tbuckley/cabot-search huggingface dataset:
M38 Health Professionals' Views Of Tuberculosis Cohort Audit In North West England
Authors: S. Wallis, K. Jehan, M. Woodhead, P. Cleary, K. Dee, S. Farrow, P. McMaster, C. Wake, J. Walker, S. Squire
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> Tuberculosis cohort audit (TBCA) was introduced across the North West in 2012 as recommended by NICE. The approach taken and the outcome measures of the 1,515 TB cases reviewed are presented in a companion abstract. TBCA over a large geographical area has not undergone formal qualitative evaluation in the UK. We conducted a qualitative evaluation to explore perceptions about implementation and impact of TBCA in the North West. <h3>Methods</h3> One researcher conducted face to face, semi-structured, recorded interviews between 06/01/14 and14/03/14 with 26 purposively sampled respondents from three groups involved in TBCA: (a) TB nurse specialists; (b) Consultant physicians; (c) Public health practitioners. Transcripts were analysed descriptively and thematically using the Framework Method. Themes were triangulated with eight key informants from the TBCA Steering Group. <h3>Results</h3> Four themes were identified: <i>Preconceptions:</i> Participants were optimistic about the potential of audit to improve practice but worried about time demands and scrutiny from colleagues. <i>Experience of TBCA:</i> All groups felt engaged and appreciated TBCA. Nurses requested more engagement from consultant colleagues. Fears about time demands and scrutiny were not realised. <i>Changes as a result of TBCA</i>: Improvements to practice were identified including harmonisation of approaches, increased HIV testing, and improved documentation. TBCA was felt to provide peer support and learning through discussion and a no-blame atmosphere. <i>Looking Ahead: </i>Suggestionsfor further improvement were captured, such as more in-depth discussion around complex cases. If TBCA were to be discontinued (e.g. because of funding contraints), adverse consequences were predicted: e.g. disappointed and disenfranchised professionals, financial and patient harms. <h3>Conclusions</h3> Overall, TBCA in the North West has led to the development of a unique and valuable community of practice. The interchange of experience and ideas across a large number of teams and professionals has enhanced mutual respect between different roles and a shared sense of purpose. TBCA is appreciated by health professionals who participate. Continuing success will require increased engagement of consultant physicians and public health practitioners, a secure an ongoing funding stream and establishment of reporting mechanisms within the new commissioning structures.
Intragraft T cell receptor transcript expression in human renal allografts.
Authors: M Pavlakis, M L Lipman, T B Strom
Journal: Journal of the American Society of Nephrology (1995)

Allograft rejection is a T cell-dependent process. It is not known whether rejection is mediated by a limited number of T cell clones or by a polyclonal population of T cells. Several studies attempting to answer this question using molecular techniques to analyze the T cell receptor (TCR) population have reached conflicting conclusions. Reverse transcription-assisted polymerase chain reaction (PCR) has been used to quantify T cell infiltration and examine TCR heterogeneity in kidney transplant biopsies from patients experiencing graft dysfunction. RNA from snap-frozen biopsies gathered on 23 transplant patients was reverse transcribed to cDNA and used as the template for PCR. The constant region gene of the TCR beta chain (C beta), 22 different variable region genes of the TCR beta chain (V beta) and the constitutively expressed glyceraldehyde phosphate dehydrogenase (GAPD) gene were amplified. T cell infiltration, as estimated by the ratio of reverse-transcribed cDNA C beta/glyceraldehyde phosphate dehydrogenase, was significantly higher in acute cellular rejection (ACR) (2.25) than in nonrejection (NR) (0.40, P < 0.05). The number of intragraft V beta families was higher in chronic rejection and acute cellular rejection (18 and 16.4, respectively) than in nonrejection (8.7). Five serial biopsies from two patients progressing to immunologic graft loss showed an increase in the number of intragraft V beta families. The finding of increased numbers of TCR V beta families amplified from acutely and chronically rejecting grafts as compared with nonrejecting graft supports the hypothesis that, at the time of clinically apparent rejection, there is a polyclonal infilitration of T cells.
Guidelines on the management of common bile duct stones (CBDS)
Authors: E J Williams, J Green, I Beckingham, R Parks, D Martin, M Lombard
Journal: Gut (2008)

The last 30 years have seen major developments in the management of gallstone-related disease, which in the United States alone costs over 6 billion dollars per annum to treat. Endoscopic retrograde cholangiopancreatography (ERCP) has become a widely available and routine procedure, whilst open cholecystectomy has largely been replaced by a laparoscopic approach, which may or may not include laparoscopic exploration of the common bile duct (LCBDE). In addition, new imaging techniques such as magnetic resonance cholangiography (MR) and endoscopic ultrasound (EUS) offer the opportunity to accurately visualise the biliary system without instrumentation of the ducts. As a consequence clinicians are now faced with a number of potentially valid options for managing patients with suspected CBDS. It is with this in mind that the following guidelines have been written.
Effect of LDL Cholesterol and Treatment With Losartan on End-Stage Renal Disease in the RENAAL Study
Authors: Andrew M. Tershakovec, William F. Keane, Zhongxin Zhang, Paulette A. Lyle, Gerald B. Appel, Janet B. McGill, Hans-Henrik Parving, Mark E. Cooper, Shahnaz Shahinfar, Barry M. Brenner
Journal: Diabetes Care (2008)

Renal pathology and dyslipidemia commonly coexist. Treatments that lower albuminuria/proteinuria may lower lipids, but it is not known whether lipid lowering independent of lessening albuminuria/proteinuria slows progression of kidney disease. We examined the association between LDL cholesterol levels and treatment with losartan on end-stage renal disease (ESRD). Lipid levels and albuminuria measurements were obtained at baseline and at year 1 in a post hoc analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study, which compared the effects of losartan- versus placebo-based antihypertensive therapy in patients with type 2 diabetes and nephropathy. LDL cholesterol lowering was associated with a lower risk of ESRD; however, this seemed to be largely an association with the reduction in albuminuria.
Reduced Ventricular Response Irregularity Is Associated With Increased Mortality in Patients With Chronic Atrial Fibrillation
Authors: Akira Yamada, Junichiro Hayano, Seiichiro Sakata, Akiyoshi Okada, Seiji Mukai, Nobuyuki Ohte, Genjiro Kimura
Journal: Circulation (2000)

Background —Variations in the ventricular response interval (VRI) during atrial fibrillation (AF) may be reduced in patients with adverse clinical outcomes. The properties of VRI dynamics associated with prognosis remain undetermined. Methods and Results —In 107 patients with chronic AF (age, 64±9 years), we analyzed a 24-hour ambulatory ECG for VRI variability (SD, SD of successive differences, and SD of 5-minute averages) and VRI irregularity (Shannon entropy of histogram, symbolic dynamics, and approximate entropy of beat-to-beat and minute-to-minute fluctuations [ApEn b-b and ApEn m-m ]). During a follow-up period of 33±16 months, 18 patients died (17%), 9 from cardiac causes, 7 from fatal strokes, and 2 from malignancies. Reductions in all VRI variability and irregularity measures were associated with an increased risk for cardiac death but not for fatal stroke. A significant association with cardiac death was also found for ejection fraction (relative risk, 1.10; 95% confidence interval [CI], 1.04 to 1.17, per 1% decrement) and ischemic AF (relative risk, 6.52; 95% CI, 1.62 to 26.3). After adjustment for these clinical variables, all irregularity measures except symbolic dynamics had predictive value (relative risks [95% CIs] per 1SD decrement: Shannon entropy of histogram, 2.03 [1.14 to 3.61]; ApEn b-b , 1.72 [1.14 to 2.60]; and ApEn m-m , 1.90 [1.03 to 3.52]); however, the predictive power of variability measures was no longer significant. When the patients were stratified with the 33rd and 67th percentile values of ApEn b-b (1.83 and 1.94, respectively), the 5-year cardiac mortality rates for the upper, middle, and lower tertiles were 0%, 13%, and 43%, respectively (log-rank test, P =0.04). Conclusions —Reduced VRI irregularity in a 24-hour ambulatory ECG has an independent prognostic value for cardiac mortality during long-term follow-up in patients with chronic AF.
THE HALF-LIFE OF PASSIVELY ACQUIRED ANTIBODY GLOBULIN MOLECULES IN INFANTS
Authors: Alexander S. Wiener
Journal: The Journal of Experimental Medicine (1951)

By following the titer of passively acquired Rh antibodies in newborn infants, it is calculated that the half-life of the placenta-passing Rh antibody molecule is approximately 30 days. Evidence is offered that this estimate applies not only to placenta-passing Rh antibodies, but also to other placenta-passing antibodies, and not improbably to serum gamma globulin molecules in general. Studies on the fate of free Rh antibodies in erythroblastotic babies show that these antibodies often are eliminated no more rapidly in Rh-positive babies than in Rh-negative babies. On the other hand, incompatible alpha and beta antibodies, as a rule, are quickly neutralized and eliminated from the body of newborn infants. These observations provide one explanation for the lower incidence of erythroblastosis due to A-B sensitization in comparison with cases resulting from Rh sensitization.
Prognostic Analysis of Early Lymphocyte Recovery in Patients with Advanced Breast Cancer Receiving High-Dose Chemotherapy with an Autologous Hematopoietic Progenitor Cell Transplant
Authors: Yago Nieto, Elizabeth J. Shpall, Ian K. McNiece, Samia Nawaz, Julie Beaudet, Steve Rosinski, Julie Pellom, Victoria Slat-Vasquez, Peter A. McSweeney, Scott I. Bearman, James Murphy, Roy B. Jones
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of this study was to evaluate the prognostic effect of early posttransplant lymphocyte recovery in patients with advanced breast cancer receiving high-dose chemotherapy with autologous hematopoietic progenitor cell transplantation. Experimental Design: We analyzed the effect of the absolute lymphocyte count on day +15 posttransplant on freedom from relapse and overall survival in patients with high-risk primary breast cancer or metastatic breast cancer, enrolled between 1990 and 2001 in prospective high-dose chemotherapy trials, using a uniform regimen of cyclophosphamide, cisplatin, and 1,3-bis(2-chloroethyl)-1-nitrosourea. Results: Four hundred and seventy-six patients (264 high-risk primary breast cancer and 212 metastatic breast cancer patients) were evaluated at median follow-up of 8 years (range, 1.5–11 years). The disease-free survival and overall survival rates in the high-risk primary breast cancer group were 67% and 70%, respectively. Patients with metastatic breast cancer patients had 21.8% disease-free survival and 31.5% overall survival rates. Day +15 absolute lymphocyte count correlated with freedom from relapse (P = 0.007) and overall survival (P = 0.04) in the metastatic breast cancer group, but not in the high-risk primary breast cancer group (P = 0.5 and 0.8, respectively). The prognostic effect of absolute lymphocyte count in metastatic breast cancer was restricted to those patients receiving unmanipulated peripheral blood progenitor cells (P = 0.04). In contrast, absolute lymphocyte count had no significant effect in those metastatic breast cancer patients receiving bone marrow or a CD34-selected product. In multivariate analyses, the prognostic effect of day +15 absolute lymphocyte count in metastatic breast cancer was independent of other predictors, such as disease status, pre-high-dose chemotherapy treatment, number of tumor sites, or HER2. Conclusions: Early lymphocyte recovery is an independent outcome predictor in metastatic breast cancer patients receiving high-dose chemotherapy and an autologous peripheral blood progenitor cell transplant. These observations suggest that immune strategies targeting minimal posttransplant residual disease may prove worthwhile.
Antigen-dependent IgM-mediated enhancement of the sheep erythrocyte response in mice. Evidence for induction of B cells with specificities other than that of the injected antibodies
Authors: B Heyman, G Andrighetto, H Wigzell
Journal: The Journal of Experimental Medicine (1982)

Monoclonal or polyclonal IgM-anti-SRBC antibodies were used to enhance the anti-SRBC PFC response in mice. For potentiation to occur, the IgM antibodies must always be presented with the antigen for which they have specificity. No enhancement of anti-SRBC response above control levels was noted with either antibodies alone or with antibodies used together with non-cross-reacting antigens. The degree of enhancement was independent of whether only one or several different monoclonal IgM antibodies were used. Likewise, the fine specificity variation among the antibody clones failed to influence the anti- SRBC potentiation, which was shown to vary only with the amount of IgM bound to SRBC measured by hemolytic titers. The response against epitopes on the SRBC other than those the IgM recognized was also enhanced. This was determined by injecting SRBC and a monoclonal anti-SRBC IgM that did not crossreact with GRBC into mice, and measuring the response against both antigens. Normally SRBC and GRBC cross- react at the B cell level to approximately 30 percent, and in this experiment they did so both in the control group and in the IgM group. Using antigens that only cross-react significantly at the T cell level (SRBC and HRBC), IgM-antibodies would only enhance the anti-HRBC response if SRBC and HRBC were inoculated together. No anti-HRBC potentiation was noted when antibodies were injected alone or together with either SRBC or HRBC. The data indicate that the constant part of the IgM molecule is of major importance in determining its enhancing properties in acute IgM-mediated potentiation of the immune responses. No evidence was obtained for a decisive role of variable regions. Furthermore, no general B cell activating properties of either mono- or polyclonal IgM-anti-SRBC antibodies could be demonstrated.
Tuberculous tonsillitis in a patient receiving etanercept treatment
Authors: C T Derk
Journal: Annals of the Rheumatic Diseases (2003)

Since the approval by the Food and Drug Administration (FDA) of tumour necrosis factor α antagonists, infections have accounted for 21% of the adverse events reported to the FDA for etanercept and 20% of those reported for infliximab.1,2

As of May 2001, from approximately 147 000 subjects receiving infliximab treatment, 70 patients have been reported to have developed active tuberculosis. Of these, 52% presented with extrapulmonary tuberculosis while 24% presented with disseminated disease.3 As of April 2001, from approximately 102 000 subjects receiving etanercept treatment, nine patients have been reported to have developed active tuberculosis.4 With the …
Effects of Dietary Composition on Energy Expenditure During Weight-Loss Maintenance
Authors: Cara B. Ebbeling, Janis F. Swain, Henry A. Feldman, William W. Wong, David L. Hachey, Erica Garcia-Lago, David S. Ludwig
Journal: JAMA (2012)

Reduced energy expenditure following weight loss is thought to contribute to weight gain. However, the effect of dietary composition on energy expenditure during weight-loss maintenance has not been studied.To examine the effects of 3 diets differing widely in macronutrient composition and glycemic load on energy expenditure following weight loss.A controlled 3-way crossover design involving 21 overweight and obese young adults conducted at Children's Hospital Boston and Brigham and Women's Hospital, Boston, Massachusetts, between June 16, 2006, and June 21, 2010, with recruitment by newspaper advertisements and postings.After achieving 10% to 15% weight loss while consuming a run-in diet, participants consumed an isocaloric low-fat diet (60% of energy from carbohydrate, 20% from fat, 20% from protein; high glycemic load), low-glycemic index diet (40% from carbohydrate, 40% from fat, and 20% from protein; moderate glycemic load), and very low-carbohydrate diet (10% from carbohydrate, 60% from fat, and 30% from protein; low glycemic load) in random order, each for 4 weeks.Primary outcome was resting energy expenditure (REE), with secondary outcomes of total energy expenditure (TEE), hormone levels, and metabolic syndrome components.Compared with the pre-weight-loss baseline, the decrease in REE was greatest with the low-fat diet (mean [95% CI], -205 [-265 to -144] kcal/d), intermediate with the low-glycemic index diet (-166 [-227 to -106] kcal/d), and least with the very low-carbohydrate diet (-138 [-198 to -77] kcal/d; overall P = .03; P for trend by glycemic load = .009). The decrease in TEE showed a similar pattern (mean [95% CI], -423 [-606 to -239] kcal/d; -297 [-479 to -115] kcal/d; and -97 [-281 to 86] kcal/d, respectively; overall P = .003; P for trend by glycemic load < .001). Hormone levels and metabolic syndrome components also varied during weight maintenance by diet (leptin, P < .001; 24-hour urinary cortisol, P = .005; indexes of peripheral [P = .02] and hepatic [P = .03] insulin sensitivity; high-density lipoprotein [HDL] cholesterol, P < .001; non-HDL cholesterol, P < .001; triglycerides, P < .001; plasminogen activator inhibitor 1, P for trend = .04; and C-reactive protein, P for trend = .05), but no consistent favorable pattern emerged.Among overweight and obese young adults compared with pre-weight-loss energy expenditure, isocaloric feeding following 10% to 15% weight loss resulted in decreases in REE and TEE that were greatest with the low-fat diet, intermediate with the low-glycemic index diet, and least with the very low-carbohydrate diet.clinicaltrials.gov Identifier: NCT00315354.
Lithium Treatment of Depressed and Nondepressed Alcoholics
Authors: Walter Dorus
Journal: JAMA (1989)

We assessed the efficacy of lithium carbonate in the treatment of 457 male alcoholics in a double-blind, placebo-controlled Department of Veterans Affairs Cooperative Study. Alcoholics either without depression or with a history of major depression, current major depression, or dysthymic disorder were studied. Two hundred eighty-six alcoholics without depression and 171 alcoholics with depression began the 52-week outpatient study; 172 alcoholics (60.1%) without depression and 108 alcoholics (63.2%) with depression completed the study. Among both all alcoholics who began the study and a subgroup who completed the study, no significant differences between alcoholics who took lithium and those who took placebo were found for the following outcome measures: number of alcoholics abstinent, number of days of drinking, number of alcohol-related hospitalizations, changes in rating of severity of alcoholism, and change in severity of depression. Similarly, no significant differences were found when only the 82 alcoholics compliant in taking lithium and the 89 alcoholics compliant in taking placebo were considered. In our study, lithium treatment did not affect the course of alcoholism in either depressed or nondepressed alcoholics. (<i>JAMA</i>. 1989;262:1646-1652)
Crenolanib Inhibits the Drug-Resistant PDGFRA D842V Mutation Associated with Imatinib-Resistant Gastrointestinal Stromal Tumors
Authors: Michael C. Heinrich, Diana Griffith, Arin McKinley, Janice Patterson, Ajia Presnell, Abhijit Ramachandran, Maria Debiec-Rychter
Journal: Clinical Cancer Research (2012)

Abstract Purpose: To determine the potential of crenolanib, a potent inhibitor of PDGFRA, to treat malignancies driven by mutant PDGFRA. Experimental Design: The biochemical activity of crenolanib was compared with imatinib using a panel of PDGFRA-mutant kinases expressed in several different cell line models, including primary gastrointestinal stromal tumors (GIST) cells. The antiproliferative activity of crenolanib was also studied in several cell lines with PDGFRA-dependent growth. Results: Crenolanib was significantly more potent than imatinib in inhibiting the kinase activity of imatinib-resistant PDGFRA kinases (D842I, D842V, D842Y, DI842-843IM, and deletion I843). For example, crenolanib was 135-fold more potent than imatinib against D842V in our isogenic model system, with an IC50 of approximately 10 nmol/L. The relative potency of crenolanib was further confirmed in BaF3 and primary GIST cells expressing PDGFRA D842V. In contrast, imatinib was at least 10-fold more potent than crenolanib in inhibiting the V561D mutation. For all other tested PDGFRA mutations, crenolanib and imatinib had comparable potency. Conclusions: Crenolanib is a potent inhibitor of imatinib-resistant PDGFRA kinases associated with GIST, including the PDGFRA D842V mutation found in approximately 5% of GISTs. The spectrum of activity of crenolanib suggests that this drug is a type I inhibitor (inhibitor of activated conformation of kinase). Based in part on these results, a phase II clinical study of this agent to treat GIST with the PDGFRA D842V mutation has been initiated. Clin Cancer Res; 18(16); 4375–84. ©2012 AACR.
D<sub>2</sub> Receptor Genetic Variation and Clinical Response to Antipsychotic Drug Treatment: A Meta-Analysis
Authors: Jian-Ping Zhang, Todd Lencz, Anil K. Malhotra
Journal: American Journal of Psychiatry (2010)

Objective Several lines of evidence suggest that antipsychotic drug efficacy is mediated by dopamine type 2 (D2) receptor blockade. Therefore, it seems plausible that variation in the DRD2 gene is associated with clinical response to antipsychotic drug treatment. The authors conducted the first meta-analysis to examine the relationship between DRD2 polymorphisms and antipsychotic drug response. Method A MEDLINE search of articles available up to December 31, 2008, yielded 18 prospective studies examining DRD2 gene variation and antipsychotic response in schizophrenia patients; of which, 10 independent studies met criteria for inclusion. Clinical response to antipsychotic treatment was defined as a 50% reduction of either the Brief Psychiatric Rating Scale total score or Positive and Negative Syndrome Scale total score at approximately 8 weeks of follow-up evaluation. Odds ratio was the primary effect-size measure and computed for each polymorphism in each study. Sufficient data were available for two DRD2 polymorphisms: –141C Ins/Del and Taq1A. Results Six studies reported results for the –141C Ins/Del polymorphism (total sample size: N=687). The Del allele carrier was significantly associated with poorer antipsychotic drug response relative to the Ins/Ins genotype. Eight studies assessed the Taq1A polymorphism and antipsychotic response (total sample size: N=748). There was no significant difference in the response rate among A1 allele carriers relative to individuals with the A2/A2 genotype or A2 allele carriers relative to individuals with the A1/A1 genotype. Conclusions The DRD2 genetic variation is associated with clinical response to antipsychotic drug treatment. These data may provide proof-of-principle for pharmacogenetic studies in schizophrenia.