tbuckley/cabot-search huggingface dataset:
Variability in ethanol biodisposition in whites is modulated by polymorphisms in the<i>ADH1B</i>and<i>ADH1C</i>genes
Authors: Carmen Martínez, Segismundo Galván, Elena Garcia-Martin, María I. Ramos, Yolanda Gutiérrez-Martín, José A.G. Agúndez
Journal: Hepatology (2009)

Association between genetic variations in alcohol-related enzymes and impaired ethanol biodisposition has not been unambiguously proven, and the effect of many newly described polymorphisms remains to be explored. The aims of this study are to elucidate the influence of genetic factors in alcohol biodisposition and effects. We analyzed alcohol pharmacokinetics and biodisposition after the administration of 0.5 g/kg ethanol; we measured ethanol effects on reaction time and motor time in response to visual and acoustic signals, and we analyzed 13 single nucleotide polymorphism (SNPs) in the genes coding for ADH1B , ADH1C , ALDH2, and CYP2E1 in 250 healthy white individuals. Variability in ethanol pharmacokinetics and biodisposition is related to sex, with women showing a higher area under the curve (AUC) ( P = 0.002), maximum concentration (Cmax) ( P &lt; 0.001) and metabolic rate ( P = 0.001). Four nonsynonymous SNPs are related to decreased alcohol metabolic rates: ADH1B rs6413413 ( P = 0.012), ADH1C rs283413 ( P &lt; 0.001), rs1693482 ( P &lt; 0.001), and rs698 ( P &lt; 0.001). Individuals carrying diplotypes combining these mutations display statistically significant decrease in alcohol biodisposition as compared with individuals lacking these mutations. Alcohol effects displayed bimodal distribution independently of sex or pharmacokinetics. Most individuals had significant delays in reaction and motor times at alcohol blood concentrations under 500 mg/L, which are the driving limits for most countries. Conclusion: Besides the identification of new genetic factors related to alcohol biodisposition relevant to whites, this study provides unambiguous identification of diplotypes related to variability in alcohol biodisposition. (Hepatology 2010;51:491–500.)
The Supply of Primary Care Physicians
Authors: Steven R. Towner
Journal: JAMA (1991)

To the Editor.  —Recently, much has been written about the paucity of young physicians entering primary care specialties. A recent article by Politzer et al 1 indicated that the primary emphasis for increasing physician supply ought to be at the level of medical education training. This analysis completely missed the main reason why more physicians have not entered primary care specialties. The reason is life-style.  Three primary life-style factors that discourage more physicians from entering primary care include the following: (1) being on call; (2) finances; and (3) spouses. To elaborate, the on-call schedule of primary care physicians is, in most circumstances, far more rigorous than that for specialists. The type of work that is done on call is often performed for little financial reward. Second, the finances of primary care physicians are such that most can prolong their medical education from 8 to 9 or 10 years, counting medical
The Problem of Overuse
Authors: Kenneth E. Covinsky
Journal: JAMA Internal Medicine (2013)

Many Veterans Affairs physicians are familiar with the steady stream of reminders generated by our electronic medical record system to order laboratory and screening tests. These reminders help clinicians meet guidelines and performance targets for screening and prevention. However, the article by Virani and colleagues demonstrating substantial overuse of repeated lipid testing in a Veterans Affairs network once again shows us how performance measurement may lead to overuse. As noted by Drozda in his commentary, although the cost of an individual lipid test is modest, the effect of high-volume, modest-cost tests on the health system is large. Furthermore, the price to a patient asked to take an additional hour or two off from work to sit in the laboratory waiting room may not be modest at all, especially if he or she needs to return for a fasting lipid panel. Manyveteranshavegreatlybenefited fromthe focusof the Department of Veterans Affairs on quality and performance measurement.However, the evidence that performancemeasurement sometimes leads tooveruseandovertreatment is accumulating. The Department of Veterans Affairs is a leader in quality of care andperformancemeasurement. It should now lead a culture change to discourage overuse, per the suggestions by Virani and colleagues and by Drozda. Higher frequency does not always mean better care.
India s treatment programme for AIDS is premature
Authors: S. Kumar
Journal: BMJ (2004)

The announcement by India's health minister—on the eve of world AIDS day in December—that from 1 April 2004 the government will provide free antiretroviral drugs to 100 000 HIV positive people in six states with high prevalence of the infection has left the bureaucracy and AIDS experts confused and in a state of shock.

The poor infrastructure, few facilities, and lack of training have prompted serious apprehension among those working in the field.

“We have burnt our fingers with tuberculosis, and now we will burn our fingers with HIV,” warned Alaka Deshpande, head of medicine at the JJ Hospital in …
Urinary Stress Incontinence in Women
Authors: Rebecca G. Rogers
Journal: New England Journal of Medicine (2008)

A 45-year-old woman reports leaking urine with coughing, laughing, or sneezing since the birth of her last baby. She has been unable to lose the 25 lb (11 kg) that she gained after that pregnancy. She voids every 3 hours and reports no urinary urgency or nocturia. Her incontinence keeps her from participating in her exercise class, and she leaks urine during sexual intercourse. Her body-mass index is 28, and a routine pelvic examination is normal. How should she be evaluated and treated?
Prognostic Value of Treadmill Exercise Testing in Elderly Persons
Authors: Tauqir Y. Goraya, Steven J. Jacobsen, Patricia A. Pellikka, Todd D. Miller, Akbar Khan, Susan A. Weston, Bernard J. Gersh, Véronique L. Roger
Journal: Annals of Internal Medicine (2000)

Background: Recent exercise testing guidelines recognized a gap in knowledge about the prognostic value of treadmill exercise testing in elderly persons. Objective: To test the hypothesis that treadmill exercise testing has equal prognostic value among elderly (≥ 65 years of age) and younger (<65 years of age) persons and to examine the incremental value of this testing over clinical data. Design: Inception cohort with a median follow-up of 6 years. Setting: Olmsted County, Minnesota. Patients: All elderly (n = 514) and younger (n = 2593) residents of Olmsted County who underwent treadmill exercise testing between 1987 and 1989. Measurements: Overall mortality and cardiac events (cardiac death, nonfatal myocardial infarction, and congestive heart failure). Results: Compared with younger patients, elderly patients had more comorbid conditions, achieved a lower workload (6.0 and 10.7 metabolic equivalents; P < 0.001), and had a greater likelihood of a positive exercise electrocardiogram (28% and 9%; P < 0.001). With median follow-up of 6 years, overall survival (63% and 92%; P < 0.001) and cardiac event–free survival (66% and 95%; P < 0.001) were worse among elderly persons than among younger persons. Workload was the only treadmill exercise testing variable associated with all-cause mortality in both age groups, and the strength of association was similar. Workload and angina with exercise testing were associated with cardiac events in both age groups, whereas a positive exercise electrocardiogram was associated with cardiac events only in younger persons (P < 0.05 for all comparisons). After adjustment for clinical variables, workload was the only additional treadmill exercise testing variable that was predictive of death (P < 0.001) and cardiac events (P < 0.05); the strength of the association was similar in both age groups. Each 1–metabolic equivalent increase in exercise capacity was associated with a 14% and 18% reduction in cardiac events among younger and elderly persons, respectively. Conclusions: In elderly persons, treadmill exercise testing provided prognostic information that is incremental to clinical data. After adjustment for clinical factors, workload was the only treadmill exercise testing variable that was strongly associated with outcome, and its prognostic effect was of the same magnitude in elderly and younger persons.
Lymphocyte-Predominant and Classical Hodgkin's Lymphoma: A Comprehensive Analysis From the German Hodgkin Study Group
Authors: Lucia Nogová, Thorsten Reineke, Corinne Brillant, Michal Sieniawski, Thomas Rüdiger, Andreas Josting, Henning Bredenfeld, Roman Skripnitchenko, Rolf-Peter Müller, Hans-Konrad Müller-Hermelink, Volker Diehl, Andreas Engert
Journal: Journal of Clinical Oncology (2007)

Lymphocyte-predominant Hodgkin's lymphoma (LPHL) is rare and differs in histologic and clinical presentation from classical Hodgkin's lymphoma (cHL). To shed more light on the prognosis and outcome of LPHL, we reviewed all LPHL patients registered in the German Hodgkin Study Group (GHSG) database, comparing patient characteristics and treatment outcome with cHL patients.We analyzed retrospectively 8,298 HL patients treated within the GHSG trials HD4 to HD12, of whom 394 had LPHL and 7,904 had cHL.Complete remission and unconfirmed complete remission after first-line treatment was achieved in 91.6% v 85.9% of patients in early favorable stages, 85.7% v 83.3% of patients in early unfavorable stages, and 76.8% v 77.8% of patients in advanced stages of LPHL compared with cHL, respectively. Tumor control (freedom from treatment failure [FFTF]) for LPHL and cHL patients at a median observation of 50 months was 88% and 82% (P = .0093) and overall survival (OS) was 96% and 92%, respectively (P = .0166). In LPHL patients, negative prognostic factors were advanced stage (P = .0092), Hb less than 10.5 g/dL (P = .0171), and lymphopenia (P = .010) for FFTF. Age >or= 45 years (P = .0125), advanced stage (P = .0153), and Hb less than 10.5 g/dL (P = .0014) were negative prognostic factors for OS.The better prognosis of LPHL as compared with cHL might allow different treatment strategies, particularly for early-stage LPHL patients.
Arrhythmogenic Right Ventricular Cardiomyopathy and Fatty Replacement of the Right Ventricular Myocardium
Authors: Allen P. Burke, Andrew Farb, Gerti Tashko, Renu Virmani
Journal: Circulation (1998)

Background —The relationship between arrhythmogenic right ventricular cardiomyopathy (ARVC) and pure fat replacement of the right ventricle is unclear. Methods and Results —Myocardial thickness, epicardial fat thickness, percent fibrosis, and intramyocardial fat infiltration were measured in 16 sections each from 25 hearts with typical (fibrofatty) ARVC, 7 hearts with fat replacement of the right ventricle without fibrosis (FaRV), and 18 control hearts from patients who died of noncardiac causes. Patients with fibrofatty ARVC were younger than those with FaRV (31±14 versus 44±13 years, P =.02), more likely to have a history of arrhythmias or a family history of premature sudden death (56% versus 0%, P =.01), more likely male (80% versus 29%, P =.02), and less likely to have coexisting conditions that might have predisposed to sudden death (12% versus 86%, P &lt;.001). Fibrofatty ARVC was characterized by right ventricular myocardial thinning, fat infiltration of the anterobasal and posterolateral apical right ventricle, subepicardial left ventricular fibrofatty replacements (64%), myocyte atrophy (96%), and lymphocytic myocarditis (80%). FaRV showed normal or increased myocardial thickness, a diffuse increase in intramyocardial and epicardial fat, little inflammation, and an absence of myocardial atrophy. Intramyocardial fat was frequently seen in normal hearts, especially in the anteroapical region, but was less extensive than in fibrofatty ARVC and FaRV. Conclusions —ARVC is a familial arrhythmogenic disease characterized by fibrofatty replacement of myocytes with scattered foci of inflammation. Fat infiltration per se is probably a different process that should not be considered synonymous with ARVC.
O76 THE OCCURRENCE OF SPONTANEOUS BACTERIAL PERITONITIS CLOSES THE THERAPEUTIC WINDOW OF OPPORTUNITY FOR NON-SELECTIVE BETA BLOCKER TREATMENT IN CIRRHOTIC PATIENTS WITH ASCITES
Authors: M. Mandorfer, S. Bota, P. Schwabl, T. Bucsics, N. Pfisterer, M. Kruzik, M. Hagmann, A. Blacky, A. Ferlitsch, W. Sieghart, M. Trauner, M. Peck-Radosavljevic, T. Reiberger
Journal: Journal of Hepatology (2014)
The Search for the Ideal Positive Inotropic Agent
Authors: Milton Packer
Journal: New England Journal of Medicine (1993)

The belief that a depression of cardiac contractility is the fundamental defect in patients with chronic heart failure has led to the development during the past 20 years of nearly 100 new drugs with positive inotropic activity. Although all these agents exert favorable hemodynamic effects, none have produced consistent improvement in symptoms or exercise tolerance, and many have shortened the survival of patients with heart failure1,2. Questions about efficacy and safety have surfaced regardless of the drug's mechanism of action, but there has been particular concern about agents that act by inhibiting cyclic AMP phosphodiesterase (e.g., milrinone)2. . . .
Regulation of human liver cytochromes P-450 in family 3A in primary and continuous culture of human hepatocytes
Authors: Erin G. Schuetz, John D. Schuetz, Stephen C. Strom, Melissa T. Thompson, Robert A. Fisher, David T. Molowa, Donna Li, Philip S. Guzelian
Journal: Hepatology (1993)

The cytochrome P-450 3A gene family comprises the dominant forms of cytochrome P-450 found in human liver. We examined as a possible useful system for studying the regulation of cytochrome P-450 3A under controlled conditions in vitro, primary monolayer cultures of human hepatocytes and compared the results with those obtained from the study of cytochrome P-450 3A in the human hepatoblastoma cell line HepG2 or in the human hepatocellular carcinoma cell line TONG/HCC. Using 3A antibodies, 3A cDNAs and 3A3, 3A4, 3A5 and 3A7 isozyme-specific oligonucleotides as probes, we determined that primary human hepatocyte cultures routinely expressed a 3A3/4* immunoreactive protein and 3A mRNA. These gene products were well maintained for many days and were induced by treatment of the cultures with dexamethasone, phenobarbital, macrolide antibiotics, the HMG CoA reductase inhibitor lovastatin or an antifungal agent, clotrimazole. Of six donor livers examined, only two contained mRNA or protein for 3A5, a form found in only a few adult human subjects. In cultures prepared from one of these two livers, 3A5 mRNA was detectable for several days. In cultures of hepatocytes from the remaining four human livers that did not contain 3A5 mRNA or protein, we detected neither spontaneous nor inducible 3A5 proteins or mRNAs. HepG2 cells contained only 3A7 protein, a form found in human fetal liver, even after treatment with inducers. treatment of HepG2 cells with dexamethasone, macrolide antibiotics, phenobarbital and phenobarbital-like inducers or lovastatin produced dose-dependent induction of 3A7 mRNA and 3A7 immunoreactive protein. TONG/HCC cells contained 3A3, 3A4 and 3A5 mRNAs, but only 3A5 immunoreactive protein could be detected.(ABSTRACT TRUNCATED AT 250 WORDS)
OPSONIC THERAPY IN SKIN DISEASES.
Authors: H. R. VARNEY
Journal: JAMA (1907)

It is now a universal belief that a number of diseases owe their origin to the invasion of the body by specific micro-organisms, and the true etiology of a class of affections of the skin is based on this belief. Hence the most successful treatment has been the application of that which would kill the invading microbe—without injuring the skin structure. The skin is constantly being invaded by micro-organisms which produce disease when the patients are physically below normal, and, to combat these infections more successfully, constitutional treatment has been found necessary. All this was realized, but until Leischman, in 1902, gave to the profession his method of measuring phagocytic activity the progress of the treatment could be noted clinically only. Sir A. E. Wright and his associates, Leischman and Douglas, demonstrated by a series of experiments, based on the theory of phagocytosis, that there are properties in the blood
Haploidentical bone marrow transplantation with post-grafting cyclophosphamide: multicenter experience with an alternative salvage strategy
Authors: S Tuve, J Gayoso, C Scheid, J Radke, A Kiani, D Serrano, U Platzbecker, G Rodríguez-Macías, M Wermke, U Holtick, P Balsalobre, J M Middeke, N Shayegi, J M Chemnitz, A Krause, N Gruner, M Füssel, J Schetelig, C Thiede, G Ehninger, M Hallek, J L Díez-Martín, M Bornhäuser
Journal: Leukemia (2011)
Correction: Incorrect Statement
Authors: J. Fleetwood
Journal: Annals of Internal Medicine (1994)

Corrections15 July 1994Correction: Incorrect StatementFREEJ. Fleetwood and S. S. UngerJ. FleetwoodSearch for more papers by this author and S. S. UngerSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-2-199407150-00030 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In the recent article by Fleetwood and Unger [1], it was stated that “Maryland's statute does not offer legal protection to health care professionals who implement a committee's advice.” This statement is no longer accurate. Under the Maryland Health Care Decisions Act, which became effective on 1 October 1993, when a dispute among surrogate decision makers goes to a patient care advisory committee, “a physician who acts in accordance with the recommendation of the committee is not subject to liability for any claim based on lack of consent or authorization for the action”REFERENCE1. Fleetwood J, Unger SS. Institutional ethics committees and the shield of immunity. Ann Intern Med. 1994; 120:320-5. Google Scholar Comments 0 Comments Sign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: J. Fleetwood; S. S. Unger PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 July 1994Volume 121, Issue 2 Page: 154 Keywords Health care Patients ePublished: 15 August 2000 Issue Published: 15 July 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Dependence on Cyanocobalamin Injections-Reply
Authors: David Ringdahl
Journal: JAMA (1989)

<h3>In Reply.—</h3> The comments by Drs Newbold and Tilkian underscore the fact that some aspects of vitamin B<sub>12</sub>metabolism in humans remain elusive despite 40 years of intensive study and thousands of publications.<sup>1</sup> Dr Newbold points out that the hereditary defects of vitamin B<sub>12</sub>metabolism are not addressed in our article. Since these disorders have been considered rare and since they are often detected in infancy or childhood, it seemed unlikely that the adults in our study population would have been affected. However, two reports<sup>2,3</sup>suggesting that these inborn errors of metabolism may not manifest themselves until adolescence or adulthood raise the possibility that the clinical spectrum of these disorders is broader than previously suspected and that the potential benefits of cyanocobalamin therapy have been underestimated in certain patient populations. We agree with Dr Tilkian that much can be learned from routine laboratory tests. We specifically
The Social Impact of Liver Disease
Authors: Hans Popper, Charles S. Davidson, Carroll M. Leevy, Fenton Schaffner
Journal: New England Journal of Medicine (1969)

Abstract Although knowledge of hepatic biology and pathology is advanced, the prevention and treatment of liver disease lag sadly. This discrepancy is attributable to lack of facilities and trained personnel. Morbidity and mortality of liver disease are increasing in frequency because alcoholism, adverse reactions from drug use and abuse, and viral hepatitis are more prevalent. As the nature of these factors suggests, the disadvantaged are particularly at risk. To promote the application of scientific knowledge to the control of liver disease, clinical centers developed with community participation and devoted to the management of liver disease are proposed. These would improve hospital and ambulatory care for a disease that is often curable; provide medical and paramedical personnel with the specialized knowledge needed for the management of a debilitating disease, including its psychiatric overtones; facilitate further research; and ensure community participation in controlling a serious socio-economic burden.
Young People May Face Huge Tobacco Toll
Authors: Rebecca Voelker
Journal: JAMA (1995)

WHEN THE WORLD Health Organization (WHO) broke tradition and observed World No-Tobacco Day outside its Geneva, Switzerland, headquarters in May, it was because the second international congress on children's health in Vancouver, British Columbia, was deemed a more fitting venue. There, Hu Ching-Li, MD, WHO's assistant director-general, presented sobering statistics on the fate millions of youths face if tobacco use patterns remain unchanged.  It is estimated that, of all beginning smokers who start using tobacco in adolescence and continue smoking throughout their lives, half will be killed by tobacco, and half of those will succumb to a fatal tobacco-caused disease before age 70. Those who die before age 70 from a tobacco-related cause will lose, on average, 22 years of life expectancy, said Hu.  If current smoking trends persist, WHO estimates that we can expect 200 million to 300 million children and adolescents under 20 currently alive to eventually be
Art and the Hospital
Authors: Robert H. Thoeny
Journal: JAMA (1971)

<h3>To The Editor.—</h3> The emotional and aesthetic impact of hospital surroundings on entering patients has often been overlooked. The stereotyped austerity which has given rise to such terms as "hospital white" and "hospital green" has been defended on grounds of necessity for cleanliness and minimal patient cost. In designing a new Radiation Therapy Department for our hospital, we recently attempted to improve the appearance for these very ill patients who would require multiple visits to the hospital for treatment. Since our hospital is located in the Southwest, we chose an Indian motif designed to convey a sense of hope and timelessness. The assistance of a hospital board member who was in the interior decorating business was enlisted to plan and execute the basic decor of the Department. We then approached a local museum of Southwest anthropology and requested the loan of various Indian artifacts for decorations. Their response was most