Biomedical subjects
Publications and source records attributed to J Descotes.
Recent studies showed that lead acetate has an important immunotoxicity for the phagocytic activity as well as humoral and cell-mediated immunity. We studied the influence of lead acetate on immediate and delayed hypersensitivity. The lead acetate exerts an important action on hypersensitivity reactions whether on rat mast cells degranulation (immediate hypersensitivity) or on contact hypersensitivity.
Histamine release is generally thought to play a major role in anaesthetic-induced anaphylactoid reactions. In 12 patients who were developing such a reaction at the start of a slow rate intra-venous infusion of alphadione, serum histamine was measured using the enzyme-isotopic assay from a blood sample drawn within the first 5 minutes following the onset of clinical signs. Histaminemia above normal value was noted in 3 patients only without clear clinical correlation. These results would suggest that histamine release is unlikely to be principally involved in this kind of adverse reaction.
Pathologic study of lesions involves atheromatous aneurysms initially, with analysis of particular features related to localization and to microscopic changes. Discussions then concern media dystrophy localized to the proximal aorta and to the limb arteries, with a description of macroscopic and of optical and electron microscopy findings.
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Inhibition of hepatic drug metabolizing enzymes is an important cause of clinically relevant drug interactions. A close correlation was found between influence of pentobarbital-induced sleeping time in outbred Swiss mice and hepatic drug metabolism in man for several established inhibitors, i.e. chloramphenicol, cimetidine, idrocilamide, isoniazid, metronidazole, miconazole and triacetyloleandomycin, and control drugs, i.e. baclofen, ranitidine and spiramycin. Provided that room temperature is carefully controlled, barbiturate sleeping time is a simple, inexpensive and reproducible predictive tool for the experimental detection of pharmacological agents likely to inhibit hepatic drug metabolism.
Although aneurysms of the common iliac artery are a rare occurrence they should be investigated routinely in patients with urinary or thrombo-embolic venous manifestations in the pelvis minor. Clinical signs are inconstant and diagnosis requires the use of abdominopelvic ultrasound tomography. Venous and urinary complications constitute warning signals suggesting the need for surgery to avoid sudden or untimely rupture. Operation in patients with a poor general condition should be performed as a function of the course of the lesion.
Triacetyloleandomycin and josamycin, when administered to inbred Balb/c mice orally twice daily at a dose of 12.5 or 25 mg per kg over 3 days, were found to increase barbiturate sleeping time significantly. In contrast, erythromycin ethylsuccinate, erythromycin propionate, midecamycin and spiramycin were devoid of any such activity under the same conditions.
The effects of two selective histamine H2 receptor antagonists on delayed-type hypersensitivity to sheep red blood cells were studied in Balb/c mice. While cimetidine significantly enhanced DTH response when given from immunization to challenge via the intraperitoneal route (10-30 mg/kg twice daily), ranitidine (5-20 mg/kg) did not produce any effect. Both drugs proved ineffective on acquisition as well as expression of DTH. These results suggest that most immunopharmacological effects of cimetidine may not be mediated through histamine H2 receptors, but may possibly be mediated through its imidazole moeity.
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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