tbuckley/cabot-search huggingface dataset:
CLINICAL GUIDELINE, PART 2: Cholesterol Screening in Asymptomatic Adults, Revisited
Authors: Alan M. Garber
Journal: Annals of Internal Medicine (1996)

Objective: To assess the role of serum lipid levels as screening tests in adults. Design: Pooled analysis of clinical trials, supplemented by analysis of data from the Framingham Heart Study, to estimate the effect of cholesterol reduction in patient groups stratified by cardiac risk. Study Selection: Published randomized, controlled trials of cholesterol reduction, meta-analyses of such trials, prospective cohort studies of the association between cholesterol levels and morbidity and death related to coronary heart disease, and cost-effectiveness analyses of cholesterol reduction. Data Analysis: Two-stage logistic regression on cardiac risk factors and outcomes in the Framingham Heart Study. The first stage predicted the risk for death from coronary heart disease using standard risk factors but not cholesterol; the second stage predicted the risk for death from coronary heart disease and all causes as functions of age and cholesterol level, stratified by the risk predicted from the first stage. Results: Randomized clinical trials show that cholesterol reduction confers survival benefits in patients with symptomatic coronary disease. In asymptomatic middle-aged men, who are at lower risk for death from coronary disease, cholesterol reduction prevents coronary disease but has not been shown to prolong life. The risk model based on analysis of the data from the Framingham Heart Study is consistent with the randomized trial data and shows that in the demographic groups excluded from trials, the hypothetical benefits of cholesterol reduction are greatest when the underlying risk for coronary disease is greatest. Conclusions: Screening with total cholesterol levels is most likely to be useful when done in populations at high short-term risk for dying of coronary heart disease, such as survivors of myocardial infarction and middle-aged men with multiple cardiac risk factors. In these populations, cholesterol reduction appears to be both effective and cost-effective. In other populations, the benefits of reduction are much smaller or are uncertain. [Note that sections in this paper are numbered so that they can be identified with cross-references as supporting evidence in the article "Guidelines for Using Serum Cholesterol, High-Density Lipoprotein Cholesterol, and Triglyceride Levels as Screening Tests for Preventing Coronary Heart Disease in Adults"; see pages 515-517.]
THE PREVENTION OF MORPHINISM. A THERAPEUTIC REVOLUTION: CODEINE AND NARCEINE, VICE MORPHINE.Read before the Section of Materia Medica and Pharmacy, at the Forty-second Annual Meeting of the American Medical Association, Washington, D. C., May 6, 1891.
Authors: J. B. MATTISON
Journal: JAMA (1891)

The prevention of disease ranks higher than its cure, and he who essays the rôle of benefactor along this line, deserves well of his fellows, be results success or reverse. I shall presume to make an effort at filling that rôle to-day; shall try to command your attention by enlisting interest in what promises to remove, very largely, a stigma that has rested long and weightily on the healing art, and by wiping out this blot on the scutcheon, secure favor by virtue of not only an advance so decided as to mark a new era in therapeutics, but, above all, by lessening in large degree the main factor in a disease that spares neither sex, state nor condition, and which, sad to say, claims for its victims more of our confréres than the world will ever know. Pain and insomnia, with the use and abuse of morphia for their
The Batterer: A Psychological Profile
Authors: Bruce Danto
Journal: JAMA (1996)

<i>The Batterer</i>is excellent. With great surgical skill, it takes us beyond describing battering behavior or victimhood to provide us with an excellent picture of the personality of the batterer. The principal author, psychologist Donald Dutton, opines that the batterer indulges in such aggressive behavior to keep his personality intact, providing a self-fashioned autonomy. Battering helps not only to maintain a sense of being a whole person, but also to address a core problem, fear of abandonment. How ironic it is that he fears abandonment while giving his female victim a good reason for wanting to abandon him in order to preserve herself. Dutton's profile focuses on a well-known psychiatric diagnosis, the borderline personality. Such a person continues to act out victimizing violence patterned after the battering of his mother or of himself as a child. The father is the prototype for the batterer. Dutton skillfully outlines the personality characteristics
Distribution of apolipoprotein(a) in the plasma from patients with lipoprotein lipase deficiency and with type III hyperlipoproteinemia. No evidence for a triglyceride-rich precursor of lipoprotein(a).
Authors: C Sandholzer, G Feussner, J Brunzell, G Utermann
Journal: Journal of Clinical Investigation (1992)

Lipoprotein(a) consists of a low-density lipoprotein containing apolipoprotein (apo) B-100 and of the genetically polymorphic apo(a). It is not known where and how lipoprotein(a) is assembled and whether there exists a precursor for lipoprotein(a). We have determined the phenotype, concentration, and distribution of apo(a) in plasma from patients with lipoprotein lipase (LPL) deficiency (type I hyperlipoproteinemia, n = 14), in apo E 2/2 homozygotes with type III hyperlipoproteinemia (n = 12) and in controls (n = 16). In the two genetic conditions, there is grossly impaired catabolic conversion of apo B-100-containing precursor lipoproteins to low-density lipoproteins. Considering apo(a) type, the plasma concentration of apo(a) was normal in type III patients but significantly reduced in LPL deficiency. Despite the defects in the catabolism of other apo B-containing lipoproteins, the distribution of apo(a) was only moderately affected in both metabolic disorders, with 66.7% (type I) and 74.7% (type III) being present as the characteristic lipoprotein(a) in the density range of 1.05-1.125 g/ml (controls 81.6%). The remainder was distributed between the triglyceride-rich lipoproteins (type I 12.4%, type III 8.5%, controls 4.7%) and the lipid-poor bottom fraction (type I 19.3%, type III 15.3%, controls 12.6%). In all conditions most apo(a) (57-88%) dissociated from the triglyceride-rich lipoproteins upon recentrifugation and was recovered as lipoprotein(a). These data suggest that lipoprotein(a) is not generated from a triglyceride-rich precursor. Lipoprotein(a) may be secreted directly into plasma or may be formed by preferential binding of secreted apo(a) to existing low-density lipoprotein.
Arterial Stiffness and Osteoporosis in Chronic Obstructive Pulmonary Disease
Authors: Ramsey Sabit, Charlotte E. Bolton, Peter H. Edwards, Rebecca J. Pettit, William D. Evans, Carmel M. McEniery, Ian B. Wilkinson, John R. Cockcroft, Dennis J. Shale
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of cardiovascular events and osteoporosis. Increased arterial stiffness is an independent predictor of cardiovascular disease.We tested the hypothesis that patients with COPD would have increased arterial stiffness, which would be associated with osteoporosis and systemic inflammation.We studied 75 clinically stable patients with a range of severity of airway obstruction and 42 healthy smoker or ex-smoker control subjects, free of cardiovascular disease. All subjects underwent spirometry, measurement of aortic pulse wave velocity (PWV) and augmentation index, dual-energy X-ray absorptiometry, and blood sampling for inflammatory mediators.Mean (SD) aortic PWV was greater in patients, 11.4 (2.7) m/s, than in control subjects, 8.95 (1.7) m/s, p < 0.0001. Inflammatory mediators and augmentation index were also greater in patients. Patients with osteoporosis at the hip had a greater aortic PWV, 13.1 (1.8) m/s, than those without, 11.2 (2.7) m/s, p < 0.05. In patients, aortic PWV was related to age (r = 0.63, p < 0.0001) and log(10) IL-6 (r = 0.31, p < 0.01), and inversely to FEV(1) (r = -0.34, p < 0.01). The strongest predictors of aortic PWV in all subjects were age (p < 0.0001), percent predicted FEV(1) (p < 0.05), mean arterial pressure (p < 0.05), and log(10) IL-6 (p < 0.05).Increased arterial stiffness was related to the severity of airflow obstruction and may be a factor in the excess risk for cardiovascular disease in COPD. The increased aortic PWV in patients with osteoporosis and the association with systemic inflammation suggest that age-related bone and vascular changes occur prematurely in COPD.
The Dilemmas of Euthanasia
Authors: Glen W. Davidson
Journal: JAMA (1976)

For the reader seeking a clear and competent overview of the issues surrounding care of the dying, this is the best buy of the year. Sissela Bok, PhD, of Harvard, defines the issues in her lead essay, which also includes an excellent bibliography. Stanley Joel Reiser, MD, PhD, also of Harvard, sets the historical context in a succinct chapter that scans the past hundred years. David Meyers and Norman Cantor, attorneys, examine, respectively, the legal aspects of voluntary medical euthanasia and the termination of an incompetent patient's life-preserving care. Eric Cassell, MD, of Cornell, and Robert J. Glaser, MD, president of the Henry J. Kaiser Family Foundation, address the implications of "negative euthanasia" for the physician. Diane Crane, PhD, examines physicians' attitude toward the treatment of critically ill patients, on the basis of her sociological study of four medical specialties in 1970-1971: internal medicine, neurosurgery, pediatrics, and pediatric heart surgery.
The Effect of a Cholesterol-Free Brain Fraction against Diet-Induced Atherosclerosis
Authors: R. J. JONES, S. C. KRAFT, S. HUFFMAN, E. L. BALTER, R. B. GORDON
Journal: Circulation Research (1953)

The feeding of a lipid-poor and virtually cholesterol-free residue of mammalian brain mitigates the hypercholesteremia and atherosclerosis ordinarily seen in cholesterol-fed chicks. The probable mechanism depends on the previously demonstrated capacity of oral cerebrosides to convert a large proportion of fecal sterols into unabsorbable coprosterol, thus rendering intestinal cholesterol, unavailable to the body economy.
Weekend Versus Weekday Admission and Mortality After Acute Pulmonary Embolism
Authors: Drahomir Aujesky, David Jiménez, Maria K. Mor, Ming Geng, Michael J. Fine, Said A. Ibrahim
Journal: Circulation (2009)

Background— Optimal management of acute pulmonary embolism (PE) requires medical expertise, diagnostic testing, and therapies that may not be available consistently throughout the entire week. We sought to assess whether associations exist between weekday or weekend admission and mortality and length of hospital stay for patients hospitalized with PE. Methods and Results— We evaluated patients discharged with a primary diagnosis of PE from 186 acute care hospitals in Pennsylvania (January 2000 to November 2002). We used random-effect logistic models to study the association between weekend admission and 30-day mortality and used discrete survival models to study the association between weekend admission and time to hospital discharge, adjusting for hospital (region, size, and teaching status) and patient factors (race, insurance, severity of illness, and use of thrombolytic therapy). Among 15 531 patient discharges with PE, 3286 patients (21.2%) had been admitted on a weekend. Patients admitted on weekends had a higher unadjusted 30-day mortality rate (11.1% versus 8.8%) than patients admitted on weekdays, with no difference in length of stay. Patients admitted on weekends had significantly greater adjusted odds of dying (odds ratio 1.17, 95% confidence interval 1.03 to 1.34) than patients admitted on weekdays. The higher mortality among patients hospitalized on weekends was driven by the increased mortality rate among the most severely ill patients. Conclusions— Patients with PE who are admitted on weekends have a significantly higher short-term mortality than patients admitted on weekdays. Quality-improvement efforts should aim to ensure a consistent approach to the management of PE 7 days a week.
Abstract P3-15-10: Human neuronal model to study chemotherapeutic-induced peripheral neuropathy
Authors: ME Dolan, C Wing, M Komatsu, SM Delaney, HE Wheeler
Journal: Cancer Research (2013)

Abstract Chemotherapy-induced peripheral neuropathy is the major dose-limiting toxicity for several anti-cancer drugs including taxanes, platinating agents and microtubule inhibitors. In general, animal models have been used to study neuropathy. Our goals are twofold: 1) to create a human model for study of chemotherapeutic induced neuropathy using iCell Neurons derived from human induced pluripotent stem cells (iPSCs) and; 2) to elucidate the molecular genetic mechanisms underlying chemotherapeutic induced peripheral neuropathy by identifying genetic variants and genes that increase the likelihood of this devastating adverse event. We have used this model system to perform functional studies on candidate targets of interest from clinical studies of chemotherapeutic induced neuropathy. Upon treatment of iCell Neurons with increasing concentrations of paclitaxel (0.001-100 μM) for 72 hours, we identified a reproducible 3-5 μm (12-14%) decrease in cell median neurite process length and a 13-19 μm (10-13%) decrease in cell total neurite outgrowth per order of magnitude increase in drug. The same concentrations of vincristine and cisplatin for 72 hours result in a decrease in cell median neurite process length of 6-18% and 2-4% per order of magnitude increase in drug, respectively. No decrease in neurite length is observed with hydroxyurea, a drug that does not result in neuropathy. Paclitaxel binds to beta-tubulin to exert its cytotoxic effect and genetic variants within the promoter of TUBB2A were shown to be associated with paclitaxel induced neuropathy (Clin Cancer Res, 18(16):4441-8, 2012). As a proof of concept, we have shown that decreased expression of the beta-tubulin isotype TUBB2A by siRNA transfection causes decreased median neurite process length (interaction P = 2.0 × 10-4) and decreased total neurite outgrowth (interaction P = 6.2 × 10-10) of iCell Neurons 48 hours post-paclitaxel treatment. To determine clinical relevance, we have developed a protocol to collect blood of breast and ovarian cancer patients experiencing severe paclitaxel-induced peripheral neuropathy and matched patients without neuropathy following similar paclitaxel regimens to create iPSCs and eventually neurons. We hope to create a resource of these cells for the scientific community. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-15-10.
Lidocaine: Prophylactic Value in Myocardial Infarction
Authors: Hugh H. Hussey
Journal: JAMA (1975)

In the early phase of acute myocardial infarction, death usually results from cardiogenic shock or ventricular fibrillation. Although the latter accounts for many sudden deaths that preclude medical attention, it is nevertheless true that ventricular fibrillation may occur at any time, especially during the early hours and days of the episode, and that it often can be converted to normal rhythm by administration intravenously of lidocaine hydrochloride. The Dec 19, 1974, issue of<i>The New England Journal of Medicine</i>published back-to-back articles by Lie et al (291:1324-1326, 1974) and Valentine et al (291:1327-1331, 1974) on the value of early prophylactic administration of lidocaine in salvaging patients having acute myocardial infarction. Lie and his co-workers conducted a double-blind, randomized study of 212 consecutive patients under 70 years of age admitted to the hospital within six hours of onset of symptoms of myocardial infarction. The results of the study are succinctly told
Abstract LB-390: High throughput, quantitative ligand binding assays for human bromodomains
Authors: Elizabeth Quinn, Jeremy Hunt, Lisa Wodicka, Pietro Ciceri, Daniel K. Treiber
Journal: Cancer Research (2012)

Abstract Post translationally appended acetyl-lysine marks on histone tails are key regulatory features of the epigenetic code. Bromodomains are “readers” of this specific lysine acetylation code, playing an important role in chromatin remodeling and regulation of gene expression. Bromodomains have emerged as an important new druggable target class in small-molecule inhibitor drug discovery, and several bromodomain-containing proteins have been associated with disease. There are 57 bromodomains contained in 41 different proteins, however, few small molecule inhibitors of bromodomains have been identified to date. The primary factor limiting the discovery of new inhibitors is the absence of a comprehensive, biochemical screening platform for bromodomains. Here we describe the application of DiscoveRx Corporation's novel competitive binding assay technology (used to build the KINOMEscan panel of &amp;gt;450 kinase assays) to the development of quantitative ligand binding assays for human bromodomains. By applying our established methodologies, we have rapidly developed an assay panel that covers &amp;gt;15% of the bromodomain family, with the ultimate goal of developing a comprehensive panel, comparable to the KINOMEscan kinase assay panel. A robust bromodomain assay panel suitable for high throughput screening that delivers quantitative ligand binding data will facilitate the identification and optimization of potent and selective small molecule bromodomain inhibitors suitable for both pharmaceutical use and as tool compounds to further elucidate the roles of bromodomains in human disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-390. doi:1538-7445.AM2012-LB-390
Tuberculosis in Families with B.C.G.-vaccinated and Non-vaccinated Children
Authors: A. W. Dickie
Journal: BMJ (1952)

DIHu conditions of our experiments, the inactive representatives did not.This association suggests that the mechanism of the chemotherapeutic action and that of the depression of sensi- tivity may have some common factor.Nevettheless, it must be admitted that there is at present little evidence in favour of the closer relatlonship of cause and effect-i.e., that the antituberculous effect is in fact due to desensitization.For although the many previous attempts to desensitize tuber- culous guinea-pigs have had to be made with tuberculin, the results, taken as a whole, suggest little, if any, advantage to the host.Moreover, the present surface-active agents are equally effective in mouse and guinea-pig tuberculosis, in spite of the very different levels of allergy in these two species.Thus a tuberculin skin reaction cannot be elicited in the tuberculous mouse; and, although this animal can manifest a systemic reaction when tuberculin is given intra- venously, much larger doses are required than in the guineapig (Smith, 1928; Rees and Hart, 1952).The influence on experimental tuberculosis of a number of other substances that depress tuberculin sensitivity, such as N-acetylsphingosine (Fisher et al., 1951), dehydroascorbic acid and alloxan (Long et al., 1951c), will be investigated.If these anti-allergic substances should also prove antituberculous, the hypothesis of a causal contexion between desensitization and chemotherapeutic activity would be strengthened. SummaryThe development of experimental tuberculosis in guinea-pigs is markedly inhibited by injection of certain surface-active polyoxyethylene ethers.Using the response to intracutaneous tuberculin as a measure of allergic -hypersensitivity in albino guinea-pigs infected with B.C.G., we find that:(1) Single subcutaneous or intravenous injections of these drugs diminish sensitivity to a degree comparable to that of cortisone.(2) The chemotherapeutically active representatives of the series diminish tuberculin sensitivity, whereas the inactive members fail to do so.(3) Their mode of action differs from that of corti- sone, since it is independent of dietary factors and of thyroid activity.(4) Neither D2a, a chemotherapeutically active deter- gent, nor cortisone, in heavy continual dosage, depressed skin sensitivity to diphtheria toxin, or antitoxin levels, in guinea-pigs immunized with diphtheria toxoid (in this experiment the animals were sensitized with dead tubercle bacilli).Both drugs depressed tuberculin sensitivity.(5) The possible mode of action of these surface- active agents is discussed.We are indebted to Dr.
Antinuclear antibodies in psychiatric illness: their relationship to diagnosis and drug treatment.
Authors: E C Johnstone, K Whaley
Journal: BMJ (1975)

Antinuclear antibodies occurred more often and in higher titres in psychiatric patients than in controls. Anti-DNA antibodies were not found. We suggest that antinuclear antibodies may be drug-induced and that lithium carbonate may have a particular tendency to produce this reaction.
Employment Status of Physicians Completing Training
Authors: Henry P. Pendergrass
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The Graduate Medical Education Advisory Committee to the Council on Medical Education of the American Medical Association in its May 1996 meeting spent considerable time discussing physician workforce issues. As an important part of this discussion, we considered the article by Ms Miller and colleagues,<sup>1</sup>which is a timely and critically relevant study on the physician workforce. We believe that continued reassessment of this information is extremely important for the future of American medicine and must be made available in a timely fashion to medical educators and planners, as well as to medical students and those planning medical careers. We are deeply distressed by the professional and human issues raised by changes in physician supply and feel committed to the collection and distribution of this important information.
Lamellar bodies coexist with vesicles and micelles in human gallbladder bile. Ursodeoxycholic acid prevents cholesterol crystal nucleation by increasing biliary lamellae
Authors: Stefano Ginanni Corradini, Giuseppe Arancia, Annarica Calcabrini, Paola Della Guardia, Leonardo Baiocchi, Alessandra Nistri, Luciano Giacomelli, Mario Angelico
Journal: Journal of Hepatology (1995)