tbuckley/cabot-search huggingface dataset:
Effects of simvastatin and cholestyramine on bile lipid composition and gall bladder motility in patients with hypercholesterolaemia.
Authors: J W Smit, K J Van Erpecum, P Portincasa, W Renooij, D W Erkelens, G P Van Berge-Henegouwen
Journal: Gut (1995)

Although the effects of 3-hydroxy, 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and bile acid sequestrants on bile lipid composition have been studied separately, no data are available on combination therapy of these drugs. Moreover, the effects of prolonged (four weeks) administration of these drugs on gall bladder motility, an important determinant of cholesterol gall stone formation, have not been studied so far. A prospective study was therefore performed with eight patients who had hypercholesterolaemia (age 53 (5) (SEM), body mass index 27.4 (1.1) kg m-2, low density lipoprotein cholesterol 5.9 (0.3) mmol/l). They received treatment during three periods of four weeks with simvastatin 20 mg/day, cholestyramine 4 g twice daily, and a combination of both in random order, each treatment period separated by a two week wash out period. Before treatment and after each treatment period, postprandial gall bladder motility was studied with ultrasound, followed by duodenal bile sampling. Serum cholesterol decreased in all subjects in any treatment period illustrating good compliance. Molar percentages in duodenal bile of cholesterol, phospholipids, and bile salts were unchanged during simvastatin and cholestyramine treatment. During combined therapy percentage bile salts was lower (72.5 (2.9)% v 77.8 (1.7)% at baseline, p &lt; 0.05) whereas phospholipids were higher (21.2 (2.4)% v 16.4 (1.3)% at baseline, p &lt; 0.05). As a result cholesterol saturation index (CSI) did not change in any treatment period. No cholesterol crystals were detected in any bile sample, taken at baseline and after each treatment period. Bile salt hydrophobicity index during cholestyramine (0.19 (0.02)) and combined treatment (0.22 (0.01)) decreased strongly compared with baseline (0.34 (0.01), p &lt; 0.001, p &lt; 0.01, respectively), resulting from increased proportions of glycocholate (59.4 (3.9)% (cholestyramine), 55.6 (2.4)% (combination), and 28.2 (2.2) (baseline), p &lt; 0.001)) and decreased proportions of deoxycholic acid and chenodeoxycholic acid. Fasting gall bladder volume was increased during simvastatin (28.7 (2.8) ml) v baseline (23.2 (2.3) ml, p &lt; 0.01) whereas, residual volume did not differ (5.7 (0.9) ml (simvastatin) v 5.9 (0.7) (baseline). During cholestyramine and combined treatment, no significant differences in gall bladder motility were seen. In conclusion, this study suggests that HMG-CoA reductase inhibitors alone and combined with cholestyramine do not affect major determinants of cholesterol gall stone formation, for example, CSI and gall bladder emptying. In addition cholestyramine alone and combined with simvastatin leads to a strong decrease of bile salt hydrophobicity, which may be beneficial in the prevention of nucleation of cholesterol crystals.
829-6 A randomized trial comparing rheolytic thrombectomy before infarct artery stenting with stenting alone in patients undergoing percutaneous coronary intervention for acute myocardial infarction
Authors: Guido Parodi, Renato Valenti, Angela Migliorini, Gentian Memisha, Emilio V Dovellini, Giampaolo Cerisano, David Antoniucci
Journal: Journal of the American College of Cardiology (2004)
The Metabolic Syndrome and Total and Cardiovascular Disease Mortality in Middle-aged Men
Authors: Hanna-Maaria Lakka
Journal: JAMA (2002)

ContextThe metabolic syndrome, a concurrence of disturbed glucose and insulin metabolism, overweight and abdominal fat distribution, mild dyslipidemia, and hypertension, is associated with subsequent development of type 2 diabetes mellitus and cardiovascular disease (CVD). Despite its high prevalence, little is known of the prospective association of the metabolic syndrome with cardiovascular and overall mortality.ObjectiveTo assess the association of the metabolic syndrome with cardiovascular and overall mortality using recently proposed definitions and factor analysis.Design, Setting, and ParticipantsThe Kuopio Ischaemic Heart Disease Risk Factor Study, a population-based, prospective cohort study of 1209 Finnish men aged 42 to 60 years at baseline (1984-1989) who were initially without CVD, cancer, or diabetes. Follow-up continued through December 1998.Main Outcome MeasuresDeath due to coronary heart disease (CHD), CVD, and any cause among men with vs without the metabolic syndrome, using 4 definitions based on the National Cholesterol Education Program (NCEP) and the World Health Organization (WHO).ResultsThe prevalence of the metabolic syndrome ranged from 8.8% to 14.3%, depending on the definition. There were 109 deaths during the approximately 11.4-year follow-up, of which 46 and 27 were due to CVD and CHD, respectively. Men with the metabolic syndrome as defined by the NCEP were 2.9 (95% confidence interval [CI], 1.2-7.2) to 4.2 (95% CI, 1.6-10.8) times more likely and, as defined by the WHO, 2.9 (95% CI, 1.2-6.8) to 3.3 (95% CI, 1.4-7.7) times more likely to die of CHD after adjustment for conventional cardiovascular risk factors. The metabolic syndrome as defined by the WHO was associated with 2.6 (95% CI, 1.4-5.1) to 3.0 (95% CI, 1.5-5.7) times higher CVD mortality and 1.9 (95% CI, 1.2-3.0) to 2.1 (95% CI, 1.3-3.3) times higher all-cause mortality. The NCEP definition less consistently predicted CVD and all-cause mortality. Factor analysis using 13 variables associated with metabolic or cardiovascular risk yielded a metabolic syndrome factor that explained 18% of total variance. Men with loadings on the metabolic factor in the highest quarter were 3.6 (95% CI, 1.7-7.9), 3.2 (95% CI, 1.7-5.8), and 2.3 (95% CI, 1.5-3.4) times more likely to die of CHD, CVD, and any cause, respectively.ConclusionsCardiovascular disease and all-cause mortality are increased in men with the metabolic syndrome, even in the absence of baseline CVD and diabetes. Early identification, treatment, and prevention of the metabolic syndrome present a major challenge for health care professionals facing an epidemic of overweight and sedentary lifestyle.
"Big tobacco can be taken on and beaten," say Australian officials
Authors: M. Sweet
Journal: BMJ (2012)

Tobacco companies have failed in a critical legal challenge to Australia’s pioneering introduction of plain packaging of cigarettes, in a development described as “the worst defeat yet for Big Tobacco.”

The World Health Organization and public health leaders predict that other countries will be encouraged to also mandate plain packaging.

The WHO director general, Margaret Chan, has urged the rest of the world “to follow Australia’s tough stance on tobacco marketing.”

She said in a statement: “With Australia’s victory, public health enters a brave new world of tobacco control. With so many countries lined up to ride on Australia’s coat tails, what we hope to see is a domino …
The anxious child.
Authors: A Bolton
Journal: BMJ (1972)

Anxiety is an appropriate reaction to some circumstances of stress and danger, when the traditional "fight or flight" be- haviour serves a useful purpose.Indeed, in man a conspicuous absence of anxiety when it would normally be expected is re- garded as pathological.Thus, such an absence may denote either the excessive use of defence mechanisms or a diminished aware- ness or appreciation of a reality-based threat-a feature which may occur in some organic or psychotic states.In adults the ego
Identification of Retinoid-Modulated Proteins in Squamous Carcinoma Cells Using High-Throughput Immunoblotting
Authors: Hyun-Jung Kim, Reuben Lotan
Journal: Cancer Research (2004)

Abstract Retinoids have shown clinical efficacy in cancer chemoprevention and therapy presumably by modulating the growth, differentiation, and apoptosis of normal, premalignant, and malignant cells. To better understand the mechanisms by which retinoids exert their effects, we used a high-throughput Western blotting method (Becton-Dickinson PowerBlot) to evaluate changes in the levels of cellular signaling proteins in head and neck squamous cell carcinoma cells treated with the cytostatic all-trans-retinoic acid or with the proapoptotic retinoids 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid or N-(4-hydroxyphenyl)retinamide. Treatments of the head and neck squamous cell carcinoma cells with these retinoids for 24 h resulted in increased levels of 14, 22, and 22 proteins and decreased levels of 5, 10, and 7 proteins, respectively. The changes in the levels of the following proteins were confirmed by conventional western immunoblotting: all-trans-retinoic acid increased ELF3, topoisomerase II α, RB2/p130, RIG-G, and EMAPII and decreased MEF2D and cathepsin L. N-(4-Hydroxyphenyl)retinamide up-regulated ELF3, c-Jun, Rb2/p130, JAK1, p67phox, Grb2, O6-methylguanine-DNA methyltransferase, and Ercc-1. 6-[3-(1-Adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid increased Rb2/p130, c-Jun, Sp1, Sin, and tomosyn and decreased cathepsin L, Mre11, and topoisomerase II α. Some of these proteins were also modulated by these retinoids in other human cancer cell lines. A subset of the proteins were modulated similarly by the different retinoids, whereas changes in other proteins were unique for each retinoid. These results suggest that the mechanisms by which these retinoids modulate proteins are distinct but may overlap. Some of the retinoid-modulated proteins identified in this study may be novel candidates for mediating different responses to retinoids.
Childhood Epilepsy: A Pediatric-Psychiatric Approach
Authors: Louis D. Boshes
Journal: JAMA (1978)

Childhood epilepsy, like that in the adult, was once managed by merely prescribing a drug or a combination of drugs, titrating them until an optimum effect was achieved. Little if any consideration was ever given to the total care of that patient. Now in the case of a child with seizures, this ongoing deficit of the past has been better recognized, and aggressive efforts are now made to treat other associated handicaps, to include scholastic, social, and emotional problems in that youngster.  This premise is embodied in the present lucid, concise, ambitious little volume. The authors recognized that this symptom complex has numerous etiologic factors, and that the episodic manifestations depend on which part of the brain is involved, as well as on those routes over which the abnormal paroxysmal discharges are dispersed within the CNS.  A charming historical introduction with clever linkage to psychoanalytic precepts indicates to the reader
Selecting an internationally diverse medical workforce
Authors: Ed Peile
Journal: BMJ (2014)

Doing it with respect is in everyone’s best interests

Two new linked studies tackle difficult educational issues concerning international medical graduates practising medicine in the UK. Tiffin et al1 report that international graduates, mainly from outside the European Union, achieve less satisfactory outcomes than UK graduates at annual appraisals known as Annual Review Competency Panels (ARCP). McManus and Wakeford2 find that they perform less well than UK graduates in postgraduate examinations for trainees in internal medicine (Membership of the Royal Colleges of Physicians (MRCP)) and family medicine (Membership of the Royal Collage of General Practitioners (MRCGP)).

Both these data linkage studies were commissioned by the UK regulator, the General Medical Council (GMC), which is considering revising the two examinations that currently determine an international graduate’s fitness for medical registration in the UK. Importantly, both studies show that the two examinations, set by the Professional and Linguistics Assessment Board (PLAB Part 1 and PLAB Part 2), predict performance in later professional assessments. They also agree that international graduates who do better at compulsory English language tests do better in postgraduate training.

McManus and Wakeford use two different approaches to quantify how much the pass marks for PLAB examinations would have to change to select international graduates who would perform as well as UK graduates. Both methods yielded similar results and confirmed …
B7-1 Engagement of Cytotoxic T Lymphocyte Antigen 4 Inhibits T Cell Activation in the Absence of CD28
Authors: Francesca Fallarino, Patrick E. Fields, Thomas F. Gajewski
Journal: The Journal of Experimental Medicine (1998)

Ligation of cytotoxic T lymphocyte antigen 4 (CTLA4) appears to inhibit T cell responses. Four mechanisms have been proposed to explain the inhibitory activity of CTLA4: competition for B7-1 and B7-2 binding by CD28; sequestration of signaling molecules away from CD28 via endocytosis; delivery of a signal that antagonizes a CD28 signal; and delivery of a signal that antagonizes a T cell receptor (TCR) signal. As three of these potential mechanisms involve functional antagonism of CD28, an experimental model was designed to determine whether CTLA4 could inhibit T cell function in the absence of CD28. TCR transgenic/recombinase activating gene 2–deficient/CD28–wild-type or CD28-deficient mice were generated and immunized with an antigen-expressing tumor. Primed T cells from both types of mice produced cytokines and proliferated in response to stimulator cells lacking B7 expression. However, whereas the response of CD28+/+ T cells was augmented by costimulation with B7-1, the response of the CD28−/− T cells was strongly inhibited. This inhibition was reversed by monoclonal antibody against B7-1 or CTLA4. Thus, CTLA4 can potently inhibit T cell activation in the absence of CD28, indicating that antagonism of a TCR-mediated signal is sufficient to explain the inhibitory effect of CTLA4.
NHS could save 170m by improving diabetes care, estimates watchdog
Authors: I. Torjesen
Journal: BMJ (2012)

NHS diabetes services are not delivering value for money because patients are not getting regular checks and treatment to control their condition and are ending up in hospital as a result, says a report by the National Audit Office.

The report estimates that the NHS in England could save £170m (€210m; $270m) a year if patients received basic assessments and follow-up care to control their diabetes and to help prevent complications.1

Programme budgeting data from the Department of Health indicate that in 2009-10 the NHS spent £1.3bn on care of patients with diabetes, up from £0.9bn in 2006-7. But David Moon, director of health value for money studies at the National Audit Office, pointed out that this was a substantial underestimate and that the true cost was likely now to be at least £3.9bn.

“We estimate that by managing patients better and potentially preventing readmissions the NHS could save at …
Popliteal cyst rupture in normal knee joints
Authors: F G Simpson, P J Robinson, M Bark, M Losowsky
Journal: BMJ (1980)

to mention the possibility that joint rupture could be the presenting feature of inflammatory arthritis.When joint rupture complicates arthritis it is almost always restricted to early joint involvement.'In patients presenting with joint rupture systemic examin- ation and the investigation should be performed to exclude this possibility.Even if no obvious cause is found at the time of presentation many patients will develop frank local synovitis or evidence of a generalised rheu- matic disease within a year or two.
A Prospective Study of Coffee Consumption and the Risk of Symptomatic Gallstone Disease in Men
Authors: Michael F. Leitzmann
Journal: JAMA (1999)

Coffee has several metabolic effects that could reduce the risk of gallstone formation.To examine the association between coffee consumption and the risk of symptomatic gallstone disease in men.The Health Professionals Follow-up Study, a prospective cohort study, in which the consumption of coffee and other caffeinated drinks was assessed starting in 1986 as part of the 131-item food frequency questionnaire given to US male health professionals with follow-up through 1996.A total of 46008 men, aged 40 to 75 years in 1986, without history of gallstone disease.Newly symptomatic gallstone disease (diagnosed by ultrasonography or x-ray) or a cholecystectomy.During 404 166 person-years of follow-up, 1081 subjects reported symptomatic gallstone disease, of whom 885 required cholecystectomy. After adjusting for other known or suspected risk factors, compared with men who did not consume regular coffee in 1986 and 1990, the adjusted relative risk (RR) for those who consistently drank 2 to 3 cups of regular coffee per day was 0.60 (95% confidence interval [CI], 0.42-0.86) and for those who drank 4 or more cups per day the RR was 0.55 (95% CI, 0.33-0.92). All coffee brewing methods showed a decreased risk. The risk of symptomatic gallstone disease also declined with increasing caffeine intake (P for trend = .005). After controlling for known or suspected risk factors, the RR for men in the highest category of caffeine intake (>800 mg/d) compared with men in the lowest category (< or =25 mg/d) was 0.55 (95% CI, 0.35-0.87). In contrast, decaffeinated coffee was not associated with a decreased risk.In this cohort of US men, coffee consumption may have helped to prevent symptomatic gallstone disease.
ESTROGENIC HORMONES AND CARCINOGENESIS
Authors: LEO LOEB
Journal: JAMA (1935)

<h3>Note.</h3> —This article and the articles in the previous issues ofThe Journalare part of a series published under the auspices of the Council on Pharmacy and Chemistry. Other articles will appear in succeeding issues. When completed, the series will be. published in book form.—Ed. Three lines of investigation, conducted more or less independently of one another for a number of years, have led recently to the conclusion that a remarkably close relation in chemical constitution as well as in biologic effects exists between estrogenic hormones and certain hydrocarbons that occur in tar and are able to induce cancer. The facts that resulted directly in the formulation of this problem came in part from investigations of Kennaway, Cook and Dodds and their collaborators concerning the chemical constitution of the carcinogenic constituents of tar and the ability of these and related substances to induce estrus and in part from another
Increased alveolar nitric oxide concentration in asthmatic patients with nocturnal symptoms
Authors: L. Lehtimäki, H. Kankaanranta, S. Saarelainen, V. Turjanmaa, E. Moilanen
Journal: European Respiratory Journal (2002)

Nocturnal asthma symptoms and impaired lung function at night are related to inflammatory activity in the peripheral lung compartment. Exhaled nitric oxide (NO) measurement at multiple exhalation flow rates can be used to separately assess alveolar and bronchial NO production and inflammation. The authors hypothesised that asthmatic patients with nocturnal symptoms have a higher alveolar NO concentration than those with only daytime symptoms. The authors asked 40 patients with newly-diagnosed steroid-naïve asthma about their nocturnal asthma symptoms through the use of a written questionnaire. Alveolar NO concentration and bronchial NO flux were assessed in the 40 asthmatics and 40 healthy controls. Nineteen of the 40 patients reported nocturnal symptoms. Patients with nocturnal symptoms had a higher alveolar NO concentration (1.7±0.3 (mean±sem) parts per billion (ppb)) than patients without nocturnal symptoms (0.8±0.3 ppb, p=0.012) or healthy controls (1.0±0.1 ppb, p=0.032). Bronchial NO flux was higher both in patients with (2.4±0.4 nL·s −1 , p&lt;0.001) and without (2.6±0.4 nL·s −1 , p&lt;0.001) nocturnal symptoms, compared to controls (0.7±0.1 nL·s −1 ). Nocturnal symptoms in asthmatic patients are related to a higher alveolar nitric oxide concentration. The results suggest that assessment of alveolar nitric oxide concentration can be used to detect the parenchymal inflammation in asthmatic patients with nocturnal symptoms.
Letter: Liver flukes: a warning.
Authors: A T Hunt
Journal: BMJ (1975)

<h3>Background</h3> Brazil has a nationwide antimicrobial susceptibility surveillance program for Neisseria gonorrhoeae. Gonorrhoea, however, is not a notifiable disease and there are limited data on the burden of infection in the country. <h3>Methods</h3> We searched Embase PubMed, LILACS, Scielo for studies in any language providing data on the prevalence of urogenital gonorrhoea in 2000 or later in Brazil, with a sample size of 50 or more, and that used an internationally recognized diagnostic test on urine, urethral, or cervicovaginal specimens. The latest search was done on 10 November, 2020. In addition, we searched abstracts from the Brazilian STI congress (years 2010 to 2019) and Ministry of Health reports. The Spectrum-STI statistical model was used to estimate prevalence trends in 15–49 years-old men and women in the general population (excluding STI patients, HIV-positive populations and Transgender women). Prevalence trends were estimated for sexually active women and men, female sex workers and men who have sex with men. For populations with 3 or fewer prevalence data points Spectrum-STI uses time constant prevalence ratios from the WHO 2016 global STI estimates. Population size estimates were from Brazil’s National Survey of Knowledge, Attitudes and Practices of HIV and other STIs (PCAP-2013). <h3>Results</h3> We identified 48 studies that met the study entry criteria providing 47 data points for women and 7 for men. After excluding studies done exclusively in HIV positive individuals or individuals seeking STI treatment we had 29 data points for women and 6 for men. The Spectrum-STI national prevalence estimate for 2020 for adult women was 0.63%(0.13–2.23) and for men 0.70%(0.16–2.44). <h3>Conclusion</h3> The prevalence of urogenital gonorrhoea in Brazil appears to be low. Data on the prevalence in men, however, are very limited. The results from this study are being used to inform the design and prioritization of new surveillance surveys.
Nuclear Magnetic Resonance Lipoprotein Abnormalities in Prediabetic Subjects in the Insulin Resistance Atherosclerosis Study
Authors: Andreas Festa, Ken Williams, Anthony J.G. Hanley, James D. Otvos, David C. Goff, Lynne E. Wagenknecht, Steven M. Haffner
Journal: Circulation (2005)

Background— Subjects with type 2 diabetes have smaller LDL and HDL particles in addition to higher levels of triglycerides and lower HDL cholesterol. Elevated insulin resistance, blood pressure, and dyslipidemia (including small dense LDL) predicted incident diabetes. In the Insulin Resistance Atherosclerosis Study (IRAS) we studied nuclear magnetic resonance (NMR) lipoprotein particle measures in prediabetic individuals, considering potentially modifying covariates, including insulin resistance, as directly measured using a frequently sampled intravenous glucose tolerance test. Methods and Results— Of 830 subjects who were nondiabetic at baseline, 130 (15.7%) developed diabetes after a mean follow-up of 5.2 years. Various lipoprotein abnormalities were found in prediabetic subjects compared with subjects who stayed nondiabetic at follow-up. In logistic regression analyses (demographically adjusted), VLDL particles, large VLDL, LDL particles, small LDL, large HDL, small HDL, VLDL size, LDL size, and HDL size were related to incident diabetes. The relation of VLDL size and small HDL to incident diabetes was independent of waist (odds ratio [OR] [95% CI], 1.43 [1.18 to 1.73] and 1.23 [1.01 to 1.51] for VLDL size and small HDL, respectively) and independent of conventionally (chemically) measured triglycerides and HDL cholesterol (OR [95% CI], 1.45 [1.18 to 1.78] and 1.30 [1.06 to 1.60], respectively). Insulin sensitivity attenuated the relation to incident diabetes of VLDL size (OR [95% CI], 1.25 [1.01 to 1.53]) but not of small HDL particles (OR [95% CI], 1.25 [1.02 to 1.54]). Conclusions— We have shown a range of lipoprotein abnormalities in prediabetic individuals, including compositional changes in HDL and VLDL. These findings extend previous work indicating a proatherogenic state in healthy, nondiabetic subjects who subsequently develop diabetes.