tbuckley/cabot-search huggingface dataset:
Aldose Reductase–Mediated Phosphorylation of p53 Leads to Mitochondrial Dysfunction and Damage in Diabetic Platelets
Authors: Wai Ho Tang, Jeremiah Stitham, Yu Jin, Renjing Liu, Seung Hee Lee, Jing Du, Gourg Atteya, Scott Gleim, Geralyn Spollett, Kathleen Martin, John Hwa
Journal: Circulation (2014)

Background— Platelet abnormalities are well-recognized complications of diabetes mellitus. Mitochondria play a central role in platelet metabolism and activation. Mitochondrial dysfunction is evident in diabetes mellitus. The molecular pathway for hyperglycemia-induced mitochondrial dysfunction in platelets in diabetes mellitus is unknown. Methods and Results— Using both human and humanized mouse models, we report that hyperglycemia-induced aldose reductase activation and subsequent reactive oxygen species production lead to increased p53 phosphorylation (Ser15), which promotes mitochondrial dysfunction, damage, and rupture by sequestration of the antiapoptotic protein Bcl-x L . In a glucose dose–dependent manner, severe mitochondrial damage leads to loss of mitochondrial membrane potential and platelet apoptosis (cytochrome c release, caspase 3 activation, and phosphatidylserine exposure). Although platelet hyperactivation, mitochondrial dysfunction, aldose reductase activation, reactive oxygen species production, and p53 phosphorylation are all induced by hyperglycemia, we demonstrate that platelet apoptosis and hyperactivation are 2 distinct states that depend on the severity of the hyperglycemia and mitochondrial damage. Combined, both lead to increased thrombus formation in a mouse blood stasis model. Conclusions— Aldose reductase contributes to diabetes-mediated mitochondrial dysfunction and damage through the activation of p53. The degree of mitochondrial dysfunction and damage determines whether hyperactivity (mild damage) or apoptosis (severe damage) will ensue. These signaling components provide novel therapeutic targets for thrombotic complications in diabetes mellitus.
Treating fissure in ano in outpatients: what dose of local anaesthetic?
Authors: S. L. Jensen, F. Lund, O. V. Nielsen, G. Tange
Journal: BMJ (1984)

may represent an absence of vascular response to ketanserin at the latter site but could be due to technical problems of using this method to assess circulation in sclerodermatous skin.The results of ketanserin treatment for ulceration in scleroderma appear to be less favourable than the results in treating Raynaud's pheno-
PREVALENCE AND CHARACTERISTICS OF PATIENTS ELIGIBLE FOR CATHETER–BASED RENAL ARTERIAL DENERVATION IN AN ACADEMIC CARDIOLOGY CLINIC
Authors: Salim Hayek, Mahmoud Abdou, Benjamin Demoss, Juan Ortega–Legaspi, Emir Veledar, Anjan Deka, Sandeep Krishnan, Kobina Wilmot, Aalok Patel, Vikas Kumar, Maya Pudi, Chandan Devireddy
Journal: Journal of the American College of Cardiology (2013)
Small Hairpin RNAs Efficiently Inhibit Hepatitis C IRES–Mediated Gene Expression in Human Tissue Culture Cells and a Mouse Model
Authors: Qian Wang, Christopher H. Contag, Heini Ilves, Brian H. Johnston, Roger L. Kaspar
Journal: Molecular Therapy (2005)

Treatment and prevention of hepatitis C virus (HCV) infections remain a major challenge for controlling this worldwide health problem; existing therapies are only partially effective and no vaccine is currently available. RNA interference offers the potential of a novel therapeutic approach for treating HCV infections. Toward this end, we evaluated small hairpin interfering RNAs (shRNAs) targeting the conserved internal ribosome entry site (IRES) element of the HCV genome for their ability to control gene expression in human cells and animals. We used a reporter gene plasmid in which firefly luciferase (fLuc) expression is dependent on the HCV IRES. Direct delivery of HCV IRES shRNAs efficiently blocked HCV IRES-mediated fLuc expression in transfected human 293FT cells as well as in a mouse model in which nucleic acids were delivered to liver cells by hydrodynamic transfection via the tail vein. These results indicate that shRNAs, delivered as RNA or expressed from viral or nonviral vectors, may be effective agents for the control of HCV and related viruses.
Insulin Treatment and Diabetic Vascular Complications
Authors: Charles Kilo, Joseph R. Williamson, Sung C. Choi, J. Philip Miller
Journal: JAMA (1979)

<h3>To the Editor.—</h3> University Group Diabetes Program (UGDP) investigators recently reported (240:37, 1978) that the cardiovascular death rate in two groups of patients with mild, maturity-onset diabetes treated with insulin did not differ from that of subjects receiving placebo medication even though fasting blood glucose levels were significantly lower in one group of insulin-treated subjects (insulin variable) than in the placebo group. On the basis of these observations they concluded that administration of insulin to normalize blood glucose does not protect asymptomatic maturity-onset diabetics from cardiovascular complications of diabetes and that there is no reason, therefore, to administer insulin for that purpose. After careful examination of patient data recently released by the UGDP coordinating center, we are convinced that this conclusion is erroneous and is attributable to inclusion of numerous inappropriate (in our opinion) subjects in the data analysis. Since the primary objective of the study was to determine whether
More than a billion people can't afford costs of healthcare, says WHO
Authors: J. Zarocostas
Journal: BMJ (2010)

The world’s healthcare systems are estimated to be wasting between 20% and 40% of their resources, but smarter spending and tackling leakages could increase healthcare coverage of their populations by similar amounts, says a new World Health Organization report.

The study also says that more than a billion poor people, mostly in poor nations, don’t have access to the health services they need because they can’t afford to pay for them.

“In ethical terms, no one in need of healthcare, whether curative or preventive, should risk financial ruin as a result of paying for this care,” said Margaret Chan, WHO’s director general, at the launch of the report in Berlin this week.

The report says, “Worldwide, about 150 million people a year face catastrophic health costs …
Publicity for GMC candidates
Authors: J. Potter
Journal: BMJ (1984)

oldest case of fibrolamellar hepatoma to be reported.Her serum B12 concentration was actually low (96 pmol/l (130 ng/l); normal range 147-737 pmol/l (200-1000 ng/l)) al- though the binding capacity was not measured.We have showed that measurement of urinary dopa metabolites may be misleading, that fibrolamellar hepatocellular carcinoma is not confined to the young, and that thorough investigation of a mass in the liver of a 65 year old is always necessary.
SOME SUGGESTIONS CONCERNING THE EXAMINATION AND COMMITMENT OF THE INSANE.
Authors: G. J. PRESTON
Journal: JAMA (1898)

demands made on us in the sick room.A clear rec- ognition of this fact of the part of the professional man, coupled with a sincere regard for stating, when on the witness stand, only what are known to be estab- lished facts, and a disposition not to allow the erudite attorneys to lead him to become a partisan, will I think, contribute very greatly to advance the esteem in which expert medical testimony is held by the courts and the general public.These remarks are intended to apply more particularly to the general masses of the profession, the practical men who help nature save and prolong the lives of their fellow-crea- tures.Can not these gentlemen, so clamorous for special legislation, see that the very fact of their more or less valuable services being had by either side in any case, carries with it the death-warrant of the call for professional experts in the courts of justice.The American people are of a very practical type, and a few more exhibitions of medical experts à la Luetgert style will make the masses feel that these experts are all frauds.But long after this genus shall have for remembrance only a "trace of mould" in the sociologie layers of the past, there will still be more or less fre- quent calls from the courts of the land for some plain, practical observations on medical questions coming before them, from the plain every-day common-sense doctors who have opinions only about things of which they know (and are not embarrassed at not knowing all things), and not based on what might, could, would, should, or did not happen.
blockers and calcium antagonists equally effective for hypertension
Authors: S. Gottlieb
Journal: BMJ (2003)

Hypertensive patients with coronary artery disease had similar outcomes regardless of whether they took a β blocker or a calcium antagonist for primary control of their blood pressure.

Dr Carl Pepine of the University of Florida College of Medicine, Gainesville, and colleagues randomised 22 576 patients with hypertension and coronary artery disease 50 years and older to receive either sustained release verapamil or atenolol as first line treatment for their high blood pressure. The study enrolled patients from 862 sites in 14 countries …
Left ventricular mass in normotensive subjects with autosomal dominant polycystic kidney disease
Authors: A. K Saggar-Malik, C. G Missouris, J. S Gill, D. R J Singer, N. D Markandu, G. A MacGregor
Journal: BMJ (1994)

Autosomal dominant polycystic kidney disease increases the risk of premature cardiovascular disease and sudden death.'One possible mechanism may be left ventricular hypertrophy, which exacerbates cardiac risk in patients with other types of disease.We assessed whether disproportionate cardiac hypertrophy occurs in polycystic kidney disease. Subjects, methods, and resultsAsymptomatic, untreated subjects with normal renal function and no history of hypertension were selected from our polycystic register.Fourteen out of 23 eligible white subjects were recruited (10 women and four men, mean age 32 (SD 12) years (range 16- 55), mean supine blood pressure 122/76 mm Hg (range
Nifedipine for Hypertensive Emergencies-Reply
Authors: Margaret A. Winker
Journal: JAMA (1997)

<h3>In Reply.</h3> —I appreciate the many responses regarding use of short-acting nifedipine for hypertensive emergencies and pseudoemergencies. Dr DiMichele raises an interesting point when he states, "Significant morbidity is often an acceptable cost if we know that the therapeutic risk is outweighed by the benefit of therapy." What is the benefit of therapy? Two uses of nifedipine were discussed in the article by Dr Grossman and colleagues<sup>1</sup>and my Editorial. The first use, for hypertensive pseudoemergencies or "urgencies" according to the Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure,<sup>2</sup>are "situations in which it is desirable to reduce blood pressure within 24 hours," including "accelerated or malignant hypertension without severe symptoms or progressive target organ complications and severe perioperative hypertension."<sup>2</sup>For control of hypertension, the duration of action of nifedipine is too short to be an effective long-term antihypertensive. The second
Phosphodiesterase-4 Inhibition and Brain Tumor Growth
Authors: Anna Laura Schmidt, Caroline Brunetto de Farias, Ana Lucia Abujamra, Algemir Lunardi Brunetto, Gilberto Schwartsmann, Rafael Roesler
Journal: Clinical Cancer Research (2009)

To the Editor: We read with great interest the December 1, 2008, article by Goldhoff et al. ([1][1]) on the role of cyclic AMP phosphodiesterase-4 (PDE4) in brain tumor growth. The authors found that PDE4 is expressed in human brain tumors of glial and neuronal lineage (glioblastoma, medulloblastoma
Michael James Riddell
Authors: N. Riddell
Journal: BMJ (2011)

Having won a scholarship to St Thomas’ Hospital at 17, Michael James Riddell qualified during the Blitz, with memories of the bombing of the private wing at the hospital in which several colleagues were killed. He enlisted in the Royal Army Medical Corps (RAMC) and was posted to north Africa to a field ambulance, just in time for El Alamein; he …
p120-catenin is essential for maintenance of barrier function and intestinal homeostasis in mice
Authors: Whitney G. Smalley-Freed, Andrey Efimov, Patrick E. Burnett, Sarah P. Short, Michael A. Davis, Deborah L. Gumucio, M. Kay Washington, Robert J. Coffey, Albert B. Reynolds
Journal: Journal of Clinical Investigation (2010)

Epithelial-cadherin (E-cadherin) is a master organizer of the epithelial phenotype. Its function is regulated in part by p120-catenin (referred to herein as p120), a cytoplasmic binding partner that directly regulates cadherin stability. As it has been suggested that cadherins have a role in inflammatory bowel disease (IBD), we sought to investigate this further by assessing the effect of p120 deficiency in mouse small intestine and colon. p120 conditional KO mice were superficially normal at birth but declined rapidly and died within 21 days. Cell-cell adhesion defects and inflammation led to progressive mucosal erosion and terminal bleeding, similar to what is observed in a dominant-negative cadherin mouse model of IBD. Additionally, selective loss of adherens junctions and accumulation of atypical COX-2–expressing neutrophils in p120-null areas of the colon were observed. To elucidate the mechanism, direct effects of p120 deficiency were assessed in vitro in a polarizing colon cancer cell line. Notably, transepithelial electrical resistance was dramatically reduced, neutrophil binding was increased 30 fold, and levels of COX-2, an enzyme associated with IBD, were markedly increased in neutrophils. Our data suggest that p120 loss disrupts the neonatal intestinal barrier and amplifies neutrophil engagement and that these changes lead to catastrophic inflammation during colonization of the neonatal gut with bacteria and other luminal antigens. Thus, we conclude that p120 has an essential role in barrier function and epithelial homeostasis and survival in the intestine.
Book: The Strange Case of Dr Simmonds and Dr Glas
Authors: C. McKenna
Journal: BMJ (2002)

Dannie Abse Robson Books, £14.95, pp 195 ISBN 1 86105 504 8 Rating:![Graphic][1]</img>![Graphic][2]</img> The Shipman killings have made this tale of a doctor with murderous intent and the tremendous power that doctors have over life especially topical. One question hangs pelmet like over this novel: “Are there not occasions and honesties when it is just to submit to the holiness of the god, Dionysus, and to act with evil intent out of pure altruism?” The novel, which explores the themes of unrequited love, loneliness, unfulfilled potential, and the central tenets … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif
In the Spotlight: Health Information Systems — PHR and Value Based Healthcare \hfill
Authors: N. Saranummi
Journal: IEEE Reviews in Biomedical Engineering (2009)

The author discusses recent progress in personal health records (PHR). The column is structured as follows: first, a look at what is driving health reform concluding with the need to make "value" the first priority. The role of citizens and patients in the value drive is then discussed. They must be empowered to act as co-producers in cooperation with healthcare professionals. Lastly, the role of the PHR and services based on the PHR will be elaborated.
TCT-154 Impact of Intracoronary Injection of CD133+ Bone Marrow Stem Cells on Coronary Atherosclerotic Progression in Patients with STEMI: A COMPARE-AMI IVUS Substudy
Authors: Fuyu Qiu, Akiko Maehara, Ramez El Khoury, Philippe Genereux, Laura LaSalle, Gary S. Mintz, Nicolas Noiseux, François Gobeil, Louis-Mathieu Stevens, Francois Reeves, Alain Rivard, Samer Mansour
Journal: Journal of the American College of Cardiology (2014)
EFFECT OF ROSUVASTATIN THERAPY ON ARTERIAL WALL CHANGES IN CHILDREN AND ADOLESCENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA: RESULTS FROM THE CHARON STUDY
Authors: Gisle Langslet, Marjet JAM Braamskamp, Brian McCrindle, David Cassiman, Gordon Francis, Claude Gagné, Daniel Gaudet, Katherine M. Morrison, Albert Wiegman, Traci Turner, Elinor Miller, Joel Raichlen, Paula G. Martin, Evan Stein, John Kastelein
Journal: Journal of the American College of Cardiology (2014)
A NOTE ON THE VALUE OF AUSCULTATORY-RESONANCE AND AUSCULTATORY-PERCUSSION AS AIDS IN DIAGNOSIS.
Authors: CARL C. WARDEN
Journal: JAMA (1903)

The purpose of this note is to bring more generally before the profession the art of auscultatory-percussion and auscultatory-resonance. Auscultation and percussion, together with palpation and inspection, have long been the foundations of diagnostic structure, but even with foundations laid we frequently build no higher than the first story because of inaccuracies of interpretation or for the reason that the draught of our plans misleads us. To be able accurately to map out the normal viscera of the body on its surface is a great achievement, but under pathologic conditions the task becomes more difficult and one is not infrequently baffled outright in the attempt. An opportunity to observe the remarkable results to be obtained by a combination of auscultation and percussion was recently afforded in the clinic of Dr. S. H. Habershon, physician to the out-patient department of the Brompton Hospital for Diseases of the
THE VALVULOARTERIAL IMPEDANCE AS A PROGNOSTIC FACTOR IN PATIENTS WITH AORTIC STENOSIS
Authors: Na Young Kim, Dong Heon Yang, Sun Hee Park, Myung Hwan Bae, Jang Hoon Lee, hun sik park, Yongkeun Cho, Shung Chull Chae
Journal: Journal of the American College of Cardiology (2012)
BENIGN MELANOSIS; A SUPPLEMENTARY REPORT
Authors: J. CLARK STEWART
Journal: JAMA (1913)

In June, 1907, I reported<sup>1</sup>"A Case of Benign Melanosis" before the Section on Surgery of the American Medical Association at Atlantic City. Briefly: A laparotomy in 1892 exposed a right ovarian cyst, black in color, and multiple small nodules studding the peritoneum. The operation was abandoned, a diagnosis of melanosarcoma made and several of the small nodules were removed. These nodules proved to be not melanosarcoma, but cysts containing very dark material which showed no cells capable of taking a stain. During convalescence the patient's urine, milk and sweat were deeply pigmented, but she made a good recovery. In 1895, the patient passed through a normal confinement and was delivered of a healthy child. At this time the milk and urine again became black, the condition lasting only a few days. In view of the extreme rarity of this condition the subsequent history is of great interest:
The Changing Face of AIDS in Argentina
Authors: Claude D. Betts
Journal: JAMA (1996)

THE NUMBER of individuals infected with and affected by the human immunodeficiency virus (HIV) continues to increase worldwide. The Pan American Health Organization (PAHO) estimates that approximately 2 million people have been infected with HIV in the Region of the Americas.<sup>1</sup>As of June 10, 1995, more than 580 000 cases of the acquired immunodeficiency syndrome (AIDS) and 304 493 AIDS-related deaths had been officially reported since 1981.<sup>1</sup>Argentina reported the second highest incidence rate of AIDS cases (41 per million) in South America during 1993 (the most recent year with complete reporting for the Region of the Americas), preceded only by Brazil (80 per million).<sup>2</sup> <h3>AIDS Surveillance</h3> In Argentina, AIDS data are obtained from case reports filed by physician assistants, which are sent systematically to the National AIDS Program of Argentina, through the municipal or provincial level. At the national level, reported AIDS cases are reviewed
CORRELATION BETWEEN INTELLIGENCE TESTS AND WRITTEN AND PRACTICAL EXAMINATIONS
Authors: R. C. Garry
Journal: BMJ (1930)

Sir TJhomas Horder also reminded his audience that their work, like that of the medical practitioner, was based on science.The temptation to hlutmbtug " a patienit-and there were patienits who liked to be humbugged "-must be resisted3.Mlassage was too valuable, too integral a part of plhysiotherapy to be placed in the background while one talked to the patient of bones out of place, of which there was no evidence, and so forth.Many of them could douible their incomes if they svere prepared to substitute for good hionest seientific work a certain amouint of humbug.Finally, 1he spoke of the mor,al effect of the masseur's work.The encouraginig manner of the
Plasmatic Level of Leukocyte-Derived Microparticles Is Associated With Unstable Plaque in Asymptomatic Patients With High-Grade Carotid Stenosis
Authors: Gabrielle Sarlon-Bartoli, Youssef Bennis, Romaric Lacroix, Marie Dominique Piercecchi-Marti, Michel A. Bartoli, Laurent Arnaud, Julien Mancini, Audrey Boudes, Emmanuelle Sarlon, Benjamin Thevenin, Aurelie S. Leroyer, Christian Squarcioni, Pierre Edouard Magnan, Françoise Dignat-George, Florence Sabatier
Journal: Journal of the American College of Cardiology (2013)
Protective Effect of Antibody to Parainfluenza Type 1 Virus
Authors: Charles B. Smith, Robert H. Purcell, Joseph A. Bellanti, Robert M. Chanock, Patricia Laine
Journal: New England Journal of Medicine (1966)

PARAINFLUENZA Type 1 virus is an important cause of acute respiratory disease in infants and children.1 , 2 During primary infection the lower respiratory tract is often involved, and illness may be quite severe. Initial infection usually occurs during childhood, and most older children and adults have serum neutralizing antibody to this virus.2 Reinfection with Type 1 virus has been observed in adults under both experimental and natural conditions despite the presence of serum neutralizing antibody.3 4 5 Illness associated with reinfection is generally mild and limited to the upper respiratory tract.Adults and older children undergoing reinfection probably constitute an important source of . . .
Integration of Early Physiological Responses Predicts Later Illness Severity in Preterm Infants
Authors: Suchi Saria, Anand K. Rajani, Jeffrey Gould, Daphne Koller, Anna A. Penn
Journal: Science Translational Medicine (2010)

Physiological data are routinely recorded in intensive care, but their use for rapid assessment of illness severity or long-term morbidity prediction has been limited. We developed a physiological assessment score for preterm newborns, akin to an electronic Apgar score, based on standard signals recorded noninvasively on admission to a neonatal intensive care unit. We were able to accurately and reliably estimate the probability of an individual preterm infant's risk of severe morbidity on the basis of noninvasive measurements. This prediction algorithm was developed with electronically captured physiological time series data from the first 3 hours of life in preterm infants (< or =34 weeks gestation, birth weight < or =2000 g). Extraction and integration of the data with state-of-the-art machine learning methods produced a probability score for illness severity, the PhysiScore. PhysiScore was validated on 138 infants with the leave-one-out method to prospectively identify infants at risk of short- and long-term morbidity. PhysiScore provided higher accuracy prediction of overall morbidity (86% sensitive at 96% specificity) than other neonatal scoring systems, including the standard Apgar score. PhysiScore was particularly accurate at identifying infants with high morbidity related to specific complications (infection: 90% at 100%; cardiopulmonary: 96% at 100%). Physiological parameters, particularly short-term variability in respiratory and heart rates, contributed more to morbidity prediction than invasive laboratory studies. Our flexible methodology of individual risk prediction based on automated, rapid, noninvasive measurements can be easily applied to a range of prediction tasks to improve patient care and resource allocation.