tbuckley/cabot-search huggingface dataset:
The new BMJ series on therapeutics
Authors: R. E. Ferner, P. A. Routledge, M. Chew
Journal: BMJ (2011)

Will discuss how to prescribe effectively and safely

Which drug to choose? As doctors, we all try to keep our patients’ needs, values, and expectations uppermost in decision making, as other parties jostle to influence our prescribing choices. Guideline bodies issue advice; authorities warn of cost; pharmaceutical companies ply us with their wares; new studies may throw accepted practice into doubt. Responding to its readers’ call for practical, evidence based advice, the BMJ is launching a new therapeutics series. Its last concerted foray into this field was a series called “New Drugs,” which ended in the 1990s. The new series will mostly cover drug classes used to treat common conditions and serious conditions with high morbidity or mortality, especially new drugs and old drugs with important new indications or about which controversy exists⇓.



Sung-Il Kim/Corbis

Rational prescribing—that is, safe, effective, and cost effective prescribing—still requires evaluation of the potential benefits of treatment, ensuring that these outweigh any likely harm, and wherever possible tailoring the treatment to the individual …
Moderate Alcohol Intake, Increased Levels of High-Density Lipoprotein and Its Subfractions, and Decreased Risk of Myocardial Infarction
Authors: J. Michael Gaziano, Julie E. Buring, Jan L. Breslow, Samuel Z. Goldhaber, Bernard Rosner, Martin VanDenburgh, Walter Willett, Charles H. Hennekens
Journal: New England Journal of Medicine (1993)

Previous studies have suggested that moderate alcohol intake exerts a protective effect against coronary heart disease. Alterations in plasma lipoprotein levels represent one plausible mechanism of this apparent protective effect.
Glucose-Induced Hyperkalemia with Normal Aldosterone Levels
Authors: RANDALL A. AMMON
Journal: Annals of Internal Medicine (1978)

A diabetic patient exhibited glucose-induced hyperkalemia despite normal plasma and urinary aldosterone levels. The patient received no diuretics, was not acidotic, and had a creatinine clearance of 39 ml/min. Insulin or pharmacologic doses of desoxycorticosterone acetate eliminated the glucose-induced hyperkalemia. Normal aldosterone levels may be insufficient to protect certain diabetic patients from glucose-induced hyperkalemia.
Hyperventilation Syndrome
Authors: Jose C. Missri
Journal: JAMA (1978)

THE HYPERVENTILATION syndrome is a common, often disabling, and frequently inadequately treated clinical problem. Diagnosis is often missed, perhaps because physicians are not sufficiently aware of it or because patients rarely demonstrate the classic textbook picture of obvious overbreathing, paresthesia, and tetany. More commonly, symptoms are subtle and often mimic those of other clinical conditions, either organic or functional. Indeed, many patients with this affliction wander from one physician to another either vainly undergoing increasingly complex diagnostic procedures or being dismissed as anxious or neurotic. The purpose of this brief review is to emphasize the clinical importance of this syndrome, its common clinical signs and symptoms, and its metabolic and physiologic consequences, and to define effective management. <h3>DEFINITION AND INCIDENCE</h3> Hyperventilation is defined as ventilation in excess of that required to maintain normal blood Pao<sub>2</sub>and Paco<sub>2</sub>. It may be produced either by an increase in frequency or
NOVASUROL IN THE TREATMENT OF ASCITES IN HEPATIC DISEASE
Authors: LEONARD G. ROWNTREE
Journal: JAMA (1925)

Novasurol is a double salt of sodium mercurichlorphenyl oxycetate with diethylbarbituric acid (barbital), and contains 33.9 per cent, of mercury. It was introduced originally by Zieler 1 as a remedy for syphilis, but at present it is being used largely as a diuretic. Since the beginning of the nineteenth century, mercury compounds have been recommended as diuretics by certain authors, but these have failed of general application because of ineffectiveness or of untoward or toxic effects. Novasurol has an advantage over metallic mercury and calomel in that it is freely soluble in water and may be administered by subcutaneous, intramuscular or intravenous injections.  Our interest in this drug was incited by a statement of Wenckebach, in whose clinic Saxl and Heilig 2 first proved its efficacy in cases of cardiac dropsy, in the treatment of which its best results have been obtained. It often succeeds in cases in which the
The 'Terrible' Question
Authors: Stanley M. Bierman
Journal: JAMA (1985)

The wide-eyed and fearful expression on the face of the 68-year-old, heavy-set Russian immigrant did not betray any hidden secret as she sat across from my office desk while I read the hand-scribed physician's prescription, on which was written: Please examine Mrs G. for a 1:16 serologic test for syphilis. It is probably a biologic false-positive test.  Mrs G. appeared worn and tired, although her graying hair was covered with a brightly colored babushka. Her stout physical habitus and plain, though not unattractive, appearance was strikingly similar to that of my own grandmother, who had died during my childhood. Both were poor, unschooled Russian peasants who, despite their humble origins, maintained a special dignity in their bearing and demeanor.  Given the fact that my grandmother had fled Russian pogroms and my grandfather came to America to avoid conscription into the Czar's army, there was an instinctive identification with, and special
Obesity in asthma: more neutrophilic inflammation as a possible explanation for a reduced treatment response
Authors: E. D. Telenga, S. W. Tideman, H. A. M. Kerstjens, N. H. T. ten Hacken, W. Timens, D. S. Postma, M. van den Berge
Journal: Allergy (2012)

The incidence of asthma and obesity is increasing worldwide, and reports suggest that obese patients have more severe asthma. We investigated whether obese asthma patients have more severe airway obstruction and airway hyper-responsiveness and a different type of airway inflammation than lean asthmatics. Furthermore, we assessed the effect of obesity on corticosteroid treatment response.Patient data from four well-documented asthma cohorts were pooled (n = 423). We evaluated FEV(1) , bronchial hyper-responsiveness (PC(20) ) to either methacholine/histamine or adenosine 5'-monophosphate (AMP) (differential) cell counts in induced sputum and blood and corticosteroid treatment response in 118 patients.At baseline, FEV(1) , PC(20) methacholine or histamine, and PC(20) AMP values were comparable in 63 obese (BMI ≥ 30 kg/m(2) ) and 213 lean patients (BMI <25 kg/m(2) ). Obese patients had significantly higher blood neutrophils. These higher blood neutrophils were only seen in obese women and not in obese men. After a two-week treatment with corticosteroids, we observed less corticosteroid-induced improvement in FEV(1) %predicted in obese patients than in lean patients (median 1.7% vs 6.3% respectively, P = 0.04). The percentage of sputum eosinophils improved significantly less with higher BMI (P = 0.03), and the number of blood neutrophils increased less in obese than in lean patients (0.32 x10(3) /μl vs 0.57 x10(3) /μl, P = 0.046).We found no differences in asthma severity between obese and nonobese asthmatics. Interestingly, obese patients demonstrated more neutrophils in sputum and blood than nonobese patients. The smaller improvement in FEV(1) and sputum eosinophils suggests a worse corticosteroid treatment response in obese asthmatics.
Silica radical-induced DNA damage and lipid peroxidation.
Authors: X Shi, Y Mao, L N Daniel, U Saffiotti, N S Dalal, V Vallyathan
Journal: Environmental Health Perspectives (1994)

In recent years, more attention has been given to the mechanism of disease induction caused by the surface properties of minerals. In this respect, specific research needs to be focused on the biologic interactions of oxygen radicals generated by mineral particles resulting in cell injury and DNA damage leading to fibrogenesis and carcinogenesis. In this investigation, we used electron spin resonance (ESR) and spin trapping to study oxygen radical generation from aqueous suspensions of freshly fractured crystalline silica. Hydroxyl radical (.OH), superoxide radical (O2.-) and singlet oxygen (1O2) were all detected. Superoxide dismutase (SOD) partially inhibited .OH yield, whereas catalase abolished .OH generation. H2O2 enhanced .OH generation while deferoxamine inhibited it, indicating that .OH is generated via a Haber-Weiss type reaction. These spin trapping measurements provide the first evidence that aqueous suspensions of silica particles generate O2.- and 1O2. Oxygen consumption measurements indicate that freshly fractured silica uses molecular oxygen to generate O2.- and 1O2. Electrophoretic assays of in vitro DNA strand breakages showed that freshly fractured silica induced DNA strand breakage, which was inhibited by catalase and enhanced by H2O2. In an argon atmosphere, DNA damage was suppressed, showing that molecular oxygen is required for the silica-induced DNA damage. Incubation of freshly fractured silica with linoleic acid generated linoleic acid-derived free radicals and caused dose-dependent lipid peroxidation as measured by ESR spin trapping and malondialdehyde formation. SOD, catalase, and sodium benzoate inhibited lipid peroxidation by 49, 52, and 75%, respectively, again showing the role of oxygen radicals in silica-induced lipid peroxidation.(ABSTRACT TRUNCATED AT 250 WORDS)
Improved outcome with longer radiation sources: final results of the RENO registry in 1098 patients
Authors: Sigmund Silber, Dietrich Baumgart, Antonio Colombo, Patrick Serruys, David Meerkin, Thomas Schiele, Rolf Dörr, Klaus Kleinertz, We. Auch-Schwelck, William Wijns, Eric Eeckhout, Philip Urban
Journal: Journal of the American College of Cardiology (2002)
CONTRIBUTION TO OUR KNOWLEDGE OF TUBERCULOSIS ANTITOXIN.
Authors: C. FISCH
Journal: JAMA (1899)

It is very probable that in the future the serum of geese will prove to be a very efficient toxin-carrier Injections (intraperitoneal) of high doses of TBET, etc. (from human tuberculosis) act in them, stimulating to a much higher degree; antitoxin is readily produced and accumulated. I shall report as to my experiments in this line, as well as a series of experiments with the serum of a number of immunized horses, in another paper. I will only mention here that I can fully substantiate my former conclusions by repeated investigations, although I must admit that a number of animals reported on in my previous paper afterward died; some of them succumbed to a very slow form of tuberculosis, while others died from intercurrent diseases, mostly intestinal adhesions and constrictions following the injections. Still, a great number have survived until today, and have repeatedly propagated and given life to several
Direct comparison of RD114-pseudotyped versus amphotropic-pseudotyped retroviral vectors for transduction of rhesus macaque long-term repopulating cells
Authors: Jiong Hu, Patrick Kelly, Aylin Bonifacino, Brian Agricola, Robert Donahue, Elio Vanin, Cynthia E Dunbar
Journal: Molecular Therapy (2003)

Recently, RD114 (feline endogenous retrovirus envelope protein)-pseudotyped retroviral particles have been shown to transduce human NOD/SCID repopulating cells efficiently. In this study, we compared directly transduction of repopulating cells with RD114-pseudotyped vector to that with standard amphotropic vector in the rhesus macaque model. G-CSF/SCF-mobilized CD34(+) rhesus peripheral blood cells were cultured in the presence of SCF, Flt-3 ligand, and MGDF on Retronectin-coated flasks. To assess directly the ability of the two pseudotypes to transduce primitive cells, both vectors were added simultaneously to the target cells every 24 h, for a total of four exposures in 96 h. The cells were reinfused after the animals received 1000 cGy total body irradiation. At the end of transduction, gene marking efficiency of CFU was higher with amphotropic LNL6 vector (mean 88.4%) vs RD114-G1Na vector (mean 18.5%). After long-term engraftment in three animals, total neo gene marking levels were 4-5% in PBMNCs and 1.5-4% in granulocytes. The RD114-G1Na marking levels were consistently higher in granulocytes than in mononuclear cells, while amphotropic LNL6 marking levels were higher in PBMNCs than in granulocytes. The differential gene marking patterns suggest that RD114 and amphotropic vectors may target distinct progenitor or stem cell populations. There was no clear advantage for RD114-pseudotyped vectors in this predictive preclinical model in terms of overall long-term marking levels; however, optimization of transduction conditions by increasing m.o.i. or inducing the receptor could potentially improve results with this novel vector system.
Cellular kinetics in a patient with sezary syndrome
Authors: P. Chandra, A. D. Chanana, G. Chikkappa, E. P. Cronkite
Journal: American Journal of Hematology (1981)

Cellular kinetics and proliferation of Sezary cells (SC) were studied in a 48-year-old woman with Sezary syndrome (SS). In vitro flash labeling indices of peripheral blood (PB) SC were studied by labeling with tritiated thymidine (3HTdR) and tritiated cytidine (3HCdR). Intradermal SC were labeled in vivo by local injection of 3HTdR followed by skin biopsies of the injected sites. Traffic patterns of DNA labeled PB SC were studied by intravenous 3HTdR followed by sampling of PB, skin, lymph node (LN), and bone marrow (BM). Fluxes of PB SC in various tissues were investigated by autotransfusion of 3HCdR labeled PB SC followed by serial sampling of PB, LN, BM, and skin. In vitro response of PB SC followed by serial sampling of PB, LN, BM, and skin. In vitro response of PB SC to phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed (PWM) were also investigated. The results from these studies in this patient indicate that 1) proliferation of SC was primarily in the skin, 2) there was a negligible flux of SC from blood into skin, LN, and BM, and 3) the mitogenic response of PB mononuclear cells (mostly SC) to PHA, PWM, and Con A was poor.
K r /K c but not d N /d S correlates positively with body mass in birds, raising implications for inferring lineage-specific selection
Authors: Claudia C Weber, Benoit Nabholz, Jonathan Romiguier, Hans Ellegren
Journal: Genome biology (2014)

Abstract Background The ratio of the rates of non-synonymous and synonymous substitution ( d N / d S ) is commonly used to estimate selection in coding sequences. It is often suggested that, all else being equal, d N / d S should be lower in populations with large effective size ( N e ) due to increased efficacy of purifying selection. As N e is difficult to measure directly, life history traits such as body mass, which is typically negatively associated with population size, have commonly been used as proxies in empirical tests of this hypothesis. However, evidence of whether the expected positive correlation between body mass and d N / d S is consistently observed is conflicting. Results Employing whole genome sequence data from 48 avian species, we assess the relationship between rates of molecular evolution and life history in birds. We find a negative correlation between d N / d S and body mass, contrary to nearly neutral expectation. This raises the question whether the correlation might be a method artefact. We therefore in turn consider non-stationary base composition, divergence time and saturation as possible explanations, but find no clear patterns. However, in striking contrast to d N / d S , the ratio of radical to conservative amino acid substitutions ( K r / K c ) correlates positively with body mass. Conclusions Our results in principle accord with the notion that non-synonymous substitutions causing radical amino acid changes are more efficiently removed by selection in large populations, consistent with nearly neutral theory. These findings have implications for the use of d N / d S and suggest that caution is warranted when drawing conclusions about lineage-specific modes of protein evolution using this metric.
PHRENOPHAGIA: A FORM OF HUMAN ARTIFICIAL SELECTION
Authors: J. M. RADZINSKI
Journal: American Journal of Psychiatry (1956)

A process of human artificial selection has been described as it has been practiced for many generations in areas of the world under Russian control. In essence, the process consists of suppression and liquidation of individuals whose personalities and convictions are incompatible with slavish conformity to an arbitrary supreme authority. The essential continuity of this process through Tsarist and Communist periods of Russian history has been traced. The word phrenophagia is proposed to symbolize it. The grave implications of phrenophagia to mankind are stressed and one remedial measure is proposed.
1014-215 Improved electrocardiographic detection of left ventricular hypertrophy in women: Validation by cardiovascular magnetic resonance
Authors: Michael L Chuang, Yoram Ariel, Carol J Salton, Kraig V Kissinger, Patricia A Arand, Lois A Goepfert, Robert A Warner, Warren J Manning
Journal: Journal of the American College of Cardiology (2004)
A Trial of Contraceptive Methods in Women with Systemic Lupus Erythematosus
Authors: Jorge Sánchez-Guerrero, América G. Uribe, Luisa Jiménez-Santana, Marilú Mestanza-Peralta, Pilar Lara-Reyes, Armando H. Seuc, María-del-Carmen Cravioto
Journal: New England Journal of Medicine (2005)

The effects of estrogen-containing contraceptives on disease activity in women with systemic lupus erythematosus have not been determined.We conducted a single-blind clinical trial involving 162 women with systemic lupus erythematosus who were randomly assigned to combined oral contraceptives, a progestin-only pill, or a copper intrauterine device (IUD). Disease activity was assessed at 0, 1, 2, 3, 6, 9, and 12 months according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The primary outcome was global disease activity, which we estimated by measuring the area under the SLEDAI curve. Secondary outcomes included the maximum SLEDAI score, change in SLEDAI score, incidence of lupus flares, median time to first flare, systemic lupus erythematosus treatment, and adverse events. The results were analyzed by the intention-to-treat method.At baseline, all demographic features and disease characteristics were similar in the three groups. The mean (+/-SD) SLEDAI score was 6.1+/-5.6 in the group assigned to combined oral contraceptives, 6.4+/-4.6 in the group assigned to the progestin-only pill, and 5.0+/-5.3 in the group assigned to the IUD (54 patients in each group) (P=0.36). Disease activity remained mild and stable in all groups throughout the trial. There were no significant differences among the groups during the trial in global or maximum disease activity, incidence or probability of flares, or medication use. The median time to the first flare was three months in all groups. Thromboses occurred in four patients (two in each of the two groups receiving hormones), and severe infections were more frequent in the IUD group. One patient receiving combined oral contraceptives died from amoxicillin-related severe neutropenia.Global disease activity, maximum SLEDAI score, incidence of flares, time to first flare, and incidence of adverse events were similar among women with systemic lupus erythematosus, irrespective of the type of contraceptive they were using.
More on glucose transporters: The acinar organization for hepatic glucose transport Tal M, Schneider DL, Thorens B, Lodish HF. Restricted expression of the erythroid/brain lgucose transporter isoform to perivenous hepatocytes in rats: modulation by glucose. J Clin Invest 1990;86:986–992
Authors: B Bilir
Journal: Hepatology (1991)
Preventing thromboembolism after myocardial infarction: effect of low-dose heparin or smoking.
Authors: P A Emerson, P Marks
Journal: BMJ (1977)

A trial of low-dose subcutaneous heparin to prevent thromboembolic complications after myocardial infarction was carried out in 78 patients. Of the 37 heparin-treated patients only two (5%) developed evidence of leg vein thrombosis, while 14 (34%) of the 41 controls did so, and five controls developed pulmonary emboli. Leg vein thrombosis developed in 12 (50%) of the 24 controls who did not smoke cigarettes but in only two (13%) of the 17 controls who were cigarette smokers. Non-smokers who have a myocardial infarction should be given low-dose heparin subcutaneously to prevent leg vein thrombosis and pulmonary embolism.
A double-blind, placebo-controlled comparison of sodium cromoglycate and ketotifen in the treatment of childhood asthma
Authors: J. Croce, E. B. Negreiros, J. A.M. Mazzei, G. Isturiz
Journal: Allergy (1995)

We compared three treatments: sodium cromoglycate 5 mg aerosol and placebo syrup (39 patients), placebo aerosol and ketotifen syrup (39 patients), and placebo aerosol and syrup (36 patients). The patients (mean age 11.7 years) had mostly allergic, moderately severe asthma. Treatments were added to current therapy (mostly bronchodilators only) for 3 months. Aerosols were taken four times daily and syrups twice daily. The following results were significant at a level of 5%. At the final clinic visit, the changes from baseline in lung function favored sodium cromoglycate over the other treatments. During month 3, sodium cromoglycate was superior to ketotifen for night symptoms, morning tightness, daytime symptoms, and cough. Bronchodilator use decreased more with sodium cromoglycate than ketotifen. Patients’ and clinicians’ overall opinions of treatment effectiveness favored sodium cromoglycate over ketotifen and placebo. In these patients, sodium cromoglycate was both effective and superior to ketotifen.
Jejunal Perfusion of Simple and Conjugated Folates in Tropical Sprue
Authors: José J. Corcino, Ann M. Reisenauer, Charles H. Halsted
Journal: Journal of Clinical Investigation (1976)

Absorption of labeled simple 3′,5′,9′-3H pteroylmonoglutamate, ([3H]PG-1) and conjugated pteroyl-μ[14C]glutamyl-γ-hexaglutamate, ([14C]PG-7) folates was assessed in six patients with tropical sprue, before and after 6 mo of treatment, utilizing jejunal perfusion and urinary recovery techniques. Degradation products of [14C]PG-7 which were produced during perfusion were identified by DEAE-cellulose column chromatography. Jejunal mucosal activities of folate conjugase, lactase, sucrase, and maltase were measured in every patient. Malabsorption of both [3H]PG-1 and [14C]PG-7 was found in every untreated patient, with significant improvement after therapy. The urinary excretion of 3H and 14C paralleled the luminal disappearance of both isotopes. The chromatographic patterns of intraluminal degradation products of [14C]PG-7 obtained during perfusion did not differ from those previously found in normal subjects and were similar in studies performed before and after treatment. The activity of folate conjugase was increased in the mucosa of the untreated patients when compared to the post-treatment levels while the activities of mucosal lactase, sucrase, and maltase were originally low and increased significantly after therapy. These observations suggest that folate conjugase originates at a different mucosal locus than the brush border disaccharidases, and are consistent with previous evidence that folate conjugase is an intracellular enzyme. The present studies have demonstrated unequivocal malabsorption of both simple and conjugated folates in tropical sprue. In tropical sprue, folate malabsorption is the reflection of impaired folate transport and not of impaired hydrolysis.