tbuckley/cabot-search huggingface dataset:
Two cases of ethambutol nephrotoxicity.
Authors: J Collier, A M Joekes, P E Philalithis, F D Thompson
Journal: BMJ (1976)

Severe allergic reaction to chlormethiazole Allergic reactions are not a recognised side effect of treatment with chlormethiazole.This paper describes a patient who suffered such a reaction after being treated for acute alcoholic withdrawal symptoms with chlormethiazole. Case reportThe patient was a married woman aged 48 years, Scottish by birth and unemployed.She was of medium build and weighed 57 kg.She was admitted to Hill Hospital, Hartwood, for treatment of chronic alcoholism.On admission she smelt of alcohol and was visually hallucinated with delirium tremens.On physical examination she was healthy, and all systems were normal.Treatment-She was started on oral chlormethiazole (Heminevrin), 2 capsules three times a day.No other drugs were prescribed.Adverse effect-Twelve hours later the patient developed a severe allergic reaction with profuse rash on her face, neck, and arms.The rash was blotchy in distribution with severe itching.Her face was swollen and she was in pain.The drug was withdrawn and she was started on the antihistamine chlorpheniramine maleate, one tablet three times a day, and given an antihistamine cream for local application.The rash and swelling disappeared after 24 hours, leaving behind some chaffing of the skin.
Pemphigus foliaceus induced by rifampicin
Authors: C.W. LEE, J.H. LIM, H.J. KANG
Journal: British Journal of Dermatology (1984)

Pemphigus foliaceus was seen in a patient with pulmonary tuberculosis during rifampicin therapy. The skin lesions were eczematoid patches, flaccid bullae and crusted plaques on the trunk and extremities, histologically showing a high epidermal blister with acantholysis. The diagnosis was confirmed by immunofluorescent studies. After the patient discontinued rifampicin, the skin lesions cleared completely within 5 weeks without any systemic medication.
Gonadotropic Activity of Anterior Pituitary
Authors: W. R. Henderson, I. W. Rowlands
Journal: BMJ (1938)

ness.The period between consumption of milk and onset of symptoms was twelve to twenty-four hours in those cases where this could be determined. Additional InquiriesOn January 11, when the cause of the outbreak first became clear, all the medical practitioners in the town were informed of the facts and were asked for informa- tion as to any further cases which might come to their knowledge.Inquiries were also addressed to the larger local works.
117. AAV-Mediated Erythropoietin Gene Transfer Protects from Genetic and Light-Induced Retinal Degeneration
Authors: Mariacarmela Allocca, Tonia S. Rex, Luciano Domenici, Jean Bennet, Victor M. Rivera, Alberto Auricchio
Journal: Molecular Therapy (2005)

Retinitis pigmentosa (RP) is a group of inherited retinal degenerations for which no treatment is available. Despite their genetic heterogeneity, common mechanisms, like apoptosis, are responsible for photoreceptor cell death. This allows testing strategies aim at retarding or arresting apoptosis independently from the mutation causing the disease. Various molecules with neurotrophic activity are being evaluated for treatment of RP in animal models. In particular, we have explored the potential neurotrophic effect of Erythropoietin (Epo) by adeno-associated viral (AAV) vectors gene transfer to the retina and muscle of three RP models: the light-damaged albino Lewis rat, rds and rd10 mice. Interestingly, following systemic but not intraocular Epo delivery, morphological and functional photoreceptor protection was observed in the light-damage and rds models, thus suggesting that the Epo neurotrophic effect might not be exerted directly on the RP retina. To gain further insight into the mechanism of Epo photoreceptor protection we are currently characterizing Epo processing from AAV transduced muscle and retina which might account for their different neuroprotective properties. In addition, using AAV we are transfering to the retina of our models a chimeric Epo receptor (Fv2EpoR) which can be activated by a small dimerizer drug, AP20187. Upon AP20187 administration and Fv2EpoR activation the Epo signalling cascade is triggered in photoreceptors. This will help understand if Epo's retinal neuroprotection is direct and whether activation of the Epo pathway might be considered for therapy of some retinal degenerations.
Binding of thrombin to subendothelial extracellular matrix. Protection and expression of functional properties.
Authors: R Bar-Shavit, A Eldor, I Vlodavsky
Journal: Journal of Clinical Investigation (1989)

We have analyzed the binding of thrombin, a serine protease with central roles in hemostasis, to the subendothelial extracellular matrix (ECM) produced by cultured endothelial cells. This substrate provides a thrombogenic surface where hemostasis is initiated. Binding was saturable and equilibrium was achieved after 3 h incubation with 125I-alpha-thrombin. Scatchard analysis of thrombin binding revealed the presence of 5.1 X 10(9) binding sites per squared millimeter ECM, with an apparent Kd of 13 nM. The catalytically blocked enzyme, diisofluorophosphate (DIP)-alpha-thrombin competed efficiently with 125I-alpha-thrombin, indicating that the binding was independent of its catalytic site. Moreover, high concentrations of the synthetic tetradecapeptide, representing residues 367-380 of thrombin B chain (the macrophage mitogenic domain of thrombin), competed with thrombin binding to ECM, indicating that the binding site may reside in the vicinity of "loop B" region. Thrombin binds to dermatan sulfate in the ECM, as demonstrated by the inhibition of 125I-alpha-thrombin binding to ECM pretreated with chondroitinase ABC, but not with heparitinase or chondroitinase AC. This stands in contrast to 125I-FGF (fibroblast growth factor) binding to ECM, which was inhibited by heparitinase but not by chondroitinase ABC, ECM-bound thrombin exhibits an exposed proteolytic site as monitored by the Chromozyme TH assay and by its ability to convert fibrinogen to a fibrin clot and to induce platelet activation as indicated by 14C-serotonin release. ECM-bound thrombin failed to form a complex with its major circulating inhibitor-antithrombin III (AT III), compared with rapid complex formation with soluble thrombin. We propose that thrombin binds to subendothelial ECM where it remains functionally active, localized, and protected from inactivation by circulating inhibitors.
Neurocirculatory Abnormalities in Chronic Orthostatic Intolerance
Authors: David S. Goldstein, Basil Eldadah, Courtney Holmes, Sandra Pechnik, Jeffrey Moak, Yehonatan Sharabi
Journal: Circulation (2005)

Chronic orthostatic intolerance (COI) occurs in postural tachycardia syndrome (POTS) and in some individuals with repeated neurocardiogenic syncope/presyncope (NCS), without POTS. This study addressed whether patients with COI and POTS or NCS have neurocirculatory abnormalities during supine rest.Adult patients referred for COI who had POTS (n=90, mean+/-SEM age 40+/-1 years, 86% women) or NCS (n=36, 41+/-2 years old, 78% women) underwent measurements of plasma levels of catecholamines and forearm hemodynamics. Comparison data were obtained from 32 age- and gender-matched normal volunteers (39+/-2 years old, 81% women). The POTS group had a relatively fast mean heart rate (79+/-2 bpm) during supine rest compared with the NCS group (69+/-1.6 bpm, P=0.03) and normal volunteers (66+/-3 bpm, P=0.0004). The POTS group also had higher mean arterial norepinephrine (1.61+/-0.11 nmol/L, n=37) and epinephrine (0.39+/-0.03 nmol/L, n=37) concentrations than the NCS group (1.03+/-0.12 nmol/L, n=20, P=0.0012; 0.21+/-0.03 nmol/L, n=20, P=0.0005) and normal volunteers (1.13+/-0.11 nmol/L, n=20, P=0.006; 0.17+/-0.03 nmol/L, n=15, P=0.0001). The NCS group had higher mean forearm vascular resistance (52+/-6 U) than the POTS group (36+/-2 U, P=0.003).Overall, POTS features increased heart rate and sympathetic nervous and adrenomedullary hormonal system outflows during supine rest. Increased sympathetic outflow may contribute to the relative tachycardia in POTS. NCS features forearm vasoconstriction during supine rest but not sympathoneural or adrenomedullary activation.
REPORT ON THERAPEUTIC PROPERTIES OF PENICILLIN: VI. Local Penicillin for Breast Abscess
Authors: D. B. Fraser
Journal: BMJ (1944)

MEDICATIJOURNAL 523 (b) If reinfection of a wound occurs after sterilization by penicillin a sensitivity test should be done on the new invader, as it may be resistant.Case 7.-A soldier aged 23 was undergoing total reconstruction of the thumb.A pedicle graft had been raised and transferred to the thenar remnant, and aL this stage both ends of the pedicle were attached to the hand.As the result of some slight trauma the pedicle ulcerated and became infected with penicillin-sensitive Staph.alurelus.Penicillin cream was used as a dressing, and sterility was obtained in five days.The wound remained sterile for 16 days without any clinical change and then became reinfected with staphylococci.Penicillin was continued for 27 days without clinical or bacteriological effect.Finally treatment was stopped and the ulcer eventually healed.(c) Although sensitive organisms may disappear from culture, the wound may be so infected with pyocyaneus, proteus, or the coliforms as secondary invaders that no clinical improvement is noted or indeed can be expected.This was a common finding, particularly in this group of cases.(d) Penicillin can be a useful adjunct to surgery, but does not replace it.Certain surgical principles may need modifica- tion to comply with the requirements of penicillin application.Summary These experiments with the local use of penicillin to date indicate that we have an effective weapon in the fight against tissue invasion by certain of the pyogenic cocci.The points that emerge are:1. Early application is most desirable.2. Efficient technique must be used to bring penicillin into contact with the infective process.3. Tissues necrosed as the result of infection are removed by natural processes.Many wounds containing slough or sequestra resist sterilization by penicillin.In some of these cases it is probable that attempts at sterilization impede slough removal and so delay healing.4. Penicillin as an adjunct to adequate surgical technique is a valuable advance in the treatment of wounds infected with sensitive organisms.
European court rules minimum cigarette prices illegal
Authors: R. Watson
Journal: BMJ (2010)

It is illegal for European governments to impose minimum retail prices on cigarettes as a deterrent against smoking, the European Court of Justice has ruled. However, the Luxembourg based judges confirmed that it is quite legitimate to impose heavy taxes on tobacco products to discourage consumption.

The ruling came in cases the European Commission had brought against France, Austria, and Ireland, all of which have imposed minimum prices on cigarettes, expressed …
Use of coughing test to diagnose peritonitis
Authors: H D Bennett, L J M T Tambeur, W B Campbell
Journal: BMJ (1994)

The test for rebound tenderness is advocated for diagnosing general or localised irritation of the peritoneum, but the diagnostic accuracy and patients' acceptance of the test have been questioned.1,2 Other methods for identifying peritonitis include asking patients to cough and percussion of the abdomen. We routinely ask patients to cough and have evaluated this coughing test for diagnosing peritonitis.

One hundred and fifty consecutive patients (70 male, 80 female; range 4-95 years, median 46) who were admitted for emergency treatment with abdominal pain were examined in a prospective study. The patients were asked to cough, and …
Metabolism of the food-borne carcinogens 2-amino-3-methylimidazo-[4,5-f]quinoline and 2-amino-3,8- dimethylimidazo[4,5-f]-quinoxaline in the rat as a model for human biomonitoring.
Authors: R J Turesky, W G Stillwell, P L Skipper, S R Tannenbaum
Journal: Environmental Health Perspectives (1993)

Metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazol[4,5-f]quinoxaline (MeIQx) and their binding to blood proteins were examined in the rat to develop methods of human biomonitoring. Hemoglobin and serum albumin were among many blood proteins modified. Approximately 0.01% of the dose for both compounds was bound to these proteins, and induction of cytochrome P-450 with polychlorobiphenyls resulted in decreased levels of adduction. Hemoglobin sulfinic acid amide adducts could not be detected for either amine, however, as much as 10% of the IQ bound to albumin was characterized as an N2-cysteine(34)sulfinyl-IQ linkage. Human dosimetry of these carcinogens through such adducts may prove difficult due to the low levels of protein binding. Major routes of detoxification of both contaminants included cytochrome P-450-mediated ring hydroxylation at the C-5 position followed by conjugation to glucuronic or sulfuric acid. Direct conjugation to the exocyclic amine group through N-glucoronidation and sulfamate formation were other important routes of inactivation, but N-acetylation was a minor pathway. The N-glucoronide conjugate of the mutagenic metabolite N-hydroxy-MeIQx was also detected in urine. Rats given MeIQx at 10 micrograms/kg excreted 20% of the dose in urine within 24 hr and the remainder was recovered in feces. The N2-glucuronide was the major metabolite found in urine and accounted for 4% of the total dose. The other metabolites cited above also were excreted in urine at amounts ranging from 0.5 to 3% of the dose, whereas 0.5 to 2% was detected as unmetabolized MeIQx.(ABSTRACT TRUNCATED AT 250 WORDS)
Response of Rheumatoid Arthritis with Leukopenia to Gold Salts
Authors: James D. C. Gowans, Mohammad Salami
Journal: New England Journal of Medicine (1973)

The place of gold salts in the treatment of rheumatoid arthritis, after many years of controversy, was firmly established in a multicenter controlled trial in 1960.1 Severe cases of rheumatoid arthritis are frequently complicated by granulocytopenia. The safety and effectiveness of gold salts in these cases has not been well established. Leukopenia is a known complication of therapy, and is listed as a relative contraindication.Many patients with rheumatoid arthritis and leukopenia also have splenomegaly, and to these cases the term Felty's syndrome2 has been applied. Leukopenia was thought to be the result of entrapment and destruction of the white . . .
Electroporation-mediated PDGF receptor-IgG chimera gene transfer ameliorates experimental glomerulonephritis
Authors: Hiroyuki Nakamura, Yoshitaka Isaka, Michiko Tsujie, Yoshitaka Akagi, Tetsuo Sudo, Noriko Ohno, Enyu Imai, Masatsugu Hori
Journal: Kidney International (2001)
Initial cardiac tamponade in acute leukaemia.
Authors: S. M. Rab, A. Yee
Journal: BMJ (1967)

Preliminary Communications MBIABLJOURNALBoth drugs increased heart rate in cats, heart rate and cardiac contractile force in dogs, and heart rate and forearm blood flow in man.Both drugs acted by stimulating adrenergic a-receptors, as their effects were antagonized by propranolol.Isoprenaline was found to be about 40 times more active than orciprenaline in cats, 10 to 20 times more active in dogs, and 10 to 40 times more active in humans.These observations suggest that orciprenaline may be of value in patients in whom side-effects have occurred from blockade of adrenergic a-receptors.
Renin Release during Acute Reduction of Arterial Pressure in Normotensive Subjects and Patients with Renovascular Hypertension*
Authors: Yoshihiro Kaneko, Takao Ikeda, Tadanao Takeda, Hideo Ueda
Journal: Journal of Clinical Investigation (1967)

In normotensive subjects, acute reduction of mean arterial pressure to from 60 to 75 mm Hg by infusion of sodium nitroprusside caused significant increase in renin activity of renal venous plasma and also in the renal-systemic difference of renin activity. At the same time, the products of the renal-systemic difference of renin activity and renal plasma flow increased significantly, whereas renin substrate activity of plasma was unchanged, indicating that there was an increase in renin release during reduction in pressure. Renin activity of renal venous plasma, expressed in logarithms, showed a significant correlation with the degree of reduction in pressure; an increase in renin activity became significant when mean arterial pressure was reduced to below a level of 70 to 75 mm Hg. There was a striking difference in the renal response to reduction in pressure between patients with renovascular hypertension and normotensive subjects. In 10 renovascular hypertensive patients, significant increase in renin release occurred from the involved kidney at mean arterial pressures ranging from 90 to 137 mm Hg; the threshold at which renin release increased was shifted to a range much higher than that in normotensive subjects. Furthermore, the magnitude of renin release from the involved kidney was significantly greater when compared to that in normotensive subjects. In contrast, in the contralateral uninvolved kidney, no significant release of renin was detected during reduction in pressure. The renal mechanism controlling renin secretion appears to be operative at higher systemic arterial pressure levels and with enhanced responsiveness in the involved kidney of renovascular hypertensive patients; the findings are consistent with the hypothesis that the renin-angiotensin system participates in maintaining hypertension in this disease.
PERSONALITY AS IT AFFECTS THE COURSE OF DRUNKENNESS.Read before the Section of Medical Jurisprudence and Neurology, at the Forty-second Annual Meeting of the American Medical Association, held at Washington, D. C., May, 1891.
Authors: T. L. WRIGHT
Journal: JAMA (1891)

When the elements of the human character are observed in any individual, there will be per¬ ceived a number-sometimes more and some¬ times less-of intervening, interrupting, inter¬ polating, constitutional characteristics that, abstractly, are not really necessary to the com¬ pleteness of human nature.And these charac¬ teristics, while non-essential, may nevertheless be, so far as the individual is concerned, domi¬ nant and decisive in the aggregate and sum total of life's history.Such peculiarities in the elements of person¬ ality indicate imperfections in the constitutional stamina of separate and distinct persons.In some cases they have been impressed upon the individual by ancestry-pointing to a history of disease, or of profound physical injury, or of mental and moral suffering, or inquietude, or
516 DIFFERENTIAL REGULATION OF SODIUM/IODIDE SYMPORTER NIS GENE PROMOTER BY P53, P63 AND P73 IN HUMAN CHOLANGIOCARCINOMA (CCA) AND HEPATOCELLULAR (HCC) CELL LINES
Authors: F. Guerrieri, V. Schinzari, J. Herve', D. Samuel, C. Brechot, J. Faivre, M. Levrero
Journal: Journal of Hepatology (2009)
BASELINE RENAL FUNCTION AND CARDIOVASCULAR RISK IN PATIENTS TREATED WITH SAXAGLIPTIN: OBSERVATIONS FROM THE SAVOR-TIMI 53 TRIAL
Authors: Jacob A. Udell, Benjamin Scirica, Matthew A. Cavender, Ofri Mosenzon, Philippe Steg, Jaime Davidson, Boaz Hirshberg, Kyungah (Kelly) Im, Itamar Raz, Deepak Bhatt
Journal: Journal of the American College of Cardiology (2014)
Optimized Lentiviral Vectors for HIV Gene Therapy: Multiplexed Expression of Small RNAs and Inclusion of MGMTP140K Drug Resistance Gene
Authors: Janet Chung, Lisa J Scherer, Angel Gu, Agnes M Gardner, Monica Torres-Coronado, Elizabeth W Epps, David L DiGiusto, John J Rossi
Journal: Molecular Therapy (2014)

Gene therapy with hematopoietic stem and progenitor cells is a promising approach to engineering immunity to human immunodeficiency virus (HIV) that may lead to a functional cure for acquired immunodeficiency syndrome (AIDS). In support of this approach, we created lentiviral vectors with an engineered polycistronic platform derived from the endogenous MCM7 gene to express a diverse set of small antiviral RNAs and a drug resistance MGMTP140K marker. Multiple strategies for simultaneous expression of up to five RNA transgenes were tested. The placement and orientation of each transgene and its promoter were important determinants for optimal gene expression. Antiviral RNA expression from the MCM7 platform with a U1 promoter was sufficient to provide protection from R5-tropic HIV in macrophages and resulted in reduced hematopoietic toxicity compared with constructs expressing RNA from independent RNA polymerase III promoters. The addition of an HIV entry inhibitor and nucleolar TAR RNA decoy did not enhance antiviral potency over constructs that targeted only viral RNA transcripts. We also demonstrated selective enrichment of gene-modified cells in vivo using a humanized mouse model. The use of these less toxic, potent anti-HIV vectors expressing a drug selection marker is likely to enhance the in vivo efficacy of our stem cell gene therapy approach in treating HIV/AIDS. Gene therapy with hematopoietic stem and progenitor cells is a promising approach to engineering immunity to human immunodeficiency virus (HIV) that may lead to a functional cure for acquired immunodeficiency syndrome (AIDS). In support of this approach, we created lentiviral vectors with an engineered polycistronic platform derived from the endogenous MCM7 gene to express a diverse set of small antiviral RNAs and a drug resistance MGMTP140K marker. Multiple strategies for simultaneous expression of up to five RNA transgenes were tested. The placement and orientation of each transgene and its promoter were important determinants for optimal gene expression. Antiviral RNA expression from the MCM7 platform with a U1 promoter was sufficient to provide protection from R5-tropic HIV in macrophages and resulted in reduced hematopoietic toxicity compared with constructs expressing RNA from independent RNA polymerase III promoters. The addition of an HIV entry inhibitor and nucleolar TAR RNA decoy did not enhance antiviral potency over constructs that targeted only viral RNA transcripts. We also demonstrated selective enrichment of gene-modified cells in vivo using a humanized mouse model. The use of these less toxic, potent anti-HIV vectors expressing a drug selection marker is likely to enhance the in vivo efficacy of our stem cell gene therapy approach in treating HIV/AIDS.
How smart can simple heuristics be?
Authors: Nick Chater
Journal: Behavioral and Brain Sciences (2000)

This commentary focuses on three issues raised by Gigerenzer, Todd, and the ABC Research Group (1999). First, I stress the need for further experimental evidence to determine which heuristics people use in cognitive judgment tasks. Second, I question the scope of cognitive models based on simple heuristics, arguing that many aspects of cognition are too sophisticated to be modeled in this way. Third, I note the complementary role that rational explanation can play to Gigenerenzer et al.'s “ecological” analysis of why heuristics succeed.
US aims to cut antibiotic use in new five year plan to combat antibiotic resistant bacteria
Authors: M. McCarthy
Journal: BMJ (2015)

The Obama administration released a five year plan on 27 March to combat the rise of antibiotic resistant bacteria. The White House said that the document, The National Action Plan for Combating Antibiotic Resistant Bacteria ,1 would guide federal agencies’ activities until 2020.

The document noted not only that the rise of antibiotic resistance “means we can no longer take for granted the quick and reliable treatment of rare or common bacterial infections” but that it threatens the loss of the “benefits of a range of modern medical procedures—from hip replacements to organ transplants—whose safety depends on our ability to treat bacterial infections that may arise as post-surgical complications.”

The US Centers for Disease Control and Prevention (CDC) has estimated that antibiotic resistant bacteria are currently responsible for …