Influence of donor and recipient DRw6 status on outcome of cadaver kidney transplantation.
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Adult↗
Biomedical subjects
E Dupont
Publications and source records attributed to E Dupont.
[In vitro effects of 3 immunosuppressive drugs. Comparison of the effect of cyclosporin A, methylprednisolone and 6-mercaptopurine].
Several tests of cellular immunity representing in vitro correlates of early lymphocytes activation have been studied with 3 immunosuppressive drugs currently used in organ transplantation, 6-mercaptopurine, cyclosporin A and methylprednisolone. Despite its significant antiproliferative action, 6-mercaptopurine does not affect interleukin 2 production nor Ia antigen induction on lymphocytes after stimulation with phytohemagglutinin. In contrast, cyclosporin A and methylprednisolone strongly block this reaction. Both immuno-suppressive drugs disclose equivalent blocking action on all proliferative reactions with the exception of proliferation induced by phorbol myristate acetate which is resistant to cyclosporin A but inhibited by methylprednisolone.
Antibodies, Monoclonal↗
Differential in vitro actions of cyclosporin, methylprednisolone, and 6-mercaptopurine: implications for drugs' influence on lymphocyte activation mechanisms.
In vitro effects of three immunosuppressive drugs, cyclosporin, methylprednisolone, and 6-mercaptopurine (the active moiety of azathioprine), have been assessed by various proliferative assays including mixed lymphocyte reaction (MLR), concanavalin A (Con A), OKT3 monoclonal antibody (MoAb), phorbol myristate acetate (PMA), and A23187 ionophore-induced mitogenesis. The influence of these drugs on the capacity to produce interleukin-2 (IL-2) after phytohemagglutinin (PHA) induction has also been evaluated. Depending upon the nature of the stimulus used, differences were found among the three immunosuppressive drugs, suggesting that different T-cell activation mechanisms are involved. The response to alloantigens (MLR) or to mitogens (Con A and OKT3 MoAb) resulted in significant inhibition by all three immunosuppressive agents, although 6-mercaptopurine was somewhat less potent at the pharmacological concentration of 0.1 microgram/ml. When PMA (which activates cells through protein kinase C) and A23187 ionophore (which enhances Ca2+ influx into the cytoplasm through membrane channels) were used, dissociations were observed, suggesting that drugs act differentially on early stages of T-cell activation. Inhibition of PMA-induced activation by cyclosporin was very limited in contrast to the potent effect of methylprednisolone. The latter drug could thus preferentially affect an activation step involving the PMA receptor. Furthermore, the inhibitory influence of methylprednisolone on A23187 ionophore-induced proliferation was equivalent to that of cyclosporin, while 6-mercaptopurine had no effect except at the high concentration of 1 microgram/ml in which direct inhibition of DNA replication is probably involved. IL-2 production induced by PHA was strongly blocked by methylprednisolone and cyclosporin but not by 6-mercaptopurine, at least when a pharmacological concentration was used. In view of the relative independence of ionophore-induced activation from the influence of IL-2, this response could be linked to the intrinsic mechanism of antiproliferative activity of immunosuppressive drugs which probably act mostly at the level of IL-2 production. These results also provide a cellular approach to the synergies between immunosuppressive drugs. Most of the tests are more strongly affected by cyclosporin than by 6-mercaptopurine, probably explaining the potent steroid-sparing effect of cyclosporin.
Cyclosporins↗
Factors involved in decreased detection of class II histocompatibility antigens on blood mononuclear cells from transplanted patients receiving immunosuppressive drugs.
Class II histocompatibility antigens were assessed by complement-dependent cytotoxicity on B enriched mononuclear cells and on purified monocytes isolated from the peripheral blood of renal patients before and after transplantation. After transplantation, a significant decrease of detection of DR alloantigens (cytotoxicity score before transplantation 3 +/- 0.1; after transplantation 0.95 +/- 0.1; p less than 0.001) was found. A similar defect was observed both on B enriched frozen cells and on purified monocytes isolated during the post-transplant period. Nevertheless, antigens could be adequately detected by a sensitive microabsorption method and by a procedure involving preincubation of mononuclear cells at 37 degrees C for 3 h followed by B cells enrichment by rosetting. The 37 degrees C induced reexpression could be inhibited by 10 micrograms/ml cycloheximide and by 50 microM monensin. No difference was found in the magnitude either of decreased expression or of temperature-induced reexpression between patients treated by CyS-Pred and those receiving Aza-Pred. It is concluded that transplanted recipients disclose a reversible defect of the expression of class II histocompatibility antigens probably related to perturbation of various steps of intracellular biosynthesis and traffic of these molecules.
Antibodies, Monoclonal↗
Mesulergine in early Parkinson's disease: a double blind controlled trial.
The efficacy and tolerance of treatment with an 8-alpha-amino-ergoline derivative CU32-o85, Mesulergine, were compared with levodopa/benserazide (Madopar) in a 3 month double-blind controlled trial in 31 patients with Parkinson's disease, not previously treated with levodopa. The two treatments were equally well tolerated, and neither dyskinesias nor dose-related fluctuations developed. In 90% of the patients treated with Mesulergine, Parkinsonian symptoms improved, and at the dose given the overall therapeutical response was two-thirds that of levodopa. During further 9 months of open study the beneficial effect was maintained equally well in both groups. Compared with other dopamine agonists Mesulergine has a considerable antiparkinsonian effect. Unfortunately, further clinical evaluation of the compound recently has been stopped owing to sex and species specific histological alterations in rats. It is suggested that Mesulergine derivatives might well be of value in future treatment of early Parkinson's disease and of late incompensated stages.
Aged↗
Impairment of phagocyte oxidative metabolism in hemodialyzed patients with iron overload.
In order to study the influence of iron overload on the polymorphonuclear leucocyte (PMN) metabolism of patients on chronic hemodialysis, generation of superoxide anion (O2-) by PMN in whole blood was compared in two groups of hemodialyzed patients: group A consisted of twenty-one individuals with serum ferritin levels above 1000 ng/ml and group B of nineteen individuals with serum ferritin levels below 1000 ng/ml. Whereas basal production of O2- was similar in the two groups (6.3 +/- 4.6 vs 11.5 +/- 8.3 nmoles O2- 10(6) granulocytes-1 15 min-1) (mean +/- s.e.m.), PMN response to opsonized zymosan was significantly lower in group A as compared with group B (86.5 +/- 6.3 vs 120.4 +/- 8.2 nmoles O2- 10(6) granulocytes-1 15 min-1) (p less than 0.01). Superoxide anion generation induced by the dialysis procedure was reduced in eight patients from group A (89.2 +/- 32.1) as compared with eight patients from group B (374.3 +/- 100.0 nmoles O2- 10(6) granulocytes-1 15 min-1) (p less than 0.05). These data suggest that iron overload may be involved in the impairment of neutrophil phagocytosis in patients on chronic hemodialysis.
Blood Transfusion↗
Prevalences of CT-detected calcification in the basal ganglia in idiopathic hypoparathyroidism and pseudohypoparathyroidism.
Sixteen patients with idiopathic hypoparathyroidism (IHP) and eight patients with pseudohypoparathyroidism (PHP) were examined by CT scan of the brain. Calcification in the basal ganglia was observed in 11 patients with IHP (69%) and in all eight patients with PHP. Of the 19 patients with basal ganglia calcification, nine had calcification in the cerebral cortex (47%), and four had calcification in the cerebellum (21%). Observation of basal ganglia calcification on CT gave rise to suspicion of IHP or PHP in three patients (12%). The remaining patients were examined at varying time after diagnosis. Since arrest in growth of calcification after institution of treatment has never been proven, the reported prevalences of calcification may not be valid to the situation at the time of diagnosis.
Adolescent↗
Peroneal motor nerve conduction velocity in diabetic children and adolescents. Relationships to metabolic control, HLA-DR antigens, retinopathy, and EEG.
To investigate incipient diabetic neuropathy, peroneal motor nerve conduction velocity (PMNCV) was measured in 61 diabetic children and adolescents whose type 1 diabetes became clinically apparent before the age of 14 years. PMNCV in diabetic patients (48.3 +/- 5.6 m/s) was significantly lower than in controls (56.5 +/- 5.5 m/s), 23 diabetics (36%) having a value more than 2 SD below the mean for normals. There was a highly significant negative correlation between PMNCV and HbA1 levels concomitant with PMNCV measurement or mean annual HbA1 concentrations preceding PMNCV. The relationship between PMNCV and the clinical score of diabetic control since the onset of the disease was also significant. Age, duration of diabetes and HLR-DR antigens were unrelated to PMNCV. EEG abnormalities and retinopathy, whose pathogenesis is different, were not necessarily associated with subclinical neuropathy. Being easy and sensitive, PMNCV determination provides the paediatric diabetologist and the patient himself with an important motivation to improve diabetic control.
Adolescent↗
Influence of in vivo immunosuppressive drugs on production of lymphokines.
The influence in vivo of immunosuppressive drugs (cyclosporine, azathioprine, and corticosteroids) on the production of various lymphokines (alpha and gamma interferon, interleukin 2), both in organ transplant recipients and in normal volunteers taking 100 mg hydrocortisone orally has been studied. To avoid interference with the rejection process or viral infection, patients were studied in a steady state with low maintenance immunosuppression consisting of prednisolone combined with azathioprine or with cyclosporine. In patients treated with both drug regimens, significant depression of production of the three lymphokines was found. Normal volunteers challenged with 100 mg hydrocortisone showed inhibition of production of interleukin 2 and alpha and gamma interferon in 4 hr, a time corresponding to the nadir of T cell lymphopenia, affecting the OKT4 subset preferentially. The percentage of OKT8 cells remained unchanged. Percentages of large granular lymphocytes increased, but their absolute number was not significantly modified. Changes in lymphocyte markers were fully reversible after 24 hr, but interleukin 2 production remained markedly depressed, showing that the redistribution patterns induced by corticosteroids on lymphocyte subsets may be dissociated from functional consequences.
Adrenal Cortex Hormones↗
Progabide in the treatment of hyperkinetic extrapyramidal movement disorders.
The ability of the selective GABA-receptor agonist, progabide, to suppress abnormal involuntary movements was evaluated in a preliminary open pilot study. 17 patients, 10 males and 7 females, aged 10-78 years, with hyperkinetic movement disorders were included in the study. Daily doses of progabide ranged from 900 to 3600 mg (median 2400 mg) corresponding to 14-45 mg/kg (median 45 mg/kg), while the duration of treatment varied from 2 to 52 weeks. Improvement, with a reduction of involuntary movements exceeding 25%, occurred in two of four patients with Gilles de la Tourette's syndrome, and in two of three patients with postanoxic intention myoclonus, while no consistent beneficial effects were registered in ten patients with Huntington's chorea, postanoxic choreoathetosis, torsion dystonia, tardive dyskinesia, action tremor, essential myoclonus, or oro-branchio-respiratory myoclonus.
Adolescent↗
[Chronic cirrhogenic hepatitis caused by amineptin (Survector)?].
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Antidepressive Agents, Tricyclic↗
Deficient natural killer function in patients receiving immunosuppressive drugs: analysis at the cellular level.
Renal transplant recipients receiving low maintenance immunosuppression (azathioprine, 2 mg/kg/day, and prednisolone, 10 mg/day), tolerating their transplants well, and without viral infection disclose a profound depression of NK activity as assessed by 51Cr-release assay. By combining the analysis of the different steps of cytolysis with the agarose single-effector assays and the estimation of circulating large granular lymphocytes (LGL), the defect is shown to be due to a significant decrease of the number of NK cells capable of binding (% target-binding cells 2.0 +/- 0.3 versus 5.7 +/- 0.7 in normals, P less than 0.001) and killing (% cytotoxic target-binding cells 12.4 +/- 1.9 versus 22.0 +/- 0.5 in normals, P less than 0.001) of targets. There is also a significant reduction (P less than 0.001) of both percentages (1.0 +/- 0.2 versus 3.3 +/- 0.4 in normals) and absolute values (9.8 +/- 2.4 versus 62.3 +/- 8.0/microliters in normals) of LGL. These observations indicate that depressed NK activity is due mostly to depletion of NK cells. Functional impairment of NK cells can also be involved. Lack of direct in vitro effects of drugs (6-mercaptopurine, hydrocortisone, and methylprednisolone) at concentrations likely to be reached in vivo during treatments and relative resistance of NK activity after in vivo steroid administration suggest that immunosuppressive drugs act at the precursor cell level or on regulatory mechanisms. Despite functional integrity of two suppressor cell systems of allogeneic NK activity (suppression induced by preculture of lymphocytes with Con A and suppressor granulocytes) in immunosuppressed patients, tested on normal NK cells, NK cells of immunosuppressed patients did not disclose greater susceptibility to Con A-induced suppression. This analysis indicates that the depletion phenomenon is probably a major mechanism in NK depression of patients receiving immunosuppressive drugs.
Azathioprine↗
Glucocorticosteroids and organ transplantation.
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Antibody Formation↗
Parkinson's disease and benign essential tremor: somatostatin-like immunoreactivity in the cerebrospinal fluid.
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Adult↗
Depressed natural killer function in transplant recipients: an analysis.
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Azathioprine↗
Familial association of schizophrenia and ankylosing spondylitis.
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Adult↗
A simple classification of the risk in cardiac surgery.
A new risk classification for patients undergoing cardiac surgery has been used for the last two years by the anaesthesiologists of the Montreal Heart Institute. The following factors known to be associated with a greater operative morbidity and mortality were selected: (1) poor left ventricular function, (2) congestive heart failure, (3) unstable angina or recent (less than 6 weeks) myocardial infarction, (4) age over 65 years, (5) severe obesity (Body Mass Index greater than 30), (6) reoperation, (7) emergency surgery, (8) other significant or uncontrolled systemic disturbances. Patients with none of the above factors were classified as normal risks; those presenting with one of those selected factors were classified as increased risks, and those with more than one factor were said to carry a high risk. In a prospective study of 500 consecutive open-heart surgery patients classified according to this method, we found that the operated population at normal risk (50 per cent of cases) had a mortality of 0.4 per cent, the patient group with increased risk (32 per cent of cases) had a mortality of 3.1 per cent, and the high risk group (18 per cent of cases) had a 12.2 per cent mortality. Furthermore, 50 deaths following open-heart surgery were assessed retrospectively using the classification; 58 per cent of these patients were classified as high risk, 34 per cent had an increased risk, and only eight per cent were found to be in the normal risk group. Thus, this new risk classification has proven to be a reliable and useful tool for preoperative assessment of patients undergoing open-heart surgery and for teaching purposes.
Age Factors↗
The active rosette mixed-lymphocyte reaction: an early marker of lymphocyte activation linked to HLA-D-DR differences.
A new approach to rapidly determine human mixed-lymphocyte culture (MLC) is presented. It is based on the identification of an early increase in the percentages of active T rosettes (TEa) in the MLC tubes. Active T rosettes represent a subset of T cells with high-avidity receptors for sheep red blood cells. All subjects tested had a full determination of their HLA-A, -B,-C, and -D-DR. The following observations were made: (1) When the MLC was done between 10 pairs of fully HLA-A,-B,-C, and -D-DR incompatible subjects, a highly significant increase (P less than 0.001) was observed after 2 hr of MLC in all pairs tested. (2) The same increase was observed in all 10 pairs of identical HLA-A,-B, and -C subjects but not sharing HLA-D-DR antigens. (3) In the cases of HLA-D-DR semi-identity, the increase in TEa percentages was less marked after 2 hr of culture (P less than 0.05) and delayed in time to reach the significance level of P less than 0.001 after 4 hr of culture. (4) In contrast, in the case of full HLA-D-DR identity, no increase in TEa percentages was observed at any time in the culture (2, 4, and 24 hr and 4 days) in nine pairs of subjects tested (two pairs of identical twins). In conclusion, these results indicate that the active T rosette MLC is a rapid approach (2 hr) to evaluate HLA-D-DR differences without influence by HLA-A,-B, or -C. As such it is an early marker for HLA-D-DR determination and may become a useful tool in the field of human histocompatibility to study the HLA-D-DR region.
HLA-DR Antigens↗