tbuckley/cabot-search huggingface dataset:
Fear of minimum alcohol pricing spreading to other countries led to opposition in Scotland
Authors: B. Christie
Journal: BMJ (2009)

Infection of C57Bl/6 mice with influenza virus is accompanied by morbidity manifested as weight loss and lung pathology. We have found that mice that have an inactivating mutation in the leucocyte-specific phosphoinositide kinase 3 (PIK3) isoform p110delta (p110delta-/- on a C57BL/6 background manifest significantly reduced morbidity after influenza virus infection compared to C57BL/6 mice. RAG-/- mice also showed reduced morbidity compared to wild type animals, indicating a role for lymphocytes in this pathology. At day 6 postinfection activated pulmonary T cells and NK cells were greatly reduced in p110delta-/- mice. At day 10 postinfection, however, numbers of lymphocytes, B cells, CD4+ T cells, macrophages and granulocytes infiltrating the lungs of p110delta-/- mice were reduced compared to C57Bl/6 mice, without reaching statistical significance. Total number of CD8+ and virus-specific CD8+ T cells found in the lungs of infected p110delta-/- mice were significantly reduced by 2-fold compared to wild-type mice (p=0.03 for both). However, this reduction in the magnitude of the immune response did not affect viral clearance. Our data suggest that p110delta plays an important role in the lymphocyte mediated immunopathology associated with influenza virus infection and suggests that p110delta may be an important therapeutic target for influenza virus infection.
Review: In pulmonary embolism, thrombolytic therapy reduces all-cause mortality but increases major bleeding
Authors: Elie A. Akl, Gordon H. Guyatt
Journal: Annals of Internal Medicine (2014)

Source Citation Chatterjee S, Chakraborty A, Weinberg I, et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014;311:2414-21. 24938564
A FOLLOW-UP REPORT ON RHEUMATIC SUBJECTS TREATED WITH SULFANILAMIDE
Authors: A. F. Coburn
Journal: JAMA (1941)

The use of sulfanilamide to prevent hemolytic streptococcus infections and recrudescences of acute rheumatism in persons known to be subject to rheumatic fever has given encouraging results. The observations by Thomas and her collaborators<sup>1</sup>working with adults in Baltimore, and observations on children in New York<sup>2</sup>indicated that a level of sulfanilamide in the blood of about 40 micrograms per cubic centimeter maintained throughout the school year protected against streptococcic pharyngitis and rheumatic recrudescences. One factor that it was impossible to control in the New York study was the increasing age of the group. Between 1936 and 1939 many of the children passed puberty, and, as is well recognized, rheumatic subjects tend to have fewer recrudescences in adolescence than during childhood. It was therefore possible to regard the increasing age of our patients as largely contributory to the decreased incidence of rheumatic fever. One way of determining whether
Impaired Hearing in X-Linked Hypophosphataemic (Vitamin-D-Resistant) Osteomalacia
Authors: MICHAEL DAVIES
Journal: Annals of Internal Medicine (1984)

We assessed the hearing of 25 patients with X-linked hypophosphataemic osteomalacia. Twelve patients had subjective hearing loss and 2 had had episodic tinnitus, deafness, and vertigo similar to that in Ménière's disease. On pure-tone audiometry, 19 patients were shown to have sensorineural hearing loss, 3 of whom had evidence of an added conductive element. Tests were done to delineate sensory (cochlear) from neural deafness. Analysis of the stapedius reflex threshold, percentage speech discrimination score, tone decay, and loudness recruitment showed a disturbance of cochlear function. The possible mechanisms responsible for this dysfunction are discussed in the light of pathologic characteristics of familial hypophosphataemia and its extraosseous manifestations. Sensorineural hearing loss, a previously unrecognised complication of familial hypophosphataemic osteomalacia, occurs frequently.
Laboratory of Pharmacology: Summary Statement
Authors: Larry Hart
Journal: Environmental Health Perspectives (1977)

The Laboratory of Pharmacology initiates and carries out research programs that are primarily concerned with (1) mechanisms by which environ- mental pollutants and effectors cause toxicity, (2) the development of better test systems for detecting and evaluating early toxic effects of chemicals oc- curring as environmental contaminants, and (3) ex- trapolating from animal test systems across species and to man.The Laboratory is organized into three formal sections and one work group.The sections are Toxication-Detoxication, Marine Pharmacol- ogy and Biomedicine, and Pharmacokinetics; the work group is Molecular Pharmacology and Biomedicine.
Influence of KATP channel modulation on net potassium efflux from ischaemic mammalian cardiac tissue
Authors: B Vanheel, A d. Hemptinne
Journal: Cardiovascular Research (1992)

Objective: The aim was to investigate the effect of pre-exposure to inhibitors or activators of the ATP regulated K+ (KATP) channels on the ischaemia induced early changes of the extracellular K+ concentration, the extracellular pH, and the action potential in mammalian cardiac tissue. Methods: An in vitro model simulating ischaemia was applied to isolated guinea pig papillary muscles while simultaneous microelectrode measurements of the transmembrane potentials and of the pH and K+ activity at the surface of the preparation (pHs and asK respectively) were made. Results: During conditions of superfusion arrest, when accumulation of metabolic acids causes acidification of pHs, the simultaneous development of a true hypoxic state of the muscle is required in order to induce shortening of the action potential duration and accumulation of extracellular K+ with associated membrane depolarisation. Glibenclamide (10-50 μM) slowed the decrease of the action potential duration in 50% of the muscles, while the increase of aSK was only moderately (∼20%) influenced. In the presence of 200 μM of the KATP channel inhibitor, the mean K+ accumulation was not significantly different from the control. The presence of tolbutamide (1 mM) had no effect on the decrease of action potential duration, but moderately slowed the increase of asK Superfusion with lemakalim (BRL 38227) decreased action potential duration dose dependently. In papillary muscles in which action potential duration was shortened to ~60% of the control duration by presuperfusion with lemakalim, a subsequent ischaemic episode did not increase but rather delayed the rise in asK. During simulated ischaemia in the presence of Ba2+ ions (1 mM), asK showed a transient decrease followed by a rise at a rate similar to that in the absence of Ba2+. Conclusions: Early ischaemic K+ accumulation and surface acidification are relatively insensitive to KATP channel inhibition or activation prior to the ischaemic insult. The rather loose coupling of the increase of aSK and the decrease of action potential duration, as well as the limited effect of sulphonylureas on the K+ increase, suggests that mechanisms other than KATP channel opening could possibly contribute to the initial phase of ischaemic K+ accumulation. Cardiovascular Research 1992;26:1030-1039
Interleukin-2-activated natural killer cells can induce both apoptosis and necrosis in rat hepatocytes
Authors: Marty W. Blom, Hans J.G.M. De Bont, Irma Meijerman, Peter J.K. Kuppen, Gerard J. Mulder, Fred J. Nagelkerke
Journal: Hepatology (1999)

Natural killer (NK) cells play a crucial role in the elimination of virus-infected or transformed cells in the liver. In this article, we describe the mechanism by which liver cells are killed by NK cells. Interleukin-2-activated natural killer (A-NK) cells from the rat induced apoptotic cell death in 30% of freshly isolated rat hepatocytes within 60 minutes. Recognition by the A-NK cells of the hepatocytes as nonself was established by masking the major histocompatibility complex (MHC) class I molecules on the hepatocytes with the OX18 antibody. During the killing process, a decrease of the mitochondrial membrane potential (MMP), formation of blebs, phosphatidyl serine (PS) externalization, chromatin condensation, and nuclear fragmentation were observed. The hepatocytes became apoptotic before permeabilization of the plasma membrane occurred, suggesting that the observed cytolysis was caused by secondary necrosis. The apoptotic process was completely abolished by the caspase inhibitors, Z-Val-Ala-DL-Asp fluormethylketone (zVAD-fmk) and Ac-Asp-Glu-Val-aldehyde (DEVD-cho). However, under these conditions, A-NK cells killed a smaller fraction of the hepatocytes by (primary) necrosis. These results indicate that apoptosis is the major cytotoxic process induced by A-NK cells in hepatocytes. If apoptosis is prevented, a more limited necrotic effect is induced. Therefore, this study shows that NK cells are fully equipped to induce both apoptosis and necrosis in hepatocytes, but appear to prefer the apoptotic route.
Abstract 2873: Elucidation of dietary omega-6/omega-3 ratio effects on chemopreventive activity using mammographic density as a surrogate marker in rats
Authors: Zongjian Zhu, John N. McGinley, Weiqin Jiang, Andrea Manni, Karam El-Bayoumy, Henry J. Thompson
Journal: Cancer Research (2010)

Abstract Although beneficial effects of omega-3 fatty acids in breast cancer prevention have been reported, the optimal dietary omega-6/omega-3 (n-6/n-3) ratio for chemoprevention has not been established. Although n-6 and n-3 fatty acids are essential for the normal development and maintenance of biological function, both classes of fatty acid share metabolizing enzymes and thus have the potential to antagonize each other's metabolism. Therefore, experiments were undertaken to elucidate the ratio(s) of dietary n-6/n-3 that is optimal for chemoprevention in the absence of adverse effects on normal development using mammographic density as a surrogate marker for breast cancer risk. Female Sprague Dawley rats (n=9/group, 32 days of age) were randomized to one of 7 dietary formulations that varied in their ratio of n-6/n-3 as follows: 25:1, 10:1, 5:1, 1:1, 1:5, 1:10, 1:25. The percent of dietary calories from fat was 30% across all 7 formulations. Mammary gland density was determined via digital analyses of abdominal-inguinal mammary gland whole mounts stained with alum carmine. Density was calculated using either area or integrated optical density and expressed as the percent of the mammary gland fat pad occupied by mammary epithelium. Mammographic density was unaffected in the high n-6 arm of the study; whereas, it was significantly reduced in the high omega-3 arm (16%, p&amp;lt;0.03). Efforts are ongoing to determine: 1) whether reduced density is accounted for by effects on cell cycle flux or induction of a pro-apoptotic environment, 2) the extent to which these effects are mediated by altered signaling via activated protein kinase B (Akt), and 3) the mechanism(s) by which the n-6/n-3 ratio alters eicosanoid-mediated bioactivity. Supported by grant KG081632 from the Susan G. Komen Foundation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2873.
Fundamental Problems in the Pathology of Multiple Sclerosis and Allied Demyelinating Diseases
Authors: C. E. Lumsden
Journal: BMJ (1951)

<h3>Background</h3> Distributed medical education (DME) programmes, in which training occurs in underserviced areas, have been established as a strategy to increase recruitment and retention of new physicians following graduation to these areas. Little is known about what makes physicians remain in the area in which they train. <h3>Objectives</h3> To explore the factors that contributed to family physician9s decisions to practice in an underserviced area following graduation from a DME programme. <h3>Methods</h3> Semistructured inperson interviews were conducted with 19 family physicians who graduated from a DME residency training programme. Programme records were reviewed to identify practice location of DME programme graduates. <h3>Results</h3> Of the 32 graduates to date from this DME programme, 66% (N=21) and all of the interview participants established their practices in this region after completing their residency training. Five key themes were identified from the interview analysis as impacting physicians’ decisions to establish their practice in an underserviced area following graduation: familial ties to the region, practice opportunities, positive clerkship and residency experiences, established relationships with specialists and services in the area and lifestyle opportunities afforded by the location. <h3>Conclusions</h3> This study suggests that DME programmes can be an effective strategy for equalising the distribution of family physicians and highlights the ways in which these programmes can facilitate recruitment and retention in underserviced areas, including being responsive to residents’ personal preferences and objectives for learning and shaping their residency experiences to meet to these objectives.
The West of Scotland coronary prevention study: economic benefit analysis of primary prevention with pravastatin
Authors: J Caro, W Klittich, A McGuire, I Ford, J Norrie, D Pettitt, J McMurray, J Shepherd
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> To estimate the economic efficiency of using pravastatin to prevent the transition from health to cardiovascular disease in men with hypercholesterolaemia. <b>Design:</b> Economic benefit analysis based on data from the West of Scotland coronary prevention study. Treatment specific hazards of developing cardiovascular disease according to various definitions were estimated. Scottish record linkage data provided disease specific survival. Cost estimates were based on extracontractual tariffs and event specific average lengths of stay calculated from the West of Scotland coronary prevention study. <b>Subjects:</b> Men with hypercholesterolaemia similar to the subjects in the West of Scotland coronary prevention study. <b>Main outcome:</b> Cost consequences, the number of transitions from health to cardiovascular disease prevented, the number needed to start treatment, and cost per life year gained. <b>Results:</b> If 10 000 of these men started taking pravastatin, 318 of them would not make the transition from health to cardiovascular disease (number needed to treat, 31.4), at a net discounted cost of £20m over 5 years. These benefits imply an undiscounted gain of 2460 years of life, and thus £8121 per life year gained, or £20 375 per life year gained if benefits are discounted. Restriction to the 40% of men at highest risk reduces the number needed to treat to 22.5 (£5601 per life year gained (undiscounted) and £13 995 per life year gained (discounted)). <b>Conclusions:</b> In subjects without evidence of prior myocardial infarction but who have hypercholesterolaemia, the use of pravastatin yields substantial health benefits at a cost that is not prohibitive overall and can be quite efficient in selected high risk subgroups. <h3>Key messages</h3> The West of Scotland coronary prevention study showed that pravastatin can prevent cardiovascular disease in men with hypercholesterolaemia So far, reports have deemed this prevention unjustified due to adverse economic implications This analysis, based on data from the West of Scotland coronary prevention study and extensive data from the Scottish record linkage system, shows that using pravastatin in this way is worth considering because of its substantial clinical benefit at a reasonable cost Practitioners must now consider using pravastatin to prevent cardiovascular disease in men with hypercholesterolaemia Increased economic efficiency may be obtained by restricting prevention to patients with additional risk factors
Comparison of Bedtime Insulin Regimens in Patients with Type 2 Diabetes Mellitus
Authors: Hannele Yki-Järvinen
Journal: Annals of Internal Medicine (1999)

Background: Compared with other insulin regimens, combination therapy with oral hypoglycemic agents and bedtime insulin produces similar improvement in glycemic control but induces less weight gain. Objective: To determine whether bedtime insulin regimens differ with respect to their effects on weight gain in patients with type 2 diabetes. Design: Randomized, controlled trial. Setting: Four outpatient clinics at central hospitals. Patients: 96 patients (mean age, 58 ± 1 years; mean body mass index, 29 ± 1 kg/m2) whose type 2 diabetes was poorly controlled with sulfonylurea therapy (mean glycosylated hemoglobin value, 9.9% ± 0.2%; mean fasting plasma glucose level, 11.9 ± 0.3 mmol/L [214 ± 5 mg/dL]). Intervention: Random assignment to 1 year of treatment with bedtime intermediate-acting insulin plus glyburide (10.5 mg) and placebo, metformin (2 g) and placebo, glyburide and metformin, or a second injection of intermediate-acting insulin in the morning. Patients were taught to adjust the bedtime insulin dose on the basis of fasting glucose measurements. Measurements: Body weight, biochemical and symptomatic hypoglycemias, and indices of glycemic control. Results: At 1 year, body weight remained unchanged in patients receiving bedtime insulin plus metformin (mean change, 0.9 ± 1.2 kg; P < 0.001 compared with all other groups) but increased by 3.9 ± 0.7 kg, 3.6 ± 1.2 kg, and 4.6 ± 1.0 kg in patients receiving bedtime insulin plus glyburide, those receiving bedtime insulin plus both oral drugs, and those receiving bedtime and morning insulin, respectively. The greatest decrease in the glycosylated hemoglobin value was observed in the bedtime insulin and metformin group (from 9.7% ± 0.4% to 7.2% ± 0.2% [difference, −2.5 ± 0.4 percentage points] at 1 year; P < 0.001 compared with 0 months and P < 0.05 compared with other groups). This group also had significantly fewer symptomatic and biochemical cases of hypoglycemia (P < 0.05) than the other groups. Conclusions: Combination therapy with bedtime insulin plus metformin prevents weight gain. This regimen also seems superior to other bedtime insulin regimens with respect to improvement in glycemic control and frequency of hypoglycemia.
OC-065 Functional Cortical Swallowing Activity And Neurotransmitters Concentrations Are Altered Following Neurostimulation Of Pharyngeal Motor Cortex: An Fmri And Resonance Spectroscopy (mrs) Study
Authors: E Michou, S Mistry, R Vidyasagar, D Downey, S Williams, S Hamdy
Journal: Gut (2014)

<h3>Introduction</h3> Combined pharyngeal electrical and transcranial-magnetic-stimulation or paired associative stimulation (PAS) is shown to induce beneficial neurophysiological and behavioural effects on swallowing in health and dysphagic stroke patients (Michou <i>et al</i>., <i>Gastroenterology</i> 2012). Here, we investigate brain changes during swallowing following application of PAS, using fMRI and MR spectroscopy to measure neural activity and GABA concentrations in the motor cortices. <h3>Methods</h3> Healthy adults (n = 11, 38 ± 9 yoa) were randomised to receive real and sham PAS on 2 separate visits. Event-related fMRI was performed to assess changes in brain activations in response to water and saliva swallowing and during rest. Data were analysed (SPM8), applying p &lt; 0.001 uncorrected thresholds with contrasts of ‘water swallowing-rest’ and ‘saliva swallowing-rest’. MRS data were acquired before and after the fMRI on both visits and GABA concentrations were measured (AMARES, jMRUI). <h3>Results</h3> Following real PAS, group analyses of ‘water swallowing-rest’ and ‘saliva swallowing-rest’ showed increased activation in motor and premotor areas bilaterally. Moreover, real PAS increased activations prominently in premotor areas contralateral to PAS (Figure 1 group mean brain activations following real PAS). Following real PAS, GABA concentrations in motor cortex decreased significantly both ipsilateral (P = 0.008) and contralateral (P = 0.013) to PAS. <h3>Conclusion</h3> Targeted neurostimulation applied to the human pharyngeal motor cortex induces local and remote changes in both primary and non-primary areas for water and saliva tasks. Moreover, stimulation leads to reduction of the inhibitory neurotransmitter GABA, when associated with swallowing. These findings allow us to understand the mechanisms underlying the beneficial effects of neurostimulation in modulating the brain swallowing network. <h3>Disclosure of Interest</h3> None Declared.
Discussion Sections in Reports of Controlled Trials Published in General Medical Journals
Authors: Mike Clarke
Journal: JAMA (2002)

Reliable interpretation of the results of a controlled trial entails setting its results in the context of similar research. A previous study showed that most reports of controlled trials published in 5 general medical journals in May 1997 were deficient in this respect. We assessed the extent to which reports of controlled trials published in the same 5 journals discussed new results in light of the totality of evidence from other controlled trials.Assessment of the discussion sections in all 33 reports of randomized trials published during May 2001 in Annals of Internal Medicine, BMJ, JAMA, The Lancet, and The New England Journal of Medicine.Three reports appeared to have been the first published trials to address the questions studied. In none of the remaining 30 reports were the results of the new trial discussed in the context of an updated systematic review of other trials. Although reference was made to relevant systematic reviews in 3 of these 30 reports, there was no integration, quantitative or qualitative, of the results of the new trials in an update of these reviews. In the remaining 27 reports, there was no evidence that any systematic attempt had been made to set the new results in the context of previous trials.Between 1997 and 2001, there was no evidence of progress in the proportion of reports of trials published in general medical journals that discussed the new results within the context of, or with reference to, up-to-date systematic reviews of relevant evidence from other controlled trials.
The association of hepatitis A and <i>Helicobacter pylori</i> with sensitization to common allergens, asthma and hay fever in a population of young British adults
Authors: D. Jarvis, C. Luczynska, S. Chinn, P. Burney
Journal: Allergy (2004)

Background: A negative association of oro‐faecally spread infection with serological markers of sensitization and allergic disease has been reported. Method: Previous infection with hepatitis A and Helicobacter pylori was assessed in a community‐based sample of young British adults and associations with serum‐specific IgE to environmental allergens, asthma‐like symptoms and hay fever were examined. Results: There was no association of previous infection with hepatitis A or H. pylori with wheeze or hay fever. There was no evidence of an association of infection with either agent and sensitization except for the isolated finding of a lower prevalence of sensitization to grass in those with IgG antibodies to H. pylori (OR 0.65, 95% CI 0.43–0.99). This association did not explain the negative association of family size with sensitization to grass. Conclusion: In this population, there was no evidence that infection with hepatitis A or H. pylori was associated with lower levels of IgE sensitization, asthma or hay fever except for an isolated finding of a negative association of H. pylori infection with sensitization to grass.