maitah, Ma'in; Batchu, Ramesh B.; Prasad, Madhu; Bryant, Christopher S.; Weaver, Donald W.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. RP Shammas, MA (reprint author), Harvard Dana Farber Canc Inst, Boston, MA USA. EM masood_shammas@dfci.harvard.edu FU Department of Veterans Affairs; National Institutes of Health [RO1-124929, P50-100007, PO1-78378]; Karmanos Cancer Institute and Department of Surgery, Wayne State University, Detroit, MI; [R01CA125711] FX This work was supported by grants from R01CA125711 to MAS, from the Department of Veterans Affairs Merit Review Awards and from the National Institutes of Health grant RO1-124929 to NCM and grants P50-100007 and PO1-78378 to NCM and Dr. K. C. Anderson and by funds from Karmanos Cancer Institute and Department of Surgery, Wayne State University, Detroit, MI. NR 48 TC 28 Z9 29 U1 0 U2 8 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1936-5233 J9 TRANSL ONCOL JI Transl. Oncol. PD DEC PY 2010 VL 3 IS 6 BP 389 EP 399 DI 10.1593/tlo.10235 PG 11 WC Oncology SC Oncology GA 736LQ UT WOS:000288496600007 PM 21151478 ER PT J AU Ning, MM Lo, EH AF Ning, MingMing Lo, Eng H. TI Opportunities and Challenges in Omics SO TRANSLATIONAL STROKE RESEARCH LA English DT Article DE Proteomics; Proteome; Genome; Reproducibility; Noise; Continued convergence; Discovery proteomics; Targeted proteomics; Multiple reaction monitoring; Translational stroke research; Neurovascular research C1 [Ning, MingMing; Lo, Eng H.] Massachusetts Gen Hosp, Clin Prote Res Ctr, Boston, MA 02114 USA. [Ning, MingMing; Lo, Eng H.] Harvard Univ, Sch Med, Boston, MA USA. [Ning, MingMing; Lo, Eng H.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol & Radiol, Boston, MA 02114 USA. RP Ning, MM (reprint author), Massachusetts Gen Hosp, Clin Prote Res Ctr, Boston, MA 02114 USA. EM Ning@hms.harvard.edu; Lo@helix.mgh.harvard.edu FU US National Institutes of Health/NINDS FX Supported in part by grants from the US National Institutes of Health/NINDS. We also thank Dr David McMullin for his thoughtful contribution in the discussion and preparation of this manuscript. NR 20 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1868-4483 EI 1868-601X J9 TRANSL STROKE RES JI Transl. Stroke Res. PD DEC PY 2010 VL 1 IS 4 SI SI BP 233 EP 237 DI 10.1007/s12975-010-0048-y PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V23ET UT WOS:000208326800002 PM 22140416 ER PT J AU Ning, MM Sarracino, DA Buonanno, FS Krastins, B Chou, S McMullin, D Wang, XY Lopez, M Lo, EH AF Ning, MingMing Sarracino, David A. Buonanno, Ferdinando S. Krastins, Bryan Chou, Sherry McMullin, David Wang, Xiaoying Lopez, Mary Lo, Eng H. TI Proteomic Protease Substrate Profiling of tPA Treatment in Acute Ischemic Stroke Patients: A Step Toward Individualizing Thrombolytic Therapy at the Bedside SO TRANSLATIONAL STROKE RESEARCH LA English DT Article DE Proteomics; Mass spectrometry; Blood-brain barrier; Matrix metalloproteinase; Neuroprotection; Translational; Biomarker AB Tissue plasminogen activator (tPA) is the only FDA-approved medical therapy for acute ischemic stroke. But as a serine peptidase, intravenous tPA can affect the expression of other proteases that may be implicated in blood-brain barrier breakdown. Such parallel cascades of cell signaling may be involved in intracranial hemorrhage, the major side effect of tPA. Here, we describe an initial attempt in proteomic substrate profiling, i.e., degradomics in human plasma within the context of acute stroke. Plasma from acute stroke patients were analyzed pre- and post-intravenous tPA using tandem mass spectrometry and protein array profiling to identify substrates and proteases of interest. In non-tPA-treated stroke plasma, degradomic patterns indicated a rapid induction of protease activity within 3 h of stroke onset that mostly stabilized by 24 h. But in tPA-treated patients, pre- and post-tPA samples from the same patient demonstrated distinct degradomic patterns that persisted even up to 3-5 days after stroke onset. Matching control patients without strokes had little change in degradomic profiles over time. Our findings demonstrate that tPA treatment changes the plasma degradomic profiles in acute stroke patients. These composite proteolytic profiles may provide a glimpse of the pleiotropic effects of tPA on cellular signaling cascades at the bedside. This study supports the feasibility of performing pharmaco-proteomics at the bedside, which may ultimately allow us to dissect mechanisms of thrombolysis-related therapeutic efficacy in stroke. C1 [Ning, MingMing; Sarracino, David A.; Buonanno, Ferdinando S.; Krastins, Bryan; Chou, Sherry; McMullin, David; Wang, Xiaoying; Lopez, Mary; Lo, Eng H.] Massachusetts Gen Hosp, Dept Neurol, Clin Proteom Res Ctr, Boston, MA 02114 USA. [Sarracino, David A.; Buonanno, Ferdinando S.; Krastins, Bryan; Chou, Sherry; McMullin, David; Wang, Xiaoying; Lopez, Mary; Lo, Eng H.] Massachusetts Gen Hosp, Dept Radiol, Clin Proteom Res Ctr, Boston, MA 02114 USA. [Ning, MingMing; Sarracino, David A.; Buonanno, Ferdinando S.; Krastins, Bryan; Chou, Sherry; McMullin, David; Wang, Xiaoying; Lopez, Mary; Lo, Eng H.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Boston, MA 02114 USA. [Ning, MingMing; Sarracino, David A.; Buonanno, Ferdinando S.; Krastins, Bryan; Chou, Sherry; McMullin, David; Wang, Xiaoying; Lopez, Mary; Lo, Eng H.] Harvard Univ, Sch Med, Boston, MA USA. RP Ning, MM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Clin Proteom Res Ctr, Boston, MA 02114 USA. EM Ning@hms.harvard.edu; lo@helix.mgh.harvard.edu RI Chou, Sherry/G-5779-2015 FU NIH [K23-NS51588, R21-NS52498, R01-NS67139, R37-NS37074, P01-NS55104] FX This study is supported in part by NIH grants K23-NS51588, R21-NS52498, R01-NS67139, R37-NS37074, and P01-NS55104. NR 46 TC 15 Z9 15 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1868-4483 EI 1868-601X J9 TRANSL STROKE RES JI Transl. Stroke Res. PD DEC PY 2010 VL 1 IS 4 SI SI BP 268 EP 275 DI 10.1007/s12975-010-0047-z PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V23ET UT WOS:000208326800007 PM 22140417 ER PT J AU Liu, J Gao, BB Feener, EP AF Liu, Jia Gao, Ben-Bo Feener, Edward P. TI Proteomic Identification of Novel Plasma Kallikrein Substrates in the Astrocyte Secretome SO TRANSLATIONAL STROKE RESEARCH LA English DT Article DE Astrocyte; Secretome; Plasma kallikrein; Matrix protein; Proteolysis AB Plasma kallikrein (PK) is activated during hemorrhage and has been implicated in cerebral vascular permeability and edema. To further characterize the potential effects of PK on the brain that may follow cerebral vascular injury, we have utilized a proteomics approach to search for novel PK substrates in the astrocyte secretome. Extracellular proteins released by astrocytes are critical mediators of cerebral homeostasis, including roles in synapse function and vascular integrity. We identified 1,108 proteins in astrocyte condition medium and 295 of these were annotated as secreted proteins. The total abundance of nine proteins was changed after treatment with PK. Characterization of the secreted proteins revealed low molecular weight fragments for 59 proteins in conditioned media exposed to PK that were not observed in untreated controls. The most striking finding from this study was the appearance of fragmentation of 26 extracellular matrix-associated proteins including collagen isoforms 1-6 and11, nidogen-1 and -2, lysyl oxidase-like protein 1, and matrix metalloproteinase 19 in the presence of PK. We also demonstrated that PK induced the fragmentation of non-matrix proteins, including apolipoprotein E. This report further characterizes the astrocyte secretome and identifies novel potential targets of PK-induced proteolysis that may contribute to its effects on the brain following vascular injury. C1 [Liu, Jia; Gao, Ben-Bo; Feener, Edward P.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Feener, EP (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM edward.feener@joslin.harvard.edu FU US National Institutes of Health [EY19029, DK36836]; American Heart Association [0855905D] FX This work was supported in part by the US National Institutes of Health (grants EY19029 and DK36836) and the American Heart Association (0855905D). NR 51 TC 8 Z9 8 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1868-4483 EI 1868-601X J9 TRANSL STROKE RES JI Transl. Stroke Res. PD DEC PY 2010 VL 1 IS 4 SI SI BP 276 EP 286 DI 10.1007/s12975-010-0039-z PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V23ET UT WOS:000208326800008 PM 24323554 ER PT J AU Sun, HY Shields, RK Cacciarelli, TV Muder, RR Singh, N AF Sun, H. -Y. Shields, R. K. Cacciarelli, T. V. Muder, R. R. Singh, N. TI A novel combination regimen for the treatment of refractory bacteremia due to multidrug-resistant Pseudomonas aeruginosa in a liver transplant recipient SO TRANSPLANT INFECTIOUS DISEASE LA English DT Article DE multidrug resistant; Pseudomonas aeruginosa; liver transplant; biliary cast syndrome; combination regimen ID BILIARY CAST SYNDROME; GRAM-NEGATIVE BACILLI; BLOOD-STREAM INFECTIONS; BETA-LACTAM MONOTHERAPY; ACINETOBACTER-BAUMANNII; INTRAVENOUS COLISTIN; MOUSE MODEL; THERAPY; METAANALYSIS; RIFAMPIN AB P>Both bacteremia and biliary cast syndrome are serious post-transplant complications in liver transplant recipients. In the setting of increasing drug resistance in the current era, management of infections caused by multidrug-resistant (MDR) bacteria has proven challenging. We present a case of a liver transplant recipient who developed biliary cast syndrome and intractable MDR Pseudomonas bacteremia that failed to resolve with conventional antimicrobial therapy and which was finally controlled by a novel combination regimen of colistimethate, doripenem, and tobramycin. Future studies validating the clinical efficacy of this combination strategy are warranted. C1 [Sun, H. -Y.; Cacciarelli, T. V.; Muder, R. R.; Singh, N.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Sun, H. -Y.] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Sun, H. -Y.] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan. [Shields, R. K.; Muder, R. R.; Singh, N.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Shields, R. K.] Univ Pittsburgh, Med Ctr, Antibiot Management Program, Pittsburgh, PA USA. [Cacciarelli, T. V.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15260 USA. RP Singh, N (reprint author), VA Med Ctr, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. EM nis5@pitt.edu OI SUN, HSIN-YUN/0000-0003-0074-7721 NR 44 TC 11 Z9 11 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-2273 J9 TRANSPL INFECT DIS JI Transpl. Infect. Dis. PD DEC PY 2010 VL 12 IS 6 BP 555 EP 560 DI 10.1111/j.1399-3062.2010.00543.x PG 6 WC Immunology; Infectious Diseases; Transplantation SC Immunology; Infectious Diseases; Transplantation GA 689BS UT WOS:000284902900014 PM 20626709 ER PT J AU Schneeberger, S Amberger, A Mandl, J Hautz, T Renz, O Obrist, P Meusburger, H Brandacher, G Mark, W Strobl, D Troppmair, J Pratschke, J Margreiter, R Kuznetsov, AV AF Schneeberger, Stefan Amberger, Albert Mandl, Julia Hautz, Theresa Renz, Oliver Obrist, Peter Meusburger, Hugo Brandacher, Gerald Mark, Walter Strobl, Daniela Troppmair, Jakob Pratschke, Johann Margreiter, Raimund Kuznetsov, Andrey V. TI Cold ischemia contributes to the development of chronic rejection and mitochondrial injury after cardiac transplantation SO TRANSPLANT INTERNATIONAL LA English DT Article DE cardiac transplantation; chronic rejection; cold ischemia; mitochondrial function; respirometry ID CORONARY-ARTERY-DISEASE; REAL-TIME PCR; HEART-TRANSPLANTATION; ALLOGRAFT-REJECTION; REPERFUSION INJURY; MUSCLE-FIBERS; MINIMUM INFORMATION; MICROARRAY DATA; RAT-HEART; MODEL AB P>Chronic rejection (CR) remains an unsolved hurdle for long-term heart transplant survival. The effect of cold ischemia (CI) on progression of CR and the mechanisms resulting in functional deficit were investigated by studying gene expression, mitochondrial function, and enzymatic activity. Allogeneic (Lew -> F344) and syngeneic (Lew -> Lew) heart transplantations were performed with or without 10 h of CI. After evaluation of myocardial contraction, hearts were excised at 2, 10, 40, and 60 days for investigation of vasculopathy, gene expression, enzymatic activities, and mitochondrial respiration. Gene expression studies identified a gene cluster coding for subunits of the mitochondrial electron transport chain regulated in response to CI and CR. Myocardial performance, mitochondrial function, and mitochondrial marker enzyme activities declined in all allografts with time after transplantation. These declines were more rapid and severe in CI allografts (CR-CI) and correlated well with progression of vasculopathy and fibrosis. Mitochondria related gene expression and mitochondrial function are substantially compromised with the progression of CR and show that CI impacts on progression, gene profile, and mitochondrial function of CR. Monitoring mitochondrial function and enzyme activity might allow for earlier detection of CR and cardiac allograft dysfunction. C1 [Schneeberger, Stefan; Hautz, Theresa; Renz, Oliver; Meusburger, Hugo; Brandacher, Gerald; Mark, Walter; Strobl, Daniela; Troppmair, Jakob; Pratschke, Johann; Margreiter, Raimund; Kuznetsov, Andrey V.] Innsbruck Med Univ, Daniel Swarovski Res Lab, Ctr Operat Med, Dept Visceral Transplant & Thorac Surg, A-6020 Innsbruck, Austria. [Schneeberger, Stefan; Brandacher, Gerald] UPMC, Div Plast Surg, Dept Surg, Pittsburgh, PA USA. [Schneeberger, Stefan] VA Univ Dr, Dept Surg, Pittsburgh, PA USA. [Schneeberger, Stefan] VA Pittsburgh Healthcare Syst, Univ Dr Div, Dept Surg, Pittsburgh, PA USA. [Amberger, Albert; Mandl, Julia] Innsbruck Med Univ, Tyrolean Canc Res Inst, A-6020 Innsbruck, Austria. [Obrist, Peter] St Vinzenz Hosp Zams, Dept Pathol, Zams, Austria. [Kuznetsov, Andrey V.] Innsbruck Med Univ, Cardiac Surg Res Lab, Dept Cardiac Surg, Ctr Operat Med, A-6020 Innsbruck, Austria. RP Schneeberger, S (reprint author), Innsbruck Med Univ, Daniel Swarovski Res Lab, Ctr Operat Med, Dept Visceral Transplant & Thorac Surg, Anichstr 35, A-6020 Innsbruck, Austria. EM stefan.schneeberger@i-med.ac.at RI Brandacher, Gerald/L-7540-2016 FU Austrian Cancer Society/Tyrol; Medizinischer Forschungsfonds Tirol (MFF) [23]; Tiroler Versicherungen; Hypo Bank Tirol FX This work was supported by the Austrian Cancer Society/Tyrol, the Medizinischer Forschungsfonds Tirol (MFF, grant #. 23) and unrestricted educational grants from the 'Tiroler Versicherungen' and the 'Hypo Bank Tirol' awarded to Stefan Schneeberger. NR 43 TC 6 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0934-0874 J9 TRANSPL INT JI Transpl. Int. PD DEC PY 2010 VL 23 IS 12 BP 1282 EP 1292 DI 10.1111/j.1432-2277.2010.01126.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 678JN UT WOS:000284070000011 PM 20561305 ER PT J AU Orloff, MJ Isenberg, JI Wheeler, HO Haynes, KS Jinich-Brook, H Rapier, R Vaida, F Hye, RJ Orloff, SL AF Orloff, M. J. Isenberg, J. I. Wheeler, H. O. Haynes, K. S. Jinich-Brook, H. Rapier, R. Vaida, F. Hye, R. J. Orloff, S. L. TI Liver Transplantation in a Randomized Controlled Trial of Emergency Treatment of Acutely Bleeding Esophageal Varices in Cirrhosis SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 23rd International Congress of the-Transplantation-Society CY AUG 15-19, 2010 CL Vancouver, CANADA SP Transplantat Soc ID PORTOSYSTEMIC STENT-SHUNT; PRIOR PORTASYSTEMIC SHUNT; PORTACAVAL-SHUNT; PORTAL-HYPERTENSION; CONSORT STATEMENT; HEMORRHAGE; SURVIVAL; ENCEPHALOPATHY; MANAGEMENT; SCLEROTHERAPY AB Background. Bleeding esophageal varices (BEV) in cirrhosis has been considered an indication for liver transplantation (LT). This issue was examined in a randomized controlled trial (ROT) of unselected, consecutive patients with advanced cirrhosis and BEV that compared endoscopic sclerotherapy (EST; n = 106) to emergency direct portacaval shunt (EPCS; n = 105). Methods. Diagnostic work-up and treatment were initiated within 8 hours. Patients were evaluated for LT on admission and repeatedly thereafter; 96% underwent over 10 years of regular follow-up. The analysis was supplemented by 1300 unrandomized cirrhotic patients who previously underwent portacaval shunt (PCS) with 100% follow-up. Results. In the RCT long-term bleeding control was 100% following EPCS, only 20% following EST. Also, 3-, 5-, 10-, and 15-year survival rates were 75%, 73%, 46%, and 46%, respectively, following EPCS compared with 44%, 21%, 9%, and 9% following EST, respectively (P <.001). Only 13 RCT patients (6%) were ultimately referred for LT mainly because of progressive liver failure; only 7 (3%) were approved for LT and only 4 (2%) underwent LT. The 1- and 5-year LT survival rates were 0.68% and 0, respectively, compared with 81% and 73%, respectively, after EPCS. In the 1300 unrandomized PCS patients, 50 (3.8%) were referred and 19 (1.5%) underwent LT. The 5-year survival rate was 53% compared with 72% for all 1300 patients. Conclusions. If bleeding is permanently controlled, as occurred invariably following EPCS, cirrhotic patients with BEV seldom require LT. PCS is effective first-line and long-term treatment. Should LT be required in patients with PCS, although technically more demanding, numerous studies have shown that PCS does not increase mortality or complications. EST is not effective emergency or long-term therapy. C1 [Orloff, M. J.; Hye, R. J.] UCSD Med Ctr, Dept Surg, San Diego, CA 92103 USA. [Isenberg, J. I.; Wheeler, H. O.; Haynes, K. S.; Jinich-Brook, H.; Rapier, R.] UCSD Med Ctr, Dept Med Gastroenterol, San Diego, CA 92103 USA. [Vaida, F.] UCSD Med Ctr, Dept Family & Prevent Med Biostat & Bioinformat, San Diego, CA 92103 USA. [Orloff, S. L.] Oregon Hlth & Sci Univ, Dept Surg, Div Abdominal Organ Transplantat, Portland, OR 97201 USA. [Orloff, S. L.] Portland VA Med Ctr, Portland, OR USA. RP Orloff, MJ (reprint author), UCSD Med Ctr, Dept Surg, 200 W Arbor Dr, San Diego, CA 92103 USA. EM morloff@ucsd.edu OI Hye, Robert/0000-0002-7733-6173 FU NIDDK NIH HHS [R01 DK041920, R01 DK041920-07]; PHS HHS [234-2005-370011C] NR 47 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD DEC PY 2010 VL 42 IS 10 BP 4101 EP 4108 DI 10.1016/j.transproceed.2010.09.035 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 700IQ UT WOS:000285732200054 PM 21168637 ER PT J AU Brown, DL Andreotti, RF Lee, SI Allison, SOD Bennett, GL Dubinsky, T Glanc, P Horrow, MM Lev-Toaff, AS Horowitz, NS Podrasky, AE Scoutt, LM Zelop, CM AF Brown, Douglas L. Andreotti, Rochelle F. Lee, Susanna I. Allison, Sandra O. DeJesus Bennett, Genevieve L. Dubinsky, Theodore Glanc, Phyllis Horrow, Mindy M. Lev-Toaff, Anna S. Horowitz, Neil S. Podrasky, Ann E. Scoutt, Leslie M. Zelop, Carolyn M. TI ACR Appropriateness Criteria (c) Ovarian Cancer Screening SO ULTRASOUND QUARTERLY LA English DT Article DE appropriateness criteria; ovarian cancer; screening; ultrasound ID TRANSVAGINAL SONOGRAPHY; EARLY-STAGE; POSTMENOPAUSAL WOMEN; PATHOGENESIS; CARCINOMA; HISTORY; MASSES AB The majority of women with ovarian cancer have advanced stage disease at the time of diagnosis and a poor 5 year survival rate. Hence, screening has been investigated in the hopes of improving survival by diagnosing ovarian cancer at an earlier stage. Most screening methods thus far have included ultrasound and/or serum tumor markers. However, low prevalence of the disease, high false positive rate of current screening methods, and the probable rapid growth of most ovarian carcinomas from no defined precursor lesion, all contribute to difficulty in screening for ovarian cancer. While screening may be able to detect ovarian cancer at an earlier stage, adequate data is presently lacking on whether screening improves survival. The results of ongoing large clinical trials will be available in a few years and should provide critical information regarding the usefulness of screening. Pending results of those large clinical trials, screening is not currently recommended for women at average risk for ovarian cancer. Screening is most likely to be performed in women with an increased familial risk of ovarian cancer, but patients should be aware that even with this risk factor, there is currently insufficient evidence to know if screening is effective. New screening methods, including new or multiple serum markers and proteomics, are also being investigated. C1 [Brown, Douglas L.] Mayo Clin, Rochester, MN USA. [Andreotti, Rochelle F.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Lee, Susanna I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Allison, Sandra O. DeJesus] Georgetown Univ Hosp, Washington, DC 20007 USA. [Bennett, Genevieve L.] NYU, Med Ctr, New York, NY 10016 USA. [Dubinsky, Theodore] Univ Washington, Sch Med, Seattle, WA USA. [Glanc, Phyllis] Womens Coll Hosp, Toronto, ON M5S 1B2, Canada. [Horrow, Mindy M.] Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. [Lev-Toaff, Anna S.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Horowitz, Neil S.] Brigham & Womens Hosp, Soc Gynecol Oncologists, Boston, MA 02115 USA. [Podrasky, Ann E.] Baptist Hosp Miami, S Miami Ctr Women & Infants, Miami, FL USA. [Scoutt, Leslie M.] Yale Univ, Sch Med, New Haven, CT USA. [Zelop, Carolyn M.] St Francis Hosp & Med Ctr, Amer Coll Obstet & Gynecol, Hartford, CT USA. RP Brown, DL (reprint author), Amer Coll Radiol, Dept Qual & Safety, 1891 Preston White Dr, Reston, VA 20191 USA. NR 27 TC 5 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-8771 J9 ULTRASOUND Q JI Ultrasound Q. PD DEC PY 2010 VL 26 IS 4 BP 219 EP 223 DI 10.1097/RUQ.0b013e3181fdd604 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 854XC UT WOS:000297527100005 PM 21084936 ER PT J AU Martin, EG Paltiel, AD Walensky, RP Schackman, BR AF Martin, Erika G. Paltiel, A. David Walensky, Rochelle P. Schackman, Bruce R. TI Expanded HIV Screening in the United States: What Will It Cost Government Discretionary and Entitlement Programs? A Budget Impact Analysis SO VALUE IN HEALTH LA English DT Article DE AIDS; budget impact analysis; computer simulation; cost analysis ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEALTH-CARE SETTINGS; FOR-DISEASE-CONTROL; ANTIRETROVIRAL THERAPY; EMERGENCY-DEPARTMENT; PREVALENCE AREA; PREVENTION; INFECTION; CENTERS; RECOMMENDATIONS AB Objective: The US Centers for Disease Control and Prevention (CDC) recently revised their HIV screening guidelines to promote testing and earlier entry to care. Prior analyses have examined the policy's cost-effectiveness but have not evaluated its impact on government budgets. Methods: We used a simulation model of HIV screening, disease, and treatment to determine the budget impact of expanded HIV screening to US government discretionary, entitlement, and testing programs. We estimated total and incremental testing and treatment costs over a 5-year time horizon under current and expanded screening scenarios. We used CDC estimates of HIV prevalence and annual incidence, and considered variations in screening frequency, test return rates, linkage to care, test characteristics, and eligibility for government screening and treatment programs. Results: Under current practice, 177,000 new HIV cases will be identified over 5 years. Expanded screening will identify an additional 46,000 cases at an incremental 5-year cost of $2.7 billion. The financial burden of expanded HIV screening will fall disproportionately on discretionary programs that fund care for newly identified patients and will not be offset by entitlement program savings. Testing will represent a small proportion (18%) of the total budget increase. Costs are sensitive to the frequency of screening and the proportion linked to care. Conclusions: The expanded HIV screening program will have a large downstream impact on government programs that fund HIV care. Expanded HIV screening will not meet early treatment goals unless government programs have sufficient budgets to expand testing and provide care for newly identified cases. C1 [Martin, Erika G.] SUNY Albany, Rockefeller Coll Publ Affairs & Policy, Albany, NY 12222 USA. [Paltiel, A. David] Yale Univ, Sch Publ Hlth, Div Hlth Policy & Adm, New Haven, CT USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis & Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Walensky, Rochelle P.] Harvard Univ, Ctr AIDS Res, Harvard Med Sch, Cambridge, MA 02138 USA. [Schackman, Bruce R.] Weill Cornell Med Coll, Div Hlth Policy, Dept Publ Hlth, New York, NY USA. RP Martin, EG (reprint author), SUNY Albany, Rockefeller Coll Publ Affairs & Policy, Milne 300E,1400 Washington Ave, Albany, NY 12222 USA. EM emartin@albany.edu OI Walensky, Rochelle P./0000-0002-8795-379X FU National Institute on Drug Abuse [R01DA015612]; National Institute of Allergy and Infectious Disease [R37AI042006]; Agency for Health Research and Quality [T32HS017589]; National Institute of Mental Health [R01MH65869, R01MH073445]; Doris Duke Charitable Foundation FX This work was supported by the National Institute on Drug Abuse (R01DA015612), National Institute of Allergy and Infectious Disease (R37AI042006), the Agency for Health Research and Quality (T32HS017589), the National Institute of Mental Health (R01MH65869 and R01MH073445), and the Doris Duke Charitable Foundation (Clinical Scientist Development Award). NR 63 TC 11 Z9 12 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD DEC PY 2010 VL 13 IS 8 BP 893 EP 902 DI 10.1111/j.1524-4733.2010.00763.x PG 10 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 691FR UT WOS:000285066200007 PM 20950323 ER PT J AU Perlowski, AA Jaff, MR AF Perlowski, Alice A. Jaff, Michael R. TI Vascular disorders in athletes SO VASCULAR MEDICINE LA English DT Article DE exercise; iliac artery; intermittent claudication; lower extremity; peripheral vascular diseases; review; venous thrombosis ID EXTERNAL ILIAC ARTERY; ADVENTITIAL CYSTIC-DISEASE; EXERTIONAL COMPARTMENT SYNDROME; POPLITEAL VEIN ENTRAPMENT; PAGET-SCHROETTER-SYNDROME; THORACIC OUTLET SYNDROME; COMMON FEMORAL-ARTERY; SURGICAL-MANAGEMENT; ENDOFIBROSIS; LEG AB Athletes rarely present with symptoms or clinical findings suggestive of vascular disease. However, vascular etiologies should be considered when an athlete complains of persistent symptoms which are refractory to conservative therapies commonly used for presumed musculoskeletal injuries. A comprehensive history should be performed, with special consideration to the postures the athlete assumes repeatedly during their chosen sport. Musculoskeletal anatomy surrounding the vascular bed of interest should be thoroughly reviewed. Physical examination should include provocative maneuvers specific to the suspected vascular disorder. The proper use of noninvasive diagnostic studies, including duplex ultrasonography, computerized tomography (CT), and magnetic resonance imaging (MRI), along with catheter-based angiography, when indicated, can ensure prompt diagnosis. Appropriate, multifaceted treatment of an athlete affected by a vascular disorder can facilitate an expeditious return to previous levels of activity. C1 [Perlowski, Alice A.; Jaff, Michael R.] Massachusetts Gen Hosp, Sect Vasc Med, Div Cardiovasc Med, Boston, MA 02114 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ctr, Boston, MA 02114 USA. RP Jaff, MR (reprint author), 55 Fruit St,GB 800, Boston, MA 02114 USA. EM mjaff@partners.org NR 74 TC 3 Z9 3 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PD DEC PY 2010 VL 15 IS 6 BP 469 EP 479 DI 10.1177/1358863X10382944 PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 698EF UT WOS:000285574400005 PM 20884798 ER PT J AU Lisovsky, M Ogawa, F Dresser, K Woda, B Lauwers, GY AF Lisovsky, Mikhail Ogawa, Fumihiro Dresser, Karen Woda, Bruce Lauwers, Gregory Y. TI Loss of cell polarity protein Lgl2 in foveolar-type gastric dysplasia: correlation with expression of the apical marker aPKC-zeta SO VIRCHOWS ARCHIV LA English DT Article DE Foveolar-type; Gastric dysplasia; Lg12; aPKC; Adenocarcinoma; Stomach ID LETHAL GIANT LARVAE; EPITHELIAL DYSPLASIA; BARRETT-ESOPHAGUS; TUMOR SUPPRESSORS; INTESTINAL-TYPE; DROSOPHILA; CANCER; COMPLEX; CARCINOMA; GENE AB Recognition of gastric epithelial dysplasia, although a key to cancer prevention, can be challenging. In this study, we evaluated whether Lgl2 can serve as a marker of gastric foveolar-type dysplasia. Since atypical protein kinase C (aPKC) is a partner of Lgl2 in the control of apical-basal polarity we also investigated whether aPKC-zeta can compliment Lgl2 as a marker of dysplasia. Routinely processed specimens included 64 normal mucosa, 35 reactive gastropathies, 31 chronic gastritides, 65 gastric dysplasias (25 foveolar; 40 adenomatous), and 34 gastric adenocarcinomas. Twenty (80%) foveolar-type dysplasias showed absence of Lgl2 immunoreactivity, while normal basolateral expression of Lgl2 was consistently seen in normal gastric epithelium (n = 20) and chronic gastritis (n = 22; p < 0.00001). Loss of Lgl2 was similar in the groups with low-grade and high-grade foveolar-type dysplasia, 79% and 83%, respectively. Linear apical anti-aPKC-zeta immunoreactivity was consistently present in the normal epithelium and was preserved in 91% of reactive gastropathies and 87% of chronic gastritides. In contrast, loss of apical aPKC-zeta staining was observed in 47% and 65% of low-grade dysplasias of foveolar and adenomatous types, respectively (p < 0.005) and in nonsignificantly higher percentage of high-grade dysplasias. Apical aPKC-zeta staining was lost in 97% of gastric adenocarcinomas. Our data suggest a role of Lgl2 immunohistochemistry as an adjunct in the diagnosis of foveolar-type gastric dysplasia. aPKC-zeta had moderate sensitivity as a marker of gastric dysplasia and additional studies are needed to establish its role in the diagnosis of dysplasia. C1 [Lisovsky, Mikhail] Dartmouth Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03766 USA. [Lisovsky, Mikhail; Dresser, Karen; Woda, Bruce] UMassMem Med Ctr, Dept Pathol, Worcester, MA USA. [Lisovsky, Mikhail; Dresser, Karen; Woda, Bruce] Univ Massachusetts, Sch Med, Worcester, MA USA. [Lisovsky, Mikhail; Ogawa, Fumihiro; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lisovsky, Mikhail; Ogawa, Fumihiro; Lauwers, Gregory Y.] Harvard Univ, Sch Med, Boston, MA USA. RP Lisovsky, M (reprint author), Dartmouth Hitchcock Med Ctr, Dept Pathol, 1 Med Ctr Dr, Lebanon, NH 03766 USA. EM mikhail.lisovsky@hitchcock.org NR 40 TC 8 Z9 8 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD DEC PY 2010 VL 457 IS 6 BP 635 EP 642 DI 10.1007/s00428-010-0990-9 PG 8 WC Pathology SC Pathology GA 682BD UT WOS:000284371200002 PM 20941506 ER PT J AU Suri, P Hunter, DJ Katz, JN Li, L Rainville, J AF Suri, Pradeep Hunter, David J. Katz, Jeffrey N. Li, Ling Rainville, James TI Bias in the physical examination of patients with lumbar radiculopathy SO BMC MUSCULOSKELETAL DISORDERS LA English DT Article ID LOW-BACK-PAIN; DIAGNOSTIC-TESTS; CLINICAL HISTORY; ACCURACY; SPINE; RADIOGRAPHY; AGREEMENT; IMPACT AB Background: No prior studies have examined systematic bias in the musculoskeletal physical examination. The objective of this study was to assess the effects of bias due to prior knowledge of lumbar spine magnetic resonance imaging findings (MRI) on perceived diagnostic accuracy of the physical examination for lumbar radiculopathy. Methods: This was a cross-sectional comparison of the performance characteristics of the physical examination with blinding to MRI results (the 'independent group') with performance in the situation where the physical examination was not blinded to MRI results (the 'non-independent group'). The reference standard was the final diagnostic impression of nerve root impingement by the examining physician. Subjects were recruited from a hospital-based outpatient specialty spine clinic. All adults age 18 and older presenting with lower extremity radiating pain of duration <= 12 weeks were evaluated for participation. 154 consecutively recruited subjects with lumbar disk herniation confirmed by lumbar spine MRI were included in this study. Sensitivities and specificities with 95% confidence intervals were calculated in the independent and non-independent groups for the four components of the radiculopathy examination: 1) provocative testing, 2) motor strength testing, 3) pinprick sensory testing, and 4) deep tendon reflex testing. Results: The perceived sensitivity of sensory testing was higher with prior knowledge of MRI results (20% vs. 36%; p = 0.05). Sensitivities and specificities for exam components otherwise showed no statistically significant differences between groups. Conclusions: Prior knowledge of lumbar MRI results may introduce bias into the pinprick sensory testing component of the physical examination for lumbar radiculopathy. No statistically significant effect of bias was seen for other components of the physical examination. The effect of bias due to prior knowledge of lumbar MRI results should be considered when an isolated sensory deficit on examination is used in medical decision-making. Further studies of bias should include surgical clinic populations and other common diagnoses including shoulder, knee and hip pathology. C1 [Suri, Pradeep; Rainville, James] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02115 USA. [Suri, Pradeep] Spaulding Rehabil Hosp Network, Boston, MA USA. [Suri, Pradeep; Hunter, David J.; Li, Ling; Rainville, James] New England Baptist Hosp, Boston, MA USA. [Suri, Pradeep] VA Boston Healthcare Syst, Boston, MA USA. [Hunter, David J.] Univ Sydney, No Clin Sch, Sydney, NSW 2006, Australia. [Katz, Jeffrey N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy,Dept Med, Boston, MA 02115 USA. [Katz, Jeffrey N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. RP Suri, P (reprint author), Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02115 USA. EM psuri@caregroup.harvard.edu RI Hunter, David/A-4622-2010 OI Hunter, David/0000-0003-3197-752X FU Rehabilitation Medicine Scientist Training Program (RMSTP); National Institutes of Health [K12 HD001097-12]; NIH/NIAMS [K24 AR 02123, P60 AR 47782]; ARC FX Dr. Suri is funded by the Rehabilitation Medicine Scientist Training Program (RMSTP) and the National Institutes of Health (K12 HD001097-12). Dr. Katz is funded in part by NIH/NIAMS K24 AR 02123 and NIH/NIAMS P60 AR 47782. Dr Hunter is funded by an ARC Future Fellowship. NR 25 TC 5 Z9 5 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2474 J9 BMC MUSCULOSKEL DIS JI BMC Musculoskelet. Disord. PD NOV 30 PY 2010 VL 11 AR 275 DI 10.1186/1471-2474-11-275 PG 8 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 698HV UT WOS:000285585800001 PM 21118558 ER PT J AU Tearney, GJ Bouma, BE AF Tearney, Guillermo J. Bouma, Brett E. TI Shedding Light on Bioabsorbable Stent Struts Seen by Optical Coherence Tomography in the ABSORB Trial SO CIRCULATION LA English DT Editorial Material DE Editorials; animal model; biodegradable polymer; drug eluting stents; optical coherence tomography ID ELUTING CORONARY STENT; INTRAVASCULAR ULTRASOUND; MAGNESIUM STENT; SYSTEM; ARTERY C1 [Tearney, Guillermo J.; Bouma, Brett E.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Bouma, Brett E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Tearney, Guillermo J.; Bouma, Brett E.] Harvard Univ, Sch Med, Boston, MA USA. [Tearney, Guillermo J.; Bouma, Brett E.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA USA. RP Tearney, GJ (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR703, Boston, MA 02114 USA. EM gtearney@partners.org FU NHLBI NIH HHS [R01 HL093717] NR 13 TC 4 Z9 5 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 30 PY 2010 VL 122 IS 22 BP 2234 EP 2235 DI 10.1161/CIRCULATIONAHA.110.980730 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 686JD UT WOS:000284691700009 PM 20974997 ER PT J AU Sakhuja, R Suh, WM Jaffer, FA Jang, IK AF Sakhuja, Rahul Suh, William M. Jaffer, Farouc A. Jang, Ik-Kyung TI Residual Thrombogenic Substrate After Rupture of a Lipid-Rich Plaque Possible Mechanism of Acute Stent Thrombosis? A Near-Infrared Spectroscopy Study SO CIRCULATION LA English DT Editorial Material C1 [Jang, Ik-Kyung] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Long Beach Mem Med Ctr, Div Cardiol, Long Beach, CA USA. RP Jang, IK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM ijang@partners.org OI Jaffer, Farouc/0000-0001-7980-384X NR 2 TC 21 Z9 22 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 30 PY 2010 VL 122 IS 22 BP 2349 EP 2350 DI 10.1161/CIRCULATIONAHA.110.970079 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 686JD UT WOS:000284691700022 PM 21147731 ER PT J AU Chen, DH Sul, Y Weiss, M Hillel, A Lipe, H Wolff, J Matsushita, M Raskind, W Bird, T AF Chen, D. -H. Sul, Y. Weiss, M. Hillel, A. Lipe, H. Wolff, J. Matsushita, M. Raskind, W. Bird, T. TI CMT2C with vocal cord paresis associated with short stature and mutations in the TRPV4 gene SO NEUROLOGY LA English DT Article ID SPINAL MUSCULAR-ATROPHY; MARIE-TOOTH DISEASE; SENSORY NEUROPATHY; HEREDITARY MOTOR; LOCALIZATION; DISORDERS; SPECTRUM; HMSN2C; TYPE-2 AB Background: Recently, mutations in the transient receptor potential cation channel, subfamily V, member 4 gene (TRPV4) have been reported in Charcot-Marie-Tooth Type 2C (CMT2C) with vocal cord paresis. Other mutations in this same gene have been described in separate families with various skeletal dysplasias. Further clarification is needed of the different phenotypes associated with this gene. Methods: We performed clinical evaluation, electrophysiology, and genetic analysis of the TRPV4 gene in 2 families with CMT2C. Results: Two multigenerational families had a motor greater than sensory axonal neuropathy associated with variable vocal cord paresis. The vocal cord paresis varied from absent to severe, requiring permanent tracheotomy in 2 subjects. One family with mild neuropathy also manifested pronounced short stature, more than 2 SD below the average height for white Americans. There was one instance of dolichocephaly. A novel S542Y mutation in the TRPV4 gene was identified in this family. The other family had a more severe, progressive, motor neuropathy with sensory loss, but less remarkable short stature and an R315W mutation in TRPV4. Third cranial nerve involvement and sleep apnea occurred in one subject in each family. Conclusion: CMT2C with axonal neuropathy, vocal cord paresis, and short stature is a unique syndrome associated with mutations in the TRPV4 gene. Mutations in TRPV4 can cause abnormalities in bone, peripheral nerve, or both and may result in highly variable orthopedic and neurologic phenotypes. Neurology (R) 2010;75:1968-1975 C1 [Chen, D. -H.; Weiss, M.; Bird, T.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Sul, Y.; Matsushita, M.; Raskind, W.; Bird, T.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Hillel, A.] Univ Washington, Sch Med, Dept Otolaryngol, Seattle, WA 98195 USA. [Raskind, W.; Bird, T.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Lipe, H.; Wolff, J.; Bird, T.] VA Puget Sound Hlth Care Syst, Res Educ Ctr, Geriatr, Seattle, WA USA. [Lipe, H.; Wolff, J.; Bird, T.] VA Puget Sound Hlth Care Syst, Ctr Clin, Geriatr, Seattle, WA USA. [Raskind, W.] VA Puget Sound Hlth Care Syst, Ctr Clin, Mental Illness, Seattle, WA USA. [Raskind, W.] VA Puget Sound Hlth Care Syst, Res Educ Ctr, Mental Illness, Seattle, WA USA. RP Bird, T (reprint author), 1660 S Columbian Way,S-182 GRECC, Seattle, WA 98108 USA. EM tomnroz@uw.edu FU Athena Diagnostics, Inc.; Department of Veterans Affairs Merit Review; NIH [R01 NS069719, R01 HD054562, HD054562, RC1 AG035681, RC2 HG005608, R01 AG033693, P50 HD055782, AG005136, R01 MH069867]; Seattle Puget Sound Veterans Affairs Mental Illness Research, Education and Clinical Center; Puget Sound Veterans Affairs Medical Center; Department of Veterans Affairs; Springer-Verlag GmbH Biomedical Sciences FX Dr. Chen receives licensing fees for PKCgamma in diagnosis of SCA14 from Athena Diagnostics, Inc. Ms. Sul reports no disclosures. Dr. Weiss has received speaker honoraria from Athena Diagnostics, Inc., and Talecris Biotherapeutics; serves on the editorial boards of Muscle and Nerve and the Journal of Clinical Neuromuscular Disease; has served as a consultant for Genzyme Corporation and for Washington State Department of Labor and Industries; and serves on the speakers' bureau for Athena Diagnostics, Inc. Dr. Hillel reports no disclosures. Ms. Lipe receives research support from a Department of Veterans Affairs Merit Review Grant. Mr. Wolff reports no disclosures. Mr. Matsushita receives research support from the NIH (R01 NS069719 [technician] and R01 HD054562 [technician]), and from the Seattle Puget Sound Veterans Affairs Mental Illness Research, Education and Clinical Center. Dr. Raskind serves on the editorial boards of the American Journal of Medical Genetics (Neuropsychiatric Genetics Section); the Journal of Learning Disabilities, The Open Genomics Journal, and Neuropsychopharmacology; receives licensing fees for PKCgamma in diagnosis of SCA14 from Athena Diagnostics, Inc.; receives research support from the NIH (R01 NS069719 [PI], HD054562 [PI], RC1 AG035681 [PI], RC2 HG005608 [PI], R01 AG033693 [coinvestigator], and P50 HD055782 [coinvestigator]) and from the Puget Sound Veterans Affairs Medical Center; and her spouse serves on the editorial boards of the Journal of Geriatric Psychiatry and Neurology, Alzheimer Disease and Associated Disorders: An International Journal, and the European Neurological Journal; receives research support from the NIH (AG005136 and R01 MH069867) and from the Department of Veterans Affairs; and served as an expert witness on behalf of Johnson & Johnson on galantamine patent case. Dr. Bird serves on scientific advisory boards for the Association for Frontotemporal Dementia and the CMT Association; has received funding for travel and speaker honoraria from Athena Diagnostics, Inc.; serves on the editorial boards of Brain and Neurology Today; is listed as a co-inventor on and receives license fees from Athena Diagnostics, Inc. for patents re: PKCgamma in diagnosis of SCA14 and Mutations Associated With A Human Demyelinating Neuropathy (Charcot-Marie-Tooth Disease Type 1C); receives royalties from the publication of Human Genetics: Principles and Approaches, 4th ed. (Springer-Verlag GmbH Biomedical Sciences, 2010); serves on the speakers' bureau for Athena Diagnostics, Inc.; and receives research support from the Department of Veterans Affairs. NR 26 TC 33 Z9 34 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 30 PY 2010 VL 75 IS 22 BP 1968 EP 1975 DI 10.1212/WNL.0b013e3181ffe4bb PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 686GW UT WOS:000284685800009 PM 21115951 ER PT J AU Cheng, EM Tonn, S Swain-Eng, R Factor, SA Weiner, WJ Bever, CT AF Cheng, E. M. Tonn, S. Swain-Eng, R. Factor, S. A. Weiner, W. J. Bever, C. T., Jr. CA Amer Acad Neurology Parkinson Dis TI Quality improvement in neurology: AAN Parkinson disease quality measures Report of the Quality Measurement and Reporting Subcommittee of the American Academy of Neurology SO NEUROLOGY LA English DT Article ID MOVEMENT-DISORDER SOCIETY; JOINT TASK-FORCE; STANDARDS SUBCOMMITTEE; PRACTICE PARAMETER; OF-NEUROLOGY; THERAPEUTIC MANAGEMENT; PHYSICIAN PERFORMANCE; EUROPEAN FEDERATION; INVITED ARTICLE; HEALTH AB Background: Measuring the quality of health care is a fundamental step toward improving health care and is increasingly used in pay-for-performance initiatives and maintenance of certification requirements. Measure development to date has focused on primary care and common conditions such as diabetes; thus, the number of measures that apply to neurologic care is limited. The American Academy of Neurology (AAN) identified the need for neurologists to develop measures of neurologic care and to establish a process to accomplish this. Objective: To adapt and test the feasibility of a process for independent development by the AAN of measures for neurologic conditions for national measurement programs. Methods: A process that has been used nationally for measure development was adapted for use by the AAN. Topics for measure development are chosen based upon national priorities, available evidence base from a systematic literature search, gaps in care, and the potential impact for quality improvement. A panel composed of subject matter and measure development methodology experts oversees the development of the measures. Recommendation statements and their corresponding level of evidence are reviewed and considered for development into draft candidate measures. The candidate measures are refined by the expert panel during a 30-day public comment period and by review by the American Medical Association for Current Procedural Terminology (CPT) II codes. All final AAN measures are approved by the AAN Board of Directors. Results: Parkinson disease (PD) was chosen for measure development. A review of the medical literature identified 258 relevant recommendation statements. A 28-member panel approved 10 quality measures for PD that included full specifications and CPT II codes. Conclusion: The AAN has adapted a measure development process that is suitable for national measurement programs and has demonstrated its capability to independently develop quality measures. Neurology (R) 2010;75:2021-2027 C1 [Tonn, S.; Swain-Eng, R.] Amer Acad Neurol, St Paul, MN 55116 USA. [Cheng, E. M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Cheng, E. M.] VA Greater Angeles, Dept Neurol, Los Angeles, CA USA. [Factor, S. A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Weiner, W. J.; Bever, C. T., Jr.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Bever, C. T., Jr.] VA Maryland Hlth Care Syst, Res Serv, Baltimore, MD USA. [Bever, C. T., Jr.] VA Maryland Hlth Care Syst, Dept Neurol, Baltimore, MD USA. RP Cheng, EM (reprint author), Amer Acad Neurol, 1080 Montreal Ave, St Paul, MN 55116 USA. EM quality@aan.com FU NIH/NINDS [K23NS058571]; VA Parkinson's Disease Research, Education, and Clinical Center; Department of Veterans Affairs; California Office of Statewide Planning and Development; National Multiple Sclerosis Society; American Heart Association; Pfizer Inc.; CDC; Parkinson's Disease Diagnosis and Clinical Management (Demos); Drug Induced Movement Disorders (Blackwell Futura); Teva Pharmaceutical Industries Ltd.; Ipsen; UCB; Schering-Plough Corp.; publication of Neurology for the Non-Neurologist; Hopkins University; Handbook of Clinical Neurology Hyperkinetic Disorders; Novartis; Santhera Pharmaceuticals; Boehringer Ingelheim; Abraxis BioScience, Inc.; publication of Ambulatory Medicine; National MS Society FX Dr. Cheng serves as a consultant for the National Parkinson Foundation and receives research support from the NIH/NINDS (K23NS058571 [PI]), the VA Parkinson's Disease Research, Education, and Clinical Center, the Department of Veterans Affairs, the California Office of Statewide Planning and Development, the National Multiple Sclerosis Society, and the American Heart Association. Ms. Tonn is a full-time employee of the American Academy of Neurology (AAN) and served as project director for AAN grants from Pfizer Inc. and the CDC. Ms. Swain-Eng is a full-time employee of the American Academy of Neurology. Dr. Factor has served on scientific advisory boards for Lundbeck Inc., Allergan, Inc., and UCB; serves as a section editor for Current Treatment Options in Neurology; receives royalties from the publication of Parkinson's Disease Diagnosis and Clinical Management (Demos, 2008) and Drug Induced Movement Disorders (Blackwell Futura, 2005); has given expert testimony, prepared affidavits, and served as a consultant for Boehringer Ingelheim; and receives research support from Teva Pharmaceutical Industries Ltd., Ipsen, UCB, and Schering-Plough Corp. Dr. Weiner has served on scientific advisory boards for Santhera Pharmaceuticals and Rexahn Pharmaceuticals, Inc.; serves on the editorial boards of Parkinsonism and Related Disorders and Neurological Reviews, and as Editor of Treatment Options in Neurology; receives royalties from the publication of Neurology for the Non-Neurologist (6th edition, Kluwer/Lippincott 2010), Parkinson's Disease: A Complete Guide for Patients and Family (Hopkins University Press 2nd edition, 2007), and Handbook of Clinical Neurology Hyperkinetic Disorders (Elsevier, 2011); has received honoraria from Santhera Pharmaceuticals and Novartis; has received research support from Novartis, Santhera Pharmaceuticals, Boehringer Ingelheim, and has provided expert testimony and served as a subject matter expert in legal proceedings. Dr. Bever serves on the editorial board of the MS Quarterly Report; is listed as a co-inventor on and receives royalties from Abraxis BioScience, Inc. for a pending patent re: Use of hematogenous stem cells in neuronal replacement therapy and gene delivery; receives royalties from the publication of Ambulatory Medicine (Lippincott Williams & Wilkins, 7th edition, 2006); and has received research support from the Department of Veterans Affairs and the National MS Society. NR 39 TC 42 Z9 43 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 30 PY 2010 VL 75 IS 22 BP 2021 EP 2027 DI 10.1212/WNL.0b013e3181ff96dd PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 686GW UT WOS:000284685800017 PM 21115958 ER PT J AU Yehuda, R Golier, JA Bierer, LM Mikhno, A Pratchett, LC Burton, CL Makotkine, I Devanand, DP Pradhaban, G Harvey, PD Mann, JJ AF Yehuda, Rachel Golier, Julia A. Bierer, Linda M. Mikhno, Arthur Pratchett, Laura C. Burton, Charles L. Makotkine, Iouri Devanand, D. P. Pradhaban, Gnanavalli Harvey, Philip D. Mann, J. John TI Hydrocortisone responsiveness in Gulf War veterans with PTSD: Effects on ACTH, declarative memory hippocampal [(18)F]FDG uptake on PET SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE PTSD; Gulf War veterans; Hippocampus; Cortisol; Glucocorticoid receptors; Episodic memory; [(18)F]FDG-PET ID POSTTRAUMATIC-STRESS-DISORDER; MILD COGNITIVE IMPAIRMENT; CHILDHOOD SEXUAL-ABUSE; GLUCOCORTICOID-RECEPTORS; COMBAT VETERANS; ALZHEIMERS-DISEASE; MAJOR DEPRESSION; HOLOCAUST SURVIVORS; TRAUMA SURVIVORS; PLASMA-CORTISOL AB Neuroendocrine, cognitive and hippocampal alterations have been described in Gulf War (GW) veterans, but their inter-relationships and significance for posttraumatic stress disorder (PTSD) have not been described. Hydrocortisone (Hcort) was administered to GW veterans with (PTSD+ n = 12) and without (PTSD- n = 8) chronic PTSD in a randomized, placebo-controlled, double-blind challenge. Changes in plasma ACTH, memory, and hippocampal [(18)F]FDG uptake on positron emission tomography were assessed. The low-dose dexamethasone suppression test was also administered. The PTSD+ group showed greater cortisol and ACTH suppression, reflecting greater peripheral glucocorticoid receptor (GR) responsiveness, and did not show an Hcort-induced decrement in delayed recall or retention. The groups had comparable relative regional hippocampal [(18)F]FDG uptake at baseline, but only the PTSD group had an Hcort-associated decrease in hippocampal [(18)F]FDG uptake. Asymmetry in hippocampal hemispheric volumes differed between PTSD+ and PTSD- groups. This asymmetry was associated with cortisol, ACTH, retention and functional hippocampal asymmetry before, but not after, Hcort administration. Differences in brain metabolic responses between GW veterans with and without PTSD may reflect differences in peripheral and central GR responsiveness. Published by Elsevier Ireland Ltd. C1 [Yehuda, Rachel; Golier, Julia A.; Bierer, Linda M.; Pratchett, Laura C.; Burton, Charles L.; Makotkine, Iouri] Mt Sinai Sch Med, Dept Psychiat, Traumat Stress Studies Div, New York, NY 10029 USA. [Yehuda, Rachel; Golier, Julia A.; Bierer, Linda M.; Pratchett, Laura C.; Burton, Charles L.; Makotkine, Iouri] James J Peters Vet Affairs Med Ctr, PTSD Program, Bronx, NY USA. [Devanand, D. P.; Pradhaban, Gnanavalli; Harvey, Philip D.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. [Devanand, D. P.] Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY USA. [Mikhno, Arthur; Mann, J. John] New York State Psychiat Inst & Hosp, Dept Mol Imaging & Neuropathol, New York, NY 10032 USA. [Devanand, D. P.; Pradhaban, Gnanavalli; Harvey, Philip D.] Columbia Univ, Coll Phys & Surg, Div Geriatr Psychiat, New York, NY USA. [Harvey, Philip D.] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. RP Yehuda, R (reprint author), Mt Sinai Sch Med, Dept Psychiat, Traumat Stress Studies Div, New York, NY 10029 USA. EM rachel.yehuda@va.gov FU VA MERIT; National Center for Research Resources, National Institutes of Health [5 MO1 RR00071] FX This grant was primarily supported by a VA MERIT entitled "Glucocorticoid Responsivity in Gulf War Veterans." In addition, partial support was obtained by a grant (5 MO1 RR00071) for the Mount Sinai General Clinical Research Center from the National Center for Research Resources, National Institutes of Health. The authors would like to acknowledge several colleagues for work on this project. First, thanks to Josef Machac, M.D. and Ash Rafique, B.S. at the Mount Sinai Hospital Clinical Neuroimaging Laboratory, to Janelle Wohltmann, B.A., Research Coordinator, to Lisa Tischler, Ph.D., Sharon Y. Jedel, Psy.D., and Ellen Labinsky, Ph.D. for psychological assessments of the subjects, to Ken Belzer, Ph.D., for statistical consultation, and most of all, the Gulf War Veterans who participated in this research. NR 99 TC 20 Z9 20 U1 2 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD NOV 30 PY 2010 VL 184 IS 2 BP 117 EP 127 DI 10.1016/j.pscychresns.2010.06.010 PG 11 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 681TF UT WOS:000284341500007 PM 20934312 ER PT J AU Qiu, WQ Claunch, J Kong, JA Nixon, EE Fang, JL Li, M Vangel, M Hui, KKS AF Qiu, Wei Qiao Claunch, Joshua Kong, Jian Nixon, Erika E. Fang, Jiliang Li, Ming Vangel, Mark Hui, Kathleen Kin-Sang TI The effects of acupuncture on the brain networks for emotion and cognition: An observation of gender differences SO BRAIN RESEARCH LA English DT Article DE Acupuncture; Brain activity; Sex; Gender ID ADULT HUMAN BRAIN; SEX-DIFFERENCES; FUNCTIONAL CONNECTIVITY; RESTING-STATE; DEFAULT MODE; AMYGDALA RESPONSE; FMRI; MEMORY; STRESS; MRI AB Acupuncture modulates brain activity at the limbic paralimbic neocortical network (LPNN) and the default mode network (DMN). Since these brain networks show gender differences when mediating emotional and cognitive tasks, we thus hypothesize that women and men may also respond differently to acupuncture procedure at these brain regions. In order to test this hypothesis, we retrieved the data of 38 subjects, 19 females and 19 males, who had brain fMRI during acupuncture from previous studies and reanalyzed them based on sex status. Deactivation at the LPNN/DMN during needle manipulation of acupuncture was more extensive in females than in males, particularly in the posterior cingulate (BA31), precuneus (BA7m) and angular gyms (BA39). The functional correlations between the right BA31 and pregenual cingulate (BA32), hippocampus or contralateral BA31 were significantly stronger in females than in males. The angular gyrus (BA39) was functionally correlated with BA31 in females; in contrast, it was anticorrelated with BA31 in males. Soreness, a major component of the psychophysical responses to needle manipulation, deqi, was correlated in intensity with deactivation of the angular gyrus in females; no such relationships were observed in males. In contrast to lesser deactivation at the LPNN/DMN networks, needle manipulation during acupuncture induced greater activation at the secondary somatosensory cortex and stronger functional connectivity with the anterior-middle cingulate (BA32/24) in males than in females. Our study suggests that brains with sex dimorphism may process the acupuncture stimulation differently between women and men. (C) 2010 Elsevier B.V. All rights reserved. C1 [Qiu, Wei Qiao] Tufts Univ, Dept Psychiat, Tufts Med Ctr, Sch Med, Medford, MA 02155 USA. [Claunch, Joshua; Kong, Jian; Nixon, Erika E.; Fang, Jiliang; Li, Ming; Vangel, Mark] Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Cambridge, MA USA. [Kong, Jian] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Kong, Jian] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Qiu, WQ (reprint author), Boston Univ Med Campus,72 E Concord St,R-623D, Boston, MA 02118 USA. EM wqiu67@bu.edu OI Qiu, Wendy/0000-0002-2082-2410 FU NIA [K23AG-022476]; NIH/National Center for Complementary and Alternative Medicine [R21AT00978, 1-P01-002048-01, K01 AT003883, R21AT004497]; National Center for Research Resources [P41RR14075]; Mental Illness and Neuroscience Discovery Institute; Brain Project [NS 34189] FX The manuscript is dedicated to Dr. Kathleen Kin-Sang Hui, who made a seminal contribution to link the acupuncture treatment with the modulation of brain function. We are saddened that she passed away while this manuscript was under review and consideration. This work was supported in part by a grant from the NIA, K23AG-022476 for W.Q.Q and grants from the NIH/National Center for Complementary and Alternative Medicine (R21AT00978) (1-P01-002048-01) for K.K.H, (K01 AT003883) and (R21AT004497) for J.K., the National Center for Research Resources (P41RR14075), the Mental Illness and Neuroscience Discovery Institute and the Brain Project Grant NS 34189. NR 62 TC 25 Z9 30 U1 2 U2 20 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 29 PY 2010 VL 1362 BP 56 EP 67 DI 10.1016/j.brainres.2010.09.040 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 685ZU UT WOS:000284667400007 PM 20851113 ER PT J AU Blood, AJ Iosifescu, DV Makris, N Perlis, RH Kennedy, DN Dougherty, DD Kim, BW Lee, MJ Wu, S Lee, S Calhoun, J Hodge, SM Fava, M Rosen, BR Smoller, JW Gasic, GP Breiter, HC AF Blood, Anne J. Iosifescu, Dan V. Makris, Nikos Perlis, Roy H. Kennedy, David N. Dougherty, Darin D. Kim, Byoung Woo Lee, Myung Joo Wu, Shirley Lee, Sang Calhoun, Jesse Hodge, Steven M. Fava, Maurizio Rosen, Bruce R. Smoller, Jordan W. Gasic, Gregory P. Breiter, Hans C. CA Phenotype Genotype Project Addicti TI Microstructural Abnormalities in Subcortical Reward Circuitry of Subjects with Major Depressive Disorder SO PLOS ONE LA English DT Article ID LATE-LIFE DEPRESSION; DORSOLATERAL PREFRONTAL CORTEX; WHITE-MATTER MICROSTRUCTURE; DIFFUSION ANISOTROPY; ANTERIOR CINGULATE; PARKINSONS-DISEASE; TREATMENT RESPONSE; NUCLEUS-ACCUMBENS; EXPECTANCY BIAS; MOOD DISORDERS AB Background: Previous studies of major depressive disorder (MDD) have focused on abnormalities in the prefrontal cortex and medial temporal regions. There has been little investigation in MDD of midbrain and subcortical regions central to reward/aversion function, such as the ventral tegmental area/substantia nigra (VTA/SN), and medial forebrain bundle (MFB). Methodology/Principal Findings: We investigated the microstructural integrity of this circuitry using diffusion tensor imaging (DTI) in 22 MDD subjects and compared them with 22 matched healthy control subjects. Fractional anisotropy (FA) values were increased in the right VT and reduced in dorsolateral prefrontal white matter in MDD subjects. Follow-up analysis suggested two distinct subgroups of MDD patients, which exhibited non-overlapping abnormalities in reward/aversion circuitry. The MDD subgroup with abnormal FA values in VT exhibited significantly greater trait anxiety than the subgroup with normal FA values in VT, but the subgroups did not differ in levels of anhedonia, sadness, or overall depression severity. Conclusions/Significance: These findings suggest that MDD may be associated with abnormal microstructure in brain reward/aversion regions, and that there may be at least two subtypes of microstructural abnormalities which each impact core symptoms of depression. C1 [Blood, Anne J.; Iosifescu, Dan V.; Makris, Nikos; Perlis, Roy H.; Dougherty, Darin D.; Kim, Byoung Woo; Lee, Myung Joo; Wu, Shirley; Lee, Sang; Calhoun, Jesse; Hodge, Steven M.; Fava, Maurizio; Smoller, Jordan W.; Gasic, Gregory P.; Breiter, Hans C.] Massachusetts Gen Hosp, Dept Psychiat, Lab Neuroimaging & Genet, Depress Clin & Res Program, Boston, MA 02114 USA. [Blood, Anne J.; Iosifescu, Dan V.; Makris, Nikos; Perlis, Roy H.; Dougherty, Darin D.; Kim, Byoung Woo; Lee, Myung Joo; Wu, Shirley; Lee, Sang; Calhoun, Jesse; Hodge, Steven M.; Fava, Maurizio; Smoller, Jordan W.; Gasic, Gregory P.; Breiter, Hans C.] Massachusetts Gen Hosp, Dept Psychiat, Lab Neuroimaging & Genet, Mood & Motor Control Lab,Addict Res Program, Boston, MA 02114 USA. [Blood, Anne J.; Iosifescu, Dan V.; Makris, Nikos; Perlis, Roy H.; Kennedy, David N.; Dougherty, Darin D.; Kim, Byoung Woo; Lee, Myung Joo; Wu, Shirley; Lee, Sang; Calhoun, Jesse; Hodge, Steven M.; Fava, Maurizio; Rosen, Bruce R.; Smoller, Jordan W.; Gasic, Gregory P.; Breiter, Hans C.] Harvard Univ, Sch Med, Boston, MA USA. [Perlis, Roy H.; Fava, Maurizio; Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodevelopmental Genet Unit, Boston, MA 02114 USA. [Perlis, Roy H.; Fava, Maurizio; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Blood, Anne J.; Kim, Byoung Woo; Lee, Myung Joo; Lee, Sang; Calhoun, Jesse; Hodge, Steven M.; Rosen, Bruce R.; Gasic, Gregory P.; Breiter, Hans C.] Massachusetts Gen Hosp, Dept Radiol, MENC, Boston, MA 02114 USA. [Blood, Anne J.; Kim, Byoung Woo; Lee, Myung Joo; Lee, Sang; Calhoun, Jesse; Hodge, Steven M.; Rosen, Bruce R.; Gasic, Gregory P.; Breiter, Hans C.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Makris, Nikos; Kennedy, David N.; Hodge, Steven M.] Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. [Makris, Nikos; Kennedy, David N.; Hodge, Steven M.] Massachusetts Gen Hosp, Ctr Integrat Informat, Boston, MA 02114 USA. [Blood, Anne J.; Kennedy, David N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Iosifescu, Dan V.] Mt Sinai Sch Med, New York, NY USA. RP Blood, AJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Lab Neuroimaging & Genet, Depress Clin & Res Program, Boston, MA 02114 USA. EM hbreiter@partners.org RI Kennedy, David/H-3627-2012; OI Lee, Sang Han/0000-0001-9760-393X FU NIDA, Bethesda, MD [R01 14118, R21 026104, P20 026002]; Office of National Drug Control Policy - Counterdrug Technology Assessment Center (ONDCP-CTAC), Washington, [DABK39-03-C-0098]; NINDS [R01 NS052368]; NCRR [P41RR14075]; Mental Illness and Neuroscience Discovery (MIND) Institute; MGH Department of Radiology FX This work was supported by a grant to H.C.B. (R01 14118, R21 026104, P20 026002) from NIDA, Bethesda, MD, and a grant (DABK39-03-C-0098; The Phenotype Genotype Project in Addiction and Depression) from the Office of National Drug Control Policy - Counterdrug Technology Assessment Center (ONDCP-CTAC), Washington, D.C. Further support was provided by a grant to A.J.B. (R01 NS052368) from NINDS, by the MGH Department of Radiology to H.C.B., by NCRR (P41RR14075), and by the Mental Illness and Neuroscience Discovery (MIND) Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 95 TC 61 Z9 62 U1 5 U2 13 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 29 PY 2010 VL 5 IS 11 AR e13945 DI 10.1371/journal.pone.0013945 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 686HD UT WOS:000284686500001 PM 21124764 ER PT J AU Tien, PC Schneider, MF Cox, C Cohen, M Karim, R Lazar, J Young, M Glesby, MJ AF Tien, Phyllis C. Schneider, Michael F. Cox, Christopher Cohen, Mardge Karim, Roksana Lazar, Jason Young, Mary Glesby, Marshall J. TI HIV, HAART, and lipoprotein particle concentrations in the Women's Interagency HIV Study SO AIDS LA English DT Article DE HAART; HIV; lipids; lipoprotein particle concentrations; women ID MAGNETIC-RESONANCE SPECTROSCOPY; REGIONAL ADIPOSE-TISSUE; ANTIRETROVIRAL THERAPY; CARDIOVASCULAR-DISEASE; INFECTED WOMEN; HEART-DISEASE; MEN; RISK; SIZE; HETEROGENEITY AB Background: Changes in lipoprotein particle concentrations, especially greater small low-density lipoprotein particle (LDL-p) and lower small high-density lipoprotein particle (HDL-p) may provide information regarding cardiovascular disease (CVD) risk above and beyond that which is provided by standard lipids. We quantified the association HIV and HAART use had with LDL-p and HDL-p. Methods: Cross-sectional study of 1077 individuals classified by HIV/HAART status (361 HIV-uninfected, 128 HIV-infected/HAART naive, 588 HIV-infected/on HAART) enrolled in the Women's Interagency HIV Study. Nuclear magnetic resonance spectroscopy estimated total and subclass lipoprotein particle concentrations. Quantile regression models were used to estimate differences in the 10th, 25th, 50th, 75th, and 90th percentiles of the distributions of lipoprotein particle concentrations between the two HIV-infected exposure groups and HIV-uninfected controls after adjustment for demographic, nonlipid metabolic factors, and standard lipids. Results: Compared with HIV-uninfected women, those on HAART had greater 75th and 90th percentiles of small LDL-p; there was little difference between HIV-infected/HAART naive and HIV-uninfected women. After adjustment for triglycerides, the association of HAART with greater 75th and 90th percentiles of small LDL-p was attenuated and no longer significant. In contrast, after adjustment for triglycerides, HIV infection irrespective of HAART status remained associated with significantly lower 10th, 25th, 50th, 75th, and 90th percentiles of small HDL-p. Conclusion: Our findings suggest that testing for LDL-p confers little additional information beyond triglycerides levels when assessing CVD risk. Further investigation is needed to examine the role of HDL-p in the link between HIV and CVD in women. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Tien, Phyllis C.] Univ Calif San Francisco, VAMC, Infect Dis Sect, Dept Med, San Francisco, CA 94121 USA. [Tien, Phyllis C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Schneider, Michael F.; Cox, Christopher] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Cohen, Mardge] Stroger Hosp, Dept Med, Chicago, IL USA. [Cohen, Mardge] Rush Univ, Dept Med, Chicago, IL 60612 USA. [Karim, Roksana] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Lazar, Jason] SUNY Hlth Sci Ctr, Dept Med, Brooklyn, NY 11203 USA. [Young, Mary] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. [Glesby, Marshall J.] Weill Cornell Med Coll, Dept Med, New York, NY USA. RP Tien, PC (reprint author), Univ Calif San Francisco, VAMC, Infect Dis Sect, Dept Med, 111W,4150 Clement St, San Francisco, CA 94121 USA. EM ptien@ucsf.edu FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590, K23-AI-66943-04, K24-AI-078884]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI ) [UL1 RR024131] FX Data in this manuscript were collected by the WIHS Collaborative Study Group with centers (principal investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, New York (Howard Minkoff); Washington DC Metropolitan Consortium (M.Y.); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (M. C.); Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study is co-funded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). P. C. T. and M.J.G. are supported by the National Institute of Allergy and Infectious Diseases through K23-AI-66943-04 and K24-AI-078884, respectively. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. All authors played a role in editing the manuscript and approved the text as submitted to AIDS. P. C. T. designed the study and wrote the manuscript. M. F. S. and C. C. performed the data analysis and assisted in the interpretation of statistical data. M. C., R. K., M.Y., J.L., and M.J.G. reviewed and edited the manuscript. NR 28 TC 9 Z9 9 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 27 PY 2010 VL 24 IS 18 BP 2809 EP 2817 DI 10.1097/QAD.0b013e32833fcb3b PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 678EU UT WOS:000284057300007 PM 20871387 ER PT J AU Bangsberg, DR Ragland, K Monk, A Deeks, SG AF Bangsberg, David R. Ragland, Kathleen Monk, Alex Deeks, Steven G. TI A single tablet regimen is associated with higher adherence and viral suppression than multiple tablet regimens in HIV plus homeless and marginally housed people SO AIDS LA English DT Article DE adherence; dosing frequency; drug use; homeless; mental illness; once daily; one pill; pill-burden ID ACTIVE ANTIRETROVIRAL THERAPY; INHIBITOR THERAPY; PROTEASE; POPULATION; RESISTANCE; OUTCOMES; COHORT; NAIVE; LOAD; AIDS AB Background: Although, single-tablet regimen (STR) efavirenz, emtricibine, and tenofovir disoproxil fumarate (EFV/FTC/TDF) may be appealing in HIV-infected persons who are at high risk for nonadherence, the degree to which this simplified formulation affects adherence is not known. The virologic effectiveness of this STR in a potentially nonadherent population remains a concern, given the rapid selection of drug resistance seen with these drugs. Method: We performed a prospective observational study assessing adherence and virologic response to EFV/FTC/TDF STR among a cohort of homeless and marginally housed individuals. We compared adherence and viral suppression to historical controls followed in the same cohort. Results: Adherence was higher in EFV/FTC/TDF STR regimen compared to non-one-pill-once-daily therapy (P = 0.006) after controlling for multiple confounders. Viral suppression (HIV RNA <50 copies/ml) was greater in EFV/FTC/TDF STR than non-one-pill-once-daily regimens (69.2 versus 46.5%; P = 0.02), but there was no difference in viral suppression after controlling for adherence. Conclusion: Once-daily EFV/TNF/FTC STR appears to be a reasonable option for individuals with multiple barriers to adherence. Randomized clinical trials addressing various therapeutic strategies for this patient population are needed. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Bangsberg, David R.] Harvard Univ, Sch Med, Ragon Inst MGH MIT & Harvard, Massachusetts Gen Hosp Ctr Global Hlth, Boston, MA USA. [Ragland, Kathleen; Monk, Alex; Deeks, Steven G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Bangsberg, DR (reprint author), Ragon Inst MGH MIT & Harvard, MGH Ctr Global Hlth, 104 Mt Auburn St, Cambridge, MA 02138 USA. EM dbangsberg@partners.org FU National Institutes of Health [MH54907, AI069994]; UCSF Clinical and Translational Research Institute Clinical Research Center [UL1 RR024131]; Gilead Sciences; Bristol-Myers Squibb; [MH87227] FX The work was supported by National Institutes of Health (MH54907, AI069994); the UCSF Clinical and Translational Research Institute Clinical Research Center (UL1 RR024131), Gilead Sciences and Bristol-Myers Squibb. Dr Bangsberg received additional funding from MH87227. HIV RNA kits were donated by Roche. The funders had no role in the data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 88 Z9 89 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 27 PY 2010 VL 24 IS 18 BP 2835 EP 2840 DI 10.1097/QAD.0b013e328340a209 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 678EU UT WOS:000284057300010 PM 21045636 ER PT J AU Dutta, P Hullett, DA Roenneburg, DA Torrealba, JR Sollinger, HW Harn, DA Burlingham, WJ AF Dutta, Partha Hullett, Debra A. Roenneburg, Drew A. Torrealba, Jose R. Sollinger, Hans W. Harn, Donald A. Burlingham, William J. TI Lacto-N-fucopentaose III, a Pentasaccharide, Prolongs Heart Transplant Survival SO TRANSPLANTATION LA English DT Article DE LNFPIII; Alternatively activated macrophages; PD-L1 ID T-CELL; ALTERNATIVE ACTIVATION; MACROPHAGES; MICE; INDUCTION; REJECTION; ANTIGENS; LIGANDS; TISSUE AB Background. Lacto-N-fucopentaose III (LNFPIII) is a pentasaccharide containing the Lewis(X) trisaccharide that is found on schistosome eggs and in breast milk. LNFPIII conjugates suppress host immune responses and have therapeutic efficacy in mouse models of psoriasis and type 1 diabetes. Methods. We used nonvascularized neonatal ear-heart transplantation and heterotopic vascularized heart transplantation models to evaluate immunosuppressive effects of LNFPIII and subsequently analyzed the mechanism. Results. We found that administration of LNFPIII conjugates prolonged median graft survival by 80% when 1-day-old DBA/2 hearts were transplanted into ears of B6 mice. A similar graft prolongation was observed in a fully vascularized heterotopic heart transplantation model (DBA/2 into B6), No prolongation was observed with carrier protein (human serum albumin [HSA] or dextran) alone. We found increased programmed death ligand 1 (PD-L1) expression on F4/80(+) macrophages, CD4(+) T cells, and CD11b(+) CD11c(+) (myeloid) dendritic cells, and increased arginase1 and Ym1 expression, typical of alternatively activated macrophages, in the draining (cervical) lymph node cells. We found accumulation of Foxp3(+) regulatory T cells (Tregs) in the lymph nodes draining donor hearts, suggesting a possible role of Treg induction in graft prolongation. Anti-PD-L1 antibody treatment abrogated LNFPIII-mediated the graft survival benefit and Treg accumulation. LNFPIII-treated macrophages had increased PD-L1 expression and significantly prolonged DBA/2 allograft survival when injected intraperitoneally into B6 recipient mice. Conclusions. LNFPIII prolongs fully allogeneic graft survival in both vascularized and nonvascularized allograft transplantation models. The mechanism of graft prolongation seems to involve both alternatively activated PDL-1(+) macrophages and recruitment of Foxp3(+) Treg cells. C1 [Dutta, Partha; Hullett, Debra A.; Roenneburg, Drew A.; Sollinger, Hans W.; Burlingham, William J.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI USA. [Dutta, Partha] Univ Wisconsin, Dept Pathobiol Sci, Sch Vet Med, Madison, WI 53706 USA. [Dutta, Partha] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Torrealba, Jose R.] Univ Wisconsin, Dept Pathol, Madison, WI 53706 USA. [Harn, Donald A.] Univ Georgia, Coll Vet Med, Dept Infect Dis, Athens, GA USA. RP Burlingham, WJ (reprint author), H4-749 Clin Sci Ctr,600 Highland Ave, Madison, WI 53792 USA. EM burlingham@surgery.wisc.edu FU Department of Surgery, University of Wisconsin-Madison; NIH [R01-AI066229] FX This work was supported by the Department of Surgery, University of Wisconsin-Madison, and by NIH grant R01-AI066229 (to W.J.B.). NR 20 TC 15 Z9 15 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 27 PY 2010 VL 90 IS 10 BP 1071 EP 1078 DI 10.1097/TP.0b013e3181f8f296 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 681JX UT WOS:000284309500007 PM 20885339 ER PT J AU Mandal, CC Ghosh-Choudhury, T Yoneda, T Choudhury, GG Ghosh-Choudhury, N AF Mandal, Chandi Charan Ghosh-Choudhury, Triparna Yoneda, Toshi Choudhury, Goutam Ghosh Ghosh-Choudhury, Nandini TI Fish oil prevents breast cancer cell metastasis to bone SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Osteolytic metastasis; DHA; EPA; Fish oil diet ID NUDE-MICE; LUNG METASTASIS; CD44; GROWTH; PROGRESSION; EXPRESSION; OMEGA-3-FATTY-ACIDS; HYALURONAN; TUMORS; ACID AB The data derived from epidemiological and animal models confirm a beneficial effect of fish oil (rich in omega-3 polyunsaturated fatty acids) in the amelioration of tumor growth and progression including breast cancer The breast cancer patients often develop bone metastasis evidenced by osteolytic lesions leading to severe pain and bone fracture Using a mouse model of MDA-MB-231 human breast cancer cell metastasis to bone here we show that fish oil diet enriched in DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) prevents the formation of osteolytic lesions in bone indicating suppression of cancer cell metastasis to bone These results are supported by our data showing both DHA and EPA significantly attenuate the migration/invasion of MDA-MB-231 breast cancer cells in culture The mechanism that limits breast cancer cells to selective metastasis to bone remains hitherto unexplored Aberrant Increased expression of CD44 is associated with generation of cancer stem cells which contribute to metastasis of breast cancer cells We demonstrate that DHA and EPA significantly inhibit the expression of CD44 protein and mRNA by a transcriptional mechanism Furthermore we show markedly reduced levels of CD44 mRNA and protein in the tumors of mice which were fed fish oil diet than those in control diet Our data provide the first evidence for a salutary effect of fish oil on breast cancer metastasis to bone Our results identify a novel function of the fish oil active components DHA and EPA which target the cell-intrinsic pro-metastatic molecule CD44 to inhibit migration/invasion Published by Elsevier Inc C1 [Choudhury, Goutam Ghosh; Ghosh-Choudhury, Nandini] VA Res S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Mandal, Chandi Charan; Ghosh-Choudhury, Triparna; Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. [Yoneda, Toshi; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP Choudhury, GG (reprint author), VA Res S Texas Vet Hlth Care Syst, San Antonio, TX USA. FU NIH [RO1 DK50190, RO1 AR52425]; Juvenile Diabetes Research Foundation [1-2008-185]; Cancer Therapy and Research Center University of Texas Health Science Center at San Antonio; VA FX NIH RO1 AR52425 VA Merit review grants and Ronald Williams Orthopedic Award (Cancer Therapy and Research Center University of Texas Health Science Center at San Antonio) to NGC supported this work GGC is a recipient of VA Senior Research Career Scientist Award and is supported by VA Research Service Merit Review grant NIH RO1 DK50190 grant and Juvenile Diabetes Research Foundation 1-2008-185 grant NR 34 TC 28 Z9 34 U1 6 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 26 PY 2010 VL 402 IS 4 BP 602 EP 607 DI 10.1016/j.bbrc.2010.10.063 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 692QW UT WOS:000285171200005 PM 20971068 ER PT J AU Ma, J Lin, JY Alloo, A Wilson, BJ Schatton, T Zhan, QA Murphy, GF Waaga-Gasser, AM Gasser, M Hodi, FS Frank, NY Frank, MH AF Ma, Jie Lin, Jennifer Y. Alloo, Allireza Wilson, Brian J. Schatton, Tobias Zhan, Qian Murphy, George F. Waaga-Gasser, Ana-Maria Gasser, Martin Hodi, F. Stephen Frank, Natasha Y. Frank, Markus H. TI Isolation of tumorigenic circulating melanoma cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Tumor xenotransplantation; Immunocompromised mice; Interleukin-2 receptor gamma; Circulating tumor cells; Metastasis; Melanoma ID HUMAN-MALIGNANT MELANOMA; TUMOR-CELLS; P-GLYCOPROTEIN; INITIATING CELLS; PROGNOSTIC VALUE; CANCER-CELLS; METASTASIS; MARKERS; ACTIVATION; GROWTH AB Circulating tumor cells (CTC) have been identified in several human malignancies including malignant melanoma However whether melanoma CTC are tumorigenic and cause metastatic progression is currently unknown Here we isolate for the first time viable tumorigenic melanoma CTC and demonstrate that this cell population is capable of metastasis formation in human-to-mouse xenotransplantation experiments The presence of CTC among peripheral blood mononuclear cells (PBMC) of murine recipients of subcutaneous (s c) human melanoma xenografts could be detected based on mRNA expression for human GAPDH and/or ATP-binding cassette subfamily B member 5 (ABCB5) a marker of malignant melanoma-initiating cells previously shown to be associated with metastatic disease progression in human patients ABCB5 expression could also be detected in PBMC preparations from human stage IV melanoma patients but not healthy controls The detection of melanoma CTC in human-to-mouse s c tumor xenotransplantation models correlated significantly with pulmonary metastasis formation Moreover prospectively isolated CTC from murine recipients of s c melanoma xenografts were capable of primary tumor initiation and caused metastasis formation upon xenotransplantation to secondary murine NOD-scid IL2R gamma(null) recipients Our results provide initial evidence that melanoma CTC are tumorigenic and demonstrate that CTC are capable of causing metastatic tumor progression These findings suggest a need for CTC eradication to inhibit metastatic progression and provide a rationale for assessment of therapeutic responses of this tumorigenic cell population to promising emerging melanoma treatment modalities (C) 2010 Elsevier Inc All rights reserved C1 [Ma, Jie; Alloo, Allireza; Wilson, Brian J.; Schatton, Tobias; Frank, Markus H.] Harvard Univ, Sch Med, Transplantat Res Ctr, Childrens Hosp Boston, Boston, MA 02115 USA. [Ma, Jie; Lin, Jennifer Y.; Alloo, Allireza; Wilson, Brian J.; Schatton, Tobias; Frank, Markus H.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Zhan, Qian; Murphy, George F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Waaga-Gasser, Ana-Maria; Gasser, Martin] Univ Wurzburg, Sch Med, Dept Surg, Wurzburg, Germany. [Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Frank, Natasha Y.] VA Boston Healthcare Syst, Dept Med, Boston, MA USA. [Frank, Natasha Y.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. RP Frank, MH (reprint author), Harvard Univ, Sch Med, Transplantat Res Ctr, Childrens Hosp Boston, 300 Longwood Ave, Boston, MA 02115 USA. RI Frank, Markus/O-1625-2014 OI Murphy, George/0000-0003-3464-793X; Frank, Markus/0000-0002-1312-0488 FU NIH/NCI [1RO1CA113796, 1R01CA138231, 2P50CA093683] FX This work was supported by the NIH/NCI (grants 1RO1CA113796 and 1R01CA138231 to M H Frank and grant 2P50CA093683 (Specialized Program of Research Excellence in Skin Cancer) to M H Frank and G F Murphy NR 26 TC 27 Z9 27 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 26 PY 2010 VL 402 IS 4 BP 711 EP 717 DI 10.1016/j.bbrc.2010.10.091 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 692QW UT WOS:000285171200023 PM 20977885 ER PT J AU Leuschner, F Panizzi, P Chico-Calero, I Lee, WW Ueno, T Cortez-Retamozo, V Waterman, P Gorbatov, R Marinelli, B Iwamoto, Y Chudnovskiy, A Figueiredo, JL Sosnovik, DE Pittet, MJ Swirski, FK Weissleder, R Nahrendorf, M AF Leuschner, Florian Panizzi, Peter Chico-Calero, Isabel Lee, Won Woo Ueno, Takuya Cortez-Retamozo, Virna Waterman, Peter Gorbatov, Rostic Marinelli, Brett Iwamoto, Yoshiko Chudnovskiy, Aleksey Figueiredo, Jose-Luiz Sosnovik, David E. Pittet, Mikael J. Swirski, Filip K. Weissleder, Ralph Nahrendorf, Matthias TI Angiotensin-Converting Enzyme Inhibition Prevents the Release of Monocytes From Their Splenic Reservoir in Mice With Myocardial Infarction SO CIRCULATION RESEARCH LA English DT Article DE monocyte; spleen; ACE inhibitor; myocardial infarction; heart failure ID HEART-FAILURE; REPERFUSION INJURY; COLLAGEN MATRIX; ACE-INHIBITORS; INFLAMMATION; TISSUE; MORTALITY; SURVIVAL; ATHEROSCLEROSIS; HEMODYNAMICS AB Rationale: Monocytes recruited to ischemic myocardium originate from a reservoir in the spleen, and the release from their splenic niche relies on angiotensin (Ang) II signaling. Objective: Because monocytes are centrally involved in tissue repair after ischemia, we hypothesized that early angiotensin-converting enzyme (ACE) inhibitor therapy impacts healing after myocardial infarction partly via effects on monocyte traffic. Methods and Results: In a mouse model of permanent coronary ligation, enalapril arrested the release of monocytes from the splenic reservoir and consequently reduced their recruitment into the healing infarct by 45%, as quantified by flow cytometry of digested infarcts. Time-lapse intravital microscopy revealed that enalapril reduces monocyte motility in the spleen. In vitro migration assays and Western blotting showed that this was caused by reduced signaling through the Ang II type 1 receptor. We then studied the long-term consequences of blocked splenic monocyte release in atherosclerotic apolipoprotein (apo)E-/- mice, in which infarct healing is impaired because of excessive inflammation in the cardiac wound. Enalapril improved histologic healing biomarkers and reduced inflammation in infarcts measured by FMT-CT (fluorescence molecular tomography in conjunction with x-ray computed tomography) of proteolytic activity. ACE inhibition improved MRI-derived ejection fraction by 14% on day 21, despite initially comparable infarct size. In apoE(-/-) mice, ischemia/reperfusion injury resulted in larger infarct size and enhanced monocyte recruitment and was reversible by enalapril treatment. Splenectomy reproduced antiinflammatory effects of enalapril. Conclusion: This study suggests that benefits of early ACE inhibition after myocardial infarction can partially be attributed to its potent antiinflammatory impact on the splenic monocyte reservoir. (Circ Res. 2010;107:1364-1373.) C1 [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu; mnahrendorf@mgh.harvard.edu RI Lee, Won Woo/J-5589-2012; OI Panizzi, Peter/0000-0003-0141-8807 FU National Heart, Lung, and Blood Institute [R01HL095629, R01HL096576]; American Heart Association [SDG0835623D]; NIH [R24-CA92782, U01-HL08073]; Deutsche Herzstiftung e. V.; Korea Research Foundation [KRF-2009-013-E00027] FX This work was funded in part by National Heart, Lung, and Blood Institute grants R01HL095629 and R01HL096576 and American Heart Association Grant SDG0835623D (to M.N.); NIH grants R24-CA92782 and U01-HL08073 (to R. W.); Deutsche Herzstiftung e. V. (to F. L.); and Korea Research Foundation grant KRF-2009-013-E00027 (to W.W.L.). NR 53 TC 92 Z9 94 U1 0 U2 6 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 26 PY 2010 VL 107 IS 11 BP 1364 EP 1373 DI 10.1161/CIRCRESAHA.110.227454 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 684WN UT WOS:000284586100010 PM 20930148 ER PT J AU Eid, AA Ford, BM Block, K Kasinath, BS Gorin, Y Ghosh-Choudhury, G Barnes, JL Abboud, HE AF Eid, Assaad A. Ford, Bridget M. Block, Karen Kasinath, Balakuntalam S. Gorin, Yves Ghosh-Choudhury, Goutam Barnes, Jeffrey L. Abboud, Hanna E. TI AMP-activated Protein Kinase (AMPK) Negatively Regulates Nox4-dependent Activation of p53 and Epithelial Cell Apoptosis in Diabetes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NADPH OXIDASES; MEMBRANE THICKNESS; PODOCYTE DEPLETION; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; SKELETAL-MUSCLE; TRANSGENIC MICE; GLUCOSE-UPTAKE; RAT-KIDNEY; YEAST SNF1 AB Diabetes and high glucose (HG) increase the generation of NADPH oxidase-derived reactive oxygen species and induce apoptosis of glomerular epithelial cells (podocytes). Loss of podocytes contributes to albuminuria, a major risk factor for progression of kidney disease. Here, we show that HG inactivates AMP-activated protein kinase (AMPK), up-regulates Nox4, enhances NADPH oxidase activity, and induces podocyte apoptosis. Activation of AMPK blocked HG-induced expression of Nox4, NADPH oxidase activity, and apoptosis. We also identified the tumor suppressor protein p53 as a mediator of podocyte apoptosis in cells exposed to HG. Inactivation of AMPK by HG up-regulated the expression and phosphorylation of p53, and p53 acted downstream of Nox4. To investigate the mechanism of podocyte apoptosis in vivo, we used OVE26 mice, a model of type 1 diabetes. Glomeruli isolated from these mice showed decreased phosphorylation of AMPK and enhanced expression of Nox4 and p53. Pharmacologic activation of AMPK by 5-aminoimidazole-4-carboxamide-1-riboside in OVE26 mice attenuated Nox4 and p53 expression. Administration of 5-aminoimidazole-4-carboxamide-1-riboside also prevented renal hypertrophy, glomerular basement thickening, foot process effacement, and podocyte loss, resulting in marked reduction in albuminuria. Our results uncover a novel function of AMPK that integrates metabolic input to Nox4 and provide new insight for activation of p53 to induce podocyte apoptosis. The data indicate the potential therapeutic utility of AMPK activators to block Nox4 and reactive oxygen species generation and to reduce urinary albumin excretion in type 1 diabetes. C1 [Abboud, Hanna E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. [Block, Karen; Kasinath, Balakuntalam S.; Ghosh-Choudhury, Goutam; Barnes, Jeffrey L.; Abboud, Hanna E.] Vet Affairs Res, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Goutam] S Texas Vet Healthcare Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Abboud, HE (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM abboud@uthscsa.edu OI Gorin, Yves/0000-0003-4048-6925 FU National Institutes of Health [CA131272, R01 DK079996, R01 DK50190, R01 DK080106, DK-R01-078971]; George O'Brien Kidney Center [DK061597]; National Kidney Foundation; Juvenile Diabetes Research Foundation; Veterans Affairs FX This work was supported, in whole or in part, by National Institutes of Health Grants CA131272 (to K. B.), R01 DK079996 (to Y. G.), R01 DK50190 (to G. G.-C.), R01 DK080106 (to J. L. B.), and DK-R01-078971 (to H. E. A.) and George O'Brien Kidney Center-Morphology Core Grant DK061597 (to J. L. B.). This work was also supported by a National Kidney Foundation postdoctoral fellowship grant and a Juvenile Diabetes Research Foundation grant (to A. A. E.), a Juvenile Diabetes Research Foundation regular research grant (to Y. G.), and a Juvenile Diabetes Research Foundation grant and a Veterans Affairs merit review grant (to H. E. A.). NR 71 TC 91 Z9 94 U1 2 U2 8 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 26 PY 2010 VL 285 IS 48 BP 37503 EP 37512 DI 10.1074/jbc.M110.136796 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 682ST UT WOS:000284424000042 PM 20861022 ER PT J AU Mesa, RA Yao, XP Cripe, LD Li, CY Litzow, M Paietta, E Rowe, JM Tefferi, A Tallman, MS AF Mesa, Ruben A. Yao, Xiaopan Cripe, Larry D. Li, Chin Yang Litzow, Mark Paietta, Elisabeth Rowe, Jacob M. Tefferi, Ayalew Tallman, Martin S. TI Lenalidomide and prednisone for myelofibrosis: Eastern Cooperative Oncology Group (ECOG) phase 2 trial E4903 SO BLOOD LA English DT Article ID INTERNATIONAL-WORKING-GROUP; MYELOID METAPLASIA; SCORING SYSTEM; THALIDOMIDE; EFFICACY; CRITERIA; THERAPY AB A multicenter Eastern Cooperative Group (ECOG) phase 2 trial assessed whether adding prednisone to lenalidomide would improve previously reported responses in persons with myelofibrosis (MF). Forty-eight subjects with anemia (42 evaluable) received lenalidomide, 10 mg/d, with a 3-month low-dose prednisone taper. Ten subjects received 3 months, and 25 received 6 months of therapy. Myelosup- pression was the main toxicity with 88% with >= grade 3 hematologic toxicity and 45% >= grade 3 nonhematologic toxicity. There were responses in 10 subjects (23%) using the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT)-defined clinical improvement of anemia in 8 (19%) and/or decreased spleen size in 4 (10%). Serial bone marrow analysis showed no resolution of disease-related fibrosis or angiogenesis. With a median follow-up of 2.3 years, 23 subjects are alive. Lenalidomide and prednisone for myelofibrosis evaluated through a multicentered-cooperative group mechanism is only modestly active and myelosuppresive. This study was registered at http://clinicaltrials.gov as NCT00227591. (Blood. 2010;116(22):4436-4438) C1 [Mesa, Ruben A.] Mayo Clin, Div Hematol & Oncol, Scottsdale, AZ 85259 USA. [Yao, Xiaopan] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cripe, Larry D.] Indiana Univ, Indianapolis, IN 46204 USA. [Li, Chin Yang; Litzow, Mark; Tefferi, Ayalew] Mayo Clin, Rochester, MN USA. [Paietta, Elisabeth] Montefiore Med Ctr, Bronx, NY 10467 USA. [Rowe, Jacob M.] Technion Israel Inst Technol, Rambam Med Ctr, Haifa, Israel. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Mesa, RA (reprint author), Mayo Clin, Div Hematol & Oncol, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA. EM mesa.ruben@mayo.edu FU NCI NIH HHS [U24 CA114737] NR 14 TC 65 Z9 70 U1 1 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 25 PY 2010 VL 116 IS 22 BP 4436 EP 4438 DI 10.1182/blood-2010-05-287417 PG 3 WC Hematology SC Hematology GA 685BT UT WOS:000284599900015 PM 20651074 ER PT J AU Hoang, B Frost, P Shi, YJ Belanger, E Benavides, A Pezeshkpour, G Cappia, S Guglielmelli, T Gera, J Lichtenstein, A AF Hoang, Bao Frost, Patrick Shi, Yijiang Belanger, Eileen Benavides, Angelica Pezeshkpour, Gholam Cappia, Susanna Guglielmelli, Tommasina Gera, Joseph Lichtenstein, Alan TI Targeting TORC2 in multiple myeloma with a new mTOR kinase inhibitor SO BLOOD LA English DT Article ID MAMMALIAN TARGET; AKT KINASE; PHASE-I; RAPAMYCIN; CELLS; PHOSPHORYLATION; TRANSLATION; MUTATIONS; RICTOR; DEXAMETHASONE AB Although preclinical work with rapalogs suggests potential in treatment of multiple myeloma (MM), they have been less successful clinically. These drugs allostearically inhibit the mammalian target of rapamycin kinase primarily curtailing activity of the target of rapamycin complex (TORC)1. To assess if the mammalian target of rapamycin within the TORC2 complex could be a better target in MM, we tested a new agent, pp242, which prevents activation of TORC2 as well as TORC1. Although comparable to rapamy-cin against phosphorylation of the TORC1 substrates p70S6kinase and 4E-BP-1, pp242 could also inhibit phosphorylation of AKT on serine 473, a TORC2 substrate, while rapamycin was ineffective. pp242 was also more effective than rapamycin in achieving cytoreduction and apoptosis in MM cells. In addition, pp242 was an effective agent against primary MM cells in vitro and growth of 8226 cells in mice. Knockdown of the TORC2 complex protein, rictor, was deleterious to MM cells further supporting TORC2 as the critical target for pp242. TORC2 activation was frequently identified in primary specimens by immunostaining for AKT phosphorylation on serine 473. Potential mechanisms of up-regulated TORC2 activity in MM were stimulation with interleukin-6 or insulin-like growth factor 1, and phosphatase and tensin homolog or RAS alterations. Combining pp242 with bortezomib led to synergistic anti-MM effects. These results support TORC2 as a therapeutic target in MM. (Blood. 2010; 116(22): 4560-4568) C1 [Hoang, Bao; Frost, Patrick; Shi, Yijiang; Belanger, Eileen; Benavides, Angelica; Gera, Joseph; Lichtenstein, Alan] Univ Calif Los Angeles, Div Hematol Oncol, Greater Los Angeles Vet Adm VA Healthcare Ctr, Los Angeles, CA USA. [Hoang, Bao; Frost, Patrick; Shi, Yijiang; Belanger, Eileen; Benavides, Angelica; Gera, Joseph; Lichtenstein, Alan] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. [Pezeshkpour, Gholam] Greater Los Angeles VA Healthcare Ctr, Dept Pathol, Los Angeles, CA USA. [Pezeshkpour, Gholam] Univ So Calif, Sch Med, Los Angeles, CA USA. [Cappia, Susanna; Guglielmelli, Tommasina] Univ Turin, Turin, Italy. [Cappia, Susanna; Guglielmelli, Tommasina] San Luigi Hosp, Turin, Italy. RP Lichtenstein, A (reprint author), W Los Angeles Vet Adm Hosp, W111H,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM alan.lichtenstein@med.va.gov OI Frost, Patrick/0000-0003-3348-5983 FU National Institutes of Health [RO1 CA109312, RO1 CA111448]; Department of Defense; Veterans Administration FX This work was supported by National Institutes of Health grants RO1 CA109312 and RO1 CA111448 and research funds of the Department of Defense and Veterans Administration. NR 37 TC 61 Z9 66 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 25 PY 2010 VL 116 IS 22 BP 4560 EP 4568 DI 10.1182/blood-2010-05-285726 PG 9 WC Hematology SC Hematology GA 685BT UT WOS:000284599900029 PM 20686120 ER PT J AU Shah, ND Montori, VM Krumholz, HM Tu, K Alexander, GC Jackevicius, CA AF Shah, Nilay D. Montori, Victor M. Krumholz, Harlan M. Tu, Karen Alexander, G. Caleb Jackevicius, Cynthia A. TI Responding to an FDA Warning - Geographic Variation in the Use of Rosiglitazone. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Shah, Nilay D.; Montori, Victor M.] Mayo Clin, Knowledge & Encounter Res Unit, Rochester, MN 55905 USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, New Haven, CT USA. [Krumholz, Harlan M.] Yale New Haven Med Ctr, New Haven, CT 06504 USA. [Tu, Karen; Jackevicius, Cynthia A.] Univ Toronto, Toronto, ON, Canada. [Tu, Karen] Toronto Western Hosp, Family Hlth Team, Toronto, ON M5T 2S8, Canada. [Tu, Karen; Jackevicius, Cynthia A.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Alexander, G. Caleb] Univ Chicago, Chicago, IL 60637 USA. [Alexander, G. Caleb] Univ Illinois, Chicago Sch Pharm, Chicago, IL USA. [Jackevicius, Cynthia A.] Western Univ Hlth Sci, Los Angeles, CA USA. [Jackevicius, Cynthia A.] Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Shah, ND (reprint author), Mayo Clin, Knowledge & Encounter Res Unit, Rochester, MN 55905 USA. OI Montori, Victor/0000-0003-0595-2898 NR 6 TC 36 Z9 36 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 25 PY 2010 VL 363 IS 22 BP 2081 EP 2084 DI 10.1056/NEJMp1011042 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 684XE UT WOS:000284587800001 PM 21083379 ER PT J AU Stankovic, KM Juliano, AF Hasserjian, RP AF Stankovic, Konstantina M. Juliano, Amy F. Hasserjian, Robert P. TI Case 36-2010: A 50-Year-Old Woman with Pain and Loss of Hearing in the Left Ear SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE MYELOID-LEUKEMIA; OTOLOGIC MANIFESTATIONS; GRANULOCYTIC-SARCOMA; TEMPORAL BONE; POLYCYTHEMIA-VERA; INVOLVEMENT; HYDROXYUREA C1 [Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Juliano, Amy F.] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. [Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Juliano, Amy F.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Hasserjian, Robert P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Stankovic, KM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 29 TC 0 Z9 0 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 25 PY 2010 VL 363 IS 22 BP 2146 EP 2156 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 684XE UT WOS:000284587800011 PM 21105797 ER PT J AU Sebastian, C Mostoslavsky, R AF Sebastian, Carlos Mostoslavsky, Raul TI SIRT3 in Calorie Restriction: Can You Hear Me Now? SO CELL LA English DT Editorial Material ID SIRTUINS; PHYSIOLOGY C1 [Sebastian, Carlos; Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Mostoslavsky, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. EM rmostoslavsky@mgh.harvard.edu FU NIDDK NIH HHS [R01 DK088190]; NIGMS NIH HHS [R01 GM093072] NR 10 TC 11 Z9 13 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD NOV 24 PY 2010 VL 143 IS 5 BP 667 EP 668 DI 10.1016/j.cell.2010.11.009 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 684VX UT WOS:000284583500006 PM 21111225 ER PT J AU Gomez-del Arco, P Kashiwagi, M Jackson, AF Naito, T Zhang, JW Liu, FF Kee, B Vooijs, M Radtke, F Redondo, JM Georgopoulos, K AF Gomez-del Arco, Pablo Kashiwagi, Mariko Jackson, Audrey F. Naito, Taku Zhang, Jiangwen Liu, Feifei Kee, Barbara Vooijs, Marc Radtke, Freddy Miguel Redondo, Juan Georgopoulos, Katia TI Alternative Promoter Usage at the Notch1 Locus Supports Ligand-Independent Signaling in T Cell Development and Leukemogenesis SO IMMUNITY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; IKAROS GENE; GENOME-WIDE; C-MYC; CHROMATIN; MICE; FATE; DIFFERENTIATION; TRANSCRIPTION; MECHANISMS AB Loss of the transcription factor Ikaros is correlated with Notch receptor activation in T cell acute lymphoblastic leukemia (T-ALL). However, the mechanism remains unknown. We identified promoters in Notch1 that drove the expression of Notch1 proteins in the absence of a ligand. Ikaros bound to both canonical and alternative Notch1 promoters and its loss increased permissive chromatin, facilitating recruitment of transcription regulators. At early stages of leukemogenesis, increased basal expression from the canonical and 5'-alternative promoters initiated a feedback loop, augmenting Notch1 signaling. Ikaros also repressed intragenic promoters for ligand-independent Notch1 proteins that are cryptic in wild-type cells, poised in preleukemic cells, and active in leukemic cells. Only ligand-independent Notch1 isoforms were required for Ikaros-mediated leukemogenesis. Notch1 alternative-promoter usage was observed during T cell development and T-ALL progression. Thus, a network of epigenetic and transcriptional regulators controls conventional and unconventional Notch signaling during normal development and leukemogenesis. C1 [Gomez-del Arco, Pablo; Kashiwagi, Mariko; Jackson, Audrey F.; Naito, Taku; Liu, Feifei; Georgopoulos, Katia] Harvard Univ, Sch Med, Mass Gen Hosp, CBRC, Boston, MA 02129 USA. [Gomez-del Arco, Pablo; Miguel Redondo, Juan] CNIC, Vasc Biol & Inflammat Dept, Madrid 28029, Spain. [Gomez-del Arco, Pablo] UAM, Dept Biol Mol, Madrid 28049, Spain. [Zhang, Jiangwen] Harvard Univ, Sch Med, FAS Ctr Syst Biol, Cambridge, MA 02138 USA. [Kee, Barbara] Univ Chicago, Dept Pathol & Med, Chicago, IL 60637 USA. [Vooijs, Marc] Maastricht Univ, Med Ctr, Dept Radiat Oncol MAASTRO, GROW Sch Oncol & Dev Biol, NL-6200 MD Maastricht, Netherlands. [Radtke, Freddy] Univ Lausanne, Ludwig Inst Canc Res, CH-1066 Epalinges, Switzerland. RP Georgopoulos, K (reprint author), Harvard Univ, Sch Med, Mass Gen Hosp, CBRC, Boston, MA 02129 USA. EM katia.georgopoulos@cbrc2.mgh.harvard.edu RI Zhang, Jiangwen/A-7654-2013; Redondo, Juan Miguel/H-6351-2015; Gomez-del Arco, Pablo/L-2728-2013 OI Redondo, Juan Miguel/0000-0001-5779-9122; Gomez-del Arco, Pablo/0000-0001-6748-7157 FU European Research Council under the European Community [208259]; Spanish Ministry of Science and Innovation; Pro-CNIC Foundation; Ramon y Cajal Grant; NIH; [NIH-R01-AI1 380342]; [SAF2009-.10708] FX This work was supported by NIH-R01-AI1 380342 to K.G and by SAF2009-.10708 to CNIC and J.M.R and by the European Research Council under the European Community Seventh Framework Programme (FP7/2007-2013)/ERC Grant 208259 to M.V. The CNIC is supported by the Spanish Ministry of Science and Innovation and the Pro-CNIC Foundation. P.G.A. is supported by a Ramon y Cajal Grant and A.F.J. by an NIH training grant in Transplantation Biology. We thank T. Honjo, R. Kopan, A. Ferrando, W. Pear, M.L. Toribio, F. Gounari, and M. Dose for providing reagents used in this study and to B. Czyzewski for mouse husbandry. We also thank B. Morgan, M. Dose, I. Joshi and T. Yoshida for review of the manuscript. NR 55 TC 44 Z9 44 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV 24 PY 2010 VL 33 IS 5 BP 685 EP 698 DI 10.1016/j.immuni.2010.11.008 PG 14 WC Immunology SC Immunology GA 704VB UT WOS:000286082600008 PM 21093322 ER PT J AU Neves, P Lampropoulou, V Calderon-Gomez, E Roch, T Stervbo, U Shen, P Kuhl, AA Loddenkemper, C Haury, M Nedospasov, SA Kaufmann, SHE Steinhoff, U Calado, DP Fillatreau, S AF Neves, Patricia Lampropoulou, Vicky Calderon-Gomez, Elisabeth Roch, Toralf Stervbo, Ulrik Shen, Ping Kuehl, Anja A. Loddenkemper, Christoph Haury, Matthias Nedospasov, Sergei A. Kaufmann, Stefan H. E. Steinhoff, Ulrich Calado, Dinis P. Fillatreau, Simon TI Signaling via the MyD88 Adaptor Protein in B Cells Suppresses Protective Immunity during Salmonella typhimurium Infection SO IMMUNITY LA English DT Article ID GAMMA-INTERFERON PRODUCTION; NATURAL-KILLER-CELLS; DENDRITIC CELLS; DEFICIENT MICE; T-CELLS; TOLERANCE INDUCTION; IFN-GAMMA; LISTERIA-MONOCYTOGENES; BACTERIAL CLEARANCE; HUMORAL IMMUNITY AB The myeloid differentiation primary response gene 88 (Myd88) is critical for protection against pathogens. However, we demonstrate here that MyD88 expression in B cells inhibits resistance of mice to Salmonella typhimurium infection. Selective deficiency of Myd88 in B cells improved control of bacterial replication and prolonged survival of the infected mice. The B cell-mediated suppressive pathway was even more striking after secondary challenge. Upon vaccination, mice lacking Myd88 in B cells became completely resistant against this otherwise lethal infection, whereas control mice were only partially protected. Analysis of immune defenses revealed that MyD88 signaling in B cells suppressed three crucial arms of protective immunity: neutrophils, natural killer cells, and inflammatory T cells. We further show that interleukin-10 is an essential mediator of these inhibitory functions of B cells. Collectively, our data identify a role for MyD88 and B cells in regulation of cellular mechanisms of protective immunity during infection. C1 [Neves, Patricia; Lampropoulou, Vicky; Calderon-Gomez, Elisabeth; Roch, Toralf; Stervbo, Ulrik; Shen, Ping; Nedospasov, Sergei A.; Fillatreau, Simon] Leibniz Inst, Deutsch Rheuma Forshungszentrum, D-10117 Berlin, Germany. [Kuehl, Anja A.; Loddenkemper, Christoph] Charite, Inst Pathol, RCIS, D-12200 Berlin, Germany. [Haury, Matthias; Calado, Dinis P.] Inst Gulbenkian Ciencias, P-2780156 Oeiras, Portugal. [Nedospasov, Sergei A.] VA Engelhardt Mol Biol Inst, Moscow 119991, Russia. [Kaufmann, Stefan H. E.; Steinhoff, Ulrich] Max Planck Inst Infect Biol, D-10117 Berlin, Germany. [Calado, Dinis P.] Harvard Univ, Sch Med, Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Calado, Dinis P.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Fillatreau, S (reprint author), Leibniz Inst, Deutsch Rheuma Forshungszentrum, Charitepl 1, D-10117 Berlin, Germany. EM fillatreau@drfz.de RI Nedospasov, Sergei/J-5936-2013; Roch, Toralf/K-9531-2013; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016; Kaufmann, Stefan HE/I-5454-2014; OI Kaufmann, Stefan HE/0000-0001-9866-8268; Calderon-Gomez, Elisabeth/0000-0002-0675-0959; Stervbo, Ulrik/0000-0002-2831-8868 FU Deutsche Forschungsgemeinschaft [SFB-650, SFB633, DFG FI1238/1-1]; Hertie Stiftung FX We thank C. Romagnani, P. Boudinot, and O. Neyrolles for critical reading of the manuscript. We thank O. Neyrolles for help with infection experiments and S. Spieckermann, K. Grollich, and I. Eickmeier for excellent help and technical assistance. We thank A. Radbruch, F. Melchers, I. MacLenann, C. Berek, A. Hamann, U. Hoffmann, T. Barr, and D. Gray for helpful discussions and advices. We thank E. Schott for allowing us to perform the ALT and AST measurements in his laboratory, and S. Akira for providing the Myd88-/-, TIr2-/-, and Tlr4-/- mice. Further enquiries for the IL-10.eGFP reporter mice should be addressed to D. Calado (calado@idi.harvard.edu). This work was supported by the Deutsche Forschungsgemeinschaft (SFB-650, SFB633, and DFG FI1238/1-1) and the Hertie Stiftung. NR 59 TC 112 Z9 118 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV 24 PY 2010 VL 33 IS 5 BP 777 EP 790 DI 10.1016/j.immuni.2010.10.016 PG 14 WC Immunology SC Immunology GA 704VB UT WOS:000286082600015 PM 21093317 ER PT J AU Lubitz, SA Yin, XY Fontes, JD Magnani, JW Rienstra, M Pai, M Villalon, ML Vasan, RS Pencina, MJ Levy, D Larson, MG Ellinor, PT Benjamin, EJ AF Lubitz, Steven A. Yin, Xiaoyan Fontes, Joao D. Magnani, Jared W. Rienstra, Michiel Pai, Manju Villalon, Mark L. Vasan, Ramachandran S. Pencina, Michael J. Levy, Daniel Larson, Martin G. Ellinor, Patrick T. Benjamin, Emelia J. TI Association Between Familial Atrial Fibrillation and Risk of New-Onset Atrial Fibrillation SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MIDDLE-AGED ADULTS; CARDIOVASCULAR-DISEASE; COMMON VARIANTS; PR INTERVAL; AGGREGATION; HISTORY; REGRESSION; COHORT; ZFHX3; SCORE AB Context Although the heritability of atrial fibrillation (AF) is established, the contribution of familial AF to predicting new-onset AF remains unknown. Objective To determine whether familial occurrence of AF is associated with new-onset AF beyond established risk factors. Design, Setting, and Participants The Framingham Heart Study, a prospective community-based cohort study started in 1948. Original and Offspring Cohort participants were aged at least 30 years, were free of AF at the baseline examination, and had at least 1 parent or sibling enrolled in the study. The 4421 participants in this analysis (mean age, 54 [SD, 13] years; 54% women) were followed up through December 31, 2007. Main Outcome Measures Incremental predictive value of incorporating different features of familial AF (any familial AF, premature familial AF [onset <65 years old], number of affected relatives, and youngest age of onset in a relative) into a risk model for new-onset AF. Results Across 11 971 examinations during the period 1968-2007, 440 participants developed AF. Familial AF occurred among 1185 participants (26.8%) and premature familial AF occurred among 351 participants (7.9%). Atrial fibrillation occurred more frequently among participants with familial AF than without familial AF (unadjusted absolute event rates of 5.8% and 3.1%, respectively). The association was not attenuated by adjustment for AF risk factors (multivariable-adjusted hazard ratio, 1.40; 95% confidence interval [CI], 1.13-1.74) or reported AF-related genetic variants. Among the different features of familial AF examined, premature familial AF was associated with improved discrimination beyond traditional risk factors to the greatest extent (traditional risk factors, C statistic, 0.842 [95% CI, 0.826-0.858]; premature familial AF, C statistic, 0.846 [95% CI, 0.831-0.862]; P=.004). Modest changes in integrated discrimination improvement were observed with premature familial AF (2.1%). Net reclassification improvement (assessed using 8-year risk thresholds of <5%, 5%-10%, and >10%) did not change significantly with premature familial AF (index statistic, 0.011; 95% CI, -0.021 to 0.042; P=.51), although categoryless net reclassification was improved (index statistic, 0.127; 95% CI, 0.064-0.189; P=.009). Conclusions In this cohort, familial AF was associated with an increased risk of AF that was not attenuated by adjustment for AF risk factors including genetic variants. Assessment of premature familial AF was associated with a very slight increase in predictive accuracy compared with traditional risk factors. JAMA. 2010;304(20):2263-2269 www.jama.com C1 [Yin, Xiaoyan; Fontes, Joao D.; Magnani, Jared W.; Vasan, Ramachandran S.; Pencina, Michael J.; Levy, Daniel; Larson, Martin G.; Benjamin, Emelia J.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Lubitz, Steven A.; Rienstra, Michiel; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Lubitz, Steven A.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Fontes, Joao D.; Magnani, Jared W.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. [Pai, Manju; Villalon, Mark L.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Pencina, Michael J.; Larson, Martin G.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Benjamin, Emelia J.] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. RP Benjamin, EJ (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA. EM emelia@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336; Rienstra, Michiel/0000-0002-2581-070X FU National Institutes of Health (NIH) [T32HL007575, 6R01-NS17950, HL092577, R01AG028321, RC1-HL01056, 1R01HL102214, DA027021, HL104156]; American Heart Association [09FTF2190028]; Netherlands Organization for Scientific Research [825.09.020] FX Dr Lubitz was supported by a National Institutes of Health (NIH) training grant in the Epidemiology of Cardiovascular Disease (grant T32HL007575). Dr Magnani is supported by American Heart Association grant 09FTF2190028. Dr Rienstra is supported by a Rubicon grant from the Netherlands Organization for Scientific Research (grant 825.09.020). Dr Benjamin is supported by NIH grant 6R01-NS17950. This work was supported by grants from the NIH to Drs Benjamin and Ellinor (grant HL092577), Dr Benjamin (grants R01AG028321, RC1-HL01056, and 1R01HL102214), and Dr Ellinor (grants DA027021 and HL104156). NR 33 TC 103 Z9 104 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 24 PY 2010 VL 304 IS 20 BP 2263 EP 2269 DI 10.1001/jama.2010.1690 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 684KI UT WOS:000284548400025 PM 21076174 ER PT J AU Gaziano, JM AF Gaziano, J. Michael TI The Evolution of Population Science Advent of the Mega Cohort SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Gaziano, J. Michael] VA Boston Healthcare Syst, MAVERIC, Boston, MA 02130 USA. [Gaziano, J. Michael] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Aging, Boston, MA 02115 USA. [Gaziano, J. Michael] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Cardiovasc Med, Boston, MA 02115 USA. [Gaziano, J. Michael] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Prevent Med, Boston, MA 02115 USA. RP Gaziano, JM (reprint author), VA Boston Healthcare Syst, MAVERIC MAV 151, 150 S Huntington Ave, Boston, MA 02130 USA. EM jmgaziano@partners.org NR 10 TC 10 Z9 11 U1 0 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 24 PY 2010 VL 304 IS 20 BP 2288 EP 2289 DI 10.1001/jama.2010.1691 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 684KI UT WOS:000284548400028 PM 21098773 ER PT J AU Powner, MW Sutherland, JD Szostak, JW AF Powner, Matthew W. Sutherland, John D. Szostak, Jack W. TI Chemoselective Multicomponent One-Pot Assembly of Purine Precursors in Water SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PRIMORDIAL INFORMATIONAL OLIGOMERS; POTENTIALLY PREBIOTIC SYNTHESIS; AMINO-ACIDS; RECOGNITION ELEMENTS; ALPHA-AMINONITRILES; CHEMICAL EVOLUTION; STRECKER SYSTEMS; HYDROGEN CYANIDE; AMMONIUM CYANIDE; CODED PEPTIDES AB The recent development of a sequential, high-yielding route to activated pyrimidine nucleotides, under conditions thought to be prebiotic, is an encouraging step toward the greater goal of a plausible prebiotic pathway to RNA and the potential for an RNA world. However, this synthesis has led to a disparity in the methodology available for stepwise construction of the canonical pyrimidine and purine nucleotides. To address this problem, and further explore prebiotically accessible chemical systems, we have developed a high-yielding, aqueous, one-pot, multicomponent reaction that tethers masked-sugar moieties to prebiotically plausible purine precursors. A pH-dependent three-component reaction system has been discovered that utilizes key nucleotide synthons 2-aminooxazole and 5-aminoimidazoles, which allows the first divergent purine/pyrimidine synthesis to be proposed. Due to regiospecific aminoimidazole tethering, the pathway allows N9 purination only, thus suggesting the first prebiotically plausible mechanism for regiospecific N9 purination. C1 [Powner, Matthew W.; Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Powner, Matthew W.; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Powner, Matthew W.; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Sutherland, John D.] MRC Lab Mol Biol, Cambridge CB2 OQH, England. RP Powner, MW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, 185 Cambridge St, Boston, MA 02114 USA. EM powner@molbio.mgh.harvard.edu OI Powner, Matthew/0000-0002-6368-3190 FU Harvard Origins Initiative FX M.W.P was supported by a Fellowship from the Harvard Origins Initiative. J.W.S is an investigator of the Howard Hughes Medical Institute. The authors thank Dr. Na Zheng for assistance with NMR spectroscopy and Dr. Shao-Liang Zheng, of the Harvard X-ray Crystallography Centre, for X-ray diffraction and analysis. NR 64 TC 64 Z9 67 U1 3 U2 49 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 24 PY 2010 VL 132 IS 46 BP 16677 EP 16688 DI 10.1021/ja108197s PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA 687QC UT WOS:000284792000061 PM 21043502 ER PT J AU Del Bianco, C Vedenko, A Choi, SH Berger, MF Shokri, L Bulyk, ML Blacklow, SC AF Del Bianco, Cristina Vedenko, Anastasia Choi, Sung Hee Berger, Michael F. Shokri, Leila Bulyk, Martha L. Blacklow, Stephen C. TI Notch and MAML-1 Complexation Do Not Detectably Alter the DNA Binding Specificity of the Transcription Factor CSL SO PLOS ONE LA English DT Article ID C. ELEGANS; IN-VITRO; MICROARRAYS; MASTERMIND; SEQUENCE; COACTIVATOR; RECOGNITION; ACTIVATION; REPRESSOR; NETWORK AB Background: Canonical Notch signaling is initiated when ligand binding induces proteolytic release of the intracellular part of Notch (ICN) from the cell membrane. ICN then travels into the nucleus where it drives the assembly of a transcriptional activation complex containing the DNA-binding transcription factor CSL, ICN, and a specialized co-activator of the Mastermind family. A consensus DNA binding site motif for the CSL protein was previously defined using selection-based methods, but whether subsequent association of Notch and Mastermind-like proteins affects the DNA binding preferences of CSL has not previously been examined. Principal Findings: Here, we utilized protein-binding microarrays (PBMs) to compare the binding site preferences of isolated CSL with the preferred binding sites of CSL when bound to the CSL-binding domains of all four different human Notch receptors. Measurements were taken both in the absence and in the presence of Mastermind-like-1 (MAML1). Our data show no detectable difference in the DNA binding site preferences of CSL before and after loading of Notch and MAML1 proteins. Conclusions/Significance: These findings support the conclusion that accrual of Notch and MAML1 promote transcriptional activation without dramatically altering the preferred sites of DNA binding, and illustrate the potential of PBMs to analyze the binding site preferences of multiprotein-DNA complexes. C1 [Del Bianco, Cristina; Choi, Sung Hee; Blacklow, Stephen C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Del Bianco, Cristina; Choi, Sung Hee; Bulyk, Martha L.; Blacklow, Stephen C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Vedenko, Anastasia; Berger, Michael F.; Shokri, Leila; Bulyk, Martha L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Vedenko, Anastasia; Berger, Michael F.; Shokri, Leila; Bulyk, Martha L.; Blacklow, Stephen C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Berger, Michael F.; Bulyk, Martha L.; Blacklow, Stephen C.] Harvard Univ, Comm Higher Degrees Biophys, Cambridge, MA 02138 USA. [Bulyk, Martha L.; Blacklow, Stephen C.] Harvard Univ, Sch Med, Div Hlth Sci & Technol, Boston, MA USA. [Blacklow, Stephen C.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Del Bianco, C (reprint author), Univ Trent, Cibio Ctr Interdipartimentale Biol Integrata, Trento, Italy. EM mlbulyk@receptor.med.harvard.edu; sblacklow@partners.org RI Del Bianco, Cristina/J-4665-2012 FU National Institutes of Health/National Human Genome Research Institute [R01 HG003985, R01 CA092433] FX This work was funded by grant # R01 HG003985 from National Institutes of Health/National Human Genome Research Institute to M. L. B. and grant # R01 CA092433 to S. C. B. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 13 Z9 13 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 24 PY 2010 VL 5 IS 11 AR e15034 DI 10.1371/journal.pone.0015034 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 684TK UT WOS:000284572000021 PM 21124806 ER PT J AU Geng, EH Bwana, MB Kabakyenga, J Muyindike, W Emenyonu, NI Musinguzi, N Mugyenyi, P Martin, JN Bangsberg, DR AF Geng, Elvin H. Bwana, Mwebesa B. Kabakyenga, Jerome Muyindike, Winnie Emenyonu, Nneka I. Musinguzi, Nicholas Mugyenyi, Peter Martin, Jeffrey N. Bangsberg, David R. TI Diminishing Availability of Publicly Funded Slots for Antiretroviral Initiation among HIV-Infected ART-Eligible Patients in Uganda SO PLOS ONE LA English DT Article ID SUB-SAHARAN AFRICA; ADHERENCE; IMPACT AB Background: The impact of flat-line funding in the global scale up of antiretroviral therapy (ART) for HIV-infected patients in Africa has not yet been well described. Methods: We evaluated ART-eligible patients and patients starting ART at a prototypical scale up ART clinic in Mbarara, Uganda between April 1, 2009 and May 14, 2010 where four stakeholders sponsor treatment - two PEPFAR implementing organizations, the Ugandan Ministry of Health - Global Fund (MOH-GF) and a private foundation named the Family Treatment Fund (FTF). We assessed temporal trends in the number of eligible patients, the number starting ART and tabulated the distribution of the stakeholders supporting ART initiation by month and quartile of time during this interval. We used survival analyses to assess changes in the rate of ART initiation over calendar time. Findings: A total of 1309 patients who were eligible for ART made visits over the 14 month period of the study and of these 819 started ART. The median number of ART eligible patients each month was 88 (IQR: 74 to 115). By quartile of calendar time, PEPFAR and MOH sponsored 290, 192, 180, and 49 ART initiations whereas the FTF started 1, 2, 1 and 104 patients respectively. By May of 2010 (the last calendar month of observation) FTF sponsored 88% of all ART initiations. Becoming eligible for ART in the 3(rd) (HR = 0.58, 95% 0.45-0.74) and 4(th) quartiles (HR = 0.49, 95% CI: 0.36-0.65) was associated with delay in ART initiation compared to the first quartile in multivariable analyses. Interpretation: During a period of flat line funding from multinational donors for ART programs, reductions in the number of ART initiations by public programs (i.e., PEPFAR and MOH-GF) and delays in ART initiation became apparent at the a large prototypical scale-up ART clinic in Uganda. C1 [Geng, Elvin H.; Martin, Jeffrey N.] San Francisco Gen Hosp, Dept Med, Div HIV AIDS, San Francisco, CA 94110 USA. [Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Bwana, Mwebesa B.; Kabakyenga, Jerome; Muyindike, Winnie; Emenyonu, Nneka I.; Musinguzi, Nicholas; Mugyenyi, Peter; Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Emenyonu, Nneka I.; Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst,Massachusetts Inst Technol & Harvard,C, Boston, MA USA. RP Geng, EH (reprint author), San Francisco Gen Hosp, Dept Med, Div HIV AIDS, San Francisco, CA 94110 USA. EM dbangsberg@partners.org FU National Institutes of Health [K23 AI084544, U01 AI069911, R01 MH054907, P30 AI027763, K24 MH87227]; Mark and Lisa Schwartz Family Foundation; United States President's Emergency Plan for AIDS Relief (PEPFAR) FX National Institutes of Health (K23 AI084544, U01 AI069911, R01 MH054907, P30 AI027763, K24 MH87227), The Mark and Lisa Schwartz Family Foundation, and the United States President's Emergency Plan for AIDS Relief (PEPFAR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 14 TC 26 Z9 26 U1 2 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 24 PY 2010 VL 5 IS 11 AR e14098 DI 10.1371/journal.pone.0014098 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 684TK UT WOS:000284572000004 PM 21124842 ER PT J AU Cannon, CP Shah, S Dansky, HM Davidson, M Brinton, EA Gotto, AM Stepanavage, M Liu, SX Gibbons, P Ashraf, TB Zafarino, J Mitchel, YB Barter, P AF Cannon, Christopher P. Shah, Sukrut Dansky, Hayes M. Davidson, Michael Brinton, Eliot A. Gotto, Antonio M., Jr. Stepanavage, Michael Liu, Sherry Xueyu Gibbons, Patrice Ashraf, Tanya B. Zafarino, Jennifer Mitchel, Yale B. Barter, Philip TI Primary Results of the DEFINE trial: Determining the EFficacy and Tolerability of CETP INhibition With AnacEtrapid SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Scientific Sessions 2010 on Resuscitation Science Symposium CY NOV 13-17, 2010 CL Chicago, IL SP Amer Heart Assoc C1 [Cannon, Christopher P.] TIMI Study Grp, Boston, MA USA. [Shah, Sukrut; Dansky, Hayes M.; Stepanavage, Michael; Liu, Sherry Xueyu; Gibbons, Patrice; Ashraf, Tanya B.; Zafarino, Jennifer; Mitchel, Yale B.] Merck, Rahway, NJ USA. [Davidson, Michael] Univ Chicago Med Cente, Chicago, IL USA. [Brinton, Eliot A.] Univ Utah, Sch Med, Salt Lake City, UT USA. [Gotto, Antonio M., Jr.] Cornell Med Sch, New York, NY USA. [Barter, Philip] Heart Rsch Inst, Sydney, NSW, 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 23 PY 2010 VL 122 IS 21 BP 2219 EP 2220 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 683JJ UT WOS:000284471800035 ER PT J AU Januzzi, J Rehman, SU Mohammed, AA Bhardwaj, A Barajas, L Barajas, J Kim, HN Baggish, AL Weiner, RB Chen-Tournoux, AA Marshall, JE Moore, SA Carlson, W Lewis, GD Shin, J Sullivan, D Parks, K Wang, T Gregory, SA Uthamalingam, S Semigran, MJ AF Januzzi, James Rehman, Shafiq U. Mohammed, Asim A. Bhardwaj, Anju Barajas, Linda Barajas, Justine Kim, Han-Na Baggish, Aaron L. Weiner, Rory B. Chen-Tournoux, Annabel A. Marshall, Jane E. Moore, Stephanie A. Carlson, William Lewis, Gregory D. Shin, Jordan Sullivan, Dorothy Parks, Kimberly Wang, Thomas Gregory, Shawn A. Uthamalingam, Shanmugam Semigran, Marc J. TI Benefits of Natriuretic Peptide Guided Heart Failure Therapy for Patients With Chronic Left Ventricular Systolic Dysfunction: Primary Results of the Pro-BNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) Study SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Scientific Sessions 2010 on Resuscitation Science Symposium CY NOV 13-17, 2010 CL Chicago, IL SP Amer Heart Assoc C1 [Januzzi, James; Rehman, Shafiq U.; Mohammed, Asim A.; Bhardwaj, Anju; Barajas, Linda; Barajas, Justine; Kim, Han-Na; Baggish, Aaron L.; Weiner, Rory B.; Chen-Tournoux, Annabel A.; Marshall, Jane E.; Moore, Stephanie A.; Carlson, William; Lewis, Gregory D.; Shin, Jordan; Sullivan, Dorothy; Parks, Kimberly; Wang, Thomas; Gregory, Shawn A.; Uthamalingam, Shanmugam; Semigran, Marc J.] 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 23 PY 2010 VL 122 IS 21 BP 2221 EP 2221 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 683JJ UT WOS:000284471800041 ER PT J AU Steg, PG James, S Harrington, RA Ardissino, D Becker, RC Cannon, CP Emanuelsson, H Finkelstein, A Husted, S Katus, H Kilhamn, J Olofsson, S Storey, RF Weaver, D Wallentin, L AF Steg, Philippe Gabriel James, Stefan Harrington, Robert A. Ardissino, Diego Becker, Richard C. Cannon, Christopher P. Emanuelsson, Hakan Finkelstein, Ariel Husted, Steen Katus, Hugo Kilhamn, Jan Olofsson, Sylvia Storey, Robert F. Weaver, Douglas Wallentin, Lars CA PLATO Study Grp TI Ticagrelor Versus Clopidogrel in Patients With ST-Elevation Acute Coronary Syndromes Intended for Reperfusion With Primary Percutaneous Coronary Intervention A Platelet Inhibition and Patient Outcomes (PLATO) Trial Subgroup Analysis SO CIRCULATION LA English DT Article DE acute coronary syndrome; hemorrhage; myocardial infarction; platelets; thrombosis ID ACUTE MYOCARDIAL-INFARCTION; P2Y(12) RECEPTOR ANTAGONIST; 2007 FOCUSED UPDATE; SEGMENT ELEVATION; DOUBLE-BLIND; ASPIRIN; MANAGEMENT; AZD6140; EVENTS; ASSOCIATION AB Background-Aspirin and clopidogrel are recommended for patients with acute coronary syndromes (ACS) or undergoing coronary stenting. Ticagrelor, a reversible oral P2Y12-receptor antagonist, provides faster, greater, and more consistent platelet inhibition than clopidogrel and may be useful for patients with acute ST-segment elevation (STE) ACS and planned primary percutaneous coronary intervention. Methods and Result-Platelet Inhibition and Patient Outcomes (PLATO), a randomized, double-blind trial, compared ticagrelor with clopidogrel for the prevention of vascular events in 18 624 ACS patients. This report concerns the 7544 ACS patients with STE or left bundle-branch block allocated to either ticagrelor 180-mg loading dose followed by 90 mg twice daily or clopidogrel 300-mg loading dose (with provision for 300 mg clopidogrel at percutaneous coronary intervention) followed by 75 mg daily for 6 to 12 months. The reduction of the primary end point (myocardial infarction, stroke, or cardiovascular death) with ticagrelor versus clopidogrel (10.8% versus 9.4%; hazard ratio [HR], 0.87; 95% confidence interval, 0.75 to 1.01; P=0.07) was consistent with the overall PLATO results. There was no interaction between presentation with STE/left bundle-branch block and randomized treatment (interaction P=0.29). Ticagrelor reduced several secondary end points, including myocardial infarction alone (HR, 0.80; P=0.03), total mortality (HR, 0.82; P=0.05), and definite stent thrombosis (HR, 0.66; P=0.03). The risk of stroke, low in both groups, was higher with ticagrelor (1.7% versus 1.0%; HR, 1.63; 95% confidence interval, 1.07 to 2.48; P=0.02). Ticagrelor did not affect major bleeding (HR, 0.98; P=0.76). Conclusion-In patients with STE-ACS and planned primary percutaneous coronary intervention, the effects of ticagrelor were consistent with those observed in the overall PLATO trial. C1 [Steg, Philippe Gabriel] INSERM, U698, Paris, France. [Steg, Philippe Gabriel] Hop Bichat Claude Bernard, AP HP, F-75877 Paris 18, France. [Steg, Philippe Gabriel] Univ Paris 07, Paris, France. [James, Stefan; Olofsson, Sylvia; Wallentin, Lars] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden. [James, Stefan; Olofsson, Sylvia; Wallentin, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Harrington, Robert A.; Becker, Richard C.] Duke Clin Res Inst, Durham, NC USA. [Ardissino, Diego] Azienda Osped Univ Parma, Parma, Italy. [Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Emanuelsson, Hakan; Kilhamn, Jan] AstraZeneca Res & Dev, Molndal, Sweden. [Finkelstein, Ariel] Tel Aviv Med Ctr & Sch Med, Tel Aviv, Israel. [Husted, Steen] Aarhus Univ, Aarhus, Denmark. [Katus, Hugo] Univ Klinikum Heidelberg, Heidelberg, Germany. [Storey, Robert F.] Univ Sheffield, Sheffield, S Yorkshire, England. [Weaver, Douglas] Henry Ford Hosp, Detroit, MI 48202 USA. RP Steg, PG (reprint author), Ctr Hosp Bichat Claude Bernard, 46 Rue H Huchard, F-75018 Paris, France. EM gabriel.steg@bch.aphp.fr RI Katus, Hugo/P-1712-2016 FU AstraZeneca; sanofi-aventis; Servier; Astellas; Bayer; Boehringer-Ingelheim,; Bristol-Myers Squibb; Daiichi-Sankyo; Endotis; Glaxo Smith Kline; Menarini; Medtronic; Merck-Sharpe-Dohme; Nycomed; Otsuka; Pierre Fabre; Schering Plough; Eli-Lilly; Portola Pharmaceuticals; Novartis; Merck; Millenium Pharmaceuticals; Medicines Co; Pfizer; Boston Scientific; Regado Biosciences; Daichii Sankyo; Accumetrics; Intekrin Therapeutics; Merck/Schering Plough Partnership; Takeda; Eli Lilly/Daiichi Sankyo Alliance; Dynabyte; Teva; Regado; Athera FX The PLATO trial was supported by AstraZeneca. The statistical analyses for this manuscript were performed at Uppsala Clinical Research Center and Department Medical Sciences, Uppsala University, Uppsala, Sweden.; Dr Steg reports receiving research grants from sanofi-aventis, Servier; receiving speaking or consulting fees from Astellas, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Endotis Glaxo Smith Kline, Menarini, Medtronic, Merck-Sharpe-Dohme, Nycomed, Otsuka, Pierre Fabre, sanofi-aventis, Servier, and The Medicines Co; and being a stockholder in Aterovax. Dr James reports receiving research grants and advisory board fees from AstraZeneca and honoraria from AstraZeneca, Bristol Myers Squibb, Schering Plough, and Eli-Lilly. Dr Harrington reports receiving consulting fees and advisory board fees from Bristol-Myers Squibb, Sanofi-Aventis, Portola Pharmaceuticals, Schering-Plough, AstraZeneca, Novartis, and Merck; lecture fees from Schering-Plough, Bristol-Myers Squibb, Sanofi-Aventis, and Eli Lilly; grant support from Millenium Pharmaceuticals, Schering-Plough, The Medicines Co, Merck, Portola Pharmaceuticals, Astra Zeneca, and Bristol-Myers Squibb; and honoraria from Eli Lilly and The Medicines Co. Dr Ardissino reports receiving research grants from AstraZeneca, Eli Lilly, Pfizer, and Boston Scientific; speakers' bureau payments and honoraria from Glaxo, Boehringer Ingelheim, Sanofi-Aventis, Pfizer, Eli Lilly, AstraZeneca, Schering-Plough, Daiiki Sankyo, Merck, and Boston Scientific; and advisory board fees from Sanofi-Aventis, Pfizer, Eli Lilly, AstraZeneca, Schering-Plough, Daiiki Sankyo, and Medtronic. Dr Becker reports receiving research grants from AstraZeneca, Regado Biosciences, Bayer, and Bristol Myers Squibb and consultant fees from Daichii Sankyo, Boehringer Ingelheim, and AstraZeneca. Dr Cannon reports receiving research grants from Accumetrics, AstraZeneca, Bristol-Myers Squibb/Sanofi Partnership, Glaxo Smith Kline, Intekrin Therapeutics, Merck, Merck/Schering Plough Partnership, Novartis, and Takeda; being an expert witness at the University Michigan Hospital; and having equity ownership interest in Automedics. Dr Emanuelsson reports being an employee of AstraZeneca. Dr Husted reports receiving research grants from AstraZeneca, Bristol Myers Squibb, Pfizer, and Bayer and consultant fees from Sanofi-Aventis, Pfizer, and AstraZeneca. Dr Katus has received honoraria from Eli-Lilly, GlaxoSmithKline, Roche, and Bayer. Dr Katus holds a patent jointly with Roche and receives royalties for this patent. Dr Kilhamn reports being an employee and stockholder of AstraZeneca. Dr Storey reports receiving research grants from AstraZeneca, Eli Lilly/Daiichi Sankyo Alliance, and Schering Plough; research support from Dynabyte; honoraria from AstraZeneca, Eli Lilly/Daiichi Sankyo, and Schering Plough; and consultant fees from AstraZeneca, Eli Lilly/Daiichi Sankyo, Schering Plough, Teva, and The Medicines Co. Dr Weaver reports being an Executive Committee member for AstraZeneca and Data Safety Monitoring Committee member for The Medicines Co, Eli Lilly, and Bayer. Dr Wallentin reports receiving research grants from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Glaxo Smith Kline, and Schering Plough; honoraria from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Glaxo Smith Kline, Schering Plough, and Eli-Lilly; and consultant fees from Regado, Athera, Boehringer Ingelheim, AstraZeneca, and Glaxo Smith Kline. The other authors report no conflicts. NR 27 TC 221 Z9 237 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 23 PY 2010 VL 122 IS 21 BP 2131 EP 2141 DI 10.1161/CIRCULATIONAHA.109.927582 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 683JJ UT WOS:000284471800013 PM 21060072 ER PT J AU Bangalore, S Qin, J Sloan, S Murphy, SA Cannon, CP AF Bangalore, Sripal Qin, Jie Sloan, Sarah Murphy, Sabina A. Cannon, Christopher P. CA PROVE IT-TIMI 22 Trial Investigato TI What Is the Optimal Blood Pressure in Patients After Acute Coronary Syndromes? Relationship of Blood Pressure and Cardiovascular Events in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction (PROVE IT-TIMI) 22 Trial SO CIRCULATION LA English DT Article DE blood pressure; hypertension; prognosis; acute coronary syndrome ID J-CURVE; RANDOMIZED-TRIAL; HEART-DISEASE; HYPERTENSIVE PATIENTS; RISK; PREVENTION; MANAGEMENT; REDUCTION; DEATH; MORTALITY AB Background-Aggressive blood pressure (BP) control has been advocated in patients with acute coronary syndrome, but few data exist in this population relative to cardiovascular outcomes. Methods and Results-We evaluated 4162 patients enrolled in the PRavastatin Or atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction (PROVE IT-TIMI) 22 trial (acute coronary syndrome patients randomized to pravastatin 40 mg versus atorvastatin 80 mg). The average follow-up BP (systolic and diastolic) was categorized into 10-mm Hg increments. The primary outcome was a composite of death due to any cause, myocardial infarction, unstable angina requiring rehospitalization, revascularization after 30 days, and stroke. The secondary outcome was a composite of death due to coronary heart disease, nonfatal myocardial infarction, or revascularization. The relationship between BP (systolic or diastolic) followed a J- or U-shaped curve association with primary, secondary, and individual outcomes, with increased events rates at both low and high BP values, both unadjusted and after adjustment for baseline variables, baseline C-reactive protein, and on-treatment average levels of low-density lipoprotein cholesterol. A nonlinear Cox proportional hazards model showed a nadir of 136/85 mm Hg (range 130 to 140 mm Hg systolic and 80 to 90 mm Hg diastolic) at which the incidence of primary outcome was lowest. The curve was relatively flat for systolic pressures of 110 to 130 mm Hg and diastolic pressures of 70 to 90 mm Hg. Conclusions-After acute coronary syndrome, a J- or U-shaped curve association existed between BP and the risk of future cardiovascular events, with lowest event rates in the BP range of approximately 130 to 140 mm Hg systolic and 80 to 90 mm Hg diastolic and a relatively flat curve for systolic pressures of 110 to 130 mm Hg and diastolic pressures of 70 to 90 mm Hg, which suggests that too low of a pressure (especially <110/70 mm Hg) may be dangerous. C1 [Cannon, Christopher P.] Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Div Cardiovasc Med, Boston, MA 02115 USA. [Bangalore, Sripal] NYU, Sch Med, New York, NY USA. RP Cannon, CP (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Div Cardiovasc Med, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM cpcannon@partners.org RI Bangalore, Sripal/B-6246-2013; OI Bangalore, Sripal/0000-0001-9485-0652 FU Bristol-Myers-Squibb; Sankyo; Accumetrics; AstraZeneca; GlaxoSmithKline; Intekrin Therapeutics; Merck; Takeda FX PROVE IT-TIMI 22 was supported by a research grant from Bristol-Myers-Squibb and Sankyo.; Dr Cannon has received research grants/support from Accumetrics, AstraZeneca, GlaxoSmithKline, Intekrin Therapeutics, Merck, and Takeda; has served on advisory boards (but donated the funds therefrom to charity) for Alnylam, Bristol-Myers Squibb/Sanofi Partnership, and Novartis; and has received honoraria for independent educational conferences from Pfizer and AstraZeneca; he also holds an equity interest in Automedics Medical Systems. The remaining authors report no conflicts. NR 30 TC 96 Z9 103 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 23 PY 2010 VL 122 IS 21 BP 2142 EP 2151 DI 10.1161/CIRCULATIONAHA.109.905687 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 683JJ UT WOS:000284471800014 PM 21060068 ER PT J AU Ellenbogen, KA Gold, M Lemke, B Lozano, I Meyer, T Mittal, S Singh, J Spinale, F Stein, K Van Eyk, J Waggoner, A AF Ellenbogen, Kenneth A. Gold, Michael Lemke, Bernd Lozano, Ignacio Meyer, Timothy Mittal, Suneet Singh, Jagmeet Spinale, Francis Stein, Kenneth Van Eyk, Jennifer Waggoner, Alan TI Primary Results From the SMART AV Trial: A Randomized Trial Comparing Empiric, Echocardiographic Guided and Algorithmic AV Delay Programming in Cardiac Resynchronization Therapy (CRT) SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Scientific Sessions 2010 on Resuscitation Science Symposium CY NOV 13-17, 2010 CL Chicago, IL SP Amer Heart Assoc C1 [Ellenbogen, Kenneth A.] Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. [Gold, Michael; Spinale, Francis] Med Univ S Carolina, Charleston, SC 29425 USA. [Lemke, Bernd] Ruhr Univ Bochum, Bochum, Germany. [Lozano, Ignacio] Hosp Puerta de Hierro, Madrid, Spain. [Meyer, Timothy; Stein, Kenneth] Boston Sci, St Paul, MN USA. [Mittal, Suneet] St Lukes Roosevelt Hosp, New York, NY USA. [Singh, Jagmeet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Van Eyk, Jennifer] Johns Hopkins Univ, Baltimore, MD USA. [Waggoner, Alan] Washington Univ, Sch Med, St Louis, MO 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 23 PY 2010 VL 122 IS 21 BP 2217 EP 2217 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 683JJ UT WOS:000284471800027 ER PT J AU Silberman, GA Fan, THM Jiao, Z Boulden, BM Widder, J Fredd, S Dikalov, S Harrison, DG Lovelock, JD Xiao, HD Wolska, BM Liu, H Dudley, SC Bernstein, KE AF Silberman, Gad A. Fan, Tai-Hwang M. Jiao, Zhe Boulden, Beth M. Widder, Julian Fredd, Scott Dikalov, Sergey Harrison, David G. Lovelock, Joshua D. Xiao, Hong D. Wolska, Beata M. Liu, Hong Dudley, Samuel C., Jr. Bernstein, Kenneth E. TI Reply to Letter Regarding Article, "Uncoupled Cardiac Nitric Oxide Synthase Mediates Diastolic Dysfunction" SO CIRCULATION LA English DT Letter ID TETRAHYDROBIOPTERIN; SAPROPTERIN C1 [Silberman, Gad A.; Fan, Tai-Hwang M.; Jiao, Zhe; Boulden, Beth M.; Widder, Julian; Fredd, Scott; Dikalov, Sergey; Harrison, David G.; Lovelock, Joshua D.] Emory Univ, Sch Med, Div Cardiol, Dept Med, Atlanta, GA 30322 USA. [Xiao, Hong D.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wolska, Beata M.; Liu, Hong; Dudley, Samuel C., Jr.] Univ Illinois, Cardiol Sect, Chicago, IL USA. [Bernstein, Kenneth E.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Silberman, GA (reprint author), Emory Univ, Sch Med, Div Cardiol, Dept Med, Atlanta, GA 30322 USA. RI Warren, Beth/B-6918-2017 OI Warren, Beth/0000-0003-4416-3031 NR 4 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 23 PY 2010 VL 122 IS 21 BP E559 EP E559 DI 10.1161/CIRCULATIONAHA.110.962183 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 683JJ UT WOS:000284471800004 ER PT J AU Ahmed, W Blankstein, R Truong, Q DeFontes, J Rogers, I Nasir, K Bamberg, F Brady, TJ Nagurney, JT Hoffmann, U AF Ahmed, Waleed Blankstein, Ron Quynh Truong DeFontes, Joao Rogers, Ian Nasir, Khurram Bamberg, Fabian Brady, Thomas J. Nagurney, John T. Hoffmann, Udo TI The Utility of Exercise Stress Test in Predicting Coronary Plaque and Stenosis as detected by Coronary Computed Tomography Angiography: The ROMICAT Study SO CIRCULATION LA English DT Meeting Abstract DE Cardiac CT; Exercise tests; Plaque C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Univ, Med Cntr, Boston, MA 02215 USA. Stanford Univ, Med Cntr, Stanford, CA 94305 USA. Univ Munich, Munich, 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 23 PY 2010 VL 122 IS 21 SU S MA A21495 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231603850 ER PT J AU Baicu, CF Li, JY Zhang, YH Kasiganesan, H Yamane, K Zile, MR Bradshaw, AD AF Baicu, Catalin F. Li, Jiayu Zhang, Yuhua Kasiganesan, Harinath Yamane, Kentaro Zile, Michael R. Bradshaw, Amy D. TI Increased Interstitial Collagen in Chronic Pressure Overload Hypertrophy is Associated with a Change in Cardiac Fibroblast Phenotype and An Increase in SPARC Expression SO CIRCULATION LA English DT Meeting Abstract DE Hypertrophy; Cells; Remodeling C1 [Baicu, Catalin F.; Li, Jiayu; Zhang, Yuhua; Kasiganesan, Harinath; Yamane, Kentaro; Zile, Michael R.; Bradshaw, Amy D.] Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 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 23 PY 2010 VL 122 IS 21 SU S MA A13030 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231601132 ER PT J AU Bhardwaj, A Peacock, WF Yeo, KTJ Storrow, A Truong, Q Thomas, S Curtis, KM Foote, RS Lee, HK Miller, KF Januzzi, JL AF Bhardwaj, Anju Peacock, W. Frank Yeo, Kiang-Teck J. Storrow, Alan Truong, Quynh Thomas, Stephen Curtis, Kevin M. Foote, Robert S. Lee, Hong K. Miller, Karen F. Januzzi, James L. TI A Multi-center Comparison of Established and Emerging Cardiac Biomarkers for the Diagnostic Evaluation of Chest Pain in the Emergency Department. SO CIRCULATION LA English DT Meeting Abstract DE Acute coronary syndromes; Biomarkers; Troponin C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Chicago, Chicago, IL 60637 USA. Vanderbilt Univ, Med Cntr, Nashville, TN USA. Univ Oklahoma, Oklahoma City, OK USA. Dartmouth Hitchcock Med Cntr, Lebanon, NH 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 23 PY 2010 VL 122 IS 21 SU S MA A12590 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600900 ER PT J AU Bostrom, PA Mann, N Wu, J Quintero, PA Plovie, ER Gupta, R MacRae, C Rosenzweig, A Spiegelman, BM AF Bostrom, Pontus A. Mann, Nina Wu, Jun Quintero, Pablo A. Plovie, Eva R. Gupta, Rana MacRae, Calum Rosenzweig, Anthony Spiegelman, Bruce M. TI C/ebpb Controls Cardiac Growth During Exercise SO CIRCULATION LA English DT Meeting Abstract DE Cardiac hypertrophy; Physical activity; Genetic techniques; Molecular biology; Contractility C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Cntr, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 23 PY 2010 VL 122 IS 21 SU S MA A13238 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231601204 ER PT J AU Bradley, SM Bryson, CL Maynard, C Maddox, TM Fihn, SD AF Bradley, Steven M. Bryson, Chris L. Maynard, Charles Maddox, Thomas M. Fihn, Stephan D. TI Influence of Recent Hospitalization for Non-coronary Events on the Use of Preventive Medications for Coronary Artery Disease SO CIRCULATION LA English DT Meeting Abstract DE Coronary artery disease; Prevention; Drugs; Health services research; Patient care C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Colorado, Denver Vet Affairs Med Cntr, Denver, CO 80202 USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 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 23 PY 2010 VL 122 IS 21 SU S MA A12098 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600739 ER PT J AU Chuang, ML Gona, P Oyama, N Jaffer, FA Salton, CJ Blease, SJ Larson, MG Jhaveri, RR Lahiri, MK Levy, D O'Donnell, CJ Manning, WJ AF Chuang, Michael L. Gona, Philimon Oyama, Noriko Jaffer, Farouc A. Salton, Carol J. Blease, Susan J. Larson, Martin G. Jhaveri, Rahul R. Lahiri, Marc K. Levy, Daniel O'Donnell, Christopher J. Manning, Warren J. TI Longitudinal Change in Aortic Plaque Volume Using Cardiovascular Magnetic Resonance: Clinical Correlates SO CIRCULATION LA English DT Meeting Abstract DE Arteriosclerosis; Epidemiology; Magnetic resonance imaging; Risk factors C1 Beth Israel Deaconess Med Cntr, Boston, MA USA. NHLBI, Cntr Populat Studies, Framingham, MA USA. Hokkaido Univ, Sapporo, Hokkaido, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Oyama-Manabe, Noriko/A-5212-2012 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 23 PY 2010 VL 122 IS 21 SU S MA A13199 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231601183 ER PT J AU Conen, D Chae, CU Glynn, RJ Tedrow, UB Everett, BJ Buring, JE Albert, CM AF Conen, David Chae, Claudia U. Glynn, Robert J. Tedrow, Usha B. Everett, Brendan J. Buring, Julie E. Albert, Christine M. TI New-onset Atrial Fibrillation is Associated with an Increased Risk of Cardiovascular Morbidity and Mortality in Initially Healthy Women SO CIRCULATION LA English DT Meeting Abstract DE Atrial fibrillation; Cardiovascular disease; Stroke; Myocardial infarction; Epidemiology C1 Univ Basel Hosp, CH-4031 Basel, Switzerland. Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 23 PY 2010 VL 122 IS 21 SU S MA A11330 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600684 ER PT J AU Contreras-Valdes, F Heist, EK Danik, SB Barrett, CD Ruskin, JN Mansour, M AF Contreras-Valdes, Fernando Heist, E. Kevin Danik, Stephan B. Barrett, Conor D. Ruskin, Jeremy N. Mansour, Moussa TI Progression of Esophageal Injury after Radiofrequency Catheter Ablation for Atrial Fibrillation. SO CIRCULATION LA English DT Meeting Abstract DE Ablation, radiofrequency; Atrial fibrillation; Prognosis C1 [Contreras-Valdes, Fernando; Heist, E. Kevin; Danik, Stephan B.; Barrett, Conor D.; Ruskin, Jeremy N.; 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 23 PY 2010 VL 122 IS 21 SU S MA A18675 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231602910 ER PT J AU Cosgrove, NM Moreyra, AE Wilson, AC Shao, YH Kostis, WJ Kostis, JB AF Cosgrove, Nora M. Moreyra, Abel E. Wilson, Alan C. Shao, Yu-Hsuan Kostis, William J. Kostis, John B. CA Myocardial Infarction Data TI Clinical Characteristics and Outcomes of Centenarians with Acute Myocardial Infarction SO CIRCULATION LA English DT Meeting Abstract DE Aging; Myocardial infarction C1 UMDNJ Robert Wood Johnson Med Sch, New Brunswick, NJ USA. 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 23 PY 2010 VL 122 IS 21 SU S MA A9193 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600369 ER PT J AU Cubeddu, R Lago, R Mendoza, I Lovett, AF Zelevinsky, K Crane, AM Crane, AM Witzke, C Normand, SL Pomerantsev, E Palacios, IF AF Cubeddu, Roberto Lago, Rodrigo Mendoza, Ivan Lovett, Ann F. Zelevinsky, Katya Crane, Ashley M. Crane, Ashley M. Witzke, Christian Normand, Sharon-Lise Pomerantsev, Eugene Palacios, Igor F. TI No Mortality Advantage of "On" versus "Off"-hours Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction: Results from the Massachusetts Data Analysis Center Registry SO CIRCULATION LA English DT Meeting Abstract DE STEMI; Percutaneous coronary intervention C1 Aventura Hosp, Aventura, FL USA. Cleveland Clin Fl, Weston, FL USA. Harvard Univ, Sch Med, Boston, MA USA. Med Cntr, Aventura, FL USA. Mass Gen Hosp, Boston, MA USA. Harvard Univ, Sch Publ Hlth Care, 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 23 PY 2010 VL 122 IS 21 SU S MA A19994 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231603352 ER PT J AU Das, S Xiao, CY Hessler, K Knight, A Graham, EL Rosenzweig, A AF Das, Saumya Xiao, Chun Yang Hessler, Katherine Knight, Ashley Graham, Evan L. Rosenzweig, Anthony TI Serum and Glucocorticoid-Regulated Kinase 1 (SGK1) Activation Predisposes to Lethal Reperfusion Ventricular Arrhythmias while Inhibition Is Protective in a Mouse Model of Ischemia-Reperfusion SO CIRCULATION LA English DT Meeting Abstract DE Ion channels; Infarct size; Apoptosis; Ventricular arrhythmia C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 23 PY 2010 VL 122 IS 21 SU S MA A20353 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231603476 ER PT J AU Das, S Aiba, T Hessler, K Rosenberg, M Xiao, CY Quintero, P Ottaviano, F Morissette, M delMonte, F Ellinor, P Tomaselli, GF Rosenzweig, A AF Das, Saumya Aiba, Takeshi Hessler, Katherine Rosenberg, Michael Xiao, Chun Yang Quintero, Pablo Ottaviano, Filomena Morissette, Michael delMonte, Federica Ellinor, Patrick Tomaselli, Gordon F. Rosenzweig, Anthony TI Serum- and Glucocorticoid-Regulated Kinase 1 Contributes to Adverse Electrical Remodeling by Regulating Cardiac Na+ Channels SO CIRCULATION LA English DT Meeting Abstract DE Sodium channel; Ventricular arrhythmia; Heart failure; Ion channels C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Johns Hopkins Med Sch, Baltimore, MA USA. W Virginia Univ, Morgantown, WV 26506 USA. 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 23 PY 2010 VL 122 IS 21 SU S MA A20389 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231603485 ER PT J AU Derwall, M Malhotra, R McManus, P Beppu, Y Zapol, WM Bloch, KD Yu, PB AF Derwall, Matthias Malhotra, Rajeev McManus, Patrick Beppu, Yuko Zapol, Warren M. Bloch, Kenneth D. Yu, Paul B. TI Identification of a Critical Role for BMP Signaling in Atherogenesis SO CIRCULATION LA English DT Meeting Abstract DE Cardiovascular disease; Signal transduction; Foam cells; Calcification; Lipoproteins 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 23 PY 2010 VL 122 IS 21 SU S MA A10990 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600602 ER PT J AU DeSantis, SM Toole, JM Kratz, JM Uber, WE Wheat, MJ Stroud, MR Ikonomidis, JS Spinale, FG AF DeSantis, Stacia M. Toole, J. M. Kratz, John M. Uber, Walter E. Wheat, Margaret J. Stroud, Martha R. Ikonomidis, John S. Spinale, Francis G. TI Early Postoperative Outcomes and Blood Product Utilization in Adult Cardiac Surgery: The Post-Aprotinin Era SO CIRCULATION LA English DT Meeting Abstract DE Cardiac surgery; Fibrinolytic agents C1 Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 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 23 PY 2010 VL 122 IS 21 SU S MA A9456 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600410 ER PT J AU Di Carli, M Johnson, JR Hlatky, MA Shaw, LJ Ridner, ML Dorbala, S Beanlands, RS Chow, BJ Branscomb, E Chareonthaitawee, P Weigold, WG Voros, S Abbara, S Yasuda, T Jacobs, JE Lesser, J Berman, DS Thomson, L Raman, S Heller, GV Schussheim, A Brunken, R Williams, KA Farkas, S Delbeke, D Schoepf, UJ Reichek, N Rabinowitz, S Sigman, SR Johnson, B Gaber, M Williams, JA Foster, C Hainer, J Hachamovitch, R AF Di Carli, Marcelo Johnson, James R. Hlatky, Mark A. Shaw, Leslee J. Ridner, Michael L. Dorbala, Sharmila Beanlands, Rob S. Chow, Benjamin J. Branscomb, Elizabeth Chareonthaitawee, Panithaya Weigold, W. G. Voros, Szilard Abbara, Suhny Yasuda, Tsunehiro Jacobs, Jill E. Lesser, John Berman, Daniel S. Thomson, Louise Raman, Subha Heller, Gary V. Schussheim, Adam Brunken, Richard Williams, Kim A. Farkas, Susan Delbeke, Dominique Schoepf, U. J. Reichek, Nathaniel Rabinowitz, Stuart Sigman, Steven R. Johnson, Barbara Gaber, Masha Williams, Julie A. Foster, Courtney Hainer, Jon Hachamovitch, Rory TI Incremental Value of Noninvasive Cardiac Imaging in Risk Prediction: Results from the SPARC Study SO CIRCULATION LA English DT Meeting Abstract DE Cardiac imaging; Noninvasive cardiac imaging; Cardiac CT; Positron emission tomography C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Stanford Univ, Stanford, CA 94305 USA. Emory Univ Med Cntr, Atlanta, GA USA. Heart Cntr Huntsville Hosp, Huntsville, AL USA. Univ Ottawa, Inst Heart, Ottawa, ON, Canada. CardioVasc Associates, Birmingham, AL USA. Mayo Clin, Rochester, MN USA. Washington Hosp Cntr, Washington, DC USA. Piedmont Heart Inst, Atlanta, GA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NYU Langone Med Cntr, New York, NY USA. Minneapolis Heart Inst, Minneapolis, MN USA. Cedars Sinai Med Cntr, Los Angeles, CA USA. Ohio State Univ Med Cntr, Columbus, OH USA. Hartford Hosp, Hartford, CT 06115 USA. Cardiac Specialists, Trumbull, CT USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Chicago, Chicago, IL 60637 USA. Meritcare Heart Cntr, Fargo, ND USA. Vanderbilt Univ Med Cntr, Nashville, TN USA. Med Univ S Carolina, Charleston, SC 29425 USA. St Francis Hosp, Roslyn, NY USA. Sinai Hosp, Baltimore, MD 21215 USA. Emory Univ, Sch Med, Atlanta, GA 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 23 PY 2010 VL 122 IS 21 SU S MA A12921 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231601103 ER PT J AU Dixon, JA Gaillard, WF Rivers, WT Koval, CN Stroud, RE Mukherjee, R Spinale, FG AF Dixon, Jennifer A. Gaillard, William F. Rivers, William T. Koval, Christine N. Stroud, Robert E. Mukherjee, Rupak Spinale, Francis G. TI Identification of a Unique Proteolytic-Profibrotic Interaction Following Myocardial Infarction Which is Amplified Following a Second Episode of Ischemia-Reperfusion SO CIRCULATION LA English DT Meeting Abstract DE Myocardial infarction; Ischemia reperfusion; Proteolytic enzymes C1 Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 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 23 PY 2010 VL 122 IS 21 SU S MA A13284 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231601217 ER PT J AU Dixon, JA Gorman, RC Stroud, RE Meyer, EC O'Quinn, EC Baker, NL Morita, M Hamamoto, H Ryan, LP Gorman, JH Spinale, FG AF Dixon, Jennifer A. Gorman, Robert C. Stroud, Robert E. Meyer, Evan C. O'Quinn, Elizabeth C. Baker, Nathaniel L. Morita, Masato Hamamoto, Hirotsugu Ryan, Liam P. Gorman, Joseph H. Spinale, Francis G. TI Targeted Regional Injection of Biocomposite Microspheres Alters Post Myocardial Infarction Remodeling and Matrix Proteolytic Pathways SO CIRCULATION LA English DT Meeting Abstract DE Myocardial infarction; Remodeling; Proteolytic enzymes C1 Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 USA. Univ Penn, Philadelphia, PA 19104 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 23 PY 2010 VL 122 IS 21 SU S MA A9196 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600370 ER PT J AU Dixon, JA Goodman, AM Gaillard, WF Rivers, WT McKinney, RA Mukherjee, R Baker, NL Ikonomidis, JS Spinale, FG AF Dixon, Jennifer A. Goodman, Amy M. Gaillard, William F. Rivers, William T. McKinney, Richard A. Mukherjee, Rupak Baker, Nathaniel L. Ikonomidis, John S. Spinale, Francis G. TI Hemodynamics and Myocardial Blood Flow Patterns Following Placement of a Cardiac Passive Restraint Device in a Model of Dilated Cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract DE Cardiomyopathy; Surgery; Device; Blood flow C1 Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 USA. Paracor, Sunnyvale, CA 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 23 PY 2010 VL 122 IS 21 SU S MA A9037 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600347 ER PT J AU Fang, MC Go, AS Chang, YC Borowsky, LH Pomernacki, NK Udaltsova, N Singer, DE AF Fang, Margaret C. Go, Alan S. Chang, Yuchiao Borowsky, Leila H. Pomernacki, Niela K. Udaltsova, Natalia Singer, Daniel E. TI Development of a New Risk Stratification Scheme to Predict Warfarin-Associated Hemorrhage: the AnTicoagulation and Risk Factors In Atrial Fibrillation (ATRIA) Study SO CIRCULATION LA English DT Meeting Abstract DE Anticoagulation; Atrial fibrillation; Risk factors C1 UCSF, San Francisco, CA USA. Kaiser Permanente No Calif, Oakland, CA USA. 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 23 PY 2010 VL 122 IS 21 SU S MA A16443 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231602165 ER PT J AU Feuchtner, G Goetti, R Plass, A Wieser, M Scheffel, H Wyss, C Friedrich, G Leschka, S Alkadhi, H Cury, R AF Feuchtner, Gudrun Goetti, Robert Plass, Andre Wieser, Monika Scheffel, Hans Wyss, Christophe Friedrich, Guy Leschka, Sebastian Alkadhi, Hatem Cury, Ricardo TI Adenosine Stress High-Pitch 128-Slice Dual Source Flash Computed Tomography for Imaging of Reversible Myocardial Ischemia and Coronary Arteries SO CIRCULATION LA English DT Meeting Abstract DE Cardiovascular imaging; Coronary heart disease; Myocardial perfusion; Cardiac CT; Cardiac MRI C1 Innsbruck Med Univ, Innsbruck, Austria. Univ Zurich, Zurich, Switzerland. Univ Zurich, Zurich, Austria. Univ Zurich Hosp, CH-8091 Zurich, Switzerland. Boston Massachussets Gen Hosp, Boston, MA USA. Baptist Cardiac & Vasc Inst, Miami, FL, Austria. RI Goetti, Robert/I-8961-2012 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 23 PY 2010 VL 122 IS 21 SU S MA A16091 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231602069 ER PT J AU Figueroa, AL Fontanez, SI Lawler, MA Subramanian, S Marincheva-Savcheva, G Fifer, KM Brady, TJ Tawakol, A AF Figueroa, Amparo L. Fontanez, Sara I. Lawler, Meredith A. Subramanian, Sharath Marincheva-Savcheva, Gergana Fifer, Kenneth M. Brady, Thomas J. Tawakol, Ahmed TI Obesity is Independently Associated With Vascular Inflammation in Low-Risk Individuals SO CIRCULATION LA English DT Meeting Abstract DE Positron emission tomography; Inflammation; Obesity C1 [Figueroa, Amparo L.; Fontanez, Sara I.; Lawler, Meredith A.; Subramanian, Sharath; Marincheva-Savcheva, Gergana; Fifer, Kenneth M.; 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 23 PY 2010 VL 122 IS 21 SU S MA A20935 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231603657 ER PT J AU Fontes, JD Lyass, A Massaro, JM Schnabel, RB Wang, TJ Vasan, RS Lubitz, SA Magnani, JW Ellinor, PT Fox, CS Benjamin, EJ AF Fontes, Joao D. Lyass, Asya Massaro, Joseph M. Schnabel, Renate B. Wang, Thomas J. Vasan, Ramachandran S. Lubitz, Steven A. Magnani, Jared W. Ellinor, Patrick T. Fox, Caroline S. Benjamin, Emelia J. TI Insulin Resistance Does Not Increase Risk Of Incident Atrial Fibrillation: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract DE Atrial fibrillation; Insulin resistance; Epidemiology; Risk factors C1 Boston Univ, Framingham, MA USA. Boston Univ, Boston, MA 02215 USA. Johannes Gutenberg Univ Mainz, Mainz, Germany. Massachusetts Gen Hosp, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NHLBI, Framingham, MA 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 23 PY 2010 VL 122 IS 21 SU S MA A18418 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231602828 ER PT J AU Gleva, MJ Holcomb, R Mela, T Chung, M Gottipaty, V Borge, R Shinn, T Uslan, D Dan, D Jenkins, M Poole, J AF Gleva, Marye J. Holcomb, Richard Mela, Theofanie Chung, Mina Gottipaty, Venkateshwar Borge, Richard Shinn, Timothy Uslan, Daniel Dan, Dan Jenkins, Matthew Poole, Jeanne TI A Simple Approach to Determine Risk Associated with Pacemaker and Implantable Cardioverter Defibrillator Replacements: The REPLACE Score SO CIRCULATION LA English DT Meeting Abstract DE Implantable cardioconvert defibrillator; Pacemakers; Resynchronization therapy; Risk factors; Clinical trials C1 Washington Univ, Sch Med, St Louis, MO USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cleveland Clin, Cleveland, OH 44106 USA. S Carolina Heart Cntr, Columbia, SC USA. Abington Med Specialists, Abington, PA USA. Michigan Heart, Ypsilanti, MI USA. UCLA Med Cntr, Los Angeles, CA USA. Peidmont Heart Inst, Atlanta, GA USA. BIOTRONK Inc, Lake Oswego, OR USA. Univ Washington, Seattle, WA 98195 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 23 PY 2010 VL 122 IS 21 SU S MA A18458 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231602842 ER PT J AU Go, AS Fan, DJ Chang, YC Chan, J Lieu, TA Magid, DJ Schmelzer, JR Shah, NR Witt, DM Yale, SH Sung, SH Singer, DE AF Go, Alan S. Fan, Dongjie Chang, Yuchiao Chan, James Lieu, Tracy A. Magid, David J. Schmelzer, John R. Shah, Nirav R. Witt, Daniel M. Yale, Steven H. Sung, Sue Hee Singer, Daniel E. CA CVRN WAVE Study Grp TI Quality of Anticoagulation Management in Atrial Fibrillation and Venous Thromboembolism: The CVRN WAVE Study SO CIRCULATION LA English DT Meeting Abstract DE Atrial fibrillation; Venous thrombosis; Anticoagulation; Quality assessment; Healthcare delivery systems C1 Kaiser Permanente No Calif, Oakland, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Harvard Pilgrim Hlth Care Inst, Sch Med, Boston, MA USA. Kaiser Permanente Colorado, Denver, CO USA. Marshfield Clin Rsch Fdn, Marshfield, WI USA. Geisinger Hlth Syst, Danville, PA USA. Kaiser Permanente Colorado, Aurora, 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 23 PY 2010 VL 122 IS 21 SU S MA A14870 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231601697 ER PT J AU Go, AS Reynolds, K Fang, MC Udaltsova, N Wei, R Chang, YC Pomernacki, N Borowsky, LH Harrison, TN Singer, DE AF Go, Alan S. Reynolds, Kristi Fang, Margaret C. Udaltsova, Natalia Wei, Rong Chang, Yuchiao Pomernacki, Niela Borowsky, Leila H. Harrison, Teresa N. Singer, Daniel E. TI Contemporary Rates and Correlates of Warfarin Use in 33,570 Adults with Atrial Fibrillation: The ATRIA2-CVRN Study SO CIRCULATION LA English DT Meeting Abstract DE Atrial fibrillation; Atrial flutter; Anticoagulation; Prevention; Quality assessment C1 Kaiser Permanente No Calif, Oakland, CA USA. Kaiser Permanente So Calif, Pasadena, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. 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 23 PY 2010 VL 122 IS 21 SU S MA A13727 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231601339 ER PT J AU Goldstein, DJ Maybaum, S MacGillivray, TE Moore, SA Bogaev, RC Farrar, DJ Frazier, OH AF Goldstein, Daniel J. Maybaum, Simon MacGillivray, Thomas E. Moore, Stephanie A. Bogaev, Rogerta C. Farrar, David J. Frazier, O. H. CA HeartMate II Clinical TI Young Patients With Non-Ischemic Cardiomyopathy Have Higher Likelihood of Left Ventricular Recovery During HeartMate II Support: Data From the Bridge and Destination Therapy Trials SO CIRCULATION LA English DT Meeting Abstract DE Ventricular assist devices; Heart failure C1 Montefiore Med Cntr, Bronx, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Texas Heart Inst, Houston, TX 77025 USA. Thoratec Corp, Pleasanton, 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 23 PY 2010 VL 122 IS 21 SU S MA A18067 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231602699 ER PT J AU Goodman, E Dolan, LM Daniels, SR AF Goodman, Elizabeth Dolan, Lawrence M. Daniels, Stephen R. TI Stability of Metabolic Syndrome During the Transition to Adulthood: A 7-Year Follow Up Study SO CIRCULATION LA English DT Meeting Abstract DE Obesity; Metabolic syndrome; Children; Epidemiology C1 MassGen Hosp Children, Boston, MA USA. Cincinnati Children Hosp Med Cntr, Cincinnati, OH USA. Denver Children Hosp, Denver, CO 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 23 PY 2010 VL 122 IS 21 SU S MA A10180 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600444 ER PT J AU Goodman, SG Clare, R Pieper, KS James, SK Nicolau, JC Storey, RF Cantor, WJ Angiolillo, DJ Husted, S Cannon, CP Steg, PG Mahaffey, KW Kilhamn, J Harrington, RA Wallentin, L AF Goodman, Shaun G. Clare, Robert Pieper, Karen S. James, Stefan K. Nicolau, Jose C. Storey, Robert F. Cantor, Warren J. Angiolillo, Dominick J. Husted, Steen Cannon, Christopher P. Steg, Ph Gabriel Mahaffey, Kenneth W. Kilhamn, Jan Harrington, Robert A. Wallentin, Lars TI Proton Pump Inhibitor Use is Likely a Marker for, Rather than a Cause of, a Higher Risk of Cardiovascular Events: Insights from PLATO SO CIRCULATION LA English DT Meeting Abstract DE Antiplatelet drugs; Acute coronary syndromes C1 St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Canadian Heart Rsch Cntr, Toronto, ON, Canada. Duke Clin Rsch Inst, Durham, NC USA. Uppsala Clin Rsch Cntr, Uppsala, Sweden. Univ Sao Paulo, Sch Med, Inst Heart, Clin Hosp, Sao Paulo, Brazil. Univ Sheffield, Sheffield S10 2TN, S Yorkshire, England. Southlake Reg Hlth Cntr, Newmarket, ON, Canada. Univ Florida, Coll Med, Jacksonville, FL USA. Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Univ Paris 07, INSERM U 698, AP HP, F-75018 Paris, France. Duke Clin Rsch Inst, Durham, NC USA. AstraZeneca, Molndal, Sweden. Uppsala Clin Rsch Cntr, Uppsala, Sweden. RI Nicolau, Jose/E-1487-2012 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 23 PY 2010 VL 122 IS 21 SU S MA A12092 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600735 ER PT J AU Graham, EM Atz, AM Butts, RJ Baker, NL Stroud, RE Deardorff, RL Reeves, ST Bradley, SM Spinale, FG AF Graham, Eric M. Atz, Andrew M. Butts, Ryan J. Baker, Nathaniel L. Stroud, Robert E. Deardorff, Rachael L. Reeves, Scott T. Bradley, Scott M. Spinale, Francis G. TI Preoperative Steroid Treatment Does Not Improve Markers of Inflammation or Outcomes Following Cardiac Surgery in Neonates SO CIRCULATION LA English DT Meeting Abstract DE Pediatrics; Cardiac surgery; Inflammation C1 Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 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 23 PY 2010 VL 122 IS 21 SU S MA A10816 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600550 ER PT J AU Graham, EM Atz, AM Butts, RJ Baker, NL Zyblewski, SC Deardorff, RL Reeves, ST Bradley, SM Spinale, FG AF Graham, Eric M. Atz, Andrew M. Butts, Ryan J. Baker, Nathaniel L. Zyblewski, Sinai C. Deardorff, Rachael L. Reeves, Scott T. Bradley, Scott M. Spinale, Francis G. TI Standardized Preoperative Corticosteroid Treatment in Neonates Undergoing Cardiac Surgery-Results From a Randomized Trial SO CIRCULATION LA English DT Meeting Abstract DE Cardiac surgery; Pediatrics C1 Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 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 23 PY 2010 VL 122 IS 21 SU S MA A10814 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600549 ER PT J AU Greyson, CR Ye, SY Lu, L Xu, Y Schwartz, GG Ahmad, H AF Greyson, Clifford R. Ye, Shuyu Lu, Li Xu, Ya Schwartz, Gregory G. Ahmad, Hasan TI Acute Right Ventricular Pressure Overload Disrupts Organization of the Focal Adhesion Protein Talin SO CIRCULATION LA English DT Meeting Abstract DE Pulmonary heart disease; Proteolytic enzymes; Acute heart failure; Contractility; Pathology C1 [Greyson, Clifford R.; Ye, Shuyu; Lu, Li; Xu, Ya; Schwartz, Gregory G.; Ahmad, Hasan] Denver VAMC, Denver, CO USA. NR 0 TC 1 Z9 1 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 23 PY 2010 VL 122 IS 21 SU S MA A16249 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231602115 ER PT J AU Gruberg, L Jeremias, A Rundback, J Anderson, VH Spertus, J Kennedy, KF Rosenfield, K AF Gruberg, Luis Jeremias, Allen Rundback, John Anderson, Vernon H. Spertus, John Kennedy, Kevin F. Rosenfield, Kenneth TI Impact of Glomerular Filtration Rate on Clinical Outcomes Following Carotid Artery Revascularization in 12,304 Patients from the CARE Registry (R) SO CIRCULATION LA English DT Meeting Abstract DE Carotid arteries; Renal function C1 Stony Brook Univ Hosp Cntr, Stony Brook, NY USA. Holy Name Med Cntr, Teaneck, NJ USA. Univ Texas Hlth Sci Cntr, Houston, TX USA. St Lukes Hosp, Kansas City, MO USA. 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 23 PY 2010 VL 122 IS 21 SU S MA A21070 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231603704 ER PT J AU Hariharan, P Kabrhel, C AF Hariharan, Praveen Kabrhel, Christopher TI Association between Biomarker, Computed Tomography and Echocardiography Results, and Five-Day Clinical Adverse Events after Pulmonary Embolism SO CIRCULATION LA English DT Meeting Abstract DE Pulmonary embolism C1 Boston Univ Med Cntr, Boston, MA USA. 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 23 PY 2010 VL 122 IS 21 SU S MA A20804 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231603628 ER PT J AU Heist, EK Barrett, C Perna, F Danik, S Ruskin, JN Mansour, M AF Heist, E. Kevin Barrett, Conor Perna, Francesca Danik, Stephan Ruskin, Jeremy N. Mansour, Moussa TI Direct Visualization of Epicardial Structures and Ablation Utilizing a Visually-Guided Laser Balloon Catheter SO CIRCULATION LA English DT Meeting Abstract DE Catheter ablation; Pericardium; Ventricular arrhythmia C1 [Heist, E. Kevin; Barrett, Conor; Perna, Francesca; Danik, Stephan; Ruskin, Jeremy N.; Mansour, Moussa] 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 23 PY 2010 VL 122 IS 21 SU S MA A16064 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231602057 ER PT J AU Hughes, GC Zhao, Y Rankin, JS O'Brien, S Bavaria, JE Wolfe, WG Gaca, JG Gammie, JS Shahian, DM Smith, PK AF Hughes, G. Chad Zhao, Yue Rankin, J. Scott O'Brien, Sean Bavaria, Joseph E. Wolfe, Walter G. Gaca, Jeffrey G. Gammie, James S. Shahian, David M. Smith, Peter K. TI Effects of Institutional Volumes on Operative Outcomes for Combined Aortic Valve and Ascending Aortic Surgery SO CIRCULATION LA English DT Meeting Abstract DE Aortic aneurysm; Aortic valve; Epidemiology C1 Duke Univ, Med Ctr, Durham, NC USA. Vanderbilt Univ, Nashville, TN USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Boston, MA 02114 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 23 PY 2010 VL 122 IS 21 SU S MA A11225 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600659 ER PT J AU Ikonomidis, JS Jones, JA O'Quinn, EC Elefteriades, JA Stroud, RE Bavaria, JE Gorman, JH Gorman, RC Spinale, FG AF Ikonomidis, John S. Jones, Jeffrey A. O'Quinn, Elizabeth C. Elefteriades, John A. Stroud, Robert E. Bavaria, Joseph E. Gorman, Joseph H. Gorman, Robert C. Spinale, Francis G. TI Direct Profiling of MicroRNA in Thoracic Aortic Aneurysms: Relationship to Aortic Expansion and Growth SO CIRCULATION LA English DT Meeting Abstract DE Aortic aneurysm; Remodeling C1 Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 USA. Yale Univ, New Haven, CT USA. Univ Penn, Philadelphia, PA 19104 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 23 PY 2010 VL 122 IS 21 SU S MA A15773 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231601934 ER PT J AU Jiang, YD Marchese, AD Shelton, K Kacmrek, RM AF Jiang, Yandong Marchese, Andrew D. Shelton, Kenneth Kacmrek, Robert M. TI Validating Effectiveness of Ventilation Generated by Chest Compression Alone in the Model Lung SO CIRCULATION LA English DT Meeting Abstract DE Cardiopulmonary resuscitation; Ventilation; Oxygen uptake C1 [Jiang, Yandong; Marchese, Andrew D.; Shelton, Kenneth; Kacmrek, Robert M.] Mass 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 23 PY 2010 VL 122 IS 21 SU S MA A62 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600054 ER PT J AU Jones, JA Bouges, S Zavadzkas, JA Rivers, WT Brinsa, TA Stroud, RE Spinale, FG Mukherjee, R Ikonomidis, JS AF Jones, Jeffrey A. Bouges, Shenikqua Zavadzkas, Jouzas A. Rivers, William T. Brinsa, Thersa A. Stroud, Robert E. Spinale, Francis G. Mukherjee, Rupak Ikonomidis, John S. TI Membrane Type-1 Matrix Metalloproteinase Activity and in vivo Abundance Using Targeted Microbubble Imaging, Intensify During Thoracic Aortic Aneurysm Formation: Relationship to Change in Aortic Diameter SO CIRCULATION LA English DT Meeting Abstract DE Aortic aneurysm; Remodeling; Proteolytic enzymes C1 [Jones, Jeffrey A.; Bouges, Shenikqua; Zavadzkas, Jouzas A.; Rivers, William T.; Brinsa, Thersa A.; Stroud, Robert E.; Spinale, Francis G.; Mukherjee, Rupak; Ikonomidis, John S.] Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 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 23 PY 2010 VL 122 IS 21 SU S MA A12403 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600827 ER PT J AU Jones, JA Prescott, CB Stroud, RE Spinale, FG Ikonomidis, JS AF Jones, Jeffrey A. Prescott, Corey B. Stroud, Robert E. Spinale, Francis G. Ikonomidis, John S. TI Latent Transforming Growth Factor-beta Binding Protein-1 is Cleaved by Matrix Metalloproteinase-2 During Thoracic Aortic Aneurysm Development SO CIRCULATION LA English DT Meeting Abstract DE Aortic aneurysm; Remodeling; Proteolytic enzymes C1 Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 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 23 PY 2010 VL 122 IS 21 SU S MA A12406 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600829 ER PT J AU Khan, ADM Reingold, JS Scherrer-Crosbie, M Chen-Tournoux, A Barth, M McCabe, EL Arora, P Cange, A Ryan, A Durrani, S Newton-Cheh, C Gerszten, RE Kaplan, LM Wang, TJ AF Khan, Abigail D. May Reingold, Jason S. Scherrer-Crosbie, Marielle Chen-Tournoux, Annabel Barth, Marita McCabe, Elizabeth L. Arora, Pankaj Cange, Abby Ryan, Allicia Durrani, Sofia Newton-Cheh, Christopher Gerszten, Robert E. Kaplan, Lee M. Wang, Thomas J. TI Improvements in Cardiometabolic Biomarkers Occur Early after Bariatric Surgery SO CIRCULATION LA English DT Meeting Abstract DE Obesity; Biomarkers C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 23 PY 2010 VL 122 IS 21 SU S MA A19727 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231603245 ER PT J AU Kim, JW Yoo, HK Calfon, MA Mauskapf, A Bouma, BE Tearney, GJ Jaffer, FA AF Kim, Jin Won Yoo, Hongki Calfon, Marcella A. Mauskapf, Adam Bouma, Brett E. Tearney, Guillermo J. Jaffer, Farouc A. TI In vivo Dual-Modality Molecular Imaging of Atheroma Inflammation via An Integrated Near-infrared Fluorescence and Optical Frequency Domain Imaging System SO CIRCULATION LA English DT Meeting Abstract DE Molecular; Imaging agents; Inflammation; Cardiovascular imaging C1 Cardiovasc Cntr Korea Unvers, Seoul, South Korea. Massachusetts Gen Hosp, Cardiovasc Rsch Cntr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Cntr Photomed, Boston, MA 02114 USA. RI Yoo, Hongki/B-6421-2013 OI Yoo, Hongki/0000-0001-9819-3135 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 23 PY 2010 VL 122 IS 21 SU S MA A18785 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231602943 ER PT J AU Kohli, P Morrow, DA Jarolim, P Sloan, S Sabatine, MS AF Kohli, Payal Morrow, David A. Jarolim, Petr Sloan, Sarah Sabatine, Marc S. TI Myeloperoxidase (MPO) is an Independent Predictor of Adverse Cardiovascular Outcomes in Patients with Stable Coronary Artery Disease SO CIRCULATION LA English DT Meeting Abstract DE Biomarkers; Coronary artery disease; Heart failure; Oxidative stress C1 Brigham & Womens Hosp, TIMI Study Grp, 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 23 PY 2010 VL 122 IS 21 SU S MA A13175 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231601176 ER PT J AU Kostis, WJ Deng, YZ Pantazopoulos, JS Moreyra, AE Kostis, JB AF Kostis, William J. Deng, Yingzi Pantazopoulos, John S. Moreyra, Abel E. Kostis, John B. CA Myocardial Infarction Data TI Trends in Mortality of Acute Myocardial Infarction After Discharge From the Hospital SO CIRCULATION LA English DT Meeting Abstract DE Myocardial infarction; Prognosis; Coronary heart disease; Epidemiology; Aging C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. UMDNJ Robert Wood Johnson Med Sch, New Brunswick, NJ 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 23 PY 2010 VL 122 IS 21 SU S MA A9112 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600363 ER PT J AU Lam, CS Cheng, S Coviello, AD Larson, MG Murabito, JM Newton-Cheh, C Bhasin, S McCabe, EL Miller, KK Redfield, MM Vasan, RS Wang, TJ AF Lam, Carolyn S. Cheng, Susan Coviello, Andrea D. Larson, Martin G. Murabito, Joanne M. Newton-Cheh, Christopher Bhasin, Shalender McCabe, Elizabeth L. Miller, Karen K. Redfield, Margaret M. Vasan, Ramachandran S. Wang, Thomas J. TI Association of Sex Hormone Status with Circulating Natriuretic Peptides SO CIRCULATION LA English DT Meeting Abstract DE Natriuretic peptide C1 Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Mayo Clin, Rochester, 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 23 PY 2010 VL 122 IS 21 SU S MA A12271 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600795 ER PT J AU Langer, A McLaughlin, VV Dragomir, A Casanova, A Tan, M Oudiz, RJ Clements, PJ Tapson, VF Channick, RN Rubin, LJ AF Langer, Anatoly McLaughlin, Vallerie V. Dragomir, Alina Casanova, Amparo Tan, Mary Oudiz, Ronald J. Clements, Philip J. Tapson, Victor F. Channick, Richard N. Rubin, Lewis J. TI Diagnosis and Management of PAH: An Initiative to Close the Care Gap SO CIRCULATION LA English DT Meeting Abstract DE Pulmonary hypertension; Quality assessment C1 Canadian Heart Resc Cntr, Toronto, ON, Canada. Univ Michigan Hlth Syst, Ann Arbor, MI USA. Univ Calif Los Angeles, LA Biomed Rsch Inst Harbor, Torrance, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Duke Univ, Durham, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Diego, San Diego, CA 92103 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 23 PY 2010 VL 122 IS 21 SU S MA A11192 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600652 ER PT J AU Leonardi, S Stebbins, A Lopes, RD Lokhnygina, Y Bhatt, DL Stone, GW Lincoff, MA Dauerman, HL Gibson, CM White, HD Parick, K Gruberg, L Herrmann, HC McLaurin, BT Goodman, S Harrington, RA Mahaffey, KW AF Leonardi, Sergio Stebbins, Amanda Lopes, Renato D. Lokhnygina, Yuliya Bhatt, Deepak L. Stone, Gregg W. Lincoff, Michael A. Dauerman, Harold L. Gibson, C. Michael White, Harvey D. Parick, Keyur Gruberg, Luis Herrmann, Howard C. McLaurin, Brent T. Goodman, Shaun Harrington, Robert A. Mahaffey, Kenneth W. TI Pre-Treatment With Thienopyridines Reduces The Amount of Myonecrosis in Acute Coronary Syndrome Patients Invasively Managed: Insights from the CHAMPION trials SO CIRCULATION LA English DT Meeting Abstract DE Acute coronary syndromes; Antiplatelet drugs; Myocardial infarction C1 Duke Clin Rsch Inst, Durham, NC USA. VA Boston Healthcare Syst, Boston, MA USA. Cardiovasc Rsch Fdn, New York, NY USA. Cleveland Clin, Coordinating Cntr Clin Rsch, Cleveland, OH 44106 USA. Univ Vermont, Coll Med, Burlington, VT USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Green Lane Cardiovasc Rsch Unit, Durham, New Zealand. Care Inst Med Sci, Ahmadabad, Gujarat, India. SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA. Hosp Univ Penn, Philadelphia, PA USA. AnMed Hlth, Anderson, SC USA. Canadian Heart Rsch Cntr, Toronto, ON, Canada. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Duke Clin Rsch Inst, Durham, NC 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 23 PY 2010 VL 122 IS 21 SU S MA A14813 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231601681 ER PT J AU Leuschner, F Panizzi, P Chico-Calero, I Cortez-Retamozo, V Waterman, P Gorbatov, R Marinelli, B Iwamoto, Y Chudnovskiy, A Figueiredo, JL Lee, WW Sosnovik, DE Pittet, MJ Swirski, FK Weissleder, R Nahrendorf, M AF Leuschner, Florian Panizzi, Peter Chico-Calero, Isabel Cortez-Retamozo, Virna Waterman, Peter Gorbatov, Rostic Marinelli, Brett Iwamoto, Yoshiko Chudnovskiy, Aleksey Figueiredo, Jose-Luiz Lee, Won W. Sosnovik, David E. Pittet, Mikael J. Swirski, Filip K. Weissleder, Ralph Nahrendorf, Matthias TI ACE Inhibition prevents the Release of Monocytes from their Splenic Reservoir in Mice with Myocardial Infarction SO CIRCULATION LA English DT Meeting Abstract DE Myocardial infarction; Inflammation; Angiotensin II; Remodeling; Imaging agents C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 23 PY 2010 VL 122 IS 21 SU S MA A17181 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231602393 ER PT J AU Lipshultz, SE Miller, TL Scully, RE Lipsitz, SR Rifai, N Silverman, LB Colan, SD Neuberg, DS Dahlberg, SE Henkel, JM Asselin, BL Athale, U Clavell, LA Laverdiere, C Michon, B Schorin, MA Sallan, SE AF Lipshultz, Steven E. Miller, Tracie L. Scully, Rebecca E. Lipsitz, Stuart R. Rifai, Nader Silverman, Lewis B. Colan, Steven D. Neuberg, Donna S. Dahlberg, Suzanne E. Henkel, Jacqueline M. Asselin, Barbara L. Athale, Uma Clavell, Luis A. Laverdiere, Caroline Michon, Bruno Schorin, Marshall A. Sallan, Stephen E. TI Diagnostic Value of Cardiac Troponin T, N-Terminal Pro-Brain Natriuretic Peptide, and High-Sensitivity C-Reactive Protein During Doxorubicin Therapy in Children with Acute Lymphoblastic Leukemia SO CIRCULATION LA English DT Meeting Abstract DE Biomarkers; Cardiomyopathy; Pediatrics C1 Univ Miami, Miami, FL USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Rochester, Sch Med & Dent, Rochester, NY USA. McMaster Univ, Hamilton, ON, Canada. San Jorge Childrens Hosp, San Juan, PR USA. Hop St Justine, Montreal, PQ H3T 1C5, Canada. Le Cntr Hospier LUniv, Laval, PQ, Canada. Inova Fairfax Hosp Children, Fairfax, VA 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 23 PY 2010 VL 122 IS 21 SU S MA A20432 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231603495 ER PT J AU Losordo, DW Kibbe, M Mendelsohn, F Martson, W Driver, VR Sharafuddin, M Teodorescu, V Wiechmann, B Thompson, C Kraiss, L Carman, T Dohad, S Huang, PP Runyon, JP Schainfeld, RM AF Losordo, Douglas W. Kibbe, Melina Mendelsohn, Farrell Martson, William Driver, Vickie R. Sharafuddin, Mel Teodorescu, Victoria Wiechmann, Bret Thompson, Charles Kraiss, Larry Carman, Teresa Dohad, Suhail Huang, Paul P. Runyon, John Paul Schainfeld, Robert M. TI Randomized, Double-Blind, Placebo Controlled Trial of Autologous CD34+Cell Therapy for Critical Limb Ischemia: 1 Year Results SO CIRCULATION LA English DT Meeting Abstract DE Angiogenesis; Endothelial progenitor cell; Stem cell therapy; Vascular disease; Clinical trials C1 Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Cardiol PC, Birmingham, AL USA. Univ N Carolina, Chapel Hill, NC USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Iowa, Iowa City, IA USA. Mt Sinai Sch Med, New York, NY USA. Florida Rsch Network LLC, Gainesville, FL USA. Orlando Reg Med Cntr, Orlando, FL USA. Univ Utah, Salt Lake City, UT USA. Univ Hosp Cleveland, Case Med Cntr, Cleveland, OH 44106 USA. Cardiovasc Med Grp So Calif, Beverly Hills, CA USA. Swedish Med Cntr, Seattle, WA USA. Christ Hosp, Cincinnati, OH 45219 USA. Massachusetts Gen Hosp W, Waltham, 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 23 PY 2010 VL 122 IS 21 SU S MA A16920 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231602308 ER PT J AU Losordo, DW Henry, TD Schatz, RA Lee, JS Costa, M Bass, T Schaer, GL 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 Raval, AN Sherman, W Kereiakes, D Strumpf, RK Port, S Pieper, K Ewenstein, B Story, KO Barker, KB Harrington, RA AF Losordo, Douglas W. Henry, Timothy D. Schatz, Richard A. Lee, Joon Sup Costa, Marco Bass, Theodore Schaer, Gary L. 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 Raval, Amish N. Sherman, Warren Kereiakes, Dean Strumpf, Robert K. Port, Steven Pieper, Karen Ewenstein, Bruce Story, Kenneth O. Barker, Kerry B. Harrington, Robert A. TI Randomized, Double-Blind, Placebo-Controlled Trial of Autologous CD34+Cell Therapy for Refractory Angina: 2-Year Safety Analysis SO CIRCULATION LA English DT Meeting Abstract C1 Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Abbott NW Hosp, Minneapolis, MN 55407 USA. Scripps Green Hosp, La Jolla, CA USA. Univ Pittsburgh, Pittsburgh, PA USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. UF Coll Med Jacksonville, Jacksonville, FL USA. Rush Univ, Med Cntr, Chicago, IL 60612 USA. Holy Cross Hosp, Ft Lauderdale, FL USA. Cardiol PC, Birmingham, AL USA. Washington Hosp Cntr, Washington, DC USA. St Elizabeths Med Cntr, Boston, MA USA. St Josephs Hosp, Atlanta, GA USA. Mayo Clin, Coll Med, Phoenix, AZ USA. Swedish Med Cntr, Seattle, WA USA. Univ Cincinnati, Cincinnati, OH USA. Stanford Sch Med, Stanford, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Weill Cornell Med Coll, New York, NY USA. Cent Florida Cardiol Grp, Orlando, FL USA. Univ Wisconsin, Madison, WI USA. Columbia Univ, Med Cntr, New York, NY USA. Ohio State Univ, Cincinnati, OH USA. Arizona Heart Inst, Phoenix, AZ USA. St Lukes Med Cntr, Milwaukee, WI USA. Duke Univ, Med Cntr, Durham, NC USA. Baxter Healthcare Corp, Deerfield, IL 60015 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 23 PY 2010 VL 122 IS 21 SU S MA A15621 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231601899 ER PT J AU Magnani, JW Johnson, VM Sullivan, LM Gorodeski, EZ Lubitz, SA Ellinor, PT Benjamin, EJ AF Magnani, Jared W. Johnson, Victor M. Sullivan, Lisa M. Gorodeski, Eiran Z. Lubitz, Stephen A. Ellinor, Patrick T. Benjamin, Emelia J. TI Association of P Wave Indices with Atrial Fibrillation and Mortality Risk in the Community: the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract DE Electrocardiography; Atrial fibrillation; Epidemiology; Risk factors C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Cleveland Clin, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 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 23 PY 2010 VL 122 IS 21 SU S MA A14649 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231601640 ER PT J AU Magnani, JW Gorodeski, EZ Johnson, VM Sullivan, LM Benjamin, EJ Ellinor, PT AF Magnani, Jared W. Gorodeski, Eiran Z. Johnson, Victor M. Sullivan, Lisa M. Benjamin, Emelia J. Ellinor, Patrick T. TI P Wave Duration is Associated with All-cause Mortality: the National Health and Nutrition Epidemiology Survey SO CIRCULATION LA English DT Meeting Abstract DE Electrocardiography; Epidemiology; Atrial function; Risk factors C1 Boston Univ, Boston, MA 02215 USA. Cleveland Clin, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 23 PY 2010 VL 122 IS 21 SU S MA A10135 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600434 ER PT J AU Malhotra, R Hess, D Lewis, GD Bloch, KD Waxman, AB Semigran, MJ AF Malhotra, Rajeev Hess, Dean Lewis, Gregory D. Bloch, Kenneth D. Waxman, Aaron B. Semigran, Marc J. TI Vasoreactivity to Inhaled Nitric Oxide Predicts Longt-erm Survival in Pulmonary Arterial Hypertension SO CIRCULATION LA English DT Meeting Abstract DE Pulmonary hypertension; Vasodilator agents; Nitric oxide C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 23 PY 2010 VL 122 IS 21 SU S MA A11025 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600613 ER PT J AU Maurovich-Horvat, P Alkadhi, H Stolzmann, P Vorpahl, M Nakano, M Kriegel, M Kaple, RM Do, S Scheffel, H Virmani, R Hoffmann, U AF Maurovich-Horvat, Pal Alkadhi, Hatem Stolzmann, Paul Vorpahl, Marc Nakano, Masataka Kriegel, Matthias Kaple, Ryan M. Do, Synho Scheffel, Hans Virmani, Renu Hoffmann, Udo TI Identifying Advanced Coronary Atherosclerotic Plaques: An Ex Vivo Study Using Computed Tomography and Intravascular Ultrasound SO CIRCULATION LA English DT Meeting Abstract DE Arteriosclerosis; Vulnerable plaque; Coronary artery disease; Cardiac CT; Intravascular ultrasound/Doppler C1 Semmelweis Univ, Budapest, Hungary. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. CVPath Inst Inc, 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 23 PY 2010 VL 122 IS 21 SU S MA A19845 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231603285 ER PT J AU Medina, HM Bezerra, H Kyono, H Rojas, CA Techasith, T Ghoshhajra, B Maurovich-Harvat, P Brady, TJ Cury, RC AF Medina, Hector M. Bezerra, Hiram Kyono, Hiroyuki Rojas, Carlos A. Techasith, Tust Ghoshhajra, Brian Maurovich-Harvat, Pal Brady, Thomas J. Cury, Ricardo C. TI Comparison of Diagnostic Accuracy of Coronary CT Angiography during Vasodilator Stress with Routine Clinical Rest CTA SO CIRCULATION LA English DT Meeting Abstract DE Cardiac CT; Stress; Coronary artery disease C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. 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 23 PY 2010 VL 122 IS 21 SU S MA A17826 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231602609 ER PT J AU Minamishima, S Sips, PY Kosugi, S Tokuda, K Kida, K Brouckaert, P Bloch, KD Ichinose, F AF Minamishima, Shizuka Sips, Patrick Y. Kosugi, Shizuko Tokuda, Kentaro Kida, Kotaro Brouckaert, Peter Bloch, Kenneth D. Ichinose, Fumito TI Inhaled Nitric Oxide Improves Long-term Outcome After Successful Cardiopulmonary Resuscitation in Mice SO CIRCULATION LA English DT Meeting Abstract DE Nitric oxide; Cardiac arrest; Cardiopulmonary resuscitation C1 Massachusetts Gen Hosp, Charlestown, MA USA. Univ Ghent VIB, Ghent, Belgium. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 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 23 PY 2010 VL 122 IS 21 SU S MA A15606 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231601891 ER PT J AU Minamishima, S Liu, CH Wang, HF Ichinose, F AF Minamishima, Shizuka Liu, Christina H. Wang, Huifang Ichinose, Fumito TI Hydrogen Sulfide Prevents the Disruption of Blood Brain Barrier After Cardiac Arrest and CPR in Mice SO CIRCULATION LA English DT Meeting Abstract DE Cardiac arrest; Cardiopulmonary resuscitation; Magnetic resonance imaging C1 [Minamishima, Shizuka; Liu, Christina H.; Wang, Huifang; Ichinose, Fumito] Massachusetts Gen Hosp, Charlestown, 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 23 PY 2010 VL 122 IS 21 SU S MA A177 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600166 ER PT J AU Mogabgab, ON Wiviott, SD Antman, EM Foody, JM Wang, TY Sabatine, MS Cannon, CP Mohanavelu, S Li, S Giugliano, RP AF Mogabgab, Owen N. Wiviott, Stephen D. Antman, Elliot M. Foody, Joanne M. Wang, Tracy Y. Sabatine, Marc S. Cannon, Christopher P. Mohanavelu, Satishkumar Li, Shuang Giugliano, Robert P. TI Timing of ST Elevation MI is Related to Patient Baseline Characteristics SO CIRCULATION LA English DT Meeting Abstract DE Circadian rhythm; STEMI; Obesity; Smoking; Beta-blocker C1 Univ Texas SW Med Sch, Dallas, TX USA. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Duke Clin Rsch Inst, Durham, NC 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 23 PY 2010 VL 122 IS 21 SU S MA A12497 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600859 ER PT J AU Moore, SA Horne, BD Januzzi, JL Galenko, O Snow, GL Brunisholz, KD Muhlestein, JB Alharethi, R Carlquist, J Budge, D Kfoury, AG AF Moore, Stephanie A. Horne, Bejamin D. Januzzi, James L. Galenko, Oxana Snow, Gregory L. Brunisholz, Kim D. Muhlestein, Joseph B. Alharethi, Rami Carlquist, John Budge, Deborah Kfoury, Abdallah G. TI Utility of the Interleukin Receptor Family Member ST2 in Predicting Allograft Rejection and Long-term Survival After Heart Transplantation SO CIRCULATION LA English DT Meeting Abstract DE Biomarkers; Transplantation/medical aspects; Prognosis C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Intermt Healthcare, Salt Lake City, UT 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 23 PY 2010 VL 122 IS 21 SU S MA A17331 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231602451 ER PT J AU Mukherjee, R Adams, DK Clarke, EK McClure, CD Stroud, RE McKinney, RA Spinale, FG Gold, MR AF Mukherjee, Rupak Adams, Deborah K. Clarke, Elizabeth K. McClure, Catherine D. Stroud, Robert E. McKinney, Richard A. Spinale, Francis G. Gold, Michael R. TI Differential Plasma Profiles of Matrix Metalloproteinases and Tissue Inhibitors of the Metalloproteinases with Atrial Fibrillation: Relation to Recurrence Following Cardioversion SO CIRCULATION LA English DT Meeting Abstract DE Atrial fibrillation; Biomarkers; Proteolytic enzymes C1 [Mukherjee, Rupak; Adams, Deborah K.; Clarke, Elizabeth K.; McClure, Catherine D.; Stroud, Robert E.; McKinney, Richard A.; Spinale, Francis G.; Gold, Michael R.] Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 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 23 PY 2010 VL 122 IS 21 SU S MA A13798 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231601367 ER PT J AU Mukherjee, R Rivers, WT Patel, RK Stroud, RE Spinale, FG AF Mukherjee, Rupak Rivers, William T. Patel, Risha K. Stroud, Robert E. Spinale, F. G. TI Membrane Type-1 Matrix Metalloproteinase Activity and Specific In Vivo Quantitation Using Specific Targeted Microbubble Imaging: Relation to Left Ventricular Remodeling Following Myocardial Infarction SO CIRCULATION LA English DT Meeting Abstract DE Myocardial infarction; Proteolytic enzymes; Imaging agents C1 [Mukherjee, Rupak; Rivers, William T.; Patel, Risha K.; Stroud, Robert E.; Spinale, F. G.] Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 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 23 PY 2010 VL 122 IS 21 SU S MA A10086 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600426 ER PT J AU Mukherjee, R Rivers, WT Stroud, RE Patel, RK Ruddy, JM Spinale, FG AF Mukherjee, Rupak Rivers, William T. Stroud, Robert E. Patel, Risha K. Ruddy, Jean M. Spinale, Francis G. TI Chronic Localized High-Frequency Electrical Stimulation Within the Myocardial Infarct Attenuates Infarct Expansion Through Transforming Growth Factor-beta Signaling SO CIRCULATION LA English DT Meeting Abstract DE Myocardial infarction; Remodeling; Growth factors C1 Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 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 23 PY 2010 VL 122 IS 21 SU S MA A10085 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V21UD UT WOS:000208231600425 ER EF