tbuckley/cabot-search huggingface dataset:
Cholesterol Lowering With Simvastatin Improves Prognosis of Diabetic Patients With Coronary Heart Disease: A subgroup analysis of the Scandinavian Simvastatin Survival Study (4S)
Authors: K Pyörälä, Terje R Pedersen, John Kjekshus, Ole Faergeman, Anders G Olsson, Gudmundur Thorgeirsson
Journal: Diabetes Care (1997)

OBJECTIVE To assess in diabetic patients with coronary heart disease (CHD) the effect of cholesterol lowering with simvastatin on mortality and the risk of CHD and other atherosclerotic events. RESEARCH DESIGN AND METHODS A post hoc subgroup analysis was carried out on data from 202 diabetic patients and 4,242 nondiabetic patients with previous myocardial infarction or angina pectoris, serum total cholesterol 5.5–8.0 mmol/l, and serum triglycerides ≤ 2.5 mmol/l who were participating in the Scandinavian Simvastatin Survival Study (4S). Participants in the 4S were randomly assigned to double-blind treatment with simvastatin, 20 mg daily, with blinded dosage titration up to 40 mg daily, according to cholesterol response during the first 6–18 weeks, or placebo. Endpoints were 1) total mortality, 2) major CHD events (CHD death or nonfatal myocardial infarction), 3) other acute atherosclerotic events, 4) myocardial revascularization procedures. RESULTS Over the 5.4-year median follow-up period, simvastatin treatment produced mean changes in serum lipids in diabetic patients similar to those observed in nondiabetic patients. The relative risks (RRs) of main endpoints in simvastatin-treated diabetic patients were as follows: total mortality 0.57 (95% CI, 0.30–1.08; P = 0.087), major CHD events 0.45 (95% CI, 0.27–0.74; P = 0.002), and any atherosclerotic event 0.63 (95% CI, 0.43–0.92; P = 0.018). The corresponding RRs in nondiabetic patients were the following: 0.71 (95% CI, 0.58–0.87; P = 0.001), 0.68 (95% CI, 0.60–0.77; P &amp;lt; 0.0001), and 0.74 (95% CI, 0.68–0.82; P &amp;lt; 0.0001). CONCLUSIONS The results strongly suggest that cholesterol lowering with simvastatin improves the prognosis of diabetic patients with CHD. The absolute clinical benefit achieved by cholesterol lowering may be greater in diabetic than in nondiabetic patients with CHD because diabetic patients have a higher absolute risk of recurrent CHD events and other atherosclerotic events.
Apolipoprotein E Genotype and the Diagnostic Accuracy of Cerebrospinal Fluid Biomarkers for Alzheimer Disease
Authors: Ronald Lautner, Sebastian Palmqvist, Niklas Mattsson, Ulf Andreasson, Anders Wallin, Erik Pålsson, Joel Jakobsson, Sanna-Kaisa Herukka, Rikard Owenius, Bob Olsson, Harald Hampel, Dan Rujescu, Michael Ewers, Mikael Landén, Lennart Minthon, Kaj Blennow, Henrik Zetterberg, Oskar Hansson
Journal: JAMA Psychiatry (2014)

Several studies suggest that the apolipoprotein E (APOE) ε4 allele modulates cerebrospinal fluid (CSF) levels of β-amyloid 42 (Aβ42). Whether this effect is secondary to the association of the APOE ε4 allele with cortical Aβ deposition or whether APOE ε4 directly influences CSF levels of Aβ42 independently of Aβ pathology remains unknown.To evaluate whether the APOE genotype affects the diagnostic accuracy of CSF biomarkers for Alzheimer disease (AD), in particular Aβ42 levels, and whether the association of APOE ε4 with CSF biomarkers depends on cortical Aβ status.We collected data from 4 different centers in Sweden, Finland, and Germany. Cohort A consisted of 1345 individuals aged 23 to 99 years with baseline CSF samples, including 309 with AD, 287 with prodromal AD, 399 with stable mild cognitive impairment, 99 with dementias other than AD, and 251 controls. Cohort B included 105 nondemented younger individuals (aged 20-34 years) with CSF samples available. Cohort C included 118 patients aged 60 to 80 years with mild cognitive symptoms who underwent flutemetamol F 18 ([18F]flumetamol) positron emission tomography amyloid imaging and CSF tap.Standard care.Cerebrospinal fluid levels of Aβ42 and total and phosphorylated tau in relation to the APOE ε2/ε3/ε4 polymorphism in different diagnostic groups and in cases with or without cortical uptake of [18F]flutemetamol.The CSF levels of Aβ42 but not total and phosphorylated tau were lower in APOE ε4 carriers compared with noncarriers irrespective of diagnostic group (cohort A). Despite this, CSF levels of Aβ42 differed between participants with AD when compared with controls and those with stable mild cognitive impairment, even when stratifying for APOE genotype (P < .001 to P = .006). Multiple binary logistic regression revealed that CSF levels of Aβ42 and APOE ε4 genotype were independent predictors of AD diagnosis. In cohort B, APOE ε4 carrier status did not influence CSF levels of Aβ42. Moreover, when stratifying for cortical uptake of [18F]flutemetamol in cohort C, APOE ε4 genotype did not influence CSF levels of Aβ42. This result was replicated in a cohort with individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) using carbon 11-labeled Pittsburgh Compound B scanning.Cerebrospinal fluid levels of Aβ42 are strongly associated with the diagnosis of AD and cortical Aβ accumulation independent of APOE genotype. The clinical cutoff for CSF levels of Aβ42 should be the same for all APOE genotypes.
Rosuvastatin Decreases Caveolin-1 and Improves Nitric Oxide–Dependent Heart Rate and Blood Pressure Variability in Apolipoprotein E <sup>−/−</sup> Mice In Vivo
Authors: Michel Pelat, Chantal Dessy, Paul Massion, Jean-Pierre Desager, Olivier Feron, Jean-Luc Balligand
Journal: Circulation (2003)

Decreased heart rate variability (HRV) and increased blood pressure variability (BPV), determined in part by nitric oxide (NO)-dependent endothelial dysfunction, are correlated with adverse prognosis in cardiovascular diseases. We examined potential alterations in BPV and HRV in genetically dyslipidemic, apolipoprotein (apo) E-/-, and control mice and the effect of chronic statin treatment on these parameters in relation to their NO synthase (NOS)-modifying properties.BP and HR were recorded in unrestrained, nonanesthetized mice with implanted telemetry devices with or without rosuvastatin. Cardiac and aortic expression of endothelial NOS and caveolin-1 were measured by immunoblotting. Both systolic BP and HR were elevated in apoE-/- mice, with abolition of their circadian cycles. Spectral analysis showed an increase in their systolic BPV in the very-low-frequency (+17%) band and a decrease in HRV in the high-frequency (-57%) band, reflecting neurohumoral and autonomic dysfunction. Decreased sensitivity to acute injection of atropine or an NOS inhibitor indicated basal alterations in both parasympathetic and NOS regulatory systems in apoE-/- mice. Aortic caveolin-1 protein, an inhibitor of endothelial NOS, was also increased in these mice by 2.0-fold and correlated positively with systolic BPV in the very-low-frequency band. Rosuvastatin treatment corrected the hemodynamic and caveolin-1 expression changes despite persisting elevated plasma cholesterol levels.Rosuvastatin decreases caveolin-1 expression and promotes NOS function in apoE-/-, dyslipidemic mice in vivo, with concurrent improvements in BPV and HRV. This highlights the beneficial effects of rosuvastatin on cardiovascular function beyond those attributed to lipid lowering.
Human Regulatory T Cells with Alloantigen Specificity Are More Potent Inhibitors of Alloimmune Skin Graft Damage than Polyclonal Regulatory T Cells
Authors: Pervinder Sagoo, Niwa Ali, Garima Garg, Frank O. Nestle, Robert I. Lechler, Giovanna Lombardi
Journal: Science Translational Medicine (2011)

Alloantigen-specific human regulatory T cells may improve immunosuppressive therapy after transplantation.
Age and sensitivity to lead toxicity: a review.
Authors: E B McCabe
Journal: Environmental Health Perspectives (1979)

During the past 20 years considerable attention has been focused on the epidemiologic features of childhood lead poisoning in the United States. Large numbers of children with symptomatic intoxication, as well as those with incipient symptoms, were commonplace a decade ago for physicians working in inner-city hospitals. With the recent availability of improved screening techniques, as well as a variety of environmental control measures, the incidence of symptomatic lead poisoning in children has diminished significantly in recent years. With the focus shifting from children with dangerously elevated body lead burdens to those with less significant exposures, increased attention has been directed to the various inherent metabolic and physical characteristics of the young that may influence the toxic effects of lead exposure. A number of differences with respect to lead exposure, absorption and retention, and varying nutritional conditions between children and older individuals are discussed. Experimental studies dealing with age differences of lead-treated animals are examined, and relevant human studies are reviewed.
You Don't Have to Be a Neuroscientist to Forget Everything With Triazolam—But It Helps
Authors: Luigi Di Maio
Journal: JAMA (1988)

<h3>To the Editor.</h3> —The report by Morris and Estes<sup>1</sup>warns against taking triazolam or other benzodiazepines to prevent jet lag, particularly if ethyl alcohol is consumed. The occurrence of transient global amnesia after taking triazolam actually "may be common"<sup>2</sup>and not necessarily related to alcohol consumption or travel across time zones. Alternatively, it may be that stress and disrupted sleep trigger the abnormal response to benzodiazepine ingestion. <h3>Report of a Case.</h3> —A 29-year-old Italian neurologist took 0.5mg of triazolam to ensure a good night's sleep. He had not slept well during the previous week, feeling pressured by an upcoming move to the United States. After a light dinner, not including alcohol, he went to bed at 11 PM but did not sleep well. He awoke at 5 AM, had breakfast, caught a bus to the railroad station, and then took a train to another city, arriving three hours
Mass Radiography. With Special Reference to Screen Photography and Pulmonary Tuberculosis
Authors: F. J. Bentley, Z. A. Leitner
Journal: BMJ (1940)

NMass radiography may be carried out in different ways.Many such investigations directed towards the discovery of pulmonary tuberculosis have been conducted in the past on large selected groups of population by ordinary x-ray methods.The work of Opie,57 Hetherington,"' Rath- bone,6" and Wakefield86 in the United States is well known in this connexion.Wingfield," and more recently D'Arcy Hart and Morland,25 have undertaken work on similar lines in this country.Mass use of the full-size x-ray film must necessarily have limited application on grounds chiefly of expense, and the fluorescent screen alone has accordingly found favour with many workers, particularly in France.The greatest drawback to screening alone is the absence of any record.In America a method of mass radiography by means of a paper roll casette has been invented, and this has been further elaborated in Germany,
A SIMPLE APPARATUS FOR TESTING AND WASHING FILTER CANDLES
Authors: F. H. Krock
Journal: JAMA (1923)

The importance of testing filter candles by the air pressure method has been pointed out by Bulloch and Craw<sup>1</sup>and by Ferry.<sup>2</sup>The apparatus here described was designed to simplify the test, and to give greater control over the manipulations. It consists of a 4-liter aspirator bottle,<i>A</i>, and an S-open-end manometer,<i>B</i>, as shown in the illustration. The manometer is more accurate, cheaper, and more useful than <h3>PURPOSES FOR WHICH APPARATUS MAY BE USED</h3> 1.<i>Testing the initial capillary pressure of a filter candle</i>. The candle, previously dried for about one hour at 100 C., is attached at<i>E</i>, the tubing clamped at 3, and the candle immersed in clean water in an open vessel,<i>C</i>. The pressure caused by the water soaking into the pores of the candle and displacing the contained air is recorded on the manometer,<i>B</i>, and can be read by moving the
Analysis of target cell susceptibility as a basis for the development of a chemoprotective strategy against benzene-induced hematotoxicities.
Authors: M A Trush, L E Twerdok, S J Rembish, H Zhu, Y Li
Journal: Environmental Health Perspectives (1996)

A goal of our research is to identify biochemical factors that underlie the susceptibility of bone marrow cell populations to benzene metabolites so as to develop a mechanistically based chemoprotective strategy that may be used in susceptible humans exposed to benzene. By doing biochemical risk analysis of bone marrow stromal cells from mice and rats and the human myeloid cell lines, HL-60 and ML-1; and by using buthionine sulfoximine and dicumarol we have observed that the susceptibility of these cell populations to hydroquinone (HQ) correlates with their concentration of glutathione (GSH) and activity of quinone reductase (QR). Accordingly, the induction of QR and GSH by 1,2-dithiole-3-thione (D3T) in these cell populations has resulted in a significant protection against the following hydroquinone-mediated toxicities: inhibition of cell proliferation and viability; reduced ability of stromal cells to support myelopoiesis; and altered differentiated of ML-1 cells to monocytes/macrophages. Preliminary in vivo experiments indicate that feeding mice D3T results in an induction of QR in the bone marrow compartment such that stromal cells are more resistant to hydroquinone-induced cytotoxicity in vitro. Overall, these studies suggest that in addition to hepatic cytochrome P4502E1, bone marrow QR and GSH are factors that could determine an individual's relative susceptibility to the toxic effects of benzene.
Psychotherapy Reduces Disability, Saves Money
Authors: Lynne Lamberg
Journal: JAMA (1997)

REPORTS OF psychotherapy's death are greatly exaggerated, its proponents say. Psychotherapy works. It saves money for patients and insurers. It improves job and social performance, prevents lost workdays, reduces the inappropriate use of other medical services, and enhances quality of life, the American Psychiatric Association (APA) Commission on Psychotherapy by Psychiatrists (COPP) asserted, offering a wealth of data to support these claims at the APA annual meeting in San Diego, Calif, in May. "The social costs of untreated psychiatric illness are enormous," said Norman Clemens, MD, COPP chair, clinical professor of psychiatry at Case Western Reserve University, Cleveland, Ohio, and a member of the APA Board of Trustees. "These disorders not only harm individuals in their work and family lives but also reverberate through society," he said. "This is dramatically apparent in the welfare and criminal justice systems." <h3>Relic or Potential Help?</h3> With increasingly effective psychotropic medications and unrelenting pressure
NHS trust made 300 000 by selling drugs to wholesaler for export
Authors: J. Laurance
Journal: BMJ (2010)

A bizarre twist in the unfolding story of drug shortages in the NHS emerged last week with the disclosure that an NHS trust had sold millions of pounds worth of drugs abroad because it saw an opportunity to make a fast profit.

The Royal Surrey County Hospital NHS Foundation Trust said it had spent £4.6m (€5.2m; $7.1m) over a period of 10 months buying up drugs at the NHS price and selling them to a wholesaler for export, making a profit of £300 000. It later defended its activities on the grounds that trusts had been encouraged to be “entrepreneurial” and continued the practice for six months after government warnings that its behaviour …
Spinal Epidural Abscess
Authors: Rabih O Darouiche
Journal: New England Journal of Medicine (2006)

Spinal epidural abscesses are often initially misdiagnosed, particularly in neurologically intact patients. Epidural infections can cause injury to the spinal cord. The incidence of these infections has increased with increasing use of spinal instrumentation, vascular access, and injection drugs. This review explains the diagnostic and therapeutic challenges and how to avoid spinal cord infarction.
Arteriographic evidence of coronary arterial spasm in acute myocardial infarction.
Authors: P B Oliva, J C Breckinridge
Journal: Circulation (1977)

Coronary arteriography was performed before and after the intracoronary injection of nitroglycerin to determine the presence or absence of spasm in patients within the first 12 hours of acute myocardial infarction. Coronary arterial spasm was demonstrated in six of fifteen (40%) acute myocardial infarctions associated with coronary artery disease. In five of the six instances the interval from the onset of symptoms to arteriography was less than 6 hours. Spasm was superimposed on a high-grade atherosclerotic obstruction and was separated from the catheter tip by a segment of normal vessel in each instance. The coronary artery remained patent (following the initial relief of spasm) in two patients maintained on sublingual nitrates and heparin. Spasm, superimposed on an atherosclerotic obstruction, may be the primary event or a secondary occurrence in the pathophysiology of acute myocardial infarction. Catecholamines could play an important role in the early pathophysiology of acute myocardial infarction by producing spasm and/or platelet aggregation at the site of an atherosclerotic obstruction. A dynamic interaction between spasm, platelet aggregates and the atherosclerotic plaque may precede coronary thrombosis.
Sequential gene expression profiling during treatment for identification of predictive markers and novel therapeutic targets in chronic lymphocytic leukemia
Authors: M Shehata, D Demirtas, S Schnabl, M Hilgarth, R Hubmann, C Fonatsch, I Schwarzinger, G Hopfinger, K Eigenberger, D Heintel, E Porpaczy, K Vanura, A Hauswirth, J D Schwarzmeier, A Gaiger, S Stilgenbauer, M Hallek, M Bilban, U Jäger
Journal: Leukemia (2010)
Rash and fever after sulfasalazine use
Authors: N. Raithatha, S. Mehrtens, M. Mouyis, J. Manson
Journal: BMJ (2014)

A 28 year old Afro-Caribbean woman presented to our hospital with a three day history of an acute, diffuse, urticarial, papular rash on her trunk, limbs, and face. She also had facial swelling and fever. The mucosa and conjunctiva were not affected. Her medical history was unremarkable until a recent diagnosis of seronegative inflammatory arthritis during her second trimester of pregnancy, for which she was initially treated with corticosteroids and hydroxychloroquine. After a miscarriage at 30 weeks, this was switched to sulfasalazine for the three weeks before this admission.

On examination she had a fever (38.5°C), tachycardia, bilateral cervical and groin lymphadenopathy, generalised facial swelling (fig 1⇓), and a diffuse erythrodermic rash covering her trunk, face, and limbs (fig 2⇓).





A full blood count showed haemoglobin 120 g/L (reference range 115-165), white cell count 5.4×109/L (4.5-11), neutrophils 3.48×109/L (2-7.5), lymphocytes 3.26×109/L (1.3-4), eosinophils 0.16×109/L (0-0.45), and platelets 150×109/L (150-440). A blood film showed a few atypical lymphocytes and reactive lymphocytosis.

Liver function tests showed bilirubin 9 mmol/L (5-17), alanine transaminase 415 IU/L (10-35), alkaline phosphatase 145 IU/L (35-104). Her previous liver function test results had been within the reference range. C reactive protein was 32 mg/L (0-5); a viral screen was negative; and an immunology screen showed that antinuclear antibodies, immunoglobulins, and complement were all within the normal range. A microbiology screen showed that urine and blood cultures were negative 

A chest radiograph was clear. Skin biopsy showed leucocytosis and early vasculitis.



### 1. What are the important differential diagnoses in patients admitted to hospital with acute rash after drug exposure?

#### Short answer

Toxic epidermal necrolysis, Stevens-Johnson syndrome, drug …
Is pentagastrin-stimulated secretion mediated by histamine?
Authors: W K Man, C J Ingoldby, J Spencer
Journal: Gut (1984)

Patients with duodenal ulcer disease received either a two hour pentagastrin infusion test or a similar test with the addition of a bolus of cimetidine, 200 mg, after one hour of pentagastrin. Pentagastrin induced secretion of acid and histamine, the secretion patterns of the two being similar. Total histamine output in the gastric aspirate in the first hour of pentagastrin infusion was related to total acid output (r = 0.58, p less than 0.01). A similar correlation was observed during the second hour of pentagastrin infusion (r = 0.61, p less than 0.05). Plasma histamine concentration rose to a peak coinciding with maximal acid secretion. After cimetidine blockade, gastric acid fell rapidly but gastric histamine output did not change. Plasma histamine concentration increased further. These results suggest that pentagastrin induced gastric histamine release is not affected by an acid inhibiting dose of cimetidine. Cimetidine caused histamine release into the circulation in both healthy volunteers and patients after total gastrectomy. The rise in plasma histamine concentration, however, was transient. In contrast, during pentagastrin infusion, the plasma histamine concentration remained high. These data support the hypothesis that histamine release induced by pentagastrin is a major stimulant of gastric acid secretion.
Government underestimated dengue fever in India by factor of 282, finds study
Authors: P. Pulla
Journal: BMJ (2014)

Official estimates of the annual incidence of dengue fever in India are lower than the actual number by a factor of 282, a study has found.

The researchers estimated that between 2006 and 2012 the average number of new cases of dengue fever was 5 778 476 a year, instead of the 20 474 reported by India’s National Vector Borne Disease Control Programme. The study was published in the American Journal of Tropical Medicine and Hygiene .1

Since India experienced its first epidemic of dengue fever in 1963-64 outbreaks have grown larger and more frequent. Severity of symptoms and numbers of deaths from the disease have also increased, with the first epidemic of dengue haemorrhagic fever and dengue shock syndrome occurring in Delhi in 1996. While an episode of the illness is mild in …
A national screening programme for diabetic retinopathy
Authors: U. Freudenstein
Journal: BMJ (2001)

Retinopathy is the biggest single cause of blindness in the United Kingdom.1 Laser coagulation of high risk lesions detected by screening can significantly reduce the likelihood of blindness and deteriorating vision. 2 3 Screening for diabetic retinopathy has been available in some areas of the United Kingdom since the late 1980s, but access is uneven, screening techniques of differing effectiveness have been used, 3 4 quality assurance may not be an integral part, and the resources available are variable. A national screening programme has now been recommended, but several organisational issues need to be tackled if this programme is not to repeat the problems incurred by earlier national screening programmes.

In 1999 the UK National Screening Committee asked the British Diabetic Association (now Diabetes UK) to convene an advisory panel to produce a model for a cost effective national screening programme. The panel's recommendations are now published on the national screening committee's website (www.diabetic-retinopathy.screening.nhs.uk/index.html). The preferred method for screening is digital retinal photography. …
Treatment of Refractory Uveitis with Adalimumab: A Prospective Multicenter Study of 131 Patients
Authors: Manuel Díaz-Llopis, David Salom, Carmen Garcia-de-Vicuña, Miguel Cordero-Coma, Gabriela Ortega, Norberto Ortego, Marta Suarez-de-Figueroa, Maria J. Rio-Pardo, Carlos Fernandez-Cid, Alex Fonollosa, Ricardo Blanco, Angel M. Garcia-Aparicio, Jose M. Benitez-del-Castillo, Jose L. Olea, J. Fernando Arevalo
Journal: Ophthalmology (2012)
653 TOLL-LIKE RECEPTOR-DEPENDENT IFN I AND III SUBTYPES INDUCTION IN HUMAN PERIPHERAL BLOOD MONONUCLEAR CELLS FROM PATIENTS WITH HCV INFECTION
Authors: Y. Ling, S.-Y. Zhang, X.-H. Li, X.-F. Kong, B.-L. Yao, D.-M. Yu, G.-D. Jin, Z.-M. Lu, X.-X. Zhang
Journal: Journal of Hepatology (2009)