tbuckley/cabot-search huggingface dataset:
No Effect of Statin Therapy on Silent Myocardial Ischemia in Patients With Type 2 Diabetes Without Manifest Cardiovascular Disease
Authors: Edith D. Beishuizen, J. Wouter Jukema, Jouke T. Tamsma, Marcel A. van de Ree, J. Carel M. van der Vijver, Hein Putter, Arie C. Maan, A. Edo Meinders, Menno V. Huisman
Journal: Diabetes Care (2005)

OBJECTIVE—Coronary artery disease is the most important cause of mortality in patients with type 2 diabetes. We aimed to determine the prevalence of silent myocardial ischemia (SMI) and the effect of statin therapy on SMI in type 2 diabetic patients without manifest cardiovascular disease. RESEARCH DESIGN AND METHODS—A randomized, placebo-controlled, double-blind trial was performed in 250 patients with type 2 diabetes without manifest cardiovascular disease. Patients were given either 0.4 mg cerivastatin or placebo daily. In August 2001, when cerivastatin was withdrawn from the market, cerivastatin 0.4 mg was replaced by 20 mg simvastatin without deblinding the study. The primary end point was the change in ischemic episodes, duration, and burden as measured by 48-h ambulatory electrocardiography (AECG) over 2 years. RESULTS—At baseline, 47 of 233 (20%) evaluable ambulatory electrocardiograms showed evidence of ischemia. After 2 years, there was a trend toward more ischemia in both treatment groups, without significant differences between the changes in ischemic parameters (episodes P = 0.498; duration P = 0.697; burden P = 0.798) in the two treatment groups. Cardiovascular events occurred in 12 patients in the placebo group and in two patients in the statin group (P = 0.006). There was no relationship between these cardiovascular events and the presence of SMI at baseline. CONCLUSIONS—SMI occurred in 20% of type 2 diabetes patients without manifest cardiovascular disease. There was no effect from 2 years of statin therapy on SMI. In contrast, we observed a significantly lower cardiovascular event rate on statin therapy. AECG may not be a proper tool for risk stratification in patients with type 2 diabetes.
Apoptosis induced by vitamin A signaling is crucial for connecting the ureters to the bladder
Authors: Ekatherina Batourina, Sheaumei Tsai, Sarah Lambert, Preston Sprenkle, Renata Viana, Sonia Dutta, Terry Hensle, Fengwei Wang, Karen Niederreither, Andrew P McMahon, Thomas J Carroll, Cathy L Mendelsohn
Journal: Nature Genetics (2005)
Loss of Nix in Pdx1-deficient mice prevents apoptotic and necrotic β cell death and diabetes
Authors: Kei Fujimoto, Eric L. Ford, Hung Tran, Burton M. Wice, Seth D. Crosby, Gerald W. Dorn, Kenneth S. Polonsky
Journal: Journal of Clinical Investigation (2010)

Mutations in pancreatic duodenal homeobox (PDX1) are linked to human type 2 diabetes and maturity-onset diabetes of the young type 4. Consistent with this, Pdx1-haploinsufficient mice develop diabetes. Both apoptosis and necrosis of β cells are mechanistically implicated in diabetes in these mice, but a molecular link between Pdx1 and these 2 forms of cell death has not been defined. In this study, we introduced an shRNA into mouse insulinoma MIN6 cells to deplete Pdx1 and found that expression of proapoptotic genes, including NIP3-like protein X (Nix), was increased. Forced Nix expression in MIN6 and pancreatic islet β cells induced programmed cell death by simultaneously activating apoptotic and mitochondrial permeability transition–dependent necrotic pathways. Preventing Nix upregulation during Pdx1 suppression abrogated apoptotic and necrotic β cell death in vitro. In Pdx1-haploinsufficient mice, Nix ablation normalized pancreatic islet architecture, β cell mass, and insulin secretion and eliminated reactive hyperglycemia after glucose challenge. These results establish Nix as a critical mediator of β cell apoptosis and programmed necrosis in Pdx1-deficient diabetes.
Specific interaction of lymphocyte function-associated antigen 3 with CD2 can inhibit T cell responses.
Authors: G T Miller, P S Hochman, W Meier, R Tizard, S A Bixler, M D Rosa, B P Wallner
Journal: The Journal of Experimental Medicine (1993)

Accessory cell surface molecules, such as T cell antigen CD2 and its ligand lymphocyte function-associated antigen 3 (LFA-3; CD58), are critical costimulatory pathways for optimal T cell activation in response to antigens. Interaction of CD2 with cell surface LFA-3 not only increases T cell/accessory cell adhesion, but also induces signal transduction events involved in the regulation of T cell responses. In this report, we show that specific interactions of LFA-3 with CD2 can result in T cell unresponsiveness to antigenic or mitogenic stimuli in vitro. By deletion of certain regions of the extracellular domain of LFA-3, we localized the CD2 binding site to the first domain of LFA-3. We then demonstrated that a soluble, purified first domain-LFA-3/IgG1 fusion protein (LFA3TIP) interacts with CD2 and binds to the same CD2 epitope as purified multimeric or cell surface-expressed LFA-3. LFA3TIP inhibits tetanus toxoid, hepatitis B surface antigen, anti-CD3 mAb, Con A, and phytohemagglutinin P-induced T cell proliferation, as well as xenogeneic and allogeneic mixed lymphocyte reactions (MLR). Unlike anti-LFA-3 or anti-CD2 monoclonal antibodies (mAbs) which inhibit T cell responses by blocking LFA-3/CD2 binding, LFA3TIP is capable of rendering T cells unresponsive to antigenic stimuli in situations where T cell activation is independent of CD2/LFA-3 interactions. Furthermore, LFA3TIP, but not blocking anti-CD2 mAbs, is capable of inducing T cell unresponsiveness to secondary stimulation in allogeneic MLR. This inhibition of T cell responses by LFA3TIP occurs through a different mechanism from that of mAbs to LFA-3 or CD2.
The reliability of team-based primary data collectors for the collection of exposure and protective equipment use data in community sport: Table 1
Authors: R A Braham, C F Finch
Journal: British Journal of Sports Medicine (2004)

Objective: Reliable data allows for the generalisation of study findings to the wider population. The aim of this study was to assess the reliability of using community team based primary data collectors for the collection of exposure and protective equipment use data. Methods: Nine clubs (23 teams) from a metropolitan Australian Football league in Victoria each provided one primary data collector to monitor exposure and protective equipment use over a regular playing season. Four random audits of this data collection for each team were conducted throughout the regular playing season. The audits were compared with data collected by the club data collectors and the level of agreement assessed. Results: Although exposure data agreement was higher during competition and protective equipment use agreement higher during training, there was no significant difference in data collected by the primary data collectors and the random audits. Conclusions: The use of trained data collectors associated with Australian Football teams provides reliable information about player exposure and protective equipment use in community intervention studies.
Alcohol and Mortality
Authors: ARTHUR L. KLATSKY
Journal: Annals of Internal Medicine (1981)

We studied 10-year mortality in relation to baseline alcohol use habits among four groups of 2015 persons, well matched for age, sex, race, and cigarette smoking. Persons reporting daily use of two drinks or fewer fared best; the heaviest drinkers (six or more drinks) had a doubled mortality rate, and users of three to five drinks had a mortality rate approximately 50% higher. The nondrinkers had a mortality rate similar to that of users of three to five drinks per day. Cancer, cirrhosis, accidents, and nonmalignant respiratory conditions contributed significantly to the excess mortality of the heavier drinkers; coronary disease mortality was significantly higher among nondrinkers. Smoking intensity was a possible factor in the increased mortality of heavier drinkers, but the data were also compatible with the hypothesis that smoking and drinking are synergistic in the production of certain cancers and nonmalignant chronic respiratory illness. Other traits associated with alcohol use or abstinence are possible contributors to the excess mortality of both heavy drinkers and nondrinkers.
An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease
Authors: Anne E. Holland, Martijn A. Spruit, Thierry Troosters, Milo A. Puhan, Véronique Pepin, Didier Saey, Meredith C. McCormack, Brian W. Carlin, Frank C. Sciurba, Fabio Pitta, Jack Wanger, Neil MacIntyre, David A. Kaminsky, Bruce H. Culver, Susan M. Revill, Nidia A. Hernandes, Vasileios Andrianopoulos, Carlos Augusto Camillo, Katy E. Mitchell, Annemarie L. Lee, Catherine J. Hill, Sally J. Singh
Journal: European Respiratory Journal (2014)

Field walking tests are commonly employed to evaluate exercise capacity, assess prognosis and evaluate treatment response in chronic respiratory diseases. In recent years, there has been a wealth of new literature pertinent to the conduct of the 6-min walk test (6MWT), and a growing evidence base describing the incremental and endurance shuttle walk tests (ISWT and ESWT, respectively). The aim of this document is to describe the standard operating procedures for the 6MWT, ISWT and ESWT, which can be consistently employed by clinicians and researchers. The Technical Standard was developed by a multidisciplinary and international group of clinicians and researchers with expertise in the application of field walking tests. The procedures are underpinned by a concurrent systematic review of literature relevant to measurement properties and test conduct in adults with chronic respiratory disease. Current data confirm that the 6MWT, ISWT and ESWT are valid, reliable and responsive to change with some interventions. However, results are sensitive to small changes in methodology. It is important that two tests are conducted for the 6MWT and ISWT. This Technical Standard for field walking tests reflects current evidence regarding procedures that should be used to achieve robust results.
Hemorrhagic Events during Therapy with Recombinant Tissue-Type Plasminogen Activator, Heparin, and Aspirin for Acute Myocardial Infarction
Authors: Edwin G. Bovill, Michael L. Terrin, David C. Stump, Andrew D. Berke, Margaret Frederick, Désiré Collen, Frederick Feit, Joel M. Gore, L. David Hillis, Costas T. Lambrew, Roy Leiboff, Kenneth G. Mann, John E. Markis, Craig M. Pratt, Scott W. Sharkey, George Sopko, Russell P. Tracy, James H. Chesebro
Journal: Annals of Internal Medicine (1991)

Objectives: To assess the effects of invasive procedures, hemostatic and clinical variables, the timing of beta-blocker therapy, and the doses of recombinant plasminogen activator (rt-PA) on hemorrhagic events. Design: A multicenter, randomized, controlled trial. Setting: Hospitals participating in the Thrombolysis in Myocardial Infarction, Phase II trial (TIMI II). Interventions: Patients received rt-PA, heparin, and aspirin. The total dose of rt-PA was 150 mg for the first 520 patients and 100 mg for the remaining 2819 patients. Patients were randomly assigned to an invasive strategy (coronary arteriography with percutaneous angioplasty [if feasible] done routinely 18 to 48 hours after the start of thrombolytic therapy) or to a conservative strategy (coronary arteriography done for recurrent spontaneous or exercise-induced ischemia). Eligible patients were also randomly assigned to either immediate intravenous or deferred beta-blocker therapy. Measurements: Patients were monitored for hemorrhagic events during hospitalization. Main Results: In patients on the 100-mg rt-PA regimen, major and minor hemorrhagic events were more common among those assigned to the invasive than among those assigned to the conservative strategy (18.5% versus 12.8%, P < 0.001). Major or minor hemorrhagic events were associated with the extent of fibrinogen breakdown, peak rt-PA levels, thrombocytopenia, prolongation of the activated partial thromboplastin time (APTT) to more than 90 seconds, weight of 70 kg or less, female gender, and physical signs of cardiac decompensation. Immediate intravenous beta-blocker therapy had no important effect on hemorrhagic events when compared with delayed beta-blocker therapy. Intracranial hemorrhages were more frequent among patients treated with the 150-mg rt-PA dose than with the 100-mg rt-PA dose (2.1% versus 0.5%, P < 0.001). The extent of the plasmin-mediated hemostatic defect was also greater in patients receiving the 150-mg dose. Conclusions: Increased morbidity due to hemorrhagic complications is associated with an invasive management strategy in patients with acute myocardial infarction. Our findings show the complex interaction of several factors in the occurrence of hemorrhagic events during thrombolytic therapy.
Salvage chemotherapy with mini-BEAM for relapsed or refractory non-Hodgkin's lymphoma prior to autologous bone marrow transplantation
Authors: C. Girouard, J. Dufresne, K. Imire, A.K. Stewart, J. Brandwein, H.M. Prince, D. Pantolony, A. Keating, M. Crump
Journal: Annals of Oncology (1997)
Adaptation to intermittent positive pressure ventilation applied through the nose during day and night
Authors: DO Rodenstein, DC Stanescu, P Delguste, G Liistro, G Aubert-Tulkens
Journal: European Respiratory Journal (1989)

A 49 yr old poliomyelitic patient had been under cuirass-type nocturnal negative pressure ventilation for more than 20 yrs. He had a severe restrictive ventilatory impairment, and normal awake blood gases at rest and during light exercise. He was offered a trial of intermittent positive pressure ventilation applied through the nose (nIPPV). Two daytime studies and one night study were carried out under nIPPV, and one night study was performed under negative pressure ventilation. Tidal volume, respiratory frequency (Respitrace), blood gases and electromyogram (EMG) of the diaphragm (DEMG, oesophageal electrode) and/or sternocleidomastoid (ScEMG, surface electrodes) were measured. During daytime studies under nIPPV, the DEMG (and/or the ScEMG) did not decrease by more than 25% (p less than 0.005). However, when the patient was encouraged to relax, the DEMG decreased by 62% (p less than 0.001). Tidal volume and ventilation significantly increased during daytime nIPPV (p less than 0.025), whereas blood gases were kept at physiological levels. At night, the ScEMG was present and prominent until sleep onset. Thereafter it disappeared and remained silent, including periods of wakefulness during sleep time, until final awakening in the morning. This was true for both negative pressure ventilation and nIPPV. Snoring was present throughout sleep under negative pressure ventilation but not under nIPPV. We conclude that the behavioural response of the subject may determine the electrical activity of respiratory muscles during assisted ventilation.
Years in Cologne
Authors: Klaus Rajewsky
Journal: Annual Review of Immunology (2012)

This review describes the building and scientific activity of the Immunology Department at the Institute for Genetics in Cologne, cofounded by Max Delbrück in post-World War II Germany. The protagonist, a child of Russian emigrants, became interested in antibodies as a postdoc at the Pasteur Institute in Paris and a proponent of the antigen-bridge model of T-B cell collaboration during his early time in Cologne. He was challenged by the gap between cellular immunology and molecular genetics and profited from the advances of the latter as well as postwar economic growth in Germany. The Immunology Department became a place, and little universe in itself, where young scientists from all over the world came together to study cellular and molecular mechanisms of antibody formation. This included work on normal and malignant B cells in the human, particularly the origin of Hodgkin lymphoma, but the main focus was on B cell development and homeostasis, the germinal center reaction, and immunological memory, developing recombinase-assisted and conditional gene targeting in mice as a main technical tool.
Recent improvement in long-term survival after a COPD hospitalisation
Authors: P. Almagro, M Salvado, C Garcia-Vidal, M Rodriguez-Carballeira, M Delgado, B Barreiro, J L Heredia, J. B Soriano
Journal: Thorax (2010)

Evidence-based international guidelines on chronic obstructive pulmonary disease (COPD), and their corresponding recommendations, were established to improve individual COPD prognosis, and ultimately to improve survival. The aim of this study was to determine whether the long-term mortality after discharge from a COPD hospitalisation has improved recently, and the effect of co-morbidity treatment in improving COPD prognosis.In a prospective cohort study design of two cohorts 7 years apart, patients discharged from the same university hospital after a COPD exacerbation were followed-up, and their outcomes compared. Demographic and clinical variables, as well as lung function, were collected with the same protocol by the same investigators. Comprehensive assessments of co-morbidities and treatments were undertaken. Kaplan-Meier survival curves were estimated, and outcomes were compared by means of Cox regression methods.Overall, 135 participants in the 1996-7 cohort and 181 participants in the 2003-4 cohort were studied. Both cohorts were comparable in their baseline demographic and clinical variables, and median follow-up was 439 days. The 3-year mortality was lower in the 2003-4 cohort (38.7%) than in the 1996-7 cohort (47.4%) (p=0.017), and the RR of death after adjustment for gender, age, body mass index, co-morbidities, lung function and mMRC (modified Medical Research Council scale) dyspnoea was 0.66 (95% CI 0.45 to 0.97). Long-term survival improved in the second cohort for patients with COPD with heart failure or cancer (p<0.001).A recent trend towards better prognosis of patients with COPD after hospital discharge is described and is likely to be associated with better management and treatment of COPD and co-morbidities.
Comparative effectiveness of radical prostatectomy and radiotherapy in prostate cancer: observational study of mortality outcomes
Authors: P. Sooriakumaran, T. Nyberg, O. Akre, L. Haendler, I. Heus, M. Olsson, S. Carlsson, M. J. Roobol, G. Steineck, P. Wiklund
Journal: BMJ (2014)

<b>Objective</b> To compare the survival outcomes of patients treated with surgery or radiotherapy for prostate cancer. <b>Design</b> Observational study. <b>Setting</b> Sweden, 1996-2010. <b>Participants</b> 34 515 men primarily treated for prostate cancer with surgery (n=21 533) or radiotherapy (n=12 982). Patients were categorised by risk group (low, intermediate, high, and metastatic), age, and Charlson comorbidity score. <b>Main outcome measures</b> Cumulative incidence of mortality from prostate cancer and other causes. Competing risks regression hazard ratios for radiotherapy versus surgery were computed without adjustment and after propensity score and traditional (multivariable) adjustments, as well as after propensity score matching. Several sensitivity analyses were performed. <b>Results</b> Prostate cancer mortality became a larger proportion of overall mortality as risk group increased for both the surgery and the radiotherapy cohorts. Among patients with non-metastatic prostate cancer the adjusted subdistribution hazard ratio for prostate cancer mortality favoured surgery (1.76, 95% confidence interval 1.49 to 2.08, for radiotherapy <i>v</i> prostatectomy), whereas there was no discernible difference in treatment effect among men with metastatic disease. Subgroup analyses indicated more clear benefits of surgery among younger and fitter men with intermediate and high risk disease. Sensitivity analyses confirmed the main findings. <b>Conclusions</b> This large observational study with follow-up to 15 years suggests that for most men with non-metastatic prostate cancer, surgery leads to better survival than does radiotherapy. Younger men and those with less comorbidity who have intermediate or high risk localised prostate cancer might have a greater benefit from surgery.
Tubulin polymerization modifies cardiac sodium channel expression and gating
Authors: Simona Casini, Hanno L. Tan, Ilker Demirayak, Carol Ann Remme, Ahmad S. Amin, Brendon P. Scicluna, Houssine Chatyan, Jan M. Ruijter, Connie R. Bezzina, Antoni C.G. van Ginneken, Marieke W. Veldkamp
Journal: Cardiovascular Research (2009)

Treatment with the anticancer drug taxol (TXL), which polymerizes the cytoskeleton protein tubulin, may evoke cardiac arrhythmias based on reduced human cardiac sodium channel (Nav1.5) function. Therefore, we investigated whether enhanced tubulin polymerization by TXL affects Nav1.5 function and expression and whether these effects are β1-subunit-mediated. Human embryonic kidney (HEK293) cells, transfected with SCN5A cDNA alone (Nav1.5) or together with SCN1B cDNA (Nav1.5 + β1), and neonatal rat cardiomyocytes (NRCs) were incubated in the presence and in the absence of 100 μM TXL. Sodium current (INa) characteristics were studied using patch-clamp techniques. Nav1.5 membrane expression was determined by immunocytochemistry and confocal microscopy. Pre-treatment with TXL reduced peak INa amplitude nearly two-fold in both Nav1.5 and Nav1.5 + β1, as well as in NRCs, compared with untreated cells. Accordingly, HEK293 cells and NRCs stained with anti-Nav1.5 antibody revealed a reduced membrane-labelling intensity in the TXL-treated groups. In addition, TXL accelerated INa decay of Nav1.5 + β1, whereas INa decay of Nav1.5 remained unaltered. Finally, TXL reduced the fraction of channels that slow inactivated from 31% to 18%, and increased the time constant of slow inactivation by two-fold in Nav1.5. Conversely, slow inactivation properties of Nav1.5 + β1 were unchanged by TXL. Enhanced tubulin polymerization reduces sarcolemmal Nav1.5 expression and INa amplitude in a β1-subunit-independent fashion and causes INa fast and slow inactivation impairment in a β1-subunit-dependent way. These changes may underlie conduction-slowing-dependent cardiac arrhythmias under conditions of enhanced tubulin polymerization, e.g. TXL treatment and heart failure.
TCT-228 Long-term Safety and Efficacy of Sirolimus Eluting Stent Implantation for Unprotected Left Main Trunk Bifurcation Lesion with Single Stent Strategy Versus Left Anterior Descending Artery Lesion
Authors: Takayoshi Toba, Shinichiro Yamada, Yoshinori Yasaka, Shogo Oishi, Takahiro Sawada, Kiminobu Yokoi, Seiichi Kobayashi, Akira Shimane, Hiroya Kawai
Journal: Journal of the American College of Cardiology (2014)