Biomedical subjects
Publications and source records attributed to J Descotes.
Male and female mice, IOPS OF1 strain, received an i.p. injection of diazepam 1,2,4 or 8 mg/kg daily for 3 days prior to i.p. challenge with Klebsiella pneumoniae. Diazepam pretreatment increased mortality due to Klebsiella pneumoniae indicating that diazepam alters natural resistance to infection. The mechanism has not been elucidated but would appear to involve T cells and/or macrophages.
The pharmaceutical formulation of Althesin was shown to have a weak allergenic potential in the guinea pig maximization test. Alphadolone and alphaxalone acetate were found to be devoid of such potential, while the status of Cremophor EL remained equivocal.
Two cases of hypersensitivity reactions in the course of slow infusion of Althesin are reported. Serial examination of their complement system showed a marked activation of the alternate pathway which returned almost to normal within 24 hours.
Cremophor Elo proved as potent as Freund's complete adjuvant for eliciting skin reactivity to bovine serum albumin in guinea pigs. It enhanced delayed hypersensitivity to sheep erythrocytes in mice while hemagglutinin antibody titers were not affected. This adjuvant activity is likely to play a critical role in hypersensitivity reactions to Cremophor-containing drugs, e.g. alphadione.
Propranolol pretreatment (0.1 mg X kg-1) significantly increased the lengthening induced by diltiazem (0.15 mg X kg-1 + 0.01 mg X kg-1 X min-1, 20 min) of the A-H interval of His bundle potential recordings in the dog. In the presence of propranolol, diltiazem also significantly increased the atrioventricular effective refractory period. The results suggest the possible occurrence of AV blocks as a result of the use of a diltiazem-beta blocker combination in clinical practice.
Diazepam, a benzodiazepine derivative useful in the treatment of anxiety disorders, was found to depress both primary antibody to sheep red blood cells and delayed-type hypersensitivity responses in normal mice. This immunodepressant activity warrants further investigation owing to its potential consequences on human health and the putative involvement of specific receptors on immunocompetent cells.
Chlorpromazine, a phenothiazine derivative useful in the treatment of various mental disorders, was found to depress contact hypersensitivity to dinitrochlorobenzene in guinea-pigs. This drug proved equipotent on the various phases of this delayed-type immune response. The observed immunodepression is consistent with previously reported untoward reactions to chlorpromazine and might have consequences which deserve further evaluation in the management of psychiatric patients.
A 57 years old man had a two months history of chills and fever with abdominal pain. Blood cultures were positive for Salmonella ohio. He suddenly became hypotensive with oedema of lower limbs. Angiographic findings were infrarenal aortic rupture with pseudoaneurysm formation and inferior vena cava compression. After ligation of the aorta and both common iliac arteries, an axillo-bi-femoral graft was constructed to bypass the infection area. Subsequent occurrence of lumbar osteomyelitis required debridement and drainage of retroperitoneum. The patient was discharged on oral amoxicilline given for eleven months. Two years postoperatively he is able to walk without evidence of further infection. With a review of 32 other cases in the literature, emphasis is placed on theories of pathogenesis and on modes of surgical management.
Isotope phlebography is a reliable examination in the diagnosis of deep venous thrombosis. Too complicated and expensive to be suggested for the purpose of routine detection, it nevertheless is of definite interest in three circumstances: --Suspicion of pulmonary embolism, with visualisation of any possible reservoir of peripheral clot and proof of the embolism. --Postoperatively, for repeated follow up to evaluate permeability after surgical procedures. --Finally, dynamic information by calculation of transit time of the radioactive embolus. Combined with Doppler measurement of peripheral venous pressures, it reflects the emptying capacities of a limb affected by post-phlebitis syndrome and hence plays a role in the decision to stop oral anticoagulants.
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The myocardial depressant action of aminoglycosides has been known for a number of years but there was no available data on newer derivatives. We have thus studied the contractile responses of isolated guinea pig left atria to increasing concentrations of gentamicin, tobramycin, lividomycin and amikacin (0.02, 0.04, 0.08, 0.13, 0.17 and 0.22 mM). Our results are consistent with those of previous workers and show that newer aminoglycosides do exert a similar depressant action. As gentamicin and tobramycin are more depressant than lividomycin, then amikacin at similar concentrations, no clear-cut difference was obtained when respecting a relative range of concentrations mimicking that of clinical situations. However, these depressant effects were attained using concentrations far exceeding those reached in man.
In search for an effective treatment of human poisonings with ajmaline, a potent antiarrhythmic drug, the use of specific antibodies as neutralizing agents was explored in a preliminary animal model. For this purpose, New Zealand white rabbits were immunized with the antigen obtained after coupling the 17-hemisuccinate ester of ajmaline-21-acetate to bovine serum albumin, whereas other rabbits were immunized with the protein carrier only. While seven control rabbits receiving 0.625 mg/kg/min. ajmaline intravenously until death, died within 54.8 +/- 5.2 min. death was delayed until 137.7 +/- 15.5 min in seven ajmaline bovine serum albumin-immunized rabbits (p less than 0.001). Three bovine serum albumin-immunized rabbits behaved as controls. These results provide evidence that an immunological protection against ajmaline toxicity can be obtained in laboratory animals.
The effects of intravenously infused succinylcholine (SCh): 1 mg/kg/minute during 30 minutes were assessed in anesthetized dogs on spontaneous heart rate, conduction within the atrio-ventricular node and the His-Purkinje system and on atrial (AERP) and atrio-ventricular (AVERP) effective refractory periods with varying levels of vagal tone and under mild hyperkalemia. 1) The heart rate which was not affected by SCh in the absence of vagal tone was by contrast increased by 50 p. cent when vagal tone was maintained. Under hyperkalemia, the vagolysis-mediated tachycardia did not prove more marked. 2) The conduction velocity, which was never modified by SCh in either the atria or the His-Purkinje system, was always accelerated with vagal tone. This acceleration is directly related to the vagolytic properties of SCh, but also partly to a mild hyperkalemia. The changes of potassium blood levels tend to reverse the potassium outflow due to the parasympathetic neuromediator. 3) The AERP was was lengthened by SCh and hyperkalemia; the latter impaired the outflow of potassium ions responsible for repolarization. The AVERP was always shortened when the vagal tone is maintained, however less largely under mild hyperkalemia which limits SCh anticholinergic effect owing to its own anticholinergic action.
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The effects of diltiazem, a new slow channel inhibitor, on the cardiac conduction and refractoriness have been studied using His bundle recordings and the extrastimulus method. In order to determine the role played by possible changes in vagal tone, diltiazem (0.15 mg.kg-1, followed immediately by a 30 min infusion of 0.01 mg.kg-1.min-1) has been administered intravenously to six atropinized dogs, anesthetized with chloralose (100 mg.kg-1) ("atropine group") and to six others which were given chloralose (80 mg.kg-1) and dextromoramide (0.1 mg.kg-1) to ensure the persistence of vagal tone ("vagal tone group"). In the "atropine group", atrioventricular (AV) nodal conduction time increased by 137% and AV node effective refractory period by 55%. Heart rate was slowed down by 15% and arterial pressure fell slightly. In the "vagal tone group", the only significant changes were a 26% increase in AV nodal conduction time and a slight fall in arterial pressure. Inhibition of the slow channel accounts for the effects of diltiazem within the "atropine group". A reflex decrease in vagal tone is probably responsible for the somewhat different results observed in the "vagal tone group". Diltiazem resembles verapamil and should share its antiarrhythmic properties.
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Effects of mild hyperkalemia on conduction velocity, effective refractory periods (ERPs) and sinus rate were studied on 16 anesthetized dogs, using endocavitary His bundle recordings, the extrastimulus method and standard electrocardiogram. Six dogs were placed under acetylcholine infusion (300 micrograms/kg/min) (ACh group), 10 received atropine sulfate 0.2 mg/kg intravenously (atropine group). Intraventricular conduction time, ventricular ERP and QRS duration of the EKG were studied on 7 other open-chested dogs (ventricular group). During a 60 min potassium chloride infusion (0.025 mmol/kg/min, 30 min, then 0.05 mmol/kg/min, 30 min), following observations were made: - In the ACh group, AV node conduction time (A-H interval) decreased by 20% and AV node ERP by 17%, whereas, in the atropine group, the former parameter was not affected and atrial ERP increased by 29%. - At the same time, sinus rate increased in the ACh group and was unaffected in the atropine group. - Conduction times in atrial contractile tissue (S-A interval), His-Purkinje system (H-V interval) and ventricular contractile tissue, like ventricular ERP, exhibited no variation or very slight, occasionally biphasic variations under both conditions. These results can be accounted for by an "anticholinergic" effect of mild hyperkalemia which is discussed.