FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Bilimoria, KY Balch, CM Bentrem, DJ Talamonti, MS Ko, CY Lange, JR Winchester, DP Wayne, JD AF Bilimoria, Karl Y. Balch, Charles M. Bentrem, David J. Talamonti, Mark S. Ko, Clifford Y. Lange, Julie R. Winchester, David P. Wayne, Jeffrey D. TI Complete lymph node dissection for sentinel node-positive melanoma: Assessment of practice patterns in the United States SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 61st Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 13-16, 2008 CL Chicago, IL SP Soc Surg Oncol DE melanoma; skin neoplasm; sentinel lymph node biopsy; completion lymph node dissection; lymph node; surgery ID STAGE-III MELANOMA; CANCER DATA-BASE; MALIGNANT-MELANOMA; BREAST-CANCER; BIOPSY; MORBIDITY; SURVIVAL; QUALITY; TERM; CARE AB Background: Currently, complete lymph node dissection (CLND) is recommended after identification of a metastatic lymph node by sentinel lymph node biopsy (SLNB). Guidelines suggest that CLND should be performed as a separate procedure, and a sufficient number of nodes should be examined. Our objective was to examine the utilization, timing, and adequacy of CLND for melanoma in the United States. Methods: From the National Cancer Data Base, patients diagnosed with stage I to III melanoma during 2004-2005 were identified. Multiple logistic regression was used to assess factors associated with CLND utilization, timing (separate operation from SLNB), and adequacy (examination of >= 10 nodes). Results: Of the 44,548 patients identified, 47.5% were pathologic stage IA, 23.8% stage IB, 14.1% stage II, and 14.6% stage III. Of the 17% (2942 of 17,524) with nodal metastases on SLNB, only 50% underwent a CLND. Patients were significantly less likely to undergo a CLND after SLNB if > 75 years old or had lower extremity melanomas. Of the patients who underwent a CLND, only 42% underwent the CLND at a separate procedure after the SLNB. Of those who underwent a CLND, 69.2% had >= 10 nodes examined. Patients were significantly less likely to have >= 10 nodes examined if they were > 75 years old or had lower extremity melanomas. Patients treated at NCCN/NCI-designated centers were significantly more likely to undergo nodal evaluation in concordance with established guidelines. Conclusions: Only half of patients with sentinel node-positive melanoma underwent CLND. Quality surveillance measures are needed to monitor, standardize, and improve the care of patients with malignant melanoma. C1 [Bilimoria, Karl Y.; Ko, Clifford Y.; Winchester, David P.] Amer Coll Surg, Canc Programs, Chicago, IL USA. [Bilimoria, Karl Y.; Bentrem, David J.; Talamonti, Mark S.; Winchester, David P.; Wayne, Jeffrey D.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. [Balch, Charles M.; Lange, Julie R.] Johns Hopkins Sch Med, Dept Surg, Baltimore, MD USA. [Talamonti, Mark S.; Winchester, David P.] Evanston NW Healthcare, Dept Surg, Evanston, IL 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 Bilimoria, KY (reprint author), Amer Coll Surg, Canc Programs, Chicago, IL USA. EM k-bilimoria@northwestern.edu NR 45 TC 74 Z9 74 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUN PY 2008 VL 15 IS 6 BP 1566 EP 1576 DI 10.1245/s10434-008-9885-2 PG 11 WC Oncology; Surgery SC Oncology; Surgery GA 299FM UT WOS:000255741500005 PM 18414952 ER PT J AU Wright, CD Gaissert, HA Grab, JD O'Brien, SM Peterson, ED Allen, MS AF Wright, Cameron D. Gaissert, Henning A. Grab, Joshua D. O'Brien, Sean M. Peterson, Eric D. Allen, Mark S. TI Predictors of prolonged length of stay after lobectomy for lung cancer: A society of thoracic surgeons general thoracic surgery database risk-adjustment model SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 28-30, 2008 CL Ft Lauderdale, FL SP Soc Thorac Surg ID RESECTION AB Background. Few reliable estimations of operative risk exist for lung cancer patients undergoing lobectomy. This study identified risk factors associated with prolonged length of hospital stay (PLOS) after lobectomy for lung cancer as a surrogate for perioperative morbid events. Methods. The Society of Thoracic Surgeons (STS) General Thoracic Surgery Database was queried for patients with lobectomy for lung cancer. A model of preoperative risk factors was developed by multivariate stepwise logistic regression setting the threshold for PLOS at 14 days. Morbidity was measured as postoperative events as defined in the STS database. Risk-adjusted results were reported to participating sites. Results. From January 2002 to June 2006, 4979 lobectomies were performed for lung cancer at 56 STS sites, and 351 (7%) had a PLOS. They had more postoperative events than patients without PLOS (3.4 vs 1.2; p < 0.0001). Patients with PLOS also had higher mortality than those with normal LOS, at 10.8% (38 of 351) vs 0.7% (33 of 4628; p < 0.0001). Significant predictors of PLOS included age per 10 years (odds ratio [ OR], 1.30, p < 0.001), Zubrod score (OR, 1.51; p < 0.001), male sex (OR, 1.45; p = 0.002), American Society of Anesthesiology score (OR, 1.54; p < 0.001), insulin-dependent diabetes (OR. 1.71; p = 0.037), renal dysfunction (OR, 1.79; p = 0.004), induction therapy (OR, 1.65; p = 0.001), percentage predicted forced expiratory volume in 1 second in 10% increments (OR, 0.88; p < 0.001), and smoking (OR, 1.33; p = 0.095). After risk adjustment, twofold interhospital variability existed in PLOS among STS sites Conclusions. We identified significant predictors of PLOS, a surrogate morbidity marker after lobectomy for lung cancer. This model may be used to provide meaningful risk-adjusted outcome comparisons to STS sites for quality improvement purposes. C1 [Wright, Cameron D.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Duke Univ, Duke Clin Res Inst, Durham, NC USA. Mayo Clin, Sch Med, Div Gen Thorac Surg, Minneapolis, MN USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570, Boston, MA 02114 USA. EM cdwright@partners.org RI O'Brien, Sean/H-6268-2013 NR 10 TC 91 Z9 94 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 2008 VL 85 IS 6 BP 1857 EP 1865 DI 10.1016/j.athoracsur.2008.03.024 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 303PH UT WOS:000256052200003 PM 18498784 ER PT J AU Azor, M Gene, J Cano, J Sutton, DA Fothergill, AW Rinaldi, MG Guarrol, J AF Azor, Monica Gene, Josepa Cano, Josep Sutton, Deanna A. Fothergill, Annette W. Rinaldi, Michael G. Guarrol, Josep TI In vitro antifungal susceptibility and molecular characterization of clinical isolates of Fusarium verticillioides (F-moniliforme) and Fusarium thapsinum SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID FUJIKUROI SPECIES COMPLEX; INFECTIONS AB A microdilution method was used to test 11 antifungal drugs against clinical isolates of Fusarium thapsinum and three different phylogenetic clades of Fusarium verticillioides that were characterized by sequencing a region of the P-tubulin gene. Terbinafine was the most-active drug against both species, followed by posaconazole against F. verticillioides. C1 [Azor, Monica; Gene, Josepa; Cano, Josep; Guarrol, Josep] Univ Rovira & Virgili, Unitat Microbiol, Fac Med & Ciencies Salut, Tarragona 43201, Spain. [Sutton, Deanna A.; Fothergill, Annette W.; Rinaldi, Michael G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78229 USA. [Rinaldi, Michael G.] Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RP Guarrol, J (reprint author), Univ Rovira & Virgili, Unitat Microbiol, Fac Med & Ciencies Salut, C St Llorenc 21, Tarragona 43201, Spain. EM josep.guarro@urv.cat OI Cano-Lira, Jose F./0000-0003-4495-4394; Guarro, Josep/0000-0002-7839-7568 NR 22 TC 27 Z9 27 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 2008 VL 52 IS 6 BP 2228 EP 2231 DI 10.1128/AAC.00176-08 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 306UG UT WOS:000256272700044 PM 18391027 ER PT J AU Schwarzschild, MA Schwid, SR Marek, K Watts, A Lang, AE Oakes, D Shoulson, I Ascherio, A AF Schwarzschild, Michael A. Schwid, Steven R. Marek, Kenneth Watts, Arthur Lang, Anthony E. Oakes, David Shoulson, Ira Ascherio, Alberto CA Parkinson Study Grp PRECEPT Invest TI Serum urate as a predictor of clinical and radiographic progression in Parkinson disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID URIC-ACID LEVELS; DAIRY-PRODUCTS; MULTIPLE-SCLEROSIS; RISK-FACTORS; PEROXYNITRITE; CONSUMPTION; XANTHINE; MEN; METABOLISM; DISABILITY AB Objective: To determine whether concentration of serum urate, a purine metabolite and potent antioxidant that has been linked to a reduced risk of Parkinson disease (PD), predicts prognosis in PD. Design: Prospective study. Setting: The Parkinson Research Examination of CEP-1347 Trial (PRECEPT) study, which investigated the effects of a potential neuroprotectant on rates of PD progression, was conducted between April 2002 and August 2005 (average follow-up time 21.4 months). Participants: Eight hundred four subjects with early PD enrolled in the PRECEPT study. Main Outcome Measures: The primary study end point was progression to clinical disability sufficient to warrant dopaminergic therapy. Cox proportional hazards models were used to estimate the hazard ratio (HR) of reaching end point according to quintiles of baseline serum urate concentration, adjusting for sex, age, and other potential covariates. Change in striatal uptake of iodine I123-labeled 2-beta-carbomethoxy-3-beta-(4-iodophenyl) tropane ([I-123]beta-CIT), amarker for the presynaptic dopamine transporter, was assessed with linear regression for a subset of 399 subjects. Results: The adjusted HR of reaching end point declined with increasing baseline concentrations of urate; subjects in the top quintile reached the end point at only half the rate of subjects in the bottom quintile (HR, 0.51; 95% confidence interval [CI], 0.37-0.72; P for trend <. 001). This association was markedly stronger in men (HR, 0.39; 95% CI, 0.26-0.60; P for trend <. 001) than in women (HR, 0.77; 95% CI, 0.39-1.50; P for trend=. 33). The percentage of loss in striatal [I-123] beta-CIT uptake also improved with increasing serum urate concentrations (overall P for trend=. 002; men, P=. 001; women, P=. 43). Conclusions: These findings identify serum urate as the first molecular factor directly linked to the progression of typical PD and suggest that targeting urate or its determinants could be aneffective disease-modifying therapy in PD. C1 [Lang, Anthony E.] Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. [Marek, Kenneth] Inst Neurodegenerat Disorders, New Haven, CT USA. [Schwid, Steven R.; Watts, Arthur; Oakes, David; Shoulson, Ira] Univ Rochester, Dept Neurol, Rochester, NY USA. [Schwid, Steven R.; Watts, Arthur; Oakes, David; Shoulson, Ira] Univ Rochester, Dept Biostat, Rochester, NY USA. [Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ascherio, Alberto] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02114 USA. [Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Ascherio, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave,Bldg 2, Boston, MA 02115 USA. EM aascheri@hsph.harvard.edu FU NIEHS NIH HHS [ES010804, R01 ES010804, R01 ES010804-05]; NINDS NIH HHS [NS048517, R01 NS048517, R01 NS048517-03] NR 46 TC 133 Z9 140 U1 1 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUN PY 2008 VL 65 IS 6 BP 716 EP 723 DI 10.1001/archneur.2008.65.6.nct70003 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 310RZ UT WOS:000256549100005 PM 18413464 ER PT J AU Locascio, JJ Fukumoto, H Yap, L Bottiglieri, T Growdon, JH Hyman, BT Irizarry, MC AF Locascio, Joseph J. Fukumoto, Hiroaki Yap, Liang Bottiglieri, Teodoro Growdon, John H. Hyman, Bradley T. Irizarry, Michael C. TI Plasma amyloid beta-protein and C-reactive protein in relation to the rate of progression of Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; APOLIPOPROTEIN-E GENOTYPE; CEREBROSPINAL-FLUID; DECLINE; DEMENTIA; RISK; HOMOCYSTEINE; INFLAMMATION; ASSOCIATION; PERFORMANCE AB Objective: To examine whether plasma markers of amyloid precursor protein metabolism (amyloid beta-protein ending in Val-40 [A beta 40] and Ala-42 [A beta 42]), inflammation (high-sensitivity C-reactive protein), and folic acid metabolism (folic acid, vitamin B(12), and total homocysteine levels) are associated with the rate of cognitive and functional decline in persons with Alzheimer disease. Design: Longitudinal study across a mean (SD) of 4.2 (2.6) years with assessments at approximately 6-to 12-month intervals. Setting: Outpatient care. Patients: A cohort of 122 patients having a clinical diagnosis of probable Alzheimer disease, each with at least 2 assessments across time. Main Outcome Measures: Scores on the cognitive Information-Memory- Concentration subscale of the Blessed Dementia Scale and the functional Weintraub Activities of Daily Living Scale. Results: Low plasma levels of A beta 40, A beta 42, and high-sensitivity C-reactive protein were associated with a significantly more rapid cognitive decline, as indexed using the Blessed Dementia Scale, than were high levels. Low levels of A beta 42 and high-sensitivity C-reactive protein were significantly associated with more rapid functional decline on the Weintraub Activities of Daily Living Scale than were high levels. These plasma markers contributed about 5% to 12% of the variance accounted for on the Blessed Dementia Scale and the Activities of Daily Living Scale by fixed-effects predictors. Measures of folic acid metabolism were not associated with changes on either the Blessed Dementia Scale or the Activities of Daily Living Scale. Conclusions: Plasma markers of amyloid precursor protein metabolism and C-reactive protein may be associated with the rate of cognitive and functional decline in patients with Alzheimer disease. C1 [Locascio, Joseph J.; Fukumoto, Hiroaki; Yap, Liang; Growdon, John H.; Hyman, Bradley T.; Irizarry, Michael C.] Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Wang Ambulatory Care Ctr, Boston, MA 02114 USA. [Fukumoto, Hiroaki] Takeda Chem Co, Osaka, Japan. [Bottiglieri, Teodoro] Baylor Inst Metab Dis, Dallas, TX USA. RP Locascio, JJ (reprint author), Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Wang Ambulatory Care Ctr, Suite 720,Room 731-G,15 Parkman St, Boston, MA 02114 USA. EM jlocascio@partners.org FU NCCIH NIH HHS [R21 AT002311-01A2, R21 AT002311]; NIA NIH HHS [AG05134, P50 AG005134]; NINDS NIH HHS [T32 NS048005, T32 NS048005-04, T32 NS048005-05, T32NS048005] NR 40 TC 44 Z9 49 U1 3 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUN PY 2008 VL 65 IS 6 BP 776 EP 785 DI 10.1001/archneur.65.6.776 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 310RZ UT WOS:000256549100011 PM 18541797 ER PT J AU Shen, LQ Child, A Weber, GM Folkman, J Aiello, LP AF Shen, Lucy Q. Child, Angie Weber, Griffin M. Folkman, Judah Aiello, Lloyd Paul TI Rosiglitazone and delayed onset of proliferative diabetic retinopathy SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RECEPTOR-GAMMA LIGANDS; MACULAR EDEMA; THIAZOLIDINEDIONES; GLUCOSE; TRIAL; RISK; NEOVASCULARIZATION; MICROALBUMINURIA; COMPLICATIONS AB Objective: To evaluate whether rosiglitazone maleate, an oral peroxisome-proliferating activated receptor gamma agonist and oral insulin sensitizing agent with potential antiangiogenic activity, delays onset of proliferative diabetic retinopathy (PDR). Methods: Longitudinal medical record review of all patients treated with rosiglitazone receiving both medical and ophthalmic care at the Joslin Diabetes Center from May 1, 2002, to May 31, 2003 (N=124), and matched control patients not taking a glitazone drug (N=158). The mean duration of follow-up was 2.8 years (range, 0.3-9.0 years). Results: Baseline characteristics and final hemoglobin A(1c) values (7.6% and 7.8%, respectively) were similar in the rosiglitazone and control groups (P=.10). In eyes with severe nonproliferative diabetic retinopathy at baseline (rosiglitazone group, 14 eyes; control group, 24 eyes), progression to PDR over 3 years occurred in 19.2% in the rosiglitazone group and 47.4% in the control group, representing a 59% relative risk reduction (Wilcoxon, P=.045; log-rank, P=.059). Fewer eyes in the rosiglitazone group experienced 3 or more lines of visual acuity loss (P=.03). The incidence of diabetic macular edema was similar in both groups. Conclusions: Rosiglitazone may delay the onset of PDR, possibly because of its antiangiogenic activity. Future clinical investigations should consider analysis of this potential benefit along with ongoing evaluation of potential cardiac risk in studies where the risk-benefit profiles are deemed appropriate. C1 [Aiello, Lloyd Paul] Joslin Diabet Ctr, Eye Res Sect, Boston, MA 02215 USA. [Aiello, Lloyd Paul] Beetham Eye Inst, Boston, MA USA. [Shen, Lucy Q.; Child, Angie; Weber, Griffin M.; Folkman, Judah; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Weber, Griffin M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Folkman, Judah] Childrens Hosp Boston, Boston, MA USA. [Shen, Lucy Q.] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. RP Aiello, LP (reprint author), Joslin Diabet Ctr, Eye Res Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM lpaiello@joslin.harvard.edu OI Weber, Griffin/0000-0002-2597-881X NR 49 TC 46 Z9 50 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9950 EI 1538-3601 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 2008 VL 126 IS 6 BP 793 EP 799 DI 10.1001/archopht.126.6.793 PG 7 WC Ophthalmology SC Ophthalmology GA 310RX UT WOS:000256548900004 PM 18541841 ER PT J AU Moore, MG Lin, DT Mikulec, AA McKenna, MJ Varvares, MA AF Moore, Michael G. Lin, Derrick T. Mikulec, Anthony A. McKenna, Michae J. Varvares, Mark A. TI The occipital flap for reconstruction after lateral temporal bone resection SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the North-America-Skull-Base-Society CY FEB 16-19, 2006 CL Phoenix, AZ SP N Amer Skull Base Soc ID FREE-TISSUE TRANSFER; NECK RECONSTRUCTION; PEDICLED FLAP; SCALP FLAP; HEAD; DEFECTS; SURGERY; COMPLICATIONS; MANAGEMENT AB Objective: To investigate the use of the occipital rotational flap as an alternative reconstructive technique following lateral temporal bone resection. Methods: A retrospective medical record review of 10 patients who underwent reconstruction with an occipital rotational flap after auriculectomy or lateral temporal bone resection. Patient and operative variables included age, preoperative ASA (American Society of Anesthesiologists) classification, operative time, total length of hospital stay, and use of preoperative and postoperative radiotherapy. Patient demographic characteristics and medical comorbidities were also recorded. Clinical outcomes included medical complications, minor and major wound complications, and donor site complications. Results: Patients' mean age was 73.9 years, and mean ASA classification was 2.8. The mean operative time was 8.1 hours, and the mean length of hospital stay was 5.3 days. Three patients received preoperative radiotherapy, and 7 received postoperative radiotherapy. Two patients developed postoperative medical complications, 2 developed minor wound breakdown, and I developed a donor site complication. Conclusion: The occipital flap method is reliable and should be considered as an option for reconstruction after lateral temporal bone resection in select patients. C1 [Moore, Michael G.; Lin, Derrick T.; McKenna, Michae J.] Harvard Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Mikulec, Anthony A.; Varvares, Mark A.] St Louis Univ, Sch Med, St Louis, MO USA. RP Moore, MG (reprint author), Harvard Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 20 TC 4 Z9 5 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUN PY 2008 VL 134 IS 6 BP 587 EP 591 DI 10.1001/archotol.134.6.587 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 312KZ UT WOS:000256671600003 PM 18559723 ER PT J AU Tambouret, RH Misdraji, J Wilbur, DC AF Tambouret, Rosemary H. Misdraji, Joseph Wilbur, David C. TI Longitudinal clinical evaluation of a novel antibody cocktail for detection of high-grade squamous intraepithelial lesions on cervical cytology specimens SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID THINPREP PAP TEST; HUMAN-PAPILLOMAVIRUS; AUTOCYTE PREP; GYNECOLOGIC CYTOLOGY; PAPANICOLAOU SMEAR; PRETERM DELIVERY; IMAGING-SYSTEM; UTERINE CERVIX; AUTOPAP SYSTEM; YOUNG-WOMEN AB Context.-Although cervical cancer screening by cytology is successful, the test continues to show relatively poor operating characteristics. Cell cycle markers may enhance detection of high-grade squamous intraepithelial lesions. Objective.-To determine the clinical usefulness of ProExC, an immunocytochemical assay for cell cycle components, performed on routine cervical cytology samples. Design.-Cervical cytology samples were collected using the SurePath method. Residual cells remaining after preparation of the Papanicolaou-stained slide were used to make a second slide for ProExC staining using an indirect polymer-based immunoperoxidase method. Only adequately cellular slides were evaluated for the presence of nuclear staining within cytologically abnormal epithelial cells. Results were correlated with clinical follow-up. Results.-Six hundred twenty-four samples were satisfactorily cellular and stained. Correlation with clinical follow-up for subsequent cervical intraepithelial neoplasia 2+ on biopsy/high-grade squamous intraepithelial lesion on cytology (CIN 2+/HSIL) showed that 434 results were true negative, 78 true positive, 18 false-negative, and 94 false-positive, resulting in a sensitivity/specificity of 81%/82%. When ProExC results were combined with any level of cytologic atypia, sensitivity for CIN 2 +/HSIL was 92% and specificity was 84%. Conclusions.-ProExC shows promise as an aid in enhancing the sensitivity and specificity of cervical cytology for subsequent CIN 2+/HSIL and may be useful in identifying those cervical lesions most apt to progress. C1 [Tambouret, Rosemary H.; Misdraji, Joseph; Wilbur, David C.] Massachusetts Gen Hosp, Dept Pathol, Div Cytopathol, James Homer Wright Pathol Lab, Boston, MA 02114 USA. RP Tambouret, RH (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Cytopathol, James Homer Wright Pathol Lab, 55 Fruit St, Boston, MA 02114 USA. EM rtambouret@partners.org NR 52 TC 21 Z9 21 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JUN PY 2008 VL 132 IS 6 BP 918 EP 925 PG 8 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 309HU UT WOS:000256452100007 PM 18517273 ER PT J AU Chan, L Ciol, MA Shumway-Cook, A Yorkston, KM Dudgeon, BJ Asch, SM Hoffman, JM AF Chan, Leighton Ciol, Marcia A. Shumway-Cook, Anne Yorkston, Kathryn M. Dudgeon, Brian J. Asch, Steven M. Hoffman, Jeanne M. TI A longitudinal evaluation of persons with disabilities: Does a longitudinal definition help define who receives necessary care? SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE disability evaluation; medicare; rehabilitation ID MEDICARE BENEFICIARIES; HEALTH-CARE; POPULATION; SERVICES; SATISFACTION; PEOPLE; COSTS AB Objective: To assess, using a longitudinal definition, the impact of disability on a broad range of objective health care quality indicators. Design: Longitudinal cohort study following up with patients over several years. The first 2 interviews, 1 year apart, were used to determine each patient's disability status in activities of daily living (ADLs). Assessment of the health care indicators commenced after the second interview and continued throughout the survey period (an additional 1-3y). Setting: National survey. Participants: Participants (N = 29,074) of the Medicare Current Beneficiary Survey (1992-2001) with no, increasing, decreasing, and stable ADL disability. Interventions: Not applicable. Main Outcome Measure: The incidence of 5 avoidable outcomes, receipt of 3 preventive care measures, and adherence to 32 diagnostically based indicators assessing the quality of treatment for acute myocardial infarction [AMI], angina, breast cancer, cerebrovascular accident, transient ischemic attack, cholelithiasis, chronic obstructive pulmonary disease [COPD], congestive heart failure, depression, gastrointestinal bleeding, diabetes, and hypertension. Results: For most indicators, less than 75% of eligible patients received necessary care, regardless of disability status. For 5 indicators, less than 50% of patients received appropriate treatment. In a logistic regression analysis that controlled for patient age, sex, race, and income, disability status was a significant factor in 7 quality measures (AMI, breast cancer, COPD, diabetes, angina, pneumonia, annual visits). Conclusions: Using a longitudinal definition of disability and objective health quality indicators, we found that disability status can be an important factor in determining receipt of quality health care in a broad range of diagnostic categories. However, the impact of disability status varies depending on the indicator measured. In this cohort of patients, the changing nature of a person's disability seems to have less impact than whether they ever have had any functional deficits. C1 [Chan, Leighton] NIH, Dept Rehabil Med, Clin Res Ctr, Bethesda, MD 20892 USA. [Ciol, Marcia A.; Shumway-Cook, Anne; Yorkston, Kathryn M.; Dudgeon, Brian J.; Asch, Steven M.] Univ Washington, Sch Med, Seattle, WA USA. [Hoffman, Jeanne M.] W Los Angeles Vet Affairs Med Ctr, Hlth Serv Res & Dev Serv, Los Angeles, CA 90073 USA. RP Chan, L (reprint author), NIH, Dept Rehabil Med, Clin Res Ctr, Bldg 10,Room 1-1469,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. EM chanle@cc.nih.gov FU Intramural NIH HHS [ZIA CL060072-04]; PHS HHS [MM-0625-04/04] NR 20 TC 16 Z9 16 U1 2 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUN PY 2008 VL 89 IS 6 BP 1023 EP 1030 DI 10.1016/j.apmr.2007.10.045 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 310TN UT WOS:000256553400003 PM 18503795 ER PT J AU Karmarkar, A Cooper, RA Liu, HY Connor, S Puhlman, J AF Karmarkar, Amol Cooper, Rory A. Liu, Hsin-yi Connor, Sam Puhlman, Jeremy TI Evaluation of pushrim-activated power-assisted wheelchairs using ANSI/RESNA standards SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT Annual Meeting of RESNA CY JUN 15-19, 2007 CL Phoenix, AZ SP RESNA DE quality assurance; health care; rehabilitation; wheelchairs ID MANUAL WHEELCHAIR; PERFORMANCE; TETRAPLEGIA; DURABILITY; INJURIES AB Objective: To determine and compare performance of pushrim-activated power-assisted wheelchairs (PAPAW) (iGLIDE, e-motion, Xtender) on national standards. Design: Engineering performance and safety evaluation. Setting: A Veteran Affairs and university-based research center. Specimens: Nine PAPAWs. Interventions: Not applicable. Main Outcome Measures: Static, dynamic stability, brake effectiveness, maximum speed, acceleration, retardation, energy consumption, static, impact, and fatigue strength. Results: There was no significant difference among the 3 models in forward stability. The iGLIDE was the most stable, whereas the e-motion was the least stable model in the rearward stability tests. All PAPAWs performed equally on the slopes of 3 degrees and 6 degrees in the forward and rearward directions. Braking distance was the highest for e-motion (5.64 +/- 0.28m) and the lowest (1.13 +/- 0.03m) for the iGLIDE in forward direction. The average equivalent cycles of all PAPAWs were 318,292 +/- 112,776.6 cycles (n=8) on the fatigue tests. All PAPAWs passed the impact and static strength tests. Conclusions: The standards of the American National Standards Institute and the Rehabilitation Engineering and Assistive Technology Society of North America could act as quality assurance tool for wheelchairs. The standards for wheelchairs were first approved in 1990; after 17 years, exceeding the minimum values in the standards would be a reasonable expectation. C1 [Karmarkar, Amol; Cooper, Rory A.; Liu, Hsin-yi; Connor, Sam; Puhlman, Jeremy] VA Pittsburgh Healthcare Syst, VA Rehabil Res & Dev Serv, Human Engn Res Labs, Pittsburgh, PA 15260 USA. [Karmarkar, Amol; Liu, Hsin-yi] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Cooper, Rory A.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Cooper, Rory A.; Puhlman, Jeremy] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151 R1 HD, 7180 Highland Dr, Pittsburgh, PA 15260 USA. EM rcooper@pitt.edu RI Karmarkar, Amol/E-6030-2011 OI Karmarkar, Amol/0000-0001-8355-1585 NR 18 TC 6 Z9 6 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUN PY 2008 VL 89 IS 6 BP 1191 EP 1198 DI 10.1016/j.apmr.2007.10.029 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 310TN UT WOS:000256553400027 PM 18503819 ER PT J AU Gray, SH Vick, CC Graham, LA Finan, KR Neumayer, LA Hawn, MT AF Gray, Stephen H. Vick, Catherine C. Graham, Laura A. Finan, Kelly R. Neumayer, Leigh A. Hawn, Mary T. TI Risk of complications from enterotomy or unplanned bowel resection during elective hernia repair SO ARCHIVES OF SURGERY LA English DT Article ID OF-VETERANS-AFFAIRS; INCISIONAL HERNIA; POLYPROPYLENE MESH; ABDOMINAL-WALL; ADHESION FORMATION; SURGICAL CARE; SURGERY; PREVENTION; INFECTION; OUTCOMES AB Hypothesis: Enterotomy or unplanned bowel resection (EBR) may occur during elective incisional hernia repair (IHR) and significantly affects surgical outcomes and hospital resource use. Design: Retrospective review of patients undergoing IHR between January 1998 and December 2002. Setting: Sixteen tertiary care Veterans Affairs medical centers. Patients: A total of 1124 elective incisional hernia repairs identified in the National Surgical Quality Improvement Program data set. Intervention: Elective IHR. Main Outcome Measures: Thirty-day postoperative complication rate, return to operating room, length of stay, and operative time. Results: Of the 1124 elective procedures, 74.1% were primary IHR, 13.3% were recurrent prior mesh IHR, and 12.6% were recurrent prior suture. Overall, 7.3% had an EBR. The incidence of EBR was increased in patients with prior repair: 5.3% for primary repair, 5.7% for recurrent prior suture, and 20.3% for prior mesh repair (P <.001). The occurrence of EBR was associated with increased postoperative complications (31.7% vs 9.5%; P <.001), rate of reoperation within 30 days (14.6% vs 3.6%; P <.001), and development of enterocutaneous fistula (7.3% vs 0.7%; P <.001). After adjusting for procedure type, age, and American Society of Anesthesiologists class, EBR was associated with an increase in median operative time (1.7 to 3.5 hours; P <.001) and mean length of stay (4.0 to 6.0 days; P <.001). Conclusions: Enterotomy or unplanned bowel resection is more likely to complicate recurrent IHR with prior mesh. The occurrence of EBR is associated with increased postoperative complications, return to the operating room, risk of enterocutaneous fistula, length of hospitalization, and operative time. C1 [Gray, Stephen H.; Vick, Catherine C.; Graham, Laura A.; Finan, Kelly R.; Hawn, Mary T.] Univ Alabama, Birmingham Vet Affairs Med Ctr, Deep S Ctr Effectiveness Res, Birmingham, AL 35294 USA. [Gray, Stephen H.; Vick, Catherine C.; Graham, Laura A.; Finan, Kelly R.; Hawn, Mary T.] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. [Gray, Stephen H.] Univ Alabama, Hlth Serv & Outcomes Res Traininng Program, Dept Med, Birmingham, AL 35294 USA. [Neumayer, Leigh A.] Univ Utah, Dept Surg, Salt Lake City, UT USA. [Neumayer, Leigh A.] Univ Utah, Vet Affairs Med Ctr, Salt Lake City, UT USA. RP Hawn, MT (reprint author), Univ Alabama, Birmingham Vet Affairs Med Ctr, Deep S Ctr Effectiveness Res, 1530 3rd Ave S,KB 429, Birmingham, AL 35294 USA. EM mhawn@uab.edu OI Gray, Stephen/0000-0002-5702-7226 FU AHRQ HHS [HS013852, 5 T32 HS013852]; None [HS013852] NR 30 TC 43 Z9 43 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JUN PY 2008 VL 143 IS 6 BP 582 EP 586 DI 10.1001/archsurg.143.6.582 PG 5 WC Surgery SC Surgery GA 314FP UT WOS:000256795200015 PM 18559752 ER PT J AU Porrett, PM Lee, MK Lian, MM Wang, J Caton, AJ Deng, S Markmann, JF Moore, DJ AF Porrett, Paige M. Lee, Major K. Lian, Moh Moh Wang, Jing Caton, Andrew J. Deng, Shaoping Markmann, James F. Moore, Daniel J. TI A direct comparison of rejection by CD8 and CD4 T cells in a transgenic model of allotransplantation SO ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS LA English DT Article DE CD4; CD8; proliferation; differentiation; transplantation; rejection ID SKIN ALLOGRAFT-REJECTION; IN-VIVO; TRANSPLANTATION TOLERANCE; MEDIATED REJECTION; CELLULAR BASIS; CUTTING EDGE; ACTIVATION; ANTIBODY; ANTIGEN; MICE AB Introduction: The relative contributions of CD4(+) and CD8(+) T cells to transplant rejection remain unknown. The authors integrated a previous model of CD4-mediated graft rejection with a complementary model of CD8-mediated rejection to directly compare the function of graft-reactive CD4(+) and CD8(+) lymphocytes in vivo in a model where rejection requires transgenic T cells. These studies allow direct comparison of CD4 and CD8 T cell responses to the same antigen without the confounding effects of T cell depletion or homeostatic proliferation. Materials and Methods: Clone 4 and TS1 mice possess MHC class I- and II-restricted CD8(+) and CD4(+) T cells, respectively, which express transgenic T cell receptors that recognize the influenza hemagglutinin antigen (HA). We compared the in vivo response of CFSE-labeled, HA-specific transgenic CD8(+) and CD4(+) T cells after adoptive transfer into syngeneic BALB/c mice grafted with HA-expressing skin. Results: As in the authors' CD4(+) model, HA104 skin was consistently rejected by both Clone 4 mice (n=9, MST: 14.2) and by 5 x 10(5) Clone 4 lymphocytes transferred to naive BALB/c hosts that do not otherwise reject HA(+) grafts. Rejection correlated with extensive proliferation of either graft-reactive T cell subset in the draining lymph nodes, and antigen-specific CD4(+) and CD8(+) cells acquired effector function and proliferated with similar kinetics. Conclusions: These data extend the authors' unique transgenic transplantation model to the investigation of CD8 T cell function. The initial results confirm fundamental functional similarity between the CD4 and CD8 T cell subsets and provide insight into the considerable redundancy underlying T cell mechanisms mediating allograft rejection. C1 [Moore, Daniel J.] Vanderbilt Childrens Hosp, Dept Pediat, Div Endocrinol & Diabet, Nashville, TN 37232 USA. [Porrett, Paige M.; Lee, Major K.; Lian, Moh Moh; Wang, Jing; Moore, Daniel J.] Hosp Univ Penn, Dept Surg, Harrison Dept Surg Res, Philadelphia, PA 19104 USA. [Caton, Andrew J.] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. [Deng, Shaoping; Markmann, James F.] Massachusetts Gen Hosp, Dept Transplantat, Div Surg, Boston, MA 02114 USA. RP Moore, DJ (reprint author), Vanderbilt Childrens Hosp, Dept Pediat, Div Endocrinol & Diabet, 2200 Childrens Way,11136 Doctors Off Tower, Nashville, TN 37232 USA. EM daniel.moore@vanderbilt.edu RI Moore, Daniel/A-4924-2008 OI Moore, Daniel/0000-0002-6889-9345 FU NIAID NIH HHS [R01 AI048820, R01-AI48820]; NIDDK NIH HHS [F32 DK083161, F32 DK083161-01] NR 27 TC 4 Z9 5 U1 0 U2 0 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 0004-069X J9 ARCH IMMUNOL THER EX JI Arch. Immunol. Ther. Exp. PD JUN PY 2008 VL 56 IS 3 BP 193 EP 200 DI 10.1007/s00005-008-0019-0 PG 8 WC Immunology SC Immunology GA 316CU UT WOS:000256927300005 PM 18512028 ER PT J AU Dole, VS Matuskova, J Vasile, E Yesilaltay, A Bergmeier, W Bernimoulin, M Wagner, DD Krieger, M AF Dole, Vandana S. Matuskova, Jana Vasile, Eliza Yesilaltay, Ayce Bergmeier, Wolfgang Bernimoulin, Michael Wagner, Denisa D. Krieger, Monty TI Thrombocytopenia and platelet abnormalities in high-density lipoprotein receptor-deficient mice SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE HDL receptor; SR-BI; platelet; thrombocytopenia; clearance ID B TYPE-I; CORONARY-HEART-DISEASE; SR-BI; SCAVENGER RECEPTOR; APOLIPOPROTEIN-E; SEVERE HYPERCHOLESTEROLEMIA; BLOOD-PLATELETS; TANGIER-DISEASE; P-SELECTIN; LIFE-SPAN AB Objective-High-density lipoprotein (HDL) receptor, scavenger receptor class B, type I (SR-BI), mediated cellular uptake of lipoprotein cholesterol controls HDL structure and plasma HDL and biliary cholesterol levels. In SR-BI knockout (KO) mice, an unusually high plasma unesterified-to-total cholesterol ratio (UC:TC) and abnormally large HDL particles apparently contribute to pathology, including female infertility, susceptibility to atherosclerosis and coronary heart disease, and anemia. Here we examined the influence of SR-BI deficiency on platelets. Methods and Results-The high plasma UC: TC ratio in SR-BI KO mice was correlated with platelet abnormalities, including high cholesterol content, abnormal morphologies, high clearance rates, and thrombocytopenia. One day after platelets from wild-type mice were infused into SR-BI KO mice, they exhibited abnormally high cholesterol content and clearance rates similar to those of endogenous platelets. Platelets from SR-BI KO mice exhibited in vitro a blunted aggregation response to the agonist ADP but a normal response to PAR4. Conclusions-In SR-BI KO mice abnormal circulating lipoproteins, particularly their high UC: TC ratio-rather than the absence of SR-BI in platelets themselves-induce defects in platelet structure and clearance, together with a mild defect in function. C1 [Dole, Vandana S.; Vasile, Eliza; Yesilaltay, Ayce; Krieger, Monty] MIT, Dept Biol, Cambridge, MA 02139 USA. [Matuskova, Jana; Bergmeier, Wolfgang; Bernimoulin, Michael; Wagner, Denisa D.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Matuskova, Jana; Bergmeier, Wolfgang; Bernimoulin, Michael; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Krieger, M (reprint author), MIT, Dept Biol, Room 68-483,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM Krieger@MIT.edu FU NHLBI NIH HHS [P01 HL066105-08, P01 HL066105-080006, P01 HL066105-089001, P01 HL066105-089002, P01 HL066105, R01 HL052212, R01 HL052212-15] NR 48 TC 45 Z9 47 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2008 VL 28 IS 6 BP 1111 EP 1116 DI 10.1161/ATVBAHA.108.162347 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 303PS UT WOS:000256053400013 PM 18436807 ER PT J AU O'Donnell, CJ Demissie, S Kimura, M Levy, D Gardner, JP White, C D'Agostino, RB Wolf, PA Polak, J Cupples, LA Aviv, A AF O'Donnell, Christopher J. Demissie, Serkalem Kimura, Masayuki Levy, Daniel Gardner, Jeffery P. White, Charles D'Agostino, Ralph B. Wolf, Philip A. Polak, Joseph Cupples, L. Adrienne Aviv, Abraham TI Leukocyte telomere length and carotid artery intimal medial thickness - The Framingham Heart Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE telomeres; atherosclerosis; leukocytes; obesity; sex; smoking ID MYOCARDIAL-INFARCTION; INSULIN-RESISTANCE; PULSE PRESSURE; CARDIOVASCULAR-DISEASE; HYPERTENSIVE SUBJECTS; METABOLIC SYNDROME; OXIDATIVE STRESS; OLDER-ADULTS; RISK; ATHEROSCLEROSIS AB Background and Purpose-Leukocyte telomere length (LTL) is relatively short in individuals who have evidence of cardiovascular disease. The purpose of this study was to examine the link between LTL and the predisposition to atherosclerosis, as determined by carotid artery intimal medial thickness (IMT) in participants of the Framingham Offspring Study. Methods and Results-LTL was assayed by the mean length of the terminal restriction fragments and carotid artery IMT by B-mode ultrasonography in 1062 individuals (496 men, 566 women) aged 33 to 86 years. In the whole sample, there was a significant association of age-and sex-adjusted LTL with internal carotid artery IMT (ICA-IMT) (r= -0.07, P = 0.02). In sex-stratified analysis, this association remained significant for men (r = -0.11, P = 0.02) but not for women (r = -0.04, P = 0.36). After further adjustment for cigarette smoking and BMI, a borderline significant association persisted in men (P = 0.06). In secondary analysis, the age-adjusted LTL was significantly (and negatively) associated with ICA-IMT (r = -0.28, p = 0.0006) in obese (BMI > 30kg/m(2)) men but not in nonobese (BMI <= 30 kg/m(2)) men. In addition, age-adjusted LTL was significantly shorter in men (6.89 +/- 0.02 kb) than women (7.01 +/- 0.02 kb; P < 0.0009) and in current cigarette smokers (6.87 +/- 0.05 kb) than never smokers (6.99 +/- 0.03 kb; P = 0.0006). Although there was no significant association of LTL with common carotid artery-IMT or with carotid artery stenosis, there was a significant inverse association of LTL with common carotid artery IMT in obese men. Conclusion-In obese men, shortened LTL is a powerful marker of increased carotid IMT. Given the public health impact of atherosclerosis and in particular the current epidemic of obesity, the associations noted in obese men warrant further confirmation. C1 [O'Donnell, Christopher J.; Levy, Daniel] NHLBIs Framingham Heart Study, Framingham, MA 01702 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Demissie, Serkalem; White, Charles; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Kimura, Masayuki; Gardner, Jeffery P.; Aviv, Abraham] Univ Med & Dent New Jersey, Ctr Human Dev & Aging, Newark, NJ 07103 USA. [D'Agostino, Ralph B.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Wolf, Philip A.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Polak, Joseph] Tufts Univ New England Med Ctr, Dept Radiol, Boston, MA USA. RP O'Donnell, CJ (reprint author), NHLBIs Framingham Heart Study, 73 Mt Wayte Ave 2, Framingham, MA 01702 USA. EM codonnell@nih.gov OI Cupples, L. Adrienne/0000-0003-0273-7965 FU Intramural NIH HHS [Z99 HL999999]; NHLBI NIH HHS [N01 HC025195, N01-HC-25195, N01HC25195]; NIA NIH HHS [AG021593, R01 AG021593, R01 AG021593-01] NR 43 TC 79 Z9 79 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2008 VL 28 IS 6 BP 1165 EP 1171 DI 10.1161/ATVBAHA.107.154849 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 303PS UT WOS:000256053400021 PM 18388332 ER PT J AU Ibebuogu, UN Nasir, K Gopal, A Ahmadi, N Pal, R Flores, F Mao, SS Young, E Honoris, L Nuguri, VK Lee, RS Usman, N Rostami, B Budoff, MJ AF Ibebuogu, Uzoma N. Nasir, Khuram Gopal, Ambarish Ahmadi, Naser Pal, Raveen Flores, Ferdinand Mao, Song S. Young, Emily Honoris, Lily Nuguri, Vivek K. Lee, Robert S. Usman, Nudrat Rostami, Babak Budoff, Matthew J. TI Comparison of coronary atherosclerotic plaque burden and composition between diabetic and nondiabetic patients by noninvasive CT angiography SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 16-18, 2008 CL Atlanta, GA C1 [Ibebuogu, Uzoma N.] Med Coll Georgia, Augusta, GA 30912 USA. [Nasir, Khuram] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gopal, Ambarish; Ahmadi, Naser; Pal, Raveen; Flores, Ferdinand; Mao, Song S.; Young, Emily; Honoris, Lily; Nuguri, Vivek K.; Lee, Robert S.; Usman, Nudrat; Rostami, Babak; Budoff, Matthew J.] Univ Calif Los Angeles, Los Angeles Biomed Rsch Inst Harbor, Torrance, 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2008 VL 28 IS 6 MA P558 BP E134 EP E135 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 303PS UT WOS:000256053400552 ER PT J AU Keebler, M Sanders, CL Surti, A Guiducci, C Burtt, NP Kathiresan, S AF Keebler, Mary Sanders, Christopher L. Surti, Aarti Guiducci, Candace Burtt, Noel P. Kathiresan, Sekar TI Association testing of 7 new loci for blood lipoproteins and lipids in a multiethnic US population-based sample SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 16-18, 2008 CL Atlanta, GA C1 [Keebler, Mary; Kathiresan, Sekar] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sanders, Christopher L.] Cntrs Dis Control & Prevent, Atlanta, GA USA. [Surti, Aarti; Guiducci, Candace; Burtt, Noel P.] Harvard Univ, MIT, Broad Inst, Cambridge, MA 02139 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2008 VL 28 IS 6 MA 38 BP E39 EP E39 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 303PS UT WOS:000256053400066 ER PT J AU Leduc, MS Korstanje, R Orho-Melander, M Kathiresan, S Paigen, B AF Leduc, Magalie S. Korstanje, Ron Orho-Melander, Marju Kathiresan, Sekar Paigen, Beverly TI Using the mouse model to confirm genes identified by genomewide association studies for the complex trait HDL cholesterol SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 16-18, 2008 CL Atlanta, GA C1 [Leduc, Magalie S.; Korstanje, Ron; Paigen, Beverly] Jackson Lab, Bar Harbor, ME 04609 USA. [Orho-Melander, Marju] Lund Univ, Univ Hosp Malmo, Malmo, Sweden. [Kathiresan, Sekar] 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2008 VL 28 IS 6 MA 22 BP E36 EP E36 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 303PS UT WOS:000256053400050 ER PT J AU Manning, JJ Moore, KJ Bell, SA Alvarez-Leite, JI de Winther, MP Seimon, TA Tabas, I Freeman, MW AF Manning, Jennifer J. Moore, Kathryn J. Bell, Susan A. Alvarez-Leite, Jacqueline I. de Winther, Menno P. Seimon, Tracie A. Tabas, Ira Freeman, Mason W. TI Despite unaltered lesion area and foam cell formation, atherosclerotic inflammation and lesion complexity are reduced in mice lacking both SR-A and CD36 SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 16-18, 2008 CL Atlanta, GA C1 [Manning, Jennifer J.; Moore, Kathryn J.; Bell, Susan A.; Alvarez-Leite, Jacqueline I.; Freeman, Mason W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [de Winther, Menno P.] Maastricht Univ, Cardiovasc Rsch Inst Maastricht, Maastricht, Netherlands. [Seimon, Tracie A.; Tabas, Ira] Columbia Univ, New York, NY USA. RI de Winther, Menno/E-8721-2012 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2008 VL 28 IS 6 MA P310 BP E90 EP E90 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 303PS UT WOS:000256053400322 ER PT J AU Rousou, LJ Thatte, HS Taylor, KB Lu, XG Healey, HA Crittenden, MD Haime, M Khuri, SF AF Rousou, Laki J. Thatte, Hemant S. Taylor, Kristin B. Lu, Xiu-Gui Healey, Healey A. Crittenden, Michael D. Haime, Miguel Khuri, Shukri F. TI Endoscopic saphenous vein harvest has detrimental impact on endothelial function SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 16-18, 2008 CL Atlanta, GA C1 [Rousou, Laki J.; Thatte, Hemant S.; Taylor, Kristin B.; Lu, Xiu-Gui; Healey, Healey A.; Crittenden, Michael D.; Haime, Miguel; Khuri, Shukri F.] VA Boston Healthcare Syst, W Roxbury, 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2008 VL 28 IS 6 MA P593 BP E141 EP E141 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 303PS UT WOS:000256053400583 ER PT J AU Seimon, TA Magallon, J Moore, KJ Tabas, IA AF Seimon, Tracie A. Magallon, Jorge Moore, Kathryn J. Tabas, Ira A. TI CD36 triggers macrophage apoptosis during ER stress by a mechanism distinct from the type a scavenger receptor SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 16-18, 2008 CL Atlanta, GA C1 [Seimon, Tracie A.; Magallon, Jorge; Tabas, Ira A.] Columbia Univ, New York, NY USA. [Moore, Kathryn J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bosten, 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2008 VL 28 IS 6 MA 46 BP E40 EP E40 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 303PS UT WOS:000256053400074 ER PT J AU Stewart, CR Stuart, LM Deng, JS Richard, J Wilkinson, K Frazier, WA Moore, KJ AF Stewart, Cameron R. Stuart, Lynda M. Deng, Jiusheng Richard, James Wilkinson, Kimberly Frazier, William A. Moore, Kathryn J. TI CD36 orchestrates inflammatory signaling by atherogenic lipids via assembly of a novel toll-like receptor heterodimer SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 16-18, 2008 CL Atlanta, GA C1 [Stewart, Cameron R.; Stuart, Lynda M.; Deng, Jiusheng; Richard, James; Wilkinson, Kimberly; Moore, Kathryn J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Frazier, William A.] Washington Univ, St Louis, MO USA. RI Stewart, Cameron/E-6823-2011 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2008 VL 28 IS 6 MA P505 BP E125 EP E125 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 303PS UT WOS:000256053400502 ER PT J AU Sundararaj, KP Li, YC Samuvel, DJ Nareika, A Lopes-Virella, MF Huang, Y AF Sundararaj, Kamala P. Li, Yanchun Samuvel, Devadoss J. Nareika, Alena Lopes-Virella, Maria F. Huang, Yan TI Simvastatin suppresses LPS-induced MMP-1 expression in U937 mononuclear cells by inhibiting Ras and Rac protein isoprenylation-mediated ERK activation SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 16-18, 2008 CL Atlanta, GA C1 [Sundararaj, Kamala P.; Nareika, Alena; Huang, Yan] Med Univ S Carolina, Charleston, SC 29425 USA. [Li, Yanchun; Huang, Yan] Ralph H Johnson VA Med Ctr, Charleston, SC 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2008 VL 28 IS 6 MA P117 BP E55 EP E55 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 303PS UT WOS:000256053400143 ER PT J AU Cooper, RA Cooper, R Boninger, ML AF Cooper, Rory A. Cooper, Rosemarie Boninger, Michael L. TI Trends and issues in wheelchair technologies SO ASSISTIVE TECHNOLOGY LA English DT Article DE manual wheelchair; power wheelchair; bariatric wheelchair; pushrim-activated power-assist wheelchairs (PA-PAW); independence 3000 IBOT transporter; wheelchair usage; wheelchair transportation; wheelchair marketplace; emerging trends ID POWER-ASSISTED WHEELCHAIR; WHOLE-BODY VIBRATION; MULTIPLE-SCLEROSIS; MANUAL WHEELCHAIRS; PEOPLE; DEVICES; SYSTEM; ADULTS; LIFE; HOME AB There is an overwhelming need for wheelchairs and the research and development required to make them safer, more effective, and widely available. The following areas are of particular importance: practitioner credentials, accreditation, device evaluation, device user training, patient education, clinical prescribing criteria, national contracts, and access to new technology. There are over 170 U.S. wheelchair manufacturers with a total reported income of $1.33 billion. However, of these companies, only five had sales in excess of $100 million. Wheelchairs account for about 1% of Medicare spending. Use of assistive technology is an increasingly common way of adapting to a disability. The emergence of advanced mobility devices shows promise for the contribution of engineering to the amelioration of mobility impairments for millions of people who have disabilities or who are elderly. Some of the trends in wheelchairs are going to require new service delivery mechanisms, changes to public policy, and certainly greater coordination between consumers, policy makers, manufacturers, researchers, and service providers. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Rehabil Res & Dev Ctr Excellence Wheel Chairs, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151 R1, 7180 Highland Dr, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X NR 76 TC 25 Z9 25 U1 0 U2 12 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PD SUM PY 2008 VL 20 IS 2 BP 61 EP 72 PG 12 WC Rehabilitation SC Rehabilitation GA 318IC UT WOS:000257083800001 PM 18646429 ER PT J AU Nimmegeers, S Sips, P Buys, E Thoonen, R Decaluwe, K Brouckaert, P Van de Voorde, J AF Nimmegeers, S. Sips, P. Buys, E. Thoonen, R. Decaluwe, K. Brouckaert, P. Van de Voorde, J. TI Functional importance of the sGC isoforms (alpha(1)beta(1) and alpha(2)beta(1)) in vascular smooth muscle relaxation SO BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY LA English DT Meeting Abstract C1 [Nimmegeers, S.; Decaluwe, K.; Van de Voorde, J.] Univ Ghent, Dept Physiol & Physiopathol, B-9000 Ghent, Belgium. [Sips, P.; Buys, E.; Thoonen, R.; Brouckaert, P.] Univ Ghent, Dept Mol Biol, B-9000 Ghent, Belgium. [Buys, E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Crit Care Res, Dept Anesthesia & Crit Care, Boston, MA USA. [Sips, P.; Buys, E.; Thoonen, R.; Brouckaert, P.] Univ Ghent VIB, Dept Mol Biomed Res, B-9052 Ghent, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-7835 J9 BASIC CLIN PHARMACOL JI Basic Clin. Pharmacol. Toxicol. PD JUN PY 2008 VL 102 SU 1 BP 39 EP 39 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 309YF UT WOS:000256495400116 ER PT J AU Ho, VT Cutler, C AF Ho, Vincent T. Cutler, Corey TI Current and novel therapies in acute GVHD SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Review DE GVHD; BMT; stem cell transplant; HSCT ID VERSUS-HOST-DISEASE; STEROID-REFRACTORY ACUTE; STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; RECEPTOR MONOCLONAL-ANTIBODY; REGULATORY T-CELLS; LOW-DOSE METHOTREXATE; HUMAN DENDRITIC CELLS; MYCOPHENOLATE-MOFETIL; ANTITHYMOCYTE GLOBULIN AB Despite improvements in our understanding of transplant immunology and clinical and supportive care, acute graft-versus-host disease (GVHD) remains a clinical challenge and a major cause of morbidity and mortality for patients after allogeneic hematopoietic stem-cell transplantation. While systemic corticosteroid is standard primary therapy for acute GVHD, there is no established standard treatment in the steroid-refractory setting. New generations of monoclonal antibodies, biologies, and chemotherapeutics with immunomodulatory effects have been developed over the past decade, and are being tested as novel therapies in this disease. Many of these agents - including, among others, mycophenolate mofetil, anti-tumor necrosis factor-alpha antibodies, denileukin diftitox, and anti-interleukin-2R alpha-chain antibodies - have demonstrated promising activity in steroid-refractory acute GVHD. Despite the high response rates, however, long-term survival remains poor due to a high incidence of infections. The key to improving acute GVHD outcomes may, in fact, rest upon successful initial therapy, and timely taper of corticosteroids to promote healthier immune reconstitution. Clinical trials combining these newer agents with systemic corticosteroids as initial treatment are under way, and will determine whether fortifying initial therapy will indeed reduce the development of steroid-refractory GVHD and improve long-term outcomes. In this article, we review current and novel agents available for acute GVHD, and discuss newer investigational approaches - such as phototherapy and cellular therapies - in the management of this common transplant complication. C1 [Ho, Vincent T.; Cutler, Corey] Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Adult Oncol, Dana Farber Canc Inst,Ctr Hematol Oncol, Boston, MA 02115 USA. RP Ho, VT (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Adult Oncol, Dana Farber Canc Inst,Ctr Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. EM vincent_ho@dfci.harvard.edu NR 104 TC 24 Z9 29 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD JUN PY 2008 VL 21 IS 2 BP 223 EP 237 DI 10.1016/j.beha.2008.02.009 PG 15 WC Hematology SC Hematology GA 317FN UT WOS:000257005500011 PM 18503988 ER PT J AU Alyea, EP AF Alyea, Edwin P. TI Modulating graft-versus-host disease to enhance the graft-versus-leukemia effect SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article DE graft-versus-leukemia (GVL); donor lymphocyte infusion (DLI); graft-versus-host disease ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; DONOR LYMPHOCYTE INFUSIONS; DOSE RECOMBINANT INTERLEUKIN-2; REGULATORY T-CELLS; RELAPSED MULTIPLE-MYELOMA; MINIMAL RESIDUAL DISEASE; PERIPHERAL-BLOOD CELLS AB Graft-versus-host disease (GVHD) has been linked with a potent anti-cancer effect referred to as the graft-versus-leukemia (GVL) or graft-versus-malignancy effect. In some experimental models these processes may be distinct, but in clinical practice they are very closely linked. Induction of GVHD using donor lymphocyte infusion has been used to treat relapse after transplantation. Modulation of GVHD has been explored as a method to reduce the risk of relapse after transplantation. Methods explored include altering GVHD prophylaxis after transplant, selection of peripheral-blood stem cells, prophylactic donor lymphocyte infusion, and use of cytokines. Given the toxicity associated with GVHD, defining the balance between GVHD and induction of GVL is of critical importance in transplantation. Laboratory efforts to identify the targets of GVHD and GVL may allow for more specific and effective therapies to be developed while minimizing toxicity. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 01770 USA. RP Alyea, EP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 01770 USA. EM edwin_alyea@dfci.harvard.edu NR 89 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD JUN PY 2008 VL 21 IS 2 BP 239 EP 250 DI 10.1016/j.beha.2008.02.012 PG 12 WC Hematology SC Hematology GA 317FN UT WOS:000257005500012 PM 18503989 ER PT J AU Simao, S Pedrosa, R Hopfer, U Mount, DB Jose, PA Soares-da-Silva, P AF Simao, Sonia Pedrosa, Rui Hopfer, Ulrich Mount, David B. Jose, Pedro A. Soares-da-Silva, Patricio TI Short-term regulation of the Cl-/HCO3- exchanger in immortalized SHR proximal tubular epithelial cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Cl-/HCO3- exchanger; PKA; PKC; p38 MAPK; hypertension; SHR; WKY ID RECEPTOR-MEDIATED INHIBITION; PROTEIN-KINASE-C; SPONTANEOUSLY HYPERTENSIVE-RAT; ESTRONE SULFATE TRANSPORT; K+-ATPASE ACTIVITY; NA+-H+ EXCHANGER; RENAL OK CELLS; INTERFERON-GAMMA; SIGNALING CASCADES; DOPAMINE AB The present study evaluated the activity of Cl-/HCO3- exchanger and the abundance of Slc26a6 in immortalized renal proximal tubular epithelial (PTE) cells from the Wistar-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR) and identified the signaling pathways that regulate the activity of the transporter. The affinity for HCO3- was identical in WKY and SHR PTE cells, but V-max values (in pH units/min) in SHR PTE cells (0.4016) were significantly higher than in WKY PTE cells (0.2304). The expression of Slc26a6 in SHR PTE cells was sevenfold that in WKY PTE cells. Dibutyryl-cAMP (db-cAMP) or forskolin, which increased endogenous cAMP, phorbol-12,13-dibutyrate (PDBu) and anisomycin, significantly (P < 0.05) increased the Cl-/HCO3- exchanger activity in WKY and SHR PTE cells to a similar extent. The stimulatory effects of db-cAMP and forskolin were prevented by the PKA inhibitor H89, but not by chelerythrine. The stimulatory effects of PDBu were prevented by both chelerythrine and SB 203580, but not by H89 or the MEK inhibitor PD 98059. The stimulatory effect of anisomycin was prevented by SB 203580, but not by chelerythrine. Increases in phospho-p38 MAPK by anisomycin were identical in WKY and SHR PTE cells, this being sensitive to SB 203580 but not to chelerythrine. It is concluded that SHR PTE cells, which overexpress the Slc26a6 protein, are endowed with an enhanced activity of the Cl-/HCO3- exchanger. The Cl-/HCO3- exchanger is an effector protein for PKA, PKC and p38 MAPK in both WKY and SHR PTE cells. (C) 2008 Elsevier Inc. All rights reserved. C1 [Simao, Sonia; Pedrosa, Rui; Soares-da-Silva, Patricio] Fac Med, Inst Pharmacol & Therapeut, P-4200 Oporto, Portugal. [Hopfer, Ulrich] Case Western Reserve Sch Med, Dept Physiol & Biophys, Cleveland, OH USA. [Mount, David B.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Mount, David B.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Div Gen Internal Med, Boston, MA 02115 USA. RP Soares-da-Silva, P (reprint author), Fac Med, Inst Pharmacol & Therapeut, P-4200 Oporto, Portugal. EM psoaresdasilva@netcabo.pt RI Hopfer, Ulrich`/B-5463-2009; Soares-da-Silva, Patricio/A-6704-2015; Pedrosa, Rui/B-4815-2015; OI Soares-da-Silva, Patricio/0000-0002-2446-5078; Pedrosa, Rui/0000-0003-0970-0575; Simao, Sonia/0000-0002-0245-0633 FU NHLBI NIH HHS [P01 HL068686, P01 HL068686-070004, R01 HL023081, R01 HL023081-26]; NIDDK NIH HHS [R01 DK039308-21S1, R01 DK039308] NR 38 TC 5 Z9 5 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUN 1 PY 2008 VL 75 IS 11 BP 2224 EP 2233 DI 10.1016/j.bcp.2008.03.003 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 310EJ UT WOS:000256511400017 PM 18407247 ER PT J AU Bonner-Weir, S Inada, A Yatoh, S Li, WC Aye, T Toschi, E Sharma, A AF Bonner-Weir, Susan Inada, Akari Yatoh, Shigeru Li, Wan-Chun Aye, Tandy Toschi, Elena Sharma, Arun TI Transdifferentiation of pancreatic ductal cells to endocrine beta-cells SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT Biochemical-Society Focused Meeting on Pancreatic Beta-Cell: Birth, Life and Death CY DEC 03-04, 2007 CL Kings Coll, London Sch Med, London, ENGLAND SP Biochem Soc HO Kings Coll, London Sch Med DE beta-cell; diabetes neogenesis; pancreatic ductal cell; pancreatic progenitor; pancreatic regeneration ID INSULIN-PRODUCING CELLS; IN-VITRO; PRECURSOR CELLS; AR42J CELLS; EMBRYONIC-DEVELOPMENT; SECRETING CELLS; TRANSGENIC MICE; ADULT EXOCRINE; GROWTH-FACTOR; HUMAN ISLETS AB The regenerative process in the pancreas is of particular interest, since diabetes, whether Type 1 or Type 2, results from an inadequate amount of insulin-producing p-cells. islet neogenesis, or the formation of new islets, seen as budding of hormone-positive cells from the ductal epithelium, has long been considered to be one of the mechanisms of normal islet growth after birth and in regeneration, and suggested the presence of pancreatic stem cells. Results from the rat regeneration model of partial pancreatectomy led us to hypothesize that differentiated pancreatic ductal cells were the pancreatic progenitors after birth, and that with replication they regressed to a less differentiated phenotype and then could differentiate to form new acini and islets. There are numerous supportive results for this hypothesis of neogenesis, including the ability of purified primary human ducts to form insulin-positive cells budding from ducts. However, to rigorously test this hypothesis, we took a direct approach of genetically marking ductal cells using CAII (carbonic anhydrase II) as a duct-cell-specific promoter to drive Cre recombinase in lineage-tracing experiments using the Cre-Lox system. We show that CAII-expressing pancreatic cells act as progenitors that give rise to both new islets and acini after birth and after injury (ductal ligation). This identification of a differentiated pancreatic cell type as an in vivo progenitor for all differentiated pancreatic cell types has implications for a potential expandable source for new islets for replenishment therapy for diabetes either in vivo or ex vivo. C1 [Bonner-Weir, Susan] Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Bonner-Weir, S (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM Susan.Bonner-Weir@joslin.Harvard.edu OI Bonner-Weir, Susan/0000-0003-4682-0656 NR 37 TC 88 Z9 95 U1 0 U2 2 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 EI 1470-8752 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD JUN PY 2008 VL 36 BP 353 EP 356 DI 10.1042/BST0360353 PN 3 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311OH UT WOS:000256609000018 PM 18481956 ER PT J AU Outeiro, TF Marques, O Kazantsev, A AF Outeiro, Tiago Fleming Marques, Oldriska Kazantsev, Aleksey TI Therapeutic role of sirtuins in neurodegenerative disease SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Review DE sirtuins; neurodegeneration; therapeutic targets; aging; metabolism ID HISTONE DEACETYLASE INHIBITORS; FAMILIAL ALZHEIMERS-DISEASE; POLYMERASE-I TRANSCRIPTION; EXTENDS LIFE-SPAN; HUNTINGTONS-DISEASE; CALORIE RESTRICTION; SACCHAROMYCES-CEREVISIAE; WALLERIAN DEGENERATION; MITOCHONDRIAL-FUNCTION; PROTEIN DEACETYLASES AB The sirtuins are a family of enzymes which control diverse and vital cellular functions, including metabolism and aging. Manipulations of sirtuin activities cause activation of anti-apoptotic, anti-inflammatory, anti-stress responses, and the modulation of an aggregation of proteins involved in neurodegenerative disorders. Recently, sirtuins were found to be disease-modifiers in various models of neurodegeneration. However, almost in all instances, the exact mechanisms of neuroprotection remain elusive. Nevertheless, the manipulation of sirtuin activities is appealing as a novel therapeutic strategy for the treatment of currently fatal human disorders such as Alzheimer's and Parkinson's diseases. Here, we review current data which support the putative therapeutic roles of sirtuin in aging and in neurodegenerative diseases and the feasibility of the development of sirtuin-based therapies. (C) 2008 Elsevier B.V. All rights reserved. C1 [Outeiro, Tiago Fleming; Kazantsev, Aleksey] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Outeiro, Tiago Fleming; Marques, Oldriska] Univ Lisbon, Fac Med, Inst Fisiol, Inst Mol Med,Cellular & Mol Neurosci Unit, P-1649028 Lisbon, Portugal. RP Kazantsev, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, CNY114 16th St, Charlestown, MA 02129 USA. EM akazantsev@partners.org RI Outeiro, Tiago/C-1067-2008 OI Outeiro, Tiago/0000-0003-1679-1727 NR 95 TC 78 Z9 79 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD JUN PY 2008 VL 1782 IS 6 BP 363 EP 369 DI 10.1016/j.bbadis.2008.02.010 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 312FV UT WOS:000256655400001 PM 18373985 ER PT J AU Morinelli, TA Walker, LP Ullian, ME AF Morinelli, Thomas A. Walker, Linda P. Ullian, Michael E. TI COX-2 expression stimulated by Angiotensin II depends upon AT(1) receptor internalization in vascular smooth muscle cells SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE Angiotensin; G protein-coupled receptor; cyclooxygenase 2; signal transduction; endocytosis ID PROXIMAL TUBULE CELLS; GROWTH-FACTOR RECEPTOR; EGF RECEPTOR; MEDIATED ENDOCYTOSIS; NUCLEAR-LOCALIZATION; TYPE-1 RECEPTOR; MESSENGER-RNA; ANG-II; CYCLOOXYGENASE-2; TRANSACTIVATION AB Previously, we demonstrated that nuclear localization of the Angiotensin II AT(1A) receptor was associated with the activation of transcription for the COX-2 gene, PTGS-2. The hypothesis of the present study is that AT(1A)R internalization from the plasma membrane is a first step in the nuclear localization of the endogenous AT(1A)R of rat aortic vascular smooth muscle cells and the resultant increase of COX-2 protein expression. Angiotensin II produced both a time- and concentration-dependent increase in COX-2 protein expression in these cells. Treatment with sucrose or phenylarsine oxide, inhibitors of receptor internalization, significantly inhibited AT(1A)R internalization and abolished the increase in COX-2 protein produced by Angiotensin II without affecting COX-2 expression on its own. Sucrose pre-treatment of rat aortic vascular smooth muscle cells resulted in an increase in p42/44 and p38 activation, while phenylarsine oxide pre-treatment activated only p38 kinase without inhibiting activation of p42/44 produced by Angiotensin II. These results demonstrate that inhibiting the internalization of the AT(1A)R results in a loss of ability of Angiotensin II to increase the protein expression of COX-2, thus supporting previous work showing a relationship between AT(1A)R nuclear localization and activation of COX-2 gene expression. Surprisingly, in contrast to other studies, the data also indicates that activation of p42/44 and/or p38 does not correlate with the increased expression of COX-2. (C) 2008 Elsevier B.V. All rights reserved. C1 [Morinelli, Thomas A.; Walker, Linda P.; Ullian, Michael E.] Med Univ S Carolina, Div Nephrol, Dept Med, Charleston, SC 29425 USA. [Morinelli, Thomas A.; Ullian, Michael E.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Morinelli, TA (reprint author), Med Univ S Carolina, Div Nephrol, Dept Med, Jonathan Lucas St,POB 250623, Charleston, SC 29425 USA. EM morinelt@musc.edu NR 35 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JUN PY 2008 VL 1783 IS 6 BP 1048 EP 1054 DI 10.1016/j.bbamcr.2008.01.012 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 312FX UT WOS:000256655600010 PM 18267125 ER PT J AU Lu, Y Papagerakis, P Yamakoshi, Y Hu, JCC Bartlett, JD Simmer, JP AF Lu, Yuhe Papagerakis, Petros Yamakoshi, Yasuo Hu, Jan C. -C. Bartlett, John D. Simmer, James P. TI Functions of KLK4 and MMP-20 in dental enamel formation SO BIOLOGICAL CHEMISTRY LA English DT Article; Proceedings Paper CT 2nd International Symposium on Kallikrein and Kallikrein-Related Peptidases (ISK 2007) CY OCT 16-18, 2007 CL Santorini, GREECE SP Hellen Anticanc Inst DE amelogenesis imperfecta; EMSP1; enamelysin; kallikrein; matrix metalloproteinase; tooth enamel ID HYPOMATURATION AMELOGENESIS-IMPERFECTA; DEVELOPING BOVINE ENAMEL; MATRIX PROTEINS; TISSUE KALLIKREINS; MOLECULAR-CLONING; SERINE PROTEASES; MATURATION STAGE; EXPRESSION; MOUSE; TOOTH AB Two proteases are secreted into the enamel matrix of developing teeth, The early protease is enamelysin (MMP-20). The late protease is kallikrein 4 (KLK4). Mutations in MMP20 and KLK4 both cause autosomal recessive amelogenesis imperfecta, a condition featuring soft, porous enamel containing residual protein. MMP-20 is secreted along with enamel proteins by secretory-stage ameloblasts. Enamel protein-cleavage products accumulate in the space between the crystal ribbons, helping to support them. MMP-20 steadily cleaves accumulated enamel proteins, so their concentration decreases with depth. KLK4 is secreted by transition- and maturation-stage ameloblasts. KLK4 aggressively degrades the retained organic matrix following the termination of enamel protein secretion. The principle functions of MMP-20 and KLK4 in dental enamel formation are to facilitate the orderly replacement of organic matrix with mineral, generating an enamel layer that is harder, less porous, and unstained by retained enamel proteins. C1 [Lu, Yuhe; Yamakoshi, Yasuo; Simmer, James P.] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. [Papagerakis, Petros; Hu, Jan C. -C.] Univ Michigan, Sch Dent, Dept Orthodont & Pediat Dent, Ann Arbor, MI 48109 USA. [Bartlett, John D.] Forsyth Inst, Harvard Forsyth Dept Oral Biol, Dept Cytokine Biol, Boston, MA 02115 USA. RP Simmer, JP (reprint author), Univ Michigan, Sch Dent, Dept Biol & Mat Sci, 1011 N Univ, Ann Arbor, MI 48109 USA. EM jsimmer@umich.edu FU NIDCR NIH HHS [DE015846, DE016276, R01 DE015846, R01 DE015846-05, R01 DE016276, R01 DE016276-03, R56 DE016276] NR 59 TC 115 Z9 121 U1 1 U2 8 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD JUN PY 2008 VL 389 IS 6 BP 695 EP 700 DI 10.1515/BC.2008.080 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 326PN UT WOS:000257671500010 PM 18627287 ER PT J AU Barr, RS Pizzagalli, DA Culhane, MA Goff, DC Evins, AE AF Barr, Ruth S. Pizzagalli, Diego A. Culhane, Melissa A. Goff, Donald C. Evins, A. Eden TI A single dose of nicotine enhances reward responsiveness in nonsmokers: Implications for development of dependence SO BIOLOGICAL PSYCHIATRY LA English DT Article DE anhedonia; drug addiction; nicotine; nonsmokers; reward; reward responsiveness ID DEFICIT HYPERACTIVITY DISORDER; NUCLEUS-ACCUMBENS; MENTAL-ILLNESS; D-AMPHETAMINE; DOPAMINE; SMOKING; SENSITIVITY; ATTENTION; SCHIZOPHRENIA; PREVALENCE AB Background: Tobacco smoking, driven by the addictive properties of nicotine, is the most prevalent preventable cause of death in the Western world. Accumulated evidence suggests that nicotine may increase appetitive responding for nondrug incentives in the environment. Methods: To test this hypothesis, we conducted a randomized, double-blind, placebo-controlled, crossover study of the effect of a single dose of transdermal nicotine on reward responsiveness in 30 psychiatrically healthy nonsmokers. A novel signal detection task in which correct responses were differentially rewarded in a 3:1 ratio was used to assess the extent to which participants modulated their behavior as a function of reward. Results: Despite expected adverse effects such as nausea, nicotine significantly increased response bias toward the more frequently rewarded condition, at the expense of accuracy, independent of effects on attention or overall vigilance. Additionally, response bias on placebo was greater in participants who received nicotine in the first session, indicating that an effect of nicotine on reward responsiveness or reward-based learning persisted for at least 1 week. Conclusions: These findings suggest that a single dose of nicotine enhances response to non-drug-related rewards in the environment, with lasting effects. This effect may contribute to reinforcement of early smoking behavior and development of nicotine dependence. C1 [Barr, Ruth S.; Culhane, Melissa A.; Goff, Donald C.; Evins, A. Eden] Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. [Barr, Ruth S.; Culhane, Melissa A.; Evins, A. Eden] Massachusetts Gen Hosp, Addict Res Program, Boston, MA 02114 USA. [Barr, Ruth S.; Goff, Donald C.; Evins, A. Eden] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Pizzagalli, Diego A.] Harvard Univ, Dept Psychol, Boston, MA 02115 USA. RP Evins, AE (reprint author), Massachusetts Gen Hosp, Schizophrenia Program, 60 Staniford St, Boston, MA 02114 USA. EM a_eden_evins@hms.harvard.edu FU NIDA NIH HHS [K23 DA000510-03, K23 DA000510-02, K23 DA000510-01, K23 DA000510-05, 1K23DA00510, K23 DA000510, K23 DA000510-04]; NIMH NIH HHS [R01 MH068376] NR 28 TC 58 Z9 58 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2008 VL 63 IS 11 BP 1061 EP 1065 DI 10.1016/j.biopsych.2007.09.015 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 302ML UT WOS:000255972300009 PM 17976537 ER PT J AU Lee, SJ Zelen, M AF Lee, Sandra J. Zelen, Marvin TI Mortality modeling of early detection programs SO BIOMETRICS LA English DT Article DE breast cancer; clinical trials; early detection of disease; probability models; stochastic modeling ID BREAST-CANCER; DISEASE AB Consider a group of subjects who are offered an opportunity to receive a sequence of periodic special examinations for the purpose of diagnosing a chronic disease earlier relative to usual care. The mortality for the early detection group is to be compared with a group receiving usual care. Benefit is reflected in a potential reduction in mortality. This article develops a general probability model that can be used to predict cumulative mortality for each of these groups. The elements of the model assume (i) a four-state progressive disease model in which a subject may be in a disease-free state (or a disease state that cannot be detected), preclinical disease state (capable of being diagnosed by a special exam), clinical state (diagnosis by usual care), and a death state; (ii) age-dependent transitions into the states; (iii) age-dependent examination sensitivity; (iv) age-dependent sojourn time in each state; and (v) the distribution of disease stages on diagnosis conditional on modality of detection. The model may be used to (i) compare mortality rates for different screening schedules; (ii) explore potential benefit of subpopulations; and (iii) compare relative reductions in disease-specific mortality due to advances and dissemination of both treatment and early detection screening programs. C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lee, SJ (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM lee.sandra@jimmy.harvard.edu FU NCI NIH HHS [CA-78607, CA-88270] NR 16 TC 11 Z9 11 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2008 VL 64 IS 2 BP 386 EP 395 DI 10.1111/j.1541-0420.2007.00893.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 302HN UT WOS:000255959500008 PM 17725809 ER PT J AU Vansteelandt, S DeMeo, DL Lasky-Su, J Smoller, JW Murphy, AJ McQueen, M Schneiter, K Celedon, JC Weiss, ST Silverman, EK Lange, C AF Vansteelandt, Stijn DeMeo, Dawn L. Lasky-Su, Jessica Smoller, Jordan W. Murphy, Amy J. McQueen, Matt Schneiter, Kady Celedon, Juan C. Weiss, Scott T. Silverman, Edwin K. Lange, Christoph TI Testing and estimating gene-environment interactions in family-based association studies SO BIOMETRICS LA English DT Article DE causal inference; confounding; family-based designs; interaction; semiparametric models; statistical genetics; TDT ID OBSTRUCTIVE PULMONARY-DISEASE; POPULATION ADMIXTURE; QUANTITATIVE TRAITS; UNIFIED APPROACH; POLYMORPHISM; EXPOSURE; LINKAGE; DESIGN; ASTHMA; AGE AB We propose robust and efficient tests and estimators for gene-environment/gene-drug interactions in family-based association studies in which haplotypes, dichotomous/quantitative phenotypes, and complex exposure/treatment variables are analyzed. Using causal inference methodology, we show that the tests and estimators are robust against unmeasured confounding due to population admixture and stratification, provided that Mendel's law of segregation holds and that the considered exposure/treatment variable is not affected by the candidate gene under study. We illustrate the practical relevance of our approach by an application to a chronic obstructive pulmonary disease study. The data analysis suggests a gene-environment interaction between a single nucleotide polymorphism in the Serpine2 gene and smoking status/pack-years of smoking. Simulation studies show that the proposed methodology is sufficiently powered for realistic sample sizes and that it provides valid tests and effect size estimators in the presence of admixture and stratification. C1 [Vansteelandt, Stijn] Univ Ghent, Dept Appl Math & Comp Sci, B-9000 Ghent, Belgium. [DeMeo, Dawn L.; Lasky-Su, Jessica; Murphy, Amy J.; Celedon, Juan C.; Weiss, Scott T.; Silverman, Edwin K.; Lange, Christoph] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [McQueen, Matt] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. [Schneiter, Kady] Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA. [Celedon, Juan C.; Weiss, Scott T.; Silverman, Edwin K.; Lange, Christoph] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Celedon, Juan C.; Weiss, Scott T.; Silverman, Edwin K.; Lange, Christoph] Brigham & Womens Hosp, Ctr Genom Med, Boston, MA 02115 USA. [Lange, Christoph] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Vansteelandt, S (reprint author), Univ Ghent, Dept Appl Math & Comp Sci, Krijgslaan 281, B-9000 Ghent, Belgium. EM stijn.vansteelandt@ugent.be FU NICHD NIH HHS [R01 HD060726]; NIMH NIH HHS [R01MH59532] NR 26 TC 29 Z9 30 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2008 VL 64 IS 2 BP 458 EP 467 DI 10.1111/j.1541-0420.2007.00925.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 302HN UT WOS:000255959500016 PM 17970814 ER PT J AU Gottardo, R Li, W Johnson, WE Liu, XS AF Gottardo, Raphael Li, Wei Johnson, W. Evan Liu, X. Shirley TI A flexible and powerful bayesian hierarchical model for ChIP-chip experiments SO BIOMETRICS LA English DT Article DE affymetrix tiling arrays; Bayesian hierarchical model; empirical Bayes; heteroscedasticity; Markov chain Monte Carlo; mixture distribution; multiple testing; outlier; spatial statistics ID DIFFERENTIAL GENE-EXPRESSION; MICROARRAY DATA; INFERENCE; ARRAYS AB Chromatin-immunoprecipitation microarrays (ChIP-chip) that enable researchers to identify regions of a given genome that are bound by specific DNA-binding proteins present new challenges for statistical analysis due to the large number of probes, the high noise-to-signal ratio, and the spatial dependence between probes. We propose a method called BAC (Bayesian analysis of ChIP-chip) to detect transcription factor bound regions, which incorporate the dependence between probes while making little assumptions about the bound regions (e.g., length). BAC is robust to probe outliers with an exchangeable prior for the variances, which allows different variances for the probes but still shrink extreme empirical variances. Parameter estimation is carried out using Markov chain Monte Carlo and inference is based on the joint distribution of the parameters. Bound regions are detected using posterior probabilities computed from the joint posterior distribution of neighboring probes. We show that these posterior probabilities are well calibrated and can be used to obtain an estimate of the false discovery rate. The method is illustrated using two publicly available ChIP-chip data sets containing 18 experimentally validated regions. We compare our method to four other baseline and commonly used techniques, namely, the Wilcoxon's rank sum test, TileMap, HGMM, and MAT. We found BAC and HGMM to perform best at detecting validated regions. However, HGMM appears to be very sensitive to probe outliers compared to BAC. In addition, we present a simulation study, which shows that BAC is more powerful than the other four techniques under various simulation scenarios while being robust to model misspecification. C1 [Gottardo, Raphael] Univ British Columbia, Dept Stat, Vancouver, BC V5Z 1M9, Canada. [Li, Wei; Johnson, W. Evan; Liu, X. Shirley] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gottardo, R (reprint author), Univ British Columbia, Dept Stat, Vancouver, BC V5Z 1M9, Canada. EM raph@stat.ubc.ca RI Li, Wei/A-8544-2009 FU NCI NIH HHS [T32 CA009337]; NHGRI NIH HHS [1R01 HG004069-01, R01 HG004069, R01 HG004069-02, R01 HG004069-03] NR 26 TC 24 Z9 24 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2008 VL 64 IS 2 BP 468 EP 478 DI 10.1111/j.1541-0420.2007.00899.x PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 302HN UT WOS:000255959500017 PM 17888037 ER PT J AU Wang, ZH Birch, CM Deisboeck, TS AF Wang, Zhihui Birch, Christina M. Deisboeck, Thomas S. TI Cross-scale sensitivity analysis of a non-small cell lung cancer model: Linking molecular signaling properties to cellular behavior SO BIOSYSTEMS LA English DT Article DE agent-based model; cellular behavior; epidermal growth factor; expansion rate; non-small cell lung cancer; sensitivity analysis ID GROWTH-FACTOR RECEPTOR; MATHEMATICAL-MODEL; SYSTEMS BIOLOGY; KINASE; PATHWAY; IDENTIFICATION; TRANSDUCTION; GEFITINIB; MECHANISM; PROLIFERATION AB Sensitivity analysis is an effective tool for systematically identifying specific perturbations in parameters that have significant effects on the behavior of a given biosystem, at the scale investigated. In this work, using a two-dimensional, multiscale non-small cell lung cancer (NSCLC) model, we examine the effects of perturbations in system parameters which span both molecular and cellular levels, i.e. across scales of interest. This is achieved by first linking molecular and cellular activities and then assessing the influence of parameters at the molecular level on the tumor's spatio-temporal expansion rate, which serves as the output behavior at the cellular level. Overall, the algorithm operated reliably over relatively large variations of most parameters, hence confirming the robustness of the model. However, three pathway components (proteins PKC, MEK, and ERK) and eleven reaction steps were determined to be of critical importance by employing a sensitivity coefficient as an evaluation index. Each of these sensitive parameters exhibited a similar changing pattern in that a relatively larger increase or decrease in its value resulted in a lesser influence on the system's cellular performance. This study provides a novel cross-scaled approach to analyzing sensitivities of computational model parameters and proposes its application to interdisciplinary biomarker studies. (c) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Wang, Zhihui; Deisboeck, Thomas S.] Harvard Univ, Massachusetts Gen Hosp, MIT, Athinoula A Martinos Ctr Biomed Imaging,Complex B, Charlestown, MA 02129 USA. [Birch, Christina M.] Univ Arizona, Dept Biochem & Mol Biophys, Tucson, AZ 85721 USA. RP Deisboeck, TS (reprint author), Harvard Univ, Massachusetts Gen Hosp, MIT, Athinoula A Martinos Ctr Biomed Imaging,Complex B, 2301 Bldg 149,13th St, Charlestown, MA 02129 USA. EM deisboec@helix.mgh.harvard.edu FU NCI NIH HHS [U56 CA113004-01, CA113004, U56 CA113004, U56 CA113004-010001, U56 CA113004-02, U56 CA113004-020001, U56 CA113004-02S1, U56 CA113004-03, U56 CA113004-030001, U56 CA113004-03S1, U56 CA113004-03S2] NR 50 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0303-2647 EI 1872-8324 J9 BIOSYSTEMS JI Biosystems PD JUN PY 2008 VL 92 IS 3 BP 249 EP 258 DI 10.1016/j.biosystems.2008.03.002 PG 10 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 310YC UT WOS:000256565900006 PM 18448237 ER PT J AU Morgan, SC Relaix, F Sandell, LL Loeken, MR AF Morgan, Sarah C. Relaix, Frederic Sandell, Lisa L. Loeken, Mary R. TI Oxidative stress during diabetic pregnancy disrupts cardiac neural crest migration and causes outflow tract defects SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article; Proceedings Paper CT 67th Annual Meeting of the American-Diabetes-Association CY JUN 22-26, 2007 CL Chicago, IL SP Amer Diabet Assoc DE cardiac neural crest; outflow tract; Pax3; diabetic pregnancy; oxidative stress; diabetic teratogenesis ID PERSISTENT TRUNCUS ARTERIOSUS; SPLOTCH SP(2H) MUTANT; TUBE DEFECTS; CARDIOVASCULAR MALFORMATIONS; CONGENITAL-ANOMALIES; GENE-EXPRESSION; WOMEN; RISK; MOUSE; CELLS AB BACKGROUND: Maternal diabetes increases risk for congenital malformations, particularly cardiac outflow tract defects. Maternal diabetes inhibits expression of Pax3 in neuroepithelium through hyperglycemia-induced oxidative stress. The neuroepithelium gives rise to the neural crest, and Pax3 expression in cardiac neural crest (CNC) is required for CNC migration to the heart and for outflow tract septation. Here we tested whether maternal diabetes, through hyperglycemia-induced oxidative stress, before the onset of CNC delamination, impairs CNC migration and cardiac outflow tract septation. METHODS: CNC migration was mapped in mouse embryos whose mothers were diabetic, or transiently hyperglycemic, or in which oxidative stress was transiently induced, using reporters linked to Pax3 expression. CNC apoptosis was examined by TUNEL assay. Outflow tract septation was examined histologically and by gross inspection. RESULTS: Few, if any, migrating CNC cells were observed in embryos of diabetic mice, and this was associated with increased apoptosis along the path of CNC migration. Outflow tract defects were significantly increased in fetuses of diabetic mice. Notably, induction of hyperglycemia or oxidative stress on the day prior to the onset of Pax3 expression and CNC migration also impaired CNC migration, increased apoptosis, and caused outflow tract defects. However, antioxidants administered on the day prior to the onset of Pax3 expression and CNC migration prevented these effects of hyperglycemia or oxidative stress. CONCLUSIONS: In diabetic pregnancy, oxidative stress, which inhibits expression of genes required for CNC viability, causes subsequent CNC depletion by apoptosis during migration, which leads to outflow tract defects. C1 [Morgan, Sarah C.; Loeken, Mary R.] Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, Boston, MA 02215 USA. [Relaix, Frederic] Univ Paris 06, INSERM, UMR S 787, Fac Med Pitie Salpetriere, F-75634 Paris 13, France. [Sandell, Lisa L.] Stowers Inst Med Res, Kansas City, MO 64110 USA. RP Loeken, MR (reprint author), Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM mary.foeken@joslin.harvard.edu RI Sandell, Lisa/M-4238-2013; OI Sandell, Lisa/0000-0002-1735-8223; Loeken, Mary/0000-0002-8056-9816 FU NIDDK NIH HHS [DK52865, R01 DK052865] NR 46 TC 55 Z9 60 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD JUN PY 2008 VL 82 IS 6 BP 453 EP 463 DI 10.1002/bdra.20457 PG 11 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 316JM UT WOS:000256945600004 PM 18435457 ER PT J AU Signoretti, S Regan, M Atkins, M AF Signoretti, Sabina Regan, Meredith Atkins, Michael TI Carbonic anhydrase IX as a predictive biomarker of response to kidney cancer therapy SO BJU INTERNATIONAL LA English DT Article; Proceedings Paper CT International Carbonic Anhydrase IX (CAIX) Symposium CY NOV, 2007 CL Brussels, BELGIUM ID RENAL-CELL CARCINOMA; MAMMALIAN TARGET; INTERFERON-ALPHA; PHASE-II; RAPAMYCIN; MTOR; INTERLEUKIN-2; TEMSIROLIMUS; EXPRESSION; INHIBITORS C1 [Signoretti, Sabina] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Regan, Meredith] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Atkins, Michael] Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Kidney Canc Program,Dana Farber Harvard Canc Ctr, Boston, MA USA. RP Signoretti, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. EM ssignoretti@partners.org NR 36 TC 10 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD JUN PY 2008 VL 101 SU 4 BP 31 EP 35 DI 10.1111/j.1464-410X.2008.07646.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 292KD UT WOS:000255264000007 PM 18430120 ER PT J AU Smith, MR O'Malley, AJ Keating, NL AF Smith, Matthew R. O'Malley, A. James Keating, Nancy L. TI Gonadotrophin-releasing hormone agonists, diabetes and cardiovascular disease in men with prostate cancer: Which metabolic syndrome? SO BJU INTERNATIONAL LA English DT Editorial Material ID ANDROGEN-DEPRIVATION THERAPY; ARTERIAL STIFFNESS; BODY-COMPOSITION; HEART-DISEASE; HYPERINSULINEMIA; BLOCKADE; RISK C1 [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. [O'Malley, A. James; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Smith, Matthew R.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Yawkey 7038,55 Fruit St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu FU NCI NIH HHS [K24 CA121990-03, K24 CA121990-02, K24 CA121990] NR 18 TC 6 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD JUN PY 2008 VL 101 IS 11 BP 1335 EP 1336 DI 10.1111/j.1464-410X.2008.07707.07635.x PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 295LO UT WOS:000255476200002 PM 18454791 ER PT J AU Wagner, DD Frenette, PS AF Wagner, Denisa D. Frenette, Paul S. TI The vessel wall and its interactions SO BLOOD LA English DT Review ID VON-WILLEBRAND-FACTOR; WEIBEL-PALADE BODIES; HUMAN-ENDOTHELIAL CELLS; KRUPPEL-LIKE FACTOR-2; E-SELECTIN LIGANDS; P-SELECTIN; IN-VIVO; ACTIVATED PLATELETS; LEUKOCYTE ADHESION; VONWILLEBRAND-FACTOR AB Blood cell interactions with the vessel wall were first documented almost 170 years ago. Modern advances have revealed that leukocyte and platelet interactions with the endothelium are at the nexus of complex, dynamic cellular and molecular networks that, when dysregulated, may lead to pathological inflammation and thrombosis, which are major sources of morbidity and mortality in the Western world. In this review, we relate the history of blood cell interactions with the vasculature, discuss recent progress, and raise some unresolved questions awaiting the field. C1 [Wagner, Denisa D.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Frenette, Paul S.] Mt Sinai Sch Med, Black Family Stem Cell Inst, Dept Med, New York, NY USA. [Frenette, Paul S.] Mt Sinai Sch Med, Inst Immunol, New York, NY USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. EM wagner@idi.harvard.edu; paul.frenette@mssm.edu RI Frenette, Paul/J-8272-2012 FU NHLBI NIH HHS [P01 HL056949, P01 HL066105, R01 HL069438, R01 HL69438, R37 HL041002]; NIAID NIH HHS [R01 AI069402]; NIDDK NIH HHS [R01 DK056638] NR 135 TC 147 Z9 149 U1 1 U2 10 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2008 VL 111 IS 11 BP 5271 EP 5281 DI 10.1182/blood-2008-01-078204 PG 11 WC Hematology SC Hematology GA 307RR UT WOS:000256336500008 PM 18502843 ER PT J AU Wittrant, Y Gorin, Y Woodruff, K Horn, D Abboud, HE Mohan, S Abboud-Werner, SL AF Wittrant, Y. Gorin, Y. Woodruff, K. Horn, D. Abboud, H. E. Mohan, S. Abboud-Werner, S. L. TI High D(+)glucose concentration inhibits RANKL-induced osteoclastogenesis SO BONE LA English DT Article DE oteoclast; glucose; RANKL; reactive oxygen species; differentiation ID KAPPA-B LIGAND; REACTIVE OXYGEN; BONE-RESORPTION; OSTEOPROTEGERIN LIGAND; MATRIX METALLOPROTEINASES; FIBRONECTIN EXPRESSION; RECEPTOR ACTIVATOR; DIABETES-MELLITUS; OXIDATIVE STRESS; DIFFERENTIATION AB Diabetes is a chronic disease associated with hyperglycemia and altered bone metabolism that may lead to complications including osteopenia, increased risk of fracture and osteoporosis. Hyperglycemia has been implicated in the pathogenesis of diabetic bone disease; however, the biologic effect of glucose on osteoclastogenesis is unclear. In the present study, we examined the effect of high D(+)glucose (D-Glc) and L(-)glucose (L-Glc; osmotic control) on RANKL-induced osteoclastogenesis using RAW264.7 cells and Bone Marrow Macrophages (BMM) as models. Cells were exposed to sustained high glucose levels to mimic diabetic conditions. Osteoclast formation was analyzed using tartrate resistant acid phosphatase (TRACP) assay, expression of calcitonin receptor (CrR) and cathepsin K mRNAs, and Cultures were examined for reactive oxygen species (ROS) using dichlorodihydrofluorescein diacetate (DCF-DA) fluorescence, caspase-3 and Nuclear Factor kappaB (NF-kappa B) activity. Cellular function was assessed using a migration assay. Results show, for the first time, that high D-Glc inhibits osteoclast formation, ROS production, caspase-3 activity and migration in response to RANKL through a metabolic pathway. Our findings also suggest that high D-Glc may alter RANKL-incluced osteoclast formation by inhibiting redox-sensitive NF-kappa B activity through an anti-oxidative mechanism. This study increases our understanding of the role of glucose in diabetes-associated bone disease. Our data suggest that high glucose levels may alter bone turnover by decreasing osteoclast differentiation and function in diabetes and provide new insight into the biologic effects of glucose on osteoclastogenesis. (C) 2008 Elsevier Inc. All rights reserved. C1 [Gorin, Y.; Abboud, H. E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Nephrol, San Antonio, TX 78229 USA. [Wittrant, Y.; Woodruff, K.; Horn, D.; Mohan, S.; Abboud-Werner, S. L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Wittrant, Y.; Gorin, Y.; Woodruff, K.; Horn, D.; Abboud, H. E.; Mohan, S.; Abboud-Werner, S. L.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. RP Wittrant, Y (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM wittrant@uthscsa.edu; gorin@uthscsa.edu; woodruff@uthscsa.edu; hornd@uthscsa.edu; abboud@uthscsa.edu; mohan@uthscsa.edu; AbboudWerner@uthscsa.edu FU NIAMS NIH HHS [AR-42306, R01 AR042306, R01 AR042306-05A1]; NIDCR NIH HHS [R01 DE015857] NR 45 TC 60 Z9 69 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JUN PY 2008 VL 42 IS 6 BP 1122 EP 1130 DI 10.1016/j.bone.2008.02.006 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 307PE UT WOS:000256330000014 PM 18378205 ER PT J AU Duncan, CN Buonanno, MR Barry, EV Myers, K Peritz, D Lehmann, L AF Duncan, C. N. Buonanno, M. R. Barry, E. V. Myers, K. Peritz, D. Lehmann, L. TI Bronchiolitis obliterans following pediatric allogeneic hematopoietic stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE stem cell transplant; bronchiolitis obliterans; pediatric ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; OBSTRUCTIVE LUNG-DISEASE; PULMONARY-FUNCTION; RESPIRATORY-FUNCTION; RISK-FACTORS; CHILDREN; LEUKEMIA; COMPLICATIONS; THERAPY AB Bronchiolitis obliterans (BrOb) is a well-recognized complication of allogeneic hematopoietic stem cell transplantation (HSCT). It is associated with substantial morbidity and mortality in adult patients. However, the incidence and morbidity of this complication have not been well described in the pediatric population. We report our experience of BrOb in 216 pediatric allogeneic HSCT patients between 1 January 2001 and 31 December 2005. In total 18 of 216 patients developed BrOb during this time. The diagnosis of BrOb was based on pulmonary function abnormalities, radiographic findings or lung biopsy. In total 14 of 18 patients with BrOb received stem cells from unrelated donors. In total 17 of 18 patients received bone marrow as a stem cell source, and 1 received peripheral blood stem cells. All pediatric patients in this report had a known risk factor for BrOb, most commonly chronic GVHD (18 of 18 patients). Additionally, 7 of 18 patients had either toxic lung injury or virally mediated pulmonary disease before the diagnosis of BrOb. With a median of 45.1 months of follow-up, the outcomes were 5 of 18 patients died of lung disease, 2 died of other causes, 3 had progressive lung disease, 6 achieved partial resolution of disease and 2 had stable disease. BrOb, while uncommon, is associated with considerable morbidity and mortality in pediatric HSCT. C1 [Duncan, C. N.; Buonanno, M. R.; Barry, E. V.; Myers, K.; Peritz, D.; Lehmann, L.] Dana Farber Canc Inst, Dept Pediat, Jimmy Fund Clin, Boston, MA 02115 USA. RP Duncan, CN (reprint author), Dana Farber Canc Inst, Dept Pediat, Jimmy Fund Clin, 44 Binney St, Boston, MA 02115 USA. EM christine_duncan@dfci.harvard.edu NR 23 TC 24 Z9 27 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUN PY 2008 VL 41 IS 11 BP 971 EP 975 DI 10.1038/bmt.2008.19 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 311SN UT WOS:000256620000010 PM 18297116 ER PT J AU Kuter, I Hegg, R Singer, CF Badwe, R Lowe, E AF Kuter, I. Hegg, R. Singer, C. F. Badwe, R. Lowe, E. CA NEWEST Investigators TI Fulvestrant 500 mg vs 250 mg: first results from NEWEST, a randomized, phase II neoadjuvant trial in postmenopausal women with locally advanced, estrogen receptor-positive breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Sao Paulo, Sch Med, BR-05508 Sao Paulo, Brazil. Med Univ Vienna, Vienna, Austria. Tata Mem Hosp, Bombay 400012, Maharashtra, India. AstraZeneca, Wilmington, DE USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2008 VL 109 IS 3 BP 589 EP 590 PG 2 WC Oncology SC Oncology GA 300UY UT WOS:000255851900032 ER PT J AU Purdon, P Pierce, E Bonmassar, G Walsh, J Harrell, G Kwo, J Deschler, D Mullaly, C Barlow, M Merhar, R Lamus, C Maginnis, S Skoniecki, D Sullivan, M Higgins, HA Brown, E AF Purdon, P. Pierce, E. Bonmassar, G. Walsh, J. Harrell, G. Kwo, J. Deschler, D. Mullaly, C. Barlow, M. Merhar, R. Lamus, C. Maginnis, S. Skoniecki, D. Sullivan, M. Higgins, H. -A. Brown, E. TI Multimodal functional imaging of auditory processing during propofol-induced loss of consciousness SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Meeting Abstract CT 7th International Symposium of Memory and Awareness in Anaesthesia CY MAR 13-15, 2008 CL Munich, GERMANY DE propofol; EEG; fMRI C1 [Purdon, P.; Pierce, E.; Bonmassar, G.; Walsh, J.; Harrell, G.; Kwo, J.; Deschler, D.; Mullaly, C.; Barlow, M.; Merhar, R.; Lamus, C.; Maginnis, S.; Skoniecki, D.; Sullivan, M.; Higgins, H. -A.; Brown, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD JUN PY 2008 VL 100 IS 6 BP 869P EP 869P PG 1 WC Anesthesiology SC Anesthesiology GA 302RV UT WOS:000255987900034 ER PT J AU Dai, T Tegos, GP Rolz-Cruz, G Cumbie, WE Hamblin, MR AF Dai, T. Tegos, G. P. Rolz-Cruz, G. Cumbie, W. E. Hamblin, M. R. TI Ultraviolet C inactivation of dermatophytes: implications for treatment of onychomycosis SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE dermatophytes; ex vivo nail infection; onychomycosis; ultraviolet C ID TOENAIL ONYCHOMYCOSIS; NAIL PLATE; THERAPY; MANAGEMENT AB Background Onychomycosis responds to systemic antifungals and sometimes to topical lacquers, but alternative treatments are desirable. Topical application of germicidal ultraviolet (UV) C radiation may be an acceptable and effective therapy for infected nails. Objectives To test the ability of UVC to inactivate dermatophyte suspensions in vitro and to sterilize a novel ex vivo model of nail infection. Methods Trichophyton rubrum, T. mentagrophytes, Epidermophyton floccosum and Microsporum canis suspensions were irradiated with UVC (254 nm) at a radiant exposure of 120 mJ cm(-2) and surviving colony-forming units quantified. T. rubrum infecting porcine hoof slices and human toenail clippings was irradiated with UVC at radiant exposures of 36-864 J cm(-2). Results In vitro studies showed that 3-5 logs of cell inactivation in dermatophyte suspensions were produced with 120 mJ cm(-2) UVC irradiation. Depending on factors such as the thickness and infectious burden of the ex vivo cultures, the radiant exposure of UVC needed for complete sterilization was usually in the order of tens to hundreds of J cm(-2). Resistance of T. rubrum to UVC irradiation did not increase after five cycles of subtotal inactivation in vitro. Conclusions UVC irradiation may be a less invasive treatment option for onychomycosis, when the appropriate consideration is given to safety. C1 [Dai, T.; Tegos, G. P.; Rolz-Cruz, G.; Hamblin, M. R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Dai, T.; Tegos, G. P.; Rolz-Cruz, G.; Hamblin, M. R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Cumbie, W. E.] Keraderm LLC, Hampton, VA USA. [Hamblin, M. R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Tegos, George/C-8830-2011; OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R41 AI069641-01, R41 AI069641] NR 25 TC 23 Z9 23 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JUN PY 2008 VL 158 IS 6 BP 1239 EP 1246 DI 10.1111/j.1365-2133.2008.08549.x PG 8 WC Dermatology SC Dermatology GA 302HV UT WOS:000255960300009 PM 18410410 ER PT J AU Ishitsuka, K Hideshima, T Neri, P Vallet, S Shiraishi, N Okawa, Y Shen, Z Raje, N Kiziltepe, T Ocio, EM Chauhan, D Tassone, P Munshi, N Campbell, RM De Dios, A Shih, C Starling, JJ Tamura, K Anderson, KC AF Ishitsuka, Kenji Hideshima, Teru Neri, Paola Vallet, Sonia Shiraishi, Norihiko Okawa, Yutaka Shen, Zhenxin Raje, Noopur Kiziltepe, Tanyel Ocio, Enrique M. Chauhan, Dharminder Tassone, Pierfrancesco Munshi, Nikhil Campbell, Robert M. De Dios, Alfonso Shih, Chuan Starling, James J. Tamura, Kazuo Anderson, Kenneth C. TI p38 mitogen-activated protein kinase inhibitor LY2228820 enhances bortezomib-induced cytotoxicity and inhibits osteoclastogenesis in multiple myeloma; therapeutic implications SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE multiple myeloma; microenvironment; p38 mitogen-activated protein kinase; osteoclastogenesis; LY2228820 ID ACID-PHOSPHATASE 5B; KAPPA-B LIGAND; CYTOKINE MESSENGER-RNAS; RECEPTOR ACTIVATOR; IN-VITRO; CELL-GROWTH; BONE-MARROW; MAP KINASE; PATHWAY; INTERLEUKIN-6 AB The interaction between multiple myeloma (MM) cells and the bone marrow (BM) microenvironment induces proliferation and survival of MM cells, as well as osteoclastogenesis. This study investigated the therapeutic potential of novel p38 mitogen-activated protein kinase (p38MAPK) inhibitor LY2228820 (LY) in MM. Although cytotoxicity against MM cell lines was modest, LY significantly enhanced the toxicity of bortezomib by down-regulating bortezomib-induced heat shock protein 27 phosphorylation. LY inhibited interleukin-6 secretion from long term cultured-BM stromal cells and BM mononuclear cells (BMMNCs) derived from MM patients in remission. LY also inhibited macrophage inflammatory protein-1 alpha secretion from patient MM cells and BMMNCs as well as normal CD14 positive osteoclast precursor cells. Moreover, LY significantly inhibited in vitro osteoclastogenesis from CD14 positive cells induced by macrophage-colony stimulating factor and soluble receptor activator of nuclear factor-kappa B ligand. Finally, LY also inhibited in vivo osteoclatogenesis in a severe combined immunodeficiency mouse model of human MM. These results suggest that LY represents a promising novel targeted approach to improve MM patient outcome both by enhancing the effect of bortezomib and by reducing osteoskeletal events. C1 [Ishitsuka, Kenji; Hideshima, Teru; Neri, Paola; Vallet, Sonia; Shiraishi, Norihiko; Okawa, Yutaka; Raje, Noopur; Kiziltepe, Tanyel; Ocio, Enrique M.; Chauhan, Dharminder; Tassone, Pierfrancesco; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myloma Ctr, Boston, MA 02115 USA. [Ishitsuka, Kenji; Hideshima, Teru; Neri, Paola; Vallet, Sonia; Shiraishi, Norihiko; Okawa, Yutaka; Raje, Noopur; Kiziltepe, Tanyel; Ocio, Enrique M.; Chauhan, Dharminder; Tassone, Pierfrancesco; Munshi, Nikhil; Anderson, Kenneth C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ishitsuka, Kenji; Tamura, Kazuo] Fukuoka Univ, Dept Internal Med, Div Hematol & Oncol, Fukuoka 81401, Japan. [Shen, Zhenxin] Beth Israel Deaconess Med Ctr, Orthopaed Biomech Lab, Boston, MA USA. [Campbell, Robert M.; De Dios, Alfonso; Shih, Chuan; Starling, James J.] Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [R01 CA124929, IP50 CA10070-01, P01 CA078378, P50 CA100707, R0-1 CA 50947]; NIAMS NIH HHS [R01 AR 47901]; PHS HHS [P0-1 78378] NR 41 TC 31 Z9 31 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2008 VL 141 IS 5 BP 598 EP 606 DI 10.1111/j.1365-2141.2008.07044.x PG 9 WC Hematology SC Hematology GA 297UU UT WOS:000255643700004 PM 18397345 ER PT J AU Harissi-Dagher, M Azar, DT AF Harissi-Dagher, Mona Azar, Dimitri T. TI Femtosecond laser astigmatic keratotomy for postkeratoplasty astigmatism SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE LA English DT Article; Proceedings Paper CT 2nd International Conference on Femtosecond Lasers in Ophthalmology CY JUN 01, 2007 CL Montreal, CANADA DE penetrating keratoplasty; astigmatism; astigmatic keratotomy; femtosecond laser; IntraLase ID PENETRATING KERATOPLASTY AB Case report: Two eyes of 2 patients with high astigmatism following penetrating keratoplasty were treated with femtosecond laser-assisted paired arcuate keratotomies in the donor cornea. Outcome measures included best-corrected visual acuity, refraction, keratometry, and topographic findings. The preoperative cylinder was 8.5 diopters (D) in the first case and 7.0 D in the second case. Respectively, the postoperative cylinder improved to 4.9 D after a follow-up of 8 months and to 4.3 D after a follow-up of 7 months. Best-corrected visual acuity improved from 20/100 to 20/30 in the first case and from 20/200 to 20/60 in the second case. No complications were encountered; no microperforations were observed, and neither graft rejection nor failure occurred. Comments: The results of astigmatic keratotomy performed with femtosecond laser were reliable and predictable. Femtosecond astigmatic keratotomy may prove to be a safe procedure with satisfactory results. C1 [Azar, Dimitri T.] Univ Illinois, Eye & Ear Infirm, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. [Harissi-Dagher, Mona; Azar, Dimitri T.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Azar, DT (reprint author), Univ Illinois, Eye & Ear Infirm, Dept Ophthalmol & Visual Sci, 1855 W Taylor St, Chicago, IL 60612 USA. EM dazar@uic.edu NR 9 TC 31 Z9 32 U1 0 U2 1 PU CANADIAN OPHTHAL SOC PI OTTAWA PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA SN 0008-4182 J9 CAN J OPHTHALMOL JI Can. J. Opthalmol.-J. Can. Opthalmol. PD JUN PY 2008 VL 43 IS 3 BP 367 EP 369 DI 10.3129/i08-043 PG 3 WC Ophthalmology SC Ophthalmology GA 367RO UT WOS:000260570200018 PM 18443607 ER PT J AU Eichler, AF Kuter, I Ryan, P Schapira, L Younger, J Henson, JW AF Eichler, April F. Kuter, Irene Ryan, Paula Schapira, Lidia Younger, Jerry Henson, John W. TI Survival in patients with brain metastases from breast cancer SO CANCER LA English DT Article DE breast cancer; neoplasm metastasis; brain neoplasms; HER-2 protooncogene protein ID NERVOUS-SYSTEM METASTASES; PROGNOSTIC-FACTORS; SURGICAL-TREATMENT; RANDOMIZED-TRIAL; NATURAL-HISTORY; TRASTUZUMAB; CARCINOMA; ESTROGEN; THERAPY; TRENDS AB BACKGROUND. Brain metastases (BM) are the most common intracranial tumors in adults. To the authors' knowledge, established prognostic factors for survival after the diagnosis of BM in breast cancer patients do not take into account HER-2 status, which may have increasing relevance in the trastuzumab therapy era. METHODS. The authors identified 83 patients with breast cancer and new parenchymal BM diagnosed between January 1, 2001 and December 31, 2005 who were treated at Massachusetts General Hospital. Survival was estimated using the Kaplan-Meier method and curves were compared using the log-rank test. A Cox proportional hazards model was used to determine independent predictors of survival. RESULTS. The median overall survival from the time of BM was 8.3 months. On univariate analysis, HER-2-positive patients were found to have prolonged survival after BM compared with HER-2-negative patients (17.1 months vs 5.2 months). Patients with triple negative disease had a median survival of 4.0 months, compared with 11.2 months for all other patients. Additional predictors of improved survival on univariate analysis included <= 3 BM, controlled or absent systemic disease, and controlled local disease. On multivariate analysis, only HER-2 status, number of BM, and local disease status remained independent predictors of survival. CONCLUSIONS. HER-2 status is a strong predictor of survival after the diagnosis of BM. The survival of breast cancer patients with BM appears to be improving, but a better understanding of both the predictors of brain recurrence and the delayed effects of treatment is needed to properly counsel patients regarding the risk-benefit ratio of various treatment modalities. C1 [Eichler, April F.; Kuter, Irene; Ryan, Paula; Schapira, Lidia; Younger, Jerry; Henson, John W.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kuter, Irene; Ryan, Paula; Schapira, Lidia; Younger, Jerry] Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Dept Med, Boston, MA 02114 USA. [Henson, John W.] Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. [Eichler, April F.; Henson, John W.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Dept Neurol, Boston, MA 02114 USA. RP Eichler, AF (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Dept Neurol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM aeichler@partners.org NR 31 TC 84 Z9 89 U1 1 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 2008 VL 112 IS 11 BP 2359 EP 2367 DI 10.1002/cncr.23468 PG 9 WC Oncology SC Oncology GA 304TS UT WOS:000256132600006 PM 18361426 ER PT J AU Sartor, AO Tangen, CM Hussain, MHA Eisenberger, MA Parab, M Fontana, JA Chapman, RA Mills, GM Raghavan, D Crawford, ED AF Sartor, A. Oliver Tangen, Catherine M. Hussain, Maha H. A. Eisenberger, Mario A. Parab, Minoti Fontana, Joseph A. Chapman, Robert A. Mills, Glenn M. Raghavan, Derek Crawford, E. David TI Antiandrogen withdrawal in castrate-refractory prostate cancer SO CANCER LA English DT Article DE antiandrogen withdrawal; prostate cancer; PSA; prognosis; survival; secondary hormonal therapy; hormone-refractory prostate cancer ID METASTATIC BREAST-CANCER; FLUTAMIDE WITHDRAWAL; ANTIGEN DECLINE; MEGESTROL-ACETATE; CLINICAL-TRIALS; SURVIVAL; DIETHYLSTILBESTROL; DISCONTINUATION; COMBINATION; PROGRESSION AB BACKGROUND. Antiandrogen withdrawal is a potential therapeutic maneuver for patients with progressive prostate cancer. This study was designed to examine antiandrogen withdrawal effects within the context of a large multi-institutional prospective trial. METHODS. Eligibility criteria included progressive prostate adenocarcinoma despite combined androgen blockade. Eligible patients received prior initial treatment with an antiandrogen plus orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist. Patients were stratified according to type of antiandrogen, type of progression (prostate-specific antigen [PSA] or radiographic), presence or absence of metastatic disease, and prior LHRH agonist versus surgical castration. RESULTS. A total of 210 eligible and evaluable patients had a median follow-up of 5.0 years; 64% of patients previously received flutamide, 32% bicalutamide, and 3% nilutamide. Of the 210 patients, 21% of patients had confirmed PSA decreases of >= 50% (95% CI, 16% to 27%). No radiographic responses were recorded. Median progression-free survival (PFS) was 3 months (95% CI, 2 months to 4 months); however, 19% had 12-month or greater progression-free intervals. Median overall survival (OS) after antiandrogen withdrawal was 22 months (20 and 40 months for those with and without radiographic evidence of metastatic disease, respectively). Multivariate analyses indicated that longer duration of antiandrogen use, lower PSA at baseline, and PSA-only progression at study entry were associated with both longer PFS and OS. Longer antiandrogen use was the only significant predictor of PSA response. CONCLUSIONS. These data indicate a relatively modest rate of PSA response in patients who were undergoing antiandrogen withdrawal; however, PFS can be relatively prolonged (>= 1 year) in approximately 19% of patients. C1 [Sartor, A. Oliver] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Sartor, A. Oliver; Mills, Glenn M.] Louisiana State Univ, Hlth Sci Ctr, Dept Med, Shreveport, LA 71105 USA. [Tangen, Catherine M.] SW Oncol Grp, Ctr Stat, Seattle, WA USA. [Hussain, Maha H. A.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Eisenberger, Mario A.] Johns Hopkins Oncol Ctr, Dept Urol & Oncol, Baltimore, MD USA. [Parab, Minoti] Carolina Hlth Specialists, Dept Family Med, Myrtle Beach, SC USA. [Fontana, Joseph A.] Wayne State Univ, Med Ctr, Dept Med, Detroit, MI 48202 USA. [Chapman, Robert A.] Henry Ford Hosp, Dept Med Oncol, Detroit, MI 48202 USA. [Raghavan, Derek] Cleveland Clin Fdn, Taussig Canc Ctr, Cleveland, OH 44195 USA. [Crawford, E. David] Univ Colorado, Hlth Sci Ctr, Dept Surg, Denver, CO 80262 USA. RP Sartor, AO (reprint author), Tulane Med Sch, Dept Urol, Box SL-42,1430 Tulane Ave, New Orleans, LA USA. EM osarto@yahoo.com FU NCI NIH HHS [U10 CA074647, CA04920, CA12213, CA12644, CA14028, CA20319, CA22433, CA35090, CA35261, CA37981, CA42777, CA45377, CA46113, CA46136, CA46282, CA58416, CA58658, CA58723, CA58861, CA58882, CA74647, CA76132, CA76429, CA76447, N01 CA004919, N01 CA027057, N01 CA032102, N01 CA035119, N01 CA035176, N01 CA035178, N01 CA035431, N01 CA038926, N01 CA046441, N01 CA067575, U10 CA004919, U10 CA004919-40, U10 CA012213-28, U10 CA012644-32, U10 CA014028, U10 CA014028-31, U10 CA020319, U10 CA020319-23, U10 CA022433-22, U10 CA027057, U10 CA027057-20, U10 CA032102, U10 CA032102-21, U10 CA035090, U10 CA035090-17, U10 CA035119, U10 CA035119-16, U10 CA035176, U10 CA035176-16, U10 CA035178, U10 CA035178-16, U10 CA035261, U10 CA035261-17, U10 CA035431, U10 CA035431-17, U10 CA037981, U10 CA037981-17, U10 CA038926, U10 CA038926-14, U10 CA042777, U10 CA042777-14, U10 CA045377, U10 CA045377-14, U10 CA046113-13, U10 CA046282, U10 CA046282-13, U10 CA046441, U10 CA046441-12, U10 CA058416-08, U10 CA058658-08, U10 CA058861, U10 CA058861-08, U10 CA058882, U10 CA058882-07, U10 CA067575, U10 CA074647-03, U10 CA076429-02, U10 CA076447-03, U10 CA180846]; NHLBI NIH HHS [R01 HL058723, R01 HL058723-02, T32 HL076132, T32 HL076132-01]; NIAID NIH HHS [R01 AI041440, R01 AI049200, R01 AI049200-01]; NINDS NIH HHS [F30 NS046136-02] NR 31 TC 68 Z9 70 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 2008 VL 112 IS 11 BP 2393 EP 2400 DI 10.1002/cncr.23473 PG 8 WC Oncology SC Oncology GA 304TS UT WOS:000256132600010 PM 18383517 ER PT J AU Mack, JW Nilsson, M Balboni, T Friedlander, RJ Block, SD Trice, E Prigerson, HG AF Mack, Jennifer W. Nilsson, Matthew Balboni, Tracy Friedlander, Robert J. Block, Susan D. Trice, Elizabeth Prigerson, Holly G. TI Peace, equanimity, and acceptance in the cancer experience (PEACE) - Validatlon of a scale to assess acceptance and struggle with terminal illness SO CANCER LA English DT Article DE cognitive acceptance; end-of-life care; prognosis communication; self-reported peacefulness; symptom burden; terminal illness ID QUALITY-OF-LIFE; PALLIATIVE CARE; TREATMENT PREFERENCES; DISCUSSING PROGNOSIS; DECISION-MAKING; WANT; END; HOPE; QUESTIONNAIRE; DISCLOSURE AB BACKGROUND. The role of emotional acceptance of a terminal illness in end-of-life (EOL) care is not known. The authors developed a measure of peaceful acceptance at the EOL, and evaluated the role of peaceful acceptance in EOL decision-making and care. METHODS. The authors developed the Peace, Equanimity, and Acceptance in the Cancer Experience (PEACE) questionnaire to measure the extent to which patients with advanced cancer have a sense of peaceful acceptance of their terminal illness. The scale was administered to 160 patients with advanced cancer along with measures of other attributes that hypothetically are related to acceptance, including cognitive acceptance of terminal illness. EOL outcomes in 56 patients who died during the study also were examined. RESULTS. The 12-item PEACE questionnaire had 2 subscales: a 7-item Struggle With Illness subscale (Cronbach alpha=.81) and a 5-item Peaceful Acceptance subscale (alpha=.78). Both subscales were associated with patients' self-reported peacefulness (correlation coefficient [r] = 0.66 for acceptance [P <.0001]; r=-0.37 for struggle [P <.0001]) Struggle With Illness scores were associated with.. cognitive terminal illness acknowledgment (mean scores, 14.9 vs 12.4 for patients who were not aware that their illness was terminal; P=.001) and with some aspects of advance care planning (living will or healthcare proxy: mean scores, 13.9 vs 11.5; P =.02). In addition, among patients who had died, the use of a feeding tube at the EOL was associated inversely with Peaceful Acceptance (P=.015). CONCLUSIONS. The current study indicated that the PEACE questionnaire is a valid and reliable measure of peaceful acceptance and struggle with illness. Scores were associated with some choices for EOL care among patients with advanced cancer. C1 [Mack, Jennifer W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Mack, Jennifer W.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Mack, Jennifer W.] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Nilsson, Matthew; Balboni, Tracy; Block, Susan D.; Trice, Elizabeth; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. [Balboni, Tracy] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Radiat Oncol, Boston, MA 02115 USA. [Friedlander, Robert J.] New Hampshire Oncol Hematol PA, Hooksett, NH USA. [Trice, Elizabeth] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Mack, JW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM jennifer_mack@dfci.harvard.edu FU NCI NIH HHS [T32 CA009172, R01 CA106370, CA106370]; NIMH NIH HHS [MH63892] NR 37 TC 36 Z9 37 U1 2 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 2008 VL 112 IS 11 BP 2509 EP 2517 DI 10.1002/cncr.23476 PG 9 WC Oncology SC Oncology GA 304TS UT WOS:000256132600024 PM 18429006 ER PT J AU Irwin, ML Cadmus, L Alvarez-Reeves, M O'Neil, M Mierzejewski, E Latka, R Yu, H DiPietro, L Jones, B Knobf, MT Chung, GG Mayne, ST AF Irwin, Melinda L. Cadmus, Lisa Alvarez-Reeves, Marty O'Neil, Mary Mierzejewski, Eileen Latka, Rebecca Yu, Herbert DiPietro, Loretta Jones, Beth Knobf, M. Tish Chung, Gina G. Mayne, Susan T. TI Recruiting and retaining breast cancer survivors into a randomized controlled exercise trial - The yale exercise and survivorship SO CANCER LA English DT Article DE physical activity; fitness; survival; recurrence; death; body fat; obesity; weight ID QUALITY-OF-LIFE; PHYSICAL-ACTIVITY; POSTMENOPAUSAL WOMEN; RECEIVING CHEMOTHERAPY; BODY-COMPOSITION; FASTING INSULIN; PUBLIC-HEALTH; DAILY FATIGUE; RISK; DIAGNOSIS AB BACKGROUND. Given observational findings that physical activity reduces breast cancer risk, improves survival, and improves quality of life in breast cancer survivors, a need has been identified for randomized controlled trials that testthe efficacy of exercise on biological mechanisms associated with breast cancer survival. The primary aims of the Yale Exercise and Survivorship Study were to 1) determine the feasibility of recruiting breast cancer survivors into a randomized controlled trial of the effects of exercise on biological markers and/or mechanisms associated with survival, 2) compare the effectiveness of various recruitment strategies on accrual rates and baseline characteristics, and 3) report adherence to the exercise trial. METHODS. Seventy-five postmenopausal breast cancer survivors self-referred into the trial or were recruited through the Connecticut Tumor Registry and randomly assigned to an exercise (n = 37) or usual-care (n = 38) group. The exercise group participated in 150 min/wk of supervised gym-based and home-based aerobic exercise for 6 months. The usual-care group was instructed to maintain current physical activity level. RESULTS. A total of 75 women (an accrual rate of 9.5%) were randomized to the trial. Rates of accrual were higher for women who self-referred into the study (19.8%) compared with women recruited via the cancer registry (7.6%); however, demographic, physiologic, and prognostic characteristics did not differ between the 2 recruitment strategies. On average, exercisers increased moderate-intensity to vigorous-intensity aerobic exercise by 129 minutes per week compared with 44 minutes per week among usual-care participants (P <.001). Women in the exercise-intervention group increased their average pedometer steps by 1621 steps per day compared with a decrease of 60 steps per day among women in the usual-care group (P <.01). CONCLUSIONS. Findings from this study will provide useful information for investigators who are conducting exercise trials in cancer populations, clinicians who are treating women diagnosed with breast cancer, and exercise professionals who are developing community-based exercise programs for cancer survivors. C1 [Irwin, Melinda L.; Cadmus, Lisa; O'Neil, Mary; Mierzejewski, Eileen; Latka, Rebecca; Yu, Herbert; Jones, Beth; Chung, Gina G.; Mayne, Susan T.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. [Alvarez-Reeves, Marty] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [DiPietro, Loretta] John B Pierce Fdn Lab, New Haven, CT 06519 USA. [Knobf, M. Tish] Yale Univ, Sch Nursing, New Haven, CT 06536 USA. RP Irwin, ML (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, POB 208034, New Haven, CT 06520 USA. EM melinda.irwin@yale.edu FU NCRR NIH HHS [M01 RR000125, M01-RR00125] NR 48 TC 44 Z9 44 U1 3 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JUN 1 PY 2008 VL 112 IS 11 SU S BP 2593 EP 2606 DI 10.1002/cncr.23446 PG 14 WC Oncology SC Oncology GA 304TT UT WOS:000256132700007 PM 18428192 ER PT J AU Sablina, AA Hahn, WC AF Sablina, Anna A. Hahn, William C. TI SV40 small T antigen and PP2A phosphatase in cell transformation SO CANCER AND METASTASIS REVIEWS LA English DT Review DE protein phosphatase 2A; SV40 small t antigen; transformation; cancer ID SMALL TUMOR-ANTIGEN; SIMIAN-VIRUS 40; ANCHORAGE-INDEPENDENT GROWTH; 2A SUBUNIT INTERACTION; CYCLIN-A PROMOTER; NF-KAPPA-B; PROTEIN PHOSPHATASE-2A; REGULATORY SUBUNIT; RAL-GTPASES; PPP2R1B GENE AB The SV40 early region protein, SV40 small t antigen, promotes cell transformation through negative regulation of the protein phosphatase 2A (PP2A) family of serine-threonine phosphatases. More recently, reduced levels of PP2A activity have been found in different types of human cancer. This occurs either through inactivating mutations of PP2A structural subunits, or by upregulation of the cellular PP2A inhibitors, CIP2A and SET. Several distinct PP2A complexes have been identified that contribute directly to tumor suppression by regulating specific phosphorylation events. These studies provide us with new insights into the role of protein phosphatases in cancer initiation and maintenance. C1 [Hahn, William C.] Broad Inst Harvard, Cambridge, MA 02142 USA. [Hahn, William C.] MIT, Cambridge, MA 02142 USA. [Sablina, Anna A.; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sablina, Anna A.; Hahn, William C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Sablina, Anna A.; Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Hahn, WC (reprint author), Broad Inst Harvard, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM William_Hahn@dfci.harvard.edu FU NCI NIH HHS [P01 CA 50661] NR 113 TC 54 Z9 56 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD JUN PY 2008 VL 27 IS 2 BP 137 EP 146 DI 10.1007/s10555-008-9116-0 PG 10 WC Oncology SC Oncology GA 296HZ UT WOS:000255535400003 PM 18214640 ER PT J AU Faber, J Gregory, RI Armstrong, SA AF Faber, Joerg Gregory, Richard I. Armstrong, Scott A. TI Linking miRNA regulation to BCR-ABL expression: The next dimension SO CANCER CELL LA English DT Editorial Material ID BLAST-CRISIS; LEUKEMIA; MECHANISMS; MICRORNAS AB The introduction of tyrosine kinase inhibitors in the treatment of BCR-ABL1-rearranged malignancies has revolutionized therapy, but the prognosis for acute leukemias remains suboptimal. In this issue of Cancer Cell, Bueno et al. (2008) add a new dimension to the regulation of ABL1 expression. The authors demonstrate that ABL1 is a direct target of miR-203, miR-203 is silenced by genetic and epigenetic mechanisms in hematopoietic malignancies expressing either ABL1 or BCR-ABL1, and restoration of miR-203 expression reduces ABL1 and BCR-ABL1 levels and inhibits cell proliferation. These findings may have broad implications for mechanisms underlying malignant transformation in hematopoietic and other malignancies. C1 [Armstrong, Scott A.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Armstrong, SA (reprint author), Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Div Hematol Oncol, Boston, MA 02115 USA. EM scott.armstrong@childrens.harvard.edu NR 10 TC 25 Z9 30 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUN PY 2008 VL 13 IS 6 BP 467 EP 469 DI 10.1016/j.ccr.2008.05.013 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 313GA UT WOS:000256727900002 PM 18538729 ER PT J AU Tomlins, SA Rhodes, DR Yu, JJ Varambally, S Mehra, R Perner, S Demichelis, F Helgeson, BE Laxman, B Morris, DS Cao, Q Cao, XH Andren, O Fall, K Johnson, L Wei, JT Shah, RB Al-Ahmadie, H Eastham, JA Eggener, SE Fine, SW Hotakainen, K Stenman, UH Tsodikov, A Gerald, WL Lilja, H Reuter, VE Kantoff, PW Scardino, PT Rubin, MA Bjartell, AS Chinnaiyan, AM AF Tomlins, Scott A. Rhodes, Daniel R. Yu, Jianjun Varambally, Sooryanarayana Mehra, Rohit Perner, Sven Demichelis, Francesca Helgeson, Beth E. Laxman, Bharathi Morris, David S. Cao, Qi Cao, Xuhong Andren, Ove Fall, Katja Johnson, Laura Wei, John T. Shah, Raja B. Al-Ahmadie, Hikmat Eastham, James A. Eggener, Scott E. Fine, Samson W. Hotakainen, Kristina Stenman, Ulf-Hakan Tsodikov, Alex Gerald, William L. Lilja, Hans Reuter, Victor E. Kantoff, Phillip W. Scardino, Peter T. Rubin, Mark A. Bjartell, Anders S. Chinnaiyan, Arul M. TI The role of SPINK1 in ETS rearrangement-negative prostate cancers SO CANCER CELL LA English DT Article ID SECRETORY TRYPSIN-INHIBITOR; TMPRSS2-ERG GENE FUSION; RADICAL PROSTATECTOMY; EXPRESSION; PROGRESSION; DISEASE; GROWTH; CELLS; RECURRENCE; NOMOGRAM AB ETS gene fusions have been characterized in a majority of prostate cancers; however, the key molecular alterations in ETS-negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier expression exclusively in a subset of ETS rearrangement-negative cancers (similar to 10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively in urine, and observed that SPINK1 outlier expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier expression model and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement-negative prostate cancers. C1 [Tomlins, Scott A.; Rhodes, Daniel R.; Yu, Jianjun; Varambally, Sooryanarayana; Mehra, Rohit; Helgeson, Beth E.; Laxman, Bharathi; Cao, Qi; Cao, Xuhong; Shah, Raja B.; Tsodikov, Alex; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA. [Cao, Xuhong; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. [Tomlins, Scott A.; Rhodes, Daniel R.; Varambally, Sooryanarayana; Mehra, Rohit; Helgeson, Beth E.; Laxman, Bharathi; Cao, Qi; Shah, Raja B.; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. [Rhodes, Daniel R.; Yu, Jianjun; Tsodikov, Alex; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Ctr Computat Med & Biol, Ann Arbor, MI 48109 USA. [Wei, John T.; Shah, Raja B.; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA. [Varambally, Sooryanarayana; Mehra, Rohit; Shah, Raja B.; Tsodikov, Alex; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Perner, Sven; Kantoff, Phillip W.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Demichelis, Francesca; Rubin, Mark A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Demichelis, Francesca; Johnson, Laura; Kantoff, Phillip W.; Rubin, Mark A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kantoff, Phillip W.; Rubin, Mark A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Perner, Sven] Univ Hosp Ulm, Inst Pathol, D-89081 Ulm, Germany. [Andren, Ove] Orebro Univ Hosp, Dept Urol, SE-70185 Orebro, Sweden. [Fall, Katja] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Al-Ahmadie, Hikmat; Fine, Samson W.; Gerald, William L.; Reuter, Victor E.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Eastham, James A.; Eggener, Scott E.; Lilja, Hans; Scardino, Peter T.; Bjartell, Anders S.] Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10065 USA. [Lilja, Hans] Mem Sloan Kettering Canc Ctr, Dept Surg, Dept Clin Labs & Med, New York, NY 10065 USA. [Hotakainen, Kristina; Stenman, Ulf-Hakan] Univ Helsinki, Cent Hosp, Dept Clin Chem, FIN-00290 Helsinki, Finland. [Tsodikov, Alex] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Lilja, Hans] Lund Univ, Univ Hosp UMAS, Dept Lab Med, SE-20502 Malmo, Sweden. [Bjartell, Anders S.] Lund Univ, Univ Hosp UMAS, Dept Urol, SE-20502 Malmo, Sweden. RP Chinnaiyan, AM (reprint author), Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA. EM arul@umich.edu RI Cao, Qi/A-5517-2010; Fall, Katja/A-9186-2012; Wei, John/E-8967-2012; OI Cao, Qi/0000-0002-5140-3681; Al-Ahmadie, Hikmat/0000-0002-2938-6627; Lilja, Hans/0000-0001-5871-7846; Rubin, Mark/0000-0002-8321-9950; Demichelis, Francesca/0000-0002-8266-8631; Fall, Katja/0000-0002-3649-2639 FU Howard Hughes Medical Institute; NCI NIH HHS [U01 CA111275, P50 CA069568, P50 CA069568-06A10016, P50 CA069568-110020, P50 CA092629, P50 CA69568, P50 CA92629, T32 CA082088, U01 CA111275-01, U01 CA111275-03, U01 CA111275-04, U01 CA113913]; NIDA NIH HHS [U54 DA021519, U54 DA021519-01A1] NR 47 TC 173 Z9 178 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUN PY 2008 VL 13 IS 6 BP 519 EP 528 DI 10.1016/j.ccr.2008.04.016 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 313GA UT WOS:000256727900008 PM 18538735 ER PT J AU Tworoger, SS Spentzos, D Grall, FT Liebermann, TA Hankinson, SE AF Tworoger, Shelley S. Spentzos, Dimitrios Grall, Franck T. Liebermann, Towia A. Hankinson, Susan E. TI Reproducibility of proteomic profiles over 3 years in postmenopausal women not taking postmenopausal hormones SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MASS-SPECTROMETRY; OVARIAN-CANCER; BREAST-CANCER; SERUM; BIOMARKERS; SPECIMENS; RISK AB Most proteomics studies examine one blood specimen per participant; however, it is unknown how well measures at one time point reflect an individual's long-term proteome pattern. Therefore, we examined the stability of the proteome over 3 years in postmenopausal women not taking hormones for at least 3 months using surface-enhanced laser desorption and ionization time-of-flight mass spectrometry. Using the Nurses' Health Study blood cohort, we randomly selected 60 women from a subset providing 2 to 3 blood samples over 3 years. Four different protein chip surfaces/plasma fractions were examined: unfractionated plasma on a CM10 and H50 chip, pH >= 9, plasma fraction on a CM10 chip, and the organic fraction on the H50 chip, all with a low- and high-energy transfer protocol. Participant and quality control samples were aligned to a reference sample and then peak intensity was assessed for all peaks identified in the reference sample. The average coefficient of variation (CV) of the peak intensity within conditions ranged from 16% (H50, organic, low protocol) to 63% (CM10, pH >= 9, high protocol). Generally, the CV and mean peak intensity of the quality control samples were inversely correlated (median -0.48). The mean intraclass correlation (ICC) within conditions ranged from 0.37 (H50, unfractionated, low protocol) to 0.68 (CM10, unfractionated, high protocol). For a signal-to-noise cutoff of 2.0, we observed 334 peaks, of which 241 (72%) had an ICC of >= 0.40. Although we observed a large range of CVs and ICCs, sufficient numbers of peaks had reasonable ICCs to suggest that protein peak reproducibility over 3 years was reasonable among postmenopausal women not taking hormones. C1 [Tworoger, Shelley S.; Hankinson, Susan E.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Tworoger, Shelley S.; Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA USA. [Tworoger, Shelley S.; Hankinson, Susan E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Spentzos, Dimitrios] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Spentzos, Dimitrios; Grall, Franck T.; Liebermann, Towia A.] Beth Israel Deaconess Med Ctr, Dana Farber Harvard Canc Ctr Proteom Core, Boston, MA 02215 USA. [Spentzos, Dimitrios; Grall, Franck T.; Liebermann, Towia A.] Beth Israel Deaconess Med Ctr, BIDMC Genom Ctr, Boston, MA 02215 USA. [Liebermann, Towia A.] Beth Israel Deaconess Med Ctr, Div Interdisciplinary Med & Biotechnol, Boston, MA 02215 USA. RP Tworoger, SS (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave,3rd Floor, Boston, MA 02115 USA. EM nhsst@channing.harvard.edu RI Libermann, Towia/F-9866-2010; OI Tworoger, Shelley/0000-0002-6986-7046 FU NCI NIH HHS [CA119139, CA006516, CA017352, CA49449, P50 CA105009] NR 15 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2008 VL 17 IS 6 BP 1480 EP 1485 DI 10.1158/1055-9965.EPI-07-2725 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 315PC UT WOS:000256890900025 PM 18559564 ER PT J AU Cho, NL Redston, M Zauber, AG Carothers, AM Hornick, J Wilton, A Sontag, S Nishioka, N Giardiello, FM Saltzman, JR Gostout, C Eagle, CJ Hawk, ET Bertagnolli, MM AF Cho, Nancy L. Redston, Mark Zauber, Ann G. Carothers, Adelaide M. Hornick, Jason Wilton, Andrew Sontag, Stephen Nishioka, Norman Giardiello, Francis M. Saltzman, John R. Gostout, Chris Eagle, Craig J. Hawk, Ernest T. Bertagnolli, Monica M. TI Aberrant Crypt Foci in the Adenoma Prevention with Celecoxib Trial SO CANCER PREVENTION RESEARCH LA English DT Article ID COLORECTAL-CANCER; RAT COLON; CYCLOOXYGENASE-2 INHIBITOR; MURINE COLON; ASPIRIN; QUANTIFICATION; EXPRESSION; POLYPOSIS; FEATURES; LESIONS AB Aberrant crypt foci (ACF) are the earliest visible neoplastic lesions in the colorectum. The natural history of these lesions and their role in the adenoma-carcinoma sequence are unknown. We studied ACF in a subset of patients randomized to placebo (n = 17), celecoxib (200 mg twice daily; n = 15), or celecoxib (400 mg twice daily; n = 13) in the Adenoma Prevention with Celecoxib (APC) trial. Magnification chromoendoscopy was done to identify, count, and biopsy ACF within the rectum at baseline and after 8 to 12 months of treatment. A total of 655 ACF were identified in 45 patients. We examined 70 of these ACF histologically, and all 70 were nondysplastic. Cohort characteristics and APC trial treatment results for substudy patients were similar to those of the overall APC trial. There was no significant modulation of ACF by celecoxib (versus placebo; P = 0.77). Immunohistochemical comparison of ACF with adjacent normal mucosa showed that ACF had an increased proliferative index as determined by Ki-67 (P < 0.0001), but lacked other features of neoplasia such as increased cyclooxygenase-2 expression and microvessel density, nuclear localization of beta-catenin, or decreased expression of the tumor suppressors SMAD4, Estrogen Receptor alpha, or MGMT. Only baseline SMAD4 expression in ACF correlated with posttreatment adenoma recurrence (independent of treatment arm; P = 0.01). The presence or number of nondysplastic ACF did not correlate with a higher risk of synchronous advanced or recurrent adenomas. Our overall results indicated that nondysplastic ACF were not accurate surrogate endpoint biomarkers of recurrent colorectal adenomas in the APC trial. C1 [Cho, Nancy L.; Carothers, Adelaide M.; Bertagnolli, Monica M.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Redston, Mark; Hornick, Jason] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Saltzman, John R.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Hawk, Ernest T.] NCI, Bethesda, MD 20892 USA. [Gostout, Chris] Mayo Clin, Dept Med, Rochester, MN USA. [Giardiello, Francis M.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. [Sontag, Stephen] Edward Hines Vet Adm Med Ctr, Hines, IL 60141 USA. [Wilton, Andrew] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Eagle, Craig J.] Pfizer Inc, New York, NY USA. [Nishioka, Norman] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. RP Bertagnolli, MM (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM mbertagnolli@partners.org NR 31 TC 37 Z9 37 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JUN PY 2008 VL 1 IS 1 BP 21 EP 31 DI 10.1158/1940-6207.CAPR-07-0011 PG 11 WC Oncology SC Oncology GA 417UQ UT WOS:000264104400006 PM 19138933 ER PT J AU Yamazaki, M Nakamura, K Mizukami, Y Ii, M Sasajima, J Sugiyama, Y Nishikawa, T Nakano, Y Yanagawa, N Sato, K Maemoto, A Tanno, S Okumura, T Karasaki, H Kono, T Fujiya, M Ashida, T Chung, DC Kohgo, Y AF Yamazaki, Madoka Nakamura, Kazumasa Mizukami, Yusuke Ii, Masaaki Sasajima, Junpei Sugiyama, Yoshiaki Nishikawa, Tomoya Nakano, Yasuhiro Yanagawa, Nobuyuki Sato, Kazuya Maemoto, Atsuo Tanno, Satoshi Okumura, Toshikatsu Karasaki, Hidenori Kono, Toru Fujiya, Mikihiro Ashida, Toshifumi Chung, Daniel C. Kohgo, Yutaka TI Sonic hedgehog derived from human pancreatic cancer cells augments angiogenic function of endothelial progenitor cells SO CANCER SCIENCE LA English DT Article ID PRECURSOR CELLS; DUCTAL ADENOCARCINOMA; INTERACTING PROTEIN; BINDING-PROTEIN; HIGH EXPRESSION; POOR-PROGNOSIS; GROWTH-FACTOR; TUMOR; BONE; NEOVASCULARIZATION AB Hedgehog signaling is important in the pathogenesis of pancreatic cancer. Several recent observations suggest the involvement of sonic hedgehog (SHH) in postnatal neovascularization. We identified a novel role for SHH in tumor-associated angiogenesis in pancreatic cancer. Immunohistochemical analysis revealed that patched homolog 1 (PTCH1), both a receptor for and transcriptional target of hedgehog signaling, was expressed in a small fraction of endothelial cells within pancreatic cancer, but not in normal pancreatic tissue. When endothelial progenitor cells (EPC) isolated from human peripheral blood were cultured with supernatant from SHH-transfected 293 cells or pancreatic cancer cells, mRNA levels of vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 and angiopoietin-1 were significantly increased, whereas no such induction was observed in human umbilical vein endothelial cell (HUVEC) and human dermal microvascular endothelial cell (HMVEC). HUVEC tube formation was stimulated when cocultured with EPC, and preconditioning EPC with supernatant from KP-1 N pancreatic cancer cells highly expressing SHH significantly enhanced the effect. The effect was partially attenuated by specific inhibition of SHH with cyclopamine or a neutralizing antibody. These findings suggest that tumor-derived SHH can induce angiogenesis, and this is mediated by its effects on EPC specifically. Targeting SHH would be a novel therapeutic approach that can inhibit not only proliferation of cancer cells but also EPC-mediated angiogenesis. C1 [Yamazaki, Madoka; Nakamura, Kazumasa; Mizukami, Yusuke; Sasajima, Junpei; Sugiyama, Yoshiaki; Nishikawa, Tomoya; Nakano, Yasuhiro; Yanagawa, Nobuyuki; Sato, Kazuya; Fujiya, Mikihiro; Ashida, Toshifumi; Kohgo, Yutaka] Asahikawa Med Coll, Div Gastroenterol Hematol Oncol, Dept Med, Asahikawa, Hokkaido 0788510, Japan. [Maemoto, Atsuo] Asahikawa Med Coll, Dept Gastrointestinal Immunol & Regenerat Med, Asahikawa, Hokkaido 0788510, Japan. [Tanno, Satoshi; Okumura, Toshikatsu] Asahikawa Med Coll, Dept Gen Med, Asahikawa, Hokkaido 0788510, Japan. [Karasaki, Hidenori; Kono, Toru] Asahikawa Med Coll, Div Gastroenterol & Gen Surg, Dept Surg, Asahikawa, Hokkaido 0788510, Japan. [Ii, Masaaki] Inst Biomed Res & Innovat, Grp Vasc Regenerat Med, Kobe, Hyogo 6500047, Japan. [Chung, Daniel C.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chung, Daniel C.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Mizukami, Y (reprint author), Asahikawa Med Coll, Div Gastroenterol Hematol Oncol, Dept Med, Asahikawa, Hokkaido 0788510, Japan. EM mizu@asahikawa-med.ac.jp NR 38 TC 39 Z9 42 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD JUN PY 2008 VL 99 IS 6 BP 1131 EP 1138 DI 10.1111/j.1349-7006.2008.00795.x PG 8 WC Oncology SC Oncology GA 301OT UT WOS:000255906200009 PM 18422746 ER PT J AU Weisbord, SD Hartwig, KC Sonel, AF Fine, MJ Palevsky, P AF Weisbord, Steven D. Hartwig, Kathryn C. Sonel, Ali F. Fine, Michael J. Palevsky, Paul TI The incidence of clinically significant contrast-induced nephropathy following non-emergent coronary angiography SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE contrast-induced nephropathy; outcomes; mortality; contrast media; angiography; coronary; complications ID ACUTE-RENAL-FAILURE; RANDOMIZED CONTROLLED-TRIAL; CHRONIC KIDNEY-DISEASE; CARDIAC ANGIOGRAPHY; N-ACETYLCYSTEINE; SERUM CREATININE; PREVENTION; AGENT; MEDIA; NEPHROTOXICITY AB Objectives: The primary aim of this study was to assess the incidence of clinically significant contrast-induced nephropathy (CIN) among patients undergoing non-emergent coronary angiography. Background: Although retrospective analyses have emphasized the association of CIN with adverse patient outcomes, the actual incidence of clinically significant CIN following non-emergent coronary angiography is not clear. Methods: We prospectively identified patients with baseline estimated glomerular filtration rates (eGFR) < 60 ml/min/1.73 m(2) undergoing non-emergent coronary angiography. We measured serum creatinine 48-96 hr following angiography and assessed the incidence of CIN using two definitions, a rise in Scr >= 25% and >= 0.5 mg/dl. We tracked the need for dialysis, hospitalization related to kidney injury, and 30-day mortality to examine the association of CIN with these outcomes. Results: We enrolled 181 patients with a median eGFR of 52 ml/min/1.73 m(2). Of the 165 patients (91%) with post-procedure Scr data, the incidence of CIN was 6.1-8.5%. One patient required dialysis (0.55%) and one (0.55%) died within 30 days. Although 38 patients required hospital admission, CIN was not associated with the need for hospitalization. Patients with an increase in Scr >= 25% demonstrated a trend toward increased risk for 30-day mortality (P = 0.09), whereas those with increments in Scr >= 0.5 mg/dl had a marginally higher risk for dialysis (P = 0.06) and 30-day mortality (P = 0.06), although these associations failed to meet the level of statistical significance. Conclusions: Biochemically defined CIN occurs in a small, but notable proportion of patients undergoing non-emergent coronary angiography. However, clinically significant CIN is very uncommon. (C) 2008 Wiley-Liss, Inc. C1 [Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15214 USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Mailstop 111 F-U,7E Room 120, Pittsburgh, PA 15214 USA. EM weisbordsd@upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 FU NIAID NIH HHS [K24 AI001769] NR 42 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JUN 1 PY 2008 VL 71 IS 7 BP 879 EP 885 DI 10.1002/ccd.21565 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 308SD UT WOS:000256409400004 PM 18412255 ER PT J AU Schainfeld, RM AF Schainfeld, Robert M. TI "Dizzie-ness:" Is it really "all that jazz?" SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material ID ARTERY C1 Massachusetts Gen Hosp, Sect Vasc Med, Div Cardiol, Boston, MA 02451 USA. RP Schainfeld, RM (reprint author), Massachusetts Gen Hosp, Sect Vasc Med, Div Cardiol, Boston, MA 02451 USA. EM rschainfeld@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JUN 1 PY 2008 VL 71 IS 7 BP 969 EP 971 DI 10.1002/ccd.21627 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 308SD UT WOS:000256409400023 PM 18500703 ER PT J AU Gilbert, RJ Gaige, TA Wang, RP Benner, T Dai, GP Glickman, JN Wedeen, VJ AF Gilbert, Richard J. Gaige, Terry A. Wang, Ruopeng Benner, Thomas Dai, Guangping Glickman, Jonathan N. Wedeen, Van J. TI Resolving the three-dimensional myoarchitecture of bovine esophageal wall with diffusion spectrum imaging and tractography SO CELL AND TISSUE RESEARCH LA English DT Article DE esophageal muscle; myoarchitecture; diffusion weighted magnetic resonance imaging; bovine ID IN-VIVO; TONGUE; VIBRATIONS; TRANSPORT AB In order to determine the three-dimensional (3D) resolved muscular anatomy of the mammalian esophagus, we have examined its myoarchitecture with diffusion spectrum magnetic resonance imaging (DSI) and tractography. DSI measures diffusion displacement as a function of magnetic gradients of varied direction and intensity and displays the displacement profile as a 3D contour per voxel. In tractography, the orientation vectors of maximum diffusion/voxel are identified, and intervoxel associations are constructed by a streamline algorithm based on angular similarity in order to generate mesoscale myofiber tracts. We demonstrate that the proximal body of the esophagus consists of helically aligned crossing fiber populations that overlap between layers in the form of a "zipper" region along the length of the tissue. With increasingly distal position along the length of the tissue, helix angle and skeletal muscle prevalence are reduced such that fibers align themselves in the most distal location into distinct inner circular and outer longitudinal smooth muscle layers. We conclude that esophageal myoanatomy consists of crossing myofibers exhibiting a decreasing degree of helicity as a function of axial position and propose that this unique geometric construct provides a mechanism to resist distension and promote aboral flow. C1 [Gilbert, Richard J.; Gaige, Terry A.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Wang, Ruopeng; Benner, Thomas; Dai, Guangping; Wedeen, Van J.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Imaging Ctr, Boston, MA 02114 USA. [Glickman, Jonathan N.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Gilbert, RJ (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rgilbert@mit.edu FU NIDCD NIH HHS [R01 DC 05604]; NIMH NIH HHS [R01 MH 64044] NR 25 TC 13 Z9 14 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD JUN PY 2008 VL 332 IS 3 BP 461 EP 468 DI 10.1007/s00441-008-0601-0 PG 8 WC Cell Biology SC Cell Biology GA 307YC UT WOS:000256354500008 PM 18401597 ER PT J AU Jette, CA Flanagan, AM Ryan, J Pyati, UJ Carbonneau, S Stewart, RA Langenau, DM Look, AT Letai, A AF Jette, C. A. Flanagan, A. M. Ryan, J. Pyati, U. J. Carbonneau, S. Stewart, R. A. Langenau, D. M. Look, A. T. Letai, A. TI BIM and other BCL-2 family proteins exhibit cross-species conservation of function between zebrafish and mammals SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE bim; bad; bid; bcl-2; zebrafish; apoptosis ID APOPTOTIC FUNCTION; BH3-ONLY PROTEINS; BH3 DOMAIN; CELL-DEATH; BAX; PHOSPHORYLATION; MITOCHONDRIA; PROMOTES; PATHWAY; MEMBERS AB Here we investigate the function of zebrafish Bcl-2 family proteins and demonstrate important conservation of function across zebrafish and mammalian systems. We have isolated a zebrafish ortholog of mammalian BIM and show that it is the most toxic of the zebrafish BH3-only genes examined, sharing this characteristic with the mammalian BIM gene. The zebrafish bad gene shows a complete lack of embryonic lethality, but like mammalian BAD, its pro-apoptotic activity is regulated through phosphorylation of critical serines. We also found that the pattern of mitochondrial dysfunction observed by zebrafish BH3 domain peptides in a mammalian cytochrome c release assay recapitulates the pattern of embryonic lethality induced by the respective mRNA injections in vivo. In contrast to zebrafish Bim, Bid exhibited only weak binding to zebrafish Bcl-2 and moderate-to-weak overall lethality in zebrafish embryos and isolated mitochondria. Given that zebrafish Bcl-2 binds strongly to mammalian BID and BIM peptides and proteins, the protein identified as the zebrafish Bid ortholog has different properties than mammalian BID. Overall, our results demonstrate the high degree of functional conservation between zebrafish and mammalian Bcl-2 family proteins, thus validating the zebrafish as a model system to further dissect the molecular mechanisms that regulate apoptosis in future forward genetic and chemical modifier screens. C1 [Jette, C. A.; Pyati, U. J.; Carbonneau, S.; Stewart, R. A.; Look, A. T.] Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. [Flanagan, A. M.; Ryan, J.; Letai, A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Langenau, D. M.] Harvard Univ, Sch Med, Childrens Hosp, Dept Hematol Oncol, Boston, MA 02115 USA. RP Look, AT (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu; anthony_letai@dfci.harvard.edu OI Stewart, Rodney/0000-0003-1220-1830 FU NCI NIH HHS [K08 CA102548-05, K08 CA102548, K08CA10254, P01 CA068484, P01CA068484, R01 CA119066, R01CA119066]; NHLBI NIH HHS [5T32HL07623-20, T32 HL007623]; NIDDK NIH HHS [K01DK0745551]; NINDS NIH HHS [K99 NS058608, K99 NS058608-01, K99 NS058608-02, K99NS058608, R00 NS058608, R00 NS058608-03] NR 35 TC 26 Z9 28 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD JUN PY 2008 VL 15 IS 6 BP 1063 EP 1072 DI 10.1038/cdd.2008.42 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 303VC UT WOS:000256068000011 PM 18404156 ER PT J AU Janzen, V Fleming, HE Riedt, T Karlsson, G Riese, MJ Lo Celso, C Reynolds, G Milne, CD Paige, CJ Karlsson, S Woo, M Scadden, DT AF Janzen, Viktor Fleming, Heather E. Riedt, Tamara Karlsson, Goeran Riese, Matthew J. Lo Celso, Cristina Reynolds, Griffin Milne, Craig D. Paige, Christopher J. Karlsson, Stefan Woo, Minna Scadden, David T. TI Hematopoietic stem cell responsiveness to exogenous signals is limited by Caspase-3 SO CELL STEM CELL LA English DT Article ID BONE-MARROW CELLS; DIFFERENTIATION; APOPTOSIS; ACTIVATION; PROLIFERATION; CONSEQUENCE; INHIBITOR; SUBSTRATE; PATHWAY; ERK2 AB Limited responsiveness to inflammatory cytokines is a feature of adult hematopoietic stem cells and contributes to the relative quiescence and durability of the stem cell population in vivo. Here we report that the executioner Caspase, Caspase-3, unexpectedly participates in that process. Mice deficient in Caspase-3 had increased numbers of immunophenotypic long-term repopulating stem cells in association with multiple functional changes, most prominently cell cycling. Though these changes were cell autonomous, they reflected altered activation by exogenous signals. Caspase-3(-/-) cells exhibited cell type-specific changes in phosphorylated members of the Ras-Raf-MEK-ERK pathway in response to specific cytokines, while notably, members of other pathways, such as pSTAT3, pSTAT5, pAKT, pp38 MAPK, pSmad2, and pSmad3, were unaffected. Caspase-3 contributes to stem cell quiescence, dampening specific signaling events and thereby cell responsiveness to microenvironmental stimuli. C1 [Janzen, Viktor; Fleming, Heather E.; Riese, Matthew J.; Lo Celso, Cristina; Reynolds, Griffin; Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med,Canc Ctr, Boston, MA 02114 USA. [Janzen, Viktor; Fleming, Heather E.; Lo Celso, Cristina; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Janzen, Viktor; Riedt, Tamara] Univ Tubingen, Dept Internal Med 2, Div Hematol Oncol & Immunol, D-72076 Tubingen, Germany. [Karlsson, Goeran; Karlsson, Stefan] Univ Lund Hosp, Inst Lab Med, Dept Mol Med & Gene Therapy, SE-22184 Lund, Sweden. [Karlsson, Goeran; Karlsson, Stefan] Lund Strateg Res Ctr Stem Cell Biol & Cell Therap, SE-22184 Lund, Sweden. [Milne, Craig D.; Paige, Christopher J.] Univ Toronto, Ontario Canc Inst, Dept Immunol, Univ Hlth Network, Toronto, ON M5G 2M9, Canada. [Woo, Minna] Univ Toronto, Ontario Canc Inst, Dept Med Biophys, Toronto, ON M5G 2M9, Canada. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med,Canc Ctr, Boston, MA 02114 USA. EM scadden.david@mgh.harvard.edu OI Lo Celso, Cristina/0000-0002-1163-4207; Karlsson, Goran/0000-0001-8197-754X FU NIDDK NIH HHS [R01 DK050234-14, R01 DK050234-11A2, R01 DK050234, R01 DK050234-13, R01 DK050234-12] NR 34 TC 62 Z9 63 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD JUN PY 2008 VL 2 IS 6 BP 584 EP 594 DI 10.1016/j.stem.2008.03.012 PG 11 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 315HT UT WOS:000256870000016 PM 18522851 ER PT J AU Han, S Witt, RM Santos, TM Polizzano, C Sabatini, BL Ramesh, V AF Han, Sangyeul Witt, Rochelle M. Santos, Tulio M. Polizzano, Carolyn Sabatini, Bernardo L. Ramesh, Vijaya TI Pam (Protein associated with Myc) functions as an E3 Ubiquitin ligase and regulates TSC/mTOR signaling SO CELLULAR SIGNALLING LA English DT Article DE TSC; tuberin; hamartin; mammalian target of rapamycin; ubiquitination; Pam; RING finger ID TERM SYNAPTIC PLASTICITY; C-ELEGANS RPM-1; UBIQUITIN LIGASE; TUBEROUS SCLEROSIS; TUMOR-SUPPRESSOR; GENE-PRODUCT; TRANSLATIONAL CONTROL; RAPAMYCIN PATHWAY; FORMATION REVEALS; MAMMALIAN TARGET AB The tumor suppressor tuberin, encoded by the Tuberous Sclerosis Complex (TSC) gene TSC2, negatively regulates the mammalian target of rapamycin (mTOR) pathway, which plays a key role in the control of cell growth and proliferation. In addition to naturally occurring mutations, several kinases including Akt, RSK1, and ERK are known to phosphorylate and inactivate tuberin. We demonstrate a novel mechanism of tuberin inactivation through ubiquitination by Pam, a putative RING finger-containing E3 ubiquitin (Ub) ligase in mammalian cells. We show that Pam associates with E2 ubiquitin-conjugating enzymes, and tuberin can be ubiquitinated by Pam through its RING finger domain. Tuberin ubiquitination is independent of its phosphorylation by Akt, RSK1, and ERK kinases. Pam is also self-ubiquitinated through its RING finger domain. Moreover, the TSC1 protein hamartin, which forms a heterodimer with tuberin, protects tuberin from ubiquitination by Pam. However, TSC1 fails to protect a disease-associated missense mutant of TSC2 from ubiquitination by Pam. Furthermore, Pam knockdown by RNA interference (RNAi) in rat primary neurons elevates the level of tuberin, and subsequently inhibits the mTOR pathway. Our results provide novel evidence that Pam can function as an E3 Ub ligase toward tuberin and regulate mTOR signaling, suggesting that Pam can in turn regulate cell growth and proliferation as well as neuronal function through the TSC/mTOR pathway in mammalian cells. (C) 2008 Elsevier Inc. All rights reserved. C1 [Han, Sangyeul; Santos, Tulio M.; Polizzano, Carolyn; Ramesh, Vijaya] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Witt, Rochelle M.; Sabatini, Bernardo L.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Ramesh, V (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM ramesh@helix.mgh.harvard.edu FU Autism Speaks [AS1862]; NIMH NIH HHS [R21 MH079213-01A1]; NINDS NIH HHS [NS24279, NS45776, P01 NS024279, P01 NS024279-120008, P30 NS045776, R01 NS052707, R01 NS052707-03] NR 48 TC 33 Z9 37 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD JUN PY 2008 VL 20 IS 6 BP 1084 EP 1091 DI 10.1016/j.cellsig.2008.01.020 PG 8 WC Cell Biology SC Cell Biology GA 306HJ UT WOS:000256238600010 PM 18308511 ER PT J AU Bar, M Aminoff, E Ishai, A AF Bar, Moshe Aminoff, Elissa Ishai, Alumit TI Famous faces activate contextual associations in the parahippocampal cortex SO CEREBRAL CORTEX LA English DT Article DE associations; context; face processing; parahippocampal cortex ID MEDIAL TEMPORAL-LOBE; DISTRIBUTED CORTICAL NETWORK; NEURAL REPRESENTATION; ORBITOFRONTAL CORTEX; RECOGNITION MEMORY; SPATIAL CONTEXT; BRAIN ACTIVITY; FMRI; PERCEPTION; HIPPOCAMPUS AB The parahippocampal cortex (PHC) has been traditionally implicated both in place processing and in episodic memory. How could the same cortical region mediate these cognitive functions that seem quite different? We have recently proposed that the PHC should be seen as more generally mediating contextual associative processing, which is required for both navigation and memory. We therefore predicted that any associative objects should activate the PHC. To test this generalization, we investigated the extent to which common stimuli that are nonspatial by nature, namely faces, activate the PHC, although their perception is typically associated with other cortical structures. Specifically, we compared the activation elicited by famous faces, which are highly associated with rich pictorial and contextual information (e.g., Tom Cruise) and are not associated with a specific place, with activation elicited by unfamiliar faces. Consistent with our prediction, contrasting famous with unfamiliar faces revealed significant activation within the PHC. Taken collectively, these findings indicate that the PHC should be regarded as mediating contextual associations in general and not necessarily spatial or episodic information. C1 [Ishai, Alumit] Univ Zurich, Inst Neuroradiol, CH-8057 Zurich, Switzerland. [Bar, Moshe; Aminoff, Elissa] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr, Charlestown, MA 02129 USA. RP Ishai, A (reprint author), Univ Zurich, Inst Neuroradiol, CH-8057 Zurich, Switzerland. EM ishai@hifo.uzh.ch OI Aminoff, Elissa/0000-0002-6455-8930 FU NCRR NIH HHS [P41RR14075]; NIMH NIH HHS [T32MH070328]; NINDS NIH HHS [NS050615, NS044319] NR 75 TC 46 Z9 50 U1 3 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUN PY 2008 VL 18 IS 6 BP 1233 EP 1238 DI 10.1093/cercor/bhm170 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 302RY UT WOS:000255988200001 PM 17934188 ER PT J AU Singer, DE Albers, GW Dalen, JE Fang, MC Go, AS Halperin, JL Lip, GYH Manning, WJ AF Singer, Daniel E. Albers, Gregory W. Dalen, James E. Fang, Margaret C. Go, Alan S. Halperin, Jonathan L. Lip, Gregory Y. H. Manning, Warren J. TI Antithrombotic therapy in atrial fibrillation SO CHEST LA English DT Review DE antithrombotic; atrial fibrillation; mitral stenosis; prophylaxis; stroke ID CORONARY-ARTERY-BYPASS; RANDOMIZED CONTROLLED-TRIAL; DIRECT THROMBIN INHIBITOR; DIRECT-CURRENT CARDIOVERSION; ORAL ANTICOAGULANT-THERAPY; SPONTANEOUS ECHO CONTRAST; VON-WILLEBRAND-FACTOR; HIGH-RISK PATIENTS; ECHOCARDIOGRAPHIC-GUIDED CARDIOVERSION; CLINICAL CLASSIFICATION SCHEMES AB This chapter about antithrombotic therapy in atrial fibrillation (AF) is part of the American College of Chest Physicians Evidence-Based Guidelines Clinical Practice Guidelines (8th Edition). Grade I recommendations indicate that most patients would make the same choice and Grade 2 suggests that individual patient's values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2008; 133[suppI]:123S-131S). Among the key recommendations in this chapter are the following (all vitamin K antagonist [VKA] recommendations have a target international normalized ratio [INR] of 2.5; range 2.0-3.0, unless otherwise noted). In patients with AF, including those with paroxysmal AF, who have had a prior ischemic stroke, transient ischemic attack (TIA), or systemic embolism, we recommend long-term anticoagulation with an oral VKA, such as warfarin, because of the high risk of future ischemic stroke faced by this set of patients (Grade 1A). In patients with AF, including those,with paroxysmal AF, who have two or more of the risk factors for future ischemic stroke listed immediately below, we recommend long-term anticoagulation with an oral VKA. (Grade 1A). Two or more of the following]risk factors apply: age > 75 years, history of hypertension, diabetes mellitus, moderately or severely impaired left ventricular systolic function and/or heart failure. In patients with AF, including those with paroxysmal AF, with only one of the risk factors listed immediately above, we recommend long-term antithrombotic therapy (Grade 1A), either as anticoagulation with an oral VKA, such as warfarin (Grade 1A), or as aspirin, at a dose of 75-325 mg/d (Grade 1B). In these patients at intermediate risk of ischemic stroke we suggest a VKA rather than aspirin (Grade 2A). in patients with AF. including those with paroxysmal AF, age :5 75 years and with none of the other risk factors listed above, we recommend long-term aspirin therapy at a dose of 75-325 mg/d (Grade 1B), because of their low risk of ischemic stroke. For patients with atrial flutter, we recommend that antithrombotic therapy decisions follow the same risk-based recommendations as for AF (Grade 1C). For patients with AF and mitral stenosis, we recommend long-term anticoagulation with an oral VKA (Grade 1B). For patients with AF and prosthetic heart valves we recommend long-term anticoagulation with an oral VKA at an intensity appropriate for the specific type of prosthesis (Grade 1B). See CHEST 2008; 133(suppl):593S-629S. For patients with AF of >= 48 h or of unknown duration for whom pharmacologic or electrical cardioversion is Planned, we recommend anticoagulation with an oral VKA, such as warfarin, for 3 weeks before elective cardioversion and for at. least 4 weeks after sinus rhythm has been maintained (Grade 1C). For patients, with AF of ! 48 h or of unknown duration undergoing pharmacological or electrical cardioversion, we also recommend either immediate anticoagulation with unfractionated IV heparin, or low-molecular-weight heparin (LMWH), or at least 5 days of warfarin by the time of cardioversion (achieving an INR of 2.0-3.0) as well as a screening multiplane transesophageal echocardiography (TEE). If no thrombus is seen, cardioversion is successful, and sinus rhythm is maintained, we recommend anticoagulation for at least 4 weeks. If a thrombus is seen on TEE, then cardioversion should be postponed and anticoagulation should be continued indefinitely. We recommend obtaining a repeat TEE before attempting later cardioversion (Grade 1B addressing the equivalene of TEE-guided vs non-TEE-guided cardioversion). For patients with AF of known duration < 48 h, we suggest cardioversion without prolonged anticoagulation (Grade 2C). However, in patients without contraindications to anticoagulation, we suggest beginning IV heparin or LMWH at presentation (Grade 2C). C1 [Singer, Daniel E.] Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, Boston, MA 02114 USA. [Albers, Gregory W.] Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. [Dalen, James E.] Univ Arizona, Tucson, AZ 85721 USA. [Fang, Margaret C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Halperin, Jonathan L.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Lip, Gregory Y. H.] Univ Birmingham, Dept Med, Birmingham, W Midlands, England. [Manning, Warren J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Singer, DE (reprint author), Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, S50-9, Boston, MA 02114 USA. EM dsinger@partners.org FU NIA NIH HHS [AG 15478] NR 282 TC 440 Z9 454 U1 3 U2 25 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUN PY 2008 VL 133 IS 6 SU S BP 546S EP 592S DI 10.1378/chest.08-0678 PG 47 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 319GJ UT WOS:000257151800015 PM 18574273 ER PT J AU Sobel, M Verhaeghe, R AF Sobel, Michael Verhaeghe, Raymond TI Antithrombotic therapy for peripheral artery occlusive disease SO CHEST LA English DT Review DE anticoagulation; antiplatelet therapy; aspirin; atherosclerosis; carotid artery; haparin; intermittent claudication; peripheral vascular disease; randomized controlled trial; review; thrombolysis; vascular surgery ID DOUBLE-BLIND TRIAL; RANDOMIZED CONTROLLED-TRIAL; MOLECULAR-WEIGHT HEPARIN; LOWER-EXTREMITY BYPASS; LOW-DOSE ASPIRIN; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; KNEE FEMOROPOPLITEAL BYPASS; PROSTAGLANDIN I-2 ANALOG; FEMORO-POPLITEAL GRAFTS; HUMAN UMBILICAL VEIN AB This chapter is devoted to antithrombotic therapy for peripheral artery occlusive disease as part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see the "Grades of Recommendation" chapter by Guyatt et al, CHEST 2008; 133:123S-131S). Among the key recommendations in this chapter are the following: We recommend lifelong antiplatelet therapy in comparison to no antiplatelet therapy in pulmonary artery disease (PAD) patients with clinically manifest coronary or cerebrovascular disease (Grade 1A), and also in those without clinically manifest coronary or cerebrovascular disease (Grade 1B). In patients with PAD and intermittent claudication, we recommend against the use of anticoagulants (Grade 1A). For patients with moderate to severe disabling intermittent claudication who do not respond to exercise therapy, and who are not candidates for surgical or catheter-based intervention, we recommend cilostazol (Grade 1A). We suggest that clinicians not use cilostazol in those with less-disabling claudication (Grade 2A). In patients with short-term (< 14 days) arterial thrombosis or embolism, we suggest intraarterial thrombolytic therapy (Grade 2B), provided they are at low risk of myonecrosis and ischemic nerve damage developing during the time to achieve revascularization. For patients undergoing major vascular reconstructive procedures, we recommend IV unfractionated heparin (UFH) prior to the application of vascular cross clamps (Grade 1A). For all patients undergoing infrainguinal arterial reconstruction, we recommend aspirin (75-100 mg, begun preoperatively) [Grade 1A]. For routine autogenous vein infrainguinal bypass, we recommend aspirin (75-100 mg, begun preoperatively) [Grade 1A]. For routine prosthetic infrainguinal bypass, we recommend aspirin (75-100 mg, begun preoperatively) [Grade 1A]. In patients undergoing carotid endarterectomy, we recommend that aspirin, 75-100 mg, be administered preoperatively and continued indefinitely (75-100 mg/d) [Grade 1A]. In nonoperative patients with asymptomatic carotid stenosis (primary or recurrent), we suggest that dual antiplatelet therapy with aspirin and clopidogrel be avoided (Grade 1B). For all patients undergoing lower-extremity balloon angioplasty (with or without stenting), we recommend long-term aspirin, 75-100 mg/d (Grade 1C). C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Sobel, Michael] Univ Washington, Sch Med, Seattle, WA USA. [Verhaeghe, Raymond] Katholieke Univ Leuven, Louvain, Belgium. RP Sobel, M (reprint author), Mailstop S-112,1660 S Columbian Way, Seattle, WA 98108 USA. EM michael.sobel@va.gov NR 203 TC 83 Z9 89 U1 1 U2 11 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUN PY 2008 VL 133 IS 6 SU S BP 815S EP 843S DI 10.1378/chest.08-0686 PG 29 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 319GJ UT WOS:000257151800021 PM 18574279 ER PT J AU Rehman, SU Martinez-Rumayor, A Mueller, T Januzzi, JL AF Rehman, Shafiq U. Martinez-Rumayor, Abelardo Mueller, Thomas Januzzi, James L., Jr. TI Independent and incremental prognostic value of multimarker testing in acute dyspnea: Results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study SO CLINICA CHIMICA ACTA LA English DT Article DE dyspnea; mortality; multimarker score (MMS) ID ACUTE CORONARY SYNDROMES; OBSTRUCTIVE PULMONARY-DISEASE; DECOMPENSATED HEART-FAILURE; BRAIN NATRIURETIC PEPTIDE; AMINO-TERMINAL PROBNP; BLOOD UREA NITROGEN; SOLUBLE ST2 PROTEIN; C-REACTIVE PROTEIN; FAMILY-MEMBER ST2; LOW-RISK PATIENTS AB Background: Acute dyspnea is common in the emergency department (ED) and is associated with mortality. Biomarkers may help stratify risk in this setting. Methods: Among 577 dyspneic subjects we identified 5 candidate biomarkers with prognostic value: amino terminal B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), the interleukin family member ST2, hemoglobin and blood urea nitrogen (BUN): these were assessed using both receiver operating characteristic curve and Cox proportional hazards analyses. Results were validated in a population of dyspneic patients from a distinct cohort. Results: At 1 y follow up, 93 (16.1%) patients had died. Independent predictive ability was established in an age-adjusted Cox model containing all markers: NT-proBNP (HR=1.89); CRP (HR=1.95); ST2 (HR=7.17); hemoglobin (HR=1.68); BUN (HR=2.06) (all P <.05). Following categorical assessment based on number of abnormal markers, the 1-y risk of death increased in a monotonic fashion with mortality rates of 0%, 2.0%, 7.8%. 22.3%, 29.3%, and 57.6% respectively: similar results were seen in the validation set. Conclusion: Simultaneous assessment of pathophysiologically diverse markers in acute dyspnea provides powerful, independent and incremental prognostic information. (c) 2008 Elsevier B.V. All rights reserved. C1 [Rehman, Shafiq U.; Martinez-Rumayor, Abelardo; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Rehman, Shafiq U.; Martinez-Rumayor, Abelardo; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Mueller, Thomas] Konventhosp Barmherzige Brueder, Dept Lab Med, Linz, Austria. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM jjanuzzi@partners.org NR 39 TC 33 Z9 33 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JUN PY 2008 VL 392 IS 1-2 BP 41 EP 45 DI 10.1016/j.cca.2008.03.002 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 311DQ UT WOS:000256581000009 PM 18387360 ER PT J AU Stern, JNH Keskin, DB Barteneva, N Zuniga, J Yunis, EJ Ahmed, AR AF Stern, J. N. H. Keskin, D. B. Barteneva, N. Zuniga, J. Yunis, E. J. Ahmed, A. R. TI Possible role of natural killer cells in pemphigus vulgaris - preliminary observations SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE B cell; MHC class II; natural killer cells; T lymphocyte ID NK CELLS; DENDRITIC CELLS; IGG SUBCLASS; B-CELLS; ACTIVATION; EXPRESSION; CD56(BRIGHT); DISEASE; AUTOANTIBODIES; INTERLEUKIN-6 AB Pemphigus vulgaris (PV) is an autoimmune blistering disease that affects the skin and multiple mucous membranes, and is caused by antibodies to desmoglein (Dsg) 1 and 3. Natural killer (NK) cells have a role in autoimmunity, but their role in PV is not known. NK cells in the peripheral blood leucocytes (PBL) of 15 untreated Caucasian patients with active PV were studied and compared with healthy controls for the expression of major histocompatibility complex (MHC) class II and co-stimulatory molecules. CD56(+) CD16(-) CD3(-) NK or CD56(+) CD16(+) CD3(-) NK cells from the PBL of PV patients co-express MHC class II and co-stimulatory molecule B7-H3 without exogenous stimulation. CD4(+) T cells from the PBL and perilesional skin of PV patients were co-cultured with CD56(+) CD3(-) NK cells from the PBL of the same patients; in the presence of Dsg3 peptides underwent statistically significant proliferation, indicating that NK cells functioned as antigen-presenting cells. Supernatants from these co-cultures and serum of the same patients with active PV had statistically significantly elevated levels of interleukin (IL)-6, IL-8 and interferon-gamma, compared with controls indicating that the NK cells stimulated CD4(+) T cells to produce proinflammatory cytokines. In these experiments, we present preliminary evidence that NK cells may play a role in the pathobiology of PV. C1 [Ahmed, A. R.] New England Baptist Hosp, Ctr Blistering Dis, Dept Med, Boston, MA USA. [Stern, J. N. H.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Stern, J. N. H.; Keskin, D. B.; Zuniga, J.; Yunis, E. J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Barteneva, N.] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA USA. [Zuniga, J.; Yunis, E. J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ahmed, AR (reprint author), New England Baptist Hosp, Ctr Blistering Dis, Dept Med, Boston, MA USA. EM arahmedmd@msn.com OI Stern, Joel N.H./0000-0002-1259-2256 FU NHLBI NIH HHS [HL29583, HL59838, P01 HL029583, R01 HL059838] NR 39 TC 17 Z9 17 U1 2 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JUN PY 2008 VL 152 IS 3 BP 472 EP 481 DI 10.1111/j.1365-2249.2008.03638.x PG 10 WC Immunology SC Immunology GA 297UV UT WOS:000255643800011 PM 18373702 ER PT J AU Lee, DBN Roberts, M AF Lee, David B. N. Roberts, Martin TI A peritoneal-based automated wearable artificial kidney SO CLINICAL AND EXPERIMENTAL NEPHROLOGY LA English DT Review DE automated wearable artificial kidney; AWAK; peritoneal dialysis ID SALICYLATE INTOXICATION; DIALYSIS BAGS; ZIRCONIA; INTERMITTENT; REMOVAL; SYSTEM; ERYTHROPOIETIN; REGENERATION; HEMODIALYSIS; REPLACEMENT AB Work on wearable kidneys has evolved around the technology of hemodialysis or hemofiltration, which call for continuous anticoagulation of the extracoporeal circulation and are encumbered with potential immunologic and non-immunologic complications of continuous blood-artificial membrane interactions. A peritoneal-based automated wearable artificial kidney (AWAK) requires no extracorporeal circulation and is therefore "bloodless.'' Because AWAK is designed to continuously regenerate and reuse the spent dialysate in perpetuity, it is also "waterless.'' A sorbent-based assembly regenerates both the aqueous and the protein components (AqC and PrC) of the spent dialysate, producing a novel, autologous protein-containing dialysate. The regenerated AqC has the same composition as the commercially available peritoneal dialysate, but contains bicarbonate instead of lactate and has a more physiological pH. The regenerated PrC is recycled back into the peritoneal cavity, thereby ameliorating or eliminating protein loss. Depending on the steady-state protein concentrations that can be achieved ( under the condition of continuous dialysate regeneration and recycling), the PrC also has the potential of both augmenting ultrafiltration and mediating the removal of protein-bound toxins. Additional sorbents can be incorporated into AWAK for the removal of middle molecular weight uremic toxins. At a regeneration rate of 4 l/h, AWAK provides a dialysate flow of 96 l/day (8-12 times the current rate). Round-the-clock dialysis and ultrafiltration provide steady-state metabolic-biochemical and fluid balance regulation, thereby eliminating "shocks'' of abrupt changes in these parameters that characterize the current dialytic modalities. Dialysis-on-the-go, made possible by AWAK's "wearability'' and automation, frees end-stage renal failure patients from the servitude that is demanded by the current dialytic regimentations. C1 [Lee, David B. N.; Roberts, Martin] VA Greater LA Healthcare Syst, Sepulveda Ambulatory Care Ctr & Nursing Home, LAKID, Los Angeles, CA USA. [Lee, David B. N.; Roberts, Martin] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Lee, DBN (reprint author), 16016 Jeanne Lane, Encino, CA 91436 USA. EM dbnlee@ucla.edu NR 58 TC 22 Z9 23 U1 3 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1342-1751 J9 CLIN EXP NEPHROL JI Clin. Exp. Nephrol. PD JUN PY 2008 VL 12 IS 3 BP 171 EP 180 DI 10.1007/s10157-008-0050-9 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 343IM UT WOS:000258846800002 PM 18386116 ER PT J AU Bunnell, C Vahdat, L Schwartzberg, L Gralow, J Klimovsky, J Poulart, V Peck, R Thomas, E AF Bunnell, Craig Vahdat, Linda Schwartzberg, Lee Gralow, Julie Klimovsky, Judith Poulart, Valerie Peck, Ronald Thomas, Eva TI Phase I/II study of ixabepilone plus capecitabine in anthracycline-pretreated/resistant and taxane-resistant metastatic breast cancer SO CLINICAL BREAST CANCER LA English DT Article DE epothilones; maximum tolerated dose; microtubule inhibitors ID EPOTHILONE-B ANALOG; II CLINICAL-TRIAL; ORAL CAPECITABINE; BMS-247550; PACLITAXEL; MULTICENTER; THERAPY; BEVACIZUMAB AB Purpose: The aim of this study was to determine the safety, maximum tolerated dose (MTD), recommended phase II dose, and efficacy of the epothilone B analogue ixabepilone plus capecitabine in anthracycline-pretreated/resistant and taxane-resistant metastatic breast cancer (MBC). Patients and Methods: A total of 106 patients were enrolled. The study consisted of a dose-escalation phase (phase I) and a tumor response rate evaluation phase (phase II). Seventy-four patients were treated in phase I with schedule A (ixabepilone 40 mg/m(2) intravenously on day 1 plus capecitabine 1650-2000 mg/m(2) on days 1-14 of a 21-day cycle) or schedule B (ixabepilone 8-10 mg/m(2) on days 1-3 plus capecitabine 1650 mg/m(2) on days 1-14 of a 21-day cycle). Results: No dose-limiting toxicities (DLTs) were observed in the 8/1650 mg/m(2) and 10/1650 mg/m(2) cohorts; 1 of 30 patients in the 40/1650 mg/m(2) cohort and 2 of 30 patients in the 40/2000 mg/m(2) cohort had a DLT consisting of grade 3 plantar-palmar erythrodysesthesia (PPE). The 40/2000 mg/m(2) dose was defined as the MTD for schedule A, and a total of 62 patients were treated for the phase II portion of the trial, which examined tumor response. The objective response rate was 30%, median time-to-response was 6 weeks, median duration of response was 6.9 months, and median progression-free survival was 3.8 months. Grade 3/4 treatment-related events in phase II included fatigue (34%), PPE (34%), myalgia (23%), nausea (16%), peripheral neuropathy (19%), and diarrhea/vomiting (10%). Grades 3/4 neutropenia (69%) and leukopenia (55%) were managed primarily by dose reduction/treatment interruption. Conclusion: Ixabepilone plus capecitabine demonstrated clinical activity and an acceptable safety profile in patients with anthracycline-pretreated/resistant and taxane-resistant MBC. Ixabepilone was recently approved in the United States for the treatment of resistant/refractory locally advanced or MBC. C1 [Bunnell, Craig] Dana Farber Canc Inst, Boston, MA 02115 USA. [Vahdat, Linda] Weill Cornell Breast Ctr, New York, NY USA. [Schwartzberg, Lee] W Canc Clin, Memphis, TN USA. [Gralow, Julie] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Klimovsky, Judith] Merck & Co Inc, Somerset, NJ USA. [Poulart, Valerie; Peck, Ronald] Bristol Myers Squibb Co, Res & Dev, Oakland, CA USA. [Thomas, Eva] Kaiser Permanente, Oakland, CA USA. RP Bunnell, C (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM craig_bunnell@dfci.harvard.edu OI Vahdat, Linda/0000-0002-3522-7382 NR 40 TC 41 Z9 41 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD JUN PY 2008 VL 8 IS 3 BP 234 EP 241 DI 10.3816/CBC.2008.n.026 PG 8 WC Oncology SC Oncology GA 315XZ UT WOS:000256914800004 PM 18650153 ER PT J AU Partridge, A Winer, JP Golshan, M Bellon, JR Blood, E Dees, EC Sampson, E Emmons, KM Winer, E AF Partridge, Ann Winer, Jeffrey P. Golshan, Mehra Bellon, Jennifer R. Blood, Emily Dees, E. Claire Sampson, Ebonie Emmons, Karen M. Winer, Eric TI Perceptions and management approaches of physicians who care for women with ductal carcinoma in situ SO CLINICAL BREAST CANCER LA English DT Article DE emotional distress; negative re-excision; noninvasive breast cancer; risk perception ID INVASIVE BREAST-CANCER; LYMPH-NODE BIOPSY; SURGICAL ADJUVANT BREAST; CONSERVING THERAPY; RADIATION-THERAPY; RISK PERCEPTION; TAMOXIFEN; DISEASE AB Purpose: Limited previous data suggest that heterogeneity exists in the treatment approaches for women with ductal carcinoma in situ (DCIS). We sought in a longitudinal cohort study of women with DCIS to assess the attitudes and management approaches toward DICIS among physicians who provide care to women. Materials and Methods: Eligible physicians were invited to participate In a 1-time mailed survey. A financial incentive and reminders were used to enhance the response rate. Physician perception of risks associated with DCIS for patients and management approaches were evaluated. Results: Two hundred and eight physicians were identified, and 151 (73%) completed the survey. Respondents had a median age of 49 years (range, 32-75 years), and most were surgeons or medical oncologists (66%). Eighty-eight percent reported seeing an average of >= 1 new patient with DCIS per month. In a multivariable model, physicians who cared for proportionately fewer patients with breast cancer were more likely to view DICIS as a riskier disease to a patient's overall health compared with physicians who cared for more women with breast cancer (odds ratio, 2.2; 95% CI, 1.1-4.6; P = .036). Physicians exhibited differences in management approaches when considering theoretical patients with DICIS and did not use consistent terms when speaking with patients with DCIS. Conclusion: Substantial variation exists among physicians regarding perceptions and management approaches for women with DCIS. In some settings, risks of physician-recommended therapy might outweigh benefits. Further evaluation of the effects of physician management approaches and attitudes about DCIS on patient outcomes is warranted. C1 [Partridge, Ann; Winer, Jeffrey P.; Golshan, Mehra; Bellon, Jennifer R.; Blood, Emily; Sampson, Ebonie; Emmons, Karen M.; Winer, Eric] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. [Dees, E. Claire] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Partridge, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, 44 Binney St, Boston, MA 02115 USA. EM ahpartridge@partners.org FU NCI NIH HHS [5 P50 CA89393-03] NR 30 TC 16 Z9 17 U1 1 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD JUN PY 2008 VL 8 IS 3 BP 275 EP 280 DI 10.3816/CBC.2008.n.032 PG 6 WC Oncology SC Oncology GA 315XZ UT WOS:000256914800010 PM 18650159 ER PT J AU Wapnir, IL Aebi, S Geyer, CE Zahrieh, D Gelber, RD Anderson, SJ Robidoux, A Bernhard, J Maibach, R Castiglione-Gertsch, M Coates, AS Piccart, MJ Clemons, MJ Costantino, JP Wolmark, N AF Wapnir, Irene L. Aebi, Stefan Geyer, Charles E. Zahrieh, David Gelber, Richard D. Anderson, Stewart J. Robidoux, Andre Bernhard, Juerg Maibach, Rudolf Castiglione-Gertsch, Monica Coates, Alan S. Piccart, Martine J. Clemons, Mark J. Costantino, Joseph P. Wolmark, Norman TI A randomized clinical trial of adjuvant chemotherapy for radically resected locoregional relapse of breast cancer: IBCSG 27-02, BIG 1-02, and NSABP B-37 SO CLINICAL BREAST CANCER LA English DT Article DE ipsilateral breast cancer; radiation therapy; recurrence ID LOCAL RECURRENCE; CONSERVATIVE SURGERY; RADIATION-THERAPY; TUMOR RECURRENCE; MULTIVARIATE-ANALYSIS; REGIONAL RECURRENCE; SALVAGE MASTECTOMY; SYSTEMIC THERAPY; RISK-FACTORS; PROGNOSIS AB In this phase III, multinational, randomized trial, the International Breast Cancer Study Group, Breast International Group, and the National Surgical Adjuvant Breast and Bowel Project will attempt to define the effectiveness of cytotoxic therapy for patients with locoregional recurrence of breast cancer. We will evaluate whether chemotherapy prolongs disease-free survival and, secondarily, whether its use improves overall survival and systemic disease-free survival. Quality of life measurements will be monitored during the first 12 months of the study. Women who have had a previous diagnosis of invasive breast cancer treated by mastectomy or breast-conserving surgery and who have undergone complete surgical excision of all macroscopic disease but who subsequently develop isolated local and/or regional ipsilateral invasive recurrence are eligible. Patients are randomized to observation/no adjuvant chemotherapy or to adjuvant chemotherapy; all suitable patients receive radiation, hormonal, and trastuzumab therapy. Radiation therapy is recommended for patients who have not received previous adjuvant radiation therapy but is required for those with microscopically positive margins. The radiation field must encompass the tumor bed plus a surrounding margin to a dose of >= 40 Gy. Radiation therapy will be administered before, during, or after chemotherapy. All women with estrogen receptor-positive and/or progesterone receptor-positive recurrence must receive hormonal therapy, with the agent and duration to be determined by the patient's investigator. Adjuvant trastuzumab therapy is permitted for those with HER2-positive tumors, provided that intent to treat is declared before randomization. Although multidrug regimens are preferred, the agents, doses, and use of supportive therapy are at the discretion of the investigator. C1 [Wapnir, Irene L.] Stanford Univ, Dept Surg, Sch Med, Stanford, CA 94305 USA. [Wapnir, Irene L.; Geyer, Charles E.; Anderson, Stewart J.; Robidoux, Andre; Clemons, Mark J.; Costantino, Joseph P.; Wolmark, Norman] Operat Off, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. [Wapnir, Irene L.; Geyer, Charles E.; Anderson, Stewart J.; Clemons, Mark J.; Costantino, Joseph P.; Wolmark, Norman] Ctr Biostat, Pittsburgh, PA USA. [Aebi, Stefan; Zahrieh, David; Gelber, Richard D.; Bernhard, Juerg; Maibach, Rudolf; Castiglione-Gertsch, Monica; Coates, Alan S.] Int Breast Canc Study Grp, Bern, Switzerland. [Aebi, Stefan] Univ Hosp Bern, Dept Med Oncol, CH-3010 Bern, Switzerland. [Geyer, Charles E.; Wolmark, Norman] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Zahrieh, David; Gelber, Richard D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Anderson, Stewart J.; Costantino, Joseph P.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15260 USA. [Robidoux, Andre] CHU Montreal, Quebec City, PQ, Canada. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. [Piccart, Martine J.] Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium. [Piccart, Martine J.] Breast Int Grp, Brussels, Belgium. [Clemons, Mark J.] Princess Margaret Hosp Med Oncol, Toronto, ON, Canada. RP Wapnir, IL (reprint author), Stanford Univ, Dept Surg, Sch Med, 300 Pasteur Dr,H3625, Stanford, CA 94305 USA. EM wapnir@stanford.edu RI Aebi, Stefan/F-2004-2010; OI Aebi, Stefan/0000-0002-3383-9449; Anderson, Stewart/0000-0001-8948-0650 FU NCI NIH HHS [U10CA-69651, CA-75362, U10CA-12027, U10CA-37377, U10CA-69974, UG1 CA189867] NR 40 TC 15 Z9 15 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD JUN PY 2008 VL 8 IS 3 BP 287 EP 292 DI 10.3816/CBC.2008.n.035 PG 6 WC Oncology SC Oncology GA 315XZ UT WOS:000256914800013 PM 18650162 ER PT J AU Sharma, S Nemeth, E Chen, YH Goodnough, J Huston, A Roodman, GD Ganz, T Lichtenstein, A AF Sharma, Sanjai Nemeth, Elizabeta Chen, Yi-Hsiang Goodnough, Julia Huston, Alissa Roodman, G. D. Ganz, Tomas Lichtenstein, Alan TI Involvement of hepcidin in the anemia of multiple myeloma SO CLINICAL CANCER RESEARCH LA English DT Article ID ERYTHROID COLONY FORMATION; MONOCLONAL GAMMOPATHY; CHRONIC DISEASE; IRON; EXPRESSION; CELLS; ERYTHROPOIETIN; INFLAMMATION; IL-6; IDENTIFICATION AB Purpose: Hepcidin is a liver-produced peptide implicated in the anemia of inflammation. Because interleukin (IL)-6 is a potent inducer of hepcidin expression and its levels are elevated in multiple myeloma, we studied the role of hepcidin in the anemia of multiple myeloma. Experimental Design: Urinary hepcidin and serum levels of IL-6, ferritin, C-reactive protein, tumor necrosis factor-alpha, and IL-1 beta were studied in newly diagnosed myeloma patients. In vitro hepcidin induction assay was assessed by real-time PCR assay. Results: Pretreatment urinary hepcidin levels in 44 patients with stage III multiple myeloma were 3-fold greater than normal controls. In the subset of multiple myeloma patients without renal insufficiency (n = 27), a marked inverse correlation was seen between hemoglobin at diagnosis and urinary hepcidin level (P = 0.014) strongly supporting a causal relationship between up-regulated hepcidin expression and anemia. The urinary hepcidin also significantly (P < 0.05) correlated with serum ferritin and C-reactive protein, whereas its correlation with serum IL-6 levels was of borderline significance (P = 0.06). Sera from 14 multiple myeloma patients, with known elevated urinary hepcidin, significantly induced hepcidin mRNA in the Hep3B cells, whereas normal sera had no effect. For 10 patients, the ability of anti-IL-6 and anti-IL-6 receptor antibodies to prevent the serum-induced hepcidin RNA was tested. In 6 of these patients, hepcidin induction was abrogated by the anti-IL-6 antibodies, but in the other 4 patients, the neutralizing antibodies had no effect. Conclusions: These results indicate hepcidin is up-regulated in multiple myeloma patients by both IL-6-dependent and IL-6-independent mechanisms and may play a role in the anemia of multiple myeloma. C1 [Sharma, Sanjai; Lichtenstein, Alan] Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. [Huston, Alissa; Roodman, G. D.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Huston, Alissa; Roodman, G. D.] Univ Pittsburgh, Pittsburgh VA Med Ctr, Pittsburgh, PA USA. [Chen, Yi-Hsiang] Univ Illinois, Chicago, IL USA. [Chen, Yi-Hsiang] Jesse Brown VA Med Ctr, Chicago, IL USA. [Nemeth, Elizabeta; Goodnough, Julia; Ganz, Tomas] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. RP Sharma, S (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,Blvd 304,Room E1-115, Los Angeles, CA 90073 USA. EM sasharma@mednet.ucia.edu FU NCI NIH HHS [R01CA111448, R01CA96920]; NIDDK NIH HHS [KO1 DK07538, R01 DK065029] NR 33 TC 52 Z9 61 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2008 VL 14 IS 11 BP 3262 EP 3267 DI 10.1158/1078-0432.CCR-07-4153 PG 6 WC Oncology SC Oncology GA 308RY UT WOS:000256408900005 PM 18519751 ER PT J AU Rodig, SJ Ouyang, J Juszczynski, P Currie, T Law, K Neuberg, DS Rabinovich, GA Shipp, MA Kutok, JL AF Rodig, Scott J. Ouyang, Jing Juszczynski, Przemyslaw Currie, Treeve Law, Kenneth Neuberg, Donna S. Rabinovich, Gabriel A. Shipp, Margaret A. Kutok, Jeffery L. TI AP1-dependent galectin-1 expression delineates classical Hodgkin and anaplastic large cell lymphomas from other lymphoid malignancies with shared molecular features SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-IMMUNE PRIVILEGE; REED-STERNBERG CELLS; NF-KAPPA-B; C-JUN; REGULATED EXPRESSION; ACTIVATION; KINASE; TRAF1 AB Purpose: Galectin-1 (Gal1) is an immunomodulatory glycan-binding protein regulated by an AP1-dependent enhancer in Hodgkin Reed-Sternberg cells. We recently found that Reed-Sternberg cell Gall promotes the immunosuppressive T-helper 2/T-regulatory cell - skewed microenvironment in classical Hodgkin lymphoma (cHL). We sought to investigate whether the coordinate expression of activated AP1 pathway components and Gall serves as a diagnostic signature of cHL. In addition, because there are common signaling and survival pathways in cHL and additional non - Hodgkin lymphomas, we also evaluated whether the AP1/Gal1 signature is shared by other molecularly or morphologically related lymphomas. Experimental Design: We evaluated 225 cases of primary cHL and non - Hodgkin lymphoma for evidence of a functional AP1/Gal1 signature by immunohistochemical techniques. Results: Gall is selectively expressed by malignant Reed-Sternberg cells in >90% of primary cHLs, and Gal1 expression is concordant with the activated AP1 component, c-Jun. In contrast, diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, and another Hodgkin-related entity, nodular lymphocyte-predominant Hodgkin lymphoma, do not express Gall. However, anaplastic large cell lymphoma (ALCL), consistently expresses both Gall and its transcriptional regulator, c-Jun. The presence of activated c-Jun, indicative of functional AP1 activity, was confirmed by phospho-c-Jun immunostaining in cHL and ALCL. Conclusions: These findings establish a functional AP1 signature that includes Gall expression in cHL and ALCL and suggests a common mechanism for tumor immunotolerance in these diseases. In addition, the combination of Gall and c-Jun serve as diagnostic biomarkers that delineate cHL and ALCL from other lymphomas with shared morphologic and/or molecular features. C1 [Rodig, Scott J.; Currie, Treeve; Law, Kenneth; Kutok, Jeffery L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ouyang, Jing; Juszczynski, Przemyslaw; Neuberg, Donna S.; Shipp, Margaret A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Rabinovich, Gabriel A.] Consejo Nacl Invest Cient & Tecn, Inst Biol & Expt Med IBYME, Immunopathol Lab, RA-1033 Buenos Aires, DF, Argentina. RP Kutok, JL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM Jkutok@partners.org NR 31 TC 36 Z9 37 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2008 VL 14 IS 11 BP 3338 EP 3344 DI 10.1158/1078-0432.CCR-07-4709 PG 7 WC Oncology SC Oncology GA 308RY UT WOS:000256408900015 PM 18519761 ER PT J AU Mosquera, JM Perner, S Genega, EM Sanda, M Hofer, MD Mertz, KD Paris, PL Simko, J Bismar, TA Ayala, G Shah, RB Loda, M Rubin, MA AF Mosquera, Juan-Miguel Perner, Sven Genega, Elizabeth M. Sanda, Martin Hofer, Matthias D. Mertz, Kirsten D. Paris, Pamela L. Simko, Jeff Bismar, Tarek A. Ayala, Gustavo Shah, Rajal B. Loda, Massimo Rubin, Mark A. TI Characterization of TMPRSS2-ERG fusion high-grade prostatic intraepithelial neoplasia and potential clinical implications SO CLINICAL CANCER RESEARCH LA English DT Article ID IN-SITU HYBRIDIZATION; SMALL ACINAR PROLIFERATION; GENE FUSION; NEEDLE-BIOPSY; CHROMOSOMAL-ANOMALIES; CANCER PROGRESSION; REPEAT BIOPSY; FOLLOW-UP; CARCINOMA; MEN AB Purpose: More than 1,300,000 prostate needle biopsies are done annually in the United States with up to 16% incidence of isolated high-grade prostatic intraepithelial neoplasia (HGPIN). HGPIN has low predictive value for identifying prostate cancer on subsequent needle biopsies in prostate-specific antigen-screened populations, In contemporary series, prostate cancer is detected in similar to 20% of repeat biopsies following a diagnosis of HGPIN. Further, discrete histologic subtypes of HGPIN with clinical implication in management have not been characterized. The TMPRSS2-ERG gene fusion that has recently been described in prostate cancer has also been shown to occur in a subset of HGPIN. This may have significant clinical implications given that TMPRSS2-ERG fusion prostate cancer is associated with a more aggressive clinical course. Experimental Design: In this study, we assessed a series of HGPIN lesions and paired prostate cancer for the presence of TMPRSS2-ERG gene fusion. Results: Fusion-positive HGPIN was observed in 16% of the 143 number of lesions, and in all instances, the matching cancer shared the same fusion pattern. Sixty percent of TMPRSS2-ERG fusion prostate cancer had fusion-negative HGPIN. Conclusions: Given the more aggressive nature of TMPRSS2-ERG prostate cancer, the findings of this study raise the possibility that gene fusion-positive HGPIN lesions are harbingers of more aggressive disease. To date, pathologic, molecular, and clinical variables do not help stratify which men with HGPIN are at increased risk for a cancer diagnosis. Our results suggest that the detection of isolated TMPRSS2-ERG fusion HGPIN would improve the positive predictive value of finding TMPRSS2-ERG fusion prostate cancer in subsequent biopsies. C1 [Loda, Massimo; Rubin, Mark A.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Loda, Massimo; Rubin, Mark A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Shah, Rajal B.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Shah, Rajal B.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. [Ayala, Gustavo] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. [Ayala, Gustavo] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. [Bismar, Tarek A.] McGill Univ, Fac Med, Dept Pathol, Montreal, PQ, Canada. [Bismar, Tarek A.] McGill Univ, Fac Med, Dept Oncol, Montreal, PQ, Canada. [Paris, Pamela L.; Simko, Jeff] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Perner, Sven] Univ Ulm, Dept Pathol, Ulm, Germany. [Loda, Massimo; Rubin, Mark A.] Dana Farber Harvard Comprehens Canc Ctr, Boston, MA USA. [Genega, Elizabeth M.; Sanda, Martin] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Genega, Elizabeth M.; Sanda, Martin] Beth Israel Deaconess Med Ctr, Dept Urol, Boston, MA 02215 USA. [Mosquera, Juan-Miguel; Perner, Sven; Genega, Elizabeth M.; Hofer, Matthias D.; Mertz, Kirsten D.; Loda, Massimo; Rubin, Mark A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Mosquera, Juan-Miguel; Perner, Sven; Hofer, Matthias D.; Mertz, Kirsten D.; Loda, Massimo; Rubin, Mark A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Rubin, MA (reprint author), Weill Cornell Med Coll, Dept Pathol, C-410A,1300 York Ave, New York, NY 10065 USA. EM rubinma@med.cornell.edu RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015; OI Rubin, Mark/0000-0002-8321-9950 FU NCI NIH HHS [P50 CA090381, P50 CA089520, P50CA89520, U01 CA113913, UO1 CA113913]; NIA NIH HHS [R01 AG021404, R01AG21404] NR 48 TC 123 Z9 127 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2008 VL 14 IS 11 BP 3380 EP 3385 DI 10.1158/1078-0432.CCR-07-5194 PG 6 WC Oncology SC Oncology GA 308RY UT WOS:000256408900021 PM 18519767 ER PT J AU Kelley-Hedgepeth, A Lloyd-Jones, DM Colvin, A Matthews, KA Johnston, J Sowers, MR Sternfeld, B Pasternak, RC Chae, CU AF Kelley-Hedgepeth, Alyson Lloyd-Jones, Donald M. Colvin, Alicia Matthews, Karen A. Johnston, Janet Sowers, MaryFran R. Sternfeld, Barbara Pasternak, Richard C. Chae, Claudia U. CA SWAN Investigators TI Ethnic differences in C-reactive protein concentrations SO CLINICAL CHEMISTRY LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; AMERICAN-HEART-ASSOCIATION; METABOLIC SYNDROME; CARDIOVASCULAR EVENTS; INSULIN-RESISTANCE; DISEASE-CONTROL; WOMENS HEALTH; RISK-FACTOR; CRP LEVELS; POPULATION AB BACKGROUND: Limited data exist regarding the ethnic differences in C-reactive protein (CRP) concentrations, an inflammatory marker associated with risk of cardiovascular disease (CVD). We hypothesized that known CVD risk factors, including anthropometric characteristics, would explain much of the observed ethnic variation in CRP. METHODS: We performed a cross-sectional analysis of 3154 women, without known CVD and not receiving hormone therapy, enrolled in the Study of Women's Health Across the Nation (SWAN), a multiethnic prospective study of pre- and perimenopausal women. RESULTS: The study population was 47.4% white, 27.7% African-American, 8.5% Hispanic, 7.7% Chinese, and 8.6% Japanese; mean age was 46.2 years. African-American women had the highest median CRP concentrations (3.2 mg/L), followed by Hispanic (2.3 mg/L), white (1.5 mg/L), Chinese (0.7 mg/L), and Japanese (0.5 mg/L) women (all pairwise P < 0.001 compared with white women). Body mass index (BMI) markedly attenuated the association between ethnicity and CRP. After adjusting for age, socioeconomic status, BMI, and other risk factors, African-American ethnicity was associated with CRP concentrations > 3 mg/L (odds ratio 1.37, 95% CI 1.07-1.75), whereas Chinese and Japanese ethnicities were inversely related (0.58, 0.35-0.95, and 0.43, 0.260.72, respectively). CONCLUSIONS: Modifiable risk factors, particularly BMI, account for much but not all of the ethnic differences in CRP concentrations. Further study is needed of these ethnic differences and their implications for the use of CRP in CVD risk prediction. (c) 2008 American Association for Clinical Chemistry. C1 [Chae, Claudia U.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kelley-Hedgepeth, Alyson] Tufts Univ, Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. [Lloyd-Jones, Donald M.] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. [Lloyd-Jones, Donald M.] Northwestern Univ, Div Cardiol, Chicago, IL 60611 USA. [Colvin, Alicia] Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA USA. [Matthews, Karen A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Johnston, Janet] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Sowers, MaryFran R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Sternfeld, Barbara] Kaiser Permanente Med Care Program, Div Res, Dept Epidemiol & Biostat, Oakland, CA 94611 USA. [Pasternak, Richard C.] Merck & Co Inc, Rahway, NJ 07065 USA. RP Chae, CU (reprint author), Massachusetts Gen Hosp, Div Cardiol, YAW 5800,55 Fruit St, Boston, MA 02114 USA. EM cchae@partners.org RI Lloyd-Jones, Donald/C-5899-2009 FU NIA NIH HHS [AG012495, AG012505, AG012531, AG012535, AG012539, AG012546, AG012553, AG012554, U01 AG012553]; NINR NIH HHS [5U01NR004061, NR004061] NR 35 TC 100 Z9 102 U1 0 U2 2 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 JUN PY 2008 VL 54 IS 6 BP 1027 EP 1037 DI 10.1373/clinchem.2007.098996 PG 11 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 307NO UT WOS:000256325800014 PM 18403563 ER PT J AU Collinson, PO Hildebrand, P Gaze, DC Senior, R Januzzi, J Doughty, R Richards, A AF Collinson, P. O. Hildebrand, P. Gaze, D. C. Senior, R. Januzzi, J. Doughty, R. Richards, A. TI The second international COllaborative study of N-terminal pro B type natriuretic peptide NTproBNP in primary care (ICON II-PC) SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 27-31, 2008 CL Washington, DC SP Amer Assoc Clin Chem C1 [Collinson, P. O.; Gaze, D. C.] Univ London St Georges Hosp, London, England. [Senior, R.] Northwick Pk Hosp & Clin Res Ctr, London, England. Univ Auckland, Boston, MA USA. [Collinson, P. O.; Gaze, D. C.] St George Hosp, London, England. [Hildebrand, P.] Univ Copenhagen Hosp, DK-2100 Copenhagen, Denmark. [Senior, R.] Northwick Pk Hosp & Clin Res Ctr, London, England. [Januzzi, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Doughty, R.] Univ Auckland, Auckland 1, New Zealand. [Richards, A.] Univ Otago, Otago, New Zealand. NR 0 TC 0 Z9 0 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 JUN PY 2008 VL 54 IS 6 SU S MA B146 BP A95 EP A96 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 307NN UT WOS:000256325700293 ER PT J AU Edwards, M Haverstick, DM Sluss, PM Young, J Schmidt, E Kettlety, T AF Edwards, M. Haverstick, D. M. Sluss, P. M. Young, J. Schmidt, E. Kettlety, T. TI Analytical evaluation of the new Abbott ARCHITECT Cyclosporine assay SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 27-31, 2008 CL Washington, DC SP Amer Assoc Clin Chem C1 [Edwards, M.; Haverstick, D. M.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Sluss, P. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Young, J.; Schmidt, E.; Kettlety, T.] Fujirebio Diagnost Inc, Malvern, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2008 VL 54 IS 6 SU S MA A55 BP A19 EP A19 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 307NN UT WOS:000256325700056 ER PT J AU Gamache, P Ullucci, PA Lensmeyer, G Flood, J AF Gamache, P. Ullucci, P. A. Lensmeyer, G. Flood, J. TI Validated assay for 25-hydroxyvitamin D using HPLC with coulometric detection SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 27-31, 2008 CL Washington, DC SP Amer Assoc Clin Chem C1 [Gamache, P.; Ullucci, P. A.] ESA Biosci Inc, Chelmsford, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lensmeyer, G.] Univ Wisconsin Hosp, Madison, WI USA. [Flood, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2008 VL 54 IS 6 SU S MA C133 BP A141 EP A142 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 307NN UT WOS:000256325700436 ER PT J AU Keevil, BG Owen, LJ Blincko, S Ramsay, CS Sluss, PM Van Uytfanghe, K Thienpont, LM AF Keevil, B. G. Owen, L. J. Blincko, S. Ramsay, C. S. Sluss, P. M. Van Uytfanghe, K. Thienpont, L. M. TI Comparison of a routine LC-MS/MS assay for testosterone against an isotope dilution GCMS reference method SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 27-31, 2008 CL Washington, DC SP Amer Assoc Clin Chem C1 [Keevil, B. G.; Owen, L. J.] Univ S Manchester Hosp, Manchester M20 8LR, Lancs, England. [Ramsay, C. S.] Abbott Diagnost, Abbott Pk, IL USA. [Sluss, P. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Van Uytfanghe, K.; Thienpont, L. M.] Univ Ghent, B-9000 Ghent, Belgium. NR 0 TC 0 Z9 0 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 JUN PY 2008 VL 54 IS 6 SU S MA C11 BP A104 EP A104 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 307NN UT WOS:000256325700317 ER PT J AU Khoury, R Gandhi, A Salmon, BP Ryzhkova, I Gudaitis, P Gudaitis, D Sluss, P Gudaitis, AV AF Khoury, R. Gandhi, A. Salmon, B. P. Ryzhkova, I. Gudaitis, P. Gudaitis, D. Sluss, P. Gudaitis, A. V. TI Incidence of UTI and associated organisms in an elderly population SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 27-31, 2008 CL Washington, DC SP Amer Assoc Clin Chem C1 [Khoury, R.; Gandhi, A.; Salmon, B. P.; Ryzhkova, I.; Gudaitis, P.; Gudaitis, D.; Gudaitis, A. V.] Aculabs Inc, E Brunswick, NJ USA. [Sluss, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 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 JUN PY 2008 VL 54 IS 6 SU S MA A144 BP A46 EP A46 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 307NN UT WOS:000256325700143 ER PT J AU Maltzman, J Blackwell, K Stein, S Martin, A Westland, R Burstein, H Gomez, H Gartner, N Platek, G Newmiller, M Lipton, A Carney, WP AF Maltzman, J. Blackwell, K. Stein, S. Martin, A. Westland, R. Burstein, H. Gomez, H. Gartner, N. Platek, G. Newmiller, M. Lipton, A. Carney, W. P. TI Serum HER-2/neu levels in clinical studies with lapatinib in HER-2/neu positive breast cancer SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 27-31, 2008 CL Washington, DC SP Amer Assoc Clin Chem C1 [Maltzman, J.; Stein, S.; Martin, A.; Westland, R.] GlaxoSmithKline Inc, Collegeville, PA USA. [Blackwell, K.; Gartner, N.; Platek, G.; Newmiller, M.] Duke Univ, Med Ctr, Durham, NC USA. [Burstein, H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gomez, H.] Inst Nacl Enfermedades Neoplas, Lima, Peru. [Lipton, A.] Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. [Carney, W. P.] Siemens Healthcare Diagnost, Oncogene Sci Grp, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2008 VL 54 IS 6 SU S MA C95 BP A130 EP A130 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 307NN UT WOS:000256325700400 ER PT J AU Mosley, S Pomerantz, M Oh, W Glick, J AF Mosley, S. Pomerantz, M. Oh, W. Glick, J. TI Validation of different extraction solvents for estrogen metabolites of premarin drug therapy for AIPC patients using HPLC with electrochemical detection SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 27-31, 2008 CL Washington, DC SP Amer Assoc Clin Chem C1 [Mosley, S.; Glick, J.] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Pomerantz, M.; Oh, W.] Brigham & Womens Hosp, Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 0 Z9 0 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 JUN PY 2008 VL 54 IS 6 SU S MA E104 BP A226 EP A227 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 307NN UT WOS:000256325700697 ER PT J AU Brown, JA Boussiotis, VA AF Brown, Julia A. Boussiotis, Vassiliki A. TI Umbilical cord blood transplantation: Basic biology and clinical challenges to immune reconstitution SO CLINICAL IMMUNOLOGY LA English DT Review DE cord blood transplantation; tolerance; immune reconstitution; post-transplant infections ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; T-LYMPHOCYTE CLONES; UNRELATED DONORS; INFECTIOUS COMPLICATIONS; ACUTE-LEUKEMIA; NOD/SCID MICE; CD34(+) CELLS; ADULT RECIPIENTS AB Allogeneic stem cell transplantation has continued to evolve as a common procedure for the treatment of hematological. malignancies and bone marrow failure. Donor bone marrow and mobilized peripheral stem cells are routinely employed for the reconstitution of immune function in leukemia and lymphoma patients following radiation and/or chemotherapy. Unfortunately, only 30% of patients have an HLA-identical sibling donor and the identification of matched unrelated donors, particularly for minorities, can present an exceptional challenge. The transplantation of umbilical cord blood (UCB) represents the most recent strategy to expand the potential donor pool while maintaining an acceptable level of treatment-related complications. First utilized in children, UCB transplantation permits a higher degree of HLA disparity while demonstrating a reduction in the incidence and severity of graft-versus-host disease (GvHD) compared to previous transplantation modalities. Despite the apparent decrease in GvHD, relapse rates remain comparable to transplantation with bone marrow or mobilized peripheral blood suggesting a strong graft-versus-leukemia/lymphoma (GvL) effect. However, several issues complicate the use of UCB transplantation and its extension to the treatment of adults. Many infections that afflict transplant patients are particularly frequent and more severe in the context of UCB transplantation. UCB T-cells are naive and therefore display less proliferation and IFN-gamma production in response to cognate antigen and also appear to demonstrate defects in signal transduction mechanisms. In addition, UCB contains T regulatory cells (Treg) with more potent suppressor function than adult Treg. Furthermore, adult patients often require more total cells and CD34+ progenitors for transplantation than a single UCB unit can provide. Thus, strategies to expand selected subpopulations from UCB and the use of multi-unit transplantation are areas of active research. This review will provide a condensed summary of the clinical history of UCB transplantation and emphasize the advantages and disadvantages of this approach to hematological malignancies in comparison to other methods of hematopoietic stem cell transplantation. Subsequently, it will mainly focus on the current challenges to immune reconstitution presented by UCB transplantation, recent research into their cellular and molecular mechanisms, and experimental approaches to overcome them. (c) 2008 Elsevier Inc. All rights reserved. C1 [Brown, Julia A.; Boussiotis, Vassiliki A.] Harvard Univ, Sch Med, Dept Surg Oncol, Massachusetts Gen Hosp,Canc Ctr, Boston, MA 02114 USA. [Boussiotis, Vassiliki A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol & Oncol,Dept Med, Boston, MA 02114 USA. RP Boussiotis, VA (reprint author), Harvard Univ, Sch Med, Dept Surg Oncol, Massachusetts Gen Hosp,Canc Ctr, 55 Fruit St,GRJ 904, Boston, MA 02114 USA. EM vboussiotis@partners.org FU NCI NIH HHS [CA104596, R01 CA104596, R01 CA104596-03]; NIAID NIH HHS [R21 AI043552-06, R01 AI043552, R01 AI043552-08, R21 AI043552, R56 AI043552]; PHS HHS [AL 43552] NR 78 TC 96 Z9 101 U1 3 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUN PY 2008 VL 127 IS 3 BP 286 EP 297 DI 10.1016/j.clim.2008.02.008 PG 12 WC Immunology SC Immunology GA 308FL UT WOS:000256373600005 PM 18395491 ER PT J AU Kambugu, A Meya, DB Rhein, J O'Brien, M Janoff, EN Ronald, AR Kamya, MR Mayanja-Kizza, H Sande, MA Bohjanen, PR Boulware, DR AF Kambugu, Andrew Meya, David B. Rhein, Joshua O'Brien, Meagan Janoff, Edward N. Ronald, Allan R. Kamya, Moses R. Mayanja-Kizza, Harriet Sande, Merle A. Bohjanen, Paul R. Boulware, David R. TI Outcomes of cryptococcal meningitis in Uganda before and after the availability of highly active antiretroviral therapy SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID HIV-INFECTED PATIENTS; RECONSTITUTION INFLAMMATORY SYNDROME; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; EARLY MORTALITY; AMPHOTERICIN-B; AIDS; DISEASE; FLUCONAZOLE; IMPACT; DETERMINANTS AB Background. Cryptococcal meningitis (CM) is the proximate cause of death in 20%-30% of persons with acquired immunodeficiency syndrome in Africa. Methods. Two prospective, observational cohorts enrolled human immunodeficiency virus (HIV)-infected, antiretroviral-naive persons with CM in Kampala, Uganda. The first cohort was enrolled in 2001-2002 (n = 92), prior to the availability of highly active antiretroviral therapy (HAART), and the second was enrolled in 2006 2007 (n = 44), when HAART was available. Results. Ugandans presented with prolonged CM symptoms (median duration, 14 days; interquartile range, 7-21 days). The 14-day survival rates were 49% in 2001-2002 and 80% in 2006 (P < .001). HAART was started 35 +/- 13 days after CM diagnosis and does not explain the improved 14-day survival rate in 2006. In 2006-2007, the survival rate continued to decrease after hospitalization, with only 55% surviving to initiate HAART as an outpatient. Probable cryptococcal-related immune reconstitution inflammatory syndrome occurred in 42% of patients, with 4 deaths. At 6 months after CM diagnosis, 18 persons (41%) were alive and receiving HAART in 2007. The median cerebral spinal fluid (CSF) opening pressure was 330 mm H2O; 81% of patients had elevated pressure (1200 mm H2O). Only 5 patients consented to therapeutic lumbar puncture. There was a trend for higher mortality for pressures 1250 mm H2O (odds ratio [OR], 2.1; 95% confidence interval [CI], 0.9-5.2; P = .09). Initial CSF WBC counts of <5 cells/mL were associated with failure of CSF sterilization (OR, 17.3; 95% CI, 3.1-94.3; P < .001), and protein levels <35 mg/dL were associated with higher mortality (OR, 2.0; 95% CI, 1.2-3.3; P = .007). Conclusions. Significant CM-associated mortality persists, despite the administration of amphotericin B and HIV therapy, because of the high mortality rate before receipt of HAART and because of immune reconstitution inflammatory syndrome-related complications after HAART initiation. Approaches to increase acceptance of therapeutic lumbar punctures are needed. C1 [Kamya, Moses R.; Mayanja-Kizza, Harriet] Makerere Univ, Sch Med, Dept Med, Kampala, Uganda. [Kambugu, Andrew; Meya, David B.; Ronald, Allan R.; Kamya, Moses R.; Mayanja-Kizza, Harriet; Sande, Merle A.] Makerere Univ, Infect Dis Inst, Kampala, Uganda. [Rhein, Joshua; Bohjanen, Paul R.; Boulware, David R.] Univ Minnesota, Dept Med, Div Infect Dis & Int Med, Minneapolis, MN 55455 USA. [Bohjanen, Paul R.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA. [Bohjanen, Paul R.; Boulware, David R.] Univ Minnesota, Ctr Infect Dis & Microbiol Translat Res, Minneapolis, MN 55455 USA. [O'Brien, Meagan] NYU, Sch Med, Div Infect Dis, Dept Med, New York, NY USA. [Janoff, Edward N.] Univ Colorado, Sch Med,Div Infect Dis, Denver Vet Affairs Med Ctr,Colorado Ctr AIDS Res, Mucosal & Vaccine Res Program Colorado MAVRC, Denver, CO USA. [Ronald, Allan R.] Univ Manitoba, Winnipeg, MB, Canada. RP Boulware, DR (reprint author), MMC 250,420 Delaware St SE, 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; Mayanja-Kizza, Harriet/0000-0002-9297-6208; Ronald, Allan/0000-0002-5746-3490; Boulware, David/0000-0002-4715-0060 FU FIC NIH HHS [D43 TW000011, TW000011]; NCRR NIH HHS [K12 RR023247, K12 RR023247-01, K12RR023247]; NIAID NIH HHS [L30 AI066779, L30 AI066779-02, L30AI066779, P30 AI054907, P30AI054907, T32 AI055433, T32AI055433] NR 31 TC 134 Z9 140 U1 1 U2 5 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 JUN 1 PY 2008 VL 46 IS 11 BP 1694 EP 1701 DI 10.1086/587667 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 297HC UT WOS:000255606700008 PM 18433339 ER PT J AU Murphy, RA AF Murphy, Richard A. TI The emerging crisis of drug-resistant tuberculosis in South Africa: Lessons from New York City SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID MYCOBACTERIUM-TUBERCULOSIS; HIV-INFECTION; OUTBREAK; THERAPY AB Multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis have emerged as important infections in South Africa among patients infected with human immunodeficiency virus (HIV). In the face of this new epidemic, South Africa must rededicate itself to the task of tuberculosis control and treatment with a rapid, multifaceted approach. Priorities include expansion of second-line treatment capacity, investment in clinical laboratories, a system to ensure supervised treatment for all patients, and enhancement of infection control procedures. In New York City, where drug-resistant tuberculosis emerged 2 decades ago-also in the context of a large HIV-infected population and an underfunded public health infrastructure similar steps were successful in leading to the rapid decrease in rates of drug resistance among tuberculosis isolates. With refinements based on local resource constraints, urgent measures could potentially arrest the alarming increase in multidrug-resistant and extensively drug-resistant tuberculosis cases in South Africa. Unlike many countries in sub-Saharan Africa, South Africa has the capacity to mount a rapid and large-scale response before drug-resistant tuberculosis envelops a much larger and far poorer region. C1 [Murphy, Richard A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Murphy, Richard A.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Murphy, RA (reprint author), Med Sans Frontieres, 333 7th Ave,2nd FL, New York, NY 10001 USA. EM richard.murphy@newyork.msf.org NR 15 TC 4 Z9 4 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2008 VL 46 IS 11 BP 1729 EP 1732 DI 10.1086/587903 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 297HC UT WOS:000255606700013 PM 18426372 ER PT J AU Bertolotti, P Bilotti, E Colson, K Curran, K Doss, D Faiman, B Gavino, M Jenkins, B Lilleby, K Love, G Mangan, PA McCullagh, E Miceli, T Miller, K Rogers, K Rome, S Sandifer, S Smith, LC Tariman, JD Westphal, J AF Bertolotti, Page Bilotti, Elizabeth Colson, Kathleen Curran, Kathleen Doss, Deborah Faiman, Beth Gavino, Maria Jenkins, Bonnie Lilleby, Kathy Love, Ginger Mangan, Patricia A. McCullagh, Emily Miceli, Teresa Miller, Kena Rogers, Kathryn Rome, Sandra Sandifer, Stacey Smith, Lisa C. Tariman, Joseph D. Westphal, Jeanne TI Management of side effects of novel therapies for multiple myeloma: Consensus statements developed by the International Myeloma Foundation's Nurse Leadership Board SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID DEXAMETHASONE; CARE AB Nurses play an essential role in managing the care of patients with multiple myeloma, who require education and support to receive and adhere to optimal therapy. The International Myeloma Foundation created a Nurse Leadership Board comprised of oncology nurses from leading cancer centers and community practices. An assessment survey identified the need for specific recommendations for managing key side effects of novel antimyeloma agents. Myelosuppression, thromboembolic events, peripheral neuropathy, steroid toxicities, and gastrointestinal side effects were selected for the first consensus statements. The board developed recommendations for healthcare providers in any medical setting, including grading of side-effect toxicity and strategies for managing the side effects in general, with specific recommendations pertaining to the novel agents. C1 [Bertolotti, Page] Samuel Oschin Comprehens Canc Inst, Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA USA. [Bilotti, Elizabeth] St Vincents Comprehens Canc Ctr, New York, NY USA. [Colson, Kathleen; Doss, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. [Curran, Kathleen] Univ Pittsburgh, Med Ctr, Shadyside Hosp, Pittsburgh, PA USA. [Faiman, Beth] Cleveland Clin, Taussing Canc Inst, Multiple Myeloma Program, Cleveland, OH 44106 USA. [Gavino, Maria] Univ Texas MD Anderson Canc Ctr, Dept Myeloma Lymphoma, Houston, TX 77030 USA. [Jenkins, Bonnie] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Lilleby, Kathy] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Love, Ginger] Univ Cincinnati Hem Onc Care, Cincinnati, OH USA. [Mangan, Patricia A.] Univ Penn, Abramson Canc Ctr, Bone Marrow & Stem Cell Transplant Program, Philadelphia, PA 19104 USA. [McCullagh, Emily] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Miceli, Teresa] Mayo Clin, Rochester, MN USA. [Miller, Kena] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Rogers, Kathryn] Johns Hopkins Univ, Baltimore, MD USA. [Rome, Sandra] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Smith, Lisa C.] Canc Ctr Carolinas, Greenville, SC USA. [Tariman, Joseph D.] Univ Washington, Seattle, WA 98195 USA. [Westphal, Jeanne] Meeker Cty Mem Hosp, Litchfield, MN USA. RP Bertolotti, P (reprint author), Samuel Oschin Comprehens Canc Inst, Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA USA. EM page.bertolotti@cshs.org FU NINR NIH HHS [F31 NR011124, T32 NR007106] NR 19 TC 11 Z9 11 U1 0 U2 0 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 EI 1538-067X J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD JUN PY 2008 VL 12 IS 3 SU S BP 9 EP 12 DI 10.1188/08.CJON.S1.9-12 PG 4 WC Oncology; Nursing SC Oncology; Nursing GA 311RY UT WOS:000256618500002 PM 18490252 ER PT J AU Miceli, T Colson, K Gavino, M Lilleby, K AF Miceli, Teresa Colson, Kathleen Gavino, Maria Lilleby, Kathy CA IMF Nurse Leadership Board TI Myelosuppression associated with novel therapies in patients with multiple myeloma: Consensus statement of the IMF Nurse Leadership Board SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID BORTEZOMIB; DEXAMETHASONE; CANCER; CARE AB Novel therapies for multiple myeloma include the immunomodulatory drugs lenalidomide and thalidomide and the proteasome inhibitor bortezomib, which have increased response rates and survival times. However, the agents can cause myelosuppression, which, if not managed effectively, can be life threatening and interfere with optimal therapy and quality of life. The International Myeloma Foundation's Nurse Leadership Board developed a consensus statement that includes toxicity grading, strategies for monitoring and managing myelosuppression associated with novel therapies, and educational recommendations for patients and their caregivers. Although anemia, neutropenia, and thrombocytopenia are expected side effects of novel therapies for multiple myeloma, they are manageable with appropriate interventions and education. C1 [Miceli, Teresa] Mayo Med Ctr, Rochester, MN USA. [Colson, Kathleen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gavino, Maria] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Lilleby, Kathy] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Miceli, T (reprint author), Mayo Med Ctr, Rochester, MN USA. EM miceli.teresa@mayo.edu NR 40 TC 7 Z9 7 U1 0 U2 1 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD JUN PY 2008 VL 12 IS 3 SU S BP 13 EP 19 DI 10.1188/08.CJON.S1.13-19 PG 7 WC Oncology; Nursing SC Oncology; Nursing GA 311RY UT WOS:000256618500003 PM 18490253 ER PT J AU Rome, S Doss, D Miller, K Westphal, J AF Rome, Sandra Doss, Deborah Miller, Kena Westphal, Jeanne CA IMF Nurse Leadership Borad TI Thromboembolic events associated with novel therapies in patients with multiple myeloma: Consensus statement of the IMF Nurse Leadership Board SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID DEEP-VEIN THROMBOSIS; VENOUS THROMBOEMBOLISM; RISK-FACTORS; PULMONARY-EMBOLISM; CANCER-PATIENTS; LENALIDOMIDE; THALIDOMIDE; DEXAMETHASONE; CARE; PREVENTION AB Patients with myeloma are at risk for serious and life-threatening thromboembolic events because of their disease, individual risk factors, and antimyeloma or other medications. The International Myeloma Foundation's Nurse Leadership Board developed this consensus statement for assessment and prevention of thromboembolic events. Prophylactic measures are categorized as mechanical, regimen related, and antithrombotic drug, based on individual and myeloma-related risk factors. Aspirin is suggested for patients with no or one risk factor, low-molecular-weight heparin or full-dose warfarin for patients with two or more risk factors, and low-molecular-weight heparin or full-dose warfarin for all patients with therapy-related risks, including high-dose dexamethasone, doxorubicin, or multiagent chemotherapy. C1 [Rome, Sandra] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Doss, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. [Miller, Kena] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Westphal, Jeanne] Meeker Cty Mem Hosp, Litchfield, MN USA. RP Rome, S (reprint author), Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. EM romes@cshs.org NR 50 TC 9 Z9 9 U1 0 U2 1 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 EI 1538-067X J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD JUN PY 2008 VL 12 IS 3 SU S BP 21 EP 27 DI 10.1188/08.CJON.S1.21-27 PG 7 WC Oncology; Nursing SC Oncology; Nursing GA 311RY UT WOS:000256618500004 PM 18490254 ER PT J AU Bossi, LM Jane, M DeCristofaro, S AF Bossi, Larraine M. Jane, Mary DeCristofaro, Susan TI Reiki as a clinical intervention in oncology nursing practice SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID THERAPEUTIC TOUCH; HEALING TOUCH; PAIN AB Oncology nurses and their patients are frequently on the cutting edge of new therapies and interventions that support coping, health, and healing. Reiki is a practice that is requested with increasing frequency, is easy to learn, does not require expensive equipment, and in preliminary research, elicits a relaxation response and helps patients to feel more peaceful and experience less pain. Those who Practice Reiki report that it supports them in self-care and a healthy lifestyle. This article will describe the process of Reiki, review current literature, present vignettes of patients responses to the intervention, and make recommendations for future study. C1 [Bossi, Larraine M.] Childrens Hosp Boston, Boston, MA USA. [Jane, Mary; DeCristofaro, Susan] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bossi, LM (reprint author), Childrens Hosp Boston, Boston, MA USA. EM larraine.bossi@childrens.harvard.edu NR 37 TC 11 Z9 12 U1 1 U2 11 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD JUN PY 2008 VL 12 IS 3 BP 489 EP 494 DI 10.1188/08.CJON.489-494 PG 6 WC Oncology; Nursing SC Oncology; Nursing GA 309XQ UT WOS:000256493900022 PM 18515247 ER PT J AU Cohen, AL Ridpath, A Noble-Wang, J Jensen, B Peterson, AM Arduino, M Jernigan, D Srinivasan, A AF Cohen, Adam L. Ridpath, Alison Noble-Wang, Judith Jensen, Bette Peterson, Alicia M. Arduino, Matt Jernigan, Dan Srinivasan, Arjun TI Outbreak of Serratia morcescens bloodstream and central nervous system infections after interventional pain management procedures SO CLINICAL JOURNAL OF PAIN LA English DT Article DE Serratia marcescens; bacteremia; central nervous system infections; pain clinic; low back pain; infection control ID MULTIPLE-DOSE VIALS; NOSOCOMIAL OUTBREAK; HEPATITIS-B; EXTRINSIC CONTAMINATION; PSEUDOMONAS-AERUGINOSA; TAP-WATER; MARCESCENS; TRANSMISSION; BACTEREMIA; HANDS AB Objectives: To determine the cause of an outbreak of Serratia marcescens infections in patients after interventional pain management procedures at an outpatient pain clinic. Methods: We conducted a case-control study and collected clinical and environmental samples. Results: We identified 5 culture-confirmed case-patients and 2 presumptive case-patients who had no bacteria recovered from cultures. The 7 case-patients were compared with 28 controls who underwent procedures at the same clinic but did not develop symptoms of infection. All confirmed case-patients had S. marcescens bloodstream infections; 2 had concurrent S. marcescens central nervous system infections. Case-patients were more likely than controls to have procedures that used contrast solution or entered the epidural or intervertebral disc space (P <= 0.01 for each). All S. marcescens clinical isolates were indistinguishable by pulsed-field gel electrophoresis. We did not isolate S. marcescens from medications or environmental samples; however, S. marcescens was shown to survive and grow in contrast solution that was experimentally contaminated for up to 30 days. Single-dose vials of medication, including contrast solution, were used for multiple procedures; multiple medications were accessed with a common needle and syringe. Discussion: The findings of this investigation suggest contamination of a common medication, likely contrast solution, as the source of the outbreak. Practices, such as reusing single-dose medication vials and using a common needle and syringe to access multiple medications, could have led to contamination and propagation of S. marcescens and should be avoided in interventional pain management procedures. C1 [Jernigan, Dan] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA 30333 USA. [Cohen, Adam L.] Ctr Dis Control & Prevent, Epidem Intelligence Serv, Off Workforce & Career Dev, Atlanta, GA 30333 USA. [Cohen, Adam L.; Ridpath, Alison; Noble-Wang, Judith; Jensen, Bette; Peterson, Alicia M.; Arduino, Matt; Jernigan, Dan; Srinivasan, Arjun] Ctr Dis Control & Prevent, Epidemiol & Lab Branch, Div Healthcare Qual Promot, Atlanta, GA 30333 USA. [Ridpath, Alison] Massachusetts Gen Hosp, Brigham & Womens Hosp, Emergency Med Residency Program, Boston, MA 02114 USA. RP Cohen, AL (reprint author), Ctr Dis Control & Prevent, Resp Dis Branch, Div Bacterial Dis, 1600 Clifton Rd NE,MS C-23, Atlanta, GA 30333 USA. EM ALCohen1@cdc.gov RI Arduino, Matthew/C-1461-2012 OI Arduino, Matthew/0000-0001-7072-538X NR 39 TC 20 Z9 20 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-8047 J9 CLIN J PAIN JI Clin. J. Pain PD JUN PY 2008 VL 24 IS 5 BP 374 EP 380 DI 10.1097/AJP.0b013e31816157db PG 7 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 305XA UT WOS:000256209900002 PM 18496300 ER PT J AU Sawamura, C Hornicek, FJ Gebhardt, MC AF Sawamura, Chigusa Hornicek, Francis J. Gebhardt, Mark C. TI Complications and risk factors for failure of rotationplasty: Review of 25 patients SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PEDIATRIC-ONCOLOGY-GROUP; PATHOLOGICAL FRACTURE; SURGICAL TECHNIQUE; LIMB-SALVAGE; OSTEOSARCOMA; KNEE; SURGERY; TUMOR; CHEMOTHERAPY; RESECTION AB Rotationplasty is one treatment option for femoral bone sarcomas in skeletally immature patients. This procedure enables patients to avoid phantom pain, limb length discrepancy, or loosening of an endoprosthesis, and good functional outcome has been reported. However, rotationplasty is only rarely indicated and the surgical complications or risk factors for failure of the procedure that might influence choices of treatment or patient counseling have not been well described. We reviewed 25 patients who underwent rotationplasty focusing on risk factors for failure and postoperative complications. Three of 25 patients had vascular compromise resulting in amputation. All three had vascular anastomosis and were resistant to chemotherapy with less than 95% of tumor necrosis. Two of the three patients who underwent amputation had a pathologic fracture before surgery. Late complications included one patient with a tibial fracture, two with wound complications treated with skin grafts, one with nonunion, and one with subsequent slipped capital femoral epiphysis. Rotationplasty was successfully accomplished in 22 of the 25 patients. Patients with large tumors unresponsive to chemotherapy or preoperative pathologic fracture appear at higher risk for failure of rotationplasty presumably as a result of compromise of venous drainage of the leg. Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. C1 [Gebhardt, Mark C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Sawamura, Chigusa; Gebhardt, Mark C.] Childrens Hosp, Boston, MA 02115 USA. [Sawamura, Chigusa; Hornicek, Francis J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gebhardt, MC (reprint author), Beth Israel Deaconess Med Ctr, Shapiro CC2-330 Brookline Ave, Boston, MA 02215 USA. EM mgebhardt@bidmc.harvard.edu NR 20 TC 18 Z9 18 U1 0 U2 2 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 JUN PY 2008 VL 466 IS 6 BP 1302 EP 1308 DI 10.1007/s11999-008-0231-6 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 300WI UT WOS:000255855600006 PM 18404295 ER PT J AU Tobia, CC Aspinall, SL Good, CB Fine, MJ Hanlon, JT AF Tobia, Colleen Cook Aspinall, Sherrie L. Good, Chester B. Fine, Michael J. Hanlon, Joseph T. TI Appropriateness of antibiotic prescribing in veterans with community-acquired pneumonia, sinusitis, or acute exacerbations of chronic bronchitis: A cross-sectional study SO CLINICAL THERAPEUTICS LA English DT Article DE antibiotic; Medication Appropriateness Index; respiratory tract infections ID OBSTRUCTIVE PULMONARY-DISEASE; ANTIMICROBIAL THERAPY; MANAGEMENT; ADULTS; RELIABILITY; PREVENTION; GUIDELINES; RESISTANCE; DIAGNOSIS; OUTCOMES AB Background: Studies that have assessed antibiotic appropriateness in acute respiratory tract infections (RTIs) with a likely bacterial etiology have focused only on antibiotic choice and ignored other important aspects of prescribing, such as dosing, drug-drug interactions, and duration of treatment. Objective: The aim of this study was to determine the prevalence and predictors of inappropriate antibiotic prescribing practices in outpatients with acute bacterial RTIs (community-acquired pneumonia [CAP], sinusitis, or acute exacerbations of chronic bronchitis [AECB]). Methods: This retrospective, cross-sectional study enrolled outpatients with CAP, sinusitis, or AECB who were evaluated in a Veterans Affairs emergency department over a 1-year period. Using electronic medical records, trained research assistants completed data-collection forms that included patient characteristics (eg, marital status, history of alcohol abuse), diagnosis, comorbidities, concurrent medications, and antibiotics prescribed. To assess antimicrobial appropriateness, a trained clinical pharmacist reviewed the data-collection forms and applied a Medication Appropriateness Index (MAI), which rated the appropriateness of a medication using 10 criteria: indication, effectiveness, dosage, directions, practicality (defined as capability of being used or being put into practice), drug-drug interactions, drug-disease interactions, unnecessary duplication, duration, and expensiveness (defined as the cost of the drug compared with other agents of similar efficacy and tolerability). Previous studies have found good inter- and intrarater reliabilities between a clinical pharmacist's and an internal medicine physician's MAI ratings (kappa = 0.83 and 0.92, respectively). Results: One hundred fifty-three patients were included (mean age, 58 years; 92% male; and 65% white). Overall, 99 of 153 patients (65%) had inappropriate antibiotic prescribing as assessed using the MAI. Expensiveness (60 patients [39%]), impracticality (32 [21%]), and incorrect dosage (15 [10%]) were the most frequently rated problem. Penicillins, quinolones, and macrolides were the most common antibiotic classes prescribed inappropriately. A history of alcohol abuse was associated with a lower likelihood of inappropriate prescribing compared with no history of alcohol abuse (adjusted odds ratio [AOR], 0.32; 95% CI, 0.10-0.98), while patients who were married were more likely to receive inappropriately prescribed antibiotics than those who were not married (AOR, 2.64; 95% CI, 1.25-5.59). Conclusions: Inappropriate antibiotic prescribing based on the MAI criteria was common (65%) in this selected patient population with acute bacterial RTIs, and often involved problems with expensiveness (39%), impracticality (21%), and incorrect dosage (10%). Future interventions to improve antibiotic prescribing should consider aspects beyond choice of agent. C1 [Tobia, Colleen Cook] Vet Affairs Pittsburgh Healthcare Syst, Dept Pharm, Pittsburgh, PA USA. [Aspinall, Sherrie L.; Good, Chester B.; Fine, Michael J.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Aspinall, Sherrie L.; Good, Chester B.; Fine, Michael J.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. [Aspinall, Sherrie L.; Good, Chester B.; Fine, Michael J.] Hines Vet Affairs Med Ctr, Vet Affairs Ctr Medicat Safety, Hines, IL USA. [Good, Chester B.; Fine, Michael J.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Tobia, CC (reprint author), VA Pittsburgh Healthcare Syst, Dept Pharm, Pittsburgh, PA 15240 USA. EM colleen.tobla@va.gov FU NIA NIH HHS [P30 AG024827, R01 AG027017, R01AG027017, P30AG024827] NR 31 TC 7 Z9 7 U1 0 U2 1 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 JUN PY 2008 VL 30 IS 6 BP 1135 EP 1144 DI 10.1016/j.clinthera.2008.06.009 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 326ZS UT WOS:000257698900007 PM 18640469 ER PT J AU Owens, RL Stigler, WS Hess, DR AF Owens, Robert L. Stigler, William S. Hess, Dean R. TI Do newer monitors of exhaled gases, mechanics, and esophageal pressure add value? SO CLINICS IN CHEST MEDICINE LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; ACUTE LUNG INJURY; TIDAL VOLUME VENTILATION; BREATH CONDENSATE COLLECTION; CHEST-WALL MECHANICS; HYDROGEN-PEROXIDE; AIRWAY PRESSURE; EXPIRED BREATH; TRANSPULMONARY PRESSURES AB The current understanding of lung mechanics and ventilator-induced lung injury suggests that patients who have acute respiratory distress syndrome should be ventilated in such a way as to minimize alveolar over-distension and repeated alveolar collapse. Clinical trials have used such lung protective strategies and shown a reduction in mortality; however, there is data that these "one-size fits all" strategies do not work equally well in all patients. This article reviews other methods that may prove useful in monitoring for potential lung injury: exhaled breath condensate, pressure-volume curves, and esophageal manometry. The authors explore the concepts, benefits, difficulties, and relevant clinical trials of each. C1 [Owens, Robert L.; Hess, Dean R.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Owens, Robert L.; Stigler, William S.; Hess, Dean R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Stigler, William S.] Massachusetts Gen Hosp, Wang Ambulatory Care Ctr 645, Boston, MA 02114 USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Cox 2,Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 87 TC 5 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD JUN PY 2008 VL 29 IS 2 BP 297 EP + DI 10.1016/j.ccm.2008.02.001 PG 18 WC Respiratory System SC Respiratory System GA 304TM UT WOS:000256132000009 PM 18440438 ER PT J AU Wang, XY Rosell, A Lo, EH AF Wang, Xiaoying Rosell, Anna Lo, Eng H. TI Targeting Extracellular Matrix Proteolysis for Hemorrhagic Complications of tPA Stroke Therapy SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Review DE tPA; extracellular protease; matrix metalloproteinases; extracellular proteolysis; blood-brain barrier; intracerebral hemorrhage; combination therapy ID TISSUE-PLASMINOGEN ACTIVATOR; FOCAL CEREBRAL-ISCHEMIA; BLOOD-BRAIN-BARRIER; NEURONAL CELL-DEATH; SPIN TRAP AGENT; GENE KNOCK-OUT; EMBOLIC STROKE; RAT MODEL; PROTEIN-C; INTRACEREBRAL HEMORRHAGE AB To date, tPA-based thrombolytic therapy is the only FDA-approved treatment for achieving vascular reperfusion and clinical benefit, but this agent is given to only about 2-5% of stroke patients in the United States of America. This may be related, in part, to the elevated risks of symptomatic intracranial hemorrhage, and the consequently reduced therapeutic time window. Recent efforts have aimed at identifying new combination strategies that might increase thrombolytic efficacy of tPA to benefit reperfusion, while reducing its associated neurotoxicity and hemorrhagic complications. Emerging experimental studies demonstrate that the breakdown of neurovascular matrix initiates blood-brain barrier disruption with edema and/or hemorrhage. Perturbation of extracellular homeostasis triggered by dysregulated extracellular proteases may underlie processes responsible for the hemorrhagic complications of thrombolytic stroke therapy. This short review summarizes experimental investigations of this field in pre-clinical stroke models. The data strongly suggest that targeting the extracellular matrix proteolytic imbalance within the neurovascular unit may provide new approaches for improving the safety and efficacy of thrombolytic reperfusion therapy of stroke. C1 [Wang, Xiaoying] Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA 02129 USA. RP Wang, XY (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, 149 13th St,Room 2411A, Charlestown, MA 02129 USA. EM wangxi@helix.mgh.harvard.edu FU American Heart Association [0435087N]; National Institute of Health [R01-NS049476, R01-NS37074, R01NS48422, R01-NS53560, P50-NS10828] FX This work was supported in part by Scientist Development Grant 0435087N from the American Heart Association, National Institute of Health grant R01-NS049476 (to X. W.), National Institute of Health grants R01-NS37074, R01NS48422, R01-NS53560 and P50-NS10828 (to E. H. L.). NR 109 TC 21 Z9 24 U1 2 U2 3 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 JUN PY 2008 VL 7 IS 3 BP 235 EP 242 DI 10.2174/187152708784936635 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 397HW UT WOS:000262654500003 PM 18673208 ER PT J AU Hoge, EA Worthington, JJ Kaufman, RE Delong, HR Pollack, MH Simon, NM AF Hoge, Elizabeth A. Worthington, John J., III Kaufman, Rebecca E. Delong, Hannah R. Pollack, Mark H. Simon, Naomi M. TI Aripiprazole as augmentation treatment of refractory generalized anxiety disorder and panic disorder SO CNS SPECTRUMS LA English DT Article ID OPEN-LABEL TRIAL; QUALITY-OF-LIFE; OLANZAPINE AUGMENTATION; ANXIOLYTIC-LIKE; RATING-SCALE; TERM; DEPRESSION; PLACEBO; SCHIZOPHRENIA; DISABILITY AB Introduction: Individuals with anxiety disorders often remain symptomatic despite treatment with a first-line pharmacologic agent. More research examining pharmacotherapy augmentation strategies to improve outcomes is needed. Methods: In an 8-week, open-label, prospective augmentation study, we examined the efficacy and tolerability of the novel antipsychotic agent aripiprazole for adult outpatients with generalized anxiety disorder (n=13) or panic disorder (n=10) who remained symptomatic despite treatment for at least 8 weeks with an adequate (or maximally tolerated) dose of typical pharmacotherapy. Results: Aripiprazole augmentation was associated with a significant reduction in Clinical Global Impressions-Severity scores (paired t=4.41, df=22, P<.001) in the intent-to-treat sample of 23 individuals. Three subjects (13%) discontinued due to sedation, chest discomfort, and restlessness, respectively. Conclusion: These data provide preliminary evidence that aripiprazole may be a useful augmentation strategy for individuals with generalized anxiety disorder or panic disorder who show a limited response to initial pharmacotherapy. C1 [Hoge, Elizabeth A.; Worthington, John J., III; Pollack, Mark H.; Simon, Naomi M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Kaufman, Rebecca E.; Delong, Hannah R.; Pollack, Mark H.; Simon, Naomi M.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. RP Hoge, EA (reprint author), Massachusetts Gen Hosp, Simches Res Bldg,185 Cambridge St,Suite 2200,2nd, Boston, MA 02114 USA. EM ehoge@partners.org RI Hoge, Elizabeth/H-5879-2012; OI Hoge, Elizabeth/0000-0002-5513-2292; Sripada, Rebecca/0000-0002-2844-3458 NR 38 TC 29 Z9 29 U1 1 U2 1 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD JUN PY 2008 VL 13 IS 6 BP 522 EP 527 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 315XW UT WOS:000256914500014 PM 18567977 ER PT J AU Huang, P Duda, DG Jain, RK Fukumura, D AF Huang, Peigen Duda, Dan G. Jain, Rakesh K. Fukumura, Dai TI Histopathologic findings and establishment of novel tumor lines from spontaneous tumors in FVB/N mice SO COMPARATIVE MEDICINE LA English DT Article ID MAMMARY HYPERPLASIA; STROMAL CELLS; SCID MICE; GROWTH; MOUSE; ANGIOGENESIS; XENOGRAFTS AB The inbred FVB mouse strain is used extensively in cancer research. Transgenic mice with an FVB/N background in which the expression of green fluorescent protein is under the control of various promoters have been used widely for the last decade. However, little is known about the incidence and characteristics of spontaneous tumors in these mice. In addition, only a few tumor lines have been established for use in this particular mouse strain. Our aim was to initiate a database of spontaneous tumors in our retired FVB/N breeders, analyze the histopathologic characteristics of these tumors, and establish novel tumor lines in vivo and in vitro. A total of 234 (40 male, 194 female) breeder mice were observed during their natural lifespans. The incidence of spontaneous tumors was 45.0% in male mice and 52.8% in female mice. All tumors in male mice were lung alveolar-bronchiolar (AB) neoplasms, except for 1 testis interstitial cell tumor. In female mice, histopathologic examination revealed 48 lung AB tumors, 27 mammary gland tumors, 13 ovarian tumors, and 14 other tumors. Several of these spontaneous tumors have been transplanted into FVB/N mice. One mammary adenocarcinoma (MCaP0008) and 1 lung AB carcinoma (LAP0297) were successfully transplanted subcutaneously and passaged serially in vivo. Subsequently, we established cell lines from both tumors, which were maintained in monolayer in vitro. Both of the grafted tumors and cell lines are tumorigenic in VEGF(p)-GFP/FVB and Tie2(p)-GFP/FVB mice. Establishment of these novel tumor lines will benefit both in vivo and in vitro studies on the pathophysiology of cancer in this relatively new but widely used mouse strain. C1 [Huang, Peigen; Duda, Dan G.; Jain, Rakesh K.; Fukumura, Dai] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. RP Huang, P (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. EM peigen@steele.nigh.harvard.edu FU NCI NIH HHS [R01 CA085140-08, P01 CA080124-08, P01 CA080124, R01 CA096915, R01 CA115767, R01 CA115767-04, R01-CA115767, R01-CA85140, R01 CA085140] NR 19 TC 11 Z9 11 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD JUN PY 2008 VL 58 IS 3 BP 253 EP 263 PG 11 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 315HZ UT WOS:000256870700004 PM 18589867 ER PT J AU Zhou, XZ Bao, HH Al-Hashem, R Ji, HB Albert, M Wong, KK Sun, YP AF Zhou, Xiangzhi Bao, Haihua Al-Hashem, Ruqayyah Ji, Hongbin Albert, Mitchell Wong, Kwok-Kin Sun, Yanping TI Magnetic resonance imaging of the response of a mouse model of non-small cell lung cancer to tyrosine kinase inhibitor treatment SO COMPARATIVE MEDICINE LA English DT Article ID RAT LUNG; MUTATIONS; EXPRESSION; MRI; RECONSTRUCTION; MICROSCOPY; TUMORS AB Mutational activation of the gene for epidermal growth factor receptor (EGFR) is 1 of the main ways by which this receptor induces non-small cell lung cancers (NSCLC). Variant III EGFR (EGFRvIII) is a potential therapeutic target in NSCLC treatment because of the high frequency of deletion mutations in this protein. This study used noninvasive magnetic resonance imaging (MRI) to investigate the role of an EGFRvIII mutant in lung tumorigenesis and tumor maintenance as well as its response to the EGFR small molecule inhibitor erlotinib (Tarceva) on bitransgenic mice. Both spin-echo and gradient-echo sequences with and without cardiac and respiratory gating were performed to image the invasive mouse lung tumor driven by EGFRvIII mutation. Tumor volumes were measured based on 2-dimensional axial MRI; 3-dimensional rendering of the images were obtained to demonstrate the spatial location and distribution of the tumor in the lung. The MRI results indicated that the tumor driven by the EGFRvIII mutation was generated and maintained in the bitransgenic mice with the use of doxycycline. Tumor monitoring via MRI showed that Erlotinib can significantly inhibit the growth of tumor in vivo. MRI has the ability to image mouse lung tumor with different sequences focusing on tissue contrasts between tumor and surroundings. The MRI approaches in this work can be applied on other antitumor drug treatment evaluation in vivo when appropriate sequences are chosen. C1 [Zhou, Xiangzhi; Bao, Haihua; Al-Hashem, Ruqayyah; Albert, Mitchell; Sun, Yanping] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Ji, Hongbin; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Zhou, XZ (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM xiazhou@bwh.harvard.edu NR 23 TC 5 Z9 5 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD JUN PY 2008 VL 58 IS 3 BP 276 EP 281 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 315HZ UT WOS:000256870700007 PM 18589870 ER PT J AU Avins, AL Bent, S Staccone, S Badua, E Padula, A Goldberg, H Neuhaus, J Hudes, E Shinohara, K Kane, C AF Avins, Andrew L. Bent, Stephen Staccone, Suzanne Badua, Evelyn Padula, Amy Goldberg, Harley Neuhaus, John Hudes, Esther Shinohara, Katusto Kane, Christopher TI A detailed safety assessment of a saw palmetto extract SO COMPLEMENTARY THERAPIES IN MEDICINE LA English DT Article DE saw palmetto; drug toxicity; benign prostatic; hyperplasia ID BENIGN PROSTATIC HYPERPLASIA; SERENOA-REPENS; COMPLEMENTARY; PERMIXON(R); CANCER; CARE AB Background: Saw palmetto is commonly used by men for tower-urinary tract symptoms. Despite its widespread use, very little is known about the potential toxicity of this dietary supplement. Methods: The Saw palmetto for Treatment of Enlarged Prostates (STEP) study was a randomized clinical trial performed among 225 men with mode rate-to-severe symptoms of benign prostatic hyperplasia, comparing a standardized extract of the saw palmetto berry (160 mg twice daily) with a placebo over a 1-year period. As part of this study, detailed data were collected on serious and non-serious adverse events, sexual functioning, and laboratory tests of blood and urine. Between-group differences were assessed with mixed-effects regression models. Results: There were no significant differences observed between the saw palmetto and placebo-allocated participants in the risk of suffering at least one serious adverse event (5.4% vs. 9.7%, respectively; p = 0.31) or non-serious symptomatic adverse event (34.8% vs. 30.1%, p = 0.48). There were few significant between-group differences in sexual functioning or for most laboratory analyses, with only small differences observed in changes over time in total bilirubin (p = 0.001), potassium (p = 0.03), and the incidence of glycosuria (0% in the saw palmetto group vs. 3.7% in the placebo group, p = 0.05). Conclusions: Despite careful assessment, no evidence for serious toxicity of saw palmetto was observed in this clinical trial. Given the sample size and length of this study, however, these data do not rule out potential rare adverse effects associated with the use of saw palmetto. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Avins, Andrew L.; Goldberg, Harley] No Calif Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Avins, Andrew L.; Bent, Stephen; Staccone, Suzanne; Padula, Amy] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. [Bent, Stephen] Univ Calif San Francisco, Dept Med, Osher Ctr Integrat Med, San Francisco, CA USA. [Avins, Andrew L.; Neuhaus, John; Hudes, Esther] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Badua, Evelyn; Shinohara, Katusto; Kane, Christopher] Son Francisco VA Med Ctr, Urol Sect, San Francisco, CA USA. [Shinohara, Katusto; Kane, Christopher] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. RP Avins, AL (reprint author), No Calif Kaiser Permanente, Div Res, 2000 Broadway,3rd Floor, Oakland, CA 94612 USA. EM andrew.avins@ucsf.edu FU NCCIH NIH HHS [K08 AT001338]; NIDDK NIH HHS [R01 DK56199, R01 DK056199-01, R01 DK056199] NR 28 TC 26 Z9 27 U1 0 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 0965-2299 J9 COMPLEMENT THER MED JI Complement. Ther. Med. PD JUN PY 2008 VL 16 IS 3 BP 147 EP 154 DI 10.1016/j.ctim.2007.10.005 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 322MG UT WOS:000257378700005 PM 18534327 ER PT J AU Patterson, M Maurer, S Adler, SR Avins, AL AF Patterson, Michael Maurer, Stephanie Adler, Shelley R. Avins, Andrew L. TI A novel clinical-trial design for the study of massage therapy SO COMPLEMENTARY THERAPIES IN MEDICINE LA English DT Article DE massage therapy; cancer; clinical trials; methodology ID ONSET MUSCLE SORENESS; LOW-BACK-PAIN; MULTIPLE-SCLEROSIS; BENEFIT; MOTHERS; QUALITY AB Objectives: To develop and test the feasibility and acceptability of a structured design for a massage therapy clinical trial that included a treatment arm designed to control for the non-specific effects of a massage therapy intervention. Design: Pilot randomized controlled clinical trial. Setting: University-integrated medicine research clinic. Interventions: Participants were randomized to a structured Swedish-style massage therapy intervention, a light-touch bodywork control intervention, or usual medical care. Details of the interventions are provided. Main outcome measures: The primary outcome measures were the adherence of the participants to the study protocol and the perception of the intervention experience. Results: Forty-four participants were randomized. Participants often found adherence to the twice-weekly outpatient bodywork interventions to be somewhat difficult; white, overall, 84% of participants completed the study, only 76% of those in an intervention arm successfully completed the trial. Participants randomized to the massage arm expressed uniformly positive attitudes both before and after the intervention. White some participants randomized to the light-touch bodywork arm initially expressed some reservations about their randomization assignment, all participants available for interview were pleased with their experience after the intervention period. Conclusions: The proposed design was found to be relatively straightforward to implement and acceptable to participants. Early disappointment with not receiving massage therapy expressed by the tight-touch intervention participants dissipated quickly. Twice-weekly outpatient intervention appointments were found to be highly burdensome for many patients actively undergoing chemotherapy, thus reducing adherence. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Avins, Andrew L.] No Calif Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Patterson, Michael; Maurer, Stephanie; Adler, Shelley R.; Avins, Andrew L.] Univ Calif San Francisco, Osher Ctr Integrat Med, San Francisco, CA 94143 USA. [Patterson, Michael; Maurer, Stephanie] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Adler, Shelley R.] Univ Calif San Francisco, Dept Family & Community Med, San Francisco, CA 94143 USA. [Avins, Andrew L.] San Francisco VA Med Ctr, Dept Med, Gen Internal Med Sect, San Francisco, CA USA. [Avins, Andrew L.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Avins, AL (reprint author), No Calif Kaiser Permanente, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM andrew.avins@ucsf.edu FU NCCIH NIH HHS [R21 AT000348, R21 AT000348-01] NR 34 TC 6 Z9 6 U1 1 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0965-2299 J9 COMPLEMENT THER MED JI Complement. Ther. Med. PD JUN PY 2008 VL 16 IS 3 BP 169 EP 176 DI 10.1016/j.ctim.2007.08.001 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 322MG UT WOS:000257378700008 PM 18534330 ER PT J AU Zhou, XH Cheng, H AF Zhou, Xiao-Hua Cheng, Hao TI A computer program for estimating the re-transformed mean in heteroscedastic two-part models SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE LA English DT Article DE computer programs; nonparametric; confidence intervals; skewed data; costs AB The population of health care costs is typically skewed, heteroscedastic, and may include zero costs. Without proper accounting for these special distributional features, resulting prediction may be biased, and wrong inferences about the distribution of patients' health care costs may be made. Welsh and Zhou [A.H. Welsh, X.H. Zhou, Estimating the retransformed mean in a heteroscedastic two-part model, J. Stat. Plan. inference 136 (2006) 860-881] proposed a semi-parametric regression model, which addressed these special features. In this paper we developed a software program to implement this statistical method, which would provide better prediction of health care costs for clinical researchers. Our program computed two mean estimators, their asymptotical standard deviation, confidence interval, and optional bootstrap confidence interval. Our program included user-friendly interactive mode and more efficient and flexible batch mode. It was written in free statistical computing language R and could be run on a wide variety of platforms. (c) 2008 Published by Elsevier Ireland Ltd. C1 [Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98108 USA. [Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98108 USA. [Cheng, Hao] SAS Inst Inc, Dept Operat Res, Cary, NC 27513 USA. RP Zhou, XH (reprint author), VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, 1100 Olive Way 1400, Seattle, WA 98108 USA. EM azhou@u.washington.edu; hao.cheng@sas.com FU AHRQ HHS [R01HS013105] NR 5 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-2607 J9 COMPUT METH PROG BIO JI Comput. Meth. Programs Biomed. PD JUN PY 2008 VL 90 IS 3 BP 210 EP 216 DI 10.1016/j.cmpb.2008.01.004 PG 7 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA 304VW UT WOS:000256138200003 PM 18355938 ER PT J AU Barrios, V Kwan, VSY Ganis, G Gorman, J Romanowski, J Keenan, JP AF Barrios, Veronica Kwan, Virginia S. Y. Ganis, Giorgio Gorman, Jaime Romanowski, Jennifer Keenan, Julian Paul TI Elucidating the neural correlates of egoistic and moralistic self-enhancement SO CONSCIOUSNESS AND COGNITION LA English DT Article; Proceedings Paper CT Interdisciplinary Conference on Consciousness and Cognition CY 2007 CL Hanse Inst Adv Studies, Delmenhorst, GERMANY HO Hanse Inst Adv Studies DE self-deception; medial prefrontal cortex; MPFC; transcranial magnetic stimulation; TMS; self-awareness; self-enhancement ID TRANSCRANIAL MAGNETIC STIMULATION; PERSONALITY; DEPRESSION; CORTEX; BRAIN; FMRI; PERSPECTIVE; PERCEPTION; NARCISSISM; CIRCUITS AB Self-enhancement is the biasing of one's view of oneself in a positive direction. The brain correlates of self-enhancement remain unclear though it has been reported that the medial prefrontal cortex (MPFC) may be important for producing self-enhancing responses. Previous studies have not examined whether the neural correlates of self-enhancement depend on the particular domain in which individuals are enhancing themselves. Both moralistic and egoistic words were presented to participants while transcranial magnetic stimulation (TMS) was applied to the MPFC, precuneus or in a sham orientation. Participants were asked to make decisions as to the words describing themselves, some of which were positive and some of which were negative. It was found the MPFC TMS significantly disrupted egoistic self-enhancement when TMS was delivered to the MPFC. judgments involving moralistic words were not influenced by TMS. These data provide further evidence that MPFC is involved in self-enhancement, and that the role of MPFC may be selective in this regard. (C) 2008 Elsevier Inc. All rights reserved. C1 [Barrios, Veronica; Gorman, Jaime; Romanowski, Jennifer; Keenan, Julian Paul] Montclair State Univ, Cognit Neuroimaging Lab, Montclair, NJ 07043 USA. [Kwan, Virginia S. Y.] Princeton Univ, Dept Psychol, Princeton, NJ 08540 USA. [Ganis, Giorgio] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Ganis, Giorgio] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Ganis, Giorgio] Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Keenan, JP (reprint author), Montclair State Univ, Cognit Neuroimaging Lab, 219 Dickson Hall, Montclair, NJ 07043 USA. EM keenanj@mail.montclair.edu OI Gorman, Jamie/0000-0002-8506-1181; Ganis, Giorgio/0000-0001-6175-2618 NR 44 TC 8 Z9 11 U1 1 U2 7 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 JUN PY 2008 VL 17 IS 2 BP 451 EP 456 DI 10.1016/j.concog.2008.03.006 PG 6 WC Psychology, Experimental SC Psychology GA 309WE UT WOS:000256490100005 PM 18417363 ER PT J AU Chia, S Raffel, OC Takano, M Tearney, GJ Bouma, BE Jang, IK AF Chia, Stanley Raffel, Owen Christopher Takano, Masamichi Tearney, Guillermo J. Bouma, Brett E. Jang, Ik-Kyung TI Association of statin therapy with reduced coronary plaque rupture: an optical coherence tomography study SO CORONARY ARTERY DISEASE LA English DT Article DE optical coherence tomography; plaque rupture; plaque stabilization; statin ID INCREASES COLLAGEN CONTENT; LIPID-LOWERING THERAPY; INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUES; HEART-DISEASE; MYOCARDIAL-INFARCTION; PRAVASTATIN TREATMENT; CHOLESTEROL LEVELS; CONTROLLED-TRIAL; IN-VIVO AB Objective Statin therapy induces plaque regression and may stabilize atheromatous plaques. Optical coherence tomography (OCT) is a high-resolution in-vivo imaging modality that allows characterization of atherosclerotic plaques. We aimed to demonstrate the potential utility of OCT in evaluating coronary plaques in patients with or without statin therapy. Methods Patients undergoing cardiac catheterization were enrolled. We identified culprit lesions and performed intracoronary OCT imaging. Plaque lipid pool, fibrous cap thickness, and frequency of thin-cap fibroatheroma were evaluated using previously validated criteria. Macrophage density was determined from optical signals within fibrous caps. Presence of calcification, thrombosis, and rupture was assessed. Results Forty-eight patients were included (26 on statins, 22 without statins). Baseline characteristics were similar apart from lipid profile. Patients on statin therapy had lower total and low-density lipoprotein cholesterol concentrations (4.45 +/- 1.35 vs. 5.26 +/- 0.83 mmol/l, P=0.02; 2.23 +/- 0.78 vs. 3.26 +/- 0.62 mmol/l, P < 0.001, respectively). Frequencies of lipid-rich plaque (69 vs. 82%), thin-cap fibroatheroma (31 vs. 50%), plaque calcification (15 vs. 5%) and thrombosis (15 vs. 32%), and fibrous cap macrophage density were comparable between statin and nonstatin groups (5.9 vs. 6.3%; all P=NS). Ruptured plaques were, however, significantly less frequent in patients on established statin therapy (8 vs. 36%; P=0.03) with a trend toward increased minimum fibrous cap thickness (78 vs. 49 pm; P=0.07). Conclusion We demonstrated the use of OCT in plaque characterization and found that patients on prior statin therapy have reduced incidence of ruptured plaques and a trend toward thicker fibrous caps. This suggests that statins may stabilize coronary plaques. C1 [Chia, Stanley; Raffel, Owen Christopher; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Tearney, Guillermo J.; Bouma, Brett E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Takano, Masamichi] Chiba Hokusoh Hosp, Nippon Med Sch, Dept Internal Med, Chiba, Japan. RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 55 Fruit St GRB 800, Boston, MA 02114 USA. EM ijang@partners.org FU NHLBI NIH HHS [R01-HL70039, R01 HL070039, R01 HL070039-03] NR 35 TC 26 Z9 29 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD JUN PY 2008 VL 19 IS 4 BP 237 EP 242 DI 10.1097/MCA.0b013e32830042a8 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 307KN UT WOS:000256317900004 PM 18480667 ER PT J AU Senkfor, AJ Van Petten, C Kutas, M AF Senkfor, Ava J. Van Petten, Cyma Kutas, Marta TI Enactment versus conceptual encoding: Equivalent item memory but different source memory SO CORTEX LA English DT Article DE enactment; subject-performed task; levels of processing; source memory; retrieval orientation ID SUBJECT-PERFORMED TASKS; EVENT-RELATED POTENTIALS; VISUAL OBJECT IDENTIFICATION; RETRIEVAL ORIENTATION; RECOGNITION MEMORY; AGE-DIFFERENCES; ALZHEIMERS-DISEASE; DIVIDED ATTENTION; EXPLICIT MEMORY; ORIENTING TASKS AB It has been suggested that performing a physical action (enactment) is an optimally effective encoding task, due to the incorporation of motoric information in the episodic memory trace, and later retrieval of that information. The current study contrasts old/new recognition of objects after enactment to a conceptual encoding task of cost estimation. Both encoding tasks yielded high accuracy, and robust differences in brain activity as compared to new objects, but no differences between encoding tasks. These results are not supportive of the idea that encoding by enactment leads to the spontaneous retrieval of motoric information. When participants were asked to discriminate between the two classes of studied objects during a source memory task, perform-encoded objects elicited higher accuracy and different brain activity than cost-encoded objects. The extent and nature of what was retrieved from memory thus depended on its utility for the assigned memory test: object information during the old/new recognition test, but additional information about the encoding task when necessary for a source memory test. Event-related potentials (ERPs) recorded during the two memory tests showed two orthogonal effects during an early (300800 msec) time window: a differentiation between studied and unstudied objects, and a test-type (retrieval orientation) effect that was equivalent for old and new objects. Later brain activity (800-1300 msec) differentiated perform- from cost-encoded objects, but only during the source memory test, suggesting temporally distinct phases of retrieval. (C) 2007 Elsevier Masson Srl. All rights reserved. C1 [Senkfor, Ava J.] Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA. [Senkfor, Ava J.] Massachusetts Gen Hosp, Charlestown, MA USA. [Kutas, Marta] Univ Calif San Diego, La Jolla, CA 92093 USA. [Van Petten, Cyma] SUNY Binghamton, Binghamton, NY USA. [Van Petten, Cyma] Univ Arizona, Tucson, AZ USA. RP Senkfor, AJ (reprint author), Wayne State Univ, Dept Psychol, 5057 Woodward Ave,7th Floor, Detroit, MI 48202 USA. EM senkfor@nmr.mgh.harvard.edu FU NIA NIH HHS [AG 14792, AG 08313, R01 AG008313, R01 AG014792-06A2, R01 AG014792]; NIMH NIH HHS [MH 52893] NR 94 TC 10 Z9 10 U1 3 U2 5 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD JUN PY 2008 VL 44 IS 6 BP 649 EP 664 DI 10.1016/j.cortex.2007.12.004 PG 16 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 310CG UT WOS:000256505900005 PM 18472035 ER PT J AU Siegel, MD Hayes, E Vanderwerker, LC Loseth, DB Prigerson, HG AF Siegel, Mark D. Hayes, Earle Vanderwerker, Lauren C. Loseth, Diane B. Prigerson, Holly G. TI Psychiatric illness in the next of kin of patients who die in the intensive care unit SO CRITICAL CARE MEDICINE LA English DT Article DE bereavement; death; major depression; psychiatric illness; intensive care unit; next of kin; family support ID OF-LIFE CARE; COMPLICATED GRIEF; FAMILY-MEMBERS; SUSTAINING TREATMENT; DEPRESSIVE EPISODES; DECISION-MAKING; BEREAVEMENT; SYMPTOMS; ICU; END AB Objectives: To determine the rates of psychiatric illness in next of kin following the death of a relative in a medical intensive care unit. Design: Cross-sectional survey. Setting: A university teaching hospital, New Haven, CT. Patients: Forty-one next of kin who had served as primary surrogate decision makers before the death of their loved one in the intensive care unit 3-12 months previously. Interventions: Structured Clinical Interviews for DSM-IV and the Inventory of Complicated Grief-Revised were used to determine prevalence of psychiatric illness. Formal questionnaires were used to evaluate key features of the intensive care unit experience. Bivariate statistics were used to identify factors associated with the presence of psychiatric illness. Measurements and Main Results: Following 107 patient deaths, 51 next of kin were successfully contacted and 41 (80%) agreed to study participation. Thirty-four percent (95% confidence interval, 200/6 to 51%) met criteria for at least one psychiatric illness: major depressive disorder (27%), generalized anxiety disorder (10%), panic disorder (10%), or complicated grief disorder (5%). Disorders were more common in spouses than other kinship relations (63% vs. 16%, p =.002), those experiencing additional stressors after the loss (53% vs. 21%, p =.03), those who said the patient was ill < 5 yrs (45% vs. 8%, p =.03), and those who said the patient's physician was not comforting (71% vs. 23%, p =.02). Conclusions: In a cohort of bereaved next of kin of patients who died in the intensive care unit, we identified a high prevalence of psychiatric illness, particularly major depressive disorder. More work is needed to identify those at risk for psychiatric illness so that appropriate interventions may be targeted. C1 [Siegel, Mark D.] Yale Univ, Sch Med, Yale New Haven Hosp, New Haven, CT 06520 USA. [Hayes, Earle] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Vanderwerker, Lauren C.] Union Theol Seminary, New York, NY 10027 USA. James Canc & Solove Res Inst, Pain & Palliat Med Program, Columbus, OH USA. [Prigerson, Holly G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Psycho Oncol & Palliat Care Res, Boston, MA 02115 USA. RP Siegel, MD (reprint author), Yale Univ, Sch Med, Yale New Haven Hosp, New Haven, CT 06520 USA. EM mark.siegel@yale.edu FU NCI NIH HHS [CA106370]; NIMH NIH HHS [MH56529, MH63892] NR 44 TC 107 Z9 109 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2008 VL 36 IS 6 BP 1722 EP 1728 DI 10.1097/CCM.0b013e318174da72 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 310EZ UT WOS:000256513000004 PM 18520637 ER PT J AU Lee, JM Yanagawa, J Peebles, KA Sharma, S Mao, JT Dubinett, SM AF Lee, Jay M. Yanagawa, Jane Peebles, Katherine A. Sharma, Sherven Mao, Jenny T. Dubinett, Steven M. TI Inflammation in lung carcinogenesis: New targets for lung cancer chemoprevention and treatment SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE inflammation; lung cancer; cyclooxygenase 2; COX-2; NSCLC; chemoprevention; targeted therapy; bronchogenic carcinoma ID GROWTH-FACTOR RECEPTOR; REGULATORY T-CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; OBSTRUCTIVE PULMONARY-DISEASE; MYELOID SUPPRESSOR-CELLS; ACUTE MYOCARDIAL-INFARCTION; TYROSINE KINASE; SELF-TOLERANCE; CYCLOOXYGENASE-2-DEPENDENT REGULATION; PROGNOSTIC-SIGNIFICANCE AB Lung carcinogenesis is a complex process involving the acquisition of genetic mutations that confer cancer development and the malignant phenotype, and is critically linked to apoptosis resistance, unregulated proliferation, invasion, metastasis, and angiogenesis. Epithelial mesenchymal transition (EMT) in cancer is an unregulated process in a host environment with deregulated inflammatory response that impairs cell-mediated immunity and permits cancer progression. Given the immunosuppressive tumor environment, strategies to reverse these events by stimulating host immune responses are an important area of investigation. Cyclooxygenase 2 (COX-2) and its downstream signaling pathways are potential targets for lung cancer chemoprevention and therapy. Clinical trials are underway to evaluate COX-2 inhibitors as adjuvants to chemotherapy in patients with lung cancer and to determine efficacy in prevention of bronchogenic carcinoma. The understanding of molecular mechanisms involved in inflammation and lung carcinogenesis provide insight for new drug development that target reversible, non-mutational events in the chemoprevention and treatment of lung cancer. Published by Elsevier Ireland Ltd. C1 [Lee, Jay M.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, David Geffen Sch Med, UCLA Lung Canc Res Program,Dept Surg,Div Cardioth, Los Angeles, CA 90095 USA. [Yanagawa, Jane; Peebles, Katherine A.; Mao, Jenny T.; Dubinett, Steven M.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, David Geffen Sch Med, UCLA Lung Canc Res Program,Dept Med,Div Pulm & Cr, Los Angeles, CA 90095 USA. [Sharma, Sherven] Univ Calif Los Angeles, W Los Angeles VA, David Geffen Sch Med,Jonsson Comprehens Canc Ctr, UCLA Lung Canc Res Program,Dept Med,Div Pulm & Cr, Los Angeles, CA 90073 USA. RP Lee, JM (reprint author), Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, David Geffen Sch Med, UCLA Lung Canc Res Program,Dept Surg,Div Cardioth, Los Angeles, CA 90095 USA. EM jaymoonlee@mednet.ucla.edu; jyanagawa@mednet.ucla.edu; Katherine.peebles@gmail.com; sharmasp@ucla.edu; jmao@mednet.ucla.edu; sdubinett@mednet.ucla.edu FU NCI NIH HHS [K12 CA076905, K12 CA076905-10, K23 CA131577, P50 CA090388, P50 CA090388-05S3] NR 114 TC 82 Z9 84 U1 3 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD JUN PY 2008 VL 66 IS 3 BP 208 EP 217 DI 10.1016/j.critrevonc.2008.01.004 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 305SZ UT WOS:000256199400004 PM 18304833 ER PT J AU He, XM Park, EYH Fowler, A Yarmush, ML Toner, M AF He, Xiaoming Park, Eric Y. H. Fowler, Alex Yarmush, Martin L. Toner, Mehmet TI Vitrification by ultra-fast cooling at a low concentration of cryoprotectants in a quartz micro-capillary: A study using murine embryonic stem cells SO CRYOBIOLOGY LA English DT Article DE cryopreservation; vitrification; 1,2-propanediol; trehalose; murine ES cells; quartz micro-capillary; plastic straw; open-pulled straw; French-type straw; cooling rate ID BOILING HEAT-TRANSFER; AQUEOUS-SOLUTIONS; BIOLOGICAL CELLS; LIQUID-NITROGEN; MOUSE EMBRYOS; CRYOPRESERVATION; TREHALOSE; SUSPENSIONS; KINETICS; SURVIVAL AB Conventional cryopreservation protocols for slow-freezing or vitrification involve cell injury due to ice formation/cell dehydration or toxicity of high cryoprotectant (CPA) concentrations, respectively. In this study, we developed a novel cryopreservation technique to achieve ultra-fast cooling rates using a quartz micro-capillary (QMC). The QMC enabled vitrification of murine embryonic stem (ES) cells using an intracellular cryoprotectant concentration in the range used for slowing freezing (1-2 M). The cryoprotectants used included 2 M 1,2-propanediol (PROH, cell membrane permeable) and 0.5 M extracellular trehalose (cell membrane impermeable). More than 70% of the murine ES cells post-vitrification attached with respect to non-frozen control cells, and the proliferation rates of the two groups were similar. Preservation of undifferentiated properties of the pluripotent murine ES cells post-vitrification cryopreservation was verified using three different types of assays: the expression of transcription factor Oct-4, the presentation of the membrane surface glycoprotein SSEA-1, and the elevated expression of the intracellular enzyme alkaline phosphatase. These results indicate that vitrification at a low concentroition (2 M) of intracellular cryoprotectants is a viable and effective approach for the cryopreservation of murine embryonic stem cells. (C) 2008 Elsevier Inc. All rights reserved. C1 [He, Xiaoming; Park, Eric Y. H.; Yarmush, Martin L.; Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. [He, Xiaoming; Park, Eric Y. H.; Yarmush, Martin L.; Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg Serv, Boston, MA 02114 USA. [He, Xiaoming; Park, Eric Y. H.; Yarmush, Martin L.; Toner, Mehmet] Shriners Hosp Children, Boston, MA 02114 USA. [Fowler, Alex] Univ Massachusetts, Dept Mech Engn, N Dartmouth, MA 02747 USA. RP He, XM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, 51 Blossom St, Boston, MA 02114 USA. EM xmhe@sc.edu RI He, Xiaoming/C-5499-2008 OI He, Xiaoming/0000-0003-0125-6086 FU NIBIB NIH HHS [EB002340, R01 EB002340, R01 EB002340-05] NR 44 TC 54 Z9 55 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0011-2240 J9 CRYOBIOLOGY JI Cryobiology PD JUN PY 2008 VL 56 IS 3 BP 223 EP 232 DI 10.1016/j.cryobiol.2008.03.005 PG 10 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 317HO UT WOS:000257010900008 PM 18462712 ER PT J AU Muntoni, S Muntoni, S Draznin, B AF Muntoni, Sergio Muntoni, Sandro Draznin, Boris TI Effects of Chronic Hyperinsulinemia in Insulin-Resistant Patients SO CURRENT DIABETES REPORTS LA English DT Article ID TYPE-2 DIABETES-MELLITUS; CORONARY-HEART-DISEASE; ACTIVATED PROTEIN-KINASE; MACROVASCULAR DISEASE; MOLECULAR-MECHANISMS; COLORECTAL-CANCER; ENDOTHELIAL-CELLS; GLYCEMIC CONTROL; MORTALITY; THERAPY AB Selective insulin resistance influences pathogenesis and treatment of type 2 diabetes and metabolic syndrome. Downregulation of the antiatherogenic pathway and maintained activity of the proatherogenic and cancerogenic pathways lead to atherosclerosis and cancer. Exogenous insulin added to "compensatory" hyperinsulinemia might worsen the primary end points, resulting in potential increase in cardiovascular and cancer events in spite of improvement of surrogate metabolic end points. Conversely, metformin can improve primary and surrogate end points. C1 [Draznin, Boris] Univ Colorado, Hlth Sci Ctr, ACOS R&D, Denver VA Med Ctr, Denver, CO 80220 USA. RP Draznin, B (reprint author), Univ Colorado, Hlth Sci Ctr, ACOS R&D, Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM boris.draznin@va.gov NR 49 TC 12 Z9 14 U1 0 U2 2 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 JUN PY 2008 VL 8 IS 3 BP 233 EP 238 DI 10.1007/s11892-008-0040-z PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 375FV UT WOS:000261100400010 PM 18625122 ER PT J AU Goodfriend, TL AF Goodfriend, Theodore L. TI Obesity, sleep apnea, aldosterone, and hypertension SO CURRENT HYPERTENSION REPORTS LA English DT Article ID AMBULATORY BLOOD-PRESSURE; POSITIVE AIRWAY PRESSURE; RESISTANT HYPERTENSION; METABOLIC SYNDROME; ADIPOSE-TISSUE; CARDIOVASCULAR-DISEASE; PLASMA-ALDOSTERONE; RISK-FACTORS; WEIGHT-LOSS; INSULIN AB The pathogenesis of hypertension associated with obesity is unclear. This review provides evidence supporting excess visceral fat as an early aspect, and obstructive sleep apnea and elevated levels of aldosterone as factors closer to hypertension in the mechanistic chain. Features of visceral obesity and obstructive sleep apnea that may stimulate aldosterone secretion are described here. Possible therapeutic interventions addressing the hypertension associated with obesity are briefly mentioned. C1 William S Middleton Mem Vet Adm Med Ctr, Res Serv, Madison, WI 53705 USA. RP Goodfriend, TL (reprint author), William S Middleton Mem Vet Adm Med Ctr, Res Serv, 2500 Overlook Terrace, Madison, WI 53705 USA. EM theodore.goodfriend@med.va.gov NR 44 TC 17 Z9 18 U1 0 U2 7 PU CURRENT SCIENCE INC PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1522-6417 J9 CURR HYPERTENS REP JI Curr. Hypertens. Rep. PD JUN PY 2008 VL 10 IS 3 BP 222 EP 226 DI 10.1007/s11906-008-0042-x PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 310MC UT WOS:000256532700013 PM 18765094 ER PT J AU Erwin, JA Lee, JT AF Erwin, Jennifer A. Lee, Jeannie T. TI New twists in X-chromosome inactivation SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID XIST RNA; DOSAGE COMPENSATION; TSIX TRANSCRIPTION; DNA METHYLATION; STEM-CELLS; GENE; MOUSE; INITIATION; CHROMATIN; CHOICE AB Dosage compensation, the mechanism by which organisms equalize the relative gene expression of dimorphic sex chromosomes, requires action of a diverse range of epigenetic mechanisms. The mammalian form, 'named X-chromosome inactivation' (XCI), involves silencing of one X chromosome in the female cell and regulation by genes that make noncoding RNAs (ncRNA). With large-scale genomic and transcriptome studies pointing to a crucial role for noncoding elements in organizing the epigenome, XCI emerges as a major paradigm and a focus of active research worldwide. With more surprising twists, recent advances point to the significance of RNA-directed chromatin change, chromosomal trans-interactions, nuclear organization, and evolutionary change. These findings have impacted our understanding of general gene regulation and are discussed herein. C1 [Erwin, Jennifer A.; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. [Erwin, Jennifer A.; Lee, Jeannie T.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu FU NIGMS NIH HHS [R01 GM058839-10, R01 GM058839] NR 74 TC 41 Z9 45 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD JUN PY 2008 VL 20 IS 3 BP 349 EP 355 DI 10.1016/j.ceb.2008.04.007 PG 7 WC Cell Biology SC Cell Biology GA 317ZY UT WOS:000257060700015 PM 18508252 ER PT J AU Rao, A Calame, K AF Rao, Anjana Calame, Kathryn TI Introduction to COI volume on lymphocyte activation 2008 SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material C1 [Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Rao, Anjana] Immune Dis Inst, Boston, MA 02115 USA. [Calame, Kathryn] Columbia Univ, Coll Phys & Surg, Dept Microbiol, New York, NY 10025 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM arao@idi.harvard.edu; klcl@columbia.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2008 VL 20 IS 3 BP 247 EP 249 DI 10.1016/j.coi.2008.05.006 PG 3 WC Immunology SC Immunology GA 326JQ UT WOS:000257655200001 PM 18554886 ER PT J AU Oh-Hora, M Rao, A AF Oh-Hora, Masatsup Rao, Anjana TI Calcium signaling in lymphocytes SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID OPERATED CA2+ ENTRY; STROMAL INTERACTION MOLECULE-1; T-CELL DEVELOPMENT; PLASMA-MEMBRANE; CRAC CHANNEL; ENDOPLASMIC-RETICULUM; STORE DEPLETION; TRANSCRIPTIONAL REGULATION; THYMOCYTE DEVELOPMENT; POSITIVE SELECTION AB In cells of the immune system, calcium signals are essential for diverse cellular functions including differentiation, effector function, and gene transcription. After the engagement of immunoreceptors such as T-cell and B-cell antigen receptors and the Fc receptors on mast cells and NK cells, the intracellular concentration of calcium ions is increased through the sequential operation of two interdependent processes: depletion of endoplasmic reticulum Ca2+ stores as a result of binding of inositol trisphosphate (IP3) to IP3 receptors, followed by 'store-operated' Ca2+ entry through plasma membrane Ca2+ channels. In lymphocytes, mast cells and other immune cell types, store-operated Ca2+ entry through specialized Ca2+ release-activated calcium (CRAC) channels constitutes the major pathway of intracellular Ca2+ increase. A recent breakthrough in our understanding of CRAC channel function is the identification of stromal interaction molecule (STIM) and ORAI, two essential regulators of CRAC channel function. This review focuses on the signaling pathways upstream and downstream of Ca2+ influx (the STIM/ORAI and calcineurin/NFAT pathways, respectively). C1 [Oh-Hora, Masatsup; Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Boston, MA 02115 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Room 152,Warren Alpert Bldg,200 Longwood Ave, Boston, MA 02115 USA. EM arao@idi.harvard.edu FU NIAID NIH HHS [R01 AI040127, R01 AI040127-17, R01 AI040127-18, R01 AI070788, R01 AI070788-01A1, R01 AI070788-02]; NIGMS NIH HHS [R01 GM075256-03, R01 GM075256, R01 GM075256-02] NR 77 TC 199 Z9 201 U1 1 U2 21 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2008 VL 20 IS 3 BP 250 EP 258 DI 10.1016/j.coi.2008.04.004 PG 9 WC Immunology SC Immunology GA 326JQ UT WOS:000257655200002 PM 18515054 ER PT J AU Burwick, N Roccaro, AM Leleu, X Ghobrial, IM AF Burwick, Nicholas Roccaro, Aldo M. Leleu, Xavier Ghobrial, Irene M. TI Targeted therapies in Waldenstrom macroglobulinemia SO CURRENT OPINION IN INVESTIGATIONAL DRUGS LA English DT Review DE bone marrow microenvironment; cell signaling; novel therapeutics; proteasome; Waldenstrom macroglobulinemia ID INTERNATIONAL WORKSHOP; RITUXIMAB THERAPY; PROTEASOME; RECOMMENDATIONS; CELLS AB Waldenstrom macroglobulinemia (WM) is a B-cell malignancy characterized by diffuse bone marrow (BM) infiltration, hepatosplenomegaly, lymphadenopathy, and the presence of a serum IgM monoclonal protein. Clinically, patients may present with fatigue, weight loss, peripheral neuropathy or symptoms of hyperviscosity, including headache, blurred vision or epistaxis. WM is an indolent disease, although it remains incurable with a median survival of five to six years. There are no FDA-approved drugs specifically for the treatment of WM, but chemotherapeutic agents used extensively in WM include alkylating agents (chlorambucil and cyclophosphamide) or nucleoside analogs (fludarabine), alone, or in combination with corticosteroids. However, these agents are limited by their toxicity profiles, low efficacy, and adverse effect on future stem cell harvesting. In addition, patients with relapsed/refractory disease are still in need of novel therapeutic options. As a result, there has been strong interest in discovering and translating targeted therapies in WM. The prototype for this is rituximab, the anti-CD20 mAb that specifically targets B-cells and has become one of the main treatment options in WM. Several new targeted therapies have been tested preclinically in WM, with diffuse molecular targets, including the ubiquitin-proteasome pathway, PI3-kinase/Akt and mTOR signaling pathways, as well as the BM microenvironment. These studies have resulted in several new promising clinical phase trials in WM over the last five years, providing hope for shifting the treatment paradigm in WM. In this review, the novel therapeutics that target these pathways are discussed. C1 [Burwick, Nicholas; Roccaro, Aldo M.; Leleu, Xavier; Ghobrial, Irene M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Burwick, Nicholas; Roccaro, Aldo M.; Leleu, Xavier; Ghobrial, Irene M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Ghobrial, IM (reprint author), Harvard Univ, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu NR 17 TC 5 Z9 6 U1 0 U2 0 PU THOMSON SCIENTIFIC PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND STREET, LONDON, W1T 4JE, ENGLAND SN 1472-4472 J9 CURR OPIN INVEST DR JI Curr. Opin. Investig. Drugs PD JUN PY 2008 VL 9 IS 6 BP 631 EP 637 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 305PR UT WOS:000256190800009 PM 18516762 ER PT J AU Choueiri, TK AF Choueiri, Toni K. TI Axitinib, a novel anti-angiogenic drug with promising activity in various solid tumors SO CURRENT OPINION IN INVESTIGATIONAL DRUGS LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; HUMAN PANCREATIC-CANCER; MYELOID-LEUKEMIA AML; BREAST-CANCER; PROGNOSTIC VALUE; ANTITUMOR-ACTIVITY; FACTOR EXPRESSION; PHASE-I; C-FMS AB Axitinib is an oral inhibitor of the VEGF, PDGF and colony stimulating factor-1 receptor tyrosine kinases and is currently in development by Pfizer Inc for the potential treatment of various solid tumors. Phase II trials with this agent alone or in combination with chemotherapeutic drugs were reported in several types of malignancy, with activity observed in thyroid, pancreatic, lung, renal, breast and colorectal cancers, melanoma and other carcinomas. Although frequent side effects have included fatigue, hypertension, diarrhea, hand-foot syndrome and proteinuria, axitinib was well tolerated overall. Larger, randomized phase II/III studies were ongoing at the time of publication. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Lank Ctr Genitourinary Onco, Boston, MA 02115 USA. RP Choueiri, TK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Lank Ctr Genitourinary Onco, 44 Binney St,Dana 1230, Boston, MA 02115 USA. EM Toni_Choueiri@dfci.harvard.edu NR 104 TC 46 Z9 46 U1 0 U2 5 PU THOMSON SCIENTIFIC PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND STREET, LONDON, W1T 4JE, ENGLAND SN 1472-4472 J9 CURR OPIN INVEST DR JI Curr. Opin. Investig. Drugs PD JUN PY 2008 VL 9 IS 6 BP 658 EP 671 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 305PR UT WOS:000256190800012 PM 18516765 ER PT J AU Lemaitre, B Ausubel, FM AF Lemaitre, Bruno Ausubel, Frederick M. TI Animal models for host-pathogen interactions SO CURRENT OPINION IN MICROBIOLOGY LA English DT Editorial Material C1 [Lemaitre, Bruno] Ecole Polytech Fed Lausanne, Global Hlth Inst, CH-1015 Lausanne, Switzerland. [Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Lemaitre, B (reprint author), Ecole Polytech Fed Lausanne, Global Hlth Inst, Stn 15, CH-1015 Lausanne, Switzerland. EM bruno.lemaitre@epfl.ch; ausubel@molbio.mgh.harvard.edu OI Lemaitre, Bruno/0000-0001-7970-1667 NR 0 TC 5 Z9 6 U1 0 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD JUN PY 2008 VL 11 IS 3 BP 249 EP 250 DI 10.1016/j.mib.2008.05.002 PG 2 WC Microbiology SC Microbiology GA 330XA UT WOS:000257974900009 PM 18539076 ER PT J AU Cosker, KE Courchesne, SL Segal, RA AF Cosker, Katharina E. Courchesne, Stephanie L. Segal, Rosalind A. TI Action in the axon: generation and transport of signaling endosomes SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID MOTOR-NEURON DISEASE; CYTOPLASMIC DYNEIN; RETROGRADE TRANSPORT; SYMPATHETIC NEURONS; NERVOUS-SYSTEM; NEUROTROPHIN RECEPTORS; ALS2-DEFICIENT MICE; DISTAL AXONOPATHY; MUTANT DYNACTIN; SENSORY NEURONS AB Neurons extend axonal processes over long distances, necessitating efficient transport mechanisms to convey target-derived neurotrophic survival signals from remote distal axons to cell bodies. Retrograde transport, powered by dynein motors, supplies cell bodies with survival signals in the form of 'signaling endosomes'. In this review, we will discuss new advances in our understanding of the motor proteins that bind to and move signaling components in a retrograde direction and discuss mechanisms that might specify distinct neuronal responses to spatially restricted neurotrophin signals. Disruption of retrograde transport leads to a variety of neurodegenerative diseases, highlighting the role of retrograde transport of signaling endosomes for axonal maintenance and the importance of efficient transport for neuronal survival and function. C1 [Cosker, Katharina E.; Courchesne, Stephanie L.; Segal, Rosalind A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Cosker, Katharina E.; Courchesne, Stephanie L.; Segal, Rosalind A.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Segal, RA (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM rosalind_segal@dfci.harvard.edu FU NINDS [NS050674]; Stuart HZ & Victorria Qan Fellowship FX We would like to apologise to those authors whose work was not included in this review owing to space constraints. Our thanks go to Maria Pazyra-Murphy for helpful comments and editing. We also thank the NINDS (NS050674) and the Stuart HZ & Victorria Qan Fellowship Program at Harvard Medical School for funding. NR 49 TC 92 Z9 92 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD JUN PY 2008 VL 18 IS 3 BP 270 EP 275 DI 10.1016/j.conb.2008.08.005 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 371GQ UT WOS:000260820200007 PM 18778772 ER PT J AU Eikermann-Haerter, K Moskowitz, MA AF Eikermann-Haerter, Katharina Moskowitz, Michael A. TI Animal models of migraine headache and aura SO CURRENT OPINION IN NEUROLOGY LA English DT Review DE canimal models of migraine; aura; cortical spreading depression; trigeminovascular-mediated nociception ID CORTICAL SPREADING DEPRESSION; TRIGEMINAL NUCLEUS CAUDALIS; FOS-LIKE IMMUNOREACTIVITY; FAMILIAL HEMIPLEGIC MIGRAINE; SUPERIOR SAGITTAL SINUS; GENE-RELATED PEPTIDE; CEREBRAL-BLOOD-FLOW; CAROTID ARTERIOVENOUS ANASTOMOSES; RECEPTOR ANTAGONIST BIBN4096BS; PLASMA-PROTEIN EXTRAVASATION AB Purpose of review Over the past 30 years, animal models of migraine have led to the identification of novel drug targets and drug treatments as well as helped to clarify a mechanism for abortive and prophylactic drugs. Animal models have also provided translational knowledge and a framework to think about the impact of hormones, genes, and environmental factors on migraine pathophysiology. Although most acknowledge that these animal models have significant shortcomings, promising new drugs are now being developed and brought to the clinic using these preclinical models. Hence, it is timely to provide a short overview examining the ways in which animal models inform us about underlying migraine mechanisms. Recent findings First generation migraine models mainly focused on events within pain-generating intracranial tissues, for example, the dura mater and large vessels, as well as their downstream consequences within brain. Upstream events such as cortical spreading depression have also been modeled recently and provide insight into mechanisms of migraine prophylaxis. Mouse mutants expressing human migraine mutations have been genetically engineered to provide an understanding of familial hemiplegic migraine and possibly, by extrapolation, may reflect on the pathophysiology of more common migraine subtypes. Summary Animal models of migraine reflect distinct facets of this clinically heterogeneous disorder and contribute to a better understanding of its pathophysiology and pharmacology. C1 [Eikermann-Haerter, Katharina; Moskowitz, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. [Eikermann-Haerter, Katharina] Univ Duisburg Essen, Dept Neurol, Essen, Germany. RP Moskowitz, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Stroke & Neurovasc Regulat Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [1 RO1 NS054052-02, 2 PO1 NS35611-11, R01 NS048198-04] NR 101 TC 24 Z9 25 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD JUN PY 2008 VL 21 IS 3 BP 294 EP 300 DI 10.1097/WCO.0b013e3282fc25de PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 305MV UT WOS:000256183400012 PM 18451713 ER PT J AU Watnick, S Rueda, J AF Watnick, Suzanne Rueda, Jose TI Reproduction and contraception after kidney transplantation SO CURRENT OPINION IN OBSTETRICS & GYNECOLOGY LA English DT Article DE contraception; kidney transplantation; reproduction ID RENAL-TRANSPLANTATION; ORGAN TRANSPLANT; PREGNANCY; DISEASE; ISSUES; WOMEN; RECIPIENTS AB Purpose of review In this manuscript we review the most recent data regarding birth rates and complications in the kidney transplant population. Despite improved fertility, contraceptive counseling is infrequent and contraceptive use engenders many problems not frequently seen in women of childbearing age. Recent findings Pregnancy outcomes in this population are improving, but these patients are still considered 'high risk'. With improved fertility after transplantation, contraception should be viewed as essential in those who wish to avoid pregnancy. Many forms of contraception are viable for women with a kidney transplant. Summary Given increased rates of preeclampsia, preterm delivery, low birth weight, and increased risk of cesarean section, a multidisciplinary team must be involved, which will tend to everything from general fetal and maternal monitoring, serial measurement of kidney function, and medication adjustment. For all these reasons, contraceptive counseling is necessary for all women of childbearing age, both pre and posttransplantation. Specific methods of contraception can be individualized to a patient's needs and should be discussed between patient and provider. Future study of both reproduction and contraception use in kidney transplant recipients is sorely needed. C1 [Watnick, Suzanne] Portland VA Med Ctr, Div Hosp & Specialty Med, Portland, OR 97239 USA. [Watnick, Suzanne; Rueda, Jose] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. RP Watnick, S (reprint author), Portland VA Med Ctr, Div Hosp & Specialty Med, PP262,3710 SW US Vet Hosp Dr, Portland, OR 97239 USA. EM watnicks@ohsu.edu NR 30 TC 24 Z9 25 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-872X J9 CURR OPIN OBSTET GYN JI Curr. Opin. Obstet. Gynecol. PD JUN PY 2008 VL 20 IS 3 BP 308 EP 312 DI 10.1097/GCO.0b013e3282f8b009 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 304XP UT WOS:000256142700017 PM 18460947 ER PT J AU Yeh, H Olthoff, KM AF Yeh, Heidi Olthoff, Kim M. TI Live donor adult liver transplantation SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE donor morbidity; liver transplantation; living donor; posttransplant outcome ID ANTIBODY-POSITIVE DONORS; HEPATITIS-C RECURRENCE; HEPATOCELLULAR-CARCINOMA; HILAR CHOLANGIOCARCINOMA; POTENTIAL DONORS; ORPHAN GRAFT; SURVIVAL; OUTCOMES; EXPERIENCE; RECIPIENTS AB Purpose of review Because the gap between liver organ supply and demand continues to increase, adult living-donor liver transplantation continues to represent a significant pool of organs. Recent findings With this in mind, we discuss recent issues in adult living-donor liver transplantation, including issues with donor evaluation and selection, donor liver biopsy, orphan organ allocation, donor morbidity and mortality, outcomes compared with deceased donor liver transplant from time of evaluation, death on the waiting list, and evolving recipient indications for living-donor liver transplantation. Summary Increasing the number of living-donor liver transplants would allow us to expedite transplant, avoid death on the waitlist, and possibly save more lives by expanding the criteria for transplant. These benefits must always be weighed against the potential risks and complications to the donor, which can be significant. C1 [Olthoff, Kim M.] Univ Penn, Div Transplantat, Liver Transplant Program, Penn Transplant Inst,Dept Surg, Philadelphia, PA 19104 USA. [Yeh, Heidi] Massachusetts Gen Hosp, Div Transplantat, Boston, MA 02114 USA. RP Olthoff, KM (reprint author), Univ Penn, Div Transplantat, Liver Transplant Program, Penn Transplant Inst,Dept Surg, 2 Dulles 3400 Spruce St, Philadelphia, PA 19104 USA. NR 46 TC 5 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1087-2418 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD JUN PY 2008 VL 13 IS 3 BP 241 EP 246 DI 10.1097/MOT.0b013e328300a352 PG 6 WC Transplantation SC Transplantation GA 309VV UT WOS:000256489200003 PM 18685310 ER PT J AU Mehta, DD Hillman, RE AF Mehta, Daryush D. Hillman, Robert E. TI Voice assessment: updates on perceptual, acoustic, aerodynamic, and endoscopic imaging methods SO CURRENT OPINION IN OTOLARYNGOLOGY & HEAD AND NECK SURGERY LA English DT Article DE acoustic voice analysis; aerodynamics of voice production; high-speed endoscopic imaging; perception of voice; voice quality assessment ID ESTIMATING SUBGLOTTAL PRESSURE; AIR-FLOW; QUALITY ASSESSMENT; MODEL; CLASSIFICATION; RECORDINGS; SIGNALS AB Purpose of review This paper describes recent advances in perceptual, acoustic, aerodynamic, and endoscopic imaging methods for assessing voice function. Recent findings We review advances from four major areas. Perceptual assessment: Speech-language pathologists are being encouraged to use the new consensus auditory-perceptual evaluation of voice inventory for auditory-perceptual assessment of voice quality, and recent studies have provided new insights into listener reliability issues that have plagued subjective perceptual judgments of voice quality. Acoustic assessment: Progress is being made on the development of algorithms that are more robust for analyzing disordered voices, including the capability to extract voice quality-related measures from running speech segments. Aerodynamic assessment: New devices for measuring phonation threshold air pressures and air flows have the potential to serve as sensitive indices of glottal phonatory conditions, and recent developments in aeroacoustic theory may provide new insights into laryngeal sound production mechanisms. Endoscopic imaging: The increased light sensitivity of new ultra high-speed color digital video processors is enabling high-quality endoscopic imaging of vocal fold tissue motion at unprecedented image capture rates, which promises to provide new insights into the mechanisms of normal and disordered voice production. Summary Some of the recent research advances in voice function assessment could be more readily adopted into clinical practice, whereas others will require further development. C1 [Mehta, Daryush D.; Hillman, Robert E.] Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Massachusetts Gen Hosp,Ctr Laryngeal Surg & Voice, Boston, MA 02114 USA. RP Mehta, DD (reprint author), Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Massachusetts Gen Hosp,Ctr Laryngeal Surg & Voice, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM dmehta@mit.edu FU NIDCD NIH HHS [T32 DC000038] NR 23 TC 36 Z9 47 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9508 J9 CURR OPIN OTOLARYNGO JI Curr. Opin. Otolaryngol. Head Neck Surg. PD JUN PY 2008 VL 16 IS 3 BP 211 EP 215 DI 10.1097/MOO.0b013e3282fe96ce PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 395KX UT WOS:000262524100006 PM 18475073 ER PT J AU Mak, KK Kronenberg, HM Chuang, PT Mackem, S Yang, YZ AF Mak, Kinglun Kingston Kronenberg, Henry M. Chuang, Pao-Tien Mackem, Susan Yang, Yingzi TI Indian hedgehog signals independently of PTHrP to promote chondrocyte hypertrophy SO DEVELOPMENT LA English DT Article DE Ihh; patched 1; cartilage; PTHrP; chondrocyte hypertrophy ID HORMONE-RELATED-PROTEIN; GROWTH-PLATE; CARTILAGE DEVELOPMENT; ENDOCHONDRAL BONE; DIFFERENTIATION; IHH; PATHWAYS; PROLIFERATION; OSTEOBLAST; SKELETON AB Chondrocyte hypertrophy is an essential process required for endochondral bone formation. Proper regulation of chondrocyte hypertrophy is also required in postnatal cartilage homeostasis. Indian hedgehog (Ihh) and PTHrP signaling play crucial roles in regulating the onset of chondrocyte hypertrophy by forming a negative feedback loop, in which Ihh signaling regulates chondrocyte hypertrophy by controlling PTHrP expression. To understand whether there is a PTHrP-independent role of Ihh signaling in regulating chondrocyte hypertrophy, we have both activated and inactivated Ihh signaling in the absence of PTHrP during endochondral skeletal development. We found that upregulating Ihh signaling in the developing cartilage by treating PTHrP(-/-) limb explants with sonic hedgehog (Shh) protein in vitro, or overexpressing Ihh in the cartilage of PTHrP(-/-) embryos or inactivating patched 1 (Ptch1), a negative regulator of hedgehog (Hh) signaling, accelerated chondrocyte hypertrophy in the PTHrP(-/-) embryos. Conversely, when Hh signaling was blocked by cyclopamine or by removing Smoothened (Smo), a positive regulator of Hh signaling, chondrocyte hypertrophy was delayed in the PTHrP(-/-) embryo. Furthermore, we show that upregulated Hh signaling in the postnatal cartilage led to accelerated chondrocyte hypertrophy during secondary ossification, which in turn caused reduction of joint cartilage. Our results revealed a novel role of Ihh signaling in promoting chondrocyte hypertrophy independently of PTHrP, which is particularly important in postnatal cartilage development and homeostasis. In addition, we found that bone morphogenetic protein (Bmp) and Wnt/beta-catenin signaling in the cartilage may both mediate the effect of upregulated Ihh signaling in promoting chondrocyte hypertrophy. C1 [Mak, Kinglun Kingston; Yang, Yingzi] NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. [Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Kronenberg, Henry M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chuang, Pao-Tien] Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA. [Mackem, Susan] NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Yang, YZ (reprint author), NHGRI, Genet Dis Res Branch, 49 Covent Dr,MSC 4472, Bethesda, MD 20892 USA. EM yingzi@mail.nih.gov FU NHLBI NIH HHS [HL66600, HL67822]; NIDDK NIH HHS [DK56246] NR 27 TC 111 Z9 126 U1 1 U2 14 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN 1 PY 2008 VL 135 IS 11 BP 1947 EP 1956 DI 10.1242/dev.018044 PG 10 WC Developmental Biology SC Developmental Biology GA 299HW UT WOS:000255747700006 PM 18434416 ER PT J AU Lu, J Guo, S Ebert, BL Zhang, H Peng, X Bosco, J Pretz, J Schlanger, R Wang, JY Mak, RH Dombkowski, DM Preffer, FI Scadden, DT Golub, TR AF Lu, Jun Guo, Shangqin Ebert, Benjamin L. Zhang, Hao Peng, Xiao Bosco, Jocelyn Pretz, Jennifer Schlanger, Rita Wang, Judy Y. Mak, Raymond H. Dombkowski, David M. Preffer, Frederic I. Scadden, David T. Golub, Todd R. TI MicroRNA-mediated control of cell fate in megakaryocyte-erythrocyte progenitors SO DEVELOPMENTAL CELL LA English DT Article ID C-MYB GENE; TRANSCRIPTIONAL REGULATION; T-CELLS; IN-VIVO; EXPRESSION; DIFFERENTIATION; HEMATOPOIESIS; ERYTHROPOIESIS; TARGETS; MIR-150 AB Lineage specification is a critical issue in developmental and regenerative biology. We hypothesized that microRNAs (miRNAs) are important participants in those processes and used the poorly understood regulation of megakaryocyte-erythrocyte progenitors (MEPs) in hematopoiesis as a model system. We report here that miR-150 modulates lineage fate in MEPs. Using a novel methodology capable of profiling miRNA expression in small numbers of primary cells, we identify miR-150 as preferentially expressed in the megakaryocytic lineage. Through gain- and loss-of-function experiments, we demonstrate that miR-150 drives MEP differentiation toward megakaryocytes at the expense of erythroid cells in vitro and in vivo. Moreover, we identify the transcription factor MYB as a critical target of miR-150 in this regulation. These experiments show that miR-150 regulates MEP fate, and thus establish a role for miRNAs in lineage specification of mammalian multipotent cells. C1 [Lu, Jun; Ebert, Benjamin L.; Zhang, Hao; Peng, Xiao; Bosco, Jocelyn; Pretz, Jennifer; Wang, Judy Y.; Mak, Raymond H.; Golub, Todd R.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Lu, Jun; Ebert, Benjamin L.; Zhang, Hao; Peng, Xiao; Bosco, Jocelyn; Pretz, Jennifer; Wang, Judy Y.; Mak, Raymond H.; Golub, Todd R.] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. [Lu, Jun; Ebert, Benjamin L.; Golub, Todd R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02129 USA. [Guo, Shangqin; Schlanger, Rita; Scadden, David T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02129 USA. [Dombkowski, David M.; Preffer, Frederic I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA. [Guo, Shangqin; Schlanger, Rita; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Golub, Todd R.] Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Ebert, Benjamin L.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. RP Golub, TR (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM golub@broad.mit.edu FU Howard Hughes Medical Institute NR 37 TC 186 Z9 193 U1 1 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JUN PY 2008 VL 14 IS 6 BP 843 EP 853 DI 10.1016/j.devcel.2008.03.012 PG 11 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 312EP UT WOS:000256652200007 PM 18539114 ER PT J AU Egede, LE Ellis, C AF Egede, Leonard E. Ellis, Charles TI The effects of depression on diabetes knowledge, diabetes self-management, and perceived control in indigent patients with type 2 diabetes SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID MEDICATION ADHERENCE; AFRICAN-AMERICANS; HEALTH LITERACY; CARE PROFILE; SYMPTOMS; SCALE; DISEASE; LIFE; HYPERTENSION; RELIABILITY AB Background: This study was designed to assess differences in diabetes knowledge, diabetes self-management, and perceived control among depressed and nondepressed individuals in an indigent population with type 2 diabetes. Research Design and Methods: Depressed and nondepressed patients with the clinical diagnosis of type 2 diabetes were recruited from an indigent care clinic. Subjects completed validated surveys to assess diabetes knowledge, diabetes self-management, and perceived control of diabetes. We compared demographic characteristics and diabetes knowledge, diabetes self-management, and perceived control of diabetes by depression status. Statistical analysis was performed with SPSS version 14.0 (SPSS, Inc., Chicago, IL). Results: Of the 201 subjects with diagnosed type 2 diabetes enrolled in the study, approximately 20% (n = 40) of the sample was depressed. Subjects with depression were more likely to report self-care control problems (mean = 2.2 +/- 1.0 vs. 1.5 +/- 0.6, P < 0.001) and less likely to report positive attitude (mean = 2.9 +/- 0.7 vs. 3.7 +/- 0.5, P < 0.001), self-care ability (mean = 3.2 +/- 3.6 vs. 3.7 +/- 0.5, P < 0.001), and self-care adherence (mean = 3.3 +/- 0.9 vs. 4.1 +/- 0.6, P < 0.001). Depressed patients were less likely to report perceived control of diabetes (mean = 47.7 +/- 8.5 vs. 57.8 +/- 7.4, P < 0.001). There were no significant differences in diabetes knowledge, self-care understanding, and Perceived importance of self-care between depressed and nondepressed patients. Conclusions: In this indigent population with type 2 diabetes, diabetes knowledge did not differ significantly by depression status, but diabetes self-management practices and perceived control of diabetes differed significantly by depression status. Patients who were depressed had poorer diabetes self-care and felt they had less control over their disease. C1 [Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, Charleston, SC 29425 USA. [Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Charleston VA Targeted Res Enhancement Program, Charleston, SC USA. [Ellis, Charles] Med Univ S Carolina, Dept Rehabil Sci, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, 135 Rutledge Ave,Room 280H, Charleston, SC 29425 USA. EM egedel@musc.edu FU AHRQ HHS [5K08HS114418, K08 HS011418] NR 39 TC 39 Z9 40 U1 4 U2 12 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD JUN PY 2008 VL 10 IS 3 BP 213 EP 219 DI 10.1089/dia.2007.0278 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 311PD UT WOS:000256611200009 PM 18473696 ER PT J AU Cibas, ES Alexander, EK Benson, CB de Agustin, PP Doherty, GM Faquin, WC Middleton, WD Miller, T Raab, SS White, ML Mandel, SJ AF Cibas, Edmund S. Alexander, Erik K. Benson, Carol B. de Agustin, Pedro Patricio Doherty, Gerard M. Faquin, William C. Middleton, William D. Miller, Theodore Raab, Stephen S. White, Matthew L. Mandel, Susan J. TI Indications for thyroid FNA and Pre-FNA requirements: A Synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT National-Cancer-Institute Conference on Thyroid Fine-Needle Aspiratin State of the Science CY OCT 22-23, 2007 CL Bethesda, MD SP Natl Canc Inst DE thyroid; cytology; fine-needle aspiration; indications; consent form ID POSITRON-EMISSION-TOMOGRAPHY; PHYSICIAN-PATIENT COMMUNICATION; MOLECULAR-WEIGHT HEPARIN; INFORMED CONSENT FORMS; ENDEMIC GOITER AREA; HASHIMOTOS-THYROIDITIS; PAPANICOLAOU-SOCIETY; DIAGNOSTIC-ACCURACY; HEALTHY-SUBJECTS; DECISION-MAKING AB The National Cancer Institute (NCI) sponsored the NCI Thyroid Fine-Needle Aspiration (FNA) State of the Science Conference on October 22-23, 2007 in Bethesda, MD. The 2-day meeting was accompanied by a permanent informational website and several on-line discussions between May 1 and December 15, 2007 (http://thyroidfna.cancer.gov). This document summarizes the indications for performing an FNA of a nodule discovered by physical examination or an imaging study; the indications for using ultrasound versus palpation for guidance when performing a thyroid FNA; the issues surrounding informed consent for thyroid FNA; and the information required on a requisition form that accompanies a thyroid FNA specimen. C1 [Cibas, Edmund S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Cibas, Edmund S.; Faquin, William C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Alexander, Erik K.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Alexander, Erik K.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Benson, Carol B.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Benson, Carol B.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [de Agustin, Pedro Patricio] Univ Hosp 12 de Octubre, Dept Pathol, Madrid, Spain. [Doherty, Gerard M.; White, Matthew L.] St Joseph Mercy Hosp, Dept Surg, Ann Arbor, MI 48104 USA. [Doherty, Gerard M.; White, Matthew L.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Middleton, William D.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Miller, Theodore] Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA. [Raab, Stephen S.] Univ Colorado Denver, Dept Pathol, Aurora, CO USA. [Mandel, Susan J.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. RP Cibas, ES (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM ecibas@partners.org OI Doherty, Gerard/0000-0002-1685-9552 NR 109 TC 54 Z9 56 U1 3 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD JUN PY 2008 VL 36 IS 6 BP 390 EP 399 DI 10.1002/dc.20827 PG 10 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 312EN UT WOS:000256652000008 PM 18478607 ER PT J AU Pitman, MB Abele, J Ali, SZ Duick, D Elsheikh, TM Jeffrey, RB Powers, CN Randolph, G Renshaw, A Scoutt, L AF Pitman, Martha Bishop Abele, John Ali, Syed Z. Duick, Dan Elsheikh, Tarik M. Jeffrey, R. Brooke Powers, Celeste N. Randolph, Gregory Renshaw, Andrew Scoutt, Leslie TI Techniques for thyroid FNA: A Synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT National-Cancer-Institute Conference on Thyroid Fine-Needle Aspiratin State of the Science CY OCT 22-23, 2007 CL Bethesda, MD SP Natl Canc Inst DE thyroid; fine-needle aspiration biopsy; technique; methods; ultrasound; core biopsy; adequacy; adverse reactions ID SMEAR CYTOPREPARATORY TECHNIQUES; GUIDED CORE BIOPSY; DIAGNOSTIC-ACCURACY; PAPILLARY CARCINOMA; ADEQUACY ASSESSMENT; SPECIMEN ADEQUACY; CELL BLOCK; THINPREP(R) PREPARATIONS; CYTOLOGIC PREPARATIONS; FOLLICULAR VARIANT AB The National Cancer Institute (NCI) sponsored the NCI Thyroid fine-needle aspiration (FNA) State of the Science Conference on October 22-23, 2007 in Bethesda, MD. The 2-day meeting was accompanied by a permanent informational website and several on-line discussion periods between May I and December 15, 2007 (http://tliyroidfna.cancer.gov). This document summarizes matters addressing manual and ultrasound guided FNA technique and related issues. Specific topics covered include details regarding aspiration needles, devices, and methods, including the use of core needle biopsy; the pros and cons of anesthesia; the influence of thyroid lesion location, size, and characteristics on technique; the role of ultrasound in the FNA of a palpable thyroid nodule; the advantages and disadvantages of various specialists performing a biopsy; the optimal number of passes and tissue preparation methods; sample adequacy criteria for solid and cystic nodules, and management of adverse reactions from the procedure. C1 [Pitman, Martha Bishop] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Abele, John] Univ Calif San Francisco, Sacramento, CA USA. [Ali, Syed Z.] Johns Hopkins Univ, Johns Hopkins Hosp, Dept Pathol, Baltimore, MD USA. [Duick, Dan] Endocrinol Associates PA, Phoenix, AZ USA. [Elsheikh, Tarik M.] Ball Mem Hosp, PA Labs, Muncie, IN 47303 USA. [Jeffrey, R. Brooke] Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA. [Powers, Celeste N.] Virginia Commonwealth Univ, Med Coll Virginia Hosp, Dept Pathol, Richmond, VA USA. [Randolph, Gregory] Massachusetts Eye & Ear Infirm, Dept Surg, Boston, MA 02114 USA. [Randolph, Gregory] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Renshaw, Andrew] Baptist Hosp Miami, Dept Pathol, Miami, FL USA. [Scoutt, Leslie] Yale Univ, Dept Radiol, New Haven, CT USA. RP Pitman, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM mpitman@partners.org NR 136 TC 62 Z9 65 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD JUN PY 2008 VL 36 IS 6 BP 407 EP 424 DI 10.1002/dc.20829 PG 18 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 312EN UT WOS:000256652000010 PM 18478608 ER PT J AU Dang, H Elliott, JJ Lin, AL Zhu, B Katz, MS Yeh, CK AF Dang, Howard Elliott, James J. Lin, Alan L. Zhu, Bing Katz, Michael S. Yeh, Chih-Ko TI Mitogen-activated protein kinase up-regulation and activation during rat parotid gland atrophy and regeneration: role of epidermal growth factor and beta 2-adrenergic receptors SO DIFFERENTIATION LA English DT Article DE salivary gland; extracellular signal-regulated kinase; p38; tissue regeneration ID ELECTRON MICROSCOPIC ALTERATIONS; SUBMANDIBULAR-GLANDS; MYOEPITHELIAL CELLS; SIGNALING PATHWAY; SALIVARY-GLANDS; DUCT LIGATION; ACINAR-CELLS; OBSTRUCTION; RECOVERY; ISOPROTERENOL AB The rat secretory ductal obstruction model has been widely used to assess salivary gland injury, growth, and differentiation. In this study, a novel ductal obstruction and release procedure was used to explore the signaling pathways leading to salivary gland regeneration. Rats underwent bilateral parotid ductal obstruction in which the duct was occluded against a plastic disk subcutaneously and released by external ligature removal. This ductal obstruction/release procedure was validated to produce glandular atrophy and regeneration with histological analysis and periodic acid-Schiff staining. Immunoblot analysis indicated that during ductal obstruction and the early post-release period (day 7), expression of immunoreactive proliferating cell nuclear antigen and vimentin was increased in the parotid glands compared with sham-operated animals. Immunohistochemical staining and immunoblots revealed up-regulation of the mitogen-activated protein kinases (MAPKs), extracellular signal-regulated receptor kinase (ERK)1/2, and p38 during the atrophic and regeneration phases of ductal obstruction/release. Similarly, increases in activated, i.e., phosphorylated, ERK1/2 (pERK1/2) and p38 (phospho-p38) were demonstrable in both ductal and recovering acinar cells, with pERKs expressed predominantly in the nuclei and phospho-p38 distributed throughout the cells. Furthermore, levels of epidermal growth factor (EGF) receptor and beta 2-adrenergic receptor (beta 2-AR) were elevated in the ligated glands and at day 7 post-release; beta 1-AR levels did not change over the same time period. These results support the view that cell proliferation is involved in duct ligation-induced atrophy of the rat parotid gland and gland recovery upon ligature removal. Up-regulation of ERKs and p38, and the activation of these MAPKs by up-regulated EGF and beta 2-ARs, may be important signaling components underlying glandular atrophy and subsequent regeneration. C1 [Lin, Alan L.; Yeh, Chih-Ko] Univ Texas Hlth Sci Ctr San Antonio, Dept Dent Diagnost Sci, San Antonio, TX 78249 USA. [Dang, Howard] Univ Texas Hlth Sci Ctr San Antonio, Dept Community Dent, San Antonio, TX USA. [Elliott, James J.] Univ Texas Hlth Sci Ctr San Antonio, Lab Anim Resource, San Antonio, TX USA. [Lin, Alan L.; Zhu, Bing; Katz, Michael S.; Yeh, Chih-Ko] Audie L Murphy Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Audie L Murphy Div, San Antonio, TX 78229 USA. [Katz, Michael S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78284 USA. RP Yeh, CK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Dent Diagnost Sci, San Antonio, TX 78249 USA. EM Yeh@uthscsa.edu FU NIDCR NIH HHS [R21DE15381] NR 42 TC 10 Z9 11 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD JUN PY 2008 VL 76 IS 5 BP 546 EP 557 DI 10.1111/j.1432-0436.2007.00251.x PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 304NZ UT WOS:000256117500010 PM 18177419 ER PT J AU Leung, FW AF Leung, Felix W. TI Methods of reducing discomfort during colonoscopy SO DIGESTIVE DISEASES AND SCIENCES LA English DT Review DE colonoscopy; sedated; unsedated; as-needed; on-demand ID RANDOMIZED CONTROLLED-TRIAL; PATIENT-CONTROLLED SEDATION; VARIABLE-STIFFNESS COLONOSCOPE; CARBON-DIOXIDE INSUFFLATION; COLORECTAL-CANCER; NITROUS-OXIDE; INCOMPLETE COLONOSCOPY; UNSEDATED ENDOSCOPY; CONSCIOUS SEDATION; SELECTIVE SEDATION AB In the United States sedation for colonoscopy is usual practice. Unsedated colonoscopy is limited to a small proportion of unescorted patients and those with a personal preference for no sedation. Over 80% of patients who accept the option of as-needed sedation can complete colonoscopy without sedation. Colonoscopy in these unsedated patients is performed with techniques similar to those used in the sedated patients. Uncontrolled observations indicate willingness to repeat colonoscopy amongst these patients was correlated significantly with low discomfort score during the examination. Methods reported to minimize patient discomfort or enhance cecal intubation during sedated or unsedated colonoscopy included use of pediatric colonoscope, variable stiffness colonoscope, gastroscope, and inhalation of nitrous oxide or insufflation of carbon dioxide, hypnosis, music, audio distraction, or simply allowing the patients to participate in administration of the medication. Research focusing on confirming the efficacy of a simple inexpensive nonmedication dependent method for minimizing discomfort will likely improve the outcome of care and more importantly will ensure compliance with future surveillance in patients accepting the unsedated option. C1 [Leung, Felix W.] Sepulveda Ambulatory Care Ctr, Div Gastroenterol 111G, Sepulveda, CA 91343 USA. [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Leung, Felix W.] VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Res & Med Serv, Los Angeles, CA USA. RP Leung, FW (reprint author), Sepulveda Ambulatory Care Ctr, Div Gastroenterol 111G, 16111 Plummer St, Sepulveda, CA 91343 USA. EM felix.leung@va.gov NR 66 TC 41 Z9 42 U1 1 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUN PY 2008 VL 53 IS 6 BP 1462 EP 1467 DI 10.1007/s10620-007-0025-9 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 302GB UT WOS:000255955700004 PM 17999189 ER PT J AU Leung, FW AF Leung, Felix W. TI Endoscopic reflectance spectrophotometry and visible light spectroscopy in clinical gastrointestinal studies SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE mucosal blood flow; reflectance spectrophotometry; visible light spectroscopy ID PORTAL-HYPERTENSIVE GASTROPATHY; GASTRIC-MUCOSAL HEMODYNAMICS; BLOOD-FLOW; CIRRHOTIC-PATIENTS; OXYGEN-SATURATION; DUODENAL-ULCERS; PERFUSION; VASOPRESSIN; ISCHEMIA; COLON AB The use of reflectance spectrophotometry (RS) for mucosal hemodynamic measurement relies on the recognition of changes in indexes of mucosal hemoglobin concentration and oxygen saturation. Endoscopic application in clinical studies has confirmed important observations demonstrated in animal experiments. The vasoconstriction induced by propranolol, vasopressin, glypressin, or somatostatin in the portal hypertensive gastric mucosa and the reduction of gastroduodenal mucosal perfusion by nonsteroidal anti-inflammatory drugs (NSAIDs) or smoking, mesenteric venoconstriction associated with systemic hypoxia, and acid-induced duodenal hyperemia are important examples. Prognostic predictions include the development of stress-induced gastric ulcerations in patients with significant reductions in gastric perfusion after thermal or head injury, or the demonstration of delayed gastric or duodenal ulcer healing when the hyperemia at the ulcer margin fails to materialize. In mechanical-ventilator-dependent patients with sepsis, a significantly reduced gastric mucosal RS measurement portends a grave prognosis (mortality >80%). Recent advances in technology resulted in the construction and validation of instruments for visible light spectroscopy. Measurements focused on tissue oxygen saturation demonstrated epinephrine and vessel-ligation-induced vasoconstriction, the absence of ischemia in radiation-induced rectal telangiectasias, and gut ischemia responsive to revascularization treatment. Endoscopic RS and visible light spectroscopy are suitable for assessing the role of blood flow in conditions with a lesser degree of ischemia and for testing the hypothesis that functional dyspepsia and dysmotility syndromes may be due to gut ischemia. C1 [Leung, Felix W.] VA Greater Los Angeles Healthcare Syst, Div Gastroenterol 111G, Res & Med Serv, Sepulveda Ambulatory Care Ctr, Sepulveda, CA 91343 USA. [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Leung, FW (reprint author), VA Greater Los Angeles Healthcare Syst, Div Gastroenterol 111G, Res & Med Serv, Sepulveda Ambulatory Care Ctr, 16111 Plummer St,North Hills, Sepulveda, CA 91343 USA. EM felix.leung@va.gov NR 43 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUN PY 2008 VL 53 IS 6 BP 1669 EP 1677 DI 10.1007/s10620-007-0026-8 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 302GB UT WOS:000255955700031 PM 17932761 ER PT J AU Tabibian, JH Wirshing, DA Pierre, JM Guzik, LH Kisicki, MD Danovitch, I Mena, SJ Wirshing, WC AF Tabibian, James H. Wirshing, Donna A. Pierre, Joseph M. Guzik, Lisa H. Kisicki, Michael D. Danovitch, Itai Mena, Shirley J. Wirshing, William C. TI Hepatitis B and C among veterans on a psychiatric ward SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE hepatitis; epidemiology; psychiatric; veterans; risk factors ID VIRUS-INFECTION; MENTAL-DISORDERS; SUBSTANCE-ABUSE; SEXUAL-BEHAVIOR; RISK BEHAVIOR; PREVALENCE; HIV; SCHIZOPHRENIA; INPATIENTS; THERAPY AB Hepatitis B and C are public health problems. Psychiatric patients may be at risk of hepatitis B and C exposure due to lifestyle and inadequate health care. We aimed to determine prevalence of hepatitis B and C virus exposure and associated risk factors in acutely hospitalized psychiatric veterans. A total of 234 individuals consecutively admitted to the psychiatric wards at the West Los Angeles Veterans Affairs Hospital were asked to participate. A total of 129 patients consented and were screened for viral hepatitis risk factors, hepatitis B surface antigen, hepatitis B surface and core antibodies, and hepatitis C antibodies. About 31 and 38% of the patients had been exposed to hepatitis B and C viruses, respectively. Several risk factors were associated with exposure. Inpatient psychiatric veterans seem to have increased rates of hepatitis B and C exposure. This highlights the need for prevention of risk behavior in this vulnerable population. C1 [Tabibian, James H.; Wirshing, Donna A.; Pierre, Joseph M.; Guzik, Lisa H.; Kisicki, Michael D.; Danovitch, Itai; Mena, Shirley J.; Wirshing, William C.] Univ Calif Los Angeles, Dept Psychiat, W Los Angeles Vet Affairs Hosp, David Geffen Sch Med, Los Angeles, CA 90024 USA. RP Tabibian, JH (reprint author), Univ Calif Los Angeles, Dept Psychiat, W Los Angeles Vet Affairs Hosp, David Geffen Sch Med, 1440 Vet Ave 601, Los Angeles, CA 90024 USA. EM jhtabib@ucla.edu NR 30 TC 8 Z9 9 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUN PY 2008 VL 53 IS 6 BP 1693 EP 1698 DI 10.1007/s10620-007-0045-5 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 302GB UT WOS:000255955700034 PM 17932751 ER PT J AU Mirchandani, KD McCaffrey, RM D'Andrea, AD AF Mirchandani, Kanchan D. McCaffrey, Ryan M. D'Andrea, Alan D. TI The Fanconi anemia core complex is required for efficient point mutagenesis and Rev1 foci assembly SO DNA REPAIR LA English DT Article DE Fanconi anemia; translesion synthesis; mutagenesis; DNA repair ID TRANSLESION DNA-SYNTHESIS; CELL NUCLEAR ANTIGEN; UV-INDUCED MUTATIONS; HOMOLOGOUS RECOMBINATION; BRCT DOMAIN; MONOUBIQUITINATED FANCD2; FUNCTIONAL INTERACTION; PROTEIN INTERACTS; DAMAGE TOLERANCE; MAMMALIAN-CELLS AB Fanconi anemia (FA) is a chromosome instability syndrome characterized by congenital abnormalities, cellular hypersensitivity to DNA crosslinking agents, and heightened cancer risk. Eight of the thirteen identified FA genes encode subunits of a nuclear FA core complex that monoubiquitinates FANCD2 and FANCI to maintain genomic stability in response to replication stress. The FA pathway has been implicated in the regulation of error-prone DNA damage tolerance via an undefined molecular mechanism. Here, we show that the FA core complex is required for efficient spontaneous and UVC-induced point mutagenesis, independently of FANCD2 and FANCI Consistent with the observed hypomutability of cells deficient in the FA core complex, we also demonstrate that these cells are impaired in the assembly of the error-prone translesion DNA synthesis polymerase Rev1 into nuclear foci. Consistent with a role downstream of the FA core complex and like known FA proteins, Rev1 is required to prevent DNA crosslinker-induced chromosomal aberrations in human cells. Interestingly, proliferating cell nuclear antigen (PCNA) monoubiquitination, known to contribute to Rev1 recruitment, does not require FA core complex function. Our results suggest a role for the FA core complex in regulating Rev1-dependent DNA damage tolerance independently of FANCD2, FANCI, and PCNA monoubiquitination. (c) 2008 Elsevier B.V. All rights reserved. C1 [D'Andrea, Alan D.] Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Canc Inst,Div Genom Stabil & DNA Repa, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Canc Inst,Div Genom Stabil & DNA Repa, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu FU NHLBI NIH HHS [P50 HL054785-060007, R01 HL052725, R01 HL052725-10, R37 HL052725, P50 HL054785, P01-HL54785, R01-HL52725]; NIDDK NIH HHS [R01 DK043889, R01 DK043889-10, R01-DK43889] NR 59 TC 65 Z9 66 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD JUN 1 PY 2008 VL 7 IS 6 BP 902 EP 911 DI 10.1016/j.dnarep.2008.03.001 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 317VU UT WOS:000257049200008 PM 18448394 ER PT J AU Wilens, TE Biederman, J Adamson, JJ Henin, A Sgambati, S Gignac, M Sawtelle, R Santry, A Monuteaux, MC AF Wilens, Timothy E. Biederman, Joseph Adamson, Joel J. Henin, Aude Sgambati, Stephanie Gignac, Martin Sawtelle, Robert Santry, Alison Monuteaux, Michael C. TI Further evidence of an association between adolescent bipolar disorder with smoking and substance use disorders: A controlled study SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE adolescent; mania; bipolar disorder; substance abuse ID DEFICIT HYPERACTIVITY DISORDER; PROSPECTIVE FOLLOW-UP; COMORBIDITY SURVEY REPLICATION; NATIONAL EPIDEMIOLOGIC SURVEY; MANIC-DEPRESSIVE ILLNESS; PAST 10 YEARS; CONDUCT DISORDER; DRUG-ABUSE; COCAINE ABUSERS; PSYCHIATRIC-DIAGNOSIS AB Although previous work suggests that juvenile onset bipolar disorder increases risk for substance use disorders and cigarette smoking, the literature on the subject is limited. We evaluated the association of risk for substance use disorders and cigarette smoking with bipolar disorder in adolescents in a case-control study of adolescents with bipolar disorder (n = 105, age 13.6 +/- 2.5 years [mean]; 70% male) and without bipolar disorder ("controls"; it = 98, age 13.7 +/- 2.1 years; 60% male). Rates of substance use and other disorders were assessed with structured interviews (KSADS-E for subjects younger than 18, SCID for 18-year-old subjects). Bipolar disorder was associated with a significant age-adjusted risk for any substance use disorder (hazard ratio[95% confidence interval] = 8.68[3.02 25.0], chi(2) = 16.06, p < 0.001, df = 1), alcohol abuse (7.66 [2.20 26.7], chi(2) = 10.2, p = 0.001, df = 1), drug abuse (18.5 [2.46 139.10], chi(2) = 8.03, p = 0.005, df = 1) and dependence (12.1 [1.54 95.50], chi(2) = 5.61, p = 0.02, df = 1), and cigarette smoking (12.3 [2.83 53.69], chi(2) = 11.2, p < 0.001, df = 1), independently of attention deficit/hyperactivity disorder, multiple anxiety, and conduct disorder (CD). The primary predictor of substance use disorders in bipolar youth was older age (BPD - SUD versus BPD + SUD, logistic regression: chi(2) = 89.37, p < 0.001). Adolescent bipolar disorder is a significant risk factor for substance use disorders and cigarette smoking, independent of psychiatric comorbidity. Clinicians should carefully screen adolescents with bipolar disorder for substance and cigarette use. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Wilens, Timothy E.; Biederman, Joseph; Adamson, Joel J.; Henin, Aude; Sgambati, Stephanie; Sawtelle, Robert; Santry, Alison; Monuteaux, Michael C.] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Wilens, Timothy E.; Biederman, Joseph; Monuteaux, Michael C.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Gignac, Martin] Univ Montreal, Inst Philippe Pinel, Montreal, PQ H3C 3J7, Canada. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 32 Fruit St,YAW 6A, Boston, MA 02114 USA. EM twilens@partners.org OI Adamson, Joel/0000-0002-1399-5786 FU NIDA NIH HHS [K24 DA016264, K24 DA016264-04, R01 DA012945, R01 DA012945-08] NR 89 TC 48 Z9 48 U1 7 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUN 1 PY 2008 VL 95 IS 3 BP 188 EP 198 DI 10.1016/j.drugalcdep.2007.12.016 PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 308RM UT WOS:000256407700001 PM 18343050 ER PT J AU Nagai, H Russell, JA Jackson, MA Connor, NP AF Nagai, Hiromi Russell, John A. Jackson, Michelle A. Connor, Nadine P. TI Effect of aging on tongue protrusion forces in rats SO DYSPHAGIA LA English DT Article DE dysphagia; tongue force; aging; deglutition; deglutition disorders ID CONTRACTILE PROPERTIES; RETRACTOR MUSCLES; SWALLOWING DISORDERS; MOTOR UNITS; AGE; PHARYNGEAL; PROTRUDOR; FATIGUABILITY; COACTIVATION; STIMULATION AB The purpose of this study was to ascertain the effect of aging on muscle contractile properties associated with tongue protrusion in a rat model. Fischer 344/Brown Norway hybrid rats, ten young (9 months old) and ten old (32 months old), were used to measure protrusive contractile properties. Results showed a significant reduction in tetanic forces in the old animals. The following measures of muscle contraction were not different between age groups: mean twitch contraction force, twitch contraction time, twitch contraction half-decay time, and a calculated measure of fatigability. In conclusion, aging influenced protrusive tongue muscle contractions in a rat model such that tetanic forces were reduced. The reduction of tetanus force may parallel findings in human subjects relative to isometric tongue force generation and may be associated with age-related disorders of swallowing. C1 [Nagai, Hiromi; Jackson, Michelle A.; Connor, Nadine P.] Univ Wisconsin, Dept Surg, Div Otolaryngol Head & Neck Surg, Madison, WI 53792 USA. [Nagai, Hiromi] Kitasato Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Kanagawa, Japan. [Russell, John A.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53792 USA. [Connor, Nadine P.] Univ Wisconsin, Dept Communicat Disorders, Madison, WI 53792 USA. RP Connor, NP (reprint author), 600 Highland Ave,Room K4-711, Madison, WI 53792 USA. EM Connor@surgery.wisc.edu FU NIDCD NIH HHS [R01 DC005935, R01 DC005935-03, R01 DC008149, R01 DC008149-01A1, R01DC005935, R01DC008149] NR 30 TC 12 Z9 12 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD JUN PY 2008 VL 23 IS 2 BP 116 EP 121 DI 10.1007/s00455-007-9103-6 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 307LH UT WOS:000256319900004 PM 17694408 ER PT J AU Gross, RD Atwood, CW Ross, SB Eichhorn, KA Olszewski, JW Doyle, PJ AF Gross, Roxann Diez Atwood, Charles W., Jr. Ross, Sheryl B. Eichhorn, Kimberly A. Olszewski, Joan W. Doyle, Patrick J. TI The coordination of breathing and swallowing in Parkinson's disease SO DYSPHAGIA LA English DT Article DE Parkinson's disease; oropharyngeal dysphagia; swallowing; respiratory control; deglutition; deglutition disorders; subglottic air pressure ID TRACHEOSTOMY SPEAKING VALVE; INTENSIVE SPEECH TREATMENT; PASSY-MUIR VALVE; SUBTHALAMIC NUCLEUS; PULMONARY DYSFUNCTIONS; RESPIRATORY PATTERNS; ELDERLY-PATIENTS; FOLLOW-UP; ASPIRATION; DYSPHAGIA AB Multiple investigations have determined that healthy adults swallow most often during exhalation and that exhalation regularly follows the swallow, even when a swallow occurs during inhalation. We hypothesized that persons with idiopathic Parkinson's disease would demonstrate impaired breathing and swallowing coordination during spontaneous eating. Twenty-five healthy volunteers and 25 Parkinson's disease patients spontaneously swallowed calibrated pudding and cookie portions while simultaneous nasal airflow and respiratory inductance plethysmography were used to track spontaneous breathing. Surface EMG was used to record the timing of each swallow within the respiratory cycle. When compared to the healthy control group, those with Parkinson's disease swallowed significantly more often during inhalation and at low tidal volumes. The Parkinson's participants also exhibited significantly more postswallow inhalation for both consistencies. Only the healthy subjects exhibited significantly longer deglutitive apnea when swallows that occurred during inhalation were compared with those that occurred during exhalation. The high incidence of oropharyngeal dysphagia and risk of aspiration pneumonia found in Parkinson's disease patients may be partially attributable to impaired coordination of breathing and swallowing. C1 [Gross, Roxann Diez; Ross, Sheryl B.] Univ Pittsburgh, Inst Eye & Ear, Div Otolaryngol, Pittsburgh, PA 15213 USA. [Atwood, Charles W., Jr.; Eichhorn, Kimberly A.; Doyle, Patrick J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Olszewski, Joan W.] Henry Ford Hosp, Detroit, MI 48202 USA. RP Gross, RD (reprint author), Univ Pittsburgh, Inst Eye & Ear, Div Otolaryngol, Suite 500,200 Lothrop St, Pittsburgh, PA 15213 USA. EM Grossrd@upmc.edu NR 68 TC 34 Z9 41 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD JUN PY 2008 VL 23 IS 2 BP 136 EP 145 DI 10.1007/s00455-007-9113-4 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA 307LH UT WOS:000256319900007 PM 18027027 ER PT J AU Bao, YW Newburg, DS AF Bao, Yuanwu Newburg, David S. TI Capillary electrophoresis of acidic oligosaccharides from human milk SO ELECTROPHORESIS LA English DT Review DE capillary electrophoresis; human milk oligosaccharides; sialyloligosaccharides ID LASER-INDUCED FLUORESCENCE; ANION-EXCHANGE CHROMATOGRAPHY; PULSED AMPEROMETRIC DETECTION; N-LINKED OLIGOSACCHARIDES; SELECTIVE PRECOLUMN DERIVATIZATION; PERFORMANCE LIQUID-CHROMATOGRAPHY; SULFATE-DERIVED DISACCHARIDES; TANDEM MASS-SPECTROMETRY; BREAST-FED INFANTS; ZONE-ELECTROPHORESIS AB Interest in defining the array of oligosaccharides of human milk has been increasing. Pathogens that bind glycans on their host mucosal surfaces may be inhibited by human milk oligosaccharides. It has been postulated that acidic oligosaccharides in human milk may inhibit binding by pathogens that bind acidic glycans in the gut, but testing this hypothesis requires their reliable quantification in milk. Sialyloligosaccharides of human milk have been quantified by HPLC and CE. A recent CE technique uses the MEKC mode with direct detection at 205 nm to resolve and quantify, in the native form, the 12 most dominant sialyloligosaccharides of human milk in a single 35-min run. The method gives a linear response from 39 to 2500 mu g/mL with a coefficient of variation between 2 to 9% and accuracy from 93 to 109%. This was used to detect variation in expression of specific sialyloligosaccharides in milk. Individual sialyloligosaccharide concentrations in milk differ among individual donors and between less and more mature milk. Thus, CE can be used to measure variation in sialyloligosaccharide expression in milk, and thereby test the relationship of this variation-to-variation in risk of specific diseases in breastfed infants. C1 [Newburg, David S.] Massachusetts Gen Hosp, Program Glycobiol Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. [Bao, Yuanwu; Newburg, David S.] Harvard Univ, Sch Med, Boston, MA USA. RP Newburg, DS (reprint author), Massachusetts Gen Hosp, Program Glycobiol Pediat Gastroenterol & Nutr, 114 16th St, Charlestown, MA 02129 USA. EM dnewburg@partners.org FU NICHD NIH HHS [HD013021]; NIDDK NIH HHS [DK040561] NR 78 TC 17 Z9 17 U1 5 U2 29 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0173-0835 EI 1522-2683 J9 ELECTROPHORESIS JI Electrophoresis PD JUN PY 2008 VL 29 IS 12 BP 2508 EP 2515 DI 10.1002/elps.200700873 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 323XI UT WOS:000257481300008 PM 18512675 ER PT J AU Huang, ST Boulos, MNK Dellavalle, RP AF Huang, Stephen T. Boulos, Maged N. Kamel Dellavalle, Robert P. TI Scientific discourse 2.0 - Will your next poster session be in Second Life (R)? SO EMBO REPORTS LA English DT Editorial Material ID VIRTUAL WORLDS; EDUCATION; HEALTH C1 [Huang, Stephen T.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Boulos, Maged N. Kamel] Univ Plymouth, Plymouth PL4 8AA, Devon, England. [Dellavalle, Robert P.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Dellavalle, Robert P.] Univ Colorado, Denver, CO 80202 USA. RP Huang, ST (reprint author), Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. EM robert.dellavalle@uchsc.edu RI Dellavalle, Robert/L-2020-2013; Kamel Boulos, Maged/B-3728-2013 OI Dellavalle, Robert/0000-0001-8132-088X; Kamel Boulos, Maged/0000-0003-2400-6303 NR 28 TC 16 Z9 16 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD JUN PY 2008 VL 9 IS 6 BP 496 EP 499 DI 10.1038/embor.2008.86 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 307GW UT WOS:000256308400003 PM 18516082 ER PT J AU Ellis, C Breland, HL Egede, LE AF Ellis, Charles Breland, Hazel L. Egede, Leonard E. TI RACIAL/ETHNIC DIFFERENCES IN UTILIZATION OF POST-STROKE REHABILITATION SERVICES: A SYSTEMATIC REVIEW SO ETHNICITY & DISEASE LA English DT Review DE Stroke; Rehabilitation; Race/Ethnicity ID HEALTH-CARE SYSTEM; INPATIENT STROKE REHABILITATION; ISCHEMIC-STROKE; RACIAL DISPARITIES; UNITED-STATES; ETHNIC-DIFFERENCES; VETERANS AFFAIRS; HIP FRACTURE; MORTALITY; OUTCOMES AB Objective: To examine racial/ethnic differences in utilization of stroke-related rehabilitation. Methods: We searched Medline (from 1966-2007), CINAHL (from 1982-2007), PsycINFO (1966-2007), REHABDATA (1966-2007), the Cochrane Library, and reference lists of published articles. We identified 82 studies in our initial search, including randomized and quasi-randomized controlled trials, working papers, technical reports, and conference presentations of stroke patients that reported utilization of rehabilitation services including physical therapy (PT), occupational therapy (OT), speech-language pathology (SLP), and at least two groups that differed by race/ethnicity. Because of limited information on outcomes and heterogeneity of the studies, a formal meta-analysis was not conducted. A qualitative aggregation of study findings was performed instead. Results: Ten studies involving 214,229 patients met the final criteria for review. Racial/ethnic minorities were more likely to receive rehabilitation and have longer lengths of stays in studies that reported use of rehabilitation services. In contrast, when studies reported discipline-specific (PT, OT, SLP) utilization of services, the results were mixed. Conclusions: Racial/ethnic differences in the utilization of rehabilitation services primarily reflected the manner in which service utilization was reported. Future studies should be designed to ensure an accurate comparison of service utilization by race/ethnicity. (Ethn Dis. 2008; 18:365-372) C1 [Ellis, Charles; Breland, Hazel L.] Med Univ S Carolina, Dept Rehabil Sci, Charleston, SC 29425 USA. [Egede, Leonard E.] Med Univ S Carolina, Dept Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Charleston VA TREP, Charleston, SC USA. RP Ellis, C (reprint author), Med Univ S Carolina, Dept Rehabil Sci, 151-B Rutledge Ave, Charleston, SC 29425 USA. EM ellisc@musc.edu NR 40 TC 9 Z9 9 U1 0 U2 1 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 SUM PY 2008 VL 18 IS 3 BP 365 EP 372 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 489MC UT WOS:000269423200016 PM 18785453 ER PT J AU van der Meer, P Lok, DJ Januzzi, JL de la Porte, PWBA Lipsic, E van Wijngaarden, J Voors, AA van Gilst, WH van Veldhuisen, DJ AF van der Meer, Peter Lok, Dirk J. Januzzi, James L. de la Porte, Pieta W. Bruggink-Andre Lipsic, Erik van Wijngaarden, Jan Voors, Adriaan A. van Gilst, Wiek H. van Veldhuisen, Dirk J. TI Adequacy of endogenous erythropoietin levels and mortality in anaemic heart failure patients SO EUROPEAN HEART JOURNAL LA English DT Article DE heart failure; anaemia; erythropoietin; prognosis ID SERUM ERYTHROPOIETIN; PROGNOSTIC VALUE; RENAL-FUNCTION; IRON; TRANSPLANTATION; DIAGNOSIS; DISEASE; MARKERS; TRIAL AB Aims We examined the adequacy of endogenous erythropoietin (EPO) levels for the degree of anaemia in patients with chronic heart failure (CHF) and its relation to prognosis. Methods and results We studied 74 anaemic CHF patients from a cohort of 240 patients. The adequacy of endogenous EPO levels was assessed by derived observed/predicted (O/P) ratio. A ratio value < 0.92 indicates EPO levels lower than expected, whereas a value > 1.09 indicates EPO levels higher than expected. The primary endpoint was mortality. During a median follow up of 4.9 years, 35 of the 74 (47.3%) anaemic patients died. EPO levels lower than expected were observed in 29 patients (39%), whereas EPO levels higher than expected were present in 22 anaemic patients (29%). The Kaplan-Meier analysis revealed that anaemic patients with EPO levels higher than expected had a significantly higher mortality rate compared to patients with EPO levels as expected or EPO levels lower than expected (log-rank: P = 0.024). A higher O/P ratio was an independent predictor of increased mortality risk adjusted for variables including age, sex, haemoglobin, NT-proBNP, and renal function; hazard ratio (HR): 1.020 95%CI (1.004-1.036), P = 0.012. Conclusion EPO levels higher than expected, suggesting resistance to the hormone, are common in CHF patients and are associated with a higher mortality. C1 [van der Meer, Peter; Voors, Adriaan A.; van Gilst, Wiek H.; van Veldhuisen, Dirk J.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 AV Groningen, Netherlands. [van der Meer, Peter; Januzzi, James L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [van der Meer, Peter; Januzzi, James L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med, Boston, MA 02114 USA. [Lok, Dirk J.; de la Porte, Pieta W. Bruggink-Andre; Lipsic, Erik; van Wijngaarden, Jan] Deventer Hosp, Dept Cardiol, Deventer, Netherlands. RP van der Meer, P (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 AV Groningen, Netherlands. EM pvandermeer@partners.org RI van Gilst, Wiek/C-3828-2008; van Veldhuisen, Dirk Jan/E-8967-2014 NR 27 TC 45 Z9 46 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JUN PY 2008 VL 29 IS 12 BP 1510 EP 1515 DI 10.1093/eurheartj/ehn205 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 316VK UT WOS:000256977600009 PM 18495690 ER PT J AU Harland, M Goldstein, AM Kukalizch, K Taylor, C Hogg, D Puig, S Badenas, C Gruis, N ter Huurne, J Bergman, W Hayward, NK Stark, M Tsao, H Tucker, MA Landi, MT Scarra, GB Ghiorzo, P Kanetsky, PA Elder, D Mann, GJ Holland, EA Bishop, DT Bishop, JN AF Harland, Mark Goldstein, Alisa M. Kukalizch, Kairen Taylor, Claire Hogg, David Puig, Susana Badenas, Celia Gruis, Nelleke ter Huurne, Jeanet Bergman, Wilma Hayward, Nicholas K. Stark, Mitchell Tsao, Hensin Tucker, Margaret A. Landi, Maria Teresa Scarra, Giovanna Bianchi Ghiorzo, Paola Kanetsky, Peter A. Elder, David Mann, Graham J. Holland, Elizabeth A. Bishop, D. Timothy Bishop, Julia Newton CA GenoMEL Melanoma Genetics Consorti TI A comparison of CDKN2A mutation detection within the Melanoma Genetics Consortium (GenoMEL) SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE CDKN2A; melanoma; mutation detection; sequencing; polymorphism; audit; DHPLC; false negative ID PERFORMANCE LIQUID-CHROMATOGRAPHY; GERMLINE MUTATIONS; FAMILIAL MELANOMA; DENATURING HPLC; DHPLC; CDK4; P16(INK4A); PREVALENCE; PEDIGREES; DELETIONS AB CDKN2A is the major melanoma susceptibility gene so far identified, but only 40% of three or more case families have identified mutations. A comparison of mutation detection rates was carried out by "blind" exchange of samples across GenoMEL, the Melanoma Genetics Consortium, to establish the false negative detection rates. Denaturing high performance liquid chromatography (DHPLC) screening results from 451 samples were compared to screening data from nine research groups in which the initial mutation screen had been done predominantly by sequencing. Three samples with mutations identified at the local centres were not detected by the DHPLC screen. No additional mutations were detected by DHPLC. Mutation detection across groups within GenoMEL is carried out to a consistently high standard. The relatively low rate of CDKN2A mutation detection is not due to failure to detect mutations and implies the existence of other high penetrance melanoma susceptibility genes. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Harland, Mark; Kukalizch, Kairen; Bishop, D. Timothy; Bishop, Julia Newton] St James Univ Hosp, Canc Res UK Canc Ctr Leeds, Leeds Inst Mol Med, Div Epidemiol & Biostat, Leeds LS9 7TF, W Yorkshire, England. [Goldstein, Alisa M.; Tucker, Margaret A.; Landi, Maria Teresa] DHHS, NIH, Natl Canc Inst, Div Canc Epidemiol & Genet,Genet Epidemiol Branch, Bethesda, MD USA. [Taylor, Claire] St James Univ Hosp, Canc Res UK, Mutat Detect Facil, Leeds LS9 7TF, W Yorkshire, England. [Hogg, David] Univ Toronto, Inst Med Sci, Dept Med Biophys, Toronto, ON M5S 1A1, Canada. [Puig, Susana; Badenas, Celia] IDIBAPS, Dept Dermatol, Barcelona, Spain. [Puig, Susana; Badenas, Celia] IDIBAPS, Genet Serv, Hosp Clin, Barcelona, Spain. [Gruis, Nelleke; ter Huurne, Jeanet; Bergman, Wilma] LUMC, Dept Dermatol, Leiden, Netherlands. [Gruis, Nelleke; ter Huurne, Jeanet; Bergman, Wilma] LUMC, Ctr Human & Clin Genet, Leiden, Netherlands. [Hayward, Nicholas K.; Stark, Mitchell] Queensland Inst Med Res, Human Genet Lab, Brisbane, Qld 4006, Australia. [Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. [Scarra, Giovanna Bianchi; Ghiorzo, Paola; Kanetsky, Peter A.] Univ Genoa, Dept Oncol Biol & Genet, I-16126 Genoa, Italy. [Kanetsky, Peter A.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Kanetsky, Peter A.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Elder, David] Univ Penn, Pathol & Lab Med, Philadelphia, PA 19104 USA. [Mann, Graham J.; Holland, Elizabeth A.] Univ Sydney, Westmead Millennium Inst, Westmead Inst Canc Res, Westmead, NSW 2145, Australia. RP Bishop, JN (reprint author), St James Univ Hosp, Canc Res UK Canc Ctr Leeds, Leeds Inst Mol Med, Div Epidemiol & Biostat, Leeds LS9 7TF, W Yorkshire, England. EM j.a.newton-bishop@leeds.ac.uk RI Stark, Mitchell/E-3542-2010; Mann, Graham/G-4758-2014; Bianchi Scarra, Giovanna/G-8933-2014; Tucker, Margaret/B-4297-2015; hayward, nicholas/C-1367-2015; OI Stark, Mitchell/0000-0002-4510-2161; Mann, Graham/0000-0003-1301-405X; Puig, Susana/0000-0003-1337-9745; Bianchi Scarra, Giovanna/0000-0002-6127-1192; hayward, nicholas/0000-0003-4760-1033; Badenas, Celia/0000-0002-0621-0477; Gruis, Nelleke/0000-0002-5210-9150; Bishop, Tim/0000-0002-8752-8785; Newton Bishop, Julia/0000-0001-9147-6802 FU Cancer Research UK [A4994]; Intramural NIH HHS; NCI NIH HHS [R01 CA 83115, R01 CA 88363, R01 CA083115, R01 CA083115-01A2, R01 CA088363, R01 CA088363-01A1] NR 37 TC 17 Z9 18 U1 0 U2 0 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 JUN PY 2008 VL 44 IS 9 BP 1269 EP 1274 DI 10.1016/j.ejca.2008.03.005 PG 6 WC Oncology SC Oncology GA 326CZ UT WOS:000257636900023 PM 18394881 ER PT J AU Moreau, AS Sebti, Y Duhamel, A Roccaro, AM Coiteux, V Gastinne, T Le Friec, G Burwick, N Amiot, L Ho, AW Poulain, S Hennache, B Hunter, ZR Dessaint, JP Ghobrial, IM Treon, SP Facon, T Zorn, E Leleu, X AF Moreau, Anne-Sophie Sebti, Yasmine Duhamel, Alain Roccaro, Aldo M. Coiteux, Valerie Gastinne, Thomas Le Friec, Gaelle Burwick, Nicholas Amiot, Laurence Ho, Allen W. Poulain, Stephanie Hennache, Bernadette Hunter, Zachary R. Dessaint, Jean-Paul Ghobrial, Irene M. Treon, Steven P. Facon, Thierry Zorn, Emmanuel Leleu, Xavier TI Clinical relevance of soluble HLA class I molecules in Waldenstrom Macroglobulinemia SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE Waldenstrom Macroglobulinemia; IgM-monoclonal gammopathy of undetermined significance; serum total soluble HLA-I molecule; serum HLA-Gs molecule ID UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; MULTIPLE-MYELOMA; MIXED CRYOGLOBULINEMIA; T-LYMPHOCYTES; G EXPRESSION; LEUKEMIA; CELLS; INVOLVEMENT; DISORDERS AB Objectives: Waldenstrom Macroglobulinemia (WM) is a B-cell neoplasm characterised by secretion of IgM by lymphoplasmacytic bone marrow cells and by cytopenias and hypogammaglobulinemia in a subset of patients. Beta-2 microglobulin (b2m) is a major prognostic factor in WM and the heavy chain of HLA class I molecules, which are known to have immunosuppressive properties and have been implicated in the pathogeny of several malignancies. Methods: We assessed the serum levels of the total soluble HLA-I molecules and the HLA-Gs molecules in 105 patients with IgM-related disorders [WM (n = 42) and IgM MGUS (n = 63)], and compared the results to 41 healthy subjects. Results: We found higher levels of HLA-Is in WM, compared to IgM MGUS and healthy donors. HLA-Gs levels were similar in WM and in IgM MGUS, but higher than in healthy donors. The association between HLA-Is at the cut-off of 1.8 mu g/mL and known markers of poor prognosis was then evaluated among WM patients using univariate and multivariate methods. Based on this, high HLA-Is level was strongly associated with high serum beta 2M level > 3 mg/L [OR = 2, (CI 95% 1.1-5.7); P = 0.04], age > 65 yrs [OR = 1.5, (CI 95% 0.5-4.1), P = 0.06] and haemoglobin <= 11.5 g/dL [OR = 3.3, (CI 95% 1.2-9.7); P = 0.03]. High levels of serum HLA-Is were also found in patients with cryoglobulinemia, however irrespectively of WM or IgM-MGUS status. Conclusion: Together our results suggest a possible role for soluble MHC class I molecules in WM disease. Further investigations are necessary to further demonstrate the prognostic impact of soluble MHC class I molecules in Waldenstrom Macroglobulinemia. C1 [Moreau, Anne-Sophie; Roccaro, Aldo M.; Burwick, Nicholas; Ho, Allen W.; Hunter, Zachary R.; Ghobrial, Irene M.; Treon, Steven P.; Leleu, Xavier] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Moreau, Anne-Sophie; Coiteux, Valerie; Gastinne, Thomas; Facon, Thierry; Leleu, Xavier] CHRU, Serv Malad Sang, Lille, France. [Moreau, Anne-Sophie; Roccaro, Aldo M.; Burwick, Nicholas; Ho, Allen W.; Hunter, Zachary R.; Ghobrial, Irene M.; Treon, Steven P.; Leleu, Xavier] Harvard Univ, Sch Med, Boston, MA USA. [Sebti, Yasmine; Le Friec, Gaelle; Amiot, Laurence] CHU, UPRES 38 89, Lab Hematol & Immunol, Rennes, France. [Duhamel, Alain] CHRU, Lab Biostat & Biomath, Lille, France. [Poulain, Stephanie] CH, Mol Biol Lab, Valenciennes, France. [Hennache, Bernadette] CHRU, Biochim Lab, Lille, France. [Dessaint, Jean-Paul] CHRU, Immunol Lab, Lille, France. [Zorn, Emmanuel] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Leleu, X (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM xavier_leleu@dfci.harvard.edu RI Ho, Allen/B-3017-2011; Duhamel, Alain/B-8624-2011; Hunter, Zachary/H-3018-2013; FACON, THIERRY/M-9736-2014; Duhamel, Alain/A-4899-2013; Amiot, laurence/J-5955-2015; OI Hunter, Zachary/0000-0002-1689-1691; FACON, THIERRY/0000-0001-7705-8460; Roccaro, Aldo/0000-0002-1872-5128 NR 36 TC 2 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD JUN PY 2008 VL 80 IS 6 BP 503 EP 509 DI 10.1111/j.1600-0609.2008.01060.x PG 7 WC Hematology SC Hematology GA 298QF UT WOS:000255701500007 PM 18331603 ER PT J AU Polansky, JK Kretschmer, K Freyer, J Floess, S Garbe, A Baron, U Olek, S Hamann, A von Boehmer, H Huehn, J AF Polansky, Julia K. Kretschmer, Karsten Freyer, Jennifer Floess, Stefan Garbe, Annette Baron, Udo Olek, Sven Hamann, Alf von Boehmer, Harald Huehn, Jochen TI DNA methylation controls Foxp3 gene expression SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE epigenetic modification; lineage differentiation; regulatory T cell ID REGULATORY T-CELLS; TRANSCRIPTION FACTOR FOXP3; RETINOIC-ACID; IN-VIVO; DEPENDENT MECHANISM; DENDRITIC CELLS; DIFFERENTIATION; INDUCTION; GROWTH; ANTIGEN AB Compelling evidence suggests that Foxp3-expressing CD25(+)CD4(+) regulatory T cells (Treg) are generated within the thymus as a separate lineage. However, Foxp3(+)CD4(+) Treg can also be generated de novo in a TGF-beta-dependent process from naive T cells by TCR triggering. Recently, we have shown that naturally occurring, but not in vitro TGF-beta-induced Foxp3(+) Treg display stable Foxp3 expression that was associated with selective demethylation of an evolutionarily conserved element within the Foxp3 locus named TSDR (Treg-specific demethylated region). Here, we report that inhibition of DNA methylation by azacytidine, even in absence of exogenous TGF-beta, not only promoted de novo induction of Foxp3 expression during priming, but also conferred stability of Foxp3 expression upon restimulation. Most notably, such stable Foxp3 expression was found only for cells displaying enhanced TSDR demethylation. In contrast, in vitro TSDR methylation diminished its transcriptional activity. Foxp3(+) Treg generated in vivo by DEC-205-mediated targeting of agonist ligands to dendritic cells showed long-term survival in the absence of the inducing antigen and exhibited efficient TSDR demethylation. Together, our data suggest that TSDR is an important methylation-sensitive element regulating Foxp3 expression and demonstrate that epigenetic imprinting in this region is critical for establishment of a stable Treg lineage. C1 [Polansky, Julia K.; Freyer, Jennifer; Floess, Stefan; Hamann, Alf; Huehn, Jochen] Charite Univ Med Berlin, DRFZ, D-10117 Berlin, Germany. [Kretschmer, Karsten; Garbe, Annette; von Boehmer, Harald] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Kretschmer, Karsten; Garbe, Annette; von Boehmer, Harald] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Baron, Udo; Olek, Sven] Epiontis GmbH, Berlin, Germany. RP Huehn, J (reprint author), Charite Univ Med Berlin, DRFZ, Charitepl 1, D-10117 Berlin, Germany. EM Harald_von_Boehmer@dfci.harvard.edu; Huehn@drfz.de RI Kretschmer, Karsten/E-8174-2010; Garbe, Annette/A-4824-2014; OI Polansky, Julia K./0000-0003-4727-2540 NR 48 TC 328 Z9 342 U1 1 U2 19 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUN PY 2008 VL 38 IS 6 BP 1654 EP 1663 DI 10.1002/eji.200838105 PG 10 WC Immunology SC Immunology GA 313TH UT WOS:000256762400019 PM 18493985 ER PT J AU Exley, MA Hou, RH Shaulov, A Tonti, E Dellabona, P Casorati, G Akbari, O Akman, HO Greenfield, EA Gumperz, JE Boyson, JE Balk, SP Wilson, SB AF Exley, Mark A. Hou, Runhua Shaulov, Angela Tonti, Elena Dellabona, Paolo Casorati, Giulia Akbari, Omid Akman, H. Orhan Greenfield, Edward A. Gumperz, Jenny E. Boyson, Jonathan E. Balk, Steven P. Wilson, S. Brian TI Selective activation, expansion, and monitoring of human iNKT cells with a monoclonal antibody specific for the TCR alpha-chain CDR3 loop SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE anti-TCR; clonotypic; cyclic peptide; IL-4; invariant NKT ID KILLER T-CELLS; MYELOID DENDRITIC CELLS; NKT CELLS; ANTIGEN PRESENTATION; CYTOKINE SECRETION; PERIPHERAL-BLOOD; DISTINCT SUBSETS; BRONCHIAL-ASTHMA; CANCER-PATIENTS; TUMOR-IMMUNITY AB A significant fraction of CD1d-restricted T cells express an invariant T cell receptor (TCR) alpha-chain. These highly conserved invariant NKT (iNKT) populations are important regulators of a wide spectrum of immune responses. The ability to directly identify and manipulate iNKT cells is essential to understanding their function and to exploit their therapeutic potential. To this end, we sought monoclonal and polyclonal antibodies specific for iNKT cells by immunizing CD1d KO mice, which lack iNKT cells, with a cyclic peptide modeled after the TCR alpha CDR3 loop. One mAb (6B11) was specific for cloned and primary human but not rodent iNKT cells and the human invariant TCR alpha, as shown by transfection and reactivity with human invariant TCRa transgenic T cells ex vivo and in situ. 6B11 was utilized to identify, purify, and expand iNKT cells from an otherwise minor component of human peripheral blood lymphocytes and to specifically identify human iNKT cells in tissue. Thus, we report a novel and general strategy for the generation of mAb specific for the CDR3 loop encoded by the TCR of interest. Specifically, an anti-V alpha 24J alpha 18 CDR3 loop clonotypic TCR mAb is available for the enumeration and therapeutic manipulation of human and non-human primate iNKT populations. C1 [Hou, Runhua; Wilson, S. Brian] Massachusetts Gen Hosp, Diabet Unit, Cambridge, MA USA. [Exley, Mark A.; Shaulov, Angela; Akman, H. Orhan; Balk, Steven P.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Tonti, Elena; Dellabona, Paolo; Casorati, Giulia] DIBIT San Raffaele Sci Inst, Milan, Italy. [Akbari, Omid] Childrens Hosp, Boston, MA 02115 USA. [Greenfield, Edward A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gumperz, Jenny E.] Univ Wisconsin, Madison, WI USA. [Boyson, Jonathan E.] Univ Vermont, Burlington, VT USA. [Exley, Mark A.; Akbari, Omid; Balk, Steven P.; Wilson, S. Brian] Harvard Univ, Sch Med, Boston, MA USA. RP Wilson, SB (reprint author), Massachusetts Gen Hosp, Diabet Unit, Cambridge, MA USA. EM bwilson@rics.bwh.harvard.edu FU NCI NIH HHS [R21 CA089567, CA 89567, R21 CA089567-01, R21 CA089567-02]; NCRR NIH HHS [P20 RR021905, P20 RR021905-019004, P20 RR021905-027752, P20 RR021905-037042, P20 RR021905-045989]; NHLBI NIH HHS [R01 HL071590]; NIAID NIH HHS [AI 42955, AI 45051, R01 AI045051, R01 AI060777, R01 AI067897, R01 AI067897-01A2, R01 AI067897-02, R01 AI067897-03, U19 AI046130]; NIDDK NIH HHS [DK 066917, R01 DK066917, R01 DK066917-01, R01 DK066917-02, R01 DK066917-03, R01 DK066917-04, R01 DK066917-04S1, R01 DK066917-05]; PHS HHS [U19 046130-06]; Associazione Italiana per la Ricerca sul Cancro NR 54 TC 49 Z9 50 U1 1 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUN PY 2008 VL 38 IS 6 BP 1756 EP 1766 DI 10.1002/eji.200737389 PG 11 WC Immunology SC Immunology GA 313TH UT WOS:000256762400028 PM 18493987 ER PT J AU Gutweiler, JR LaBelle, J Suh, MY Misra, MV Ahmed, M Lee, EY Vargas, SO Kim, HB Weldon, CB AF Gutweiler, J. R. LaBelle, J. Suh, M. Y. Misra, M. V. Ahmed, M. Lee, E. Y. Vargas, S. O. Kim, H. B. Weldon, C. B. TI A familial case of pleuropulmonary blastoma SO EUROPEAN JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE pleuropulmonary blastoma; PPB; congenital cystic adenomatoid malformation; CCAM ID CYSTIC ADENOMATOID MALFORMATION; NEPHROMA; REGISTRY AB Purpose: Pleuropulmonary blastoma (PPB) is a rare intrathoracic neoplasm of early childhood arising in the lung or visceral pleura. Approximately 150 cases have been reported in the literature, with only one previously documented case of PPB in siblings. Patients and Methods: We present the case of two brothers diagnosed with PPB. Results: A two month-old. boy with an abnormal breathing pattern was referred for evaluation of a cystic mass discovered on chest radiograph. Computed tomography (CT) of the chest was performed at our institution which revealed findings compatible with congenital cystic adenomatoid malformation (CCAM) of the right middle and lower lobes. The patient underwent urgent thoracic exploration one week later after developing severe respiratory distress. Histological examination revealed PPB type I (cystic). The patient's 15-month-old brother was presumed to have a CCAM noted radiographically months earlier during an asthma exacerbation. He underwent elective cyst resection and was also found to have type I PPB. The index patient was treated with adjuvant chemotherapy due to the large size of the PPB and intraoperative spillage of cystic fluid during the emergent surgery. In contrast, the brother is being followed without adjuvant chemotherapy, given the much smaller size of the PPB, wide margins of resection, and lack of spillage. Family history included an uncle diagnosed at age 11 with an unusual form of T cell acute lymphoblastic leukemia. Conclusion: Although PPB is known to have a familial association with other neoplasms, this case represents only the second report of PPB occurring in siblings. The importance of thoroughly investigating and resecting pulmonary cystic masses in the pediatric population is highlighted by these cases. C1 [Gutweiler, J. R.; Suh, M. Y.; Misra, M. V.; Kim, H. B.; Weldon, C. B.] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [LaBelle, J.] Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. [Ahmed, M.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Lee, E. Y.] Childrens Hosp, Dept Radiol & Med, Div Pulm, Boston, MA 02115 USA. [Vargas, S. O.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Weldon, CB (reprint author), Childrens Hosp, Dept Surg, 300 Longwood Ave,Fegan 3, Boston, MA 02115 USA. EM christopher.weldon@childrens.harvard.edu NR 10 TC 10 Z9 11 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0939-7248 J9 EUR J PEDIATR SURG JI Eur. J. Pediatr. Surg. PD JUN PY 2008 VL 18 IS 3 BP 192 EP 194 DI 10.1055/s-2008-1038484 PG 3 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 307IV UT WOS:000256313500014 PM 18493897 ER PT J AU Bjugstad, KB Teng, YD Redmond, DE Elsworth, JD Roth, RH Cornelius, SK Snyder, EY Sladek, JR AF Bjugstad, Kimberly B. Teng, Yang D. Redmond, D. Eugene, Jr. Elsworth, John D. Roth, Robert H. Cornelius, Shannon K. Snyder, Evan Y. Sladek, John R., Jr. TI Human neural stem cells migrate along the nigrostriatal pathway in a primate model of Parkinson's disease SO EXPERIMENTAL NEUROLOGY LA English DT Article ID SPINAL-CORD-INJURY; RAT MODEL; STEM/PROGENITOR CELLS; FUNCTIONAL RECOVERY; PROGENITOR CELLS; IN-VIVO; TYROSINE-HYDROXYLASE; DOPAMINERGIC-NEURONS; NEUROTROPHIC FACTORS; HUNTINGTONS-DISEASE AB Although evidence of damage-directed neural stem cell (NSC) migration has been well-documented in the rodent, to our knowledge it has never been confirmed or quantified using human NSC (hNSC) in an adult non-human primate modeling a human neurodegenerative disease state. In this report, we attempt to provide that confirmation, potentially advancing basic stem cell concepts toward clinical relevance. hNSCs were implanted into the caudate nucleus (bilaterally) and substantia nigra (unilaterally) of 7, adult St. Kitts African green monkeys (Chlorocebus sabaeus) with previous exposure to systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that disrupts the dopaminergic nigrostriatal pathway. A detailed quantitative analysis of hNSC migration patterns at two time points (4 and 7 months) following transplantation was performed. Density contour mapping of hNSCs along the dorsal-ventral and medial-lateral axes of the brain suggested that > 80% of hNSCs migrated from the point of implantation to and along the impaired nigrostriatal pathway. Although 2/3 of hNSCs were transplanted within the caudate, < 1% of 3 x 10(6) total injected donor cells were identified at this site. The migrating hNSC did not appear to be pursuing a neuronal lineage. In the striatum and nigrostriatal pathway, but not in the substantia nigra, some hNSCs were found to have taken a glial lineage. The property of neural stem cells to align themselves along a neural pathway rendered dysfunctional by a given disease is potentially a valuable clinical tool. (c) 2008 Elsevier Inc. All rights reserved. C1 [Bjugstad, Kimberly B.; Cornelius, Shannon K.; Sladek, John R., Jr.] Univ Colorado, Hlth Sci Ctr, Dept Pediat, Program Neurosci, Denver, CO 80262 USA. [Teng, Yang D.; Snyder, Evan Y.] Harvard Univ, Sch Med, Dept Neurol & Neurosurg, Boston, MA USA. [Teng, Yang D.] VA Boston Healthcare Syst, Div SCI Res, Boston, MA USA. [Redmond, D. Eugene, Jr.] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA. [Redmond, D. Eugene, Jr.; Elsworth, John D.; Roth, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Snyder, Evan Y.] Burnham Inst Med Res, Program Stem Cell & Regenerat Biol, La Jolla, CA USA. RP Bjugstad, KB (reprint author), UCHSC Fitzsimmons, Dept Pediat, Mail Stop F8342,POB 6511, Aurora, CO 80045 USA. EM kimberly.bjugstad@uchsc.edu FU NINDS NIH HHS [R01 NS040822, R01 NS040822-03, R01-NS40822, R21 NS053935, R21 NS053935-02, R21NS053935] NR 57 TC 52 Z9 60 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUN PY 2008 VL 211 IS 2 BP 362 EP 369 DI 10.1016/j.expneurol.2008.01.025 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 306UH UT WOS:000256272800008 PM 18394605 ER PT J AU Chen, YB LaCasce, AS AF Chen, Yi-Bin LaCasce, Ann S. TI Enzastaurin SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Article DE angiogenesis; enzastaurin; protein kinase C-beta inhibitor ID PROTEIN-KINASE-C; B-CELL LYMPHOMA; BETA INHIBITOR; MULTIPLE-MYELOMA; AKT PATHWAY; PKC-BETA; SMALL-MOLECULE; BREAST-CANCER; PHASE-II; IN-VITRO AB Background: Enzastaurin is a novel antineoplastic and antiangiogenic agent that acts through inhibition of protein kinase C (PKC). Objective: This review summarizes the scientific rationale and current clinical evidence for the use of enzastaurin in oncology. Methods: We performed a systematic review of the literature using the keywords protein kinase C-beta and enzastaurin in order to characterize the therapeutic target PKC-beta. We then reviewed the in-vitro, Phase I, and Phase II data for enzastaurin with a focus on hematologic malignancies. Results/conclusions: After preliminary Phase I trials established a favorable toxicity profile, enzastaurin has been studied in completed and ongoing Phase II and III studies in solid and hematologic malignancies, including B-cell lymphomas where the rationale for its use is most promising. C1 [LaCasce, Ann S.] Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP LaCasce, AS (reprint author), Massachusetts Gen Hosp, Dana Farber Canc Inst, GRB 740,44 Binney St, Boston, MA 02115 USA. EM Ann_LaCasce@dfci.harvard.edu NR 45 TC 44 Z9 45 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD JUN PY 2008 VL 17 IS 6 BP 939 EP 944 DI 10.1517/13543780802094552 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 311CD UT WOS:000256576800010 PM 18491994 ER PT J AU Miyahara, S Almulki, L Noda, K Nakazawa, T Hisatomi, T Nakao, S Thomas, KL Schering, A Zandi, S Frimmel, S Tayyari, F Garland, RC Miller, JW Gragoudas, ES Masli, S Hafezi-Moghadam, A AF Miyahara, Shinsuke Almulki, Lama Noda, Kousuke Nakazawa, Toru Hisatomi, Toshio Nakao, Shintaro Thomas, Kennard L. Schering, Alexander Zandi, Souska Frimmel, Sonja Tayyari, Faryan Garland, Rebecca C. Miller, Joan W. Gragoudas, Evangelos S. Masli, Sharmila Hafezi-Moghadam, Ali TI In vivo imaging of endothelial injury in choriocapillaris during endotoxin-induced uveitis SO FASEB JOURNAL LA English DT Article DE inflammation; adhesion molecules; subclinical diagnosis; noninvasive molecular imaging; vascular diseases ID SELECTIN GLYCOPROTEIN LIGAND-1; OCULAR BLOOD-FLOW; P-SELECTIN; CHOROIDAL CIRCULATION; MACULAR DEGENERATION; LEUKOCYTE; RETINA; CELLS; ANGIOGRAPHY; NEUTROPHILS AB Early detection of ocular inflammation may prevent the occurrence of structural damage or vision loss. Here, we introduce a novel noninvasive technique for molecular imaging and quantitative evaluation of endothelial injury in the choriocapillaris of live animals, which detects disease earlier than currently possible. Using an established model of ocular inflammation, endotoxin-induced uveitis (EIU), we visualized the rolling and adhesive interaction of fluorescent microspheres conjugated to recombinant P-selectin glycoprotein ligand-Ig (rPSGL-Ig) in choriocapillaris using a scanning laser ophthalmoscope (SLO). The number of rolling microspheres in the choriocapillaris peaked 4-10 h after LPS injection. The number of the accumulated microspheres peaked 4 h after LPS injection in the temporal choriocapillaris and 4 and 36 h after LPS injection in the central areas around the optic disk. Furthermore, we semiquantified the levels of P-selectin mRNA expression in the choroidal vessels by reverse transcription-PCR and found its pattern to match the functional microsphere interactions, with a peak at 4 h after LPS injection. These results indicate that PSGL-1-conjugated fluorescent microspheres allow specific detection of endothelial P-selectin expression in vivo and noninvasive assessment of endothelial injury. This technique may help to diagnose subclinical signs of ocular inflammatory diseases. C1 [Miyahara, Shinsuke; Almulki, Lama; Noda, Kousuke; Nakazawa, Toru; Hisatomi, Toshio; Nakao, Shintaro; Thomas, Kennard L.; Schering, Alexander; Zandi, Souska; Frimmel, Sonja; Tayyari, Faryan; Garland, Rebecca C.; Miller, Joan W.; Gragoudas, Evangelos S.; Hafezi-Moghadam, Ali] Massachusetts Eye & Ear Infirm, Angiogenesis Lab, Boston, MA 02114 USA. [Miyahara, Shinsuke; Almulki, Lama; Noda, Kousuke; Nakazawa, Toru; Hisatomi, Toshio; Nakao, Shintaro; Thomas, Kennard L.; Schering, Alexander; Zandi, Souska; Frimmel, Sonja; Tayyari, Faryan; Garland, Rebecca C.; Miller, Joan W.; Gragoudas, Evangelos S.; Masli, Sharmila; Hafezi-Moghadam, Ali] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Masli, Sharmila] Schepens Eye Res Inst, Boston, MA USA. RP Hafezi-Moghadam, A (reprint author), Massachusetts Eye & Ear Infirm, Angiogenesis Lab, Boston, MA 02114 USA. EM ahm@meei.harvard.edu OI Hafezi-Moghadam, Ali/0000-0002-5336-0697; Hisatomi, Toshio/0000-0003-2552-9595 FU NEI NIH HHS [EY14104]; NIAID NIH HHS [AI050775] NR 34 TC 11 Z9 12 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUN PY 2008 VL 22 IS 6 BP 1973 EP 1980 DI 10.1096/fj.07-096891 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307XK UT WOS:000256352700036 PM 18216288 ER PT J AU Lesic, B Lepine, F Deziel, E Starkey, M He, J Castonguay, MH Milot, S Tzika, AA Rahme, L AF Lesic, B. Lepine, F. Deziel, E. Starkey, M. He, J. Castonguay, M. -H. Milot, S. Tzika, A. A. Rahme, L. TI Quorum sensing in mammalian pathogens: MvfR controls hydroxy-quinolines synthesis in Pseudomonas aeruginosa SO FEBS JOURNAL LA English DT Meeting Abstract CT Joint Conference of the 33rd FEBS Congress/11th IUBMB Conference CY JUN 28-JUL 03, 2008 CL Athens, GREECE C1 [Lesic, B.; Starkey, M.; He, J.; Tzika, A. A.; Rahme, L.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Lesic, B.; Starkey, M.; He, J.; Tzika, A. A.; Rahme, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lesic, B.; Starkey, M.; He, J.; Tzika, A. A.; Rahme, L.] Shriners Res Inst, Boston, MA USA. [Lesic, B.; Starkey, M.; He, J.; Rahme, L.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Lepine, F.; Deziel, E.; Castonguay, M. -H.; Milot, S.] Univ Quebec, Inst Armand Frappier, INRS, Laval, PQ, Canada. RI Deziel, Eric/A-7678-2008 OI Deziel, Eric/0000-0002-4609-0115 NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUN PY 2008 VL 275 SU 1 BP 43 EP 43 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311XI UT WOS:000256633300119 ER PT J AU Maherali, N Sridharan, R Xie, W Utikal, J Eminli, S Arnold, K Stadtfeld, M Yachechko, R Tchieu, J Jaenisch, R Plath, K Hochedlinger, K AF Maherali, N. Sridharan, R. Xie, W. Utikal, J. Eminli, S. Arnold, K. Stadtfeld, M. Yachechko, R. Tchieu, J. Jaenisch, R. Plath, K. Hochedlinger, K. TI Global epigenetic reprogramming by defined transcription factors SO FEBS JOURNAL LA English DT Meeting Abstract CT Joint Conference of the 33rd FEBS Congress/11th IUBMB Conference CY JUN 28-JUL 03, 2008 CL Athens, GREECE C1 [Maherali, N.; Utikal, J.; Eminli, S.; Arnold, K.; Stadtfeld, M.; Hochedlinger, K.] Harvard Stem Cell Inst, Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Maherali, N.; Utikal, J.; Eminli, S.; Arnold, K.; Stadtfeld, M.; Hochedlinger, K.] Harvard Stem Cell Inst, Ctr Regenrat Med, Boston, MA USA. [Maherali, N.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Sridharan, R.; Xie, W.; Yachechko, R.; Tchieu, J.; Plath, K.] Univ Calif Los Angeles, Sch Med, Johnson Comprehens Canc Ctr, Dept Biol Chem, Los Angeles, CA USA. [Sridharan, R.; Xie, W.; Yachechko, R.; Tchieu, J.; Plath, K.] Univ Calif Los Angeles, Sch Med, Inst Stem Cell Biol, Los Angeles, CA USA. [Plath, K.] Univ Calif Los Angeles, Sch Med, Johnson Comprehens Canc Ctr, Inst Mol Biol, Los Angeles, CA USA. [Jaenisch, R.] MIT, Dept Biol, Cambridge, MA USA. [Jaenisch, R.] MIT, Whitehead Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUN PY 2008 VL 275 SU 1 BP 53 EP 53 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311XI UT WOS:000256633300144 ER PT J AU Orkin, SH Wang, J Kim, J Chu, J Rao, S Shen, X Levasseur, D AF Orkin, S. H. Wang, J. Kim, J. Chu, J. Rao, S. Shen, X. Levasseur, D. TI The transcriptional network controlling pluripotency in ES cells SO FEBS JOURNAL LA English DT Meeting Abstract CT Joint Conference of the 33rd FEBS Congress/11th IUBMB Conference CY JUN 28-JUL 03, 2008 CL Athens, GREECE C1 Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Harvard Stem Cell Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 3 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUN PY 2008 VL 275 SU 1 BP 53 EP 53 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311XI UT WOS:000256633300143 ER PT J AU Tsamadou, A Tsiftsoglou, SA Tsiftsoglou, AS AF Tsamadou, A. Tsiftsoglou, S. A. Tsiftsoglou, A. S. TI Transport, distribution and interactions of hemin with cytoplasmic and nuclear components in human K562 leukemia cells SO FEBS JOURNAL LA English DT Meeting Abstract CT Joint Conference of the 33rd FEBS Congress/11th IUBMB Conference CY JUN 28-JUL 03, 2008 CL Athens, GREECE C1 [Tsamadou, A.; Tsiftsoglou, A. S.] Aristotle Univ Thessaloniki, GR-54006 Thessaloniki, Greece. [Tsiftsoglou, S. A.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Tsiftsoglou, S. A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUN PY 2008 VL 275 SU 1 BP 299 EP 299 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311XI UT WOS:000256633301017 ER PT J AU Styer, AK Wright, DL Wolkovich, AM Veiga, C Toth, TL AF Styer, Aaron K. Wright, Diane L. Wolkovich, Anne M. Veiga, Christine Toth, Thomas L. TI Single-blastocyst transfer decreases twin gestation without affecting pregnancy outcome SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med DE elective single embryo transfer; blastocyst; in vitro fertilization; cryopreservation; twin gestation ID IN-VITRO FERTILIZATION; ASSISTED REPRODUCTIVE TECHNOLOGY; INTRACYTOPLASMIC SPERM INJECTION; DOUBLE-EMBRYO-TRANSFER; MULTIPLE-GESTATION; TRIAL; BIRTHS; IMPACT; RATES; RISK AB Objective: To compare the respective pregnancy outcomes of cycles undergoing fresh elective single-blastocyst transfer (eSBT) and double-blastocyst transfer (DBT) after IVF. Design: Retrospective medical record review. Setting: Academic medical center. Patient(s): Couples undergoing fresh blastocyst transfer after IVF. Intervention(s): One thousand, four hundred, ninety-nine consecutive IVF cycles from January 1, 2002 through March 31, 2006 at the Massachusetts General Hospital Fertility Center were reviewed. Patients undergoing fresh blastocyst transfer (eSBT, n = 52; DBT, n = 187) were identified. Main Outcome Measure(s): Respective pregnancy outcomes and the trend in twin gestations in all cycles undergoing blastocyst transfer, before and after the introduction of the eSBT program. Result(s): Statistically similar rates of biochemical pregnancy (76.9% vs. 77.6%), clinical pregnancy (61% vs. 63.4%), live birth (53.8% vs. 54.4%), and pregnancy loss (20% vs. 18.6%) per embryo transfer were observed for fresh eSBT and DBT cycles, respectively. Twin rates for eSBT were statistically significantly lower than for DBT cycles (3.1% vs. 51%). Fresh eSBT and DBT cryopreserved 2.8 vs. 1.7 blastocysts per cycle, respectively. Twenty-four months after the start of eSBT, the twin rate per transfer for all cycles undergoing blastocyst transfer (1, 2, or 3 blastocysts) was statistically significantly reduced from 47.2% to 22.9%, whereas the twin rate per transfer for all embryo transfers in women younger than 35 years of age was statistically significantly reduced from 28.8% to 15.6%. Conclusion(s): Given the promising potential of eSBT to markedly reduce the risk of twin gestation without a significant compromise to pregnancy outcomes, an active attempt should be made to consider and use eSBT in the young, favorable-prognosis patient who has good-quality embryos available for transfer and cryopreservation. (Fertil Steril (R) 2008;89:1702-8. (c) 2008 by American Society for Reproductive Medicine.). C1 [Styer, Aaron K.; Wright, Diane L.; Wolkovich, Anne M.; Veiga, Christine; Toth, Thomas L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv,Fertil Ctr, Boston, MA 02114 USA. RP Styer, AK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv,Fertil Ctr, Yawkey 10A,55 Fruit St, Boston, MA 02114 USA. EM astyer@partners.org NR 24 TC 35 Z9 41 U1 0 U2 1 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 JUN PY 2008 VL 89 IS 6 BP 1702 EP 1708 DI 10.1016/j.fertnstert.2007.05.036 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 315PT UT WOS:000256892600020 PM 17644095 ER PT J AU Roefaro, J Daryanani, AA AF Roefaro, John Daryanani, Anita A. TI Review of inhaled corticosteroid/long-acting beta(2)-agonist combinations SO FORMULARY LA English DT Review ID SALMETEROL FLUTICASONE PROPIONATE; OBSTRUCTIVE PULMONARY-DISEASE; METERED-DOSE INHALER; SALMETEROL/FLUTICASONE PROPIONATE; PERSISTENT ASTHMA; TRIAL; BUDESONIDE/FORMOTEROL; EXACERBATIONS; FORMOTEROL; BUDESONIDE AB Treatment guidelines for patients with the respiratory conditions asthma and chronic obstructive pulmonary disease (COPD) call for complex drug regimens, including multiple inhaled medications from different classes. In an effort to simplify therapy for these patients, products have been designed that combine medications from 2 separate therapeutic classes. This review focuses on inhaled corticosteroid/long-acting beta(2)-agonist combinations that are available for use for these disease states. The evidence supporting their use in each of these disease states is reviewed, as well as how the agents fit into accepted treatment guidelines. The genesis of the boxed warnings carried by these medications is also described. C1 [Roefaro, John; Daryanani, Anita A.] VA Boston Hlth Care Syst, Boston, MA USA. RP Roefaro, J (reprint author), VA Boston Hlth Care Syst, Boston, MA USA. EM john.roefaro@va.gov NR 24 TC 0 Z9 0 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 1082-801X J9 FORMULARY JI Formulary PD JUN PY 2008 VL 43 IS 6 BP 204 EP + PG 12 GA 315JX UT WOS:000256875900004 ER PT J AU Nakamoto, N Kaplan, DE Coleclough, J Li, Y Valiga, ME Kaminski, M Shaked, A Olthoff, K Gostick, E Price, DA Freeman, GJ Wherry, EJ Chang, KM AF Nakamoto, Nobuhiro Kaplan, David E. Coleclough, Jennifer Li, Yun Valiga, Mary E. Kaminski, Mary Shaked, Abraham Olthoff, Kim Gostick, Emma Price, David A. Freeman, Gordon J. Wherry, E. John Chang, Kyong-Mi TI Functional restoration of HCV-specific CD8 T cells by PD-1 blockade is defined by PD-1 expression and compartmentalization SO GASTROENTEROLOGY LA English DT Article ID HEPATITIS-C-VIRUS; REVERSIBLE IMMUNE DYSFUNCTION; DISEASE PROGRESSION; UP-REGULATION; INFECTION; LIVER; RESPONSES; SUPPRESSION; ACTIVATION; EXHAUSTION AB Background & Aims: The immunoinhibitory receptor programmed death-1 (PD-1) is up-regulated on dysfunctional virus-specific CD8 T cells during chronic viral infections, and blockade of PD-1/PD-ligand (PD-L) interactions can restore their function. As hepatitis C virus (HCV) persists in the liver with immune-mediated disease pathogenesis, we examined the role of PD-1/PD-L pathway in antigen-specific CD8 T-cell dysfunction in the liver and blood of HCV-infected patients. Methods: PD-1 expression and function of circulating CD8 T cells specific for HCV, Epstein-Barr virus, and influenza virus were examined ex vivo and following antigenic stimulation in vitro in patients with acute, chronic, and resolved HCV infection using class I tetramers and flow cytometry. Intrahepatic CD8 T cells were examined from liver explants of chronically HCV-infected transplant recipients. Results: Intrahepatic HCV-specific CD8 T cells from chronically HCV-infected patients were highly PD-1 positive, profoundly dysfunctional, and unexpectedly refractory to PD-1/PD-L blockade, contrasting from circulating PD-1-intermediate HCV-specific CD8 T cells with responsiveness to PD-1/PD-L blockade. This intrahepatic functional impairment was HCV-specific and directly associated with the level of PD-1 expression. Highly PD-1-positive intrahepatic CD8 T cells were more phenotypically exhausted with increased cytotoxic T-lymphocyte antigen 4 and reduced CD28 and CD127 expression, suggesting that active antigen-specific stimulation in the liver induces a profound functional exhaustion not reversible by PD-1/PD-L blockade alone. Conclusions: HCV-specific CD8 T-cell dysfunction and responsiveness to PD-1/PD-L blockade are defined by their PD-1 expression and compartmentalization. These findings provide new and clinically relevant insight to differential antigen-specific CD8 T-cell exhaustion and their functional restoration. C1 [Nakamoto, Nobuhiro; Kaplan, David E.; Coleclough, Jennifer; Li, Yun; Valiga, Mary E.; Chang, Kyong-Mi] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Nakamoto, Nobuhiro; Kaplan, David E.; Coleclough, Jennifer; Li, Yun; Valiga, Mary E.; Chang, Kyong-Mi] Univ Penn, Sch Med, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Kaminski, Mary; Shaked, Abraham; Olthoff, Kim] Hosp Univ Penn, Dept Surg, Penn Liver Transplant Ctr, Philadelphia, PA 19104 USA. [Gostick, Emma; Price, David A.] Cardiff Univ, Dept Med Biochem & Immunol, Sch Med, Cardiff, Wales. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Wherry, E. John] Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA. RP Chang, KM (reprint author), Philadelphia Vet Affairs Med Ctr, A424 Med Res,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM kmchang@mail.med.upenn.edu RI Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Kaplan, David E./0000-0002-3839-336X FU Medical Research Council [, G0501963]; NCI NIH HHS [P30 CA016520]; NCRR NIH HHS [M01 RR000040, M01-RR00040]; NIAAA NIH HHS [AA12849, R01 AA012849, R01 AA012849-05]; NIAID NIH HHS [AI56299, AI47519, P01 AI056299, R01 AI047519, R01 AI047519-08, R01 AI047519-09]; NIDDK NIH HHS [P30 DK050306, P30DK50306] NR 35 TC 148 Z9 156 U1 2 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2008 VL 134 IS 7 BP 1927 EP 1937 DI 10.1053/j.gastro.2008.02.033 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 312QR UT WOS:000256686400018 PM 18549878 ER PT J AU Huett, A Xavier, RJ AF Huett, Alan Xavier, Ramnik J. TI Neither hide nor hair: The difficulty of identifying useful disease biomarkers SO GASTROENTEROLOGY LA English DT Editorial Material ID GENOME-WIDE ASSOCIATION; INFLAMMATORY BOWEL DISEASES; CROHNS-DISEASE; SUSCEPTIBILITY; TUBERCULOSIS; CELLS; EXPRESSION; AUTOPHAGY; DIAGNOSIS; MARKERS C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Huett, A (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 29 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2008 VL 134 IS 7 BP 2164 EP 2168 DI 10.1053/j.gastro.2008.04.013 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 312QR UT WOS:000256686400040 PM 18486617 ER PT J AU Sawalha, AH Jeffries, M Webb, R Lu, Q Gorelik, G Ray, D Osban, J Knowlton, N Johnson, K Richardson, B AF Sawalha, A. H. Jeffries, M. Webb, R. Lu, Q. Gorelik, G. Ray, D. Osban, J. Knowlton, N. Johnson, K. Richardson, B. TI Defective T-cell ERK signaling induces interferon-regulated gene expression and overexpression of methylation-sensitive genes similar to lupus patients SO GENES AND IMMUNITY LA English DT Article DE epigenetics; T cell; autoimmunity; interferon; methylation; lupus ID DRUG-INDUCED LUPUS; PERIPHERAL-BLOOD CELLS; DNA METHYLATION; INDUCIBLE EXPRESSION; SYNGENEIC MICE; IN-VITRO; ERYTHEMATOSUS; PROCAINAMIDE; DEMETHYLATION; HYDRALAZINE AB Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies against a host of nuclear antigens. The pathogenesis of lupus is incompletely understood. Environmental factors may play a role via altering DNA methylation, a mechanism regulating gene expression. In lupus, genes including CD11a and CD70 are overexpressed in T cells as a result of promoter hypomethylation. T-cell DNA methyltransferase expression is regulated in part by the extracellular signal-regulated kinase (ERK) signaling pathway. In this study, we investigate the effects of decreased ERK pathway signaling in T cells using transgenic animals. We generated a transgenic mouse that inducibly expresses a dominant-negative MEK in T cells in the presence of doxycycline. We show that decreased ERK pathway signaling in T cells results in decreased expression of DNA methyltransferase 1 and overexpression of the methylation-sensitive genes CD11a and CD70, similar to T cells in human lupus. Our transgenic animal model also develops anti-dsDNA antibodies. Interestingly, microarray expression assays revealed overexpression of several interferon-regulated genes in the spleen similar to peripheral blood cells of lupus patients. This model supports the contention that ERK pathway signaling defects in T cells contribute to the development of autoimmunity. C1 [Sawalha, A. H.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, Dept Med, Oklahoma City, OK 73104 USA. [Sawalha, A. H.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Sawalha, A. H.; Jeffries, M.; Webb, R.; Osban, J.; Knowlton, N.] Oklahoma Med Res Fdn, Arthritis & Immunol Program, Oklahoma City, OK 73104 USA. [Lu, Q.] Cent S Univ, Xiangya Hosp 2, Changsha 410083, Peoples R China. [Gorelik, G.; Ray, D.; Richardson, B.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Johnson, K.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Richardson, B.] US Dept Vet Affairs, Med Ctr, Ann Arbor, MI USA. RP Sawalha, AH (reprint author), Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, Dept Med, 825 NE 13th St,MS 24, Oklahoma City, OK 73104 USA. EM amr-sawalha@omrf.ouhsc.edu FU NCRR NIH HHS [P20 RR016478, P20 RR017703, P20 RR020143, P20RR017703, P20 RR015577, P20RR020143, P20RR15577, P20RR016478, P20-RR015577]; NIA NIH HHS [AG25877, R01 AG025877, R01 AG025877-04]; NIAID NIH HHS [U19AI062629, U19 AI062629]; NIAMS NIH HHS [AR42525, R21 AR056370-01, R21 AR056370, R01 AR042525, R01 AR042525-09, P30 AR053483, R01 AR042525-14]; NIEHS NIH HHS [ES015214, R01 ES015214-04, T32 ES007062, R01 ES015214] NR 46 TC 78 Z9 82 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD JUN PY 2008 VL 9 IS 4 BP 368 EP 378 DI 10.1038/gene.2008.29 PG 11 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 308KJ UT WOS:000256388500013 PM 18523434 ER PT J AU Haverty, PM Fridlyand, J Li, L Getz, G Beroukhim, R Lohr, S Wu, TD Cavet, G Zhang, ZM Chant, J AF Haverty, Peter M. Fridlyand, Jane Li, Li Getz, Gad Beroukhim, Rameen Lohr, Scott Wu, Thomas D. Cavet, Guy Zhang, Zemin Chant, John TI High-resolution genomic and expression analyses of copy number alterations in breast tumors SO GENES CHROMOSOMES & CANCER LA English DT Article ID GENE-EXPRESSION; CHROMOSOMAL-ABERRATIONS; CELL-LINES; ARRAY CGH; CANCER; HYBRIDIZATION; DNA; AMPLICON; PATTERNS; 8P11-12 AB Analysis of recurrent DNA amplification can lead to the identification of cancer driver genes, but this process is often hampered by the low resolution of existing copy number analysis platforms. Fifty-one breast tumors were profiled for copy number alterations (CNAs) with the high-resolution Affymetrix 500K SNP array. These tumors were also expression-profiled and surveyed for mutations in selected genes commonly mutated in breast cancer (TP53, CDKN2A, ERBB2, KRAS, PIK3CA, PTEN). Combined analysis of common CNAs and mutations revealed putative associations between features. Analysis of both the prevalence and amplitude of CNAs defined regions of recurrent alteration. Compared with previous array comparative genomic hybridization studies, our analysis provided boundaries for frequently altered regions that were approximately one-fourth the size, greatly reducing the number of potential alteration-driving genes. Expression data from matched tumor samples were used to further interrogate the functional relevance of genes located in recurrent amplicons. Although our data support the importance of some known driver genes such as ERBB2, refined amplicon boundaries at other locations, such as 8p11-12 and 11q13.5-q14.2, greatly reduce the number of potential driver genes and indicate alternatives to commonly suggested driver genes in some cases. For example, the previously reported recurrent amplification at 17q23.2 is reduced to a 249 kb minimal region containing the putative driver RPS6KB1 as well as the putative oncogenic microRNA mir-21. High-resolution copy number analysis provides refined insight into many breast cancer amplicons and their relationships to gene expression, point mutations and breast cancer subtype classifications. This article contains Supplementary Material available at http:// www.interscience.wiley.com/jpages/1045-2257/suppmat. (C) 2008 Wiley-Liss, Inc. C1 [Haverty, Peter M.; Li, Li; Lohr, Scott; Wu, Thomas D.; Cavet, Guy; Zhang, Zemin] Genentech Inc, Dept Bioinformat, San Francisco, CA 94080 USA. [Fridlyand, Jane] Genentech Inc, Dept Early Clin Dev Stat, San Francisco, CA 94080 USA. [Getz, Gad] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. [Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chant, John] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA. RP Zhang, ZM (reprint author), Genentech Inc, Dept Bioinformat, 1 DNA Way, San Francisco, CA 94080 USA. EM zemin@gene.com; jehant@gcne.com FU NCI NIH HHS [K08 CA122833, K08 CA122833-01A1] NR 43 TC 94 Z9 94 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 JUN PY 2008 VL 47 IS 6 BP 530 EP 542 DI 10.1002/gcc.20558 PG 13 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 294EH UT WOS:000255386700009 PM 18335499 ER PT J AU De Gasperi, R Rocher, AB Sosa, MAG Wearne, SL Perez, GM Friedrich, VL Hof, PR Elder, GA AF De Gasperi, Rita Rocher, Anne B. Sosa, Miguel A. Gama Wearne, Susan L. Perez, Gissel M. Friedrich, Victor L., Jr. Hof, Patrick R. Elder, Gregory A. TI The IRG mouse: A two-color fluorescent reporter for assessing Cre-mediated recombination and imaging complex cellular relationships in situ SO GENESIS LA English DT Article DE Cre recombinase; loxP; conditional gene activation; DsRed-express; red fluorescent protein; enhanced green fluorescent protein; transgenic mice ID EXPRESSION; STRAIN; CELLS; MICE; PROTEIN; GENE; INSULATORS; ACTIVATION; EXCISION; LINEAGE AB The Cre-loxP system is widely used for making conditional alterations to the mouse genome. Cre-mediated recombination is frequently monitored using reporter lines in which Cre expression activates a reporter gene driven by a ubiquitous promoter. Given the distinct advantages of fluorescent reporters, we developed a transgenic reporter line, termed IRG, in which DsRed-Express, a red fluorescent protein (RFP) is expressed ubiquitously prior to Cre-mediated recombination and an enhanced green fluorescent protein (EGFP) following recombination. Besides their utility for monitoring Cre-mediated recombination, we show that in IRG mice red and green native fluorescence can be imaged simultaneously in thick tissue sections by confocal microscopy allowing for complex reconstructions to be created that are suitable for analysis of neuronal morphologies as well as neurovascular interactions in brain. IRG mice should provide a versatile tool for analyzing complex cellular relationships in both neural and nonneural tissues. C1 [De Gasperi, Rita; Sosa, Miguel A. Gama; Perez, Gissel M.; Elder, Gregory A.] James J Peters Dept Vet Affairs Med Ctr, Res & Dev, Bronx, NY USA. [De Gasperi, Rita; Sosa, Miguel A. Gama; Perez, Gissel M.; Elder, Gregory A.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Rocher, Anne B.; Wearne, Susan L.; Friedrich, Victor L., Jr.; Hof, Patrick R.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Wearne, Susan L.] Mt Sinai Sch Med, Ctr Biomath Sci, New York, NY USA. [Wearne, Susan L.; Hof, Patrick R.] Mt Sinai Sch Med, Computat Neurobiol & Imaging Ctr, New York, NY USA. [Friedrich, Victor L., Jr.] Mt Sinai Sch Med, Microscopy Shared Res Facil, New York, NY USA. [Hof, Patrick R.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. [Elder, Gregory A.] James J Peters Dept Vet Affairs Med Ctr, Rehabil Med Serv, Bronx, NY USA. RP Elder, GA (reprint author), James J Peters VA Med Ctr Res & Dev 3F22, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM gregory.elder@mssm.edu FU NCI NIH HHS [5R24 CA095823-04, R24 CA095823-04, R24 CA095823]; NIA NIH HHS [R03 AG021305-01, P01 AG002219-28, P01 AG002219, P50 AG005138-24, AG021305, R03 AG021305, AG05138, R21 AG023599, R21 AG023599-02, P50 AG005138, AG023599, P50 AG005138-25, AG02219]; NIMH NIH HHS [P50 MH058911-10, MH58911, MH070603, P50 MH058911, R03 MH070603, R03 MH070603-02] NR 27 TC 24 Z9 24 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-954X J9 GENESIS JI Genesis PD JUN PY 2008 VL 46 IS 6 BP 308 EP 317 DI 10.1002/dvg.20400 PG 10 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 323XE UT WOS:000257480900005 PM 18543298 ER PT J AU Shields, AE Burke, W Levy, DE AF Shields, Alexandra E. Burke, Wylie Levy, Douglas E. TI Differential use of available genetic tests among primary care physicians in the United States: results of a national survey SO GENETICS IN MEDICINE LA English DT Article DE physicians; genomics; genetic screening; clinical integration; new technologies ID BREAST-CANCER; HUNTINGTONS-DISEASE; RACIAL DISPARITIES; ETHNIC-DIFFERENCES; FAMILY-HISTORY; OVARIAN-CANCER; INCREASED RISK; WOMEN; ATTITUDES; SMOKING AB Purpose: This study assesses primary care physicians' experience ordering and referring patients for genetic testing, and whether minority-serving physicians are less likely than those serving fewer minorities to offer such services. Methods: Survey of a random sample of 2000 primary care physicians in the United States (n = 1120, 62.3% response rate based on eligible respondents) conducted in 2002 to assess what proportion have (1) ever ordered a genetic test in general or for select conditions; (2) ever referred a patient for genetic testing to a genetics center or counselor, a specialist, a clinical research trial, or to any site of care. Results: Nationally, 60% of primary care physicians have ordered a genetic test and 74% have referred a patient for genetic testing. Approximately 62% of physicians have referred a patient for genetic testing to a genetics center/counselor or to a specialist, and 17% to a clinical trial. Minority-serving physicians were significantly less likely to have ever ordered a genetic test for breast cancer, colorectal cancer, or Huntington disease, or to have ever referred a patient for genetic testing relative to those serving fewer minorities. Conclusions: Reduced utilization of genetic tests/referrals among minority-serving physicians emphasizes the importance of tracking the diffusion of genomic medicine and assessing the potential impact on health disparities. C1 [Shields, Alexandra E.; Levy, Douglas E.] Massachusetts Gen Hosp, Ctr Genom Vulnerable Populat & Hlth Disparities, Boston, MA 02114 USA. [Shields, Alexandra E.; Levy, Douglas E.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Shields, Alexandra E.; Levy, Douglas E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Burke, Wylie] Univ Washington, Dept Med Hist & Eth, Seattle, WA 98195 USA. RP Shields, AE (reprint author), Massachusetts Gen Hosp, Ctr Genom Vulnerable Populat & Hlth Disparities, 50 Staiford St,Suite 901, Boston, MA 02114 USA. EM ashields@partners.org FU NHGRI NIH HHS [P50 HG003374-01, P20 HG003400, P20 HG003400-01, P50 HG003374] NR 49 TC 41 Z9 41 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD JUN PY 2008 VL 10 IS 6 BP 404 EP 414 DI 10.1097/GIM.0b013e3181770184 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 316OP UT WOS:000256959900005 PM 18496223 ER PT J AU Chittenden, TW Howe, EA Culhane, AC Sultana, R Taylor, JM Holmes, C Quackenbush, J AF Chittenden, Thomas W. Howe, Eleanor A. Culhane, Aedin C. Sultana, Razvan Taylor, Jennifer M. Holmes, Chris Quackenbush, John TI Functional classification analysis of somatically mutated genes in human breast and colorectal cancers SO GENOMICS LA English DT Article DE breast cancer; colorectal cancer; genomics; bioinformatics ID GROWTH-FACTOR-BETA; PATHWAYS; CELLS; TOOL AB A recent study published by Sjoblom and colleagues [T. Sjoblom, S. Jones, L.D. Wood, D.W. Parsons, J. Lin, T.D. Barber, D. Mandelker, RJ. Leary,J. Ptak, N. Silliman, S. Szabo, P. Buckhaults, C. Farrell, P. Meeh, S.D. Markowitz,J. Willis, D. Dawson,J.K. Willson, A.F. Gazdar, J. Hartigan, L. Wu, C. Liu, G. Parmigiani, B.H. Park, K.E. Bachman, N. Papadopoulos, B. Vogelstein, K.W. Kinzler, V.E. Velculescu, The consensus coding sequences of human breast and colorectal cancers. Science 314 (2006) 268-274.] performed comprehensive sequencing of 13,023 human genes and identified mutations in genes specific to breast and colorectal tumors, providing insight into organ-specific tumor biology. Here we present a systematic analysis of the functional classifications of Sjoblom's "CAN" genes, a subset of these validated mutant genes, that identifies novel organ-specific biological themes and molecular pathways associated with disease-specific etiology. This analysis links four somatically mutated genes associated with diverse oncological types to colorectal and breast cancers through established TGF-beta 1-regulated interactions, revealing mechanistic differences in these cancers and providing potential diagnostic and therapeutic targets. (C) 2008 Elsevier Inc. All rights reserved. C1 [Chittenden, Thomas W.; Howe, Eleanor A.; Culhane, Aedin C.; Sultana, Razvan; Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Chittenden, Thomas W.; Howe, Eleanor A.; Culhane, Aedin C.; Sultana, Razvan; Quackenbush, John] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Chittenden, Thomas W.; Culhane, Aedin C.; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Chittenden, Thomas W.; Holmes, Chris] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Taylor, Jennifer M.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 3TG, England. [Holmes, Chris] MRC, Mammalian Genet Unit, Harwell, Berks, England. RP Quackenbush, J (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM johnq@jimmy.harvard.edu RI Taylor, Jennifer/A-1686-2010 OI Taylor, Jennifer/0000-0003-4231-0181 FU NCI NIH HHS [R01 CA098522, R01 CA098522-05]; NHGRI NIH HHS [P50 HG004233-01, P50 HG004233]; NLM NIH HHS [R01 LM008795, R01 LM008795-03] NR 19 TC 34 Z9 35 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 2008 VL 91 IS 6 BP 508 EP 511 DI 10.1016/j.ygeno.2008.03.002 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 315YJ UT WOS:000256915800004 PM 18434084 ER PT J AU Braun, UK Pham, C Kunik, ME AF Braun, Ursula K. Pham, Catherine Kunik, Mark E. TI Recognizing and managing depression at end of life SO GERIATRICS LA English DT Article DE depression; end of life; terminal illness ID PRIMARY-CARE; ANXIETY; MANAGEMENT AB The dying process is characterized by feelings of sadness and fear. It is normal for patients at the end of life to worry and grieve the loss of their health. However, when these feelings become excessive and interfere with all aspects of the patient's life, they are abnormal responses to the stress of terminal illness. Screening for depression in terminally ill patients can optimize their physical comfort at the end of life and provide them the opportunity to confront and prepare for death. C1 [Braun, Ursula K.] Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Sect Geriatr & Hlth Serv Res, Houston, TX 77030 USA. [Braun, Ursula K.] Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Sect Dev Serv, Houston, TX 77030 USA. [Braun, Ursula K.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Kunik, Mark E.] Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Little Rock, AR USA. [Kunik, Mark E.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Little Rock, AR USA. [Kunik, Mark E.] Baylor Coll Med, Dept Med, Little Rock, AR USA. [Kunik, Mark E.] VA S Cent MIRECC, Little Rock, AR USA. [Pham, Catherine] Texas A&M Univ, College Stn, TX USA. RP Braun, UK (reprint author), Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Sect Geriatr & Hlth Serv Res, Houston, TX 77030 USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 0016-867X J9 GERIATRICS JI Geriatrics PD JUN PY 2008 VL 63 IS 6 BP 25 EP 27 PG 3 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 314AG UT WOS:000256780500004 PM 18512998 ER PT J AU Papas, A Russell, D Singh, M Kent, R Triol, C Winston, A AF Papas, Athena Russell, David Singh, Mabi Kent, Ralph Triol, Cal Winston, Anthony TI Caries clinical trial of a remineralising toothpaste in radiation patients SO GERODONTOLOGY LA English DT Article DE radiation; remineralising; caries; saliva hypofunction; calcium phosphate ID ROOT-SURFACE CARIES; SALIVARY FLOW-RATE; NECK-CANCER; STREPTOCOCCUS-MUTANS; INDUCED XEROSTOMIA; DENTAL-CARIES; ORAL COMPLICATIONS; CALCIUM-PHOSPHATE; HEAD; RADIOTHERAPY AB Objectives: The purpose of this study was to determine the efficacy and safety of a specially formulated remineralising toothpaste in controlling caries in a high-risk population: head and neck radiation patients. Design: The study compared the performance of the remineralising toothpaste with a conventional fluoride dentifrice using double-blind randomisation. Materials and methods: Test products: The products compared contained equivalent quantities of fluoride (1100 p.p.m.). The dual-phase remineralising toothpaste, Enamelon (R), also delivered soluble calcium and phosphate ions, essential components of teeth, from separate phases. Both groups had all caries restored at baseline and used a fluoride rinse daily. Subjects: Fifty-seven subjects who received radiation to the head and neck causing saliva hypofunction, entered the study, while 44 completed the 10-12 month visit. Measurements: Examinations included coronal and root caries using the Pitts Diagnostic Criteria, salivary flow rate, plaque and gingival indices and microbiological counts over a 1-year period. Results: The average net increment per year for root caries per subject was 0.04 (+/-.052) in subjects completing the study using the remineralising toothpaste and 1.65 (+/- 0.51) for root caries in subjects completing the study using the conventional fluoride dentifrice. The difference was statistically significant (p = 0.03), suggesting lower net root surface increment/year for the remineralising toothpaste relative to the conventional toothpaste. No significant differences were noted on coronal surfaces. Conclusion: The results indicate that the remineralising toothpaste provides a significant benefit in preventing and remineralising root caries in high-risk patients. C1 [Papas, Athena; Russell, David; Singh, Mabi; Triol, Cal; Winston, Anthony] Tufts Univ, Sch Dent Med, Boston, MA 02111 USA. [Kent, Ralph] Forsyth Inst, Boston, MA USA. RP Papas, A (reprint author), Tufts Univ, Sch Dent Med, Boston, MA 02111 USA. EM athena.papas@tufts.edu NR 80 TC 35 Z9 35 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0734-0664 J9 GERODONTOLOGY JI Gerodontology PD JUN PY 2008 VL 25 IS 2 BP 76 EP 88 DI 10.1111/j.1741-2358.2007.00199.x PG 13 WC Dentistry, Oral Surgery & Medicine; Geriatrics & Gerontology SC Dentistry, Oral Surgery & Medicine; Geriatrics & Gerontology GA 301VB UT WOS:000255922700003 PM 18485139 ER PT J AU Naik, AD Burnett, J Pickens-Pace, S Dyer, CB AF Naik, Aanand D. Burnett, Jason Pickens-Pace, Sabrina Dyer, Carmel B. TI Impairment in instrumental activities of daily living and the geriatric syndrome of self-neglect SO GERONTOLOGIST LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriatr Soc DE elder mistreatment; functional assessment; geriatric self-neglect; geriatric syndrome ID COMMUNITY-DWELLING ELDERS; OLDER-ADULTS; PHYSICAL-PERFORMANCE; DEPENDENCE; DISABILITY; MORTALITY; UTILITY; RISK AB Purpose: We sought to characterize self-neglect definitively as a geriatric syndrome by identifying an association with functional impairment. Design and Methods: We performed a cross-sectional home evaluation of 100 community-living older adults referred by Adult Protective Services for geriatric self-neglect and 100 matched adults from a community geriatrics clinic. We made our assessments by using two manual muscle tests, a timed-gait test, a modified Physical Performance Test (mPPT), and the Kohlman Evaluation of Living Skills (KELS). Results: Participants in the self-neglect group had impaired mPPT (p <.077) and KELS (p <.001) scores compared with community-controls. Using analysis of covariance models, we found that self-neglect referral explained a significant proportion of the variance in KELS scores (32%; p <.001) but not in mPPT scores (22%; p =.49). Implications: The geriatric syndrome of self-neglect is associated with increased morbidity and mortality and appears to be independently associated with impairments in instrumental activities of daily living. The evaluation and treatment of geriatric self-neglect should be consistent with that of other geriatric syndromes. C1 [Naik, Aanand D.] Baylor Coll Med, Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Burnett, Jason; Pickens-Pace, Sabrina; Dyer, Carmel B.] CREST, Houston, TX USA. [Burnett, Jason; Pickens-Pace, Sabrina; Dyer, Carmel B.] Univ Texas Houston, Hlth Sci Ctr, Dept Internal Med, Houston, TX 77030 USA. RP Naik, AD (reprint author), Michael E DeBakey VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. FU NCRR NIH HHS [P20 RR020626, P20 RR020626-01, P20-RR020626]; NIA NIH HHS [K23 AG027144-03, K23AG027144, K23 AG027144] NR 24 TC 23 Z9 25 U1 3 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD JUN PY 2008 VL 48 IS 3 BP 388 EP 393 PG 6 WC Gerontology SC Geriatrics & Gerontology GA 322ZZ UT WOS:000257415100012 PM 18591364 ER PT J AU Xavier, RJ Huett, A Rioux, JD AF Xavier, Ramnik J. Huett, Alan Rioux, John D. TI Autophagy as an important process in gut homeostasis and Crohn's disease pathogenesis SO GUT LA English DT Article ID GENOME-WIDE ASSOCIATION; CELL-DEATH; SUSCEPTIBILITY; PROTEIN; INNATE; RECOGNITION; SALMONELLA; RESISTANCE; IMMUNITY; GTPASES C1 [Rioux, John D.] Univ Montreal, Res Ctr, Montreal, PQ H1T 1C8, Canada. [Rioux, John D.] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. [Xavier, Ramnik J.; Huett, Alan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Xavier, Ramnik J.; Huett, Alan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. RP Rioux, JD (reprint author), Univ Montreal, Res Ctr, 5000 Belanger St, Montreal, PQ H1T 1C8, Canada. EM john.rioux@inflammgen.org RI Rioux, John/A-9599-2015 OI Rioux, John/0000-0001-7560-8326 FU NIAID NIH HHS [AI062773, AI065687, AI067152, P01 AI065687, P01 AI065687-020001, R01 AI062773, U19 AI067152, U19 AI067152-040006]; NIDDK NIH HHS [P30 DK043351, DK062432, DK064869, DK43351, R01 DK064869, R01 DK064869-05S1, U01 DK062432, U01 DK062432-07] NR 44 TC 44 Z9 46 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD JUN PY 2008 VL 57 IS 6 BP 717 EP 720 DI 10.1136/gut.2007.134254 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 300CW UT WOS:000255802900001 PM 18272545 ER PT J AU Wong, JYY Huggins, GS Debidda, M Munshi, NC De Vivo, I AF Wong, Jason Y. Y. Huggins, Gordon S. Debidda, Marcella Munshi, Nikhil C. De Vivo, Iminaculata TI Dichloroacetate induces apoptosis in endometrial cancer cells SO GYNECOLOGIC ONCOLOGY LA English DT Article DE dichloroacetate; endometrial; cancer; apoptosis; mitochondria ID IN-VITRO; GENE-EXPRESSION; CARCINOMA; LINE; ADENOCARCINOMA; GROWTH; PUMA; P53; MEMBRANE; SURVIVIN AB Purpose. A recent landmark study demonstrated that Dichloroacetate (DCA) treatment promoted apoptosis in lung, breast, and glioblastoma cancer cell lines by shifting metabolism from aerobic glycolysis to glucose oxidation coupled with NFAT-Kv1.5 axis remodeling. The objective of this study was to determine whether DCA induces apoptosis in endometrial cancer cells and to assess apoptotic mechanism. Methods. A panel of endometrial cancer cell lines with varying degrees of differentiation was treated with DCA and analyzed for apoptosis via flow cytometry. Biological correlates such as gene expression, intracellular Ca2+, and mitochondrial membrane potential were examined to assess apoptotic mechanism. Results. Initiation of apoptosis was observed in five low to moderately invasive cancer cell lines including Ishikawa, RL95-2, KLE, AN3CA, and SKUT1B while treatment had no effect on non-cancerous 293T cells. Two highly invasive endometrial adenocarcinoma cell lines, HEC1A and HEC1B, were found to be resistant to DCA-inducedapoptosis. Apoptotic responding cell lines had a significant increase in early and late apoptotis, a decrease in mitochondrial membrane potential, and decreased Survivin transcript abundance, which are consistent with a mitochondrial-regulated mechanism. DCA treatment decreased intracellular calcium levels in most apoptotic responding cell lines which suggests a contribution from the NFAT-Kv 1.5 -mediated pathway. DCA treatment increased p53 upregulated modulator of apoptosis (PUMA) transcripts in cell lines with an apoptotic response, suggesting involvement of a p53-PUMA-mediated mechanism. Conclusions. Dichloroacetate effectively sensitizes most endometrial cancer cell lines to apoptosis via mitochondrial, NFAT-Kv 1.5, and PUMA-mediated mechanisms. Further investigation of the cancer therapeutic potential of DCA is warranted. (c) 2008 Elsevier Inc. All rights reserved. C1 [Wong, Jason Y. Y.; De Vivo, Iminaculata] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Wong, Jason Y. Y.; De Vivo, Iminaculata] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Huggins, Gordon S.] Tufts Univ New England Med Ctr, Mol Cardiol Res Inst, Boston, MA USA. [De Vivo, Iminaculata] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Debidda, Marcella; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP De Vivo, I (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM devivo@channing.harvard.edu OI Wong, Jason/0000-0002-8167-540X FU NCI NIH HHS [CA082838, CA101501, R01 CA082838, R01 CA082838-09, R03 CA101501, R03 CA101501-01, R03 CA101501-02] NR 43 TC 111 Z9 124 U1 2 U2 18 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 JUN PY 2008 VL 109 IS 3 BP 394 EP 402 DI 10.1016/j.ygyno.2008.01.038 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 315PW UT WOS:000256892900015 PM 18423823 ER PT J AU Cappellini, MD Cox, T Giannini, EH Grabowski, GA Hwu, WL Mankin, H Martins, AM Sawyer, C Dahl, SV Weinreb, N Yeh, M Zimran, A AF Cappellini, M. D. Cox, T. Giannini, E. H. Grabowski, G. A. Hwu, W. L. Mankin, H. Martins, A. M. Sawyer, C. Dahl, S. Vom Weinreb, N. Yeh, M. Zimran, A. TI DEVELOPMENT OF A DISEASE SEVERITY SCORING SYSTEM FOR TYPE 1 GAUCHER DISEASE SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 13th Congress of the European-Hematology-Association CY JUN 12-15, 2008 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Cappellini, M. D.] Univ Milan, Milan, Italy. [Cox, T.] Univ Cambridge, Cambridge, England. [Giannini, E. H.; Grabowski, G. A.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Hwu, W. L.] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Mankin, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Martins, A. M.] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Dahl, S. Vom] St Franziskus Hosp, Cologne, Germany. [Zimran, A.] Shaare Zedek Med Ctr, Jerusalem, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2008 VL 93 MA 0049 BP 19 EP 19 PG 1 WC Hematology SC Hematology GA 408JB UT WOS:000263430200050 ER PT J AU Guilhot, E Goldberg, SL Stone, RM Mauro, M Matloub, Y Chen, TT Khoury, HJ AF Guilhot, E. Goldberg, S. L. Stone, R. M. Mauro, M. Matloub, Y. Chen, T. T. Khoury, H. J. TI DASATINIB LACK OF CROSS INTOLERANCE TO IMATINIB IN PATIENTS WITH CHRONIC MYELOGENOUS LEUKEMIA IN CHRONIC PHASE (CML-CP) WHO ARE INTOLERANT TO IMATINIB - A RETROSPECTIVE SAFETY ANALYSIS SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 13th Congress of the European-Hematology-Association CY JUN 12-15, 2008 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Guilhot, E.] CHU Poitiers, Poitiers, France. [Goldberg, S. L.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Stone, R. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mauro, M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Matloub, Y.; Chen, T. T.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Khoury, H. J.] Emory Univ, Sch Med, Atlanta, GA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 JUN PY 2008 VL 93 MA O128 BP 51 EP 51 PG 1 WC Hematology SC Hematology GA 408JB UT WOS:000263430200129 ER PT J AU Podar, K Zhang, J Tonon, G Sattler, M Vallet, S Raab, MS Chauhan, D Anderson, KC AF Podar, K. Zhang, J. Tonon, G. Sattler, M. Vallet, S. Raab, M. S. Chauhan, D. Anderson, K. C. TI THE TYROPHOSTIN ADAPHOSTIN (NSC680410) INHIBITS MULTIPLE MYELOMA BONE MARROW ANGIOGENESIS IN IN VITRO AND IN VIVO SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 13th Congress of the European-Hematology-Association CY JUN 12-15, 2008 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Podar, K.; Zhang, J.; Tonon, G.; Sattler, M.; Vallet, S.; Raab, M. S.; Chauhan, D.; Anderson, K. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2008 VL 93 MA 0189 BP 75 EP 75 PG 1 WC Hematology SC Hematology GA 408JB UT WOS:000263430200190 ER PT J AU Palumbo, A Schlag, R Khuageva, N Shpilberg, O Dimopoulos, M Kropff, M Spicka, I Petrucci, M Delforge, M Mateos, M Esseltine, D Liu, K Deraedt, W Van de Velde, H Richardson, P San-Miguel, J AF Palumbo, A. Schlag, R. Khuageva, N. Shpilberg, O. Dimopoulos, M. Kropff, M. Spicka, I. Petrucci, M. Delforge, M. Mateos, M. Esseltine, D. Liu, K. Deraedt, W. Van de Velde, H. Richardson, P. San-Miguel, J. TI PROLONGED THERAPY WITH BORTEZOMIB PLUS MELPHALAN-PREDNISONE (VMP) RESULTS IN IMPROVED QUALITY AND DURATION OF RESPONSE IN THE PHASE III VISTA STUDY IN PREVIOUSLY UNTREATED MULTIPLE MYELOMA (MM) SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 13th Congress of the European-Hematology-Association CY JUN 12-15, 2008 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Palumbo, A.] Univ Turin, Div Ematol, Turin, Italy. [Schlag, R.] Praxisklin Dr Schlag, Wurzburg, Germany. [Khuageva, N.] SP Botkin Moscow City Clin Hosp, Moscow, Russia. [Shpilberg, O.] Rabin Med Ctr, Petah Tiqwa, Israel. [Dimopoulos, M.] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Kropff, M.] Univ Munster, Munster, Germany. [Spicka, I.] Univ Hosp, Prague, Czech Republic. [Petrucci, M.] Univ Roma La Sapienza, Rome, Italy. [Delforge, M.] Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. [Mateos, M.; San-Miguel, J.] CSIC, USAL, IBMCC, CIC,Hosp Univ Salamanca, Salamanca, Spain. [Esseltine, D.] Millennium Pharmaceut Inc, Cambridge, MD USA. [Liu, K.] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. [Deraedt, W.; Van de Velde, H.] Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. [Richardson, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 7 Z9 7 U1 0 U2 0 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 JUN PY 2008 VL 93 MA 0207 BP 83 EP 83 PG 1 WC Hematology SC Hematology GA 408JB UT WOS:000263430200208 ER PT J AU Sezer, O Kaiser, M Siegel, D Prosser, I Mateos, MV Kangas, M Jalaluddin, M Bourquelot, P Blade, J Miguel, JS Anderson, K Bradner, J AF Sezer, O. Kaiser, M. Siegel, D. Prosser, I. Mateos, M. V. Kangas, M. Jalaluddin, M. Bourquelot, P. Blade, J. Miguel, J. San Anderson, K. Bradner, J. TI A PHASE IB, MULTI-CENTER, OPEN-LABEL, DOSE-ESCALATION STUDY OF ORAL PANOBINOSTAT (LBH589) AND IV BORTEZOMIB IN ADULT PATIENTS WITH MULTIPLE MYELOMA (MM) SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 13th Congress of the European-Hematology-Association CY JUN 12-15, 2008 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Sezer, O.; Kaiser, M.] Charite Univ Med Berlin, Berlin, Germany. [Siegel, D.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Prosser, I.] Canberra Hosp, Canberra, ACT, Australia. [Mateos, M. V.; Miguel, J. San] Hosp Univ Salamanca, Salamanca, Spain. [Kangas, M.; Bourquelot, P.] Nova Pharma AG, Basel, Switzerland. [Jalaluddin, M.] Nova Pharmaceut Corp, Florham Pk, NJ USA. [Blade, J.] Hosp Clin Barcelona, Barcelona, Spain. [Anderson, K.; Bradner, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2008 VL 93 MA 0437 BP 176 EP 176 PG 1 WC Hematology SC Hematology GA 408JB UT WOS:000263430200438 ER PT J AU Gerstner, R Abrey, LE Schiff, D Ferreri, AJM Lister, A Montoto, S Tsang, R Thiel, E Graus, F Behringer, D Illerhaus, G Weaver, S Wen, P Harris, NL Batchelor, TT AF Gerstner, R. Abrey, L. E. Schiff, D. Ferreri, A. J. M. Lister, A. Montoto, S. Tsang, R. Thiel, E. Graus, F. Behringer, D. Illerhaus, G. Weaver, S. Wen, P. Harris, N. L. Batchelor, T. T. TI CNS HODGKIN LYMPHOMA: AN INTERNATIONAL PRIMARY CNS LYMPHOMA COLLABORATIVE GROUP (IPCG) REPORT OF 18 CASES SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 13th Congress of the European-Hematology-Association CY JUN 12-15, 2008 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Gerstner, R.; Harris, N. L.; Batchelor, T. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Abrey, L. E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Schiff, D.] Univ Virginia, Charlottesville, VA USA. [Ferreri, A. J. M.] Ist Sci San Raffaele, Milan, Italy. [Lister, A.; Montoto, S.] St Bartholomews Hosp, London, England. [Tsang, R.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Thiel, E.] Charite Campus Benjamin Franklin, Berlin, Germany. [Graus, F.] Hosp Clin Barcelona, Barcelona, Spain. [Behringer, D.] Augusta Kranken Anstali, Bochum, Germany. [Illerhaus, G.] Univ Hosp Freiburg, Freiburg, Germany. [Weaver, S.] Albany Med Ctr, Albany, NY USA. [Wen, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Ferreri, Andres Jose Maria/A-6662-2013 OI Ferreri, Andres Jose Maria/0000-0001-9606-6124 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2008 VL 93 MA 0470 BP 191 EP 191 PG 1 WC Hematology SC Hematology GA 408JB UT WOS:000263430200471 ER PT J AU San-Miguel, J Schlag, R Khuageva, N Dimopoulos, M Shpilberg, O Kropff, M Spicka, I Petrucci, M Palumbo, A Samoilova, O Dmoszynska, A Abdulkadyrov, K Schots, R Jiang, B Mateos, M Anderson, K Esseltine, D Liu, K Cakana, A Van De Velde, H Richardson, P AF San-Miguel, J. Schlag, R. Khuageva, N. Dimopoulos, M. Shpilberg, O. Kropff, M. Spicka, I. Petrucci, M. Palumbo, A. Samoilova, O. Dmoszynska, A. Abdulkadyrov, K. Schots, R. Jiang, B. Mateos, M. Anderson, K. Esseltine, D. Liu, K. Cakana, A. Van de Velde, H. Richardson, P. TI SUPERIOR EFFICACY WITH BORTEZOMIB PLUS MELPHALAN-PREDNISONE (VMP) VERSUS MELPHALAN-PREDNISONE (MP) ALONE IN PREVIOUSLY UNTREATED MULTIPLE MYELOMA (MM): RESULTS OF THE PHASE III MMY-3002 VISTA STUDY SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 13th Congress of the European-Hematology-Association CY JUN 12-15, 2008 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [San-Miguel, J.; Mateos, M.] Hosp Univ Salamanca, Salamanca, Spain. [Schlag, R.] Praxisklin Dr Schlag, Wurzburg, Germany. [Khuageva, N.] SP Botkin Moscow City Clin Hosp, Moscow, Russia. [Dimopoulos, M.] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Shpilberg, O.] Rabin Med Ctr, Petah Tiqwa, Israel. [Kropff, M.] Univ Munster, Munster, Germany. [Spicka, I.] Univ Hosp, Prague, Czech Republic. [Petrucci, M.] Univ Roma La Sapienza, Rome, Italy. [Palumbo, A.] Univ Turin, Turin, Italy. [Samoilova, O.] Nizhnii Novgorod Reg Clin Hosp, Novgorod, Russia. [Dmoszynska, A.] Med Univ Lublin, Lublin, Poland. [Abdulkadyrov, K.] St Petersburg Clin Res Inst Hematol & Transfusiol, St Petersburg, Russia. [Schots, R.] Belgian Hematol Soc, Myeloma Study Grp, Brussels, Belgium. [Jiang, B.] Peking Univ, Peoples Hosp, Beijing, Peoples R China. [Anderson, K.; Richardson, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Liu, K.] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. [Cakana, A.; Van de Velde, H.] Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. NR 0 TC 2 Z9 2 U1 0 U2 0 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 JUN PY 2008 VL 93 MA 0473 BP 192 EP 193 PG 2 WC Hematology SC Hematology GA 408JB UT WOS:000263430200474 ER PT J AU Mateos, MV Cibeira, MT Blade, J Richardson, PG Prosper, F Oriol, A de la Rubia, J Alegre, A Lahuerta, JJ Garcia-Sanz, R Espinoza, J Mitsiades, K Anderson, K Miguel, JFS AF Mateos, M. V. Cibeira, M. T. Blade, J. Richardson, P. G. Prosper, F. Oriol, A. de la Rubia, J. Alegre, A. Lahuerta, J. J. Garcia-Sanz, R. Espinoza, J. Mitsiades, K. Anderson, K. Miguel, J. F. San TI PHASE II TRIAL WITH PLITIDEPSIN (APLIDIN) ALONE AND IN COMBINATION WITH DEXAMETHASONE (DEX) IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA; PROMISING ACTIVITY WITH MANAGEABLE TOXICITY SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 13th Congress of the European-Hematology-Association CY JUN 12-15, 2008 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Mateos, M. V.; Garcia-Sanz, R.; Miguel, J. F. San] Univ Hosp Salamanca, Salamanca, Spain. [Cibeira, M. T.; Blade, J.] Hosp Clin Barcelona, Barcelona, Spain. [Richardson, P. G.; Mitsiades, K.; Anderson, K.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Prosper, F.] Clin Univ, Navarra, Spain. [Oriol, A.] Hosp Germans Trials & Pujol, Badalona, Spain. [de la Rubia, J.] Hosp La Fe, E-46009 Valencia, Spain. [Alegre, A.] Hosp La Princesa, Madrid, Spain. [Lahuerta, J. J.] Hosp 12 Octubre, Madrid, Spain. [Espinoza, J.] Colmenar Viejo, Clin R&D, PharmaMar SAU, Madrid, Spain. NR 0 TC 0 Z9 0 U1 1 U2 1 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 JUN PY 2008 VL 93 MA 0643 BP 258 EP 259 PG 2 WC Hematology SC Hematology GA 408JB UT WOS:000263430200644 ER PT J AU Cervantes, F Baccarani, M Lipton, J Matloub, Y Sinha, R Stone, RM Mauro, M AF Cervantes, F. Baccarani, M. Lipton, J. Matloub, Y. Sinha, R. Stone, R. M. Mauro, M. TI DASATINIB LONG-TERM EFFICACY IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA IN CHRONIC PHASE (CML-CP) WITH RESISTANCE OR INTOLERANCE TO IMATINIB: A TWO-YEAR UPDATE OF THE START-C STUDY SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 13th Congress of the European-Hematology-Association CY JUN 12-15, 2008 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Cervantes, F.] Hosp Clin Prov 1, Barcelona, Spain. [Baccarani, M.] Univ Bologna, S Orsola M Malpighi Hosp, Bologna, Italy. [Lipton, J.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Matloub, Y.; Sinha, R.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Stone, R. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mauro, M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 12 Z9 12 U1 0 U2 0 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 JUN PY 2008 VL 93 MA 0934 BP 372 EP 372 PG 1 WC Hematology SC Hematology GA 408JB UT WOS:000263430201174 ER PT J AU Newland, C Sanz, MA Bourgeois, E Grande, C Boekhorst, PAWT Vellenga, E Shi, Y Berger, D Kuter, DJ AF Newland, C. Sanz, M. A. Bourgeois, E. Grande, C. Boekhorst, P. A. W. te Vellenga, E. Shi, Y. Berger, D. Kuter, D. J. TI EVALUATING THE LONG-TERM EFFICACY OF ROMIPLOSTIM (AMG 531) IN PATIENTS WITH CHRONIC IMMUNE THROMBOCYTOPENIC PURPURA (ITP) DURING AN OPEN-LABEL EXTENSION STUDY SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 13th Congress of the European-Hematology-Association CY JUN 12-15, 2008 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Newland, C.] Royal London Hosp, London E1 1BB, England. [Sanz, M. A.] Hosp La Fe, E-46009 Valencia, Spain. [Bourgeois, E.] CHRU Claude Huriez, Lille, France. [Grande, C.] Hosp 12 Octubre, E-28041 Madrid, Spain. [Boekhorst, P. A. W. te] Erasmus MC, Rotterdam, Netherlands. [Vellenga, E.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Shi, Y.; Berger, D.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Kuter, D. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 U1 0 U2 1 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 JUN PY 2008 VL 93 SU 1 MA 0945 BP 377 EP 377 PG 1 WC Hematology SC Hematology GA 408JB UT WOS:000263430201185 ER PT J AU Roti, G Ross, K Mecucci, C Aster, J Stegmaier, K AF Roti, G. Ross, K. Mecucci, C. Aster, J. Stegmaier, K. TI MODULATING NOTCH1 WITH SIGNATURE-BASED SMALL MOLECULE LIBRARY SCREENING SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 13th Congress of the European-Hematology-Association CY JUN 12-15, 2008 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Roti, G.; Stegmaier, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ross, K.] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. [Ross, K.] MIT, Cambridge, MA 02139 USA. [Mecucci, C.] Univ Perugia, IBIT Fdn, I-06100 Perugia, Italy. [Aster, J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Stegmaier, K.] Broad Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 JUN PY 2008 VL 93 MA 0954 BP 381 EP 381 PG 1 WC Hematology SC Hematology GA 408JB UT WOS:000263430201194 ER PT J AU Malagola, M Peli, A Damiani, D Candoni, A Tiribelli, M Martinelli, G Piccaluga, PP Paolini, S De Rosa, F Lauria, F Monica, B Marco, G Pierri, I Zaccaria, A Zuffa, E Mazza, P Priccolo, G Gugliotta, L Bonini, A Visani, G Skert, C Bergonzi, C Roccaro, AM Fili, C Fanin, R Baccarani, M Russo, D AF Malagola, M. Peli, A. Damiani, D. Candoni, A. Tiribelli, M. Martinelli, G. Piccaluga, P. P. Paolini, S. De Rosa, F. Lauria, F. Monica, B. Marco, G. Pierri, I. Zaccaria, A. Zuffa, E. Mazza, P. Priccolo, G. Gugliotta, L. Bonini, A. Visani, G. Skert, C. Bergonzi, C. Roccaro, A. M. Fili, C. Fanin, R. Baccarani, M. Russo, D. TI INCIDENCE OF BACTERIAL AND FUNGAL INFECTIONS IN NEWLY DIAGNOSED ACUTE MYELOID LEUKAEMIA PATIENTS TREATED WITH INDUCTION REGIMENS INCLUDING FLUDARABINE: RETROSPECTIVE ANALYSIS OF 224 CASES SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 13th Congress of the European-Hematology-Association CY JUN 12-15, 2008 CL Copenhagen, DENMARK SP European Hematol Assoc C1 [Malagola, M.; Peli, A.; Damiani, D.; Candoni, A.; Tiribelli, M.; Martinelli, G.; Piccaluga, P. P.; Paolini, S.; De Rosa, F.; Lauria, F.; Monica, B.; Marco, G.; Pierri, I.; Skert, C.; Bergonzi, C.; Fili, C.; Fanin, R.; Baccarani, M.; Russo, D.] Chair Hematol, Brescia, Italy. [Zaccaria, A.; Zuffa, E.; Mazza, P.; Priccolo, G.; Gugliotta, L.; Bonini, A.; Visani, G.] Hematol Unit, Ravenna, Italy. [Roccaro, A. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Paolini, Stefania/K-9514-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2008 VL 93 MA 0959 BP 383 EP 383 PG 1 WC Hematology SC Hematology GA 408JB UT WOS:000263430201199 ER PT J AU Tang, MH Hill, KS Boudreau, AA Yucel, RM Perrin, JM Kuhlthau, KA AF Tang, Michael H. Hill, Kristen S. Boudreau, Alexy A. Yucel, Recai M. Perrin, James M. Kuhlthau, Karen A. TI Medicaid managed care and the unmet need for mental health care among children with special health care needs SO HEALTH SERVICES RESEARCH LA English DT Article DE Medicaid; children with special needs; mental health; managed care; carve-out ID IDENTIFYING CHILDREN; SERVICES; DISABILITIES; PREVALENCE; INSURANCE; PATTERNS; IMPACT AB Objective. To determine the association between Medicaid managed care pediatric behavioral health programs and unmet need for mental health care among children with special health care needs (CSHCN). Data Source. The National Survey of CSHCN (2000-2002), using subsets of 4,400 CSHCN with Medicaid and 1,856 CSHCN with Medicaid and emotional problems. Additional state-level sources were used. Study Design. Multilevel models investigated the association between managed care program type (carve-out, integrated) or fee-for-service (FFS) and reported unmet mental health care need. Data Collection/Extraction Methods. The National Survey of CSHCN conducted telephone interviews with a sample representative at both the national and state levels. Principal Findings. In multivariable models, among CSHCN with only Medicaid, living in states with Medicaid managed care (odds ratio [OR]=1.81; 95 percent confidence interval: 1.04-3.15) or carve-out programs (OR=1.93; 1.01-3.69) were associated with greater reported unmet mental health care need compared with FFS programs. Among CSHCN on Medicaid with emotional problems, the association between managed care and unmet need was stronger (OR=2.48; 1.38-4.45). Conclusions. State Medicaid pediatric behavioral health managed care programs were associated with greater reported unmet mental health care need than FFS programs among CSHCN insured by Medicaid, particularly for those with emotional problems. C1 [Hill, Kristen S.; Boudreau, Alexy A.; Perrin, James M.; Kuhlthau, Karen A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Tang, Michael H.] Harvard Univ, Sch Med, Boston, MA USA. [Yucel, Recai M.] SUNY Albany, Div Epidemiol Biostat, Albany, NY 12222 USA. RP Kuhlthau, KA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. FU PHS HHS [U36/CCU319276] NR 45 TC 16 Z9 16 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD JUN PY 2008 VL 43 IS 3 BP 882 EP 900 DI 10.1111/j.1475-6773.2007.00811.x PG 19 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 295NM UT WOS:000255481200006 PM 18454773 ER PT J AU Korngold, EC Jaffer, FA Weissleder, R Sosnovik, DE AF Korngold, Ethan Chauncey Jaffer, Farouc Amin Weissleder, Ralph Sosnovik, David Edwin TI Noninvasive imaging of apoptosis in cardiovascular disease SO HEART FAILURE REVIEWS LA English DT Article DE noninvasive imaging; molecular imaging; apoptosis; cardiovascular; annexin ID ACUTE MYOCARDIAL-INFARCTION; IN-VIVO DETECTION; ACUTE CORONARY SYNDROMES; PROGRAMMED CELL-DEATH; FAILING HUMAN HEART; ANNEXIN-V; ATHEROSCLEROTIC LESIONS; CARDIOMYOCYTE APOPTOSIS; REPERFUSION INJURY; PLAQUE INSTABILITY AB Recent advances in molecular imaging have permitted the noninvasive imaging of apoptosis, a critical process underlying the pathogenesis of many diseases of the cardiovascular system including atherosclerotic vascular disease, myocardial ischemia and reperfusion injury, chronic heart failure, myocarditis, and cardiac allograft rejection. Multiple molecular targets including phosphatidylserine, phosphatidylinositol 3-kinase, and caspases have been targeted by a variety of imaging agents and modalities such as nuclear scintigraphy, PET, MRI, and fluorescent and bioluminescent imaging. Translationally, methods utilizing radiolabeled annexin V have proven promising in several clinical trials of ischemia-reperfusion injury and cardiac allograft rejection. New approaches using novel molecular imaging agents show great potential for the ability to image apoptosis in the research and clinical setting. Ultimately the ability to detect apoptosis noninvasively would help to identify patients for emerging anti-apoptotic therapies and guide clinical management with the aim of maximal myocardial preservation. C1 [Korngold, Ethan Chauncey; Jaffer, Farouc Amin; Weissleder, Ralph; Sosnovik, David Edwin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. [Korngold, Ethan Chauncey; Jaffer, Farouc Amin; Sosnovik, David Edwin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA 02114 USA. RP Sosnovik, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, 149 13th St,5th Floor, Boston, MA 02129 USA. EM sosnovik@nmr.mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU NHLBI NIH HHS [K08 HL079984, K08 HL079984-03, U01 HL080731, UO1-HL080731] NR 79 TC 31 Z9 32 U1 1 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1382-4147 J9 HEART FAIL REV JI Heart Fail. Rev. PD JUN PY 2008 VL 13 IS 2 BP 163 EP 173 DI 10.1007/s10741-007-9068-4 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 278RB UT WOS:000254302900006 PM 18074226 ER PT J AU d'Avita, A AF d'Avita, Andre TI Epicardial catheter ablation of ventricular tachycardia SO HEART RHYTHM LA English DT Article; Proceedings Paper CT California Heart Rhythm Symposium CY OCT 18-19, 2007 CL Santa Monica, CA SP UCLA, Electrophysiol Programs, UCSF, UCSD, Heart Rhythm Soc DE ventricular tachycardia; catheter ablation; epicardium C1 [d'Avita, Andre] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [d'Avita, Andre] Harvard Univ, Sch Med, Boston, MA USA. RP d'Avita, A (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St GRB 109, Boston, MA 02114 USA. EM adavila@partners.org RI d'Avila, Andre/F-8009-2010 OI d'Avila, Andre/0000-0001-8769-1411 NR 17 TC 12 Z9 12 U1 0 U2 0 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 JUN PY 2008 VL 5 IS 6 SU S BP S73 EP S75 DI 10.1016/j.hrthm.2008.01.035 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 312NT UT WOS:000256678800016 PM 18456208 ER PT J AU Love-Gregory, L Sherva, R Sun, LW Wasson, J Schappe, T Doria, A Rao, DC Hunt, SC Klein, S Neuman, RJ Permutt, MA Abumrad, NA AF Love-Gregory, Latisha Sherva, Richard Sun, Lingwei Wasson, Jon Schappe, Timothy Doria, Alessandro Rao, D. C. Hunt, Steven C. Klein, Samuel Neuman, Rosalind J. Permutt, M. Alan Abumrad, Nada A. TI Variants in the CD36 gene associate with the metabolic syndrome and high-density lipoprotein cholesterol SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE LINKAGE; BLOOD-PRESSURE PROGRAM; CORONARY-HEART-DISEASE; DEFECTIVE FATTY-ACID; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; MEXICAN-AMERICANS; NATURAL-SELECTION; RECEPTOR CD36; DEFICIENCY AB A region along chromosome 7q was recently linked to components of the metabolic syndrome (MetS) in several genome-wide linkage studies. Within this region, the CD36 gene, which encodes a membrane receptor for long-chain fatty acids and lipoproteins, is a potentially important candidate. CD36 has been documented to play an important role in fatty acid metabolism in vivo and subsequently may be involved in the etiology of the MetS. The protein also impacts survival to malaria and the influence of natural selection has resulted in high CD36 genetic variability in populations of African descent. We evaluated 36 tag SNPs across CD36 in the HyperGen population sample of 2020 African-Americans for impact on the MetS and its quantitative traits. Five SNPs associated with increased odds for the MetS [P = 0.0027-0.03, odds ratio (OR) = 1.3-1.4]. Coding SNP, rs3211938, previously shown to influence malaria susceptibility, is documented to result in CD36 deficiency in a homozygous subject. This SNP conferred protection against the MetS (P = 0.0012, OR = 0.61, 95%CI: 0.46-0.82), increased high-density lipoprotein cholesterol, HDL-C (P = 0.00018) and decreased triglycerides (P = 0.0059). Fifteen additional SNPs associated with HDL-C (P = 0.0028-0.044). We conclude that CD36 variants may impact MetS pathophysiology and HDL metabolism, both predictors of the risk of heart disease and type 2 diabetes. C1 [Love-Gregory, Latisha; Schappe, Timothy; Klein, Samuel; Abumrad, Nada A.] Washington Univ, Sch Med, Dept Med, Ctr Human Nutr, St Louis, MO 63110 USA. [Wasson, Jon; Permutt, M. Alan] Washington Univ, Sch Med, Div Diabet & Lipid Metab, St Louis, MO 63110 USA. [Sherva, Richard; Sun, Lingwei; Neuman, Rosalind J.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Rao, D. C.; Neuman, Rosalind J.] Washington Univ, Sch Med, Dept Human Genet, Div Biostat, St Louis, MO 63110 USA. [Hunt, Steven C.] Univ Utah, Sch Med, Cardiovasc Genet Div, Salt Lake City, UT 84108 USA. [Doria, Alessandro] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Love-Gregory, L (reprint author), Washington Univ, Sch Med, Dept Med, Ctr Human Nutr, Campus Box 8031, St Louis, MO 63110 USA. EM lgregory@im.wustl.edu FU NHLBI NIH HHS [U10 HL054471, U10 HL054471-05, U10 HL054472, U10 HL054472-05, U10 HL054473, U10 HL054473-05, U10 HL054495-05, U10 HL054496, U10 HL054496-05, U10 HL054497-05, U10 HL054509, U10 HL054509-05, U10 HL054515-05, U10 HL54471, U10 HL54472, U10 HL54473, U10 HL54495, U10 HL54496, U10 HL54497, U10 HL54509, U10 HL54515]; NIDDK NIH HHS [DK56351, P30 DK056341, P30 DK056341-08, R01 DK033301, R01 DK060022, R01 DK060022-07, R01 DK60022, R37 DK016746, R37 DK016746-35] NR 54 TC 88 Z9 95 U1 1 U2 8 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 JUN 1 PY 2008 VL 17 IS 11 BP 1695 EP 1704 DI 10.1093/hmg/ddn060 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 305IE UT WOS:000256170800018 PM 18305138 ER PT J AU Schnabel, R Larson, MG Dupuis, J Lunetta, KL Lipinska, I Meigs, JB Yin, XY Rong, J Vita, JA Newton-Cheh, C Levy, D Keaney, JF Vasan, RS Mitchell, GF Benjamin, EJ AF Schnabel, Renate Larson, Martin G. Dupuis, Josee Lunetta, Kathryn L. Lipinska, Izabella Meigs, James B. Yin, Xiaoyan Rong, Jian Vita, Joseph A. Newton-Cheh, Christopher Levy, Daniel Keaney, John F., Jr. Vasan, Ramachandran S. Mitchell, Gary F. Benjamin, Emelia J. TI Relations of inflammatory biomarkers and common genetic variants with arterial stiffness and wave reflection SO HYPERTENSION LA English DT Article DE tonometry; inflammation; epidemiology; polymorphism; single nucleotide; genetics ID C-REACTIVE-PROTEIN; SERUM OSTEOPROTEGERIN LEVELS; SYSTEMIC INFLAMMATION; MENDELIAN RANDOMIZATION; ESSENTIAL-HYPERTENSION; JAPANESE SUBJECTS; AORTIC STIFFNESS; BLOOD-PRESSURE; OLDER-ADULTS; HEALTHY-MEN AB Inflammation causes vascular dysfunction and perpetuates proatherosclerotic processes. We hypothesized that a broad panel of inflammatory biomarkers and single nucleotide polymorphisms in inflammatory genes is associated with vascular stiffness. We assessed 12 circulating inflammatory biomarkers (C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase-A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, osteoprotegerin, P-selectin, and tumor necrosis factor receptor-II) in relation to tonometry variables (central pulse pressure, mean arterial pressure, forward pressure wave, reflected pressure wave, carotid-femoral pulse wave velocity, and augmentation index) measured in 2409 Framingham Heart Study participants (mean age: 60 years; 55% women; 13% ethnic/racial minorities). Single nucleotide polymorphisms (n=2195) in 240 inflammatory candidate genes were related to tonometry measures in 1036 white individuals. In multivariable analyses, biomarkers explained < 1% of any tonometry measure variance. Applying backward elimination, markers related to tonometry (P < 0.01) were as follows: tumor necrosis factor receptor-II ( inversely) with mean arterial pressure; C-reactive protein (positively) and lipoprotein-associated phospholipase-A2 (inversely) with reflected pressure wave; and interleukin-6 and osteoprotegerin (positively) with carotid-femoral pulse wave velocity. In genetic association analyses, lowest P values (false discovery rate < 0.50) were observed for rs10509561 (FAS), P=6.6x10(-5) for central pulse pressure and rs11559271 (ITGB2), P=1.1x10(-4) for mean arterial pressure. These data demonstrate that, in a community-based sample, circulating inflammatory markers tumor necrosis factor receptor-II (mean arterial pressure), C-reactive protein, lipoprotein-associated phospholipase-A2 activity (reflected pressure wave), interleukin-6, and osteoprotegerin (carotid-femoral pulse wave velocity) were significantly but modestly associated with measures of arterial stiffness and wave reflection. Additional studies are needed to determine whether variation in inflammatory marker genes is associated with tonometry measures. C1 [Schnabel, Renate; Larson, Martin G.; Dupuis, Josee; Lunetta, Kathryn L.; Lipinska, Izabella; Newton-Cheh, Christopher; Levy, Daniel; Vasan, Ramachandran S.; Benjamin, Emelia J.] Natl Heart Lung & Blood Inst Framingham Study, Framingham, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Dupuis, Josee; Lunetta, Kathryn L.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Benjamin, Emelia J.] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. [Vita, Joseph A.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Whitaker Cardiovasc Inst, Boston, MA 02215 USA. [Vita, Joseph A.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Evans Mem Dept Med, Boston, MA 02215 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Dept Prevent Med, Sch Med, Boston, MA 02215 USA. [Levy, Daniel] Ctr Populat Studies, NHLBI, Bethesda, MD USA. [Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Newton-Cheh, Christopher] Harvard Univ, Sch Med, Div Cardiol, Massachusetts Gen Hosp, Boston, MA USA. [Keaney, John F., Jr.] Univ Massachusetts, Sch Med, Cambridge, MA USA. [Newton-Cheh, Christopher] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. [Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Waltham, MA USA. RP Benjamin, EJ (reprint author), Boston Univ, Sch Med, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM emelia@bu.edu RI Schnabel, Renate/F-6527-2014; OI Vita, Joseph/0000-0001-5607-1797; Lunetta, Kathryn/0000-0002-9268-810X; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Dupuis, Josee/0000-0003-2871-3603; Benjamin, Emelia/0000-0003-4076-2336 FU NCRR NIH HHS [M01 RR001066, M01 RR001066-26, M01-RR-01066]; NHLBI NIH HHS [R01 HL077447, HL04334, HL064753, HL076784, HL077447, HL080025, HL080124, HL60040, HL70139, K23 HL080025, K23 HL080025-05, K24 HL004334, K24 HL004334-08, N01 HC025195, N01-HC-25195, N01HC25195, R01 HL060040, R01 HL060040-04, R01 HL064753, R01 HL064753-04, R01 HL071039, R01 HL071039-02, R01 HL076784, R01 HL076784-05, R01 HL077447-05, R01 HL080124, R01 HL080124-05, U01 HL066582, U01 HL066582-04S1, U01-HL66582]; NIA NIH HHS [AG028321, R01 AG028321, R01 AG028321-04]; NIDDK NIH HHS [K24 DK080140-01] NR 48 TC 82 Z9 88 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD JUN PY 2008 VL 51 IS 6 BP 1651 EP 1657 DI 10.1161/HYPERTENSIONAHA.107.105668 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 303PT UT WOS:000256053500042 PM 18426996 ER PT J AU Khanicheh, A Mintzopoulos, D Weinberg, B Tzika, AA Mavroidis, C AF Khanicheh, Azadeh Mintzopoulos, Dionyssios Weinberg, Brian Tzika, A. Aria Mavroidis, Constantinos TI Evaluation of electrorheological fluid dampers for applications at 3-T MRI environment SO IEEE-ASME TRANSACTIONS ON MECHATRONICS LA English DT Article DE actuator; brake; damper; electrorheological fluid (ERF); functional magnetic resonance imaging (fMRI); magnetic resonance (MR) compatible robotic/mechatronic systems; magnetic resonance imaging (MRI) ID INTRAOPERATIVE MRI; REHABILITATION; FIELD AB This paper evaluates the use of electrorheological fluids (ERFs) within a magnetic resonance imaging (MRI) environment. ERF is a semiactive variable impedance material, which could be used as an alternative type of resistive force/torque-generation or in combination with other actuators as a damper/clutch to modulate the output force/torque of the actuator. In this paper, an ERF damper/brake is introduced and its magnetic resonance (MR) compatibility is examined at a 3-T MR imaging environment by measuring the output performance of the damper and the SNR of the MRI images. The experimental results showed that damper's resistive force generation while positioned within the MRI is almost the same as that in normal operation. The signal-to-noise investigation was performed both with a phantom and human. The results indicated that the ERF damper did not affect the MRI images when it was operated over 30 cm away from the MRI's RF coil. We hope that the synthesis and tables presented in this paper can facilitate the choice of ERF brake actuation principle to various applications in an MR environment. C1 [Khanicheh, Azadeh; Weinberg, Brian; Mavroidis, Constantinos] Northeastern Univ, Dept Mech & Ind Engn, Boston, MA 02115 USA. [Mintzopoulos, Dionyssios; Tzika, A. Aria] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Mintzopoulos, Dionyssios; Tzika, A. Aria] Harvard Univ, Sch Med, Shriners Burns Inst, Boston, MA 02114 USA. RP Khanicheh, A (reprint author), Northeastern Univ, Dept Mech & Ind Engn, Boston, MA 02115 USA. EM azadeh@coe.neu.edu; dionyssi@nmr.mgh.harvard.edu; weinberg@coe.neu.edu; aaria_tzika@hms.harvard.edu; mavro@coe.neu.edu NR 13 TC 19 Z9 21 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1083-4435 J9 IEEE-ASME T MECH JI IEEE-ASME Trans. Mechatron. PD JUN PY 2008 VL 13 IS 3 BP 286 EP 294 DI 10.1109/TMECH.2008.924043 PG 9 WC Automation & Control Systems; Engineering, Manufacturing; Engineering, Electrical & Electronic; Engineering, Mechanical SC Automation & Control Systems; Engineering GA 316RF UT WOS:000256966700004 ER PT J AU Shaltis, PA Reisner, AT Asada, HH AF Shaltis, Phillip A. Reisner, Andrew T. Asada, H. Harry TI Cuffless blood pressure monitoring using hydrostatic pressure changes SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE blood pressure (BP) measurement; cuffless blood pressure; hydrostatic pressure; noninvasive sensors; oscillometry; wearable sensor ID MEAN ARTERIAL-PRESSURE; OSCILLOMETRIC METHOD; HUMAN FINGER AB This paper presents a new principle for noninvasive blood pressure measurements through a modified volume-oscillometric technique that eliminates an inflatable pressure cuff, and instead takes advantage of natural hydrostatic pressure changes caused by raising and lowering the subject's arm. This new methodology provides the distinct advantage of using an absolute gauge pressure reference for measurements, and does not necessarily require additional actuation. C1 [Asada, H. Harry] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM pshaltis@alum.mit.edu; areisner@partners.org; asada@mit.edu NR 9 TC 19 Z9 19 U1 0 U2 11 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD JUN PY 2008 VL 55 IS 6 BP 1775 EP 1777 DI 10.1109/TBME.2008.919142 PG 3 WC Engineering, Biomedical SC Engineering GA 305BX UT WOS:000256153900016 PM 18714843 ER PT J AU Boverman, G Miller, EL Brooks, DH Isaacson, D Fang, QQ Boas, DA AF Boverman, Gregory Miller, Eric L. Brooks, Dana H. Isaacson, David Fang, Qianqian Boas, David A. TI Estimation and statistical bounds for three-dimensional polar shapes in diffuse optical tomography SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE optical tomography; image reconstruction; inverse problems; shape-based imaging ID GLOBAL CONFIDENCE-REGIONS; INVERSE SCATTERING; POSED PROBLEMS; L-CURVE; RECONSTRUCTION; BREAST; REGULARIZATION; ALGORITHM; FORMULAS; TISSUE AB Voxel-based reconstructions in diffuse optical tomography (DOT) using a quadratic regularization functional tend to produce very smooth images due to the attenuation of high spatial frequencies. This then causes difficulty in estimating the spatial extent and contrast of anomalous regions such as tumors. Given an assumption that the target image is piecewise constant, we can employ a parametric model to estimate the boundaries and contrast of an inhomogeneity directly. In this paper, we describe a method to directly reconstruct such a shape boundary from diffuse optical measurements. We parameterized the object boundary using a spherical harmonic basis, and derived a method to compute sensitivities of measurements with respect to shape parameters. We introduced a centroid constraint to ensure uniqueness of the combined shape/center parameter estimate, and a projected Newton method was utilized to optimize the object center position and shape parameters simultaneously. Using the shape Jacobian, we also computed the Cramer-Rao lower bound on the theoretical estimator accuracy given a particular measurement configuration, object shape, and level of measurement noise. Knowledge of the shape sensitivity matrix and of the measurement noise variance allows us to visualize the shape uncertainty region in three dimensions, giving a confidence region for our shape estimate. We have implemented our shape reconstruction method, using a finite-difference-based forward model to compute the forward and adjoint fields. Reconstruction results are shown for a number of simulated target shapes, and we investigate the problem of model order selection using realistic levels of measurement noise. Assuming a signal-to-noise ratio in the amplitude measurements of 40 dB and a standard deviation in the phase measurements of 0.1 degrees, we are able to estimate an object represented with an eighth-order spherical harmonic model having an absorption contrast of 0.15 cm(-1) and a volume of 4.82 cm(3) with errors of less than 10% in object volume and absorption contrast. We also investigate the robustness of our shape-based reconstruction approach to a violation of the assumption that the medium is purely piecewise constant. C1 [Boverman, Gregory] Rensselaer Polytech Inst, Dept Biomed Engn, Troy, NY 12180 USA. [Miller, Eric L.] Tufts Univ, Dept Elect & Comp Engn, Medford, MA 02155 USA. [Brooks, Dana H.] Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. [Isaacson, David] Rensselaer Polytech Inst, Dept Math Sci, Troy, NY 12180 USA. [Fang, Qianqian; Boas, David A.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Boverman, G (reprint author), Rensselaer Polytech Inst, Dept Biomed Engn, 7046 Jonsson Engn Ctr, Troy, NY 12180 USA. EM boverg@rpi.edu RI Miller, Eric/B-2546-2008 OI Miller, Eric/0000-0002-3156-6002 FU NCI NIH HHS [R01 CA097305-05, R01 CA097305] NR 48 TC 8 Z9 8 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JUN PY 2008 VL 27 IS 6 BP 752 EP 765 DI 10.1109/TMI.2007.911492 PG 14 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 307YD UT WOS:000256354600003 PM 18541483 ER PT J AU Jarlskog, CZ Paganetti, H AF Jarlskog, Christina Zacharatou Paganetti, Harald TI Physics settings for using the Geant4 toolkit in proton therapy SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article DE Geant4; Monte Carlo; physics validation; proton therapy ID MONTE-CARLO SIMULATIONS; NUCLEAR-INTERACTIONS; MODELS; ALGORITHM AB We simulated electromagnetic and nuclear processes induced by clinical proton beams in order to select the physics setting for the 8.1 version of the Geant4 toolkit. A modular physics list was constructed allowing for alternative processes and models to be invoked in the simulations. We validated the Monte Carlo by means of measured depth-dose distributions in water for 86 MeV and 209 MeV beams and measured longitudinal charge profiles in a stack of polyethylene absorbers (multilayer Faraday cup) for a 160 MeV beam. Best agreement between simulation and measurement was found for the standard electromagnetic and binary cascade models of Geant4. C1 [Jarlskog, Christina Zacharatou; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Jarlskog, Christina Zacharatou; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jarlskog, CZ (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 33 TC 69 Z9 69 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD JUN PY 2008 VL 55 IS 3 BP 1018 EP 1025 DI 10.1109/TNS.2008.922816 PN 1 PG 8 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 316RO UT WOS:000256967600025 ER PT J AU Relloso, M Cheng, TY Im, JS Parisini, E Roura-Mir, C DeBono, C Zajonc, DM Murga, LF Ondrechen, MJ Wilson, IA Porcelli, SA Moody, DB AF Relloso, Miguel Cheng, Tan-Yun Im, Jin S. Parisini, Emilio Roura-Mir, Carme DeBono, Charles Zajonc, Dirk M. Murga, Leonel F. Ondrechen, Mary Jo Wilson, Ian A. Porcelli, Steven A. Moody, D. Branch TI pH-dependent interdomain tethers of CD1b regulate its antigen capture SO IMMUNITY LA English DT Article ID DIFFERENT CELLULAR COMPARTMENTS; T-CELLS; CRYSTAL-STRUCTURE; LIPOGLYCAN ANTIGENS; LIPID ANTIGENS; FORCE-FIELD; CONFORMATIONAL FLEXIBILITY; MYCOBACTERIUM-TUBERCULOSIS; MOLECULAR RECOGNITION; PRESENTING MOLECULES AB As CD1 proteins recycle between the cell surface and endosomes, they show altered receptiveness to lipid antigen loading. We hypothesized that changes in proton concentration encountered within distinct endosomal compartments influence the charge state of residues near the entrance to the CD1 groove and thereby control antigen loading. Molecular dynamic models identified flexible areas of the CD1b heavy chain in the superior and lateral walls of the A' pocket. In these same areas, residues that carry charge in a pH-dependent manner (D60, E62) were found to tether the rigid alpha 1 helix to flexible areas of the alpha 2 helix and the 50-60 loop. After disruption of these tethers with acid pH or mutation, we observed increased association and dissociation of lipids with CD1b and preferential presentation of antigens with bulky lipid tails. We propose that ionic tethers act as molecular switches that respond to pH fluxes during endosomal recycling and regulate the conformation of the CD1 heavy chain to control the size and rate of antigens captured. C1 [Relloso, Miguel; Cheng, Tan-Yun; Roura-Mir, Carme; DeBono, Charles; Moody, D. Branch] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Relloso, Miguel; Cheng, Tan-Yun; Roura-Mir, Carme; DeBono, Charles; Moody, D. Branch] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Im, Jin S.; Porcelli, Steven A.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. [Parisini, Emilio] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Lab Immunobiol,Dept Med Oncol, Boston, MA 02115 USA. [Murga, Leonel F.; Ondrechen, Mary Jo] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Zajonc, Dirk M.; Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. RP Moody, DB (reprint author), Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Smith Bldg Room 514,1 Jimmy Fund Way, Boston, MA 02115 USA. EM bmoody@rics.bwh.harvard.edu RI Roura-Mir, Carme/D-4538-2013 OI Roura-Mir, Carme/0000-0003-0514-337X FU NCI NIH HHS [R01 CA058896, CA58896]; NIAID NIH HHS [AI 071155, AI063537, AI45889, R01 AI045889-06, R01 AI045889-08, R01 AI071155, P01 AI063537, R01 AI045889, R01 AI045889-07, R01 AI049313]; NIAMS NIH HHS [R01 AR048632, AR048632]; NIGMS NIH HHS [GM62116, U54 GM062116] NR 70 TC 33 Z9 33 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 2008 VL 28 IS 6 BP 774 EP 786 DI 10.1016/j.immuni.2008.04.017 PG 13 WC Immunology SC Immunology GA 313SL UT WOS:000256760200009 PM 18538591 ER PT J AU Scalapino, KJ Daikh, DI AF Scalapino, Kenneth J. Daikh, David I. TI CTLA-4: a key regulatory point in the control of autoimmune disease SO IMMUNOLOGICAL REVIEWS LA English DT Review DE Tcells; regulatory T cells; suppression; autoimmunity ID CYTOTOXIC-T-LYMPHOCYTE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; IMMUNOLOGICAL SELF-TOLERANCE; B-CELL ACTIVATION; A-G POLYMORPHISM; ANTIGEN-4 MONOCLONAL-ANTIBODY; COLONY-STIMULATING FACTOR; PHASE-I TRIAL; GRAVES-DISEASE; RHEUMATOID-ARTHRITIS AB Chronic autoimmune disease in humans is the result of a failure to control autoreactive immune cells in the periphery. This control is largely achieved by inhibition of newly activated and memory cells. A number of negative immune regulatory pathways have been characterized. The cell surface coreceptor cytotoxic T-lymphocyte antigen-4 (CTLA-4) has emerged as a critical attenuator of T-cell activation and an essential component of the regulatory systems that serve to maintain peripheral tolerance. CTLA-4 expression is induced on the surface of T cells after they have received a costimulatory signal from antigen-presenting cells (APCs) via engagement of CD28 on the T-cell surface. CTLA-4 attenuates this costimulation by competing for CD28 ligands and through direct effects on APCs via the same ligands utilized by CD28. A large number of genetic association studies suggest that the CTLA-4 gene is a locus of susceptibility to autoimmune disease. However, specific functional defects in the CTLA-4 gene in patients have not been identified to date. Elucidating the role of CTLA-4 in immune tolerance has also led to a number of therapeutic applications, particularly in the treatment of malignancy and autoimmune disease. C1 [Scalapino, Kenneth J.] Univ Calif San Francisco, Div Rheumatol, Dept Med, San Francisco, CA 94143 USA. [Daikh, David I.] San Francisco VA Med Ctr, Arthrit Immunol Sect, San Francisco, CA USA. RP Daikh, DI (reprint author), Arthrit Immunology 111R,4150 Clement St, San Francisco, CA 94121 USA. EM david.daikh@ucsf.edu NR 164 TC 92 Z9 100 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 EI 1600-065X J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 2008 VL 223 BP 143 EP 155 DI 10.1111/j.1600-065X.2008.00639.x PG 13 WC Immunology SC Immunology GA 325CG UT WOS:000257565200009 PM 18613834 ER PT J AU Gibbons, C Sykes, M AF Gibbons, Carrie Sykes, Megan TI Manipulating the immune system for anti-tumor responses and transplant tolerance via mixed hematopoietic chimerism SO IMMUNOLOGICAL REVIEWS LA English DT Review DE hematopoietic cell transplantation; mixed chimerism; graft-versus-host disease; graft-versus-tumor; tolerance ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; REGULATORY T-CELLS; NATURAL-KILLER-CELLS; LONG-TERM SURVIVAL; RECIPIENT LEUKOCYTE INFUSIONS; DONOR-SPECIFIC TRANSFUSION; RENAL-ALLOGRAFT REJECTION; WHOLE-BODY IRRADIATION AB Stem cells (SCs) with varying potentiality have the capacity to repair injured tissues. While promising animal data have been obtained, allogeneic SCs and their progeny are subject to immune-mediated rejection. Here, we review the potential of hematopoietic stem cells (HSCs) to promote immune tolerance to allogeneic and xenogeneic organs and tissues, to reverse autoimmunity, and to be used optimally to cure hematologic malignancies. We also review the mechanisms by which hematopoietic cell transplantation (HCT) can promote anti-tumor responses and establish donor-specific transplantation tolerance. We discuss the barriers to clinical translation of animal studies and describe some recent studies indicating how they can be overcome. The recent achievements of durable mixed chimerism across human leukocyte antigen barriers without graft-versus-host disease and of organ allograft tolerance through combined kidney and bone marrow transplantation suggest that the potential of this approach for use in the treatment of many human diseases may ultimately be realized. C1 [Gibbons, Carrie; Sykes, Megan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,Bone Marrow Transplanta, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,Bone Marrow Transplanta, MGH E Bldg 149,5102 13th St, Boston, MA 02129 USA. EM Megan.Sykes@tbrc.mgh.harvard.edu FU NCI NIH HHS [R01 CA079989-09, P01 CA111519, P01 CA111519-02, P01 CA111519-020001, R01 CA079989, P01 CA111519-030001, P01 CA111519-03]; NHLBI NIH HHS [R01 HL049915, P01 HL018646-300014, P01 HL018646, R01 HL049915-15]; NIAID NIH HHS [P01 AI045897-080007, P01 AI045897] NR 275 TC 18 Z9 20 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 EI 1600-065X J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 2008 VL 223 BP 334 EP 360 DI 10.1111/j.1600-065X.2008.00636.x PG 27 WC Immunology SC Immunology GA 325CG UT WOS:000257565200021 PM 18613846 ER PT J AU Lonyai, A Kodama, S Burger, D Faustman, DL AF Lonyai, Anna Kodama, Shohta Burger, Douglas Faustman, Denise L. TI Fetal Hox11 expression patterns predict defective target organs: a novel link between developmental biology and autoimmunity SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Article DE Hox11; hearing loss; cochlea; autoimmunity; tongue ID TYPE-1 DIABETES-MELLITUS; SJOGRENS-SYNDROME; CELIAC-DISEASE; ADDISONS-DISEASE; HEARING-LOSS; NOD MICE; MOUSE; PREVALENCE; MODEL; ABNORMALITIES AB Developmental biology has long been ignored in the etiology and diverse manifestations of autoimmune diseases. Yet a role for development is suggested by intriguing overlaps in particular organs targeted in autoimmune diseases, in this case type 1 diabetes and Sjogren's syndrome. Patients with type 1 diabetes have high rates of co-occurring Sjogren's syndrome, and both conditions are associated with hearing loss and tongue abnormalities. All of these co-occurrences are found in organs tracing their lineage to the developmental transcription factor Hox11, which is expressed in embryonic cells destined for the pancreas, salivary glands, tongue, cranial nerves and cochlea. To determine whether development contributes to autoimmunity, we compared four target organs in NOD mice (an animal model for type 1 diabetes and Sjogren's syndrome) with NOD-SCID mice (which lack lymphocytes) and normal controls. We examined the structure and/or function of the cochlea, salivary glands, pancreas and tongue at early time points after birth. Before the usual time of the onset of type 1 diabetes or Sjogren's syndrome, we show that all four Hox11-derived organs are structurally abnormal in both NOD mice and NOD-SCID mice versus controls. The most striking functional defect is near complete hearing loss occurring before the normal time of the onset of autoimmunity. The hearing loss is associated with severe structural defects in the cochlea, suggesting that near-deafness occurs independent of autoimmune attack. The pancreas and salivary glands are also structurally abnormal in NOD and NOD-SCID mice, but they are functionally normal. This suggests that autoimmune attack of these two organs is required for functional failure. We conclude that a developmental lineage of cells contributes to autoimmunity and predicts which organs may be targeted, either structurally and/or functionally. Taken together, our findings challenge the orthodoxy that autoimmunity is solely caused by a defective immune system. C1 [Lonyai, Anna; Burger, Douglas; Faustman, Denise L.] Massachusetts Gen Hosp, Immunobiol Labs, Charlestown, MA 02129 USA. [Lonyai, Anna; Burger, Douglas; Faustman, Denise L.] Harvard Univ, Sch Med, Charlestown, MA 2129 USA. [Kodama, Shohta] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Faustman, DL (reprint author), Massachusetts Gen Hosp, Immunobiol Labs, Bldg 149,13th St,Room 3602, Charlestown, MA 02129 USA. EM faustman@helix.mgh.harvard.edu FU NIDDK NIH HHS [P30 DK057521] NR 41 TC 11 Z9 11 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD JUN PY 2008 VL 86 IS 4 BP 301 EP 309 DI 10.1038/icb.2008.6 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 299KU UT WOS:000255755300005 PM 18301381 ER PT J AU Hurley, BP McCormick, BA AF Hurley, Bryan P. McCormick, Beth A. TI Multiple roles of phospholipase A(2) during lung infection and inflammation SO INFECTION AND IMMUNITY LA English DT Review ID PLATELET-ACTIVATING-FACTOR; RESPIRATORY-DISTRESS-SYNDROME; SURFACTANT PROTEIN-A; OBSTRUCTIVE PULMONARY-DISEASE; AIRWAY EPITHELIAL-CELLS; MICE OVEREXPRESSING PEROXIREDOXIN-6; CYSTEINYL LEUKOTRIENE SYNTHESIS; PSEUDOMONAS-AERUGINOSA EXOU; GROUP IIA PHOSPHOLIPASE-A2; ARACHIDONIC-ACID RELEASE C1 Massachusetts Gen Hosp, Mucosal Immun Labs, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Hurley, BP (reprint author), Massachusetts Gen Hosp, Mucosal Immun Labs, CNY 114 114-3503, Charlestown, MA 02129 USA. EM Bphurley@partners.org FU NIAID NIH HHS [K22 AI065425-01A2] NR 137 TC 24 Z9 24 U1 0 U2 3 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 JUN PY 2008 VL 76 IS 6 BP 2259 EP 2272 DI 10.1128/IAI.00059-08 PG 14 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 304SH UT WOS:000256128900001 PM 18411286 ER PT J AU Song, YL Pittet, JF Huang, XZ He, H Lynch, SV Violette, SM Weinreb, PH Horan, GS Carmago, A Sawa, Y Bernstein, XL Wiener-Kronish, JP AF Song, Yuanlin Pittet, Jean Francois Huang, Xiaozhu He, Hong Lynch, Susan V. Violette, Shelia M. Weinreb, Paul H. Horan, Gerald S. Carmago, Amua Sawa, Yoriko Bernstein, Xin Liu Wiener-Kronish, Jeanine P. TI Role of integrin alpha v beta 6 in acute lung injury induced by Pseudomonas aeruginosia SO INFECTION AND IMMUNITY LA English DT Article ID GROWTH-FACTOR-BETA; TGF-BETA; PULMONARY-FIBROSIS; INFLAMMATION; EXPRESSION; PNEUMONIA; INTEGRINS; SUBUNIT; MICE; INHIBITION AB Deletion of integrin alpha v beta 6 has been associated with significant protection in experiments where lung injury was induced by bleomycin, lipophilic polysaccharides, and high tidal volume ventilation. This has led to the suggestion that antibody blockade of this integrin is a novel therapy for acute lung injury. We questioned whether beta 6 gene deletion would also protect against Pseudomonas aeruginosa-induced acute lung injury. Wild-type and littermate beta 6-null mice, as well as recombinant soluble TGF-beta receptor type II-Fc (rsTGFPRII-Fc) and anti-alpha v beta 6 treated wild-type mice, were instilled with live P. aeruginosa. Four or 8 h after bacterial instillation, the mice were euthanized, and either bronchoalveolar lavage fluid or lung homogenates were obtained. Deletion of the 06 gene resulted in an overall increase in inflammatory cells in the lungs. Bacterial numbers from the lung homogenates of infected beta 6-null mice were significantly decreased compared to the numbers in the wild-type mice (1.6 x 10(6) CFU versus 4.2 x 10(6) CFU [P < 0.01]). There were no significant differences in P. aeruginosa-mediated increases in lung endothelial permeability between wild-type and beta 6-null mice. Similarly, pretreatment with the alpha v beta 6 antibody or with rsTGF-beta RII-Fc did not significantly affect the P. aeruginosa-induced lung injury or rate of survival compared to pretreatment with control immunoglobulin G. We conclude that deletion or inhibition of the integrin alpha v beta 6 did not protect animals from P. aeruginosa-induced lung injury. However, these therapies also did not increase the lung injury, suggesting that host defense was not compromised by this promising new therapy. C1 [Song, Yuanlin; Pittet, Jean Francois; He, Hong; Lynch, Susan V.; Carmago, Amua; Sawa, Yoriko; Wiener-Kronish, Jeanine P.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. [Huang, Xiaozhu; Bernstein, Xin Liu] Univ Calif San Francisco, Lung Biol Ctr, Dept Med, San Francisco, CA 94143 USA. [Violette, Shelia M.; Weinreb, Paul H.; Horan, Gerald S.] Biogen Idec Inc, Cambridge, MA USA. [He, Hong] Fudan Univ, Canc Hosp, Shanghai 200032, Peoples R China. RP Wiener-Kronish, JP (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, GRB 444,55 Fruit St, Boston, MA 02114 USA. EM jwiener-kronish@partners.org RI Lynch, Susan/B-6272-2009 FU NHLBI NIH HHS [HL074005, HL69809, HL74005, P50 HL074005, R01 HL069809] NR 27 TC 6 Z9 6 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 JUN PY 2008 VL 76 IS 6 BP 2325 EP 2332 DI 10.1128/IAI.01431-07 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 304SH UT WOS:000256128900007 PM 18378634 ER PT J AU Patel, M Weinheimer, JD Waites, KB Baddley, JW AF Patel, Mukesh Weinheimer, Jeffrey D. Waites, Ken B. Baddley, John W. TI Active surveillance to determine the impact of methicillin-resistant Staphylococcus aureus colonization on patients in intensive care units of a Veterans Affairs Medical Center SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 47th Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 17-20, 2007 CL Chicago, IL ID RISK-FACTORS; NASAL COLONIZATION; HOSPITAL ADMISSION; INFECTION; MRSA; BACTEREMIA; PREVALENCE; MORTALITY; CULTURES AB OBJECTIVE. The impact of methicillin-resistant Staphylococcus aureus (MRSA) colonization on mortality has not been well characterized. We sought to describe the impact of MRSA colonization on patients admitted to intensive care units (ICUs) in the Birmingham Veterans Affairs Medical Center (VAMC). METHODS. We conducted a retrospective cohort study of ICU patients at the Birmingham VAMC during 2005 to evaluate the predictors of MRSA colonization and determine its effect on clinical outcomes. Surveillance cultures for MRSA were performed on admission to the ICU and weekly thereafter. Clinical findings, the incidence of MRSA infection, and mortality within 3 months after ICU admission were recorded. Predictors of mortality and S. aureus colonization were determined using multivariable models. RESULTS. S. aureus colonization was present in 97 (23.3%) of 416 patients screened, of whom 67 (16.1%) were colonized with methicillin-susceptible S. aureus (MSSA) and 30 (7.2%) with MRSA. All-cause mortality at 3 months among MRSA-colonized patients was significantly greater than that among MSSA-colonized patients (46.7% vs 19.4%; P = .009). MRSA colonization was an independent predictor of death (adjusted odds ratio [OR], 3.7 [95% confidence interval {CI}, 1.5-8.9]; P = .003) and onset of MRSA infection after hospital discharge (adjusted OR, 7.6 [95% CI, 2.48-23.2]; P < .001). Risk factors for MRSA colonization included recent antibiotic use (adjusted OR, 4.8 [ 95% CI, 1.9-12.2]; P = .001) and dialysis (adjusted OR, 18.9 [95% CI, 2.1-167.8]; P = .008). CONCLUSIONS. Among ICU patients, MRSA colonization is associated with subsequent MRSA infection and an all-cause mortality that is greater than that for MSSA colonization. Active surveillance for MRSA colonization may identify individuals at risk for these adverse outcomes. Prospective studies of outcomes in MRSA-colonized patients may better define the role of programs for active MRSA surveillance. C1 [Patel, Mukesh; Baddley, John W.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Patel, Mukesh] Univ Alabama, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. [Weinheimer, Jeffrey D.] Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA. [Waites, Ken B.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. RP Patel, M (reprint author), Univ Alabama, Dept Med, Div Infect Dis, Univ Blvd,229 Tinsley Harrison Tower, Birmingham, AL 35294 USA. EM mukesh@uab.edu NR 22 TC 25 Z9 29 U1 0 U2 0 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 JUN PY 2008 VL 29 IS 6 BP 503 EP 509 DI 10.1086/588161 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 307JI UT WOS:000256314800005 PM 18510459 ER PT J AU Okike, K Kocher, MS Mehlman, CT Bhandari, M AF Okike, Kanu Kocher, Mininder S. Mehlman, Charles T. Bhandari, Mohit TI Industry-sponsored research SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Review DE conflicts of interest; industry; biomedical research; financial ID CONFLICTS-OF-INTEREST; CLINICAL-TRIAL AGREEMENTS; ACADEMIC MEDICAL-CENTERS; ORTHOPEDIC RESEARCH; PHARMACEUTICAL-INDUSTRY; BIOMEDICAL-RESEARCH; PUBLICATION BIAS; FUNDING SOURCE; DRUG TRIALS; ASSOCIATION AB Financial conflicts of interest are exceedingly common in biomedical research. Investigators with conflicts of interest are more likely to arrive at positive conclusions, perhaps as a result of biased study design, industry suppression of negative results, preferential funding by industry of projects that are likely to succeed, or biased interpretation of results on the part of investigators. Government and professional organisations have proposed guidelines for managing conflicts of interest, but in practice it is the policies of universities and medical journals that direct the actions of investigators. Academic researchers and the media have expressed concern about the influence of industry sponsorship on biomedical research, white industry is increasingly turning to private entities (such as contract research organisations) to conduct clinical trials. Research participants appear less concerned with conflicts of interest in biomedical research, perhaps due to a faith that such conflicts are being appropriately managed by institutions. After reviewing the literature, we provide recommendations for the ethical conduct of biomedical research in the presence of financial conflicts of interest. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Okike, Kanu] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. [Kocher, Mininder S.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Childrens Hosp, Boston, MA 02114 USA. [Mehlman, Charles T.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Div Pediat Orthopaed Surg, Cincinnati, OH USA. [Bhandari, Mohit] McMaster Univ, Dept Orthopaed Surg, Hamilton Gen Hosp, Hamilton, ON L8S 4L8, Canada. RP Okike, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM okike@post.harvard.edu OI Okike, Kanu/0000-0001-9310-9969 NR 108 TC 26 Z9 26 U1 0 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 J9 INJURY JI Injury-Int. J. Care Inj. PD JUN PY 2008 VL 39 IS 6 BP 666 EP 680 DI 10.1016/j.injury.2008.02.013 PG 15 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA 324PO UT WOS:000257530700008 PM 18508054 ER PT J AU Bauer-Wu, S Sullivan, AM Rosenbaum, E Ott, MJ Powell, M McLoughlin, M Healey, MW AF Bauer-Wu, Susan Sullivan, Amy M. Rosenbaum, Elana Ott, Mary Jane Powell, Mark McLoughlin, Margo Healey, Martha W. TI Facing the challenges of hematopoietic stem cell transplantation with mindfulness meditation: A pilot study SO INTEGRATIVE CANCER THERAPIES LA English DT Article DE mindfulness; meditation; MBSR; mind-body; bone marrow transplant; stem cell transplant; cancer ID BONE-MARROW TRANSPLANTATION; CONTROLLED CLINICAL-TRIAL; STRESS REDUCTION; CANCER-TREATMENT; PSYCHOSOCIAL INTERVENTIONS; DEPRESSION; RELAXATION; SYMPTOMS; ANXIETY; CARE AB The hematopoietic stem cell transplant (HSCT) experience is emotionally and physically stressful for cancer patients who undergo this procedure. Mindfulness-based interventions have been studied in patients with various diagnoses, including cancer, although minimal work has applied this intervention to hospitalized patients. Use of mindfulness meditation has potential to provide HSCT patients with coping skills to deal with unpleasant symptoms and an uncertain future. This exploratory study examined feasibility, physiological arousal, and psychological and physical symptoms in HSCT patients participating in a mindfulness meditation intervention that begins before and continues throughout hospitalization and involves one-on-one guided sessions and daily practice using a 17-minute meditation CD. Of the 20 participants, 78.9% completed the intervention. Statistically significant decreases in heart and respiratory rates and improvements in symptoms immediately before and after each session were found. These findings demonstrate feasibility and preliminary support of a mindfulness meditation intervention with symptomatic, hospitalized cancer patients. C1 [Bauer-Wu, Susan] Emory Univ, Nell Hodgson Woodruff Sch Nursing, Atlanta, GA 30322 USA. [Sullivan, Amy M.] Virginia Commonwealth Univ, Sch Med, Richmond, VA USA. [Ott, Mary Jane; Powell, Mark] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bauer-Wu, S (reprint author), 1520 Clifton Rd,Room 440, Atlanta, GA 30322 USA. EM sbauerw@emory.edu NR 37 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 1534-7354 J9 INTEGR CANCER THER JI Integr. Cancer Ther. PD JUN PY 2008 VL 7 IS 2 BP 62 EP 69 DI 10.1177/1534735408319068 PG 8 WC Oncology; Integrative & Complementary Medicine SC Oncology; Integrative & Complementary Medicine GA 316FG UT WOS:000256934000002 PM 18550888 ER PT J AU Berra, L Curto, F Bassi, GL Laquerriere, P Pitts, B Baccarelli, A Kolobow, T AF Berra, Lorenzo Curto, Francesco Bassi, Gianluigi Li Laquerriere, Patrice Pitts, Betsey Baccarelli, Andrea Kolobow, Theodor TI Antimicrobial-coated endotracheal tubes: an experimental study SO INTENSIVE CARE MEDICINE LA English DT Article DE endotracheal tube; mechanical ventilation; bacterial biofilm; ventilator-associated pneumonia; silver sulfadiazine ID VENTILATOR-ASSOCIATED PNEUMONIA; INTENSIVE-CARE UNITS; BACTERIAL-COLONIZATION; URINARY CATHETERS; HOSPITALIZED-PATIENTS; INFECTION; BIOFILM; PREVENTION; RESISTANCE; ADHESION AB Objective: Antibiotic-resistant bacterial biofilm may quickly form on endotracheal tubes ( ETTs) and can enter the lungs, potentially causing pneumonia. In an attempt to prevent bacterial colonization, we developed and tested in an in-vitro study and animal study several antibacterial-coated ETTs ( silver sulfadiazine with and without carbon in polyurethane, silver sulfadiazine and chlorhexidine with and without carbon in polyurethane, silver-platinum with and without carbon in polyurethane, in polyurethane, and rose bengal for UV light). Design, setting, animals, interventions: After preliminary silver sulfadiazine in ( SSD-ETT) was selected among the coatings to be challenged every 24 h with 10(4)-10(6) Pseudomonas aeruginosa/ml and evaluated at 6 h, 24 h, and 72 h with standard microbiological studies, scanning electron microscopy, and confocal scanning microscopy. Subsequently, eight sheep were randomized to receive either a SSD-ETT or a standard ETT ( St-ETT). After 24 h of mechanical ventilation, standard microbiological studies were performed together with scanning electron microscopy and confocal microscopy. Measurements and results: In the in-vitro study SSD-ETT remained bacteria-free for up to 72 h, whereas St-ETT showed heavy P. aeruginosa growth and biofilm formation ( p < 0.01). In sheep, the SSD-ETT group showed no bacterial growth in the ETT, ventilator tubing, and lower respiratory tract, while heavy colonization was found in the St-ETT ( p < 0.01), ventilator tubing ( p = 0.03), and lower respiratory tract ( p < 0.01). Conclusion: This study describes several effective and durable antibacterial coatings for ETTs. Particularly, SSD-ETT showed prevention against P. aeruginosa biofilm formation in a 72-h in-vitro study and lower respiratory tract colonization in sheep mechanically ventilated for 24 h. C1 [Berra, Lorenzo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02215 USA. [Curto, Francesco; Bassi, Gianluigi Li; Kolobow, Theodor] NHLBI, NIH, Pulm & Crit Care Med Branch, Bethesda, MD 20892 USA. [Laquerriere, Patrice] Univ Reims, INSERM, ERM 0203, Lab Microscopie Elect,UFR Sci, F-51685 Reims, France. [Pitts, Betsey] Montana State Univ, Ctr Biofilm Engn, Bozeman, MT 59717 USA. [Pitts, Betsey] Montana State Univ, Dept Chem Engn, Bozeman, MT 59717 USA. [Baccarelli, Andrea] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. RP Berra, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St,Boston WHT-4-436, Boston, MA 02215 USA. EM lberra@partners.org RI Laquerriere, Patrice/P-1025-2016; OI Laquerriere, Patrice/0000-0001-7637-9094; Baccarelli, Andrea/0000-0002-3436-0640 NR 31 TC 29 Z9 35 U1 1 U2 12 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 JUN PY 2008 VL 34 IS 6 BP 1020 EP 1029 DI 10.1007/s00134-008-1099-3 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 319QZ UT WOS:000257180100008 PM 18418572 ER PT J AU Berra, L Kolobow, T Laquerriere, P Pitts, B Bramati, S Pohlmann, J Marelli, C Panzeri, M Brambillasca, P Villa, F Baccarelli, A Bouthors, S Stelfox, HT Bigatello, LM Moss, J Pesenti, A AF Berra, Lorenzo Kolobow, Theodor Laquerriere, Patrice Pitts, Betsey Bramati, Simone Pohlmann, Joshua Marelli, Chiara Panzeri, Miriam Brambillasca, Pietro Villa, Federico Baccarelli, Andrea Bouthors, Sylvie Stelfox, Henry T. Bigatello, Luca M. Moss, Joel Pesenti, Antonio TI Internally coated endotracheal tubes with silver sulfadiazine in polyurethane to prevent bacterial colonization: a clinical trial SO INTENSIVE CARE MEDICINE LA English DT Article DE endotracheal tube; mechanical ventilation; bacterial biofilm; ventilator-associated pneumonia; silver sulfadiazine ID VENTILATOR-ASSOCIATED PNEUMONIA; NOSOCOMIAL INFECTIONS; LEUKOPENIA SECONDARY; TRACHEAL TUBE; BIOFILM; THERAPY; PATIENT; ARGYRIA; CREAM AB Objective: Coated medical devices have been shown to reduce catheter-related infections. We coated endotracheal tubes ( ETT) with silver sulfadiazine ( SSD), and tested them in a clinical study to assess the feasibility, safety, and efficacy of preventing bacterial colonization. Design: A prospective, randomized clinical trial, phase I-II. Setting: Academic intensive care unit ( ICU). Participants: Forty-six adult patients expected to need 12-24 h of intubation were randomized into two groups. Interventions: Patients were randomized to be intubated with a standard non-coated ETT ( St-ETT, n = 23; control group), or with a SSD-coated ETT ( SSD-ETT, n = 23). Measurements and results: Coating with SSD prevented bacterial colonization of the ETT ( frequency of colonization: SSD-ETT 0/23, St-ETT 8/23; p < 0.01). No organized bacterial biofilm could be identified on the lumen of any ETT; however, SSD was associated with a thinner mucus layer ( in the SSD-ETT secretion deposits ranged from 0 to 200 mu m; in the St-ETT deposits ranged between 50 and 700 mu m). No difference was observed between the two groups in the tracheobronchial brush samples ( frequency of colonization: SSD-ETT 0/23, St-ETT 2/23; p = 0.48). No adverse reactions were observed with the implementation of the novel device. Conclusion: SSD-ETT can be safely used in preventing bacterial colonization and narrowing of the ETT in patients intubated for up to 24 h ( mean intubation time 16 h). C1 [Berra, Lorenzo; Villa, Federico; Stelfox, Henry T.; Bigatello, Luca M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Kolobow, Theodor; Baccarelli, Andrea; Moss, Joel] NHLBI, NIH, Pulm & Crit Care Med Branch, Bethesda, MD 20892 USA. [Laquerriere, Patrice; Bouthors, Sylvie] Univ Reims, INSERM, ERM 0203, UFR Sci,Lab Microscopie Elect, F-51685 Reims, France. [Pitts, Betsey] Montana State Univ, Ctr Biofilm Engn, Bozeman, MT 59717 USA. [Pitts, Betsey] Montana State Univ, Dept Chem Engn, Bozeman, MT 59717 USA. [Bramati, Simone; Pohlmann, Joshua; Marelli, Chiara; Panzeri, Miriam; Brambillasca, Pietro; Pesenti, Antonio] Milano Bicocca Univ, San Gerardo Hosp, I-20052 Monza Milan, Italy. RP Berra, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM lberra@partners.org RI Pesenti, Antonio/H-7483-2012; Laquerriere, Patrice/P-1025-2016; OI Laquerriere, Patrice/0000-0001-7637-9094; Baccarelli, Andrea/0000-0002-3436-0640 NR 40 TC 36 Z9 45 U1 1 U2 8 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 JUN PY 2008 VL 34 IS 6 BP 1030 EP 1037 DI 10.1007/s00134-008-1100-1 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 319QZ UT WOS:000257180100009 PM 18418571 ER PT J AU Shimomura, Y Mizoguchi, E Sugimoto, K Kibe, R Benno, Y Mizoguchi, A Bhan, AK AF Shimomura, Yasuyo Mizoguchi, Emiko Sugimoto, Ken Kibe, Ryoko Benno, Yoshimi Mizoguchi, Atsushi Bhan, Atul K. TI Regulatory role of B-1B cells in chronic colitis SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE B-1B cells; hygiene hypothesis; IBD; KO mice; regulatory B cells; TCR alpha ID INFLAMMATORY-BOWEL-DISEASE; TOLL-LIKE RECEPTORS; ALPHA MUTANT MICE; B-CELLS; INTERLEUKIN-10-DEFICIENT MICE; INTESTINAL INFLAMMATION; HYGIENE HYPOTHESIS; INTERFERON-GAMMA; MODELS; INTERLEUKIN-4 AB According to the 'hygiene hypothesis', enhanced microbial exposure due to early childhood infections leads to a reduction of T(h)2-mediated allergic diseases and inflammatory bowel disease. To begin to elucidate the mechanisms underlying this hypothesis, we studied development of T(h)2-mediated colitis of the TCR alpha knockout (KO) mouse in both a specific pathogen-free (SPF) facility and a conventional (CV) facility. After more than five generations in each facility, TCR alpha KO mice kept in the CV facility developed dramatically less colitis than mice that were kept in the SPF facility. Surprisingly, the suppression of colitis in the CV facility correlated with a significant increase in natural IgM production by B-1 B cells. In contrast, B cell-deficient TCR alpha double-knockout (alpha mu DKO) mice maintained in the CV facility continued to develop severe colitis, strongly suggesting that B-1 B cells contributed to the suppression of colitis. Indeed, the adoptive transfer of B-1 B cells isolated from the peritoneal cavity of TCR alpha KO mice (SPF) into alpha mu DKO mice (CV) suppressed the development of colitis in the recipient mice. We conclude that B-1 cells play a regulatory role in T(h)2-mediated colitis under non-hygienic conditions, possibly by generating natural antibodies in response to microbial flora. C1 [Shimomura, Yasuyo; Sugimoto, Ken; Mizoguchi, Atsushi; Bhan, Atul K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shimomura, Yasuyo; Mizoguchi, Emiko; Sugimoto, Ken; Mizoguchi, Atsushi; Bhan, Atul K.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Mizoguchi, Emiko] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Kibe, Ryoko; Benno, Yoshimi] RIKEN, BioResource Ctr, Japan Collection Microorganisms, Saitama 310198, Japan. RP Bhan, AK (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM abhan@partners.org FU NIDDK NIH HHS [DK43351, DK74454, DK47677, DK64289, DK064351] NR 42 TC 61 Z9 62 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUN PY 2008 VL 20 IS 6 BP 729 EP 737 DI 10.1093/intimm/dxn031 PG 9 WC Immunology SC Immunology GA 306VM UT WOS:000256275900002 PM 18375938 ER PT J AU Valadares, HMS Pimenta, JR de Freitas, JM Duffy, T Bartholomeu, DC Oliveira, RD Chiari, E Moreira, MDV Filho, GB Schijman, AG Franco, GR Machado, CR Pena, SDJ Macedo, AM AF Silva Valadares, Helder Magno Pimenta, Juliana Ramos de Freitas, Jorge Marcelo Duffy, Tomas Bartholomeu, Daniella C. Oliveira, Riva de Paula Chiari, Egler Vieira Moreira, Maria da Consolacao Filho, Geraldo Brasileiro Schijman, Alejandro Gabriel Franco, Gloria Regina Machado, Carlos Renato Junho Pena, Sergio Danilo Macedo, Andrea Mara TI Genetic profiling of Trypanosoma cruzi directly in infected tissues using nested PCR of polymorphic microsatellites SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Article DE Trypanosoma cruzi; chagas disease; genome project; polymorphic microsatellites; full nested PCR ID POLYMERASE-CHAIN-REACTION; CHAGAS-DISEASE; RIBOSOMAL-RNA; AMAZONIAN BRAZIL; LINEAGE-I; SEQUENCES; STRAINS; CLONES; POPULATIONS; PATIENT AB The investigation of the importance of the genetics of Trypanosoma cruzi in determining the clinical course of Chagas disease will depend on precise characterisation of the parasites present in the tissue lesions. This can be adequately accomplished by the use of hypervariable nuclear markers such as microsatellites. However the unilocal nature of these loci and the scarcity of parasites in chronic lesions make it necessary to use high sensitivity PCR with nested primers, whose design depends on the availability of long flanking regions, a feature not hitherto available for any known T. cruzi micro satellites. Herein, making use of the extensive T. cruzi genome sequence now available and using the Tandem Repeats Finder software, it was possible to identify and characterise seven new microsatellite loci - six composed of trinucleotide (TcTAC15, TcTAT20, TcAAT8, TcATT14, TcGAG10 and TcCAA10) and one composed of tetranucleotide (TcAAAT6) motifs. All except the TcCAA10 locus were physically mapped onto distinct intergenic regions of chromosome III of the CL Brener clone contigs. The TcCAA10 locus was localised within a hypothetical protein gene in the T. cruzi genome. All microsatellites were polymorphic and useful for T. cruzi genetic variability studies. Using the TcTAC15 locus it was possible to separate the strains belonging to the T. cruzi I lineage (DTU I) from those belonging to T. cruzi II (DTU IIb), T. cruzi III (DTU IIc) and a hybrid group (DTU IId, IIe). The long flanking regions of these novel microsatellites allowed construction of nested primers and the use of full nested PCR protocols. This strategy enabled us to detect and differentiate T. cruzi strains directly in clinical specimens including heart, blood, CSF and skin tissues from patients in the acute and chronic phases of Chagas disease. (C) 2007 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved. C1 [Silva Valadares, Helder Magno; Pimenta, Juliana Ramos; de Freitas, Jorge Marcelo; Franco, Gloria Regina; Machado, Carlos Renato; Junho Pena, Sergio Danilo; Macedo, Andrea Mara] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, BR-30161970 Belo Horizonte, MG, Brazil. [Duffy, Tomas; Schijman, Alejandro Gabriel] Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol Mol, Lab Biol Mol Enfermedad Chagas, RA-1033 Buenos Aires, DF, Argentina. [Bartholomeu, Daniella C.; Chiari, Egler] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Parasitol, Belo Horizonte, MG, Brazil. [Oliveira, Riva de Paula] Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, Boston, MA 02215 USA. [Vieira Moreira, Maria da Consolacao] Univ Fed Minas Gerais, Fac Med, Dept Clin Med, Belo Horizonte, MG, Brazil. [Filho, Geraldo Brasileiro] Univ Fed Minas Gerais, Fac Med, Dept Anat Patol & Med Legal, Belo Horizonte, MG, Brazil. RP Macedo, AM (reprint author), Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Av Antonio Carlos 6627,Caixa Postal 486, BR-30161970 Belo Horizonte, MG, Brazil. EM andrea@icb.ufmg.br RI Franco, Gloria/I-3654-2013; Oliveira, Riva/J-8408-2013; Vacinas, Inct/J-9431-2013; Nbiofar, Inct/J-9539-2013; MACHADO, CARLOS/H-1043-2015; Bartholomeu, Daniella/J-4714-2015 OI Franco, Gloria/0000-0001-5245-2365; Oliveira, Riva/0000-0002-4917-7646; Bartholomeu, Daniella/0000-0003-0974-7357 NR 42 TC 35 Z9 36 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD JUN PY 2008 VL 38 IS 7 BP 839 EP 850 DI 10.1016/j.ijpara.2007.10.017 PG 12 WC Parasitology SC Parasitology GA 300VJ UT WOS:000255853000011 PM 18154957 ER PT J AU Buck, T Hwang, SM Plicht, B Mucci, RA Hunold, P Erbel, R Levine, RA AF Buck, Thomas Hwang, Shawn M. Plicht, Bjoern Mucci, Ronald A. Hunold, Peter Erbel, Raimund Levine, Robert A. TI Automated flow quantification in valvular heart disease based on backscattered Doppler power analysis: implementation on matrix-array ultrasound imaging systems SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE echocardiography; flow quantification; matrix-array transducer; magnetic resonance imaging; mitral regurgitation; spectral doppler power ID SURFACE-AREA METHOD; MITRAL REGURGITATION; AORTIC REGURGITATION; ORIFICE AREA; VOLUME FLOW; BLOOD-FLOW; ECHOCARDIOGRAPHY; SEVERITY; DETERMINANTS; FLOWMETER AB Objective Cardiac ultrasound imaging systems are limited in the noninvasive quantification of valvular regurgitation due to indirect measurements and inaccurate hemodynamic assumptions. We recently demonstrated that the principle of integration of backscattered acoustic Doppler power times velocity can be used for flow quantification in valvular regurgitation directly at the vena contracta of a regurgitant flow jet. We now aimed to accomplish implementation of automated Doppler power flow analysis software on a standard cardiac ultrasound system utilizing novel matrix-array transducer technology with detailed description of system requirements, components and software contributing to the system. Methods This system based on a 3.5 MHz, matrix-array cardiac ultrasound scanner (Sonos 5500, Philips Medical Systems) was validated by means of comprehensive experimental signal generator trials, in vitro flow phantom trials and in vivo testing in 48 patients with mitral regurgitation of different severity and etiology using magnetic resonance imaging (MRI) for reference. Results All measurements displayed good correlation to the reference values, indicating successful implementation of automated Doppler power flow analysis on a matrix-array ultrasound imaging system. Systematic underestimation of effective regurgitant orifice areas > 0.65 cm(2) and volumes > 40 ml was found due to currently limited Doppler beam width that could be readily overcome by the use of new generation 2D matrix-array technology. Conclusion Automated flow quantification in valvular heart disease based on backscattered Doppler power can be fully implemented on board a routinely used matrix-array ultrasound imaging systems. Such automated Doppler power flow analysis of valvular regurgitant flow directly, noninvasively, and user independent overcomes the practical limitations of current techniques. C1 [Buck, Thomas; Plicht, Bjoern; Erbel, Raimund] Univ Duisburg Essen, W German Heart Ctr, Dept Cardiol, D-45122 Essen, Germany. [Hwang, Shawn M.] MIT, Dept Elect Engn & Comp Sci, Boston, MA USA. [Mucci, Ronald A.; Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. [Hunold, Peter] Univ Duisburg Essen, Inst Diagnost & Intervent Radiol, Essen, Germany. RP Buck, T (reprint author), Univ Duisburg Essen, W German Heart Ctr, Dept Cardiol, Hufelandstr 55, D-45122 Essen, Germany. EM thomas.buck@uk-essen.de FU NHLBI NIH HHS [R01 HL38176, HL53702, K24 HL67434] NR 30 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD JUN PY 2008 VL 24 IS 5 BP 463 EP 477 DI 10.1007/s10554-008-9302-8 PG 15 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 299FQ UT WOS:000255741900002 PM 18311592 ER PT J AU Zhao, XM Huang, MX Fingeroth, J AF Zhao, Xiaomin Huang, Mingxia Fingeroth, Joyce TI Unique role(s) of Epstein Barr Virus thymidine kinase in viral pathogenesis SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [Zhao, Xiaomin; Fingeroth, Joyce] Harvard Univ, Sch Med, Div Infect Dis, BIDMC, Boston, MA USA. [Huang, Mingxia] Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD JUN PY 2008 VL 12 SU 2 MA 118 BP S48 EP S48 DI 10.1016/S1201-9712(08)60120-4 PG 1 WC Infectious Diseases SC Infectious Diseases GA 326MB UT WOS:000257662300118 ER PT J AU Tzika, AA Astrakas, LG Cao, HH Mintzopoulos, D Zhang, QH Padfield, K Yu, HU Mindrinos, MN Rahme, LG Tompkins, RG AF Tzika, A. Aria Astrakas, Loukas G. Cao, Haihui Mintzopoulos, Dionyssios Zhang, Qunhao Padfield, Katie Yu, Hongue Mindrinos, Michael N. Rahme, Laurence G. Tompkins, Ronald G. TI Murine intramyocellular lipids quantified by NMR act as metabolic biomarkers in burn trauma SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE nuclear magnetic resonance; skeletal muscle; burn trauma; lipids; PGC-1 beta; mitochondria; metabolism; biomarkers ID MAGNETIC-RESONANCE-SPECTROSCOPY; INDUCED INSULIN-RESISTANCE; FREE FATTY-ACID; SKELETAL-MUSCLE; IN-VIVO; THERMAL-INJURY; TRIGLYCERIDE CONTENT; BRAIN-TUMORS; COACTIVATORS; SENSITIVITY AB It has been suggested that intramyocellular lipids (IMCLs) may serve as biomarkers of insulin resistance and mitochondrial dysfunction. Using a hind-limb mouse model of burn trauma, we tested the hypothesis that severe localized burn trauma involving 5% of the total body surface area causes a local increase in IMCLs in the leg skeletal muscle. We quantified IMCLs from ex vivo intact tissue specimens using High-Resolution Magic Angle Spinning (HRMAS) H-1 NMR and characterized the accompanying gene expression patterns in burned versus control skeletal muscle specimens. We also quantified plasma-free fatty acids (FFAs) in burn versus control mice. Our results from HRMAS H-1 NMR measurements indicated that IMCL levels were significantly increased in mice exposed to burn trauma. Furthermore, plasma FFA levels were also significantly increased, and gene expression of Glut4, insulin receptor substrate 1 (IRS1), glycolytic genes, and PGC-1 beta was downregulated in these mice. Backward stepwise multiple linear regression analysis demonstrated that IMCL levels correlated significantly with FFA levels, which were a significant predictor of IRS1 and PGC-1 beta gene expression. We conclude from these findings that IMCLs can serve as metabolic biomarkers in burn trauma and that FFAs and IMCLs may signal altered metabolic gene expression. This signaling may result in the observed burn-induced insulin resistance and skeletal muscle mitochondrial dysfunction. We believe that IMCLs may therefore be useful biomarkers in predicting the therapeutic effectiveness of hypolipidernic agents for patients with severe burns. C1 [Tzika, A. Aria; Astrakas, Loukas G.; Cao, Haihui; Mintzopoulos, Dionyssios; Zhang, Qunhao; Padfield, Katie; Yu, Hongue] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,NMR Surg Lab, Boston, MA 02114 USA. [Tzika, A. Aria; Astrakas, Loukas G.; Cao, Haihui; Mintzopoulos, Dionyssios; Zhang, Qunhao; Padfield, Katie; Yu, Hongue; Rahme, Laurence G.; Tompkins, Ronald G.] Harvard Univ, Shriners Burn Inst, Sch Med, Boston, MA 02114 USA. [Tzika, A. Aria; Astrakas, Loukas G.; Cao, Haihui; Mintzopoulos, Dionyssios; Zhang, Qunhao; Yu, Hongue] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA 02114 USA. [Mindrinos, Michael N.] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. RP Tzika, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,NMR Surg Lab, Room 261,51 Blossom St, Boston, MA 02114 USA. EM atzika@partners.org RI Astrakas, Loukas/F-5918-2011 FU NIGMS NIH HHS [P50GM021700] NR 50 TC 10 Z9 11 U1 0 U2 0 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 EI 1791-244X J9 INT J MOL MED JI Int. J. Mol. Med. PD JUN PY 2008 VL 21 IS 6 BP 825 EP 832 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 304SC UT WOS:000256128400021 PM 18506378 ER PT J AU Wilk, JB Laramie, JM Latourelle, JC Williamson, S Nagle, MW Tobin, JE Foster, CL Eckfeldt, JH Province, MA Borecki, IB Myers, RH AF Wilk, J. B. Laramie, J. M. Latourelle, J. C. Williamson, S. Nagle, M. W. Tobin, J. E. Foster, C. L. Eckfeldt, J. H. Province, M. A. Borecki, I. B. Myers, R. H. TI NYD-SP18 is associated with obesity in the NHLBI family heart study SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE leptin; single nucleotide polymorphism; association ID BODY-MASS INDEX; GENOME-WIDE ASSOCIATION; ADULT OBESITY; FTO GENE; LEPTIN; TESTOSTERONE; EFFICIENCY; CHILDHOOD; VARIANTS; LINKAGE AB Objective: The NHLBI Family Heart Study (FHS) genome-wide linkage scan identified a region of chromosome 7q with a logarithm of odds score of 4.9 for body mass index (BMI). Design: We report the results of fine mapping the linkage peak using 1020 single nucleotide polymorphisms ( SNPs) to test for association to obesity in families exhibiting linkage to chromosome 7. Association observed in linked families ( 284 obese cases/381 controls) was examined in an independent set of unrelated FHS participants (172 obese cases/308 controls) to validate the observed association. Two dichotomous obesity phenotypes were studied based on clinical BMI cutoffs and the sex-specific distribution of both BMI and leptin levels. Results: Using a P-value of 0.01 as criteria for association in the linked families, a P-value of 0.05 as criteria for association in the unrelated sample, and requiring consistency in the direction of the effect of the minor allele between the two samples, we identified two coding SNPs in the NYD-SP18 gene with minor alleles increasing the risk of obesity. Adjustment for exercise, smoking and FTO genotype did not influence the result in linked families, but improved the result in the unrelated sample. Carrying a minor allele of the nonsynonymous SNP rs6971091 conferred an odds ratio of at least 2 for obesity defined by both BMI and leptin levels. Conclusion: The effect of the NYD-SP18 SNP on obesity was larger than the effect of FTO in FHS families. Publicly available results from genome-wide association studies support the association between NYD-SP18 and BMI. The NYD-SP18 gene is described as testes development related, but little is known about the gene's function or the mechanism by which it may influence risk for obesity. C1 [Wilk, J. B.; Laramie, J. M.; Latourelle, J. C.; Williamson, S.; Nagle, M. W.; Tobin, J. E.; Myers, R. H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Wilk, J. B.; Myers, R. H.] Boston Univ, Sch Med, Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. [Laramie, J. M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Tobin, J. E.] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. [Foster, C. L.; Eckfeldt, J. H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Province, M. A.; Borecki, I. B.] Washington Univ, Sch Med, Ctr Human Genome Sci, St Louis, MO USA. RP Wilk, JB (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St,E-338, Boston, MA 02118 USA. EM jwilk@bu.edu OI Latourelle, Jeanne/0000-0002-4218-9572; Myers, Richard/0000-0002-8365-2674 FU NHLBI NIH HHS [R0-1 HL68891-06, R01 HL068891, R01 HL068891-06] NR 21 TC 6 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD JUN PY 2008 VL 32 IS 6 BP 930 EP 935 DI 10.1038/ijo.2008.23 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 314DF UT WOS:000256788500007 PM 18317470 ER PT J AU Spiro, A Brady, C AF Spiro, I. I. I. Avron Brady, Christopher TI Impact of vascular disease on cognitive aging SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 [Spiro, I. I. I. Avron] VA Med Ctr, MAVERIC, Boston, MA USA. [Brady, Christopher] VA Boston Healthcare Syst, MAVERIC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PD JUN-AUG PY 2008 VL 43 IS 3-4 BP 553 EP 554 PG 2 WC Psychology, Multidisciplinary SC Psychology GA 349EO UT WOS:000259264306497 ER PT J AU Payne, J Stickgold, R Swanberg, K Kensinger, E AF Payne, Jessica Stickgold, Robert Swanberg, Kelley Kensinger, Elizabeth TI Sleep preferentially enhances memory for emotional components of scenes SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 [Payne, Jessica; Swanberg, Kelley] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Stickgold, Robert] Harvard Univ, Sch Med, BIDMC, Dept Psychiat, Boston, MA USA. [Kensinger, Elizabeth] Boston Coll, Dept Psychol, Chestnut Hill, MA 02167 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PD JUN-AUG PY 2008 VL 43 IS 3-4 BP 735 EP 735 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 349EO UT WOS:000259264308647 ER PT J AU Curran, WJ Machtay, M Wasserman, T Shipley, WU AF Curran, Walter J., Jr. Machtay, Mitchell Wasserman, Todd Shipley, William U. TI Celebrating 40 years of clinical inquiry: The RTOG'S ruby anniversary SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID PHASE-III TRIAL; RADIATION-THERAPY; PROSTATE-CANCER; RADIOTHERAPY; CHEMOTHERAPY; CARCINOMA C1 [Curran, Walter J., Jr.] Emory Univ, Dept Radiat Oncol, Atlanta, GA 30322 USA. [Machtay, Mitchell] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Wasserman, Todd] Washington Univ, St Louis, MO USA. [Shipley, William U.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Curran, WJ (reprint author), Emory Univ, Dept Radiat Oncol, 1365 Clifton Rd NE, Atlanta, GA 30322 USA. NR 13 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 1 PY 2008 VL 71 IS 2 BP 321 EP 323 DI 10.1016/j.ijrobp.2008.03.034 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 302LZ UT WOS:000255971100001 PM 18474307 ER PT J AU Ng, AK Li, SG Recklitis, C Diller, LR Neuberg, D Silver, B Mauch, PM AF Ng, Andrea K. Li, Sigui Recklitis, Christopher Diller, Lisa R. Neuberg, Donna Silver, Barbara Mauch, Peter M. TI Health practice in long-term survivors of Hodgkin's lymphoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Hodgkin's lymphoma; cancer survivorship; health behavior ID CHILDHOOD-CANCER SURVIVOR; ADULT SURVIVORS; BREAST-CANCER; DISEASE; ALCOHOL; TOXICITY; CARE; RADIOTHERAPY; THERAPY; COHORT AB Purpose: To compare the health practice of Hodgkin's lymphoma (HL) survivors and their siblings, and to assess the impact of socioeconomic status and disease history on health practice of HL survivors. Methods and Materials: We conducted a questionnaire study on long-term HL survivors and their siblings on health care utilization, health habits, and screening behavior. Results: A total of 511 HL survivors (response rate of 50%, including survivors lost to contact) and 224 siblings (response rate, 58%) participated. Median time from HL diagnosis was 15 years. Significantly more survivors than siblings had a physical examination in the past year (63% vs. 49%,p = 0.0001). Male survivors were significantly more likely than siblings to perform monthly self-testicular examinations (19% vs. 9%,p = 0.02). Among survivors, higher household income (p = 0.01) independently predicted for having had a physical examination in the past year. Lower educational level (p = 0.0004) and history of relapsed HL (p = 0.03) were independent predictors for smoking, moderate/heavy alcohol use, and/or physical inactivity. Conclusions: Compared with siblings, long-term HL survivors have a higher level of health care utilization and better screening practice. Survivors from lower socioeconomic background had lower adherence to routine health care and greater report of unhealthy habits. Survivors with history of relapsed HL were also more likely to engage in unhealthy habits. (c) 2008 Elsevier Inc. C1 [Ng, Andrea K.; Silver, Barbara; Mauch, Peter M.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Li, Sigui; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Recklitis, Christopher; Diller, Lisa R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Ng, AK (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM ang@lroc.harvard.edu NR 31 TC 6 Z9 6 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 1 PY 2008 VL 71 IS 2 BP 468 EP 476 DI 10.1016/j.ijrobp.2007.09.028 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 302LZ UT WOS:000255971100024 PM 18234434 ER PT J AU Drummond, MF Schwartz, JS Jonsson, B Luce, BR Neumann, PJ Siebert, U Sullivan, SD AF Drummond, Michael F. Schwartz, J. Sanford Jonsson, Bengt Luce, Bryan R. Neumann, Peter J. Siebert, Uwe Sullivan, Sean D. TI Key principles for the improved conduct of health technology assessments for resource allocation decisions SO INTERNATIONAL JOURNAL OF TECHNOLOGY ASSESSMENT IN HEALTH CARE LA English DT Article DE cost-effectiveness analysis; health policy ID ECONOMIC-EVALUATION; COVERAGE; INFORMATION; POLICY; TRIALS; NICE AB Health technology assessment (HTA) is a dynamic, rapidly evolving process, embracing different types of assessments that inform real-world decisions about the value (i.e., benefits, risks, and costs) of new and existing technologies. Historically, most HTA agencies have focused on producing high quality assessment reports that can be used by a range of decision makers. However, increasingly organizations are undertaking or commissioning HTAs to inform a particular resource allocation decision, such as listing a drug on a national or local formulary, defining the range of coverage under insurance plans, or issuing mandatory guidance on the use of health technologies in a particular healthcare system. A set of fifteen principles that can be used in assessing existing or establishing new HTA activities is proposed, providing examples from existing HTA programs. The principal focus is on those HTA activities that are linked to, or include, a particular resource allocation decision. In these HTAs, the consideration of both costs and benefits, in an economic evaluation, is critical. It is also important to consider the link between the HTA and the decision that will follow. The principles are organized into four sections: (i) "Structure" of HTA programs; (ii) "Methods" of HTA; (iii) "Processes for Conduct" of HTA; and (iv) "Use of HTAs in Decision Making." C1 [Drummond, Michael F.] Univ York, Ctr Hlth Econ, York YO10 5DD, N Yorkshire, England. [Schwartz, J. Sanford] Univ Penn, Dept Med, Sch Med, Philadelphia, PA 19104 USA. [Schwartz, J. Sanford] Univ Penn, Dept Hlth Care Management, Sch Med, Philadelphia, PA 19104 USA. [Schwartz, J. Sanford] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Jonsson, Bengt] Stockholm Sch Econ, Dept Econ, SE-11383 Stockholm, Sweden. [Luce, Bryan R.] United BioSource Corp, Dept Policy Sci, Bethesda, MD 20814 USA. [Neumann, Peter J.] Tufts Univ, Medford, MA 02155 USA. [Neumann, Peter J.] Tufts Med Ctr, Ctr Evaluat Value & Risk Hlth, Boston, MA 02111 USA. [Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Med Decis Making & Hlth Technol As, Eduard Wallnoefer Ctr 1, A-6060 Hall In Tirol, Austria. [Siebert, Uwe] Harvard Univ, MGH Inst Technol Assessment, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Siebert, Uwe] Harvard Univ, Dept Radiol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sullivan, Sean D.] Univ Washington, Pharmaceut Outcomes Res & Policy Program, Seattle, WA 98195 USA. RP Drummond, MF (reprint author), Univ York, Ctr Hlth Econ, Alcuin A Block, York YO10 5DD, N Yorkshire, England. EM md18@york.ac.uk; schwartz@wharton.upenn.edu; Bengt.Jonsson@hhs.se; bryan.luce@unitedbiosource.com; pneumann@tuftsmedicalcenter.org; public-health@umit.at; sdsull@u.washington.edu NR 41 TC 125 Z9 131 U1 6 U2 31 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0266-4623 J9 INT J TECHNOL ASSESS JI Int. J. Technol. Assess. Health Care PD SUM PY 2008 VL 24 IS 3 BP 244 EP 258 DI 10.1017/S0266462308080343 PG 15 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics GA 331ZI UT WOS:000258050800002 PM 18601792 ER PT J AU Kukluk, JP Holder, LB Cook, DJ AF Kukluk, Jacek P. Holder, Lawrence B. Cook, Diane J. TI Inference of edge replacement graph grammars SO INTERNATIONAL JOURNAL ON ARTIFICIAL INTELLIGENCE TOOLS LA English DT Article; Proceedings Paper CT 20th International-Florida-AI-Research-Society Conference CY MAY, 2007 CL Key West, FL SP Int Florida Artificial Intelligence Res Soc DE grammar induction; graph grammars; graph mining ID COMPLEX NETWORKS AB We describe an algorithm and experiments for inference of edge replacement graph grammars. This method generates candidate recursive graph grammar productions based on isomorphic subgraphs which overlap by two nodes. If there is no edge between the two overlapping nodes, the method generates a recursive graph grammar production with a virtual edge. We guide the search for the graph grammar based on the size of the grammar and the portion of the graph described by the grammar. We show experiments where we generate graphs from known graph grammars, use our method to infer the grammar from the generated graphs, and then measure the error between the original and inferred grammars. Experiments show that the method performs well on several types of grammars, and specifically that error decreases with increased numbers of unique labels in the graph. C1 [Kukluk, Jacek P.] Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Holder, Lawrence B.; Cook, Diane J.] Washington State Univ, Dept Elect Engn & Comp Sci, Pullman, WA 99164 USA. RP Kukluk, JP (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, 75 Francis St, Boston, MA 02115 USA. EM jkukluk@lroc.harvard.edu; holder@wsu.edu; cook@eecs.wsu.edu NR 18 TC 3 Z9 3 U1 0 U2 1 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0218-2130 EI 1793-6349 J9 INT J ARTIF INTELL T JI Int. J. Artif. Intell. Tools PD JUN PY 2008 VL 17 IS 3 BP 539 EP 554 DI 10.1142/S0218213008004047 PG 16 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications SC Computer Science GA 327XQ UT WOS:000257762200009 ER PT J AU Treiber, KA Lyketsos, CG Corcoran, C Steinberg, M Norton, M Green, RC Rabins, P Stein, DM Welsh-Bohmer, KA Breitner, JCS Tschanz, JT AF Treiber, Katherine A. Lyketsos, Constantine G. Corcoran, Chris Steinberg, Martin Norton, Maria Green, Robert C. Rabins, Peter Stein, David M. Welsh-Bohmer, Kathleen A. Breitner, John C. S. Tschanz, JoAnn T. TI Vascular factors and risk for neuropsychiatric symptoms in Alzheimer's disease: the Cache County Study SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Article DE dementia; Alzheimer's disease; neuropsychiatric; disturbance; risk factors; vascular ID APOLIPOPROTEIN-E GENOTYPE; CEREBRAL-BLOOD-FLOW; E E4 ALLELE; BEHAVIORAL DISTURBANCES; PSYCHIATRIC-SYMPTOMS; PSYCHOLOGICAL SYMPTOMS; NONCOGNITIVE SYMPTOMS; COGNITIVE IMPAIRMENT; AGGRESSIVE-BEHAVIOR; MEDICAL COMORBIDITY AB Objective: To examine, in an exploratory analysis, the association between vascular conditions and the occurrence of neuropsychiatric symptoms (NPS) in a population-based sample of incident Alzheimer's disease (AD). Methods: The sample consisted of 254 participants, identified through two waves of assessment. NPS were assessed using the Neuropsychiatric Inventory. Prior to the onset of AD, data regarding a history of stroke, hypertension, hyperlipidemia, heart attack or coronary artery bypass graft (CABG), and diabetes were recorded. Logistic regression procedures were used to examine the relationship of each vascular condition to individual neuropsychiatric symptoms. Covariates considered were age, gender, education, APOE genotype, dementia severity, and overall health status. Results: One or more NPS were observed in 51 % of participants. Depression was most common (25.8%), followed by apathy (18.6%), and irritability (17.7%). Least common were elation (0.8%), hallucinations (5.6%), and disinhibition (6.0%). Stroke prior to the onset of AD was associated with increased risk of delusions (OR=4.76, p=0.02), depression (OR=3.87, p=0.03), and apathy (OR=4.48, p=0.02). Hypertension was associated with increased risk of delusions (OR= 2.34, p =0.02), anxiety (OR= 4.10, p=0.002), and agitation/aggression (OR= 2.82, p=0.01). No associations were observed between NPS and diabetes, hyperlipidemia, heart attack or CABG, or overall health. Conclusions: Results suggest that a history of stroke and hypertension increase the risk of specific NPS in patients with AD. These conditions may disrupt neural circuitry in brain areas involved in NPS. Findings may provide an avenue for reduction in occurrence of NPS through the treatment or prevention of vascular risk conditions. C1 [Tschanz, JoAnn T.] Utah State Univ, Ctr Epidemiol Studies, UMC 4440, Dept Psychol, Logan, UT 84322 USA. [Lyketsos, Constantine G.; Steinberg, Martin; Rabins, Peter] Johns Hopkins Univ, Johns Hopkins Bayview, Dept Psychiat, Baltimore, MD USA. [Lyketsos, Constantine G.; Steinberg, Martin; Rabins, Peter] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Corcoran, Chris] Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA. [Norton, Maria] Utah State Univ, Dept Family & Human Dev, Logan, UT 84322 USA. [Green, Robert C.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Welsh-Bohmer, Kathleen A.] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. [Breitner, John C. S.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Breitner, John C. S.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Green, Robert C.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Tschanz, JT (reprint author), Utah State Univ, Ctr Epidemiol Studies, UMC 4440, Dept Psychol, Logan, UT 84322 USA. EM joannt@cc.usu.edu RI Corcoran, Chris/F-2155-2010; Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013 FU National Institute on Aging [R01AG21136, R01AG1183, R01AG18712] FX This research was supported by National Institute on Aging grants R01AG21136, R01AG1183 and R01AG18712. We wish to thank Dr. Truls Ostbye for his thoughtful review of this manuscript. We are grateful to the neurogenetics laboratory of the Bryan Alzheimer's Disease Research Center at Duke University for the APOE genotyping, and to Cara Brewer, Tony Calvert, Michelle McCart, Tiffany Newman, Roxane Pfister, Dr. Nancy Sassano and Joslin Werstack for expert technical assistance. Other Cache County Study of Memory, Health, and Aging Investigators include: Dr. James Anthony, Dr. Erin Bigler, Dr. Ron Brookmeyer, Dr. James Burke, Dr. Eric Christopher, Dr. Jane Gagliardi, Michael Helms, Dr. Christine Hulette, Liz Klein, Carol Leslie, Dr. Lawrence Mayer, Dr. John Morris, Dr. Ronald G. Munger, Dr. Chiadi Onyike, Dr. Truls Ostbye, Dr. Ron Petersen, Dr. Kathy Piercy, Dr. Carl Pieper, Dr. Brenda Plassman, Dr. Pritham Raj, Russell Ray, Linda Sanders, Dr. Ingmar Skoog, Dr. David Steffens, Dr. Marty Toohill, Leslie Toone, Dr. Jeannette Townsend, Lauren Warren, Dr. Michael Williams and Dr. Bonita Wyse.; The board-certified or board-eligible geriatric psychiatrists or neurologists who examined the study members included Drs Steinberg, Breitner, Steffens, Lyketsos, and Green. Dr. Williams also examined several subjects and provided expert neurologic consultation. Autopsy examinations were conducted by Dr. Townsend. Ms. Leslie coordinated the autopsy enrollment program. Diagnosticians at the expert consensus conferences included Drs Breitner, Burke, Lyketsos, Plassman, Steffens, Steinberg, Tschanz and Welsh-Bohmer. NR 58 TC 38 Z9 39 U1 1 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PD JUN PY 2008 VL 20 IS 3 BP 538 EP 553 DI 10.1017/S1041610208006704 PG 16 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 352SZ UT WOS:000259519000009 PM 18289451 ER PT J AU Yu, HG Liu, XQ Kiss, S Connolly, E Gragoudas, ES Michaud, NA Bulgakov, OV Adamian, M DeAngelis, MM Miller, JW Li, T Kim, IK AF Yu, Hyeong Gon Liu, Xiaoqing Kiss, Szilard Connolly, Edward Gragoudas, Evangelos S. Michaud, Norman A. Bulgakov, Oleg V. Adamian, Michael DeAngelis, Margaret M. Miller, Joan W. Li, Tiansen Kim, Ivana K. TI Increased choroidal Neovascularization following laser induction in mice lacking lysyl oxidase-like 1 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ELASTIN-DERIVED PEPTIDES; MACULAR DEGENERATION; UP-REGULATION; BRUCHS MEMBRANE; LYSYL OXIDASE; ANGIOGENESIS; MT1-MMP; MATRIX; EXPRESSION AB PURPOSE. Age-related degradation of the elastic lamina in Bruch's membrane may have a permissive effect on the growth of choroidal neovascularization (CNV). This study investigated the influence of defective elastic fiber maintenance in the development of laser-induced CNV. METHODS. A mouse lacking lysyl oxidase-like (LOXL)-1, an enzyme essential for elastin polymerization, was studied. The morphologic characteristics of the elastic lamina within Bruch's membrane were examined in mutant and wild-type (WT) eyes. Laser-induced CNV was evaluated by fluorescein angiography and choroidal flat mounts. Immunohistochemistry for elastin was performed on the CNV lesions, and vascular endothelial growth factor (VEGF) levels were determined by ELISA. Soluble elastin and matrix metalloproteinase (MMPs) levels were also analyzed by immunoblotting. RESULTS. The elastic lamina of Bruch's membrane in the LOXL1-deficient mice was fragmented and less continuous than in the WT controls. The mutant mice showed increased levels of soluble elastin peptides and reduced elastin polymer deposition in neovascular membranes. Significantly larger CNV with greater leakage on fluorescein angiography developed in mutant mice. VEGF levels in the RPE/choroid were higher in the knockout mice on days 7 and 14 after laser (P < 0.05). MT1-MMP (MMP14) was also elevated after laser in the LOXL1 mutant eyes compared to the WT controls. CONCLUSIONS. These results show that a systemic defect in elastic fiber deposition affects Bruch's membrane integrity and leads to more aggressive CNV growth. The latter may be partially mediated by abnormal signaling from the accumulation of soluble elastin peptides. C1 [DeAngelis, Margaret M.; Kim, Ivana K.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Mol Genet Lab,Dept Ophthalmol, Boston, MA 02114 USA. [Yu, Hyeong Gon; Kiss, Szilard; Connolly, Edward; Gragoudas, Evangelos S.; Miller, Joan W.; Kim, Ivana K.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Angiogenesis Lab & Laser Lab,Retina Res Inst, Boston, MA 02114 USA. [Liu, Xiaoqing; Bulgakov, Oleg V.; Adamian, Michael; Li, Tiansen] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. [Michaud, Norman A.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Howe Lab, Boston, MA 02114 USA. [Yu, Hyeong Gon] Seoul Natl Univ, Coll Med, Dept Ophthalmol, Seoul, South Korea. RP Kim, IK (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Mol Genet Lab,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM ivana_kim@meei.harvard.edu RI Yu, Hyeong Gon/J-2772-2012; DeAngelis, e/J-7863-2015; OI Yu, Hyeong Gon/0000-0002-1795-202X FU NEI NIH HHS [EY10309, R01 EY010309, R01 EY010309-07] NR 22 TC 30 Z9 31 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 JUN PY 2008 VL 49 IS 6 BP 2599 EP 2605 DI 10.1167/iovs.07-1508 PG 7 WC Ophthalmology SC Ophthalmology GA 307GG UT WOS:000256306800041 PM 18296663 ER PT J AU Li, J Udayasankar, UK Toth, TL Small, WC Kalra, MK AF Li, Jianhai Udayasankar, Unni K. Toth, Thomas L. Small, William C. Kalra, Mannudeep K. TI Application of automatic vertical positioning software to reduce radiation exposure in multidetector row computed tomography of the chest SO INVESTIGATIVE RADIOLOGY LA English DT Article DE multidetector row computed tomography; radiation; automatic vertical positioning; patient mispositioning ID Z-AXIS MODULATION; CT; CANCER; RISK; OPTIMIZATION; PROTOCOL AB Objective: To determine the effect of automatic vertical positioning (AVP) software on radiation dose reduction in multidetector row computed tomography of the chest. Materials and Methods: Two hundred forty-three consecutive patients (mean age, 54; range, 20-93 years), who underwent 64-slice multidetector row computed tomography of the chest from November 2005 to April 2006, were included in this study. This study was approved by our institutional review board with waiver of informed consent. Technologists initially positioned the patient in the gantry by adjusting the table height (vertical positioning) using a laser guidance system and patient surface anatomy. AVP software was then used to determine the true vertical positioning of the patient based on matching the individual patient's mean centroid (center of mass) throughout the chest as determined by the lateral projection with the gantry isocenter and center of the bow-tie filter. The resultant reduction in surface radiation dose with this attenuation-based vertical positioning was then calculated. Software-determined changes in patient vertical positioning and resultant radiation dose savings were analyzed using the t test and Pearson correlation statistics. Results: Vertical positioning of the patients by the technologist differed from AVP with the bow-tie filter in 95.5% (232 of 243) of patients with an average vertical mispositioning distance of 33.2 +/- 1.1 mm (range, 5.1-97 mm). Among mispositioned patients, 97% (225 of 232) were vertically mispositioned below the isocenter with a mean distance of 33.8 +/- 1.1 turn (range, 5.1-97 mm) and 3% (7 of 232) patients were vertically mispositioned above the isocenter, with a mean distance of 12.7 +/- 2.8 mm (range, 6-28 mm). The average surface radiation dose reduction with AVP software was 19% +/- 1% (range, 1%-46.6%). There was a strong correlation between vertical mispositioning distance and the surface radiation dose reduction facilitated by AVP software (r(2) = 0.9, P < 0.001). Conclusion: AVP software can help in optimum patient vertical positioning leading to substantial reduction in surface radiation dose. C1 [Li, Jianhai; Udayasankar, Unni K.; Small, William C.] Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. [Toth, Thomas L.] Gen Elect Healthcare Technol, Waukesha, WI USA. [Kalra, Mannudeep K.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Small, WC (reprint author), Emory Univ, Sch Med, Dept Radiol, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. EM wsmall@emory.edu NR 20 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JUN PY 2008 VL 43 IS 6 BP 447 EP 452 DI 10.1097/RLI.0b013e318169005e PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 305UV UT WOS:000256204200015 PM 18496051 ER PT J AU Colby, K AF Colby, Kathryn TI Changing times for pediatric keratoplasty SO JOURNAL OF AAPOS LA English DT Editorial Material ID ENDOTHELIAL KERATOPLASTY C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Colby, K (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St,Suite 808, Boston, MA 02114 USA. EM kacolby@meei.harvard.edu NR 8 TC 5 Z9 5 U1 0 U2 0 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 JUN PY 2008 VL 12 IS 3 BP 223 EP 224 DI 10.1016/j.jaapos.2008.05.001 PG 2 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 324YU UT WOS:000257556100002 PM 18589383 ER PT J AU Shaikh, S Hull, MJ Bishop, KA Griggs, DA Long, WH Nixon, AL Flood, JG AF Shaikh, Salima Hull, Mindy J. Bishop, Kenneth A. Griggs, David A. Long, William H. Nixon, Andrea L. Flood, James G. TI Effect of tramadol use on three point-of-care and one instrument-based Immunoassays for urine buprenorphine SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID ASSAY C1 [Shaikh, Salima; Hull, Mindy J.; Bishop, Kenneth A.; Griggs, David A.; Long, William H.; Nixon, Andrea L.; Flood, James G.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Shaikh, Salima; Hull, Mindy J.; Flood, James G.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Flood, JG (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,GRJ 5, Boston, MA 02114 USA. EM jflood@partners.org NR 11 TC 8 Z9 8 U1 2 U2 2 PU PRESTON PUBL INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD JUN PY 2008 VL 32 IS 5 BP 339 EP 343 PG 5 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 313WE UT WOS:000256769900002 PM 18544218 ER PT J AU Ouhara, K Komatsuzawa, H Kawai, T Nishi, H Fujiwara, T Fujiue, Y Kuwabara, M Sayama, K Hashimoto, K Sugai, M AF Ouhara, Kazuhisa Komatsuzawa, Hitoshi Kawai, Toshihisa Nishi, Hiromi Fujiwara, Tamaki Fujiue, Yoshihiro Kuwabara, Masao Sayama, Koji Hashimoto, Koji Sugai, Motoyuki TI Increased resistance to cationic antimicrobial peptide LL-37 in methicillin-resistant strains of Staphylococcus aureus SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE cathelicidin family peptide; human beta-defensin; clinical isolates; antibiotic susceptibility; innate immunity ID BETA-DEFENSINS; SUSCEPTIBILITY; SKIN AB Objectives: The susceptibility of clinical isolates of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), to host-derived cationic antimicrobial peptides was investigated. Methods: We examined the susceptibility of 190 clinical strains of methicillin-susceptible S. aureus (MSSA) and 304 strains of MRSA to two different classes of cationic antimicrobial peptides: LL-37 and human beta-defensin-3 (hBD3). Out of the total 494 clinical strains, a random selection of 54 S. aureus strains was examined to establish the relationship between the net charge, or zeta potential, of each strain and its susceptibility to hBD3 or LL-37. To further confirm bacterial susceptibility to either hBD3 or LL-37, we concurrently measured: (i) percentage survival after in vitro bacterial exposure and (ii) MBCs for both MRSA and MSSA strains. Results: Of the 54 randomly selected S. aureus strains, those MRSA strains resistant to LL-37 showed significantly higher zeta potentials than those susceptible to LL-37 (P < 0.05). In contrast, there was no difference in bacterial zeta potentials for MRSA strains that showed either resistance or susceptibility to hBD3. In addition, resistance to LL-37, but not to hBD3, as determined by either percentage survival or MBC, was significantly elevated in highly methicillin-resistant strains of S. aureus when compared with MSSA strains (P < 0.01). Conclusions: Clinical strains of MRSA, but not MSSA, that demonstrated an increased net charge also showed elevated resistance to LL-37, but not to hBD3. C1 [Ouhara, Kazuhisa; Komatsuzawa, Hitoshi; Nishi, Hiromi; Fujiwara, Tamaki; Sugai, Motoyuki] Hiroshima Univ, Grad Sch Biomed Sci, Dept Bacteriol, Hiroshima, Japan. [Ouhara, Kazuhisa; Kawai, Toshihisa] Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. [Fujiue, Yoshihiro] Hiroshima Prefectural Hosp, Dept Pathol & Lab Med, Hiroshima 7348530, Japan. [Kuwabara, Masao] Hiroshima Prefectural Hosp, Dept Internal Med, Hiroshima 7348530, Japan. [Sayama, Koji; Hashimoto, Koji] Ehime Univ, Sch Med, Dept Dermatol, Onsen Gun, Ehime 7910295, Japan. RP Komatsuzawa, H (reprint author), Kagoshima Univ, Grad Sch Med & Dental Serv, Dept Oral Microbiol, 8-35-1 Sakuragaoka, Kagoshima 8908544, Japan. EM hkomatsu@denta.hal.kagoshima-u.ac.jp FU NIDCR NIH HHS [DE-018310] NR 10 TC 35 Z9 35 U1 3 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUN PY 2008 VL 61 IS 6 BP 1266 EP 1269 DI 10.1093/jac/dkn106 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 305IY UT WOS:000256172900013 PM 18367458 ER PT J AU Taylor, CT Hirshfeld-Becker, DR Ostacher, MJ Chow, CW LeBeau, RT Pollack, MH Nierenberg, AA Simon, NM AF Taylor, Charles T. Hirshfeld-Becker, Dina R. Ostacher, Michael J. Chow, Candice W. LeBeau, Richard T. Pollack, Mark H. Nierenberg, Andrew A. Simon, Naomi M. TI Anxiety is associated with impulsivity in bipolar disorder SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE bipolar disorder; anxiety disorder; anxiety; impulsivity; comorbidity; behavioral disinhibition ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; TREATMENT ENHANCEMENT PROGRAM; SUICIDE ATTEMPTS; DSM-IV; SEROTONIN CONTENT; STEP-BD; COMORBIDITY; BEHAVIOR; SEVERITY; SYMPTOMS AB Impulsivity and anxiety, common features of bipolar disorder (BD), are each associated with a number of negative outcomes in BD. The relationship between anxiety and impulsivity, however, has not been a focus of study in BD. In this paper, we present data regarding the association between anxiety and impulsivity as measured by the Barratt impulsiveness scale (BIS-11) in 114 outpatients with BD. Results revealed that patients with a comorbid anxiety disorder displayed significantly higher levels of impulsivity relative to patients without an anxiety disorder. Moreover, a broad range of anxiety-related symptom domains was associated with greater impulsivity. Exploratory analyses also revealed that baseline anxiety symptoms were associated with elevated impulsivity at 9-month follow-up, although these relationships were less robust after covariate adjustment. These data demonstrate that anxiety is positively associated with impulsivity in patients with BD. Further studies are needed to elucidate the implications of and reasons for this association. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Simon, Naomi M.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Anxiety & Traumat Stress Disorders, Simches Res Bldg,185 Cambridge St,Suite 2200, Boston, MA 02114 USA. EM nsimon@partners.org OI Ostacher, Michael/0000-0003-0353-7535 NR 66 TC 34 Z9 34 U1 2 U2 9 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 JUN PY 2008 VL 22 IS 5 BP 868 EP 876 DI 10.1016/j.janxdis.2007.09.001 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 305PA UT WOS:000256189100011 PM 17936573 ER PT J AU Husain, Z Kelly, MA Eisenbarth, GS Pugliese, A Awdeh, ZL Larsen, CE Alper, CA AF Husain, Zaheed Kelly, M. Ann Eisenbarth, George S. Pugliese, Alberto Awdeh, Zuheir L. Larsen, Charles E. Alper, Chester A. TI The MHC type 1 diabetes susceptibility gene is centromeric to HLA-DQB1 SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE major histocompatibility complex; single nucleotide polymorphism; susceptibility gene; type 1 diabetes ID DX-ALPHA GENE; MAJOR HISTOCOMPATIBILITY COMPLEX; POLYGENIC DISEASE; HLA HAPLOTYPES; DQ SUBREGION; CHAIN GENES; MELLITUS; POLYMORPHISM; SEQUENCE; CONSERVATION AB HLA-DQB1 is widely considered to be the major histocompatibility complex (MHC) susceptibility gene for type I diabetes (T1D). However, since inheritance of the gene in T1D is recessive, the presence of the protective HLA-DQB1*0602 allele with normal nucleotide sequence in some patients raises the question of whether HLA-DQB1 is not the susceptibility locus itself but merely a good marker. HLA-DQB1*0602 is part of a conserved extended haplotype (CEH) [HLA-B7, SC31, DR2] (137, DR2) with fixed DNA over more than 1 Mb of genomic DNA that normally carries a protective allele at the true susceptibility locus. We postulated that, in patients with HLA-DQB1*0602, the protective allele at the susceptibility locus has been replaced by a susceptibility allele through an ancient crossover at meiosis centromeric to HLA-DQB1. We analyzed single nucleotide polymorphisms (SNPs) distinguishing the HLA-DQA2 (the first expressed gene centromeric to HLA-DQB1) allele on the normal HLA-B7, DR2 CEH from those on susceptibility CEHs in T1D patients and controls with HLA-DQB1*0602. All but 1 of 20 healthy control HLA-DQB1*0602 haplotypes had identical (consensus) first intron HLA-DQA2 5-SNP haplotypes. Fifteen of 19 patients with HLA-DQB1*0602 were homozygous for I or more HLA-DQA2 SNPs differing from consensus HLA-DQA2 SNPs, providing evidence of crossover involving the HLA-DQA2 locus. The remaining 4 patients were heterozygous at all positions and therefore uninformative. The loss of dominant protection usually associated with HLA-DQB1*0602 haplotypes is consistent with a locus centromeric to HLA-DQB1 being a major determinant of MHC-associated susceptibility, and perhaps the true T1D susceptibility locus. (C) 2007 Published by Elsevier Ltd. C1 [Husain, Zaheed; Awdeh, Zuheir L.; Larsen, Charles E.; Alper, Chester A.] Immune Dis Inst, Boston, MA 02115 USA. [Husain, Zaheed] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Larsen, Charles E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Alper, Chester A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Pugliese, Alberto] Univ Miami, Sch Med, Diabet Res Inst, Miami, FL 33101 USA. [Eisenbarth, George S.] Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USA. [Kelly, M. Ann] Univ Birmingham, Sch Med, Div Med Sci, Birmingham B15 2TT, W Midlands, England. RP Alper, CA (reprint author), Immune Dis Inst, 800 Huntington Ave, Boston, MA 02115 USA. EM alper@cbr.med.harvard.edu FU NHLBI NIH HHS [HL29583] NR 36 TC 9 Z9 9 U1 0 U2 0 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 JUN PY 2008 VL 30 IS 4 BP 266 EP 272 DI 10.1016/j.jaut.2007.10.006 PG 7 WC Immunology SC Immunology GA 300OO UT WOS:000255834500009 PM 18065200 ER PT J AU Chen, L McKenna, TM Reisner, AT Gribok, A Reifman, J AF Chen, Liangyou McKenna, Thomas M. Reisner, Andrew T. Gribok, Andrei Reifman, Jaques TI Decision tool for the early diagnosis of trauma patient hypovolemia SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE linear classifier; ensemble classifier; liemorrhage; hypovolemia; vital-signs; decision assist; monitoring; physiology ID LIFESAVING INTERVENTIONS; VITAL SIGNS; EPIDEMIOLOGY; CLASSIFIERS; PREDICTORS; HEMORRHAGE; DEATHS; FUSION; CURVE; BLUNT AB We present a classifier for use as a decision assist tool to identify a hypovolernic state in trauma patients during helicopter transport to a hospital, when reliable acquisition of vital-sign data may be difficult. The decision tool uses basic vital-sign variables as input into linear classifiers, which are then combined into an ensemble classifier. The classifier identifies hypovolernic patients with an area under a receiver operating characteristic curve (AUC) of 0.76 (standard deviation 0.05, for 100 randomly-reselected patient subsets,). The ensemble classifier is robust; classification performance degrades only slowly as variables are dropped, and the ensemble structure (toes not require identification of a set of variables for use as best-feature inputs into the classifier. The ensemble classifier consistently outperforms bestfeatures-based linear classifiers (the classification AUC is greater, and the standard deviation is smaller, p < 0.05). The simple computational requirements of ensemble classifiers will permit them to function in small fieldable devices for continuous monitoring of trauma patients. (c) 2007 Elsevier Inc. All rights reserved. C1 [Chen, Liangyou; McKenna, Thomas M.; Reisner, Andrew T.; Gribok, Andrei; Reifman, Jaques] USA, MRMC, Telemed & Adv Technol Res Ctr, Frederick, MD 21702 USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Gribok, Andrei] Univ Tennessee, Dept Nucl Engn, Knoxville, TN 37919 USA. RP Reifman, J (reprint author), USA, MRMC, Telemed & Adv Technol Res Ctr, Bldg 363 Miller Dr, Frederick, MD 21702 USA. EM lchen@bioanalysis.org; Thomas.McKenna2@us.army.mil; areisner@partners.org; agribok@bioanalysis.org; jaques.reifman@us.army.mil NR 44 TC 25 Z9 25 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 1532-0464 J9 J BIOMED INFORM JI J. Biomed. Inform. PD JUN PY 2008 VL 41 IS 3 BP 469 EP 478 DI 10.1016/j.jbi.2007,12.002 PG 10 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 318YR UT WOS:000257129200007 PM 18255342 ER PT J AU Madaghiele, M Sannino, A Yannas, IV Spector, M AF Madaghiele, Marta Sannino, Alessandro Yannas, Ioannis V. Spector, Myron TI Collagen-based matrices with axially oriented pores SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE collagen; scaffold; porosity; microstructure; tissue engineering ID SPINAL-CORD-INJURY; GUIDANCE SCAFFOLDS; NERVE REGENERATION; GAG SCAFFOLDS; CHANNELS; DEFECTS; GROWTH; SIZE; MEMBRANES; SPONGES AB The aim of this work was the implementation of a simple technique for the production of cylindrical collagen-based scaffolds with axially oriented pore channels. Matrices with this particular porous structure have the potential to improve the regeneration of peripheral nerves and spinal cord by physically supporting and guiding the growth of neural structures across the site of injury. The regenerative potential may be further enhanced when the collagen scaffold is used as a delivery vehicle for exogenous cells and growth factors. The scaffold manufacturing technique described here is based on unidirectional freezing of a collagen suspension and subsequent freeze-drying, which produces nearly axially oriented pores. The mean pore size is dependent on both the concentration of collagen in suspension and the temperature of freezing. Environmental scanning electron microscopy and light microscopy were used to assess qualitatively and quantitatively the pore size and the pore orientation. In particular the definition of an orientation index (OI) was employed as a means to quantify the orientation of the pore channels inside the scaffolds. (C) 2007 Wiley Periodicals, Inc. C1 [Madaghiele, Marta; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn, Boston, MA 02130 USA. [Madaghiele, Marta; Sannino, Alessandro] Univ Lecce, Dept Engn Innovat, I-73100 Lecce, Italy. [Yannas, Ioannis V.; Spector, Myron] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Yannas, Ioannis V.; Spector, Myron] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Spector, Myron] Brigham & Womens Hosp, Dept Orthopaed Surg, Harvard Med Sch, Boston, MA 02115 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Tissue Engn, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu RI Madaghiele, Marta/L-7408-2015; OI Madaghiele, Marta/0000-0003-3039-9107; Sannino, Alessandro/0000-0001-8959-4412 NR 34 TC 63 Z9 69 U1 3 U2 25 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1549-3296 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD JUN 1 PY 2008 VL 85A IS 3 BP 757 EP 767 DI 10.1002/jbm.a.31517 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 296GC UT WOS:000255530500023 PM 17896767 ER PT J AU Bhattacharyya, T Mehta, P Freiberg, AA AF Bhattacharyya, Timothy Mehta, Priyesh Freiberg, Andrew A. TI Hospital characteristics associated with success in a pay-for-performance program in orthopaedic surgery SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; TOTAL KNEE REPLACEMENT; QUALITY-OF-CARE; TOTAL HIP; PROCEDURE VOLUME; OUTCOMES; POPULATION; MORTALITY AB Background: Pay-for-performance programs are designed to link payments to clinical outcomes. We investigated the characteristics of hospitals in the United States, such as size and volume, that were associated with the receipt of a clinical performance bonus in a nationwide pay-for-performance program involving hip and knee replacement. Methods: We obtained hospital-level outcomes data from a nationwide pay-for-performance demonstration project on hip and knee replacement. We obtained data on the hospital's size, procedure volume, and case-mix index as well as whether it was a teaching hospital and then performed a multivariate analysis to determine which factors were associated with the receipt of a performance bonus. Results: Hospital size and revenue were not associated with the receipt of a performance bonus. Top-performance hospitals tended to be those specialized in orthopaedics (p < 0.002). Multivariate analysis revealed that high-performance hospitals tended to perform a high volume of hip and knee replacements (p < 0.008), to be teaching hospitals (p < 0.037), and to be located in the Midwestern United States (p < 0.001). Conclusions: Teaching hospitals that perform a high volume of hip and knee replacements will tend to succeed should pay-for-performance programs be enacted nationwide. C1 Massachusetts Gen Hosp, Partners Orthopaed Trauma Serv, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bhattacharyya, T (reprint author), Massachusetts Gen Hosp, Partners Orthopaed Trauma Serv, 55 Fruit St,Yawkey 3600, Boston, MA 02114 USA. NR 21 TC 15 Z9 15 U1 1 U2 2 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 JUN PY 2008 VL 90A IS 6 BP 1240 EP 1243 DI 10.2106/JBJS.G.01172 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 309JL UT WOS:000256456400009 PM 18519316 ER PT J AU Lozano-Calderon, SA Souer, S Mudgal, C Jupiter, JB Ring, D AF Lozano-Calderon, Santiago A. Souer, Sebastiaan Mudgal, Chaitanya Jupiter, Jesse B. Ring, David TI Wrist mobilization following volar plate fixation of fractures of the distal part of the radius SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID BRIDGING EXTERNAL FIXATION; DISPLACED INTRAARTICULAR FRACTURES; REDISPLACED UNSTABLE FRACTURES; INTERNAL-FIXATION; OPEN REDUCTION; RADIOGRAPHIC MEASUREMENTS; PERCUTANEOUS FIXATION; CONTROLLED-TRIAL; CARPAL JOINT; PALMAR AB Background: Plate fixation of the distal part of the radius is believed to improve wrist motion by allowing earlier exercises. We performed a clinical trial comparing mobilization of the wrist joint within two weeks (early motion) or at six weeks (late motion) after volar plate fixation of a fracture of the distal part of the radius in order to test the null hypothesis that there are no differences in the flexion-extension arc three and six months after surgery. Methods: Sixty patients with an isolated fracture of the distal part of the radius that was treated with a single, fixed-angle volar plate and screws were enrolled. Thirty patients were randomized to the early motion group, and thirty were randomized to the late motion group. Three and six months after surgery, patients underwent range of motion measurements, grip strength measurements, and radiographic evaluation. The patients also were evaluated according to the modified Gartland and Werley score and the Mayo wrist score, rated pain on a 10-point ordinal scale, and completed the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. Results: There were no significant differences between the early motion group and the late motion group with regard to the average flexion-extension arc of the injured wrist at three months (1040 compared with 1070; p = 0.61) or six months (1240 compared with 1260; p = 0.65) after surgery. In secondary analyses, there were no significant differences in terms of selected other motions, grip strength, radiographic parameters, or the Gartland and Werley, Mayo, pain, or DASH scores. Conclusions: The initiation of wrist exercises six weeks after volar plate fixation of a fracture of the distal part of the radius does not lead to decreased wrist motion compared with the initiation of wrist motion within two weeks after surgery. Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence. C1 [Lozano-Calderon, Santiago A.; Souer, Sebastiaan; Mudgal, Chaitanya; Jupiter, Jesse B.; Ring, David] Massachusetts Gen Hosp, Yawkey Ctr, Boston, MA 02114 USA. RP Lozano-Calderon, SA (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 40 TC 50 Z9 56 U1 1 U2 4 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 JUN PY 2008 VL 90A IS 6 BP 1297 EP 1304 DI 10.2106/JBJS.G.01368 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 309JL UT WOS:000256456400017 PM 18519324 ER PT J AU Otsuji, Y Levine, RA Takeuchi, M Sakata, R Tei, C AF Otsuji, Yutaka Levine, Robert A. Takeuchi, Masaaki Sakata, Ryuzo Tei, Chuwa TI Mechanism of ischemic mitral regurgitation SO JOURNAL OF CARDIOLOGY LA English DT Review DE heart failure; mitral valve; coronary heart disease ID PAPILLARY-MUSCLE DYSFUNCTION; INFERIOR MYOCARDIAL-INFARCTION; CARDIAC RESYNCHRONIZATION THERAPY; LEFT-VENTRICULAR DYSFUNCTION; TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; END-STAGE CARDIOMYOPATHY; DILATED CARDIOMYOPATHY; VALVE-PROLAPSE; HEART-FAILURE; PROGNOSTIC IMPLICATIONS AB The basic mechanism of ischemic mitral regurgitation (MR) is believed augmented leaflet tethering due to the outward displacement of the papillary muscles by left ventricular (LV) remodeling or dilatation. Annular dilatation and LV dysfunction may not be the central mechanism, but contribute to the development of MR in the presence of augmented tethering. Papillary muscle dysfunction was initially expected to cause leaflet prolapse and MR. However, multiple studies have confirmed that papillary muscle dysfunction per se does not usually cause ischemic MR and recent studies further suggest that papillary muscle dysfunction may occasionally attenuate tethering and MR. Although surgical annuloplasty is usually effective to treat ischemic MR, occasional patients with persistent or recurrent ischemic MR after surgical ring annuloplasty even with advanced downsizing suggest the need for approaches to address tethering. Finally, leaflet tethering in patients with ischemic MR can be heterogeneous, indicating the need for individualized approaches to correct ischemic MR in affected patients. (c) 2008 Japanese College of Cardiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Otsuji, Yutaka; Takeuchi, Masaaki] Univ Occupat & Environm Hlth, Dept Internal Med 2, Yahatanishi Ku, Kitakyushu, Fukuoka 8078555, Japan. [Levine, Robert A.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Sakata, Ryuzo] Kagoshima Univ, Dept Cardiovasc Surg, Kagoshima 890, Japan. [Tei, Chuwa] Kagoshima Univ, Dept Cardiovasc Med, Kagoshima 890, Japan. RP Otsuji, Y (reprint author), Univ Occupat & Environm Hlth, Dept Internal Med 2, Yahatanishi Ku, 1-1 Iseigaoka, Kitakyushu, Fukuoka 8078555, Japan. EM otsujiy@med.uoeh-u.ac.jp NR 74 TC 24 Z9 25 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0914-5087 J9 J CARDIOL JI J. Cardiol. PD JUN PY 2008 VL 51 IS 3 BP 145 EP 156 DI 10.1016/j.jjcc.2008.03.005 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 335OJ UT WOS:000258299600001 PM 18522789 ER PT J AU D'Avila, A Thiagalingam, A Foley, L Fox, M Ruskin, JN Reddy, VY AF D'Avila, Andre Thiagalingam, Aravinda Foley, Lori Fox, Melodie Ruskin, Jeremy N. Reddy, Vivek Y. TI Temporary occlusion of the great cardiac vein and coronary sinus to facilitate radiofrequency catheter ablation of the mitral isthmus SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; ablation; left atrium; coronary sinus; atrial flutter ID LEFT ATRIAL ISTHMUS; LINEAR ABLATION AB CS Occlusion During Mitral Isthmus Ablation. Introduction: Ablation of the mitral isthmus to achieve bidirectional conduction block is technically challenging, and incomplete block slows isthmus conduction and is often proarrhythmic. The presence of the blood pool in the coronary venous system may act as a heat-sink, thereby attenuating transmural RF lesion formation. This porcine study tested the hypothesis that elimination of this heat-sink effect by complete air occlusion of the coronary sinus (CS) would facilitate transmural endocardial ablation at the mitral isthmus. Methods: This study was performed in nine pigs using a 30 mm-long prototype linear CS balloon catheter able to occlude and displace the blood within the CS (the balloon was inflated with similar to 5 cc of air). Using a 3.5 mm irrigated catheter (35 W, 30 cc/min, 1 minute lesions), two sets of mitral isthmus ablation lines were placed per animal: one with the balloon deflated (CS open) and one inflated (CS Occluded). After ablation, gross pathological analysis of the linear lesions was performed. Results: A total of 17 ablation lines were placed: 7 with CS Occlusion, and 10 without occlusion. Despite similar biophysical characteristics of the individual lesions, lesion transmurality was consistently noted only when using the air-filled CS balloon. Conclusions: Temporary displacement of the venous blood pool using an air-filled CS balloon permits transmurality of mitral isthmus ablation; this may obviate the need for ablation within the CS to achieve bidirectional mitral isthmus conduction. C1 [D'Avila, Andre; Thiagalingam, Aravinda; Foley, Lori; Fox, Melodie; Ruskin, Jeremy N.; Reddy, Vivek Y.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [D'Avila, Andre; Thiagalingam, Aravinda; Foley, Lori; Fox, Melodie; Ruskin, Jeremy N.; Reddy, Vivek Y.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP D'Avila, A (reprint author), Univ Miami, Cardiovasc Div C205, Clin Res Bldg,Suite 1130,1120 NW 14th St, Miami, FL 33136 USA. EM adavila@med.miami.edu RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009 OI d'Avila, Andre Luiz/0000-0001-8769-1411; NR 9 TC 25 Z9 25 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD JUN PY 2008 VL 19 IS 6 BP 645 EP 650 DI 10.1111/j.1540-8167.2008.01185.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 313CJ UT WOS:000256718400013 PM 18462328 ER PT J AU Reddy, VY Ruskin, JN D'Avila, A AF Reddy, Vivek Y. Ruskin, Jeremy N. D'Avila, Andre TI Balloon occlusion of the coronary sinus to facilitate mitral isthmus ablation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Editorial Material C1 [Reddy, Vivek Y.; Ruskin, Jeremy N.; D'Avila, Andre] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Reddy, Vivek Y.; Ruskin, Jeremy N.; D'Avila, Andre] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Reddy, VY (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St GRB 109, Boston, MA 02114 USA. EM vreddy@partners.org RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009 OI d'Avila, Andre Luiz/0000-0001-8769-1411; NR 2 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD JUN PY 2008 VL 19 IS 6 BP 651 EP 651 DI 10.1111/j.1540-8167.2008.01186.x PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 313CJ UT WOS:000256718400014 PM 18462323 ER PT J AU Cruz-Gonzalez, I Pabon, P Rodriguez-Barbero, A Martin-Moreiras, J Pericacho, M Sanchez, PL Ramirez, V Sanchez-Ledesma, M Martin-Herrero, F Jimenez-Candil, J Maree, AO Sanchez-Rodriguez, A Martin-Luengo, C Lopez-Novoa, JM AF Cruz-Gonzalez, Ignacio Pabon, Pedro Rodriguez-Barbero, Alicia Martin-Moreiras, Javier Pericacho, Miguel Sanchez, Pedro L. Ramirez, Victor Sanchez-Ledesma, Maria Martin-Herrero, Francisco Jimenez-Candil, Javier Maree, Andrew O. Sanchez-Rodriguez, Angel Martin-Luengo, Candido Lopez-Novoa, Jose M. TI Identification of serum endoglin as a novel prognostic marker after acute myocardial infarction SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE endoglin; endothelial dysfunction; myocardial infarction; prognostic markers ID ACUTE CORONARY SYNDROMES; HEREDITARY HEMORRHAGIC TELANGIECTASIA; SOLUBLE ENDOGLIN; GROWTH; ANGIOGENESIS; EXPRESSION; MICE; ARTERIOGENESIS; PREECLAMPSIA; PATHOGENESIS AB Endoglin is a proliferation-associated and hypoxia-inducible protein expressed in endothelial cells. The levels of soluble circulating endoglin and their prognostic significance in patients with acute myocardial infarction (AMI) are not known. In this observational prospective study serum endoglin levels were measured by ELISA in 183 AMI patients upon admission to hospital and 48 hrs later and in 72 healthy controls. Endoglin levels in AMI patients on admission were significantly lower than in healthy controls (4.25 +/- 0.99 ng/ml versus 4.59 +/- 0.87 ng/ml; P = 0.013), and decreased further in the first 48 hours (3.65 +/- 0.76 ng/ml, P < 0.001). Upon follow-up (median 319 days), patients who died had a significantly greater decrease in serum endoglin level over the first 48 hrs than those who survived (1.03 +/- 0.91 versus 0.54 +/- 0.55 ng/ml; P = 0.025). Endoglin decrease was an independent predictor of short-term (30 days) (hazard ratio 2.33;95% CI = 1.27-4.23; P = 0.006) cardiovascular mortality, and also predicts overall cardiovascular mortality during the follow-up (median 319 days) in AMI patients (hazard ratio 2.13;95% CI = 1.20-3.78; P = 0.01). In conclusion, early changes in serum endoglin may predict mortality after AMI. C1 [Rodriguez-Barbero, Alicia; Pericacho, Miguel; Lopez-Novoa, Jose M.] Univ Salamanca, Dept Physiol & Pharmacol, Reina Sofia Inst Nephrol Invest, E-37007 Salamanca, Spain. [Cruz-Gonzalez, Ignacio; Pabon, Pedro; Martin-Moreiras, Javier; Ramirez, Victor; Martin-Herrero, Francisco; Jimenez-Candil, Javier; Martin-Luengo, Candido] Univ Hosp Salamanca, Div Cardiol, Salamanca, Spain. [Sanchez, Pedro L.] Gregorio Maranon Univ Hosp, Madrid, Spain. [Sanchez-Ledesma, Maria; Sanchez-Rodriguez, Angel] Univ Hosp Salamanca, Dept Internal Med, Salamanca, Spain. [Maree, Andrew O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Lopez-Novoa, JM (reprint author), Univ Salamanca, Dept Physiol & Pharmacol, Reina Sofia Inst Nephrol Invest, Edificio Dept,Campus Miguel Unamuno, E-37007 Salamanca, Spain. EM jmlnovoa@usal.es RI 2008, Ibsal/A-1268-2012; Pericacho, Miguel/H-1786-2016; Rodriguez-Barbero, Alicia /A-7583-2017 OI Pericacho, Miguel/0000-0003-0226-482X; Rodriguez-Barbero, Alicia /0000-0002-6774-7147 NR 28 TC 21 Z9 21 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD JUN PY 2008 VL 12 IS 3 BP 955 EP 961 DI 10.1111/j.1582-4934.2007.00156.x PG 7 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 304JG UT WOS:000256105200015 PM 18494936 ER PT J AU Sanlioglu, AD Griffith, TS Omer, A Dirice, E Sari, R Altunbas, HA Balci, MK Sanlioglu, S AF Sanlioglu, Ahter Dilsad Griffith, Thomas S. Omer, Abdulkadir Dirice, Ercument Sari, Ramazan Altunbas, Hasan Ali Balci, Mustafa Kemal Sanlioglu, Salih TI Molecular mechanisms of death ligand-mediated immune modulation: A gene therapy model to prolong islet survival in type 1 diabetes SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE type 1 diabetes; gene therapy; adenovirus; TRAIL; islet transplantation ID APOPTOSIS-INDUCING LIGAND; NF-KAPPA-B; PANCREATIC BETA-CELLS; PROSTATE CARCINOMA-CELLS; SOLUBLE FAS LIGAND; NOD MICE; TNF-ALPHA; RECEPTOR-4 EXPRESSION; TRANSGENIC EXPRESSION; CANCER CELLS AB Type 1 diabetes results from the T-cell-mediated destruction of pancreatic beta cells. Islet transplantation has recently become a potential therapeutic approach for patients with type 1 diabetes. However, islet-graft failure appears to be a challenging issue to overcome. Thus, complementary gene therapy strategies are needed to improve the islet-graft survival following transplantation. Immune modulation through gene therapy represents a novel way of attacking cytotoxic T cells targeting pancreatic islets. Various death ligands of the TNF family such as FasL, TNF, and TNF-Related Apoptosis-Inclucing Ligand (TRAIL) have been studied for this purpose. The over-expression of TNF or FasL in pancreatic islets exacerbates the onset of type 1 diabetes generating lymphocyte infiltrates responsible for the inflammation. Conversely, the lack of TRAIL expression results in higher degree of islet inflammation in the pancreas. In addition, blocking of TRAIL function using soluble TRAIL receptors facilitates the onset of diabetes. These results suggested that contrary to what was observed with TNF or FasL, adenovirus mediated TRAIL gene delivery into pancreatic islets is expected to be therapeutically beneficial in the setting of experimental models of type 1 diabetes. In conclusion; this study mainly reveals the fundamental principles of death ligand-mediated immune evasion in diabetes mellitus. C1 [Sanlioglu, Ahter Dilsad; Dirice, Ercument; Sanlioglu, Salih] Akdeniz Univ, Human Gene Therapy Unit, Fac Med, TR-07070 Antalya, Turkey. [Sanlioglu, Ahter Dilsad; Dirice, Ercument; Sanlioglu, Salih] Akdeniz Univ, Dept Med Biol & Genet, Fac Med, TR-07070 Antalya, Turkey. [Griffith, Thomas S.] Univ Iowa, Coll Med, Gene Therapy Ctr, Iowa City, IA 52242 USA. [Griffith, Thomas S.] Univ Iowa, Coll Med, Dept Urol, Iowa City, IA 52242 USA. [Omer, Abdulkadir] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. [Sari, Ramazan; Altunbas, Hasan Ali; Balci, Mustafa Kemal] Akdeniz Univ, Fac Med, Div Endocrinol & Metab, Dept Internal Med, TR-07070 Antalya, Turkey. RP Sanlioglu, S (reprint author), Akdeniz Univ, Human Gene Therapy Unit, Fac Med, B Block,1st Floor, TR-07070 Antalya, Turkey. EM sanlioglu@akdeniz.edu.tr RI BALCI, Mustafa Kemal/C-2979-2016; Altunbas, Hasan/C-4199-2016; Sanlioglu, Ahter/C-6504-2016; Sari, Ramazan/C-2868-2016; Sanlioglu, Salih/F-9305-2016; Dirice, Ercument/B-2825-2017 OI BALCI, Mustafa Kemal/0000-0002-6494-3249; Sanlioglu, Ahter/0000-0003-4504-0375; Sari, Ramazan/0000-0002-6989-1492; NR 79 TC 20 Z9 22 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUN 1 PY 2008 VL 104 IS 3 BP 710 EP 720 DI 10.1002/jcb.21677 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 311VU UT WOS:000256629300002 PM 18247339 ER PT J AU Reddy, VS Harskamp, RE Van Ginkel, MW Calhoon, J Baisden, CE Kim, IS Valente, AJ Chandrasekar, B AF Reddy, Venkatapuram Seenu Harskamp, Ralf Egan Van Ginkel, Margreet Willie Calhoon, John Baisden, Clinton Eugene Kim, In-San Valente, Anthony J. Chandrasekar, Bysani TI Interleukin-18 stimulates fibronectin expression in primary human cardiac fibroblasts via PI3K-Akt-dependent NF-kappa B activation SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID SMOOTH-MUSCLE-CELLS; GROWTH-FACTOR-BETA; GENE-EXPRESSION; MYOCARDIAL-INFARCTION; MATRIX-METALLOPROTEINASE-9 EXPRESSION; SIGNALING PATHWAY; POTENTIAL ROLE; HYPERTROPHY; MICE; FIBROSIS AB Fibronectin (FN), a key component of the extracellular matrix, is upregulated in cardiac tissue during myocardial hypertrophy and failure. Here we show that interleukin (IL)-18, a proinflammatory and pro-hypertrophic cytokine, stimulates FN expression in adult human cardiac fibroblasts (HCF), an effect blocked by either the IL-18BP:Fc chimera or IL-18 neutralizing antibodies. IL-18 stimulated FN promoter-reporter activity in HCF, a response attenuated by mutation of an NF-kappa B binding site in the FN promoter. Overexpression of p65 stimulated FN transcription. IL-18 stimulated in vitro (p65, p50) and in vivo NF-kappa B DNA binding activities, and induced kappa B-dependent reporter gene activity. These effects were inhibited by adenoviral transduction of dominant negative (dn) p65 (Ad.dnp65) and dn1KK2 (Ad.dn1KK2). Investigation of signaling intermediates revealed that IL-18 stimulated P13 kinase activity (blocked by wortmannin, LY294002, or Ad.dnP13Kp85), and Akt phosphorylation and kinase activity (blocked by SH-5 or Ad.dnAkt). Furthermore, targeting MyD88, IRAK 1, TRAF6, PI3K, Akt, and NF-kappa B by RNA interference or dn expression vectors blunted IL-18 mediated FN transcription and mRNA expression. Conversely, FIN stimulated IL-18 expression. These data provide the first evidence that IL-18 and FIN stimulate each other's expression in HCF, and suggest a role for IL-18, FN and their crosstalk in myocardial hypertrophy and remodeling, disease states characterized by enhanced FIN expression and fibrosis. C1 [Valente, Anthony J.; Chandrasekar, Bysani] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Chandrasekar, Bysani] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. [Kim, In-San] Kyungpook Natl Univ, Sch Med, Dept Cell, Taegu 702701, South Korea. [Kim, In-San] Kyungpook Natl Univ, Sch Med, Matrix Biol Lab, Taegu 702701, South Korea. [Reddy, Venkatapuram Seenu; Harskamp, Ralf Egan; Van Ginkel, Margreet Willie; Calhoon, John; Baisden, Clinton Eugene] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. RP Chandrasekar, B (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med Cardiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM chandraseka@uthscsa.edu RI Harskamp, Ralf/A-9816-2009; 김, 인산/I-8988-2014; Kim, In-San/D-3956-2017 OI Harskamp, Ralf/0000-0001-9041-0350; NR 50 TC 38 Z9 38 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUN PY 2008 VL 215 IS 3 BP 697 EP 707 DI 10.1002/jcp.21348 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 298PL UT WOS:000255699500015 PM 18064631 ER PT J AU Hobai, IA Bittner, EA Grecu, L AF Hobai, Ion A. Bittner, Edward A. Grecu, Loreta TI Perioperative spinal cord infarction in nonaortic surgery: report of three cases and review of the literature SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE epidural anesthesia; paraplegia; perioperative complications; spinal cord infarction ID THORACOABDOMINAL ANEURYSM REPAIR; CEREBROSPINAL-FLUID DRAINAGE; EPIDURAL-ANESTHESIA; ARTERY SYNDROME; VASCULAR-SURGERY; PARAPLEGIA; ANALGESIA; PARAPARESIS; OPERATIONS; PRESSURE AB Paraplegia caused by a spinal cord infarction (SCI) is a devastating perioperative complication, most often associated with aortic and spine surgery. We present two other clinical scenarios in which perioperative SCI may occur. They happened during surgical procedures performed with epidural anesthesia, in the presence of several specific risk factors such as spinal stenosis, vascular disease, intraoperative hypotension, or the use of epinephrine in the local anesthetic solution. Second, SCI may occur during episodes of postoperative hypotension in patients with a history of aortic aneurysms. (C) 2008 Published by Elsevier Inc. C1 [Hobai, Ion A.; Bittner, Edward A.; Grecu, Loreta] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Grecu, L (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM lgrecu@partners.org NR 29 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD JUN PY 2008 VL 20 IS 4 BP 307 EP 312 DI 10.1016/j.jclinane.2007.11.007 PG 6 WC Anesthesiology SC Anesthesiology GA 331LM UT WOS:000258013700015 PM 18617133 ER PT J AU Nachtigall, L Delgado, A Swearingen, B Lee, H Zerikly, R Klibanski, A AF Nachtigall, Lisa Delgado, Adriano Swearingen, Brooke Lee, Hang Zerikly, Rahfa Klibanski, Anne TI Extensive clinical experience: Changing patterns in diagnosis and therapy of acromegaly over two decades SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HORMONE-RECEPTOR ANTAGONIST; GROWTH-FACTOR-I; TRANSSPHENOIDAL SURGERY; PITUITARY SURGEON; MORTALITY; CRITERIA; EPIDEMIOLOGY; MANAGEMENT; CURE; COMPLICATIONS AB Background: The increased morbidity and mortality of acromegaly makes early diagnosis and therapy critical. However, whether the type of medical professional who first diagnoses acromegaly, the major complaint prompting medical attention, or the management paradigms used in the setting of novel medical therapies have changed over time has not been well explored. Objectives: Our objective was to identify the medical professional who first suspected acromegaly and the complaint prompting the diagnosis, and if these have changed. Additional goals were to assess the interval from symptom onset to diagnosis of acromegaly and to compare treatment trends over consecutive decades. Design: This was a case-record retrospective study. Setting: The study was performed in a neuroendocrine clinical center at a tertiary care center. Subjects: A total of 100 patients (45 men and 55 women) with acromegaly referred from 1985-2005 was included in the study. Results: Acral changes (24%) and headaches (20%) were most prevalent presenting symptoms prompting diagnosis. Eighteen percent reported no symptoms of acromegaly at diagnosis. The primary care physician most often initiated the evaluation (44%). Comorbidities were more prevalent in older patients (P = 0.001). The interval between symptom onset and diagnosis decreased, compared with previous reports. Radiation therapy was used less frequently in the decade after 1994 than in the prior (16 vs. 33%; P < 0.05). Conclusions: The primary care doctor plays the major role in diagnosis of acromegaly. The increased use of brain magnetic resonance imaging may contribute to the many incidentally discovered cases and to the shortened time interval to diagnosis. Presumably due to the availability of new medical therapies, the use of radiation therapy has decreased. C1 [Nachtigall, Lisa; Delgado, Adriano; Zerikly, Rahfa; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Swearingen, Brooke] Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457, Boston, MA 02114 USA. EM aklibanski@partners.org NR 49 TC 49 Z9 50 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2008 VL 93 IS 6 BP 2035 EP 2041 DI 10.1210/jc.2007-2149 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 310DA UT WOS:000256507900002 PM 18381584 ER PT J AU Beauregard, C Utz, AL Schaub, AE Nachtigall, L Biller, BMK Miller, KK Klibanski, A AF Beauregard, Catherine Utz, Andrea L. Schaub, Amber E. Nachtigall, Lisa Biller, Beverly M. K. Miller, Karen K. Klibanski, Anne TI Growth hormone decreases visceral fat and improves cardiovascular risk markers in women with hypopituitarism: A randomized, placebo-controlled study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GH-DEFICIENT ADULTS; INTIMA-MEDIA THICKNESS; PLASMINOGEN-ACTIVATOR INHIBITOR; HOMEOSTASIS MODEL ASSESSMENT; RECOMBINANT HUMAN GH; C-REACTIVE PROTEIN; INSULIN SENSITIVITY; BODY-COMPOSITION; INCREASED PREVALENCE; REPLACEMENT THERAPY AB Context: Data regarding gender-specific efficacy of GH on critical endpoints are lacking. There are no randomized, placebo-controlled studies of physiological GH therapy solely in women. Objective: Our objective was to determine the effects of physiological GH replacement on cardiovascular risk markers and body composition in women with GH deficiency (GHD). Design: This was a 6-month, randomized, placebo-controlled, double-blind study. Setting: The study was conducted at the General Clinical Research Center. Study Participants: 43 women with GHD due to hypopituitarism were included in the study. Intervention: Study participants were randomized to receive GH (goal mid-normal serum IGF-1) or placebo. Main Outcome Measures: Cardiovascular risk markers, including high-sensitivity C-reactive protein, tissue plasminogen activator, and body composition, including visceral adipose tissue by cross-sectional computed tomography, were measured. Results: Mean daily GH dose was 0.67 mg. The mean IGF-1 SD score increased from -2.5 +/- 0.3 to -1.4 +/- 0.9 (GH) (P < 0.0001 vs. placebo). High-sensitivity C-reactive protein decreased by 38.2 +/- 9.6% (GH) vs. 18.2 +/- 6.0% (placebo) (P = 0.03). Tissue plasminogen activator and total cholesterol decreased, and high-density lipoprotein increased. Homeostasis model assessment-insulin resistance and other markers were unchanged. Body fat decreased [-5.1 +/- 2.0 (GH) vs. 1.9 +/- 1.0% (placebo); P = 0.002] as did visceral adipose tissue [-9.0 +/- 5.9 (GH) vs. 4.3 +/- 2.7% (placebo); P = 0.03]. Change in IGF-1 level was inversely associated with percent change in visceral adipose tissue (r = -0.61; P = 0.002), total body fat (r = -0.69; P < 0.0001), and high-sensitivity C-reactive protein (r = -0.51; P = 0.003). Conclusions: Low-dose GH replacement in women with GHD decreased total and visceral adipose tissue and improved cardiovascular markers, with a relatively modest increase in IGF-1 levels and without worsening insulin resistance. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM KKMiller@partners.org FU NCRR NIH HHS [M01 RR001066, M01 RR 01066]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-13] NR 59 TC 53 Z9 53 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2008 VL 93 IS 6 BP 2063 EP 2071 DI 10.1210/jc.2007-2371 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 310DA UT WOS:000256507900006 PM 18381581 ER PT J AU Araujo, AB Travison, TG Leder, BZ McKinlay, JB AF Araujo, Andre B. Travison, Thomas G. Leder, Benjamin Z. McKinlay, John B. TI Correlations between serum testosterone, estradiol, and sex hormone-binding globulin and bone mineral density in a diverse sample of men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PHYSICAL-ACTIVITY SCALE; WHITE MEN; ELDERLY-MEN; PROSTATE-CANCER; OLDER MEN; RACIAL-DIFFERENCES; AFRICAN-AMERICAN; BODY-COMPOSITION; STEROID-LEVELS; BIOAVAILABLE ESTRADIOL AB Context: The relationship between hormones and bone mineral density (BMD) in men has received considerable attention. However, most studies have been conducted in homogenous populations, and it is not known whether differences in hormones impact racial and ethnic differences in BMD. Objective: Our objective was to examine associations of testosterone, estradiol, and sex hormone binding globulin (SHBG) with BMD in a racially and ethnically diverse population. Design: This was a population-based, observational survey. Participants: A total of 976 Black, Hispanic, and white randomly selected men ages 30-79 yr from the Boston Area Community Health/Bone Survey were included. Outcome: BMD at the hip, wrist, and spine were calculated. Results: The mean age of the sample was 46.7 +/- 12.4 yr. BMD levels were highest in black men, followed by Hispanic and then white men. Associations between hormones and BMD were consistent across racial and ethnic groups. Total and free testosterone was not correlated with BMD in age-or multivariate-adjusted models. SHBG was inversely correlated with total hip and ultra-distal radius BMD after age adjustment, but not with multivariate adjustment for age, lean mass, fat mass, physical activity, self-rated health, and smoking. Total and free estradiol levels were positively and significantly correlated with femoral neck and total hip BMD, even with multivariate adjustment (partial correlations ranged between 0.11 and 0.16). However, estradiol levels failed to account for racial and ethnic differences in hip BMD. Conclusions: In our diverse population, neither serum total nor free testosterone levels were associated with BMD. Correlations between BMD and estradiol were significant but did not appear to account for any of the observed racial and ethnic differences in BMD. These findings suggest that differences in hormone levels are not a major contributor to the observed differences in BMD between Black, Hispanic, and white men. C1 [Araujo, Andre B.; Travison, Thomas G.; McKinlay, John B.] New England Res Inst Inc, Watertown, MA 02472 USA. [Leder, Benjamin Z.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Araujo, AB (reprint author), New England Res Inst Inc, 9 Galen St, Watertown, MA 02472 USA. EM aaraujo@neriscience.com; bachbone@neriscience.com RI Travison, Thomas/C-7098-2011; Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NCRR NIH HHS [K23 RR 16310, K23 RR016310]; NIA NIH HHS [AG 20727, R01 AG020727, R01 AG020727-05A1]; NIDDK NIH HHS [DK 56842, R01 DK056842, U01 DK056842] NR 60 TC 47 Z9 51 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2008 VL 93 IS 6 BP 2135 EP 2141 DI 10.1210/jc.2007-1469 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 310DA UT WOS:000256507900017 PM 18364385 ER PT J AU Leonard, CE Haynes, K Localio, AR Hennessy, S Tjia, J Cohen, A Kimmel, SE Feldman, HI Metlay, JP AF Leonard, Charles E. Haynes, Kevin Localio, A. Russell Hennessy, Sean Tjia, Jennifer Cohen, Abigail Kimmel, Stephen E. Feldman, Harold I. Metlay, Joshua P. TI Diagnostic E-codes for commonly used, narrow therapeutic index medications poorly predict adverse drug events SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 21st International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 21-24, 2005 CL Nashville, TN DE adverse drug events; patient safety; ICD-9 CM codes; E-codes; diagnostic coding; validation study ID HOSPITAL ADMISSIONS; RISK-FACTORS; OUTPATIENTS; PREVENTABILITY; POPULATION; FREQUENCY; ADULTS; COSTS AB Objective: We sought to examine the validity of specific hospital discharge codes in identifying drug toxicity precipitating hospitalization, among elderly users of high-risk medications. Study Design and Setting: We conducted a cross-sectional evaluation assessing the diagnostic test characteristics of International Classification of Diseases-9 External-Cause-of-Injury codes (E-codes) compared with a reference standard of medical record review. This study was nested within a prospective cohort of elders using warfarin, digoxin, or phenytoin as identified in the Pharmaceutical Assistance Contract for the Elderly benefit program. Results: We identified 4,803 subjects contributing 11,409 person-years of exposure to at least one of three drug groups. Subjects experienced 8,756 hospitalizations, of which 304 were deemed, by expert review, to be a result of an adverse event of warfarin, digoxin, or phenytoin. The sensitivity, specificity, and positive (PPVs) and negative predictive values for drug-specific E-codes were warfarin-25.5%, 98.3%, 46.6%, and 95.7%; digoxin-84.0%, 99.1%, 56.8%, and 99.8%; and phenytoin-86.7%, 98.7%, 59.1%, and 99.7%. Conclusions: E-codes for digoxin and phenytoin have a high sensitivity, but E-codes for all three medications have poor PPVs, a result that might produce misclassification in studies based solely on discharge coding. Investigators should confirm such rare events via medical record review. (c) 2008 Elsevier Inc. All rights reserved. C1 [Leonard, Charles E.] Univ Penn, Ctr Clin Epidemiol & Biostat, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Leonard, Charles E.; Localio, A. Russell; Hennessy, Sean; Cohen, Abigail; Kimmel, Stephen E.; Feldman, Harold I.; Metlay, Joshua P.] Univ Penn, Program Reduct Medicat Errors, Philadelphia, PA 19104 USA. [Tjia, Jennifer] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Kimmel, Stephen E.; Feldman, Harold I.; Metlay, Joshua P.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Metlay, Joshua P.] Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Leonard, CE (reprint author), Univ Penn, Ctr Clin Epidemiol & Biostat, Sch Med, Dept Biostat & Epidemiol, 423 Guardian Dr,826 Blockley Hall, Philadelphia, PA 19104 USA. EM celeonar@mail.med.upenn.edu RI Leonard, Charles/K-3447-2012; Cohen, Abigail/K-9180-2013 OI Cohen, Abigail/0000-0002-7425-7218 FU AHRQ HHS [P01-HS11530]; NIA NIH HHS [5-F32-AG-026180, K08-AG-021527, K23-AG-000987]; NIDDK NIH HHS [K24-DK-002651] NR 21 TC 14 Z9 14 U1 4 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUN PY 2008 VL 61 IS 6 BP 561 EP 571 DI 10.1016/j.jclinepi.2007.08.003 PG 11 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 305GB UT WOS:000256164700008 PM 18471660 ER PT J AU Abbo, ED Volandes, AE AF Abbo, Elmer D. Volandes, Angelo E. TI A forced choice: The value of requiring advance directives SO JOURNAL OF CLINICAL ETHICS LA English DT Article ID LIFE-SUSTAINING TREATMENT; SERIOUSLY ILL PATIENTS; HEALTH-CARE; DECISION-MAKING; PATIENT PREFERENCES; LIVING WILL; CARDIOPULMONARY-RESUSCITATION; PHYSICIANS PREDICTIONS; HOSPITALIZED-PATIENTS; SUBSTITUTED JUDGMENT C1 [Abbo, Elmer D.] Univ Chicago, Gen Internal Med Sect, Chicago, IL 60637 USA. [Volandes, Angelo E.] Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. [Volandes, Angelo E.] Harvard Univ, Sch Med, Boston, MA USA. RP Abbo, ED (reprint author), Univ Chicago, Gen Internal Med Sect, Chicago, IL 60637 USA. EM eabbo@medicine.bsd.uchicago.edu; avolandes@partners.org NR 89 TC 0 Z9 0 U1 3 U2 5 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD SUM PY 2008 VL 19 IS 2 BP 127 EP 140 PG 14 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 340FX UT WOS:000258632600004 PM 18767473 ER PT J AU Blinderman, CD AF Blinderman, Craig D. TI Commentary on "Last Hours of Life: Encouraging End-of-life Conversations" SO JOURNAL OF CLINICAL ETHICS LA English DT Editorial Material C1 [Blinderman, Craig D.] Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. [Blinderman, Craig D.] Harvard Univ, Sch Med, Boston, MA USA. RP Blinderman, CD (reprint author), Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD SUM PY 2008 VL 19 IS 2 BP 167 EP 168 PG 2 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 340FX UT WOS:000258632600009 PM 18946949 ER PT J AU Rosendorff, C AF Rosendorff, Clive TI New Insights Into Hypertension Management in Acute Stroke: Let the CHHIPS Fall Where They May SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Editorial Material ID ISCHEMIC-STROKE; BLOOD-PRESSURE; TRIAL; OUTCOMES C1 [Rosendorff, Clive] James J Peters VA Med Ctr, Dept Med, Bronx, NY 10468 USA. [Rosendorff, Clive] Mt Sinai Sch Med, Dept Med, New York, NY USA. RP Rosendorff, C (reprint author), James J Peters VA Med Ctr, Dept Med, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM clive.rosendorff@ua.gov NR 7 TC 1 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD JUN PY 2008 VL 10 IS 6 BP 425 EP 426 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 375FP UT WOS:000261099800001 PM 18550930 ER PT J AU Hisatomi, T Nakazawa, T Noda, K Almulki, L Miyahara, S Nakao, S Ito, Y She, HC Kohno, R Michaud, N Ishibashi, T Hafezi-Moghadam, A Badley, AD Kroemer, G Miller, JW AF Hisatomi, Toshio Nakazawa, Toru Noda, Kousuke Almulki, Lama Miyahara, Shinsuke Nakao, Shintaro Ito, Yasuhiro She, Haicheng Kohno, Riichiro Michaud, Norman Ishibashi, Tatsuro Hafezi-Moghadam, Ali Badley, Andrew D. Kroemer, Guido Miller, Joan W. TI HIV protease inhibitors provide neuroprotection through inhibition of mitochondrial apoptosis in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ISCHEMIC BRAIN-INJURY; EXPERIMENTAL RETINAL-DETACHMENT; PROGRAMMED CELL-DEATH; IN-VIVO; PHOTORECEPTOR APOPTOSIS; PHARMACOLOGICAL MANIPULATION; NEURONAL APOPTOSIS; FACTOR AIF; ACTIVATION; MOUSE AB Neuroprotection can be achieved by preventing apoptotic death of postmitotic cells. Apoptotic death can occur by either a caspase-dependent mechanism, involving cytochrome c, apoptosis protease-activating factor-1 (Apaf-1), and caspase-9, or a caspase-independent mechanism, involving apoptosis-inducing factor (AIF). HIV protease inhibitors (PIs) avert apoptosis in part by preventing mitochondrial outer membrane permeabilization (MOMP), but the precise mechanism by which they work is not known. Here, we evaluated the impact of the PIs in a mouse model of retinal detachment (RD) in vivo and in murine primary retinal cell cultures in vitro. Oral administration of the PIs nelfinavir and ritonavir significantly inhibited photoreceptor apoptosis, while preventing the translocation of AIF from mitochondria to the nucleus as well as the activation of caspase-9. RD-induced photoreceptor apoptosis was similarly inhibited in mice carrying hypomorphic mutations of the genes encoding AIF or Apaf-1. Nelfinavir attenuated apoptosis as well as mitochondrial release of AIF and cytochrome c, and subsequent activation of caspase-9 in vitro, in photoreceptor cultures exposed to starvation or monocyte chemoattractant protein-l-stimulated (MCP-1-stimulated) macrophages. Our results suggest that the MOMP inhibition by PIs involved interruption of both caspase-dependent and caspase-independent apoptosis pathways and that PIs may be clinically useful for the treatment of diseases caused by excessive apoptosis. C1 [Kroemer, Guido] Inst Gustave Roussy, INSERM, U848, F-94805 Villejuif, France. [Hisatomi, Toshio; Nakao, Shintaro; Kohno, Riichiro; Ishibashi, Tatsuro] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka 812, Japan. [Badley, Andrew D.] Mayo Clin, Div Infect Dis, Rochester, MN USA. [Kroemer, Guido] Univ Paris 11, Villejuif, France. [Hisatomi, Toshio; Nakazawa, Toru; Noda, Kousuke; Almulki, Lama; Miyahara, Shinsuke; Nakao, Shintaro; Ito, Yasuhiro; She, Haicheng; Michaud, Norman; Hafezi-Moghadam, Ali; Miller, Joan W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Lab, Boston, MA 02114 USA. RP Kroemer, G (reprint author), Inst Gustave Roussy, INSERM, U848, Pavillon Rech 1, F-94805 Villejuif, France. EM kroemer@igr.fr; joan_miller@meei.harvard.edu RI Kroemer, Guido/B-4263-2013; badley, andrew/O-9022-2014; OI Hafezi-Moghadam, Ali/0000-0002-5336-0697; Hisatomi, Toshio/0000-0003-2552-9595 FU NEI NIH HHS [EY014104, P30 EY014104]; NIAID NIH HHS [R01 AI403840, AI50775, K08 AI050775, R01 AI062261, R01 AI62261] NR 62 TC 45 Z9 48 U1 0 U2 1 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 JUN PY 2008 VL 118 IS 6 BP 2025 EP 2038 DI 10.1172/JCI34267 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 309FC UT WOS:000256445100009 PM 18497877 ER PT J AU Koch, L Wunderlich, FT Seibler, J Konner, AC Hampel, B Irlenbusch, S Brabant, G Kahn, CR Schwenk, F Bruning, JC AF Koch, Linda Wunderlich, F. Thomas Seibler, Jost Konner, A. Christine Hampel, Brigitte Irlenbusch, Sigrid Brabant, Georg Kahn, C. Ronald Schwenk, Frieder Bruening, Jens C. TI Central insulin action regulates peripheral glucose and fat metabolism in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ISOLATED RAT ADIPOCYTES; WHITE ADIPOSE-TISSUE; LEPTIN RECEPTOR; DIABETES-MELLITUS; GENE KNOCKDOWN; PLASMA LEPTIN; BODY-WEIGHT; FOOD-INTAKE; OBESE GENE; IN-VIVO AB Insulin resistance is a hallmark of type 2 diabetes, and many insights into the functions of insulin have been gained through the study of mice lacking the IR. To gain a better understanding of the role of insulin action in the brain versus peripheral tissues, we created 2 mouse models with inducible IR inactivation, 1 in all tissues including brain (IR Delta wb), and 1 restricted to peripheral tissues (IR Delta per). While downregulation of IR expression resulted in severe hyperinsulinemia in both models, hyperglycemia was more pronounced in IR Delta wb mice. Both strains displayed a dramatic upregulation of hepatic leptin receptor expression, while only IR Delta per mice displayed increased hepatic Stat3 phosphorylation and 116 expression. Despite a similar reduction in IR expression in white adipose tissue (WAT) mass in both models, IR Delta wb mice had a more pronounced reduction in WAT mass and severe hypoleptinemia. Leptin replacement restored hepatic Stat3 phosphorylation and normalized glucose metabolism in these mice, indicating that alterations in glucose metabolism occur largely as a consequence of lipoathrophy upon body-wide IR deletion. Moreover, chronic intracerebroventricular insulin treatment of control mice increased fat mass, fat cell size, and adipose tissue lipoprotein lipase expression, indicating that CNS insulin action promotes lipogenesis. These studies demonstrate that central insulin action plays an important role in regulating WAT mass and glucose metabolism via hepatic Stat3 activation. C1 [Koch, Linda; Wunderlich, F. Thomas; Konner, A. Christine; Hampel, Brigitte; Irlenbusch, Sigrid; Bruening, Jens C.] Univ Cologne, Inst Genet, Dept Mouse Genet & Metab, D-50674 Cologne, Germany. [Koch, Linda; Wunderlich, F. Thomas; Konner, A. Christine; Hampel, Brigitte; Irlenbusch, Sigrid; Bruening, Jens C.] Ctr Mol Med Cologne, Cologne, Germany. [Seibler, Jost; Schwenk, Frieder] TaconicArtemis GmbH, Cologne, Germany. [Brabant, Georg] Christie Hosp, Dept Endocrinol, Manchester, Lancs, England. [Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Schwenk, Frieder] Univ Appl Sci Gelsenkirchen, Dept Appl Nat Sci, Recklinghausen, Germany. RP Bruning, JC (reprint author), Univ Cologne, Inst Genet, Dept Mouse Genet & Metab, Zulpicher Str 47, D-50674 Cologne, Germany. EM jens.bruening@uni-koeln.de OI Koch, Linda/0000-0002-2943-1993 NR 60 TC 150 Z9 160 U1 0 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2008 VL 118 IS 6 BP 2132 EP 2147 DI 10.1172/JCI31073 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 309FC UT WOS:000256445100018 PM 18451994 ER PT J AU Preza, D Olsen, I Aas, JA Willumsen, T Grinde, B Paster, BJ AF Preza, Dorita Olsen, Ingar Aas, Jorn A. Willumsen, Tiril Grinde, Bjorn Paster, Bruce J. TI Bacterial profiles of root caries in elderly patients SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HUMAN CARIOUS DENTIN; SURFACE CARIES; MOLECULAR ANALYSIS; MICROBIAL DIVERSITY; CHILDHOOD CARIES; MICROFLORA; LESIONS; PLAQUE; ASSOCIATION; POPULATIONS AB Culture-based studies have shown that Streptococcus mutans and lactobacilli are associated with root caries (RC). The purpose of the present study was to assess the bacterial diversity of RC in elderly patients by use of culture-independent molecular techniques and to determine the associations of specific bacterial species or bacterial communities with healthy and carious roots. Plaque was collected from root surfaces of 10 control subjects with no RC and from 11 subjects with RC. The bacterial 16S rRNA genes from extracted DNA were PCR amplified, cloned, and sequenced to determine species identity. From a total of 3,544 clones, 245 predominant species or phylotypes were observed, representing eight bacterial phyla. The majority (54%) of the species detected have not yet been cultivated. Species of Selenomonas and Veillonella were common in all samples. The healthy microbiota included Fusobacterium nucleatum subsp. polymorphum, Leptotrichia spp., Selenomonas noxia, Streptococcus cristatus, and Kingella oralis. Lactobacilli were absent, S. mutans was present in one, and Actinomyces spp. were present in 50% of the controls. In contrast, the microbiota of the RC subjects was dominated by Actinomyces spp., lactobacilli, S. mutans, Enterococcus faecalis, Selenomonas sp. clone CS002, Atopobium and Olsenella spp., Prevotella multisaccharivorax, Pseudoramibacter alactolyticus, and Propionibacterium sp. strain FMA5. The bacterial profiles of RC showed considerable subject-to-subject variation, indicating that the microbial communities are more complex than previously presumed. The data suggest that putative etiological agents of RC include not only S. mutans, lactobacilli, and Actinomyces but also species of Atopobium, Olsenella, Pseudoramibacter, Propionibacterium, and Selenomonas. C1 [Preza, Dorita; Olsen, Ingar; Aas, Jorn A.; Willumsen, Tiril; Grinde, Bjorn] Univ Oslo, Fac Dent, Inst Oral Biol, N-0316 Oslo, Norway. [Paster, Bruce J.] Harvard Univ, Sch Med, Forsyth Inst, Dept Mol Genet, Boston, MA USA. [Paster, Bruce J.] Harvard Univ, Sch Med, Dept Oral Med Infect & Immun, Boston, MA USA. [Grinde, Bjorn] Norwegian Inst Publ Hlth, Oslo, Norway. RP Preza, D (reprint author), Univ Oslo, Fac Dent, Inst Oral Biol, POB 1052 Blindern, N-0316 Oslo, Norway. EM doritap@odont.uio.no FU Faculty of Dentistry, University of Oslo, Oslo, Norway FX We thank the Cathinka Guldberg-Centre in Oslo, Norway, particularly Marianne Wenaasen, Sabah Tariq, and Torunn Birkeland, for patient management. Dominique A. Caugant and Jan Oksnes (Norwegian Institute of Public Health, Oslo, Norway) are kindly acknowledged for the use of laboratory facilities and for technical support in sequencing.; The study was supported by the Faculty of Dentistry, University of Oslo, Oslo, Norway. NR 33 TC 90 Z9 96 U1 2 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 2008 VL 46 IS 6 BP 2015 EP 2021 DI 10.1128/JCM.02411-07 PG 7 WC Microbiology SC Microbiology GA 341DX UT WOS:000258695500021 PM 18385433 ER PT J AU Bahrani-Mougeot, FK Paster, BJ Coleman, S Ashar, J Barbuto, S Lockhart, PB AF Bahrani-Mougeot, Farah K. Paster, Bruce J. Coleman, Shirley Ashar, Jignya Barbuto, Sara Lockhart, Peter B. TI Diverse and novel oral bacterial species in blood following dental procedures SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID PERIODONTAL-DISEASE; LYSIS-FILTRATION; BACTEREMIA; ENDOCARDITIS; RISK AB We identified oral bacterial species in blood cultures following single-tooth extraction and tooth brushing. Sequence analysis of 16S rRNA genes identified 98 different bacterial species recovered from 151 bacteremic subjects. Of interest, 48 of the isolates represented 19 novel species of Prevotella, Fusobacterium, Streptococcus, Actinomyces, Capnocytophaga, Selenomonas, and Veillonella. C1 [Bahrani-Mougeot, Farah K.] Carolinas Med Ctr, Cannon Res Ctr, Dept Oral Med, Charlotte, NC 28232 USA. [Paster, Bruce J.; Barbuto, Sara] Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Bahrani-Mougeot, FK (reprint author), Carolinas Med Ctr, Cannon Res Ctr, Dept Oral Med, POB 32861, Charlotte, NC 28232 USA. EM farah.bahrani-mougeot@carolinas.org FU NIDCR [R01-DE13559-01 A2] FX This work was supported by NIDCR grant R01-DE13559-01 A2. NR 16 TC 58 Z9 61 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 2008 VL 46 IS 6 BP 2129 EP 2132 DI 10.1128/JCM.02004-07 PG 4 WC Microbiology SC Microbiology GA 341DX UT WOS:000258695500047 PM 18434561 ER PT J AU Partridge, AH AF Partridge, Ann H. TI Fertility preservation: A vital survivorship issue for young women with breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID OVARIAN STIMULATION; TAMOXIFEN; ADJUVANT; THERAPY C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 19 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2008 VL 26 IS 16 BP 2612 EP 2613 DI 10.1200/JCO.2008.16.1976 PG 2 WC Oncology SC Oncology GA 305XC UT WOS:000256210100004 PM 18509170 ER PT J AU Cheville, AL Troxel, AB Basford, JR Kornblith, AB AF Cheville, Andrea L. Troxel, Andrea B. Basford, Jeffrey R. Kornblith, Alice B. TI Prevalence and treatment patterns of physical impairments in patients with metastatic breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FUNCTIONAL ASSESSMENT SCALES; QUALITY-OF-LIFE; INPATIENT REHABILITATION; COLORECTAL-CANCER; HEART-FAILURE; 6-MINUTE WALK; CHEMOTHERAPY; EXERCISE; PERFORMANCE; LYMPHEDEMA AB Purpose Physical impairments cause profound functional declines in patients with cancer. Although common rehabilitation measures can address many impairments, the extent of their delivery is unknown. We studied these issues by quantifying physical impairments in patients with metastatic breast cancer and by assessing how they are addressed. Patients and Methods A consecutive sample of 163 community-dwelling patients with metastatic breast cancer was stratified by Karnofsky performance score and administered the Medical Outcomes Study Physical Function Subscale and the Older Americans Resource Study Activities of Daily Living subscales. Cancer-related physical impairments were identified through a physical examination, the 6-Minute Walk Test, and the Functional Independence Measure Mobility Subscale. Patients were questioned regarding the nature, type, and setting of treatments for impairments. Physical rehabilitation needs were determined through a consensus process involving physiatrists and physical/occupational therapists specializing in cancer. Results Ninety-two percent of patients ( 150 of 163) had at least one physical impairment. Among 530 identified impairments, 484 (92%) required a physical rehabilitation intervention and 469 (88%) required physical therapy ( PT) and/or occupational therapy (OT). Only 30% of impairments requiring rehabilitation services and 21% of those requiring PT/OT received treatment. Impairments detected during hospitalization were overwhelmingly more likely to receive a rehabilitation intervention ( odds ratio [ OR] = 87.9; 95% CI, 28.5 to 271.4), and PT/OT ( OR = 558.8; 95% CI, 187.0 to 1,669.6). Low socioeconomic and minority status were significantly associated with nontreatment. Conclusion Remediable physical impairments were prevalent and poorly addressed among patients with metastatic breast cancer, drastically so in the outpatient setting. Undertreatment was particularly prominent among minority and socioeconomically disadvantaged groups. C1 [Cheville, Andrea L.] Coll Med, Mayo Clin, Dept Phys Med & Rehabil, Rochester, MN 55905 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Cheville, AL (reprint author), Coll Med, Mayo Clin, Dept Phys Med & Rehabil, Rochester, MN 55905 USA. OI Troxel, Andrea/0000-0002-1393-3075 FU NCRR NIH HHS [KL2 RR024151, KL2 RR024151-01] NR 50 TC 52 Z9 52 U1 1 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2008 VL 26 IS 16 BP 2621 EP 2629 DI 10.1200/JCO.2007.12.3075 PG 9 WC Oncology SC Oncology GA 305XC UT WOS:000256210100008 PM 18509174 ER PT J AU Polite, BN Cirrincione, C Fleming, GF Berry, DA Seidman, A Muss, H Norton, L Shapiro, C Bakri, K Marcom, K Lake, D Schwartz, JH Hudis, C Winer, EP AF Polite, Blase N. Cirrincione, Constance Fleming, Gini F. Berry, Donald A. Seidman, Andrew Muss, Hyman Norton, Larry Shapiro, Charles Bakri, Kamal Marcom, Kelly Lake, Diana Schwartz, Joel H. Hudis, Clifford Winer, Eric P. TI Racial differences in clinical outcomes from metastatic breast cancer: A pooled analysis of CALGB 9342 and 9840 - Cancer and leukemia group B SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID AFRICAN-AMERICAN WOMEN; ESTROGEN-RECEPTOR; WHITE PATIENTS; SURVIVAL; RACE; DISPARITIES; CARCINOMA; ASSOCIATION; PACLITAXEL; PROGNOSIS AB Purpose African American women are more likely to be diagnosed with metastatic breast cancer at the time of presentation than whites, and have shorter survival once diagnosed. This study examines racial differences in clinical outcomes in the setting of two large cooperative group randomized clinical trials. Patients and Methods The study cohort consisted of 787 white ( 80%) and 195 African American (20%) patients with metastatic breast cancer enrolled in two successive Cancer and Leukemia Group B (CALGB) trials using taxanes in the metastatic setting. Differences in overall survival ( OS), response incidence, and time to treatment failure (TTF) were examined by race. In addition, differences in the incidence of baseline and treatment-related toxicities were examined. Results With 779 deaths ( 166 African Americans and 613 whites), median OS was 14.3 months for African Americans and 18.75 months for whites ( hazard ratio [HR] = 1.37; 95% CI, 1.15 to 1.63). When adjusted for prognostic factors, African Americans had a 24% increase in the hazard of death compared with whites ( HR = 1.24; 95% CI, 1.02 to 1.51). No significant differences in TTF or overall response to therapy were seen. No clinically significant toxicity differences were seen. Conclusion African Americans with metastatic breast cancer have an increased hazard of death compared with whites despite the receipt of similar per-protocol treatment, but experience no differences in TTF or overall response to therapy. We hypothesize that more direct and robust measures of comorbidities, and perhaps other factors such as receipt of subsequent therapy could help further explain the observed survival difference. C1 [Polite, Blase N.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Duke Univ, Med Ctr, Canc & Leukemia Grp B Stat Ctr, Durham, NC 27706 USA. Univ N Carolina, Chapel Hill, NC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Vermont Reg Canc Ctr, Burlington, VT USA. Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Polite, BN (reprint author), Univ Chicago, Med Ctr, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. EM bpolite@medicine.bsd.uchicago.edu OI Norton, Larry/0000-0003-3701-9250 FU NCI NIH HHS [CA32291, CA33601, CA41287, CA47559, CA47577, CA77406, CA77651, CA77658, U10 CA003927, U10 CA032291, U10 CA033601, U10 CA035279, U10 CA035421, U10 CA041287, U10 CA045389, U10 CA045418, U10 CA045564, U10 CA045808, U10 CA047559, U10 CA047577, U10 CA047642, U10 CA074811, U10 CA077440, U10 CA077597, U10 CA077651, U10 CA077658] NR 36 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2008 VL 26 IS 16 BP 2659 EP 2665 DI 10.1200/JCO.2007.13.9782 PG 7 WC Oncology SC Oncology GA 305XC UT WOS:000256210100013 PM 18509177 ER PT J AU Wilson, WH Dunleavy, K Pittaluga, S Hegde, U Grant, N Steinberg, SM Raffeld, M Gutierrez, M Chabner, BA Staudt, L Jaffe, ES Janik, JE AF Wilson, Wyndham H. Dunleavy, Kieron Pittaluga, Stefania Hegde, Upendra Grant, Nicole Steinberg, Seth M. Raffeld, Mark Gutierrez, Martin Chabner, Bruce A. Staudt, Louis Jaffe, Elaine S. Janik, John E. TI Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-Cell lymphoma with analysis of germinal center and post-germinal center biomarkers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMAS; CHEMOTHERAPY PLUS RITUXIMAB; R-CHOP; ELDERLY-PATIENTS; BCL-2-ASSOCIATED RESISTANCE; PROGNOSTIC-SIGNIFICANCE; RESPONSE CRITERIA; DRUG-RESISTANCE; EXPRESSION; BCL-6 AB Purpose To assess the clinical outcome and the influence of biomarkers associated with apoptosis inhibition (Bcl- 2), tumor proliferation (MIB-1), and cellular differentiation on the outcome with dose-adjusted (DA) EPOCH ( etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) plus rituximab ( R) infusional therapy in diffuse large B-cell lymphoma (DLBCL) with analysis of germinal center B-cell (GCB) and post-GCB subtypes by immunohistochemistry. Patients and Methods Phase II study of 72 patients with untreated de novo DLBCL who were at least 18 years of age and stage II or higher. Radiation consolidation was not permitted. Results Patients had a median age of 50 years ( range, 19 to 85) and 40% had a high-intermediate or high International Prognostic Index ( IPI). At 5 years, progression-free survival (PFS) and overall survival ( OS) were 79% and 80%, respectively, with a median potential follow-up of 54 months. PFS was 91%, 90%, 67%, and 47%, and OS was 100%, 90%, 74%, and 37%, for 0 to 1, 2, 3, and 4 to 5 IPI factors, respectively, at 5 years. The Bcl- 2 and MIB-1 biomarkers were not associated with PFS or OS. Based on DA-EPOCH historical controls, rituximab only benefited Bcl- 2 positive tumors. Bcl- 6 expression was associated with higher PFS whereas GCB exhibited a marginally significant higher PFS compared with post-GCB DLBCL. Conclusion DA-EPOCH-R outcome was not affected by tumor proliferation and rituximab appeared to overcome the adverse effect of Bcl-2. Bcl-6 may identify a biologic program associated with a superior outcome. Overall, DA-EPOCH-R shows promising outcome in low and intermediate IPI groups. A molecular model of treatment outcome with rituximab and chemotherapy is presented. C1 Ctr Canc Res, Bethesda, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Connecticut, Hartford, CT 06112 USA. RP Wilson, WH (reprint author), NCI, Metab Branch, Bldg 10,Room 4N-115,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wilsonw@mail.nih.gov FU Intramural NIH HHS [Z01 SC006741-13] NR 49 TC 139 Z9 154 U1 1 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2008 VL 26 IS 16 BP 2717 EP 2724 DI 10.1200/JCO.2007.13.1391 PG 8 WC Oncology SC Oncology GA 305XC UT WOS:000256210100020 PM 18378569 ER PT J AU San-Miguel, J Harousseau, JL Joshua, D Anderson, KC AF San-Miguel, Jesus Harousseau, Jean-Luc Joshua, Douglas Anderson, Kenneth C. TI Individualizing treatment of patients with myeloma in the era of novel agents SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID STEM-CELL TRANSPLANTATION; DIAGNOSED MULTIPLE-MYELOMA; COOPERATIVE-ONCOLOGY-GROUP; INDUCTION TREATMENT PRIOR; HIGH-DOSE THERAPY; PLUS THALIDOMIDE; RANDOMIZED-TRIAL; ELDERLY-PATIENTS; GENETIC ABNORMALITIES; MELPHALAN-PREDNISONE AB Progress in the understanding of multiple myeloma (MM) cell biology has led to the identification of new relevant prognostic factors and subsequently different risk groups. This concept, together with the recent discovery of new drugs with novel mechanisms of action, will probably lead to individualized treatment according to the different patients' characteristics. In this review, we focus on current available agents already approved for MM, and discuss individualized treatment approaches for both transplantation candidates (subdivided into standard and high-risk patients) and elderly patients. Future progress in MM will be based on using science to inform the design of the optimal combined treatments, and high throughput assays that can assess the ability of combination therapies to induce death of MM cells, both alone and in the bone marrow microenvironment. C1 Univ Hosp Nantes, Nantes, France. Royal Prince Alfred Hosp, Inst Hematol, Sydney, Australia. Dana Farber Canc Inst, Boston, MA 02115 USA. [San-Miguel, Jesus] Univ Salamanca, Hosp Univ Salamanca, Serv Hematol, Ctr Invest Canc,Inst Biol Mol,Ctr Canc,CSIC, Salamanca 37007, Spain. RP San-Miguel, J (reprint author), Univ Salamanca, Hosp Univ Salamanca, Serv Hematol, Ctr Invest Canc,Inst Biol Mol,Ctr Canc,CSIC, Paseo San Vicente 58, Salamanca 37007, Spain. EM sanmigiz@usal.es RI 2008, Ibsal/A-1268-2012; OI SAN MIGUEL, JESUS/0000-0002-9183-4857 NR 52 TC 55 Z9 56 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2008 VL 26 IS 16 BP 2761 EP 2766 DI 10.1200/JCO.2007.15.2546 PG 6 WC Oncology SC Oncology GA 305XC UT WOS:000256210100026 PM 18427148 ER PT J AU Ruddy, KJ Wu, D Brown, JR AF Ruddy, Kathryn J. Wu, David Brown, Jennifer R. TI Pseudohyperkalemia in chronic lymphocytic leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID EXTREME LEUKOCYTOSIS C1 [Ruddy, Kathryn J.; Brown, Jennifer R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wu, David] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ruddy, Kathryn J.; Brown, Jennifer R.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Ruddy, KJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 4 TC 11 Z9 12 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2008 VL 26 IS 16 BP 2781 EP 2782 DI 10.1200/JCO.2008.16.3014 PG 3 WC Oncology SC Oncology GA 305XC UT WOS:000256210100030 PM 18509189 ER PT J AU Marangell, LB Dennehy, EB Wisniewski, SR Bauer, MS Miyahara, S Allen, MH Martinez, M Al Jurdi, RK Thase, ME AF Marangell, Lauren B. Dennehy, Ellen B. Wisniewski, Stephen R. Bauer, Mark S. Miyahara, Sachiko Allen, Michael H. Martinez, Melissa Al Jurdi, Rayan K. Thase, Michael E. TI Case-control analyses of the impact of pharmacotherapy on prospectively observed suicide attempts and completed suicides in bipolar disorder: Findings from STEP-BD SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID TREATMENT ENHANCEMENT PROGRAM; SEROTONIN REUPTAKE INHIBITORS; RANDOMIZED CONTROLLED-TRIALS; MOOD DISORDERS; LITHIUM; RISK; BEHAVIOR; ANTIDEPRESSANTS; PARTICIPANTS; METAANALYSIS AB Objective: Given high rates of suicide and suicide attempts in bipolar disorder and the data suggesting a suicide-protective effect of lithium, we evaluated the impact of pharmacotherapy on prospectively observed suicides and suicide attempts in subjects in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Method: The STEP-BD study enrolled 4360 participants with DSM-IV bipolar disorder diagnoses from September 1998 through November 2004. There were 270 suicide events in STEP-BD (8 completed suicides, 262 attempts). These occurred in 182 of STEP-1313 participants (cases). Inclusion criteria required cases to be white or Caucasian, have at least 1 postbaseline visit, and have prescription information within 30 days of the suicide event. This reduced the available cohort to 106 cases. Matching included age, gender, history of previous suicide attempt, and a propensity score that considered bipolar subtype, marital status, age at onset, and history of psychosis, resulting in 93 matched pairs. A secondary analysis added mood state status within 30 days of the suicide event to the propensity score (N = 54 pairs). The association of drug prescriptions with suicide attempts/completions was assessed using a conditional logistic regression model. Results: The results do not indicate a relationship between lithium use and suicide attempts or completions (p = .41). Similar findings were found for exposure to valproate, carbamazepine, lamotrigine, and the atypical antipsychotic medications. An association between selective serotonin reuptake inhibitor (SSRI) prescription and suicide events was observed (p < .0001). Findings were similar in a secondary analysis that controlled for mood state. Conclusion: Our data are not consistent with a suicide-protective effect of lithium. The association between suicide events and SSRI prescriptions requires cautious interpretation due to complex relationships between treatment, severity, and suicidality. Trial Registration: clinicaltrials.gov Identifier: NCT00012558. C1 [Marangell, Lauren B.; Martinez, Melissa; Al Jurdi, Rayan K.] Baylor Coll Med, Dept Psychiat, Mood Disorders Ctr, Houston, TX 77030 USA. [Marangell, Lauren B.; Martinez, Melissa; Al Jurdi, Rayan K.] S Cent Mental Illness Res & Educ Core, Dept Vet Affairs, Houston, TX 77030 USA. [Dennehy, Ellen B.] Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA. [Wisniewski, Stephen R.; Miyahara, Sachiko] Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA USA. [Miyahara, Sachiko] Univ Pittsburgh, Western Psychiat Inst, Dept Psychiat, Pittsburgh, PA USA. [Bauer, Mark S.] Harvard Univ, Sch Med, Boston, MA USA. [Bauer, Mark S.] Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Allen, Michael H.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Thase, Michael E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Marangell, LB (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. EM drlauren@lilly.com RI Allen, Michael/A-8776-2011; OI Wisniewski, Stephen/0000-0002-3877-9860 FU NIMH NIH HHS [N01MH80001] NR 21 TC 38 Z9 38 U1 2 U2 4 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 JUN PY 2008 VL 69 IS 6 BP 916 EP 922 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 318LI UT WOS:000257092800005 PM 18399724 ER PT J AU Kane, JM Perlis, RH Malhotra, AK AF Kane, John M. Perlis, Roy H. Malhotra, Anil K. TI Clinical insights into pharmacogenetics and schizophrnia, part 2 SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID CATECHOL-O-METHYLTRANSFERASE; TREATMENT ENHANCEMENT PROGRAM; ANTIPSYCHOTIC-DRUG TREATMENT; PREVENTION TRIAL INTERSEPT; BIPOLAR-I DISORDER; COGNITIVE DEFICITS; CLOZAPINE TREATMENT; SUICIDAL IDEATION; C/T POLYMORPHISM; STEP-BD C1 [Kane, John M.; Malhotra, Anil K.] Zucker Hillside Hosp, Dept Psychiat, Psychiat Res Program, Glen Oaks, NY USA. [Kane, John M.; Malhotra, Anil K.] Yeshiva Univ Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY 10461 USA. [Perlis, Roy H.] Harvard Univ, Sch Med, Boston, MA USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Bipolar Res Program, Boston, MA 02114 USA. RP Kane, JM (reprint author), Zucker Hillside Hosp, Dept Psychiat, Psychiat Res Program, Glen Oaks, NY USA. NR 58 TC 0 Z9 0 U1 2 U2 3 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 JUN PY 2008 VL 69 IS 6 BP 1006 EP 1013 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 318LI UT WOS:000257092800019 PM 18683996 ER PT J AU Pollack, MH Tiller, J Xie, F Trivedi, MH AF Pollack, Mark H. Tiller, Jane Xie, Fang Trivedi, Madhukar H. TI Tiagabine in adult patients with generalized anxiety disorder - Results from 3 randomized, double-blind, placebo-controlled, parallel-group studies SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID DSM-IV; GABA; ESCITALOPRAM; TRIAL; MULTICENTER; PREGABALIN; PAROXETINE; INHIBITOR; EFFICACY; LABEL AB The objective of these studies was to evaluate the efficacy and tolerability of tiagabine, a selective gamma-aminobutyric acid reuptake inhibitor, in adult patients with generalized anxiety disorder (GAD). Patients with a diagnosis of GAD were enrolled in 1 of 3 randomized, placebo-controlled 10-week studies. In each study, tiagabine was taken twice daily in divided doses - 4, 8, or 12 mg/d in a fixed-dose study and 4-16 mg/d in two flexible-dose trials. The primary efficacy measure was the change from baseline in the 14-item Hamilton Rating Scale for Anxiety (HAM-A) total score at the final visit (last observation carried forward). Additional measures included change from baseline in the anxiety subscale of the Hospital Anxiety and Depression Scale, the Sheehan Disability Scale, and Clinical Global Impressions-Improvement scale. Tolerability was assessed via spontaneous reports as well as rating scales throughout the study period.. In all 3 studies, there was no significant differentiation from placebo on the primary measure (change in HAM-A) for any tiagabine dose (P > 0.05). In the 2 flexible-dose studies, the tiagabine group showed improvements over time in the HAM-A that reached significance only in those patients who completed 10 weeks of treatment (study 2, P = 0.018; study 3, P = 0.036). The most common adverse events were dizziness, headache, nausea, fatigue, and somnolence. In conclusion, the results of these studies do not support the efficacy of tiagabine in adult patients with GAD. C1 [Pollack, Mark H.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Tiller, Jane; Xie, Fang] Cephalon Inc, Frazer, PA USA. [Trivedi, Madhukar H.] SW Texas State Univ, Dept Psychiat, Dallas, TX USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Simches Res Bldg,185Cambridge St,Suite 2000,2nd F, Boston, MA 02114 USA. EM mpollack@partners.org NR 27 TC 21 Z9 21 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 2008 VL 28 IS 3 BP 308 EP 316 DI 10.1097/JCP.0b013e318172b45f PG 9 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 301RT UT WOS:000255914000008 PM 18480688 ER PT J AU Prince, J AF Prince, Jefferson TI Catecholamine dysfunction in attention-deficit/hyperactivity disorder - An update SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; ANTERIOR CINGULATE CORTEX; DOPAMINE TRANSPORTER; PREFRONTAL CORTEX; RESPONSE SELECTION; RECEPTOR GENE; ADHD; ASSOCIATION; ADOLESCENTS; CHILDREN AB Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous disease that affects children, adolescents, and adults. Genetic research has confirmed that there is a large hereditary component to this condition and has helped identify some of the genes associated with it. Among these are several genes associated with the catecholaminergic system including the dopamine receptor genes (DRD4 and DRD5), the dopamine transporter gene, and the gene for dopamine P-hydroxylase, which catalyzes conversion of dopamine to norepinephrine. Attention-deficit/hyperactivity disorder is believed to be a result of abnormalities in the frontal regions of the brain, particularly the prefrontal cortex and associated subcortical structures and circuits. Underpinning these abnormalities are disturbances of catecholamine neurotransmission. Studies have demonstrated that patients with ADHD have depleted levels of dopamine and norepinephrine thought to be largely the result of dysfunction of their respective transporter systems. The efficacy of stimulant agents confirms that the neurotransmitter abnormalities seen in ADHD are primarily catecholaminergic in origin. This article focuses on the catecholaminergic networks of higher cognitive functions such as attention and focus and of motor functions that may be associated with such networks, reviewing both the physiology of such functions and the pathophysiology of ADHD. Researchers are currently investigating whether other neurotransmitter systems may be partially involved and are investigating whether agents that affect these other systems will prove complementary to currently used treatments. C1 Harvard Univ, Sch Med, Dept Child Psychiat, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Prince, J (reprint author), Harvard Univ, Sch Med, Dept Child Psychiat, Massachusetts Gen Hosp, 6900 Yawkey Bldg,15 Parkman St, Boston, MA 02114 USA. EM jprince@partners.org NR 66 TC 68 Z9 69 U1 4 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 2008 VL 28 IS 3 SU 2 BP S39 EP S45 DI 10.1097/JCP.0b013e318174f92a PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 301RV UT WOS:000255914200002 PM 18480676 ER PT J AU Wilens, TE AF Wilens, Timothy E. TI Effects of methylphenidate on the catecholaminergic system in attention-deficit/hyperactivity disorder SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; PET IMAGING PROBE; DOPAMINE TRANSPORTER AVAILABILITY; PREFRONTAL CORTEX; ORAL METHYLPHENIDATE; HUMAN BRAIN; DEXMETHYLPHENIDATE HYDROCHLORIDE; INTRACORTICAL INHIBITION; EXTRACELLULAR DOPAMINE; LOCUS-COERULEUS AB Stimulants are part of the standard-of-care treatment for attention-deficit/hyperactivity disorder (ADHD). Methylphenidate, with a history of use spanning approximately 5 decades, is a first-line stimulant treatment for ADHD. Methylphenidate chiefly affects the prefrontal cortex and striatum, the mechanism of action being modulation of catecholaminergic tone. Methylphenidate treatment produces an increase in dopamine (DA) signaling through multiple actions. including blockade of the DA reuptake transporter and amplification of DA response duration, disinhibition of DA D2 autoreceptors and amplification of DA tone, and activation of D1 receptors on the postsynaptic neuron. The actions of methylphenidate may also be mediated by stimulation of the noradrenergic alpha(2) receptor and DA D1 receptor in the cortex. The role of other neurotransmitters such as histamine, acetylcholine, serotonin, and alpha-agonists in modulating catecholamine pathophysiology in ADHD and ADHD treatment needs to be elucidated. Overall, the changes in catecholaminergic tone clinically manifest as improvements in attention deficit, distractibility, and motor hyperactivity in patients with ADHD. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 55 Fruit St,WRN 705, Boston, MA 02114 USA. EM twilens@partners.org NR 77 TC 101 Z9 104 U1 7 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 2008 VL 28 IS 3 SU 2 BP S46 EP S53 DI 10.1097/JCP.0b013e318173312f PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 301RV UT WOS:000255914200003 PM 18480677 ER PT J AU Coombes, JM Steiner, JF Bekelman, DB Prochazka, AV Denberg, TD AF Coombes, John M. Steiner, John F. Bekelman, David B. Prochazka, Allan V. Denberg, Thomas D. TI Clinical outcomes associated with attempts to educate patients about lower endoscopy: A narrative review SO JOURNAL OF COMMUNITY HEALTH LA English DT Article DE colonoscopy; flexible sigmoidoscopy; lower endoscopy; patient knowledge; colorectal cancer screening ID OPEN-ACCESS ENDOSCOPY; INFORMED-CONSENT; GASTROINTESTINAL ENDOSCOPY; RANDOMIZED-TRIAL; FLEXIBLE SIGMOIDOSCOPY; MALPRACTICE CLAIMS; INFORMATION; COLONOSCOPY; ANXIETY; GASTROSCOPY AB Patient knowledge about lower endoscopy might have beneficial effects on satisfaction outcomes, pre-procedure anxiety, and adherence, although this is poorly understood. Methods Searching the national and international literature, we reviewed 20 years of observational studies and randomized trials that examine possible relationships between educating patients about lower endoscopy and clinical outcomes. Twenty-three publications were included but their heterogeneity precluded meta-analyses. Standard and modified informed consent procedures and enhanced educational interventions were associated most often with levels of patient knowledge, satisfaction, anxiety, and adherence. Regardless of the approach, a large proportion of patients have poor comprehension of lower endoscopy's risks, benefits, and alternatives; patient satisfaction with information and procedures manifests ceiling effects; only a subset of patients have clinically significant pre-procedure anxiety; and providing written information and reminders may improve procedure adherence. Future work should focus on strategies for improving patient knowledge in the setting of initial screening colonoscopy within open access systems. Patient knowledge of lower endoscopy is often inadequate even though greater knowledge might be associated with better clinical outcomes for certain patient subgroups. Professional societies have an important role to play in endorsing educational strategies and in clarifying and assessing the adequacy of patient knowledge. C1 [Bekelman, David B.; Denberg, Thomas D.] Univ Colorado, Dept Med, Denver, CO 80262 USA. [Bekelman, David B.; Denberg, Thomas D.] Hlth Sci Ctr, Denver, CO 80262 USA. [Coombes, John M.] Gastroenterol Associates No New York PC, Irongate Ctr 5, Glens Falls, NY 12801 USA. [Steiner, John F.] Univ Colorado Denver, Colorado Hlth Outcomes Program, Aurora, CO 80045 USA. [Steiner, John F.] Hlth Sci Ctr, Aurora, CO 80045 USA. [Prochazka, Allan V.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Denberg, TD (reprint author), Univ Colorado, Dept Med, 4200 E 9th Ave,B180, Denver, CO 80262 USA. EM tom.denberg@uchsc.edu RI Coombes, Jeff/F-1764-2010 NR 35 TC 9 Z9 10 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0094-5145 J9 J COMMUN HEALTH JI J. Community Health PD JUN PY 2008 VL 33 IS 3 BP 149 EP 157 DI 10.1007/s10900-007-9081-5 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 285DI UT WOS:000254757100006 PM 18165928 ER PT J AU Varra, AA Hayes, SC Roget, N Fisher, G AF Varra, Alethea A. Hayes, Steven C. Roget, Nancy Fisher, Gary TI A randomized control trial examining the effect of acceptance and commitment training on clinician willingness to use evidence-based pharmacotherapy SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the Association-for-Behavioral-and-Cognitive-Therapies CY NOV, 2006 CL Chicago, IL SP Assoc Behav & Cognit Therapies DE dissemination; pharmacotherapy; substance abuse; acceptance and commitment therapy ID PSYCHOLOGICAL-RESEARCH; MENTAL-HEALTH; THERAPY; DISSEMINATION; BUPRENORPHINE; ATTITUDES; CARE; PSYCHOTHERAPY; METAANALYSIS; COUNSELORS AB This study evaluated the effectiveness of acceptance and commitment training (ACT) for increasing drug and alcohol counselors' willingness to use evidence-based agonist and antagonist pharmacotherapy. Fifty-nine drug and alcohol counselors were randomly assigned to either a 1-day ACT workshop or a 1-day educational control workshop. Both groups then attended a 2-day workshop on empirically supported treatments for substance abuse. Measures were taken at pre- and posttraining and 3-month follow-up on reported use of pharmacotherapy, willingness to use pharmacotherapy, perceived barriers to implementing new treatments, and general acceptance. As compared with those in the education alone condition, participants in the ACT condition showed significantly higher rates of referrals to pharmacotherapy at follow-up, rated barriers to learning new treatments as less believable at posttraining and follow-up, and showed greater psychological flexibility at posttraining and follow-up. Mediational analyses indicated that reduced believability of barriers and greater psychological flexibility mediated the impact of the intervention. Results support the idea that acceptance-based interventions may be helpful in addressing the psychological factors related to poor adoption of evidence-based treatments. C1 [Varra, Alethea A.] Mental Hlth Serv 116, Vet Affairs Puget Sound Healthcare Syst, Seattle, WA 98108 USA. [Hayes, Steven C.; Roget, Nancy; Fisher, Gary] Univ Nevada, Dept Psychol, Reno, NV 89557 USA. RP Varra, AA (reprint author), Mental Hlth Serv 116, Vet Affairs Puget Sound Healthcare Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM alethea.varra@va.gov RI Hayes, Steven/F-9306-2012 OI Hayes, Steven/0000-0003-4399-6859 NR 57 TC 37 Z9 40 U1 2 U2 12 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 JUN PY 2008 VL 76 IS 3 BP 449 EP 458 DI 10.1037/0022-006X.76.3.449 PG 10 WC Psychology, Clinical SC Psychology GA 307NX UT WOS:000256326700009 PM 18540738 ER PT J AU Yamazaki, H Margolis, HC AF Yamazaki, H. Margolis, H. C. TI Enhanced enamel remineralization under acidic conditions in vitro SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE dental enamel; remineralization; mineral distribution; diffusion ID SIMULTANEOUS DEMINERALIZATION REMINERALIZATION; HUMAN DENTAL ENAMEL; PLAQUE FLUID; FLUORIDE; LESIONS; INVITRO AB We conducted this study to test the hypothesis that acidic solutions undersaturated with respect to enamel and supersaturated with respect to fluorapatite can enhance enamel remineralization by reducing preferential remineralization of the outer lesion and promoting mineral ion penetration. We used quantitative microradiography to assess mineral changes in artificial surface-softened and subsurface lesions in human enamel in vitro, induced by such an acidic solution and by a neutral remineralizing solution. For surface-softened lesions, the extent of remineralization was similar for both solutions, although preferential remineralization of the outer lesion was observed with the neutral solution. For subsurface lesions, preferential remineralization of the outer lesion was not observed with either solution. However, the extent of subsurface lesion remineralization by the acidic solution was significantly greater than that observed with the neutral solution. Results obtained are noted to reflect inherent differences in lesion type and the properties of the solutions studied. C1 [Yamazaki, H.; Margolis, H. C.] Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. RP Margolis, HC (reprint author), Forsyth Inst, Dept Biomineralizat, 140 Fenway, Boston, MA 02115 USA. EM hmargolis@forsyth.org FU NIDCR NIH HHS [DE 15163] NR 26 TC 28 Z9 31 U1 0 U2 1 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 2008 VL 87 IS 6 BP 569 EP 574 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 304DN UT WOS:000256090300012 PM 18502967 ER PT J AU Fimple, JL Fontana, CR Foschi, F Ruggiero, K Song, XQ Pagonis, TC Tanner, ACR Kent, R Doukas, AG Stashenko, PP Soukos, NS AF Fimple, Jacob Lee Fontana, Carla Raquel Foschi, Federico Ruggiero, Karriann Song, Xiaoqing Pagonis, Tom C. Tanner, Anne C. R. Kent, Ralph Doukas, Apostolos G. Stashenko, Philip P. Soukos, Nikolaos S. TI Photodynamic treatment of endodontic polymicrobial infection in vitro SO JOURNAL OF ENDODONTICS LA English DT Article DE biofilms; endodontic polymicrobial infection; methylene blue; photodynamic therapy; root canals ID ROOT CANALS; DENTINAL TUBULES; LETHAL PHOTOSENSITIZATION; BACTERIA; THERAPY; DISINFECTION; TEETH; MICROORGANISMS; PENETRATION; LASER AB We investigated the photodynamic effects of methylene blue on multispecies root canal biofilms comprising Actinomyces israelii, Fusobacterium nucleatum subspecies nucleatum, Porphyromonas gingivalis, and Prevotella intermedia in experimentally infected root canals of extracted human teeth in vitro. The 4 test microorganisms were detected in root canals by using DNA probes. Scanning electron microscopy showed the presence of biofilms in root canals before therapy. Root canal systems were incubated with methylene blue (25 mu g/mL) for 10 minutes followed by exposure to red light at 665 nm with an energy fluence of 30 J/cm(2). Light was delivered from a diode laser via a 250-mu m diameter polymethyl methacrylate optical fiber that uniformly distributed light over 360 degrees. Photodynamic therapy (PDT) achieved Lip to 80% reduction of colony-forming unit counts. We concluded that PDT can be an effective adjunct to standard endodontic antimicrobial treatment when the PDT parameters are optimized. C1 [Fontana, Carla Raquel; Foschi, Federico; Ruggiero, Karriann; Song, Xiaoqing; Soukos, Nikolaos S.] Forsyth Inst, Appl Mol Photomed Lab, Boston, MA 02115 USA. [Fimple, Jacob Lee; Pagonis, Tom C.] Harvard Univ, Sch Dent Med, Div Endodont, Boston, MA 02115 USA. [Tanner, Anne C. R.] Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Forsyth Inst, Dept Biostat, Boston, MA 02115 USA. [Stashenko, Philip P.] Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. [Doukas, Apostolos G.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Soukos, NS (reprint author), Forsyth Inst, Appl Mol Photomed Lab, 140 Fenway, Boston, MA 02115 USA. EM nsoukos@forsyth.org RI Foschi, Federico /E-7531-2012; Fontana, Carla/C-2033-2012; OI Fontana, Carla/0000-0002-9135-3690; Foschi, Federico/0000-0001-6901-0280 FU NIDCR NIH HHS [R01 DE016922-02, R01 DE016922, R01 DE016922-01A1, R01 DE016922-03, R01-DE-16922] NR 35 TC 84 Z9 90 U1 1 U2 9 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 JUN PY 2008 VL 34 IS 6 BP 728 EP 734 DI 10.1016/j.joen.2008.03.011 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 309IS UT WOS:000256454500021 PM 18498901 ER PT J AU Eatock, RA Xue, JB Kalluri, R AF Eatock, Ruth Anne Xue, Jingbing Kalluri, Radha TI Ion channels in mammalian vestibular afferents may set regularity of firing SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Review DE spike regularity; inter-spike interval; afterhyperpolarization; vestibular ganglion; inner ear; eighth nerve ID PERIPHERAL INNERVATION PATTERNS; INNER HAIR-CELLS; INTRINSIC MEMBRANE-PROPERTIES; HIPPOCAMPAL PYRAMIDAL CELLS; VENTRAL COCHLEAR NUCLEUS; SPIRAL GANGLION NEURONS; DEVELOPMENTAL-CHANGES; SEMICIRCULAR CANALS; POTASSIUM CURRENTS; CALCIUM CURRENTS AB Rodent vestibular afferent neurons offer several advantages as a model system for investigating the significance and origins of regularity in neuronal firing interval. Their regularity has a bimodal distribution that defines regular and irregular afferent classes. Factors likely to be involved in setting firing regularity include the morphology and physiology of the afferents' contacts with hair cells, which may influence the averaging of synaptic noise and the afferents' intrinsic electrical properties. In vitro patch clamp studies on the cell bodies of primary vestibular afferents reveal a rich diversity of ion channels, with indications of at least two neuronal populations. Here we suggest that firing patterns of isolated vestibular ganglion somata reflect intrinsic ion channel properties, which in vivo combine with hair cell synaptic drive to produce regular and irregular firing. C1 [Eatock, Ruth Anne; Xue, Jingbing; Kalluri, Radha] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Eatock, Ruth Anne; Xue, Jingbing; Kalluri, Radha] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Eatock, RA (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM eatock@meei.harvard.edu RI Eatock, Ruth/F-6404-2013; OI Eatock, Ruth Anne/0000-0001-7547-2051 FU NIDCD NIH HHS [R01 DC002290-06, R01 DC002290-08, R01 DC002290, R01 DC002290-07] NR 90 TC 26 Z9 26 U1 3 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD JUN 1 PY 2008 VL 211 IS 11 BP 1764 EP 1774 DI 10.1242/jeb.017350 PG 11 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 303VO UT WOS:000256069200016 PM 18490392 ER PT J AU Speliotes, EK Massaro, JM Hoffmann, U Foster, MC Sahani, DV Hirschhorn, JN O'Donnell, CJ Fox, CS AF Speliotes, Elizabeth K. Massaro, Joseph M. Hoffmann, Udo Foster, Meredith C. Sahani, Dushyant V. Hirschhorn, Joel N. O'Donnell, Christopher J. Fox, Caroline S. TI Liver fat is reproducibly measured using computed tomography in the Framingham Heart Study SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE computed tomography scan; fatty liver; measurement; metabolic syndrome; reproducibility AB Background and Aims: Fatty liver is the hepatic manifestation of obesity, but community-based assessment of fatty liver among unselected patients is limited. We sought to determine the feasibility of and optimal protocol for quantifying fat content in the liver in the Framingham Heart Study using multidetector computed tomography (MDCT) scanning. Methods: Participants (n = 100, 49% women, mean age 59.4 years, mean body mass index 27.8 kg/m(2)) were drawn from the Framingham Heart Study cohort. Two readers measured the attenuation of the liver, spleen, paraspinal muscles, and an external standard from MDCT scans using multiple slices in chest and abdominal scans. Results: The mean measurement variation was larger within a single axial computed tomography (CT) slice than between multiple axial CT slices for the liver and spleen, whereas it was similar for the paraspinal muscles. Measurement variation in the liver, spleen, and paraspinal muscles was smaller in the abdomen than in the chest. Three versus six measures of attenuation in the liver and two versus three measures in the spleen gave reproducible measurements of tissue attenuation (intraclass correlation coefficient [ICCC] of 1 in the abdomen). Intrareader and interreader reproducibility (ICCC) of the liver-to-spleen ratio was 0.98 and 0.99, the liver-to-phantom ratio was 0.99 and 0.99, and the liver-to-muscle ratio was 0.93 and 0.86, respectively. Conclusion: One cross-sectional slice is adequate to capture the majority of variance of fat content in the liver per individual. Abdominal scan measures as compared to chest scan measures of fat content in the liver are more precise. The measurement of fat content in the liver on MDCT scans is feasible and reproducible. C1 [Speliotes, Elizabeth K.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Hoffmann, Udo; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Massaro, Joseph M.] Boston Univ, Dept Stat, Boston, MA 02215 USA. [Hirschhorn, Joel N.] Childrens Hosp, Dept Endocrinol & Genet, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol, Boston, MA 02115 USA. [Speliotes, Elizabeth K.; Hirschhorn, Joel N.] Broad Inst Harvard, Dept Med & Populat Genet, Cambridge, MA USA. [Speliotes, Elizabeth K.; Hirschhorn, Joel N.] MIT, Cambridge, MA 02139 USA. [Foster, Meredith C.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Speliotes, EK (reprint author), Massachusetts Gen Hosp, Dept Gastroenterol, 15 Fruit St, Boston, MA 02114 USA. EM espeliotes@partners.org; foxca@nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812 FU NHLBI NIH HHS [N01 HC025195, N01-HC25195, N01HC25195]; NIDDK NIH HHS [F32 DK079466-01, F32 DK079466, K23 DK080145, K23 DK080145-01, K23DK080145-01, T32 DK007191, T32 DK007191-32, T32 DK07191-32] NR 8 TC 53 Z9 54 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD JUN PY 2008 VL 23 IS 6 BP 894 EP 899 DI 10.1111/j.1440-1746.2008.05420.x PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 310OY UT WOS:000256540200014 PM 18565021 ER PT J AU Kelly, MM Vogt, DS Scheiderer, EM Ouimette, P Daley, J Wolfe, J AF Kelly, Megan M. Vogt, Dawne S. Scheiderer, Emily M. Ouimette, Paige Daley, Jennifer Wolfe, Jessica TI Effects of military trauma exposure on women veterans' use and perceptions of veterans health administration care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE women's health; sexual assault; combat exposure; veterans; access to care ID SEXUAL ASSAULT HISTORY; MENTAL-HEALTH; FEMALE VETERANS; PATIENT SATISFACTION; SERVICE; OUTPATIENTS; VICTIMIZATION; AFGHANISTAN; POPULATION; PREVALENCE AB BACKGROUND: Few studies have addressed how military trauma exposure, particularly sexual assault and combat exposure, affects women veterans' use and perceptions of Veterans Health Administration (VHA) care. OBJECTIVE: The aim of the present study was to evaluate the effects of military sexual assault and combat exposure on women veterans' use and perceptions of different aspects of VHA care. DESIGN: Cross-sectional telephone survey of a national sample of women veterans. PARTICIPANTS: Women from the VA's National Registry of Women Veterans. MEASUREMENTS: Sociodemographic characteristics, VHA care utilization, perceptions of care. RESULTS: Women veterans with histories of military sexual assault reported more use of VHA services, but less satisfaction, poorer perceptions of VHA facilities and staff, and more problems with VHA services compared to women veterans without histories of sexual assault. Combat exposure was related to more problems with VHA staff, although few other differences were observed for women with and without histories of combat exposure. CONCLUSIONS: Findings provide information on areas that can be targeted with respect to caring for women veterans exposed to military sexual trauma and combat exposure, including improving interactions with VHA staff and the ease of using VHA services. C1 [Kelly, Megan M.] Butler Hosp, Providence, RI 02906 USA. [Kelly, Megan M.; Vogt, Dawne S.; Scheiderer, Emily M.] Natl Ctr PTSD VA Boston Healthcare Syst, Womens Hlth Sci Div, Boston, MA USA. [Vogt, Dawne S.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Ouimette, Paige] Syracuse VA Med Ctr, VA Ctr Integrated Healthcare, Syracuse, NY USA. [Daley, Jennifer] Tenet Healthcare, Dallas, TX USA. [Daley, Jennifer] Dartmouth Med Sch, Hanover, NH USA. [Wolfe, Jessica] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kelly, MM (reprint author), Butler Hosp, 345 Blackstone Blvd, Providence, RI 02906 USA. EM mkelly@butler.org NR 38 TC 24 Z9 24 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2008 VL 23 IS 6 BP 741 EP 747 DI 10.1007/s11606-008-0589-x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 303FX UT WOS:000256027500006 PM 18414956 ER PT J AU Frank, D DeBenedetti, AF Volk, RJ Williams, EC Kivlahan, DR Bradley, KA AF Frank, Danielle DeBenedetti, Anna F. Volk, Robert J. Williams, Emily C. Kivlahan, Daniel R. Bradley, Katharine A. TI Effectiveness of the AUDIT-C as a screening test for alcohol misuse in three race/ethnic groups SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE alcohol; alcohol misuse; race; ethnicity; screening; diagnostic test ID IDENTIFICATION TEST AUDIT; PRIMARY-CARE PATIENTS; BEHAVIORAL-COUNSELING INTERVENTIONS; RANDOMIZED CONTROLLED TRIAL; US GENERAL-POPULATION; AT-RISK DRINKING; USE DISORDERS; EMERGENCY-ROOM; CONSUMPTION QUESTIONS; UNITED-STATES AB BACKGROUND: The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) is a brief validated screen for risky drinking and alcohol abuse and dependence (alcohol misuse). However, the AUDIT-C was validated in predominantly White populations, and its performance in different racial/ethnic groups is unclear. OBJECTIVE: To evaluate the validity of the AUDIT-C among primary care patients from the predominant racial/ethnic subgroups within the United States: White, African American, and Hispanic. DESIGN: Cross-sectional interview validation study. PARTICIPANTS: 1,292 outpatients from an academic family practice clinic in Texas (90% of randomly sampled eligible). MEASUREMENTS AND MAIN RESULTS: Race/ethnicity was self-reported. Areas under the receiver operating curve (AuROCs) evaluated overall AUDIT-C performance in the 3 racial/ethnic groups compared to diagnostic interviews for alcohol misuse. AUDIT-C sensitivities and specificities at recommended screening thresholds were compared across racial/ethnic groups. AuROCs were greater than 0.85 in all 3 groups, with no significant differences across racial/ethnic groups in men (P=.43) or women (P=.12). At previously recommended cut points, there were statistically significant differences by race in AUDIT-C sensitivities but not specificities. In women, the sensitivity was higher in Hispanic (85%) than in African-American (67%; P=.03) or White (70%; P=.04) women. In men, the sensitivity was higher in White (95%) than in African-American men (76%; P=.01), with no significant difference from Hispanic men (85%; P=.11). CONCLUSIONS: The overall performance of the AUDIT-C was excellent in all 3 racial/ethnic groups as reflected by high AuROCs. At recommended cut points, there were significant differences in the AUDIT-C's sensitivity but not in specificity across the 3 racial/ethnic groups. C1 [Frank, Danielle; DeBenedetti, Anna F.; Williams, Emily C.; Kivlahan, Daniel R.; Bradley, Katharine A.] VA Puget Sound Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Williams, Emily C.; Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Williams, Emily C.; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Kivlahan, Daniel R.] Univ Washington, Dept Psychiat & Biobehav Sci, Seattle, WA 98195 USA. [Volk, Robert J.] Baylor Coll Med, Dept Family & Community Med, Houston, TX 77030 USA. [Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Frank, D (reprint author), VA Puget Sound Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM diegop@u.washington.edu OI Volk, Robert/0000-0001-8811-5854 FU NIAAA NIH HHS [R21 AA014672, R21AA14672] NR 42 TC 84 Z9 85 U1 1 U2 2 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 JUN PY 2008 VL 23 IS 6 BP 781 EP 787 DI 10.1007/s11606-008-0594-0 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 303FX UT WOS:000256027500012 PM 18421511 ER PT J AU Fung, CH Setodji, CM Kung, FY Keesey, J Asch, SM Adams, J McGlynn, EA AF Fung, Constance H. Setodji, Claude M. Kung, Fuan-Yue Keesey, Joan Asch, Steven M. Adams, John McGlynn, Elizabeth A. TI The relationship between multimorbidity and patients' ratings of communication SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE multimorbidity; pay-for-performance; patient-physician communication ID QUALITY-OF-CARE; NEW-YORK-STATE; HEALTH-CARE; PERFORMANCE; COMORBIDITY; PREFERENCES; PREVALENCE; PHYSICIANS; OUTCOMES; ADULTS AB BACKGROUND: The growing interest in pay-for-performance and other quality improvement programs has generated concerns about potential performance measurement penalties for providers who care for more complex patients, such as patients with more chronic conditions. Few data are available on how multimorbidity affects common performance metrics. OBJECTIVE: To examine the relationship between multimorbidity and patients' ratings of communication, a common performance metric. DESIGN: Cross-sectional study SETTING: Nationally representative sample of U.S. residents PARTICIPANTS: A total of 15,709 noninstitutionalized adults living in the United States participated in a telephone interview. MEASUREMENTS: We used 2 different measures of multimorbidity: 1) "individual conditions" approach disregards similarities/concordance among chronic conditions and 2) "condition-groups" approach considers similarities/concordance among conditions. We used a composite measure of patients' ratings of patient-physician communication. RESULTS: A higher number of individual conditions is associated with lower ratings of communication, although the magnitude of the relationship is small (adjusted average communication scores: 0 conditions, 12.20; 1-2 conditions, 12.06; 3+ conditions, 11.90; scale range 5 = worst, 15 = best). This relationship remains statistically significant when concordant relationships among conditions are considered (0 condition groups 12.19; 1-2 condition groups 12.03; 3+ condition groups 11.94). CONCLUSIONS: In our nationally representative sample, patients with more chronic conditions gave their doctors modestly lower patient-doctor communication scores than their healthier counterparts. Accounting for concordance among conditions does not widen the difference in communication scores. Concerns about performance measurement penalty related to patient complexity cannot be entirely addressed by adjusting for multimorbidity. Future studies should focus on other aspects of clinical complexity (e.g., severity, specific combinations of conditions). C1 [Fung, Constance H.] Zynx Hlth Inc, Los Angeles, CA USA. [Setodji, Claude M.; Kung, Fuan-Yue; Keesey, Joan; Asch, Steven M.; Adams, John; McGlynn, Elizabeth A.] RAND Corp, Santa Monica, CA USA. [Asch, Steven M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Fung, CH (reprint author), 10880 Wilshire Blvd,Suite 300, Los Angeles, CA 90024 USA. EM cfung@zynx.com NR 47 TC 25 Z9 25 U1 1 U2 2 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 JUN PY 2008 VL 23 IS 6 BP 788 EP 793 DI 10.1007/s11606-008-0602-4 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 303FX UT WOS:000256027500013 PM 18427902 ER PT J AU Anaya, HD Hoang, TY Golden, JF Goetz, MB Gifford, A Bowman, C Osborn, T Owens, DK Sanders, GD Asch, SM AF Anaya, Henry D. Hoang, Tuyen Golden, Joya F. Goetz, Matthew Bidwell Gifford, Allen Bowman, Candice Osborn, Teresa Owens, Douglas K. Sanders, Gillian D. Asch, Steven M. TI Improving HIV screening and receipt of results by nurse-initiated streamlined counseling and rapid testing SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE nurse-initiated HIV screening; HIV rapid testing; streamlined counseling ID RANDOMIZED CONTROLLED-TRIAL; EMERGENCY-DEPARTMENT; PRIMARY-CARE; RISK; PREFERENCES; PREVENTION; PHYSICIANS; EFFICACY; BARRIERS; DISEASE AB BACKGROUND: HIV testing is cost-effective in unselected general medical populations, yet testing rates among those at risk remain low, even among those with regular primary care. HIV rapid testing is effective in many healthcare settings, but scant research has been done within primary care settings or within the US Department of Veteran's Affairs Healthcare System. OBJECTIVES: We evaluated three methods proven effective in other diseases/settings: nurse standing orders for testing, streamlined counseling, and HIV rapid testing. DESIGN: Randomized, controlled trial with three intervention models: model A (traditional counseling/testing); model B (nurse-initiated screening, traditional counseling/testing); model C (nurse-initiated screening, streamlined counseling/rapid testing). PARTICIPANTS: Two hundred fifty-one patients with primary/urgent care appointments in two VA clinics in the same city (one large urban hospital, one freestanding outpatient clinic in a high HIV prevalence area). MEASUREMENTS: Rates of HIV testing and receipt of results; sexual risk reduction; HIV knowledge improvement. RESULTS: Testing rates were 40.2% (model A), 84.5% (model B), and 89.3% (model C; p=<.01). Test result receipt rates were 14.6% (model A), 31.0% (model B), 79.8% (model C; all p=<.01). Sexual risk reduction and knowledge improvement did not differ significantly between counseling methods. CONCLUSIONS: Streamlined counseling with rapid testing significantly increased testing and receipt rates over current practice without changes in risk behavior or posttest knowledge. Increased testing and receipt of results could lead to earlier disease identification, increased treatment, and reduced morbidity/mortality. Policymakers should consider streamlined counseling/rapid testing when implementing routine HIV testing into primary/urgent care. C1 [Anaya, Henry D.; Hoang, Tuyen; Golden, Joya F.; Goetz, Matthew Bidwell; Gifford, Allen; Bowman, Candice; Asch, Steven M.] VA Greater Los Angeles Healthcare Syst, VA Qual Enhancement Res Initiat HIV & Hepatitis Q, Los Angeles, CA 90073 USA. [Anaya, Henry D.; Hoang, Tuyen; Golden, Joya F.; Goetz, Matthew Bidwell; Gifford, Allen; Bowman, Candice; Asch, Steven M.] VA Greater Los Angeles Healthcare Syst, VA Greater Los Angeles Hlth Serv Res & Dev HSRD C, Ctr Study Healthcare Provider Behav, Los Angeles, CA 90073 USA. [Bowman, Candice] VA San Diego Healthcare Syst, Ctr Res Patient Oriented Care, La Jolla, CA USA. [Asch, Steven M.] Univ Calif Los Angeles, Sch Med, Div Gen Internal Med & Hlth, Serv Res GIM & HSR, Los Angeles, CA USA. [Asch, Steven M.] RAND Hlth, Santa Monica, CA USA. [Gifford, Allen] VA New England Healthcare Syst, Bedford, England. [Osborn, Teresa] VA VISN22, Long Beach, CA USA. [Owens, Douglas K.] VA Palo Alto Healthcare Syst, Palo Alto, CA USA. [Owens, Douglas K.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Sanders, Gillian D.] Duke Univ, Sch Med, Durham, NC USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Goetz, Matthew Bidwell] VA Greater Los Angeles Healthcare Syst, Dept Med, Infect Dis Sect, Los Angeles, CA USA. RP Anaya, HD (reprint author), VA Greater Los Angeles Healthcare Syst, VA Qual Enhancement Res Initiat HIV & Hepatitis Q, 11301 Wilshire Blvd 111G, Los Angeles, CA 90073 USA. EM henry.anaya@va.gov OI Goetz, Matthew/0000-0003-4542-992X NR 39 TC 52 Z9 53 U1 1 U2 5 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 JUN PY 2008 VL 23 IS 6 BP 800 EP 807 DI 10.1007/s11606-008-0617-x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 303FX UT WOS:000256027500015 PM 18421508 ER PT J AU Green, AR Peters-Lewis, A Percac-Lima, S Betancourt, JR Richter, JM Janairo, MPR Gamba, GB Atlas, SJ AF Green, Alexander R. Peters-Lewis, Angelleen Percac-Lima, Sanja Betancourt, Joseph R. Richter, James M. Janairo, Maria-Pamela R. Gamba, Gloria B. Atlas, Steven J. TI Barriers to screening colonoscopy for low-income latino and white patients in an urban community health center SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE colon cancer; screening; colonoscopy; Latino; barriers; patient navigation; cultural competency; qualitative ID COLORECTAL-CANCER; AFRICAN-AMERICANS; KNOWLEDGE; PERCEPTIONS; INTERVENTION; POPULATION; BELIEFS; CARE; PREDICTORS; NAVIGATOR AB BACKGROUND: Colonoscopy is a screening modality for the early detection of colonic polyps and cancers but is underutilized, particularly among minorities. OBJECTIVE: To identify potential barriers to screening colonoscopy among low income Latino and white non-Latino patients in an urban community health center. DESIGN, PARTICIPANTS, AND APPROACH: We conducted semistructured interviews with a convenience sample of patients 53 to 70 years old, eligible for colorectal cancer screening that spoke English or Spanish. Open-ended questions explored knowledge, beliefs, and experience with or reasons for not having screening colonoscopy. We performed content analysis of transcripts using established qualitative techniques. RESULTS: Of 40 participants recruited, 57% were women, 55% Latino, 20% had private health insurance, and 40% had a prior colonoscopy. Participants described a wide range of barriers categorized into 5 major themes: (1) System barriers including scheduling, financial, transportation, and language difficulties; (2) Fear of pain or complications of colonoscopy and fear of diagnosis (cancer); (3) Lack of desire or motivation, including "laziness" and "procrastination"; (4) Dissuasion by others influencing participants' decision regarding colonoscopy; and (5) Lack of provider recommendation including not hearing about colonoscopy or not understanding the preparation instructions. CONCLUSIONS: Understanding of the range of barriers to colorectal cancer screening can help develop multimodal interventions to increase colonoscopy rates for all patients including low-income Latinos. Interventions including systems improvements and navigator programs could address barriers by assisting patients with scheduling, insurance issues, and transportation and providing interpretation, education, emotional support, and motivational interviewing. C1 [Green, Alexander R.; Peters-Lewis, Angelleen; Percac-Lima, Sanja; Betancourt, Joseph R.; Janairo, Maria-Pamela R.; Atlas, Steven J.] Massachusetts Gen Hosp, Inst Hlth Policy, Dispar Solut Ctr, Boston, MA 02114 USA. [Peters-Lewis, Angelleen; Richter, James M.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Richter, James M.; Atlas, Steven J.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Percac-Lima, Sanja; Gamba, Gloria B.] Massachusetts Gen Hosp, Chelsea Hlth Ctr, Boston, MA 02114 USA. RP Green, AR (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Dispar Solut Ctr, 50 Stanford St, Suite 901, Boston, MA 02114 USA. EM argreen@partners.org NR 47 TC 77 Z9 78 U1 0 U2 4 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 JUN PY 2008 VL 23 IS 6 BP 834 EP 840 DI 10.1007/s11606-008-0572-6 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 303FX UT WOS:000256027500021 PM 18350339 ER PT J AU Bent, S AF Bent, Stephen TI Herbal medicine in the United States: Review of efficacy, safety, and regulation - Grand rounds at University of California, San Francisco Medical Center SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE herbal medicine; efficacy; safety; regulation ID RANDOMIZED CLINICAL-TRIALS; ST-JOHNS-WORT; GINKGO-BILOBA; WEIGHT-LOSS; ECHINACEA-ANGUSTIFOLIA; RHINOVIRUS INFECTIONS; DIETARY-SUPPLEMENTS; CITRUS-AURANTIUM; METAANALYSIS; PRODUCTS AB INTRODUCTION: Herbal products have gained increasing popularity in the last decade, and are now used by approximately 20% of the population. Herbal products are complex mixtures of organic chemicals that may come from any raw or processed part of a plant, including leaves, stems, flowers, roots, and seeds. Under the current law, herbs are defined as dietary supplements, and manufacturers can therefore produce, sell, and market herbs without first demonstrating safety and efficacy, as is required for pharmaceutical drugs. Although herbs are often perceived as "natural" and therefore safe, many different side effects have been reported owing to active ingredients, contaminants, or interactions with drugs. RESULTS: Unfortunately, there is limited scientific evidence to establish the safety and efficacy of most herbal products. Of the top 10 herbs, 5 (ginkgo, garlic, St. John's wort, soy, and kava) have scientific evidence suggesting efficacy, but concerns over safety and a consideration of other medical therapies may temper the decision to use these products. CONCLUSIONS: Herbal products are not likely to become an important alternative to standard medical therapies unless there are changes to the regulation, standardization, and funding for research of these products. C1 San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Bent, Stephen] Univ Calif San Francisco, Osher Ctr Intergrat Med, San Francisco, CA 94143 USA. [Bent, Stephen] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Bent, Stephen] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. RP Bent, S (reprint author), San Francisco VA Med Ctr, 111-A1,4150 Clement St, San Francisco, CA 94121 USA. EM Stephen.Bent@ucsf.edu FU NCCIH NIH HHS [K08 AT001338]; PHS HHS [1 K08 ATO1338-01] NR 57 TC 166 Z9 172 U1 12 U2 27 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 JUN PY 2008 VL 23 IS 6 BP 854 EP 859 DI 10.1007/s11606-008-0632-y PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 303FX UT WOS:000256027500024 PM 18415652 ER PT J AU Whittle, J Good, CB AF Whittle, Jeff Good, Chester B. TI Prescription drug samples: Making decisions with imperfect data SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID COSTS C1 [Whittle, Jeff] Clement J Zablocki VA Med Ctr, Milwaukee, WI 53295 USA. [Whittle, Jeff] Med Coll Wisconsin, Dept Med, Div Gen Internal Med, Milwaukee, WI 53226 USA. [Good, Chester B.] VA Pittsburgh Healthcare Syst, Gen Internal Med Sect, Pittsburgh, PA USA. [Good, Chester B.] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Good, Chester B.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Whittle, J (reprint author), Clement J Zablocki VA Med Ctr, Mailstop 00 PC,5000 W Natl Ave, Milwaukee, WI 53295 USA. EM jeffrey.whittle@va.gov NR 13 TC 3 Z9 3 U1 0 U2 1 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 JUN PY 2008 VL 23 IS 6 BP 890 EP 892 DI 10.1007/s11606-008-0642-9 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 303FX UT WOS:000256027500031 PM 18461406 ER PT J AU Oehlberg, K Barg, FK Brown, GK Taraborelli, D Stern, MB Weintraub, D AF Oehlberg, Katherine Barg, Frances K. Brown, Gregory K. Taraborelli, Donna Stern, Matthew B. Weintraub, Daniel TI Attitudes regarding the etiology and treatment of depression in Parkinson's disease: A qualitative study SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE Parkinson's disease; depression; antidepressant; psychotherapy; qualitative interview ID ANTIDEPRESSANT; PREDICTORS; SYMPTOMS; LIFE AB Depression in Parkinson's disease (dPD) remains under recognized and under treated. As patients' beliefs may impact the reporting and treatment of depression, this study assessed the opinions of 38 dPD patients, approximately half with a self-reported poor response to antidepressant treatment, regarding the etiology and treatment of their depression using a semi-structured, audio-taped, qualitative interview. About half of the participants listed PD itself as a primary cause for their depressive symptoms, with most in this group citing psychosocial factors rather than PD-related neurobiological factors. Antidepressant therapy, psychotherapy, and self-initiated approaches were noted as preferred treatments for dPD. Many had concerns about antidepressant therapy, listing side-effects and medication dependency most frequently. About half raised concerns about psychotherapy with trust/discomfort, stigma, and transportation issues most frequently mentioned. This preliminary study suggests that many PD patients with clinically significant depressive symptoms attribute their depression to psychosocial factors and endorse nonpharmacologic treatment approaches. C1 [Oehlberg, Katherine; Brown, Gregory K.; Taraborelli, Donna; Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Barg, Frances K.] Univ Penn, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Barg, Frances K.] Univ Penn, Sch Arts & Sci, Dept Anthropol, Philadelphia, PA 19104 USA. [Stern, Matthew B.; Weintraub, Daniel] Philadelphia VA Med Ctr, PADRECC, Philadelphia, PA USA. [Weintraub, Daniel] Philadelphia VA Med Ctr, MIRECC, Philadelphia, PA USA. RP Weintraub, D (reprint author), Univ Penn, Sect Geriatr Psychiat, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu FU NIMH NIH HHS [K23 MH067894, K23 MH067894-01A1, K23 MH067894-05, K23MH067894] NR 20 TC 22 Z9 22 U1 0 U2 5 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 JUN PY 2008 VL 21 IS 2 BP 123 EP 132 DI 10.1177/0891988708316862 PG 10 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 303YS UT WOS:000256077800005 PM 18474721 ER PT J AU Spira, AP Friedman, L Aulakh, JS Lee, T Sheikh, JI Yesavage, JA AF Spira, Adam P. Friedman, Leah Aulakh, Jasdeep S. Lee, Tina Sheikh, Javaid I. Yesavage, Jerome A. TI Subclinical anxiety symptoms, sleep, and daytime dysfunction in older adults with primary insomnia SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE anxiety; depression; insomnia; actigraphy ID DSM-IV; PREVALENCE; DISORDERS AB Both insomnia complaints and anxiety disorders are common in older adults, and are associated with poor daytime functioning. The present study investigated whether subclinical levels of anxiety were associated with sleep disturbance and daytime functioning in older adults who met diagnostic criteria for primary insomnia, and therefore did not meet criteria for depression or an anxiety disorder. After adjustment for depressive symptoms, elevated state anxiety was associated with higher levels of wake after sleep onset (measured by both actigraphy and sleep log) and shorter sleep onset latency (measured by sleep log). Higher levels of trait anxiety were associated with greater wake after sleep onset (measured by sleep log). Elevated state and trait anxiety were associated with worse social functioning, and higher levels of trait anxiety were associated with worse role functioning. Thus, subclinical anxiety symptoms may be an important target for clinical intervention to improve sleep and functioning in older adults with primary insomnia. C1 [Spira, Adam P.] Univ Calif San Francisco, Div Geriatr, Dept Med, San Francisco, CA 94143 USA. [Spira, Adam P.] San Francisco VA Med Ctr, San Francisco, CA USA. [Friedman, Leah; Aulakh, Jasdeep S.; Sheikh, Javaid I.; Yesavage, Jerome A.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Aulakh, Jasdeep S.; Lee, Tina; Sheikh, Javaid I.; Yesavage, Jerome A.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. RP Spira, AP (reprint author), 4150 Clement St,181-G, San Francisco, CA USA. EM adam.spira@ucsf.edu FU NIA NIH HHS [AG 12914] NR 19 TC 12 Z9 13 U1 0 U2 2 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 JUN PY 2008 VL 21 IS 2 BP 149 EP 153 DI 10.1177/0891988707317120 PG 5 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 303YS UT WOS:000256077800008 PM 18474724 ER PT J AU Slade, JF Lozano-Calderon, S Merrell, G Ring, D AF Slade, J. F. Lozano-Calderon, S. Merrell, G. Ring, D. TI Arthroscopic-assisted percutaneous reduction and screw fixation of displaced scaphoid fractures SO JOURNAL OF HAND SURGERY-EUROPEAN VOLUME LA English DT Article DE displaced scaphoid fracture; wrist arthroscopy; percutaneous screw fixation ID CAST IMMOBILIZATION; INTERNAL-FIXATION; NATURAL-HISTORY; HERBERT SCREW; WAIST; RADIOGRAPHY; WRIST; THUMB AB Many scaphoid fractures can be treated with percutaneous screw insertion, but fracture displacement usually necessitates open reduction. Two surgeons treated 20 consecutive patients with displaced fractures of the scaphoid using arthroscopic-assisted percutaneous screw fixation. Thirteen patients had dorsal (antegrade) and seven had palmar (retrograde) percutaneous screw insertion. At an average follow-up of 18 (range 6-48) months, all of the fractures were healed and there were no implant problems. The early results of arthroscopic-assisted percutaneous screw fixation of displaced fractures of the scaphoid suggest that union can be obtained and good to excellent function achieved predictably without the need for open exposure. Avoidance of an open exposure limits wrist ligament injury and may preserve blood supply. Further evaluation of this procedure is merited. C1 [Ring, D.] Massachusetts Gen Hosp, Yawkey Ctr, Boston, MA 02114 USA. Yale Univ, Med Ctr, New Haven, CT USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 25 TC 7 Z9 8 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1753-1934 J9 J HAND SURG-EUR VOL JI J. Hand Surg.-Eur. Vol. PD JUN PY 2008 VL 33E IS 3 BP 350 EP 354 DI 10.1177/1753193408090121 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 328QF UT WOS:000257812200020 PM 18562371 ER PT J AU Kaplan, DE Ikeda, F Li, Y Nakamoto, N Ganesan, S Valiga, ME Nunes, FA Reddy, KR Chang, KM AF Kaplan, David E. Ikeda, Fusao Li, Yun Nakamoto, Nobuhiro Ganesan, Sutharsan Valiga, Mary E. Nunes, Frederick A. Reddy, K. Rajender Chang, Kyong-Mi TI Peripheral virus-specific T-cell interleukin-10 responses develop early in acute hepatitis C infection and become dominant in chronic hepatitis SO JOURNAL OF HEPATOLOGY LA English DT Article DE hepatitis C; interleukin-10; interferon-gamma; regulatory T-cells; CD8(+) T-cells; IL-10; HCV ID INTERFERON-ALPHA; IL-10 PRODUCTION; DENDRITIC CELLS; RIBAVIRIN TREATMENT; IMMUNE-RESPONSES; VIRAL CLEARANCE; IFN-ALPHA; IN-VIVO; CD4(+); LYMPHOCYTES AB Background/Aims: Interleukin-10 (IL-10) has been ascribed pro-viral but anti-fibrotic properties in chronic hepatitis C virus (HCV) infection. In this study, we examined the role of HCV-specific T-cell IL-10 response in patients with acute and chronic HCV infection. Methods: Peripheral HCV-specific T-cell IL-10 and IFN gamma responses were measured in cytokine Elispot assay using overlapping HCV-derived peptides in patients with chronic (n = 61), resolved (n = 15) and acute (n = 8) hepatitis C, looking for their onset, quantity, breadth and durability relative to clinical and virological outcomes. The source and effect of HCV-specific IL-10 response were determined in depletion and IL-10 neutralization experiments. Results: Both HCV-specific IL-10 and IFN gamma responses were detected early within 1-2 months of acute clinical hepatitis C. However, only HCV-specific IL-10 response correlated with elevated liver enzymes, increased viremia and suppressed HCV-specific CD4(+) T-cell proliferation in acute infection. While these associations were lost in established chronic infection, HCV-specific IL-10 responses were increased in patients without cirrhosis while IL-10 blockade enhanced antiviral effector IFN gamma responses. Conclusions:HCV-specific IL-10 Tr1 responses may play a dual role in HCV infection, dampening effector T-cells to promote viral persistence in acute infection but also protecting against progressive fibrosis in chronic infection. (c) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Kaplan, David E.; Chang, Kyong-Mi] Philadelphia VA Med Ctr, Res Sect, Philadelphia, PA 19104 USA. [Kaplan, David E.; Ikeda, Fusao; Li, Yun; Nakamoto, Nobuhiro; Ganesan, Sutharsan; Valiga, Mary E.; Reddy, K. Rajender; Chang, Kyong-Mi] Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Nunes, Frederick A.] Penn Hosp, Philadelphia, PA 19106 USA. RP Kaplan, DE (reprint author), Philadelphia VA Med Ctr, Res Sect, Res A216,Woodland Ave, Philadelphia, PA 19104 USA. EM dakaplan@mail.med.upenn.edu OI Kaplan, David E./0000-0002-3839-336X FU NCRR NIH HHS [K12 RR017625, K12 RR017625-01, K12-RR-017625, M01 RR000040, M01-RR00040]; NIAAA NIH HHS [R01 AA012849, R01 AA012849-01, R01 AA012849-02, R01 AA012849-03, R01 AA012849-04, R01 AA012849-05, R01-AA-12849]; NIAID NIH HHS [R01 AI047519, R01 AI047519-01, R01 AI047519-02, R01 AI047519-03, R01 AI047519-04, R01 AI047519-05, R01 AI047519-06, R01 AI047519-07, R01 AI047519-08, R01 AI047519-09, R01 AI047519-10, R01-AI-47519]; NIDDK NIH HHS [P30DK50306, L30 DK069063, L30 DK069063-01, P30 DK050306, P30 DK050306-06, T32 DK 07066, T32 DK007066, T32 DK007066-25] NR 61 TC 55 Z9 56 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD JUN PY 2008 VL 48 IS 6 BP 903 EP 913 DI 10.1016/j.jhep.2008.01.030 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 312PK UT WOS:000256683100004 PM 18384906 ER PT J AU Oberley, TD Swanlund, JM Zhang, HJ Kregel, KC AF Oberley, Terry D. Swanlund, Jamie M. Zhang, Hannah J. Kregel, Kevin C. TI Aging results in increased autophagy of mitochondria and protein nitration in rat hepatocytes following heat stress SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE mitochondria; 3-nitrotyrosine; autophagy; heat stress; oxidative stress ID OXIDATIVE STRESS; NITRIC-OXIDE; TYROSINE NITRATION; SHOCK PROTEINS; LIVER-INJURY; CELL-DEATH; EXPRESSION; OXIDANTS; DISEASES; DAMAGE AB The natural breakdown of cells, tissues, and organ systems is a significant consequence of aging and is at least partially caused by a decreased ability to tolerate environmental stressors. Based on quantitative ultrastructural analysis using transmission electron microscopy and computer imaging, we show significant differences in hepatocyte morphology between young and old rats during a 48-hr recovery period following a 2-day heat stress protocol. Mitochondrial injury was greater overall in old compared with young rats. Autophagy was observed in both young and old rats, with autophagy greater overall in old compared with young hepatocytes. Lipid peroxidation and protein nitration were evaluated by localization and quantification of 4-hydroxy-2-nonenal (4-HNE)-modified protein adducts and 3-nitrotyrosine (3-NT) levels, respectively. Levels of 3-NT but not 4-HNE-protein adducts were significantly elevated in hepatocytes of old rats in comparison with young at 90 min after heat stress, suggesting a major role for reactive nitrogen species in the pathology observed at this time point. These results show a differential response of hepatocyte mitochondria to heat stress with aging, as well as greater levels of both autophagic and nitrative damage in old vs young hepatocytes. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. C1 [Oberley, Terry D.; Swanlund, Jamie M.] William S Middleton Mem Vet Adm Med Ctr, Dept Pathol & Lab Med, Madison, WI 53705 USA. [Oberley, Terry D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI USA. [Zhang, Hannah J.; Kregel, Kevin C.] Univ Iowa, Dept Radiat Oncol, Radiat Biol Program, Iowa City, IA USA. [Zhang, Hannah J.; Kregel, Kevin C.] Univ Iowa, Dept Integrat Physiol & Free Rad, Iowa City, IA USA. RP Oberley, TD (reprint author), William S Middleton Mem Vet Adm Med Ctr, Dept Pathol & Lab Med, Room A-35,2500 Overlook Terrace, Madison, WI 53705 USA. EM toberley@wisc.edu; kevin-kregel@uiowa.edu FU NIA NIH HHS [AG012350, R01 AG012350] NR 51 TC 30 Z9 31 U1 0 U2 4 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JUN PY 2008 VL 56 IS 6 BP 615 EP 627 DI 10.1369/jhc.2008.950873 PG 13 WC Cell Biology SC Cell Biology GA 301IT UT WOS:000255890300010 PM 18379016 ER PT J AU Eggena, P AF Eggena, P. TI Is hepatic intracellular angiotensin II of physiological significance? SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Scientific Meeting of the European-Society-of-Hypertension/22nd Scientific Meeting of the International-Society-of-Hypertension CY JUN 14-19, 2008 CL Berlin, GERMANY SP Euorpean Soc Hyperten, Deutsch Hochdruckliga C1 [Eggena, P.] Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Hlth Care Syst, Sepulveda, 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 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JUN PY 2008 VL 26 SU 1 BP S511 EP S511 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 319WZ UT WOS:000257197003486 ER PT J AU Krum, H Curtis, SP Brater, DC Laine, L Kaur, A Wang, H Smugar, SS Swergold, G Cannon, CP AF Krum, H. Curtis, S. P. Brater, D. C. Laine, L. Kaur, A. Wang, H. Smugar, S. S. Swergold, G. Cannon, C. P. CA MEDAL Steering Comm TI Which baseline parameters influence risk of congestive heart failure in arthritis patients receiving NSAIDs & COX-2 inhibitors? Multivariate analysis of 34,701 patients in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) program SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Annual Meeting of the European-Society-of-Hypertension/22nd Scientific Meeting of the International-Society-of-Hypertension CY JUN 14-19, 2008 CL Berlin, GERMANY SP European Soc Hypertens, Deutsch Hochdruckliga, Int Soc Hypertens C1 [Krum, H.] Monash Univ, Alfred Hosp, NHMRC Ctr Clin Res Excellence Therapeut, Melbourne, Vic 3181, Australia. [Curtis, S. P.; Kaur, A.; Wang, H.; Smugar, S. S.; Swergold, G.] Merck Res Labs, Rahway, NJ USA. [Brater, D. C.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Laine, L.] Univ So Calif, Sch Med, Los Angeles, CA USA. [Cannon, C. P.] Brigham & Womens Hosp, TIMI Study Grp, 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 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JUN PY 2008 VL 26 SU 1 BP S480 EP S480 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 319WZ UT WOS:000257197003346 ER PT J AU Krum, H Curtis, SP Brater, DC Laine, L Weir, MR Kaur, A Wang, H Smugar, SS Cannon, CP AF Krum, H. Curtis, S. P. Brater, D. C. Laine, L. Weir, M. R. Kaur, A. Wang, H. Smugar, S. S. Cannon, C. P. CA MEDAL Steering Comm TI Background antihypertensive drug class influences blood pressure response to NSAIDs & COX-2 inhibitors: Multivariate analysis of the multinational etoricoxib and diclofenac arthritis long-term (MEDAL) study SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Scientific Meeting of the European-Society-of-Hypertension/22nd Scientific Meeting of the International-Society-of-Hypertension CY JUN 14-19, 2008 CL Berlin, GERMANY SP Euorpean Soc Hyperten, Deutsch Hochdruckliga C1 [Krum, H.] Monash Univ, Alfred Hosp, NHMRC Ctr Clin Res Excellence Therapeut, Melbourne, Australia. [Curtis, S. P.; Kaur, A.; Wang, H.; Smugar, S. S.] Merck Res Labs, Rahway, NJ USA. [Brater, D. C.] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. [Laine, L.] Univ So Calif, Sch Med, Los Angeles, CA USA. [Weir, M. R.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Cannon, C. P.] Harvard Univ, 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 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JUN PY 2008 VL 26 SU 1 BP S455 EP S455 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 319WZ UT WOS:000257197003235 ER PT J AU Krum, K Curtis, SP Brater, DC Laine, L Kaur, A Wang, H Smugar, SS Cannon, CP AF Krum, K. Curtis, S. P. Brater, D. C. Laine, L. Kaur, A. Wang, H. Smugar, S. S. Cannon, C. P. TI Which baseline parameters influence risk of blood pressure increases in arthritis patients receiving NSAIDs & COX-2 inhibitors? A multivariate analysis of 23,498 patients in the multinational etoricoxib and diclofenac arthritis long-term (MEDAL) study SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Scientific Meeting of the European-Society-of-Hypertension/22nd Scientific Meeting of the International-Society-of-Hypertension CY JUN 14-19, 2008 CL Berlin, GERMANY SP Euorpean Soc Hyperten, Deutsch Hochdruckliga C1 [Krum, K.] Monash Univ, Alfred Hosp, NHMRC, Ctr Clin Res Excellence Therapeut, Melbourne, Vic 3181, Australia. [Curtis, S. P.; Kaur, A.; Wang, H.; Smugar, S. S.] Merck Res Labs, Rahway, NJ USA. [Brater, D. C.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Laine, L.] Univ So Calif, Sch Med, Los Angeles, CA USA. [Cannon, C. P.] Brigham & Womens Hosp, TIMI Study Grp, 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 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JUN PY 2008 VL 26 SU 1 BP S468 EP S468 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 319WZ UT WOS:000257197003294 ER PT J AU Nyby, M Abedi, K Smutko, V Ibrahim, E Wijesuriya, J Tuck, M AF Nyby, M. Abedi, K. Smutko, V. Ibrahim, E. Wijesuriya, J. Tuck, M. TI Rosiglitazone increases expression of oxidative stress and inflammation associated genes in hearts from fructose-fed rats SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Scientific Meeting of the European-Society-of-Hypertension/22nd Scientific Meeting of the International-Society-of-Hypertension CY JUN 14-19, 2008 CL Berlin, GERMANY SP Euorpean Soc Hyperten, Deutsch Hochdruckliga C1 [Nyby, M.; Tuck, M.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Sepulveda, 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 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JUN PY 2008 VL 26 SU 1 BP S317 EP S317 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 319WZ UT WOS:000257197002211 ER PT J AU Palomino, Z Bouley, R Casarini, DE Jung, F AF Palomino, Z. Bouley, R. Casarini, D. E. Jung, F. TI Bradykinin and PGE2 mediate Ang-(1-7) effect on aquaporin-1 in renal proximal tubules (IRPTC) SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Scientific Meeting of the European-Society-of-Hypertension/22nd Scientific Meeting of the International-Society-of-Hypertension CY JUN 14-19, 2008 CL Berlin, GERMANY SP Euorpean Soc Hyperten, Deutsch Hochdruckliga C1 [Palomino, Z.; Casarini, D. E.] Univ Fed Sao Paulo, Div Nephrol, Sao Paulo, Brazil. [Bouley, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Jung, F.] Univ Maryland, Dept Pediat, Baltimore, MD 21201 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 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JUN PY 2008 VL 26 SU 1 BP S522 EP S522 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 319WZ UT WOS:000257197003539 ER PT J AU Poioga, LH Romero, JR Ricchiuti, V Yao, TM Loutraris, P Stone, JR Adler, GK Williams, GH AF Poioga, L. H. Romero, J. R. Ricchiuti, V. Yao, T. M. Loutraris, P. Stone, J. R. Adler, G. K. Williams, G. H. TI Caveolin-1 modulates hormonal-mediated cardiovascular damage via a mechanism independent of blood pressure levels SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 18th Scientific Meeting of the European-Society-of-Hypertension/22nd Scientific Meeting of the International-Society-of-Hypertension CY JUN 14-19, 2008 CL Berlin, GERMANY SP Euorpean Soc Hyperten, Deutsch Hochdruckliga C1 [Poioga, L. H.; Romero, J. R.; Ricchiuti, V.; Yao, T. M.; Loutraris, P.; Adler, G. K.; Williams, G. H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Hypertens & Diabet, Boston, MA USA. [Stone, J. R.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen 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 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JUN PY 2008 VL 26 SU 1 BP S86 EP S86 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 319WZ UT WOS:000257197000376 ER PT J AU Kikushige, Y Yoshimoto, G Miyamoto, T Iino, T Mori, Y Iwasaki, H Niiro, H Takenaka, K Nagafuji, K Harada, M Ishikawa, F Akashi, K AF Kikushige, Yoshikane Yoshimoto, Goichi Miyamoto, Toshihiro Iino, Tadafumi Mori, Yasuo Iwasaki, Hirorni Niiro, Hiroaki Takenaka, Katsuto Nagafuji, Koji Harada, Mine Ishikawa, Fumihiko Akashi, Koichi TI Human Flt3 is expressed at the hematopoietic stem cell and the granulocyte/macrophage progenitor stages to maintain cell survival SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN BONE-MARROW; ACUTE MYELOGENOUS LEUKEMIA; RECEPTOR TYROSINE KINASE; ACUTE MYELOID-LEUKEMIA; HUMAN CORD BLOOD; DENDRITIC CELLS; INTERLEUKIN-7 RECEPTOR; CD34(+) CD38(-); GROWTH-FACTOR; C-KIT AB FLT3/FLK2, a member of the receptor tyrosine kinase family, plays a critical role in maintenance of hematopoietic homeostasis, and the constitutively active form of the FLT3 mutation is one of the most common genetic abnormalities in acute myelogenous leukemia. In murine hematopoiesis, Flt3 is not expressed in self-renewing hematopoietic stem cells, but its expression is restricted to the multipotent and the lymphoid progenitor stages at which cells are incapable of self-renewal. We extensively analyzed the expression of Flt3 in human (h) hematopoiesis. Strikingly, in both the bone marrow and the cord blood, the human hematopoietic stem cell population capable of long-term reconstitution in xenogeneic hosts uniformly expressed Flt3. Furthermore, human Flt3 is expressed not only in early lymphoid progenitors, but also in progenitors continuously along the granulocyte/macrophage pathway, including the common myeloid progenitor and the granulocyte/macrophage progenitor. We further found that human Flt3 signaling prevents stem and progenitors from spontaneous apoptotic cell death at least through up-regulating Mcl-1, an indispensable survival factor for hematopoiesis. Thus, the distribution of Flt3 expression is considerably different in human and mouse hematopoiesis, and human FLT3 signaling might play an important role in cell survival, especially at stem and progenitor cells that are critical cellular targets for acute myelogenous leukemia transformation. C1 [Kikushige, Yoshikane; Yoshimoto, Goichi; Miyamoto, Toshihiro; Iino, Tadafumi; Mori, Yasuo; Iwasaki, Hirorni; Niiro, Hiroaki; Akashi, Koichi] Kyushu Univ, Grad Sch Med Sci, Ctr Cellular & Mol Med, Fukuoka 812, Japan. [Ishikawa, Fumihiko] RIKEN, Ctr Allergy & Immunol, Res Unit Human Dis Model, Kanagawa, Japan. [Iino, Tadafumi; Akashi, Koichi] Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Akashi, K (reprint author), Kyushu Univ, Grad Sch Med Sci, Higashi Ku, 3-1-1 Maidashi, Fukuoka 812, Japan. EM akashi@med.kyushu-u.ac.jp RI 石川, 文彦/L-4488-2014 NR 57 TC 63 Z9 68 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 JUN 1 PY 2008 VL 180 IS 11 BP 7358 EP 7367 PG 10 WC Immunology SC Immunology GA 324GX UT WOS:000257507300032 PM 18490735 ER PT J AU Aqel, RA Zoghbi, GJ Hage, FG Dell'Italia, L AF Aqel, Raed A. Zoghbi, Gilbert J. Hage, Fadi G. Dell'Italia, Louis TI Three-Dimensional Balloon Catheter Sizing Identifies Significant Underdeployed Stents Using Conventional Methods in Renal Artery Interventions SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Article AB Background. Renal artery stent restenosis remains a significant impediment that in part is attributed to suboptimal stent deployment. We tested the hypothesis that optimal stent deployment during renal artery interventions can be achieved using the Metricath (MC) system, a balloon-catheter sizing device. Methods. The MC low-pressure balloon derives accurate vessel lumen dimensions from the three-dimensional reconstruction of volume of fluid and pressure within the inflated balloon. We systematically compared the Anal visual assessment of renal artery intervention with a subsequent MC minimal lumen diameter (MLD) in patients undergoing renal artery stenting. Results. Sixteen patients underwent angioplasry and stenting of 20 renal artery lesions. MC guidance resulted in adjunctive intervention in 90% of lesions, increasing MLD from 4.40 +/- 0.77 mm before to 5.17 +/- 0.82 mm (p < 0.001) after adjunctive intervention. The MC MLD to the angiographic reference vessel diameter improved from 77.4 +/- 15.2% to 91.2 +/- 17.5% (p < 0.001), and the MC MLD to the nominal stent diameter improved from 76.2 +/- 7.1% to 90.0 +/- 9.4% (p < 0.001) after adjunctive intervention. Stent expansion was more pronounced at its distal site compared to the lesion site where the postinterventional distal stent MLD was 5.52 +/- 0.93 mm (p = 0.23), and the lesion MLD was 5.17 0.82 (p = 0.001) compared to a nominal stent diameter of 5.78 +/- 0.88 mm. An MC MLD-to-nominal scent diameter ratio >= 85% occurred in 10% of lesions before adjunctive dilatation and in 65% of lesions after adjunctive balloon post dilatation. Conclusions. MC guidance during renal interventions revealed a large proportion of underdeployed stents that were further optimized by adjunctive intervention. C1 [Aqel, Raed A.; Zoghbi, Gilbert J.; Dell'Italia, Louis] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Aqel, Raed A.; Zoghbi, Gilbert J.; Hage, Fadi G.; Dell'Italia, Louis] Univ Alabama, Birmingham, AL USA. RP Aqel, RA (reprint author), BDB 383,1530 3rd Ave S, Birmingham, AL 35294 USA. EM raed.aqel@med.va.gov OI Hage, Fadi/0000-0002-1397-4942 FU Angiometrx Inc FX This study was funded by a grant from Angiometrx Inc. NR 26 TC 1 Z9 1 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD JUN PY 2008 VL 20 IS 6 BP 270 EP 276 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V14MQ UT WOS:000207738900005 PM 18523318 ER PT J AU Ebrahimi, R Saleh, J Toggart, E Shah, AP Azmoon, S Babaei, H Lee, J Smith, R Movahed, MR Rubin, SA AF Ebrahimi, Ramin Saleh, Jahandar Toggart, Edward Shah, Atman P. Azmoon, Shahdad Babaei, Hormoz Lee, James Smith, Ryan Movahed, M. Reza Rubin, Stanley A. TI Effect of Preprocedural Statin Use on Procedural Myocardial Infarction and Major Cardiac Adverse Events in Percutaneous Coronary Intervention: A Meta-Analysis SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Review ID AVERAGE CHOLESTEROL LEVELS; HEART-DISEASE; PRIMARY PREVENTION; RANDOMIZED-TRIAL; PRAVASTATIN; THERAPY; ATORVASTATIN; INFLAMMATION; INHIBITORS; SURVIVAL AB Background. Multiple primary and secondary prevention trials demonstrate significant reduction in adverse cardiovascular outcomes in patients with, or at risk of, coronary artery disease as a result of swirl therapy. This study was conducted to determine whether statin use prior to elective percutaneous coronary intervention (PCI) is associated with lower procedural myocardial infarction (MI) and major adverse cardiovascular events (MACE) in the form of a meta-analysis. Methods. Trials were eligible for inclusion if they included patients who received a statin prior to PCI and if appropriate documentation of procedural MI was performed. Studies that included acute coronary syndrome patients were excluded. For each trial, the results immediately post intervention and at the longest follow up (up to 12 months) were extracted and analyzed based on an intention-to-treat principle. Six trials involving 2,996 subjects met the inclusion criteria for periprocedural MI and were included in the analysis. Three trials involving 6,723 subjects had appropriate follow up and were analyzed for MACE (the combined endpoint of death, nonfatal MI or target vessel revascularization) up to 12 months after PCI. Results. When the 6 trials included in the main analysis were combined, the summary effect of statins on reducing procedural MI was -5.44% (95% CI -8.2% to -2.7% [p < 0.0001]). There was no evidence of heterogeneity between trials (p = 0.66). The relative risk reduction was 59.3% (9.17% vs. 3.73%; p < 0.001). Sensitivity analysis did not alter this finding. The MACE rates were 19.5% and 15.5% in the control and statin groups, respectively. The overall MACE risk difference was -4.0%, (95% CI -11.4% to +3.4% [p = 0.2900]). The corresponding overall relative risk reduction was 20.5%. C1 [Ebrahimi, Ramin; Saleh, Jahandar; Toggart, Edward; Babaei, Hormoz; Rubin, Stanley A.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Cardiol, Los Angeles, CA USA. [Ebrahimi, Ramin; Toggart, Edward; Shah, Atman P.; Azmoon, Shahdad; Lee, James; Smith, Ryan; Rubin, Stanley A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Movahed, M. Reza] Univ Arizona, Coll Med, Tucson, AZ USA. RP Ebrahimi, R (reprint author), VA Med Ctr Greater Los Angeles Healthcare Syst, Div Cardiol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ebrahimi@ucla.edu NR 20 TC 14 Z9 15 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 EI 1557-2501 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD JUN PY 2008 VL 20 IS 6 BP 292 EP 295 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V14MQ UT WOS:000207738900010 PM 18523323 ER PT J AU Moghadam-Kia, S Gaines, E Costner, M Rose, M Okawa, J Werth, V AF Moghadam-Kia, S. Gaines, E. Costner, M. Rose, M. Okawa, J. Werth, V. TI Initial analysis of a collaborative web-based database for skin manifestations of lupus erythematosus: 102 prospectively enrolled patients SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Dermatology CY FEB 01-05, 2008 CL San Antonio, TX SP Amer Acad Dermatol C1 [Moghadam-Kia, S.; Gaines, E.; Rose, M.; Okawa, J.; Werth, V.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Costner, M.] Univ Texas SW Med Ctr Dallas, Dallas, TX USA. [Werth, V.] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 2008 VL 128 IS 6 MA 2 BP 1606 EP 1606 PG 1 WC Dermatology SC Dermatology GA 302FG UT WOS:000255953600047 ER PT J AU DiLaura, R Turisco, F McGrew, C Reel, S Glaser, J Crowley, WF AF DiLaura, Robert Turisco, Fran McGrew, Cherri Reel, Stephanie Glaser, John Crowley, William F., Jr. TI Use of informatics and information technologies in the clinical research enterprise within US academic medical centers: Progress and challenges from 2005 to 2007 SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE biomedical research; academic medical center; information systems; research support; informatics; computerized medical records systems AB Background: Data on the state of information systems infrastructures used in the clinical research enterprise of academic medical centers are limited and mostly anecdotal. What has been published is slowly beginning to make important distinctions, such as clinical trials as a specialized form of clinical research and between "Informatics" in an academic setting from health care information technology. However, this field continues to undergo fundamental changes, accelerated by the National Institutes of Health's creation of Clinical and Translational Science Awards to build a new "home" for biomedical research. Methods: We surveyed all Clinical Research Forum member institutions regarding their enterprise infrastructure and use of information systems in support of clinical research. The questions in this on-line study expanded on one first done in 2005. Of the 52 sites invited, 19 (37%) responded. We analyzed the responses and also made matched comparisons for those organizations that participated in both surveys. Results: Although there continues to be conceptual agreement on information system elements for the clinical research enterprise, no single institution achieved the ideal, a similar result to the 2005 survey. Indeed, little progress was made over the past 2 years at most locations other than in information technology planning, strategy, and governance. Conclusions: There is increased recognition of the importance of information systems infrastructure and expertise for biomedical research, but the needs are accelerating much faster than institutions can build or pay for. A much greater realization of and innovative solution for this growing chasm is urgently required. C1 Johns Hopkins Univ, Baltimore, MD USA. Partners Healthcare, Boston, MA USA. Massachusetts Gen Hosp, Dept Clin Res, Boston, MA 02114 USA. Clin Res Forum, Dept Clin Res, Boston, MA USA. Comp Sci Corp, Lexington, MA USA. Cleveland Clin, Cleveland, OH 44106 USA. Case Western Reserve Univ, Lerner Res Inst, Cleveland, OH 44106 USA. Clin Res Forum, Washington, DC 20036 USA. RP DiLaura, R (reprint author), Clin Res Forum, 1350 Connecticut Ave NW,Suite 850, Washington, DC 20036 USA. EM kkeamey@clinicalresearchforum.org NR 13 TC 6 Z9 6 U1 0 U2 1 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JUN PY 2008 VL 56 IS 5 BP 770 EP 779 PG 10 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 311FP UT WOS:000256586400021 PM 18525452 ER PT J AU Choi, W Kwon, KY Kim, JM Quinn, DA Hales, CA Seo, JW AF Choi, Won-Il Kwon, Kun Young Kim, Jin Mo Quinn, Deborah A. Hales, Charles A. Seo, Jeong Wook TI Atelectasis induced by thoracotomy causes lung injury during mechanical ventilation in endotoxemic rats SO JOURNAL OF KOREAN MEDICAL SCIENCE LA English DT Article DE atelectasis; functional residual capacity; lung injury; nitric oxide synthase; nitric oxide synthase inhibitor ID NITRIC-OXIDE SYNTHASE; RESPIRATORY-DISTRESS SYNDROME; PULMONARY-EDEMA; TIDAL VOLUME; IN-VIVO; COLLAPSE; INHIBITION; EXPRESSION; GROWTH; 1400W AB Atelectasis can impair arterial oxygenation and decrease lung compliance. However, the effects of atelectasis on endotoxemic lungs during ventilation have not been well studied. We hypothesized that ventilation at low volumes below functional residual capacity (FRC) would accentuate lung injury in lipopolysaccharide (LPS)-pretreated rats. LPS-pretreated rats were ventilated with room air at 85 breaths/min for 2 hr at a tidal volume of 10 mL/kg with or without thoracotomy. Positive end-expiratory pressure (PEEP) was applied to restore FRC in the thoracotomy group. While LPS or thoracotomy alone did not cause significant injury, the combination of endotoxemia and thoracotomy caused significant hypoxemia and hypercapnia. The injury was observed along with a marked accumulation of inflammatory cells in the interstitium of the lungs, predominantly comprising neutrophils and mononuclear cells. Immunohistochemistry showed increased inducible nitric oxide synthase (NOS) expression in mononuclear cells accumulated in the interstitium in the injury group. Pretreatment with PEEP or an NOS inhibitor (1400 W) attenuated hypoxemia, hypercapnia, and the accumulation of inflammatory cells in the lung. In conclusion, the data suggest that atelectasis induced by thoracotomy causes lung injury during mechanical ventilation in endotoxemic rats through NOS expression. C1 [Choi, Won-Il] Keimyung Univ, Dongsan Hosp, Dept Med, Taegu 712700, South Korea. [Kwon, Kun Young] Keimyung Univ, Dongsan Hosp, Dept Pathol, Taegu 712700, South Korea. [Kim, Jin Mo] Keimyung Univ, Dongsan Hosp, Dept Anesthesiol, Taegu 712700, South Korea. [Quinn, Deborah A.; Hales, Charles A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm Crit Care Unit, Boston, MA USA. [Seo, Jeong Wook] Seoul Natl Univ Hosp, Dept Pathol, Seoul 110744, South Korea. RP Choi, W (reprint author), Keimyung Univ, Dongsan Hosp, Dept Med, 194 Dongsan Dong, Taegu 712700, South Korea. EM wichoi@dsmc.or.kr RI Seo, Jeong-Wook/C-3494-2009; Seoul National University, Pathology/B-6702-2012 OI Seo, Jeong-Wook/0000-0003-0242-1805; FU NHLBI NIH HHS [R01 HL039150, HL 039150] NR 32 TC 2 Z9 2 U1 0 U2 0 PU KOREAN ACAD MEDICAL SCIENCES PI SEOUL PA 302 75 DONG DU ICHON, DONG YONGSAN KU, SEOUL 140 031, SOUTH KOREA SN 1011-8934 J9 J KOREAN MED SCI JI J. Korean Med. Sci. PD JUN PY 2008 VL 23 IS 3 BP 406 EP 413 DI 10.3346/jkms.2008.23.3.406 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 323JL UT WOS:000257442300009 PM 18583875 ER PT J AU Miller, FG Mello, MM Joffe, S AF Miller, Franklin G. Mello, Michelle M. Joffe, Steven TI Incidental findings in human subjects research: What do investigators owe research participants? SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article; Proceedings Paper CT Symposium on Findings in Human Subjects Research - From Imaging to Genomics CY MAY, 2007 CL Univ Minnesota, Minneapolis, MN HO Univ Minnesota ID CARE RESPONSIBILITIES; NEUROIMAGING RESEARCH; MEDICAL RESEARCHERS; CLINICAL CARE AB The use of brain imaging technology as a common tool of research has spawned concern and debate over how investigators should respond to incidental findings discovered in the course of research. In this article, we argue that investigators have an obligation to respond to incidental findings in view of their entering into a professional relationship with research participants in which they are granted privileged access to private information with potential relevance to participants' health. We discuss the scope and limits of this professional obligation to respond to incidental findings, bearing in mind that the relationship between investigators and research participants differs fundamentally from the doctor-patient relationship. C1 [Mello, Michelle M.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Joffe, Steven] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Joffe, Steven] Dana Farber Canc Inst, Boston, MA 02115 USA. [Joffe, Steven] Childrens Hosp, Boston, MA 02115 USA. OI Joffe, Steven/0000-0002-0667-7384 FU NHGRI NIH HHS [R01 HG 003178, R01 HG003178, R01 HG003178-02] NR 17 TC 57 Z9 57 U1 2 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SUM PY 2008 VL 36 IS 2 BP 271 EP 279 DI 10.1111/j.1748-720X.2008.00269.x PG 9 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 308SX UT WOS:000256411400005 PM 18547194 ER PT J AU Barry, MJ Wescott, PH Reifler, EJ Chang, YC Moulton, BW AF Barry, Michael J. Wescott, Pamela H. Reifler, Ellen J. Chang, Yuchaio Moulton, Benjamin W. TI Reactions of potential jurors to a hypothetical malpractice suit alleging failure to perform a prostate-specific antigen test SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID UNITED-STATES; CANCER; SYSTEM; MEN AB We conducted focus groups with 47 potential jurors who were presented with different scenarios in a hypothetical malpractice case involving failure to order a PSA test. Better documentation that a patient made an informed decision to decline a PSA test appeared to provide more medical-legal protection for physicians, especially with the use of a decision aid. C1 [Barry, Michael J.] Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. [Chang, Yuchaio] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. NR 12 TC 12 Z9 12 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SUM PY 2008 VL 36 IS 2 BP 396 EP + DI 10.1111/j.1748-720X.2008.00283.x PG 8 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 308SX UT WOS:000256411400019 PM 18547208 ER PT J AU Osorio, Y Bonilla, DL Peniche, AG Melby, PC Travi, BL AF Osorio, Yaneth Bonilla, Diana L. Peniche, Alex G. Melby, Peter C. Travi, Bruno L. TI Pregnancy enhances the innate immune response in experimental cutaneous leishmaniasis through hormone-modulated nitric oxide production SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE leishmania; hamster; estrogen ID SYNTHASE GENE-EXPRESSION; VISCERAL LEISHMANIASIS; NEUTROPHIL GRANULOCYTES; MACROPHAGE FUNCTION; MAJOR INFECTION; MESSENGER-RNA; CUTTING EDGE; ESTROGEN; HAMSTER; GAMMA AB The maintenance of host defense during pregnancy may depend on heightened innate immunity. We evaluated the immune response of pregnant hamsters during early infection with Leishmania (Viannia) panamensis, a cause of American cutaneous leishmaniasis. At 7 days post-infection, pregnant animals showed a lower parasite burden compared with nonpregnant controls at the cutaneous infection site (P = 0.0098) and draining lymph node (P = 0.02). Resident peritoneal macrophages and neutrophils from pregnant animals had enhanced Leishmania killing capacity compared with nonpregnant controls (P = 0.018 each). This enhanced resistance during pregnancy was associated with increased expression of inducible NO synthase (iNOS) mRNA in lymph node cells (P = 0.02) and higher NO production by neutrophils (P = 0.0001). Macrophages from nonpregnant hamsters infected with L. panamensis released high amounts of NO upon estrogen exposure (P = 0.05), and addition of the iNOS inhibitor L-N6-(1-iminoethyl) lysine blocked the induction of NO production (P = 0.02). Infected, nonpregnant females treated with estrogen showed a higher percentage of cells producing NO at the infection site than controls (P = 0.001), which correlated with lower parasite burdens (P = 0.036). Cultured macrophages or neutrophils from estrogen-treated hamsters showed significantly increased NO production and Leishmania killing compared with untreated controls. iNOS was identified as the likely source of estrogen-induced NO in primed and naive macrophages, as increased transcription was evident by real-time PCR. Thus, the innate defense against Leishmania infection is heightened during pregnancy, at least in part as a result of estrogen-mediated up-regulation of iNOS expression and NO production. C1 [Osorio, Yaneth; Melby, Peter C.; Travi, Bruno L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Osorio, Yaneth; Bonilla, Diana L.; Peniche, Alex G.; Travi, Bruno L.] Ctr Int Entrenamiento & Invest Med CIDEIM, Cali, Colombia. [Osorio, Yaneth; Melby, Peter C.; Travi, Bruno L.] S Texas Vet Hlth Care System, Res Serv, Dept Vet Affairs Med Ctr, San Antonio, TX USA. RP Travi, BL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr,Mailcode 7881, San Antonio, TX 78229 USA. EM travi@uthscsa.edu FU NIAID NIH HHS [R01 AI061624, AI 061624] NR 51 TC 22 Z9 23 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUN 1 PY 2008 VL 83 IS 6 BP 1413 EP 1422 DI 10.1189/jlb.0207130 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 331NV UT WOS:000258019800014 PM 18347075 ER PT J AU Ordway, D Henao-Tamayo, M Smith, E Shanley, C Harton, M Troudt, J Bai, XY Basaraba, RJ Orme, IM Chan, ED AF Ordway, Diane Henao-Tamayo, Marcela Smith, Erin Shanley, Crystal Harton, Marisa Troudt, JoLynn Bai, Xiyuan Basaraba, Randall J. Orme, Ian M. Chan, Edward D. TI Animal model of Mycobacterium abscessus lung infection SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE T cells; dendritic cells; macrophages; cytokines ID RAPIDLY GROWING MYCOBACTERIA; DENDRITIC CELLS; IMMUNE-RESPONSE; TUBERCULOSIS INFECTION; GAMMA-INTERFERON; HOST-DEFENSE; T-CELLS; LEPTIN; MICE; PNEUMONIA AB Chronic lung disease as a result of Mycobacterium abscessus is an emerging infection in the United States. We characterized the lung immune responses in mice and guinea pigs infected with M. abscessus. C57BL/6 and leptin-deficient ob/ob mice challenged with a low-dose aerosol (LDA) of M. abscessus did not develop an infection. However, when challenged with a high-dose aerosol (HDA), C57BL/6 and ob/ob mice developed an established infection and a pulmonary immune response consisting of an early influx of IFN-gamma+ CD4+ T cells; this immune response preceded the successful clearance of M. abscessus in both strains of mice, although mycobacterial elimination was delayed in the ob/ob mice. Infected guinea pigs showed an increased influx of lymphocytes into the lungs with bacterial clearance by Day 60. In contrast to the C57BL/6 and ob/ob mice and guinea pigs, IFN-gamma knockout (GKO) mice challenged with a LDA or HDA of M. abscessus showed a progressive lung infection despite a robust influx of T cells, macrophages, and dendritic cells, culminating in extensive lung consolidation. Furthermore, with HDA challenge of the GKO mice, emergence of IL-4- and IL-10-producing CD4+ and CD8+ T cells was seen in the lungs. In conclusion, IFN-gamma is critically important in the host defense against M. abscessus. As the number of effective drugs against M. abscessus is limited, the GKO mice provide a model for in vivo testing of novel drugs. C1 [Ordway, Diane; Henao-Tamayo, Marcela; Smith, Erin; Shanley, Crystal; Harton, Marisa; Troudt, JoLynn; Basaraba, Randall J.; Orme, Ian M.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Mycobacteria Res Labs, Ft Collins, CO 80523 USA. [Chan, Edward D.] Univ Colorado, Sch Med, Div Pulm Sci & Crit Care Med, Denver, CO USA. [Bai, Xiyuan; Chan, Edward D.] Natl Jewish Med & Res Ctr, Denver, CO USA. [Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Ordway, D (reprint author), Colorado State Univ, Dept Microbiol Immunol & Pathol, Mycobacteria Res Labs, Ft Collins, CO 80523 USA. EM D.Ordway-Rodriguez@colostate.edu RI Henao-Tamayo, Marcela/D-8189-2017 OI Henao-Tamayo, Marcela/0000-0002-4249-9650 FU NIAID NIH HHS [AI 040091, AI 44072] NR 45 TC 51 Z9 51 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUN 1 PY 2008 VL 83 IS 6 BP 1502 EP 1511 DI 10.1189/jlb.1007696 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 331NV UT WOS:000258019800024 PM 18310351 ER PT J AU Christensen, S Calamante, F Hjort, N Wu, O Blankholm, AD Desmond, P Davis, S Ostergaard, L AF Christensen, Soren Calamante, Fernando Hjort, Niels Wu, Ona Blankholm, Anne Dorte Desmond, Patricia Davis, Stephen Ostergaard, Leif TI Inferring origin of vascular supply from tracer arrival timing patterns using bolus tracking MRI SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE bolus tracking MRI; collateral flow; collaterals; stroke ID SINGULAR-VALUE DECOMPOSITION; HIGH-RESOLUTION MEASUREMENT; BLOOD-FLOW; DECONVOLUTION; PASSAGES; VELOCITY; TISSUE; STROKE AB Purpose: To investigate the potential of novel postprocessing and visualization techniques to distinguish presence of collateral flow using Bolus Tracking MRI. Collateral blood supply is believed to be of paramount importance in acute stroke, yet clinical evaluation is challenging as the gold standard digital subtraction angiography is often not feasible in the acute scenario. Materials and Methods: In principle, bolus arrival delay data contains information about the route of blood supply into tissue and hereby presence of collateral flow patterns. We first examined the potential of current clinical bolus tracking protocols to accurately characterize bolus arrival delay. Using the simulation results, we analyzed bolus tracking data from one normal volunteer and one acute stroke patient. Results: The bolus arrival patterns in the volunteer and in the normal hemisphere of the patient were found to be qualitatively similar and in good agreement with physiology. The bolus was seen to spread from the larger arteries toward the periphery. The stroke hemisphere in the patient indicated a retrograde direction of flow on the cortical mantle consistent with leptomeningeal vessels. Conclusion: Bolus tracking MRI can likely be used to distinguish collateral flow patterns from normal flow patterns. C1 [Christensen, Soren; Hjort, Niels; Blankholm, Anne Dorte] Aarhus Univ Hosp, Dept Neuroradiol, Ctr Functionally Integrat Neurosci, DK-8000 Aarhus C, Denmark. [Christensen, Soren; Desmond, Patricia] Univ Melbourne, Dept Radiol, Melbourne, Vic, Australia. [Calamante, Fernando] Univ Melbourne, Brain Res Inst, Melbourne, Vic, Australia. [Calamante, Fernando] Univ Melbourne, Dept Med, Melbourne, Vic, Australia. [Wu, Ona] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA USA. [Blankholm, Anne Dorte] Aarhus Univ Hosp, Dept Diagnost Imaging, Skejby, Denmark. [Davis, Stephen] Royal Melbourne Hosp, Dept Neurol, Melbourne, Vic, Australia. [Davis, Stephen] Univ Melbourne, Melbourne, Vic 3010, Australia. RP Christensen, S (reprint author), Aarhus Univ Hosp, Dept Neuroradiol, Ctr Functionally Integrat Neurosci, Bldg 30,Norrebrogade 44, DK-8000 Aarhus C, Denmark. EM chr@pet.auh.dk RI Bonefeld, Birgit/B-7936-2010; Ostergaard, Leif/A-9281-2008; Desmond, Patricia /D-1966-2014; Davis, Stephen/L-5260-2013 OI Ostergaard, Leif/0000-0003-2930-6997; Desmond, Patricia /0000-0002-4803-6323; Davis, Stephen/0000-0003-0962-2300 NR 18 TC 26 Z9 26 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JUN PY 2008 VL 27 IS 6 BP 1371 EP 1381 DI 10.1002/jmri.21386 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 307OH UT WOS:000256327700025 PM 18504757 ER PT J AU Smith, J AF Smith, Jason TI Therapy analysis and evidenced-based treatment guidelines (including review of antiviral medications) SO JOURNAL OF MANAGED CARE PHARMACY LA English DT Article ID CHRONIC HEPATITIS-B; HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTION; LAMIVUDINE TREATMENT; TREATMENT ALGORITHM; UNITED-STATES; TENOFOVIR; ADEFOVIR; EFFICACY; SAFETY AB OBJECTIVE: To summarize current treatment options and guidelines for treatment of HBV infection and HIV-HBV co-infection, including a review of the relevant antiviral agents. SUMMARY. Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infection have caused large global epidemics, which may overlap because they are transmitted by similar routes, including sex and injection drug use. About 30% of individuals with chronic HBV infection develop cirrhosis, and 5% to 10% develop hepatocellular cancer (HCC). In HBV-HIV co-infection, HIV decreases the rate at which hepatitis B "E" antigen (HBeAg) is lost, increases levels of HBV DNA, and increases the progression to cirrhosis, the number of liver-related complications, and mortality. Three classes of oral antiviral agents for HBV are approved in the United States. L-nucleoside analogs include lamivudine, emtricitabine, and telbivudine. Acyclic adenine phosphonates are adefovir and tenofovir, which is not yet approved for HBV infection. Entecavir is a guanine nucleoside analog. HBV resistance to antiviral agents arises because of HBV's rapid viral production and the high rate of spontaneous mutations. Anti-HBV therapy is also effective in patients with HIV-HBV co-infection. The decision to treat HBV in a patient with HIV-HBV co-infection depends on whether highly active antiretroviral therapy (HAART) for HIV is indicated, the severity of the liver disease, the likelihood of response, and the potential for adverse events. CONCLUSION: Effective treatment of HBV infection is important to reduce risk of cirrhosis, HCC, and death. Treatment of HBV infection in HIV-infected persons should consider the activity of the antiviral agents used against both viruses. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Smith, J (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd 111C, Los Angeles, CA 90073 USA. EM jason.smith2@va.gov NR 38 TC 0 Z9 0 U1 0 U2 1 PU ACAD MANAGED CARE PHARMACY PI ALEXANDRIA PA 100 N PITT ST, 400, ALEXANDRIA, VA 22314-3134 USA SN 1083-4087 J9 J MANAGE CARE PHARM JI J. Manag. Care Pharm. PD JUN PY 2008 VL 14 IS 5 SU A BP S7 EP S11 PG 5 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 326TP UT WOS:000257682100002 ER PT J AU Maher, MM Rizzo, S Kalra, M Mc Sweeney, SE Arellano, R Hahn, P Gervais, D Mueller, P AF Maher, M. M. Rizzo, S. Kalra, M. Mc Sweeney, S. E. Arellano, R. Hahn, P. Gervais, D. Mueller, P. TI Radiological management of patients with urinary obstruction following urinary diversion procedures: Technical factors, complications, long-term management and outcome. Experience with 378 procedures SO JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY LA English DT Article DE interventional radiology; urinary diversions; urology ID RADICAL CYSTECTOMY; ILEAL CONDUIT; STRICTURES; STENTS AB We aimed to assess management by interventional radiology techniques of patients with urinary diversion procedures (UD) complicated by urinary obstruction (UO). A 12-year electronic database of interventional cases was searched for urinary access in patients with UD. Patients' records were assessed for aetiology of obstruction, indication for procedure, types of interventional radiology, complications and outcome. Management issues included frequency of visits for catheter care, type of catheter placement and technical problems associated with catheter maintenance. Three hundred and seventy eight procedures were carried out in 25 patients (mean age 70 years; Male : Female ratio 13:12). Indications for UD were malignancy (n = 22) and neuropathic bladder (n = 3). UD included ileal conduits (n = 17), cutaneous ureterostomy (n = 3 (2 patients)) and sigmoid colon urinary conduit (n = 6). In most patients, catheters were placed antegradely through nephrostomy tract, but subsequent access was through the UD. Twenty of 25 patients had unilateral stents where as 5 had bilateral stents (8-10- Fr pigtail catheters (20-45 cm in length)). The mean number of procedures including catheter changes was 15 +/- 4 per patient and 331 of 378 procedures (87 %) were carried out as outpatients. Since catheter placement, 11 patients required hospital admission on 22 occasions for catheter-related complications. Ureteric strictures in patients with UD can be successfully managed by interventional radiology. C1 [Maher, M. M.; Mc Sweeney, S. E.] Cork Univ Hosp, Univ Coll Cork, Dept Radiol, Cork, Ireland. [Maher, M. M.; Rizzo, S.; Kalra, M.; Arellano, R.; Hahn, P.; Gervais, D.; Mueller, P.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Maher, MM (reprint author), Cork Univ Hosp, Univ Coll Cork, Dept Radiol, Cork, Ireland. EM m.maher@ucc.ie NR 10 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0004-8461 J9 J MED IMAG RADIAT ON JI J. Med. Imag. Radiat. Oncol. PD JUN PY 2008 VL 52 IS 3 BP 237 EP 243 DI 10.1111/j.1440-1673.2008.01953.x PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 309CK UT WOS:000256438100007 PM 18477118 ER PT J AU Perlick, DA Rosenheck, RA Miklowitz, DJ Kaczynski, R Link, B Ketter, T Wisniewski, S Wolff, N Sachs, G AF Perlick, Deborah A. Rosenheck, Robert A. Miklowitz, David J. Kaczynski, Richard Link, Bruce Ketter, Terence Wisniewski, Stephen Wolff, Nancy Sachs, Gary CA Step-BD Family Experience Collabor TI Caregiver burden and health in bipolar disorder - A cluster analytic approach SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE caregiving; profiles; strain; health ID TREATMENT ENHANCEMENT PROGRAM; MENTAL-ILLNESS; DEPRESSIVE SYMPTOMS; CLINICAL-TRIALS; SOCIAL SUPPORT; FAMILY; CARE; ILL; SCHIZOPHRENIA; RATIONALE AB To identify caregivers at risk for adverse health effects associated with caregiving, the stress, coping, health and service use of 500 primary caregivers of patients with bipolar disorder were assessed at baseline, 6, and 12 months. K-means cluster analysis and ANOVA identified and characterized groups with differing baseline stress/coping profiles. Mixed effects models examined the effects of cluster, time, and covariates on health outcomes. Three groups were identified. Burdened caregivers had higher burden and avoidance coping levels, and lower mastery and social support than effective and stigmatized caregivers; stigmatized caregivers reported the highest perceived stigma (p < 0.05). Effective and stigmatized groups had better health outcomes and less service use than the burdened group over time; stigmatized caregivers had poorer self-care than effective caregivers. Cluster analysis is a promising method for identifying subgroups of caregivers with different stress and coping profiles associated with different health-related outcomes. C1 [Perlick, Deborah A.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10019 USA. [Rosenheck, Robert A.; Kaczynski, Richard] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Miklowitz, David J.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. [Rosenheck, Robert A.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Link, Bruce] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Ketter, Terence] Stanford Univ, Dept Psychiat, Palo Alto, CA 94304 USA. [Wisniewski, Stephen] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Wolff, Nancy] Rutgers State Univ, Sch Planning & Publ Policy, New Brunswick, NJ 08903 USA. [Sachs, Gary] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Perlick, DA (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl, New York, NY 10019 USA. EM deborah.perlick@mssm.edu RI Link, Bruce/N-9087-2013; OI Link, Bruce/0000-0001-9980-7450; Wisniewski, Stephen/0000-0002-3877-9860 FU NIMH NIH HHS [MH-65015, N01 MH080001, N0MH-8001, R01 MH065015] NR 47 TC 29 Z9 29 U1 1 U2 2 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 JUN PY 2008 VL 196 IS 6 BP 484 EP 491 DI 10.1097/NMD.0b013e3181773927 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 312FY UT WOS:000256655700007 PM 18552626 ER PT J AU Kesari, S Kim, RS Markos, V Drappatz, J Wen, PY Pruitt, AA AF Kesari, Santosh Kim, Ryung S. Markos, Vassilios Drappatz, Jan Wen, Patrick Y. Pruitt, Amy A. TI Prognostic factors in adult brainstem gliomas: a multicenter, retrospective analysis of 101 cases SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE brainstem glioma; natural history; chemotherapy; radiation; surgery; prognostic factors ID CHILDRENS CANCER GROUP; TUMORS; MANAGEMENT; ASTROCYTOMA; CHILDHOOD; DIAGNOSIS; SELECTION; THERAPY; LASSO AB Background Adult brainstem gliomas (BSG) are uncommon and poorly understood with respect to prognostic factors. We retrospectively evaluated the clinical, radiographic, histologic, and treatment features from 101 adults with presumed or biopsy proven BSG to determine prognostic factors. Patients and Methods We reviewed the records of patients diagnosed from 1987-2005. We used Cox proportional hazard models to determine prognostic factors. Results These 50 male and 51 female patients ranged in age from 18 to 79 years at diagnosis (median 36 years) with follow-ups from I to 261 months (median 47 months). The overall survival for all patients at 5 and 10 years was 58% and 41%, respectively, with a median survival of 85 months (range 1-228). Out of 24 candidate prognosis factors, we selected seven covariates for proportional hazards model by Lasso procedure: age of diagnosis, ethnicity, need for corticosteroids, tumor grade, dysphagia, tumor location, and karnofsky performance status (KPS). Univariate analysis showed that these seven factors are significantly associated with survival. Multivariate analysis showed that four covariates significantly increased hazard for survival: ethnicity, tumor location, age of diagnosis, and tumor grade. Conclusions In this study, we identified four prognostic factors that were significantly associated with survival in adults with BSGs. Overall, these patients have a better prognosis than children with BSGs reported in the literature. These results call for larger prospective studies to fully assess the importance of these factors in the clinical setting and to help stratify patients in future clinical studies. C1 [Kesari, Santosh; Markos, Vassilios; Drappatz, Jan; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. [Kesari, Santosh; Drappatz, Jan; Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Canc Neurol, Boston, MA 02115 USA. [Kesari, Santosh; Drappatz, Jan; Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kim, Ryung S.] Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01602 USA. [Markos, Vassilios] Univ Gen Hosp, Dept Med Oncol, Iraklion, Greece. [Pruitt, Amy A.] Univ Penn, Med Ctr, Dept Neurol, Hosp Univ Penn, Philadelphia, PA 19104 USA. RP Kesari, S (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, SW430,44 Binney St, Boston, MA 02115 USA. EM skesari@partners.org RI Kesari, Santosh/E-8461-2013 NR 41 TC 32 Z9 36 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JUN PY 2008 VL 88 IS 2 BP 175 EP 183 DI 10.1007/s11060-008-9545-1 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 307IS UT WOS:000256313200007 PM 18365144 ER PT J AU Saad, A Tuli, S Ali, EN Houtchens, M Delalle, I Kesari, S AF Saad, Ali Tuli, Sagun Ali, Eman N. Houtchens, Maria Delalle, Ivana Kesari, Santosh TI Pilocytic astrocytoma of the spinal cord in an adult SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article C1 [Kesari, Santosh] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. [Ali, Eman N.; Houtchens, Maria; Kesari, Santosh] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Tuli, Sagun] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Saad, Ali; Tuli, Sagun; Ali, Eman N.; Houtchens, Maria; Delalle, Ivana; Kesari, Santosh] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Saad, Ali; Delalle, Ivana] Brigham & Womens Hosp, Div Neuropathol, Dept Pathol, Boston, MA 02115 USA. RP Kesari, S (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, SW460,44 Binney St, Boston, MA 02115 USA. EM skesari@partners.org RI Kesari, Santosh/E-8461-2013 NR 4 TC 3 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JUN PY 2008 VL 88 IS 2 BP 189 EP 191 DI 10.1007/s11060-008-9547-z PG 3 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 307IS UT WOS:000256313200009 PM 18340405 ER PT J AU Ehsani, S Hodaie, M Liebsch, NJ Gentili, F Kiehl, TR AF Ehsani, Sepehr Hodaie, Mojgan Liebsch, Norbert J. Gentili, Fred Kiehl, Tim-Rasmus TI Anaplastic glioma after high-dose proton-photon radiation treatment for low-grade skull base chondrosarcoma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE anaplastic glioma; brain tumor; oligoastrocytoma; proton radiation therapy; radiation-associated tumor; skull base chondrosarcoma ID CERVICAL-SPINE; THERAPY; GLIOBLASTOMA; CHORDOMAS; OLIGODENDROGLIOMA; IRRADIATION; DIAGNOSIS; SURGERY; RISK AB We report the case of a 63-year-old man who developed an anaplastic oligoastrocytoma of the brain stem and midbrain 13 years after postoperative high-dose proton-photon radiation therapy for a recurrent low-grade chondrosarcoma of the skull base. To our knowledge, this is the first reported case of an anaplastic glioma after proton-photon irradiation. C1 [Kiehl, Tim-Rasmus] Univ Hlth Network, Dept Pathol, Toronto, ON M5G 2C4, Canada. [Liebsch, Norbert J.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Hodaie, Mojgan; Gentili, Fred] Univ Toronto, Dept Surg, Div Neurosurg, Toronto, ON, Canada. [Hodaie, Mojgan; Gentili, Fred] Univ Hlth Network, Krembil Neurosci Ctr, Toronto, ON, Canada. [Hodaie, Mojgan; Gentili, Fred] Univ Hlth Network, Toronto Western Res Inst, Toronto, ON, Canada. [Ehsani, Sepehr; Kiehl, Tim-Rasmus] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. RP Kiehl, TR (reprint author), Univ Hlth Network, Dept Pathol, 200 Elizabeth St,11E 444, Toronto, ON M5G 2C4, Canada. EM rasmus.kiehl@uhn.on.ca NR 24 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JUN PY 2008 VL 88 IS 2 BP 231 EP 236 DI 10.1007/s11060-008-9560-2 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 307IS UT WOS:000256313200017 PM 18345517 ER PT J AU Montezuma, SR Gopal, H Savar, A Turalba, A Cestari, DM Torun, N AF Montezuma, Sandra R. Gopal, Harsha Savar, Aaron Turalba, Angela Cestari, Dean M. Torun, Nurhan TI Silent sinus syndrome presenting as enophthalmos long after orbital trauma SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY; BLOWOUT FRACTURES; MAXILLARY SINUS; FLOOR AB Late enophthalmos is a well-known consequence of large orbital floor fractures. In rare cases, late enophthalmos can occur after direct trauma to the maxillary ostiomeatal complex and present as silent sinus syndrome (SSS). We report two cases of SSS manifesting as enophthalmos years after facial trauma. The first patient developed SSS 4 years after a minimally displaced orbital floor fracture. The second patient had progressive enophthalmos as a result of atelectasis of the maxillary sinus years after facial trauma and surgical repair of nasal fractures. There have been two prior reports of SSS presenting after orbital trauma. Our patients differ from these prior reports in that the enophthalmos was discovered years after the initial facial trauma. In the first patient, surgery addressing the blockage of the ostiomeatal complex arrested the enophthalmos; in the second patient, it reversed the enophthalmos. C1 [Montezuma, Sandra R.; Savar, Aaron; Turalba, Angela; Cestari, Dean M.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Gopal, Harsha] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Otolaryngol, Boston, MA 02114 USA. [Torun, Nurhan] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Ophthalmol, Boston, MA 02114 USA. RP Montezuma, SR (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM sandra_montezuma@meei.harvard.edu NR 21 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD JUN PY 2008 VL 28 IS 2 BP 107 EP 110 DI 10.1097/WNO.0b013e3181772956 PG 4 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 310NZ UT WOS:000256537600005 PM 18562841 ER PT J AU Giri, S Khan, M Nath, N Singh, I Singh, AK AF Giri, Shailendra Khan, Mushfiquddin Nath, Narender Singh, Inderjit Singh, Avtar K. TI The role of AMPK in psychosine mediated effects on oligodendrocytes and astrocytes: Implication for Krabbe Disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE AMP-activated protein kinase; astrocytes; inflammation; Krabbe disease; oligodendrocyte; psychosine ID ACTIVATED PROTEIN-KINASE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; GLOBOID-CELL LEUKODYSTROPHY; CENTRAL-NERVOUS-SYSTEM; C6 GLIAL-CELLS; ADIPOCYTE DIFFERENTIATION; TWITCHER MICE; 5-AMINOIMIDAZOLE-4-CARBOXAMIDE RIBONUCLEOSIDE; INHIBITION; EXPRESSION AB Krabbe disease (KD) is an inherited neurological disorder caused by the deficiency of galactocerebrosidase activity resulting in accumulation of psychosine, which leads to energy depletion, loss of oligodendrocytes, induction of gliosis, and inflammation by astrocytes in CNS. In this study, for the first time, we report the regulation of 'cellular energy switch,'AMP-activated protein kinase (AMPK), by psychosine in oligodendrocytes and astrocytes. Psychosine treatment significantly down-regulated AMPK activity, resulting in increased biosynthesis of lipids including cholesterol and free fatty acid in oligodendrocytes cell line (MO3.13) and primary astrocytes. Pharmacological activator of AMPK, 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) attenuated the psychosine-mediated down-regulation of AMPK and restored altered biosynthesis of lipids. AICAR treatment also down-regulated psychosine induced expression of proinflammatory cytokines and inducible nitric oxide synthase in primary astrocytes. However, AICAR treatment had no effect on psychosine incluced-reactive oxygen species generation, arachidonic acid release, and death of oligodendrocytes; suggesting the specific role of AMPK in regulation of psychosine-mediated inflammatory response of astrocytes but not in cell death of oligodendrocytes. This study delineates an explicit role for AMPK in psychosine induced inflammation in astrocytes without directly affecting the cell death of oligodendrocytes. It also suggests that AMPK activating agents act as anti-inflammatory agents and can hold a therapeutic potential in Krabbe disease/twitcher disease, particularly when used in combination with drugs, which protect oligodendrocyte cell loss, such as sPLA2 inhibitor C1 [Singh, Avtar K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph Johnson Vet Affairs Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. [Giri, Shailendra; Khan, Mushfiquddin; Nath, Narender; Singh, Inderjit] Med Univ S Carolina, Dept Pediat, Charles P Darby Childrens Res Inst, Charleston, SC 29425 USA. RP Singh, AK (reprint author), Med Univ S Carolina, Dept Pathol & Lab Med, 516 Darby Childrens Res Inst, Charleston, SC 29425 USA. EM singhi@musc.edu FU NCRR NIH HHS [C06 RR018823]; NINDS NIH HHS [R01 NS022576, R37 NS022576, R01 NS040810-05, R01 NS040810, R01 NS037766-10, R01 NS037766, R01 NS034741-12, R01 NS034741, R01 NS022576-17, NS-40810, NS-37766, NS-34741, NS-22576] NR 56 TC 47 Z9 48 U1 2 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2008 VL 105 IS 5 BP 1820 EP 1833 DI 10.1111/j.1471-4159.2008.05279.x PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 300OQ UT WOS:000255835000022 PM 18248608 ER PT J AU Seminara, SB Crowley, WF AF Seminara, S. B. Crowley, W. F., Jr. TI Kisspeptin and GPR54: Discovery of a novel pathway in reproduction SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Review DE kisspeptin; GPR54; metastin; genetics; hypogonadotrophic hypogonadism ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; HORMONE-RELEASING ACTIVITY; RECEPTOR GPR54; KISS-1 PEPTIDE; GENE; MUTATIONS; PUBERTY; RAT; G-PROTEIN-COUPLED-RECEPTOR-54; EXPRESSION AB In order to find novel modulators of gonadotrophin-releasing hormone (GnRH) secretion, genetic tools were employed in patients with idiopathic hypogonadotrophic hypogonadism (IHH). Mutations in a G-protein coupled receptor, GPR54, were identified, making this receptor a genetic determinant and indisputable gatekeeper of normal reproductive function. This article places these investigations into historical context and reviews some of the new findings relevant to this pathway. C1 [Seminara, S. B.; Crowley, W. F., Jr.] Massachusetts Gen Hosp, Harvard Partners Reprod Sci Ctr, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Harvard Partners Reprod Sci Ctr, Reprod Endocrine Unit, Boston, MA 02114 USA. EM sseminara@partners.org FU NICHD NIH HHS [U54 HD028138, R01 HD015788, U54 HD028138-19, R01 HD043341] NR 31 TC 47 Z9 46 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD JUN PY 2008 VL 20 IS 6 BP 727 EP 731 DI 10.1111/j.1365-2826.2008.01731.x PG 5 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 311EG UT WOS:000256582900016 PM 18601695 ER PT J AU Coelho, T Waddington-Cruz, M Plante-Bordeneuve, V Cros, D Grogan, DR Packman, J AF Coelho, T. Waddington-Cruz, M. Plante-Bordeneuve, V. Cros, D. Grogan, D. Roy Packman, J. TI Correlation of clinical outcomes and disease burden in patients with transthyretin (TTR) amyloid polyneuropathy: study Fx-005, a landmark clinical trial of Fx-1006A, a novel small molecule TTR stabiliser SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 18th Meeting of the European-Neurological-Society CY JUN 07-11, 2008 CL Nice, FRANCE SP European Neurolog Soc C1 Hosp Santo Antonio, Oporto, Portugal. Hosp Univ Clementino Fraga Filho, Rio De Janeiro, Brazil. CHU Creteil, Paris, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. FoldRx Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 3 Z9 3 U1 1 U2 3 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD JUN PY 2008 VL 255 SU 2 MA P318 BP 78 EP 78 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 299HP UT WOS:000255747000283 ER PT J AU Waddington-Cruz, M Coelho, T Maia, L da Silva, AM Plante-Bordeneuve, V Suhr, O Campistol, J Conceicao, I Schmidt, H Trigo, P Cros, D Grogan, DR Packman, J AF Waddington-Cruz, M. Coelho, T. Maia, L. da Silva, A. Martins Plante-Bordeneuve, V. Suhr, O. Campistol, J. Conceicao, I. Schmidt, H. Trigo, P. Cros, D. Grogan, D. Roy Packman, J. TI A landmark clinical trial of a novel small molecule transthyretin (TTR) stabiliser, Fx-1006A, in patients with TTR amyloid polyneuropathy: a phase II/III, randomised, double-blind, placebo-controlled study SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 18th Meeting of the European-Neurological-Society CY JUN 07-11, 2008 CL Nice, FRANCE SP European Neurol Soc C1 Hosp Univ Clementino Fraga Filho, Rio De Janeiro, Brazil. Hosp Santo Antonio, Oporto, Portugal. CHU Creteil, Paris, France. Umea Univ Hosp, S-90185 Umea, Sweden. Hosp Clin Barcelona, Barcelona, Spain. Hosp Santa Maria, Lisbon, Portugal. Univ Klin Munster, Munster, Germany. FLENI, Buenos Aires, DF, Argentina. Massachusetts Gen Hosp, Boston, MA 02114 USA. FoldRx Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD JUN PY 2008 VL 255 SU 2 MA P432 BP 107 EP 107 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 299HP UT WOS:000255747000396 ER PT J AU Miller, SL Fenstermacher, E Bates, J Blacker, D Sperling, RA Dickerson, BC AF Miller, S. L. Fenstermacher, E. Bates, J. Blacker, D. Sperling, R. A. Dickerson, B. C. TI Hippocampal activation in adults with mild cognitive impairment predicts subsequent cognitive decline SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID SURFACE-BASED ANALYSIS; ALZHEIMERS-DISEASE; DIAGNOSTIC-CRITERIA; OLDER PERSONS; DEMENTIA; MRI; NEUROPATHOLOGY; AD; SEGMENTATION; ATROPHY AB Objective: To use functional MRI (fMRI) to investigate whether hippocampal activation during a memory task can predict cognitive decline in individuals with mild cognitive impairment (MCI). Methods: 25 older individuals with MCI performed a visual scene encoding task during fMRI scanning, and were followed clinically for at least 4 years after scanning. A hypothesis driven analysis of fMRI data was performed. First, fMRI data were analysed at the group level to identify the regions of the hippocampal formation that were engaged by this memory task. Parameter estimates of each subject's memory related hippocampal activation (% signal change) were extracted and were analysed with a linear regression model to determine whether hippocampal activation predicted the degree or rate of cognitive decline, as measured by change in Clinical Dementia Rating Sum-of-Boxes (CDR-SB). Results: Over 5.9 (1.2) years of follow-up after scanning, subjects varied widely in degree and rate of cognitive decline (change in CDR-SB ranged from 0 to 6, and the rate ranged from 0 to 1 CDR-SB unit/year). Greater hippocampal activation predicted greater degree and rate of subsequent cognitive decline (p < 0.05). This finding was present even after controlling for baseline degree of impairment (CDR-SB), age, education and hippocampal volume, as well as gender and apolipoprotein E status. In addition, an exploratory whole brain analysis produced convergent results, demonstrating that the hippocampal formation was the only brain region where activation predicted cognitive decline. Conclusions: In individuals with MCI, greater memory task related hippocampal activation is predictive of a greater degree and rate of cognitive decline subsequent to scanning. fMRI may provide a physiological imaging biomarker useful for identifying the subgroup of MCI individuals at highest risk of cognitive decline for potential inclusion in disease modifying clinical trials. C1 [Miller, S. L.; Fenstermacher, E.; Bates, J.; Blacker, D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Miller, S. L.; Fenstermacher, E.; Bates, J.; Blacker, D.; Sperling, R. A.; Dickerson, B. C.] Harvard Univ, Sch Med, Boston, MA USA. [Sperling, R. A.; Dickerson, B. C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Blacker, D.; Sperling, R. A.; Dickerson, B. C.] Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA. [Sperling, R. A.; Dickerson, B. C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Sperling, R. A.; Dickerson, B. C.] Brigham & Womens Hosp, Dept Neurol, Div Cognit & Behav Neurol, Boston, MA 02115 USA. RP Dickerson, BC (reprint author), Gerontol Res Unit, 149 13th St,Suite 2691, Charlestown, MA 02129 USA. EM bradd@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41 RR014075, P41-RR14075]; NIA NIH HHS [K23 AG022509, K23 AG022509-05, K23-AG22509, P01 AG004953, P01-AG04953, R01 AG029411, R01 AG029411-01A1, R01 AG029411-02]; NINDS NIH HHS [K23-NS02189, K23 NS002189] NR 39 TC 118 Z9 121 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JUN PY 2008 VL 79 IS 6 BP 630 EP 635 DI 10.1136/jnnp.2007.124149 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 302FS UT WOS:000255954800007 PM 17846109 ER PT J AU Behn, CGD Kopell, N Brown, EN Mochizuki, T Scammell, TE AF Behn, C. G. Diniz Kopell, N. Brown, E. N. Mochizuki, T. Scammell, T. E. TI Delayed orexin signaling consolidates wakefulness and sleep: Physiology and modeling SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID VENTROLATERAL PREOPTIC NUCLEUS; LOCUS-COERULEUS NEURONS; BASAL FOREBRAIN; REM-SLEEP; HYPOCRETIN/OREXIN NEURONS; WAKING CYCLE; OREXIN/HYPOCRETIN NEURONS; SUPRACHIASMATIC NUCLEUS; NORADRENALINE RELEASE; CIRCADIAN REGULATION AB Orexin-producing neurons are clearly essential for the regulation of wakefulness and sleep because loss of these cells produces narcolepsy. However, little is understood about how these neurons dynamically interact with other wake- and sleep-regulatory nuclei to control behavioral states. Using survival analysis of wake bouts in wild-type and orexin knockout mice, we found that orexins are necessary for the maintenance of long bouts of wakefulness, but orexin deficiency has little impact on wake bouts <1 min. Since orexin neurons often begin firing several seconds before the onset of waking, this suggests a surprisingly delayed onset (>1 min) of functional effects. This delay has important implications for understanding the control of wakefulness and sleep because increasing evidence suggests that different mechanisms are involved in the production of brief and sustained wake bouts. We incorporated these findings into a mathematical model of the mouse sleep/wake network. Orexins excite monoaminergic neurons and we hypothesize that orexins increase the monoaminergic inhibition of sleep-promoting neurons in the ventrolateral preoptic nucleus. We modeled orexin effects as a time-dependent increase in the strength of inhibition from wake- to sleep-promoting populations and the resulting simulated behavior accurately reflects the fragmented sleep/wake behavior of narcolepsy and leads to several predictions. By integrating neurophysiology of the sleep/wake network with emergent properties of behavioral data, this model provides a novel framework for investigating network dynamics and mechanisms associated with normal and pathologic sleep/wake behavior. C1 [Behn, C. G. Diniz; Mochizuki, T.; Scammell, T. E.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Behn, C. G. Diniz; Kopell, N.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Behn, C. G. Diniz; Kopell, N.] Univ Michigan, Ctr BioDynam, Ann Arbor, MI 48109 USA. [Brown, E. N.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Behn, CGD (reprint author), Univ Michigan, Dept Math, 2074 E Hall,530 Church St, Ann Arbor, MI 48109 USA. EM cdbehn@umich.edu RI Diniz Behn, Cecilia/L-1643-2013 FU NHLBI NIH HHS [HL-007901, HL-60292, P50 HL060292, T32 HL007901]; NIH HHS [DP1 OD003646, DP1OD003646]; NINDS NIH HHS [NS-055367, R01 NS055367, R01 NS055367-07] NR 64 TC 37 Z9 38 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 2008 VL 99 IS 6 BP 3090 EP 3103 DI 10.1152/jn.01243.2007 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 311XB UT WOS:000256632600032 PM 18417630 ER PT J AU Herrmann, P Druckrey-Fiskaaen, C Kouznetsova, E Heinitz, K Bigl, M Cotman, SL Schliebs, R AF Herrmann, Philipp Druckrey-Fiskaaen, Caroline Kouznetsova, Elena Heinitz, Katrin Bigl, Marina Cotman, Susan L. Schliebs, Reinhard TI Developmental impairments neurotransmitter systems in Cln3(Delta ex7/8) knock-in mice, an animal model of juvenile neuronal ceroid lipofuscinosis SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE neurodegenerative disease; neurodegeneration; mouse mutant; inflammation; immunocytochemical studies ID MITOCHONDRIAL ATP SYNTHASE; UNDERLYING BATTEN-DISEASE; NITRIC-OXIDE SYNTHASE; ALZHEIMERS-DISEASE; MOUSE MODEL; ARGININE TRANSPORT; GLIAL ACTIVATION; LYSOSOMAL PH; CLN3 PROTEIN; NOS-ISOFORMS AB The neuronal ceroidlipofuscinoses (NCL) are a group of neurodegenerative disorders and are the most common lysosomal storage diseases of infancy and childhood. Juvenile NCL is caused by CLN3 mutation, producing retinal degeneration, uncontrollable seizures, cognitive and motor decline, and early death before the age of 30 years. To study the pathogenetic mechanisms of the disease, Cln3 knock-in mice (Cln3(Delta ex-7/8)) have been generated, which reproduce the 1.02-kb deletion in the CLN3 gene observed in more than 85% of juvenile NCL patients. To characterize the impact of the common Cln3 mutation on development of auto-fluorescent storage material, gliosis, glucose metabolism, oxidative stress, and transmitter receptors during postnatal brain maturation, brain tissue of Cln3(Delta ex7/8) mice at the ages of 3, 4, 5, 6, 9, and 19 months was subjected to immunocytochemistry to label gliotic markers and nitric oxide synthases; photometric assays to assess enzyme activities of glycolysis and antioxidative defense systems; and level of reactive nitrogen species as well as quantitative receptor autoradiography to detect select cholinergic, glutamatergic, and GABAergic receptor subtypes. The developmental increase in cerebral cortical autofluorescent lipofuscin-like deposition is accompanied by a significant astro- and microgliosis, increased activities of lactate dehydrogenase and phosphofructokinase, decreased level of glutathione peroxidase, enhanced amount of reactive nitrogen species, and lowered binding levels of N-methyl-D-aspartate- and M1-muscarinic acetylcholine receptors in select brain regions but hardly in GABA(A) receptor sites compared with wild-type mice. Detailed elucidation of the sequence of pathological events during postnatal development highlights new potential strategies for symptomatic treatment of the disease. (c) 2008 Wiley-Liss, Inc. C1 [Herrmann, Philipp; Druckrey-Fiskaaen, Caroline; Kouznetsova, Elena; Heinitz, Katrin; Schliebs, Reinhard] Univ Leipzig, Dept Neurochem, Paul Flechsig Inst Brain Res, D-04109 Leipzig, Germany. [Bigl, Marina] Univ Leipzig, Inst Biochem, D-04109 Leipzig, Germany. [Cotman, Susan L.] Massachusetts Gen Hosp, Simches Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA. RP Schliebs, R (reprint author), Univ Leipzig, Dept Neurochem, Paul Flechsig Inst Brain Res, Jahnallee 59, D-04109 Leipzig, Germany. EM schre@medizin.uni-leipzig.de NR 65 TC 15 Z9 15 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0360-4012 EI 1097-4547 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUN PY 2008 VL 86 IS 8 BP 1857 EP 1870 DI 10.1002/jnr.21630 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 312CJ UT WOS:000256646400018 PM 18265413 ER PT J AU Erickson, JI Ditornassi, MO Jones, DA AF Erickson, Jeanette Ives Ditornassi, Marianne O. Jones, Dorothy A. TI Interdisciplinary Institute for Patient Care: Advancing clinical excellence SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID SHORTAGE C1 [Erickson, Jeanette Ives; Ditornassi, Marianne O.] Massachusetts Gen Hosp, Patient Care Serv Operat, Boston, MA 02114 USA. [Jones, Dorothy A.] Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Boston, MA 02114 USA. RP Ditornassi, MO (reprint author), Massachusetts Gen Hosp, Patient Care Serv Operat, 55 Fruit St,BUL 230, Boston, MA 02114 USA. EM mditomassi@partners.org NR 19 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD JUN PY 2008 VL 38 IS 6 BP 308 EP 314 DI 10.1097/01.NNA.0000312786.10965.5c PG 7 WC Nursing SC Nursing GA 313SD UT WOS:000256759400010 PM 18562836 ER PT J AU Sintuu, C Murray, SS Behnam, K Simon, R Jawien, J Silva, JD Duarte, ME Brochmann, EJ AF Sintuu, Chananit Murray, Samuel S. Behnam, Keyvan Simon, Robert Jawien, Janusz Prado Silva, Jose Denison Leite Duarte, Maria Eugenia Brochmann, Elsa J. TI Full-length bovine spp24 [spp24 (24-203)] inhibits BMP-2 induced bone formation SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE bone formation; spp24; bone morphogenetic protein ID MORPHOGENETIC PROTEIN; TRANSGENIC MICE; II RECEPTOR; OSTEOCALCIN; SEQUENCE; BINDING AB Secreted phosphoprotein 24 kDa (spp24) is a bone matrix protein. It contains a TGF-beta receptor II homology 1(TRH1) domain. A cyclic, synthetic 19 amino acid peptide (bone morphogenetic protein binding peptide or BBP) based on the sequence of the TRH1 domain enhances BMP-2 induced osteogenesis. Many observations suggest that different size forms of this protein have very different effects (inhibiting or enhancing) on BMP-2 induced osteogenesis. Using the stable recombinant Met(His)(6)-tagged secretory form of full-length (fl) bovine spp24 [Met(His)(6)-spp24 (residues 24-203)] and transgenic (TG) mice expressing fl bovine spp24 (residues 1-203), we have demonstrated that spp24 inhibits BMP-2 induced bone formation. The effects of Met(His)(6)-spp24 (24-203) were determined in the ectopic bone-forming bioassay in male mice. Implantation of 5 mu g of BMP-2 stimulated bone formation, assessed densitometrically as bone area and mineral content. When Met(His)(6)-spp24 (24-203) was implanted with BMP-2, it elicited a dose-dependent decrease in BMP-2-medicated ectopic bone formation. When added at a 50-fold excess (w/w), Met(His)(6)-spp24 (24-203) completely ablated the effects of BMP-2, while addition of a 10-fold excess had no effect. Constitutive expression of fl bovine spp24 (1-203) under the control of the osteocalcin promoter in TG female mice reduced femoral and vertebral bone mineral density at 3 months of age and reduced femoral BMD at 8 months of age, but had no effects in male mice, which can exhibit less osteocalcin-promoter driven gene transcription than females. Histomorphometric analysis demonstrated that bone volume and trabecular thickness were lower in TG female mice at 3 months of age than in sex- and age-matched wild type (WT) controls. Thus, fl spp24 and its secretory isoform (Met(His)(6)-spp24 [24-203]), which contain a BMP-binding or TRH1 motif, inhibit ectopic bone formation in male mice and adversely affects BMD and histological parameters related to bone mass and formation in female mice expressing the human transgene. Under these conditions, fl spp24 acts as a BMP antagonist in vivo. 2008 Orthopaedic Research Society.* Published by Wiley Periodicals, Inc. C1 [Murray, Samuel S.; Simon, Robert; Jawien, Janusz; Brochmann, Elsa J.] VA Greater Los Angeles Hlthcare Syst, Geriatr Res Educ & Clin Ctr 11 E, Sepulveda, CA 91343 USA. [Sintuu, Chananit] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90024 USA. [Murray, Samuel S.; Brochmann, Elsa J.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Behnam, Keyvan] Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90024 USA. [Prado Silva, Jose Denison] Univ Fed Alagoas, Dept Histol, BR-29222222 Maceio, AL, Brazil. [Leite Duarte, Maria Eugenia] Natl Inst Traumatol & Orthopaed, BR-20230020 Rio De Janeiro, Brazil. RP Murray, SS (reprint author), VA Greater Los Angeles Hlthcare Syst, Geriatr Res Educ & Clin Ctr 11 E, 16111 Plummer St, Sepulveda, CA 91343 USA. EM samuel.murray@med.va.gov FU NIAMS NIH HHS [5R21AR53259] NR 13 TC 19 Z9 20 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD JUN PY 2008 VL 26 IS 6 BP 753 EP 758 DI 10.1002/jor.20580 PG 6 WC Orthopedics SC Orthopedics GA 304FJ UT WOS:000256095100003 PM 18253966 ER PT J AU Hu, HM Zielinska-Kwiatkowska, A Munro, K Wilcox, J Wu, DY Yang, L Chansky, HA AF Hu, Hsien-Ming Zielinska-Kwiatkowska, Anna Munro, Karen Wilcox, Jason Wu, Daniel Y. Yang, Liu Chansky, Howard A. TI EWS/FLI1 suppresses retinoblastoma protein function and senescence in Ewing's sarcoma cells SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE Ewing's sarcoma; EWS/FLI1; retinoblastoma; senescence; cyclin D1 ID ONCOGENIC FUSION PROTEIN; DNA-BINDING; CYCLIN D1; GROWTH; GENE; EWS-FLI1; TRANSLOCATION; TRANSFORMATION; SUFFICIENT; FIBROBLAST AB Ewing's Family Tumors (EFTs) most commonly harbor a specific t(11;22) translocation that generates the EWS/FLI1 fusion protein responsible for malignant transformation. Many potential downstream targets of EWS/FLI1 have been identified but a detailed mechanism by which the fusion protein brings about transformation remains unknown. In this report, we show that depletion of EWS/FLI1 in Ewing's cell lines results in a senescence phenotype, a marked increase in expression of the G1/S regulatory proteins p27(kip1) and p57(kip2), and a significant decrease in cyclin D1 and CDK2. We also demonstrate for the first time, to our knowledge, that knockdown of EWS/FLI1 leads to hypophosphorylation and functional activation of the retinoblastoma (pRb) family of proteins. Consistent with activation of the pRb proteins, E2F-responsive genes such as cyclin A are repressed in EWS/FLI1-depleted cells. Together, these results support the role of EWS/LI1 as an inhibitor of cellular senescence and implicate the retinoblastoma family of proteins as key mediators of this inhibition. (C) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. C1 [Hu, Hsien-Ming; Zielinska-Kwiatkowska, Anna; Munro, Karen; Wilcox, Jason; Yang, Liu; Chansky, Howard A.] Univ Washington, Dept Orthopaed & Sports Med, Sch Med, Seattle, WA 98108 USA. [Wu, Daniel Y.] Univ Washington, Dept Med Oncol, Sch Med, Seattle, WA 98195 USA. [Wu, Daniel Y.; Chansky, Howard A.] VA Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98108 USA. RP Chansky, HA (reprint author), Univ Washington, Dept Orthopaed & Sports Med, Sch Med, 1660 S Columbian Way,ORT112, Seattle, WA 98108 USA. EM chansky@u.washington.edu FU NCI NIH HHS [R01 CA90941] NR 26 TC 17 Z9 19 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD JUN PY 2008 VL 26 IS 6 BP 886 EP 893 DI 10.1002/jor.20597 PG 8 WC Orthopedics SC Orthopedics GA 304FJ UT WOS:000256095100022 PM 18271016 ER PT J AU Blinderman, CD Hornel, P Billings, JA Portenoy, RK Tennstedt, SL AF Blinderman, Craig D. Hornel, Peter Billings, J. Andrew Portenoy, Russell K. Tennstedt, Sharon L. TI Symptom distress and quality of life in patients with advanced congestive heart failure SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE congestive heart failure; quality of life; symptom distress ID VENTRICULAR SYSTOLIC DYSFUNCTION; ELDERLY-PATIENTS; PREVALENCE; POPULATION; COMMUNITY; DISEASE; EPIDEMIOLOGY; ROTTERDAM; PROGNOSIS; SURVIVAL AB Little is known about the burden of illness associated with advanced congestive heart failure (CHF). Understanding the needs of this population requires further information about symptoms and other factors related to quality of life. We studied a convenience sample of 103 community-dwelling patients with New York Heart Association Class III/IV CHF. The primary outcome, quality of life, was measured with the Multidimensional Index of Life Quality. Potential correlates of quality of life included overall symptom burden (Memorial Symptom Assessment Scale, MSAS), including global symptom distress (MSAS Global Distress Index, GDI); psychological state (Mental Health Inventory-5); functional status (Sickness Impact Profile); spirituality (Functional Assessment of Chronic Illness Therapy-Spirituality Scale); and co-morbid conditions (Charlson Comorbidity Index). Patients had a mean age of 67.1 years (SD = 12.1); were mostly white (72.8%), male (71.8%), and married (51.5%); and had a mean ejection fraction of 22.3% (SD = 6 8). The most prevalent symptoms were lack of energy (66 %), dry mouth (62 %), shortness of breath (56 %), and drowsiness (52 %). Pain was reported by about one-third of patients. For each of these symptoms, high symptom-related distress was reported by 14.1%-54.1%. Quality of life was moderately compromised (Multidimensional Index of Life Quality composite, median = 56, possible range 12-84). Impairment in quality of life was strongly associated with global symptom distress (MSAS GDI; r = 0.74, P < 0.001); burden of comorbid conditions (r = -0.32, P = 0.002), female sex (r = -0.22, P = 0.03), functional impairment, particularly psychological impairment (r = -0.55, P < 0.001), and poorer psychological well-being (r = 0.68, P < 0.001). In multivariate analyses, impairment in quality of life was significantly related to high symptom distress, poorer psychological well-being, and poor functional mobility (R-2 = 0.67; P = 0.002 for all). Distressful symptoms related to impaired quality of life included lack of energy (P = 0.04), irritability (P = 0.03), and drowsiness (P = 0.02). Community-dwelling patients with advanced CHF experience numerous symptoms, significant symptom distress, and a compromised quality of life. Overall quality of life was strongly associated with symptom distress, psychological well-being and functional status. A focus on ameliorating prevalent physical symptoms and psychological distress, along with supportive measures that promote functional mobility, may lead to an improvement in the overall quality of life in this patient population. C1 [Blinderman, Craig D.; Billings, J. Andrew] Massachusetts Gen Hosp, Dept Med, Palliat Care Serv, Boston, MA 02114 USA. [Blinderman, Craig D.; Billings, J. Andrew] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. [Hornel, Peter; Portenoy, Russell K.] Beth Israel Deaconess Med Ctr, Dept Pain Med & Palliat Care, New York, NY 10003 USA. [Tennstedt, Sharon L.] New England Res Inst, Watertown, MA 02172 USA. RP Blinderman, CD (reprint author), Massachusetts Gen Hosp, Dept Med, Palliat Care Serv, Founder 600,55 Fruit St, Boston, MA 02114 USA. EM cblinderman@partners.org FU NINR NIH HHS [NR05154, R01 NR005154-01] NR 33 TC 107 Z9 109 U1 1 U2 8 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 JUN PY 2008 VL 35 IS 6 BP 594 EP 603 DI 10.1016/j.jpainsymman.2007.06.007 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 313FG UT WOS:000256725900006 PM 18215495 ER PT J AU Goy, ER Carter, JH Ganzini, L AF Goy, Elizabeth R. Carter, Julie H. Ganzini, Linda TI Needs and experiences of caregivers for family members dying with Parkinson disease SO JOURNAL OF PALLIATIVE CARE LA English DT Article ID COMPLICATED GRIEF; SYMPTOMS; PREDICTORS; BURDEN; SCALE; CARE AB The caregiver burdens and unmet needs of patients with Parkinson disease (PD) in the final months of life are poorly documented. We surveyed 47 family caregivers of PD patients a median of 18 months after death. We measured caregiver preparedness for their role, assistance provided the patient, and types and settings of care received by the patient. Typical caregivers were older female spouses. Though 66% of patients resided in a care facility during the last month, over half received care from hospice, 36% from a home health agency, and 43% by privately paid aide in the months before death. Caregivers rated tasks involving physical effort as most difficult. While most caregivers felt prepared for their role, one-third or more were unprepared for the stress and physical strain encountered. These data suggest that increasing education and assistance with physical tasks may address unmet needs of PID caregivers. C1 [Goy, Elizabeth R.; Ganzini, Linda] Portland VA Med Ctr, HSR&D, Res Career Dev Award Program, Portland, OR USA. [Goy, Elizabeth R.; Ganzini, Linda] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Goy, Elizabeth R.; Ganzini, Linda] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Ganzini, Linda] Oregon Hlth & Sci Univ, Div Geriatr Psychiat, Portland, OR 97201 USA. RP Goy, ER (reprint author), Portland VA Med Ctr, HSR&D, Res Career Dev Award Program, 66 POB 1034, Portland, OR USA. NR 13 TC 12 Z9 12 U1 0 U2 5 PU CENTER BIOETHICS CLIN RES INST MONTREAL PI MONTREAL PA 110 PINE AVE W, MONTREAL, QUEBEC H2W 1R7, CANADA SN 0825-8597 J9 J PALLIAT CARE JI J. Palliative Care PD SUM PY 2008 VL 24 IS 2 BP 69 EP 75 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 322UP UT WOS:000257401100002 PM 18681242 ER PT J AU Lorenz, K AF Lorenz, Karl TI Progress in measuring and improving palliative and end-of-life quality SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material ID CANCER CARE; INDICATORS C1 VA Greater Los Angeles Healthcare Syst, Vet Integrated Palliat Program, Los Angeles, CA 90073 USA. RP Lorenz, K (reprint author), VA Greater Los Angeles Healthcare Syst, Vet Integrated Palliat Program, 11301 Wilshire Blvd,Code 111-G, Los Angeles, CA 90073 USA. EM Karl.Lorenz@va.gov NR 16 TC 2 Z9 2 U1 0 U2 6 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 JUN PY 2008 VL 11 IS 5 BP 682 EP 684 DI 10.1089/jpm.2008.9906 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 324RG UT WOS:000257535100007 PM 18588397 ER PT J AU Volandes, AE Ariza, M Abbo, ED Paasche-Orlow, M AF Volandes, Angelo E. Ariza, Miguel Abbo, Elmer D. Paasche-Orlow, Michael TI Overcoming educational barriers for advance care planning in Latinos with video images SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; OF-LIFE; DECISION-MAKING; DIRECTIVES; PREFERENCES; ETHNICITY; POPULATION; ATTITUDES; PICTURES; RACE AB Background: Studies of end-of-life care have shown that Latino patients want more aggressive care compared to white patients. While this has been attributed to aspects of ethnicity, national origin, and religion, it is possible that limited education might obscure the true relationship between Latino patients and their end-of-life care preferences. Methods: Spanish-speaking subjects presenting to their primary care doctors were asked their preferences for end-of-life care before watching a video of advanced dementia. Subjects then viewed a 2-minute video of a patient with advanced dementia and were asked again about their preferences. Unadjusted and adjusted logistic regression models were fit using stepwise algorithms to examine factors related to preferences. Results: A total of 104 subjects completed the interview. Before seeing the video, 42 (40%) subjects preferred comfort care; 43 (41%) desired life-prolonging care; 11 (11%) chose limited care; and 8 (8%) were unsure of their preferences. Subject preferences changed significantly after the video: 78 (75%) of the subjects chose comfort care; 8 (8%) desired life-prolonging care; 14 (13%) chose limited care; and, 4 (4%) were unsure of their preferences (p < 0.001). Unadjusted and adjusted analyses revealed a statistically significant difference regarding prevideo preferences based on educational level. After the video, differences in preferences based on educational level disappeared. Conclusions: Educational level was an independent predictor of end-of-life preferences after hearing a verbal description of advanced dementia. After viewing a video of a patient with advanced dementia there were no longer any differences in the distribution of preferences according to educational level. These findings suggest that educational level is an important variable to consider in research and in patient care when communicating about end-of-life care preferences. While attention to patients' culture is important, it is also important to avoid ascribing choices to culture that may actually reflect inadequate comprehension. Attention to communication barriers with techniques like the video used in the current study may help ensure optimal end-of-life care for Latino patients irrespective of educational level. C1 [Volandes, Angelo E.] Massachusetts Gen Hosp, Gen Internal Med Unit, Boston, MA 02114 USA. [Ariza, Miguel; Paasche-Orlow, Michael] Boston Med Ctr, Dept Med, Boston, MA USA. [Abbo, Elmer D.] Univ Chicago, Dept Med, Gen Internal Med Sect, Chicago, IL 60637 USA. RP Volandes, AE (reprint author), Massachusetts Gen Hosp, Gen Internal Med Unit, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM avolandes@partners.org OI Paasche-Orlow, Michael/0000-0002-9276-7190 NR 23 TC 36 Z9 37 U1 4 U2 14 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 JUN PY 2008 VL 11 IS 5 BP 700 EP 706 DI 10.1089/jpm.2007.0172 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 324RG UT WOS:000257535100011 PM 18588401 ER PT J AU Volandes, AE Paasche-Orlow, M Gillick, MR Cook, EF Shaykevich, S Abbo, ED Lehmann, L AF Volandes, Angelo E. Paasche-Orlow, Michael Gillick, Muriel R. Cook, E. F. Shaykevich, Shimon Abbo, Elmer D. Lehmann, Lisa TI Health literacy not race predicts end-of-life care preferences SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; SHARED DECISION-MAKING; ADVANCE DIRECTIVES; SUSTAINING TREATMENTS; ATTITUDES; VIDEO; AID; COMMUNICATION; VACCINATION; ETHNICITY AB Background: Several studies have reported that African Americans are more likely than whites to prefer aggressive treatments at the end of life. Objective: Since the medical information presented to subjects is frequently complex, we hypothesized that apparent differences in end-of-life preferences and decision making may be due to disparities in health literacy. A video of a patient with advanced dementia may overcome communication barriers associated with low health literacy. Design: Before and after oral survey. Participants: Subjects presenting to their primary care doctors. Methods: Subjects were asked their preferences for end-of-life care after they heard a verbal description of advanced dementia. Subjects then viewed a 2-minute video of a patient with advanced dementia and were asked again about their preferences. For the analysis, preferences were dichotomized into comfort care and aggressive care. Health literacy was measured using the Rapid Estimate of Adult Literacy in Medicine (REALM) and subjects were divided into three literacy categories: low (0-45, sixth grade and below), marginal (46-60, seventh to eighth grade) and adequate (61-66, ninth grade and above). Unadjusted and adjusted logistic regression models were fit using stepwise algorithms to examine factors related to initial preferences before the video. Results: A total of 80 African Americans and 64 whites completed the interview. In unadjusted analyses, African Americans were more likely than whites to have preferences for aggressive care after the verbal description, odds ratio (OR) 4.8 ( 95% confidence interval [CI] 2.1-10.9). Subjects with low or marginal health literacy were also more likely than subjects with adequate health literacy to have preferences for aggressive care after the verbal description, OR 17.3 (95% CI 6.0-49.9) and OR 11.3 (95% CI 4.2-30.8) respectively. In adjusted analyses, health literacy (low health literacy: OR 7.1, 95% CI 2.1-24.2; marginal health literacy OR 5.1, 95% CI 1.6-16.3) but not race (OR 1.1, 95% CI 0.3-3.2) was an independent predictor of preferences after the verbal description. After watching a video of advanced dementia, there were no significant differences in the distribution of preferences by race or health literacy. Conclusions: Health literacy and not race was an independent predictor of end-of-life preferences after hearing a verbal description of advanced dementia. In addition, after viewing a video of a patient with advanced dementia there were no longer any differences in the distribution of preferences according to race and health literacy. These findings suggest that clinical practice and research relating to end-of-life preferences may need to focus on a patient education model incorporating the use of decision aids such as video to ensure informed decision-making. C1 [Volandes, Angelo E.] Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. [Paasche-Orlow, Michael] Boston Med Ctr, Dept Med, Boston, MA USA. [Gillick, Muriel R.] Harvard Univ, Sch Med, Boston, MA USA. [Cook, E. F.; Shaykevich, Shimon] Brigham & Womens Hosp, Boston, MA 02115 USA. [Abbo, Elmer D.] Univ Chicago, Dept Med, Gen Internal Med Sect, Chicago, IL 60637 USA. RP Volandes, AE (reprint author), Massachusetts Gen Hosp, Gen Med Unit, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM avolandes@partners.org OI Paasche-Orlow, Michael/0000-0002-9276-7190 NR 36 TC 85 Z9 86 U1 1 U2 10 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD JUN PY 2008 VL 11 IS 5 BP 754 EP 762 DI 10.1089/jpm.2007.0224 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 324RG UT WOS:000257535100018 PM 18588408 ER PT J AU Chang, HL Rosenberg, AE Friedmann, AM Ryan, DP Masiakos, PT AF Chang, Henry L. Rosenberg, Andrew E. Friedmann, Alison M. Ryan, Daniel P. Masiakos, Peter T. TI Primary pulmonary rhabdomyosarcoma in a 5-month-old boy - A case report SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE primary pulmonary rhabdomyosarcoma; anaplasia; pediatric pulmonary tumors ID CYSTIC ADENOMATOID MALFORMATION; INTERGROUP-RHABDOMYOSARCOMA AB Primary pulmonary rhabdomyosarcoma (RMS) in the pediatric population is a rare entity. A 5-month-old boy initially treated for pneumonia was proven to have a primary pulmonary RMS, which was resected via thoracotomy. After a course of chemotherapy following the Children's Oncology Group low-risk RMS protocol (ARST0331), a restaging chest computerized tomography scan showed local recurrence, which was also resected by open thoracotomy. The patient is currently undergoing local radiotherapy and salvage chemotherapy regimen. This patient is the youngest reported to date with this entity. The prognostic significance of his young age and the morphologic findings of his tumor are unclear. C1 [Chang, Henry L.; Ryan, Daniel P.; Masiakos, Peter T.] Massachusetts Gen Hosp Children, Dept Surg, Div Pediat Surg, Boston, MA USA. [Friedmann, Alison M.] Massachusetts Gen Hosp Children, Dept Pediat, Div Pediat Hematol Oncol, Boston, MA USA. [Rosenberg, Andrew E.] Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Masiakos, PT (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Pediat Surg, 55 Fruit St,WRN 11, Boston, MA 02114 USA. EM pmasiakos@partners.org FU NCI NIH HHS [U10 CA098543] NR 10 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD JUN PY 2008 VL 30 IS 6 BP 461 EP 463 DI 10.1097/MPH.0b013e318165b2b1 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 310NB UT WOS:000256535200010 PM 18525465 ER PT J AU Monica, JT Waters, PM Bae, DS AF Monica, James T. Waters, Peter M. Bae, Donald S. TI Radial Nerve Palsy in the Newborn A Report of Four Cases and Literature Review SO JOURNAL OF PEDIATRIC ORTHOPAEDICS LA English DT Article DE neonatal radial nerve palsy; brachial plexus birth palsy; intrauterine compression ID BRACHIAL-PLEXUS; PRESSURE; ULNAR; BAND; ARM AB Background: Radial nerve palsy in the neonate is a rare clinical entity but must be distinguished from the more common brachial plexus birth palsy which occurs during the perinatal period. Although longer term upper-limb function following brachial plexus birth palsy is highly variable depending on the extent of neurological involvement, sparse reports of neonates with radial nerve palsy have nearly universal spontaneous recovery with normal upper-limb function. Methods: We report 4 cases of patients born with findings consistent with radial nerve palsy. Results: All 4 cases of neonatal radial nerve palsy supported a common etiology of intrauterine compression and resulted in spontaneous recovery of radial nerve function. Conclusion: Neonatal radial nerve palsy should be suspected in newborns presenting with absent wrist and digital extension but intact deltoid, biceps, and triceps function with wrist and digital flexor function. The presence of ecchymosis and/or fat necrosis along the posterolateral brachium may support the notion that neonatal radial nerve palsy is caused by a compression injury during or before labor. Complete spontaneous recovery of radial nerve function may be anticipated if there is no associated infectious or constriction band pathology. C1 [Monica, James T.; Waters, Peter M.; Bae, Donald S.] Harvard Univ, Sch Med, Childrens Hosp, Dept Orthopaed Surg, Boston, MA USA. RP Monica, JT (reprint author), Massachusetts Gen Hosp, Orthopaed Teaching Off, White 535,55 Fruit St, Boston, MA 02114 USA. EM jmonica@partners.org NR 15 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-6798 J9 J PEDIATR ORTHOPED JI J. Pediatr. Orthop. PD JUN PY 2008 VL 28 IS 4 BP 460 EP 462 PG 3 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA 392EQ UT WOS:000262286100013 PM 18520284 ER PT J AU Steigman, SA Armant, M Bayer-Zwirello, L Kao, GS Silberstein, L Ritz, J Fauza, DO AF Steigman, Shaun A. Armant, Myriam Bayer-Zwirello, Lucy Kao, Grace S. Silberstein, Leslie Ritz, Jerome Fauza, Dario O. TI Preclinical regulatory validation of a 3-stage amniotic mesenchyma stem cell manufacturing protocol SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the American-Academy-of-Pediatrics CY OCT 27-30, 2007 CL San Francisco, CA SP Amer Acad Pediat DE amniotic fluid; mesenchymal amniocytes; amniocytes; mesenchymal stem cells; fetal cells; tissue engineering; fetal tissue engineering; cell therapy; cryopreservation; fetus ID PROGENITOR CELLS; FETAL; FLUID; AMNIOCYTES; RECONSTRUCTION AB Purpose: Because of the 4 to 6-month interval between a diagnostic amniocentesis and birth, clinical application of amniotic mesenchymal stem cell (AMSC)-based therapies demands a 3-stage cell manufacturing process, including isolation/primary expansion, cryopreservation, and thawing/secondary expansion. We sought to determine the feasibility and cell yield of such a staged cell manufacturing process, within regulatory guidelines. Methods: Human AMSCs isolated from diagnostic amniocentesis samples (n = 11) were processed under Food and Drug Administration-accredited good manufacturing practice. Expanded cells were characterized by flow cytometry and cryopreserved for 3 to 5 months. Cell release criteria included more than 90% CD29+, CD73+, and CD44+; less than 5% CD34+ and CD45+; negative mycoplasma quantitative polymerase chain reaction (QPCR) and endotoxin assay; and at least 70% viability. Results: Isolation and ample expansion of AMSCs was achieved in 54.5% (6/11) of the samples. Early processing and at least a 2-mL sample were necessary for reliable cell manufacturing. Cell yield before cryopreservation was 223.2 +/- 65.4 x 10(6) cells (44.6-fold expansion), plus a 14.7 x 10(6)-cell backup, after 36.3 +/- 7.8 days. Cell viability postthaw was 88%. Expanded cells maintained a multipotent mesenchymal progenitor profile. Conclusions: Human amniotic mesenchymal stem cells can be manufactured in large numbers from diagnostic amniocentesis, by an accredited staged processing, under definite procurement guidelines. These data further support the viability of clinical trials of amniotic mesenchymal stem cell-based therapies. (C) 2008 Elsevier Inc. All rights reserved. C1 [Steigman, Shaun A.; Fauza, Dario O.] Harvard Univ, Sch Med, Dept Surg, Childrens Hosp Boston, Boston, MA 02115 USA. [Armant, Myriam; Kao, Grace S.; Silberstein, Leslie; Ritz, Jerome] Harvard Univ, Sch Med, CBR Inst Biomed Res, Ctr Human Cell Therapy, Boston, MA 02115 USA. [Bayer-Zwirello, Lucy] Tufts Univ, Sch Med, Caritas St Elizabeths Med Ctr, Boston, MA 02135 USA. [Fauza, Dario O.] Harvard Univ, Sch Med, Childrens Hosp Boston, Adv Fetal Care Ctr, Boston, MA 02135 USA. RP Fauza, DO (reprint author), Harvard Univ, Sch Med, Dept Surg, Childrens Hosp Boston, Boston, MA 02115 USA. EM dario.fauza@childrens.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 FU NHLBI NIH HHS [U24 HL074355-02, U24 HL074355-03, U24 HL074355-01A1, U24 HL074355, U24 HL074355-04] NR 16 TC 28 Z9 30 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JUN PY 2008 VL 43 IS 6 BP 1164 EP 1169 DI 10.1016/j.jpedsurg.2008.02.052 PG 6 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 326CR UT WOS:000257636000046 PM 18558201 ER PT J AU Gao, BB Chen, XH Timothy, N Aiello, LP Feener, EP AF Gao, Ben-Bo Chen, Xiaohong Timothy, Nigel Aiello, Lloyd Paul Feener, Edward P. TI Characterization of the vitreous proteome in diabetes without diabetic retinopathy and diabetes with proliferative diabetic retinopathy SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE proliferative diabetic retinopathy; human vitreous; LC-MS/MS; quantitative proteomics; kallikrein-kinin system; extracellular matrix ID ENDOTHELIAL GROWTH-FACTOR; DECOY SEARCH STRATEGY; SUBCELLULAR-LOCALIZATION; GEL-ELECTROPHORESIS; MASS-SPECTROMETRY; SOLUBLE-PROTEINS; ANGIOGENESIS; EXPRESSION; ACID; RESOURCE AB An understanding of the diabetes-induced alterations in vitreous protein composition in the absence and in the presence of proliferative diabetic retinopathy (PDR) may provide insights into factors and mechanisms responsible for this disease. We have performed a comprehensive proteomic analysis and comparison of vitreous samples from individuals with diabetes but without diabetic retinopathy (noDR) or with PDR and nondiabetic individuals (NDM). Using preparative one-dimensional SIDS-PAGE and nano-LC/MS/MS of 17 independent vitreous samples, we identified 252 proteins from human vitreous. Fifty-six proteins were differentially abundant in noDR and PDR vitreous compared with NDM vitreous, including 32 proteins increased and 10 proteins decreased in PDR vitreous compared with NDM vitreous. Comparison of noDR and PDR groups revealed increased levels of angiotensinogen and decreased levels of calsyntenin-1, interphotoreceptor retinoid-binding protein, and neuroserpin in PDR vitreous. Biological pathway analysis revealed that vitreous contains 30 proteins associated with the kallikrein-kinin, coagulation, and complement systems. Five of them (complement C3, complement factor 1, prothrombin, alpha-l-antitrypsin, and antithrombin III) were increased in PDR vitreous compared with NDM vitreous. Factor XII was detected in PDR vitreous but not observed in either NDM or noDR vitreous. PDR vitreous also had increased levels of peroxiredoxin-1 and decreased levels of extracellular superoxide dismutase, compared with noDR or NDM vitreous. These data provide an in depth analysis of the human vitreous proteome and reveal protein alterations that are associated with PDR. C1 [Gao, Ben-Bo; Chen, Xiaohong; Aiello, Lloyd Paul; Feener, Edward P.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Gao, Ben-Bo; Feener, Edward P.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Timothy, Nigel; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. [Aiello, Lloyd Paul] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. RP Feener, EP (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM edward.feener@joslin.harvard.edu FU NIDDK NIH HHS [DK 36836, P30 DK036836, DK 60165] NR 34 TC 94 Z9 99 U1 0 U2 7 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 JUN PY 2008 VL 7 IS 6 BP 2516 EP 2525 DI 10.1021/pr800112g PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 311KL UT WOS:000256599000034 PM 18433156 ER PT J AU Milad, MR Orr, SP Lasko, NB Chang, YC Rauch, SL Pitman, RK AF Milad, Mohammed R. Orr, Scott P. Lasko, Natasha B. Chang, Yuchiao Rauch, Scott L. Pitman, Roger K. TI Presence and acquired origin of reduced recall for fear extinction in PTSD: Results of a twin study SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE stress disorders; post-traumatic; fear; conditioning; classical; galvanic skin response; memory; twins; monozygotic ID POSTTRAUMATIC-STRESS-DISORDER; VENTROMEDIAL PREFRONTAL CORTEX; CORTICOLIMBIC BLOOD-FLOW; COMBAT EXPOSURE; PSYCHOPHYSIOLOGICAL ASSESSMENT; FACIAL EXPRESSIONS; HUMANS; MEMORY; RESPONSES; VETERANS AB Recall of fear extinction, which is thought to aid in recovery from a psychologically traumatic event, is hypothesized to be deficient in post-traumatic stress disorder (PTSD), but this has not yet been demonstrated in the laboratory, nor has its origin been investigated. To address these two issues, 14 pairs of monozygotic twins discordant for combat exposure, in 7 of which the combat-exposed twin had PTSD, underwent a two-day fear conditioning and extinction procedure. On Day 1, subjects viewed colored light conditioned stimuli, some of which were paired with mild electric shock, followed by extinction of the conditioned responses. On Day 2, recall of Day I extinction learning (i.e., extinction retention) was assessed. Skin conductance response (SCR) was the dependent measure. There were no group differences during acquisition or extinction learning. However, a significant PTSD Diagnosis (in the exposed twin) x combat Exposure interaction emerged during extinction recall, with the PTSD combat veterans having larger SCRs than their own co-twins, and than the non-PTSD combat veterans and their co-twins. These results indicate that retention of extinction of conditioned fear is deficient in PTSD. Furthermore, they support the conclusion that this deficit is acquired as a result of combat trauma leading to PTSD, rather than being a predisposing factor to developing PTSD upon the stress of combat. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Milad, Mohammed R.; Orr, Scott P.; Lasko, Natasha B.; Rauch, Scott L.; Pitman, Roger K.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Milad, Mohammed R.; Orr, Scott P.; Lasko, Natasha B.; Rauch, Scott L.; Pitman, Roger K.] Harvard Univ, Sch Med, Boston, MA USA. [Orr, Scott P.] Vet Affairs Med Ctr, Res Serv, Manchester, NH USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Rauch, Scott L.] McLean Hosp, Belmont, MA 02178 USA. RP Milad, MR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Blgd 149,13th St,2nd Floor, Charlestown, MA 02129 USA. EM milad@nmr.harvard.edu FU NIMH NIH HHS [2R01MH54636, R01 MH054636, R01 MH054636-09] NR 35 TC 189 Z9 191 U1 3 U2 23 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 JUN PY 2008 VL 42 IS 7 BP 515 EP 520 DI 10.1016/j.jpsychires.2008.01.017 PG 6 WC Psychiatry SC Psychiatry GA 294RU UT WOS:000255424000001 PM 18313695 ER PT J AU Matthews, JD Blais, M Park, L Welch, C Baity, M Murakami, J Sklarsky, K Homberger, C Fava, M AF Matthews, John D. Blais, Mark Park, Lawrence Welch, Charles Baity, Matthew Murakami, Jessica Sklarsky, Katherine Homberger, Caitlin Fava, Maurizio TI The impact of galantamine on cognition and mood during electroconvulsive therapy: A pilot study SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE electroconvulsive therapy (ECT); acetylcholinesteras inhibitors; galantamine (reminyl); nicotinic receptor ID PLACEBO-CONTROLLED TRIAL; ACETYLCHOLINE-RECEPTORS; MEMORY; ECT; DEPRESSION; RETROGRADE; AD AB Objectives: The purpose of this study was to: (1) assess the effectiveness of galantamine in the prevention of cognitive impairments during ECT treatment and (2) to explore the safety and tolerability of galantamine during ECT treatment. Methods: Nine consecutive ECT patients were given galantamine 4 mg bid throughout the course of their ECT treatments followed by a second cohort of eight consecutive ECT patients who did not receive galantamine. Objective measures of cognitive functioning and depression severity were performed pre-ECT and post-ECT. Subjective ratings of depression, confusion, and side effects were obtained weekly. Results: The two groups were similar in age, gender and admission Global Assessment Functioning (GAF) scores. There were no significant between group differences found with regards to mean seizure duration, energy administered to induce seizures, blood pressure, or heart rate during and post-ECT treatment. None of the patients discontinued galantamine due to side effects and there were no severe adverse drug reactions. Patients receiving galantamine performed significantly better on delayed memory and abstract reasoning following ECT. The galantamine group showed a greater but non-significant mood improvement (repeated measure ANOVA). Conclusions: Our data support the hypothesis that galantamine may reduce cognitive impairment during ECT, especially with regards to new learning. In addition, galantamine may also enhance the antidepressant action of ECT. Galantamine was both safe and well tolerated during ECT. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Matthews, John D.; Blais, Mark; Park, Lawrence; Welch, Charles; Baity, Matthew; Murakami, Jessica] Massachusetts Gen Hosp, Inpatient Psychiat Serv, Boston, MA 02114 USA. [Sklarsky, Katherine; Homberger, Caitlin; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Matthews, JD (reprint author), Massachusetts Gen Hosp, Inpatient Psychiat Serv, 55 Fruit St,Warren 1220, Boston, MA 02114 USA. EM jdmatthews@partners.org NR 28 TC 8 Z9 8 U1 0 U2 0 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 JUN PY 2008 VL 42 IS 7 BP 526 EP 531 DI 10.1016/j.jpsychires.2007.06.002 PG 6 WC Psychiatry SC Psychiatry GA 294RU UT WOS:000255424000003 PM 17681545 ER PT J AU Nery, FG Hatch, JP Glahn, DC NiColetti, MA Monkul, ES Najt, P Fonseca, M Bowden, CL Cloninger, CR Soares, JC AF Nery, Fabiano G. Hatch, John P. Glahn, David C. NiColetti, Mark A. Monkul, E. Serap Najt, Pablo Fonseca, Manoela Bowden, Charles L. Cloninger, C. Robert Soares, Jair C. TI Temperament and character traits in patients with bipolar disorder and associations with comorbid alcoholism or anxiety disorders SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article; Proceedings Paper CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat DE bipolar disorder; personality; comorbidity; alcoholism; anxiety disorders; psychopathology ID TRIDIMENSIONAL PERSONALITY QUESTIONNAIRE; MANIC-DEPRESSIVE PATIENTS; PSYCHIATRIC-DISORDERS; MAJOR DEPRESSION; HARM AVOIDANCE; DIMENSIONS; INVENTORY; PROFILE; STATE; TCI AB Temperament and character traits may determine differences in clinical presentations and outcome of bipolar disorder. We compared personality traits in bipolar patients and healthy individuals using the Temperament and Character Inventory (TCI) and sought to verify whether comorbidity with alcoholism or anxiety disorders is associated with specific personality traits. Seventy-three DSM-IV bipolar patients were compared to 63 healthy individuals using the TCI. In a second step, the bipolar sample was subgrouped according to the presence of psychiatric comorbidity (alcoholism, n = 10; anxiety disorders; n = 23; alcoholism plus anxiety disorders, n = 21; no comorbidity, n = 19). Bipolar patients scored statistically higher than the healthy individuals on novelty seeking, harm avoidance and self-transcendence and lower on self-directedness and cooperativeness. Bipolar patients with only comorbid alcoholism scored statistically lower than bipolar patients without any comorbidity on persistence. Bipolar patients with only comorbid anxiety disorders scored statistically higher on harm avoidance and lower on self-directedness than bipolar patients without any comorbidity. Limitations of this study include the cross-sectional design and the small sample size, specifically in the analysis of the subgroups. However, our results suggest that bipolar patients exhibit a different personality structure than healthy individuals and that presence of psychiatric comorbidity in bipolar disorder is associated with specific personality traits. These findings suggest that personality, at least to some extent, mediates the comorbidity phenomena in bipolar disorder. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Soares, Jair C.] Univ N Carolina, Sch Med, Dept Psychiat, CERT BD, Chapel Hill, NC 27599 USA. [Nery, Fabiano G.; Hatch, John P.; Glahn, David C.; NiColetti, Mark A.; Monkul, E. Serap; Najt, Pablo; Fonseca, Manoela; Bowden, Charles L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Nery, Fabiano G.; NiColetti, Mark A.; Monkul, E. Serap; Najt, Pablo; Fonseca, Manoela] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Nery, Fabiano G.] Univ Sao Paulo, Sch Med, Dept Psychiat, Bipolar Disorder Res Program, Sao Paulo, Brazil. [Hatch, John P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Orthodont, San Antonio, TX 78229 USA. [Monkul, E. Serap] Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. [Cloninger, C. Robert] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. RP Soares, JC (reprint author), Univ N Carolina, Sch Med, Dept Psychiat, CERT BD, 10616 Neurosci Hosp CB 7160, Chapel Hill, NC 27599 USA. EM jsoares@med.unc.edu RI Cloninger, Claude/F-5357-2012 OI Cloninger, Claude/0000-0003-3096-4807 FU NCRR NIH HHS [K24 RR020571, K24 RR020571-01A1, K24 RR020571-02, K24 RR020571-03, K24 RR020571-04, K24 RR020571-05, M01 RR001346, M01-RR-01346, RR020571]; NIMH NIH HHS [P20 MH068662, K23 MH001736, K23 MH001736-05, MH 01736, MH 068662, MH 068766, R01 MH068766, R01 MH068766-01A2, R01 MH068766-02, R01 MH068766-03, R01 MH068766-04, R01 MH068766-05] NR 42 TC 43 Z9 44 U1 3 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JUN PY 2008 VL 42 IS 7 BP 569 EP 577 DI 10.1016/j.jpsychires.2007.06.004 PG 9 WC Psychiatry SC Psychiatry GA 294RU UT WOS:000255424000008 PM 17675066 ER PT J AU Hinton, DE Chhean, D Hofmann, SG Orr, SP Pitman, RK AF Hinton, Devon E. Chhean, Dara Hofmann, Stefan G. Orr, Scott P. Pitman, Roger K. TI Dizziness- and palpitations-predominant orthostatic panic: Physiology, flashbacks, and catastrophic cognitions SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE orthostatic challenge; panic disorder; PTSD; finapres; blood pressure; Cambodian; cross-cultural psychiatry ID POSTTRAUMATIC-STRESS-DISORDER; ADMINISTERED PTSD SCALE; CAMBODIAN REFUGEES; POSTURAL CHANGE; CARDIOVASCULAR-RESPONSE; BEHAVIOR THERAPY; CO2 INHALATION; ANXIETY; ATTACKS; DYSREGULATION AB In an orthostatic challenge, Cambodian patients with orthostatic panic in the last month (OP patients) sometimes panicked during orthostatic challenge, whereas those without orthostatic panic in the last month (NOP patients) did not. Also, OP patients with primarily dizziness during orthostatic challenge panic (OPOCP-D) had a less vigorous physiological response than two other groups: (a) OP patients with primarily palpitations during orthostatic challenge panic (OPOCP-P) and (b) NOP patients who had no symptoms during orthostatic challenge (NOPNOCP-NS). Among the patients experiencing orthostatic challenge-induced panic (i.e., the OPOCP-D and OPOCP-P patients), there were prominent orthostatic challenge-induced flashbacks and catastrophic cognitions, and the severity of orthostatic challenge-induced flashbacks and catastrophic cognitions correlated with the severity of orthostatic panic in the previous month and with the severity of orthostatic challenge-induced panic. C1 [Hinton, Devon E.; Pitman, Roger K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Hinton, Devon E.; Chhean, Dara] SW Asian Clin, Lowell, MA USA. [Hofmann, Stefan G.] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. [Orr, Scott P.] Vet Affairs Med Ctr, Manchester, NH USA. RP Hinton, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM devon_hinton@hms.harvard.edu RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 NR 52 TC 3 Z9 4 U1 2 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD JUN PY 2008 VL 30 IS 2 BP 100 EP 110 DI 10.1007/s10862-007-9059-8 PG 11 WC Psychology, Clinical SC Psychology GA 296JK UT WOS:000255539100003 ER PT J AU Auba, E Kagan, L Huertas, PE AF Auba, E. Kagan, L. Huertas, P. E. TI Pregnancy outcome in a Mind-Body medicine group intervention for women with infertility. Preliminary data SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Meeting Abstract C1 [Auba, E.; Kagan, L.; Huertas, P. E.] Massachusetts Gen Hosp, Benson Henry Inst, Boston, MA USA. [Auba, E.] Univ Navarra, Univ Hosp, Dept Psychiat, Pamplona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD JUN PY 2008 VL 64 IS 6 MA 10 BP 637 EP 638 PG 2 WC Psychiatry SC Psychiatry GA 309JA UT WOS:000256455300022 ER PT J AU Maserejian, NN Trachtenberg, F Link, C Tavares, M AF Maserejian, Nancy Nairi Trachtenberg, Felicia Link, Carol Tavares, Mary TI Underutilization of dental care when it is freely available: A prospective study of the New England Children's Amalgam Trial SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE utilization; disparities; dental care delivery; dental care for children; oral health ID ORAL-HEALTH; BEHAVIORAL-MODEL; NATIONAL SURVEYS; MEDICAL-CARE; ACCESS; DISPARITIES; SCHOOLCHILDREN; SERVICES; PROGRAM; EXPERIENCE AB Objective: This study aims to prospectively examine the trends and reasons for the underutilization of free semiannual preventive dental care provided to children with unmet dental needs who participated in the 5-year New England Children's Amalgam Trial. Methods: Children aged 6 to 10 at baseline (1997-99) with >= 2 posterior carious teeth were recruited from rural Maine (n = 232) and urban Boston (n = 266). Interviewer-administered questionnaires assessed demographic and personal characteristics. Reasons for missed appointments were recorded during follow-up and are descriptively presented. We used an ordinal logistic regression to analyze the utilization of semiannual dental visits. Results: On average, urban children utilized 69 percent of the visits and rural children utilized 82 percent of the visits. For both sites, utilization steadily decreased until the end of the 5-year trial. Significant predictors of underutilization in the multivariate model for urban children were non-White race, household welfare use, deep debt, and distance to dental clinic. Among the relatively less-diverse rural children, caregiver education level and a greater number of decayed tooth surfaces at baseline (i.e., need for care) were significantly associated with underutilization. Among all children, the common reasons for missed visits included guardian scheduling and transportation difficulties; reasons among urban participants also indicated a low priority for dental care. Conclusions: Among these children with unmet dental needs, the provision of free preventive dental care was insufficient to remove the disparities in utilization and did not consistently result in high utilization through follow-up. Differences between educational levels, ethnicities, and rural/urban location suggest that public health programs need to target the social settings in which financial burdens exist. C1 [Maserejian, Nancy Nairi] New England Res Inst, Watertown, MA 02472 USA. [Tavares, Mary] Forsyth Inst, Boston, MA USA. RP Maserejian, NN (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM nmaserejian@neriscience.com FU NIDCR NIH HHS [U01 DE11886] NR 35 TC 16 Z9 16 U1 0 U2 2 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD SUM PY 2008 VL 68 IS 3 BP 139 EP 148 DI 10.1111/j.1752-7325.2007.00074.x PG 10 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 347OO UT WOS:000259151100005 PM 18248343 ER PT J AU Hall, DE Meador, KG Koenig, HG AF Hall, Daniel E. Meador, Keith G. Koenig, Harold G. TI Measuring religiousness in health research: Review and critique SO JOURNAL OF RELIGION & HEALTH LA English DT Review DE religiousness; spirituality; measurement; philosophy; worldview ID WELL-BEING SCALE; SPIRITUAL EXPERIENCE; NONDISABLED PERSONS; INITIAL DEVELOPMENT; CONSTRUCT-VALIDITY; CANCER-PATIENTS; UNITED-STATES; MENTAL-HEALTH; ITEM SCALES; ORIENTATION AB Although existing measures of religiousness are sophisticated, no single approach has yet emerged as a standard. We review the measures of religiousness most commonly used in the religion and health literature with particular attention to their limitations, suggesting that vigilance is required to avoid over-generalization. After placing the development of these scales in historical context, we discuss measures of religious attendance, private religious practice, and intrinsic/extrinsic religious motivation. We also discuss measures of religious coping, wellbeing, belief, affiliation, maturity, history, and experience. We also address the current trend in favor of multi-dimensional and functional measures of religiousness. We conclude with a critique of the standard, "context-free" approach aimed at measuring "religiousness-in-general", suggesting that future work might more fruitfully focus on developing ways to measure religiousness in specific, theologically relevant contexts. C1 [Hall, Daniel E.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Hall, Daniel E.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Meador, Keith G.; Koenig, Harold G.] Duke Univ, Med Ctr, Durham, NC USA. [Koenig, Harold G.] Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC 27705 USA. RP Hall, DE (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. EM hallde@upmc.edu RI Koenig, Harold/F-7379-2011; Hall, Daniel/H-4843-2013; OI Hall, Daniel/0000-0001-6382-0522 NR 140 TC 74 Z9 75 U1 5 U2 35 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-4197 J9 J RELIG HEALTH JI J. Relig. Health PD JUN PY 2008 VL 47 IS 2 BP 134 EP 163 DI 10.1007/s10943-008-9165-2 PG 30 WC Public, Environmental & Occupational Health; Religion SC Public, Environmental & Occupational Health; Religion GA 299HQ UT WOS:000255747100002 PM 19105008 ER PT J AU Cherry, JA Hou, X Rueda, BR Davis, JS Townson, DH AF Cherry, Jessica Ann Hou, Xiaoying Rueda, Bo Ruben Davis, John Stewart Townson, David Harrison TI Microvascular endothelial cells of the bovine corpus luteum: A comparative examination of the estrous cycle and pregnancy SO JOURNAL OF REPRODUCTION AND DEVELOPMENT LA English DT Article DE bovine; corpus luteum; cytokine; enclothelial cell; lectin ID NECROSIS-FACTOR-ALPHA; MONOCYTE CHEMOATTRACTANT PROTEIN-1; SIMULATED EARLY-PREGNANCY; INTERFERON-GAMMA; GROWTH-FACTOR; CORPORA-LUTEA; SURFACE GLYCOPROTEINS; MENSTRUAL-CYCLE; KAPPA-B; EXPRESSION AB Endothelial cells derived from the corpus luteum (CLENDOs) exhibit diverse characteristics presumably serving their wide-ranging roles in luteal function and fate. Here, several attributes of CLENDOs derived from cows at midcycle (days 9-12 of the estrous cycle) were compared with CLENDOs from early pregnancy (day 60 of pregnancy). Flow cytometric analysis of cells fluorescently-tagged with the lectins Bandeiraea simplicifolia (BS-1) and Concanavalin A (ConA) indicated that CLENDOs of midcycle CL do not differ from those of pregnancy. Mean fluorescence intensity for BS-1 was 15 +/- 1 and 23 +/- 7 fluorescent units for midcycle CLENDOs and CLENDOs of pregnancy, respectively (P > 0.05). For ConA, mean fluorescence was 25 2 and 26 1 fluorescent units, respectively (P > 0.05). The CLENDCs were also exposed to cytokines to assess differences in activation of nuclear factor kappa B signaling (NF-kappa B), induction of the transcription factor interferon regulatory factor 1 (IRF1), cytokine production, and cytokine-induced cell death. In response to TNF, for instance, both types of CLENDOs exhibited a rapid, 5-fold decrease in NF-kappa B inhibitor alpha (NFKBIA) protein expression (P < 0.05), and a 4-fold increase in IRF1 expression (P < 0.05), that did not differ with phenotype (P > 0.05). Similarly, both types of CLENDCs produced tumor necrosis factor alpha and chemokine ligand 2 in response to IFNG stimulation (P < 0.05) that did not differ with phenotype (P > 0.05). Lastly, extended exposure of CLENDOs of midcycle CL to cytokines induced cell death (similar to 50% cell death vs. control) similar to the incidence of cell death seen previously in CLENDOs of early pregnancy. The results indicate that several physical and functional characteristics of CLENDOs of midcycle CL are retained through early pregnancy, including lectin-binding properties, sensitivity to cytokines, and the activation of cytokine-initiated intracellular signals. C1 [Cherry, Jessica Ann; Townson, David Harrison] Univ New Hampshire, Dept Anim & Nutr Sci, Durham, NH 03824 USA. [Hou, Xiaoying; Davis, John Stewart] Univ Nebraska Med Ctr, Vet Affairs Med Ctr, Omaha, NE 68198 USA. [Hou, Xiaoying; Davis, John Stewart] Univ Nebraska Med Ctr, Olson Ctr Womens Hlth, Omaha, NE 68198 USA. [Rueda, Bo Ruben] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. RP Townson, DH (reprint author), Univ New Hampshire, Dept Anim & Nutr Sci, Durham, NH 03824 USA. EM dave.townson@unh.edu FU NICHD NIH HHS [HD 48754, HD 35934] NR 48 TC 5 Z9 5 U1 0 U2 2 PU SOCIETY REPRODUCTION & DEVELOPMENT-SRD PI TSUKUBA PA C/O KAZUHIRO KIKUCHI, PHD DVM, NATL INST AGROBIOLOGICAL SCIENCES KANNONDAI 2-1-2, TSUKUBA, IBARAKI 305-8602, JAPAN SN 0916-8818 J9 J REPROD DEVELOP JI J. Reprod. Dev. PD JUN PY 2008 VL 54 IS 3 BP 183 EP 191 DI 10.1262/jrd.19182 PG 9 WC Agriculture, Dairy & Animal Science; Reproductive Biology SC Agriculture; Reproductive Biology GA 318ZQ UT WOS:000257131800006 PM 18296866 ER PT J AU Lyamin, OI Lapierre, JL Kosenko, PO Mukhametov, LM Siegel, JM AF Lyamin, Oleg I. Lapierre, Jennifer L. Kosenko, Peter O. Mukhametov, Lev M. Siegel, Jerome M. TI Electroencephalogram asymmetry and spectral power during sleep in the northern fur seal SO JOURNAL OF SLEEP RESEARCH LA English DT Article DE asymmetry index; eeg asymmetry; northern fur seal; pinnipedia; spectral analysis; unihemispheric sleep ID SLOW-WAVE SLEEP; UNILATERAL CORTICAL APPLICATION; INTERHEMISPHERIC EEG ASYMMETRY; UNIHEMISPHERIC SLEEP; WAKING; RAT; DEPRIVATION; STIMULATION; WAKEFULNESS; PATTERNS AB The fur seal (Callorhinus ursinus), a member of the Pinniped family, displays a highly expressed electroencephalogram (EEG) asymmetry during slow wave sleep (SWS), which is comparable with the unihemispheric sleep in cetaceans. In this study, we investigated the EEG asymmetry in the fur seal using spectral analysis. Four young (2-3 years old) seals were implanted with EEG electrodes for polygraphic sleep recording. In each animal, EEG spectral power in the frequency range of 1.2-16 Hz was computed in symmetrical cortical recordings over two consecutive nights. The degree of EEG asymmetry was measured by using the asymmetry index [AI = (L - R)/(L + R), where L and R are the spectral powers in the left and right hemispheres, respectively]. In fur seals, EEG asymmetry, as measured by the percent of 20-s epochs with absolute AI > 0.3 and > 0.6, was expressed in the entire frequency range (1.2-16 Hz). The asymmetry was significantly greater during SWS (25.6-44.2% of all SWS epochs had an absolute AI > 0.3 and 2.1-12.2% of all epochs had AI > 0.6) than during quiet waking (11.0-20.3% and 0-1.9% of all waking epochs, respectively) and REM sleep (4.2-8.9% of all REM sleep epochs and no epochs, respectively). EEG asymmetry was recorded during both low- and high-voltage SWS, and was maximal in the range of 1.2-4 and 12-16 Hz. As shown in this study, the degree of EEG asymmetry and the frequency range in which it is expressed during SWS in fur seals are profoundly different from those of terrestrial mammals and birds. C1 Univ Calif Los Angeles, Sepulveda, CA USA. VA GLAHS, Sepulveda, CA USA. [Lyamin, Oleg I.; Kosenko, Peter O.; Mukhametov, Lev M.] Utrish Dolphinarium Ltd, Moscow, Russia. RP Lyamin, OI (reprint author), VA GLAHS Sepulveda, Neurobiol Res 151A3,16111 Plummer St, North Hills, CA USA. EM olyamin@ucla.edu NR 40 TC 21 Z9 21 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0962-1105 J9 J SLEEP RES JI J. Sleep Res. PD JUN PY 2008 VL 17 IS 2 BP 154 EP 165 DI 10.1111/j.1365-2869.2008.00639.x PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 300OR UT WOS:000255835300005 PM 18482104 ER PT J AU Ishizuka, S Kurihara, N Hiruma, Y Miura, D Namekawa, JI Tamura, A Kato-Nakamura, Y Nakano, Y Takenouchi, K Hashimoto, Y Nagasawa, K Roodman, GD AF Ishizuka, Seiichi Kurihara, Noriyoshi Hiruma, Yuko Miura, Daishiro Namekawa, Jun-ichi Tamura, Azusa Kato-Nakamura, Yuko Nakano, Yusuke Takenouchi, Kazuya Hashimoto, Yuichi Nagasawa, Kazuo Roodman, G. David TI 1 alpha,25-dihydroxyvitamin D(3)-26,23-lactam analogues function as vitamin D receptor antagonists in human and rodent cells SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE vitamin D receptor antagonist; 1 alpha,25-dihydroxyvitamin D(3)-26,23-lactam analogues; HL-60 cell differentiation; osteoclast formation; gene expression ID PROMYELOCYTIC LEUKEMIA-CELLS; INHIBITS OSTEOCLAST FORMATION; CARBOXYLIC ESTER ANTAGONISTS; BONE-MARROW CULTURES; PAGETS-DISEASE; D-3-26,23-LACTONE ANALOGS; 1,25-DIHYDROXYVITAMIN D-3; MOLECULAR-MECHANISM; HL-60 CELLS; DIFFERENTIATION AB (23S,25S)-N-Benzyl-1 alpha,25-dihydroxyvitamin D(3)-26,23-lactam ((23S,25S)-N-benzyl-1 alpha,25-(OH)(2)D(3)-26,23-lactam, (23S,25S)-DLAM-1P) antagonizes nuclear vitamin D receptor (VDR)-mediated differentiation of human promyelocytic leukemia (HL-60) cells [Y. Kato, Y. Nakano, H. Sano, A. Tanatani, H. Kobayashi, R. Shimazawa, H. Koshino, Y. Hashimoto, K. Nagasawa, Synthesis of 1 alpha,25-dihydroxy vitamin D(3)-26,23-lactams (DLAMs), a novel series of 1 alpha,25-dihydroxy vitamin D(3) antagonist, Bioorg. Med. Chem. Lett. 14 (2004) 2579-2583]. To enhance its VDR antagonistic actions, we synthesized multiple analogues of 1 alpha,25-(OH)(2)D(3)-26,23-lactam. Among these analogues, (23S,25S)-N-phenetyl-1 alpha,25-(OH)(2)D(3)-26,23-lactam, ((23S,25S)-DLAM-2P) had the strongest VDR binding affinity, which was 3 times higher than that of (23S,25S)-DLAM-1P. The 1 alpha,25-(OH)(2)D(3)-26,23-lactam analogues never induced HL-60 cell differentiation even at 10(-6) M, but (23S,25S)-DLAM-1P and (23S,25S)-DLAM-2P significantly and dose-dependently inhibited HL-60 differentiation induced by 10(-8) M 1 alpha,25-dihydroxyvitamin D(3) (1 alpha,25-(OH)(2)D(3)). These compounds also inhibited human and mouse cultures of osteoclast formation by marrow cells treated with 1 alpha,25-(CH)(2)D(3)- Moreover, the 1 alpha,25-(OH)(2)D(3)-26,23-lactam analogues minimally induced 25-hydroxyvitamin D(3)-24-hydroxylase gene expression in HL-60 cells and human and mouse osteoblastic cells, but 10(-6) M (23S,25S)-DLAM-1P or (23S,25S)-DLAM-2P significantly blocked 24-hydroxylase gene expression induced by 10(-8) M 1 alpha,25-(OH)(2)D(3). (23S,25S)-DIAM-2P was 5-12 times more potent as a vitamin D antagonist than (23S,25S)-DLAM-1P in HL-60 cells, human and mouse bone marrow cultures. These results demonstrate that (23S,25S)-DLAM-1P and (23S,25S)-DLAM-2P antagonize HL-60 cell differentiation and osteoclast formation by human and mouse osteoclast precursors induced by 1 alpha,25-(OH)(2)D(3) through blocking VDR-mediated gene transcription. In contrast, (23S)-25-deoxy-1 alpha-thydroxyvitamin D(3)-26,23-lactone, which only blocks human VDR, these vitamin D antagonists can block VDR in human cells and rodent cells. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Ishizuka, Seiichi; Miura, Daishiro; Namekawa, Jun-ichi; Tamura, Azusa; Kato-Nakamura, Yuko; Takenouchi, Kazuya] Teijin Inst Biomed Res, Hino, Tokyo 1918512, Japan. [Ishizuka, Seiichi; Kurihara, Noriyoshi; Hiruma, Yuko; Roodman, G. David] Univ Pittsburgh, Sch Med, Div Hematol Oncol, Pittsburgh, PA 15261 USA. [Nakano, Yusuke; Hashimoto, Yuichi] Univ Tokyo, Inst Mol & Cell Biosci, Bunkyo Ku, Tokyo 110031, Japan. [Nagasawa, Kazuo] Tokyo Univ Agr & Technol, Fac Technol, Dept Biotechnol & Life Sci, Koganei, Tokyo 1848588, Japan. [Roodman, G. David] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu RI Nagasawa, Kazuo/B-9959-2013 FU NIAMS NIH HHS [P01 AR 049363, P01 AR049363, P01 AR049363-05] NR 30 TC 7 Z9 7 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD JUN PY 2008 VL 110 IS 3-5 BP 269 EP 277 DI 10.1016/j.jsbmb.2007.11.007 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 326DY UT WOS:000257639600010 PM 18501591 ER PT J AU Pettinati, HM Kampman, KM Lynch, KG Suh, JJ Dackis, CA Oslin, DW O'Brien, CP AF Pettinati, Helen M. Kampman, Kyle M. Lynch, Kevin G. Suh, Jesse J. Dackis, Charles A. Oslin, David W. O'Brien, Charles P. TI Gender differences with high-dose naltrexone in patients with co-occurring cocaine and alcohol dependence SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 14-19, 2003 CL Bal Harbour, FL SP Coll Problems Drug Dependence DE naltrexone; cocaine dependence; alcohol dependence; CBT; BRENDA; adverse events ID RELAPSE PREVENTION TREATMENT; RANDOMIZED CONTROLLED-TRIAL; ADDICTION SEVERITY INDEX; PLACEBO-CONTROLLED TRIAL; SEX-DIFFERENCES; SELF-REPORTS; BEHAVIORAL PHARMACOLOGY; ETHANOL INGESTION; DRINKING BEHAVIOR; CONCURRENT USE AB This is a randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy of a higher-than-typical daily dose of naltrexone (150 mg/day), taken for 12 weeks, in 164 patients (n = 116 men and n = 48 women) with co-occurring cocaine and alcohol dependence. Patients were stratified by gender and then randomly assigned to either naltrexone or placebo, and to either cognitive-behavioral therapy or a type of medical management. The two primary outcomes were cocaine use and alcohol use. Significant Gender x Medication interactions were found for cocaine use via urine drug screens (three way, with time) and self-reports (two way) for drug severity (two way) and alcohol use (two way). The type of psychosocial treatment did not affect outcomes. Thus, 150 mg/day naltrexone added to a psychosocial treatment resulted in reductions in cocaine and alcohol use and drug severity in men, compared to higher rates of cocaine and alcohol use and drug severity in women. (C) 2008 Elsevier Inc. All rights reserved. C1 [Pettinati, Helen M.; Kampman, Kyle M.; Lynch, Kevin G.; Suh, Jesse J.; Dackis, Charles A.; Oslin, David W.; O'Brien, Charles P.] Univ Penn, Sch Med, Dept Psychiat, Ctr Study Addict, Philadelphia, PA 19104 USA. [Oslin, David W.; O'Brien, Charles P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Pettinati, HM (reprint author), Univ Penn, Dept Psychiat, Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM pettinati_h@mail.trc.upenn.edu FU NIDA NIH HHS [P60 DA005186-13S10014, P50 DA012756, P50 DA012756-02, P50 DA012756-03, P50 DA012756-09, P50 DA012756-099001, P50 DA12756, P60 DA005186, P60 DA005186-110014, P60 DA005186-120014, P60 DA005186-130014, P60 DA005186-140014, P60 DA005186-14S10014, P60 DA005186-150014, P60 DA05186] NR 74 TC 39 Z9 40 U1 4 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD JUN PY 2008 VL 34 IS 4 BP 378 EP 390 DI 10.1016/j.jsat.2007.05.011 PG 13 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 301JO UT WOS:000255892400002 PM 17664051 ER PT J AU Fowler, CG King, JL AF Fowler, Cynthia G. King, Jennifer L. TI Sudden Bilateral Sensorineural Hearing Loss Following Speedballing SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Article DE Autoimmune; bilateral hearing loss; cocaine; cochlear pathology; drug abuse; heroin; otoacoustic emissions; recreational drugs; sensorineural hearing loss; sudden hearing loss ID HEROIN; COCAINE; ADDICTS AB Background: Hearing loss is an infrequently-reported consequence of recreational drug abuse. Although there are sporadic reports of hearing loss from heroin and cocaine ingested separately, there are no reports of hearing loss resulting from the combination of both drugs ingested simultaneously in the form of speedballing. Purpose: The purpose of this report is to document a case of bilateral sensorineural hearing loss associated with an episode of speedballing. Research Design: Case Report Data Collection and Analysis: The subject of this report was a 40-year-old man with a 20-year history of substance abuse. Data collected included a case history, pure tone audiometry, tympanometry and acoustic reflexes, and transient evoked otoacoustic emissions. Results: The audiologic evaluation indicated a mild to moderate, relatively flat, bilateral sensorineural hearing loss that was worse in the right ear. Conclusions: A bilateral sensorineural hearing loss involving both cochlear and neural pathology may be a rare complication of cocaine, heroin, or the combination of the two drugs. C1 [Fowler, Cynthia G.] Univ Wisconsin, Dept Communicat Disorders, Madison, WI 53706 USA. [King, Jennifer L.] Vet Affairs Greater Los Angeles Healthcare Syst, San Luis Obispo Community Based Outpatient Ctr, San Luis Obispo, CA USA. RP Fowler, CG (reprint author), Univ Wisconsin, Dept Communicat Disorders, 1975 Willow Dr, Madison, WI 53706 USA. EM cgfowler@wisc.edu NR 18 TC 8 Z9 10 U1 0 U2 2 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD JUN PY 2008 VL 19 IS 6 BP 461 EP 464 DI 10.3766/jaaa.19.6.2 PG 4 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 386IF UT WOS:000261876200002 PM 19253779 ER PT J AU Wilens, TE Boellner, SW Lopez, FA Turnbow, JM Wigal, SB Childress, AC Abikoff, HB Manos, MJ AF Wilens, Timothy E. Boellner, Samuel W. Lopez, Frank A. Turnbow, John M. Wigal, Sharon B. Childress, Ann C. Abikoff, Howard B. Manos, Michael J. TI Varying the wear time of the methylphenidate transdermal system in children with attention-deficit/hyperactivity disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE methylphenidate transdermal system; stimulants; attention-deficit/hyperactivity disorder ID DEFICIT-HYPERACTIVITY DISORDER; ONCE-A-DAY; OROS METHYLPHENIDATE; ADHD; ADULTS; TRIAL AB Objective: Children with attention-deficit/hyperactivity disorder often have varying needs for coverage of their symptoms throughout the day. The objectives of this study were to determine the efficacy, duration of action, and safety of methylphenidate transdermal system worn for variable times by children (ages 6-12) diagnosed with ADHD. Method: Methylphenidate dose was optimized over 5 weeks using 10-, 15-, 20-, or 30-mg patches worn for 9 hours. The efficacy of 4- and 6-hour wear times was then assessed in an Analog Classroom setting during a randomized, placebo-controlled, double-blind, three-way crossover phase. The main efficacy measures were the Swanson, Kotkin, Agler, M-Flynn, and Pelham Rating Scale deportment scale and the Permanent Product Measure of Performance math test. Results: All of the efficacy measures indicated that 4- and 6-hour wear times improved ADHD symptoms and that medication effects on the Swanson, Kotkin, Agler, M-Flynn, and Pelham Rating Scale deportment scale and Permanent Product Measure of Performance math test decreased between 2 and 4 hours after patch removal. The majority of adverse events were transient and mild to moderate in severity. Conclusions: These findings suggest that the duration of medication effect is related to the wear time of the patch and may be tailored to accommodate the schedules of patients. C1 [Wilens, Timothy E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Wigal, Sharon B.] Univ Calif Irvine, Irvine, CA 92717 USA. [Abikoff, Howard B.] NYU, New York, NY 10003 USA. [Manos, Michael J.] Cleveland Clin, Cleveland, OH USA. RP Wilens, TE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit, 32 Fruit St,Suite YAW 6A, Boston, MA 02114 USA. EM twilens@partners.org NR 26 TC 33 Z9 33 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2008 VL 47 IS 6 BP 700 EP 708 DI 10.1097/CHI.0b013e31816bffdf PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 304LM UT WOS:000256111000013 PM 18434918 ER PT J AU Donovan, AL AF Donovan, Abigail L. TI Doing child and adolescent psychotherapy: Adapting psychodynamic treatment to contemporary practice, 2nd edition SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Donovan, Abigail L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Donovan, AL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM adonovan@partners.org NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2008 VL 47 IS 6 BP 724 EP 725 DI 10.1097/01.CHI.0000270814.63259.ff PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 304LM UT WOS:000256111000019 ER PT J AU Favero, M AF Favero, Marcus TI The sandbox investment SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Favero, Marcus] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Favero, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mfavero@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2008 VL 47 IS 6 BP 725 EP 726 DI 10.1097/01.CHI.0000313970.01502.aa PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 304LM UT WOS:000256111000020 ER PT J AU Kimball, AB Gladman, D Gelfand, JM Gordon, K Horn, EJ Korman, NJ Korver, G Krueger, GG Strober, BE Lebwohl, MG AF Kimball, Alexa B. Gladman, Dafna Gelfand, Joel M. Gordon, Kenneth Horn, Elizabeth J. Korman, Neil J. Korver, Gretchen Krueger, Gerald G. Strober, Bruce E. Lebwohl, Mark G. CA Natl Psoriasis Fdn TI National Psoriasis Foundation clinical consensus on psoriasis comorbidities and recommendations for screening SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Review ID TUMOR-NECROSIS-FACTOR; INFLAMMATORY-BOWEL-DISEASE; TOTAL KNEE ARTHROPLASTY; POPULATION-BASED COHORT; CORONARY-HEART-DISEASE; TRIOXSALEN BATH PUVA; NON-HODGKIN-LYMPHOMA; A RADIATION PUVA; QUALITY-OF-LIFE; CARDIOVASCULAR-DISEASE AB There have been several articles and reports in recent months about comorbidities and risks that affect psoriasis patients in addition to their underlying disease. This piece reviews the current literature and begins to address what should be done with this new information by updating the clinician about what health screening tests, preventative exams, and referrals should be considered in this population. C1 [Kimball, Alexa B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kimball, Alexa B.] Brigham & Womens Hosp, Boston, MA 02114 USA. [Kimball, Alexa B.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Korver, Gretchen; Krueger, Gerald G.] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. [Lebwohl, Mark G.] Mt Sinai Sch Med, New York, NY USA. [Gladman, Dafna] Toronto Western Hosp, Ctr Prognosis Studies, Univ Hlth Network, Toronto Western Res Inst,Psoriat Arthritis Progra, Toronto, ON M5T 2S8, Canada. [Gelfand, Joel M.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Gelfand, Joel M.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Gordon, Kenneth] Evanston NW Hlthcare, Div Dermatol, Skokie, IL USA. [Strober, Bruce E.] Case Western Reserve Univ Hosp, Cleveland, OH USA. [Lebwohl, Mark G.] NYU, Ronald O Perelman Dept Dermatol, New York, NY 10003 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, 50 Staniford St 246, Boston, MA 02114 USA. EM harvardskinstudies@partners.org FU NIAMS NIH HHS [K23 AR051125, K23AR051125-01] NR 143 TC 194 Z9 199 U1 0 U2 7 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 JUN PY 2008 VL 58 IS 6 BP 1031 EP 1042 DI 10.1016/j.jaad.2008.01.006 PG 12 WC Dermatology SC Dermatology GA 303QO UT WOS:000256055800015 PM 18313171 ER PT J AU Murrell, DE Dick, S Ahmed, AR Amagai, M Barnadas, MA Borradori, L Bystryn, JC Cianchini, G Diaz, L Fivenson, D Hall, R Harman, KE Hashimoto, T Hertl, M Hunzelmann, N Iranzo, P Joly, P Jonkman, ME Kitajima, Y Korman, NJ Martin, LK Mimouni, D Pandya, AG Payne, AS Rubenstein, D Shimizu, H Sinha, AA Sirois, D Zillikens, D Werth, VP AF Murrell, Dedee E. Dick, Sarah Ahmed, A. R. Amagai, Masayuki Barnadas, Maria A. Borradori, Luca Bystryn, Jean-Claude Cianchini, Giuseppe Diaz, Luis Fivenson, David Hall, Russell Harman, Karen E. Hashimoto, Takashi Hertl, Michael Hunzelmann, Nico Iranzo, Pilar Joly, Pascal Jonkman, Marcel E. Kitajima, Yasuo Korman, Neil J. Martin, Linda K. Mimouni, Daniel Pandya, Amit G. Payne, Aimee S. Rubenstein, David Shimizu, Hiroshi Sinha, Animesh A. Sirois, David Zillikens, Detlef Werth, Victoria P. TI Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article AB Our scientific knowledge of pemphigus has dramatically progressed in recent years. However, despite the availability of various therapeutic options for the treatment of inflammatory diseases, only a few multicenter controlled trials have helped to define effective therapies in pemphigus. A major obstacle in comparing therapeutic outcomes between centers is the lack of generally accepted definitions and measurements for the clinical evaluation of patients with pemphigus. Common terms and end points of pemphigus are needed so that experts in the field can accurately measure and assess disease extent, activity, severity, and therapeutic response, and thus facilitate and advance clinical trials. This consensus statement from the International Pemphigus Committee represents 2 years of collaborative efforts to attain mutually acceptable common definitions for pemphigus. These should assist in development of consistent reporting of outcomes in future studies. C1 [Dick, Sarah; Payne, Aimee S.; Werth, Victoria P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19119 USA. [Murrell, Dedee E.; Martin, Linda K.] Univ New S Wales, St Georges Hosp, Dept Dermatol, Sydney, NSW, Australia. [Amagai, Masayuki] Keio Univ, Sch Med, Tokyo, Japan. [Barnadas, Maria A.] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Borradori, Luca] Univ Geneva, Hop Cantonal, CH-1211 Geneva, Switzerland. [Bystryn, Jean-Claude] NYU, Med Ctr, New York, NY 10016 USA. [Diaz, Luis] Univ N Carolina, Chapel Hill, NC USA. [Hall, Russell] Duke Univ, Med Ctr, Div Dermatol, Durham, NC 27710 USA. [Harman, Karen E.] Univ Hosp Leicester, Leicester, Leics, England. [Hashimoto, Takashi] Kurume Univ, Sch Med, Kurume, Fukuoka, Japan. [Hashimoto, Takashi] Univ Giessen Klinikum, Giessen, Germany. [Hashimoto, Takashi] Marburg GmbH, Marburg, Germany. [Hunzelmann, Nico] Univ Klin Koln, Cologne, Germany. [Iranzo, Pilar] Univ Barcelona, Hosp Clin, E-08007 Barcelona, Spain. [Jonkman, Marcel E.] Univ Groningen, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands. [Kitajima, Yasuo] Gifu Univ, Sch Med, Gifu, Japan. [Korman, Neil J.] Univ Hosp, Case Med Ctr Cleveland, Cleveland, OH USA. [Mimouni, Daniel] Rabin Med Ctr, Petah Tiqwa, Israel. [Pandya, Amit G.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Shimizu, Hiroshi] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan. [Zillikens, Detlef] Med Univ Lubeck, D-23538 Lubeck, Germany. [Werth, Victoria P.] Vet Affairs Med Ctr, Philadelphia Dept, Philadelphia, PA USA. [Ahmed, A. R.] New England Baptist Hosp, Ctr Blistering Dis, Dept Med, Boston, MA USA. [Cianchini, Giuseppe] IRCCS, Inst Dermopact Immacolata, Immunodermatol Dept, Rome, Italy. [Joly, Pascal] Hop Charles Nicolle, Dermatol Clin, Rouen, France. [Sinha, Animesh A.] Michigan State Univ, Ctr Invest Dermatol, Div Dermatol & Cutaneous Sci, E Lansing, MI 48824 USA. [Sirois, David] NYU, Dept Oral Med, New York, NY 10003 USA. RP Werth, VP (reprint author), Univ Penn, Dept Dermatol, 2 Rhodes Pavill,3600 Spruce St, Philadelphia, PA 19119 USA. EM werth@mail.med.upenn.edu RI Zillikens, Detlef/C-8572-2011; Cianchini, Giuseppe/I-8877-2012; Amagai, Masayuki/K-5325-2013 OI Amagai, Masayuki/0000-0003-3314-7052 FU NIAMS NIH HHS [K08 AR053505, K24 AR002207, K24 AR002207-06A2, K24-AR 02207] NR 1 TC 193 Z9 202 U1 0 U2 12 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 JUN PY 2008 VL 58 IS 6 BP 1043 EP 1046 DI 10.1016/j.jaad.2008.01.012 PG 4 WC Dermatology SC Dermatology GA 303QO UT WOS:000256055800016 PM 18339444 ER PT J AU Bordelanou, L Vagefi, PA Sahani, D Deshpande, V Ralchlin, E Warshaw, AL Castillo, CFD AF Bordelanou, Liliana Vagefi, Parsia A. Sahani, Dushyant Deshpande, Vikrarn Ralchlin, Elena Warshaw, Andrew L. Castillo, Carlos Ferndndez-del TI Cystic pancreatic endocrine neoplasms: A distinct tumor type? SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID SEROUS CYSTADENOMA; GLUCAGONOMA; FEATURES; ADENOMA AB BACKGROUND: Cystic pancreatic endocrine neoplasms (CPENs) are considered rare, and their behavior is thought to be similar to that of solid pancreatic endocrine neoplasms (PENs). This study aims to describe the characteristics of CPENs in a large patient cohort. STUDY DESIGN: We performed a retrospective review of 170 patients who underwent resections for PENs at Massachusetts General Hospital from 1977 to 2006. Twenty-nine patients (51% men, mean age 53) with CPENs were compared with 141 patients with solid PENs. Differences in clinical presentation, pathologic and radiographic features, and survival were described. RESULTS: CPENs comprised 17% of all PENs (29 of 170) and 5.4% of all resected cystic pancreatic neoplasms(29 of 535). Ten (34%) were purely cystic and 19 (66%) were partially cystic. Compared with solid PENs, CPENs were larger (49 mm versus 23.5 mm, p < 0.05), more likely symptomatic (73% versus 45%, p < 0.05), and more likely nonfunctional (80% versus 50%, p < 0.05). They expressed synaptophysin (100%), chromogranin (82%), and cyrokeratin (CK)-19 (24%). Multiple endocrine neoplasia type 1 (MEN-1) was 3.5 times more common in CPENs than in solid tumors (2 1 % versus 6%, p < 0.05). No significant difference was found in location, propensity for metastasis, invasion, or 5-year survival (87% versus 77%, p = 0.38). CONCLUSIONS: This series, the largest report of CPENs in the literature, shows that CPENs are more common than previously thought, so they should be included in the differential of the cystic lesions of the pancreas. CPENs are larger and more likely to be symptomatic then solid PENs. They are also more likely to be associated with MEN-1 and to be nonfunctional, suggesting they may be a distinct tumor type. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Castillo, CFD (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,ACC 460, Boston, MA 02114 USA. NR 23 TC 44 Z9 46 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2008 VL 206 IS 6 BP 1154 EP 1158 DI 10.1016/j.jamcollsurg.2007.12.040 PG 5 WC Surgery SC Surgery GA 310EO UT WOS:000256511900009 PM 18501813 ER PT J AU Billingsley, KG Morris, AM Green, P Dominitz, JA Matthews, B Dobie, SA Barlow, W Baldwin, LM AF Billingsley, Kevin G. Morris, Arden M. Green, Pamela Dominitz, Jason A. Matthews, Barbara Dobie, Sharon A. Barlow, William Baldwin, Laura-Mae TI Does surgeon case volume influence nonfatal adverse outcomes after rectal cancer resection? SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID ACHIEVING EXCELLENT OUTCOMES; HOSPITAL VOLUME; ADMINISTRATIVE DATA; COLON-CANCER; COLORECTAL RESECTION; QUALITY INDICATOR; MORBIDITY; MORTALITY; SURVIVAL; POPULATION AB BACKGROUND: The aim of this study was to assess the relationship between surgeon and hospital volume and major postoperative complications after rectal cancer surgery, and to define other surgeon and hospital characteristics that may explain observed volume-complication relationships. STUDY DESIGN: This was a retrospective cohort design using data from the Surveillance, Epidemiology, and End Results (SEER) cancer registry program for individuals with stage I to III rectal cancer diagnosed between 1992 and 1999 and treated with resection. The patients' Surveillance, Epidemiology, and End Results data were linked with Medicare claims data from 1991 to 2000. The primary outcomes were 30-day postoperative procedural interventions (PPI) to treat surgical complications, such as reoperation. The association between surgeon volume and PPI was examined using logistic regression modeling with adjustment for covariates. RESULTS: The odds of a rectal cancer patient requiring a PPI is notably less if the operation is performed by one of a small subset of very high volume surgeons (unadjusted odds ratio 0.53; 95% CI 0.31 to 0.92). Board certification in colorectal surgery did not alter the relationship between surgeon volume and PPI, although surgeon age did, with mid-career surgeons having the lowest rates of PPI, regardless of practice volume. When adjusted for surgeon age, surgeon volume is no longer a marked predictor of complications (adjusted odds ratio 0.57; 95% CI 0.30 to 1.09). CONCLUSIONS: Over-all, rectal cancer operations are safe, with a low frequency of severe complications. A subset of very high volume rectal surgeons performs these operations with fewer complications that require procedural intervention or reoperation. Surgeon age, as an indicator of experience, also contributes modestly to outcomes. These data do not justify regionalizing rectal cancer care based on safety concerns. C1 Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97239 USA. Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI USA. Univ Washington, Sch Med Canc Res & Biostat, Dept Family Med, Seattle, WA 98195 USA. Univ Washington, Sch Med Canc Res & Biostat, VA Puget Sound Hlth Care Syst, Div Gastroenterol, Seattle, WA 98195 USA. RP Billingsley, KG (reprint author), Oregon Hlth & Sci Univ, Dept Surg L223A, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. OI Dominitz, Jason/0000-0002-8070-7086 FU NCI NIH HHS [R01 CA089544, R01 CA089544-01S1] NR 27 TC 25 Z9 25 U1 0 U2 2 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 JUN PY 2008 VL 206 IS 6 BP 1167 EP 1177 DI 10.1016/j.jamcollsurg.2007.12.042 PG 11 WC Surgery SC Surgery GA 310EO UT WOS:000256511900011 PM 18501815 ER PT J AU Webber, KH Tate, DF Quintiliani, LM AF Webber, Kelly H. Tate, Deborah F. Quintiliani, Lisa M. TI Motivational interviewing in Internet groups: A pilot study for weight loss SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PROMOTE PHYSICAL-ACTIVITY; WORLD CHAT ROOM; INCREASE FRUIT; LOSS PROGRAM; PAR-Q; INTERVENTION; MAINTENANCE; WOMEN; STYLE AB Motivational interviewing is a technique for developing and maintaining motivation. This pilot study examined the feasibility and acceptability of motivational interviewing in online weight-loss treatment groups. Twenty women participated in the 8-week minimal contact intervention, received weekly e-mailed lessons, and were randomized to two online groups using motivational interviewing, either with or without a discussion of values. Acceptability of format and content was measured following the second online group. Self-reported weight and motivation were measured at baseline and 8 weeks. Qualitative analysis of group transcripts examined self-motivational statements uttered by participants during online groups. Eighty-four percent of participants reported willingness to participate again and were comfortable with the discussion topics. The average number of self-motivational statements uttered by participants did not differ by group (P=0.85) and was correlated with an increase in autonomous motivation during the 8 weeks (r=0.58, P=0.05). Higher autonomous motivation at follow-up was associated with greater weight loss (r=0.51, P<0.05). This study suggests that motivational interviewing techniques are acceptable and may be useful for targeting and maintaining motivation in online weight-loss groups. C1 [Webber, Kelly H.] Univ Kentucky, Dept Nutr & Food Sci, Lexington, KY 40506 USA. [Tate, Deborah F.] Univ N Carolina, Sch Publ Hlth, Dept Nutr & Hlth Behav & Hlth Educ, Chapel Hill, NC USA. [Quintiliani, Lisa M.] Dana Farber Harvard Canc Ctr, Boston, MA USA. RP Webber, KH (reprint author), Univ Kentucky, Dept Nutr & Food Sci, 212A Funkhouser, Lexington, KY 40506 USA. EM kelly.webber@uky.edu OI Quintiliani, Lisa/0000-0002-3328-6768 NR 40 TC 25 Z9 25 U1 5 U2 12 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JUN PY 2008 VL 108 IS 6 BP 1029 EP 1032 DI 10.1016/j.jada.2008.03.005 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 309IL UT WOS:000256453800027 PM 18502239 ER PT J AU Mader, SL AF Mader, Scott L. TI In memoriam - Amasa Ford SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Biographical-Item C1 Portland VA Med Ctr, Vancouver Div, Vancouver Long Term Care Div, Portland, OR USA. RP Mader, SL (reprint author), Portland VA Med Ctr, Vancouver Div, Vancouver Long Term Care Div, Portland, OR USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 2008 VL 56 IS 6 BP 1164 EP 1164 DI 10.1111/j.1532-5415.2008.01735.x PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 308SU UT WOS:000256411100040 ER PT J AU Thomas, DR Cote, TR Lawhorne, L Levenson, SA Rubenstein, LZ Smith, DA Stefanacci, RG Tangalos, EG Morley, JE AF Thomas, David R. Cote, Todd R. Lawhorne, Larry Levenson, Steven A. Rubenstein, Laurence Z. Smith, David A. Stefanacci, Richard G. Tangalos, Eric G. Morley, John E. CA Dehydration Council TI Understanding clinical dehydration and its treatment SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Review DE dehydration; long-term care; hyperosmolar dehydration; hyponatremia dehydration; education; prevention; recombinant hyaluronidase; subcutaneous infusion of fluid; hypodermoclysis ID NURSING-HOME RESIDENTS; DWELLING OLDER-ADULTS; HEALTHY ELDERLY MEN; HYDRATION STATUS; FLUID BALANCE; THIRST; REHYDRATION; HYPERNATREMIA; PREVALENCE; HYPODERMOCLYSIS AB Dehydration in clinical practice, as opposed to a physiological definition, refers to the loss of body water, with or without salt, at a rate greater than the body can replace it. We argue that the clinical definition for dehydration, ie, loss of total body water, addresses the medical needs of the patient most effectively. There are 2 types of dehydration, namely water loss dehydration (hyperosmolar, due either to increased sodium or glucose) and salt and water loss dehydration (hyponatremia). The diagnosis requires an appraisal of the patient and laboratory testing, clinical assessment, and knowledge of the patient's history. Long-term care facilities are reluctant to have practitioners make a diagnosis, in part because dehydration is a sentinel event thought to reflect poor care. Facilities should have an interdisciplinary educational focus on the prevention of dehydration in view of the poor outcomes associated with its development. We also argue that dehydration is rarely due to neglect from formal or informal caregivers, but rather results from a combination of physiological and disease processes. With the availability of recombinant hyaluronidase, subcutaneous infusion of fluids (hypodermoclysis) provides a better opportunity to treat mild to moderate dehydration in the nursing home and at home. C1 [Thomas, David R.] St Louis Univ, Sch Med, Div Geriatr Med, St Louis, MO 63104 USA. [Cote, Todd R.] Hosp Bluegrass, Palliat Care Ctr Bluegrass, Lexington, KY USA. [Lawhorne, Larry] Wright State Univ, Boonshoft Sch Med, Dayton, OH 45435 USA. [Levenson, Steven A.] Genesis Elder Care, Baltimore, MD USA. [Rubenstein, Laurence Z.] VA Greater Los Angeles, Los Angeles, CA USA. [Rubenstein, Laurence Z.] Univ Calif Los Angeles, Los Angeles, CA USA. [Smith, David A.] Texas A&M Univ, Brownwood, TX USA. [Stefanacci, Richard G.] Allegheny Univ Hlth Sci, Ctr Medicare Medicat Management, Philadelphia, PA 19102 USA. [Tangalos, Eric G.] Mayo Clin, Rochester, MN USA. [Morley, John E.] VA Med Ctr, GRECC, St Louis, MO USA. RP Thomas, DR (reprint author), St Louis Univ, Sch Med, Div Geriatr Med, 1402 S Grand Blvd,M238, St Louis, MO 63104 USA. EM ThomasDR@slu.edu RI morley, john/F-9177-2011 OI morley, john/0000-0001-6444-2965 NR 73 TC 96 Z9 97 U1 3 U2 39 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD JUN PY 2008 VL 9 IS 5 BP 292 EP 301 DI 10.1016/j.jamda.2008.03.006 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 315PD UT WOS:000256891000004 PM 18519109 ER PT J AU Gillick, MR Volandes, AE AF Gillick, Muriel R. Volandes, Angelo E. TI The standard of caring: Why do we still use feeding tubes in patients with advanced dementia? SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE dementia; feeding tubes; ethics; standard of care ID NURSING-HOME RESIDENTS; ADVANCED COGNITIVE IMPAIRMENT; ARTIFICIAL NUTRITION; CARE; HYDRATION; FUTILITY AB A consensus among geriatricians, ethicists, and neurologists supports a palliative approach to the care of individuals with late-stage dementia. But ten years after the publication of the first large study demonstrating the lack of efficacy of percutaneous endoscopic gastrostomy (PEG) tubes in prolonging life for patients with advanced dementia, and seven years after the appearance of two articles in major medical journals arguing that tube feeding should no longer be the standard of care for individuals with advanced dementia, gastrostomy tubes remain commonplace in this population. One overlooked reason that many families and physicians continue to opt for artificial nutrition is that the case for feeding tubes is a moral one and not a scientific one. What may be at issue for families is how best to demonstrate caring, and caring is not readily amenable to empirical study. A better approach to family members who want feeding tubes for the demented is to acknowledge the symbolic value of nutrition for them and to seek an alternative means of satisfying the need to feed. C1 [Volandes, Angelo E.] Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. [Gillick, Muriel R.; Volandes, Angelo E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Gillick, Muriel R.] Harvard Med Sch Harvard Pilgrim, Dept Ambulatory Care & Prevent, Boston, MA USA. RP Volandes, AE (reprint author), Massachusetts Gen Hosp, Gen Med Unit, 50 Staniford St, Boston, MA 02114 USA. EM avolandes@partners.org NR 28 TC 28 Z9 29 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD JUN PY 2008 VL 9 IS 5 BP 364 EP 367 DI 10.1016/j.jamda.2008.03.011 PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 315PD UT WOS:000256891000015 PM 18519120 ER PT J AU Menke, J Zeller, GC Kikawada, E Means, TK Huang, XR Lan, HY Lu, B Farber, J Luster, AD Kelley, VR AF Menke, Julia Zeller, Geraldine C. Kikawada, Eriya Means, Terry K. Huang, Xiao R. Lan, Han Y. Lu, Bao Farber, Joshua Luster, Andrew D. Kelley, Vicki R. TI CXCL9, but not CXCL10, promotes CXCR3-dependent immune-mediated kidney disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; CHEMOKINE RECEPTOR CXCR3; MRL-FAS(LPR) MICE; AUTOIMMUNE-DISEASE; T-CELL; NEPHROTOXIC NEPHRITIS; ALLOGRAFT-REJECTION; GLOMERULAR INJURY; INDUCIBLE PROTEIN; RENAL-DISEASE AB Chemokines are instrumental in macrophage- and T cell-dependent diseases. The chemokine CCL2 promotes kidney disease in two models of immune-mediated nephritis (MRL-Fas(lpr) mice and the nephrotoxic serum nephritis model), but evidence suggests that multiple chemokines are involved. For identification of additional therapeutic targets for immune-mediated nephritis, chemokine ligands and receptors in CCL2(-/-) and wild-type (WT) MRL-Fas(lpr) kidneys were profiled. The focus was on intrarenal chemokine ligand/receptor pairs that were highly upregulated downstream of CCL2; the chemokine CXCL10 and its cognate receptor, CXCR3, stood out as potential therapeutic targets. However, renal disease was not suppressed in CXCL10(-/-) MRL-Fas(lpr) mice, and CXCL10(-/-) C57BL/6 mice were not protected from nephrotoxic serum nephritis compared with WT mice. Because CXCR3 engages with the ligand CXCL9, CXCR3(-/-), CXCL9(-/-), and CXCL10(-/-) B6 mice were compared with WT mice with nephrotoxic serum nephritis. Kidney disease, measured by loss of renal function and histopathology, was suppressed in both CXCR3(-/-) and CXCL9(-/-) mice but not in CXCL10(-/-) mice. With nephrotoxic serum nephritis, CXCR3(-/-) and CXCL9(-/-) mice had fewer intrarenal activated T cells and activated macrophages. Both IgG glomerular deposits and antigen-specific IgG in serum were reduced in these mice, suggesting that although CXCR3 and CXCL9 initiate nephritis through cell-mediated events, renal inflammation may be sustained by their regulation of IgG. It is concluded that specific blockade of CXCL9 or CXCR3 may be a potential therapeutic target for human immune-mediated kidney diseases. C1 [Menke, Julia; Zeller, Geraldine C.; Kikawada, Eriya; Kelley, Vicki R.] Brigham & Womens Hosp, Div Renal, Lab Mol Autoimmune Dis, Boston, MA 02115 USA. [Means, Terry K.; Luster, Andrew D.] Harvard Univ, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp, Sch Med,Ctr Immunol & Inflammatory Dis, Boston, MA 02115 USA. [Lu, Bao] Harvard Univ, Childrens Hosp, Sch Med, Perlmutter Lab, Boston, MA 02115 USA. [Huang, Xiao R.; Lan, Han Y.] Univ Hong Kong, Fac Med, Dept Med, Hong Kong, Hong Kong, Peoples R China. [Farber, Joshua] NICHHD, Informat Biol Sect, Lab Mol Immunol, NIAID,NIH, Bethesda, MD 20892 USA. RP Kelley, VR (reprint author), Harvard Univ, Inst Med, 4 Blackfan Circle, Boston, MA 02115 USA. EM vkelley@rics.bwh.harvard.edu RI Lan, hui/C-9734-2015 OI Lan, hui/0000-0003-4283-9755 FU NCI NIH HHS [R01 CA 069212, R01 CA069212]; NIAMS NIH HHS [K01 AR051367, KO1 AR 051367]; NIDDK NIH HHS [DK 36149, DK 52369, DK 56848, R01 DK036149, R01 DK052369, R01 DK056848, Z01 DK036149] NR 54 TC 44 Z9 44 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 JUN PY 2008 VL 19 IS 6 BP 1177 EP 1189 DI 10.1681/ASN.2007111179 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 307MK UT WOS:000256322800019 PM 18337479 ER PT J AU Kaufman, DW Kelly, JP Curhan, GC Anderson, TE Dretler, SP Preminger, GM Cave, DR AF Kaufman, David W. Kelly, Judith P. Curhan, Gary C. Anderson, Theresa E. Dretler, Stephen P. Preminger, Glenn M. Cave, David R. TI Oxalobacter formigenes may reduce the risk of calcium oxalate kidney stones SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; POLYMERASE-CHAIN-REACTION; URINARY OXALATE; GASTROINTESTINAL-TRACT; ENTERIC HYPEROXALURIA; DIETARY CALCIUM; UNITED-STATES; UROLITHIASIS; DISEASE; COLONIZATION AB Most kidney stones are composed primarily of calcium oxalate. Oxalobacter formigenes is a Gram-negative, anaerobic bacterium that metabolizes oxalate in the intestinal tract and is present in a large proportion of the normal adult population. It was hypothesized that the absence of O. formigenes could lead to increased colonic absorption of oxalate, and the subsequent increase in urinary oxalate could favor the development of stones. To test this hypothesis, a case-control study involving 247 adult patients with recurrent calcium oxalate stones and 259 age-, gender-, and region-matched control subjects was performed. The prevalence of O. formigenes, determined by stool culture, was 17% among case patients and 38% among control subjects; on the basis of multivariate analysis controlling demographic factors, dietary oxalate, and antibiotic use, the odds ratio for colonization was 0.3 (95% confidence interval 0.2 to 0.5). The inverse association was consistently present within strata of age, gender, race/ethnicity, region, and antibiotic use. Among the subset of participants who completed a 24-h urine collection, the risk for kidney stones was directly proportional to urinary oxalate, but when urinary factors were included in the multivariable model, the odds ratio for O. formigenes remained 0.3 (95% confidence interval 0.1 to 0.7). Surprisingly, median urinary oxalate excretion did not differ with the presence or absence of O. formigenes colonization. In conclusion, these results suggest that colonization with O. formigenes is associated with a 70% reduction in the risk for being a recurrent calcium oxalate stone former. C1 [Kaufman, David W.; Kelly, Judith P.; Anderson, Theresa E.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Curhan, Gary C.] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. [Dretler, Stephen P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Preminger, Glenn M.] Duke Univ, Med Ctr, Div Urol Surg, Durham, NC USA. [Cave, David R.] Univ Massachusetts, Mem Med Ctr, Worcester, MA 01605 USA. RP Kaufman, DW (reprint author), Boston Univ, Slone Epidemiol Ctr, 1010 Commonwealth Ave, Boston, MA 02215 USA. EM dkaufman@slone.bu.edu RI Preminger, Glenn/B-3990-2011 OI Preminger, Glenn/0000-0003-4287-602X FU NIDDK NIH HHS [R01 DK062270] NR 40 TC 85 Z9 94 U1 0 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 2008 VL 19 IS 6 BP 1197 EP 1203 DI 10.1681/ASN.2007101058 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 307MK UT WOS:000256322800021 PM 18322162 ER PT J AU Gorson, KC Hughes, RAC Cros, DP Pollard, JD Vallat, JM Riester, K Davar, G Dawson, K Sandrock, A AF Gorson, K. C. Hughes, R. A. C. Cros, D. P. Pollard, J. D. Vallat, J.-M. Riester, K. Davar, G. Dawson, K. Sandrock, A. TI Efficacy of inteferon beta 1A in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM LA English DT Meeting Abstract CT Inflammatory Neuropathy Consortium Meeting 2008 CY JUL 04-05, 2008 CL Paris, FRANCE C1 [Gorson, K. C.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Hughes, R. A. C.] Guys Hosp, London SE1 9RT, England. [Cros, D. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pollard, J. D.] Univ Sydney, Sydney, NSW 2006, Australia. [Vallat, J.-M.] Univ Limoges, F-87065 Limoges, France. [Riester, K.; Davar, G.; Dawson, K.; Sandrock, A.] Biogen Idec, Cambridge, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1085-9489 J9 J PERIPHER NERV SYST JI J. Peripher. Nerv. Syst. PD JUN PY 2008 VL 13 IS 2 BP 170 EP 170 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 316SV UT WOS:000256970900039 ER PT J AU Shahian, DM Normand, SLT AF Shahian, David M. Normand, Sharon-Lise T. TI Low-volume coronary artery bypass surgery: Measuring and optimizing performance SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material ID ADULT CARDIAC-SURGERY; HOSPITAL VOLUME; QUALITY MEASUREMENT; SURGICAL MORTALITY; RISK; OUTCOMES; CARE C1 Massachusetts Gen Hosp, Dept Surg, Ctr Quality & Safety, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Dept Surg, Ctr Quality & Safety, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org NR 25 TC 18 Z9 18 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 JUN PY 2008 VL 135 IS 6 BP 1202 EP 1209 DI 10.1016/j.jtcvs.2007.12.037 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 309XT UT WOS:000256494200004 PM 18544354 ER PT J AU Shen, KR Wain, JC Wright, CD Grillo, HC Mathisen, DJ AF Shen, K. Robert Wain, John C. Wright, Cameron D. Grillo, Hermes C. Mathisen, Douglas J. TI Postpneumonectomy syndrome: Surgical management and long-term results SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 05-09, 2007 CL Washington, DC SP Amer Assoc Thorac Surg ID PNEUMONECTOMY SYNDROME; PROSTHESIS AB Objective: Postpneumonectomy syndrome is a rare syndrome of dynamic airway obstruction caused by extreme rotation and shift of the mediastinum after pneumonectomy, resulting in symptomatic central airway compression. We have treated this syndrome by mediastinal repositioning and placement of saline-filled prostheses into the pneumonectomy space. There is a paucity of outcome data for patients treated surgically, with only a single series of 11 patients previously reported. We analyzed our recent experience with treatment of this syndrome and report on the short and long-term outcomes and quality of life assessment of the largest series ever reported of patients treated by mediastinal repositioning. Methods: Records were reviewed of all patients who underwent mediastinal repositioning for postpneumonectomy syndrome between January of 1992 and June of 2006. Long-term health-related quality of life was assessed by administration of the Saint George's Respiratory Questionnaire. Results: There were 18 patients (15 women and 3 men) with a median age of 44 years (range 14-67 years). Thirteen patients had undergone right pneumonectomy, and 5 patients had undergone left pneumonectomy. None of the patients in whom postpneumonectomy syndrome developed after left pneumonectomy had a right-sided aortic arch. Five patients had undergone pneumonectomy in childhood (age, 13 years). The median interval between pneumonectomy and mediastinal repositioning was 7.5 years (range 1.1-54.8 years). The median follow-up was 32 months (range 4-143 months). The operative mortality was 5.6% (1/18). Complications occurred in 5 patients (27.8%): pneumonia in 3 patients and acute respiratory distress syndrome in 2 patients. The median hospitalization was 6 days (range 3-155 days). Some 77% (10/13) of patients reported significant improvement in their breathing and overall state of health after surgery; 15.4% of patients (2/13) were somewhat better, and 7.7% of patients (1/13) had no improvement. No patients' condition was worse after surgery. All patients who reported improvement in their symptoms after surgery remained symptomatically improved at the time of the quality of life assessment. Some 92.3% (12/13) were not at all or only slightly limited in their social activities because of breathing problems, and 84.6% (11/13) were not at all or only slightly limited in their ability to work as a result of their physical health. Conclusion: Repositioning of the mediastinum with placement of prostheses for postpneumonectomy syndrome can be performed with low mortality and morbidity. Surgical repositioning provides immediate and lasting symptomatic relief to patients in whom postpneumonectomy syndrome develops. C1 [Shen, K. Robert; Wain, John C.; Wright, Cameron D.; Grillo, Hermes C.; Mathisen, Douglas J.] Massachusetts Gen Hosp, Gen Thorac Surg Unit, Boston, MA 02114 USA. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, Gen Thorac Surg Unit, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM dmathisen@partners.org NR 21 TC 25 Z9 26 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 JUN PY 2008 VL 135 IS 6 BP 1210 EP U43 DI 10.1016/j.jtcvs.2007.11.022 PG 16 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 309XT UT WOS:000256494200005 PM 18544355 ER PT J AU Long, JW Healy, AH Rasmusson, BY Cowley, CG Nelson, KE Kfoury, AG Clayson, SE Reid, BB Moore, SA Blank, DU Renlund, DG AF Long, James W. Healy, Aaron H. Rasmusson, Brad Y. Cowley, Cris G. Nelson, Karl E. Kfoury, Abdallah G. Clayson, Stephen E. Reid, Bruce B. Moore, Stephanie A. Blank, Douglas U. Renlund, Dale G. TI Improving outcomes with long-term "destination" therapy using left ventricular assist devices SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the Western-Thoracic-Surgical-Association CY JUN 22-25, 2005 CL Victoria, CANADA SP Western Thorac Surg Assoc ID MECHANICAL CIRCULATORY SUPPORT; REMATCH TRIAL; CARDIAC TRANSPLANTATION; EXPERIENCE; DESIGN AB Objective: Destination therapy experience using long-term left ventricular assist devices was analyzed relative to the benchmark Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial to evaluate the potential for improving outcomes with this groundbreaking therapy for advanced heart failure. Methods: The largest single-center experience with destination therapy in the United States (Utah Artificial Heart Program, LDS Hospital, Salt Lake City, UT) was retrospectively analyzed. All destination therapy recipients (n = 23) presented with chronic, advanced heart failure, meeting indications for destination therapy adopted from the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial. All received HeartMate left ventricular assist devices (Thoratec Corp, Pleasanton, Calif), with 87% receiving an improved XVE model. Advanced practice guidelines were implemented using a multidisciplinary approach. Survivals (Kaplan-Meier, log-rank analyses) and adverse events (Poisson regression) were compared with those of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device group (n = 68). Results: Survival in the destination therapy group was significantly increased (P = .007), with an overall reduction in mortality of 66%. The 2-year survival was 77% for destination therapy compared with 29% for the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device group (P < .0001). The 1-year survival was 77% for destination therapy compared with the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device rate of 52% (P = .036). Adverse events decreased by 38% (3.90 per patient-year in the destination therapy group compared with the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device rate of 6.32). Factors related to severity of illness met Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure-like criteria for both groups. Conclusions: This analysis provides evidence that long-term destination therapy can be improved well beyond the pioneering experience of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial. With continued evolution of devices, management, and patient selection, outcomes approaching those of heart transplantation may be possible. C1 [Long, James W.; Healy, Aaron H.; Rasmusson, Brad Y.; Cowley, Cris G.; Nelson, Karl E.; Kfoury, Abdallah G.; Clayson, Stephen E.; Reid, Bruce B.; Renlund, Dale G.] LDS Hosp, Utah Artificial Heart Program, Salt Lake City, UT USA. [Clayson, Stephen E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Blank, Douglas U.] Idaho Heart Inst, Idaho Falls, ID USA. RP Long, JW (reprint author), Utah Artificial Heart Program, 8th Ave & C St, Salt Lake City, UT 84143 USA. EM jimlong@ihc.com NR 22 TC 52 Z9 52 U1 0 U2 3 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 JUN PY 2008 VL 135 IS 6 BP 1353 EP 1361 DI 10.1016/j.jtcvs.2006.09.124 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 309XT UT WOS:000256494200023 PM 18544385 ER PT J AU Lynch, TJ Blumenschein, GR Engelman, JA Espinoza-Delgado, I Govindan, R Hanke, J Hanna, NH Heymach, JV Hirsch, FR Janne, PA Lilenbaum, RC Natale, RB Riely, GJ Sequist, LV Shapiro, GT Shaw, A Shepherd, FA Socinski, M Sorensen, AG Wakelee, HA Weitzman, A AF Lynch, Thomas J., Jr. Blumenschein, George R., Jr. Engelman, Jeffrey A. Espinoza-Delgado, Igor Govindan, Ramaswamy Hanke, Jeff Hanna, Nasser H. Heymach, John V. Hirsch, Fred R. Janne, Pasi A. Lilenbaum, Rogerio C. Natale, Ronald B. Riely, Gregory J. Sequist, Lecia V. Shapiro, Geoffrey T. Shaw, Alice Shepherd, Frances A. Socinski, Mark Sorensen, A. Gregory Wakelee, Heather A. Weitzman, Aaron TI Summary statement - Novel Agents in the Treatment of Lung Cancer: Fifth Cambridge Conference assessing opportunities for combination therapy SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE lung cancer; profiling; biopsies; EGFR; VEGF; novel targets AB The promise of effective targeted therapy for lung cancer requires rigorous identification of potential targets combined with intensive discovery and development efforts aimed at developing effective "drugs" for these targets. We now recognize that getting the right drug to the right target in the right patient is more complicated than one could have imagined a decade ago. As knowledge of targets and development of agents have proliferated and advanced, so too have data demonstrating the biologic heterogeneity of tumors. The finding that lung cancers are genetically diverse and can exhibit several pathways of resistance in response to targeted agents makes the prospect for curative therapy more daunting. It is becoming increasingly clear that single-agent treatment will be the exception rather than the rule. This information raises important new questions about the development and assessment of novel agents in lung cancer treatment: (1) How do we identify the most important drug targets for tumor initiation and maintenance? (2) What is the best way to assess drug candidates that may only be relevant in a small fraction of patients? (3) What models do we use to predict clinical response and identify effective combinations? And (4) how do we bring combination regimens to the clinic, particularly when the agents are not yet approved individually and may be under development from different companies? The Fifth Cambridge Conference on Novel Agents in the Treatment of Lung Cancer was held in Cambridge, Massachusetts, on October 1-2, 2007, to discuss these questions by reviewing recent progress in the field and advancing recommendations for research and patient care. New information, conclusions, and recommendations considered significant for the field by the program faculty are summarized here and presented at greater length in the individual articles and accompanying discussions that comprise the full conference proceedings. A CME activity based on this summary is also available at www.informedicalcme.com/cme. C1 [Lynch, Thomas J., Jr.; Engelman, Jeffrey A.; Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Blumenschein, George R., Jr.; Heymach, John V.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Espinoza-Delgado, Igor] NCI, Bethesda, MD 20892 USA. [Govindan, Ramaswamy] Washington Univ, Sch Med, St Louis, MO USA. [Hanke, Jeff] AstraZeneca, Waltham, MA USA. [Hanna, Nasser H.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Hirsch, Fred R.] Univ Colorado, Ctr Canc, Denver, CO 80262 USA. [Janne, Pasi A.; Shapiro, Geoffrey T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lilenbaum, Rogerio C.] Mt Sinai Comprehens Canc Ctr, Miami Beach, FL USA. [Natale, Ronald B.] Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA USA. [Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Shaw, Alice] MIT, Ctr Canc Res, Cambridge, MA 02139 USA. [Shepherd, Frances A.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Socinski, Mark] Univ N Carolina, Chapel Hill, NC USA. [Sorensen, A. Gregory] Massachusetts Gen Hosp, MGH HST AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Wakelee, Heather A.] Stanford Univ, Ctr Canc, Stanford, CA 94305 USA. [Weitzman, Aaron] Genentech Inc, San Francisco, CA 94080 USA. RP Lynch, TJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, 10 N Grove St,Lawrence House 208, Boston, MA 02114 USA. EM tlynch@partners.org NR 0 TC 7 Z9 7 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 JUN PY 2008 VL 3 IS 6 SU S BP S107 EP S112 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 314SE UT WOS:000256828300001 PM 18520291 ER PT J AU Sequist, LV AF Sequist, Lecia V. TI First-generation epidermal growth factor receptor tyrosine kinase inhibitors in EGFR mutation - Positive non-small cell lung cancer patients SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE non-small cell lung cancer; epidermal growth factor receptor; genetic screening ID VINORELBINE PLUS CISPLATIN; PHASE-II TRIAL; GENE-MUTATIONS; GEFITINIB; ERLOTINIB; CHEMOTHERAPY; THERAPY; EXON-19; ADENOCARCINOMAS; RESISTANCE AB Small molecule tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR) are important agents in the treatment of non-small cell lung cancer (NSCLC) and have enhanced activity in the subpopulation of patients with NSCLC who harbor somatic activating mutations of the EGFR gene. This review summarizes the data describing the use of EGFR tyrosine kinase inhibitors in a genotype-directed population of NSCLC patients with EGFR mutations and discusses areas that require further study. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Ctr Canc, 32 Fruit St,Suite Yawkey 7B, Boston, MA 02114 USA. EM lvsequist@partners.org NR 32 TC 9 Z9 9 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 JUN PY 2008 VL 3 IS 6 SU S BP S143 EP S145 PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 314SE UT WOS:000256828300009 PM 18520299 ER PT J AU Shimamura, T Shapiro, GI AF Shimamura, Takeshi Shapiro, Geoffrey I. TI Heat shock protein 90 inhibition in lung cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Review DE heat shock protein 90; epidermal growth factor receptor; lung cancer ID GROWTH-FACTOR RECEPTOR; PHASE-I TRIAL; ENDOPLASMIC-RETICULUM STRESS; REFRACTORY ADVANCED CANCERS; HEAT-SHOCK RESPONSE; TYROSINE KINASE; SOLID TUMORS; MOLECULAR CHAPERONE; BREAST-CANCER; EGF RECEPTOR AB The heat shock protein 90 (Hsp90) chaperone is required for the conformational maturation and stability of multiple oncogenic kinases that drive signal transduction and proliferation of lung cancer cells. The recent demonstration that mutant epidermal growth factor receptor is an Hsp90 client, irrespective of the presence of the secondary threonine-to-methionine amino acid substitution mutation at position 790 mediating anilinoquinazoline resistance, suggests Hsp90 inhibition as a novel strategy against this group of lung cancers. The rarer epidermal growth factor receptors harboring exon 20 insertions and vIII mutations are also Hsp90 clients. Lung cancers may also be driven by mutant ErbB2, mutant B-Raf, or mutant or overexpressed c-Met, all of which are also degraded on Hsp90 inhibition. Hsp90 inhibitors may be synergistic with other drugs that disrupt chaperone function, including inhibitors of histone deacetylase 6 and the proteasome and agents that inhibit Hsp70 function. Hsp90 plays a unique antiapoptotic role in small cell lung cancer cells, so that Hsp90 inhibition results in substantial cell death in both chemosensitive and chemoresistant small cell lung cancer cell lines. Clinically, the geldanamycin compounds are the most mature, with manageable toxic effects. Several new classes of Hsp90 inhibitors are emerging, including purities and pyrazoles that have entered phase I trials. The available data suggest that Hsp90 inhibitors should be evaluated in multiple lung cancer subsets. C1 [Shapiro, Geoffrey I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Shapiro, GI (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Dana 810A,44 Binney St, Boston, MA 02115 USA. EM geoffrey_shapiro@dfci.harvard.edu FU NCI NIH HHS [P50 CA090578]; PHS HHS [P20 90578, R01 90687] NR 107 TC 41 Z9 43 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 JUN PY 2008 VL 3 IS 6 SU S BP S152 EP S159 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 314SE UT WOS:000256828300012 PM 18520302 ER PT J AU Hursting, MJ Jang, IK AF Hursting, Marcie J. Jang, Ik-Kyung TI Effect of body mass index on argatroban therapy during percutaneous coronary intervention SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE argatroban; body mass index; obesity; percutaneous coronary intervention ID HEPARIN-INDUCED THROMBOCYTOPENIA; STENT PLACEMENT; ANTICOAGULATION; OBESITY; PHARMACOKINETICS; PHARMACODYNAMICS; DISEASE AB Background Obesity is common in patients undergoing percutaneous coronary intervention (PCI). Argatroban, a direct thrombin inhibitor, is used during PCI in patients with or at risk of heparin-induced thrombocytopenia ( HIT) and also has been evaluated in conjunction with glycoprotein IIb/IIIa inhibition in nonHIT patients. We investigated the effect of body mass index (BMI), and specifically obesity ( BMI > 30 kg/m(2)), on argatroban therapy during PCI. Methods From previously reported studies of argatroban therapy during PCI in patients with or at risk of HIT (ie, HIT group) or in conjunction with glycoprotein IIb/IIIa inhibition ( ie, nonHIT group), we identified patients with sufficient data to determine BMI. After an initial bolus of 350 mu g/kg ( HIT group) or 300 or 250 mu g/kg ( nonHIT group), patients received continuous argatroban 25 - 30 mu g/kg/min ( adjusted to achieve ACTs of 300 - 450 s, HIT group) or 15 mu g/kg/min ( target ACTs of 275 - 325 s, nonHIT group) during PCI, with additional 150 mu g/kg boluses allowed if needed. Regression analyses evaluated relationships between patient BMI and ACT response to initial bolus administration, mean infusion dose ( HIT group only), and rate of ACT decline after PCI. Frequencies of additional bolus usage and clinical outcomes were compared between obese and nonobese patients. Results Our analysis population included 225 patients (85 obese) in total: 73 in the HIT group and 152 in the nonHIT group (300 mu g/kg bolus, n = 101; 250 mu g/kg bolus, n = 51), with BMIs of 16.3-50.9 kg/m(2). No association was detected between BMI and the first ACT after bolus administration ( median ACTs of 361, 298, and 289 s, respectively, following 350, 300, and 250 mu g/kg bolus), mean infusion dose (24.2 +/- 4.9 mu g/kg/min overall in HIT group), or time to ACTs <= 160 s after argatroban cessation (median 4.4 h in HIT group and 1.7-2.1 h in nonHIT group). Fifteen (5 obese) patients in the HIT group and 36 (13 obese) in the nonHIT group required additional boluses, without differences by obesity versus nonobesity (P >= 0.35). Clinical outcomes did not differ (P >= 0.09) between obese and nonobese individuals: 4 (3 obese) patients in the HIT group and 4 (2 obese) in the nonHIT group had ischemic complications; 1 nonobese patient in the HIT group and 2 (1 obese) in the nonHIT group experienced major bleeding. Conclusions These findings support the use of actual body weight-adjusted (and ACT-targeted) argatroban therapy during PCI and suggest that dose adjustment for obesity (BMI up to 50.9 kg/m(2)) is unnecessary. C1 [Jang, Ik-Kyung] Massachusetts Gen Hosp, Cardiol Div Bigelow 800, Boston, MA 02114 USA. [Jang, Ik-Kyung] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hursting, Marcie J.] Clin Sci Consulting, Austin, TX USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Cardiol Div Bigelow 800, 55 Fruit St, Boston, MA 02114 USA. EM ijang@partners.org NR 23 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD JUN PY 2008 VL 25 IS 3 BP 273 EP 279 DI 10.1007/s11239-007-0051-7 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 307MQ UT WOS:000256323400007 PM 17530465 ER PT J AU Adler, AB Litz, BT Castro, CA Suvak, M Thomas, JL Burrell, L McGurk, D Wright, KM Bliese, PD AF Adler, Amy B. Litz, Brett T. Castro, Carl Andrew Suvak, Michael Thomas, Jeffrey L. Burrell, Lolita McGurk, Dennis Wright, Kathleen M. Bliese, Paul D. TI A group randomized trial of critical incident stress debriefing provided to US peacekeepers SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the International-Society-for-Traumatic-Stress-Studies CY NOV 14-18, 2004 CL New Orleans, LA SP Int Soc Traumat Stress Studies ID PERCEIVED ORGANIZATIONAL SUPPORT; TRAUMA; PERFORMANCE; VICTIMS AB In a group randomized trial of critical incident stress debriefing (CISD) with platoons of 952 peacekeepers, CISD was compared with a stress management class (SMC) and survey-only (SO) condition. Multilevel growth curve modeling found that CISD did not differentially hasten recovery compared to the other two conditions. For those soldiers reporting the highest degree of exposure to mission stressors, CYSD was minimally associated with lower reports of posttraumatic stress and aggression (vs. SMC), higher perceived organizational support (vs. SO), and more alcohol problems than SMC and SO. Soldiers reported that they liked CISD more than the SMC, and CYSD did not cause undue distress. C1 [Adler, Amy B.; Wright, Kathleen M.; Bliese, Paul D.] USA, Med Res Unit Europe, Heidelberg, Germany. [Castro, Carl Andrew; Thomas, Jeffrey L.; Burrell, Lolita; McGurk, Dennis] Walter Reed Army Inst Res, Dept Mil Psychiat, Silver Spring, MD USA. [Litz, Brett T.; Suvak, Michael] Boston Univ, VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02215 USA. [Litz, Brett T.; Suvak, Michael] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Adler, AB (reprint author), USA, Med Res Unit, APO, AE 09042 USA. EM amy.adler@us.army.mil NR 33 TC 32 Z9 35 U1 2 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 JUN PY 2008 VL 21 IS 3 BP 253 EP 263 DI 10.1002/jts.20342 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 317SF UT WOS:000257039300001 PM 18553407 ER PT J AU Arlen, PM Bianco, F Dahut, WL D'Amico, A Figg, WD Freedland, SJ Gulley, JL Kantoff, PW Kattan, MW Lee, A Regan, MM Sartor, O AF Arlen, Philip M. Bianco, Fernando Dahut, William L. D'Amico, Anthony Figg, William D. Freedland, Stephen J. Gulley, James L. Kantoff, Philip W. Kattan, Michael W. Lee, Andrew Regan, Meredith M. Sartor, Oliver TI Prostate specific antigen working group guidelines on prostate specific antigen doubling time SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; prostate-specific antigen; consensus; clinical trials as topic; biological markers ID CANCER-SPECIFIC MORTALITY; RADICAL PROSTATECTOMY; RADIATION-THERAPY; HORMONAL-THERAPY; MEN; SURVIVAL; RECURRENCE; CARCINOMA AB Purpose: Prostate specific antigen is a glycoprotein found almost exclusively in normal and neoplastic prostate cells. Prostate specific antigen doubling time, or the change in prostate specific antigen over time, has emerged as a useful predictive marker for assessing disease outcome in patients with prostate cancer. It is important to agree on definitions and values for the calculation of prostate specific antigen doubling time, and to develop a common approach to outcome analysis and reporting. Materials and Methods: In September 20,06 a conference was held at the National Cancer Institute in Bethesda, Maryland to define these parameters and develop guidelines for their use. Results: The Prostate Specific Antigen Working Group defined criteria regarding prostate specific antigen doubling time including the calculation of prostate specific antigen doubling time, evidence to support prostate specific antigen doubling time as a predictive factor in the setting of biochemical recurrence and the use of prostate specific antigen doubling time as a stratification factor in clinical trials. Conclusions: We propose that investigators calculate prostate specific antigen doubling time before enrolling patients in clinical studies and calculate it as an additional measurement of therapeutic activity. We believe we have developed practical guidelines for the calculation of prostate specific antigen doubling time and its use as a measurement of prognosis and outcome. Furthermore, the use of common standards for prostate specific antigen doubling time in clinical trials is important as we determine which treatments should progress to randomized trials in which "hard" end points such as survival will be used. C1 [Figg, William D.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Bianco, Fernando] George Washington Univ, Dept Urol, Washington, DC USA. [D'Amico, Anthony; Kantoff, Philip W.; Regan, Meredith M.; Sartor, Oliver] Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. [D'Amico, Anthony; Kantoff, Philip W.; Regan, Meredith M.; Sartor, Oliver] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Freedland, Stephen J.] Duke Univ, Div Urol, Durham, NC USA. [Freedland, Stephen J.] Duke Univ, Duke Prostate Ctr, Dept Surg, Durham, NC USA. [Kattan, Michael W.] Cleveland Clin, Cleveland, OH 44106 USA. [Lee, Andrew] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Freedland, Stephen J.] Duke Univ, Dept Pathol, Duke Prostate Ctr, Durham, NC USA. RP Figg, WD (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; FU Intramural NIH HHS [Z01 BC010453-06]; NCI NIH HHS [Z01 BC010453] NR 20 TC 65 Z9 72 U1 2 U2 6 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 JUN PY 2008 VL 179 IS 6 BP 2181 EP 2185 DI 10.1016/j.juro.2008.01.099 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 301SR UT WOS:000255916400025 PM 18423743 ER PT J AU Kerfoot, BP AF Kerfoot, B. Price TI Interactive spaced education versus web based modules for teaching urology to medical students: A randomized controlled trial SO JOURNAL OF UROLOGY LA English DT Article DE education; medical; students; medical; educational technology; urology ID SPACING REPETITIONS; UNITED-STATES; RETENTION; IMPROVES; MEMORY AB Purpose: This study is an assessment of the acceptability and short-term educational efficacy of interactive spaced education compared to web based teaching cases within the compact time frame of a clinical clerkship. Materials and Methods: All 237 third-year students completing their 3-month surgery clerkships at 2 medical schools were asked to complete a urology online-education program covering 4 core topics of benign prostatic hyperplasia, erectile dysfunction, prostate cancer and screening with prostate specific antigen. Students were stratified by clinical site and randomized to 1 of 2 cohorts. Students in cohort A received interactive spaced education on prostate cancer/prostate specific antigen and web based teaching on benign prostatic hyperplasia/erectile dysfunction. Students in cohort B received interactive spaced education on benign prostatic hyperplasia/erectile dysfunction and web based teaching on prostate cancer/prostate specific antigen. A validated 28-item test on all 4 topics was administered at the end of the 10-week program. Results: No statistically significant differences in end-of-program test scores were observed between cohorts in the topics of prostate cancer/prostate specific antigen with 87.6% (SD 12.9) for cohort A (interactive spaced education) and 82.4% (SD 19.6) for cohort B (web based teaching) (p = 0.25). Similarly there was also no statistically significant difference in test scores in the topics of benign prostatic hyperplasia/erectile dysfunction with 79.5% (SD 15.9) for cohort A (web based teaching) and 82.1% (SD 14.7) for cohort B (interactive spaced education, p = 0.28). When students were asked which format they would prefer if they were to receive all their urology online education in a single format, 55% of students (109 of 198 respondents) preferred interactive spaced education while 45% (89 of 109) preferred web based teaching (p = 0.16). Conclusions: Within the compact time frame of a clinical clerkship interactive spaced education is equivalent to web based teaching in short-term learning gains and in acceptability by medical students. C1 [Kerfoot, B. Price] VA Boston Healthcare Syst, Boston, MA USA. [Kerfoot, B. Price] Harvard Univ, Sch Med, Boston, MA USA. RP Kerfoot, BP (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,151DIA, Jamaica Plain, MA 02130 USA. EM price.kerfoot@gmail.com NR 19 TC 15 Z9 15 U1 0 U2 3 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 JUN PY 2008 VL 179 IS 6 BP 2351 EP 2356 DI 10.1016/j.juro.2008.01.126 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 301SR UT WOS:000255916400075 PM 18423715 ER PT J AU Schneidewind, A Brockman, MA Sidney, J Wang, YYE Chen, HB Suscovich, TJ Li, B Adam, RI Allgaier, RL Mothe, BR Kuntzen, T Oniangue-Ndza, C Trocha, A Yu, XG Brander, C Sette, A Walker, BD Allen, TM AF Schneidewind, Arne Brockman, Mark A. Sidney, John Wang, Yaoyu E. Chen, Huabiao Suscovich, Todd J. Bin Li Adam, Rahma I. Allgaier, Rachel L. Mothe, Bianca R. Kuntzen, Thomas Oniangue-Ndza, Cesar Trocha, Alicja Yu, Xu G. Brander, Christian Sette, Alessandro Walker, Bruce D. Allen, Todd M. TI Structural and functional constraints limit options for cytotoxic T-lymphocyte escape in the immunodominant HLA-B27-restricted epitope in human immunodeficiency virus type 1 capsid SO JOURNAL OF VIROLOGY LA English DT Article ID EVOLUTION IN-VIVO; CYCLOPHILIN-A; HIV-1 INFECTION; CELL RESPONSES; CTL ESCAPE; PEPTIDE BINDING; TERMINAL DOMAIN; POOL IMBALANCE; REPLICATION; GAG AB Control of human immunodeficiency virus type 1 (HIV-1) by HLA-B27-positive subjects has been linked to an immunodominant CD8(+) cytotoxic T-lymphocyte (CTL) response targeting the conserved KK10 epitope (KRWIILGLNK(263-272)) in p24/Gag. Viral escape in KK10 typically occurs through development of an R(264)K substitution in conjunction with the upstream compensatory mutation S(173)A, and the difficulty of the virus to escape from the immune response against the KK10 epitope until late in infection has been associated with slower clinical progression. Rare alternative escape mutations at R(264) have been observed, but factors dictating the preferential selection of R(264)K remain unclear. Here we illustrate that while all observed R(264) mutations (K, G, Q, and T) reduced peptide binding to HLA-B27 and impaired viral replication, the replicative defects of the alternative mutants were actually less pronounced than those for R(264)K. Importantly, however, none of these mutants replicated as well as an R(264)K variant containing the compensatory mutation S(173)A. In assessing the combined effects of viral replication and CTL escape using an in vitro coculture assay, we further observed that the compensated R(264)K mutant also displayed the highest replication capacity in the presence of KK10-specific CTLs. Comparisons of codon usage for the respective variants indicated that generation of the R(264)K mutation may also be favored due to a G-to-A bias in nucleotide substitutions during HIV-1 replication. Together, these data suggest that the preference for R(264)K is due primarily to the ability of the S(173)A-compensated virus to replicate better than alternative variants in the presence of CTLs, suggesting that viral fitness is a key contributor for the selection of immune escape variants. C1 [Schneidewind, Arne; Brockman, Mark A.; Wang, Yaoyu E.; Chen, Huabiao; Suscovich, Todd J.; Bin Li; Adam, Rahma I.; Allgaier, Rachel L.; Kuntzen, Thomas; Oniangue-Ndza, Cesar; Trocha, Alicja; Yu, Xu G.; Brander, Christian; Walker, Bruce D.; Allen, Todd M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. [Brockman, Mark A.; Chen, Huabiao; Walker, Bruce D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA USA. [Sidney, John; Sette, Alessandro] La Jolla Inst Allergy & Immunol, La Jolla, CA USA. [Mothe, Bianca R.] Calif State Univ, Dept Biol Sci, San Marcos, CA USA. RP Allen, TM (reprint author), Massachusetts Gen Hosp East, CNY 6625,149 13th St, Charlestown, MA 02129 USA. EM tallen2@partners.org RI Allen, Todd/F-5473-2011; OI Brander, Christian/0000-0002-0548-5778; Brockman, Mark/0000-0001-6432-1426 FU NIAID NIH HHS [P30 AI060354, R01 AI054178, R01-AI054178] NR 62 TC 99 Z9 103 U1 1 U2 2 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 JUN PY 2008 VL 82 IS 11 BP 5594 EP 5605 DI 10.1128/JVI.02356-07 PG 12 WC Virology SC Virology GA 301FN UT WOS:000255881900047 PM 18385228 ER PT J AU Lin, HW Bhattacharyya, N AF Lin, Harrison W. Bhattacharyya, Neil TI Staging and Survival Analysis for Nonsquamous Cell Carcinomas of the Larynx SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Eastern Section Meeting of the Triologic-Society CY JAN 25-27, 2008 CL Philadelphia, PA SP Triol Soc DE Cancer; larynx; head and neck cancer; survival; staging ID ADENOSQUAMOUS CARCINOMA; CARTILAGINOUS TUMORS; LYMPHOMA; NEOPLASMS; HEAD AB Objective: Determine staging and comparative survival for nonsquamous cell carcinoma (SCC) of the larynx. Study Design: Cross-sectional population analysis. Methods: Cases of non-SCC supraglottic, glottic, and subglottic cancers were extracted from the Surveillance, Epidemiology and End Results database (19882003) and the staging distribution computed. For each site, Kaplan-Meier survivals were compared according to histology, T-stage, and N-stage. Survival for non-SCC cancers for each site were compared among histologies, T-stage, and N-stage as well as with age/sex/stage-matched SCC cancers to determine differences in survival. Results: One hundred forty supraglottic non-SCC cases were identified (67% male, mean age 62.0 yr) consisting of 25 neuroendocrine, 25 small cell, and 22 lymphomas (among others), with mean survivals of 44.8, 52.1, and 80.5 months, respectively. Survival was not significantly different according to histology (log-rank, P = .440) but was significantly different according to T-stage (P = .029) and N-stage (P < .001). Seventy-eight glottic non-SCC cases were identified (83% male, mean age 66.1 yr) consisting of 32 spindle cell, 13 sarcoma, and 10 small cell (among others), with mean survivals of 114.6, 89.8, and 39.2 months, respectively. Survival was not significantly different according to histology (P = .056) but was significantly different according to T-stage (P = .002) and N-stage (P = .022). Small numbers (26) precluded subglottic analysis. For both supraglottic and glottic sites including all histologies, survival was similar for matched non-SCC and SCC cases (P = .510 and P = .930, respectively). Conclusions: Non-SCCs are more common in the supraglottic larynx. T-stage and. N-stage influence survival more than histology alone for these cancers. C1 [Bhattacharyya, Neil] Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, Boston, MA 02115 USA. [Lin, Harrison W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Lin, Harrison W.; Bhattacharyya, Neil] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Bhattacharyya, N (reprint author), Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, 45 Francis St, Boston, MA 02115 USA. EM neiloy@massmed.org NR 30 TC 27 Z9 31 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUN PY 2008 VL 118 IS 6 BP 1003 EP 1013 DI 10.1097/MLG.0b013e3181671b3d PG 11 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 368ZL UT WOS:000260662200010 PM 18388773 ER PT J AU Burns, JA Kobler, JB Heaton, JT Anderson, RR Zeitels, SM AF Burns, James A. Kobler, James B. Heaton, James T. Anderson, R. Rox Zeitels, Steven M. TI Predicting Clinical Efficacy of Photoangiolytic and Cutting/Ablating Lasers using the Chick Chorioallantoic Membrane Model: Implications for Endoscopic Voice Surgery SO LARYNGOSCOPE LA English DT Article DE Photoangiolysis; chorioallantoic membrane; laser laryngeal surgery; laser cooling; laser thermal effects ID PULSED DYE-LASER; LARYNGEAL PAPILLOMAS; GLOTTAL DYSPLASIA; THERMAL-DAMAGE; THULIUM LASER; SOFT-TISSUE; VOCAL FOLD; KTP LASER; PHOTOTHERMOLYSIS; ANGIOGENESIS AB Objectives/Hypothesis: The optimal balance between a laser's clinical efficacy and collateral thermal damage is the major determinant for selection of a particular laser in endolaryngeal surgery. The chick chorioallantoic membrane (CAM) simulates the microvasculature of the human vocal fold and is, therefore, useful for testing effects of laser settings, mode of delivery, active cooling, and wavelength. Such information is essential for optimizing the effectiveness of lasers in treating laryngeal pathology while preserving vocal function. Study Design and Methods: The thermal and coagulative effects of four lasers (585 nm PDL, 532 nm KTP, 2.01im Thulium, 10.6im CO2) were quantified at selected (and clinically relevant) energy settings before and after tissue cooling using the CAM model. Measures included imaging real-time vascular reactions in the CAM model (i.e., vessel coagulation and/or rupture), and post-procedure histologic analysis of CAM tissue. In each experiment, laser energy was applied to the CAM in a controlled manner. Cooling was done using a dermatological cold-air device, and temperatures were measured with a thermistor. Lasers tested included the photoangiolytic pulsed-dye (PDL) and KTP, as well as the ablative/cutting CO2 and thulium lasers. The vessel rupture/coagulation and thermal effects of various energy-delivery parameters on the CAM, with and without cooling, were assessed. After removal of the CAM, specimens were stained as whole-mounts, photographed at 4X magnification, and evaluated by two independent, blinded surgeon reviewers. The efficacy of increased pulse-width (KTP laser) on treating larger vessels (>0.5 mm) and the effects of extravasated blood on photoangiolysis were also evaluated. Results: Photoangiolytic lasers: Vessel coagulation/rupture rates showed that the PDL caused more frequent vessel rupture than the KTP laser. For both lasers, cooling the CAM by similar to 20 degrees C resulted in 30%-60% reduction in the thermal-damage zone (P <.05). Cooling reduced the efficacy of coagulation with the PDL but not with the KTP laser. The clinically observed phenomenon that laser heating of extravasated blood increases thermal damage and decreases efficacy of coagulation was clearly evident in the CAM model. Ablative lasers: The thermal-damage zone of the CO2 laser (0.3 mm spot size) was not significantly different with or without cooling (0.32 mm(2) and 0.34 mm(2), respectively) (P =.30). However, when the spot size was defocused to 1 mm, the thermal-damage zone was over 2x greater when the tissue was not cooled (0.74 mm(2) vs 0.35 mm(2)) (P <.002). The thermal-damage zone of the Thulium laser was reduced by an average of 58% for the three power settings tested when the CAM was air-cooled (P <.05). Conclusions: The CAM was an excellent model for studying the effects of photoangiolytic lasers, for which optimal pulse-widths exist for vessel coagulation. Smaller vessels coagulated reliably at pulse widths > 15 msec, and larger vessels required pulse widths >35 msec for optimal coagulation. Cooling the target tissue decreased the thermal-damage zone created by photoangiolytic lasers. While cooling had no effect on the efficacy of coagulation with longer pulse widths (KTP), tissue cooling decreased the coagulation rate at shorter pulse widths (PDL). The thermal effects of cutting/ablating lasers can be reduced with cooling, but the CAM was not a good model with which to study coagulation/rupture rates in cutting/ablating lasers. C1 [Burns, James A.; Kobler, James B.; Heaton, James T.; Zeitels, Steven M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Anderson, R. Rox] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Ctr Photomed, Boston, MA 02114 USA. RP Burns, JA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM Bums.james@mgh.harvard.edu NR 40 TC 17 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUN PY 2008 VL 118 IS 6 BP 1109 EP 1124 DI 10.1097/MLG.0b013e31816902bb PG 16 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 368ZL UT WOS:000260662200027 PM 18354337 ER PT J AU Hochhaus, A Baccarani, M Deininger, M Apperley, JF Lipton, JH Goldberg, SL Corm, S Shah, NP Cervantes, F Silver, RT Niederwieser, D Stone, RM Dombret, H Larson, RA Roy, L Hughes, T Muller, MC Ezzeddine, R Countouriotis, AM Kantarjian, HM AF Hochhaus, A. Baccarani, M. Deininger, M. Apperley, J. F. Lipton, J. H. Goldberg, S. L. Corm, S. Shah, N. P. Cervantes, F. Silver, R. T. Niederwieser, D. Stone, R. M. Dombret, H. Larson, R. A. Roy, L. Hughes, T. Mueller, M. C. Ezzeddine, R. Countouriotis, A. M. Kantarjian, H. M. TI Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib SO LEUKEMIA LA English DT Article DE dasatinib; imatinib; chronic myeloid leukemia ID CHRONIC MYELOID-LEUKEMIA; CLINICAL RESISTANCE; KINASE INHIBITOR; FOLLOW-UP; THERAPY; MECHANISMS; MESYLATE; FAILURE; CELLS; CONFIDENCE AB Dasatinib, a potent inhibitor of BCR-ABL in vitro, is effective for patients with chronic myelogenous leukemia (CML) resistant or intolerant to imatinib. To provide a more definitive assessment of dasatinib in chronic-phase (CP)-CML, we report extended follow-up of a phase II trial, presenting data for the entire patient cohort (N=387). Dasatinib (70 mg) twice daily was administered to patients with imatinib-resistant or -intolerant CP-CML. With median follow-up of 15.2 months (treatment duration, < 1-18.4 months), a complete hematologic response was attained or maintained in 91% of patients. A major cytogenetic response (MCyR) was attained or maintained by 59% (52% imatinib resistant and 80% imatinib intolerant); this was complete in 49% of patients (40% imatinib resistant and 75% imatinib intolerant). Of 230 patients achieving an MCyR, 7 experienced disease progression. Fifteen-month progression-free survival was 90% while overall survival was 96%. Grade 3/4 thrombocytopenia and neutropenia were reported in 48 and 49% of patients, respectively. Non-hematologic toxicity ( any grade) consisted primarily of diarrhea (37%), headache (32%), fatigue (31%), dyspnea (30%) and pleural effusion (27%). Pleural effusions were classified as grade 3 in 6% of reported events, with no incidence of grade 4. Dasatinib is associated with high response rates in patients with imatinib-resistant or -intolerant CP-CML. C1 [Hochhaus, A.] Univ Heidelberg, Med Fak Mannheim, Med Klin 3, Abt Fuer Leukaemieforsch, D-68167 Mannheim, Germany. [Baccarani, M.] Univ Bologna, S Orsola Malpighi Hosp, Dept Hematol Oncol L&A Seragnoli, Bologna, Italy. [Deininger, M.] Oregon Hlth & Sci Univ, OHSU Canc Inst, Portland, OR 97201 USA. [Apperley, J. F.] Hammersmith Hosp, Imperial Coll, Dept Hematol, London, England. [Lipton, J. H.] Princess Margaret Hosp, Dept Med Oncol & Hematol, Toronto, ON M4X 1K9, Canada. [Goldberg, S. L.] Hackensack Univ, Med Ctr, Ctr Canc, Hackensack, NJ USA. [Corm, S.] Hop Claude Huriez, Serv Malad Sang, Lille, France. [Shah, N. P.] Univ Calif San Francisco, San Francisco Sch Med, Div Hematol Oncol, San Francisco, CA 94143 USA. [Cervantes, F.] Hosp Clin Barcelona, Dept Hematol, Barcelona, Spain. [Silver, R. T.] Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, Div Hematol Oncol, New York, NY 10021 USA. [Niederwieser, D.] Univ Leipzig, Dept Hematol Oncol & Coagulat, Leipzig, Germany. [Stone, R. M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Dombret, H.] Hop St Louis, Serv Clin Malad Sang, Paris, France. [Larson, R. A.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Roy, L.] CHU Poitiers, Clin Res Ctr, Poitiers, France. [Hughes, T.] Inst Med & Vet Sci, Div Hematol, Adelaide, SA 5000, Australia. [Ezzeddine, R.; Countouriotis, A. M.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Kantarjian, H. M.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. RP Hochhaus, A (reprint author), Univ Heidelberg, Med Fak Mannheim, Med Klin 3, Abt Fuer Leukaemieforsch, Wiesbadener Str 7-11, D-68167 Mannheim, Germany. EM hochhaus@uni-hd.de OI Larson, Richard/0000-0001-9168-3203; Hochhaus, Andreas/0000-0003-0626-0834 FU NCI NIH HHS [P30 CA016672] NR 20 TC 230 Z9 243 U1 3 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUN PY 2008 VL 22 IS 6 BP 1200 EP 1206 DI 10.1038/leu.2008.84 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 311SC UT WOS:000256618900015 PM 18401416 ER PT J AU Zampa, G Moscato, M Brannigan, BW Morabito, A Bell, DW Normanno, N AF Zampa, Germano Moscato, Michele Brannigan, Brian W. Morabito, Alessandro Bell, Daphne W. Normanno, Nicola TI Prolonged control of bone metastases in non-small-cell lung cancer patients treated with gefitinib SO LUNG CANCER LA English DT Article DE NSCLC; EGFR; gefitinib; bone metastases; bone marrow stromal cells; osteoclast ID NUDE-MICE; BREAST-CANCER; PHASE-II; GROWTH; BLOCKADE AB We describe two non-small-cell tung cancer (NSCLC) patients in which treatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKIs) gefitinib produced a prolonged control of bone disease. In the first patient, a 48-year-old male with adenocarcinoma (ADC) of the tung and multiple bone metastases, the bone scan became comptetely negative following treatment with gefitinib for 9 months. The patient remained alive and with no evidence of bone metastases for 20 months, despite two local recurrences that were surgically removed. Similarly, the bone scan of the second patient, a 49-year-old mate with ADC of the tung and bone metastases, became negative after 6 months on gefitinib. The molecular mechanisms potentially involved in this phenomenon are discussed. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Normanno, Nicola] INT Fdn Pascale, Celt Biol & Preclin Models Unit, I-80131 Naples, Italy. [Zampa, Germano; Moscato, Michele] San Paolo Hosp, Oncol Unit, Civitavecchia, Italy. [Brannigan, Brian W.; Bell, Daphne W.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Brannigan, Brian W.; Bell, Daphne W.] Harvard Univ, Sch Med, Charlestown, MA USA. [Morabito, Alessandro] INT Fdn Pascale, Clin Trials Unit, I-80131 Naples, Italy. [Normanno, Nicola] CROM, Mercogliano, AV, Italy. RP Normanno, N (reprint author), INT Fdn Pascale, Celt Biol & Preclin Models Unit, I-80131 Naples, Italy. EM nicnorm@yahoo.com OI Morabito, Alessandro/0000-0002-1319-9608; Normanno, Nicola/0000-0002-7158-2605 FU Associazione Italiana per la Ricerca sul Cancro NR 15 TC 8 Z9 9 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD JUN PY 2008 VL 60 IS 3 BP 452 EP 454 DI 10.1016/i.lungcan.2007.11.002 PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 334IW UT WOS:000258216500019 PM 18079016 ER PT J AU Janne, PA AF Jaenne, Pasi A. TI Challenges of detecting EGFR T790M in gefitinib/erlotinib-resistant tumours SO LUNG CANCER LA English DT Article; Proceedings Paper CT 12th World Conference on Lung Cancer CY SEP 02-06, 2007 CL Seoul, SOUTH KOREA DE non-small cell lung cancer; acquired resistance; irreversible tyrosine kinase inhibitors; allelic dilution; epidermal growth factor receptor; T790M mutation; MET amplification ID CELL LUNG-CANCER; GROWTH-FACTOR-RECEPTOR; ACQUIRED-RESISTANCE; KINASE INHIBITORS; GEFITINIB SENSITIVITY; TYROSINE KINASE; GENE-MUTATIONS; ERLOTINIB; AMPLIFICATION; MET AB For patients with advanced non-small cell lung cancer (NSCLC), the introduction of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, into clinical practice was promising. Treatment with either of these agents is associated with an objective response in 10-20% of patients. Subsequent studies have shown that patients responsive to gefitinib/erlotinib have tumours containing somatic activating mutations in the EGFR gene. Although impressive clinical and radiological responses have been observed in these patients, tumour progression occurs after the prolonged administration of gefitinib/erlotinib as acquired resistance develops. In order to combat acquired resistance, research has been largely focused on determining the factors underlying it. Two resistance mechanisms have so far been identified: a secondary mutation in the EGFR gene, T790M, and amplification of the MET proto-oncogene. This review wilt centre on T790M, which is thought to cause steric hindrance and impair the binding of gefitinib/erlotinib. A novel class of irreversible TKIs currently under development may retain activity against some common resistance mechanisms, including T790M. The next challenge is to identify accurately the subgroup of patients with NSCLC whose tumours harbour EGFR T790M. To this end, post-treatment tumour specimens will. be needed to establish molecular profiles for each patient. In addition, novel, highly sensitive technology wilt be required to detect these mutations. This is because allelic dilution, whereby the EGFR gene is amplified but only a few copies of the T790M allele are needed to confer resistance, may obscure results of conventional sequencing methods. The importance of identifying patients who harbour T790M cannot be overstated; the development of irreversible TKIs wilt have profound implications for their treatment. In this way, treatment strategies in NSCLC are becoming increasingly tailored to the individual, and may set an example for other areas of oncology. (C) 2008 Elsevier Ireland Ltd. Ali rights reserved. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. EM pasi_janne@dfci.harvard.edu NR 42 TC 33 Z9 35 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD JUN PY 2008 VL 60 SU 2 BP S3 EP S9 DI 10.1016/S0169-5002(08)70099-0 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 313OK UT WOS:000256749700002 PM 18513582 ER PT J AU Wong, KK AF Wong, Kwok-Kin TI Searching for a magic bullet in NSCLC: the role of epidermal growth factor receptor mutations and tyrosine kinase inhibitors SO LUNG CANCER LA English DT Article; Proceedings Paper CT 12th World Conference on Lung Cancer CY SEP 02-06, 2007 CL Seoul, SOUTH KOREA DE non-small cell lung cancer; tyrosine kinase inhibitors; activating mutations; acquired resistance; T790M mutation; irreversible tyrosine; kinase inhibitors ID CELL LUNG-CANCER; ACQUIRED-RESISTANCE; GEFITINIB ZD1839; GENE-MUTATIONS; EGF-RECEPTOR; BCR-ABL; IMATINIB RESISTANCE; SOMATIC MUTATIONS; SIGNALING NETWORK; DOMAIN MUTATIONS AB The epidermal growth factor receptor (EGFR) has been implicated in the pathophysiotogy of various cancers, including non-small cell lung cancer (NSCLC). Inhibitors targeting the tyrosine kinase domain of this receptor have been seen to elicit favourable responses in a subset of NSCLC patients. Mutational analysis of the EGFR has revealed that the response to reversible tyrosine kinase inhibitors (TKIs) is a result of the presence of activating mutations present between exons 18 and 21, most frequently the exon 19 deletion and the L858R mutations. After a prolonged treatment with reversible TKIs, patients have been seen to develop resistance that results, in part, from the presence of the secondary T790M mutation in exon 20. Preclinical data suggest that second-generation TKIs may be able to overcome T790M resistance by virtue of their irreversible mode of binding. In addition to the predominant mutations in the EGFR gene, alternative genetic changes between exons 18 and 21 have been observed. Experimental models have demonstrated that TKIs exhibit differential efficacy depending on which mutations are present. Such information may result in the design of highly specific agents that target specific mutations, which could result in more efficacious treatments. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Wong, KK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM kwong1@partners.org OI wong, kwok kin/0000-0001-6323-235X NR 66 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 EI 1872-8332 J9 LUNG CANCER JI Lung Cancer PD JUN PY 2008 VL 60 SU 2 BP S10 EP S18 DI 10.1016/S0169-5002(08)70100-4 PG 9 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 313OK UT WOS:000256749700003 PM 18513579 ER PT J AU Zelinski, AC Wald, LL Setsompop, K Alagappan, V Gagoski, BA Goyal, VK Adalsteinsson, E AF Zelinski, Adam C. Wald, Lawrence L. Setsompop, Kawin Alagappan, Vijayanand Gagoski, Borjan A. Goyal, Vivek K. Adalsteinsson, Elfar TI Fast slice-selective radio-frequency excitation pulses for mitigating B-1(+) inhomogeneity in the human brain at 7 tesla SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE B-1(+) inhomogeneity mitigation; high field; RF pulse design; 3-D RF excitation; in vivo; sparse approximation ID TO-NOISE RATIO; BIRDCAGE COIL; PARALLEL EXCITATION; RF TRANSMISSION; FIELD; RESONANCE; HEAD; POWER; HOMOGENEITY; CHANNELS AB A novel radio-frequency (RF) pulse design algorithm is presented that generates fast slice-selective excitation pulses that mitigate B-1(+) inhomogeneity present in the human brain at high field. The method is provided an estimate of the B-1(+) field in an axial slice of the brain and then optimizes the placement of sinc-like "spokes" in k(z) via an L-1-norm penalty on candidate (k(x), k(y)) locations; an RF pulse and gradients are then designed based on these weighted points. Mitigation pulses are designed and demonstrated at 7T in a head-shaped water phantom and the brain; in each case, the pulses mitigate a significantly non-uniform transmit profile and produce nearly uniform flip angles across the field of excitation (FOX). The main contribution of this work, the sparsity-enforced spoke placement and pulse design algorithm, is derived for conventional single-channel excitation systems and applied in the brain at 7T, but readily extends to lower field systems, nonbrain applications, and multichannel parallel excitation arrays. C1 [Zelinski, Adam C.; Setsompop, Kawin; Gagoski, Borjan A.; Goyal, Vivek K.; Adalsteinsson, Elfar] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Wald, Lawrence L.; Alagappan, Vijayanand] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Wald, Lawrence L.; Adalsteinsson, Elfar] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Zelinski, AC (reprint author), 77 Massachusetts Ave,Bldg 36,Room 680, Cambridge, MA 02139 USA. EM zelinski@MIT.edu RI Adalsteinsson, Elfar/F-2477-2010; Setsompop, Kawin/P-1464-2014; Wald, Lawrence/D-4151-2009 OI Setsompop, Kawin/0000-0003-0455-7634; FU NCRR NIH HHS [P41 RR014075-086768, P41RR14075, P41 RR014075, P41 RR014075-098604, P41 RR014075-098608, P41 RR014075-086772]; NIBIB NIH HHS [R01 EB006847-01A2, 1R01EB006847, R01 EB000790, 1R01EB000790, R01 EB006847, R01 EB006847-02S1, R01 EB007942-01A2, R01 EB006847-02, 1R01EB007942, R01 EB007942] NR 36 TC 48 Z9 48 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JUN PY 2008 VL 59 IS 6 BP 1355 EP 1364 DI 10.1002/mrm.21585 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 306RV UT WOS:000256266400018 PM 18506800 ER PT J AU Schmitt, M Potthast, A Sosnovik, DE Polimeni, JR Wiggins, GC Triantafyllou, C Wald, LL AF Schmitt, Melanie Potthast, Andreas Sosnovik, David E. Polimeni, Jonathan R. Wiggins, Graham C. Triantafyllou, Christina Wald, Lawrence L. TI A 128-channel receive-only cardiac coil for highly accelerated cardiac MRI at 3 tesla SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MR array coil; cardiac MRI; parallel imaging ID PHASED-ARRAY; ACQUISITION; SAMPLES AB A 128-channel receive-only array coil is described and tested for cardiac imaging at 3T. The coil is closely contoured to the body with a "clam-shell" geometry with 68 posterior and 60 anterior elements, each 75 mm in diameter, and arranged in a continuous overlapped array of hexagonal symmetry to minimize nearest neighbor coupling. Signal-to-noise ratio (SNR) and noise amplification for parallel imaging (G-factor) were evaluated in phantom and volunteer experiments. These results were compared to those of commercially available 24-channel and 32-channel coils in routine use for cardiac imaging. The in vivo measurements with the 128-channel coil resulted in SNR gains compared to the 24-channel coil (up to 2.2-fold in the apex). The 128- and 32-channel coils showed similar SNR in the heart, likely dominated by the similar element diameters of these coils. The maximum G-factor values were up to seven times better for a seven-fold acceleration factor (R = 7) compared to the 24-channel coil and up to two-fold improved compared to the 32-channel coil. The ability of the 128-channel coil to facilitate highly accelerated cardiac imaging was demonstrated in four volunteers using acceleration factors up to seven-fold (R = 7) in a single spatial dimension. C1 [Schmitt, Melanie; Sosnovik, David E.; Polimeni, Jonathan R.; Wiggins, Graham C.; Triantafyllou, Christina; Wald, Lawrence L.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Potthast, Andreas] Siemens Med Solut, MR Div, Charlestown, MA USA. [Sosnovik, David E.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Triantafyllou, Christina] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Wald, Lawrence L.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Wald, LL (reprint author), Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol, Bldg 149 13th St, Charlestown, MA 02129 USA. EM wald@nmr.mgh.harvard.edu RI Triantafyllou, Christina/E-7724-2011; Polimeni, Jonathan/P-1395-2014; Wald, Lawrence/D-4151-2009 OI Polimeni, Jonathan/0000-0002-1348-1179; FU NCRR NIH HHS [P41 RR014075, P41 RR014075-086768, P41 RR014075-086772, P41 RR014075-098604, P41 RR014075-098608, P41RR14075]; NIBIB NIH HHS [R01 EB006847, 1R01EB006847, R01 EB000790, R01 EB006847-01A2, R01 EB006847-02, R01 EB006847-02S1, R01EB000790] NR 17 TC 74 Z9 77 U1 3 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JUN PY 2008 VL 59 IS 6 BP 1431 EP 1439 DI 10.1002/mrm.21598 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 306RV UT WOS:000256266400027 PM 18506789 ER PT J AU Huang, CM AF Huang, Christine M. TI Human papillomavirus and vaccination SO MAYO CLINIC PROCEEDINGS LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; YOUNG-WOMEN; PARTICLE VACCINE; QUADRIVALENT VACCINE; SUSTAINED EFFICACY; UNITED-STATES; DOUBLE-BLIND; FOLLOW-UP; INFECTION; TYPE-16 AB Human papillomavirus (HPV) infection is the most common sexually transmitted infection in the United States. Modeling estimates Suggest that more than 80% of sexually active women will have acquired genital HPV by age 50 years. Although most infections are transient and asymptomatic, persistent infection with high-risk types of HPV can lead to precancerous lesions and progress to cancer. In June 2006, the US Food and Drug Administration licensed the first vaccine to prevent cervical cancers and other diseases in women. This quadrivalent vaccine protects against HPV-6, HPV-11, HPV-16, and HPV-18, which are responsible for 70% of cervical cancers and 90% of genital warts. Several studies have been published examining the vaccine's efficacy, duration, immunogenicity, and safety. Questions and controversy remain regarding mandatory vaccination, need for booster doses, and cost-effectiveness. C1 [Huang, Christine M.] Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Healthcare Syst, Dept Internal Med, Los Angeles, CA USA. RP Huang, CM (reprint author), 11301 Wilshire Blvd PACC, Los Angeles, CA 90073 USA. NR 25 TC 13 Z9 18 U1 0 U2 3 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 JUN PY 2008 VL 83 IS 6 BP 701 EP 707 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 307PY UT WOS:000256332000013 PM 18533087 ER PT J AU Sochalski, J Konetzka, RT Zhu, JS Volpp, K AF Sochalski, Julie Konetzka, R. Tamara Zhu, Jingsan Volpp, Kevin TI Will mandated minimum nurse staffing ratios lead to better patient outcomes? SO MEDICAL CARE LA English DT Article DE nurse staffing; staffing ratios; quality of care ID ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-CARE; ADMINISTRATIVE DATA; ADVERSE EVENTS; HOSPITAL MORTALITY; MEDICARE PATIENTS; ICD-9-CM; FAILURE; RESCUE; DEATH AB Background: Mandatory hospital nurse staffing ratios are under consideration in a number of states without strong empirical evidence of the optimal ratio. Objective: To determine whether increases in medical-surgical licensed nurse staffing levels are associated with improvements in patient outcomes for hospitals having different baseline staffing levels. Research Design: Cross-sectional and fixed-effects regression analyses using a 1993-2001 panel of patient and hospital data from California. Splines define 4 staffing ratios. Subjects: Adult acute myocardial infarction (AMI) (n = 348,720) and surgical failure to rescue (FTR) (n = 109,066) patients discharged between 1993 and 2001 from 343 California acute care general hospitals. Measures: Patient outcomes are 30-day AMI mortality and surgical FTR; 4 baseline staffing levels-4 to 7 patients per licensed nurse [registered nurses (RN) and licensed vocational nurses (LVN)]. Results: Significant cross-sectional associations between higher nurse staffing and AMI mortality are reduced in the fixed-effects analyses. Improvements in outcomes were smaller in hospitals with higher baseline staffing: for each RN and RN + LVN increase, respectively, AMI mortality declined by 0.71 (P < 0.05) and by 2.75 percentage points for hospitals with more than 7 patients per nurse compared with 0.19 (P = NS) and 0.28 percentage points (P < 0.05) in hospitals with more than 4 patients per nurse. Significant cross-sectional associations between higher nurse staffing and FTR were not found in the fixed-effects analyses. Conclusions: Strong diminishing returns to nurse staffing improvements and lack of significant evidence that staffing uniformly increases improve outcomes raise questions about the likely cost-effectiveness of implementing state-wide mandatory nurse staffing ratios. C1 [Sochalski, Julie] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Konetzka, R. Tamara] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Zhu, Jingsan; Volpp, Kevin] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Volpp, Kevin] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Volpp, Kevin] Univ Penn, Wharton Sch, Dept Hlth Care Syst, Philadelphia, PA 19104 USA. RP Sochalski, J (reprint author), Univ Penn, Sch Nursing, Claire M Fagin Hall,418 Curie Blvd, Philadelphia, PA 19104 USA. EM julieas@nursing.upenn.edu NR 50 TC 28 Z9 28 U1 2 U2 11 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 JUN PY 2008 VL 46 IS 6 BP 606 EP 613 DI 10.1097/MLR.0b013e3181648e5c PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 310CR UT WOS:000256507000008 PM 18520315 ER PT J AU Tromberg, BJ Pogue, BW Paulsen, KD Yodh, AG Boas, DA Cerussi, AE AF Tromberg, Bruce J. Pogue, Brian W. Paulsen, Keith D. Yodh, Arjun G. Boas, David A. Cerussi, Albert E. TI Assessing the future of diffuse optical imaging technologies for breast cancer management SO MEDICAL PHYSICS LA English DT Article ID MONITORING NEOADJUVANT CHEMOTHERAPY; ULTRASOUND LOCALIZATION; FREQUENCY-DOMAIN; MENSTRUAL-CYCLE; TOMOGRAPHY; SPECTROSCOPY; HEMOGLOBIN; MRI; TISSUE; WOMEN AB Diffuse optical imaging (DOI) is a noninvasive optical technique that employs near-infrared (NIR) light to quantitatively characterize the optical properties of thick tissues. Although NIR methods were first applied to breast transillumination (also called diaphanography) nearly 80 years ago, quantitative DOI methods employing time- or frequency-domain photon migration technologies have only recently been used for breast imaging (i.e., since the mid-1990s). In this review, the state of the art in DOI for breast cancer is outlined and a multi-institutional Network for Translational Research in Optical Imaging (NTROI) is described, which has been formed by the National Cancer Institute to advance diffuse optical spectroscopy and imaging (DOSI) for the purpose of improving breast cancer detection and clinical management. DOSI employs broadband technology both in near-infrared spectral and temporal signal domains in order to separate absorption from scattering and quantify uptake of multiple molecular probes based on absorption or fluorescence contrast. Additional dimensionality in the data is provided by integrating and co-registering the functional information of DOSI with x-ray mammography and magnetic resonance imaging (MRI), which provide structural information or vascular flow information, respectively. Factors affecting DOSI performance, such as intrinsic and extrinsic contrast mechanisms, quantitation of biochemical components, image formation/visualization, and multimodality co-registration are under investigation in the ongoing research NTROI sites. One of the goals is to develop standardized DOSI platforms that can be used as stand-alone devices or in conjunction with MRI, mammography, or ultrasound. This broad-based, multidisciplinary effort is expected to provide new insight regarding the origins of breast disease and practical approaches for addressing several key challenges in breast cancer, including: Detecting disease in mammographically dense tissue, distinguishing between malignant and benign lesions, and understanding the impact of neoadjuvant chemotherapies. (c) 2008 American Association of Physicists in Medicine. C1 [Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Tromberg, Bruce J.; Yodh, Arjun G.; Boas, David A.; Cerussi, Albert E.] Beckman Laser Inst & Med Clin, NCI Network Translat Res Opt Imaging, Irvine, CA 92612 USA. [Tromberg, Bruce J.; Cerussi, Albert E.] Univ Calif Irvine, Beckman Laser Inst & Med Clin, Irvine, CA 92612 USA. [Yodh, Arjun G.] Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA. [Boas, David A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,NMR Ctr, Boston, MA 02129 USA. RP Pogue, BW (reprint author), Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. EM pogue@dartmouth.edu FU NCI NIH HHS [P30 CA062203, U54 CA105480, U54 CA105480-010002, U54CA105480]; NCRR NIH HHS [P41 RR001192, P41 RR001192-29] NR 31 TC 169 Z9 172 U1 4 U2 24 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 JUN PY 2008 VL 35 IS 6 BP 2443 EP 2451 DI 10.1118/1.2919078 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 307FU UT WOS:000256305600033 PM 18649477 ER PT J AU Fricchione, G Zhu, W Cadet, P Mantione, KJ Bromfield, E Madsen, J DeGirolami, U Dworetzky, B Vaccaro, B Black, P Stefano, GB AF Fricchione, Gregory Zhu, Wei Cadet, Patrick Mantione, Kirk J. Bromfield, Edward Madsen, Joseph DeGirolami, Umberto Dworetzky, Barbara Vaccaro, Bernardino Black, Peter Stefano, George B. TI Identification of endogenous morphine and a mu 3-like opiate alkaloid receptor in human brain tissue taken from a patient with intractable complex partial epilepsy SO MEDICAL SCIENCE MONITOR LA English DT Article DE morphine; endogenous morphine; epilepsy; temporal lobe; mu opiate receptors (MORs); mu-3-like opiate receptor ID NITRIC-OXIDE; ANTICONVULSANT; CELLS; MU(3) AB Background: We set out to detect whether morphine is present in tissue taken from a patient with intractable temporal lobe epilepsy and to characterize the presence and nature of mu opiate receptor sub-types in this tissue. Case Report: In temporal lobe tissue, resected during anteromedial temporal lobectomy for intractable focal epilepsy, morphine was identified by quantitative radioimmunoassay (RIA) coupled to eletro-chemical detection via high-pressure liquid chromatography (HPLC). In additon, RNA is isolated from the medial and laeal temporal lobe specimens was analyzed by conventional and real time reverse transcriptase-polymerase chain reaction (RT-PCR) for the expression of different mu opiate receptor gene transcripts. RIA revealed the presence of morphine at 3.4 nanograms per gram of tissue wet weight. Using RT-PCR and a primer specifically set for the mu3 (550 base pair fragment and) and mu4 (880 base pair fragment) MOR splice variants, a mu4 splice variant was identifed in both brain sections. Conclusions: This human brain tissue study of a subject with temporal lobe epilepsy documents the presence of endogenous morphine and of a mu4 splece variant. These findings may have implications for our understanding of the mechanism of temporal lobe epilepsy. C1 [Fricchione, Gregory] Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat & Med, Boston, MA 02114 USA. [Zhu, Wei; Cadet, Patrick; Mantione, Kirk J.; Stefano, George B.] SUNY Coll Old Westbury, Neurosci Res Inst, Old Westbury, NY 11568 USA. [Bromfield, Edward; Dworetzky, Barbara] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Madsen, Joseph] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [DeGirolami, Umberto; Black, Peter] Brigham & Womens Hosp, Dept Pathol, Div Neuropathol, Boston, MA 02115 USA. [Vaccaro, Bernardino] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Fricchione, G (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat & Med, Boston, MA 02114 USA. EM gfricchione@partners.org FU NIDA NIH HHS [DA 09010] NR 20 TC 28 Z9 28 U1 0 U2 1 PU INT SCIENTIFIC LITERATURE, INC PI ALBERTSON PA 1125 WILLIS AVE, ALBERTSON, NY 11507 USA SN 1234-1010 J9 MED SCI MONITOR JI Med. Sci. Monitor PD JUN PY 2008 VL 14 IS 6 BP CS45 EP CS49 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 347BS UT WOS:000259114600015 PM 18509280 ER PT J AU King, RK Green, AR Tan-Mcgrory, A Donahue, EJ Kimbrough-Sugick, J Betancourt, JR AF King, Roderick K. Green, Alexander R. Tan-Mcgrory, Aswita Donahue, Elizabeth J. Kimbrough-Sugick, Jessie Betancourt, Joseph R. TI A plan for action: Key perspectives from the racial/ethnic disparities strategy forum SO MILBANK QUARTERLY LA English DT Review DE disparities; quality improvement; minority health; race; ethnicity; access; disease management; data collection ID PEDIATRIC EMERGENCY-DEPARTMENT; SPANISH-SPEAKING PATIENTS; LENGTH-OF-STAY; HEALTH-CARE; QUALITY IMPROVEMENT; RACIAL-DIFFERENCES; MYOCARDIAL-INFARCTION; LANGUAGE PROFICIENCY; SOCIOECONOMIC-STATUS; ETHNIC DISPARITIES AB Context: Racial and ethnic disparities in health care in the United States have been well documented, with research largely focusing on describing the problem rather than identifying the best practices or proven strategies to address it. Methods: In 2006, the Disparities Solutions Center convened a one-and-a-half-day Strategy Forum composed of twenty experts from the fields of racial/ethnic disparities in health care, quality improvement, implementation research, and organizational excellence, with the goal of deciding on innovative action items and adoption strategies to address disparities. The forum used the Results Based Facilitation model, and several key recommendations emerged. Findings: The forum's participants concluded that to identify and effectively address racial/ethnic disparities in health care, health care organizations should: (1) collect race and ethnicity data on patients or enrollees in a routine and standardized fashion; (2) implement tools to measure and monitor for disparities in care; (3) develop quality improvement strategies to address disparities; (4) secure the support of leadership; (5) use incentives to address disparities; and (6) create a messaging and communication strategy for these efforts. This article also discusses these recommendations in the context of both current efforts to address racial and ethnic disparities in health care and barriers to progress. Conclusions: The Strategy Forum's participants concluded that health care organizations needed a multifaceted plan of action to address racial and ethnic disparities in health care. Although the ideas offered are not necessarily new, the discussion of their practical development and implementation should make them more useful. C1 [King, Roderick K.; Green, Alexander R.; Tan-Mcgrory, Aswita; Donahue, Elizabeth J.; Kimbrough-Sugick, Jessie; Betancourt, Joseph R.] Massachusetts Gen Hosp, Dispar Solut Ctr, Partners HealthCare Syst, Inst Hlth Policy, Boston, MA 02114 USA. RP King, RK (reprint author), Massachusetts Gen Hosp, Dispar Solut Ctr, Partners HealthCare Syst, Inst Hlth Policy, 50 Staniford St,Suite 942, Boston, MA 02114 USA. EM Roderick_King@hms.harvard.edu NR 102 TC 21 Z9 21 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0887-378X J9 MILBANK Q JI Milbank Q. PD JUN PY 2008 VL 86 IS 2 BP 241 EP 272 DI 10.1111/j.1468-0009.2008.00521.x PG 32 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 308TD UT WOS:000256412000003 PM 18522613 ER PT J AU Mauri, T Pivi, S Bigatello, LM AF Mauri, T. Pivi, S. Bigatello, L. M. TI Prolonged mechanical ventilation after critical illness SO MINERVA ANESTESIOLOGICA LA English DT Article; Proceedings Paper CT 19th Smart Congress CY MAY 28-30, 2008 CL Milan, ITALY DE respiration, artificial; respiratory insufficiency; intensive care unit ID INTENSIVE-CARE UNITS; WEANING CENTER; OUTCOMES; SURVIVAL; COST; LIFE AB A significant number of patients that have been critically ill require mechanical ventilation for extended periods of time as they progress towards recovery. Many of these patients can be cared for outside of the Intensive Care Unit in facilities focused on stabilizing the underlying medical problems, managing ventilatory support, and planning for rehabilitation and home care. Although these units have varied administrative structures, they have reported similar encouraging rates of weaning and survival. In a recent study about such a ward at a large academic hospital, it was observed that, although the majority of patients were liberated from the ventilator and returned home with a satisfactory activity level, a significant number of patients did not; these patients eventually died after a protracted hospital stay, mostly after a consensual withdrawal of life support. In the present article, a relevant literature review is presented concerning the outcome of patients undergoing prolonged mechanical ventilation. The main focus of the research was to address how to alleviate the burden of prolonged critical illness on mechanically ventilated patients who may eventually die after a great deal of suffering, and to identify the tangible emotional and financial costs to these patients, their families, and society. C1 [Mauri, T.; Pivi, S.; Bigatello, L. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Mauri, T.] Univ Milan, Dept Expt Med, Milan, Italy. [Pivi, S.] Univ Bologna, S Orsola M Malpighi Hosp, Dept Anesthesiol, Bologna, Italy. RP Bigatello, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM lbigatello@partners.org NR 20 TC 10 Z9 12 U1 0 U2 1 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0375-9393 J9 MINERVA ANESTESIOL JI Minerva Anestesiol. PD JUN PY 2008 VL 74 IS 6 BP 297 EP 301 PG 5 WC Anesthesiology; Critical Care Medicine SC Anesthesiology; General & Internal Medicine GA 306EE UT WOS:000256230300013 PM 18500202 ER PT J AU Flavin, RJ Smyth, PC Finn, SP Laios, A O'Toole, SA Barrett, C Ring, M Denning, KM Li, J Aherne, ST Aziz, NA Alhadi, A Sheppard, BL Loda, M Martin, C Sheils, OM O'Leary, JJ AF Flavin, Richard J. Smyth, Paul C. Finn, Stephen P. Laios, Alexandros O'Toole, Sharon A. Barrett, Ciara Ring, Martina Denning, Karen M. Li, Jinghuan Aherne, Sinead T. Aziz, Natasha A. Alhadi, Araibi Sheppard, Brian L. Loda, Massimo Martin, Cara Sheils, Orla M. O'Leary, John J. TI Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients SO MODERN PATHOLOGY LA English DT Article DE eIF6; Dicer; Drosha; microRNA machinery; microRNAs; ovarian serous carcinoma ID COMPARATIVE GENOMIC HYBRIDIZATION; EUKARYOTIC INITIATION FACTOR-6; HUMAN LUNG CANCERS; REDUCED EXPRESSION; PRECURSOR LESIONS; DOWN-REGULATION; MICRORNA; PROTEIN; CELLS; P27(BBP) AB MicroRNAs are a group of small non-coding RNAs approximately 22 nucleotides in length. Recent work has shown differential expression of mature microRNAs in human cancers. Production and function of microRNAs require coordinated processing by proteins of the microRNA machinery. Dicer and Drosha (RNase III endonucleases) are essential components of the microRNA machinery. Recently, the ribosome anti-association factor eIF6 has also been found to have a role in microRNA-mediated post-transcriptional silencing. We characterized the alterations in the expression of genes encoding proteins of microRNA machinery in ovarian serous carcinoma. Protein expression of eIF6 and Dicer was quantified in a tissue microarray of 66 ovarian serous carcinomas. Dicer, Drosha and eIF6 mRNA expression was analysed using quantitative reverse transcription-PCR on an independent set of 50 formalin-fixed, paraffin-embedded ovarian serous carcinoma samples. Expression profiles of eIF6 and Dicer were correlated with clinicopathological and patient survival data. We provide definitive evidence that eIF6 and Dicer are both upregulated in a significant proportion of ovarian serous carcinomas and are associated with specific clinicopathological features, most notably low eIF6 expression being associated with reduced disease-free survival. The status of eIF6 and proteins of the microRNA machinery may help predict toxicity and susceptibility to future interfering RNA-based therapy. C1 [Flavin, Richard J.; Smyth, Paul C.; Li, Jinghuan; O'Leary, John J.] Univ Dublin Trinity Coll, Dept Histopathol, Dublin 2, Ireland. [Finn, Stephen P.; Aziz, Natasha A.; Alhadi, Araibi; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Laios, Alexandros; O'Toole, Sharon A.] Univ Dublin Trinity Coll, Dept Obstet & Gynaecol, Dublin 2, Ireland. RP Flavin, RJ (reprint author), St James Hosp, Dept Histopathol, Phase Trinity Ctr Hlth Sci 3, Jamess St, Dublin 8, Ireland. EM flavinr@tcd.ie RI Sheils, Orla Sheils/B-8461-2015; OI Sheils, Orla Sheils/0000-0002-4493-9496; Finn, Stephen/0000-0002-8628-5814; o toole, sharon/0000-0002-9260-3225 NR 58 TC 61 Z9 62 U1 0 U2 1 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 JUN PY 2008 VL 21 IS 6 BP 676 EP 684 DI 10.1038/modpathol.2008.33 PG 9 WC Pathology SC Pathology GA 304MF UT WOS:000256112900005 PM 18327211 ER PT J AU Sue, N Jack, BHA Eaton, SA Pearson, RCM Funnell, APW Turner, J Czolij, R Denyer, G Bao, SS Molero-Navajas, JC Perkins, A Fujiwara, Y Orkin, SH Bell-Anderson, K Crossley, M AF Sue, Nancy Jack, Briony H. A. Eaton, Sally A. Pearson, Richard C. M. Funnell, Alister P. W. Turner, Jeremy Czolij, Robert Denyer, Gareth Bao, Shisan Molero-Navajas, Juan Carlos Perkins, Andrew Fujiwara, Yuko Orkin, Stuart H. Bell-Anderson, Kim Crossley, Merlin TI Targeted disruption of the basic Kruppel-like factor gene (Klf3) reveals a role in adipogenesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENHANCER-BINDING-PROTEIN; C/EBP-ALPHA GENE; ADIPOCYTE DIFFERENTIATION; TRANSCRIPTION FACTOR; FACTOR EKLF; ERYTHROID-CELLS; CO-REPRESSOR; EXPRESSION; DEHYDROGENASE; ACTIVATION AB Kruppel-like factors (KLFs) recognize CACCC and GC-rich sequences in gene regulatory elements. Here, we describe the disruption of the murine basic Kruppel-like factor gene (Bklf or Klf3). Klf3 knockout mice have less white adipose tissue, and their fat pads contain smaller and fewer cells. Adipocyte differentiation is altered in murine embryonic fibroblasts from Klf3 knockouts. Klf3 expression was studied in the 3T3-L1 cellular system. Adipocyte differentiation is accompanied by a decline in Klf3 expression, and forced overexpression of Klf3 blocks 3T3-L1 differentiation. Klf3 represses transcription by recruiting C-terminal binding protein (CtBP) corepressors. CtBPs bind NADH and may function as metabolic sensors. A Klf3 mutant that does not bind CtBP cannot block adipogenesis. Other KLFs, Klf2, Klf5, and Klf15, also regulate adipogenesis, and functional CACCC elements occur in key adipogenic genes, including in the C/ebp alpha promoter. We find that C/ebp alpha is derepressed in Klf3 and Ctbp knockout fibroblasts and adipocytes from Klf3 knockout mice. Chromatin immunoprecipitations confirm that Klf3 binds the C/ebp alpha promoter in vivo. These results implicate Klf3 and CtBP in controlling adipogenesis. C1 [Sue, Nancy; Jack, Briony H. A.; Eaton, Sally A.; Pearson, Richard C. M.; Funnell, Alister P. W.; Turner, Jeremy; Czolij, Robert; Denyer, Gareth; Bell-Anderson, Kim; Crossley, Merlin] Univ Sydney, Sch Mol & Microbial Biosci, Sydney, NSW 2006, Australia. [Bao, Shisan] Univ Sydney, Sch Med Sci, Sydney, NSW 2006, Australia. [Molero-Navajas, Juan Carlos] Garvan Inst Med Res, Diabet & Obes Program, Sydney, NSW 2010, Australia. [Perkins, Andrew] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia. [Fujiwara, Yuko; Orkin, Stuart H.] Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Crossley, M (reprint author), Univ Sydney, Sch Mol & Microbial Biosci, G08, Sydney, NSW 2006, Australia. EM m.crossley@mmb.usyd.edu.au RI denyer, gareth/E-3437-2010; Crossley, Merlin/D-7888-2011; Bell-Anderson, Kim/A-5588-2009; Pearson, Richard/J-4411-2012; Bao, Shisan/C-6072-2014; Perkins, Andrew/M-3216-2014; Denyer, Gareth/M-5417-2016; OI Crossley, Merlin/0000-0003-2057-3642; Pearson, Richard/0000-0002-7918-9111; Perkins, Andrew/0000-0003-3644-7093; Denyer, Gareth/0000-0003-1551-3936; Funnell, Alister/0000-0002-1062-5296 FU NHLBI NIH HHS [HL073443, R01 HL073443] NR 37 TC 70 Z9 79 U1 0 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 2008 VL 28 IS 12 BP 3967 EP 3978 DI 10.1128/MCB.01942-07 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 309HT UT WOS:000256452000008 PM 18391014 ER PT J AU Zheng, H Jin, B Henrickson, SE Perelson, AS von Andrian, UH Chakraborty, AK AF Zheng, Huan Jin, Bo Henrickson, Sarah E. Perelson, Alan S. von Andrian, Ulrich H. Chakraborty, Arup K. TI How antigen quantity and quality determine T-cell decisions in lymphoid tissue SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DENDRITIC CELLS; IMMUNOLOGICAL SYNAPSE; IN-VIVO; 2-PHOTON MICROSCOPY; STOP SIGNAL; NODES; RECEPTOR; ACTIVATION; IMMUNITY; DYNAMICS AB T lymphocytes (T cells) express T-cell receptor (TCR) molecules on their surface that can recognize peptides (p) derived from antigenic proteins bound to products of the major histocompatibility complex (MHC) genes. The pMHC molecules are expressed on the surface of antigen-presenting cells, such as dendritic cells (DCs). T cells first encounter antigen on DCs in lymph nodes (LN). Intravital microscopy experiments show that upon entering the LN containing antigen, CD8(+) T cells first move rapidly. After a few hours, they stop and make extended contacts with DCs. The factors that determine when and how this transition occurs are not well understood. We report results from computer simulations that suggest that the duration of phase one is related to the low probability of productive interactions between T cells and DCs. This is demonstrated by our finding that the antigen dose and type determine when such a transition occurs. These results are in agreement with experimental observations. TCR-pMHC binding characteristics and the antigen dose determine the time required for a productive T-cell-DC encounter (resulting in sustained contact). We find that the ratio of this time scale and the half-life of the pMHC complex itself provide a consolidated measure of antigen quantity and type. Results obtained upon varying different measures of antigen quantity and type fall on one curve when graphed against this ratio of time scales. Thus, we provide a mechanism for how the effects of varying one set of parameters are influenced by other prevailing conditions. This understanding should help guide future experimentation. C1 [Zheng, Huan; Jin, Bo; Chakraborty, Arup K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Chakraborty, Arup K.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Chakraborty, Arup K.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Henrickson, Sarah E.; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Henrickson, Sarah E.; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Perelson, Alan S.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA. RP Chakraborty, AK (reprint author), MIT, Dept Chem Engn, Room E19-502C,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM arupc@mit.edu RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL07623, T32 HL007623]; NIAID NIH HHS [P01 AI071195, 1 PO1 AI071195-01, AI072252, R01 AI069259, R01 AI072252, R37 AI028433, R37 AI28433]; NIAMS NIH HHS [AR42689, P30 AR042689]; NIGMS NIH HHS [T32 GM007753] NR 52 TC 36 Z9 36 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 2008 VL 28 IS 12 BP 4040 EP 4051 DI 10.1128/MCB.00136-08 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 309HT UT WOS:000256452000014 PM 18426917 ER PT J AU Clark, A Weymann, A Hartman, E Turmelle, Y Carroll, M Thurmane, JM Holers, VM Hourcade, DE Rudnick, DA AF Clark, Amelia Weymann, Alexander Hartman, Eric Turmelle, Yumirle Carroll, Michael Thurmane, Joshua M. Holers, V. Michael Hourcade, Dennis E. Rudnick, David A. TI Evidence for non-traditional activation of complement factor C3 during murine liver regeneration SO MOLECULAR IMMUNOLOGY LA English DT Article DE partial hepatectomy; alternative pathway; classical pathway; factor B; C4 ID FACTOR-B; PARTIAL-HEPATECTOMY; RAPID ACTIVATION; MICE DEFICIENT; 2 PARTS; PATHWAY; EXPRESSION; COMPONENT; ANTIBODY; INJURY AB Complement signaling has been implicated as important for normal hepatic regeneration. However, the specific mechanism by which complement is activated during liver regeneration remains undefined. To address this question, we investigated the hepatic regenerative response to partial hepatectomy in wildtype mice, C3-, C4-, and factor B-null mice, and C4-null mice treated with a factor B neutralizing antibody (mAb 1379). The results showed that following partial hepatectomy, C3-null mice exhibit reduced hepatic regeneration compared to wildtype mice as assessed by quantification of hepatic cyclin D1 expression and hepatocellular DNA synthesis and mitosis. In contrast, C4-null mice and factor B-null mice demonstrated normal liver regeneration. Moreover, animals in which all of the traditional upstream C3 activation pathways were disrupted, i.e. C4-null mice treated with mAb 1379, exhibited normal C3 activation and hepatocellular proliferation following partial hepatectomy. In order to define candidate non-traditional mechanisms of C3 activation during liver regeneration, plasmin and thrombin were investigated for their abilities to activate C3 in mouse plasma in vitro. The results showed that both proteases are capable of initiating C3 activation, and that plasmin can do so independent of the classical and alternative pathways. Conclusions: These results show that C3 is required for a normal hepatic regenerative response, but that disruption of the classical- or lectin-dependent pathways (C4-dependent), the alternative pathway (factor B-dependent), or all of these pathways does not impair the hepatic regenerative response, and indicate that non-traditional mechanisms by which C3 is activated during hepatic regeneration must exist. In vitro analysis raises the possibility that plasmin may contribute to non-traditional complement activation during liver regeneration in vivo. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Clark, Amelia; Weymann, Alexander; Hartman, Eric; Turmelle, Yumirle; Rudnick, David A.] Washington Univ, Dept Pediat, Sch Med, St Louis, MO 63110 USA. [Hourcade, Dennis E.] Washington Univ, Dept Med, Sch Med, St Louis, MO 63110 USA. [Rudnick, David A.] Washington Univ, Dept Dev Biol, Sch Med, St Louis, MO 63110 USA. [Carroll, Michael] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. [Carroll, Michael] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Thurmane, Joshua M.; Holers, V. Michael] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. RP Rudnick, DA (reprint author), Washington Univ, Dept Pediat, Sch Med, 660 S Euclid Ave,Box 8208, St Louis, MO 63110 USA. EM rudnick.d@kids.wustl.edu FU NIAID NIH HHS [AI05143]; NICHD NIH HHS [T32 HD007409, T32-HD07409]; NIDDK NIH HHS [DK064790, DK068219, K08 DK064790, P30 DK052574, P30 DK52574, R01 DK068219, R01 DK068219-01A1, R01 DK068219-02, R01 DK068219-03] NR 43 TC 38 Z9 39 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JUN PY 2008 VL 45 IS 11 BP 3125 EP 3132 DI 10.1016/j.molimm.2008.03.008 PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 317MR UT WOS:000257024800013 PM 18452991 ER PT J AU Edgar, R Rokney, A Feeney, M Semsey, S Kessel, M Goldberg, MB Adhya, S Oppenheim, AB AF Edgar, Rotem Rokney, Assaf Feeney, Morgan Semsey, Szabolcs Kessel, Martin Goldberg, Marcia B. Adhya, Sankar Oppenheim, Amos B. TI Bacteriophage infection is targeted to cellular poles SO MOLECULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; PHOSPHOTRANSFERASE SYSTEM; BACILLUS-SUBTILIS; GENOME SEQUENCE; OUTER-MEMBRANE; LAMBDA-DNA; PROTEIN; RECEPTOR; DIVISION; FTSH AB The poles of bacteria exhibit several specialized functions related to the mobilization of DNA and certain proteins. To monitor the infection of Escherichia coli cells by light microscopy, we developed procedures for the tagging of mature bacteriophages with quantum dots. Surprisingly, most of the infecting phages were found attached to the bacterial poles. This was true for a number of temperate and virulent phages of E. coli that use widely different receptors and for phages infecting Yersinia pseudotuberculosis and Vibrio cholerae. The infecting phages colocalized with the polar protein marker IcsA-GFP. ManY, an E. coli protein that is required for phage lambda DNA injection, was found to localize to the bacterial poles as well. Furthermore, labelling of lambda DNA during infection revealed that it is injected and replicated at the polar region of infection. The evolutionary benefits that lead to this remarkable preference for polar infections may be related to lambda's developmental decision as well as to the function of poles in the ability of bacterial cells to communicate with their environment and in gene regulation. C1 [Edgar, Rotem; Semsey, Szabolcs; Adhya, Sankar; Oppenheim, Amos B.] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Rokney, Assaf; Oppenheim, Amos B.] Hebrew Univ Jerusalem, Dept Mol Genet & Biotechnol, Hadassah Med Sch, IL-91120 Jerusalem, Israel. [Feeney, Morgan; Goldberg, Marcia B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. [Semsey, Szabolcs] Eotvos Lorand Univ, Dept Genet, H-1117 Budapest, Hungary. [Kessel, Martin] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Edgar, R (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM edgarr@mail.nih.gov RI Semsey, Szabolcs/L-6329-2013; OI Semsey, Szabolcs/0000-0002-4522-5495 FU Intramural NIH HHS; NIAID NIH HHS [AI071240, AI35817, R01 AI035817, R21 AI071240] NR 39 TC 41 Z9 41 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUN PY 2008 VL 68 IS 5 BP 1107 EP 1116 DI 10.1111/j.1365-2958.2008.06205.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 298WJ UT WOS:000255717500006 PM 18363799 ER PT J AU Mishra, AK Alderwick, LJ Rittmann, D Wang, C Bhatt, A Jacobs, WR Takayama, K Eggeling, L Besra, GS AF Mishra, Arun K. Alderwick, Luke J. Rittmann, Doris Wang, Cindy Bhatt, Apoorva Jacobs, William R., Jr. Takayama, Kuni Eggeling, Lothar Besra, Gurdyal S. TI Identification of a novel alpha(1 -> 6) mannopyranosyltransferase MptB from Corynebacterium glutamicum by deletion of a conserved gene, NCgl1505, affords a lipomannan- and lipoarabinomannan-deficient mutant SO MOLECULAR MICROBIOLOGY LA English DT Article ID WALL ARABINAN BIOSYNTHESIS; BOMBARDMENT MASS-SPECTROMETRY; MYCOBACTERIUM-TUBERCULOSIS; CELL-WALL; PHOSPHATIDYLINOSITOL MANNOSIDES; MONOPHOSPHOMANNOSE SYNTHASE; STRUCTURAL DEFINITION; CORYNEFORM BACTERIA; NONREDUCING TERMINI; BOVIS BCG AB Mycobacterium tuberculosis and Corynebacterium glutamicum share a similar cell wall structure and orthologous enzymes involved in cell wall assembly. Herein, we have studied C. glutamicum NCgl1505, the orthologue of putative glycosyltransferases Rv1459c from M. tuberculosis and MSMEG3120 from Mycobacterium smegmatis. Deletion of NCgl1505 resulted in the absence of lipomannan (Cg-LM-A), lipoarabinomannan (Cg-LAM) and a multi-mannosylated polymer (Cg-LM-B) based on a 1,2-di-O-C(16)/C(18:1)-(alpha-D-glucopyranosyluronic acid)-(1 -> 3)-glycerol (GlcAGroAc(2)) anchor, while syntheses of triacylated-phosphatidyl-myo-inositol dimannoside (Ac(1)PIM(2)) and Man(1)GlcAGroAc(2) were still abundant in whole cells. Cell-free incubation of C. glutamicum membranes with GDP-[(14)C]Man established that C. glutamicum synthesized a novel alpha(1 -> 6)-linked linear form of Cg-LM-A and Cg-LM-B from Ac(1)PIM(2) and Man(1)GlcAGroAc(2) respectively. Furthermore, deletion of NCgl1505 also led to the absence of in vitro synthesized linear Cg-LM-A and Cg-LM-B, demonstrating that NCgl1505 was involved in core alpha(1 -> 6) mannan biosynthesis of Cg-LM-A and Cg-LM-B, extending Ac(1)PI[(14)C]M(2) and [(14)C]Man(1)GlcAGroAc(2) primers respectively. Use of the acceptor alpha-D-Manp-(1 -> 6)-alpha-D-Manp-O-C(8) in an in vitro cell-free assay confirmed NCgl1505 as an alpha(1 -> 6) mannopyranosyltransferase, now termed MptB. While Rv1459c and MSMEG3120 demonstrated similar in vitro alpha(1 -> 6) mannopyranosyltransferase activity, deletion of the Rv1459c homologue in M. smegmatis did not result in loss of mycobacterial LM/LAM, indicating a functional redundancy for this enzyme in mycobacteria. C1 [Mishra, Arun K.; Alderwick, Luke J.; Bhatt, Apoorva; Besra, Gurdyal S.] Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England. [Rittmann, Doris; Eggeling, Lothar] Res Ctr, Inst Biotechnol 1, D-52425 Julich, Germany. [Wang, Cindy; Takayama, Kuni] William S Middleton Mem Vet Adm Med Ctr, Mycobacteriol Res Lab, Madison, WI 53705 USA. [Jacobs, William R., Jr.] Albert Einstein Coll Med, Howard Hughes Med Inst, Dept Microbiol & Immunol, Bronx, NY 10461 USA. RP Besra, GS (reprint author), Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England. EM g.besra@bham.ac.uk FU Medical Research Council [, G0600105, G9901077]; Wellcome Trust [081569/Z/06/Z] NR 77 TC 33 Z9 37 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUN PY 2008 VL 68 IS 6 BP 1595 EP 1613 DI 10.1111/j.1365-2958.2008.06265.x PG 19 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 304LJ UT WOS:000256110700021 PM 18452585 ER PT J AU Katiyar, SK AF Katiyar, Santosh K. TI Grape seed proanthocyanidines and skin cancer prevention: Inhibition of oxidative stress and protection of immune system SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Review DE Grape seed proanthocyanidins; Immunosuppression; Oxidative stress; Photocarcinogenesis; Ultraviolet radiation ID SKH-1 HAIRLESS MICE; NF-KAPPA-B; ULTRAVIOLET-RADIATION; LIPID-PEROXIDATION; MOUSE SKIN; CONTACT HYPERSENSITIVITY; TRANSPLANT RECIPIENTS; PROTEIN-KINASES; RICH EXTRACT; RISK-FACTOR AB Overexposure of the skin to UV radiation has a variety of adverse effects on human health, including the development of skin cancers. There is a need to develop nutrition-based efficient chemopreventive strategies. The proanthocyanidins present in grape seeds (Vitis vinifera) have been shown to have some biological effects, including prevention of photocarcinogenesis. The present communication discusses the in vitro and in vivo studies of the possible protective effect of grape seed proanthocyanidins (GSPs) and the molecular mechanism for these effects. In SKH-1 hairless mice, dietary supplementation with GSPs is associated with a decrease of UVB-induced skin tumor development in terms of tumor incidence, tumor multiplicity, and a decrease in the malignant transformation of papillomas to carcinomas. It is suggested that the chemopreventive effects of dietary GSPs are mediated through the attenuation of UV-induced: (i) oxidative stress; (ii) activation of mitogen-activated protein kinases and nuclear factor-kappa B (NF-kappa B) signaling pathways; and (iii) immunosuppression through alterations in immunoregulatory cytokines. Collectively, these studies indicate protective potential of GSPs against experimental photocarcinogenesis in SKH-1 hairless mice, and the possible mechanisms of action of GSPs, and suggest that dietary GSPs could be useful in the attenuation of the adverse UV-induced health effects in human skin. C1 [Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557,POB 202, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU National Cancer Institute/NIH [CA104428]; Veterans Affairs Merit Review Award FX The work reported from the author's laboratory was supported from the funds from National Cancer Institute/NIH (CA104428) and Veterans Affairs Merit Review Award. The content of this publication does not necessarily reflect the views or policies of the funding sources. Grateful thanks are due to our former and current postdoctoral fellows for their outstanding contributions. NR 57 TC 34 Z9 36 U1 2 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD JUN PY 2008 VL 52 SU 1 BP S71 EP S76 DI 10.1002/mnfr.200700198 PG 6 WC Food Science & Technology SC Food Science & Technology GA 472CC UT WOS:000268105800008 PM 18384090 ER PT J AU Sklar, P Smoller, JW Fan, J Ferreira, MAR Perlis, RH Chambert, K Nimgaonkar, VL McQueen, MB Faraone, SV Kirby, A de Bakker, PIW Ogdie, MN Thase, ME Sachs, GS Todd-Brown, K Gabriel, SB Sougnez, C Gates, C Blumenstiel, B Defelice, M Ardlie, KG Franklin, J Muir, WJ McGhee, KA MacIntyre, DJ McLean, A VanBeck, M McQuillin, A Bass, NJ Robinson, M Lawrence, J Anjorin, A Curtis, D Scolnick, EM Daly, MJ Blackwood, DH Gurling, HM Purcell, SM AF Sklar, P. Smoller, J. W. Fan, J. Ferreira, M. A. R. Perlis, R. H. Chambert, K. Nimgaonkar, V. L. McQueen, M. B. Faraone, S. V. Kirby, A. de Bakker, P. I. W. Ogdie, M. N. Thase, M. E. Sachs, G. S. Todd-Brown, K. Gabriel, S. B. Sougnez, C. Gates, C. Blumenstiel, B. Defelice, M. Ardlie, K. G. Franklin, J. Muir, W. J. McGhee, K. A. MacIntyre, D. J. McLean, A. VanBeck, M. McQuillin, A. Bass, N. J. Robinson, M. Lawrence, J. Anjorin, A. Curtis, D. Scolnick, E. M. Daly, M. J. Blackwood, D. H. Gurling, H. M. Purcell, S. M. TI Whole-genome association study of bipolar disorder SO MOLECULAR PSYCHIATRY LA English DT Article DE genetic; schizophrenia; CACNA1C; MYO5B; TSPAN8; EGFR ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; MYOSIN VB; FAMILIAL AGGREGATION; DIAGNOSTIC INTERVIEW; PSYCHOTIC SYMPTOMS; CANDIDATE GENES; MOOD DISORDERS; I DISORDER AB We performed a genome-wide association scan in 1461 patients with bipolar (BP) 1 disorder, 2008 controls drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder and the University College London sample collections with successful genotyping for 372 193 single nucleotide polymorphisms (SNPs). Our strongest single SNP results are found in myosin5B (MYO5B; P = 1.66 x 10(-7)) and tetraspanin-8 (TSPAN8; P = 6.11 x 10(-7)). Haplotype analysis further supported single SNP results highlighting MYO5B, TSPAN8 and the epidermal growth factor receptor (MYO5B; P = 2.04 x 10(-8), TSPAN8; P = 7.57 x 10(-7) and EGFR; P = 8.36 x 10(-8)). For replication, we genotyped 304 SNPs in family-based NIMH samples (n = 409 trios) and University of Edinburgh case-control samples (n = 365 cases, 351 controls) that did not provide independent replication after correction for multiple testing. A comparison of our strongest associations with the genome-wide scan of 1868 patients with BP disorder and 2938 controls who completed the scan as part of the Wellcome Trust Case-Control Consortium indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene. Given the heritability of BP disorder, the lack of agreement between studies emphasizes that susceptibility alleles are likely to be modest in effect size and require even larger samples for detection. C1 [Sklar, P.; Smoller, J. W.; Fan, J.; Ferreira, M. A. R.; Perlis, R. H.; de Bakker, P. I. W.; Ogdie, M. N.; Todd-Brown, K.; Daly, M. J.; Purcell, S. M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Sklar, P.; Smoller, J. W.; Fan, J.; Ferreira, M. A. R.; Perlis, R. H.; Ogdie, M. N.; Sachs, G. S.; Todd-Brown, K.; Purcell, S. M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sklar, P.; Smoller, J. W.; Perlis, R. H.; Sachs, G. S.; Daly, M. J.; Purcell, S. M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Sklar, P.; Smoller, J. W.; Perlis, R. H.; Sachs, G. S.; Daly, M. J.; Purcell, S. M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Sklar, P.; Smoller, J. W.; Perlis, R. H.; Sachs, G. S.; Daly, M. J.; Purcell, S. M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sklar, P.; Smoller, J. W.; Fan, J.; Ferreira, M. A. R.; Perlis, R. H.; Chambert, K.; de Bakker, P. I. W.; Ogdie, M. N.; Todd-Brown, K.; Gabriel, S. B.; Sougnez, C.; Gates, C.; Blumenstiel, B.; Defelice, M.; Ardlie, K. G.; Franklin, J.; Scolnick, E. M.; Daly, M. J.; Purcell, S. M.] Broad Inst Harvard, Cambridge, MA USA. [Sklar, P.; Smoller, J. W.; Fan, J.; Ferreira, M. A. R.; Perlis, R. H.; Chambert, K.; Kirby, A.; de Bakker, P. I. W.; Ogdie, M. N.; Todd-Brown, K.; Gabriel, S. B.; Sougnez, C.; Gates, C.; Blumenstiel, B.; Defelice, M.; Ardlie, K. G.; Franklin, J.; Scolnick, E. M.; Daly, M. J.; Purcell, S. M.] MIT, Cambridge, MA 02139 USA. [Ferreira, M. A. R.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Nimgaonkar, V. L.; Thase, M. E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Nimgaonkar, V. L.; Thase, M. E.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [McQueen, M. B.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. [Faraone, S. V.] SUNY Syracuse, Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. [Faraone, S. V.] SUNY Syracuse, Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. [Kirby, A.; de Bakker, P. I. W.; Daly, M. J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Muir, W. J.; McGhee, K. A.; MacIntyre, D. J.; McLean, A.; VanBeck, M.] Univ Edinburgh, Div Psychiat, Edinburgh, Midlothian, Scotland. [McQuillin, A.; Bass, N. J.; Robinson, M.; Lawrence, J.; Anjorin, A.; Curtis, D.; Gurling, H. M.] UCL, Windeyer Inst Med Sci, Dept Mental Hlth Sci, Mol Psychiat Lab, London, England. RP Sklar, P (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM sklar@chgr.mgh.harvard.edu RI Ferreira, Manuel/D-3609-2013; Gurling, Hugh/A-5029-2010; de Bakker, Paul/B-8730-2009; McQuillin, Andrew/C-1623-2008; OI de Bakker, Paul/0000-0001-7735-7858; McQuillin, Andrew/0000-0003-1567-2240; MacIntyre, Donald J/0000-0001-6963-1335; Todd-Brown, Katherine/0000-0002-3109-8130; Faraone, Stephen/0000-0002-9217-3982 FU Intramural NIH HHS; Medical Research Council [G9623693N, G0500791]; NICHD NIH HHS [R01 HD060726]; NIMH NIH HHS [MH059565, MH059571, MH059588, MH061675, MH062137, MH063445, MH067257, MH067288, MH59566, MH59586, MH59587, MH60870, MH63420, N01MH80001, R01 MH059533, R01 MH059534, R01 MH059535, R01 MH059545, R01 MH059548, R01 MH059553, R01 MH059556, R01 MH059565, R01 MH059566, R01 MH059567, R01 MH059571, R01 MH059586, R01 MH059587, R01 MH059588, R01 MH060068, R01 MH060870, R01 MH060879, R01 MH061675, R01 MH062137, R01 MH063420, R01 MH063445, R01 MH067257, R01 MH067288, R01 MH59533, R01 MH59535, R01 MH59545, R01 MH59553, R01 MH59567, R01 MH60068, RC2 MH089905, U01 MH060879, Z01 MH002810]; Wellcome Trust [, 066717] NR 61 TC 411 Z9 425 U1 4 U2 36 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUN PY 2008 VL 13 IS 6 BP 558 EP 569 DI 10.1038/sj.mp.4002151 PG 12 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 302FE UT WOS:000255953400001 PM 18317468 ER PT J AU Kim, JW Biederman, J McGrath, CL Doyle, AE Mick, E Fagerness, J Purcell, S Smoller, JW Sklar, P Faraone, SV AF Kim, J. W. Biederman, J. McGrath, C. L. Doyle, A. E. Mick, E. Fagerness, J. Purcell, S. Smoller, J. W. Sklar, P. Faraone, S. V. TI Further evidence of association between two NET single-nucleotide polymorphisms with ADHD SO MOLECULAR PSYCHIATRY LA English DT Article DE ADHD; NET; association; SNP; replication ID DEFICIT HYPERACTIVITY DISORDER; NOREPINEPHRINE TRANSPORTER GENE; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; NO EVIDENCE; CANDIDATE GENES; RISK-FACTORS; LINKAGE; HERITABILITY; METAANALYSIS; POPULATION AB The norepinephrine transporter (NET) gene is an attractive candidate gene for attention-deficit hyperactivity disorder (ADHD). Noradrenergic systems are critical to higher brain functions such as attention and executive function, which are defective in ADHD. The clinical efficacy of medications that target NET also supports its role in the etiology of ADHD. Here, we have applied a dense mapping strategy to capture all genetic variations within the NET gene in a large number of ADHD families (474 trios). As a result, we found association of the same alleles from two single-nucleotide polymorphisms (rs3785143 and rs11568324) previously identified in another large-scale ADHD genetic study (International Multisite ADHD Geneproject). Furthermore, the effect sizes were consistent across both studies. This is the first time that identical alleles of NET from different studies were implicated, and thus our report provides further evidence that the NET gene is involved in the etiology of ADHD. C1 [Kim, J. W.; McGrath, C. L.; Fagerness, J.; Purcell, S.; Smoller, J. W.; Sklar, P.] Harvard Univ, Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit,Med Sch, Boston, MA 02114 USA. [Faraone, S. V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. RP Kim, JW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit,Med Sch, 185 Cambridge St,6th Floor, Boston, MA 02114 USA. EM ox95ford@yahoo.co.kr OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [HD37694, HD37999]; NIMH NIH HHS [MH66877] NR 40 TC 34 Z9 37 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUN PY 2008 VL 13 IS 6 BP 624 EP 630 DI 10.1038/sj.mp.4002090 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 302FE UT WOS:000255953400007 PM 17876324 ER PT J AU Liu, TC Castelo-Branco, P Rabkin, SD Martuza, RL AF Liu, Ta-Chiang Castelo-Branco, Pedro Rabkin, Samuel D. Martuza, Robert L. TI Trichostatin A and oncolytic HSV combination therapy shows enhanced antitumoral and antiangiogenic effects SO MOLECULAR THERAPY LA English DT Article ID HISTONE-DEACETYLASE INHIBITORS; HERPES-SIMPLEX-VIRUS; CYCLIN D1; GENE-EXPRESSION; GROWTH-INHIBITION; HYDROXAMIC ACID; LEUKEMIA-CELLS; CANCER-CELLS; TUMOR-CELLS; ANGIOGENESIS AB Oncolytic herpes simplex viruses ( HSVs) possess direct oncolytic and antiangiogenic activities and are promising anticancer agents, but their efficacy, when used as single agents, leaves room for improvement. We investigated whether combination therapy of HSV with histone deacetylase inhibitor trichostatin A ( TSA), an agent that also targets cancer cells and tumor vasculature, would result in enhanced efficacy. In vitro, TSA and G47 Delta showed strong synergy of action against proliferating endothelial cells, varying degrees of synergistic action against most cancer cell lines, but no effect in quiescent, normal endothelial and prostate epithelial cells. Synergy is dependent on viral replication; however, it is not dependent on the dosing sequence of TSA and G47 Delta, viral genetic alterations, infectivity, or replication kinetics of G47 Delta. Using an isogenic cell system, we found that a high level of cellular cyclin D1 is also critically important for the interaction. Normal cells with low cyclin D1 levels were not subjected to toxicity by either agent. In tumor cells and proliferating endothelial cells, the combination treatment enhanced the inhibition of cyclin D1 and vascular endothelial growth factor ( VEGF). Concurrent systemic TSA and intratumoral G47 Delta administration resulted in enhanced antiangiogenesis and enhanced antitumoral efficacy in animal models. Therefore, combination treatment with TSA and oncolytic HSV provides a novel approach to cancer therapy. C1 [Liu, Ta-Chiang; Castelo-Branco, Pedro; Rabkin, Samuel D.; Martuza, Robert L.] Massachusetts Gen Hosp, Dept Neurosurg, Brain Tumor Res Ctr, Mol Neurosurg Lab, Boston, MA 02114 USA. [Liu, Ta-Chiang; Castelo-Branco, Pedro; Rabkin, Samuel D.; Martuza, Robert L.] Harvard Univ, Sch Med, Boston, MA USA. RP Liu, TC (reprint author), Jennerex Biotherapeut, San Francisco, CA USA. EM tachiangliu@yahoo.com RI rabkin, samuel/C-2443-2012; OI rabkin, samuel/0000-0003-2344-2795; Castelo-Branco, Pedro/0000-0002-3453-3978 FU NCI NIH HHS [CA102139]; NINDS NIH HHS [NS32677, R01 NS032677, R01 NS032677-16] NR 49 TC 36 Z9 38 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUN PY 2008 VL 16 IS 6 BP 1041 EP 1047 DI 10.1038/mt.2008.58 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 306KR UT WOS:000256247500011 PM 18388912 ER PT J AU Madsen, JC AF Madsen, Joren C. TI Sirolimus as primary immunosuppression is effective in attenuating progression of cardiac-allograft vasculopathy SO NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE LA English DT Editorial Material DE allograft vasculopathy; heart transplantation; immunosuppression ID TRANSPLANT RECIPIENTS C1 Massachusetts Gen Hosp, Transplant Ctr, Dept Surg, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, Transplant Ctr, Dept Surg, Cox 654,55 Fruit St, Boston, MA 02114 USA. EM madsen@helix.mgh.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1743-4297 J9 NAT CLIN PRACT CARD JI Nat. Clin. Pract. Cardiovasc. Med. PD JUN PY 2008 VL 5 IS 6 BP 300 EP 301 DI 10.1038/ncpcardio1213 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 304GP UT WOS:000256098300002 PM 18461047 ER PT J AU Graham, DY Shiotani, A AF Graham, David Y. Shiotani, Akiko TI New concepts of resistance in the treatment of Helicobacter pylori infections SO NATURE CLINICAL PRACTICE GASTROENTEROLOGY & HEPATOLOGY LA English DT Review DE antibiotics; cytochrome P450; Helicobacter pylori; phenotypic drug resistance; therapy ID PROTON-PUMP INHIBITOR; TRIPLE THERAPY; QUADRUPLE THERAPY; ERADICATION THERAPY; DUAL THERAPY; ANTIBIOTIC-RESISTANCE; CURE RATES; PHARMACOKINETIC CONSIDERATIONS; CYP2C19 POLYMORPHISM; SEQUENTIAL THERAPY AB The prevalence of antimicrobial drug resistance is now so high that all patients infected with Helicobacter pylori should be considered as having resistant infections. Ideally, therapy should be based on pretreatment antibiotic-susceptibility testing but this strategy is not currently practical. At present, clarithromycin-containing triple therapies do not reliably produce a >= 80% cure rate on an intention-to-treat basis and are, therefore, no longer acceptable as empiric therapy. In this Review, we discuss concepts of resistance that have become part of mainstream thinking for other infectious diseases but have not yet become so with regard to H. pylori. We also put data on the pharmacokinetics and pharmacodynamics of the drugs used in H. pylori therapy and the effect of host cytochrome P450 genotypes in context with treatment outcomes. Our primary focus is to address the problem of H. pylori resistance from a novel perspective, which also attempts to anticipate the direction that research will need to take to provide clinicians with reliable approaches to this serious infection. We also discuss current therapies that provide acceptable cure rates when used empirically (i.e. sequential therapy; four-drug, three-antibiotic, non-bismuth-containing 'concomitant' therapy; and bismuth-containing quadruple therapy) and how they might be further improved. C1 [Graham, David Y.] Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. [Graham, David Y.] Michael E DeBakey Vet Affairs Med Ctr, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Graham, David Y.] Baylor Coll Med, Houston, TX 77030 USA. [Shiotani, Akiko] Kawasaki Med Univ, Dept Internal Med, Okayama, Japan. RP Graham, DY (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, RM 3A-320 111D,2002 Holcombe Blvd, Houston, TX 77030 USA. EM dgraham@bcm.tmc.edu FU NIDDK NIH HHS [DK56338, P30 DK056338, P30 DK056338-07] NR 73 TC 155 Z9 165 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4378 J9 NAT CLIN PRACT GASTR JI Nat. Clin. Pract. Gastroenterol. Hepatol. PD JUN PY 2008 VL 5 IS 6 BP 321 EP 331 DI 10.1038/ncpgasthep1138 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 307XG UT WOS:000256352300010 PM 18446147 ER PT J AU Halasz, LM Choi, NC AF Halasz, L. M. Choi, N. C. TI Does prophylactic cranial irradiation reduce the incidence of brain metastases in extensive small-cell lung cancer? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material DE brain metastases; cranium; irradiation; prophylaxis; small-cell lung cancer C1 [Choi, N. C.] Massachusetts Gen Hosp, Dept Radiat Oncol, Ctr Canc, Boston, MA 02114 USA. [Halasz, L. M.] Harvard Univ, Sch Med, Harvard Radiat Oncol Residency Program, Boston, MA USA. RP Choi, NC (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Ctr Canc, 100 Blossom St, Boston, MA 02114 USA. EM nchoi@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD JUN PY 2008 VL 5 IS 6 BP 308 EP 309 DI 10.1038/ncponc1125 PG 2 WC Oncology SC Oncology GA 306DT UT WOS:000256229200004 PM 18431375 ER PT J AU Kondo, Y Shen, L Cheng, AS Ahmed, S Boumber, Y Charo, C Yamochi, T Urano, T Furukawa, K Kwabi-Addo, B Gold, DL Sekido, Y Huang, THM Issa, JPJ AF Kondo, Yutaka Shen, Lanlan Cheng, Alfred S. Ahmed, Saira Boumber, Yanis Charo, Chantale Yamochi, Tadanori Urano, Takeshi Furukawa, Koichi Kwabi-Addo, Bernard Gold, David L. Sekido, Yoshitaka Huang, Tim Hui-Ming Issa, Jean-Pierre J. TI Gene silencing in cancer by histone H3 lysine 27 trimethylation independent of promoter DNA methylation SO NATURE GENETICS LA English DT Article ID HISTONE LYSINE METHYLATION; CPG ISLAND MICROARRAY; EMBRYONIC STEM-CELLS; GROUP PROTEIN EZH2; CHROMATIN IMMUNOPRECIPITATION; COLORECTAL-CANCER; PROSTATE-CANCER; SUPPRESSOR GENE; H3; HYPERMETHYLATION AB Epigenetic silencing in cancer cells is mediated by at least two distinct histone modifications, polycomb-based histone H3 lysine 27 trimethylation (H3K27triM) and H3K9 dimethylation. The relationship between DNA hypermethylation and these histone modifications is not completely understood. Using chromatin immunoprecipitation microarrays (ChIP-chip) in prostate cancer cells compared to normal prostate, we found that up to 5% of promoters (16% CpG islands and 84% non-CpG islands) were enriched with H3K27triM. These genes were silenced specifically in prostate cancer, and those CpG islands affected showed low levels of DNA methylation. Downregulation of the EZH2 histone methyltransferase restored expression of the H3K27triM target genes alone or in synergy with histone deacetylase inhibition, without affecting promoter DNA methylation, and with no effect on the expression of genes silenced by DNA hypermethylation. These data establish EZH2-mediated H3K27triM as a mechanism of tumor-suppressor gene silencing in cancer that is potentially independent of promoter DNA methylation. C1 [Kondo, Yutaka; Shen, Lanlan; Ahmed, Saira; Boumber, Yanis; Charo, Chantale; Issa, Jean-Pierre J.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Kondo, Yutaka; Sekido, Yoshitaka] Aichi Canc Ctr, Res Inst, Div Mol Oncol, Chikusa Ku, Nagoya, Aichi 4648681, Japan. [Cheng, Alfred S.; Huang, Tim Hui-Ming] Ohio State Univ, Human Canc Genet Program, Dept Mol Virol Immunol & Med Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Yamochi, Tadanori] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA. [Urano, Takeshi; Furukawa, Koichi] Nagoya Univ, Grad Sch Med, Dept Biochem 2, Showa Ku, Nagoya, Aichi 4668550, Japan. [Kwabi-Addo, Bernard] Baylor Coll Med & Michael E DeBakey, Dept Pathol, Dept Vet Affairs Med Ctr, Houston, TX 77030 USA. [Gold, David L.] Univ Texas MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA. RP Issa, JPJ (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Leukemia, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM jpissa@mdanderson.org RI Kwabi-Addo, Bernard/A-6993-2016; Cheng, Alfred/C-3327-2014; Sekido, Yoshitaka/P-9756-2015; OI Kwabi-Addo, Bernard/0000-0003-3692-6350; Cheng, Alfred/0000-0003-2345-6951; Urano, Takeshi/0000-0003-3383-3554 FU NCI NIH HHS [P50CA058204, P50CA100632, R01CA098006, R33CA89837] NR 37 TC 375 Z9 389 U1 3 U2 35 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 JUN PY 2008 VL 40 IS 6 BP 741 EP 750 DI 10.1038/ng.159 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 305XV UT WOS:000256212000016 PM 18488029 ER PT J AU Loos, RJF Lindgren, CM Li, SX Wheeler, E Zhao, JH Prokopenko, I Inouye, M Freathy, RM Attwood, AP Beckmann, JS Berndt, SI Bergmann, S Bennett, AJ Bingham, SA Bochud, M Brown, M Cauchi, S Connell, JM Cooper, C Smith, GD Day, I Dina, C De, S Dermitzakis, ET Doney, ASF Elliott, KS Elliott, P Evans, DM Farooqi, IS Froguel, P Ghori, J Groves, CJ Gwilliam, R Hadley, D Hall, AS Hattersley, AT Hebebrand, J Heid, IM Herrera, B Hinney, A Hunt, SE Jarvelin, MR Johnson, T Jolley, JDM Karpe, F Keniry, A Khaw, KT Luben, RN Mangino, M Marchini, J McArdle, WL McGinnis, R Meyre, D Munroe, PB Morris, AD Ness, AR Neville, MJ Nica, AC Ong, KK O'Rahilly, S Owen, KR Palmer, CNA Papadakis, K Potter, S Pouta, A Qi, L Randall, JC Rayner, NW Ring, SM Sandhu, MS Scherag, A Sims, MA Song, K Soranzo, N Speliotes, EK Syddall, HE Teichmann, SA Timpson, NJ Tobias, JH Uda, M Vogel, CIG Wallace, C Waterworth, DM Weedon, MN Willer, CJ Wraight, VL Yuan, X Zeggini, E Hirschhorn, JN Strachan, DP Ouwehand, WH Caulfield, MJ Samani, NJ Frayling, TM Vollenweider, P Waeber, G Mooser, V Deloukas, P McCarthy, MI Wareham, NJ Barroso, I AF Loos, Ruth J. F. Lindgren, Cecilia M. Li, Shengxu Wheeler, Eleanor Zhao, Jing Hua Prokopenko, Inga Inouye, Michael Freathy, Rachel M. Attwood, Antony P. Beckmann, Jacques S. Berndt, Sonja I. Bergmann, Sven Bennett, Amanda J. Bingham, Sheila A. Bochud, Murielle Brown, Morris Cauchi, Stephane Connell, John M. Cooper, Cyrus Smith, George Davey Day, Ian Dina, Christian De, Subhajyoti Dermitzakis, Emmanouil T. Doney, Alex S. F. Elliott, Katherine S. Elliott, Paul Evans, David M. Farooqi, I. Sadaf Froguel, Philippe Ghori, Jilur Groves, Christopher J. Gwilliam, Rhian Hadley, David Hall, Alistair S. Hattersley, Andrew T. Hebebrand, Johannes Heid, Iris M. Herrera, Blanca Hinney, Anke Hunt, Sarah E. Jarvelin, Marjo-Riitta Johnson, Toby Jolley, Jennifer D. M. Karpe, Fredrik Keniry, Andrew Khaw, Kay-Tee Luben, Robert N. Mangino, Massimo Marchini, Jonathan McArdle, Wendy L. McGinnis, Ralph Meyre, David Munroe, Patricia B. Morris, Andrew D. Ness, Andrew R. Neville, Matthew J. Nica, Alexandra C. Ong, Ken K. O'Rahilly, Stephen Owen, Katharine R. Palmer, Colin N. A. Papadakis, Konstantinos Potter, Simon Pouta, Anneli Qi, Lu Randall, Joshua C. Rayner, Nigel W. Ring, Susan M. Sandhu, Manjinder S. Scherag, Andre Sims, Matthew A. Song, Kijoung Soranzo, Nicole Speliotes, Elizabeth K. Syddall, Holly E. Teichmann, Sarah A. Timpson, Nicholas J. Tobias, Jonathan H. Uda, Manuela Vogel, Carla I. Ganz Wallace, Chris Waterworth, Dawn M. Weedon, Michael N. Willer, Cristen J. Wraight, Vicki L. Yuan, Xin Zeggini, Eleftheria Hirschhorn, Joel N. Strachan, David P. Ouwehand, Willem H. Caulfield, Mark J. Samani, Nilesh J. Frayling, Timothy M. Vollenweider, Peter Waeber, Gerard Mooser, Vincent Deloukas, Panos McCarthy, Mark I. Wareham, Nicholas J. Barroso, Ines CA Prostate Lung Colorectal Ovarian KORA Nurses' Health Study Diabetes Genetics Initiative SardiNIA Study Wellcome Trust Case Control Consor FUSION TI Common variants near MC4R are associated with fat mass, weight and risk of obesity SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; MELANOCORTIN-4 RECEPTOR GENE; EARLY-ONSET OBESITY; FRAMESHIFT MUTATION; ADULT OBESITY; FTO GENE; EXPRESSION; DEFICIENCY; CHILDHOOD; DOMINANT AB To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits. C1 [Lindgren, Cecilia M.; Prokopenko, Inga; Bennett, Amanda J.; Elliott, Katherine S.; Evans, David M.; Groves, Christopher J.; Herrera, Blanca; Randall, Joshua C.; Rayner, Nigel W.; Timpson, Nicholas J.; Zeggini, Eleftheria; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Loos, Ruth J. F.; Li, Shengxu; Zhao, Jing Hua; Sandhu, Manjinder S.; Sims, Matthew A.; Wareham, Nicholas J.] Addenbrookes Hosp, MRC, Epidemiol Unit, Cambridge CB2 0QQ, England. [Loos, Ruth J. F.; Li, Shengxu; Zhao, Jing Hua; Farooqi, I. Sadaf; Ong, Ken K.; O'Rahilly, Stephen; Sims, Matthew A.; Wraight, Vicki L.; Wareham, Nicholas J.] Addenbrookes Hosp, Inst Metab Sci, Cambridge CB2 0QQ, England. [Lindgren, Cecilia M.; Prokopenko, Inga; Bennett, Amanda J.; Groves, Christopher J.; Herrera, Blanca; Karpe, Fredrik; Neville, Matthew J.; Owen, Katharine R.; Randall, Joshua C.; Rayner, Nigel W.; McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England. [Wheeler, Eleanor; Inouye, Michael; Attwood, Antony P.; Dermitzakis, Emmanouil T.; Ghori, Jilur; Gwilliam, Rhian; Hunt, Sarah E.; Keniry, Andrew; McGinnis, Ralph; Nica, Alexandra C.; Potter, Simon; Soranzo, Nicole; Deloukas, Panos; Barroso, Ines] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Freathy, Rachel M.; Hattersley, Andrew T.; Weedon, Michael N.; Frayling, Timothy M.] Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter EX1 2LU, Devon, England. [Freathy, Rachel M.; Hattersley, Andrew T.; Weedon, Michael N.; Frayling, Timothy M.] Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter EX2 5DW, Devon, England. [Attwood, Antony P.; Jolley, Jennifer D. M.; Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge, England. [Attwood, Antony P.; Jolley, Jennifer D. M.; Ouwehand, Willem H.] Cambridge Ctr, NHS Blood & Transplant, Cambridge, England. [Beckmann, Jacques S.; Bergmann, Sven; Johnson, Toby] Univ Lausanne, Dept Med Genet, CH-1011 Lausanne, Switzerland. [Beckmann, Jacques S.] CHU Vaudois, Serv Med Genet, CH-1011 Lausanne, Switzerland. [Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Bergmann, Sven; Johnson, Toby] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland. [Bingham, Sheila A.] MRC, Dunn Human Nutr Unit, Cambridge CB2 0XY, England. [Bochud, Murielle; Johnson, Toby] CHU Vaudois, Univ Inst Social & Prevent Med, CH-1011 Lausanne, Switzerland. [Brown, Morris] Univ Cambridge, Clin Pharmacol Unit, Addenbrookes Hosp, Cambridge, England. [Cauchi, Stephane; Dina, Christian; Froguel, Philippe; Meyre, David] Inst Pasteur, CNRS, Inst Biol 8090, F-5900 Lille, France. [Connell, John M.] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland. [Cooper, Cyrus; Day, Ian; Syddall, Holly E.] Univ Southampton, MRC, Epidemiol Resource Ctr, Southampton SO16 6YD, Hants, England. [Smith, George Davey; Evans, David M.; Timpson, Nicholas J.] Univ Bristol, MRC, Ctr Causal Analyses Translat Epidemiol, Bristol BS8 2PR, Avon, England. [De, Subhajyoti; Teichmann, Sarah A.] MRC, Mol Biol Lab, Cambridge CB2 2QH, England. [Doney, Alex S. F.; Morris, Andrew D.] Univ Dundee, Ninewells Hosp & Med Sch, Diabet Res Grp, Div Med & Therapeut, Dundee DD1 9SY, Scotland. [Elliott, Paul; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England. [Elliott, Paul] Univ Oulu, Dept Publ Hlth Sci & Gen Practice, FIN-90014 Oulu, Finland. [Farooqi, I. Sadaf; O'Rahilly, Stephen; Wraight, Vicki L.] Univ Cambridge, Metab Res Labs, Cambridge CB2 0QQ, England. [Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London W12 0NN, England. [Hadley, David; Papadakis, Konstantinos; Strachan, David P.] St Georges Univ London, Div Community Hlth Sci, London SW17 0RE, England. [Hall, Alistair S.] Univ Leeds, LIGHT Res Inst, Fac Med & Hlth, Leeds LS2 9JT, W Yorkshire, England. [Hebebrand, Johannes; Hinney, Anke; Vogel, Carla I. Ganz] Univ Duisburg Essen, Dept Child & Adolescent Psychiat, D-45147 Essen, Germany. [Heid, Iris M.] GSF, Inst Epidemiol, D-85764 Neuherberg, Germany. [Heid, Iris M.] Univ Munich, IBE Chair Epidemiol, D-81377 Munich, Germany. [Jarvelin, Marjo-Riitta; Pouta, Anneli] Natl Publ Hlth Inst, Dept Child & Adolescent Hlth, Oulu 90221, Finland. [Khaw, Kay-Tee; Luben, Robert N.; Sandhu, Manjinder S.] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge CB2 2SR, England. [Mangino, Massimo; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Glenfield Hosp, Leicester LE3 9QP, Leics, England. [Marchini, Jonathan] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [McArdle, Wendy L.; Ring, Susan M.] Univ Bristol, Dept Social Med, Bristol BS8 2PR, Avon, England. [Munroe, Patricia B.; Wallace, Chris; Caulfield, Mark J.] Barts & London Queen Marys Sch Med & Dent, Barts & London Genome Ctr, William Harvey Res Inst, London EC1M 6BQ, England. [Ness, Andrew R.] Univ Bristol, Dept Oral & Dent Sci, Bristol Dent Sch, Bristol BS1 2LY, Avon, England. [Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Populat Pharmacogenet Grp, Dundee DD1 9SY, Scotland. [Pouta, Anneli] Univ Hosp, Dept Obstet & Gynaecol, Oulu 90221, Finland. [Qi, Lu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Scherag, Andre] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, D-45122 Essen, Germany. [Song, Kijoung; Waterworth, Dawn M.; Yuan, Xin; Mooser, Vincent] Med Genet Clin Pharmacol & Discovery Med, King Of Prussia, PA 19406 USA. [Speliotes, Elizabeth K.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Speliotes, Elizabeth K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Speliotes, Elizabeth K.; Hirschhorn, Joel N.] MIT, Broad Inst, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Tobias, Jonathan H.] Univ Bristol, Bristol BS2 8AE, Avon, England. [Uda, Manuela] CNR, Ist Neurogenet & Neurofarmacol, I-09100 Cagliari, Italy. [Willer, Cristen J.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Willer, Cristen J.] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Vollenweider, Peter; Waeber, Gerard] CHU Vaudois, Dept Med & Internal Med, CH-1011 Lausanne, Switzerland. Bioinformed Consulting Serv, Gaithersburg, MD 20877 USA. NCI, Pediat Oncol Branch, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA. GSF, Inst Human Genet, D-85764 Neuherberg, Germany. Tech Univ Munich, Inst Human Genet, D-81671 Munich, Germany. Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Diabet & Endocrinol Res Unit, S-20502 Malmo, Sweden. Univ Helsinki, Dept Med, Helsinki Univ Hosp, Helsinki 00029, Finland. Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21244 USA. Natl Publ Hlth Inst, Diabet Unit, Dept Epidemiol & Hlth Promot, SF-00300 Helsinki, Finland. Univ Helsinki, Dept Publ Hlth, FIN-00014 Helsinki, Finland. S Ostrobothnia Cent Hosp, Seinajoki 60220, Finland. NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. RP McCarthy, MI (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England. EM mark.mccarthy@drl.ox.ac.uk; nick.wareham@mrc-epid.cam.ac.uk; ib1@sanger.ac.uk RI Colaus, PsyColaus/K-6607-2013; Ness, Andy/M-7612-2013; Tobias, Jon/E-2832-2014; Berryman, Katie/J-4236-2014; Dina, Christian/D-3535-2015; Meitinger, Thomas/O-1318-2015; Prokopenko, Inga/H-3241-2014; Burton, Paul/H-7527-2016; Study, GoDARTS/K-9448-2016; mangino, massimo/F-5134-2011; Davey Smith, George/A-7407-2013; Hinney, Anke/D-6953-2011; Hadley, David/I-6902-2012; Deloukas, Panos/B-2922-2013; HILL, Adrian/C-1306-2008; Genetic Epidemiology, Innsbruck Med.Univ./C-2095-2008; Palmer, Colin/C-7053-2008; Morris, Andrew/C-2837-2009; Abecasis, Goncalo/B-7840-2010; Bochud, Murielle/A-3981-2010; Meyre, David/D-7315-2011; Dermitzakis, Emmanouil/B-7687-2013; Beckmann, Jacques S /A-9772-2008; Li, Shengxu/D-8915-2012; Evans, David/H-6325-2013; OI Dunger, Professor David/0000-0002-2566-9304; Teichmann, Sarah/0000-0002-6294-6366; Luben, Robert/0000-0002-5088-6343; Soranzo, Nicole/0000-0003-1095-3852; Gieger, Christian/0000-0001-6986-9554; Scherag, Andre/0000-0002-9406-4704; Hayes, Richard/0000-0002-0918-661X; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Farooqi, Sadaf/0000-0001-7609-3504; Wallace, Chris/0000-0001-9755-1703; Ness, Andy/0000-0003-3548-9523; Tobias, Jon/0000-0002-7475-3932; Dina, Christian/0000-0002-7722-7348; Prokopenko, Inga/0000-0003-1624-7457; mangino, massimo/0000-0002-2167-7470; Davey Smith, George/0000-0002-1407-8314; Freathy, Rachel/0000-0003-4152-2238; Willer, Cristen/0000-0001-5645-4966; Hinney, Anke/0000-0001-5659-0706; Deloukas, Panos/0000-0001-9251-070X; Palmer, Colin/0000-0002-6415-6560; Bochud, Murielle/0000-0002-5727-0218; Beckmann, Jacques S /0000-0002-9741-1900; Zeggini, Eleftheria/0000-0003-4238-659X; sanna, serena/0000-0002-3768-1749; Johnson, Toby/0000-0002-5998-3270; Monsalve, Beatriz Elena/0000-0002-5994-866X; Lango Allen, Hana/0000-0002-7803-8688; Hunt, Sarah/0000-0002-8350-1235; Brown, Matthew A/0000-0003-0538-8211; Abecasis, Goncalo/0000-0003-1509-1825; Karpe, Fredrik/0000-0002-2751-1770; Eyre, Stephen/0000-0002-1251-6974; Evans, David/0000-0003-0663-4621; Timpson, Nicholas/0000-0002-7141-9189; Bergmann, Sven/0000-0002-6785-9034 FU British Heart Foundation; Cancer Research UK; Department of Health [DHCS/07/07/008]; Medical Research Council [, G0000934, G0000934(68341), G0400874, G0401527, G0600331, G0600705, G0601261, G0701863, G9521010, G9521010(63660), G9824984, G9828345, MC_QA137934, MC_U105161047, MC_U105630924, MC_U106179472, MC_U106188470, MC_U147585824, MC_UP_A620_1014, U.1475.00.002.00001.01 (85824)]; NIDDK NIH HHS [F32 DK079466, F32 DK079466-01, K23 DK080145, K23 DK080145-01, P30 DK040561, P30 DK040561-13, R01 DK072193]; Wellcome Trust [090532, , 068545, 076113, 077016, 079557, 084713] NR 30 TC 750 Z9 781 U1 16 U2 87 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 JUN PY 2008 VL 40 IS 6 BP 768 EP 775 DI 10.1038/ng.140 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 305XV UT WOS:000256212000019 PM 18454148 ER PT J AU Dibbens, LM Tarpey, PS Hynes, K Bayly, MA Scheffer, IE Smith, R Bomar, J Sutton, E Vandeleur, L Shoubridge, C Edkins, S Turner, SJ Stevens, C O'Meara, S Tofts, C Barthorpe, S Buck, G Cole, J Halliday, K Jones, D Lee, R Madison, M Mironenko, T Varian, J West, S Widaa, S Wray, P Teague, J Dicks, E Butler, A Menzies, A Jenkinson, A Shepherd, R Gusella, JF Afawi, Z Mazarib, A Neufeld, MY Kivity, S Lev, D Lerman-Sagie, T Korczyn, AD Derry, CP Sutherland, GR Friend, K Shaw, M Corbett, M Kim, HG Geschwind, DH Thomas, P Haan, E Ryan, S McKee, S Berkovic, SF Futreal, PA Stratton, MR Mulley, JC Gecz, J AF Dibbens, Leanne M. Tarpey, Patrick S. Hynes, Kim Bayly, Marta A. Scheffer, Ingrid E. Smith, Raffaella Bomar, Jamee Sutton, Edwina Vandeleur, Lucianne Shoubridge, Cheryl Edkins, Sarah Turner, Samantha J. Stevens, Claire O'Meara, Sarah Tofts, Calli Barthorpe, Syd Buck, Gemma Cole, Jennifer Halliday, Kelly Jones, David Lee, Rebecca Madison, Mark Mironenko, Tatiana Varian, Jennifer West, Sofie Widaa, Sara Wray, Paul Teague, John Dicks, Ed Butler, Adam Menzies, Andrew Jenkinson, Andrew Shepherd, Rebecca Gusella, James F. Afawi, Zaid Mazarib, Aziz Neufeld, Miriam Y. Kivity, Sara Lev, Dorit Lerman-Sagie, Tally Korczyn, Amos D. Derry, Christopher P. Sutherland, Grant R. Friend, Kathryn Shaw, Marie Corbett, Mark Kim, Hyung-Goo Geschwind, Daniel H. Thomas, Paul Haan, Eric Ryan, Stephen McKee, Shane Berkovic, Samuel F. Futreal, P. Andrew Stratton, Michael R. Mulley, John C. Gecz, Jozef TI X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment SO NATURE GENETICS LA English DT Article ID CADHERIN SUPERFAMILY; CONVULSIVE DISORDER; FAMILIAL FORM; EXPRESSION; BRAIN; GENES; ORGANIZATION; DIVERSITY; MEMBERS AB Epilepsy and mental retardation limited to females (EFMR) is a disorder with an X-linked mode of inheritance and an unusual expression pattern. Disorders arising from mutations on the X chromosome are typically characterized by affected males and unaffected carrier females. In contrast, EFMR spares transmitting males and affects only carrier females. Aided by systematic resequencing of 737 X chromosome genes, we identified different protocadherin 19 (PCDH19) gene mutations in seven families with EFMR. Five mutations resulted in the introduction of a premature termination codon. Study of two of these demonstrated nonsense-mediated decay of PCDH19 mRNA. The two missense mutations were predicted to affect adhesiveness of PCDH19 through impaired calcium binding. PCDH19 is expressed in developing brains of human and mouse and is the first member of the cadherin superfamily to be directly implicated in epilepsy or mental retardation. C1 [Dibbens, Leanne M.; Hynes, Kim; Bayly, Marta A.; Vandeleur, Lucianne; Shoubridge, Cheryl; Sutherland, Grant R.; Friend, Kathryn; Shaw, Marie; Corbett, Mark; Haan, Eric; Mulley, John C.; Gecz, Jozef] Womens & Childrens Hosp, Dept Med Genet, Adelaide, SA 5006, Australia. [Dibbens, Leanne M.; Sutherland, Grant R.; Mulley, John C.; Gecz, Jozef] Univ Adelaide, Sch Paediat & Reprod Hlth, Adelaide, SA 5005, Australia. [Tarpey, Patrick S.; Smith, Raffaella; Edkins, Sarah; Stevens, Claire; O'Meara, Sarah; Tofts, Calli; Barthorpe, Syd; Buck, Gemma; Cole, Jennifer; Halliday, Kelly; Jones, David; Lee, Rebecca; Madison, Mark; Mironenko, Tatiana; Varian, Jennifer; West, Sofie; Widaa, Sara; Wray, Paul; Teague, John; Dicks, Ed; Butler, Adam; Menzies, Andrew; Jenkinson, Andrew; Shepherd, Rebecca; Futreal, P. Andrew; Stratton, Michael R.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Hynes, Kim; Sutton, Edwina; Sutherland, Grant R.; Thomas, Paul; Haan, Eric; Mulley, John C.; Gecz, Jozef] Univ Adelaide, Sch Mol & Biomed Sci, Adelaide, SA 5005, Australia. [Scheffer, Ingrid E.; Turner, Samantha J.; Derry, Christopher P.; Berkovic, Samuel F.] Univ Melbourne, Epilepsy Res Ctr, Heidelberg Repatriat Hosp, Heidelberg West, Vic 3081, Australia. [Scheffer, Ingrid E.; Turner, Samantha J.; Derry, Christopher P.; Berkovic, Samuel F.] Univ Melbourne, Dept Med, Heidelberg Repatriat Hosp, Heidelberg West, Vic 3081, Australia. [Scheffer, Ingrid E.] Univ Melbourne, Dept Paediat, Royal Childrens Hosp, Parkville, Vic 3052, Australia. [Bomar, Jamee; Geschwind, Daniel H.] Univ Calif Los Angeles, Program Neurogenet & Neurobehav Genet, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Bomar, Jamee; Geschwind, Daniel H.] Univ Calif Los Angeles, Semel Inst Neurosci & Behav, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Gusella, James F.; Korczyn, Amos D.; Kim, Hyung-Goo] Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Gusella, James F.; Korczyn, Amos D.; Kim, Hyung-Goo] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Afawi, Zaid; Mazarib, Aziz; Neufeld, Miriam Y.] Tel Aviv Sourasky Med Ctr, Dept Neurol, IL-64239 Tel Aviv, Israel. [Kivity, Sara] Schneider Childrens Med Ctr, Dept Neurol, IL-49202 Petaq Tikvah, Israel. [Lev, Dorit; Lerman-Sagie, Tally] Wolfson Med Ctr, Metab Neurogenet Clin, IL-58100 Holon, Israel. [Ryan, Stephen] AstraZeneca, Wilmington, DE 19803 USA. [McKee, Shane] Belfast City Hosp, No Ireland Reg Genet Serv, Belfast BT9 7AB, Antrim, North Ireland. RP Dibbens, LM (reprint author), Womens & Childrens Hosp, Dept Med Genet, Level 9 Rieger Bldg,72 King William Rd, Adelaide, SA 5006, Australia. EM leanne.dibbens@cywhs.sa.gov.au; jozef.gecz@adelaide.edu.au RI Shoubridge, Cheryl/A-1571-2016; Korczyn, Amos/C-3461-2017; Hynes, Kim/O-3874-2015; Corbett, Mark/A-8063-2010; Sutherland, Grant/D-2606-2012; Thomas, Paul/K-4497-2012; Scheffer, Ingrid/G-1668-2013 OI Gecz, Jozef/0000-0002-7884-6861; Shoubridge, Cheryl/0000-0002-0157-3084; Korczyn, Amos/0000-0003-0125-2579; Jenkinson, Andrew/0000-0002-0703-6984; Hynes, Kim/0000-0001-8679-4400; Berkovic, Samuel/0000-0003-4580-841X; Scheffer, Ingrid/0000-0002-2311-2174 FU NICHD NIH HHS [N01-HD-4-3383, N01-HD-4-3368]; NIGMS NIH HHS [GM061354, P01 GM061354]; NIMH NIH HHS [R01 MH 64547, R01 MH064547, R01 MH064547-01, R01 MH064547-01S1, R01 MH064547-02, R01 MH064547-02S1, R01 MH064547-03, R01 MH064547-04, R01 MH064547-05]; Wellcome Trust NR 24 TC 167 Z9 173 U1 0 U2 16 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 JUN PY 2008 VL 40 IS 6 BP 776 EP 781 DI 10.1038/ng.149 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 305XV UT WOS:000256212000020 PM 18469813 ER PT J AU von Boehmer, H AF von Boehmer, Harald TI Positive and negative selection in Basel SO NATURE IMMUNOLOGY LA English DT Editorial Material ID T-CELL-RECEPTOR; CD4+8+ THYMOCYTES; TRANSGENIC MICE; BONE-MARROW; ANTIGEN; THYMUS; TOLERANCE; DIFFERENTIATION; LYMPHOCYTES; SPECIFICITY AB Harald von Boehmer describes how he used mice transgenic for T cell receptor alpha beta to identify T cell receptor dependent cellular selection and lineage commitment as mechanisms responsible for generating an effective and self-tolerant adaptive immune system. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu NR 25 TC 5 Z9 5 U1 0 U2 0 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 JUN PY 2008 VL 9 IS 6 BP 571 EP 573 DI 10.1038/ni0608-571 PG 3 WC Immunology SC Immunology GA 303VB UT WOS:000256067900002 PM 18490902 ER PT J AU Herzog, S Hug, E Meixlsperger, S Paik, JH DePinho, RA Reth, M Jumaa, H AF Herzog, Sebastian Hug, Eva Meixlsperger, Sonja Paik, Ji-Hye DePinho, Ronald A. Reth, Michael Jumaa, Hassan TI SLP-65 regulates immunoglobulin light chain gene recombination through the PI(3)K-PKB-Foxo pathway SO NATURE IMMUNOLOGY LA English DT Article ID IMMATURE B-CELLS; PROTEIN-KINASE-B; FORKHEAD TRANSCRIPTION FACTORS; NF-KAPPA-B; V(D)J RECOMBINATION; POSITIVE SELECTION; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOINOSITIDE 3-KINASE; NEGATIVE SELECTION; RAG-2 ACCUMULATION AB Although the essential role of the adaptor protein SLP-65 in pre-B cell differentiation is established, the molecular mechanism underlying its function is poorly understood. In this study, we uncover a link between SLP-65-dependent signaling and the phosphoinositide-3-OH kinase (PI(3)K)-protein kinase B (PKB)-Foxo pathway. We show that the forkhead box transcription factor Foxo3a promotes light chain rearrangement in pre-B cells. Our data suggest that PKB suppresses light chain recombination by phosphorylating Foxo proteins, whereas reconstitution of SLP-65 function counteracts PKB activation and promotes Foxo3a and Foxo1 activity in pre-B cells. Together, these data illuminate a molecular function of SLP-65 and identify a key role for Foxo proteins in the regulation of light chain recombination, receptor editing and B cell selection. C1 [Herzog, Sebastian; Hug, Eva; Meixlsperger, Sonja; Reth, Michael; Jumaa, Hassan] Max Planck Inst Immunobiol, D-79108 Freiburg, Germany. [Herzog, Sebastian; Hug, Eva; Meixlsperger, Sonja; Reth, Michael; Jumaa, Hassan] Univ Freiburg, Fac Biol, Ctr Biol Signalling Studies BIOSS, D-79104 Freiburg, Germany. [Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Appl Canc Sci,Dept Med Oncol Med & Genet, Boston, MA 02115 USA. RP Jumaa, H (reprint author), Max Planck Inst Immunobiol, D-79108 Freiburg, Germany. EM jumaa@immunbio.mpg.de NR 50 TC 74 Z9 76 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUN PY 2008 VL 9 IS 6 BP 623 EP 631 DI 10.1038/ni.1616 PG 9 WC Immunology SC Immunology GA 303VB UT WOS:000256067900012 PM 18488031 ER PT J AU Scandella, E Bolinger, B Lattmann, E Miller, S Favre, S Littman, DR Finke, D Luther, SA Junt, T Ludewig, B AF Scandella, Elke Bolinger, Beatrice Lattmann, Evelyn Miller, Simone Favre, Stephanie Littman, Dan R. Finke, Daniela Luther, Sanjiv A. Junt, Tobias Ludewig, Burkhard TI Restoration of lymphoid organ integrity through the interaction of lymphoid tissue-inducer cells with stroma of the T cell zone SO NATURE IMMUNOLOGY LA English DT Article ID FIBROBLASTIC RETICULAR CELLS; ANTIVIRAL IMMUNE-RESPONSES; SPLENIC WHITE PULP; ROR-GAMMA-T; DENDRITIC CELLS; CD4(+)CD3(-) CELLS; VIRAL PERSISTENCE; NODE DEVELOPMENT; OX40 LIGAND; B-CELLS AB The generation of lymphoid microenvironments in early life depends on the interaction of lymphoid tissue-inducer cells with stromal lymphoid tissue-organizer cells. Whether this cellular interface stays operational in adult secondary lymphoid organs has remained elusive. We show here that during acute infection with lymphocytic choriomeningitis virus, antiviral cytotoxic T cells destroyed infected T cell zone stromal cells, which led to profound disruption of secondary lymphoid organ integrity. Furthermore, the ability of the host to respond to secondary antigens was lost. Restoration of the lymphoid microanatomy was dependent on the proliferative accumulation of lymphoid tissue-inducer cells in secondary lymphoid organs during the acute phase of infection and lymphotoxin alpha(1)beta(2) signaling. Thus, crosstalk between lymphoid tissue-inducer cells and stromal cells is reactivated in adults to maintain secondary lymphoid organ integrity and thereby contributes to the preservation of immunocompetence. C1 [Scandella, Elke; Bolinger, Beatrice; Lattmann, Evelyn; Miller, Simone; Ludewig, Burkhard] Kantonal Hosp St Gallen, Res Dept, CH-9007 St Gallen, Switzerland. [Favre, Stephanie; Luther, Sanjiv A.] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. [Littman, Dan R.] NYU, Sch Med, Howard Hughes Med Inst, Skirball Inst Biomol Med, New York, NY 10016 USA. [Finke, Daniela] Univ Basel, Ctr Biomed, CH-4058 Basel, Switzerland. [Junt, Tobias] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Junt, Tobias] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Junt, Tobias] Novartis Inst BioMed Res, A-1235 Vienna, Austria. RP Ludewig, B (reprint author), Kantonal Hosp St Gallen, Res Dept, CH-9007 St Gallen, Switzerland. EM burkhard.ludewig@kssg.ch RI Luther, Sanjiv/B-4380-2016 OI Luther, Sanjiv/0000-0002-8758-957X NR 57 TC 176 Z9 178 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUN PY 2008 VL 9 IS 6 BP 667 EP 675 DI 10.1038/ni.1605 PG 9 WC Immunology SC Immunology GA 303VB UT WOS:000256067900017 PM 18425132 ER PT J AU Nosho, K Kawasaki, T Ohnishi, M Suemoto, Y Kirkner, GJ Zepf, D Yan, LY Longtine, A Fuchs, CS Ogino, S AF Nosho, Katsuhiko Kawasaki, Takako Ohnishi, Mutsuko Suemoto, Yuko Kirkner, Gregory J. Zepf, Dimity Yan, Liying Longtine, Janina A. Fuchs, Charles S. Ogino, Shuji TI PIK3CA mutation in colorectal cancer: Relationship with genetic and epigenetic alterations SO NEOPLASIA LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; FATTY-ACID SYNTHASE; POPULATION-BASED SAMPLE; GROWTH-FACTOR RECEPTOR; COLON-CANCER; MICROSATELLITE INSTABILITY; CARCINOMA CELLS; K-RAS; PROMOTER HYPERMETHYLATION; MOLECULAR-FEATURES AB Somatic PIK3CA mutations are often present in colorectal cancer. Mutant PIK3CA activates AKT signaling, which up-regulates fatty acid synthase (FASN). Microsatellite instability (MSI) and CpG island methylator phenotype ( CIMP) are important molecular classifiers in colorectal cancer. However, the relationship between PIK3CA mutation, MSI and CIMP remains uncertain. Using Pyrosequencing technology, we detected PIK3CA mutations in 91 (15%) of 590 population-based colorectal cancers. To determine CIMP status, we quantified DNA methylation in eight CIMP-specific promoters [CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1] by real-time polymerase chain reaction (MethyLight). PIK3CA mutation was significantly associated with mucinous tumors [ P = .0002; odds ratio (OR) = 2.44], KRAS mutation ( P < .0001; OR = 2.68), CIMP-high (P = .03; OR = 2.08), phospho-ribosomal protein S6 expression ( P = .002; OR = 2.19), and FASN expression ( P = .02; OR = 1.85) and inversely with p53 expression ( P = .01; OR = 0.54) and beta-catenin (CTNNB1) alteration ( P = .004; OR = 0.43). In addition, PIK3CA G-to-A mutations were associated with MGMT loss ( P = .001; OR = 3.24) but not with MGMT promoter methylation. In conclusion, PIK3CA mutation is significantly associated with other key molecular events in colorectal cancer, and MGMT loss likely contributes to the development of PIK3CA G > A mutation. In addition, Pyrosequencing is useful in detecting PIK3CA mutation in archival paraffin tumor tissue. PIK3CA mutational data further emphasize heterogeneity of colorectal cancer at the molecular level. C1 [Ogino, Shuji] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Ctr Mol Oncol Pathol, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Ctr Mol Oncol Pathol, 44 Binney St,Room JF-215C, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu RI Waha, Andreas/J-2950-2014 FU NCI NIH HHS [P50 CA127003, K07 CA122826, P01 CA055075, P01 CA087969, P01 CA55075, P01 CA87969] NR 51 TC 152 Z9 154 U1 0 U2 5 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD JUN PY 2008 VL 10 IS 6 BP 534 EP 541 DI 10.1593/neo.08336 PG 8 WC Oncology SC Oncology GA 301GU UT WOS:000255885200002 PM 18516290 ER PT J AU Kesari, S Schiff, D Henson, JW Muzikansky, A Gigas, DC Doherty, L Batchelor, TT Longtine, JA Ligon, KL Weaver, S Laforme, A Ramakrishna, N Black, PM Drappatz, J Ciampa, A Folkman, J Kieran, M Wen, PY AF Kesari, Santosh Schiff, David Henson, John W. Muzikansky, Alona Gigas, Debra C. Doherty, Lisa Batchelor, Tracy T. Longtine, Janina A. Ligon, Keith L. Weaver, Susan Laforme, Andrea Ramakrishna, Naren Black, Peter McL. Drappatz, Jan Ciampa, Abigail Folkman, Judah Kieran, Mark Wen, Patrick Y. TI Phase II study of temozolomide, thalidomide, and celecoxib for newly diagnosed glioblastoma in adults SO NEURO-ONCOLOGY LA English DT Article DE angiogenesis; chemotherapy; clinical trial; glioblastoma ID ENDOTHELIAL GROWTH-FACTOR; CELL LUNG-CANCER; DOSE METRONOMIC CHEMOTHERAPY; METASTATIC COLORECTAL-CANCER; BEVACIZUMAB PLUS IRINOTECAN; HIGH-GRADE GLIOMAS; IN-VIVO; TUMOR VASCULATURE; RADIATION-THERAPY; MALIGNANT GLIOMAS AB We conducted a phase II study of the combination of temozolomide and angiogenesis inhibitors for treating adult patients with newly diagnosed glioblastoma. Patients who had stable disease following standard radiation therapy received temozolomide for 5 days in 28-day cycles, in combination with daily thalidomide and celecoxib. Patients were treated until tumor progression or development of unacceptable toxicity. Four-month progression-free survival (PFS) from study enrollment was the primary end point, and overall survival (OS) was the secondary end point. In addition, we sought to correlate response with O-6-methylguanine-DNA methyltransferase promoter methylation status and serum levels of angiogenic peptides. Fifty patients with glioblastoma were enrolled (18 women, 32 men). Median age was 54 years (range, 29-78) and median KPS score was 90 (range, 70-100). From study enrollment, median PFS was 5.9 months (95% confidence interval [CI]: 4.2-8.0) and 4-month PFS was 63% (95% CI: 46%-75%). Median OS was 12.6 months (95% CI: 8.5-16.4) and 1-year OS was 47%. Of the 47 patients evaluable for best response, none had a complete response, five (11%) had partial response, four (9%) had minor response, 22 (47%) had stable disease, and 16 (34%) had progressive disease. Analysis of serial serum samples obtained from 47 patients for four angiogenic peptides failed to show a significant correlation with response or survival for three of the peptides; higher vascular endothelial growth factor levels showed a trend toward correlation with decreased OS (p = 0.07) and PFS (p = 0.09). The addition of celecoxib and thalidomide to adjuvant temozolomide was well tolerated but did not meet the primary end point of improvement of 4-month PFS from study enrollment. C1 [Kesari, Santosh; Gigas, Debra C.; Doherty, Lisa; Ramakrishna, Naren; Black, Peter McL.; Drappatz, Jan; Ciampa, Abigail; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. [Kesari, Santosh; Drappatz, Jan; Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Longtine, Janina A.; Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ramakrishna, Naren] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Black, Peter McL.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Kesari, Santosh; Henson, John W.; Muzikansky, Alona; Batchelor, Tracy T.; Longtine, Janina A.; Ligon, Keith L.; Ramakrishna, Naren; Black, Peter McL.; Drappatz, Jan; Folkman, Judah; Kieran, Mark; Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA USA. [Schiff, David] Univ Virginia, Neurooncol Ctr, Charlottesville, VA USA. [Henson, John W.; Batchelor, Tracy T.] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Weaver, Susan] Albany Med Ctr, Albany, NY USA. [Laforme, Andrea; Kieran, Mark] Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. [Laforme, Andrea; Folkman, Judah; Kieran, Mark] Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA. RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, 44 Binney St,SW430D, Boston, MA 02115 USA. EM pwen@partners.org RI Kesari, Santosh/E-8461-2013; OI Kieran, Mark/0000-0003-2184-7692 NR 46 TC 48 Z9 50 U1 0 U2 4 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2008 VL 10 IS 3 BP 300 EP 308 DI 10.1215/15228517-2008-005 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 316UJ UT WOS:000256974900008 PM 18403492 ER PT J AU Chi, S Fletcher, W Yao, XP Cohen, K Fisher, M Biegel, J Janss, A Goldman, S Bowers, D Manley, P Masewski, C Bendel, A Rubin, J Turner, CD Roberts, C Marcus, K Goumnerova, L Ullrich, N Chordas, C Zimmerman, MA Kieran, MW AF Chi, Susan Fletcher, William Yao, Xiaopan Cohen, Kenneth Fisher, Michael Biegel, Jaclyn Janss, Anna Goldman, Stewart Bowers, Daniel Manley, Peter Masewski, Claire Bendel, Anne Rubin, Joshua Turner, Christopher D. Roberts, Charles Marcus, Karen Goumnerova, Liliana Ullrich, Nicole Chordas, Christine Zimmerman, Mary Ann Kieran, Mark W. TI Results from a single-arm, multiinstitutional phase II study of multiagent intrathecal and systemic chemotherapy with age- and risk-adapted radiation therapy for children with newly diagnosed CNS atypical teratoid/rhabdoid tumor (DFCI 02-294) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Pediatric Neuro-Oncology CY JUN 29-JUL 02, 2008 CL Chicago, IL C1 [Chi, Susan; Fletcher, William; Yao, Xiaopan; Turner, Christopher D.; Roberts, Charles; Chordas, Christine; Zimmerman, Mary Ann; Kieran, Mark W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cohen, Kenneth] Johns Hopkins Univ, Baltimore, MD USA. [Fisher, Michael; Biegel, Jaclyn] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Janss, Anna; Masewski, Claire] Emory Univ, Decatur, GA USA. [Goldman, Stewart] Childrens Mem Hosp, Chicago, IL 60614 USA. [Bowers, Daniel] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Manley, Peter] Hasbro Childrens Hosp, Providence, RI USA. [Bendel, Anne] Childrens Hospitals & Clin, Minneapolis, MN USA. [Rubin, Joshua] Washington Univ, St Louis, MO USA. [Marcus, Karen] Childrens Hosp, Dana Farber Canc Inst, Joint Ctr Radiat Oncol, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2008 VL 10 IS 3 BP 373 EP 373 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 316UJ UT WOS:000256974900028 ER PT J AU Haas-Kogan, D Banerjee, A Kocak, M Prados, M Geyer, R Fouladi, M Mcknight, T Poussaint, TY Broniscer, A Blaney, S Boyett, J Kun, L AF Haas-Kogan, Daphne Banerjee, Anuradha Kocak, Mehmet Prados, Michael Geyer, Russell Fouladi, Maryam Mcknight, Tracy Poussaint, Tina Young Broniscer, Alberto Blaney, Susan Boyett, James Kun, Larry TI Phase II trial of tipifarnib in children with newly diagnosed intrinsic diffuse brainstem gliomas SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Pediatric Neuro-Oncology CY JUN 29-JUL 02, 2008 CL Chicago, IL C1 [Haas-Kogan, Daphne; Banerjee, Anuradha; Prados, Michael; Mcknight, Tracy] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kocak, Mehmet; Fouladi, Maryam] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Poussaint, Tina Young] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2008 VL 10 IS 3 BP 392 EP 392 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 316UJ UT WOS:000256974900091 ER PT J AU Blackman, S Bundock, E Kieran, M AF Blackman, Samuel Bundock, Elizabeth Kieran, Mark TI Spinal tanycytic ependymoma presenting as meningitis SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Pediatric Neuro-Oncology CY JUN 29-JUL 02, 2008 CL Chicago, IL C1 [Blackman, Samuel; Kieran, Mark] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Bundock, Elizabeth] Commonwealth Massachusetts, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2008 VL 10 IS 3 BP 400 EP 401 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 316UJ UT WOS:000256974900119 ER PT J AU Herrington, B Silvera, M Chen, YL Goumnerova, L Scott, M Kieran, M Ullrich, N AF Herrington, Betty Silvera, Michelle Chen, Yen-Lin Goumnerova, Liliana Scott, Michael Kieran, Mark Ullrich, Nicole TI Fiesta MR imaging for detection of early recurrence and incomplete resection in children with infratentorial ependymoma SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Pediatric Neuro-Oncology CY JUN 29-JUL 02, 2008 CL Chicago, IL C1 [Herrington, Betty; Kieran, Mark] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Yen-Lin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goumnerova, Liliana] Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2008 VL 10 IS 3 BP 429 EP 429 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 316UJ UT WOS:000256974900216 ER PT J AU Rey-Casserly, C Chordas, C Liptak, C Ullrich, N Pomeroy, S Goumnerova, L Kieran, M Turner, C AF Rey-Casserly, Celiane Chordas, Christine Liptak, Cori Ullrich, Nicole Pomeroy, Scott Goumnerova, Liliana Kieran, Mark Turner, Christopher TI IQ versus executive function ratings as predictors of adaptive skills in children treated for low-grade gliomas only with surgery SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Pediatric Neuro-Oncology CY JUN 29-JUL 02, 2008 CL Chicago, IL C1 [Rey-Casserly, Celiane; Ullrich, Nicole; Pomeroy, Scott; Goumnerova, Liliana] Childrens Hosp, Boston, MA 02115 USA. [Chordas, Christine; Liptak, Cori; Kieran, Mark; Turner, Christopher] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2008 VL 10 IS 3 BP 440 EP 440 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 316UJ UT WOS:000256974900250 ER PT J AU Chordas, C Cohen, LE Marcus, K Chi, S Stratton, N Turner, CD AF Chordas, Christine Cohen, Laurie E. Marcus, Karen Chi, Susan Stratton, Nancy Turner, Christopher D. TI Potential decreased fertility in males treated for medulloblastoma, and nursing implications SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Pediatric Neuro-Oncology CY JUN 29-JUL 02, 2008 CL Chicago, IL C1 [Chordas, Christine; Chi, Susan; Stratton, Nancy; Turner, Christopher D.] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Cohen, Laurie E.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Marcus, Karen] Joint Ctr Radiat Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2008 VL 10 IS 3 BP 459 EP 459 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 316UJ UT WOS:000256974900313 ER PT J AU Graham, K Chordas, C Kieran, M AF Graham, Kristen Chordas, Christine Kieran, Mark TI The utility of the Ommaya reservoir from a nursing perspective SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Pediatric Neuro-Oncology CY JUN 29-JUL 02, 2008 CL Chicago, IL C1 [Graham, Kristen] Dana Farber Canc Inst, Jimmy Fund Clin Dana 3, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2008 VL 10 IS 3 BP 461 EP 461 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 316UJ UT WOS:000256974900321 ER PT J AU Ullrich, N Huttner, A Smith, E Goumnerova, L Irons, M Kieran, M AF Ullrich, Nicole Huttner, Anita Smith, Edward Goumnerova, Liliana Irons, Mira Kieran, Mark TI High-grade gliomas in neurofibromatosis type 1 SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Pediatric Neuro-Oncology CY JUN 29-JUL 02, 2008 CL Chicago, IL C1 [Goumnerova, Liliana] Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Kieran, Mark] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2008 VL 10 IS 3 BP 462 EP 462 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 316UJ UT WOS:000256974900325 ER PT J AU Vannatta, K Fairclough, D Farkas-Patenaude, A Gerhardt, C Kupst, MJ Olshefski, R Rutherford, C Turner, C AF Vannatta, Kathryn Fairclough, Diane Farkas-Patenaude, Andrea Gerhardt, Cynthia Kupst, Mary Jo Olshefski, Randal Rutherford, Christina Turner, Christopher TI Peer relationships of pediatric brain tumor survivors SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Pediatric Neuro-Oncology CY JUN 29-JUL 02, 2008 CL Chicago, IL C1 [Vannatta, Kathryn; Gerhardt, Cynthia] Nationwide Childrens Hosp, Res Inst, Columbus, OH USA. [Fairclough, Diane] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Farkas-Patenaude, Andrea; Turner, Christopher] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kupst, Mary Jo] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Rutherford, Christina] Ohio State Univ, Columbus, OH 43210 USA. RI Vannatta, Kathryn/E-4237-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2008 VL 10 IS 3 BP 494 EP 494 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 316UJ UT WOS:000256974900435 ER PT J AU Bujoreanu, IS Cunningham, LK Gambhir, R Morris, M Northman, L AF Bujoreanu, I. Simona Cunningham, Leslie Kim Gambhir, Rupa Morris, Marybeth Northman, Lisa TI Retrospective analysis of the school liaison program's educational interventions for pediatric cancer survivors SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Pediatric Neuro-Oncology CY JUN 29-JUL 02, 2008 CL Chicago, IL C1 [Cunningham, Leslie Kim; Gambhir, Rupa; Morris, Marybeth; Northman, Lisa] Dana Farber Canc Inst, Div Pediat Psychosocial Serv, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2008 VL 10 IS 3 BP 495 EP 495 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 316UJ UT WOS:000256974900438 ER PT J AU Liptak, C Delaney, B Chordas, C Rey-Casserly, C Ullrich, N Goumnerova, L Scott, RM Marcus, K Zimmerman, MA Graham, K Chi, S Kieran, M Turner, C AF Liptak, Cori Delaney, Brian Chordas, Christine Rey-Casserly, Celiane Ullrich, Nicole Goumnerova, Liliana Scott, R. Michael Marcus, Karen Zimmerman, Mary Ann Graham, Kristen Chi, Susan Kieran, Mark Turner, Christopher TI Psychosocial outcomes for 331 survivors of pediatric brain tumors SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Pediatric Neuro-Oncology CY JUN 29-JUL 02, 2008 CL Chicago, IL C1 [Liptak, Cori; Delaney, Brian; Chordas, Christine; Chi, Susan; Kieran, Mark; Turner, Christopher] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Rey-Casserly, Celiane] Childrens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Ullrich, Nicole] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Goumnerova, Liliana; Scott, R. Michael] Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Marcus, Karen] Childrens Hosp, Dana Farber Canc Inst, Joint Ctr Radiat Oncol, Boston, MA 02115 USA. [Graham, Kristen] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2008 VL 10 IS 3 BP 495 EP 495 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 316UJ UT WOS:000256974900437 ER PT J AU Chen, YL Adams, J Yock, T Goumnerova, L Kieran, M Ellen, G AF Chen, Yen-Lin Adams, Judy Yock, Torunn Goumnerova, Liliana Kieran, Mark Ellen, Grant TI 3D FIESTA MR cisternography for improved target definition in radiation treatment planning of pediatric posterior fossa ependymoma SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Pediatric Neuro-Oncology CY JUN 29-JUL 02, 2008 CL Chicago, IL C1 [Chen, Yen-Lin] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2008 VL 10 IS 3 BP 496 EP 497 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 316UJ UT WOS:000256974900442 ER PT J AU Yock, T Bolle, S Pulsifer, M Ramesh, J Yeap, B Oberg, J Ebb, D Tarbell, NJ AF Yock, Torunn Bolle, Stephanie Pulsifer, Margaret Ramesh, Jay Yeap, Beow Oberg, Jennifer Ebb, David Tarbell, Nancy J. TI Clinical outcomes of proton radiation therapy for pediatric low-grade gliomas SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Pediatric Neuro-Oncology CY JUN 29-JUL 02, 2008 CL Chicago, IL C1 [Yock, Torunn] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2008 VL 10 IS 3 BP 497 EP 497 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 316UJ UT WOS:000256974900444 ER PT J AU Ziegler, D Wright, R Kesari, S Zawel, L Ramakrishna, N Kung, A AF Ziegler, David Wright, Renee Kesari, Santosh Zawel, Leigh Ramakrishna, Naren Kung, Andrew TI A small molecule IAP inhibitor overcomes resistance to cytotoxic therapies in malignant gliomas in vitro and in vivo SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 13th International Symposium on Pediatric Neuro-Oncology CY JUN 29-JUL 02, 2008 CL Chicago, IL C1 [Ziegler, David] Sydney Childrens Hosp, Ctr Childrens Canc & Blood Disorders, Randwick, NSW, Australia. [Wright, Renee; Kesari, Santosh; Ramakrishna, Naren; Kung, Andrew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zawel, Leigh] Novartis Inst Biomed Res, Cambridge, MA USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2008 VL 10 IS 3 BP 507 EP 508 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 316UJ UT WOS:000256974900478 ER PT J AU Gourcerol, G Adelson, D Million, M Wang, LX Tache, Y AF Gourcerol, Guillaume Adelson, David Million, Mulugeta Wang, Lixin Tache, Yvette TI A novel non-invasive method to monitor gastric motility in mice: role of CRF during cold stress SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Meeting Abstract C1 [Gourcerol, Guillaume; Adelson, David; Million, Mulugeta; Wang, Lixin; Tache, Yvette] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Dept Med, Div Digest Dis,VA Greater Los Angeles Healthcare, Los Angeles, CA USA. [Gourcerol, Guillaume; Adelson, David; Million, Mulugeta; Wang, Lixin; Tache, Yvette] Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, Dept Med, Div Digest Dis,VA Greater Los Angeles Healthcare, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD JUN PY 2008 VL 20 IS 6 MA 16 BP V EP VI PG 2 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 300OT UT WOS:000255835500035 ER PT J AU Franceschini, MA Nissila, I Wu, WC Diamond, SG Bonmassar, G Boas, DA AF Franceschini, Maria Angela Nissilae, Ilkka Wu, Weicheng Diamond, Solomon G. Bonmassar, Giorgio Boas, David A. TI Coupling between somatosensory evoked potentials and hemodynamic response in the rat SO NEUROIMAGE LA English DT Article ID CEREBRAL-BLOOD-FLOW; RODENT BARREL CORTEX; ACTIVITY-DEPENDENT INCREASES; DIFFUSE OPTICAL TOMOGRAPHY; NEAR-INFRARED SPECTROSCOPY; LASER-DOPPLER FLOWMETRY; NEURONAL-ACTIVITY; NEURAL ACTIVITY; BRAIN ACTIVATION; FUNCTIONAL ACTIVATION AB We studied the relationship between somatosensory evoked potentials (SEP) recorded with scalp electroencephalography (EEG) and hemoglobin responses recorded non-invasively with diffuse optical imaging (DOI) during parametrically varied electrical forepaw stimulation in rats. Using these macroscopic techniques we verified that the hemodynamic response is not linearly coupled to the somatosensory evoked potentials, and that a power or threshold law best describes the coupling between SEP and the hemoglobin response, in agreement with the results of most invasive studies. We decompose the SEP response in three components (P1, N1, and P2) to determine which best predicts the hemoglobin response. We found that N1 and P2 predict the hemoglobin response significantly better than P1 and the input stimuli (S). Previous electrophysiology studies reported in the literature show that P1 originates in layer IV directly from thalamocortical afferents, while N1 and P2 originate in layers I and II and reflect the majority of local cortico-cortical interactions. Our results suggest that the evoked hemoglobin response is driven by the cortical synaptic activity and not by direct thalamic input. The N1 and P2 components, and not P1, need to be considered to correctly interpret neurovascular coupling. (c) 2008 Elsevier Inc. All rights reserved. C1 [Franceschini, Maria Angela; Nissilae, Ilkka; Wu, Weicheng; Diamond, Solomon G.; Bonmassar, Giorgio; Boas, David A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Franceschini, MA (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 13th St Bldg 149 Room 2301, Charlestown, MA 02129 USA. EM mari@nmr.mgh.harvard.edu RI Nissila, Ilkka/G-6879-2012; OI Nissila, Ilkka/0000-0001-6534-8436; Diamond, Solomon/0000-0002-7589-2942 FU NCRR NIH HHS [P41 RR014075-09, P41 RR014075, P41 RR014075-08]; NIBIB NIH HHS [R01 EB001954, R01 EB001954-04A2, R01 EB001954-05, R01 EB001954-06, R01 EB001954-07, R01-EB001954] NR 71 TC 52 Z9 52 U1 3 U2 11 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 JUN PY 2008 VL 41 IS 2 BP 189 EP 203 DI 10.1016/j.neuroimage.2008.02.061 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 306TQ UT WOS:000256271100002 PM 18420425 ER PT J AU Becerra, L Harris, W Joseph, D Huppert, T Boas, DA Borsook, D AF Becerra, L. Harris, W. Joseph, D. Huppert, T. Boas, D. A. Borsook, D. TI Diffuse optical tomography of pain and tactile stimulation: Activation in cortical sensory and emotional systems SO NEUROIMAGE LA English DT Article DE pain; somatosensory cortex; human; oxyhemoglobin; deoxyhemoglobin; bilateral activation; near infrared spectroscopy (NIRS) ID PRIMARY SOMATOSENSORY CORTEX; FUNCTIONAL MAGNETIC-RESONANCE; POSITRON-EMISSION-TOMOGRAPHY; MEDIAN NERVE-STIMULATION; CHRONIC BACK-PAIN; HUMAN BRAIN; PREFRONTAL CORTEX; SENSORIMOTOR CORTEX; NEURAL ACTIVATION; TEMPORAL ANALYSIS AB Using diffuse optical tomography (DOT), we detected activation in the somatosensory cortex and frontal brain areas following tactile (brush) and noxious heat stimulation. Healthy volunteers received stimulation to the dorsum of the right hand. In the somatosensory cortex area, tactile stimulation produced a robust, contralateral to the stimulus, hemodynamic response with a weaker activation on the ipsilateral side. For the same region, noxious thermal stimuli produced bilateral activation of similar intensity that had a prolonged activation with a double peak similar to results that have been reported with functional MRI. Bilateral activation was observed in the frontal areas, oxyhemoglobin changes were positive for brush stimulation while they were initially negative (contralateral) for heat stimulation. These results suggest that based on the temporal and spatial characteristics of the response in the sensory cortex, it is possible to discern painful from mechanical stimulation using DOT. Such ability might have potential applications in a clinical setting in which pain needs to be assessed objectively (e. g., analgesic efficacy, pain responses during surgery). (c) 2008 Elsevier Inc. All rights reserved. C1 [Becerra, L.; Harris, W.; Borsook, D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, McLean Hosp,PAIN Grp, Cambridge, MA 02138 USA. [Harris, W.; Joseph, D.; Boas, D. A.; Borsook, D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Cambridge, MA 02138 USA. [Huppert, T.] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA. RP Becerra, L (reprint author), McLean Hosp, Brain Imaging Ctr, 115 Mill St, Belmont, MA 02478 USA. EM lbecerra@mclean.harvard.edu FU NCRR NIH HHS [P41 RR014075, P41 RR014075-106006, P41-RR14075]; NINDS NIH HHS [R01 NS042721, R01 NS042721-03, NS042721] NR 59 TC 33 Z9 34 U1 1 U2 7 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 JUN PY 2008 VL 41 IS 2 BP 252 EP 259 DI 10.1016/j.neuroimage.2008.01.047 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 306TQ UT WOS:000256271100008 PM 18394924 ER PT J AU de Geder, B van de Riet, WAC Grezes, J Denollet, J AF de Geder, B. van de Riet, W. A. C. Grezes, J. Denollet, J. TI Decreased differential activity in the amygdala in response to fearful expressions in Type D personality SO NEUROPHYSIOLOGIE CLINIQUE-CLINICAL NEUROPHYSIOLOGY LA English DT Article DE emotion; fMRI; amygdala; Type D personality ID FUNCTIONAL MAGNETIC-RESONANCE; QUALITY-OF-LIFE; MAJOR DEPRESSION; NEGATIVE AFFECTIVITY; FACIAL EXPRESSION; HEART-FAILURE; CORTEX; EMOTION; RECOGNITION; DISORDER AB Recent advances in functional brain imaging offer unique opportunities to explore the neurofunctional basis of tools used to assess personality differences which have proven their clinical usefulness. In this functional magnetic resonance imaging (fMRI) study, the focus was on the amygdala activation and we investigated whether individual differences in activity of the amygdala following presentation of emotional expressions in the face and the whole body may be systematically related to the presence of Type D (distressed) personality or to its constituting factors, Negative Affectivity (NA) and Social Inhibition (SI). Our results show that the observed difference in amygdala activity between fearful and neutral expressions was present in participants that did not meet the criteria for Type D personality, while this effect was absent in participants that could be classified as Type D personality. Our correlation analyses further showed that the activation in the left amygdala elicited by fearful, versus neutral bodily expressions correlated negatively with the Negative Affectivity score. The same pattern was observed for the right amygdala for fearful facial and bodily expressions when contrasted with neutral facial and bodily expressions. (C) 2008 Elsevier Masson SAS. All rights reserved. C1 [de Geder, B.; van de Riet, W. A. C.] Tilburg Univ, Dept Psychol, Cognit & Affect Neurosci Lab, Tilburg, Netherlands. [de Geder, B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [de Geder, B.; van de Riet, W. A. C.] FC Donders Ctr Cognit Neuroimaging, Nijmegen, Netherlands. [Grezes, J.] Ecole Normale Super, Dept Etud Cognit, INSERM, U742,Lab Neurosci Cognit, F-75231 Paris, France. [de Geder, B.; van de Riet, W. A. C.; Denollet, J.] Tilburg Univ, CoRPS, NL-5000 LE Tilburg, Netherlands. RP de Geder, B (reprint author), Tilburg Univ, Dept Psychol, Cognit & Affect Neurosci Lab, Tilburg, Netherlands. EM degelder@nmr.mgh.harvard.edu RI Grezes, Julie/E-5060-2016 NR 51 TC 6 Z9 7 U1 4 U2 6 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0987-7053 J9 NEUROPHYSIOL CLIN JI Neurophysiol. Clin.-Clin. Neurophysiol. PD JUN PY 2008 VL 38 IS 3 BP 163 EP 169 DI 10.1016/j.neucli.2008.03.002 PG 7 WC Clinical Neurology; Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 319OO UT WOS:000257173600002 PM 18539249 ER PT J AU Harris, GJ Plotkin, SR MacCollin, M Bhat, S Urban, T Lev, MH Slattery, WH AF Harris, Gordon J. Plotkin, Scott R. MacCollin, Mia Bhat, Shubha Urban, Trinity Lev, Michael H. Slattery, William H. TI Three-dimensional volumetrics for tracking vestibular schwannoma growth in neurofibromatosis type II SO NEUROSURGERY LA English DT Article DE neurofibromatosis type II; segmentation; vestibular schwannoma; volumetrics ID NATURAL-HISTORY; ACOUSTIC NEUROMAS; TESTS AB OBJECTIVE: Vestibular schwannomas (VS) are common, benign, VIIIth cranial nerve tumors. Treatment in patients with the genetic disorder neurofibromatosis type II (NF2) is complicated by their development of bilateral VS and risk of complete deafness. Intervention decisions consider several clinical factors including tumor size and growth rate evaluated using magnetic resonance imaging. The current study evaluated the relative sensitivity of volumetric versus linear diameter measurement for assessing VS growth rate and progression. METHODS: Retrospective analysis was performed on 43 magnetic resonance imaging scans acquired longitudinally (range, 2-7 yr) from 10 patients with NF2. Fifteen VS were measured (five patients had unilateral lesions meeting, inclusion criteria) using both maximum linear diameter and semiautomated volumetric analysis. Progression was defined according to Response Evaluation Criteria in Solid Tumors and its volumetric (cubed linear) equivalent. Measurement techniques were compared by assessing sensitivity to lesion growth. RESULTS: Volumetric measures were significantly more sensitive to VS growth, both for total change and change per year percentages; cubed linear growth measures (proportional to volume growth) underestimated volume growth by 50%. Seven lesions showed progression on volumetric analysis, but two of these did not snow progression based on linear measures. Thus, for 29% of lesions showing progression based on volume, linear measures did not detect progression. CONCLUSION: Linear measurements underestimate VS growth rate compared with volumetric measures in NF2 patients. These results provide! clear, quantitative proof that diameter measures are not as sensitive to change as volumetric measurements and that volumetric measurements should be strongly considered, when making VS treatment decisions. C1 [Harris, Gordon J.; Bhat, Shubha; Urban, Trinity] Massachusetts Gen Hosp, 3D Imaging Serv, Dept Radiol, Boston, MA 02114 USA. [Plotkin, Scott R.; MacCollin, Mia] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Lev, Michael H.] Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. [Slattery, William H.] House Ear Res Inst, Dept Clin Studies, Los Angeles, CA USA. RP Harris, GJ (reprint author), Massachusetts Gen Hosp, 3D Imaging Serv, Dept Radiol, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM gjharris@partners.org NR 19 TC 49 Z9 50 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUN PY 2008 VL 62 IS 6 BP 1314 EP 1319 DI 10.1227/01.NEU.0000316858.25606.8F PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 334MS UT WOS:000258226500031 PM 18824998 ER PT J AU Szentirmai, O Carter, BS AF Szentirmai, Oszkar Carter, Bob S. TI Genetic and cellular therapies for cerebral infarction SO NEUROSURGERY LA English DT Review DE cellular therapy; cerebral infarct; gene therapy; neuroregeneration; stem cells; stroke ID NEURAL STEM-CELLS; CENTRAL-NERVOUS-SYSTEM; ISCHEMIC BRAIN-INJURY; ADULT MAMMALIAN BRAIN; INTERLEUKIN-1 RECEPTOR ANTAGONIST; MOLECULAR NEUROSURGERY PATHWAYS; ENHANCES NEURONAL SURVIVAL; PROTECTS STRIATAL NEURONS; MARROW STROMAL CELLS; BONE-MARROW AB NEUROSURGEONS, WORKING AS surgical scientists, can have a prominent role in developing and implementing genetic and cellular therapies for cerebral ischemia. The rapid emergence of both genetic and cellular therapies for neural regeneration warrants a careful analysis before implementation of human studies to understand the pitfalls and promises of this strategy. In this article, we review the topic of genetic and cellular therapy for stroke to provide a foundation for practicing neurosurgeons and clinical scientists who may become involved in this type of work. In Part 1, we review preclinical approaches with gene transfer, such as 1) improved energy delivery, 2) reduction of intracellular calcium availability, 3) abrogation of effects of reactive oxygen species, 4) reduction of proinflammatory cytokine signaling, 5) inhibition of apoptosis mediators, and 6) restorative gene therapy, that are paving the way to develop new strategies to treat cerebral infarction. In Part 2, we discuss the results of studies that address the possibility of using cellular therapies for stroke in animal models and in human trials by reviewing 1) the basics of stem cell biology, 2) exogenous and 3) and endogenous cell sources for therapy, and 4) clinical considerations in cell therapy applications. These emerging technologies based on the advancements made in recent years in the fields of genetics, therapeutic cloning, neuroscience, stem cell biology, and gene therapy provide significant potential for new therapies for stroke. C1 [Szentirmai, Oszkar; Carter, Bob S.] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Szentirmai, Oszkar; Carter, Bob S.] Massachusetts Gen Hosp, Lab Genet & Cellular Engn, Boston, MA 02114 USA. [Szentirmai, Oszkar; Carter, Bob S.] Harvard Univ, Sch Med, Boston, MA USA. RP Carter, BS (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, VBK 730, Boston, MA 02114 USA. EM bcarter@partners.org NR 116 TC 3 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUN PY 2008 VL 62 IS 6 SU S BP 1465 EP 1478 DI 10.1227/01.NEU.0000129681.85731.00 PG 14 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 334MT UT WOS:000258226600096 PM 18695566 ER PT J AU Farrar, CT Dai, GP Novikov, M Rosenzweig, A Weissleder, R Rosen, BR Sosnovik, DE AF Farrar, Christian T. Dai, Guangping Novikov, Mikhail Rosenzweig, Anthony Weissleder, Ralph Rosen, Bruce R. Sosnovik, David E. TI Impact of field strength and iron oxide nanoparticle concentration on the linearity and diagnostc accuracy of off-resonance imaging SO NMR IN BIOMEDICINE LA English DT Article DE off-resonance imaging; monocrystalline iron oxide nanoparticle; diagnostic accuracy; magnetic field strength; myocardial infarction ID MAGNETIC NANOPARTICLES; IN-VIVO; CELLS; CONTRAST; MRI; SATURATION; TRACKING; MARKER; CANCER; AGENTS AB Off-resonance imaging (ORI) techniques are being increasingly used to image iron oxide imaging agents such as monocrystalline iron oxide nanoparticles (MION). However, the diagnostic accuracy, linearity, and field dependence of ORI have not been fully characterized. In this study, the sensitivity, specificity, and linearity of ORI were thus examined as a function of both MION concentration and magnetic field strength (4.7 and 14 T). MION phantoms with and without an air interface as well as MION uptake in a mouse model of healing myocardial infarction were imaged. MION-incluced resonance shifts were shown to increase linearly with MION concentration. In contrast, the ORI signal/sensitivity was highly non-linear, initially increasing with MION concentration until T-2 became comparable to the TE and decreasing thereafter. The specificity of ORI to distinguish MION-induced resonance shifts from on-resonance water was found to decrease with increasing field because of the increased on-resonance water linewidths (15Hz at 4.7T versus 45Hz at 14T). Large resonance shifts (similar to 300 Hz) were observed at air interfaces at 4.7 T, both in vitro and in vivo, and led to poor ORI specificity for MION concentrations less than 150 mu g Fe/mL. The in vivo ORI sensitivity was sufficient to detect the accumulation of MION in macrophages infiltrating healing myocardial infarcts, but the specificity was limited by non-specific areas of positive contrast at the air/tissue interfaces of the thoracic wall and the descending aorta. Improved specificity and linearity can, however, be expected at lower fields where decreased on-resonance water linewidths, reduced air-induced resonance shifts, and longer T-2 relaxation times are observed. The optimal performance of ORI will thus likely be seen at low fields, with moderate MION concentrations and with sequences containing very short TEs. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 [Farrar, Christian T.; Dai, Guangping; Rosen, Bruce R.; Sosnovik, David E.] Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Sch Med, Charlestown, MA 02129 USA. [Novikov, Mikhail; Rosenzweig, Anthony] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. [Weissleder, Ralph; Sosnovik, David E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Farrar, CT (reprint author), Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Sch Med, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM cfarrar@nmr.mgh.harvard.edu FU NCI NIH HHS [T32 CA009502, T32-CA009502-19]; NCRR NIH HHS [P41 RR014075, P41-RR14075]; NHLBI NIH HHS [K08 HL079984-04, K08-HL079984-02, K08 HL079984]; NIA NIH HHS [K25 AG029415-05, K25 AG029415-01A1, K25 AG029415-04, K25 AG029415-03, K25 AG029415-02, K25 AG029415] NR 30 TC 37 Z9 37 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD JUN PY 2008 VL 21 IS 5 BP 453 EP 463 DI 10.1002/nbm.1209 PG 11 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 319NX UT WOS:000257171800004 PM 17918777 ER PT J AU Schulte-Uentrop, L El-Awady, RA Schliecker, L Willers, H Dahm-Daphi, J AF Schulte-Uentrop, Leonie El-Awady, Raafat A. Schliecker, Lena Willers, Henning Dahm-Daphi, Jochen TI Distinct roles of XRCC4 and Ku80 in non-homologous end-joining of endonuclease- and ionizing radiation-induced DNA double-strand breaks SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DEPENDENT PROTEIN-KINASE; CELL-FREE-EXTRACTS; LIGASE-IV; V(D)J RECOMBINATION; MAMMALIAN-CELLS; KU80-DEFICIENT CELLS; EMBRYONIC LETHALITY; POLYMERASE-LAMBDA; DEFICIENT MICE; IN-VITRO AB Non-homologous end-joining (NHEJ) of DNA double-strand breaks (DSBs) is mediated by two protein complexes comprising Ku80/Ku70/DNA-PKcs/Artemis and XRCC4/LigaseIV/XLF. Loss of Ku or XRCC4/LigaseIV function compromises the rejoining of radiation-induced DSBs and leads to defective V(D)J recombination. In this study, we sought to define how XRCC4 and Ku80 affect NHEJ of site-directed chromosomal DSBs in murine fibroblasts. We employed a recently developed reporter system based on the rejoining of I-SceI endonuclease-induced DSBs. We found that the frequency of NHEJ was reduced by more than 20-fold in XRCC4-/- compared to XRCC4+/+ cells, while a Ku80 knock-out reduced the rejoining efficiency by only 1.4-fold. In contrast, lack of either XRCC4 or Ku80 increased end degradation and shifted repair towards a mode that used longer terminal microhomologies for rejoining. However, both proteins proved to be essential for the repair of radiation-induced DSBs. The remarkably different phenotype of XRCC4- and Ku80-deficient cells with regard to the repair of enzyme-induced DSBs mirrors the embryonic lethality of XRCC4 knock-out mice as opposed to the viability of the Ku80 knock-out. Thus, I-SceI-induced breaks may resemble DSBs arising during normal DNA metabolism and mouse development. The removal of these breaks likely has different genetic requirements than the repair of radiation-induced DSBs. C1 [Schulte-Uentrop, Leonie; El-Awady, Raafat A.; Schliecker, Lena; Dahm-Daphi, Jochen] Univ Med Sch Hamburg Eppendorf, Dept Radiotherapy & Radiat Oncol, Lab Radiobiol & Expt Radiat Oncol, D-20246 Hamburg, Germany. [El-Awady, Raafat A.] Cairo Univ, Natl Canc Inst, Dept Tumor Biol, Cairo, Egypt. [Willers, Henning] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Lab Cellular & Mol Radiat Oncol, Charlestown, MA 02129 USA. RP Dahm-Daphi, J (reprint author), Univ Med Sch Hamburg Eppendorf, Dept Radiotherapy & Radiat Oncol, Lab Radiobiol & Expt Radiat Oncol, Martinistr 52, D-20246 Hamburg, Germany. EM dahm@uke.uni-hamburg.de NR 56 TC 47 Z9 49 U1 0 U2 5 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 JUN PY 2008 VL 36 IS 8 BP 2561 EP 2569 DI 10.1093/nar/gkn094 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 299ML UT WOS:000255759600012 PM 18332040 ER PT J AU Pettker, CM Pocock, SB Smok, DP Lee, SM Devine, PC AF Pettker, Christian M. Pocock, Sean B. Smok, Dorothy P. Lee, Shing M. Devine, Patricia C. TI Transcervical Foley catheter with and without oxytocin for cervical ripening - A randomized controlled trial SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med ID INTRAVAGINAL MISOPROSTOL; ORAL MISOPROSTOL; LABOR INDUCTION; BALLOON; DINOPROSTONE; PROSTAGLANDIN; TERM; GEL AB OBJECTIVE: To estimate whether adding oxytocin to to transcervical Foley catheter preinduction cervical ripening improves induction success. METHODS: This trial enrolled 200 women with singleton pregnancies presenting for preinduction ripening. Patients were randomly assigned to receive either Foley catheter alone (control) or Foley catheter plus low-dose oxytocin (treatment). Providers were not blinded to use of oxytocin, and labor was managed according to routine obstetric protocols. This study was powered to detect a 20% difference in the proportion of patients delivered within 24 hours. Secondary outcomes were related to vaginal delivery rate, duration of induction, complications, and pain management. RESULTS: Results were available for 183 (92 treatment, 91 control) of 200 patients randomly assigned. There were no differences in proportions of deliveries - overall (65% compared with 60%; relative risk [RR] 1.08, 95% confidence interval [CI] 0.86-1.35, number needed to treat 21) or vaginal (48% compared with 46%; RR 1.04, 95% Cl 0.76-1.41, number needed to treat 60)-in 24 hours, or cesarean deliveries or times to deliveries between treatment or control groups. Rates of complications were comparable; however, the treatment group had a higher proportion of regional analgesia requirement during induction than controls (23% compared with 9%, P = .011; RR 2.60, 95% CI 1.21-5.56). CONCLUSION: Addition of oxytocin to transcervical Foley catheter does not shorten the time to delivery and has no effect on the likelihood of delivery within 24 hours or vaginal delivery rate, although there is an increased use of analgesia by these patients during ripening. The use of oxytocin in addition to Foley catheter ripening is not justified. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www. clinicaltrials.gov, NCT00468520. C1 [Pettker, Christian M.] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, New Haven, CT 06520 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Columbia Univ, Med Ctr, Dept Obstet & Gynecol, New York, NY USA. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. RP Pettker, CM (reprint author), Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, 333 Cedar St,POB 208063, New Haven, CT 06520 USA. EM christian.pettker@yale.edu NR 18 TC 17 Z9 18 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUN PY 2008 VL 111 IS 6 BP 1320 EP 1326 DI 10.1097/AOG.0b013e31817615a0 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 305PX UT WOS:000256191400011 PM 18515515 ER PT J AU Tracy, EE AF Tracy, Erin E. TI Confessions of an electronic medical record user SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID PRIMARY-CARE; CONFIDENTIALITY; PRIVACY; COMMUNICATION; TECHNOLOGY C1 Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA. RP Tracy, EE (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol, 55 Friut St,406 Founders House, Boston, MA 02114 USA. EM EETracy@partners.org NR 21 TC 4 Z9 5 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUN PY 2008 VL 111 IS 6 BP 1435 EP 1438 DI 10.1097/AOG.0b013e3181719bbe PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 305PX UT WOS:000256191400025 PM 18515529 ER PT J AU Soteriades, ES Hauser, R Kawachi, I Christiani, DC Kales, SN AF Soteriades, Elpidoforos S. Hauser, Russ Kawachi, Ichiro Christiani, David C. Kales, Stefanos N. TI Obesity and risk of job disability in male firefighters SO OCCUPATIONAL MEDICINE-OXFORD LA English DT Article DE BMI; firefighters; fitness for duty; job disability; obesity ID BODY-MASS INDEX; MIDDLE-AGED MEN; UNITED-STATES; CARDIORESPIRATORY FITNESS; HEART-DISEASE; HEALTH; POPULATION; PERFORMANCE; RETIREMENT; OVERWEIGHT AB Background Obesity is a major public health problem and a workplace epidemic in Western societies. However, little is known about the association between obesity and job disability in specific occupational groups. Aim To examine the association between obesity and risk of job disability among firefighters. Methods A prospective cohort study design was employed in following 358 Massachusetts firefighters enrolled in a statewide medical surveillance program. We prospectively evaluated time to development of adverse employment outcomes > 6 years of follow-up. Results In multivariable-adjusted Cox proportional hazard models, we found that every one-unit increase in body mass index (BMI) was associated with a 5% increased risk of job disability. Compared to firefighters in the lowest tertile of BMI (BMI < 27.2), those in the highest tertile (BMI >= 30.2) had a significantly increased risk of an adverse employment event with a multivariable-adjusted hazard ratio (HR) of 1.98 (95% CI 1.06-3.72). There was also a significant dose-response relationship of increasing risk across tertiles, as well as a significant trend: HR 1.39 (95% CI 1.04-1.86). The highest categories of BMI had a 60-90% increased risk of job disability compared to the lowest or normal-weight categories, respectively. Conclusions Obesity is associated with higher risk of job disability in firefighters. Additional research is needed to further explore our findings. Our study may have economic and public health implications in other occupational settings. C1 [Soteriades, Elpidoforos S.; Hauser, Russ; Christiani, David C.; Kales, Stefanos N.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Kawachi, Ichiro] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Soc, Boston, MA 02115 USA. [Kawachi, Ichiro] Harvard Univ, Sch Publ Hlth, Dept Human Dev & Hlth, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm Crit Care Unit, Boston, MA 02115 USA. [Kales, Stefanos N.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Soteriades, ES (reprint author), 2 Antigonis St, CY-2035 Nicosia, Cyprus. EM esoteria@hsph.harvard.edu NR 30 TC 33 Z9 33 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0962-7480 J9 OCCUP MED-OXFORD JI Occup. Med.-Oxf. PD JUN PY 2008 VL 58 IS 4 BP 245 EP 250 DI 10.1093/occmed/kqm153 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 306YC UT WOS:000256283400006 PM 18204003 ER PT J AU Lee, J Sung, YH Cheong, C Choi, YS Jeon, HK Sun, W Hahn, WC Ishikawa, F Lee, HW AF Lee, J. Sung, Y. H. Cheong, C. Choi, Y. S. Jeon, H. K. Sun, W. Hahn, W. C. Ishikawa, F. Lee, H-W TI TERT promotes cellular and organismal survival independently of telomerase activity SO ONCOGENE LA English DT Article DE telomerase; telomerase activity; TERT; cell death; cellular protection ID REVERSE-TRANSCRIPTASE; CATALYTIC SUBUNIT; MOUSE TELOMERASE; INDUCED-APOPTOSIS; NEURONAL DEATH; CANCER-CELLS; IN-VITRO; HTERT; MICE; INHIBITION AB The expression level of the telomerase catalytic subunit (telomerase reverse transcriptase, TERT) positively correlates with cell survival after exposure to several lethal stresses. However, whether the protective role of TERT is independent of telomerase activity has not yet been clearly explored. Here, we genetically evaluated the protective roles of both TERT and telomerase activity against cell death induced by staurosporine (STS) and N-methyl-D-aspartic acid (NMDA). First generation (G1) TERT-deficient mouse embryonic fibroblasts (MEFs) displayed an increased sensitivity to STS, while TERT transgenic MEFs were more resistant to STS-induced apoptosis than wildtype. Deletion of the telomerase RNA component (TERC) failed to alter the sensitivity of TERT transgenic MEFs to STS treatment. Similarly, NMDA-induced excitotoxic cell death of primary neurons was suppressed by TERT, but not by TERC both in vitro and in vivo. Specifically, NMDA accelerated death of TERT-deficient mice, while TERT transgenic mice showed enhanced survival when compared with wild-type littermates after administration of NMDA. In addition, the transgenic expression of TERT protected motor neurons from apoptosis induced by sciatic nerve axotomy. These results indicate that telomerase activity is not essential for the protective function of TERT. This telomerase activity-independent TERT function may contribute to cancer development and aging independently of telomere lengthening. C1 [Sung, Y. H.; Choi, Y. S.; Jeon, H. K.; Lee, H-W] Yonsei Univ, Dept Biochem, Brain Korea Program 21, Seoul 120749, South Korea. [Lee, J.; Cheong, C.] Sungkyunkwan Univ, Sch Med, Dept Mol Cell Biol, Suwon, South Korea. [Sun, W.] Korea Univ, Coll Med, Brain Korea Program 21, Dept Anat, Seoul 136705, South Korea. [Hahn, W. C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hahn, W. C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Hahn, W. C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ishikawa, F.] Kyoto Univ, Dept Gene Mech, Kyoto, Japan. RP Lee, HW (reprint author), Yonsei Univ, Dept Biochem, Brain Korea Program 21, 134 Sinchon Dong, Seoul 120749, South Korea. EM hwl@yonsei.ac.kr FU NIA NIH HHS [R01 AG23145] NR 49 TC 79 Z9 84 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN PY 2008 VL 27 IS 26 BP 3754 EP 3760 DI 10.1038/sj.onc.1211037 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 312HH UT WOS:000256659300013 PM 18223679 ER PT J AU Nguyen, PL Trofimov, A Zietman, AL AF Nguyen, Paul L. Trofimov, Alexei Zietman, Anthony L. TI Proton-beam vs intensity-modulated radiation therapy - Which is best for treating prostrate cancer? SO ONCOLOGY-NEW YORK LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; LOCALIZED PROSTATE-CANCER; INDUCED 2ND CANCERS; RADIOTHERAPY; ADENOCARCINOMA; IRRADIATION; REDUCTION; BLADDER; IMRT; RISK AB There is a growing interest in the use of proton therapy for the treatment of many cancers. With its unique dose-distribution properties, proton therapy has the potential to improve the therapeutic ratio of prostate radiation by allowing for an increase in dose without a substantial increase in side effects. While much evidence supports this notion in the context of many oncologic sites, only limited clinical data have compared protons to photons in prostate cancer. Therefore, the increasing enthusiasm for the use of protons in prostate cancer has aroused considerable concern. Some have questioned its ability to limit, morbidity, and others have questioned its value relative to the cost. In addition, theoretical concerns have been raised about a potential additional risk for secondary malignancies. In this article, we review the current status of the evidence supporting the use of protons in prostate cancer and discuss the active controversies that surround this modality. C1 [Nguyen, Paul L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Harvard Radiat Oncol Program, Boston, MA 02114 USA. RP Nguyen, PL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Harvard Radiat Oncol Program, 100,Blossom Street Cox 3, Boston, MA 02114 USA. EM pnguyen@LROC.harvard.edu NR 29 TC 13 Z9 13 U1 0 U2 4 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUN PY 2008 VL 22 IS 7 BP 748 EP 754 PG 7 WC Oncology SC Oncology GA 333SM UT WOS:000258172700004 PM 18619120 ER PT J AU Haffajee, AD Socransky, SS Patel, MR Song, X AF Haffajee, A. D. Socransky, S. S. Patel, M. R. Song, X. TI Microbial complexes in supragingival plaque SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE bacteria; ecology; microbiology; periodontal; supragingival plaque ID DNA-DNA HYBRIDIZATION; DENTAL PLAQUE AB Background/aims: To examine microbial communities in supragingival biofilm samples. Methods: Supragingival plaque samples were taken from 187 subjects at baseline (n = 4745). Fifty-five subjects provided supragingival plaque samples at 1-7 days after professional tooth cleaning (n = 1456); 93 subjects provided 8044 samples between 3 and 24 months post-therapy. All samples were individually analyzed for their content of 40 bacterial species using checkerboard DNA-DNA hybridization. Microbial associations among species were sought using cluster analysis and community ordination techniques for the three groups separately. Results: Six complexes were formed for the baseline samples. Similar complexes were formed for the samples taken 3-24 months post-therapy. However, distinct changes were observed in microbial communities in samples taken during the 7 days of plaque redevelopment. The complexes related to clinical parameters of periodontal disease. Conclusion: There were specific microbial complexes in supragingival plaque that were similar to those found in subgingival plaque samples with a few minor differences. The relation of previously unclustered taxa to the complexes was also described. C1 [Haffajee, A. D.; Socransky, S. S.; Patel, M. R.; Song, X.] Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Haffajee, AD (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. EM ahaffajee@forsyth.org FU NIDCR NIH HHS [DE-12108, DE-14368] NR 13 TC 88 Z9 91 U1 4 U2 23 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD JUN PY 2008 VL 23 IS 3 BP 196 EP 205 DI 10.1111/j.1399-302X.2007.00411.x PG 10 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 285YD UT WOS:000254811200004 PM 18402605 ER PT J AU Eslami, B Lorente, C Kieff, D Caruso, PA Faquin, WC AF Eslami, Behnam Lorente, Carol Kieff, David Caruso, Paul A. Faquin, William C. TI Ameloblastoma associated with the nevoid basal cell carcinoma (Gorlin) syndrome SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY LA English DT Article ID MANDIBULAR CORONOID PROCESSES; NEVUS SYNDROME; BILATERAL HYPERPLASIA; GENE AB Nevoid basal cell carcinoma syndrome ( NBCCS) is an autosomal dominant disorder characterized by a wide range of clinical signs and symptoms. The major criteria for the diagnosis are multiple cutaneous basal cell carcinomas, multiple odontogenic keratocysts of the jaw, palmar and plantar pits, and skeletal abnormalities. Here, we report an unusual case of NBCCS in a 68-year-old woman with late onset of clinical signs and symptoms and with an associated ameloblastoma. Only 4 other cases of this unusual association have been reported. C1 [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Caruso, Paul A.] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA USA. [Kieff, David] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA USA. [Lorente, Carol] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Lorente, Carol] Harvard Univ, Vanguard Med Assoc, Cambridge, MA 02138 USA. [Eslami, Behnam] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Cambridge, MA 02138 USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, WRN 219 55 Fruit St, Boston, MA 02114 USA. EM wfaquin@partners.org NR 19 TC 8 Z9 9 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JUN PY 2008 VL 105 IS 6 BP E10 EP E13 DI 10.1016/j.tripleo.2008.01.034 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 306QB UT WOS:000256261800028 PM 18417377 ER PT J AU Treister, NS Richardson, P Schlossman, R Miller, K Woo, SB AF Treister, Nathaniel S. Richardson, Paul Schlossman, Robert Miller, Kenneth Woo, Sook-Bin TI Painful tongue ulcerations in patients with bisphosphonate-associated osteonecrosis of the jaws SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY LA English DT Article ID ZOLEDRONIC ACID; BONE AB Objectives. Bisphosphonate-associated osteonecrosis of the jaws (BONJ) is a recently recognized and well described complication in cancer patients. While pain and associated morbidity have been reported, this has largely been attributed to localized infection of the nonvital bone and surrounding soft tissue, or in rare cases, pathologic fracture. Study design. Cancer patients who were treated with intravenous bisphosphonate therapy and subsequently developed BONJ with associated traumatic tongue ulcerations were reported. Results. We report a series of 5 patients who presented with unilateral painful tongue ulcerations secondary to the tongue rubbing against adjacent exposed mylohyoid bone on the lingual surface of the mandible. Smoothing, recontouring, or removal of the bone, and in some cases intralesional steroid therapy, resulted in complete resolution of symptoms. Conclusions. Oral health care specialists and physicians must be alert to this potential complication of BONJ because it is easily managed with conservative measures and results in rapid and significant improvement in symptoms and overall quality of life. C1 [Treister, Nathaniel S.; Woo, Sook-Bin] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Beth Israel Deaconess Med Ctr, Dana Farber Canc Inst,Brigham & Womens Hosp, Cambridge, MA 02138 USA. [Richardson, Paul; Schlossman, Robert] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Miller, Kenneth] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Treister, Nathaniel S.; Woo, Sook-Bin] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Cambridge, MA 02138 USA. RP Treister, NS (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 75 Francis St, Boston, MA 02115 USA. EM ntreister@partners.org NR 12 TC 14 Z9 14 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JUN PY 2008 VL 105 IS 6 BP E1 EP E4 DI 10.1016/j.tripleo.2008.02.010 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 306QB UT WOS:000256261800026 PM 18417376 ER PT J AU Nemec, J Swerdlow, SH Bazaz, R Saba, SF Shalaby, AA AF Nemec, Jan Swerdlow, Steven H. Bazaz, Raveen Saba, Samir F. Shalaby, Ala A. TI B-cell lymphoproliferative disorder of an ICD pocket: A diagnostic puzzle in an immunosuppressed patient SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE implantable cardioverter defibrillator; lymphoma; immune suppression ID PACEMAKER POCKET; ONCOTAXIS; LYMPHOMA AB We present a case of a patient with lymphoma in an ICD pocket in the setting of posttransplant immune suppression. Infection of the ICD system was suspected and the correct diagnosis was established by biopsy. C1 [Shalaby, Ala A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Nemec, Jan; Bazaz, Raveen; Saba, Samir F.; Shalaby, Ala A.] Univ Pittsburgh, Cardiovasc Inst, Pittsburgh, PA USA. [Swerdlow, Steven H.] Univ Pittsburgh, Dept Pathol, Div Hematopathol, Pittsburgh, PA USA. RP Shalaby, AA (reprint author), VA Pittsburgh Healthcare Syst, 111 Univ Dr C, Pittsburgh, PA 15240 USA. EM Alaa.Shalaby@med.va.gov NR 8 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD JUN PY 2008 VL 31 IS 6 BP 769 EP 771 DI 10.1111/j.1540-8159.2008.01084.x PG 3 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 306JH UT WOS:000256243600019 PM 18507553 ER PT J AU Aryana, A Fifer, MA Ruskin, JN Mela, T AF Aryana, Arash Fifer, Michael A. Ruskin, Jeremy N. Mela, Theofanie TI Short PR interval in the absence of preexcitation: A characteristic finding in a patient with Fabry disease SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article AB Fabry disease (FD) is a rare lysosomal storage disease characterized by intracellular deposition of glycosphingolipids that can involve various organs including the heart. Here, we report the finding of a short PR interval in a patient with FD and recurrent syncope associated with short atrial-His (A-H) and His-ventricular (H-V) intervals in the absence of preexcitation. While electrocardiographic abnormalities are not uncommon among FD patients, there have been few reports on electrophysiological studies performed on these patients. The exact mechanism for the short A-H and H-V intervals remains unclear, but they may result from accelerated conduction in the AV node-His-Purkinje system. C1 [Aryana, Arash; Ruskin, Jeremy N.; Mela, Theofanie] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Aryana, Arash; Ruskin, Jeremy N.; Mela, Theofanie] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mela, T (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB-109, Boston, MA 02114 USA. EM tmela@partners.org NR 5 TC 9 Z9 10 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD JUN PY 2008 VL 31 IS 6 BP 782 EP 783 DI 10.1111/j.1540-8159.2008.01088.x PG 2 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 306JH UT WOS:000256243600023 PM 18507557 ER PT J AU Rehman, SU Januzzi, JL AF Rehman, S. U. Januzzi, J. L. TI Advances in heart failure: natriuretic peptide testing SO PANMINERVA MEDICA LA English DT Review DE heart failure; natriuretic peptides; cardiovascular diseases ID LEFT-VENTRICULAR DYSFUNCTION; CARDIAC-RESYNCHRONIZATION THERAPY; CONVERTING ENZYME-INHIBITOR; EMERGENCY-DEPARTMENT PRIDE; N-TERMINAL PROBNP; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; ACUTE MYOCARDIAL-INFARCTION; C-REACTIVE PROTEIN; FUNCTIONAL-CAPACITY; GENE-EXPRESSION AB Natriuretic peptide testing in the form of B-type natriuretic peptide (BNP) or NT-proBNP measurement has revolutionized modern heart failure (HF) diagnostics for those patients with acute symptoms, and promises to have similarly profound effects not only for the earlier recognition of those with HF, but also for the therapy of patients across the entire spectrum of HF. Future efforts are necessary to better understand the complex biology of the natriuretic peptides, to further optimize use of the assays for their measurement, and to gain clarity regarding the appropriate venue for their measurement. The ultimate goal is to recognize more readily and treat the syndrome that is HF, in order to reduce the considerable morbidity and mortality among those so afflicted. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Cardiol, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Januzzi, JL (reprint author), 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM jjanuzzi@partners.org FU Balson Fund for Cardiovascular Research FX Dr.Rehman is supported by the Dennis and Marilyn Barry Fellowship in Cardiology,while Dr.Januzzi is supported in part by the Balson Fund for Cardiovascular Research. NR 116 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 0031-0808 J9 PANMINERVA MED JI Panminerva Medica PD JUN PY 2008 VL 50 IS 2 BP 139 EP 151 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 353LR UT WOS:000259569800006 PM 18607337 ER PT J AU Christo, K Prabhakaran, R Lamparello, B Cord, J Miller, KK Goldstein, MA Gupta, N Herzog, DB Klibanski, A Misra, M AF Christo, Karla Prabhakaran, Rajani Lamparello, Brooke Cord, Jennalee Miller, Karen K. Goldstein, Mark A. Gupta, Nupur Herzog, David B. Klibanski, Anne Misra, Madhusmita TI Bone metabolism in adolescent athletes with amenorrhea, athletes with eumenorrhea, and control subjects SO PEDIATRICS LA English DT Article DE adolescents; athletes; bone density; bone-turnover markers; insulin-like growth factor I ID EXERCISE-ASSOCIATED AMENORRHEA; MULTIPLE SKELETAL SITES; MINERAL DENSITY; ANOREXIA-NERVOSA; EATING-DISORDERS; HEALTHY-CHILDREN; BODY-COMPOSITION; YOUNG GIRLS; FEMALE; RUNNERS AB OBJECTIVE. We hypothesized that, despite increased activity, bone density would be low in athletes with amenorrhea, compared with athletes with eumenorrhea and control subjects, because of associated hypogonadism and would be associated with a decrease in bone formation and increases in bone-resorption markers. METHODS. In a cross-sectional study, we examined bone-density measures (spine, hip, and whole body) and body composition by using dual-energy radiograph absorptiometry and assessed fasting levels of insulin-like growth factor I and bone-turnover markers (N-terminal propeptied of type 1 procollagen and N-telopeptide) in 21 athletes with amenorrhea, 18 athletes with eumenorrhea, and 18 control subjects. Subjects were 12 to 18 years of age and of comparable chronologic and bone age. RESULTS. Athletes with amenorrhea had lower bone-density z scores at the spine and whole body, compared with athletes with eumenorrhea and control subjects, and lower hip z scores, compared with athletes with eumenorrhea. Lean mass did not differ between groups. However, athletes with amenorrhea had lower BMI z scores than did athletes with eumenorrhea and lower insulin-like growth factor I levels than did control subjects. Levels of both markers of bone turnover were lower in athletes with amenorrhea than in control subjects. BMI z scores, lean mass, insulin-like growth factor I levels, and diagnostic category were important independent predictors of bone mineral density z scores. CONCLUSIONS. Although they showed no significant differences in lean mass, compared with athletes with eumenorrhea and control subjects, athletes with amenorrhea had lower bone density at the spine and whole body. Insulin-like growth factor I levels, body-composition parameters, and menstrual status were important predictors of bone density. Follow-up studies are necessary to determine whether amenorrhea in athletes adversely affects the rate of bone mass accrual and therefore peak bone mass. C1 [Christo, Karla; Prabhakaran, Rajani; Lamparello, Brooke; Cord, Jennalee; Miller, Karen K.; Klibanski, Anne; Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Christo, Karla; Prabhakaran, Rajani; Lamparello, Brooke; Cord, Jennalee; Miller, Karen K.; Klibanski, Anne; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA USA. [Goldstein, Mark A.; Gupta, Nupur] Massachusetts Gen Hosp Children, Adolescent Med Unit, Boston, MA USA. [Prabhakaran, Rajani; Misra, Madhusmita] Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. [Herzog, David B.] Massachusetts Gen Hosp, Harris Ctr, Boston, MA 02114 USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457,55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org FU NCRR NIH HHS [K23 RR018851, M01 RR01066, M01 RR001066]; NIDDK NIH HHS [P30 DK040561, R01 DK062249, P30 DK040561-12] NR 55 TC 59 Z9 59 U1 0 U2 7 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 JUN PY 2008 VL 121 IS 6 BP 1127 EP 1136 DI 10.1542/peds.2007-2392 PG 10 WC Pediatrics SC Pediatrics GA 307IX UT WOS:000256313700043 PM 18519482 ER PT J AU Traum, AZ Kawai, T Vacanti, JP Sachs, DH Cosimi, AB Madsen, JC AF Traum, Avram Z. Kawai, Tatsuo Vacanti, Joseph P. Sachs, David H. Cosimi, A. Benedict Madsen, Joren C. TI The need for tolerance in pediatric organ transplantation SO PEDIATRICS LA English DT Editorial Material ID STAGE RENAL-DISEASE; ALLOGRAFT TOLERANCE; LYMPHOHEMATOPOIETIC CHIMERISM; CARDIOVASCULAR RISK; STEROID WITHDRAWAL; MULTIPLE-MYELOMA; ACUTE REJECTION; BONE-MARROW; RECIPIENTS; KIDNEY C1 [Traum, Avram Z.] Massachusetts Gen Hosp, Dept Pediat, Pediat Nephrol Unit, Boston, MA 02114 USA. [Kawai, Tatsuo; Sachs, David H.; Cosimi, A. Benedict; Madsen, Joren C.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Madsen, Joren C.] Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. [Vacanti, Joseph P.] Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. [Traum, Avram Z.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Kawai, Tatsuo; Vacanti, Joseph P.; Sachs, David H.; Cosimi, A. Benedict; Madsen, Joren C.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Traum, AZ (reprint author), Massachusetts Gen Hosp, Dept Pediat, Pediat Nephrol Unit, 55 Fruit St,Yawkey 6C, Boston, MA 02114 USA. EM atraum@partners.org FU NHLBI NIH HHS [P01HL18646, P01 HL018646]; NIAID NIH HHS [R01 AI037692-09, R01 AI037692, N01 AI015416, R21 AI037692, R21 AI037692-06, R01 AI037692-10, N01AI15416] NR 35 TC 12 Z9 12 U1 0 U2 0 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 JUN PY 2008 VL 121 IS 6 BP 1258 EP 1260 DI 10.1542/peds.2008-0783 PG 3 WC Pediatrics SC Pediatrics GA 307IX UT WOS:000256313700058 PM 18519497 ER PT J AU Nelson, BD Herlihy, JM Burke, TF AF Nelson, Brett D. Herlihy, Julie M. Burke, Thomas F. TI Proposal for fellowship training in pediatric global health SO PEDIATRICS LA English DT Editorial Material C1 [Nelson, Brett D.; Herlihy, Julie M.; Burke, Thomas F.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. RP Nelson, BD (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, 3 Longfellow Pl,Suite 100, Boston, MA 02114 USA. EM brett.d.nelson@gmail.com OI Nelson, Brett/0000-0002-5049-1798 NR 5 TC 9 Z9 9 U1 0 U2 0 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 JUN PY 2008 VL 121 IS 6 BP 1261 EP 1262 DI 10.1542/peds.2008-0932 PG 2 WC Pediatrics SC Pediatrics GA 307IX UT WOS:000256313700059 PM 18519498 ER PT J AU Prabhakaran, R Misra, M Miller, KK Kruczek, K Sundaralingam, S Herzog, DB Katzman, DK Klibanski, A AF Prabhakaran, Rajani Misra, Madhusmita Miller, Karen K. Kruczek, Kimberly Sundaralingam, Shankeertha Herzog, David B. Katzman, Debra K. Klibanski, Anne TI Determinants of height in adolescent girls with anorexia nervosa SO PEDIATRICS LA English DT Article DE height; anorexia nervosa; adolescents; bone age; hypogonadism; growth hormone ID CENTRAL PRECOCIOUS PUBERTY; SECRETORY DYNAMICS; HEALTHY ADOLESCENTS; GROWTH-RETARDATION; SHORT STATURE; BONE; CHILDREN; HORMONE; WEIGHT; DISEASE AB BACKGROUND. Anorexia nervosa, a condition characterized by marked caloric restriction and low insulin like growth factor-1 levels, would be expected to cause short stature. However, this disorder is also associated with hypogonadotropic hypogonadism and high growth hormone levels. Delays in growth-plate closure from associated hypogonadism may result in a longer period of time available for statural growth with protective effects on stature. In addition, growth hormone may have direct effects on the growth plate independent of insulin-like growth factor 1 to increase statural growth. OBJECTIVES AND METHODS. To determine the impact of undernutrition, hypogonadism, and acquired growth hormone resistance on height in adolescents with anorexia nervosa (aged 12 -18 years), we examined 208 girls: 110 with anorexia nervosa and 98 controls of comparable chronological age. Sixty-three girls with anorexia nervosa and 79 controls were followed prospectively over 1 year. Mean duration of illness was 11.6 +/- 13.2 months. In a subset, overnight growth hormone sampling was performed every 30 minutes for 12 hours, and fasting insulin-like growth factor 1 levels were obtained. RESULTS. The difference between height and target height and between predicted adult height and target height did not differ between the groups, indicating preservation of height potential. The groups had comparable bone age, but bone age was lower than chronological age in girls with anorexia nervosa. Girls with anorexia nervosa had lower insulin-like growth factor 1 levels and higher nadir growth hormone levels than those of controls. Nadir growth hormone levels predicted height SD scores and predicted adult-height SD scores in controls but not in the girls with anorexia nervosa. In girls with anorexia nervosa, insulin-like growth factor 1 and duration of illness predicted height measures. Height SD scores of < 0 were more likely after 32 months of illness and at insulin-like growth factor 1 levels of < 134 ng/mL. Delayed baseline bone age predicted subsequent increases in height SD scores in immature girls with anorexia nervosa. CONCLUSIONS. Our data suggest that preservation of height potential in this cohort of girls with anorexia nervosa may be a consequence of delayed bone age. Hypogonadism may negate the deleterious effects of undernutrition on stature by allowing for a longer duration of growth. C1 [Prabhakaran, Rajani; Misra, Madhusmita; Miller, Karen K.; Kruczek, Kimberly; Sundaralingam, Shankeertha; Klibanski, Anne] MassGen Hosp, Neuroendocirne Unit, Boston, MA 02114 USA. [Herzog, David B.] MassGen Hosp, Harris Ctr, Boston, MA 02114 USA. [Prabhakaran, Rajani; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA USA. [Prabhakaran, Rajani; Misra, Madhusmita] MassGen Hosp Children, Pediat Ednocrine Unit, Boston, MA USA. [Katzman, Debra K.] Hosp Sick Kids, Dept Pediat, Div Adolescent Med, Toronto, ON, Canada. RP Misra, M (reprint author), MassGen Hosp, Neuroendocirne Unit, 55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org FU NCRR NIH HHS [M01-RR-01066, K23 RR018851]; NIDDK NIH HHS [P30 DK040561-13, DK 062249, P30 DK040561] NR 24 TC 13 Z9 13 U1 0 U2 3 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 JUN PY 2008 VL 121 IS 6 BP E1517 EP E1523 DI 10.1542/peds.2007-2820 PG 7 WC Pediatrics SC Pediatrics GA 307IX UT WOS:000256313700008 PM 18519455 ER PT J AU Kobelt, P Wisser, AS Stengel, A Goebel, M Bannert, N Gourcerol, G Inhoff, T Noetzel, S Wiedenmann, B Klapp, BF Tache, Y Monnikes, H AF Kobelt, Peter Wisser, Anna-Sophia Stengel, Andreas Goebel, Miriam Bannert, Norbert Gourcerol, Guillaume Inhoff, Tobias Noetzel, Steffen Wiedenmann, Bertram Klapp, Burghard F. Tache, Yvette Moennikes, Hubert TI Peripheral obestatin has no effect on feeding behavior and brain Fos expression in rodents SO PEPTIDES LA English DT Article DE obestatin; food intake; CCK; urocortin 1; rats; mice; dark phase; light phase ID GROWTH-HORMONE-SECRETION; HYPOTHALAMIC ARCUATE NUCLEUS; GHRELIN-ASSOCIATED PEPTIDE; DORSAL VAGAL COMPLEX; REDUCES FOOD-INTAKE; RAT-BRAIN; PARAVENTRICULAR NUCLEUS; ACYLATED PEPTIDE; NEUROPEPTIDE-Y; WEIGHT-GAIN AB Obestatin is produced in the stomach from proghrelin by post-translational cleavage. The initial report claimed anorexigenic effects of obestatin in mice. Contrasting studies indicated no effect of obestatin on food intake (FI). We investigated influences of metabolic state (fed/fasted), environmental factors (dark/light phase) and brain Fos response to intraperitoneal (ip) obestatin in rats, and used the protocol from the original study assessing obestatin effects in mice. FI was determined in male rats injected ip before onset of dark or light phase, with obestatin (1 or 5 mu mol/kg), CCK8S (3.5 nmol/kg) or 0.15 M NaCl, after fasting (16 h, n = 8/group) or ad libitum (n =10-14/group) food intake. Fos expression in hypothalamic and brainstem nuclei was examined in freely fed rats 90 min after obestatin (5 mu mol/kg), CCK8S (1.75 nmol/kg) or 0.15 M NaCl (n = 4/group). Additionally, fasted mice were injected ip with obestatin (1 mu mol/kg) or urocortin 1 (2 nmol/kg) 15 min before food presentation. No effect on FI was observed after obestatin administration during the light and dark phase under both metabolic conditions while CCK8S reduced FI irrespectively of the conditions. The number of Fos positive neurons was not modified by obestatin while CCK8S increased Fos expression in selective brain nuclei. Obestatin did not influence the refeeding response to a fast in mice, while urocortin was effective. Therefore, peripheral obestatin has no effect on FI under various experimental conditions and did not induce Fos in relevant central neuronal circuitries modulating feeding in rodents. (C) 2008 Elsevier Inc. All rights reserved. C1 [Moennikes, Hubert] Charite Univ Med Berlin, Acad Teaching Inst, Martin Luther Hosp, Dept Med, D-14133 Berlin, Germany. [Moennikes, Hubert] Charite Univ Med Berlin, Acad Teaching Inst, Martin Luther Hosp, Inst Neurogastroenterol, D-14133 Berlin, Germany. [Kobelt, Peter; Klapp, Burghard F.] Charite Univ Med Berlin, Dept Med, Div Psychosomat Med & Psychotherapy, D-14133 Berlin, Germany. [Kobelt, Peter; Wisser, Anna-Sophia; Stengel, Andreas; Goebel, Miriam; Inhoff, Tobias; Noetzel, Steffen; Wiedenmann, Bertram; Moennikes, Hubert] Humboldt Univ, Charite, Div Hepatol Gastroenterol & Endocrinol, Dept Med, D-1086 Berlin, Germany. [Bannert, Norbert] Robert Koch Inst, D-1000 Berlin, Germany. [Gourcerol, Guillaume; Tache, Yvette] Univ Calif Los Angeles, Digest Dis Div, Ctr Neurobiol Stress, CURE Digest Dis Res Ctr,Dept Med, Los Angeles, CA USA. [Gourcerol, Guillaume; Tache, Yvette] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Monnikes, H (reprint author), Charite Univ Med Berlin, Acad Teaching Inst, Martin Luther Hosp, Dept Med, Caspar Theyss Str 27-31, D-14133 Berlin, Germany. EM moennikes@web.de FU NIDDK NIH HHS [R01 DK033061, R01 DK033061-23]; PHS HHS [R01 33061] NR 54 TC 31 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD JUN PY 2008 VL 29 IS 6 BP 1018 EP 1027 DI 10.1016/j.peptides.2008.01.020 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 310HE UT WOS:000256518700018 PM 18342400 ER PT J AU Ramos, AJ Cantero, MR Zhang, P Raychowdhury, MK Green, A MacPhee, D Cantiello, HF AF Ramos, A. J. Cantero, M. R. Zhang, P. Raychowdhury, M. K. Green, A. MacPhee, D. Cantiello, H. F. TI Morphological and electrical properties of human trophoblast choriocarcinoma, BeWo cells SO PLACENTA LA English DT Article DE human placenta; cytotrophoblast; human syncytiotrophoblast; TRP channels; polycystin-2; TRPP2 ID HUMAN CHORIONIC-GONADOTROPIN; CORTICOTROPIN-RELEASING-FACTOR; HUMAN PLACENTAL TROPHOBLASTS; CALCIUM-CHANNELS; CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE; HUMAN SYNCYTIOTROPHOBLAST; GENE-EXPRESSION; CATION CHANNELS; ENTRY CHANNELS; CA2+ ENTRY AB The syncytiotrophoblast of the human placenta arises from fusion of stem cells called cytotrophoblasts. The molecular mechanisms associated with cell fusion and syncytiation of cytotrophoblastic cells remain largely unknown. In the present study, we investigated the morphological and electrical properties of BeWo cells, a human choriocarcinoma-derived trophoblast cell model, with several features of the human cytotrophoblast. Cultured cells tended to cluster, but only fused into small, multinucleated syncytia in the presence of cAMP (72 h). The morphological features of both the actin and microtubular cytoskeletons indicated that within 72 h of constant exposure to cAMP, intracellular cortical actin cytoskeleton disappeared, which was the most prominent inducing factor of multi-nucleation. The presence of the cation channel protein, polycystin-2 (PC2), a TRP-type cation channel, associated with placental ion transport in term human syncytiotrophoblast, co-localised with acetylated tubulin in midbodies, but was found non-functional under any conditions. Different electrical phenotypes were observed among control BeWo cells. where only 26% (8 of 31 cells) displayed a voltage-dependent outwardly rectifying conductance. Most quiescent BeWo cells had, however. a low, slightly outwardly rectifying basal whole cell conductance. Acute exposure to intracellular cAMP (<15 min) increased the whole cell conductance by 122%, from 0.72 nS/cell to 1.60 nS/cell, and eliminated the voltage-regulated conductance. The encompassed evidence indicates that the early events in BeWo cell fusion and syncytiation occur by cAMP-associated changes in ionic conductance but not morphological changes associated to chronic exposure to the second messenger. This suggests a tight regulation, and important contribution of cation conductances in cytotrophoblastic cells prior to syncytiation. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Ramos, A. J.; Zhang, P.; Raychowdhury, M. K.; Cantiello, H. F.] Massachusetts Gen Hosp, Dept Med, Charlestown, MA USA. [Ramos, A. J.; Zhang, P.; Raychowdhury, M. K.; Cantiello, H. F.] Harvard Univ, Sch Med, Charlestown, MA USA. [Cantero, M. R.; Cantiello, H. F.] ININCA UBA CONICET, Buenos Aires, DF, Argentina. [Green, A.; MacPhee, D.] Mem Univ Newfoundland, Dept Reprod Dev Biol, Fac Med, St John, NF, Canada. RP Cantiello, HF (reprint author), Div Nephrol, MGH E,Bldg 149,13th St, Charlestown, MA 02129 USA. EM cantiello@helix.mgh.harvard.edu NR 44 TC 8 Z9 8 U1 1 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD JUN PY 2008 VL 29 IS 6 BP 492 EP 502 DI 10.1016/j.placenta.2008.02.013 PG 11 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 314TJ UT WOS:000256831400003 PM 18420268 ER PT J AU Montalbetti, N Cantero, MR Dalghi, MG Cantiello, HF AF Montalbetti, N. Cantero, M. R. Dalghi, M. G. Cantiello, H. F. TI Reactive oxygen species inhibit polycystin-2 (TRPP2) cation channel activity in term human syncytiotrophoblast SO PLACENTA LA English DT Article DE TRP channels; hydrogen peroxide; tert-butyl hydroperoxide; oxygen free radicals; placenta; TBARS; lipid peroxidation ID PLACENTAL OXIDATIVE STRESS; LIPID-PEROXIDATION; ENDOTHELIAL-CELLS; CALCIUM-CHANNELS; DEATH; INACTIVATION; PREECLAMPSIA; EXPRESSION; DROSOPHILA; PROTEINS AB Pregnancy is often associated with oxidative stress (OS) and lower antioxidant defences, which are both implicated in the pathophysiology of preeclampsia, free radical-induced birth defects, and abortions, as well as gestational diabetes mellitus (GDM), where products of lipid peroxidation are increased. The molecular target(s) of increased oxygen free radicals and consequent lipid peroxidation in the human placenta remains ill defined. The human syncytiotrophoblast (hST) expresses abundant polycystin-2 (PC2, TRPP2), a TRP-type Ca2+-permeable non-selective cation channel. Here, we explored the effect of reactive oxygen species (ROS) on PC2 channel activity of term hST. Apical membranes of the hST were reconstituted in a lipid bilayer chamber. Addition of either hydrogen-peroxide (H2O2) or tert-butyl hydroperoxide (tBHP) to the cis chamber (intracellular side) rapidly and completely inhibited PC2-mediated cation channel activity in reconstituted hST vesicles. A dose-response titration with increasing concentrations of H2O2 gave an IC50 = 131 nM. The effect of H2O2 on the isolated protein from in vitro transcribed/translated material was significantly different. H2O2 inhibited PC2 cation channel activity, with a much lower affinity (IC50 = 193 mu M). To correlate these findings with H2O2-induced lipid peroxidation, TBARS where measured in hST apical membranes incubated with H2O2. Increased TBARS by exposure of hST apical membranes to H2O2 (625 mu M) returned to control value in the presence of catalase (167 mu g/ml). Taken together these data indicate that ROS affect PC2 channel function by targetting both membrane lipids and the channel protein. Thus, OS in human pregnancy may be linked to dysregulation of channels such as PC2, which allow the transport of Ca2+ into the placenta. Oxidative complications in pregnancy may implicate dysfunctional cation transfer between mother and fetus. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Cantiello, H. F.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Charlestown, MA 02129 USA. [Cantiello, H. F.] Harvard Univ, Sch Med, Charlestown, MA USA. [Montalbetti, N.; Cantero, M. R.; Cantiello, H. F.] INICA UBA CONICET, Buenos Aires, DF, Argentina. [Dalghi, M. G.] Univ Buenos Aires, Fac Farm & Bioquim, Catedra Quim gen & Inorgan, RA-1113 Buenos Aires, DF, Argentina. RP Cantiello, HF (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, MGH E,Bldg 149,13th St, Charlestown, MA 02129 USA. EM cantiello@helix.mgh.harvard.edu OI Montalbetti, Nicolas/0000-0003-2897-9540 NR 39 TC 13 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 EI 1532-3102 J9 PLACENTA JI Placenta PD JUN PY 2008 VL 29 IS 6 BP 510 EP 518 DI 10.1016/j.placenta.2008.02.015 PG 9 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 314TJ UT WOS:000256831400005 PM 18417208 ER PT J AU Faca, VM Song, KS Wang, H Zhang, Q Krasnoselsky, AL Newcomb, LF Plentz, RR Gurumurthy, S Redston, MS Pitteri, SJ Pereira-Faca, SR Ireton, RC Katayama, H Glukhova, V Phanstiel, D Brenner, DE Anderson, MA Misek, D Scholler, N Urban, ND Barnett, MJ Edelstein, C Goodman, GE Thornquist, MD McIntosh, MW DePinho, RA Bardeesy, N Hanash, SM AF Faca, Vitor M. Song, Kenneth S. Wang, Hong Zhang, Qing Krasnoselsky, Alexei L. Newcomb, Lisa F. Plentz, Ruben R. Gurumurthy, Sushma Redston, Mark S. Pitteri, Sharon J. Pereira-Faca, Sandra R. Ireton, Renee C. Katayama, Hiroyuki Glukhova, Veronika Phanstiel, Douglas Brenner, Dean E. Anderson, Michelle A. Misek, David Scholler, Nathalie Urban, Nicole D. Barnett, Matt J. Edelstein, Cim Goodman, Gary E. Thornquist, Mark D. McIntosh, Martin W. DePinho, Ronald A. Bardeesy, Nabeel Hanash, Samir M. TI A mouse to human search for plasma Proteome changes associated with pancreatic tumor development SO PLOS MEDICINE LA English DT Article ID GENE-EXPRESSION ANALYSIS; DUCTAL ADENOCARCINOMA; ANALYSIS-SYSTEM; QUANTITATIVE-ANALYSIS; STATISTICAL-MODEL; MASS-SPECTROMETRY; OVARIAN-CARCINOMA; SERUM MARKERS; CANCER; PROTEINS AB Background The complexity and heterogeneity of the human plasma proteome have presented significant challenges in the identification of protein changes associated with tumor development. Refined genetically engineered mouse ( GEM) models of human cancer have been shown to faithfully recapitulate the molecular, biological, and clinical features of human disease. Here, we sought to exploit the merits of a well-characterized GEM model of pancreatic cancer to determine whether proteomics technologies allow identification of protein changes associated with tumor development and whether such changes are relevant to human pancreatic cancer. Methods and Findings Plasma was sampled from mice at early and advanced stages of tumor development and from matched controls. Using a proteomic approach based on extensive protein fractionation, we confidently identified 1,442 proteins that were distributed across seven orders of magnitude of abundance in plasma. Analysis of proteins chosen on the basis of increased levels in plasma from tumor-bearing mice and corroborating protein or RNA expression in tissue documented concordance in the blood from 30 newly diagnosed patients with pancreatic cancer relative to 30 control specimens. A panel of five proteins selected on the basis of their increased level at an early stage of tumor development in the mouse was tested in a blinded study in 26 humans from the CARET (Carotene and Retinol Efficacy Trial) cohort. The panel discriminated pancreatic cancer cases from matched controls in blood specimens obtained between 7 and 13 mo prior to the development of symptoms and clinical diagnosis of pancreatic cancer. Conclusions Our findings indicate that GEM models of cancer, in combination with in-depth proteomic analysis, provide a useful strategy to identify candidate markers applicable to human cancer with potential utility for early detection. C1 [Faca, Vitor M.; Song, Kenneth S.; Wang, Hong; Zhang, Qing; Krasnoselsky, Alexei L.; Newcomb, Lisa F.; Pitteri, Sharon J.; Pereira-Faca, Sandra R.; Ireton, Renee C.; Katayama, Hiroyuki; Glukhova, Veronika; Phanstiel, Douglas; Scholler, Nathalie; Urban, Nicole D.; Barnett, Matt J.; Edelstein, Cim; Goodman, Gary E.; Thornquist, Mark D.; McIntosh, Martin W.; Hanash, Samir M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Plentz, Ruben R.; Gurumurthy, Sushma] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Redston, Mark S.] Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. [Brenner, Dean E.; Anderson, Michelle A.; Misek, David] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Ctr Appl Canc Sci, Belfer Inst Innovat Canc Sci, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med & Genet, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hanash, SM (reprint author), Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. EM shanash@fhcrc.org RI Faca, Vitor/A-3989-2013; OI FACA, VITOR MARCEL/0000-0003-3205-7944 FU NCI NIH HHS [5K01CA104647, 5P01CA117969-02, K01 CA104647, P01 CA117969] NR 68 TC 171 Z9 172 U1 1 U2 12 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 JUN PY 2008 VL 5 IS 6 BP 953 EP 967 AR e123 DI 10.1371/journal.pmed.0050123 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 318QB UT WOS:000257105600020 PM 18547137 ER PT J AU Khalil, P Murty, P Palevsky, PM AF Khalil, Patricia Murty, Preethi Palevsky, Paul M. TI The patient with acute kidney injury SO PRIMARY CARE LA English DT Review ID ACUTE-RENAL-FAILURE; CONTRAST-INDUCED NEPHROPATHY; RANDOMIZED CONTROLLED-TRIAL; CRITICALLY-ILL PATIENTS; GELATINASE-ASSOCIATED LIPOCALIN; INTENSIVE-CARE-UNIT; LOW-DOSE DOPAMINE; CARDIAC-SURGERY; REPLACEMENT THERAPY; RIFLE CRITERIA AB During the past half decade there has been a paradigm shift in the view of acute kidney disease that has resulted in a change in nomenclature from the older term, "acute renal failure," to "acute kidney injury" (AKI). This article reviews the new criteria for diagnosis and staging of AKI and summarizes the current understanding of the many causes of AKI and the approach to diagnosis and management. C1 [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Univ Drive Div, Renal Sect, Pittsburgh, PA 15240 USA. [Khalil, Patricia; Murty, Preethi; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Univ Drive Div, Renal Sect, Room 7E123,111F-U, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 106 TC 7 Z9 7 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0095-4543 J9 PRIMARY CARE JI Primary Care PD JUN PY 2008 VL 35 IS 2 BP 239 EP + DI 10.1016/j.pop.2008.01.003 PG 27 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 316OR UT WOS:000256960100005 PM 18486715 ER PT J AU Bao, BY Chuang, BF Wang, Q Sartor, O Balk, SP Brown, M Kantoff, PW Lee, GSM AF Bao, Bo-Ying Chuang, Bin-Fay Wang, Qianben Sartor, Oliver Balk, Steven P. Brown, Myles Kantoff, Philip W. Lee, Gwo-Shu Mary TI Androgen receptor mediates the expression of UDP-glucuronosyltransferase 2 B15 and B17 genes SO PROSTATE LA English DT Article DE prostate cancer; androgen; androgen receptor; UGT2B15; UGT2B17 ID INDEPENDENT PROSTATE-CANCER; LNCAP CELLS; DIHYDROTESTOSTERONE LEVELS; UGT2B15; ENZYMES; THERAPY; PROLIFERATION; TARGET; GROWTH; TISSUE AB BACKGROUND. Enhanced androgen receptor (AR) activity by increased testosterone availability may play important roles in prostate cancer progressing to castration resistant state. Comparison of expression profiles in androgen dependent and independent prostate tumors demonstrated a marked increase of the expression of UDP-glucuronosyltransferase 2B15 (UGT2B15), an androgen catabolic enzyme. We investigated mechanisms controlling the differential expression of UGT2B15 and B17 in response to androgen treatments. METHODS. Gene expression was determined by RT-PCR. The association of AR with UGT2B15/B17 genes was determined by Chromatin immuno-precipitation (CHIP). RNA interference was used to knock-down gene expression. RESULTS. UGT2B15 and B17 genes were not expressed in AR negative prostate cancer cell lines, PC3 and DU145, while they were expressed in AR positive cell lines, LNCaP, LNCaP-abl (an androgen independent LNCaP sub-line), and VCaP. The expression levels of UGT2B15/B17 were up-regulated in LNCaP-abl comparing to those in LNCaP. These results suggest the requirement of AR for the expression of UGT2B15/B17. Treatment with DHT down-regulated the expression of UGT2B15/B17 in LNCaP in a time and dose dependent manner and this down-regulation was competitively antagonized by flutamide and bicalutimide, suggesting a pathway mediated by AR. Further CHIP experiments demonstrated the direct interaction of AR with the promoter regions of UGT2B15/B17 genes. Knocking down AR expression in LNCaP significantly reduced the expression of UGT2B15/B17 and completely inhibited the DHT-induced down-regulation of UGT2B15/B17 genes. CONCLUSIONS. We demonstrated that UGT2B15 and B17 are primary androgen-regulated genes and AR is required for both their basal expression and their androgen-regulated expression. C1 [Bao, Bo-Ying; Chuang, Bin-Fay; Wang, Qianben; Sartor, Oliver; Brown, Myles; Kantoff, Philip W.; Lee, Gwo-Shu Mary] Childrens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Balk, Steven P.] Beth Israel Deaconess Med Ctr, Dept Med, Canc Biol Program, Boston, MA 02215 USA. [Balk, Steven P.] Harvard Univ, Sch Med, Boston, MA USA. RP Lee, GSM (reprint author), Childrens Hosp, Dana Farber Canc Inst, Dept Med Oncol, D710B,44 Binney St, Boston, MA 02115 USA. EM gwo-shu_lee@dfci.harvard.edu RI Wang, Qianben/E-4267-2011; Bao, Bo-Ying/D-1789-2012 OI Bao, Bo-Ying/0000-0001-5510-6513 FU NCI NIH HHS [P50 CA090381-05, 2P50CA90381, P50 CA090381] NR 34 TC 34 Z9 35 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-4137 J9 PROSTATE JI Prostate PD JUN 1 PY 2008 VL 68 IS 8 BP 839 EP 848 DI 10.1002/pros.20749 PG 10 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 305UD UT WOS:000256202400005 PM 18302198 ER PT J AU Casali, M Banta, S Zambonelli, C Megeed, Z Yarmush, ML AF Casali, Monica Banta, Scott Zambonelli, Carlo Megeed, Zaki Yarmush, Martin L. TI Site-directed mutagenesis of the hinge peptide from the hemagglutinin protein: enhancement of the pH-responsive conformational change SO PROTEIN ENGINEERING DESIGN & SELECTION LA English DT Article DE circular dichroism; conformational change; hemagglutinin; site-directed mutagenesis; stimulus-responsive ID CIRCULAR-DICHROISM SPECTRA; INFLUENZA HEMAGGLUTININ; MEMBRANE-FUSION; VIRUS; HELIX; TRANSITIONS; MECHANISM; DYNAMICS; GLYCOPROTEIN; PROPENSITIES AB Environmentally responsive proteins and peptides are increasingly finding utility in various engineered systems due to their ability to respond to the presentation of external stimuli. A classic example of this behavior is the influenza hemagglutinin (HA) fusion protein. At neutral pH, HA exists in a non-fusogenic state, but upon exposure to low pH, the conformation of the structure changes to expose a fusogenic peptide. During this structural change, massive rearrangements occur in a subunit of HA (HA2). Crystallography data has shown that a loop of 28 amino acids (residues 54-81) undergoes a dramatic transition from a random coil to an alpha-helix. This segment connects to two flanking helical regions (short and long) to form a long, continuous helix. Here, we report the results of site-directed mutagenesis study on LOOP-36 to further understand the mechanism of this important stimulus-responsive peptide. The conformational transition of a bacterially expressed LOOP-36 was found to be less dramatic than has been previously reported. The systematic mutation of glutamate and histidine residues in the peptide to glutamines (glutamine scanning) did not impact the conformational behavior of the peptide, but the substitution of the glycine residue at position 22 with alanine resulted in significant pH-responsive behavior. Therefore this mutant stimulus-responsive peptide may be more valuable for future protein engineering and bionanotechnology efforts. C1 [Casali, Monica; Banta, Scott; Megeed, Zaki; Yarmush, Martin L.] Massachusetts Gen Hosp, Shriners Hosp Children, Ctr Engn Med Surg Serv, Boston, MA 02114 USA. [Casali, Monica; Banta, Scott; Megeed, Zaki; Yarmush, Martin L.] Harvard Univ, Sch Med, Boston, MA USA. [Zambonelli, Carlo] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, England. RP Casali, M (reprint author), Massachusetts Gen Hosp, Shriners Hosp Children, Ctr Engn Med Surg Serv, 51 Blossom St, Boston, MA 02114 USA. EM mcasali@med.harvard.edu NR 36 TC 11 Z9 11 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1741-0126 J9 PROTEIN ENG DES SEL JI Protein Eng. Des. Sel. PD JUN PY 2008 VL 21 IS 6 BP 395 EP 404 DI 10.1093/protein/gzn018 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 306YV UT WOS:000256285400005 PM 18411225 ER PT J AU Sutton, J Richmond, T Shi, X Athanas, M Ptak, C Gerszten, R Bonilla, L AF Sutton, Jennifer Richmond, Tori Shi, Xu Athanas, Michael Ptak, Celeste Gerszten, Robert Bonilla, Leo TI Performance characteristics of an FT MS-based workflow for label-free differential MS analysis of human plasma: standards, reproducibility, targeted feature investigation, and application to a model of controlled myocardial infarction SO PROTEOMICS CLINICAL APPLICATIONS LA English DT Article DE label-free differential mass spectrometry; myocardial infarction; plasma biomarker; quality control; standards ID MASS-SPECTROMETRY; PROTEIN MIXTURES; PROTEOMICS; IDENTIFICATION; QUANTITATION; VALIDATION; PEPTIDES; ACCURACY; DATABASE; PEDF AB Proteomics is undergoing a rapid transformation from a qualitative global peptide sequencing discipline into a quantitative, reproducibility-driven practice. Nowhere is this more evident than in the rapidly expanding field of protein biomarker discovery where the general goal is to uncover statistically robust patterns of differential expression between or among subjects/samples representing distinct biological/temporal states. This report presents the analytical characterization of a label-free LC FT-ICR-MS workflow for differential proteomics analysis of human plasma. The key elements discussed include (i) methodologies for performing properly replicated experiments with highly reproducible sample preparation and analysis, including the use of internal standards to quantify variance at different steps in the process, (ii) a new methodology for performing sample re-analysis that uses off-line targeted robotic acquisition of complementary spectral data (e.g. ECD and/or IRMPD) to enhance the identification of differentially expressed peptides/proteins, and (iii) data processing pipelines capable of integrating the automatic statistical analysis of the label-free (LC-) MS signal, together with the intuitive and highly interactive curation and annotation of differential features using the output from standard sequence database search programs. We illustrate the application of the complete sample-to-annotated-differential-peptides (-proteins) workflow by describing the acquisition and analysis of a large multidimensional dataset from patients undergoing a controlled myocardial infarction resulting in an experimental setup in which each patients serve as their own control. Furthermore, we discuss a couple illustrative examples of mid-level proteins observed in this study whose plasma concentrations change consistently within and across patients, in a treatment- and time-dependent fashion. C1 [Sutton, Jennifer; Richmond, Tori; Bonilla, Leo] BRIMS Ctr, Pittsburgh, PA 15237 USA. [Shi, Xu; Gerszten, Robert] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Shi, Xu; Gerszten, Robert] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Shi, Xu; Gerszten, Robert] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Athanas, Michael] VAST Sci, Cambridge, MA USA. [Ptak, Celeste] Advion Biosci, Ithaca, NY USA. RP Sutton, J (reprint author), BRIMS Ctr, 294 Crestmont Rd, Pittsburgh, PA 15237 USA. EM jennifer.sutton@thermofisher.com NR 26 TC 13 Z9 13 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1862-8346 J9 PROTEOM CLIN APPL JI Proteom. Clin. Appl. PD JUN PY 2008 VL 2 IS 6 BP 862 EP 881 DI 10.1002/prca.200780057 PG 20 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 319SJ UT WOS:000257183900008 PM 21136885 ER PT J AU Ronningstam, E Weinberg, I Maltsberger, JT AF Ronningstam, Elsa Weinberg, Igor Maltsberger, John T. TI Eleven deaths of Mr. K. - Contributing factors to suicide in narcissistic personalities SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID EVENTS PRECEDING SUICIDE; PSYCHIATRIC-PATIENTS; COMPLETED SUICIDE; CARE PROVIDERS; YOUNG-PEOPLE; SELF; ADOLESCENTS; DISORDER; REASONS; RISK AB The objective of this paper is to discuss and illuminate the problem of abrupt suicide in relatively well-functioning individuals without a major DSM-IV mental Illness. A case of a man diagnosed with narcissistic personality, who first allegedly staged a suicide attempt and later, without overt warning, killed himself in the context of financial losses and divorce, will be discussed. The paper addresses how and why a life event can generate an internal subjective experience that evokes a sudden deadly self-attack. Discussion of eleven explanatory hypotheses serves to further the understanding of these seemingly inexplicable events. We conclude that additional studies are necessary, especially of the interconnected interaction between life event, psychological functioning, and neurobiological correlates to expand understanding and develop proactive treatment strategies. C1 [Ronningstam, Elsa; Weinberg, Igor; Maltsberger, John T.] McLean Hosp, Belmont, MA 02478 USA. [Ronningstam, Elsa; Weinberg, Igor; Maltsberger, John T.] Harvard Univ, Sch Med, Belmont, MA 02178 USA. [Maltsberger, John T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Maltsberger, John T.] Boston Psychoanalyt Soc & Inst, Boston, MA USA. RP Ronningstam, E (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. EM ronningstam@email.com NR 71 TC 15 Z9 15 U1 0 U2 4 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD SUM PY 2008 VL 71 IS 2 BP 169 EP 182 DI 10.1521/psyc.2008.71.2.169 PG 14 WC Psychiatry SC Psychiatry GA 316OW UT WOS:000256960600004 PM 18573036 ER PT J AU Breyer, J AF Breyer, Joanna TI Honest, age-appropriate communication in pediatric oncology with families with diverse cultural traditions and individual styles SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Breyer, Joanna] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JUN PY 2008 VL 17 SU S BP S147 EP S147 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 329NL UT WOS:000257874200278 ER PT J AU Cremens, C AF Cremens, Cornelia TI The role of the psycho-oncology consultant with older patients with cancer will be described in terms of identifying the vulnerable, isolated, depressed, anxious patient SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Cremens, Cornelia] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JUN PY 2008 VL 17 SU S BP S90 EP S90 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 329NL UT WOS:000257874200169 ER PT J AU Sanfeliz, A AF Sanfeliz, Aurora TI It takes more than a good idea: implementing culturally sensitive care for Latinos in pediatric oncology SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Sanfeliz, Aurora] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUN PY 2008 VL 17 SU S BP S116 EP S117 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 329NL UT WOS:000257874200219 ER PT J AU Monson, CM Gradus, JL Young-Xu, Y Schnurr, PP Price, JL Schumm, JA AF Monson, Candice M. Gradus, Jaimie L. Young-Xu, Yinong Schnurr, Paula P. Price, Jennifer L. Schumm, Jeremiah A. TI Change in posttraumatic stress disorder symptoms: Do clinicians and patients agree? SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE PTSD; assessment; treatment outcomes; concordance; psychometrics ID THERAPY; PTSD; VETERANS; PSYCHOTHERAPY; METAANALYSIS; CHECKLIST; TRIAL AB This study assessed the longitudinal association between clinician and patient ratings of posttraumatic stress disorder (PTSD) symptoms over the course of 2 different randomized clinical trials of veterans with chronic PTSD. One trial, the Department of Veterans Affairs Cooperative Study 420 (CSP 420; N = 360) compared trauma-focused and present-centered group therapies, and the 2nd trial compared cognitive processing theory and a waitlist control condition (N = 60). Linear mixed effects modeling revealed significant associations between clinician ratings (Clinician-Administered PTSD Scale; CAPS; D. D. Blake et al., 1990) and patient ratings (Posttraumatic Stress Disorder Checklist; PCL; F. W. Weathers, B. T. Litz, J. A. Herman, J. A. Huska, & T. M. Keane, 1993) in total and symptom clusters of PTSD. Contrary to hypothesis, the amount of change on the CAPS ranged from .75 to .82 standard deviations for every I standard deviation change on the PCL. The CAPS and PCL were more closely associated in the trauma-focused vs. present-centered treatment condition in CSP 420, and especially regarding hyperarousal symptoms. When comparing categorization of clinically significant change on the CAPS and PCL, the authors found no differences in the percentages of agreement between clinicians and patients in improvement and exacerbation. The value of multimodal assessment of PTSD treatment outcomes is discussed. C1 [Monson, Candice M.] Vet Affairs Boston Hlthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. [Monson, Candice M.; Gradus, Jaimie L.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Young-Xu, Yinong; Schnurr, Paula P.] Natl Ctr PTSD, Execut Div, White River Jct, VT USA. [Schnurr, Paula P.] Dartmouth Med Sch, Dept Psychiat, Dartmouth, NS, Canada. [Price, Jennifer L.] Georgetown Coll, Dept Psychol, Georgetown, KY 40324 USA. [Schumm, Jeremiah A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Schumm, Jeremiah A.] Vet Affairs Boston Healthcare Syst, Mental Hlth Serv Line, Boston, MA USA. RP Monson, CM (reprint author), Vet Affairs Boston Hlthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, 150 S Huntington Ave 116B-3, Boston, MA 02130 USA. EM Candice.Monson@va.gov NR 26 TC 95 Z9 95 U1 3 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 JUN PY 2008 VL 20 IS 2 BP 131 EP 138 DI 10.1037/101037/1040-3590.20.2.131 PG 8 WC Psychology, Clinical SC Psychology GA 309LR UT WOS:000256462400005 PM 18557690 ER PT J AU Catalano, OA Samir, AE Sahani, DV Hahn, PF AF Catalano, Onofrio A. Samir, Anthony E. Sahani, Dushyant V. Hahn, Peter F. TI Pixel distribution analysis: Can it be used to distinguish clear cell carcinomas from angiomyolipomas with minimal fat? SO RADIOLOGY LA English DT Article ID CT HISTOGRAM ANALYSIS; IMAGE-GUIDED BIOPSY; RENAL ANGIOMYOLIPOMA; ADRENAL MASSES; DIAGNOSIS; DIFFERENTIATION AB Purpose: To retrospectively determine if pixel histogram analysis of unenhanced computed tomographic (CT) images can be used to distinguish angiomyolipomas (AMLs) with minimal fat from clear cell renal cell carcinomas (CCRCCs). Materials and Methods: The human studies committee approved this HIPAA-complaint study, with waiver of informed consent. Patients with pathologically proved AMLs lacking visible macroscopic fat at CT and patients with pathologically proved CCRCCs were included. Lesions were measured, and a histogram (number of pixels with each attenuation) was calculated electronically within a central region of interest. The percentage of pixels below the attenuation thresholds -20 HU and 10 HU was calculated in both cohorts. The unpaired Student t test was used to compare the average percentage of subthreshold pixels at each threshold. P < .05 indicated a significant difference. The number of lesions with more than the selected percentage of subthreshold pixels was calculated in both groups, and the chi(2) test was used to test the significance of differences between cohorts. The area under the receiver operating characteristic (ROC) curve was used to determine if any percentage of subthreshold pixels could be used to differentiate between the two cohorts. Results: There were 22 patients with pathologically proved AMLs lacking visible macroscopic fat on CT images. Tuberous sclerosis affected three of these patients. Mean maximal transverse lesion diameter was 20 mm (range, 11-38 mm). There were 28 patients in the CCRCC comparison group. Mean maximal transverse lesion diameter was 26 mm (range, 15-36 mm). Neither the Student t test (P < .2 for all thresholds < 0 HU) nor the chi(2) test (P < .15 for all thresholds < 0 HU) revealed a significant difference between cohorts. A lesion with more low-attenuation pixels was significantly more likely to be characterized as CCRCC than as AML with ROC curve analysis. Conclusion: Once AMLs with visible fat on CT images are excluded, pixel histogram analysis cannot be used to distinguish between AMLs and CCRCCs. (C) RSNA, 2008. C1 [Catalano, Onofrio A.; Samir, Anthony E.; Sahani, Dushyant V.; Hahn, Peter F.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Hahn, PF (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,WHT 270, Boston, MA 02114 USA. EM phahn@partners.org OI Samir, Anthony/0000-0002-7801-8724 NR 21 TC 38 Z9 42 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2008 VL 247 IS 3 BP 738 EP 746 DI 10.1148/radiol.2473070785 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 303ZL UT WOS:000256079700019 PM 18413886 ER PT J AU Wiedemann-Bidlack, FB Colman, AS Fogel, ML AF Wiedemann-Bidlack, Felicitas B. Colman, Albert S. Fogel, Marilyn L. TI Phosphate oxygen isotope analysis on microsamples of bioapatite: removal of organic contamination and minimization of sample size SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID TOOTH ENAMEL MINERALIZATION; BONE PHOSPHATE; TIME-SERIES; LASER FLUORINATION; CERLING,T.E. 2002; STABLE-ISOTOPES; BISON TEETH; DELTA-O-18; CARBONATE; RECONSTRUCTION AB Modern and fossil teeth record seasonal information on climate, diet, and migration through stable isotope compositions in enamel and dentine. Climatic signals such as seasonal variation in meteoric water isotopic composition can be recovered through a microscale histology-based sampling and isotopic analysis of enamel phosphate oxygen. The phosphate moiety in bioapatite is particularly resistant to postmortem diagenesis. In order to determine the phosphate oxygen isotope composition of enamel, phosphate must be chemically purified from other oxygen sources in the enamel lattice and matrix, mainly hydroxyl and carbonate ions, and trace quantities of organics. We present a wet chemical technique for purifying phosphate from microsampled enamel and dentine. This technique uses a sodium hypochlorite oxidation step to remove interferences from residual organic constituents of the enamel and/or dentine scaffold, isolates phosphate as relatively large and easily manipulated Ag3PO4 crystals by using a strongly buffered, moderate-temperature microprecipitation, and preserves the oxygen isotope composition of the initial tooth phosphate. The reproducibility of phosphate oxygen isotope compositions thus determined (measured as delta O-18, V-SMOW scale) is typically 0.2-0.3 parts per thousand (1 s.d.) on samples as small as 300 mu g of enamel or dentine, a considerable improvement over available techniques for analyses of bioapatite phosphate oxygen. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Wiedemann-Bidlack, Felicitas B.] George Washington Univ, Dept Anthropol, Washington, DC 20009 USA. [Colman, Albert S.; Fogel, Marilyn L.] Carnegie Inst Washington, Geophys Lab, Washington, DC 20015 USA. RP Wiedemann-Bidlack, FB (reprint author), Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. EM fbidlack@forsyth.org RI Fogel, Marilyn/M-2395-2015 OI Fogel, Marilyn/0000-0002-1176-3818 NR 50 TC 16 Z9 17 U1 2 U2 24 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PD JUN PY 2008 VL 22 IS 12 BP 1807 EP 1816 DI 10.1002/rcm.3553 PG 10 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 316YF UT WOS:000256985100006 PM 18470876 ER PT J AU Hess, DR AF Hess, Dean R. TI Aerosol delivery devices in the treatment of asthma SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT 41st Respiratory Care Journal Conference on Meeting the Challenges of Asthma CY SEP 28-30, 2007 CL Scottsdale, AZ DE aerosol; asthma; dry-powder inhaler; metered-dose inhaler; nebulizer; spacer; valved holding chamber ID METERED-DOSE INHALER; VALVED HOLDING CHAMBERS; DRY POWDER INHALERS; OBSTRUCTIVE PULMONARY-DISEASE; BREATH-SYNCHRONIZED NEBULIZATION; HUMAN RESPIRATORY-TRACT; ANGLE-CLOSURE GLAUCOMA; SOFT MIST(TM) INHALER; BUDESONIDE INHALATION SUSPENSION; DRIVEN ALBUTEROL NEBULIZATION AB Nebulizers convert solutions or suspensions into aerosols with a particle size that can be inhaled into the lower respiratory tract. There are pneumatic jet nebulizers, ultrasonic nebulizers, and mesh nebulizers. Newer nebulizer designs are breath-enhanced, breath-actuated, or have aerosol-storage bags to minimize aerosol loss during exhalation. Nebulizers can be used with helium-oxygen mixture and can be used for continuous aerosol delivery. Increased attention has recently been paid to issues related to the use of a facemask with a nebulizer. The pressurized metered-dose inhaler (pMDI) is a very commonly used device for aerosol delivery. There are press-and-breathe and breath-actuated pMDI designs. Issues related to pMDIs that have received increasing attention are the conversion to hydrofluoroalkane propellant and the use of dose counters. Many patients have poor pMDI technique. Valved holding chambers and spacers are used to improve pMDI technique and to decrease aerosol deposition in the upper airway. In recent years increasing attention has been paid to the issues of electrostatic charge and facemasks related to valved holding chambers. Many newer formulations for inhalation have been released in dry-powder inhalers, which are either unit-dose or multi-dose inhalers. Systematic reviews and meta-analyses have suggested that each of these aerosol delivery devices can work equally well in patients who can use them correctly. However, many patients use these devices incorrectly, so proper patient education in their use is critical. C1 [Hess, Dean R.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Hess, Dean R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. NR 266 TC 51 Z9 52 U1 0 U2 8 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 JUN PY 2008 VL 53 IS 6 BP 699 EP 723 PG 25 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 311KD UT WOS:000256598200003 PM 18501026 ER PT J AU Medoff, BD AF Medoff, Benjamin D. TI Invasive and noninvasive ventilation in patients with asthma SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT 41st Respiratory Care Journal Conference on Meeting the Challenges of Asthma CY SEP 28-30, 2007 CL Scottsdale, AZ DE asthma; hypoventilation; exacerbation; mechanical ventilation ID END-EXPIRATORY PRESSURE; AIR-FLOW OBSTRUCTION; ACUTE LUNG INJURY; MECHANICAL VENTILATION; DYNAMIC HYPERINFLATION; NEUROMUSCULAR BLOCKADE; ELASTIC RECOIL; MANAGEMENT; PROPOFOL; LEVEL AB Despite recent advances in our ability to manage asthma, there continues to be a small but important incidence of patients who present with severe asthma exacerbations that require ventilatory support. Mechanical ventilation in these patients is difficult and can be associated with substantial morbidity. Unfortunately, there is little in the way of randomized controlled trials to guide our therapeutic decisions in these patients. The goal is to provide adequate gas exchange while minimizing hyperinflation and ventilator-induced lung injury and administering aggressive therapy to reduce airway inflammation and bronchoconstriction. Although there is controversy on exactly what is the optimal method for mechanical ventilation in asthma, most experts agree that a general approach based on controlled hypoventilation is ideal. C1 [Medoff, Benjamin D.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Medoff, Benjamin D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Medoff, BD (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. NR 47 TC 15 Z9 18 U1 0 U2 1 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 JUN PY 2008 VL 53 IS 6 BP 740 EP 748 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 311KD UT WOS:000256598200007 PM 18501028 ER PT J AU Lee, K Fox, PT Lancaster, JL Jerabek, PA AF Lee, Kihak Fox, Peter T. Lancaster, Jack L. Jerabek, Paul A. TI A positron-probe system for arterial input function quantification for positron emission tomography in humans SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article ID CEREBRAL-BLOOD-FLOW; INTRACEREBRAL RADIOSENSITIVE PROBE; VIVO NEUROPHARMACOLOGY INVESTIGATIONS; SMALL LABORATORY-ANIMALS; INTRAVENOUS (H2O)-O-15; BETA-MICROPROBE; ERROR ANALYSIS; PET; OXYGEN; INHALATION AB We developed an intra-arterial positron-probe (beta(+)-probe) system to measure the arterial time-activity concentration in humans for quantitative compartmental modeling of positron emission tomography studies. Performance was characterized in vitro, by using a uniform phantom to calculate dead time, linearity, and absolute detector sensitivity. In vitro evaluations in a uniform phantom showed a system dead time of 2.5 mu s, linear regression between measured and true count rates with R(2)=0.999, and detector sensitivity of 6.9-7.0 counts/s kBq(-1) ml. These met or exceeded values of previously reported systems. (c) 2008 American Institute of Physics. C1 [Lee, Kihak; Fox, Peter T.; Lancaster, Jack L.; Jerabek, Paul A.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Ctr, San Antonio, TX 78229 USA. [Lee, Kihak; Fox, Peter T.; Lancaster, Jack L.] Univ Texas San Antonio, Joint Grad Program Biomed Engn, San Antonio, TX 78249 USA. [Fox, Peter T.] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78229 USA. RP Fox, PT (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Ctr, San Antonio, TX 78229 USA. EM fox@uthscsa.edu RI Lancaster, Jack/F-2994-2010; Fox, Peter/B-4725-2010 OI Fox, Peter/0000-0002-0465-2028 FU NINDS NIH HHS [R21 NS 050486, R21 NS050486] NR 35 TC 3 Z9 3 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD JUN PY 2008 VL 79 IS 6 AR 064301 DI 10.1063/1.2936880 PG 7 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 321DA UT WOS:000257283700031 PM 18601420 ER PT J AU Misra, M AF Misra, Madhusmita TI Bone density in the adolescent athlete SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS LA English DT Article DE athletes; adolescents; bone eensity; bone turnover markers; estradiol; IGF-1; ghrelin; leptin; body composition ID PEDIATRIC OSTEOPOROSIS PREVENTION; ORAL-CONTRACEPTIVE USE; LONG-DISTANCE RUNNERS; MINERAL DENSITY; LUTEINIZING-HORMONE; ANOREXIA-NERVOSA; YOUNG-WOMEN; HYPOTHALAMIC AMENORRHEA; MENSTRUAL IRREGULARITY; SCHOOL CURRICULUM AB Adolescence is a critical time for bone mass accrual, and increases in bone mass through puberty are dependent on rising levels of gonadal steroids, growth hormone and insulin like growth factor-1. Many high school girls are involved in athletic activities, and as many as 23.5% of adolescent athletes have been reported to develop amenorrhea. This review focuses on (1) factors that determine which athletes are likely to develop amenorrhea, such as a negative energy balance state, low levels of leptin and high levels of ghrelin, and (2) the impact of hypogonadism in athletes on bone metabolism. Beneficial effects of increased mechanical loading from athletic activity do not appear to protect against the deleterious effects of hypogonadism in adolescent athletes. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Misra, Madhusmita] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457, Boston, MA 02114 USA. EM mmisra@partners.org FU NCRR NIH HHS [K23 RR018851, M01-RR-01066]; NIDDK NIH HHS [P30DK040561] NR 61 TC 20 Z9 20 U1 2 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9155 J9 REV ENDOCR METAB DIS JI Rev. Endocr. Metab. Disord. PD JUN PY 2008 VL 9 IS 2 BP 139 EP 144 DI 10.1007/s11154-008-9077-1 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 291LC UT WOS:000255197800005 PM 18409004 ER PT J AU Bastepe, M Juppner, H AF Bastepe, Murat Jueppner, Harald TI Inherited hypophosphatemic disorders in children and the evolving mechanisms of phosphate regulation SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS LA English DT Article DE hypophosphatemic disorders; phosphorus; vitamin D; PTH; FGF23; PHEX; DMP1 ID FIBROBLAST GROWTH FACTOR-23; MCCUNE-ALBRIGHT-SYNDROME; STIMULATORY G-PROTEIN; VITAMIN-D METABOLISM; MATRIX EXTRACELLULAR PHOSPHOGLYCOPROTEIN; TUMOR-INDUCED OSTEOMALACIA; OSTEOGLOPHONIC DYSPLASIA; LINKED HYPOPHOSPHATEMIA; ONCOGENIC OSTEOMALACIA; PARATHYROID-HORMONE AB Phosphorous is essential for multiple cellular functions and constitutes an important mineral in bone. Hypophosphatemia in children leads to rickets resulting in abnormal growth and often skeletal deformities. Among various causes of low serum phosphorous are inherited disorders associated with increased urinary excretion of phosphate, including autosomal dominant hypophosphatemic rickets (ADHR), X-linked hypophosphatemia (XLH), autosomal recessive hypophosphatemia (ARHP), and hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Recent genetic analyses and subsequent biochemical and animal studies have revealed several novel molecules that appear to play key roles in the regulation of renal phosphate handling. These include a protein with abundant expression in bone, fibroblast growth factor 23 (FGF23), which has proven to be a circulating hormone that inhibits tubular reabsorption of phosphate in the kidney. Two other bone-specific proteins, PHEX and dentin matrix protein 1 (DMP1), appear to be necessary for limiting the expression of fibroblast growth factor 23, thereby allowing sufficient renal conservation of phosphate. This review focuses on the clinical, biochemical, and genetic features of inherited hypophosphatemic disorders, and presents the current understanding of hormonal and molecular mechanisms that govern phosphorous homeostasis. C1 [Bastepe, Murat; Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Bastepe, Murat; Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM hjueppner@partners.org NR 95 TC 34 Z9 36 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9155 J9 REV ENDOCR METAB DIS JI Rev. Endocr. Metab. Disord. PD JUN PY 2008 VL 9 IS 2 BP 171 EP 180 DI 10.1007/s11154-008-9075-3 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 291LC UT WOS:000255197800009 PM 18365315 ER PT J AU Wu, XD Tanwar, PS Raftery, LA AF Wu, Xiaodong Tanwar, Pradeep Singh Raftery, Laurel A. TI Drosophila follicle cells: Morphogenesis in an eggshell SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE review; oogenesis; migration; epithelial-mesenchymal transition; apical-basal polarity ID GERMLINE STEM-CELLS; ANTERIOR-POSTERIOR AXIS; BAG-OF-MARBLES; EGG CHAMBER FORMATION; OVARIAN-FOLLICLE; BORDER-CELLS; DE-CADHERIN; EPITHELIAL MORPHOGENESIS; CAENORHABDITIS-ELEGANS; TUMOR SUPPRESSORS AB Epithelial morphogenesis is important for organogenesis and pivotal for carcinogenesis, but mechanisms that control it are poorly understood. The Drosophila follicular epithelium is a genetically tractable model to understand these mechanisms in vivo. This epithelium of follicle cells encases germline cells to create an egg. In this review, we summarize progress toward understanding mechanisms that maintain the epithelium or permit migrations essential for oogenesis. Cell-cell communication is important, but the same signals are used repeatedly to control distinct events. Understanding intrinsic mechanisms that alter responses to developmental signals will be important to understand regulation of cell shape and organization. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Wu, Xiaodong; Tanwar, Pradeep Singh; Raftery, Laurel A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. RP Raftery, LA (reprint author), Massachusetts Gen Hosp East, 3rd Floor,Bldg 149,13Th St, Charlestown, MA 02129 USA. EM xiaodong.wu@cbrc2.mgh.harvard.edu; pradeep.tanwar@cbrc2.mgh.harvard.edu; laurel.raftery@cbrc2.mgh.harvard.edu RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 FU NIGMS NIH HHS [GM60501, R01 GM060501, R01 GM060501-08] NR 179 TC 56 Z9 56 U1 1 U2 11 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD JUN PY 2008 VL 19 IS 3 BP 271 EP 282 DI 10.1016/j.semcdb.2008.01.004 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 299BK UT WOS:000255730600008 PM 18304845 ER PT J AU Baum, B Settleman, J Quinlan, MP AF Baum, Buzz Settleman, Jeffrey Quinlan, Margaret P. TI Transitions between epithelial and mesenchymal states in development and disease SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE EMT; MET; e-cadherin; snail; cancer; gastrulation; cancer stem cell ID CELL-CELL-ADHESION; E-CADHERIN EXPRESSION; CANCER STEM-CELLS; TRANSCRIPTION FACTOR SNAIL; SEA-URCHIN EMBRYO; NEURAL CREST; DROSOPHILA GASTRULATION; TUMOR PROGRESSION; BETA-CATENIN; TGF-BETA AB The ancestors of modern Metazoa were constructed in large part by the foldings and distortions of two-dimensional sheets of epithelial cells. This changed similar to 600 million years ago with the evolution of mesenchymal cells. These cells arise as the result of epithelial cell delamination through a reprogramming process called an epithelial to mesenchymal transition (EMT) [Shook D, Keller R. Mechanisms, mechanics and function of epithelial-mesenchymal transitions in early development. Mech Dev 2003; 120: 1351-83; Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 2006; 7: 131-42]. Because mesenchymal cells are free to migrate through the body cavity, the evolution of the mesenchyme opened up new avenues for morphological plasticity, as cells evolved the ability to take up new positions within the embryo and to participate in novel cell-cell interactions; forming new types of internal tissues and organs such as muscle and bone [Thiery JP, Sleeman, JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 2006; 7: 131-42; Hay ED, Zuk A. Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced. Am J Kidney Dis 1995; 26: 678-90]. After migrating to a suitable site, mesenchymal cells coalesce and re-polarize to form secondary epithelia, in a so-called mesenchymal-epithelial transition (MET). Such switches between mesenchymal and epithelial states are a frequent feature of Metazoan gastrulation [Hay ED, Zuk A. Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced. Am J Kidney Dis 1995; 26: 678-90] and the neural crest lineage [Duband JL, Monier F, Delannet M, Newgreen D. Epitheliu-mmesenchyme transition during neural crest development. Acta Anat 1995; 154: 63-78]. Significantly, however, when hijacked during the development of cancer, the ability of cells to undergo EMT, to leave the primary tumor and to undergo MET at secondary sites can have devastating consequences on the organism, allowing tumor cells derived from epithelia to invade surrounding tissues and spread through the host [Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 2006; 7: 131-42; Hay ED, Zuk A. Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced. Am J Kidney Dis 1995; 26: 678-90]. Thus, the molecular and cellular mechanisms underpinning EMT are both an essential feature of Metazoan development and an important area of biomedical research. In this review, we discuss the common molecular and cellular mechanisms involved in EMT in both cases. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Settleman, Jeffrey; Quinlan, Margaret P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. [Settleman, Jeffrey; Quinlan, Margaret P.] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Baum, Buzz] UCL, MRC Lab Mol Cell Biol, London, England. [Baum, Buzz] UCL, Dept Cell & Dev Biol, London, England. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Boston, MA 02129 USA. EM Settleman@helix.mgh.harvard.edu RI Tang, Amy/L-3226-2016; OI Tang, Amy/0000-0002-5772-2878; Baum, Buzz/0000-0002-9201-6186 NR 187 TC 221 Z9 231 U1 6 U2 41 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD JUN PY 2008 VL 19 IS 3 BP 294 EP 308 DI 10.1016/j.semcdb.2008.02.001 PG 15 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 299BK UT WOS:000255730600010 PM 18343170 ER PT J AU Kassarjian, A Bezile, E AF Kassarjian, Ara Bezile, Etienne TI Femoroacetabular impingement: Presentation, diagnosis, and management SO SEMINARS IN MUSCULOSKELETAL RADIOLOGY LA English DT Article DE femoroacetabular; impingement; hip; MR; MR arthrography; cam; pincer; arthroscopy; sports ID MR ARTHROGRAPHY; ARTICULAR-CARTILAGE; FEMORAL-HEAD; HIP; DYSPLASIA; OSTEOARTHRITIS; RETROVERSION; ARTHROSCOPY; ACETABULUM AB Femoroacetabular impingement (FAI) is an often overlooked cause of hip pain in patients of all ages. The clinical signs and symptoms, multimodality imaging findings, treatment options, intraoperative findings, and expected outcomes for patients with FAI are illustrated and discussed. C1 [Kassarjian, Ara] Corades SL, Majadahonda 28220, Spain. [Kassarjian, Ara] Massachusetts Gen Hosp, Div Musculoskeletal Radiol, Boston, MA 02114 USA. [Kassarjian, Ara] Harvard Univ, Sch Med, Boston, MA USA. [Bezile, Etienne] CHU Quebec, Dept Orthoped Surg, Quebec City, PQ, Canada. [Bezile, Etienne] Univ Laval, Quebec City, PQ, Canada. RP Kassarjian, A (reprint author), Corades SL, Calle Galeon 2, Majadahonda 28220, Spain. EM akassarjian@partners.org NR 30 TC 13 Z9 13 U1 0 U2 4 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1089-7860 J9 SEMIN MUSCULOSKEL R JI Semin. Musculoskelet. Radiol. PD JUN PY 2008 VL 12 IS 2 BP 136 EP 145 DI 10.1055/s-2008-1078701 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 311ER UT WOS:000256584000004 PM 18509793 ER PT J AU Posner, M Vermorken, JB AF Posner, Marshall Vermorken, Jan B. TI Induction therapy in the modern era of combined-modality therapy for locally advanced head and neck cancer SO SEMINARS IN ONCOLOGY LA English DT Review ID SQUAMOUS-CELL CARCINOMA; PHASE-III TRIAL; STAGE OROPHARYNX CARCINOMA; NEOADJUVANT CHEMOTHERAPY; RADIATION-THERAPY; RANDOMIZED-TRIAL; ACCELERATED RADIOTHERAPY; CONCOMITANT CHEMOTHERAPY; UNRESECTABLE HEAD; I/II TRIAL C1 [Posner, Marshall] Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. [Vermorken, Jan B.] Univ Antwerp Hosp, Dept Med Oncol, Edegem, Belgium. RP Posner, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program, 44 Binney St,W430, Boston, MA 02115 USA. EM marshall_posner@dfci.harvard.edu NR 39 TC 32 Z9 34 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD JUN PY 2008 VL 35 IS 3 BP 221 EP 228 DI 10.1053/j.seminoncol.2008.03.007 PG 8 WC Oncology SC Oncology GA 319FV UT WOS:000257150400005 PM 18544437 ER PT J AU Jaff, MR AF Jaff, Michael R. TI Imaging the carotid bifurcation: Toward standardization SO SEMINARS IN VASCULAR SURGERY LA English DT Article ID IN-STENT RESTENOSIS; MAGNETIC-RESONANCE ANGIOGRAPHY; ENHANCED MR-ANGIOGRAPHY; DIGITAL-SUBTRACTION-ANGIOGRAPHY; NEPHROGENIC SYSTEMIC FIBROSIS; ULTRASOUND VELOCITY CRITERIA; DUPLEX ULTRASOUND; ARTERY STENOSIS; CT ANGIOGRAPHY; ROTATIONAL ANGIOGRAPHY AB Treatment of extracranial carotid artery disease has been one of the most hotly debated topics in vascular medicine. Imaging of the carotid bifurcation remains an important first step in the therapeutic decision-making process. Successful determination of the severity of carotid artery stenosis depends on several factors, including the skill and expertise of the technologists obtaining the images and the physicians providing an interpretation of the data; knowledge of the advantages and pitfalls of the specific technology; and the need for correlative imaging based on initial test findings. This article will highlight the current strategies for carotid bifurcation imaging and will provide a diagnostic algorithm useful for centers involved in the management of carotid artery disease. C1 [Jaff, Michael R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ctr, Boston, MA 02114 USA. RP Jaff, MR (reprint author), Harvard Univ, Sch Med, 55 Fruit St,Gray Bigelow 832, Boston, MA 02114 USA. EM mjaff@partners.org NR 50 TC 4 Z9 4 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 0895-7967 J9 SEMIN VASC SURG JI Semin. Vasc. Surg. PD JUN PY 2008 VL 21 IS 2 BP 73 EP 79 DI 10.1053/j.semvascsurg.2008.03.001 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 321IE UT WOS:000257297200005 PM 18565413 ER PT J AU Hough, S AF Hough, Sigmund TI Untitled 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 1 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 JUN PY 2008 VL 26 IS 2 BP 61 EP 62 DI 10.1007/s11195-008-9073-0 PG 2 WC Rehabilitation SC Rehabilitation GA 303AJ UT WOS:000256011300001 ER PT J AU Gardner, R Walzer, TB Simon, R Raemer, DB AF Gardner, Roxane Walzer, Toni B. Simon, Robert Raemer, Daniel B. TI Obstetric Simulation as a Risk Control Strategy Course Design and Evaluation SO SIMULATION IN HEALTHCARE LA English DT Article DE Obstetric simulation; Patient care/standards; Safety curriculum; Teamwork; Communication; Crisis resource management; Human patient simulation AB Introduction: Patient safety initiatives aimed at reducing medical errors and adverse events are being implemented in Obstetrics. The Controlled Risk Insurance Company (CRICO), Risk Management Foundation (RMF) of the Harvard Medical Institutions pursued simulation as an anesthesia risk control strategy. Encouraged by their success, CRICO/RMF promoted simulation-based team training as a risk control strategy for obstetrical providers. We describe the development, implementation, and evaluation of an obstetric simulation-based team training course grounded in crisis resource management (CRM) principles. Methods: We pursued systematic design of course development, implementation, and evaluation in 3 phases, including a 1-year or more posttraining follow-up with self-assessment questionnaires. Results: The course was highly rated overall by participants immediately after the course and 1-year or more after the course. Most survey responders reported having experienced a critical clinical event since the course and that various aspects of their teamwork had significantly or somewhat improved as a result of the course. Most (86%) reported CRM principles as useful for obstetric faculty and most (59%) recommended repeating the simulation course every 2 years. Conclusions: A simulation-based team-training course for obstetric clinicians was developed and is a central component of CRICO/RMF's obstetric risk management incentive program that provides a 10% reduction in annual obstetrical malpractice premiums. The course was highly regarded immediately and 1 year or more after completing the course. Most survey responders reported improved teamwork and communication in managing a critical obstetric event in the interval since taking the course. Simulation-based CRM training can serve as a strategy for mitigating adverse perinatal events. (Sim Healthcare 3: 119-127, 2008) C1 [Gardner, Roxane; Walzer, Toni B.; Simon, Robert; Raemer, Daniel B.] Ctr Med Simulat, Cambridge, MA 02139 USA. [Gardner, Roxane; Walzer, Toni B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Simon, Robert; Raemer, Daniel B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. RP Gardner, R (reprint author), Ctr Med Simulat, 65 Landsdowne St, Cambridge, MA 02139 USA. EM rgardner1@partners.org NR 37 TC 31 Z9 31 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-2332 J9 SIMUL HEALTHC JI Simul. Healthc. PD SUM PY 2008 VL 3 IS 2 BP 119 EP 127 DI 10.1097/SIH.0b013e3181671bbe PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA V11MQ UT WOS:000207536100009 PM 19088652 ER PT J AU Ouellette, H Labis, J Bredella, M Palmer, WE Sheah, K Torriani, M AF Ouellette, Hugue Labis, John Bredella, Miriam Palmer, William E. Sheah, Kenneth Torriani, Martin TI Spectrum of shoulder injuries in the baseball pitcher SO SKELETAL RADIOLOGY LA English DT Review DE baseball; pitcher; MR imaging; shoulder ID ROTATOR CUFF TEARS; INTERNAL IMPINGEMENT; GLENOID IMPINGEMENT; THROWING ATHLETE; MR ARTHROGRAPHY; BENNETT LESION; POSTERIOR; BIOMECHANICS; PREVALENCE; DIAGNOSIS AB This review describes a range of shoulder injuries experienced by baseball pitchers. It is estimated that more than 57% of pitchers suffer some form of shoulder injury during a playing season. Knowledge of the overhead throwing cycle is crucial for our understanding of these shoulder injuries. Baseball pitchers are prone to rotator cuff tears from tensile overload and impingement. Glenoid labrum degeneration or tears are also common, due to overuse syndrome (micro-instability), internal impingement and microtrauma. An understanding of the lesions involved in overhead throwing is crucial in baseball pitchers, as long-term disability can result from these injuries, sometimes with severe financial consequences to the player. C1 [Ouellette, Hugue; Bredella, Miriam; Palmer, William E.; Sheah, Kenneth; Torriani, Martin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Labis, John] Methodist Hosp, Houston, TX 77030 USA. RP Ouellette, H (reprint author), Massachusetts Gen Hosp, 55 Fruit St YAW, Boston, MA 02114 USA. EM haouellette@partners.org NR 36 TC 9 Z9 9 U1 1 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD JUN PY 2008 VL 37 IS 6 BP 491 EP 498 DI 10.1007/s00256-007-0389-0 PG 8 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 294OF UT WOS:000255414700002 PM 17912513 ER PT J AU Woolley, AW Gerbasi, ME Chabris, CF Kosslyn, SM Hackman, JR AF Woolley, Anita Williams Gerbasi, Margaret E. Chabris, Christopher F. Kosslyn, Stephen M. Hackman, J. Richard TI Bringing in the experts - How team composition and collaborative planning jointly shape analytic effectiveness SO SMALL GROUP RESEARCH LA English DT Article DE team performance; experts; collaboration; information integration ID SHARED MENTAL MODELS; GROUP-PERFORMANCE; FORMAL INTERVENTIONS; COGNITIVE-ABILITY; DECISION-MAKING; STRATEGIES; DIVERSITY; KNOWLEDGE; CONFLICT; ADAPTATION AB This study investigates the separate and joint effects of the inclusion of experts and collaborative planning on the performance of analytic teams. Teams either did or did not include members with expert-level task-relevant cognitive abilities, and either did or did not receive an intervention that fostered collaborative planning. Results support the authors' hypothesis that analytic performance requires both task-appropriate expertise and collaborative planning to identify strategies for optimally using that expertise. Indeed, high expertise in the absence of collaborative planning actually decreased team performance. Teams engaging in collaborative planning were more likely to effectively integrate their information on key aspects of the analytic problem, which significantly enhanced their analytic performance. Furthermore, information integration mediated the effects of the interaction of expertise and collaboration on performance. The implications of the findings for the optimal use of team member skills and the development of team performance strategies are discussed. C1 [Gerbasi, Margaret E.] Princeton Univ, Princeton, NJ 08544 USA. [Kosslyn, Stephen M.] Harvard Univ, Cambridge, MA 02138 USA. [Kosslyn, Stephen M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hackman, J. Richard] Harvard Univ, Cambridge, MA 02138 USA. RP Woolley, AW (reprint author), 33 Kirkland St, Cambridge, MA 02138 USA. EM anita@post.harvard.edu OI Gerbasi, Margaret/0000-0003-1786-6962 NR 46 TC 39 Z9 39 U1 3 U2 36 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1046-4964 J9 SMALL GR RES JI Small Group Res. PD JUN PY 2008 VL 39 IS 3 BP 352 EP 371 DI 10.1177/1046496408317792 PG 20 WC Psychology, Applied; Management; Psychology, Social SC Psychology; Business & Economics GA 306QG UT WOS:000256262300005 ER PT J AU Wittenberg-Lyles, EM Goldsmith, J Sanchez-Reilly, S Ragan, SL AF Wittenberg-Lyles, Elaine M. Goldsmith, Joy Sanchez-Reilly, Sandra Ragan, Sandra L. TI Communicating a terminal prognosis in a palliative care setting: Deficiencies in current communication training protocols SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE USA; end-of-life; medical education; communication; palliative care; terminal prognosis ID BREAKING BAD-NEWS; OF-LIFE CARE; CANCER; END; PERSPECTIVE; GUIDELINES AB The goal of this study was to understand the use and effectiveness of current communication protocols in terminal prognosis disclosures. Data were gathered from an interdisciplinary palliative care consultation service team at a Veterans Hospital in Texas, USA. Medical communication guidelines, a consistent component in United States palliative care education, propose models for delivery of bad news. However, there is little empirical evidence that demonstrates the effectiveness of these guidelines in disclosures of a terminal prognosis. Based on ethnographic observations of terminal prognosis meetings with dying patients, palliative care team meetings, and semi-structured interviews with palliative care team practitioners, this study notes the contradictory conceptualizations of current bad news communication guidelines and highlights that communicating a terminal prognosis also includes (1) adaptive communication based on the patient's acceptability, (2) team based/family communication as opposed to physician-patient dyadic communication, and (3) diffusion of topic through repetition and definition as opposed to singularity of topic. We conclude that environmentally based revision to communication protocol and practice in medical school training is imperative. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Wittenberg-Lyles, Elaine M.] Univ N Texas, Denton, TX 76203 USA. [Goldsmith, Joy] Young Harris Coll, Young Harris, GA USA. [Sanchez-Reilly, Sandra] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. [Ragan, Sandra L.] Univ Oklahoma, Norman, OK 73019 USA. RP Wittenberg-Lyles, EM (reprint author), Univ N Texas, POB 305268, Denton, TX 76203 USA. EM lyles@unt.edu; jgoldsmith@yhc.edu; sanchezreill@uthscsa.edu; sragan@ou.edu NR 24 TC 18 Z9 20 U1 0 U2 6 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 JUN PY 2008 VL 66 IS 11 BP 2356 EP 2365 DI 10.1016/j.socscimed.2008.01.042 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 307QW UT WOS:000256334400015 PM 18321625 ER PT J AU Ullrich, PM Jensen, MP Loeser, JD Cardenas, DD AF Ullrich, P. M. Jensen, M. P. Loeser, J. D. Cardenas, D. D. TI Pain intensity, pain interference and characteristics of spinal cord injury SO SPINAL CORD LA English DT Article DE pain site; spinal cord injury; pain; pain interference; functioning AB Study Design: Postal survey. Objectives: To examine if the intensity of pain in persons with spinal cord injury (SCI) varied as a function of pain site, and to identify the patient and SCI characteristics associated with pain location, pain intensity and pain interference in a sample of persons with SCI. Setting: Community sample, United States. Methods: A postal survey including measures of pain intensity, pain interference, other pain, demographic and medical characteristics was completed by 238 adults with SCI. Results: Average pain intensity was moderate and pain was common across the body. Demographic and medical variables, including SCI level, were generally not associated with pain prevalence, intensity and interference. However, persons with higher level injuries were more likely to report upper extremity pain than persons with paraplegic injuries. The lower body was the location of the highest pain ratings. Conclusion: Persons with SCI tend to experience high pain intensity over multiple body locations. Lower body pain was as common as upper extremity pain, but tended to be more intense. C1 [Ullrich, P. M.; Jensen, M. P.] Univ Washington, Dept Rehabil Med, Seattle, WA 98101 USA. [Ullrich, P. M.] VA Puget Sound Healthcare Syst, Spinal Cord Injury Qual Enhancement Res Initiat, Dept Vet Affairs, Seattle, WA USA. [Loeser, J. D.] Univ Washington, Dept Neurol Surg, Seattle, WA 98101 USA. [Cardenas, D. D.] Univ Miami, Miller Sch Med, Dept Rehabil Med, Miami, FL 33136 USA. RP Ullrich, PM (reprint author), Univ Washington, Dept Rehabil Med, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM philip.ullrich@va.gov FU NICHD NIH HHS [P01 HD033988, P01 HD033988-04, P01 HD33988] NR 20 TC 24 Z9 27 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD JUN PY 2008 VL 46 IS 6 BP 451 EP 455 DI 10.1038/sc.2008.5 PG 5 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 309NX UT WOS:000256468600011 PM 18283293 ER PT J AU Wang, XY Liu, JX Zhu, HH Tejima, E Tsuji, K Murata, Y Atochin, DN Huang, PL Zhang, CG Lo, EH AF Wang, Xiaoying Liu, Jianxiang Zhu, Haihao Tejima, Emiri Tsuji, Kiyoshi Murata, Yoshihiro Atochin, Dmitriy N. Huang, Paul L. Zhang, Chenggang Lo, Eng H. TI Effects of neuroglobin overexpression on acute brain injury and long-term outcomes after focal cerebral ischemia SO STROKE LA English DT Article DE neuroglobin; neuroprotection; oxidative stress; stroke ID GENE KNOCK-OUT; OXIDATIVE STRESS; OXYGEN; MATRIX-METALLOPROTEINASE-9; PROTEIN; MICE; HYPOXIA; STROKE; DAMAGE; ROLES AB Background and Purpose-Emerging data suggest that neuroglobin (Ngb) may protect against hypoxic/ ischemic neuronal insults. However, the underlying mechanisms in vivo and implications for long-term outcomes are still not well understood Methods-Using our newly created Ngb overexpressing transgenic (Ngb-Tg) mice, we measured brain infarction on day 1 and day 14 after transient focal cerebral ischemia and performed neurobehavioral assessments in sensorimotor deficits on days 1, 3, 7, and 14. To test the hypothesis that Ngb may play a role in reducing oxidative stress after stroke, intracellular malondialdehyde levels were measured and compared in Ngb-Tg and wild-type mice. Results-Increased Ngb mRNA and protein levels were identified in Ngb-Tg brains. Malondialdehyde levels in ischemic hemispheres of Ngb-Tg were significantly reduced compared with wild-type controls at 8 hours and 22 hours after transient focal cerebral ischemia. Compared with wild-type controls, brain infarction volumes 1 day and 14 days after transient focal cerebral ischemia were significantly reduced in Ngb-Tg mice. However, there were no significant improvements in sensorimotor deficits for up to 14 days after stroke in Ngb-Tg mice compared with wild-type controls. Conclusions-Ngb reduces tissue infarction and markers of oxidative stress after stroke. Tissue protection by overexpressing Ngb can be sustained for up to 2 weeks. C1 [Wang, Xiaoying; Liu, Jianxiang; Zhu, Haihao; Tejima, Emiri; Tsuji, Kiyoshi; Murata, Yoshihiro; Lo, Eng H.] Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Boston, MA 02129 USA. [Wang, Xiaoying; Liu, Jianxiang; Zhu, Haihao; Tejima, Emiri; Tsuji, Kiyoshi; Murata, Yoshihiro; Lo, Eng H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. [Wang, Xiaoying; Liu, Jianxiang; Zhu, Haihao; Tejima, Emiri; Tsuji, Kiyoshi; Murata, Yoshihiro; Lo, Eng H.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Atochin, Dmitriy N.; Huang, Paul L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA. [Zhang, Chenggang] Beijing Inst Radiat Med, Dept Mol Neurobiol, Beijing, Peoples R China. RP Wang, XY (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Boston, MA 02129 USA. EM wangxi@helix.mgh.harvard.edu RI Zhang, Chenggang/B-1480-2009; Atochin, Dmitriy/Q-3150-2016 OI Zhang, Chenggang/0000-0002-4521-3304; FU NINDS NIH HHS [P50 NS010828, R01 NS033335, R01 NS033335-14A1, R01 NS037074, P01 NS010828, R01-NS049476, P01 NS010828-330037, P50-NS10828, R01 NS048422, R01 NS049476, R01 NS049476-03, R01-NS37074] NR 33 TC 91 Z9 108 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUN PY 2008 VL 39 IS 6 BP 1869 EP 1874 DI 10.1161/STROKEAHA.107.506022 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 305FG UT WOS:000256162600040 PM 18403737 ER PT J AU Powell, AC Stratakis, CA Patronas, NJ Steinberg, SM Batista, D Alexander, HR Pingpank, JE Keil, M Bartlett, DL Libutti, SK AF Powell, Anathea C. Stratakis, Constantine A. Patronas, Nicholas J. Steinberg, Seth M. Batista, Dalia Alexander, H. Richard Pingpank, James E. Keil, Meg Bartlett, David L. Libutti, Steven K. TI Operative management of Cushing Syndrome secondary to micronodular adrenal hyperplasia SO SURGERY LA English DT Article ID NODULAR ADRENOCORTICAL-DISEASE; CARNEY COMPLEX; DIAGNOSIS; MUTATIONS; INTERLEUKIN-6; DEXAMETHASONE; EXPRESSION; PDE11A; TUMORS AB Background. We reviewed our experience with micronodular adrenal hyperplasia (MAH), its pigmented variant primary pigmented nodular adrenocortical disease (PPNAD), and the association with Carney's complex (CNC) to better characterize these disorders. Methods. This retrospective study analyzes clinical data and operative reports of 34 patients identified with MAH and/or PPNAD who underwent resection between 1969 and 2006 at the Clinical Research Center, an inpatient research hospital at the National Institutes of Health. Symptoms and anthropometric and biochemical data were used to evaluate effect of resection. Results. Fifteen patients (44%) presented as adults and 19 (56%) as children. Twenty-five patients (74%) presented with noncyclic Cushing syndrome and 9 patients (26%) presented with cyclic Cushing syndrome. Thirty-one patients underwent bilateral resection; this was curative biochemically in 30 patients. Fourteen operations were performed laparoscopically (41%), and 20 were performed as open resections (59%). There was 1 postoperative complication in the laparoscopic group (7%) and 6 complications in the open group (30%; P = .20). Follow-up was available for 25 patients (74%). Statistically significant improvements in anthropometrics were observed for both adults and children. The most frequent manifestation of CNC requiring additional operation was cardiac myxoma, which was associated strongly with an atypical (cyclic) presentation of Cushing syndrome (P = .009). Conclusion. Cushing syndrome due to AIAH and PPNAD may be cured by bilateral adrenal resection. All patients should be screened for manifestations of CNC at the time of adrenal diagnosis with particular attention to cardiac disease. C1 [Powell, Anathea C.; Alexander, H. Richard; Pingpank, James E.; Bartlett, David L.; Libutti, Steven K.] NICHHD, Tumor Angiogenesis Sect, Surg Branch, NCI,NIH, Bethesda, MD 20892 USA. [Stratakis, Constantine A.; Batista, Dalia] NICHHD, Sect Endocrinol Genet, Dev Endocrinol Branch, NCI,NIH, Bethesda, MD 20892 USA. [Stratakis, Constantine A.; Batista, Dalia; Keil, Meg] NICHHD, Pediat Endocrinol Program, NCI, NIH, Bethesda, MD 20892 USA. [Patronas, Nicholas J.] Warren F Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD USA. [Steinberg, Seth M.] NCI, Data Management Sect, Off Clin Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Batista, Dalia] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Batista, Dalia] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Libutti, SK (reprint author), NCI, Tumor Angiogenesis Sect, Ctr Canc Res, 10 Ctr Dr 4W-5940, Bethesda, MD 20892 USA. EM libuttis@mail.nih.gov FU Intramural NIH HHS [NIH0012762233]; NICHD NIH HHS [Z01 HD000642, Z01HD000642-04] NR 23 TC 21 Z9 25 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 JUN PY 2008 VL 143 IS 6 BP 750 EP 758 DI 10.1016/j.surg.2008.03.022 PG 9 WC Surgery SC Surgery GA 315DU UT WOS:000256858900007 PM 18549891 ER PT J AU Zeitels, SM AF Zeitels, Steven M. TI Re: Prospective trial of voice outcomes after thyroidectomy: Evaluation of patient-reported and clinician-determined voice assessments in identifying post-thyroidectomy dysphonia SO SURGERY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Laryngeal Surg,Dept Surg, Boston, MA 02114 USA. RP Zeitels, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Laryngeal Surg,Dept Surg, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM szeitels@partners.org 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 0039-6060 J9 SURGERY JI Surgery PD JUN PY 2008 VL 143 IS 6 BP 822 EP 823 DI 10.1016/j.surg.2008.03.003 PG 2 WC Surgery SC Surgery GA 315DU UT WOS:000256858900016 PM 18549900 ER PT J AU Donahue, J Sahani, D Tso, L Cusack, JC AF Donahue, James Sahani, Dushyant Tso, Li Cusack, James C., Jr. TI Extra-adrenal pheochromocytoma involving the organ of Zuckerkandl SO SURGERY LA English DT Editorial Material ID DIAGNOSIS C1 [Donahue, James; Cusack, James C., Jr.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Sahani, Dushyant] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Tso, Li] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Cusack, JC (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Yawkey Buldg,7th Floor,55 Fruit St, Boston, MA 02114 USA. EM jcusack@partners.org NR 5 TC 4 Z9 5 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 JUN PY 2008 VL 143 IS 6 BP 830 EP 832 DI 10.1016/j.surg.2007.11.012 PG 3 WC Surgery SC Surgery GA 315DU UT WOS:000256858900018 PM 18549902 ER PT J AU Zaslavsky, AM Zheng, H Adams, J AF Zaslavsky, Alan M. Zheng, Hui Adams, John TI Optimal sample allocation for design-consistent regression in a cancer services survey when design variables are known for aggregates SO SURVEY METHODOLOGY LA English DT Article DE descriptive population quantity; measurement error; Neyman allocation; regression models; sample design; surveys ID SURVEILLANCE; WEIGHTS; MODEL AB We consider optimal sampling rates in element-sampling designs when the anticipated analysis is survey-weighted linear regression and the estimands of interest are linear combinations of regression coefficients from one or more models. Methods are first developed assuming that exact design information is available in the sampling frame and then generalized to situations in which some design variables are available only as aggregates for groups of potential subjects, or from inaccurate or old data. We also consider design for estimation of combinations of coefficients from more than one model. A further generalization allows for flexible combinations of coefficients chosen to improve estimation of one effect while controlling for another. Potential applications include estimation of means for several sets of overlapping domains, or improving estimates for subpopulations such as minority races by disproportionate sampling of geographic areas. In the motivating problem of designing a survey on care received by cancer patients (the CanCORS study), potential design information included block-level census data on race/ethnicity and poverty as well as individual-level data. In one study site, an unequal-probability sampling design using the subjectss residential addresses and census data would have reduced the variance of the estimator of an income effect by 25%, or by 38% if the subjects' races were also known. With flexible weighting of the income contrasts by race, the variance of the estimator would be reduced by 26% using residential addresses alone and by 52% using addresses and races. Our methods would be useful in studies in which geographic oversampling by race-ethnicity or socioeconomic characteristics is considered, or in any study in which characteristics available in sampling frames are measured with error. C1 [Zaslavsky, Alan M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Adams, John] RAND Corp, Santa Monica, CA 90401 USA. RP Zaslavsky, AM (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [U01 CA093344, U01 CA093324, U01 CA093344-020002, U01 CA093348] NR 33 TC 0 Z9 0 U1 1 U2 1 PU STATISTICS CANADA PI OTTAWA PA 100 TUNNEYS PASTURE DRIVEWAY, OTTAWA, ONTARIO K1A 0T6, CANADA SN 0714-0045 J9 SURV METHODOL JI Surv. Methodol. PD JUN PY 2008 VL 34 IS 1 BP 65 EP 78 PG 14 WC Social Sciences, Mathematical Methods; Statistics & Probability SC Mathematical Methods In Social Sciences; Mathematics GA 342AK UT WOS:000258756800007 PM 19680463 ER PT J AU Kurth, T Barr, RG Gaziano, JM Buring, JE AF Kurth, T. Barr, R. G. Gaziano, J. M. Buring, J. E. TI Randomised aspirin assignment and risk of adult-onset asthma in the Women's Health Study SO THORAX LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; LOW-DOSE ASPIRIN; PRIMARY PREVENTION; CARDIOVASCULAR-DISEASE; CONTROLLED-TRIAL; PREVALENCE; POPULATION; SALICYLATE; CHILDREN; OBESITY AB Background: Randomised data in men show a small but significant reduction in the risk of adult-onset asthma among those given aspirin. The results from an observational study in women suggest that frequent use of aspirin decreases the risk of adult-onset asthma, but randomised data in women are lacking. A study was undertaken to test the effect of 100 mg aspirin or placebo on alternate days on the risk of adult-onset asthma in the Women's Health Study. Methods: A randomised, double-blind, placebo-controlled clinical trial of aspirin and vitamin E was performed in apparently healthy women with no indication or contraindication to aspirin therapy and no history of asthma at study entry. Female health professionals self-reported an asthma diagnosis on yearly questionnaires. Results: Among 37 270 women with no reported history of asthma prior to randomisation and during 10 years of follow-up, there were 872 new cases diagnosed with asthma in the aspirin group and 963 in the placebo group (hazard ratio 0.90; 95% CI 0.82 to 0.99; p = 0.027). This apparent 10% lower relative risk of incident adult-onset asthma among those assigned to aspirin was significantly modified by body mass index, with no effect in women with a body mass index of >= 30 kg/m(2). The effect of aspirin on adult-onset asthma was not significantly modified by age, smoking status, exercise levels, postmenopausal hormone use or randomised vitamin E assignment. Conclusions: In this large randomised clinical trial of apparently healthy adult women, administration of 100 mg aspirin on alternate days reduced the relative risk of a newly reported diagnosis of asthma. Trial registration number: NCT00000479. C1 [Kurth, T.; Gaziano, J. M.; Buring, J. E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Prevent Med, Boston, MA 02215 USA. [Kurth, T.; Gaziano, J. M.; Buring, J. E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Aging, Boston, MA 02215 USA. [Barr, R. G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02215 USA. [Barr, R. G.] Columbia Univ, Med Ctr, Dept Med, Div Gen Med, New York, NY USA. [Barr, R. G.] Columbia Univ, Med Ctr, Dept Epidemiol, New York, NY USA. [Kurth, T.; Buring, J. E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Gaziano, J. M.] Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Ctr, Boston, MA USA. [Buring, J. E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. RP Kurth, T (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Prevent Med, 900 Commonwealth Ave E,3rd Floor, Boston, MA 02215 USA. EM tkurth@rics.bwh.harvard.edu RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 FU NCI NIH HHS [CA-47988, R01 CA047988, R01 CA047988-14]; NHLBI NIH HHS [R01 HL043851, R01 HL043851-10] NR 34 TC 15 Z9 15 U1 0 U2 4 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 JUN PY 2008 VL 63 IS 6 BP 514 EP 518 DI 10.1136/thx.2007.091447 PG 5 WC Respiratory System SC Respiratory System GA 307AJ UT WOS:000256289600010 PM 18339679 ER PT J AU Liu, YY Brent, GA AF Liu, Yan-Yun Brent, Gregory A. TI Stealth sequences in reporter gene vectors confound studies of T3-regulated negative gene expression SO THYROID LA English DT Editorial Material ID THYROID-HORMONE RECEPTOR; LUCIFERASE; PROMOTER; CELLS C1 [Liu, Yan-Yun; Brent, Gregory A.] VA Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab, Los Angeles, CA 90073 USA. RP Liu, YY (reprint author), VA Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [NIH R01 DK67233] NR 11 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 1050-7256 J9 THYROID JI Thyroid PD JUN PY 2008 VL 18 IS 6 BP 593 EP 595 DI 10.1089/thy.2008.0138 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 327WS UT WOS:000257759800001 PM 18578606 ER PT J AU Salem, AK Fenton, MS Marion, KM Hershman, JM AF Salem, Andrew K. Fenton, Mike S. Marion, Kenneth M. Hershman, Jerome M. TI Effect of sunitinib on growth and function of FRTL-5 thyroid cells SO THYROID LA English DT Article ID SYMPORTER GENE-EXPRESSION; HYPOTHYROIDISM AB Background: Sunitinib, a multitargeted vascular endothelial growth factor and receptor tyrosine kinase inhibitor, causes hypothyroidism in patients who take it for treatment of cancer. Although the pathophysiologic mechanism of the hypothyroidism is unclear, it has been claimed that it is due to inhibition of iodide uptake. Methods: To evaluate the pathologic mechanism of induction of the hypothyroidism, we studied the effect of sunitinib on FRTL-5 rat thyroid cells. We measured the effect of sunitinib on cell growth, I-125-iodide uptake and efflux, TSH receptor (TSH-R), and sodium-iodide symporter (NIS) message. Results: At 48 hours, sunitinib caused a dose-related inhibition of growth with LC50 of 14.6 mu M, but there was no apparent inhibition of growth at 24 hours at concentrations of 0.1-25 mu M. Preincubation with sunitinib did not impair the response to TSH, indicating that it did not affect the TSH-R. Incubation with sunitinib for 24 hours caused a dose-related increase of I-125-iodide uptake and did not reduce iodide efflux or NIS mRNA expression. Conclusion: The data indicate that sunitinib is unlikely to cause hypothyroidism by inhibition of iodide uptake. C1 [Hershman, Jerome M.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare System, Endocrinol & Diabet Div, Endocrine Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. RP Hershman, JM (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare System, Endocrinol & Diabet Div, Endocrine Res Lab, Endocrinol 111D,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jhershmn@ucla.edu RI Salem, Aliasger /J-3674-2012 OI Salem, Aliasger /0000-0002-1923-6633 NR 13 TC 31 Z9 33 U1 0 U2 0 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 JUN PY 2008 VL 18 IS 6 BP 631 EP 635 DI 10.1089/thy.2007.0336 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 327WS UT WOS:000257759800007 PM 18578612 ER PT J AU Hinton, DE Hinton, SD Loeum, RJR Pich, V Pollack, MH AF Hinton, Devon E. Hinton, Susan D. Loeum, Reattidara J. -R. Pich, Vuth Pollack, Mark H. TI The 'Multiplex Model' of Somatic Symptoms: Application to Tinnitus among Traumatized Cambodian Refugees SO TRANSCULTURAL PSYCHIATRY LA English DT Article DE anxiety; Cambodian refugees; catastrophic cognitions; posttraumatic stress disorder; somatization; tinnitus ID PANIC DISORDER; DISTRESS; THERAPY; PTSD; SEVERITY; ANXIETY; ATTACKS; STRESS AB Somatic symptoms are a common clinical presentation of distress among ethnic populations in the USA, particularly traumatized refugees. In this article, we apply a 'multiplex model' of bodily experience to explain how a somatic symptom is evoked, amplified, and generates distress, particularly distress related to post-traumatic stress disorder. We illustrate the multiplex model's applicability to acute episodes of tinnitus (i.e., a buzzing-like sound in the ear) among Cambodian refugees, a common symptom in that group. The article demonstrates the importance of carefully examining somatic symptoms and associated meanings in distressed ethnic populations, especially traumatized refugees, and aims to contribute to a medical anthropology of somatic symptoms. C1 [Loeum, Reattidara J. -R.; Pich, Vuth] Arbour Counseling Serv, SE Asian Clin, Lowell, MA 01852 USA. [Pich, Vuth] Massachusetts Dept Mental Hlth, Medfield, MA 02052 USA. [Pollack, Mark H.] Massachusetts Gen Hosp, Anxiety Disorders Program, Boston, MA 02114 USA. [Hinton, Devon E.; Hinton, Susan D.; Pollack, Mark H.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Hinton, DE (reprint author), Arbour Counseling Serv, SE Asian Clin, Lowell, MA 01852 USA. EM devon_hinton@hms.harvard.edu NR 42 TC 9 Z9 9 U1 0 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1363-4615 J9 TRANSCULT PSYCHIATRY JI Transcult. Psychiatry PD JUN PY 2008 VL 45 IS 2 BP 287 EP 317 DI 10.1177/1363461508089768 PG 31 WC Anthropology; Psychiatry SC Anthropology; Psychiatry GA 369QT UT WOS:000260709700007 PM 18562496 ER PT J AU Lin, KY Maricevich, M Bardeesy, N Weissleder, R Mahmood, U AF Lin, Ken Young Maricevich, Marco Bardeesy, Nabeel Weissleder, Ralph Mahmood, Umar TI In Vivo Quantitative Microvasculature Phenotype Imaging of Healthy and Malignant Tissues Using a Fiber-Optic Confocal Laser Microprobe SO TRANSLATIONAL ONCOLOGY LA English DT Article ID PANCREATIC DUCTAL ADENOCARCINOMA; CANCER; BIOLOGY; VISUALIZATION; COMPLEXITY; FRACTALS; GROWTH; TUMORS; MODEL AB Real-time in vivo imaging of the microvasculature may help both earlier clinical detection of disease and the understanding of tumor-host interaction at various stages of progression. In vivo confocal and multiphoton microscopy is often hampered by bulky optics setup and has limited access to internal organs. A fiber-optic setup avoids these limitations and offers great user maneuverability. We report here the in vivo validation of a fiber-optic confocal fluorescence microprobe imaging system. In addition, we developed an automated fractal-based image analysis to characterize microvascular morphology based on vessel diameter distribution, density, volume fraction, and fractal dimension from real-time data. The system is optimized for use in the far-red and near-infrared region. The flexible 1.5-mm-diameter fiber-optic bundle and microprobe enable great user maneuverability, with a field of view of 423 x 423 mu m and a tissue penetration of up to 15 mu m. Lateral and axial resolutions are 3.5 and 15 mu m. We show that it is possible to obtain high temporal and spatial resolution images of virtually any abdominal viscera in situ using a far-red blood pool imaging probe. Using an orthotopic model of pancreatic ductal adenocarcinoma, we characterized the tumor surface capillary and demonstrated that the imaging system and analysis can quantitatively differentiate between the normal and tumor surface capillary. This clinically approved fiber-optic system, together with the fractal-based image analysis, can potentially be applied to characterize other tumors in vivo and may be a valuable tool to facilitate their clinical evaluation. C1 [Lin, Ken Young; Maricevich, Marco; Bardeesy, Nabeel; Weissleder, Ralph; Mahmood, Umar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02114 USA. RP Mahmood, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Simches Res Bldg,Suite 8226,185 Cambridge St, Boston, MA 02114 USA. EM mahmood@helix.mgh.harvard.edu FU National Institutes of Health (NIH) [PO1CA117969, RO1EB001872, U24CA092782] FX This work was supported by the National Institutes of Health (NIH) grants PO1CA117969, RO1EB001872, and U24CA092782. NR 26 TC 20 Z9 21 U1 1 U2 6 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 JUN PY 2008 VL 1 IS 2 BP 84 EP 94 DI 10.1593/tlo.08118 PG 11 WC Oncology SC Oncology GA 528SM UT WOS:000272467100004 PM 18633456 ER PT J AU Tolboom, H Milwid, JM Izamis, ML Uygun, K Berthiaume, F Yarmush, ML AF Tolboom, H. Milwid, J. M. Izamis, M. L. Uygun, K. Berthiaume, F. Yarmush, M. L. TI Sequential cold storage and normothermic perfusion of the ischemic rat liver SO TRANSPLANTATION PROCEEDINGS LA English DT Article ID ORGAN PRESERVATION; TRANSPLANTATION AB Extending transplant criteria to include livers obtained from donors after cardiac death (DCD) could increase the liver donor pool, but conventional simple cold storage of these ischemic organs can lead to poor graft function after transplantation. Experimental normothermic machine perfusion has previously proven to be useful for the recovery and preservation of DCD livers, but it is more complicated than conventional cold storage, and, therefore, is perhaps not practical during the entire preservation period. In clinical situations, the combined use of simple cold storage and normothermic perfusion preservation of DCD livers might be more realistic, but even a brief period of cold storage prior to normothermic preservation has been suggested to have a negative impact on graft viability. In this study we show that rat livers subjected to 45 minutes of ex vivo warm ischemia followed by 2 hours of simple cold storage can be reclaimed by 4 hours of normothermic machine perfusion. These livers could be orthotopically transplanted into syngeneic recipients with 100% survival after 4 weeks (N = 10), similar to the survival of animals that received fresh livers that were stored on ice in University of Wisconsin (UW) solution for 6 hours (N = 6). On the other hand, rats that received ischemic livers preserved on ice in UW solution for 6 hours (N = 6) all died within 12 hours after transplantation. These results suggest that normothermic perfusion can be used to reclaim DCD livers subjected to an additional period of cold ischemia during hypothermic storage. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA USA. Shriners Burns Hosp, Boston, MA USA. RP Yarmush, ML (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org FU NIDDK NIH HHS [K99 DK080942-01, K99 DK080942, R01 DK043371, R01 DK043371-08, R01 DK059766, R01 DK059766-04, R01 DK43371, R01 DK59766] NR 6 TC 12 Z9 14 U1 0 U2 3 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 JUN PY 2008 VL 40 IS 5 BP 1306 EP 1309 DI 10.1016/j.transproceed.2008.03.100 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 326YJ UT WOS:000257695300014 PM 18589093 ER PT J AU Tan, HB Feng, Y Liu, M Wu, YC AF Tan, H. -B. Feng, Y. Liu, M. Wu, Y. -C. TI Protective effects of FR167653 on chronic allograft nephropathy by inhibiting p38 MAPK in rats SO TRANSPLANTATION PROCEEDINGS LA English DT Article ID PROTEIN-KINASE ACTIVATION; GROWTH-FACTOR-BETA; GLOMERULONEPHRITIS; PHOSPHORYLATION; INJURY AB Background. Chronic allograft nephropathy (CAN) remains a challenge for transplant clinicians. Some novel intervention strategies may shed new light on its treatment. Methods. An orthotopic kidney transplant model in Fisher-to-Lewis rats was used with administration of cyclosporine alone or in combination with FR167653 (30 mg/kg/d subcuntaneously) to recipients. We analyzed renal function and urinary protein excretion. Animals were sacrificed at 30 weeks posttransplantation for histological and immunohistochemical studies. Results. Renal function among vehicle-treated rats deteriorated progressively with substantial proteinuria compared with FR167653-treated rats. FR167653 administration significantly prevented the morphlogical features of CAN and prolonged rat survivals. p38 mitogen-activated protein kinase (MAPK) expression was markedly reduced by FR167653 treatment. Meanwhile, transforming growth factor-beta 1 and monocyte chemotactic protein-1 expression were significantly down-regulated among FR167653-treated hosts. Conclusion. p38 MAPK phosphorylation correlated with CAN progression and inhibition of p38 MAPK by FR167653 may provide a potent novel therapeutic target for its prevention. C1 [Tan, H. -B.] Hebei Med Univ, Hosp 2, Dept Nephrol, Shijiazhuang 050000, Hebei, Peoples R China. [Feng, Y.] Nanjing Med Univ, Dept Nephrol, Affiliated Drum Tower Hosp, Nanjing, Jiangsu, Peoples R China. [Liu, M.] Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing, Jiangsu, Peoples R China. [Wu, Y. -C.] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Tan, HB (reprint author), Hebei Med Univ, Hosp 2, Dept Nephrol, Shijiazhuang 050000, Hebei, Peoples R China. EM huibintan@163.com OI Liu, Min/0000-0002-8117-4808 NR 20 TC 6 Z9 6 U1 0 U2 1 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 JUN PY 2008 VL 40 IS 5 BP 1685 EP 1689 DI 10.1016/j.transproceed.2008.01.073 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 326YJ UT WOS:000257695300094 PM 18589173 ER PT J AU Huttenlocher, A Poznansky, MC AF Huttenlocher, Anna Poznansky, Mark C. TI Reverse leukocyte migration can be attractive or repulsive SO TRENDS IN CELL BIOLOGY LA English DT Review ID SPHINGOSINE 1-PHOSPHATE RECEPTOR; NERVE GROWTH CONES; AXON GUIDANCE; T-CELLS; IN-VITRO; DICTYOSTELIUM-DISCOIDEUM; EUKARYOTIC CHEMOTAXIS; CYTOPLASMIC DOMAINS; SIGNAL-TRANSDUCTION; PHOSPHOLIPASE-C AB The directional migration of cells within multicellular organisms is governed by gradients of both chemical attractants and repellents in diverse processes, including leukocyte trafficking and neuronal pathfinding in vivo. These complex extracellular environments direct the orchestrated bidirectional trafficking of leukocytes between the vasculature and tissues. Substantial progress has been made in dissecting the molecular mechanisms involved in orchestrating the directed movement of leukocytes into host tissues; however, less is known about the reverse migration of leukocytes from the tissues to the vasculature. In this article, we discuss the functional interplay between chemoattraction and chemorepulsion in the bidirectional movement of cells in complex in vivo environments, and we describe how these mechanisms influence both normal physiology and human disease. C1 [Huttenlocher, Anna] Univ Wisconsin, Dept Med Microbiol & Immunol & Pediat, Madison, WI 53706 USA. [Poznansky, Mark C.] Harvard Univ, Sch Med, Dept Infect Dis, Boston, MA 02129 USA. [Poznansky, Mark C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Massachusetts Gen Hosp,Harvard Canc Ctr, Boston, MA 02129 USA. RP Huttenlocher, A (reprint author), Univ Wisconsin, Dept Med Microbiol & Immunol & Pediat, 4205 Microbial Sci Bldg,1550 Linden Dr, Madison, WI 53706 USA. EM huttenlocher@wisc.edu FU NIAID NIH HHS [R01 AI049757, R01 AI49757]; NIGMS NIH HHS [R01 GM074827-03, R01 GM074827, R01 GM074827-01, R01 GM074827-02] NR 68 TC 42 Z9 43 U1 0 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD JUN PY 2008 VL 18 IS 6 BP 298 EP 306 DI 10.1016/j.tcb.2008.04.001 PG 9 WC Cell Biology SC Cell Biology GA 323WA UT WOS:000257477900007 PM 18468440 ER PT J AU Whangbo, JS Hunter, CP AF Whangbo, Jennifer S. Hunter, Craig P. TI Environmental RNA interference SO TRENDS IN GENETICS LA English DT Review ID DOUBLE-STRANDED-RNA; TRANSMEMBRANE PROTEIN SID-1; FUNCTIONAL GENOMIC ANALYSIS; PLANT-PARASITIC NEMATODES; CAENORHABDITIS-ELEGANS; C-ELEGANS; GENETIC INTERFERENCE; CELLS; DSRNA; MECHANISMS AB The discovery of RNA interference (RNAi), the process of sequence-specific gene silencing initiated by double-stranded RNA (dsRNA), has broadened our understanding of gene regulation and has revolutionized methods for genetic analysis. A remarkable property of RNAi in the nematode Caenorhabditis elegans and in some other multicellular organisms is its systemic nature: silencing signals can cross cellular boundaries and spread between cells and tissues. Furthermore, C. elegans and some other organisms can also perform environmental RNAi: sequence-specific gene silencing in response to environmentally encountered dsRNA. This phenomenon has facilitated significant technological advances in diverse fields including functional genomics and agricultural pest control. Here, we describe the characterization and current understanding of environmental RNAi and discuss its potential applications. C1 [Whangbo, Jennifer S.; Hunter, Craig P.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Whangbo, Jennifer S.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Whangbo, Jennifer S.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Hunter, CP (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. EM hunter@mcb.harvard.edu FU NIGMS NIH HHS [R01 GM069891, R01 GM069891-04, GM069891] NR 65 TC 88 Z9 94 U1 3 U2 39 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD JUN PY 2008 VL 24 IS 6 BP 297 EP 305 DI 10.1016/j.tig.2008.03.007 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 313OP UT WOS:000256750200008 PM 18450316 ER PT J AU May, A Wang, TJ AF May, Abigail Wang, Thomas J. TI Biomarkers for cardiovascular disease: challenges and future directions SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID BRAIN NATRIURETIC PEPTIDE; C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; EMERGENCY-DEPARTMENT PRIDE; RISK PREDICTION; GENE-EXPRESSION; MYOCARDIAL-INFARCTION; NONDIABETIC INDIVIDUALS; CLINICAL-PRACTICE; PROGNOSTIC VALUE AB The accurate diagnosis and prevention of cardiovascular disease (CVD) is an important public health goal. Although clinical characteristics such as age and gender are well-established risk factors for CVD, such features are not sufficient to identify all patients at risk. Cardiovascular biomarkers have the potential to augment clinical risk stratification by aiding in screening, diagnosis and assessment of prognosis. However, most current biomarkers have only modest predictive value, and there is a need to identify additional biomarkers from new biological pathways. The availability of platforms for profiling DNA, RNA, proteins and metabolites in clinical specimens has facilitated the 'unbiased' search for new biomarkers, which can now be tested in a clinical setting. This review highlights recent developments in the field of cardiovascular biomarkers and describes the use of new technologies for the identification of biomarkers. C1 [May, Abigail; Wang, Thomas J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiol Div, Boston, MA 02114 USA. RP Wang, TJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiol Div, Boston, MA 02114 USA. EM tjwang@partners.org FU NHLBI NIH HHS [K23-HL-074077, R01-HL-083197, R01-HL-086875] NR 83 TC 23 Z9 27 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD JUN PY 2008 VL 14 IS 6 BP 261 EP 267 DI 10.1016/j.molmed.2008.04.003 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 326HH UT WOS:000257648700004 PM 18487087 ER PT J AU Ellsworth, PI Frellich, DA Lahey, S AF Ellsworth, Pamela I. Frellich, Drew A. Lahey, Susan TI Cohen cross-trigonal ureteral reimplantation: Is a one-year postoperative renal ultrasound scan necessary after normal initial postoperative ultrasound findings? SO UROLOGY LA English DT Article ID URETERONEOCYSTOSTOMY; CHILDREN; MANAGEMENT; CATHETERS; STAY AB OBJECTIVES To determine the utility of the 1-year postoperative renal ultrasound scan in children undergoing uncomplicated Cohen cross-trigonal ureteral reimplantation. METHODS A retrospective review of 108 patients (233 ureters) who had undergone uncomplicated Cohen cross-trigonal ureteral reimplantation during a 6.5-year period with a postoperative follow-up of 1 year was performed. Renal ultrasound scans were obtained at 1 month and 1 year postoperatively. RESULTS Of the 108 patients who had undergone ureteral reimplantation, 26 patients (24%) had mild to moderate hydronephrosis at 1 month postoperatively. Of these 26 patients, 20 had preexisting hydronephrosis and 6 had new hydronephrosis. Of the 20 patients with preoperative hydrone. phrosis, 19 (95 %) had similar hydronephrosis on the 1-month postoperative ultrasound scan and in 1 (5%), the hydronephrosis had resolved. At 1 year, 13 (69%) of the 20 patients with preoperative hydronephrosis had stable hydronephrosis, and it resolved in 6 (31%). In the 6 patients with new-onset hydronephrosis at 1 month postoperatively, the hydronephrosis had resolved by 1 year in 4 patients (67%) and was mild in 2 (33%). Three patients developed transient obstruction requiring stent placement. CONCLUSIONS It has been recommended that a renal ultrasound scan be obtained in children 1 year after open ureteral reimplantation to rule out delayed obstruction. Our results suggest this is of low yield in patients with uncomplicated open ureteral reimplantation. C1 Brown Univ, Hasbro Childrens Hosp, Providence, RI 02912 USA. Boston Childrens Hosp, Dept Urol, Boston, MA USA. Massachusetts Gen Hosp, Div Urol, Boston, MA 02114 USA. RP Ellsworth, PI (reprint author), Univ Urol Associates Inc, 2 Dudley St,Suite 185, Providence, RI 02905 USA. EM pamelaellsworth@aol.com NR 15 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JUN PY 2008 VL 71 IS 6 BP 1055 EP 1058 DI 10.1016/j.urology.2007.11.162 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 312FG UT WOS:000256653900021 PM 18372024 ER PT J AU Rawat, A Huynh, TT Peden, EK Kougias, P Lin, PH AF Rawat, Anish Huynh, Taro T. Peden, Eric K. Kougias, Panagiotis Lin, Peter H. TI Primary Prophylaxis of Venous Thromboembolism in Surgical Patients SO VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE venous thromboembolism; deep-venous thrombosis; pulmonary embolism; complication; heparin; inferior vena cava filter; LMWH; warfarin; mechanical prophylaxis; pharmacological prophylaxis ID DEEP-VEIN THROMBOSIS; INTERMITTENT PNEUMATIC COMPRESSION; MOLECULAR-WEIGHT HEPARINS; RISK TRAUMA PATIENTS; PULMONARY-EMBOLISM; UNFRACTIONATED HEPARIN; INDUCED THROMBOCYTOPENIA; ANTICOAGULANT-THERAPY; BYPASS-SURGERY; PREVENTION AB Venous thromboembolism is a major risk for surgical patients during the perioperative period. Prevention of perioperative venous thromboembolism remains a critical component of surgical patient care. The risk for venous thromboembolism in Surgical patients can he stratified by their risk factors and by the type of operation. Pharmacological prophylaxis for venous thromboembolism includes unfractionated heparin, low-molecular weight heparin, fondaparinux, warfarin, antiplatelet therapy, and direct thrombin inhibitors. Mechanical devices such Lis graduated compression stockings, intermittent pneumatic compressions, and venous foot pumps are also effective modalities for venous thromboembolism prophylaxis. The optimal preventive measure of venous thromboembolism should he based on the degree of risk for venous thromboembolism with the intensity of prophylaxis while balancing potential treatment benefits and risks in each individual patient. The epidemiology of venous thromboembolism, the methods for achieving venous thromboembolism prophylaxis, and the approach to institute venous thromboembolism prophylaxis in surgical patients undergoing various operative interventions are reviewed in this article. C1 [Lin, Peter H.] Baylor Coll Med, Michael E DeBakey Dept Surg, Houston VA Med Ctr, Div Vasc Surg & Endovasc Therapy, Houston, TX 77030 USA. [Peden, Eric K.] Methodist Hosp, Houston, TX 77030 USA. [Rawat, Anish; Huynh, Taro T.; Kougias, Panagiotis; Lin, Peter H.] Michael E DeBakey VA Med Ctr, Houston, TX USA. RP Lin, PH (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, Houston VA Med Ctr, Div Vasc Surg & Endovasc Therapy, 2002 Holcomh Blvd 112, Houston, TX 77030 USA. EM plin@bcm.edu NR 71 TC 9 Z9 10 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1538-5744 EI 1938-9116 J9 VASC ENDOVASC SURG JI Vasc. Endovasc. Surg. PD JUN-JUL PY 2008 VL 42 IS 3 BP 205 EP 216 DI 10.1177/1538574408315208 PG 12 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 394QY UT WOS:000262463600001 PM 18375602 ER PT J AU Barshes, NR Annambhotla, S Bechara, C Kougias, P Huynh, TT Dardik, A Silva, MB Lin, PH AF Barshes, Neal R. Annambhotla, Suman Bechara, Carlos Kougias, Panagiotis Huynh, Tam T. Dardik, Alan Silva, Michael B., Jr. Lin, Peter H. TI Endovascular Repair of Hemodialysis Graft-Related Pseudoaneurysm: An Alternative Treatment Strategy in Salvaging Failing Dialysis Access SO VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE arteriovenous grafts; endograft exclusion; endovascular repair; hemodialysis; hemodialysis complication pseudoaneurysm; stent graft repair ID STAGE RENAL-DISEASE; COVERED STENTS; ARTERIOVENOUS-FISTULAS; COMPLICATIONS; WALLGRAFT; ANEURYSMS AB Introduction Hemodialysis access-related pseudoaneurysm is a known complication in patients requiring hemodialysis via prosthetic arteriovenous grafts (AVGs). The traditional treatment strategy of AVG-related pseudoaneurysms is either AVG ligation or interposition replacement with another prosthetic graft segment or autogenous veins. Patients and methods From June 2002 to August 2007, 32 self-expanding stent grafts were implanted in 26 patients with AVG pseudoaneurysms. Indications for treatment consisted of large AVG pseudoaneurysm sire, localized pain at pseudoaneurysm site, enlarging pseudoaneurysm, and skin site breakdown. AVG pseudoaneurysm exclusion was accomplished with Wallgrafts, Viabahn endoprosthesis, and Fluency endograft. Technical success was achieved in all patients. Nineteen patients experienced a marked decrease in the size of their pseudoaneurysm following endograft exclusion. Successful hemodialysis was resumed through endograft-excluded AVG in all patients within 48 hours. Conclusions Endoluminal exclusion of AVG pseudoaneurysms using endografts is a safe and effective treatment strategy in patients with hemodialysis-related pseudoaneurysm. C1 [Lin, Peter H.] Baylor Coll Med, Houston VAMC, Michael E DeBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, Houston, TX 77030 USA. [Barshes, Neal R.; Annambhotla, Suman; Bechara, Carlos; Kougias, Panagiotis; Huynh, Tam T.; Lin, Peter H.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Dardik, Alan] Yale Univ, Sch Med, Dept Surg, Div Vasc Surg, New Haven, CT 06510 USA. [Dardik, Alan] VA Connecticut Healthcare Syst, New Haven, CT USA. [Silva, Michael B., Jr.] Univ Texas Galveston, Med Branch, Vasc Surg Sect, Dept Surg, Galveston, TX 77550 USA. RP Lin, PH (reprint author), Baylor Coll Med, Houston VAMC, Michael E DeBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, 2002 Holcomb Blvd 112, Houston, TX 77030 USA. EM plin@bcm.tmc.edu NR 21 TC 25 Z9 27 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1538-5744 J9 VASC ENDOVASC SURG JI Vasc. Endovasc. Surg. PD JUN-JUL PY 2008 VL 42 IS 3 BP 228 EP 234 DI 10.1177/1538574408314443 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 394QY UT WOS:000262463600004 PM 18375603 ER PT J AU Mechanic, MB Weaver, TL Resick, PA AF Mechanic, Mindy B. Weaver, Terri L. Resick, Patricia A. TI Mental health consequences of intimate partner abuse - A multidimensional assessment of four different forms of abuse SO VIOLENCE AGAINST WOMEN LA English DT Article DE battered women; depression; intimate partner abuse; mental health; posttraumatic stress disorder ID POSTTRAUMATIC-STRESS-DISORDER; DOMESTIC VIOLENCE; WOMENS RESPONSES; BATTERED WOMEN; SEXUAL ASSAULT; DEPRESSION; TRAUMA; TIME; STALKING; RISK AB Battered women are exposed to multiple forms of intimate partner abuse. This article explores the independent contributions of physical violence, sexual coercion, psychological abuse, and stalking on symptoms of posttraumatic stress disorder (PTSD) and depression among a sample of 413 severely battered, help-seeking women. The authors test the unique effects of psychological abuse and stalking on mental health outcomes, after controlling for physical violence, injuries, and sexual coercion. Mean scores for the sample fall into the moderate to severe range for PTSD and within the moderate category for depression scores. Hierarchical regressions test the unique effects of stalking and psychological abuse, after controlling for physical violence, injuries, and sexual coercion. Psychological abuse and stalking contribute uniquely to the prediction of PTSD and depression symptoms, even after controlling for the effects of physical violence, injuries, and sexual coercion. Results highlight the importance of examining multiple dimensions of intimate partner abuse. C1 [Mechanic, Mindy B.] Calif State Univ Fullerton, Fullerton, CA 92634 USA. [Weaver, Terri L.] St Louis Univ, St Louis, MO 63103 USA. [Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, Boston, MA USA. [Resick, Patricia A.] Boston Univ, Boston, MA 02215 USA. RP Mechanic, MB (reprint author), Calif State Univ Fullerton, Fullerton, CA 92634 USA. FU NIMH NIH HHS [1-R01-MH55542, R01 MH055542, R01 MH055542-03] NR 60 TC 107 Z9 107 U1 3 U2 28 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-8012 J9 VIOLENCE AGAINST WOM JI Violence Against Women PD JUN PY 2008 VL 14 IS 6 BP 634 EP 654 DI 10.1177/1077801208319283 PG 21 WC Women's Studies SC Women's Studies GA 314GQ UT WOS:000256798300002 PM 18535306 ER PT J AU Jensen, RJ Rizzo, JF AF Jensen, Ralph J. Rizzo, Joseph F., III TI Activation of retinal ganglion cells in wild-type and rd1 mice through electrical stimulation of the retinal neural network SO VISION RESEARCH LA English DT Article DE electrical stimulation; ganglion cell; mouse; threshold; rd1; retinal degeneration ID RETINITIS-PIGMENTOSA; MORPHOMETRIC-ANALYSIS; MOUSE RETINA; INNER RETINA; DEGENERATION; THRESHOLDS; RESPONSES; ARRAYS; LIGHT; CONES AB We compared the thresholds and response properties of extracellularly recorded retinal ganglion cells (RGCs) in wild-type and rd1 mouse retinas to electrical stimulation of the retinal neural network. Retinas were stimulated in vitro with biphasic current pulses (1 ms/phase) applied with a 400-mu m diameter, subretinal electrode. Three types of responses were observed in both wild-type and rd1 RGCs. Type I cells elicited a single burst of spikes within 20 ins following application of the electrical stimulus, type II cells elicited a single burst of spikes with a latency greater than 37 ms, and type III cells elicited two and occasionally three bursts of spikes. For all ages examined, ranging from postnatal day (P) 25 to P186, the thresholds of RGCs were overall consistently higher in tall mice. Median threshold values were 14 and 50 mu A in wild-type and rd1 mice, respectively. We propose that photoreceptors lower the thresholds for activation of RGCs whereas postreceptoral neurons determine the response properties ofRGCs to electrical stimuli. Published by Elsevier Ltd. C1 [Jensen, Ralph J.; Rizzo, Joseph F., III] VA Boston Healthcare Syst, Ctr Innovat Visual Rehabil, Boston, MA 02130 USA. [Rizzo, Joseph F., III] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Rizzo, Joseph F., III] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Jensen, RJ (reprint author), VA Boston Healthcare Syst, Ctr Innovat Visual Rehabil, 150 S Huntington Ave,Mail Stop 151E, Boston, MA 02130 USA. EM Ralph.Jensen@va.gov NR 23 TC 56 Z9 56 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 J9 VISION RES JI Vision Res. PD JUN PY 2008 VL 48 IS 14 BP 1562 EP 1568 DI 10.1016/j.visres.2008.04.016 PG 7 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 324KI UT WOS:000257517100008 PM 18555890 ER PT J AU Dominguez, I Crippa, S Thayer, SP Hung, YP Ferrone, CR Warshaw, AL Fernandez-del Castillo, C AF Dominguez, Ismael Crippa, Stefano Thayer, Sarah P. Hung, Yin P. Ferrone, Cristina R. Warshaw, Andrew L. Fernandez-del Castillo, Carlos TI Preoperative platelet count and survival prognosis in resected pancreatic ductal adenocarcinoma SO WORLD JOURNAL OF SURGERY LA English DT Article ID RENAL-CELL CARCINOMA; LUNG-CANCER; THROMBOCYTOSIS; POPULATION; ETIOLOGY; ANEMIA; STAGE AB Background High platelet counts are associated with an adverse effect on survival in various neoplastic entities. The prognostic relevance of preoperative platelet count in pancreatic cancer has not been clarified. Methods We performed a retrospective review of 205 patients with ductal adenocarcinoma who underwent surgical resection between 1990 and 2003. Demographic, surgical, and clinicopathologic variables were collected. A cutoff of 300,000/mu l was used to define high platelet count. Results Of the 205 patients, 56 (27.4%) had a high platelet count, whereas 149 patients (72.6%) comprised the low platelet group. The overall median survival was 17 (2-178) months. The median survival of the high platelet group was 18 (2-137) months, and that of the low platelet group was 15 (2-178) months (p = 0.7). On multivariate analysis, lymph node metastasis, vascular invasion, positive margins, and CA 19-9 > 200 U/ml were all significantly associated with poor survival. Conclusions There is no evidence to support preoperative platelet count as either an adverse or favorable prognostic factor in pancreatic ductal adenocarcinoma. Use of 5-year actual survival data confirms that lymph node metastases, positive margins, vascular invasion, and CA 19-9 are predictors of poor survival in resected pancreatic cancer. C1 [Dominguez, Ismael; Crippa, Stefano; Thayer, Sarah P.; Hung, Yin P.; Ferrone, Cristina R.; Warshaw, Andrew L.; Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Wang Ambulatory Care Ctr 460, Boston, MA 02114 USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, Wang Ambulatory Care Ctr 460, 15 Parkman St, Boston, MA 02114 USA. EM cfernandez@partners.org FU NCI NIH HHS [P01 CA117969]; NIDDK NIH HHS [K08 DK071329] NR 32 TC 20 Z9 22 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD JUN PY 2008 VL 32 IS 6 BP 1051 EP 1056 DI 10.1007/s00268-007-9423-6 PG 6 WC Surgery SC Surgery GA 303JN UT WOS:000256036900016 PM 18224462 ER PT J AU von Arnim, CAF von Einem, B Weber, P Wagner, M Schwanzar, D Spoelgen, R Strauss, WLS Schneckenburger, H AF von Arnim, Christine A. F. von Einem, Bjoern Weber, Petra Wagner, Michael Schwanzar, Daniel Spoelgen, Robert Strauss, Wolfgang L. S. Schneckenburger, Herbert TI Impact of cholesterol level upon APP and BACE proximity and APP cleavage SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Amyloid precursor protein (APP); beta-site APP cleaving enzyme (BACE); total internal reflection microscopy (TIRF); Alzheimer's disease; cholesterol ID AMYLOID PRECURSOR PROTEIN; RECEPTOR-RELATED PROTEIN; CELL-MEMBRANE DYNAMICS; ALZHEIMERS-DISEASE; BETA-SECRETASE; FLUORESCENCE MICROSCOPY; LIPID RAFTS; GENERATION; ENDOCYTOSIS; BIOLOGY AB Cleavage of APP by BACE is the first proteolytic step in the production of Amyloid beta (A beta, which accumulates in senile plaques in Alzheimer's disease. BACE-cleavage of APP is thought to happen in endosomes. However, there are controversial data whether APP and BACE can already interact on the cell surface dependent on the cholesterol level. To examine whether APP and BACE come into close proximity on the cell surface in living cells, we employed a novel technique by combining time-resolved Forster resonance energy transfer (FRET) measurements with total internal reflection microscopy (TIRET microscopy). Our data indicate that BACE and APP come into close proximity within the cell, but probably not on the cell surface. To analyze the impact of alterations in cholesterol level upon BACE-cleavage, we measured sAPP secretion. Alteration of APP processing and BACE proximity by cholesterol might be explained by alterations in cell membrane fluidity. (C) 2008 Elsevier Inc. All rights reserved. C1 [von Arnim, Christine A. F.; von Einem, Bjoern; Schwanzar, Daniel] Univ Ulm, Dept Neurol, D-89081 Ulm, Germany. [Spoelgen, Robert] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Alzheimers Dis Res Unit, Charlestown, MA 02129 USA. [Strauss, Wolfgang L. S.; Schneckenburger, Herbert] Univ Ulm, Inst Laser Technol Med & Metrol, D-89081 Ulm, Germany. RP von Arnim, CAF (reprint author), Univ Ulm, Dept Neurol, Albert Einstein Allee 1, D-89081 Ulm, Germany. EM christine.arnim@uni-ulm.de NR 25 TC 38 Z9 38 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 MAY 30 PY 2008 VL 370 IS 2 BP 207 EP 212 DI 10.1016/j.bbrc.2008.03.047 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 296EM UT WOS:000255526300002 PM 18374657 ER PT J AU Borger, DR Gavrilescu, LC Bucur, MC Ivan, M DeCaprio, JA AF Borger, Darrell R. Gavrilescu, L. Cristina Bucur, Maria C. Ivan, Mircea DeCaprio, James A. TI AMP-activated protein kinase is essential for survival in chronic hypoxia SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE hypoxia; AMPK; mTOR; rapamycin; apoptosis; cancer ID TUMOR-SUPPRESSOR PROTEIN; MAMMALIAN TARGET; CELLS; RAPAMYCIN; CANCER; PHOSPHORYLATION; INHIBITION; METABOLISM; THERAPY; STRESS AB This study was undertaken to interrogate cancer cell survival during long-term hypoxic stress. Two systems with relevance to carcinogenesis were employed: Fully transformed BJ cells and a renal carcinoma cell line (786-0). The dynamic of AMPK activity was consistent with a prosurvival role during chronic hypoxia. This was further supported by the effects of AMPK agonists and antagonists (AICAR and compound C). Expression of a dominant-negative AMPK alpha resulted in a decreased ATP level and significantly compromised survival in hypoxia. Dose-dependent prosurvival effects of rapamycin were consistent with mTOR inhibition being a critical downstream mediator of AMPK in persistent low oxygen. (C) 2008 Elsevier Inc. All rights reserved. C1 [Gavrilescu, L. Cristina; Bucur, Maria C.; Ivan, Mircea] Tufts Univ New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. [Borger, Darrell R.; DeCaprio, James A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Ivan, M (reprint author), Tufts Univ New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. EM mivan@tuftsmedicalcenter.org; james_decaprio@dfci.harvard.edu RI Ivan, Mircea/A-8109-2012 FU NCI NIH HHS [P01 CA050661-200008, P01 CA050661-209001, R01 CA063113-13, R01 CA063113, P01 CA050661, R01CA063113]; NIDDK NIH HHS [P30 DK034928, P30 DK-34928] NR 28 TC 16 Z9 20 U1 0 U2 3 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 MAY 30 PY 2008 VL 370 IS 2 BP 230 EP 234 DI 10.1016/j.bbrc.2008.03.056 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 296EM UT WOS:000255526300006 PM 18359290 ER PT J AU Sidi, S Sanda, T Kennedy, RD Hagen, AT Jette, CA Hoffmans, R Pascual, J Imamura, S Kishi, S Amatruda, JF Kanki, JP Green, DR D'Andrea, AA Look, AT AF Sidi, Samuel Sanda, Takaomi Kennedy, Richard D. Hagen, Andreas T. Jette, Cicely A. Hoffmans, Raymond Pascual, Jennifer Imamura, Shintaro Kishi, Shuji Amatruda, James F. Kanki, John P. Green, Douglas R. D'Andrea, Alan A. Look, A. Thomas TI Chk1 suppresses a caspase-2 apoptotic response to DNA damage that bypasses p53, Bcl-2, and caspase-3 SO CELL LA English DT Article ID CYTOCHROME-C RELEASE; CELL-DEATH; TRANSGENIC ZEBRAFISH; MITOTIC CATASTROPHE; CHECKPOINT KINASES; GENOTOXIC STRESS; GLIOMA-CELLS; S-PHASE; RADIATION; ACTIVATION AB Evasion of DNA damage-induced cell death, via mutation of the p53 tumor suppressor or overexpression of prosurvival Bcl-2 family proteins, is a key step toward malignant transformation and therapeutic resistance. We report that depletion or acute inhibition of checkpoint kinase 1 (Chk1) is sufficient to restore gamma-radiation-induced apoptosis in p53 mutant zebrafish embryos. Surprisingly, caspase-3 is not activated prior to DNA fragmentation, in contrast to classical intrinsic or extrinsic apoptosis. Rather, an alternative apoptotic program is engaged that cell autonomously requires atm (ataxia telangiectasia mutated), atr (ATM and Rad3-related) and caspase-2, and is not affected by p53 loss or overexpression of bcl-2/xl. Similarly, Chk1 inhibitor-treated human tumor cells hyperactivate ATM, ATR, and caspase-2 after gamma-radiation and trigger a caspase-2-dependent apoptotic program that bypasses p53 deficiency and excess Bcl-2. The evolutionarily conserved "Chk1-suppressed'' pathway defines a novel apoptotic process, whose responsiveness to Chk1 inhibitors and insensitivity to p53 and BCL2 alterations have important implications for cancer therapy. C1 [Sidi, Samuel; Sanda, Takaomi; Hagen, Andreas T.; Jette, Cicely A.; Hoffmans, Raymond; Pascual, Jennifer; Kanki, John P.; Look, A. Thomas] Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. [Kennedy, Richard D.; D'Andrea, Alan A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Genom Stabil & DNA Repair, Boston, MA 02115 USA. [Look, A. Thomas] Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat,Div Hematol Oncol, Boston, MA 02115 USA. [Imamura, Shintaro; Kishi, Shuji] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA. [Amatruda, James F.] Univ Texas SW Med Ctr Dallas, Dept Pediat Mol Biol & Internal Med, Dallas, TX 75390 USA. [Green, Douglas R.] St Jude Childrens Hosp, Dept Immunol, Memphis, TN 38105 USA. RP Look, AT (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu RI Kennedy, Richard/J-3489-2012 OI Kennedy, Richard/0000-0003-4737-6163 FU NHLBI NIH HHS [HL-88664, R01 HL088664, R01 HL088664-02]; NIAID NIH HHS [AI47891, R01 AI047891] NR 60 TC 175 Z9 180 U1 0 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAY 30 PY 2008 VL 133 IS 5 BP 864 EP 877 DI 10.1016/j.cell.2008.03.037 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 306UY UT WOS:000256274500018 PM 18510930 ER PT J AU Simon, DJ Madison, JM Conery, AL Thompson-Peer, KL Soskis, M Ruvkun, GB Kaplan, JM Kim, JK AF Simon, David J. Madison, Jon M. Conery, Annie L. Thompson-Peer, Katherine L. Soskis, Michael Ruvkun, Gary B. Kaplan, Joshua M. Kim, John K. TI The MicroRNA miR-1 regulates a MEF-2-dependent retrograde signal at neuromuscular junctions SO CELL LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTORS; DEVELOPING NERVOUS-SYSTEM; CAENORHABDITIS-ELEGANS; SYNAPTIC-TRANSMISSION; C-ELEGANS; MUSCLE; DIFFERENTIATION; ABUNDANCE; TARGETS; IDENTIFICATION AB We show that miR-1, a conserved muscle-specific microRNA, regulates aspects of both pre- and post-synaptic function at C. elegans neuromuscular junctions. miR-1 regulates the expression level of two nicotinic acetylcholine receptor (nAChR) subunits (UNC-29 and UNC-63), thereby altering muscle sensitivity to acetylcholine (ACh). miR-1 also regulates the muscle transcription factor MEF-2, which results in altered presynaptic ACh secretion, suggesting that MEF-2 activity in muscles controls a retrograde signal. The effect of the MEF-2-dependent retrograde signal on secretion is mediated by the synaptic vesicle protein RAB-3. Finally, acute activation of levamisole-sensitive nAChRs stimulates MEF-2-dependent transcriptional responses and induces the MEF-2-dependent retrograde signal. We propose that miR-1 refines synaptic function by coupling changes in muscle activity to changes in presynaptic function. C1 [Simon, David J.; Madison, Jon M.; Conery, Annie L.; Thompson-Peer, Katherine L.; Ruvkun, Gary B.; Kaplan, Joshua M.; Kim, John K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Simon, David J.; Soskis, Michael] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Kaplan, JM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM kaplan@molbio.mgh.harvard.edu OI Thompson-Peer, Katherine/0000-0002-4200-3870 FU NINDS NIH HHS [1F32NS10310, F32 NS010310, R01 NS032196, R01 NS032196-11, R01 NS032196-12, R01 NS032196-13, R01 NS032196-14, R01 NS032196-15] NR 48 TC 109 Z9 121 U1 1 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAY 30 PY 2008 VL 133 IS 5 BP 903 EP 915 DI 10.1016/j.cell.2008.04.035 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 306UY UT WOS:000256274500021 PM 18510933 ER PT J AU Huang, JH Qi, Z Wu, F Kotula, L Jiang, SB Chen, YH AF Huang, Jing-He Qi, Zhi Wu, Fan Kotula, Leszek Jiang, Shibo Chen, Ying-Hua TI Interaction of HIV-1 gp41 core with NPF motif in Epsin - Implication in endocytosis of HIV SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CLATHRIN-MEDIATED ENDOCYTOSIS; ENVELOPE GLYCOPROTEIN; BINDING MOTIF; EH-DOMAIN; TRANSMEMBRANE GLYCOPROTEIN; MEMBRANE-FUSION; PROTEIN; RECEPTORS; PEPTIDE AB The human immunodeficiency virus, type 1 (HIV-1), gp41 core plays an important role in fusion between viral and target cell membranes. We previously identified an HIV-1 gp41 core-binding motif HXXNPF (where X is any amino acid residue). In this study, we found that Asn, Pro, and Phe were the key residues for gp41 core binding. There are two NPF motifs in Epsin-l(470 - 499), a fragment of Epsin, which is an essential accessory factor of endocytosis that can dock to the plasma membrane by interacting with the lipid. Epsin-1-(470-499) bound significantly to the gp41 core formed by the polypeptide N36(L8)C34 and interacted with the recombinant soluble gp41 containing the core structure. A synthetic peptide containing the Epsin-1-(470 - 499) sequence could effectively block entry of HIV- 1 virions into SupT1 T cells via the endocytosis pathway. These results suggest that interaction between Epsin and the gp41 core, which may be present in the target cell membrane, is probably essential for endocytosis of HIV-1, an alternative pathway of HIV-1 entry into the target cell. C1 [Qi, Zhi; Kotula, Leszek; Jiang, Shibo] New York Blood Ctr, Lindsley F Kimball Res Inst, New York, NY 10065 USA. [Huang, Jing-He; Wu, Fan; Chen, Ying-Hua] Tsinghua Univ, Dept Biol, Immunol Lab, Prot Sci Lab,Minist Educ, Beijing 100084, Peoples R China. [Huang, Jing-He] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Parterns AIDS Res Ctr & Infect Dis Div, Boston, MA 02129 USA. RP Jiang, SB (reprint author), New York Blood Ctr, Lindsley F Kimball Res Inst, New York, NY 10065 USA. EM sjiang@nybloodcenter.org; chenyh@mail.tsinghua.edu.cn RI Jiang, Shibo/L-4500-2014; Huang, Jinghe/O-1986-2015 FU NIAID NIH HHS [R01 AI046221] NR 43 TC 10 Z9 11 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 30 PY 2008 VL 283 IS 22 BP 14994 EP 15002 DI 10.1074/jbc.M800525200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 306EV UT WOS:000256232000012 PM 18375383 ER PT J AU Rardin, MJ Wiley, SE Murphy, AN Pagliarini, DJ Dixon, JE AF Rardin, Matthew J. Wiley, Sandra E. Murphy, Anne N. Pagliarini, David J. Dixon, Jack E. TI Dual specificity phosphatases 18 and 21 target to opposing sides of the mitochondrial inner membrane SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; PYRUVATE-DEHYDROGENASE COMPLEX; RAT-LIVER MITOCHONDRIA; REVERSIBLE PHOSPHORYLATION; CYTOCHROME-C; SPECIFICITY; APOPTOSIS; MECHANISM; RELEASE; DEATH AB Although large-scale approaches have identified numerous mitochondrial phosphoproteins, little is known about the mitochondrial kinases and phosphatases that regulate these phosphoproteins. Here, we identify two members of the atypical dual specificity phosphatases (DSP), DSP18 and DSP21, that are localized in mitochondria. Although DSP18 is widely expressed in several mammalian tissues, DSP21 is selectively expressed in the testes. We demonstrate that DSP18 and DSP21 are targeted to mitochondria by cryptic internal localization signals. Sub-fractionation of mitochondria demonstrated that DSP18 is located in the intermembrane space as a peripheral membrane protein of the inner membrane. In contrast, subfractionation of rat testis mitochondria revealed DSP21 is localized to the matrix as a peripheral membrane protein of the inner membrane. Moreover, we demonstrate that a previously reported substrate for DSP18, the stress-activated protein kinase, does not localize to mitochondria in several different tissues, making it an unlikely substrate for DSP18. Finally, we show that induction of apoptosis by treatment with staurosporine causes translocation of DSP18 from the intermembrane space into the cytosol similar to other apoptogenic factors such as cytochrome c. This work rigorously demonstrates the unique location of two highly similar DSPs on opposing sides of the mitochondrial inner membrane. C1 [Rardin, Matthew J.; Wiley, Sandra E.; Murphy, Anne N.; Dixon, Jack E.] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. [Rardin, Matthew J.; Wiley, Sandra E.; Murphy, Anne N.; Dixon, Jack E.] Univ Calif San Diego, Dept Cell & Mol Med, La Jolla, CA 92093 USA. [Rardin, Matthew J.; Wiley, Sandra E.; Murphy, Anne N.; Dixon, Jack E.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. [Rardin, Matthew J.] Univ Calif San Diego, Biomed Sci Grad Program, La Jolla, CA 92093 USA. [Dixon, Jack E.] Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA. [Pagliarini, David J.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA. [Pagliarini, David J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Dixon, JE (reprint author), Univ Calif San Diego, Dept Pharmacol, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM jedixon@ucsd.edu OI Murphy, Anne N/0000-0002-5222-9902; Pagliarini, Dave/0000-0002-0001-0087 FU NIGMS NIH HHS [2T32 GM 07752-25]; PHS HHS [NIH 18849] NR 58 TC 17 Z9 20 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 30 PY 2008 VL 283 IS 22 BP 15440 EP 15450 DI 10.1074/jbc.M709547200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 306EV UT WOS:000256232000062 PM 18385140 ER PT J AU Chen, WL Song, BB Zhang, GH Marvizon, JCG AF Chen, Wenling Song, Bingbing Zhang, Guohua Marvizon, Juan Carlos G. TI Effects of veratridine and high potassium on mu-opioid receptor internalization in the rat spinal cord: Stimulation of opioid release versus inhibition of internalization SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE depolarization; dynorphin; enkephalin; internalization; Na+ channels; potassium; substance P; veratridine ID ENKEPHALIN-LIKE MATERIAL; DORSAL-HORN NEURONS; MEDIAL PREOPTIC NUCLEUS; NOXIOUS THERMAL STIMULI; PRIMARY AFFERENT-FIBERS; SUBSTANCE-P RELEASE; METHYL-D-ASPARTATE; GABA(B) RECEPTORS; SEGMENTAL RELEASE; ANESTHETIZED RATS AB Veratridine and high K+-induced mu-opioid receptor (MOR) internalization in rat spinal cord slices by evoking opioid release. Veratridine induced up to 75 % MOR internalization but showed an atypical concentration-response: its effect increased steeply from 5 mu M to 10 mu M, and declined thereafter to disappear at 100 mu M. At 100 mu M, veratridine also inhibited of MOR internalization induced by exogenous endomorphin-2. This inhibition was caused by Na+ entry, since the Ne ionophore monensin (50 mu M) also inhibited endomorphin-induced MOR internalization. In contrast, veratridine induced neurokinin 1 receptor internalization (by evoking substance P release) without any inhibition at high concentrations. KCl evoked up to 80% MOR internalization, which disappeared in the presence of lidocaine or in the absence of peptidase inhibitors, indicating that it involved neuronal firing and peptide release. Unlike veratridine, KCl did not inhibit MOR internalization at high concentrations. However, both KCl and veratridine evoked more MOR internalization when applied for 2 min than for 20 min because of a direct inhibition of MOR internalization with the longer incubation times. These results show that short incubations with 20 mu M veratridine or 30 mM KCl are optimal stimuli to evoke opioid release and MOR internalization in the spinal cord. (C) 2008 Elsevier B.V. All rights reserved. C1 [Chen, Wenling; Zhang, Guohua; Marvizon, Juan Carlos G.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Chen, Wenling; Song, Bingbing; Zhang, Guohua; Marvizon, Juan Carlos G.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress, CURE Digest Dis Res Ctr,Div Digest Dis,Dept Med, Los Angeles, CA 90095 USA. RP Marvizon, JCG (reprint author), VA Greater Los Angeles Healthcare Syst, Bldg 115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM marvizon@ucla.edu FU NIDA NIH HHS [R01 DA012609, R01 DA012609-08, R01 DA012609-07, 2-R01-DA012609] NR 52 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD MAY 30 PY 2008 VL 170 IS 2 BP 285 EP 293 DI 10.1016/j.jneumeth.2008.01.032 PG 9 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 300TX UT WOS:000255849200012 PM 18377995 ER PT J AU Simon, NM Shear, MK Fagiolini, A Frank, E Zalta, A Thompson, EH Reynolds, CF Silowash, R AF Simon, Naomi M. Shear, M. Katherine Fagiolini, Andrea Frank, Ellen Zalta, Alyson Thompson, Elizabeth H. Reynolds, Charles F., III Silowash, Russell TI Impact of concurrent naturalistic pharmacotherapy on psychotherapy of complicated grief SO PSYCHIATRY RESEARCH LA English DT Article DE treatment; antidepressant; benzodiazepine; complicated grief; traumatic grief; prolonged grief ID TRAUMATIC GRIEF; OPEN-TRIAL; NORTRIPTYLINE; BEREAVEMENT; LIFE; SYMPTOMS AB Complicated grief (CG) is a debilitating syndrome that can be reliably identified, but there is a paucity of research examining treatment of CG. A targeted psychotherapy for complicated grief (CGT) was recently shown to be efficacious [Shear, K., Frank, E., Houck, P.R., Reynolds, C.F., 3rd, 2005. Treatment of complicated grief: a randomized controlled trial. Journal of the American Medical Association 293, 2601-2608]. We provide a detailed examination of the association of naturalistic pharmacotherapy use with treatment response and study completion in the psychotherapy study. Patients on an antidepressant medication were more likely to complete a full course of CGT (91% vs. 58% completed), while antidepressant use had no effect on completion rates for the comparator, interpersonal psychotherapy (70% vs. 77%). Our naturalistic data underscore the need for prospective, randomized controlled studies of CG pharmacotherapy and psychotherapy alone and in combination. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Simon, Naomi M.; Zalta, Alyson; Thompson, Elizabeth H.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Shear, M. Katherine] Columbia Univ, Sch Social Work, New York, NY USA. [Fagiolini, Andrea; Frank, Ellen; Reynolds, Charles F., III; Silowash, Russell] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Simches Res Bldg,2nd Floor,185 Cambridge St, Boston, MA 02114 USA. EM nsimon@partners.org OI FAGIOLINI, ANDREA/0000-0001-5827-0853; Zalta, Alyson/0000-0002-5159-8431 FU NIMH NIH HHS [P30 MH71944, MH30915, MH60783, P30 MH030915, P30 MH071944, R01 MH060783, R01 MH060783-05] NR 13 TC 20 Z9 20 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAY 30 PY 2008 VL 159 IS 1-2 BP 31 EP 36 DI 10.1016/j.psychres.2007.05.011 PG 6 WC Psychiatry SC Psychiatry GA 310GU UT WOS:000256517700005 PM 18336918 ER PT J AU Fan, XD Henderson, DC Nguyen, DD Cather, C Freudenreich, O Evins, AE Borba, CP Goff, DC AF Fan, Xiaoduo Henderson, David C. Nguyen, Dana D. Cather, Corinne Freudenreich, Oliver Evins, A. Eden Borba, Christina P. Goff, Donald C. TI Posttraumatic stress disorder, cognitive function and quality of life in patients with schizophrenia SO PSYCHIATRY RESEARCH LA English DT Article DE schizophrenia; posttraumatic stress disorder; cognitive function; quality of life ID SEVERE MENTAL-ILLNESS; NEUROCOGNITIVE DEFICITS; ANXIETY DISORDERS; COMBAT VETERANS; SERVICE UTILIZATION; MEMORY FUNCTION; TRAUMA; PTSD; SYMPTOMS; IMPACT AB The purpose of the present study was to assess posttraumatic stress disorder (PTSD), cognitive function, and quality of life in patients with schizophrenia who had a self-reported history of trauma exposure. Outpatients diagnosed with schizophrenia or schizoaffective disorder were referred to the study. Each patient was assessed with the Positive and Negative Syndrome Scale (PANSS), the Harvard Trauma Questionnaire (HTQ), a cognitive assessment battery, Heinrich's Quality of Life Scale (QLS), and the Behavior and Symptom Identification Scale (BASIS). Eighty-seven subjects who reported experiencing at least one traumatic event were included in the study. Fifteen of 87 (17%) met the DSM-IV criteria for PTSD. The PTSD group had significantly worse overall cognitive performance than the non-PTSD group, especially in the domains of attention, working memory and executive function. In addition, the PTSD group showed significantly worse self-rated quality of life as measured by the BASIS total score. The development of PTSD is associated with poor cognitive function and subjectively, but not objectively, rated low quality of life in patients with schizophrenia. Evaluating PTSD in patients with schizophrenia could have important implications from both clinical and research perspectives. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Fan, Xiaoduo; Henderson, David C.; Cather, Corinne; Freudenreich, Oliver; Evins, A. Eden; Borba, Christina P.; Goff, Donald C.] Massachusetts Gen Hosp, Dept Psychiat, Schizophrenia Program, Boston, MA 02114 USA. [Fan, Xiaoduo; Henderson, David C.; Cather, Corinne; Freudenreich, Oliver; Evins, A. Eden; Goff, Donald C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Nguyen, Dana D.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. RP Fan, XD (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM xfan@partners.org NR 48 TC 26 Z9 26 U1 1 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAY 30 PY 2008 VL 159 IS 1-2 BP 140 EP 146 DI 10.1016/j.psychres.2007.10.012 PG 7 WC Psychiatry SC Psychiatry GA 310GU UT WOS:000256517700020 PM 18423611 ER PT J AU Zinzow, HM Grubaugh, AL Frueh, BC Magruder, KM AF Zinzow, Heidi M. Grubaugh, Anouk L. Frueh, Bartley Christopher Magruder, Kathryn M. TI Sexual assault, mental health, and service use among male and female veterans seen in Veterans Affairs primary care clinics: A multi-site study SO PSYCHIATRY RESEARCH LA English DT Article DE trauma; revictimization; sexual abuse; child sexual abuse; assault characteristics; psychiatric functioning; healthcare; PTSD ID POSTTRAUMATIC-STRESS-DISORDER; WOMEN VETERANS; CHILDHOOD ABUSE; RISK-FACTORS; CRIMINAL VICTIMIZATION; PSYCHOLOGICAL IMPACT; GENERAL-POPULATION; GENDER-DIFFERENCES; TRAUMATIC EVENTS; SOMATIC SYMPTOMS AB This study examined the nature and prevalence of sexual assault (SA), as well as its relationship to psychiatric sequelae and service use, among the veteran population. We performed a secondary data analysis of a cross-sectional dataset consisting of 643 male and 173 female veterans seen in four Veterans Affairs (VA) primary care clinics. Original data were obtained through semi-structured clinic assessments, structured telephone interviews, and medical chart reviews. Analyses included descriptive statistics, chi-square, analysis of variance (ANOVA), and logistic regression. The lifetime prevalence of SA was 38% among women and 6% among men. Of veterans reporting a history of SA, most experienced child sexual abuse and sexual revictimization. SA victims also had a more extensive trauma history and demonstrated greater psychological impairment in comparison to veterans reporting other types of trauma. However, only 25% of male SA survivors and 38% of female SA survivors used mental health services in the past year. These findings suggest that VA primary care clinics may benefit from expanding the current mandated screen for military sexual trauma to include lifetime experiences and trauma-related symptoms, thereby connecting more veterans with needed mental health services. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Grubaugh, Anouk L.; Magruder, Kathryn M.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Zinzow, Heidi M.] Univ Georgia, Dept Psychol, Athens, GA 30602 USA. [Grubaugh, Anouk L.; Magruder, Kathryn M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Frueh, Bartley Christopher] Univ Hawaii, Hilo, HI 96720 USA. RP Grubaugh, AL (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, POB 250861, Charleston, SC 29425 USA. EM grubaugh@musc.edu NR 60 TC 24 Z9 26 U1 6 U2 19 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAY 30 PY 2008 VL 159 IS 1-2 BP 226 EP 236 DI 10.1016/j.psychres.2007.04.008 PG 11 WC Psychiatry SC Psychiatry GA 310GU UT WOS:000256517700030 PM 18423615 ER PT J AU Sales, A Helfrich, C Ho, PM Hedeen, A Plomondon, ME Li, YF Connors, A Rumsfeld, JS AF Sales, Anne Helfrich, Christian Ho, P. Michael Hedeen, Ashley Plomondon, Mary E. Li, Yu-Fang Connors, Alison Rumsfeld, John S. TI Implementing electronic clinical reminders for lipid management in patients with ischemic heart disease in the veterans health administration: QUERI Series SO IMPLEMENTATION SCIENCE LA English DT Article ID SCANDINAVIAN SIMVASTATIN SURVIVAL; RANDOMIZED-TRIAL; PRIMARY-CARE; DECISION-SUPPORT; CORONARY EVENTS; GUIDELINES; BARRIERS; SYSTEMS; INTERVENTIONS; REDUCTION AB Background: Ischemic heart disease (IHD) affects at least 150,000 veterans annually in the United States. Lowering serum cholesterol has been shown to reduce coronary events, cardiac death, and total mortality among high risk patients. Electronic clinical reminders available at the point of care delivery have been developed to improve lipid measurement and management in the Veterans Health Administration (VHA). Our objective was to report on a hospital-level intervention to implement and encourage use of the electronic clinical reminders. Methods: The implementation used a quasi- experimental design with a comparison group of hospitals. In the intervention hospitals (N = 3), we used a multi-faceted intervention to encourage use of the electronic clinical reminders. We evaluated the degree of reminder use and how patient-level outcomes varied at the intervention and comparison sites (N = 3), with and without adjusting for self-reported reminder use. Results: The national electronic clinical reminders were implemented in all of the intervention sites during the intervention period. A total of 5,438 patients with prior diagnosis of ischemic heart disease received care in the six hospitals (3 intervention and 3 comparison) throughout the 12-month intervention. The process evaluation showed variation in use of reminders at each site. Without controlling for provider self-report of use of the reminders, there appeared to be a significant improvement in lipid measurement in the intervention sites (OR 1.96, 95% CI 1.34, 2.88). Controlling for use of reminders, the amount of improvement in lipid measurement in the intervention sites was even greater (OR 2.35, CI 1.96, 2.81). Adjusting for reminder use demonstrated that only one of the intervention hospitals had a significant effect of the intervention. There was no significant change in management of hyperlipidemia associated with the intervention. Conclusion: There may be some benefit to focused effort to implement electronic clinical reminders, although reminders designed to improve relatively simple tasks, such as ordering tests, may be more beneficial than reminders designed to improve more complex tasks, such as initiating or titrating medications, because of the less complex nature of the task. There is value in monitoring the process, as well as outcome, of an implementation effort. C1 [Sales, Anne; Connors, Alison] Univ Alberta, Edmonton, AB, Canada. [Helfrich, Christian; Hedeen, Ashley; Li, Yu-Fang] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Ho, P. Michael; Plomondon, Mary E.; Rumsfeld, John S.] VA Eastern Colorado Hlth Care Syst, Denver, CO USA. [Ho, P. Michael; Plomondon, Mary E.; Rumsfeld, John S.] Univ Denver, Hlth Sci Ctr, Denver, CO USA. RP Sales, A (reprint author), Univ Alberta, Edmonton, AB, Canada. EM anne.sales@ualberta.ca; christian.helfrich@va.gov; michael.ho@va.gov; ashley.hedeen@va.gov; meg.plomondon@va.gov; yufang.li@va.gov; lucarott@ualberta.ca; john.rumsfeld@va.gov RI Sales, Anne/D-9678-2012; Helfrich, Christian/D-2382-2016; OI Helfrich, Christian/0000-0002-9827-4768; Sales, Anne/0000-0001-9360-3334 FU Department of Veterans Affairs (VA) Health Services Research and Development Service [IHT 01-040] FX This study was supported by the Department of Veterans Affairs (VA) Health Services Research and Development Service, IHT 01-040. The views expressed in this article are those of the authors and do not necessarily represent the position or policy of the U.S. Department of Veterans Affairs. NR 38 TC 12 Z9 12 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD MAY 29 PY 2008 VL 3 AR 28 DI 10.1186/1748-5908-3-28 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 432RH UT WOS:000265151300001 PM 18510748 ER PT J AU Stetler, CB McQueen, L Demakis, J Mittman, BS AF Stetler, Cheryl B. McQueen, Lynn Demakis, John Mittman, Brian S. TI An organizational framework and strategic implementation for system-level change to enhance research-based practice: QUERI Series SO IMPLEMENTATION SCIENCE LA English DT Article ID HEALTH-CARE; QUALITY IMPROVEMENT; UNITED-STATES; VETERANS; INTERVENTIONS; TRANSLATION; PROGRAMS; ADULTS AB Background: The continuing gap between available evidence and current practice in health care reinforces the need for more effective solutions, in particular related to organizational context. Considerable advances have been made within the U.S. Veterans Health Administration (VA) in systematically implementing evidence into practice. These advances have been achieved through a system-level program focused on collaboration and partnerships among policy makers, clinicians, and researchers. The Quality Enhancement Research Initiative (QUERI) was created to generate research-driven initiatives that directly enhance health care quality within the VA and, simultaneously, contribute to the field of implementation science. This paradigm-shifting effort provided a natural laboratory for exploring organizational change processes. This article describes the underlying change framework and implementation strategy used to operationalize QUERI. Strategic approach to organizational change: QUERI used an evidence-based organizational framework focused on three contextual elements: 1) cultural norms and values, in this case related to the role of health services researchers in evidence-based quality improvement; 2) capacity, in this case among researchers and key partners to engage in implementation research; 3) and supportive infrastructures to reinforce expectations for change and to sustain new behaviors as part of the norm. As part of a QUERI Series in Implementation Science, this article describes the framework's application in an innovative integration of health services research, policy, and clinical care delivery. Conclusion: QUERI's experience and success provide a case study in organizational change. It demonstrates that progress requires a strategic, systems-based effort. QUERI's evidence-based initiative involved a deliberate cultural shift, requiring ongoing commitment in multiple forms and at multiple levels. VA's commitment to QUERI came in the form of visionary leadership, targeted allocation of resources, infrastructure refinements, innovative peer review and study methods, and direct involvement of key stakeholders. Stakeholders included both those providing and managing clinical care, as well as those producing relevant evidence within the health care system. The organizational framework and related implementation interventions used to achieve contextual change resulted in engaged investigators and enhanced uptake of research knowledge. QUERI's approach and progress provide working hypotheses for others pursuing similar system-wide efforts to routinely achieve evidence-based care. C1 [Stetler, Cheryl B.] Independent Consultant, Amherst, MA USA. [McQueen, Lynn] US Dept Vet Affairs, Off Qual Performance, Washington, DC USA. [Demakis, John] US Dept Vet Affairs, Hlth Serv Res & Dev Serv, Washington, DC USA. [Mittman, Brian S.] Vet Affairs Greater Los Angeles Healthcare Syst, VA Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. RP Stetler, CB (reprint author), Independent Consultant, Amherst, MA USA. EM Cheryl.Stetler@comcast.net; Lynn.McQueen@va.gov; jgd11@erols.com; Brian.Mittman@va.gov NR 45 TC 54 Z9 55 U1 4 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD MAY 29 PY 2008 VL 3 AR 30 DI 10.1186/1748-5908-3-30 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 432RH UT WOS:000265151300003 PM 18510750 ER PT J AU Yano, EM AF Yano, Elizabeth M. TI The role of organizational research in implementing evidence-based practice: QUERI Series SO IMPLEMENTATION SCIENCE LA English DT Article ID HEALTH-CARE-SYSTEM; PREVENTIVE SERVICE DELIVERY; RANDOMIZED CONTROLLED-TRIAL; AFFAIRS MEDICAL-CENTERS; QUALITY-IMPROVEMENT; VETERANS; INTERVENTIONS; STRATEGIES; MANAGEMENT; PERFORMANCE AB Background: Health care organizations exert significant influence on the manner in which clinicians practice and the processes and outcomes of care that patients experience. A greater understanding of the organizational milieu into which innovations will be introduced, as well as the organizational factors that are likely to foster or hinder the adoption and use of new technologies, care arrangements and quality improvement (QI) strategies are central to the effective implementation of research into practice. Unfortunately, much implementation research seems to not recognize or adequately address the influence and importance of organizations. Using examples from the U. S. Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI), we describe the role of organizational research in advancing the implementation of evidence-based practice into routine care settings. Methods: Using the six-step QUERI process as a foundation, we present an organizational research framework designed to improve and accelerate the implementation of evidence-based practice into routine care. Specific QUERI-related organizational research applications are reviewed, with discussion of the measures and methods used to apply them. We describe these applications in the context of a continuum of organizational research activities to be conducted before, during and after implementation. Results: Since QUERI's inception, various approaches to organizational research have been employed to foster progress through QUERI's six-step process. We report on how explicit integration of the evaluation of organizational factors into QUERI planning has informed the design of more effective care delivery system interventions and enabled their improved "fit" to individual VA facilities or practices. We examine the value and challenges in conducting organizational research, and briefly describe the contributions of organizational theory and environmental context to the research framework. Conclusion: Understanding the organizational context of delivering evidence-based practice is a critical adjunct to efforts to systematically improve quality. Given the size and diversity of VA practices, coupled with unique organizational data sources, QUERI is well-positioned to make valuable contributions to the field of implementation science. More explicit accommodation of organizational inquiry into implementation research agendas has helped QUERI researchers to better frame and extend their work as they move toward regional and national spread activities. C1 [Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, Vet Affairs Hlth Serv Res & Dev, Ctr Excellence Study Healthcare Provider Behav, Sepulveda, CA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RP Yano, EM (reprint author), VA Greater Los Angeles Healthcare Syst, Vet Affairs Hlth Serv Res & Dev, Ctr Excellence Study Healthcare Provider Behav, Sepulveda, CA USA. EM elizabeth.yano@va.gov FU Veterans Health Administration, VA Health Services Research & Development (HSR&D) Service through the VA Greater Los Angeles HSR&D Center of Excellence [HFP 94-028, MNT 01-027, RCS 05-195] FX This work was funded by the U.S. Department of Veterans Affairs, Veterans Health Administration, VA Health Services Research & Development (HSR&D) Service through the VA Greater Los Angeles HSR&D Center of Excellence (Project #HFP 94-028), the VA HSR&D and QUERI-funded "Regional Expansion and Testing of Depression Collaborative Care" (ReTIDES) (Project #MNT 01-027), and Dr. Yano's VA HSR&D Research Career Scientist award (Project #RCS 05-195). The author also would like to acknowledge and thank the editors and reviewers for their thoughtful critiques and useful input. NR 99 TC 32 Z9 36 U1 3 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD MAY 29 PY 2008 VL 3 AR 29 DI 10.1186/1748-5908-3-29 PG 15 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 432RH UT WOS:000265151300002 PM 18510749 ER PT J AU Michaelson, MD Iliopoulos, O McDermott, DF McGovern, FJ Harisinghani, MG Oliva, E AF Michaelson, M. Dror Iliopoulos, Othon McDermott, David F. McGovern, Francis J. Harisinghani, Mukesh G. Oliva, Esther TI A man with metastatic renal-cell carcinoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GROWTH-FACTOR ANTIBODY; CARBONIC-ANHYDRASE-IX; TUMOR-SUPPRESSOR GENE; 5-YEAR FOLLOW-UP; PHASE-III TRIAL; INTERFERON-ALPHA; SUBCUTANEOUS INTERLEUKIN-2; RADIOFREQUENCY ABLATION; DOSE INTERLEUKIN-2; PROGNOSTIC-FACTORS C1 [Michaelson, M. Dror] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Iliopoulos, Othon] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [McGovern, Francis J.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [McDermott, David F.] Harvard Univ, Sch Med, Dept Hematol Oncol, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Michaelson, M. Dror; Iliopoulos, Othon; McDermott, David F.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [McGovern, Francis J.] Harvard Univ, Sch Med, Dept Surg, Boston, MA USA. [Harisinghani, Mukesh G.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA USA. [Oliva, Esther] Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. RP Michaelson, MD (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. NR 53 TC 4 Z9 4 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 MAY 29 PY 2008 VL 358 IS 22 BP 2389 EP 2396 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 307GF UT WOS:000256306700011 PM 18509125 ER PT J AU You, FL Roberts, LA Kang, SP Nunes, RA Dias, C Iglehart, JD Solomon, NA Friedman, PN Harris, LN AF You, Fanglei Roberts, Lisa A. Kang, S. Peter Nunes, Raquel A. Dias, Cinara Iglehart, J. Dirk Solomon, Natalie A. Friedman, Paula N. Harris, Lyndsay N. TI Low-level expression of HER2 and CK19 in normal peripheral blood mononuclear cells: relevance for detection of circulating tumor cells SO JOURNAL OF HEMATOLOGY & ONCOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; BREAST-CANCER PATIENTS; BONE-MARROW MICROMETASTASES; PROGNOSTIC-SIGNIFICANCE; POSITIVE CELLS; METASTASES; CARCINOMA; AMPLIFICATION; CHEMOTHERAPY; SENSITIVITY AB Background: Detection of circulating tumor cells (CTC) in the blood of cancer patients may have prognostic and predictive significance. However, background expression of 'tumor specific markers' in peripheral blood mononuclear cells (PBMC) may confound these studies. The goal of this study was to identify the origin of Cytokeratin 19 (CK19) and HER-2 signal in PBMC and suggest an approach to enhance techniques involved in detection of CTC in breast cancer patients. Methods: PBMC from healthy donors were isolated and fractionated into monocytes, lymphocytes, natural killer cells/granulocytes and epithelial populations using immunomagnetic selection and fluorescent cell-sorting for each cell type. RNA isolated from each fraction was analyzed for CK19, HER2 and Beta 2 microglobulin (B2M) using real-time qRT-PCR. Positive selection for epithelial cells and negative selection for NK/granulocytes were used in an attempt to reduce background expression of CK19 and HER2 markers. Results: In normal PBMC, CK19 was expressed in the lymphocyte population while HER-2 expression was highest in the NK/granulocyte population. Immunomagnetic selection for epithelial cells reduced background CK19 signal to a frequency of <5% in normal donors. Using negative selection, the majority (74-98%) of HER2 signal could be removed from PBMC. Positive selection methods are variably effective at reducing these background signals. Conclusion: We present a novel method to improve the specificity of the traditional method of detecting CTC by identifying the source of the background signals and reducing them by negative immunoselection. Further studies are warranted to improve sensitivity and specificity of methods of detecting CTC will prove to be useful tools for clinicians in determining prognosis and monitoring treatment responses of breast cancer patients. C1 [Roberts, Lisa A.; Solomon, Natalie A.; Friedman, Paula N.] Abbott Mol Inc, Des Plaines, IL 60018 USA. [You, Fanglei; Nunes, Raquel A.; Dias, Cinara; Iglehart, J. Dirk] Dana Farber Canc Inst, Dept Canc Biol Adult Oncol, Boston, MA 02115 USA. [Iglehart, J. Dirk] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Kang, S. Peter; Harris, Lyndsay N.] Yale Univ, Sch Med, Sect Med Oncol, Yale Canc Ctr, New Haven, CT 06520 USA. RP Solomon, NA (reprint author), Abbott Mol Inc, 1300 E Touhy Ave, Des Plaines, IL 60018 USA. EM fangleiyou@yahoo.com; Lisa.Roberts@abbott.com; soonmo.kang@yale.edu; Raquelnunes2@yahoo.com; diascinara@yahoo.com; Jiglehart@partnes.org; natalie.solomon@abbott.com; pfriedman@uchicago.edu; lyndsay.harris@yale.edu FU Dana-Farber Harvard Cancer Center SPORE in Breast Cancer [DAMD17-01-1-0220] FX Support provided by the Dana-Farber Harvard Cancer Center SPORE in Breast Cancer, Grant #DAMD17-01-1-0220 NR 31 TC 16 Z9 16 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-8722 J9 J HEMATOL ONCOL JI J. Hematol. Oncol. PD MAY 28 PY 2008 VL 1 AR 2 DI 10.1186/1756-8722-1-2 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 521GY UT WOS:000271909800002 PM 18577250 ER PT J AU Dinov, ID Rubin, D Lorensen, W Dugan, J Ma, J Murphy, S Kirschner, B Bug, W Sherman, M Floratos, A Kennedy, D Jagadish, HV Schmidt, J Athey, B Califano, A Musen, M Altman, R Kikinis, R Kohane, I Delp, S Parker, DS Toga, AW AF Dinov, Ivo D. Rubin, Daniel Lorensen, William Dugan, Jonathan Ma, Jeff Murphy, Shawn Kirschner, Beth Bug, William Sherman, Michael Floratos, Aris Kennedy, David Jagadish, H. V. Schmidt, Jeanette Athey, Brian Califano, Andrea Musen, Mark Altman, Russ Kikinis, Ron Kohane, Isaac Delp, Scott Parker, D. Stott Toga, Arthur W. TI iTools: A Framework for Classification, Categorization and Integration of Computational Biology Resources SO PLOS ONE LA English DT Article AB The advancement of the computational biology field hinges on progress in three fundamental directions - the development of new computational algorithms, the availability of informatics resource management infrastructures and the capability of tools to interoperate and synergize. There is an explosion in algorithms and tools for computational biology, which makes it difficult for biologists to find, compare and integrate such resources. We describe a new infrastructure, iTools, for managing the query, traversal and comparison of diverse computational biology resources. Specifically, iTools stores information about three types of resources - data, software tools and web-services. The iTools design, implementation and resource meta - data content reflect the broad research, computational, applied and scientific expertise available at the seven National Centers for Biomedical Computing. iTools provides a system for classification, categorization and integration of different computational biology resources across space-and-time scales, biomedical problems, computational infrastructures and mathematical foundations. A large number of resources are already iTools-accessible to the community and this infrastructure is rapidly growing. iTools includes human and machine interfaces to its resource meta-data repository. Investigators or computer programs may utilize these interfaces to search, compare, expand, revise and mine meta-data descriptions of existent computational biology resources. We propose two ways to browse and display the iTools dynamic collection of resources. The first one is based on an ontology of computational biology resources, and the second one is derived from hyperbolic projections of manifolds or complex structures onto planar discs. iTools is an open source project both in terms of the source code development as well as its meta-data content. iTools employs a decentralized, portable, scalable and lightweight framework for long-term resource management. We demonstrate several applications of iTools as a framework for integrated bioinformatics. iTools and the complete details about its specifications, usage and interfaces are available at the iTools web page http://iTools.ccb.ucla.edu. C1 [Dinov, Ivo D.; Ma, Jeff; Parker, D. Stott; Toga, Arthur W.] Univ Calif Los Angeles, Ctr Computat Biol, Los Angeles, CA 90095 USA. [Kirschner, Beth; Jagadish, H. V.; Athey, Brian] Univ Michigan, Natl Ctr Integrat Biomed Informat, Ann Arbor, MI USA. [Floratos, Aris; Califano, Andrea] Columbia Univ, Natl Ctr Multi Scale Study Cellular Networks, New York, NY USA. [Rubin, Daniel; Musen, Mark] Stanford Univ, Natl Ctr Biomed Ontol, Stanford, CA USA. [Dugan, Jonathan; Sherman, Michael; Schmidt, Jeanette; Altman, Russ; Delp, Scott] Stanford Univ, Ctr Phys based Simulat Biol Structures, Stanford, CA USA. [Lorensen, William; Kikinis, Ron] Harvard Univ, Natl Alliance Med Imaging Comput, Cambridge, MA USA. [Murphy, Shawn; Kohane, Isaac] Harvard Univ, Informat Integrat Biol Bedside, Cambridge, MA USA. [Kennedy, David] Massachusetts General Hosp, Neurosci Ctr, Boston, MA USA. [Bug, William] Univ Calif San Diego, Natl Ctr Microscopy Imag Res, San Diego, CA USA. RP Dinov, ID (reprint author), Univ Calif Los Angeles, Ctr Computat Biol, Los Angeles, CA 90095 USA. EM toga@loni.ucla.edu RI Califano, Andrea/F-7239-2012; Kohane, Isaac Kohane/K-3716-2012; OI Kohane, Isaac Kohane/0000-0003-2192-5160; Athey, Brian/0000-0002-9793-535X; Dinov, Ivo/0000-0003-3825-4375 FU National Institutes of Health [U54-RR021813, U54-DA021519, U54-CA121852, U54-HG004028, U54-GM072970, U54-EB005149, U54-LM008748] FX This work was funded by the National Institutes of Health through the NIH Roadmap for Medical Research, Grants U54-RR021813 (CCB), U54-DA021519 (NCIBI), U54-CA121852 (MAGNet), U54-HG004028 (NCBO), U54-GM072970 (Simbios), U54-EB005149 (NA-MIC) and U54-LM008748 (I2B2). Information on the National Centers for Biomedical Computing can be obtained from nihroadmap.nih.gov/bioinformatics and www.NCBCs.org. NR 24 TC 14 Z9 14 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 28 PY 2008 VL 3 IS 5 AR e2265 DI 10.1371/journal.pone.0002265 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 391XW UT WOS:000262268500012 PM 18509477 ER PT J AU Maisel, WH Kramer, DB AF Maisel, William H. Kramer, Daniel B. TI Implantable cardioverter-defibrillator lead performance SO CIRCULATION LA English DT Editorial Material ID TERM-FOLLOW-UP; FAILURE C1 [Maisel, William H.] Beth Israel Deaconess Med Ctr, Med Device Safety Inst, Dept Med, Boston, MA 02215 USA. [Kramer, Daniel B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Maisel, WH (reprint author), Beth Israel Deaconess Med Ctr, Med Device Safety Inst, Dept Med, 185 Pilgrim Rd,Baker 4, Boston, MA 02215 USA. EM wmaisel@bidmc.harvard.edu NR 13 TC 37 Z9 38 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 MAY 27 PY 2008 VL 117 IS 21 BP 2721 EP 2723 DI 10.1161/CIRCULATIONAHA.108.776807 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700001 PM 18506015 ER PT J AU Baruch, L Agarwal, S Gupta, B Haynos, A Eng, C AF Baruch, Lawrence Agarwal, Sanjay Gupta, Bhanu Haynos, Anne Eng, Calvin TI Direct LDL measurement: Friend or foe? SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Baruch, Lawrence; Agarwal, Sanjay; Gupta, Bhanu; Haynos, Anne; Eng, Calvin] James J Peters VA Med Cntr, Bronx, NY 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 MAY 27 PY 2008 VL 117 IS 21 MA 84 BP E428 EP E428 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700102 ER PT J AU Bradley, SM Veenstra, DL AF Bradley, Steven M. Veenstra, David L. TI Cost-effectiveness of ultrafiltration for acute decompensated heart failure: A decision model approach SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Bradley, Steven M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Veenstra, David L.] 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 MAY 27 PY 2008 VL 117 IS 21 MA 130 BP E438 EP E438 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700147 ER PT J AU Bushnell, C Fagan, S Frankel, M Goldstein, LB Gorelick, P Johnston, SC Sacco, R Schwamm, L Williams, L Zorowitz, R Peterson, E AF Bushnell, Cheryl Fagan, Susan Frankel, Michael Goldstein, Larry B. Gorelick, Philip Johnston, S. C. Sacco, Ralph Schwamm, Lee Williams, Linda Zorowitz, Richard Peterson, Eric TI Gender differences in secondary prevention medication persistence following stroke SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Bushnell, Cheryl] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Fagan, Susan] Univ Georgia, Med Coll Georgia, Augusta, GA USA. [Frankel, Michael] Emory Univ, Atlanta, GA 30322 USA. [Goldstein, Larry B.; Peterson, Eric] Duke Univ, Med Ctr, Durham, NC USA. [Gorelick, Philip] Univ Illinois, Chicago, IL USA. [Johnston, S. C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Sacco, Ralph] Univ Miami, Miami, FL 33152 USA. [Schwamm, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Williams, Linda] Indiana Univ, Indianapolis, IN 46204 USA. [Zorowitz, Richard] Johns Hopkins Bayview Hosp, Baltimore, MD 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 MAY 27 PY 2008 VL 117 IS 21 MA 37 BP E418 EP E418 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700057 ER PT J AU DeVore, A Blankstein, R Arnsdorf, M Bakris, GL Sorrentino, MJ AF DeVore, Adam Blankstein, Ron Arnsdorf, Morton Bakris, George L. Sorrentino, Matthew J. TI Level of education and type of insurance but not race predict control of hypertension in a diverse, high-risk population. Data from the University of Chicago study of hypertension awareness, treatment, and control SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [DeVore, Adam] Brigham & Womens Hosp, Boston, MA 02115 USA. [Blankstein, Ron] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Arnsdorf, Morton; Bakris, George L.; Sorrentino, Matthew J.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. NR 0 TC 0 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 MAY 27 PY 2008 VL 117 IS 21 MA 141 BP E441 EP E441 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700158 ER PT J AU Fihn, SD Vaughan-Sarrazin, M Lowy, E Popescu, I Maynard, C Rosenthal, GE Sales, AE Rumsfeld, J Jesse, R Almenoff, P Fleming, B Kussman, M AF Fihn, Stephan D. Vaughan-Sarrazin, Mary Lowy, Elliott Popescu, Ioana Maynard, Charles Rosenthal, Gary E. Sales, Anne E. Rumsfeld, John Jesse, Robert Almenoff, Peter Fleming, Barbara Kussman, Michael TI Trends in mortality following acute myocardial infarction in the veterans health administration and medicare funded hospitals SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Fihn, Stephan D.; Maynard, Charles] Univ Washington, Seattle, WA 98195 USA. [Fihn, Stephan D.; Lowy, Elliott; Maynard, Charles] VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Vaughan-Sarrazin, Mary; Popescu, Ioana; Rosenthal, Gary E.] Univ Iowa, Iowa City, IA USA. [Vaughan-Sarrazin, Mary; Popescu, Ioana; Rosenthal, Gary E.] Iowa City VA Med Cntr, Iowa City, IA USA. [Sales, Anne E.] Univ Alberta, Edmonton, AB, Canada. [Rumsfeld, John] Univ Colorado, Denver, CO 80202 USA. [Rumsfeld, John] Denver VA Med Cntr, Denver, CO 80202 USA. [Jesse, Robert; Almenoff, Peter; Fleming, Barbara; Kussman, Michael] Dept Vet Affairs, Washington, DC USA. RI Sales, Anne/D-9678-2012; Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 27 PY 2008 VL 117 IS 21 MA 129 BP E438 EP E438 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700146 ER PT J AU Gropen, T Boden-Albala, B Kwiatkowski, T Lennihan, L Lukovits, TG Panagos, P Selim, M Day, D Magdon-Ismail, Z Melluzzo, S Schwamm, LH AF Gropen, Toby Boden-Albala, Bernadette Kwiatkowski, Thomas Lennihan, Laura Lukovits, Timothy G. Panagos, Peter Selim, Magdy Day, David Magdon-Ismail, Zainab Melluzzo, Shannon Schwamm, Lee H. TI Implementation of the stroke systems of care model: Preliminary work from The Northeast Cerebrovascular Consortium (NECC) SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Gropen, Toby] Long Isl Coll Hosp, Brooklyn, NY 11201 USA. [Boden-Albala, Bernadette] Columbia Presbyterian Med Ctr, New York, NY USA. [Kwiatkowski, Thomas] Long Isl Jewish Med Cntr, Long Isl City, NY USA. [Lennihan, Laura] Columbia Univ, New York, NY USA. [Lukovits, Timothy G.] Dartmouth Hitchcock Med Cntr, Lebanon, NH USA. [Panagos, Peter] Rhode Isl Hosp, Providence, RI USA. [Selim, Magdy] Beth Israel Deaconess Med Cntr, Boston, MA USA. [Day, David; Melluzzo, Shannon] Amer Stroke Associat, W Springfield, MA USA. [Magdon-Ismail, Zainab] Amer Stroke Associat, Albany, NY USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Boden Albala, Bernadette/J-5703-2013 OI Boden Albala, Bernadette/0000-0001-5664-2342 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 MAY 27 PY 2008 VL 117 IS 21 MA 85 BP E428 EP E428 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700103 ER PT J AU Heidenreich, P Sahay, A Shlipak, M Van Osteyerean, D Ansari, M Massie, B AF Heidenreich, Paul Sahay, Anju Shlipak, Michael Van Osteyerean, Denise Ansari, Maria Massie, Barry TI Cost-effectiveness of a nurse based clinic to initate beta-blocker therapy in patients with heart failure SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Heidenreich, Paul] VA Palo Alto HCS, Palo Alto, CA USA. [Shlipak, Michael; Massie, Barry] San Francisco VA Med Ctr, San Francisco, CA USA. [Van Osteyerean, Denise] Portland VA Med Cntr, Portland, OR USA. [Ansari, Maria] Kaiser Permanente, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 27 PY 2008 VL 117 IS 21 MA 112 BP E434 EP E434 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700130 ER PT J AU Ho, PM Maddox, TM Shetterly, SM Rumsfeld, JS Magid, DJ AF Ho, P. Michael Maddox, Thomas M. Shetterly, Susan M. Rumsfeld, John S. Magid, David J. TI The costs of healthcare associated with medication non-adherence SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Ho, P. Michael; Maddox, Thomas M.; Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Shetterly, Susan M.; Magid, David J.] Kaiser Pemanente Colorado, Denver, CO USA. NR 0 TC 4 Z9 4 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 MAY 27 PY 2008 VL 117 IS 21 MA 228 BP E460 EP E460 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700243 ER PT J AU Ho, PM Maddox, TM Ross, C Magid, DJ Rumsfeld, JS AF Ho, P. Michael Maddox, Thomas M. Ross, Colleen Magid, David J. Rumsfeld, John S. TI Medication adherence is associated with lower Framingham 10-year Chd risk score SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Ho, P. Michael; Maddox, Thomas M.; Rumsfeld, John S.] DENVER VA MED CTR, Denver, CO USA. [Ross, Colleen; Magid, David J.] Kaiser Permanente Colorado, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 27 PY 2008 VL 117 IS 21 MA 110 BP E434 EP E434 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700128 ER PT J AU Lei, Y Arnold, SV Morrow, DA Chan, P Mahoney, EM Wang, KJ Robertus, K Case, R Kempf, JA Cohen, DJ AF Lei, Yang Arnold, Suzanne V. Morrow, David A. Chan, Paul Mahoney, Elizabeth M. Wang, Kaijun Robertus, Katherine Case, Rebekah Kempf, Judith A. Cohen, David J. TI Impact of angina frequency on medical resource utilization and cost after non-ST elevation acute coronary syndromes: Insights from the MERLIN-TIMI 36 randomized trial SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Lei, Yang; Arnold, Suzanne V.; Chan, Paul; Mahoney, Elizabeth M.; Wang, Kaijun; Robertus, Katherine; Case, Rebekah; Cohen, David J.] Mid Amer Heart Inst, Kansas City, KS USA. [Kempf, Judith A.] CV Therapeut, Palo Alto, CA USA. [Morrow, David A.] Brigham & Womens Hosp, TIMI Study Grp, 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 MAY 27 PY 2008 VL 117 IS 21 MA 259 BP E467 EP E467 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700274 ER PT J AU Maddox, TM Plomondon, ME Ho, PM Rumsfeld, JS AF Maddox, Thomas M. Plomondon, Mary E. Ho, P. M. Rumsfeld, John S. TI Secondary prevention among patients with non-obstructive and obstructive CAD SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Maddox, Thomas M.; Plomondon, Mary E.; Ho, P. M.; Rumsfeld, John S.] Univ Colorado, Hlth Sci Ctr, Denver VAMC, Denver, CO 80202 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 MAY 27 PY 2008 VL 117 IS 21 MA 251 BP E465 EP E465 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700266 ER PT J AU Mahoney, EM Wang, KW Arnold, SV Wiviott, SD McCollam, PL Riesmeyer, J Plat, F Sankyo, D Cohen, DJ AF Mahoney, Elizabeth M. Wang, Kaijun Arnold, Suzanne V. Wiviott, Stephen D. McCollam, Patrick L. Riesmeyer, Jeffrey Plat, Francis Sankyo, Daiichi Cohen, David J. TI Index, follow-up and total hospitalization costs in patients with acute coronary syndromes undergoing planned percutaneous coronary intervention treated with prasugrel vs. clopidogrel in the TRITON-TIMI 38 trial SO CIRCULATION LA English DT Meeting Abstract CT 9th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY APR 30-MAY 02, 2008 CL Baltimore, MD C1 [Mahoney, Elizabeth M.; Wang, Kaijun; Arnold, Suzanne V.; Cohen, David J.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Wiviott, Stephen D.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [McCollam, Patrick L.; Riesmeyer, Jeffrey] Eli Lilly & Co, Indianapolis, IN 46285 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 MAY 27 PY 2008 VL 117 IS 21 MA 53 BP E421 EP E421 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 305EN UT WOS:000256160700073 ER EF