tbuckley/cabot-search huggingface dataset:
Risk of Suicide Following Deliberate Self-poisoning
Authors: Yaron Finkelstein, Erin M. Macdonald, Simon Hollands, Marco L. A. Sivilotti, Janine R. Hutson, Muhammad M. Mamdani, Gideon Koren, David N. Juurlink
Journal: JAMA Psychiatry (2015)

Suicide is the tenth leading cause of death in the United States, and its rate has risen by 16% in the past decade. Deliberate self-poisoning is the leading method of attempted suicide. Unlike more violent methods, which are almost universally fatal, survival following self-poisoning is common, providing an opportunity for secondary prevention. However, the long-term risk of suicide following a first episode of self-poisoning is unknown.To determine the risk of suicide and mortality from other causes following a first self-poisoning episode.Population-based cohort study using multiple linked health care databases. We identified all individuals with a first self-poisoning episode in Ontario, Canada, from April 1, 2002, through December 31, 2010, and followed up all surviving participants until December 31, 2011, or death, whichever occurred first. For each individual with a deliberate self-poisoning episode, we randomly selected 1 control from the same population with no such history, matched for age (within 3 months), sex, and calendar year.The primary analysis examined the risk of suicide following discharge after self-poisoning. The secondary analyses explored factors associated with suicide and examined the risk of death caused by accidents or any other cause.We identified 65 784 patients (18 482 [28.1%] younger than 20 years) who were discharged after a first self-poisoning episode. During a median follow-up of 5.3 years (interquartile range, 3.1-7.6 years), 4176 died, including 976 (23.4%) by suicide. The risk of suicide following self-poisoning was markedly increased relative to controls (hazard ratio, 41.96; 95% CI, 27.75-63.44), corresponding to a suicide rate of 278 vs 7 per 100 000 person-years, respectively. The median time from hospital discharge to completed suicide was 585 days (interquartile range, 147-1301 days). Older age, male sex, multiple intervening self-poisoning episodes, higher socioeconomic status, depression, and recent psychiatric care were strongly associated with suicide. Patients with a self-poisoning episode were also more likely to die because of accidents (hazard ratio, 10.45; 95% CI, 8.10-13.47) and all causes combined (hazard ratio, 5.55; 95% CI, 5.12-6.02).A first self-poisoning episode is a strong predictor of subsequent suicide and premature death. Most suicides occur long after the index poisoning, emphasizing the importance of longitudinal, sustained secondary prevention initiatives.
Role of diuretics, blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study
Authors: L. Shen, B. R. Shah, E. M. Reyes, L. Thomas, D. Wojdyla, P. Diem, L. A. Leiter, B. Charbonnel, V. Mareev, E. S. Horton, S. M. Haffner, V. Soska, R. Holman, M. A. Bethel, F. Schaper, J.-L. Sun, J. J. McMurray, R. M. Califf, H. Krum
Journal: BMJ (2013)

To examine the degree to which use of β blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes.Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial.NAVIGATOR trial.Patients who at baseline (enrolment) were treatment naïve to β blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control.Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment.During the median five years of follow-up, β blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas β blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively).Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of β blockers was non-significant.ClinicalTrials.gov NCT00097786.
A comparison of the cardiovascular and metabolic effects of formoterol, salbutamol and fenoterol
Authors: P Bremner, K Woodman, C Burgess, J Crane, G Purdie, N Pearce, R Beasley
Journal: European Respiratory Journal (1993)

The cardiovascular and metabolic effects of the long-acting beta 2-agonist formoterol were compared with those of salbutamol, fenoterol and placebo in 12 healthy volunteers, using a randomised, double-blind, cross-over design. On the study days, the subjects inhaled either formoterol (24 micrograms), salbutamol (400 micrograms), fenoterol (400 micrograms) or placebo, at 30 min intervals for five doses. Heart rate (HR) total electromechanical systole (Q-S2I) (a measure of inotropy), the corrected QT interval (QTc), systolic and diastolic blood pressure, plasma glucose and plasma potassium (K+) were measured prior to drug administration, 10 min after each inhalation and at 30 min intervals for 3 h after the last inhalation. All of the active agents significantly increased HR, QTc and plasma glucose, and decreased Q-S2I, diastolic blood pressure and plasma K+ compared to placebo. Fenoterol had a significantly greater maximum effect on HR, QTc and Q-S2I than either salbutamol or formoterol. Formoterol and fenoterol caused a similar maximum reduction in plasma K+, greater than that due to salbutamol. We conclude that formoterol is a more selective beta 2-agonist than fenoterol, and has similar cardiovascular effects to salbutamol when inhaled repeatedly by normal volunteers.
The induction of secondary cytolytic T lymphocytes by solubilized membrane proteins.
Authors: M Mescher, L Sherman, F Lemonnier, S Burakoff
Journal: The Journal of Experimental Medicine (1978)

Membrane-bound antigens responsible for induction of a secondary allogeneic murine cytolytic T-cell (CTL) response have been obtained in a soluble, biologically active form by deoxycholate solubilization of tumor cell plasma membranes. The active proteins are soluble by the criteria of both ultracentrifugation and gel filtration. The immunological specificity of the induced CTL and removal of the activity from solution by treatment with B6 anti-P815 (anti-H-2d) antiserum and Protein A-Sepharose demonstrate that the CTL-inducing activity is dependent upon solubilized major histocompatibility complex antigens.
Effect of eradication of Helicobacter pylori on gastric juice ascorbic acid concentrations.
Authors: G M Sobala, C J Schorah, S Shires, D A Lynch, B Gallacher, M F Dixon, A T Axon
Journal: Gut (1993)

Ascorbic acid, the reduced form of vitamin C, may protect against gastric cancer and is secreted by the normal stomach. Secretion is impaired in Helicobacter pylori (H pylori) associated chronic gastritis. This study examined if eradication of H pylori improves gastric juice ascorbate values. Fasting gastric juice and plasma samples were collected at endoscopy from patients participating in trials of H pylori eradication for duodenal ulcer disease and intestinal metaplasia before and up to 15 months after attempted eradication. Ascorbic acid and total vitamin C concentrations were determined by high performance liquid chromatography. In 12 patients in whom H pylori was successfully eradicated gastric juice ascorbate and total vitamin C concentrations and the ratio of juice to plasma vitamin C rose after treatment. Analysis after treatment suggested that the rise was greatest in patients with high final plasma vitamin C concentrations, even though these did not change with treatment. By contrast, in 22 patients in whom H pylori eradication was unsuccessful there were no significant changes in juice or plasma concentrations after treatment. It is concluded that successful eradication of H pylori improves secretion of vitamin C into gastric juice. It is speculated that this increases protection against gastric cancer.
Lewis X component in human milk binds DC-SIGN and inhibits HIV-1 transfer to CD4+ T lymphocytes
Authors: M. A. Naarding
Journal: Journal of Clinical Investigation (2005)

DC-specific ICAM3-grabbing non-integrin (DC-SIGN), which is expressed on DCs, can interact with a variety of pathogens such as HIV-1, hepatitis C, Ebola, cytomegalovirus, Dengue virus, Mycobacterium, Leishmania, and Candida albicans. We demonstrate that human milk can inhibit the DC-SIGN-mediated transfer of HIV-1 to CD4+ T lymphocytes as well as viral transfer by both immature and mature DCs. The inhibitory factor directly interacted with DC-SIGN and prevented the HIV-1 gp120 envelope protein from binding to the receptor. The human milk proteins lactoferrin, alpha-lactalbumin, lysozyme, beta-casein, and secretory leukocyte protease inhibitor did not bind DC-SIGN or demonstrate inhibition of viral transfer. The inhibitory effect could be fully alleviated with an Ab recognizing the Lewis X (LeX) sugar epitope, commonly found in human milk. LeX in polymeric form or conjugated to protein could mimic the inhibitory activity, whereas free LeX sugar epitopes could not. We reveal that a LeX motif present in human milk can bind to DC-SIGN and thereby prevent the capture and subsequent transfer of HIV-1 to CD4+ T lymphocytes. The presence of such a DC-SIGN-binding molecule in human milk may both influence antigenic presentation and interfere with pathogen transfer in breastfed infants.
AMP-Activated Protein Kinase Conducts the Ischemic Stress Response Orchestra
Authors: Lawrence H. Young
Journal: Circulation (2008)

T he heart is subjected to physiological stress in normal individuals during exercise and to pathological stress in patients with ischemic disease, ventricular pressure, or volume overload.How the heart responds depends on the type, intensity, and duration of the stress.Just as extrinsic physiological reflexes are activated when cardiac output falls, internal molecular sensors respond to changes in physiological parameters within cardiac cells.These specialized molecules sense perturbations in oxygen tension, cell stretch, pH, membrane potential, oxidative state, and intracellular energy stores, with the latter particularly pertinent to this discussion.The present article will focus on the AMP-activated protein kinase (AMPK), a molecular stress response pathway that is activated by increases in the intracellular concentration of AMP.AMP is not to be confused with cAMP, a molecular signal produced during stress by catecholamine-induced ␤-adrenergic stimulation.The AMPK pathway has received a great deal of attention because of its potential importance in the ischemic heart, 1,2 diabetes, 3 and cancer. 46][7] The present article will strive to provide a perspective that is accessible to the clinician with an interest in contemporary basic science research.It is hoped that the reader will develop an understanding of how AMPK functions in the heart to orchestrate the cellular response to ischemic stress.
Hemodynamic effects of phenoxybenzamine in anesthetized dogs
Authors: Noble O. Fowler, John C. Holmes, Thomas E. Gaffney, Philip J. Privitera, Gunter Grupp
Journal: Journal of Clinical Investigation (1970)

Our studies demonstrated that phenoxybenzamine, 10 mg/kg, administered intravenously to intact anesthetized dogs, produced an immediate and significant increase of heart rate and cardiac output. In heart-lung preparations, phenoxybenzamine had no effect or a negative cardiac inotropic effect, hence these actions were not related to direct cardiac action or to release of myocardial norepinephrine stores. Serial estimations of arterial blood catecholamines after phenoxybenzamine showed an increase of epinephrine and norepinephrine; the peak values of these catecholamines did not correlate well with the maximum cardiac output responses. Ganglionic blockade largely eliminated the early cardiac effects of phenoxybenzamine, hence its action did not appear to be upon peripheral terminals of postganglionic sympathetic or parasympathetic nerves. Phenoxybenzamine was found to have antivagal actions which might account for some of the delayed cardiac acceleration. When beta adrenergic receptor blockade was induced by sotalol, the cardiac effects of phenoxybenzamine were largely eliminated. Baroreceptor denervation prevented the increase of cardiac output after phenoxybenzamine. These observations are consistent with the concept that the increase of cardiac rate and output produced by phenoxybenzamine is principally mediated by baroreceptor reflexes acting through sympathetic cardiac nerves or circulating catecholamines.
Clinical findings just after return to play predict hamstring re-injury, but baseline MRI findings do not
Authors: Robert-Jan De Vos, Gustaaf Reurink, Gert-Jan Goudswaard, Maarten H Moen, Adam Weir, Johannes L Tol
Journal: British Journal of Sports Medicine (2014)

Acute hamstring re-injuries are common and hard to predict. The aim of this study was to investigate the association between clinical and imaging findings and the occurrence of hamstring re-injuries.We obtained baseline data (clinical and MRI findings) of athletes who sustained an acute hamstring injury within 5 days of initial injury. We also collected data of standardised clinical tests within 7 days after return to play (RTP). The number of re-injuries was recorded within 12 months. We analysed the association between the possible predictive variables and re-injuries with a multivariate Cox proportional-hazards regression model.Eighty patients were included at baseline and 64 patients could be included in the final analysis because data after RTP were not available in 16 cases. There were 17 re-injuries (27%). None of the baseline MRI findings were univariately associated with re-injury. A higher number of previous hamstring injuries (adjusted OR (AOR) 1.33; 95% CI 1.11 to 1.61), more degrees of active knee extension deficit after RTP (AOR 1.13; 95% CI 1.03 to 1.25), isometric knee flexion force deficit at 15° after RTP (AOR 1.04; 95% CI 1.01 to 1.07) and presence of localised discomfort on hamstring palpation after RTP (AOR 3.95; 95% CI 1.38 to 11.37) were significant independent predictors of re-injury. Athletes with localised discomfort on hamstring palpation just after RTP were consequently almost four times more likely to sustain a re-injury.The number of previous hamstring injuries, active knee extension deficit, isometric knee flexion force deficit at 15° and presence of localised discomfort on palpation just after RTP are associated with a higher hamstring re-injury rate. None of the baseline MRI parameters was a predictor of hamstring re-injury.ClinicalTrial.gov number NCT01812564.
Mutation of β-glucosidase 2 causes glycolipid storage disease and impaired male fertility
Authors: Yildiz Yildiz, Heidrun Matern, Bonne Thompson, Jeremy C. Allegood, Rebekkah L. Warren, Denise M.O. Ramirez, Robert E. Hammer, F. Kent Hamra, Siegfried Matern, David W. Russell
Journal: Journal of Clinical Investigation (2006)

beta-Glucosidase 2 (GBA2) is a resident enzyme of the endoplasmic reticulum thought to play a role in the metabolism of bile acid-glucose conjugates. To gain insight into the biological function of this enzyme and its substrates, we generated mice deficient in GBA2 and found that these animals had normal bile acid metabolism. Knockout males exhibited impaired fertility. Microscopic examination of sperm revealed large round heads (globozoospermia), abnormal acrosomes, and defective mobility. Glycolipids, identified as glucosylceramides by mass spectrometry, accumulated in the testes, brains, and livers of the knockout mice but did not cause obvious neurological symptoms, organomegaly, or a reduction in lifespan. Recombinant GBA2 hydrolyzed glucosylceramide to glucose and ceramide; the same reaction catalyzed by the beta-glucosidase acid 1 (GBA1) defective in subjects with the Gaucher's form of lysosomal storage disease. We conclude that GBA2 is a glucosylceramidase whose loss causes accumulation of glycolipids and an endoplasmic reticulum storage disease.
Mechanisms of Premature Atherosclerosis in Rheumatoid Arthritis and Lupus
Authors: J. Michelle Kahlenberg, Mariana J. Kaplan
Journal: Annual Review of Medicine (2012)

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), the two most common systemic autoimmune disorders, have both unique and overlapping manifestations. One feature they share is a significantly enhanced risk of atherosclerotic cardiovascular (CV) disease that significantly contributes to morbidity and mortality. The primary mechanisms that drive CV damage in these diseases remain to be fully characterized, but recent discoveries indicate that distinct inflammatory pathways and immune dysregulation characteristic of RA and SLE likely play prominent roles. This review focuses on analyzing the major mechanisms and pathways potentially implicated in the acceleration of atherothrombosis and CV risk in SLE and RA, as well as in the identification of putative preventive strategies that may mitigate vascular complications in systemic autoimmunity.
Evolution of rhythms during periodic stimulation of embryonic chick heart cell aggregates.
Authors: W Z Zeng, L Glass, A Shrier
Journal: Circulation Research (1991)

During periodic stimulation of spontaneously beating chick heart cell aggregates, there is often an evolution of coupling patterns between the stimulator and the aggregate action potential. For example, at rapid stimulation frequencies, a rhythm that is initially 1:1 (stimulus frequency:aggregate frequency) can evolve to other rhythms such as 5:4 and 4:3. Time-dependent effects generated during periodic stimulation are characterized by three types of experiments to determine 1) the effect of periodic stimulation on the intrinsic cardiac beat rate (overdrive suppression), 2) the effect of periodic stimulation on the phase resetting properties of the aggregate, and 3) the time-dependent changes in the coupling patterns between the stimulator and the aggregate during periodic stimulation. The protocols involved variations in the duration and rate of periodic stimulation. A mathematical model is developed in the form of a two-dimensional finite difference equation based on the data from experiments 1 and 2. The model is used to predict the data generated by experiment 3. There is good correspondence with the experiments in that the theory reproduces complex transitions between various rhythms and displays irregular rhythms similar to those observed experimentally. These results have implications for the evolution of cardiac arrhythmias such as atrioventricular heart block and modulated parasystole.
Interleukin 1-induced, T cell-mediated regression of immunogenic murine tumors. Requirement for an adequate level of already acquired host concomitant immunity.
Authors: R J North, R H Neubauer, J J Huang, R C Newton, S E Loveless
Journal: The Journal of Experimental Medicine (1988)

Intraperitoneal injection of human rIL-1 in a dose of 0.5 microgram daily for 5 d, or 1 microgram daily for 3 d, was capable of causing complete regression of immunogenic SA1 sarcoma growing subcutaneously in syngeneic or semisyngeneic mice. Higher doses of IL-1 were not more therapeutic against the SA1 sarcoma, but needed to be given to cause complete regression of the immunogenic L5178Y lymphoma. On the other hand, the P815 mastocytoma was much less responsive to IL-1 therapy, in that it failed to undergo complete regression in response to doses of IL-1 capable of causing regression of the L5178Y lymphoma. IL-1 caused regression of the SA1 sarcoma when given on days 6-8 of tumor growth, but not when given on days 1-3. This refractoriness of a small tumor to IL-1 therapy suggests that the antitumor action of IL-1 is based on an underlying host-immune response that is not generated until after day 3 of tumor growth. Direct evidence for the participation of host immunity in IL-1-induced tumor regression was supplied by results showing that IL-1 was not therapeutic against the SA1 sarcoma growing in T cell-deficient (TXB) mice, unless these mice were first infused with Ly-2+ and L3T4+ T cells from donor mice bearing an established SA1 sarcoma. In contrast, normal T cells, or T cells from donor mice bearing a YAC-1 lymphoma, failed to provide TXB recipients with the ability to cause regression of their SA-1 sarcoma in response to IL-1 treatment. The results are in keeping with the interpretation that exogenous IL-1, by augmenting the production of tumor-sensitized T cells, converts a subtherapeutic level of host immunity to a therapeutic level. The results suggest, in addition, that IL-1 only stimulates the replication of T cells that are already engaged in the antitumor immune response.
A Prospective Trial Comparing Consecutive Series of Open Retropubic and Robot-Assisted Laparoscopic Radical Prostatectomy in a Centre with a Limited Caseload
Authors: Giovanni B. Di Pierro, Philipp Baumeister, Patrick Stucki, Josef Beatrice, Hansjörg Danuser, Agostino Mattei
Journal: European Urology (2010)
Bioengineering of Therapeutic Aerosols
Authors: David A. Edwards, Craig Dunbar
Journal: Annual Review of Biomedical Engineering (2002)

The new field of therapeutic aerosol bioengineering (TAB), driven primarily by the medical need for inhaled insulin, is now expanding to address medical needs ranging from respiratory to systemic diseases, including asthma, growth deficiency, and pain. Bioengineering of therapeutic aerosols involves a level of aerosol particle design absent in traditional therapeutic aerosols, which are created by conventionally spraying a liquid solution or suspension of drug or milling and mixing a dry drug form into respirable particles. Bioengineered particles may be created in liquid form from devices specially designed to create an unusually fine size distribution, possibly with special purity properties, or solid particles that possess a mixture of drug and excipient, with designed shape, size, porosity, and drug release characteristics. Such aerosols have enabled several high-visibility clinical programs of inhaled insulin, as well as earlier-stage programs involving inhaled morphine, growth hormone, beta-interferon, alpha-1-antitrypsin, and several asthma drugs. The design of these aerosols, limited by partial knowledge of the lungs' physiological environment, and driven largely at this stage by market forces, relies on a mixture of new and old science, pharmaceutical science intuition, and a degree of biological-impact empiricism that speaks to the importance of an increased level of academic involvement.