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J Descotes

Publications and source records attributed to J Descotes.

At least 19 recordsLinked to original sources
PubMed1992

[Diagnosis of bacterial infections on vascular prosthesis. Histological and microbiological analysis].

A retrospective study of 212 vascular graft failures, using different criteria of infection evidenced a relatively high incidence of infectious complications. Vascular graft infection was assessed on one of the following criteria: clinical infection, positive bacteriological and/or virological examination of the graft, presence of characterized micro-organisms and of microstructures 0.1 to 0.5 micron in size at the blood/prosthesis surface at scanning electron microscopy, and presence of foci of persistent polymorphonuclear cells and lymphocytes at histological microscopy. In the absence of overlapping between these criteria, the present results raise the question of the adequacy of conventional bacteriological sampling on explanted artificial surfaces.

Blood Vessel Prosthesis↗
PubMed1992

The popliteal lymph node assay: a tool for studying the mechanisms of drug-induced autoimmune disorders.

Whereas it is still impossible to predict the risk for organ-specific drug-induced autoimmune disorders in animals, a large body of evidence suggests that the popliteal lymph node assay (PLNA) in mice or rats is instrumental to predict systemic drug-induced autoimmune disorders. Metabolites may be involved instead of the parent molecules in a few instances as shown by studies using animals pretreated with enzyme inducers. Histological examination can help distinguish primary irritants, contact sensitizers and 'autoimmunogenic' compounds. That a Graft-vs-Host (GvH)-like mechanism may be involved was further substantiated by the finding that histological features of a positive PLNA response to, e.g. streptozotocin, were quite similar to those of a 'true' local GvH response. In addition, this model is expected to be useful to improve our understanding of the mechanism(s) involved in systemic autoimmune reactions by studying the profile of PLN lymphocyte subpopulations and of released cytokines.

Animals↗
PubMed1992

Activation of CD4+ and CD8+ lymphocyte subsets by streptozotocin in murine popliteal lymph node (PLN) test.

Time-related and dose-related popliteal lymph node (PLN) enlargement and lymphocyte subset alterations owing to subcutaneous (s.c.) injection of streptozotocin (STZ) into the foot pad were determined in (C57BL/6 x DBA/2)F1 [B6D2F1] mice. Early cell activation and time-related changes in T and B lymphocyte subsets were monitored during the onset of STZ-induced lymphoproliferative reaction by flow cytometry and immunophenotyping of lymphocyte subsets stained with a panel of monoclonal antibodies. Examination of cell size and chromatin decondensing for T and B cell subsets revealed differences in their activation profiles during the early phase of STZ-induced lymph node enlargement. The kinetics of the reaction showed initial activation and proliferation of CD4+ cells associated with accumulation of CD8+ and B cells. Subsequently CD8+ cells were activated and proliferated, but there was no evidence of early or late B cell activation as shown by the lack of increase in cell size or nuclear decondensation and the low and transient synthesis of immunoglobulins. The activation characteristics for CD4+ and CD8+ cell subsets in STZ-induced node enlargement were found to be analogous with T cell activation in acute allogeneic graft-versus-host (GVH) reaction in which the F1 recipient differed from the parent at both class I and II MHC loci. Our data support a central role for T cell activation in the induction of STZ-related PLN enlargement and suggest that recirculatory host B cells can play a major role in early node enlargement.

Animals↗
PubMed1992

Activation of CD4+ and CD8+ lymphocyte subsets by streptozotocin in the popliteal lymph node assay. II. Comparison with acute graft-vs-host reaction in H-2 incompatible F1 mouse hybrids.

Changes in lymphocyte subsets during an acute GVH reaction were compared to STZ-induced PLN response in mice. The GVH reaction was induced locally by sc injection of parental C57Bl/6 [B6] spleen cells into (C57Bl/6 x DBA/2) F1 footpad [B6D2F1]. Early cell activation and time-related changes in T- and B-lymphocyte subsets were monitored during the onset of the GVH reaction by flow cytometry and immunophenotyping. Examination of cell size and chromatin decondensing for T- and B-cell subsets showed differences in activation profile during the early phase of the GVH reaction. The present study provides direct evidence for early in vivo activation of both CD4+ and CD8+ T-cells. Our data confirm the central role of T-cell activation in the induction of a GVH reaction and suggest that recirculatory host B-cells can play an important role in early GVH node enlargement. Overall, our comparative analysis supports the concept of polyclonal T-cell activation for both STZ-related and GVH-induced lymphoproliferation. Chemicals-induced lymphoproliferation leading to autoimmune reactions is a challenging issue. A number of drugs and chemicals have been tested in the PLNA assay for lymphoproliferative potential. We previously reported the activation and proliferation of T-cell subsets following STZ injection into murine footpads. The STZ-induced PLN enlargement and proliferation characteristics of T- and B-cell subsets were postulated to be similar to those of an acute allogeneic GVHR. In the present study, a cytometric analysis of T- and B-cell subsets in PLNs was performed during an acute allogeneic GVHR, for comparison purposes. Such a reaction results in a massive node enlargement five to ten times that seen after stimulation with conventional antigens. Acute GVHR is believed to be a direct consequence of the high frequency of alloreactive donor T-cells inducing a massive proliferation of B-cells, almost exclusively of host origin, in GVHR nodes. It is now widely accepted that donor T-cells activated as the result of exposure to foreign MHC antigens in the recipient, secrete various cytokines which assist the host B-cells and bypass the normal B-T cell cooperation. Induction of an acute GVHR, as in the parental B6--->recipient B6D2F1 model, requires the injection of CD4+ and CD8+ donor T-cells into an F1 recipient that differs from the parent at both MHC class I and II loci.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

[Polyaneurysmal dystrophy (ectatic medial dystrophy)].

Polyaneurysmal dystrophy is a novel form of arteriopathy which specific clinical, angiographic, anatomic and surgical features which distinguish it clearly from multiple atheromasclerotic aneurysm. It should be considered to be a local, multifocal accentuation of megadolicho-arteries, which constitute the lesions during the early stages of the disorder (fairly general elongation of the elastic arteries, with thin walls and regular increase in the caliber and multiple tortuousness). Arterial angiography identifies polyaneurysmal dystrophy; in the context of a twisted and sinuous system of large arteries, multiple spindle-shaped aneurysms can be distinguished which are frequently bilateral and symmetrical. The usual sites are the trunks of the aortic group and internal carotid, the ileo-femoral trunks and terminal aorta. The progress of the disorder is characterized by the possibility of rupture or thrombosis (particularly in the subcrural territory). The treatment is always surgical. The indication for surgery is inevitable in cases of severe ectasia, but may be avoidable in extensive forms of megadolicho-arteries with no clearly defined aneurysm: annual ultrasound monitoring is then called for. The disorder is of constitutional origin (and totally unrelated to atherosclerosis). Delayed dilatation of the aneurysms is due to the hemodynamic forces brought to bear on the fragile walls over a life-time. Multiple aneurysms occur mainly between the ages of 50 and 70 years, with a predominance of aorto-ileac sites in men, even though these subjects do not show any general elastic dysplasia. Half of the 45 patient undergoing surgery were hypertensive.

Aneurysm↗
PubMed1992

Immunotoxicology of cadmium.

A number of investigations have suggested that cadmium may exert immunosuppressive effects in animals even though conflicting findings, due mainly to varying conditions of exposure, have been reported. Overall, cadmium has been shown to enhance humoral immune responses at low levels of exposure, whereas higher ones may result in either no effect or decreased antibody production. By contrast, cell-mediated immunity was more consistently shown to be depressed. Similarly, phagocytosis, natural killer cell activity and host resistance toward experimental infections were markedly impaired in most instances. Very few data are available regarding cadmium immunotoxicity in humans. Hypersensitivity reactions have so far not been described. No immune alterations were found to be associated with "chronic cadmium disease", whereas a depressed phagocytosis, the clinical relevance of which remains to be established, was recently documented in cadmium-exposed workers. Further investigations are therefore needed to determine how immunotoxic cadmium actually is and what health consequences are to be expected in occupationally or environmentally exposed humans.

Animals↗
PubMed1992

Acute poisonings with ethyle loflazepate, flunitrazepam, prazepam and triazolam in children.

Even though acute poisonings with benzodiazepines are extremely common, less is known of the clinical toxicity of recent derivatives, particularly in children. 1,989 cases involving ethyle loflazepate, flunitrazepam, prazepam or triazolam recorded at the Lyons Poison Center and due to 1 compound and associated with clinical symptoms were selected for study. Children less than 16-y of age accounted for 482 cases. Sleepiness, agitation and ataxia were significantly more frequent in the children. Hypotonia was seldom observed but was indicative of severe poisoning. The dangerous toxic dose of these compounds in children is suggested to be 0.78-0.90 mg ethyle loflazepate/kg, 0.26-0.29 mg flunitrazepam/kg, 7.80-9.00 mg prazepam/kg and 0.06-0.07 mg triazolam/kg. These results are in keeping with the relatively low acute toxicity of the older benzodiazepines.

Adolescent↗
PubMed1992

Popliteal lymph node assay as a tool to predict drug-induced GvH-like reactions.

The popliteal lymph node (PLN) assay was proposed to study a panel of drug-induced clinical manifestations, e.g. lupus syndrome, serum sickness-like disease, lymphadenopathy, scleroderma-like reaction, the mechanism of which was suggested as being similar to a graft-versus-host (GvH) reaction, hence the term GvH-like reaction. This assay can readily be performed in either the mouse or rat. The commonest endpoint is PLN weight, but cellularity and lymphocyte-phenotype analysis can also be determined. Experiments so far show that most drugs and chemicals known to induce such complications in man can be detected by the PLN assay and false-positive responses are extremely few. Interestingly, preliminary results indicate that cimetidine, an immuno-enhancing agent, can increase the response to phenytoin, a positive reference compound in the PLN assay. Thus, in addition to predicting those drugs with the capacity to induce GvH-like reactions and investigating the mechanism involved, the PLN assay may also prove useful in the pre-clinical assessment of immunomodulating agents.

Animals↗
PubMed1992

Immunotoxicology of immunomodulators.

Immunotoxicology is the study of the immune system as a target organ for the toxicity of drugs and chemicals. As immunotoxicologists focused most of their interest on immunosuppression, the toxic consequences of immunomodulation are less clearly established. However, a number of immunopharmacologically-mediated side-effects including influenza-like symptoms, exacerbation of underlying diseases, e.g. autoimmune diseases, increase in hypersensitivity reactions against unrelated antigens and inhibition of hepatic drug metabolism have been described and may be used as a basis for further safety evaluation. Current pre-clinical assessment of immunotoxicity is usually performed in the rat during sub-chronic testing. The relevance of these protocols as far as immunomodulators are concerned is unknown. Careful attention should be paid to safety pharmacology testing, e.g. cytokine release, effects on animal models of auto-immune and hypersensitivity reactions, and hepatic drug metabolism. The role of post-marketing drug surveillance should also be emphasized. Advances in our understanding of the mechanism(s) of immunomodulation together with the development of more active immunomodulators are expected to improve the current pre-clinical safety assessment of these compounds.

Adjuvants, Immunologic↗
PubMed1991

Human vascular graft failure and frequency of infection.

Among 212 vascular prostheses collected in a vascular explant retrieval program, 50 exhibited one or more criteria of graft infection i.e., (a) clinical evidence of graft infection, (b) positive bacteriological analyses of the graft, and (c) presence at the blood-prosthetic interface of characterized microorganisms. Whereas each of these criteria was noted respectively in 25, 26, and 20 cases, there was no complete overlapping among the three criteria, but their combination led us to consider 50 cases of infected vascular grafts among the 212 collected. These results, and the occurrence in two cases among six investigations for viral infection, suggest that extensive bacteriological investigations of vascular explants should be included in an implant retrieval program, and that infection may represent a high risk in graft failure.

Aneurysm↗
PubMed1991

Immunotoxicity of bis(tri-n-butyltin) oxide in the rat.

Previous studies in the rat have shown that bis(tri-n-butyltin) oxide (TBTO), used as a biocide, was immunotoxic at dose levels that did not affect other organs. In order to determine a no-effect level, weanling rats were treated for at least 28 consecutive days with TBTO at 0, 0.5, 2, 5, or 50 mg/kg of diet. Studies on clinical chemistry, hematology, pathology, and immune function, that is, plaque-forming cell (PFC) assay, delayed-type hypersensitivity (DTH) response, and the splenic clearance of Listeria monocytogenes, were performed at the end of treatment. No treatment-related effects were noted on clinical chemistry and hematology parameters and on PFC and DTH response, whereas thymic atrophy and impaired clearance of L. monocytogenes were noted only at a dietary concentration of 50 mg/kg. These results confirm the thymus as a target organ of TBTO immunotoxicity. Under the conditions of these experiments the dietary concentration of 5 mg/kg, equivalent to a dose of 0.5 mg/kg body weight, represents a no observed effect level (NOEL) for immunotoxicity in the Sprague-Dawley rat.

Administration, Oral↗
PubMed1991

Symptomatic bradycardia caused by mianserin at therapeutic doses.

An acute episode of symptomatic sinus bradycardia, occurred in a 50-year-old female patient after she had been given a single therapeutic dose of mianserin. Heart rate was corrected by atropine injection. Re-administration of mianserin resulted in the recurrence of bradycardia. Further examination showed no cardiac abnormalities. This case is the first report of conduction defect in a patient given therapeutic doses of mianserin.

Bradycardia↗
PubMed1991

Collective human food poisonings by clenbuterol residues in veal liver.

Twenty-two patients were reported to complain of tremor, headaches, tachycardia and dizziness 1-3 h after eating veal liver. As clinical symptoms were not suggestive of an infectious cause, the presence of veterinary drug residues was suspected. Clenbuterol, a beta 2-agonist, was being illegally used in cattle because of its anabolizing properties and may explain the observed effects. Assays of clenbuterol in samples of veal liver showed concentrations of 0.375 and 0.500 micrograms/g. To our knowledge, this is one of the first reports of clinical symptoms in humans associated with the consumption of veterinary drug residue-containing food.

Animals↗
PubMed1991

Study of an inhibitor of plasminogen activator (tranexamic acid) in the treatment of experimental osteoarthritis.

The effects of tranexamic acid, an inhibitor of plasminogen activator, were evaluated in a rabbit model of osteoarthritis induced by section of the knee joint anterior cruciate ligament. Prophylactic treatment administered intramuscularly thrice weekly for 12 or 24 weeks significantly reduced cartilage destructive lesions, increased cartilage hypertrophy but did not prevent changes in cartilage water and proteoglycan content. A suppression of synovial membrane stromelysin and collagenase activity was found while phospholipase A2 activity was unaffected.

Animals↗
PubMed1990

[The Dacron vascular prosthesis in men. Mechanical performance, lesions and molecular stability].

The causes of failure of vascular prostheses implanted in man were investigated by means of histological, ultrastructural and scanning electron microscopic techniques as well as mechanical performance and macromolecular structure studies. These investigations concerned 22 out of 212 explanted prostheses from about 10 vascular surgery departments, examined over a 3-year period. The changes observed in the mechanical properties of the explanted prostheses (2 to 75 per cent reduction of resistance to rupture) and the finding of broken fibers and migrating polyester particles were confirmed by the presence of structural alterations in the polymer with, in particular, diminution of its crystalline structure. No correlation was found between the occurrence of these lesions and the type of prosthesis used and/or the duration of implantation.

Blood Vessel Prosthesis↗