tbuckley/cabot-search huggingface dataset:
Activation of peroxisome proliferator-activated receptors by chlorinated hydrocarbons and endogenous steroids.
Authors: Y C Zhou, D J Waxman
Journal: Environmental Health Perspectives (1998)

Trichloroethylene (TCE) and related hydrocarbons constitute an important class of environmental pollutants whose adverse effects on liver, kidney, and other tissues may, in part, be mediated by peroxisome proliferator-activated receptors (PPARs), ligand-activated transcription factors belonging to the steroid receptor superfamily. Activation of PPAR induces a dramatic proliferation of peroxisomes in rodent hepatocytes and ultimately leads to hepatocellular carcinoma. To elucidate the role of PPAR in the pathophysiologic effects of TCE and its metabolites, it is important to understand the mechanisms whereby PPAR is activated both by TCE and endogenous peroxisome proliferators. The investigations summarized in this article a) help clarify the mechanism by which TCE and its metabolites induce peroxisome proliferation and b) explore the potential role of the adrenal steroid and anticarcinogen dehydroepiandrosterone 3beta-sulfate (DHEA-S) as an endogenous PPAR activator. Transient transfection studies have demonstrated that the TCE metabolites trichloroacetate and dichloroacetate both activate PPAR alpha, a major liver-expressed receptor isoform. TCE itself was inactive when tested over the same concentration range, suggesting that its acidic metabolites mediate the peroxisome proliferative potential of TCE. Although DHEA-S is an active peroxisome proliferator in vivo, this steroid does not stimulate trans-activation of PPAR alpha or of two other PPAR isoforms, gamma and delta/Nuc1, when evaluated in COS-1 cell transfection studies. To test whether PPAR alpha mediates peroxisomal gene induction by DHEA-S in intact animals, DHEA-S has been administered to mice lacking a functional PPAR alpha gene. DHEA-S was thus shown to markedly increase hepatic expression of two microsomal P4504A proteins associated with the peroxisomal proliferative response in wild-type mice. In contrast, DHEA-S did not induce these hepatic proteins in PPAR alpha-deficient mice. Thus, despite its unresponsiveness to steroidal peroxisome proliferators in transfection assays, PPAR alpha is an obligatory mediator of DHEA-S-stimulated hepatic peroxisomal gene induction. DHEA-S, or one of its metabolites, may thus serve as an important endogenous regulator of liver peroxisomal enzyme expression.
Limited Transmission of Multidrug-Resistant Tuberculosis Despite a High Proportion of Infectious Cases in Los Angeles County, California
Authors: ANNETTE T. NITTA, LAURA S. KNOWLES, JAIMIN KIM, ELEANOR L. LEHNKERING, LEE A. BORENSTEIN, PAUL T. DAVIDSON, SYDNEY M. HARVEY, MURIEL L. DE KONING
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Preventing transmission of multidrug-resistant tuberculosis is critical because of treatment toxicity, cost, and the lack of effective therapy for latent infection. We attempted to determine the extent of transmission in Los Angeles County by comparing relatedness of multidrug-resistant tuberculosis cases using restriction fragment length polymorphism and by cross-matching contact information to the Tuberculosis Registry. Strain typing was done on isolates of 102 pulmonary multidrug-resistant cases identified between August 1993 and 1998. Seventy-one (70%) of the cases had cavitary lesions on chest radiograph, and 94 (92%) had sputa smear-positive for acid fast bacilli. Fifteen (15%) of the cases were known to be infected with human immunodeficiency virus. Four molecular clusters of two cases each and one closely related pair were identified among the 102 cases; contact investigation successfully identified all clusters but one. Among 946 contacts identified and cross-matched with the county's Tuberculosis Registry, one secondary case due to drug-resistant Mycobacterium bovis was found. To summarize, a very high proportion of pulmonary multidrug-resistant tuberculosis cases in Los Angeles County were infectious. Molecular strain typing indicated limited spread of disease, although it underestimated transmission compared with contact investigation. We believe aggressive surveillance and case management were critical to limiting the spread of multidrug- resistant tuberculosis.
The advent of fair treatment allocation schedules in clinical trials during the 19th and early 20th centuries
Authors: Iain Chalmers, Estela Dukan, Scott Podolsky, George Davey Smith
Journal: Journal of the Royal Society of Medicine (2012)

Methods to ensure that like will be compared with like in fair treatment comparisons were proposed at least as early as the 17th century. Reflecting a time-honoured device for ensuring fairness,13 Van Helmont14 and Starkey15 proposed casting lots to decide which patients should be assigned to orthodox physicians (to be bled and purged), and which to their own, alternative treatments. A century later, Anton Mesmer challenged his orthodox physician detractors to cast lots to decide which patients should be treated by them, and which by him, using ‘animal magnetizm’:

In order to avoid any later argument and all the questions that could be raised about differences in age, in temperament, in diseases, in their symptoms etc. the assignment of the patients shall be made by the method of lots.16 [emphasis added]

Casting lots is just one of several potentially unbiased methods that can be used to ensure that like will be compared with like in treatment comparisons. Alternation (or rotation) of successive patients to different treatments is an easily understood way of generating patient groups for fair treatment comparisons. As long as the underlying order of the patients' presentation has not been predetermined in some way that introduces bias, strict alternation ensures that no conscious or unconscious bias results in patients with better or worse prognoses being allocated to one of the treatment comparison groups. Other methods that have been used to ensure that like will be compared with like include patients' dates of birth, or the terminal digits of their case record numbers.
Treatment of Acute Bronchoconstriction in Children with Use of a Tube Spacer Aerosol and a Dry Powder Inhaler
Authors: S. Pedersen
Journal: Allergy (1985)

In a double blind cross‐over study 24 children suffering from acute bronchoconstriction were treated with either placebo, or terbutaline delivered by a pressurized aerosol with a tube spacer (TS), or salbutamol from a dry powder inhaler (Rotahaler = RO). Both active treatments resulted in a significant increase in FEV 1 as compared with placebo ( P &lt; 0.001). Furthermore, TS treatment resulted in significantly greater improvement in FEV 1 than treatment with the RO (P &lt; 0.05). Under the conditions of marked airways obstruction problems with correct handling of the RO (loading and breaking the capsule) were prevalent and many children were unable to empty the RO capsule. These difficulties seemed to account for the smaller bronchodilation after RO treatment and were not seen under quiet circumstances. It is recommended that inhalation therapy in children is supervised by an adult during periods of marked airways disease.
Bronchodilator and bronchoprotective effects of cilostazol in humans in vivo.
Authors: M Fujimura, Y Kamio, M Saito, T Hashimoto, T Matsuda
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Cilostazol is a selective orally active phosphodiesterase (PDE) III inhibitor. This study was conducted to evaluate whether inhibition of PDE subtype III can reduce bronchial responsiveness. We examined the effects of cilostazol on bronchial responsiveness to methacholine in eight normal subjects by a single-blinded, crossover study. Each subject received 200 mg of cilostazol or placebo in random order. The subjects underwent methacholine challenge test 3 h after administration of each drug on two occasions separated by 5 d or more. The geometric mean value of provocative concentration of methacholine causing a 20% fall in FEV1 (PC20-FEV1) and the mean value (+/- SEM) of maximum expiratory flow on partial flow-volume curve at isovolume of 40% FVC above residual volume (PEF40) after administration of cilostazol were 25.3 (geometric standard error of the mean [GSEM], 1.35) mg/ml and 3.78 +/- 0.31 L/s, which were significantly (p < 0.02 and p < 0.05) greater than those after the placebo administration (6.81 [GSEM, 1.42] mg/ml and 2.71 +/- 0.39 L/s). All subjects complained of mild to severe headache when cilostazol was given. These findings suggest that PDE III inhibitors such as cilostazol have bronchodilator and bronchoprotective effects in humans. Further studies regarding smaller oral dosing of or aerosol administration of cilostazol or the other PDE III inhibitors are needed to determine clinical usefulness.
Registry Research and Medical Privacy
Authors: Julie R. Ingelfinger, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2004)

Medical progress is possible largely because we learn from our successes and our failures. Researchers often make an assessment of where things stand for a given medical condition through disease registries that attempt to include everyone who has received a diagnosis of and been treated for a given condition in an institution, a region, or a nation. These critical data bases have been used to help us understand how care is delivered and the outcomes achieved. Sadly, around the world, data repositories are now at risk of significant bias because concern about privacy has led to the requirement that consent . . .
Assessing the Adequacy of Endoscopically Tied Knots: A Functional Approach
Authors: B. Hu, L. Sun, M. Karmakar, P. Cotton, C. Gostout, R. Hawes, A. Kalloo, S. Kantsevoy, P. Pasricha, S. Chung
Journal: Endoscopy (2005)

Background and Study Aims: Endoscopic intracorporeal knots have potentially enormous applications in endoscopic surgery. We describe a method for testing the security of various types of endoscopically tied knots using a vessel perfusion manometer system. Methods: A 4-cm segment of porcine splenic artery was placed on the mucosal surface of a pig stomach. The two ends of the vessel were brought out through the gastric wall and connected to a two-way manometer. One end was also joined to a pressure infusion bag. The stomach was mounted in an Erlangen training model. A long 3/0 nylon thread, previously introduced into the submucosal layer of the stomach and encircling the vessel, was brought out from the mouth. Three-throw square knots, Mayo knots, “surgeon’s” knots and five-throw square knots were tied and pushed into place using a cap attached to a gastroscope. The pressure at the two ends of the artery was compared. If the pressure could be increased to over 200 mm Hg at one end without a change in the other, the knot was considered secure. Results: Each type of knot was tested 12 times under endoscopic vision. The range for mean knotting time was 3.4 - 4.5 minutes. Five-throw knots took significantly longer to tie than three-throw knots (P < 0.005). There was one loose knot in each of the three-throw and Mayo groups, and three each in the “surgeon’s” and five-throw groups (P > 0.05). Conclusions: This system is a reliable model for testing intracorporeal knots tied endoscopically. A three-half-hitches square knot with 3/0 nylon, tied using a flexible endoscope and knot-tightening cap, can withstand pressure up to 200 mm Hg.
Tubular Reabsorption of Sodium Ion: Influence of Factors Other Than Aldosterone and Glomerular Filtration Rate
Authors: R. W. Schrier, H. E. de Wardener
Journal: New England Journal of Medicine (1971)

Autonomic Nervous System and Systemic HemodynamicsAlthough changes in renal hemodynamics may influence the reabsorption and excretion of sodium through intrarenal mechanisms, the changes in renal hemodynamics seem most likely to be integrated into the control of extracellular-fluid volume by extra-renal adjustments, such as changes in the autonomic nervous system, systemic hemodynamics or humoral mechanisms. The autonomic nervous system has been shown to be involved in the renal excretion of water. Henry and Gauer108 demonstrated that left atrial distention results in a water diuresis. The afferent limb of this "volume reflex" seems to involve the parasympathetic nervous system since this . . .
Polyfluoroalkyl Chemicals in the U.S. Population: Data from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 and Comparisons with NHANES 1999–2000
Authors: Antonia M. Calafat, Lee-Yang Wong, Zsuzsanna Kuklenyik, John A. Reidy, Larry L. Needham
Journal: Environmental Health Perspectives (2007)

BackgroundPolyfluoroalkyl chemicals (PFCs) have been used since the 1950s in numerous commercial applications. Exposure of the general U.S. population to PFCs is widespread. Since 2002, the manufacturing practices for PFCs in the United States have changed considerably.ObjectivesWe aimed to assess exposure to perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and eight other PFCs in a representative 2003–2004 sample of the general U.S. population ≥ 12 years of age and to determine whether serum concentrations have changed since the 1999–2000 National Health and Nutrition Examination Survey (NHANES).MethodsBy using automated solid-phase extraction coupled to isotope dilution–high-performance liquid chromatography–tandem mass spectrometry, we analyzed 2,094 serum samples collected from NHANES 2003–2004 participants.ResultsWe detected PFOS, PFOA, PFHxS, and PFNA in &gt; 98% of the samples. Concentrations differed by race/ethnicity and sex. Geometric mean concentrations were significantly lower (approximately 32% for PFOS, 25% for PFOA, 10% for PFHxS) and higher (100%, PFNA) than the concentrations reported in NHANES 1999–2000 (p &lt; 0.001).ConclusionsIn the general U.S. population in 2003–2004, PFOS, PFOA, PFHxS, and PFNA serum concentrations were measurable in each demographic population group studied. Geometric mean concentrations of PFOS, PFOA, and PFHxS in 2003–2004 were lower than in 1999–2000. The apparent reductions in concentrations of PFOS, PFOA, and PFHxS most likely are related to discontinuation in 2002 of industrial production by electrochemical fluorination of PFOS and related perfluorooctanesulfonyl fluoride compounds.
Histiocytosis X With Pericardial Effusion: Diagnosis Questioned
Authors: Ana Eng
Journal: JAMA (1982)

<h3>To the Editor.—</h3> The patient described in the case report by Peter V. Pickens, MD, and Marc Rosenshein, MD (1981; 246:1810), was initially seen at the University of Illinois, Abraham Lincoln School of Medicine and at Mercy Hospital and Medical Center, Chicago. Biopsy specimens of her skin lesions and submaxillary salivary glands showed changes diagnostic of multicentric reticulohistiocytosis and not histiocytosis X as reported. These were the only biopsy procedures performed on this patient. The illustrations in the article by Drs Pickens and Rosenshein do not demonstrate the findings described in their legends. Figure 1 (p 1810) shows a sebaceous unit made up of cells with clear, foamy cytoplasm rather than "mature histiocytic cells with abundant eosinophilic cytoplasm." Figure 2 (p 1810) resembles a mesothelial lining filled with plasma cells and inflammatory mononuclear cells. Our examination of the skin specimen by routine light microscopy showed that the dermis was infiltrated
Statistical Approaches to Clinical Predictions
Authors: Barbara J. McNeil, James A. Hanley
Journal: New England Journal of Medicine (1981)

What is the chance that a patient will have a particular disease, a particular test result if the disease is present, or a favorable response to therapy? Such questions are becoming increasingly common in clinical medicine as the development of predictive indexes becomes more important.In a recent issue of the Journal, Dolgin and his colleagues1 attempted to develop a method to predict which patients with radiographically detectable gallstones have cholesterol stones and which have pigment stones. Medical therapy with chenodiol is effective only for the former, and since treatment is expensive and time-consuming, it is important to be . . .
Myocardial Infarction and Ischemic Heart Disease in Overweight and Obesity With and Without Metabolic Syndrome
Authors: Mette Thomsen, Børge G. Nordestgaard
Journal: JAMA Internal Medicine (2013)

Overweight and obesity likely cause myocardial infarction (MI) and ischemic heart disease (IHD); however, whether coexisting metabolic syndrome is a necessary condition is unknown.To test the hypothesis that overweight and obesity with and without metabolic syndrome are associated with increased risk of MI and IHD.We examined 71,527 individuals from the Copenhagen General Population Study and categorized them according to body mass index (BMI) as normal weight, overweight, or obese and according to absence or presence of metabolic syndrome.Hazard ratios for incident MI and IHD according to combinations of BMI category and absence or presence of metabolic syndrome.During a median of 3.6 years' follow-up, we recorded 634 incident MI and 1781 incident IHD events. For MI, multivariable adjusted hazard ratios vs normal weight individuals without metabolic syndrome were 1.26 (95% CI, 1.00-1.61) in overweight and 1.88 (95% CI, 1.34-2.63) in obese individuals without metabolic syndrome and 1.39 (95% CI, 0.96-2.02) in normal weight, 1.70 (95% CI, 1.35-2.15) in overweight, and 2.33 (95% CI, 1.81-3.00) in obese individuals with metabolic syndrome. For IHD, results were similar but attenuated. Normal weight vs overweight vs obesity and presence vs absence of metabolic syndrome did not interact on risk of MI or IHD (P = .90 and P = .44). Among individuals both with and without metabolic syndrome there were increasing cumulative incidences of MI and IHD from normal weight through overweight to obese individuals (log-rank trend P = .006 to P < .001). Although the multivariable adjusted hazard ratio for MI in individuals with vs without metabolic syndrome was 1.54 (95% CI, 1.32-1.81) across all BMI categories, addition of metabolic syndrome to a multivariable model including BMI and other clinical characteristics improved the Harell C-statistic only slightly for risk of MI (comparison P = .03) but not for IHD (P = .41).These findings suggest that overweight and obesity are risk factors for MI and IHD regardless of the presence or absence of metabolic syndrome and that metabolic syndrome is no more valuable than BMI in identifying individuals at risk.
Do We Know What Inappropriate Laboratory Utilization Is?
Authors: Carl van Walraven, C. David Naylor
Journal: JAMA (1998)

Objective.—Laboratory utilization has steadily increased, and some studies suggest inappropriate utilization. Therefore, we wished to assess studies that measure inappropriate laboratory use in light of methodological criteria.Design.—Systematic review of published studies.Data Sources.—MEDLINE, HEALTHSTAR, and EMBASE databases were searched from 1966 to September 1997 using a broad and inclusive strategy with no language restriction. In addition, the references of all retrieved studies and 3 textbooks on diagnostic testing were hand-searched.Study Selection.—All studies that provided and applied criteria for inappropriate laboratory use.Data Extraction.—Studies were categorized based on whether the criteria were implicit (objective criteria for inappropriate utilization not provided or very broad) or explicit. Guidelines for evaluation were applied to each study by a single reviewer.Data Synthesis.—Forty-four eligible studies were identified. Eleven studies used implicit criteria for inappropriate laboratory utilization and contained small numbers of patients or physicians. Most did not adequately assess the reliability of the implicit criteria. Thirty-three studies used explicit criteria based on the appropriateness of test choice, frequency, and timing, as well as the probability of a positive result. There were large variations in the estimates of inappropriate laboratory use (4.5%-95%). Evidence supporting the explicit criteria was frequently weak by the standards suggested for therapeutic maneuvers, but was nonetheless compelling based on principles of physiology, pharmacology, and probability.Conclusions.—Many studies identify inappropriate laboratory use based on implicit or explicit criteria that do not meet methodological standards suggested for audits of therapeutic maneuvers. Researchers should develop alternative evidentiary standards for measuring inappropriateness of laboratory test use.
Polymorphisms of the CYP2C19 gene in Japanese patients with aspirin-exacerbated respiratory disease
Authors: Kenya Kohyama, Shyuzo Abe, Kazumi Kodaira, Tatsuo Yukawa, Soichiro Hozawa, Junichiro Morioka, Hiroaki Inamura, Mayumi Ota, Hironori Sagara, Motohiro Kurosawa
Journal: Journal of Allergy and Clinical Immunology (2011)
Studies with Tritiated Digoxin: Absorption, Excretion, and Enterohepatic Circulation.
Authors: James E. Doherty
Journal: Annals of Internal Medicine (1972)

Meeting Abstracts1 May 1972Studies with Tritiated Digoxin: Absorption, Excretion, and Enterohepatic Circulation.James E. Doherty, M.D., F.A.C.P., William J. Flanigan, M.D., F.A.C.P., Robert L. Clark, M.D., Marvin L. Murphy, M.D., F.A.C.P.James E. Doherty, M.D., F.A.C.P.Search for more papers by this author, William J. Flanigan, M.D., F.A.C.P.Search for more papers by this author, Robert L. Clark, M.D.Search for more papers by this author, Marvin L. Murphy, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-5-862_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptFifty-four human volunteers were given tritiated digoxin by the oral or intravenous route, or both, to determine absorption, excretion, enterohepatic circulation, and serum turnover rates. Frequent serum samples were obtained, and all stools and urine were saved for 7 days. Bile was also saved from six patients with surgically induced biliary fistula who received the drug intravenously. Specimens were extracted by column chromatography and samples counted with a liquid scintillation counter. A mean serum T½ of 33 hours was observed in those patients with normal renal function. Excretory data are shown below.Digoxin was 85% absorbed, and enterohepatic circulation was... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Little Rock, Ark. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1972Volume 76, Issue 5Page: 862-863KeywordsBileChromatographyDrugsExcretionFistulasUrine Issue Published: 1 May 1972 PDF DownloadLoading ...