tbuckley/cabot-search huggingface dataset:
74 Involvement of nitric oxide overproduction and accumulated endogenous opioids in resistance of cholestatic animals against epinephrine-induced arrhythmia
Authors: A.R. Hajrasouliha, S. Tavakoli, P. Jabehdar-Maralani, H. Shafaroodi, G. Houshmand, A.A. Borhani, A.R. Dehpour
Journal: Journal of Hepatology (2004)
Familial Association of Nerve Deafness with Nodular Goiter and Thyroid Carcinoma
Authors: Daniel S. Elman
Journal: New England Journal of Medicine (1958)

THE report presented below is a study of a family in which 4 of 7 siblings were affected by nodular enlargements of the thyroid gland and severe bilateral nerve deafness. Invasive carcinoma of the thyroid gland was found in 2 of the patients.Case ReportsCase 1. H.R., a 37-year-old woman, was first seen at Receiving Hospital, Detroit, in August, 1955. For 11 years she had suffered from shortness of breath and choking when moving her arms above her head. She had been deaf from birth and was often ill during childhood. At 11 years of age she had scarlet . . .
Recombinant Human Foamy Virus, a Novel Vector for Neurological Disorders Gene Therapy, Drives Production of GAD in Cultured Astrocytes
Authors: Wanhong Liu, Zhongchun Liu, Xiongbin Cao, Zhijian Cao, Lu Xue, Fan Zhu, Xiaohua He, Wenxin Li
Journal: Molecular Therapy (2007)

Human foamy virus (HFV), with its nonpathogenic nature and several unique features for gene transfer, is a promising vector system for neurological disorders gene therapy. The question of whether HFV vectors can be developed for the expression of therapeutic genes in primary astrocytes of the brain may be of interest. First, efficient expression for foreign genes, which is critical for the potentials of HFV-derived vector in gene therapy, was successfully demonstrated in rat-cultured astrocytes by the enhanced green fluorescent protein (EGFP) transduction through an HFV vector bearing an EGFP expression cassette. Second, HFV vectors containing human glutamic acid decarboxylase (GAD) complementary DNA, which encodes an inhibitory neurotransmitter gamma-aminobutyric acid (GABA)-producing enzyme, were used to examine the function of GAD on GABA synthesis in cultured astrocytes. We found that the transduction of GAD vector resulted in isoform-specific expression of GAD, synthesis of a significant amount of GABA and tonical GABA release, and behavioral recovery in rat Parkinson's disease (PD) models. These results suggested that HFV vector had the ability to transduce astrocytes and HFV vector-derived GAD expression in astrocytes provided a potential strategy for the treatment of neurological disorders associated with hyperexcitable or diminished inhibitory activity.
Derek Herbert Isaac
Authors: T. Isaac
Journal: BMJ (2009)

Derek Herbert Isaac was a physician of high standards who saw the birth of the NHS and strongly supported its principles and nurtured its growth and development at Musgrove Park Hospital in Taunton, particularly in the field of cardiology.

Born on 3 July 1923 in Slough the second son of Herbert and Julienne Isaac, Derek attended Felsted School and St Mary’s, Paddington, qualifying at the age of 23. He held hospital posts in Greenwich, Warminster, Weymouth, Sheffield, Plymouth, and Bristol before appointment in 1960 as consultant at Musgrove Park Hospital, Taunton, where he stayed until retirement in 1983. At Musgrove he established himself as a general …
Lack of the Burst Firing of Thalamocortical Relay Neurons and Resistance to Absence Seizures in Mice Lacking α1G T-Type Ca2+ Channels
Authors: Daesoo Kim, Inseon Song, Sehoon Keum, Taehoon Lee, Myung-Jin Jeong, Sung-Sook Kim, Maureen W. McEnery, Hee-Sup Shin
Journal: Neuron (2001)
Neutrophil implications in platelet deposition and vasoconstriction after deep arterial injury by angioplasty in pigs.
Authors: Y Merhi, L L Lacoste, J Y Lam
Journal: Circulation (1994)

BACKGROUND Experimental studies in vitro suggest that neutrophils can modulate platelet function and vasomotor responses. In the present study, the interactions among neutrophils, platelets, and arterial responses to injury in vivo were assessed. METHODS AND RESULTS The acute thrombotic and vasomotor responses of porcine carotid arteries to balloon injury in vivo were evaluated in three groups of animals: neutropenic pigs treated (n = 11) or not treated (n = 12) with aspirin and healthy untreated control pigs (n = 15). Neutropenia was achieved by treatment with cyclophosphamide (50 mg/kg, 4 days before the experiment), which decreased circulating leukocyte count by 92% and almost abolished neutrophil aggregation to N-formyl-methionyl-leucyl-phenylalanine without affecting blood platelet count, hematocrit, hemoglobin concentration, or whole blood platelet aggregation to ADP. 51Cr platelet deposition on deeply injured and uninjured arterial segments was not statistically influenced by neutrophil depletion, whereas the angiographic vasoconstrictive response at the site of endothelial injury distally was significantly reduced by 41% from 46.3 +/- 2.9% in the control group to 27.2 +/- 4.1% in the neutropenic group (P &lt; .05). Aspirin treatment in combination with neutropenia produced a 50% reduction in whole blood platelet aggregation, resulted in a significant inhibition of platelet deposition to deeply injured arteries, and decreased vasoconstriction by 66% to 15.6 +/- 3.0% (P &lt; .05 versus control and neutropenic). CONCLUSIONS Neutrophils can influence the vasoconstrictive response at the site of endothelial injury in vivo. In addition to platelets, neutrophil interaction with the injured vessel wall may be implicated in the pathophysiological response to arterial injury in vivo.
Transient siRNA-Mediated Attenuation of Liver Expression from an α-Galactosidase a Plasmid Reduces Subsequent Humoral Immune Responses to the Transgene Product in Mice
Authors: Qiuming Chu, Macy Joseph, Malgorzata Przybylska, Nelson S. Yew, Ronald K. Scheule
Journal: Molecular Therapy (2005)

Hepatocytes are an effective depot for protein production from gene therapy vectors. However, when gene transfer vectors or their delivery induces hepatic inflammation, adaptive immune responses against the transgene product can ensue. In BALB/c mice, hydrodynamic delivery of a CMV-driven plasmid DNA (pDNA) bearing human alpha-galactosidase A (alphagal) to the liver generated antibodies against alphagal. This humoral immune response was more robust in a transgenic knockout for alphagal, the Fabry mouse. The antibody response could be attenuated in both mouse strains by using a promoter more restricted to hepatocytes. In an attempt to reduce further the humoral responses to alphagal, expression from the transgene was attenuated by using siRNA during the period of initial delivery-associated liver inflammation. In both mouse models and with both promoters, codelivering an alphagal siRNA resulted in a 2 log decrease in initial expression that then increased over the next few weeks to levels generated by the pDNA alone. This strategy led to both attenuated antibodies and an immune status approximating "tolerance" to alphagal. Importantly, in the Fabry mouse, an alphagal siRNA together with a hepatocyte-restricted promoter gave minimal anti-alphagal antibodies and profound tolerance, suggesting that such an approach might have clinical utility for genetic diseases.
Universities without walls: evolving paradigms in medical education
Authors: R. Neame, B. Murphy, F. Stitt, M. Rake
Journal: BMJ (1999)

Medical education is entering a phase of renewed change driven by developments in information availability and technology. Over the past half century medical education has remained largely isolated from the changes that have swept through most other businesses: enterprise-wide computerisation, client centred thinking, and a service philosophy. 

The clients of the medical education process, who, worldwide, generally pay for themselves (though in some countries they are state funded) are guaranteed little for their money, often not even a modern, efficient, or entirely relevant educational programme. Many leave medical school financially poorer and often little enriched cognitively: they are generally weighed down under a vast burden of obsolescent information, the important elements of which could be found by an intelligent member of the lay public faster and in an updated form directly from the world wide web. They are also changed culturally, not necessarily for the better. Their time spent studying in the academic ivory towers, from which most graduate, separates them from their community roots and also reinforces the divide between primary and secondary care and does little to emphasise the essential humanity and caring intrinsic to this vocation.1

#### Summary points

A wealth of information about biomedicine and health care is available in electronic formats, and this can be synthesised into courseware for medical education and distributed electronically

For many, the study of small or larger parts of medicine could be a recreational pursuit; for others, it might be a vital venture in self understanding in order for them to manage health risks and play a greater part in decision making about their health

For much of the time, course developers, tutors, and students can readily be separated in time and space and effectively linked by electronic communications: there is no need for co-location of all resources at a single site …
LAW AND MEDICINE
Authors: Ira S. Gilbert
Journal: JAMA (1967)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Disturbed fibrinolysis in patients with inflammatory bowel disease. A study in blood plasma, colon mucosa, and faeces.
Authors: E de Jong, R J Porte, E A Knot, J H Verheijen, J Dees
Journal: Gut (1989)

Using specific assays, we studied fibrinolytic activity in plasma and colonic mucosa biopsies of 28 patients with inflammatory bowel disease (IBD) (12 with Crohn's disease, 16 with ulcerative colitis) and 28 control patients without inflammatory bowel disease or colon malignancy. Blood coagulation was studied using standard techniques. In plasma of IBD patients significantly decreased tissue type plasminogen activator activity (t-PA) (p less than 0.02), increased plasminogen activator inhibition (PAI) (p less than 0.01) and fibrinogen (p less than 0.001), and prolonged thrombin time (p less than 0.001) and prothrombintime (p less than 0.001) were found. In colon mucosa the percentage of t-PA to urokinase type plasminogen activator (u-PA) was 80:20% in the control group and 71:29% in the IBD group in non-inflamed mucosa. In inflamed mucosa the plasminogen activator percentage was 55:45%, significantly different (p less than 0.01) from the control group. There was also a significant absolute increase in u-PA activity and decrease of t-PA activity in the inflamed mucosa compared to the control group (p less than 0.001 and p less than 0.01, respectively). Patients with inflammatory bowel disease therefore have significant changes in components of the fibrinolytic and coagulation system both systemically and locally in colon mucosa. These changes might contribute to an increased risk for thromboembolic complications and possibly to the pathogenesis of the colitis and to the local complications such as bleeding.
Intensive and less-intensive renal replacement therapy did not differ for death or kidney function in critically ill patients
Authors: Robert L. Danner
Journal: Annals of Internal Medicine (2008)

ACP Journal Club18 November 2008Intensive and less-intensive renal replacement therapy did not differ for death or kidney function in critically ill patientsRobert L. Danner, MDRobert L. Danner, MDNational Institutes of Health, Bethesda, Maryland, USA (R.L.D.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-149-10-200811180-02006 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationPalevsky PM, Zhang JH, O’Connor TZ, et al. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med. 2008;359:7-20. https://pubmed.ncbi.nlm.nih.gov/18492867Clinical Impact RatingsHospitalists: Critical Care: Nephrology: Reference1 Ronco C, Bellomo R, Homel P, et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet. 2000;356:26-30. [PMID: 10892761] Google Scholar2 RCT of Normal vs Augmented Level of Renal Replacement Therapy in ICU—RENAL. www.thegeorgeinstitute.org/research/renal/studies/rct-of-normal-vs.-augmented-level-of-renal-replacement-therapy-in-icu-renal.cfm (accessed 9 Sep 08). Google Scholar Author, Article, and Disclosure InformationAuthors: Robert L. Danner, MDAffiliations: National Institutes of Health, Bethesda, Maryland, USA (R.L.D.) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 November 2008Volume 149, Issue 10 Page: JC5-6 Keywords Acute renal failure Body weight Creatinine Critical care Effluent Hospitalists Hypotension Intensive care units Kidneys Life expectancy Medical dialysis Necrosis Nephrology Renal critical care Renal transplantation Safety Sepsis Ultrafiltration Veteran care ePublished: 10 March 2020 Issue Published: 18 November 2008 Copyright & PermissionsCopyright © 2008 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Physiatry and Care of Patients With Neurofibromatosis
Authors: Charles E. Levy
Journal: JAMA (1997)

<h3>To the Editor.</h3> —In their overview of neurofibromatosis, Dr Gutmann and colleagues<sup>1</sup>present "a comprehensive approach to the diagnosis and treatment of individuals with neurofibromatosis 1 [NF1] and neurofibromatosis 2." Unfortunately, the physiatric perspective was omitted in their plan of care. We write from the perspective of a neurologist with NF1 and her physiatrist. <h3>Dr Levy's Perspective.</h3> —I have followed Dr Krietemeyer since she was a neurology resident facing increasing difficulties with ambulation and fatigue. Neurofibromas have encased virtually every spinal nerve root. Over 3 years I have prescribed ankle-foot-orthoses, canes, rollator walkers, and physical therapy to enable ambulation, and a scooter and later a powered wheelchair to conserve energy. The Ohio Bureau of Vocational Rehabilitation was enlisted, resulting in a van with a wheelchair lift and hand controls. Work site modifications (powered exam tables, powered doors) are now being pursued. Adjustment issues have also been addressed. As a
Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension
Authors: Ulf Landmesser, Sergey Dikalov, S. Russ Price, Louise McCann, Tohru Fukai, Steven M. Holland, William E. Mitch, David G. Harrison
Journal: Journal of Clinical Investigation (2003)

Tetrahydrobiopterin is a critical cofactor for the NO synthases, and in its absence these enzymes become "uncoupled," producing reactive oxygen species (ROSs) rather than NO. In aortas of mice with deoxycorticosterone acetate-salt (DOCA-salt) hypertension, ROS production from NO synthase is markedly increased, and tetrahydrobiopterin oxidation is evident. Using mice deficient in the NADPH oxidase subunit p47(phox) and mice lacking either the endothelial or neuronal NO synthase, we obtained evidence that hypertension produces a cascade involving production of ROSs from the NADPH oxidase leading to oxidation of tetrahydrobiopterin and uncoupling of endothelial NO synthase (eNOS). This decreases NO production and increases ROS production from eNOS. Treatment of mice with oral tetrahydrobiopterin reduces vascular ROS production, increases NO production as determined by electron spin resonance measurements of nitrosyl hemoglobin, and blunts the increase in blood pressure due to DOCA-salt hypertension. Endothelium-dependent vasodilation is only minimally altered in vessels of mice with DOCA-salt hypertension but seems to be mediated by hydrogen peroxide released from uncoupled eNOS, since it is inhibited by catalase. Tetrahydrobiopterin oxidation may represent an important abnormality in hypertension. Treatment strategies that increase tetrahydrobiopterin or prevent its oxidation may prove useful in preventing vascular complications of this common disease.
Hemostatic Alterations With Exercise Conditioning in NIDDM
Authors: W Guyto Hornsby, Karen A Boggess, Timothy J Lyons, William H Barnwell, John Lazarchick, John A Colwell
Journal: Diabetes Care (1990)

Various parameters of coagulation and fibrinolysis were measured in 13 men (aged 54 ± 3 yr) with non-insulindependent diabetes mellitus (NIDDM) before and after 12-14 wk of exercise training. Subjects exercised for 30 min 3 times/wk at 70% of maximum O2 consumption (Vo2max). Training increased Vo2max by 12.5% but did not alter body weight, relative body fat, blood pressure, cholesterol, triglycerides, or high-density lipoprotein cholesterol. Slight downward trends were apparent for fasting glucose and insulin, but glycosylated hemoglobin was unchanged. There were no changes in coagulation parameters of plasminogen, hematocrit, or α2-antiplasmin. Plasma fibrinogen (303 ± 24.2 vs. 256 ± 12.3 mg/dl) and fibronectin (380 ± 41.9 vs. 301 ± 22.2 μg/ml) were significantly reduced (P &amp;lt; 0.02) by exercise conditioning. Three assays of fibrinolytic activity (tissue plasminogen activator, euglobulin lysis time, and an isotopic measure of fibrinolysis) confirmed that neither basal fibrinolysis nor the fibrinolytic responses to venous occlusion and maximal exercise were significantly altered. Exercise conditioning may have antithrombotic effects in NIDDM by reducing plasma fibrinogen and fibronectin. Although the significance of the fall in fibronectin awaits further studies, the reduction in plasma fibrinogen gives a rationale for the use of exercise training in men with NIDDM.
RSR13, a Synthetic Allosteric Modifier of Hemoglobin, Improves Myocardial Recovery Following Hypothermic Cardiopulmonary Bypass
Authors: K. S. Kilgore, C. F. Shwartz, M. A. Gallagher, R. P. Steffen, R. S. Mosca, S. F. Bolling
Journal: Circulation (1999)

During hypothermic blood cardioplegia, oxygen delivery to myocytes is minimal with ineffective anaerobic metabolism predominating. RSR13, 2-[4-[[(3,5-dimethylanilino) carbonyl]methyl]phenoxy]-2-methylpropionic acid, a synthetic allosteric modifier of hemoglobin (Hb), increases release of oxygen from Hb, increasing oxygen availability to hypoxic tissues, and reverses the hypothermia-dependent increase in Hb oxygen affinity. We studied recovery of myocardial mechanical and metabolic function and examined myocardial morphology after cardioplegia, comparing RSR13 (1.75 mmol/L)-supplemented blood (RSR13-BC) to standard blood cardioplegia (BC).Twelve dogs underwent 15 minutes of 37 degrees C global ischemia on cardiopulmonary bypass, followed by 75 minutes of hypothermic cardioplegia (13 degrees C) with either BC (n=6) or RSR13-BC (n=6). There were no differences in baseline function between groups. Cardiac function was assessed after 30 minutes of 37 degrees C reperfusion (BC versus RSR13-BC, respectively) by measuring: % return to normal sinus rhythm (0/100%), % of baseline+dP/dt (33.7+/-1.7/76.3+/-1.9), % of baseline-dP/dt (26.6+/-2.0/81.1+/-1.6), stroke volume (3.5+/-0.5/7.1+/-0.9 mL), cardiac output (340+/-20/880+/-40.3 mL/min), and LVEDP (11.3+/-2.2/0. 3+/-2.9 mm Hg). Postischemic oxidative and metabolic parameters including myocardial lactate, pyruvate, ATP content, and percent water content also were determined. Histological analysis demonstrated preservation of endothelial and myocyte morphology in hearts receiving RSR13-BC compared with BC.These results indicate that in the setting of hypothermic cardiopulmonary bypass, RSR13 improves recovery of myocardial mechanical and metabolic function compared with standard hypothermic BC. Findings from this study suggest that RSR13-BC, by decreasing hemoglobin oxygen affinity, improves oxidative metabolism and preserves cellular morphology, resulting in significantly improved contractile recovery on reperfusion.
Elements of Controversy: The Atomic Energy Commission and Radiation Safety in Nuclear Weapons Testing, 1947-1974
Authors: Victor E. Archer
Journal: JAMA (1995)

The main title is meaningless without the lengthy subtitle. The controversy referred to is the repeated charges that the Atomic Energy Commission (AEC) was irresponsible and secretive in the exposure of individuals to nuclear tests and their fallout. This controversy is dealt with directly only in an epilogue. The main part of the book is a straightforward presentation of information culled from recently declassified documents, including operational reports, standard operating procedures, official documents of all sorts, and interviews with individuals who participated in the US nuclear test programs. In a sense, it is a continuation of the account begun in the author's 1987 book<i>Dragon's Tail</i>. Hacker is careful to report AEC decisions on safety and known overexposures in as unbiased a manner as possible. This is a welcome change from the biases that are rampant in other recent accounts, eg, Gould and Goldman's 1990<i>Deadly Deceit: Low-Level Radiation, High-Level</i>