tbuckley/cabot-search huggingface dataset:
Reduction of hepatic steatosis in rats and mice after treatment with a liver-targeted thyroid hormone receptor agonist
Authors: Edward E. Cable, Patricia D. Finn, Jeffrey W. Stebbins, Jinzhao Hou, Bruce R. Ito, Paul D. van Poelje, David L. Linemeyer, Mark D. Erion
Journal: Hepatology (2008)

Abstract Non-alcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease, with a prevalence ranging from 10% to 30%. The use of thyroid hormone receptor (TR) agonists for the treatment of NAFLD has not been considered viable because thyroid hormones increase free fatty acid (FFA) flux from the periphery to the liver, induce hepatic lipogenesis, and therefore could potentially cause steatosis. MB07811 is an orally active HepDirect prodrug of MB07344, a liver-targeted TR-β agonist. The purpose of these studies was to assess the effects of MB07811 on whole body and liver lipid metabolism of normal rodents and rodent models of hepatic steatosis. In the current studies, MB07811 markedly reduced hepatic steatosis as well as reduced plasma FFA and triglycerides. In contrast to MB07811, T 3 induced adipocyte lipolysis in vitro and in vivo and had a diminished ability to decrease hepatic steatosis. This suggests the influx of FFA from the periphery to the liver may partially counteract the antisteatotic activity of T 3 . Clearance of liver lipids by MB07811 results from accelerated hepatic fatty acid oxidation, a known consequence of hepatic TR activation, as reflected by increased hepatic mitochondrial respiration rates, changes in hepatic gene expression, and increased plasma acyl-carnitine levels. Transaminase levels remained unchanged, or were reduced, and no evidence for liver fibrosis or other histological liver damage was observed after treatment with MB07811 for up to 10 weeks. Additionally, MB07811, unlike T 3 , did not increase heart weight or decrease pituitary thyroid-stimulating hormone beta (TSHβ) expression. Conclusion: MB07811 represents a novel class of liver-targeted TR agonists with beneficial low-density lipoprotein cholesterol-lowering properties that may provide additional therapeutic benefit to hyperlipidemic patients with concomitant NAFLD. (Hepatology 2009.)
In vivo induction of interleukin 10 by anti-CD3 monoclonal antibody or bacterial lipopolysaccharide: differential modulation by cyclosporin A.
Authors: P Durez, D Abramowicz, C Gérard, M Van Mechelen, Z Amraoui, C Dubois, O Leo, T Velu, M Goldman
Journal: The Journal of Experimental Medicine (1993)

We investigated the in vivo effects of cyclosporin A (CsA) on the production of interleukin (IL) 10, a cytokine with major immunosuppressive properties. To elicit IL-10 production in vivo, BALB/c mice were injected either with the anti-mouse CD3 145-2C11 monoclonal antibody (mAb) (25 micrograms) or with bacterial lipopolysaccharide (LPS) (20 micrograms). A systemic release of IL-10 was observed in both models, IL-10 serum levels reaching 1.60 +/- 0.32 U/ml (mean +/- SEM) and 0.67 +/- 0.09 U/ml 6 h after injection of 145-2C11 mAb and LPS, respectively. Experiments in nude mice indicated that T cells are involved in the induction of IL-10 by anti-CD3 mAb, but not by LPS. Pretreatment with CsA (total dose: 50 mg/kg) before injection of 145-2C11 mAb completely prevented the release of IL-10 in serum as well as IL-10 mRNA accumulation in spleen cells. In contrast, CsA markedly enhanced LPS-induced IL-10 release (IL-10 serum levels at 6 h: 8.31 +/- 0.43 vs. 0.71 +/- 0.15 U/ml in mice pretreated with CsA vehicle-control, p &amp;lt; 0.001), as well as IL-10 mRNA accumulation in spleen. We conclude that CsA differentially affects IL-10 production in vivo depending on the nature of the eliciting agent. This observation might be relevant to clinical settings, especially in organ transplantation.
Exercise Tests for Pilots
Authors: Albert J. Miller
Journal: JAMA (1974)

<h3>To the Editor.—</h3> In a recent answer concerning the Wolff-Parkinson-White syndrome (224:1538, 1973), Dr. J. Robert Dille observed that Federal Aviation Administration (FAA) airmen examinations do not require routine electrocardiograms until age 35 "and only for holders of first class certificates." Dr. Malcolm Carruthers<sup>1</sup>has recently noted that physical examination and electrocardiography have limited utility in detecting early coronary heart disease. He further stated that "exercise tests do little to improve diagnostic precision, and are unpopular with aircrew, to the point being a strike issue." Dr. Carruthers presents appropriate arguments for the desirability of physical fitness and good life habits (including eating and smoking less) in his article. He advises graded exercise programs for British pilots to prevent ischemicheart disease. As a one-time flight surgeon, I am aware of the negative attitude that pilots have to any test that might serve to ground them. But as a cardiologist, I
Positive-Pressure Ventilation in Amyotrophic Lateral Sclerosis
Authors: Loutfi S. Aboussouan
Journal: Annals of Internal Medicine (1998)

Letters1 April 1998Positive-Pressure Ventilation in Amyotrophic Lateral SclerosisLoutfi S. Aboussouan, MD, Saeed U. Khan, MD, and Hiroshi Mitsumoto, MDLoutfi S. Aboussouan, MDWayne State University School of Medicine; Detroit, MI 48201Cleveland Clinic Foundation; Cleveland, OH 44195Search for more papers by this author, Saeed U. Khan, MDWayne State University School of Medicine; Detroit, MI 48201Cleveland Clinic Foundation; Cleveland, OH 44195Search for more papers by this author, and Hiroshi Mitsumoto, MDWayne State University School of Medicine; Detroit, MI 48201Cleveland Clinic Foundation; Cleveland, OH 44195Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-7-199804010-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We agree that noninvasive positive-pressure ventilation should not be restricted to nighttime. Although we emphasized nocturnal use, we also encouraged daytime use. However, tolerance of this treatment was strictly defined as the ability to sleep nightly for at least 4 consecutive hours with the device, regardless of daytime use. We did use other interfaces, including mouth pieces for daytime ventilation. Every attempt was made to control mucus plugging and secretions by using suction devices, medications, and assisted coughing. Mechanical insufflation-exsufflation was used, but only when it became available at the end of our study.In that context, our ...References1. Raphael JC, Chevret S, Chastang C, Bouvet F. Randomised trial of preventive nasal ventilation in Duchenne muscular dystrophy. French Multicentre Cooperative Group on Home Mechanical Ventilation Assistance in Duchenne de Boulogne Muscular Dystrophy. Lancet. 1994; 343:1600-4. Google Scholar Author, Article, and Disclosure InformationAffiliations: Wayne State University School of Medicine; Detroit, MI 48201Cleveland Clinic Foundation; Cleveland, OH 44195 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1998Volume 128, Issue 7Page: 602KeywordsAmyotrophic lateral sclerosisCoughingDeep vein thrombosisHospitalizationsMouthMucusMuscular dystrophiesNeuromuscular diseasesSleep Issue Published: 1 April 1998 CopyrightCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Features of Sjögren's Syndrome in Primary Biliary Cirrhosis
Authors: Donato Alarcón-Segovia, Efrain Díaz-Jouanen, Eugenia Fishbein
Journal: Annals of Internal Medicine (1973)

The sicca components of Sjögren's syndrome were investigated in 14 patients with primary biliary cirrhosis with a battery of tests that included Schirmer's test; rose bengal staining; parotid secretory sialography; scintillation scanning of salivary glands with 99mTc; radioactive counts in saliva at 15 and 60 minutes after intravenous injection of the same radionuclide, as an index of salivary gland function; and histologic study of minor salivary gland specimens obtained by lip biopsy. Abnormalities of lacrimal or salivary glands were detected by two or more tests in all patients. Presence or degree of sicca components of Sjögren's syndrome did not correlate with the duration or the degree of liver disease, the presence of autoantibodies, or the levels of immunoglobulins. Our findings indicate that primary biliary cirrhosis is a systemic disease and support the possibility that its pathogenesis is autoimmune.
Early Morbidity of Endoscopic Ultrasound: 13 Years’ Experience at a Referral Center
Authors: B. Bournet, I. Migueres, M. Delacroix, D. Vigouroux, J.-L. Bornet, J. Escourrou, L. Buscail
Journal: Endoscopy (2006)

Endoscopic ultrasonography (EUS) now has an important place in the diagnosis of gastroenteropancreatic diseases. However, prospective data on the morbidity and mortality related to its use are sparse and often retrospective. We attempted to assess the acute and immediate complications of both diagnostic and interventional EUS.At our university-affiliated tertiary care referral center, immediate (occurring during the procedure) and acute (occurring within 24 hours) complications of EUS were prospectively investigated. Over a first period, spanning 10 years, complications of diagnostic EUS involving 3207 consecutive patients were assessed. During the second period of 3 years, complications observed after EUS-guided fine-needle aspiration (FNA) biopsy were evaluated from 224 procedures. EUS was mostly done with the patient under sedation with intravenous propofol and spontaneous ventilation, and complications were evaluated by both the operator and the anesthesiologist.There were no deaths, and no surgery was required over the two periods of assessment. Three mild complications occurred among patients who underwent standard diagnostic EUS: two immediate complications were related to anesthesia and one to the procedure. There were five complications associated with interventional EUS; all were related to the procedure (acute pancreatitis, duodenal perforation, upper digestive bleeding, cyst, and mediastinal infection), with a mean delay of occurrence of 30 hours, and mean duration of hospitalization of 7 days.In our experience, which is the longest reported in Europe, the morbidity rates of diagnostic EUS and EUS-guided FNA biopsy were 0.093% and 2.2%, respectively, with no mortality.
Spontaneous Perforation of Oesophagus
Authors: J. Scholefield
Journal: BMJ (1949)

Experience of this and other epidemics has shown the frequent association of heavy nasal carriers with outbreaks of streptococcal tonsillitis in residential schools.It is impor- tant that nasal as well as throat swabs should be obtained from all cases, however mild; heavy nasal carriers should be treated until their swabs are negative.This is especially necessary with the single case or in the early stages of an outbreak before widespread contamination of the environ- ment and the build-up of a carrier rate has occurred.During the holidays every effort should be made to sterilize the noses of persistent carriers and to disinfect school premises.Summary The epidemiological and bacteriological findings in an out- break of streptococcal tonsillitis in a residential school are described.The outbreak extended over two terms, and 57 out of 340 boys were attacked.All the early cases were in the same house as the first case, a heavy nasal carrier.A nasal carrier was also associated with each of the three dormitories with the highest attack rates during the time fresh infections were occurring.In most cases, however, the dormitory did not appear to be of special impor- tance in the spread of disease, and the significance of this is discussed.The early detection and isolation of heavy nasal carriers before widespread dispersal of infection has occurred is emphasized.
The profession of medicine
Authors: K Calman
Journal: BMJ (1994)

It seems timely to define the purpose of medicine and examine the concept of a profession. This paper does so in the wider context of health, values in society, and the need to involve patients and the public as a whole. The author looks closely at what doctors do and concludes that making the diagnosis is a key element. The consultation is the building block for resource allocation. In addition to the diagnosis it sets out the prognosis and possible treatment and emphasises the importance of communicating these to the patient. Looking at the kind of doctor we need raises such issues as ethical standards, continuing professional development, team working, clinical standards, quality, outcomes, and research and development. Throughout, the role of education is seen as crucial. Leadership and vision are required by senior members of the profession if the opportunities presented are to be developed further.
ASEPSIS OF HANDS OF THE SURGEON AND SKIN OF THE PATIENT.
Authors: CARL BECK
Journal: JAMA (1899)

Ideal asepsis has become an established fact as far as all objects are concerned which stand boiling well. The atmosphere has no pernicious effects on wounds, as pathogenic bacteria fortunately have a tendency to settle, so they can only come into contact with a wound when the dust in the room is immoderately stirred up. To avoid this possibility, the air in the operating-room is saturated with moisture, at least durings two hours before the operation. This can be done simply by originating steam in a kettle. Asepsis of the hands of the surgeon as well as of the skin of the patient is still imperfect, total destruction of the bacteria of the skin being practically impossible. Asepsis must be attained principally by physical, especially mechanical, methods. Chemical processes should play but a very subordinate part. The means with which asepsis should be attained must be aseptic. This refers particularly to the
The Wise Use of Drugs
Authors: Walter Modell
Journal: JAMA (1966)

Talks on the art and the science of therapeutics usually begin with the truism that since all drugs are dangerous, their judicious use depends on how the risk of the untreated disease and the risks of the drug are balanced. But no one explains precisely how this concept is to be implemented, and to what extent it actually can be carried out to make the use of a drug a calculated risk. What need to be known in order to use a drug well are the risks of untreated disease and the predictability of the risks of the drug itself. The jeopardy of disease is generally well-established and a critical judgment is usually quite sound, and will, therefore, not be discussed here. <h3>Predictable Reactions</h3> The dangers of drugs are quite another kettle of fish, and they form the practical basis of this paper. Unfortunately, all drug reactions are not calculable
Resistance to Symptomatic Insulin Reactions after Fasting
Authors: Ernst J. Drenick, Lia C. Alvarez, Gabor C. Tamasi, Arnold S. Brickman
Journal: Journal of Clinical Investigation (1972)

This study was carried out to determine if, in fasting, an adaptation to utilization of ketones could prevent cerebral dysfunction during periods of acute, insulin-induced glucopenia. In the course of standard insulin tolerance tests (0.1-0.2 U/kg), nine obese subjects manifested frank hypoglycemic reactions resulting in an increase in urinary catecholamine excretion from 61 to 113 mug/24 hr (P < 0.01). After fasting 2 months, administration of weight-adjusted doses of insulin produced identical maximum insulin concentrations and disappearance curves. However, no insulin reactions nor significant rises in catecholamine excretion occurred despite equal extent and rate of glucose fall. Glucose concentrations as low as 0.5 mmoles/liter (9 mg/100 ml) failed to precipitate hypoglycemic reactions. During the postfast insulin tolerance tests, mean plasma 2-hydroxybutyrate (beta-OHB) decreased from 8.02 to 6.69 mmoles/liter (P < 0.01). In another five fasting subjects tested, the A-V difference for beta-OHB across brain increased progressively from 0.21 to 0.70 mmoles/liter whereas across the forearm no consistent uptake could be demonstrated. Simultaneously, the A-V difference across the brain for glucose decreased from 0.24 to 0.07 mmoles/liter of plasma. In addition to insulin-induced suppression of hepatic ketogenesis, the augmented cerebral ketone uptake during insulin hypoglycemia contributes to the net fall in plasma beta-OHB. Ketoacids, extracted by the fast-adapted brain, supplant glucose as a metabolic substrate preventing overt hypoglycemic reactions during acute glucopenia.
Smooth muscle cell proliferation. Expression and kinase activities of p34cdc2 and mitogen-activated protein kinase homologues.
Authors: M H Watson, S L Venance, S C Pang, A S Mak
Journal: Circulation Research (1993)

Rat vascular smooth muscle cells were synchronized to the quiescent state (G0) by serum deprivation and then stimulated to enter the cell cycle by serum refeeding. At various times of the cell cycle, cells were analyzed for the expression of p34cdc2 and mitogen-activated protein kinase homologues by immunoblotting and for kinase activity toward histone H1, myelin basic protein, and caldesmon. A small amount of p34cdc2 was expressed in the G0/G1 phase (0 to 8 hours). At the G1/S transition (12 hours), the level of p34cdc2 started to accumulate and increased by 60-fold at G2/M (18 hours), accompanied by a more slowly migrating band. Histone H1 kinase activity was undetectable in anti-p34cdc2 immunoprecipitates in the G0/G1 cells but appeared around the G1/S boundary and peaked at G2/M (18 hours). The caldesmon kinase activity exhibited two distinct phases: the first appeared at G0/G1 (0 to 8 hours), and the second appeared at G1/S and continued through G2/M. Two mitogen-activated protein kinase isoforms were expressed throughout the cell cycle. Anti-mitogen-activated protein kinase immunoprecipitates possessed kinase activities toward myelin basic protein and caldesmon, which were activated within 15 minutes after serum stimulation and declined within a few hours. These findings suggest that p34cdc2 and mitogen-activated protein kinase homologues may play significant roles in regulating the progression of the cell cycle of smooth muscle cells, the former at the G2/M transition and the latter at the G0/G1 transition.
Atopic eczema and other manifestations of atopy: results of a study in East and West Germany
Authors: T. Schäfer, D. Vieluf, H. Behrendt, U. Kramer, J. Ring
Journal: Allergy (1996)

Within an environmental health study, dermatologic examination of 1273 pre-school-age children (5-7 years old) was carried out in selected areas of East (n = 287) and West (n = 987) Germany in spring 1991. On the basis of comparable genetic background, the influence of a different exposure to air pollutants on the manifestation of atopic diseases was investigated. Halle an der Saale (East Germany) and Duisburg (North/South) as well as Essen (West Germany) were chosen as polluted study areas, whereas the countryside town of Borken (West Germany) served as a control region. Outdoor pollution with particles and SO2 was significantly higher in Halle an der Saale. Of the total study group, 12.9% suffered from atopic eczema at the time of examination. The prevalence was highest in East Germany (17.5%; adjusted odds ratio [OR] 1.39, confidence intervals [GI] 0.77-2.52, compared to Borken). The reported frequencies of hay fever and asthma in the total study population were 2% and 1.3%, respectively, without significant differences between study sites. Some 34.7% of the children showed at least one positive skin prick test reaction; significantly (P < 0.001) higher sensitization rates were obtained in western regions (Essen, Duisburg-South) than in the control region (Borken) and East Germany. Multivariate analysis of the prevalence of atopic eczema showed associations with parental predisposition (OR 1.52, CI 1.03-2.25), sex (for boys, OR 0.63, CI 0.43-0.92), location (Duisburg-South vs Borken OR 0.52, CI 0.30-0.96), month of investigation (May vs April, and March vs February OR 0.55, CI 0.37-0.81), contact with rabbits (for girls, OR 2.90, CI 1.36-6.19), animal fur in bedrooms (2.17, 1.01-4.67), indoor use of gas without hood (1.68, 1.11-2.56), and distance of homes from a busy road (< 50 m 1.71, 1.07-2.73). Nonsignificant associations were observed for history of helminthic infections (OR 1.61, CI 0.98-2.64) and high parental education level (OR 1.83, CI 0.83-4.02). In East and West Germany, atopic eczema seems to follow a course different from that of respiratory allergic diseases and specific sensitization, a fact which underlines the need for a differentiated analysis.
Community-Based Lifestyle Interventions to Prevent Type 2 Diabetes
Authors: Dawn W. Satterfield, Michele Volansky, Carl J. Caspersen, Michael M. Engelgau, Barbara A. Bowman, Ed W. Gregg, Linda S. Geiss, Gwen M. Hosey, Jeannette May, Frank Vinicor
Journal: Diabetes Care (2003)

To conduct a literature review of community-based interventions intended to prevent or delay type 2 diabetes.Recently published findings about the potential to prevent or delay type 2 diabetes with intensive lifestyle interventions prompted a literature search for community-based diabetes prevention interventions. The literature review design was a search of databases for publications in 1990-2001 that identified reports on community-based interventions designed to prevent or modify risk factors for type 2 diabetes.The search revealed 16 published interventions, 8 of which were conducted in the U.S. and involved populations disproportionately burdened by diabetes (e.g., American Indians, Native Hawaiians, Mexican Americans, and African Americans). Of the studies reporting results among youth, there were posttest improvements in intervention groups in knowledge, preventive behaviors, and self-esteem. Among studies reporting results among adults, most reported improvements in intervention groups in knowledge or adoption of regular physical activity. Several investigators offered important reflections about the process of engaging communities and sharing decision making in participatory research approaches, as well as insights about the expectations and limitations of community-based diabetes prevention research. Many of the studies reported limitations in their design, including the lack of control or comparison groups, low response rates or lack of information on nonresponders, or brief intervention periods.There is a critical need to conduct and publish reports on well-designed community-based diabetes prevention research and share information on the process, results, and lessons learned. Armed with recent positive findings about diabetes prevention and literature documenting community-based efforts, advocates at local, state, and national levels can collaborate to stem the rising tide of diabetes in communities.