tbuckley/cabot-search huggingface dataset:
High affinity binding of 125I-angiotensin II to rat glomerular basement membranes.
Authors: J Sraer, L Baud, J P Cosyns, P Verroust, M P Nivez, R Ardaillou
Journal: Journal of Clinical Investigation (1977)

125I-angiotensin II (AII) specifically bound to rat glomerular basement membrane (GBM). The kinetics of binding were similar to those obtained with the total glomeruli. The apparent dissociation constant was close to 50 pM with both preparations. The number of sites related to the amount of protein was two times greater with GBM than with total glomeruli. Since the amount of GBM protein extracted from a given amount of glomerular protein was about 10%, it was possible to estimate the share of the GBM binding sites for AII as representing 20% of the total number present in the entire glomerulus. Binding studies at equilibrium as a function of 125I-AII concentration and competitive binding experiments suggested either multiplicity of the binding sites or cooperativity in the binding reaction. Degradation of 125I-AII in the presence of GBM was slight and did not increase with time. The difference in the degrees of degradation of 125I-AII was too small to account for the observed difference in binding when the results obtained with GBM and isolated glomeruli preparations were compared. 125I-AII binding to GBM was increased after treatment of these membranes with collagenase, slightly diminished with neuraminidase, and almost completely abolished with trypsin suggesting the proteic nature of the receptor. 125I-AII binding to GBM was diminished after incubation of GBM with anti-GBM antibodies as a result of a decrease in the number of binding sites. 125I-AII binding was even more diminished in preparations of glomeruli isolated from rats passively immunized with anti-GBM antibodies when compared with glomeruli from control animals. This resulted from both smaller affinity for AII and decrease in the number of the binding sites. The present data provides evidence for specific binding sites for AII localized on GBM. This is noteworthy since receptors for polypeptide hormones are currently observed on the surface of cell membranes. These findings also suggest a new physiological role for AII which might involve modification of GBM permeability.
GMC reshapes procedures on fitness to practise
Authors: Caroline White
Journal: BMJ (2004)

The medical profession's regulatory body, the General Medical Council, has developed a new warning system for doctors whose performance falls below acceptable standards, but is not serious enough to warrant restrictions on their practice.

The move is part of a substantial overhaul of the council's fitness to practise procedures, designed to streamline the complaints process and boost transparency.

Under the terms of the new framework, the three separate committees on performance, conduct, and health will be abolished. Instead, a doctor's fitness to practise will be assessed “in the round.”

The complaints process …
Influence of right heart size on outcome in pulmonary atresia with intact ventricular septum.
Authors: T M Giglia, K J Jenkins, A Matitiau, V S Mandell, S P Sanders, J E Mayer, J E Lock
Journal: Circulation (1993)

BACKGROUND Neonates with pulmonary atresia and intact ventricular septum (PA-IVS) are frequently born with hypoplastic right heart structures that must grow after right ventricular decompression (RVD) procedures for a complete two-ventricle physiology to be achieved. Previous authors have asserted that neonatal right heart size or morphology will predict right heart growth potential. Since 1983, our bias has favored early RVD regardless of initial right heart size. In 1986, we recognized a subset of patients with coronary artery abnormalities associated with poor outcome after RVD and have defined these patients as having a right ventricular-dependent coronary circulation (RVDCC). METHODS AND RESULTS To assess the influence of right heart size on outcome independent of the presence of RVDCC, we measured echocardiographic right ventricular (RV) dimensions in 37 neonates with adequate studies presenting between 1983 and 1990. Coronary artery anatomy was adequately assessed by angiography in 36. RV volume and tricuspid valve (TV) diameter were significantly smaller in patients with RVDCC than in those without. However, there was no statistically significant association between RV volume or TV diameter and survival among patients with or without RVDCC: Among 29 patients without RVDCC, 23 of 24 (95.8%) who achieved RVD are alive compared with 1 of 5 (20%) who did not achieve RVD (P = .001). Twenty-one of the 23 survivors have a complete two-ventricle physiology with low right atrial pressure. Among 7 patients with RVDCC, 2 patients who underwent RVD died early of left ventricular failure, whereas 4 of 5 who did not undergo RVD have survived single ventricular palliation. CONCLUSIONS Small right heart size is associated with RVDCC but is not associated with survival in PA-IVS. Patients without RVDCC have improved survival after RVD regardless of neonatal right heart size.
Good Prognosis for Pericarditis With and Without Myocardial Involvement
Authors: Massimo Imazio, Antonio Brucato, Andrea Barbieri, Francesca Ferroni, Silvia Maestroni, Guido Ligabue, Alessandra Chinaglia, Davide Cumetti, Giovanni Della Casa, Federica Bonomi, Francesca Mantovani, Paola Di Corato, Roberta Lugli, Riccardo Faletti, Stefano Leuzzi, Rodolfo Bonamini, Maria Grazia Modena, Riccardo Belli
Journal: Circulation (2013)

Background— The natural history of myopericarditis/perimyocarditis is poorly known, and recently published studies have presented contrasting data on their outcomes. The aim of the present article is to assess the prognosis of myopericarditis/perimyocarditis in a multicenter, prospective cohort study. Methods and Results— A total of 486 patients (median age, 39 years; range, 18–83 years; 300 men) with acute pericarditis or a myopericardial inflammatory syndrome (myopericarditis/perimyocarditis; 85% idiopathic, 11% connective tissue disease or inflammatory bowel disease, 5% infective) were prospectively evaluated from January 2007 to December 2011. The diagnosis of acute pericarditis was based on the presence of 2 of 4 clinical criteria (chest pain, pericardial rubs, widespread ST-segment elevation or PR depression, and new or worsening pericardial effusion). Myopericardial inflammatory involvement was suspected with atypical ECG changes for pericarditis, arrhythmias, and cardiac troponin elevation or new or worsening ventricular dysfunction on echocardiography and confirmed by cardiac magnetic resonance. After a median follow-up of 36 months, normalization of left ventricular function was achieved in &gt;90% of patients with myopericarditis/perimyocarditis. No deaths were recorded, as well as evolution to heart failure or symptomatic left ventricular dysfunction. Recurrences (mainly as recurrent pericarditis) were the most common complication during follow-up and were recorded more frequently in patients with acute pericarditis (32%) than in those with myopericarditis (11%) or perimyocarditis (12%; P &lt;0.001). Troponin elevation was not associated with an increase in complications. Conclusions— The outcome of myopericardial inflammatory syndromes is good. Unlike acute coronary syndromes, troponin elevation is not a negative prognostic marker in this setting.
Gastric emptying after treatment of stenosis secondary to duodenal ulceration by proximal gastric vagotomy and duodenoplasty or pyloric dilatation.
Authors: C M White, L K Harding, M R Keighley, N J Dorricott, J Alexander-Williams
Journal: Gut (1978)

A consecutive series of 12 patients with stenosis secondary to duodenal ulceration were treated by proximal gastric vagotomy (PGV) and duodenoplasty or PGV and dilatation of the stenosis. Three months after operation the rate and pattern of gastric emptying of a solid meal was measured in each patient and compared with 18 patients with uncomplicated duodenal ulcer treated by PGV alone. Two patients developed gastric stasis in the early postoperative period which resolved with medical treatment. All patients were asymptomatic and were eating normally three months after operation. There was no significant difference in the rate of gastric emptying postoperatively between the patients who had stenosis and those who had uncomplicated duodenal ulcers. These results indicate that despite early postoperative difficulties in some patients pyloric dilatation or duodenoplasty with PGV are both effective treatments for stenosis due to duodenal ulceration.
Septicaemia Caused by an Organism Resembling Pasteurella Septica After a Dog-bite
Authors: E. Williams
Journal: BMJ (1960)

Abstract  The World Health Organization (WHO) has declared the 2019 novel coronavirus (2019-nCoV) infection outbreak a global health emergency. Currently, there is no effective anti-2019-nCoV medication. The sequence identity of the 3CL proteases of 2019-nCoV and SARS is 96%, which provides a sound foundation for structural-based drug repositioning (SBDR). Based on a SARS 3CL protease X-ray crystal structure, we construct a 3D homology structure of 2019-nCoV 3CL protease. Based on this structure and existing experimental datasets for SARS 3CL protease inhibitors, we develop an SBDR model based on machine learning and mathematics to screen 1465 drugs in the DrugBank that have been approved by the U.S. Food and Drug Administration (FDA). We found that many FDA approved drugs are potentially highly potent to 2019-nCoV.
Controversy Continues as Experts Ponder Zidovudine's Role in Early HIV Infection
Authors: Paul Cotton
Journal: JAMA (1990)

SCIENTISTS are not unanimous in endorsing zidovudine (azidothymidine [AZT]; Retrovir [Burroughs Wellcome Co]) therapy for patients infected with the human immunodeficiency virus (HIV) whose CD4 cell counts are above 200/mm<sup>3</sup>. Doubts are most notable among investigators at the Veterans Administration (VA) and in Europe who have not seen benefit in such patients in their own ongoing trials with the only approved drug that fights the retrovirus thought to cause acquired immunodeficiency syndrome (AIDS). The Food and Drug Administration (FDA) on March 2 extended label indications for zidovudine, raising the CD4 cell count threshhold for therapy implementation from 200 to 500. The change was based on data from two National Institute of Allergy and Infectious Diseases (NIAID) trials, dubbed numbers 016 and 019. In patients with CD4 counts between 200 and 500, low dosages (500 to 1200 mg/d) were well tolerated, significantly delayed onset of opportunistic infections but not malignancies
Sports Medicine "Webliographies"
Authors: Jayne Makepeace
Journal: British Journal of Sports Medicine (1997)

<h3>Abstract</h3> Non-pharmaceutical interventions (NPIs) have been a cornerstone in managing emergent diseases such as COVID-19<sup>1–4</sup>. However, despite their potential to contain or attenuate the epidemic, the effects of NPIs on disease dynamics are not well understood<sup>1,5–7</sup>. We show that saturation of NPIs with the increase in infected individuals, an expected consequence of limited contact tracing and healthcare capacities, produces a positive feedback in the disease growth rate and a threshold between two alternative states--containment and outbreak<sup>8</sup>. These alternative states were previously related with the strength of NPIs but not with the infection number<sup>2,9–11</sup>. Furthermore, the transition between these states involves an abrupt acceleration in disease dynamics, which we report here for several COVID-19 outbreaks around the world. The consequences of a positive feedback in population dynamics at low numbers is a phenomenon widely studied in ecology--the Allee effect. This effect is a determinant of extinction-outbreak states, geographic synchronization, spatial spread, and the effect of exogenous variables, as vaccination<sup>12–15</sup>. As countries are relaxing containing measures, recognizing an NPI-induced Allee effect may be essential for deploying containment strategies within and among countries<sup>16</sup> and acknowledges the need for early warning indicators of approaching epidemic tipping points<sup>17</sup>.
Prevention of suicide Depressed patients need more choices
Authors: D Kingdon, J Warner, C Stark, H Smith, D Hall, F O'Brien
Journal: BMJ (1994)

EDITOR, - The prevention of suicide may be controversial, but does it really warrant the pessimism expressed recently? David Gunnell and Stephen Frankel provide a comprehensive review of the prevention of suicide, but their conclusions seem unduly negative.1 Jennie McCarthy and Ian Davidson rightly see problems with the use of suicide as an indicator for the performance of mental health services.2 However, “health of the nation outcome scales” to measure improvements in the health and social functioning of mentally in people should be available soon.

Suicide is an important cause of death (5542 suicides occurred in 1992, including death undetermined cause) and is more common that deaths from road traffic accidents (3814 occurred in 1992) and from cervical cancer (1532), yet the attention paid to it is far less. Perhaps it is still viewed as a choice that should not be constrained Yet most people who commit suicide are seriously depressed,3 believing that they have no or little choice …
High-throughput sequence analysis of the tyrosine kinome in acute myeloid leukemia
Authors: Marc M. Loriaux, Ross L. Levine, Jeffrey W. Tyner, Stefan Fröhling, Claudia Scholl, Eric P. Stoffregen, Gerlinde Wernig, Heidi Erickson, Christopher A. Eide, Roland Berger, Olivier A. Bernard, James D. Griffin, Richard M. Stone, Benjamin Lee, Matthew Meyerson, Michael C. Heinrich, Michael W. Deininger, D. Gary Gilliland, Brian J. Druker
Journal: Blood (2008)
Impaired responses of peripheral blood mononuclear cells to nickel in patients with nickel-allergic contact dermatitis and concomitant atopic dermatitis
Authors: D. Buchvald, L. Lundeberg
Journal: British Journal of Dermatology (2004)

Background Allergic contact dermatitis (ACD) is pathogenetically dependent on cell‐mediated immune responses mediated by type 1 T lymphocytes. Atopic dermatitis (AD), in contrast, occurs as a result of sustained activation of type 2 subsets of T cells. Although atopic patients may become sensitized to various contact allergens, little is known about the influence of atopy on delayed‐type hypersensitivity. Objectives To investigate the in vitro responses of peripheral blood mononuclear cells (PBMC) to nickel stimulation in groups of atopic and nonatopic patients with patch test‐verified nickel ACD. Methods Ten nonatopic patients with nickel ACD, 10 patients with nickel ACD and concomitant AD, 10 patients with AD but with no contact allergy, and 10 healthy persons participated in the study. PBMC were cultured in the presence or absence of nickel sulphate, phytohaemagglutinin (PHA) or tetanus toxoid (TT). [3H]thymidine incorporation was used to measure the rate of antigen‐induced DNA synthesis and enzyme‐linked immunosorbent assay was used to measure the production of interleukin (IL)‐2 (type 1 cytokine) and IL‐5 (type 2 cytokine). Results Nickel‐stimulated PBMC of nickel‐allergic patients with AD proliferated significantly less and secreted significantly lower amounts of IL‐2 than cells of nonatopic nickel‐allergic patients. IL‐5 production was also lower in the former group, although the difference was nonsignificant. Moreover, neither the nickel‐specific DNA synthesis nor the cytokine production by PBMC of atopic nickel‐allergic patients differed significantly from those of healthy control persons and AD patients without contact allergy. Proliferative and secretory responses of PBMC to PHA or TT stimulation differed nonsignificantly between the groups. Nickel‐induced IL‐2 production correlated well with IL‐5 production in nickel‐allergic patients regardless of their atopic status. Conclusions Our results indicate that PBMC of nickel‐allergic patients with concomitant AD are characterized by impaired in vitro proliferative and secretory responses to the contact allergen nickel but not to the mitogen PHA or the recall antigen TT. The type 2 cytokine IL‐5 may play a role in the development of ACD.
Diabetes Mellitus: A Fundamental and Clinical Text
Authors: G. Stephen DeCherney
Journal: JAMA (1997)

Another diabetes text? Is there something else to know besides controlling blood sugars? According to Mayer B. Davidson, president-elect of the American Diabetes Association, 16 million Americans have diabetes mellitus. It is the most expensive disease in the Western world and the fourth leading cause of death by disease in the United States. The annual cost to the American public is $92 billion dollars, exceeding $11 000 per patient. Diabetes is the leading cause of adult blindness, kidney disease requiring dialysis, and nontraumatic amputations and is a major contributor to heart disease and stroke. Diabetes is among the "big four" for managed care organizations, the others being asthma, prenatal care, and psychiatric disorders. All four are relatively inexpensive when well managed, extraordinarily expensive when out of control. But do we need a new textbook on diabetes? <i>Diabetes Mellitus</i>, edited by LeRoith, Taylor, and Olefsky, takes a uniquely integrated approach. In
The deformational characteristics of the left ventricle in the conscious dog.
Authors: C O Olsen, J S Rankin, C E Arentzen, W S Ring, P A McHale, R W Anderson
Journal: Circulation Research (1981)

We studied left ventricular minor and major axis diameters and equatorial wall thickness in eleven conscious dogs with chronically implanted pulse-transit ultrasonic dimension transducers. Left ventricular transmural pressure was measured with micromanometers. Left ventricular volume was varied by inflation of implanted vena caval or aortic occluders. The geometry of the left ventricle was represented as a three-dimensioal ellipsoidal shell. Left ventricular eccentricity was found to be a linear function of ventricular volume during both diastole and ejection. However, the relationship was not the same for diastole and ejection, and during diastole the left ventricle was mre spherical at large volumes and more elliptical at small volumes than during ejection. The rearrangements in geometry observed during isovolumic contraction appeared to be transitional stages from the diastolic to the ejection-phase relationship. Thus, during isovolumic contraction, the left ventricle became more elliptical at large volumes and more spherical at small volumes. These relationships were not altered significantly by increased afterload or inotropic interventions. We also observed that the diastolic deformation of the ventricular chamber occurred in a set and predictable manner that seemed to be determined by the three-dimensional mechanical properties of the myocardium. The geometric inter-relationships of the ventricular wall determined the relationship between diastolic transmural pressure and mural stress. These findings probably reflect basic structural characteristics of the myocardium and provide a convenient method for quantitatively representing the dynamic geometry of the left ventricle.
A <sub>2A</sub> -Adenosine Receptor Reserve for Coronary Vasodilation
Authors: John C. Shryock, Stephen Snowdy, Pier Giovanni Baraldi, Barbara Cacciari, Giampiero Spalluto, Angela Monopoli, Ennio Ongini, Stephen P. Baker, Luiz Belardinelli
Journal: Circulation (1998)

Adenosine is a potent coronary vasodilator and causes an increase of coronary blood flow by activation of A2A-adenosine receptors (A2A-AdoRs). The purpose of this study was to test the hypothesis that the high potency of adenosine and adenosine analogues to cause coronary vasodilation is explained by the presence of a large A2A-AdoR reserve ("spare receptors").A novel, irreversible antagonist of A2A-AdoRs was used to inactivate receptors and reduce the response to agonist. Agonist-induced increases of coronary conductance before and after exposure of hearts to the irreversible antagonist were compared. Three agonists were studied: 2-p-(2-carboxyethyl)-phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS21680), adenosine, and 2-chloro-N6-cyclopentyladenosine (CCPA). Data were analyzed to determine agonist KA (equilibrium dissociation constant) and EC50 values. Values of KA for activation of A2A-AdoRs by CGS21680, adenosine, and CCPA were 105, 1800, and 2630 nmol/L, respectively. In contrast, values of EC50 for CGS21680, adenosine, and CCPA to increase coronary conductance were 1.5, 85, and 243 nmol/L, respectively. By use of the law of mass action, it was calculated that half-maximal responses to CGS21680, adenosine, and CCPA occurred when only 1.3%, 5%, and 9%, respectively, of A2A-AdoRs were occupied by agonist.Receptor reserves for 3 A2A-AdoR agonists were large. The receptor reserve for A2A-AdoRs to cause an increase of coronary conductance can explain both the high potency of adenosine to cause coronary vasodilation and the observation that an A2A-AdoR agonist can cause coronary vasodilation without systemic effects.
Another AIDS "cure" scandal hits South Africa
Authors: P. Sidley
Journal: BMJ (1998)

South Africa's drug regulatory authority, the Medicines Control Council, has acted swiftly to close down yet another clinic offering an untested, unsupervised, and illegal cure for AIDS. The latest newspaper reports, however, say that the clinic continues to operate illegally.

Last week newspapers in Johannesburg reported that a clinic calling itself the Genesis Research Centre was offering experimental “oxytherapy” to people with AIDS. This involved injecting ozone into blood vessels. It is neither the first, nor likely to be the last, of the quick “cures” being offered to the millions of people in South Africa who are HIV positive.

The most recent so called cure—the drug Virodene—continues to receive the support of the …