tbuckley/cabot-search huggingface dataset:
Oxygen free radical injury and Gs mediated signal transduction in the stunned porcine myocardium
Authors: L.-X. Fu, A. Ilebekk, K. A. Kirkeben, G. Aksnes, F. Waagstein, C.-H. Bergh, J. Hoebeke, Q.-M. Liang, A. Hjalmarson
Journal: Cardiovascular Research (1992)

Objective: The aim was to investigate involvement of oxygen free radicals and any changes in the Gs mediated β adrenergic signalling system of stunned porcine myocardium. Methods: Myocardial stunning was induced in eight pentobarbitone anaesthetised pigs by brief occlusions of the distal left anterior descending coronary artery for periods of up to 10 min. Segment length function was measured in the ischaemic region and in a control region supplied by the circumflex artery. Left ventricular biopsies were obtained from the two regions 1 h after the last occlusion for ultrastructural and biochemical studies. Timolol was been used to prevent arrhythmia during ischaemia. Results: At the time when biopsies were obtained, percent systolic shortening was reduced to 58% in the region subjected to ischaemia and was only minimally reduced in the control region. In the biopsies from the stunned region: (1) electron microscopy showed mild and reversible intracellular changes in the stunned myocardium; (2) the activities of superoxide dismutase and glutathione peroxidase were decreased by 66% and 52%, respectively; (3) the content of malondialdehyde was increased by 49%; (4) neither density nor affinity of β adrenoceptors showed any changes; (5) there were no alterations in messenger RNA encoding for the α subunit of the stimulatory guanine necleotide binding protein (Gs), demonstrated by northern and dot-blot hybridisations; (6) ELISA technique utilising a specific antipeptide antibody showed no quantitative change in Gs; (7) the activity of adenyl cyclase was unchanged. Conclusions: Even though the stunned porcine myocardium showed substantial evidence of free radical injury, the β adrenergic signalling system was intact.
Abstract 4319: Effects of chemotherapeutics on organotypic corticostriatal slice cultures identified by a new panel of fluorescent and immunohistochemical markers
Authors: Stine S. Jensen, Annette Nørregaard, Jesper Kolenda, Charlotte Aaberg-Jessen, Karina Garnier-Christensen, Poul H. Jensen, Henrik D. Schrøder, Bjarne W. Kristensen
Journal: Cancer Research (2011)

Abstract Effects of chemotherapeutics on glioma cell lines and spheroids are usually investigated without evaluating the effects of even very high concentrations of chemotherapeutics on normal brain tissue. To perform such investigations, the aim of the present study was to establish a panel of markers for detection of general cell death and more specific neuronal and glial degeneration induced by chemotherapeutics in organotypic rat corticostriatal slice cultures. Organotypic rat corticostriatal slice cultures were exposed to the alkylating agents temozolomide and nimustine, the tyrosine kinase inhibitor imatinib mesylate and the microtubule destabilizing agent vincristine. Densitometric measurements of uptake of the fluorescent dye propidium iodide were used for quantifying cellular degeneration. Moreover, paraffin sections were HE stained and immunohistochemically stained for the neuronal marker MAP2, the astroglial marker GFAP, and the oligodendrocyte marker p25α. The results showed that clinical drug concentrations were non-toxic. However, a time dependent increase in PI uptake was observed for supratherapeutic concentrations of the drugs, except for temozolomide, where no toxicity was observed at all. Corresponding immunostaining showed loss of MAP2 staining and increased expression of GFAP and p25α for cultures exposed to 1000 nM vincristine. Cultures exposed to supratherapeutic concentrations of nimustine and imatinib mesylate disintegrated, leaving no tissue for histology. In conclusion, corticostriatal slice cultures and the established panel of markers represent an excellent tool for detecting toxicity by chemotherapeutics. Toxicity was not detected at clinical concentrations, but high concentrations with toxic effects were identified suggesting that some of the earlier identified anti-cancer effects in the literature are general cytotoxic effects and not specific anti-cancer effects. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4319. doi:10.1158/1538-7445.AM2011-4319
Psychological aspects of lower urinary tract infections in women.
Authors: F. Dobbs
Journal: BMJ (1992)

resulting in inadequate monitoring of 21 patients.We have found that a mirrored counting chamber authors state that the difference in the means Secondly, urine output was not monitored in costing under £50 (Hawksley and Sons, Lancing, yielded a tstatistic of 1-998, which is significant. 34patients.Sussex) gives good definition and allows bacteria to Calculation of this statistic from their presented Thirdly, shocked patients (blood pressure be recognised easily even with a cheap light means and standard deviations, however, results in <100 mm Hg, postural drop in blood pressure, microscope.Phase contrast microscopy gives t= 1 8, which is not significant.thirst, tachycardia) were identified but not always optimum definition, and a relatively inexpensiveThe authors have assumed that patients pre- monitored as closely as they should have been.Of model is now available -namely, the updated senting with dysfunction of the lower urinary tract the eight shocked patients, four did not have a McArthur microscope (K W Kirk and Sons, who do not have a urinary tract infection have the urinary catheter, six received colloid in the first Milton, Cambridge), which has been around urethral syndrome.This is obviously incorrect as hour, and five received blood in the first four as a light microscope since 1974.This has the they have ignored the possibility of various other
Foes of Mandatory Maternal HIV Testing Fear Guidelines Will Lead to Reprisals
Authors: Rebecca Voelker
Journal: JAMA (1995)

LAST YEAR, it was cause for celebration. In clinical trials zidovudine cut the risk for mother-to-child transmission of human immunodeficiency virus (HIV) by two thirds. This year, as the basis for new federal recommendations that all pregnant women receive HIV testing and counseling, the finding has been cause for protest. Activists fear that conservative legislators and policy makers will use the clinical data to justify mandatory testing or compulsory treatment for pregnant women. The US Public Health Service's draft guidelines were published in the<i>Federal Register</i>in late February. The date coincided with "HIV Infection in Women: Setting a New Agenda," a national conference in Washington, DC. Activists, physicians, and HIV-positive women used the meeting as a forum to voice their concerns about how best to balance women's own medical needs with those of their infants. At times the sessions were heated, reminiscent of years past when gay men mobilized
The Medics' War: What Happened at Chipyong-ni-Reply
Authors: Albert E. Cowdrey
Journal: JAMA (1991)

<h3>In Reply. —</h3> Dr Hall's charge of physician bashing will be recognized as absurd by all readers of<i>The Medics' War</i>, whether they are physicians or laypersons. The theme of the book is that the army's need to attract physicians in the aftermath of World War II led the service to emphasize clinical training and specialization and, at the same time, to neglect field training for its medical officers. The result was a service of superb professional competence combined, sometimes tragically, with a lack of military knowledge and experience among the junior officers. On the very page denounced by Dr Hall, I say: "Though casualties exceeded all predictions, hospital death rates were the lowest in the history of warfare. At a time when the draft had not yet come to solve the problem of procuring doctors, this accomplishment belonged to the Medical Service almost alone, to its cadre of experienced
Evidence-based Medicine: How to Practice and Teach EBM
Authors: Saty Satya-Murti
Journal: JAMA (1997)

Evidence-based Healthcare: How to Make Health Policy and Management Decisions, by J. A. Muir Gray, 270 pp, with illus, paper, $29.95, ISBN 0-443-05721-4, New York, NY, Churchill Livingstone, 1997. We develop clinical expertise with bedside training and experience. How well do we integrate this experience with the best available external evidence for the purpose of direct patient care? I suspect that we do not carry out this function very well. Evidence-based Medicine (EBM) is the practice of applying valid evidence and data to a specific clinical question engendered during patient care. Lately, EBM has been on the lips and pen tips of clinicians, perhaps as a close runner-up to the other shibboleths managed care, gag clause, and networking. Is EBM then another mere mantra, a novel paradigm, or a practicable concept to help with ordinary, day-to-day clinical care? I believe it is the last, but you should be
Differential sensitivity of human B cell subsets to activation signals delivered by anti-mu antibody and proliferative signals delivered by a monoclonal B cell growth factor.
Authors: A Muraguchi, J L Butler, J H Kehrl, A S Fauci
Journal: The Journal of Experimental Medicine (1983)

The present study demonstrates the minimal, optimal, and synergistic signals involved in the activation of normal human peripheral blood and tonsillar B cells to proliferation. Initial activation signals were delivered to B cells by low concentrations of anti-mu antibody which did not induce proliferation by themselves. However, marked synergy was seen when anti-mu antibody was added to cultures in the presence of monoclonal B cell growth factor (BCGF) obtained from a human T-T cell hybrid such that the B cells underwent substantial proliferation. This latter proliferation was seen without maturation into Ig-secreting cells, which indicates that the BCGF is not a differentiation signal but a signal that drives the cell up to but not beyond the proliferative phase. Of note was the fact that B cells reflected differential sensitivity on the basis of size to either the activation signal delivered by anti-mu antibody or the proliferative signal delivered by BCGF. BCGF directly stimulated the larger B cells in the normal tonsillar B cell repertoire to proliferate without the requirement for an in vitro activation signal, which indicates that the cells had already received some form of activation signal in vivo. Indeed, these cells expressed the 4F2 antigen found on activated but not resting lymphocytes. In contrast, the smaller tonsillar B lymphocytes did not express the 4F2 activation antigen and required activation by anti-mu antibody, which did not of itself induce proliferation, but which acted in synergy with BCGF for substantial proliferation of the B cells. These studies thus provide a useful model of human B cell activation, proliferation, and differentiation and allow a more precise delineation of each phase in this cascade.
Coronary heart disease: Author's reply
Authors: H. Tunstall-Pedoe
Journal: BMJ (1991)

LI may outweigh the risks of its possible toxicity, and its introduction in such patients may now be appropriate" seem overenthusiastic.Certainly it is in stark contrast to an earlier editorial in the Lancet, which questioned the efficacy of LI and drew attention to the unacceptable incidence of side effects, recommending that "this compound should no longer be given to patients."4
Grading referrals to specialist breast unit may be ineffective
Authors: S Thrush
Journal: BMJ (2002)

EDITOR—Since the two week directive was introduced considerable debate has been surrounding certain aspects of it, especially how appropriate it is for general practitioners to determine urgency.1 It was our aim to examine how effective general practitioners' grading of urgency of referrals to our unit has been, comparing the referral grade with the eventual diagnosis.

The database of the breast unit at King's College Hospital retrospectively examined all general practitioners' referrals to the symptomatic breast clinic between …
The magnitude of the electromotive force of canine ventricular myocardium.
Authors: S Mashima, K Harumi, S Murao
Journal: Circulation Research (1978)

The isolated and perfused dog heart was placed in a cubic container filled with Tyrode's solution. Ventricular ectopic beats were produced by electrical stimulation of the left ventricular wall, and initial QRS vectors of these beats were determined with orthogonal leads from the surface of the container. At the same instants, the activated area on the epicardial surface was measured by means of a large number of contiguous bipolar leads from the epicardial surface. The QRS vector and the activated epicardial area were found to be nearly porportional. By use of these results and a calibration system with artificial dipoles, the double layer moment of the ventricular activation wave was calculated as 0.13 mA.cm per unit area. This value corresponds to 60% of the maximal possible strength of the tissue electromotive force. Lowering the conductivity of the surrounding solution increased the QRS voltage but not as much as the potential caused by a constant-current dipole within the solution. The relationship between the QRS voltage and the conductivity of the medium was analyzed by a simplified model of the system and was found to correspond approximately to that of a constant-current source within a spherical heart with a resistivity 2 to 3 times that of Tyrode's solution.
An adenosine A1 receptor agonist, R(-)-N-(2-phenylisopropyl)-adenosine (PIA), but not adenosine itself, acts as a therapeutic preconditioning-mimetic agent in rabbits
Authors: S. L Hale, S. D Bellows, H. Hammerman, R. A Kloner
Journal: Cardiovascular Research (1993)

Objective: A preconditioning mimetic agent could be useful therapy for cardiac ischaemic events; stimulation of adenosine receptors has been proposed as a preconditioning mediator. The ability of adenosine-receptor activation to mimic ischaemic preconditioning was tested in an in vivo rabbit model. Methods: Adenosine (15 mg. a maximally tolerated dose, n = 10) was infused over six minutes via a coronary artery and compared with saline (n = 12) in anaesthetised rabbits. Five minutes after infusion, a coronary artery was occluded for 40 minutes followed by three hours of reperfusion. In a second study, preischaemic intravenous treatment with adenosine (25 mg·kg−1 n = 9). or an Aj-adenosine agonist. R(-)-N-(2-phenylisopropyl)-adenosine (PIA, 900 μg·kg−1. n= 12). were compared with saline (n = 12), when given before 40 minutes of coronary artery ligation and three hours of reperfusion in anaesthetised rabbits. Results: Intracoronary adenosine reduced mean arterial pressure during infusion (48(3) v 80(4) mm Hg. control, p<0.001); however, infusion regional myocardial blood flow was significantly higher in adenosine treated hearts (5.00(0.90) v 2.30(0.26) ml·min−1·g−1, p<0.02) in the region later to become ischaemic. During occlusion ischaemic blood flow was similar in both groups as was the size of the ischaemic risk region, expressed as a % of the left ventricle (42(3)% adenosine and 37(3)% control, NS). Intracoronary adenosine treatment failed to reduce infarct size (52(5)% of the risk zone v 57(7)% in controls, NS). In the second protocol, heart rate immediately after treatment was reduced by both intraveous adenosine (26%) and PIA (22%) v control, indicating atrial A1 receptor activation. Treatment with PIA resulted in a significant reduction in ultimate infarct size compared with saline (38(5)% of risk region v 57(5)%, p<0.05). Adenosine, however, failed to reduce infarct size (50(8)%, NS v saline). There were no differences between area at risk or myocardial blood flow among groups. Conclusion: The adenosine agonist PIA but not adenosine itself might be a useful adjunctive therapy. Cardiovascular Research 1993;27:2140-2145
Study calculates true difference in drug prices between US and Europe
Authors: J. H. Tanne
Journal: BMJ (2010)

The price of drugs for consumers in the United States, in comparison with what Europeans pay, is not as high as has commonly been thought, a study by two researchers at the London School of Economics has found.

They write: “Large differences in prices are mainly observed at the ex-factory level [the price the manufacturer sells at the factory door], but these are not the prices that consumers and payers pay.” 

Previous studies said that US consumers paid higher prices for their drugs than those in other countries, with factory prices being twice as high in the US as in Europe and in other countries in the Organisation for Economic Co-operation …
Erving Goffman revisited
Authors: H. Merriman
Journal: BMJ (2002)

Thirty years ago, when I was a medical student, I read two of Erving Goffman's books. Asylums (1961) examined “total institutions” such as mental hospitals and prisons and showed how inmates can become degraded and dehumanised. The other was Stigma (1963), which I found harder to read, the core of which was about the persona projected by people who carry a feeling of different-ness (or stigma). Compared with the standard texts on psychiatry we were advised to read, these books, written by a Canadian sociologist, were refreshing, particularly …
A Death at Duke
Authors: Edward W. Campion
Journal: New England Journal of Medicine (2003)

Last month, a 17-year-old girl died at Duke University Medical Center after receiving a heart–lung transplant from an incompatible donor. Her blood type was O, the donor's was A, and the mismatch was not recognized until after the transplant operation was over. In rare situations, ABO-incompatible transplantations have been performed intentionally. But in this case it was not intentional. A severe rejection reaction and multiple complications followed, and the patient died. The tragic event became a national news story. When a medical mistake receives this much attention, it affects the medical profession and even public policy.The patient's story was . . .
Echocardiographic classification of ischemic mitral regurgitation based on mitral leaflet motion, left ventricular remodeling, and characteristics of the regurgitant jet
Authors: Eustachio Agricola, Michele Oppizzi, Francesco Maisano, Michele De Bonis, Lucia Torracca, Giovanni La Canna, Ottavio Alfieri
Journal: Journal of the American College of Cardiology (2003)
Annual Review of Physiology, vol 49, 1987
Authors: Howard S. Pitkow
Journal: JAMA (1987)

Edited by Berne and Hoffman, this volume has sections on seven areas of physiology: gastrointestinal, comparative, cell and molecular, endocrinologic, cardiovascular, respiratory, and the special topics of the molecular mechanism of muscle contraction and phototransduction in vertebrates. The prefatory chapter, written by the distinguished J. R. Pappenheimer of Harvard Medical School, gives an insightful chronological history of his personal life and research accomplishments. Each section begins with a brief, useful introduction by a notable section editor, which helps to orient the reader to the underlying theme of the following chapters. Written by several prominent researchers and scientists, each chapter begins with a short introductory review followed by recent work and state-of-the-art research on a particular topic. For example, the endocrinology section has chapters on thyroid hormones and brain development, insulin in the brain, sex steroids and brain sexual differentiation, central actions of ovarian steroids in feedback regulation, gastroenteropancreatic peptides and
A wide-spectrum coordination model of schizophrenia
Authors: Hendrik Pieter Barendregt
Journal: Behavioral and Brain Sciences (2003)

Abstract The target article presents a model for schizophrenia extending four levels of abstraction: molecules, cells, cognition, and syndrome. An important notion in the model is that of coordination, applicable to both the level of cells and of cognition. The molecular level provides an “implementation” of the coordination at the cellular level, which in turn underlies the coordination at the cognitive level, giving rise to the clinical symptoms.
Surgery of the Colon in a Patient With Adams-Stokes Disease
Authors: John T. Kimball
Journal: JAMA (1965)

WITH THE lengthening of life expectancy, it is anticipated that an increasing number of patients with severe cardiac disease will be considered for surgical excision of coincidental malignant neoplasia. In patients with serious cardiac arrhythmias who must undergo major cancer surgery, the control of heart rate and the maintenance of an adequate cardiac output are of paramount importance if the hazards of renal, cerebral, and myocardial anoxia are to be avoided. Cardiac output studies<sup>1</sup>in patients with fixed, slow, heart rates associated with complete heart block or disturbances of sino-atrial node activity have shown that the accompanying low cardiac outputs are due, primarily, to the bradycardia. In most patients the cardiac output returned towards normal by artificial pacing at rates of 60 to 70 beats per minute. The use of this technique might thereby lessen the risk of major surgery in patients with these types of arrhythmias. At the
Antiviral effect of adefovir in combination with a DNA vaccine in the duck hepatitis B virus infection model
Authors: Franck Le Guerhier, Alexandre Thermet, Sylvianne Guerret, Michèle Chevallier, Catherine Jamard, Craig S. Gibbs, Christian Trépo, Lucyna Cova, Fabien Zoulim
Journal: Journal of Hepatology (2003)
Therapeutic Spectrum of Uracil-Mustard, A New Oral Antitumor Drug
Authors: Edward Shanbrom
Journal: JAMA (1960)

One hundred and thirty patients with various neoplastic disorders were treated with uracil-mustard (U-8344), a new oral alkylating agent with a therapeutic spectrum similar to that of other mustard analogues. This agent was especially effective in treatment of lymphomas and chronic leukemias. Occasionally solid tumors, notably ovarian carcinoma, responded. Advantages of uracil-mustard over other similar agents are: (1) the small dosage required to obtain beneficial results; (2) uniform tolerability; and (3) simplicity of the regimen. With judicious administration long-term therapy may be carried out with continued benefit. The study suggested that the drug may be of value when other alkylating agents have failed.