ABSTRACT
A 47-year-old gamekeeper presented with an 8 month history of variable breathlessness, cough and clinical features of severe interstitial lung disease. Open lung biopsy showed an extrinsic allergic alveolitis, which we believe related to his work rearing pheasants. Initially he was resistant, despite advice, to changing his occupation but subsequently, although ceasing exposure to pheasants and beginning treatment with corticosteroids, his disease progressed to the point where he developed respiratory failure and was referred for lung transplantation. Sadly, he died of progressive respiratory failure and cor pulmonale complicated by bronchopneumonia before this could be achieved.
Subject(s)
Animal Husbandry , Bird Fancier's Lung/etiology , Occupational Diseases/etiology , Poultry , Animals , Bird Fancier's Lung/diagnosis , Bird Fancier's Lung/pathology , Fatal Outcome , Humans , Male , Middle Aged , Occupational Diseases/diagnosis , Occupational Diseases/pathologyABSTRACT
A role of nitric oxide (NO) has been suggested in the airway response to exercise. However, it is unclear whether NO may act as a protective or a stimulatory factor. Therefore, we examined the role of NO in the airway response to exercise by using N-monomethyl-L-arginine (L-NMMA, an NO synthase inhibitor), L-arginine (the NO synthase substrate), or placebo as pretreatment to exercise challenge in 12 healthy nonsmoking, nonatopic subjects and 12 nonsmoking, atopic asthmatic patients in a double-blind, crossover study. Fifteen minutes after inhalation of L-NMMA (10 mg), L-arginine (375 mg), or placebo, standardized bicycle ergometry was performed for 6 min using dry air, while ventilation was kept constant. The forced expiratory volume in 1-s response was expressed as area under the time-response curve (AUC) over 30 min. In healthy subjects, there was no significant change in AUC between L-NMMA and placebo treatment [28.6 +/- 17.0 and 1.3 +/- 20.4 (SE) for placebo and L-NMMA, respectively, P = 0.2]. In the asthmatic group, L-NMMA and L-arginine induced significant changes in exhaled NO (P < 0.01) but had no significant effect on AUC compared with placebo (geometric mean +/- SE: -204.3 +/- 1.5, -186.9 +/- 1.4, and -318.1 +/- 1.2%. h for placebo, L-NMMA, and L-arginine, respectively, P > 0.2). However, there was a borderline significant difference in AUC between L-NMMA and L-arginine treatment (P = 0.052). We conclude that modulation of NO synthesis has no effect on the airway response to exercise in healthy subjects but that NO synthesis inhibition slightly attenuates exercise-induced bronchoconstriction compared with NO synthase substrate supplementation in asthma. These data suggest that the net effect of endogenous NO is not inhibitory during exercise-induced bronchoconstriction in asthma.
Subject(s)
Asthma, Exercise-Induced/physiopathology , Nitric Oxide/physiology , Administration, Inhalation , Adult , Arginine/administration & dosage , Arginine/pharmacology , Asthma, Exercise-Induced/metabolism , Breath Tests , Cross-Over Studies , Double-Blind Method , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/pharmacology , Forced Expiratory Volume , Humans , Nitric Oxide/metabolism , Time Factors , omega-N-Methylarginine/administration & dosage , omega-N-Methylarginine/pharmacologyABSTRACT
BACKGROUND: Venlafaxine is a potent neuronal serotonin and noradrenaline re-uptake inhibitor, and to a lesser extent an inhibitor of dopamine reuptake. Paroxetine is a potent selective inhibitor of serotonin reuptake. CASE REPORT: A 27-year-old man ingested 1987.5 mg of venlafaxine and 360 mg of paroxetine. He subsequently developed systolic and diastolic hypertension, transient electrocardiographic abnormalities, and an area of persistent myocardial damage. He recovered from his overdose with his blood pressure and electrocardiogram returning to normal. The area of myocardial damage was documented on echocardiogram as an area of marked hypokinesia at the basal anterior septum. Despite the absence of confirming blood levels or the absolute exclusion of cocaine, this case indicates that venlafaxine and paroxetine have the potential for serious cardiotoxicity when taken in overdose.
Subject(s)
Cardiomyopathies/chemically induced , Cardiomyopathies/diagnosis , Cyclohexanols/poisoning , Heart/drug effects , Paroxetine/poisoning , Selective Serotonin Reuptake Inhibitors/poisoning , Adult , Anti-Arrhythmia Agents , Chest Pain/chemically induced , Electrocardiography , Humans , Hypertension/chemically induced , Hypertrophy, Left Ventricular/chemically induced , Male , Tachycardia, Sinus/chemically induced , Venlafaxine Hydrochloride , Ventricular Function, Left/drug effectsABSTRACT
Phaeanthine, a bisbenzylisoquinoline alkaloid which occurs naturally in Triclisia species, was extracted from Triclisia patens (Menispermaceae) obtained from Sierra Leone (West Africa). In vitro, phaeanthine was found to be twice as potent against a chloroquine-resistant Plasmodium falciparum strain (K1), as against a chloroquine-sensitive clone (T9-96), with 50% inhibitory concentrations of 365.85 (+/- 11.41) nM and 704.87 (+/- 81.48) nM respectively. At a sub-inhibitory concentration of 80.35 nM, chloroquine resistance was not reversed by phaeanthine. Isobolograms constructed from experiments with chloroquine/phaeanthine combinations showed antagonism in T9-96 and an additive effect in K1. In a 48-hour microtest, phaeanthine at antimalarial concentrations showed no cytotoxicity to mammalian (KB) cells in vitro.
