tbuckley/cabot-search huggingface dataset:
Patatin-like phospholipase domain-containing protein 3 genotype and hepatocellular carcinoma in chronic hepatitis C
Authors: Luca Valenti, Massimo Colombo, Silvia Fargion
Journal: Hepatology (2011)

We thank Ginanni Corradini and coworkers for their interest in our work.1 We have recently reported that the Ile148Met PNPLA3 (patatin-like phospholipase domain-containing protein 3) genotype, a strong genetic determinant of hepatic fat accumulation and progressive alcoholic as well as nonalcoholic steatohepatitis,2, 3 influences steatosis development, liver fibrosis, possibly antiviral treatment response, and the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC).1 Furthermore, almost contemporarily, Cai et al. found that, in line with our results, PNPLA3 genotype was associated with steatosis in patients with CHC who are not affected by viral genotype 3,4 whereas Müller et al. very recently confirmed the association of PNPLA3 genotype with steatosis and cirrhosis in German patients with CHC.5 These data suggest that PNPLA3 genotype (1) is a strong determinant of metabolic steatosis in CHC, (2) plays a causal role in determining the progression of liver disease, and (3) that the evaluation of PNPLA3 genotype might help identify patients who are at higher risk of complications, and in particular HCC, and might possibly be useful for the stratification of patients in studies aimed at HCC prevention. However, this latter conclusion awaits confirmation in larger prospective studies, because it was based on a retrospective analysis of 325 patients (107 with cirrhosis) who were followed at a single center.1 In response to our article, Ginanni Corradini et al. now report an association between homozygosity for the 148M PNPLA3 variant and HCC in a retrospective analysis conducted in an Italian population of 221 patients with CHC-related cirrhosis without excessive alcohol intake, which was independent of age, sex, and diabetes, thus providing an independent validation of our findings in another population, albeit of similar ethnicity.6 Strikingly, the magnitude of the association (odds ratio = 2.23, confidence interval = 1.6-3.5 and odds ratio = 2.16, confidence interval = 1.3-3.6 in this and our report, respectively) adjusted for the same confounders was also very consistent between the two studies. As previously discussed,1 we agree that larger prospective studies in ethnically different populations and different liver diseases are required to confirm the association between PNPLA3 genotype and HCC, and functional studies on the still-mysterious PNPLA3 function are urgently needed. Nevertheless, these exciting findings may open new perspectives for the prevention and treatment of the complications of liver diseases, including but not limited to CHC. Luca Valenti M.D.*, Massimo Colombo M.D.*, Silvia Fargion M.D.*, * Department of Internal Medicine, A.M. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Università degli Studi, Fondazione IRCCS "Ca' Granda", Ospedale Maggiore Policlinico, Milan, Italy.
The service provision model and inflexibility
Authors: D. Grimes
Journal: BMJ (1986)

remains to be seen whether non-antisecretory doses of prostaglandins have any therapeutic effi- cacy in duodenal ulcer.The situation may be different for gastric ulcer, where a strong correlation between acid suppression and healing rates is not seen,4 or for maintenance therapy after ulcer healing, where a drug which enhances mucosal resistance and can prevent damage to normal mucosa might be of therapeutic benefit.It would be of considerable interest to study the effects of a non-antisecretory dose of a synthetic prostaglandin in gastric ulcer.
Cost-effectiveness of Vitamin Therapy to Lower Plasma Homocysteine Levels for the Prevention of Coronary Heart Disease
Authors: Jeffrey A. Tice, Elizabeth Ross, Pamela G. Coxson, Irwin Rosenberg, Milton C. Weinstein, M. G. Myriam Hunink, Paula A. Goldman, Lawrence Williams, Lee Goldman
Journal: JAMA (2001)

A high homocysteine level has been identified as an independent modifiable risk factor for coronary heart disease (CHD) events and death. Since January 1998, the US Food and Drug Administration has required that all enriched grain products contain 140 microg of folic acid per 100 g, a level considered to decrease homocysteine levels.To examine the potential effect of grain fortification with folic acid on CHD events and to estimate the cost-effectiveness of additional vitamin supplementation (folic acid and cyanocobalamin) for CHD prevention.Cost-effectiveness analysis using the Coronary Heart Disease Policy Model, a validated, state-transition model of CHD events in adults aged 35 through 84 years. Data from the third National Health and Nutrition Examination Survey (NHANES III) were used to estimate age- and sex-specific differences in homocysteine levels.Hypothetical comparison between a diet that includes enriched grain products projected to increase folic acid intake by 100 microg/d with the same diet without folic acid fortification; and a comparison between vitamin therapy that consists of 1 mg of folic acid and 0.5 mg of cyanocobalamin and the diet that includes grains fortified with folic acid.Incidence of myocardial infarction and death from CHD, quality-adjusted life-years (QALYs) saved, and medical costs.Grain fortification with folic acid was predicted to decrease CHD events by 8% in women and 13% in men, with comparable reductions in CHD mortality. The model projected that, compared with grain fortification alone, treating all patients with known CHD with folic acid and cyanocobalamin over a 10-year period would result in 310 000 fewer deaths and lower costs. Over the same 10-year period, providing vitamin supplementation in addition to grain fortification to all men aged 45 years or older without known CHD was projected to save more than 300 000 QALYs, to save more than US $2 billion, and to be the preferred strategy. For women without CHD, the preferred vitamin supplementation strategy would be to treat all women older than 55 years, a strategy projected to save more than 140 000 QALYs over 10 years.Folic acid and cyanocobalamin supplementation may be cost-effective among many population subgroups and could have a major epidemiologic benefit for primary and secondary prevention of CHD if ongoing clinical trials confirm that homocysteine-lowering therapy decreases CHD event rates.
Comparison of the Vectorcardiogram with the Electrocardiogram in the Prediction of Left Ventricular Size
Authors: DONALD L. VINE, R. NEWELL FINCHUM, HAROLD T. DODGE, WILLIAM H. BANCROFT, DAVID C. HURST
Journal: Circulation (1971)

The vectorcardiogram has been suggested as an alternative to the electrocardiogram in the diagnosis of left ventricular enlargement. In 107 patients, precordial QRS voltage measurements were compared with vectorcardiographic spatial magnitude measurements in their relationship to angiocardiographically determined left ventricular mass and volume. Sensitivity, specificity, and linear correlations obtained with instantaneous spatial QRS magnitude measurements were similar to those obtained with selected precordial voltage measurements suggested by Sokolow and Grant. Multiple regression analysis incorporating time-strength integrals of the spatial QRS correlated more closely with left ventricular mass (R = 0.75) and total volume (R = 0.80) than did similar analysis using precordial voltages (R = 0.71). These differences are statistically significant ( P = &lt;0.01) but reduce the remaining variability of the electromotive-left ventricular size relationship by only 7 to 14% and leave 30 to 40% of the total variability unexplained. These findings do not support a large practical advantage for the vector-cardiogram over the electrocardiogram in the prediction of left ventricular size.
Optimal Level of Filling Pressure in the Left Side of the Heart in Acute Myocardial Infarction
Authors: Carlos Crexells, Kanu Chatterjee, James S. Forrester, Krishna Dikshit, H.J.C. Swan
Journal: New England Journal of Medicine (1973)

Balloon-flotation catheterization of the pulmonary artery at the bedside, a practical and safe diagnostic procedure in acutely ill patients, was used to measure pulmonary-artery occluded pressure (left ventricular filling pressure in 23 patients with acute myocardial infarction). The optimal level of this pressure was between 14 and 18 mm Hg. Manipulations that increased filling pressure above this range did not improve cardiac performance, which, in fact, usually deteriorated. On the contrary, an increase in cardiac performance could be related directly to changes in the occluded pressure when the initial value was less than 14 mm Hg. A parallel similar relation between filling pressure and performance existed in the right side of the heart. When right atrial pressure was increased up to 6 to 8 mm Hg, performance generally improved, but above that value, no consistent further improvement in right ventricular function was observed. Patients with depressed left ventricular performance also tended to demonstrate depressed right ventricular performance, but correlation of actual pressure levels was poor. (N Engl J Med 289:1263–1266, 1973)
The upregulation of specific interleukin (IL) receptor antagonists and paradoxical enhancement of neuronal apoptosis due to electrode induced strain and brain micromotion
Authors: Lohitash Karumbaiah, Sharon E. Norman, Nithish B. Rajan, Sanjay Anand, Tarun Saxena, Martha Betancur, Radhika Patkar, Ravi V. Bellamkonda
Journal: Biomaterials (2012)
Aortic Root Remodeling and Risk of Heart Failure in the Framingham Heart Study
Authors: Carolyn S.P. Lam, Philimon Gona, Martin G. Larson, Jayashri Aragam, Douglas S. Lee, Gary F. Mitchell, Daniel Levy, Susan Cheng, Emelia J. Benjamin, Ramachandran S. Vasan
Journal: JACC Heart Failure (2013)
Potassium loss during myocardial ischaemia and hypoxia: does lactate efflux play a role?
Authors: J. N Weiss, R.-C. Shieh
Journal: Cardiovascular Research (1994)

Journal Article Potassium loss during myocardial ischaemia and hypoxia: does lactate efflux play a role? Get access James N Weiss, James N Weiss Division of Cardiology, UCLA School of Medicine, 3645 MRL Building, Los Angeles, CA 90024, USA: J N Weiss, R-C Shieh. Correspondence to Dr Weiss. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ru-Chi Shieh Ru-Chi Shieh Division of Cardiology, UCLA School of Medicine, 3645 MRL Building, Los Angeles, CA 90024, USA: J N Weiss, R-C Shieh. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 8, August 1994, Pages 1125–1132, https://doi.org/10.1093/cvr/28.8.1125 Published: 01 August 1994 Article history Received: 11 February 1994 Accepted: 30 April 1994 Published: 01 August 1994
Ethosuximide, Valproic Acid, and Lamotrigine in Childhood Absence Epilepsy
Authors: Tracy A. Glauser, Avital Cnaan, Shlomo Shinnar, Deborah G. Hirtz, Dennis Dlugos, David Masur, Peggy O. Clark, Edmund V. Capparelli, Peter C. Adamson
Journal: New England Journal of Medicine (2010)

Childhood absence epilepsy, the most common pediatric epilepsy syndrome, is usually treated with ethosuximide, valproic acid, or lamotrigine. The most efficacious and tolerable initial empirical treatment has not been defined.
Cellular distribution of transforming growth factor-beta 1 and procollagen types I, III, and IV transcripts in carbon tetrachloride-induced rat liver fibrosis.
Authors: H Nakatsukasa, P Nagy, R P Evarts, C C Hsia, E Marsden, S S Thorgeirsson
Journal: Journal of Clinical Investigation (1990)

The cellular distribution and temporal expression of transcripts from transforming growth factor-beta 1 (TGF-beta 1) and procollagen alpha 1(I), alpha 1(III), and alpha 1(IV) genes were studied in carbon tetrachloride (CCl4)-induced rat liver fibrosis by using in situ hybridization technique. During the fibrotic process, TGF-beta 1 and procollagen genes were similarly and predominantly expressed in Desmin-positive perisinusoidal cells (e.g., fat-storing cells and myofibroblasts) and fibroblasts and their expression continued to be higher than those observed in control rats. These transcripts were also observed in inflammatory cells mainly granulocytes and macrophage-like cells at the early stages of liver fibrosis. The production of extracellular matrix along small blood vessels and fibrous septa coincided with the expression of these genes. Expression of TGF-beta 1 and procollagen genes were not detected in hepatocytes throughout the experiment. No significant differences in cellular distribution or time course of gene expression among procollagen alpha 1(I), alpha 1(III), and alpha 1(IV) were observed. Desmin-positive perisinusoidal cells and fibroblasts appeared to play the principal role in synthesis of collagens in CCl4-induced hepatic fibrosis. The simultaneous expression of TGF-beta 1 and procollagen genes in mesenchymal cells, including Desmin-positive perisinusoidal cells, during hepatic fibrosis suggests the possibility that TGF-beta 1 may have an important role in the production of fibrosis.
Lack of effect of high doses of inhaled morphine on exercise endurance in chronic obstructive pulmonary disease
Authors: D Jankelson, K Hosseini, LE Mather, JP Seale, IH Young
Journal: European Respiratory Journal (1997)

Systemic opiates may relieve dyspnoea and improve exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). Small doses of inhaled opiates may have similar effects; however, recent studies have shown no benefit. We studied higher doses of inhaled morphine and measured systemic absorption to determine whether any beneficial actions are local or systemic. Twenty and 40 mg doses and 0.9% saline were nebulized in a randomized, double-blind study of 16 patients with stable COPD. Patients performed 6 min walk tests immediately after the nebulized test solution (Walk 1) and again 60 min later (Walk 2). Arterial oxygen saturation (Sa,O2), modified Borg dyspnoea score and cardiac frequency were recorded during each walk. There was no difference between placebo and either dose of nebulized morphine on these measurements. The higher dose of nebulized morphine achieved a higher plasma concentration. The highest plasma concentration was measured immediately after nebulization, and this decreased steadily in the hour thereafter (p&lt;0.002). There was no correlation between the change in walk distance and the change in plasma morphine concentration after either dose of nebulized morphine. We conclude that higher doses of nebulized morphine do not improve exercise endurance or relieve dyspnoea in patients with chronic obstructive pulmonary disease, and that morphine is rapidly absorbed systemically after inhalation.
Parrish's chemical food never contained arsenic
Authors: C. M Reed
Journal: BMJ (1998)

EDITOR—I have only recently seen the short item on the Minerva page submitted by Barrett.1 It is illustrated by a colour photograph of a finely preserved bottle of Parrish's chemical food, sold by A J Jull of The Pharmacy, Charlbury, Oxfordshire.

The caption to the photograph perpetuates a popular medical misapprehension–that the iron tonic Parrish's food contained arsenic and was withdrawn from sale some 30 years ago. Having checked through the wealth of sources available in …
Effect of Smoking Status on the Long-Term Outcome after Successful Percutaneous Coronary Revascularization
Authors: David Hasdai, Kirk N. Garratt, Diane E. Grill, Amir Lerman, David R. Holmes
Journal: New England Journal of Medicine (1997)

Cigarette smoking is known to be deleterious to patients with coronary artery disease, but the effect of smoking on the clinical outcome of percutaneous coronary revascularization is unknown.Patients who had undergone successful percutaneous coronary revascularization at the Mayo Clinic between 1979 and 1995 were divided into nonsmokers (n=2009), former smokers (those who had stopped smoking before the procedure, n=2259), quitters (those who stopped smoking after the procedure, n=435), and persistent smokers (those who smoked before and after the procedure, n=734).The maximal follow-up was 16 years (mean [+/-SD], 4.5+/-3.4). The nonsmokers and former smokers had similar base-line characteristics and outcomes. The quitters and persistent smokers were younger than the nonsmokers and former smokers and had more favorable clinical and angiographic characteristics. In analyses adjusted for confounding base-line characteristics, the persistent smokers had a greater relative risk of death (1.76 [95 percent confidence interval, 1.37 to 2.26]) and of Q-wave infarction (2.08 [95 percent confidence interval, 1.16 to 3.72]) than the nonsmokers. The quitters and persistent smokers were less likely than the nonsmokers to undergo additional percutaneous coronary procedures (relative risk, 0.80 [95 percent confidence interval, 0.64 to 0.98] and 0.67 [95 percent confidence interval, 0.56 to 0.81], respectively) or coronary bypass surgery (relative risk, 0.72 [95 percent confidence interval, 0.54 to 0.95] and 0.68 [95 percent confidence interval, 0.54 to 0.86], respectively). The persistent smokers were also at greater risk for death than the quitters (relative risk, 1.44 [95 percent confidence interval, 1.02 to 2.11]).Patients who continued to smoke after successful percutaneous coronary revascularization were at greater risk for Q-wave infarction and death than nonsmokers. The cessation of smoking either before or after percutaneous revascularization was beneficial. Patients undergoing percutaneous revascularization should be encouraged to stop smoking.
Decreased mechanical efficiency in clinically stable patients with COPD
Authors: E. M. Baarends, A. M. Schols, M. A. Akkermans, E. F. Wouters
Journal: Thorax (1997)

BACKGROUND: It has recently been reported that total daily energy expenditure (TDE) is increased in patients with chronic obstructive pulmonary disease (COPD) and it was hypothesised that these patients may have a decreased mechanical efficiency during activities. The purpose of the present study was to measure the mechanical efficiency of submaximal leg exercise, and to characterise patients with a potentially low efficiency in terms of body composition, resting energy expenditure, lung function, and symptom limited exercise performance. METHODS: Metabolic and ventilatory variables were measured breath by breath during submaximal cycle ergometry exercise performed at 50% of symptom limited achieved maximal load in 33 clinically stable patients with COPD (23 men) with forced expiratory volume in one second (FEV1) of 40 (12)% predicted. Net mechanical efficiency was calculated adjusting for resting energy expenditure (REE). RESULTS: Median mechanical efficiency was 15.5% and ranged from 8.5% to 22.7%. Patients with an extremely low mechanical efficiency (&lt; 17%, n = 21) demonstrated an increased VO2/VE compared with those with a normal efficiency (median difference 4.7 ml/l, p = 0.005) during submaximal exercise. There was no difference between the groups differentiated by mechanical efficiency in blood gas tensions at rest, airflow obstruction, respiratory muscle strength, hyperinflation at rest, resting energy expenditure or body composition. There was a significant difference in total airways resistance (92% predicted, p = 0.03) between the groups differentiated by mechanical efficiency. CONCLUSIONS: It is concluded that many patients with severe COPD have decreased mechanical efficiency. Furthermore, based on the results of this study it is hypothesised that an increased oxygen cost of breathing during exercise contributes to the decreased mechanical efficiency.
Relation of Obsessional Traits to Anxiety in Patients with Ulcerative Colitis
Authors: A.D. Rabavüas, G.N. Christodoulou, J. Lappas, C. Perissaki, C. Stefanis
Journal: Psychotherapy and Psychosomatics (1980)

The obsessional personality traits and the "state" and "trait" anxiety, measured by means of self-rating inventories, were correlated in a group of patients with ulcerative colitis and a group of anxiety neurotics. The results suggest that patients with ulcerative colitis demonstrate strong positive trends, contrary to neurotics who show negative or very weak correlations, during the active period of their illness. These findings are discussed and some hypotheses concerning the different association of anxiety to obsessionality between the two groups are presented.
Thrombolytic Therapy in Acute Myocardial Infarction
Authors: Hans Martin Hoffmeister, Sebastian Szabo, Christof Kastner, Martin E. Beyer, Uwe Helber, Silke Kazmaier, Hans Peter Wendel, Wolfgang Heller, Ludger Seipel
Journal: Circulation (1998)

Background —Thrombolytic therapy in patients with acute myocardial infarction (AMI) is hampered by procoagulant effects. In vitro studies have indicated that plasmin stimulation activates the kallikrein–contact-phase system, resulting in thrombin activation. This prospective comparative study was designed to examine the procoagulant effects of streptokinase or alteplase in AMI. Methods and Results —Sixty-one patients with AMI received 1.5 million U of streptokinase or front-loaded alteplase (up to 100 mg) and systemic heparin. Twenty-four patients with AMI and no thrombolytic therapy and 30 control subjects were examined for comparison. Molecular markers of thrombin, plasmin activation, and coagulation activities were determined before therapy and serially for up to 10 days. Moderate thrombin (initial thrombin-antithrombin [TAT] complex 18±5 versus 4±0.3 μg/L, P &lt;0.05) and kallikrein (up to 45±4 versus 30±1 U/L at 3 hours, P &lt;0.01) activation occurs in patients with AMI. d -Dimers are increased ( P &lt;0.01), and plasmin is stimulated ( P &lt;0.01). Streptokinase and alteplase increase TAT to 50±17 and 51±18 μg/L at 3 hours and to 50±17 and 33±14 μg/L at 6 hours, respectively ( P &lt;0.01). Kallikrein activity is elevated ( P &lt;0.01) to 76±5 and 71±7 U/L at 3 hours and 64±6 and 47±5 U/L by streptokinase and alteplase, respectively, at 6 hours. Reductions in fibrinogen and increases in d -dimers and plasmin-antiplasmin complexes are more marked ( P &lt;0.05 and 0.01) after streptokinase versus alteplase. Correlations were found among TAT, kallikrein activity, and plasmin activation ( P &lt;0.01). Conclusions —The data indicate a more marked procoagulant action of the streptokinase regimen compared with front-loaded alteplase, thus supporting the hypothesis of a plasmin-mediated kallikrein activation with consecutive procoagulant action in vivo.
Do personal computers make doctors less personal?
Authors: J.-J. Rethans, P. Hoppener, G. Wolfs, J. Diederiks
Journal: BMJ (1988)

Ten months after the installation of a computer in a general practice surgery a postal survey (piloted questionnaire) was sent to 390 patients. The patients9 views of their relationship with their doctor after the computer was introduced were compared with their view of their relationship before the installation of the computer. More than 96% of the patients (n=263) stated that contact with their doctor was as easy and as personal as before. Most stated that the computer did not influence the duration of the consultation. Eighty one patients (30%) stated, however, that they thought that their privacy was reduced. Unlike studies of patients9 attitudes performed before any actual experience of use of a computer in general practice, this study found that patients have little difficulty in accepting the presence of a computer in the consultation room. Nevertheless, doctors should inform their patients about any connections between their computer and other, external computers to allay fears about a decrease in privacy.
Inflammatory effector mechanisms in asthma.
Authors: J M Drazen, J F Evans, R L Stevens, M A Shipp
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Each of these effector systems has the capacity to initiate airway obstruction or alter airway responsiveness in asthma. It is likely that they act in concert in certain asthmatic settings. Further basic and applied research will define their relative roles in asthma.