tbuckley/cabot-search huggingface dataset:
Treatment of Lactic Acidosis with Dichloroacetate
Authors: Peter W. Stacpoole, Eloise M. Harman, Stephen H. Curry, Thomas G. Baumgartner, Robert I. Misbin
Journal: New England Journal of Medicine (1983)

We administered dichloroacetate, which prevents or reverses hyperlactatemia in animals and lowers plasma lactate levels in human beings, to 13 patients with lactic acidosis of various causes. All had hypotension, and their acidemia had resisted treatment with sodium bicarbonate. The metabolic effects of dichloroacetate were evaluated in 11 patients. In seven dichloroacetate significantly reduced the level of arterial blood lactate (P less than 0.005) from the base-line value and raised the levels of arterial blood bicarbonate (P less than 0.02) and arterial pH (P less than 0.005). In six of these seven, the acidemia resolved completely with therapy. In 10 of the 13 patients systolic blood pressure increased by 10 to 40 mm Hg, and 4 patients had a 21 per cent increase in cardiac output (P less than 0.02). Despite improvement in their lactic acidemia, all patients but one died of their underlying disease. No serious drug-related toxicity occurred. We conclude that dichloroacetate is a safe and effective adjunct in the treatment of patients with lactic acidosis, although the ultimate prognosis may depend on the underlying disease.
Human neutrophil cytochrome b light chain (p22-phox). Gene structure, chromosomal location, and mutations in cytochrome-negative autosomal recessive chronic granulomatous disease.
Authors: M C Dinauer, E A Pierce, G A Bruns, J T Curnutte, S H Orkin
Journal: Journal of Clinical Investigation (1990)

A membrane-bound cytochrome b, a heterodimer formed by a 91-kD glycoprotein (heavy chain) and a 22-kD polypeptide (light chain), is an essential component of the phagocyte NADPH-oxidase responsible for superoxide generation. Cytochrome b is absent in two subgroups of chronic granulomatous disease (CGD), an inherited disorder characterized by the lack of oxidase activity. Mutations in the cytochrome heavy chain gene, encoded by the CYBB locus in Xp21.1, result in the X-linked form of CGD. A rare subgroup of autosomal recessive CGD also lacks cytochrome b (A- CGD), but the genetic defect has not previously been identified. In order to search for possible mutations in the cytochrome light chain locus, CYBA, the structure of this gene was characterized. The CYBA locus was localized to 16q24, and the approximately 600-bp open reading frame determined to be encoded by six exons that span approximately 8.5 kb. Three unrelated patients with A- CGD were studied for evidence of mutations in the light chain gene. One patient, whose parents were first cousins, was homozygous for a large deletion that removed all but the extreme 5' coding sequence of the gene. The other two patients had a grossly normal light chain transcript on Northern blot of mononuclear cell RNA. The light chain transcript was amplified by the polymerase chain reaction and sequenced. One patient was a compound heterozygote for two alleles containing point mutations in the open reading frame that predict a frame shift and a nonconservative amino acid replacement, respectively. The second patient, whose parents were second cousins, was homozygous for a different single-base substitution resulting in another nonconservative amino acid change. These results indicate that A- CGD can results from defects in the gene encoding the 22-kD light chain of the phagocyte cytochrome b.
Left Ventricular Geometry and Function Preceding Neurally Mediated Syncope
Authors: Jennifer E. Liu, Rebecca T. Hahn, Kenneth M. Stein, Steven M. Markowitz, Peter M. Okin, Richard B. Devereux, Bruce B. Lerman
Journal: Circulation (2000)

Background —Neurally mediated syncope has been associated with increased left ventricular (LV) fractional shortening (FS) during tilt testing, which is consistent with the hypothesis that the stimulation of LV mechanoreceptors leads to reflex hypotension and/or bradycardia. However, FS does not represent true LV contractility because of its dependence on afterload and preload. Methods and Results —To elucidate the role of increased contractility in the mediation of neurally mediated syncope, we compared echocardiographic measures of LV performance corrected for end-systolic stress (ESS) in 21 patients (13 women and 8 men) with unexplained syncope who had either positive (n=10) or negative (n=11) responses to a tilt-table test. Two-dimensional echocardiographic LV imaging was performed at baseline and during the initial 5 minutes of upright tilt. In the supine position, both groups had similar LV end-diastolic volume indexes, stroke volumes, FS, circumferential ESS, and afterload-independent measures of LV performance (stress-corrected midwall and FS). However, after 5 minutes of upright tilt, patients who subsequently had a positive test had a lower stroke volume, lower stress-corrected midwall shortening, and endocardial FS. The tilt-positive group also had a greater fall in ESS and FS early during upright tilt. Conclusions —Reduced ESS, LV volume, and chamber function during initial upright tilt are associated with a subsequent positive tilt response in patients with unexplained syncope. These data suggest that if paradoxic activation of LV mechanoreceptors has a role in mediating neurally mediated syncope, it is not triggered by LV hypercontractility or increased systolic wall stress during the initial period of upright tilt.
Crosstalk between NOTCH and AKT signaling during murine megakaryocyte lineage specification
Authors: Melanie G. Cornejo, Vinciane Mabialah, Stephen M. Sykes, Tulasi Khandan, Cristina Lo Celso, Cécile K. Lopez, Paola Rivera-Muñoz, Philippe Rameau, Zuzana Tothova, Jon C. Aster, Ronald A. DePinho, David T. Scadden, D. Gary Gilliland, Thomas Mercher
Journal: Blood (2011)
Medical vs Legal Fee Splitting
Authors: Charles Harris
Journal: JAMA (1966)

To the Editor:—  James H. Hutton, MD, compares medical fee splitting (proscribed) to fee splitting in the legal profession which is approved by the bar association. He suggests that medical fees be paid in lump sum and the doctors split them any way they see fit.  A fallacy in the comparison is that fee splitting among lawyers is self-regulating, since most fees are contingent on the size of the settlement. Therefore it is to the advantage of the client to secure lawyer A in the hope that he will get a large award. It is also to the advantage of lawyer A to secure the services of lawyer B who may be able to get an even larger award. Lawyer A can't possibly choose a less talented lawyer or his fees would suffer. The system provides for referrals of increasing- competence, and an increasing degree of protection for the client.
The analysis of left ventricular wall thickness and shear by an ultrasonic triangulation technique in the dog.
Authors: G Osakada, S Sasayama, C Kawai, A Hirakawa, W S Kemper, D Franklin, J Ross
Journal: Circulation Research (1980)

We developed a new ultrasonic triangulation technique to measure regional wall thickness and shear motion of the left ventricular wall under normal conditions and during complete and partial coronary occlusions.In 10 open-chest dogs, a left ventricular micromanometer was inserted, and a screw-driven arterial clamp and flowmeter were placed around the left circumflex coronary artery.A single miniature ultrasonic crystal was placed in the subendocardium of the left ventricular free wall in a region to be made ischemic, and three receiving crystals were sutured to the opposing epicardium at the corners of a 45-degree right triangle.By the trigonometric combination of three measured lengths from ultrasonic dimension gauges, the exact position of the endocardial crystal in X, Y, and Z coordinates could be displayed by computer.The endocardial surface moved in a longitudinal direction relative to the epicardial surface during normal systole [0.58 ± 0.26 (mean ± SEM) mm].With coronary occlusion, this myocardial shear became less marked (0.11 ± 0.12 mm), and systolic wall thickening changed to thinning.When coronary occlusion was released, end-diastolic wall thickness and percent wall thickening rapidly increased to 104.8% and 141.7% of control, respectively, concurrent with the reactive hyperemia.With partial coronary constriction, these postreperfusion changes were markedly reduced, suggesting a role for reactive hyperemia in postreperfusion wall thickness dynamics.These techniques allow measurement of shear and three-dimensional display of dimensions and thereby permit documentation of true wall thickness dynamics both during and after coronary occlusion.
Current Therapy for Hypercholesterolemia
Authors: Conrad B. Blum
Journal: JAMA (1989)

THE EVIDENCE is now in that lowering cholesterol levels reduces the risk of coronary heart disease (CHD). A century of animal data as well as morphological, genetic, and metabolic studies in man point to a strong association between serum cholesterol levels and coronary artery disease. Prospective epidemiologic studies show a graded relationship between serum cholesterol and coronary risk extending to cholesterol levels below 4.14 mmol/L (&lt;160 mg/dL), ie, well into the desirable range for serum cholesterol.<sup>1</sup>Clinical trials performed in man provide the final validation of the cholesterol-atherogenesis connection. In the Lipid Research Clinics Coronary Primary Prevention Trial, over a 7-year period a 12.5% decrease in low-density lipoprotein (LDL) cholesterol levels was associated with a 19% decrease in the incidence of myocardial infarction and CHD death.<sup>2,3</sup>In addition, treatment was associated with a significant reduction in the development of angina, a positive exercise test, and the need for
Scared to Death
Authors: George X. Trimble
Journal: JAMA (1966)

<h3>To the Editor:—</h3> Dr. Willard Goodwin's investigations in the realm of science are noted for their soundness and objectivity. I, for one, am impressed. Wolf, whose report on the effects of stress on the heart I cited in my contribution on "death from fright" (<b>195</b>:1019, 1966) now proposes that "deaths from 'fright'... may be attributable to an overexuberant oxygen-conserving reflex" (<i>Amer Heart J</i><b>71</b>:840, 1966).
Time-dependent Effects of Dog Exposure and Genotype at Immune-Related Genes on Wheezing and Atopy in Early Childhood
Authors: J. Bufford, Z. Li, C. Reardon, K.A. Roberg, C. Tisler, E. Anderson, D. DaSilva, I. Ostrovnaja, S. Hoffjan, D. Nicolae, R. Gangnon, C. Ober, R.F. Lemanske, J.E. Gern
Journal: Journal of Allergy and Clinical Immunology (2006)
Microbiological agents as health risks in indoor air.
Authors: R Burrell
Journal: Environmental Health Perspectives (1991)

Ambient air may be contaminated with or carry significant levels of a variety of potentially harmful microorganisms. There are three major sources of such microbes: a) those arising from microbial decomposition of various substrates associated with particular occupations (e.g., "moldy" hay leading to hypersensitivity pneumonitis), b) those associated with certain types of environments (e.g., Legionnaires' bacteria in water supplies), and c) those stemming from infective individuals harboring a particular pathogen (e.g., tuberculosis). This presentation deals primarily with important microorganisms from occupational and environmental sources and clearly differentiates from case to case transmission via droplet nuclei infection. Microorganisms that are uniformly injurious are differentiated from those that are more opportunistic (i.e., those that cause problems only in people with preexisting debilities). Such microorganisms are categorized according to whether they are allergenic, infectious, or capable of inducing toxic or inflammatory reactions when inhaled. Representative examples from each of these categories, which include bacteria, fungi, rickettsia, and amoebae, are discussed. The conditions responsible for the entrance of significant numbers of these microbes into the air, the mechanisms by which they produce injury, and the methods of prevention are also considered. With attention given to some of the basic sources and requirements for such microorganisms to reproduce and enter the ambient air environment, it is a relatively simple matter to prevent the occurrence of health problems.
A GAMMA LABELED PLASMA FLOW MARKER
Authors: Stephen E. Little, Jeanne M. Link, Jena L. Miller, Kenneth A. Krohn, Jamrs B. Bassingthwaighte
Journal: Clinical Nuclear Medicine (1983)

Little, Stephen E.; Link, Jeanne M.; Miller, Jena L.; Krohn, Kenneth A.; Bassingthwaighte, Jamrs B. Author Information
The Effect of Water-Soluble Preparations of Vitamin K in Dicumarol-Induced Hypoprothrombinemia
Authors: Shepard Shapiro, Murray Weiner, George Simson
Journal: New England Journal of Medicine (1950)

IN THEIR pioneer studies of the sweet-clover disease in cattle both Schofield1 and Roderick2 observed that the hemorrhagic state could be reversed by a change in the diet, and particularly by the addition of alfalfa hay, which has since been shown to be rich in vitamin K. Quick3 later noted a similar response in rabbits and chicks, but failed to relate this change to vitamin K. Link and his associates4 were the first to demonstrate in animals that it was necessary to administer 2-methyl-l, 4-naphthoquinone, a form of vitamin K, in large doses in order to prevent the hypoprothrombinemia induced . . .
Disseminated intravascular coagulation associated with toxic epidermal necrolysis (Lyell's syndrome)
Authors: JAN KAVASNIČKA, JAN ŘEZAČ, JIŘI ŠVEJDA, HANA DUCHKOVA, FRANTIŠEK KAZE, PAVEL ŽALUD, JOSEF RICHTER
Journal: British Journal of Dermatology (1979)

Evidence of disseminated intravascular coagulation was recorded in eight patients with toxic epidermal necrolysis (TEN)—Lyell's syndrome. Patients wee treated with low doses of heparin in combination with the usual treatment of TEN, i.e. maintenance of fluid and electrolyte balance, systemic corticosteroids, antibiotics and aseptic dressings, in the Intensive Care Unit environment. It is suggested that the alteration of haemostasis and inter-related biological systems, such as activation of components of complement, kinins and immunoglobulins, may affect the outcome of TEN.
Hospital management of self harm in adults in England
Authors: Alex J Mitchell
Journal: BMJ (2004)

Editor-The Data Protection Act 1998 does not prohibit the processing of personal information for medical research purposes.Indeed, it is clear from section 33 of the act that such processing is expressly permitted.If it were otherwise, then the act would be in direct conflict with the core aims of the laws that underpin it-namely, the Council of Europe Convention of 1981 and the European Union Directive of 1995.These laws seek to facilitate data processing activities, primarily "free flows" of information, rather than suppress data processing.The problems to which Peto et al refer in their editorial on data protection, informed consent, and research are not Data Protection Act problems but, rather, problems caused by ignorance and misunderstanding. 1 With basic training on the key mechanisms of the act the problems of which the authors complain can be easily overcome.Training need not be an expensive task either.Legal compliance can be achieved at comparatively modest cost.There are two additional points of note.Firstly, the Data Protection Act regulates the processing of personal information relating to living individuals.Thus, research following death is not regulated.Secondly, the act and case law make clear that information will not be "personal data" if it does not identify a living person or if it does not have the individual as its focus or is not significantly biographical.So, if medical researchers do not actually need or seek identification information the act should not be engaged.
Impact of NHS Direct on general practice consultations during the winter of 1999-2000: analysis of routinely collected data
Authors: R. S Chapman
Journal: BMJ (2002)

The impact of NHS Direct on other primary care services in the United Kingdom has been the subject of recent debate.1 A hospital bed crisis occurred in the winter of 1999-2000, but according to routine primary care surveillance systems the incidence of influenza-like illness did not reach epidemic proportions (as conventionally described). 2 3 Considerable medical and media interest was given to influenza activity during this “millennium” winter.4 There was speculation that there was a genuine influenza epidemic but that people were telephoning NHS Direct and not seeking help from their general practitioner, resulting in an artificially low incidence of influenza-like illness. At the time there was partial coverage of England and Wales by NHS Direct; we therefore used this “natural experiment” to assess whether the introduction of NHS Direct had any impact on episodes of influenza-like illness and other cases of respiratory infections seen by general practitioners. …
Coronary flow velocity immediately after reperfusion reflects myocardial microcirculation in canine acute myocardial infarction models
Authors: Koichi Sakabe, Tetsuzo Wakatsuki, Hisanori Shinohara, Akiyoshi Nishikado, Hirotsugu Yamada, Tomotsugu Tabata, Arata Iuchi, Takashi Oki, Susumu Ito
Journal: Journal of the American College of Cardiology (1996)
Risk Stratification for In-Hospital Mortality in Acutely Decompensated Heart Failure&lt;SUBTITLE&gt;Classification and Regression Tree Analysis&lt;/SUBTITLE&gt;
Authors: Gregg C. Fonarow, Kirkwood F. Adams, William T. Abraham, Clyde W. Yancy, W. John Boscardin
Journal: JAMA (2005)

EART FAILURE CAUSES CONsiderable morbidity and mortality and is responsible for a tremendous burden on the health care system in the United States. 1 It accounted for approximately 1 million hospital discharges in 2001, an increase of 164% since 1979, and is associated with an overall annual cost of nearly $29 billion. 1 Reported in-hospital mortality ranges from as low as 2.3% among patients enrolled in clinical trials to 19% in referral hospital series. 2,3espite this dramatic increase in the public health burden of hospitalization for heart failure, models for the risk stratification of patients during admission for acute decompensated heart failure (ADHF) are not well established.Clinical risk prediction tools may be helpful in guiding medical decision making.Patients estimated to be at a lower risk may be managed with less intensive monitoring and therapies available on a telemetry unit or hospital ward, whereas a patient estimated to be at a higher risk may require more intensive management in an intensive
Bile duct proliferation in Jag1/fringe heterozygous mice identifies candidate modifiers of the alagille syndrome hepatic phenotype
Authors: Matthew J. Ryan, Christina Bales, Anthony Nelson, Dorian M. Gonzalez, Lara Underkoffler, Michelle Segalov, Jeanne Wilson-Rawls, Susan E. Cole, Jennifer L. Moran, Pierre Russo, Nancy B. Spinner, Kenro Kusumi, Kathleen M. Loomes
Journal: Hepatology (2008)

Abstract Alagille syndrome (AGS) is a heterogeneous developmental disorder associated with bile duct paucity and various organ anomalies. The syndrome is caused by mutations in JAG1 , which encodes a ligand in the Notch signaling pathway, in the majority of cases and mutations in the NOTCH2 receptor gene in less than 1% of patients. Although a wide array of JAG1 mutations have been identified in the AGS population, these mutational variants have not accounted for the wide phenotypic variability observed in patients with this syndrome. The Fringe genes encode glycosyltransferases, which modify Notch and alter ligand-receptor affinity. In this study, we analyzed double heterozygous mouse models to examine the Fringe genes as potential modifiers of the Notch-mediated hepatic phenotype observed in AGS. We generated mice that were haploinsufficient for both Jag1 and one of three paralogous Fringe genes: Lunatic ( Lfng ), Radical ( Rfng ), and Manic ( Mfng ). Adult Jag1 +/− Lfng +/− and Jag1 +/− Rfng +/− mouse livers exhibited widespread bile duct proliferation beginning at 5 weeks of age and persisting up to 1 year. The Jag1 +/− Mfng +/− livers showed a subtle, yet significant increase in bile duct numbers and bile duct to portal tract ratios. These abnormalities were not observed in the newborn period. Despite the portal tract expansion by bile ducts, fibrosis was not increased and epithelial to mesenchymal transition was not shown in the affected portal tracts. Conclusion: Mice heterozygous for mutations in Jag1 and the Fringe genes display striking bile duct proliferation, which is not apparent at birth. These findings suggest that the Fringe genes may regulate postnatal bile duct growth and remodeling, and serve as candidate modifiers of the hepatic phenotype in AGS. (Hepatology 2008;48:1989–1997.)
TCT-676 Determinants of Left Ventricular Mass Regression in Patients with Severe Symptomatic Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation
Authors: Adaya Weissler-Snir, Yaron Shapira, Alexander Sagie, Abid Assali, Hana Vaknin-Assa, Tamir Bental, Pablo Codner, Katia Orvin, Ran Kornowski, Mordehay Vaturi
Journal: Journal of the American College of Cardiology (2014)
Controversy in Internal Medicine
Authors: Alvan R. Feinstein
Journal: JAMA (1966)

For the 23 different topics in this book, the 73 invited experts and the three editors demonstrate medicine's traditional capacity for reaching antipodal conclusions from what appears to be the same set of available facts.  The authorities present their varied opinions on current controversies regarding dietary treatment of atherosclerosis, duodenal ulcer, obesity, and diabetes mellitus; drugs for hypertension, myocardial infarction, anxiety, and adenocarcinoma; management of gastric ulcer, urinary catheterization, asymptomatic bacteriuria, emphysema, rheumatoid arthritis, and preoperative bowel preparation; pathogenesis of hemochromatosis, glomerulonephritis, and colonic cancer; and the additional issues of fibrinolytic therapy, classification of cirrhoses, diagnosis of unilateral renal disease, significance of the autoimmunity concept, value of boards of internal medicine, and validity of etiologic decisions made via statistical associations.  The scope of the topics, the stellar array of authors, and the laudable airing of the controversies will appeal to any alert, curious spectator of today's passing medical parade. For
1. Appropriateness of Gastroscopy: Dyspepsia 1
Authors: F. Froehlich, M. Bochud, J.-J. Gonvers, R. W. Dubois, J.-P. Vader, V. Wietlisbach, B. Burnand
Journal: Endoscopy (1999)

Dyspepsia is a very common set of clinical symptoms. Clear-cut scientific evidence of the effectiveness of diagnostic schemes is unavailable for most clinical situations related to dyspepsia. For this and other reasons, practice patterns vary widely. The development of explicit detailed criteria of appropriateness of use of endoscopy is an attempt to produce best available evidence (based on a validated panel process and expert judgment) where better evidence is lacking, with the aim to assist the clinician in daily decision making.