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Contact hypersensitivity to picryl chloride in the mouse is proposed as a valuable tool for the in vivo immunotoxicological testing of new compounds. Reproducibility was found to be excellent. Results obtained in the present work with chlorpromazine, cyclophosphamide, diazepam, haloperidol, hydrocortisone, promethazine and lead acetate, nickel chloride and selenium were similar to those previously reported regarding the effects of these compounds on cell-mediated immunity.

This study represents the third stage of a personal study on the long term fate of reconstruction and arterial restoration materials presented to the Academie de Chirurgie. 79 explanted prostheses were studied. First of all by an in depth histological study (8 cases selected from 70 reinterventions carried out before 1980), and then by a more complete protocol: scanning electron microscopy, resistance testing, programmed differential calorimetry, X-ray diffraction and biochemical analysis (71 reinterventions carried out after 1980). Our findings agree with the studies of R. Guidoin. With the exception of structural manufacturing defects or defects related to surgical manipulation, mechanical fatigue in a Dacron (PET) arterial prosthesis is inevitable: on average by the 7th to 10th year, a prosthesis looses one half of its mechanical resistance. The covering tissue, like that of the external capsule, which has poor mechanical properties, cannot compensate for prosthetic deterioration which may be considered to be complete by the 25th year. Knitted arterial prostheses, especially aortic, more rapidly undergo dilatation than woven prostheses which are much more resistant. On the other hand, the poor compliance of the latter compared with the recipient artery, perhaps favorises late anastomotic rupture. At internal capsule or pseudo-intimal level, endothelium is never present, but rather there is a permanent turnover with a variable time course, the mechanisms of which are poorly understood (role of prostaglandins?). Rather than a neo-artery, the vascular surgeon is only capable of producing an imperfect arterial tube, fragile from many points of view, and having an evolution which remains poorly understood.

Extrinsic local constraints, realised on dogs aorta are responsible for parietal lesions in the form of thickening of the arterial wall. Histological changes in the intima and media are characteristic of processes of degeneration destruction and cellular regeneration, superposed on sub-endothelial proliferation accompained by partial or total destruction of endothelial cells in the intimal layer. In addition to histological changes, there were perturbation in enzymatic activities of glycosyltransferases responsible for macromolecular constructions in the intima. Microsomic enzymes studied were: N-acetyl-glucosaminyl-transferase, sialyl-transferase and N-acetyl-galactosaminyl-transferase, and two glycosyl-transferases located in the soluble cytoplasmic phase: fucosyl and xylosyl-transferase. The changes observed were different according to the position of the sugars in the glycoprotein chains. For example the variation of fucosyl-transferase activity is significant: it disappears in group where the sialyl-transferase activity is enhanced. The transfer of xylose is decreased. Finally, changes observed in hexosaminyl-transferase activities were parallel.

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.

To test the hypothesis that hepatic drug metabolism affected the pharmacokinetics of antipyrine, 12 persons who had received vaccination against influenza were given antipyrine on the fourth day following. Plasma antipyrine was assayed from venous blood samples taken 5, 11 and 24 h later. The results indicate that the immunization procedure transiently increased the hepatic drug metabolizing enzyme activity against antipyrine.

The object of this work was to show that here exists after contact with foreign substances, a construction of protein, glycoprotein and mucopolysaccharide macromolecules at the level of the intima of the great vessels. Woven Dacron prostheses have been implanted in the arterial circulation of dogs (on the subrenal abdominal aorta). After removal of vascular segments, we carried out a subcellular fractioning, controlled and studied in an acellular system in vitro the activity of the glycosyltransferases implied in the construction of glycan chains of glyccproteins. The results are discussed in relation to the duration of implantation of the prosthesis. The modifications observed differ according to the position of the sugars in the glycan chains, in particular as far as sialic acid is concerned, and lead to an interpretation of the mechanism of endovascular reactions when faced with foreign material.

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.

The effect of levomepromazine on sinusal automaticity, myocardial excitability and auriculoventricular conduction have been studied in dogs by measuring the spontaneous heart rate, the effective refractory period of the conduction system, the time of auriculonodal and infrahisian conduction. Chloralose-anaesthetized dogs were administered 5 mg/kg levomepromazine via IV route and 10 mg/kg one hour later. While sinusal automaticity is never altered, the other parameters studied were modified only when high doses were used. Therefore these quinidine-like effects are very unlikely to come up even following suicidal massive ingestion of levomepromazine.

Nelson's agarose technique for the in vitro measurement of leukocyte chemotaxis proved to be well suited in the context of pharmaco-toxicological testings, despite several discrepancies in the literature, probably due to varied incubation conditions. Thus, doxycycline (25 micrograms/ml) when added to both the leukocyte suspension and the agarose was shown to exert a significantly more pronounced depressant effect. Using these conditions of improved sensitivity, three fluoroquinolones, i.e. norfloxacin, ofloxacin and pefloxacin (2, 10 or 25 micrograms/ml) failed to depress chemotaxis markedly.

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.

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.

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.

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 de-granulation (immediate hypersensitivity) or on contact hypersensitivity.

Pentobarbital-induced sleeping time was found to be significantly prolonged in mice within at least 4 days following either whooping cough, tetanus, rubella or poliomyelitis vaccination. By contrast, barbital-induced sleeping time remained unaffected, These findings provide further evidence of a correlation between inhibition of liver drug metabolizing enzymes and stimulation of the immune response.

Experimental autogenous grafts were made on adult Wistar rats using microvascular techniques. 3 months postoperatively, the grafts were controlled by angiography and by histopathological examination. We obtained a total patency rate of 52.7% and we observed that failure of the grafting can be explained by progressive hypertrophy of the walls of the vessels inducing thrombosis.

The authors report 13 cases of aneurysm of the abdominal aorta and common iliac arteries similar to those described by Leriche. The main morphological abnormality was major dystrophy involving the media, giving a special pathological appearance to these structures, long considered a mere morphological anomaly. In this part of the arterial system at least, they seem to evolve towards aneurysm and rupture (thin-walled aneurysm). This course requires echotomographic supervision of cases not submitted to immediate surgery, owing to the widespread nature of the process and the fact that some lesions resemble large arteries rather than aneurysms. The classic surgical technique of aortic and iliac aneurysms should often also include special technical devices. First, unilateral by-pass operation before the resection stage, and secondly aortic suture on a prosthesis to avoid tearing the arterial wall which is affected by media-spongiosis. The ten cases operated here all had a favourable course with a follow-up period of 1 to 9 years.

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.

1. In order to confirm the potential anti-anaphylactic properties of verapamil, the effects of this calcium antagonist were assessed on several experimental models: anaphylactic shock in mice, passive cutaneous anaphylaxis in Rats, and degranulation of Rat peritoneal mast cells. 2. At a dose of 5 mg/kg IP, half-an-hour before challenge, verapamil decreased systemic anaphylaxis-induced lethality significantly. On the reverse, in the same conditions, it was unable to inhibit passive cutaneous anaphylaxis at 0.1-0.5-1 or 10 mg/kg; it did even increase it at a dose of 5 mg/kg IP over the last 3 days. However, specific degranulation of rat peritoneal mast cells was significantly decreased after in vitro incubation with verapamil (0.25 and 1.25 micrograms/ml or after pretreatment with 5 mg/kg/day over 3 days). 3. These early results confirm the hypothesis of verapamil anti-anaphylactic properties whose consequences warrant further investigation.

Evidence suggests that stimulation of the immune response may be associated with impairment of hepatic drug metabolism. Antipyrine kinetics has therefore been determined in 12 patients on the fourth day following tetanus vaccination. Under these conditions, antipyrine plasma half-life was found to be 14.8 h. Despite the lack of control over antipyrine kinetics, these preliminary results indicate that tetanus vaccination is likely to impair the antipyrine metabolism.