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Biomedical subjects

P Michielsen

Publications and source records attributed to P Michielsen.

At least 73 records · Page 4Linked to original sources
PubMed1988

Treatment of murine lupus nephritis with cyclophosphamide or total lymphoid irradiation.

Untreated 9 to 11 month-old, female NZB/W F1 mice all died within six weeks (wks) after the occurrence of nephrotic range proteinuria (greater than or equal to 3 g/liter). Significant prolonged survival could be obtained in similar groups of animals either by weekly i.v. pulses of cyclophosphamide (CY, 25 mg/kg, 40% survival 20 wks after start of treatment) or by administering total lymphoid irradiation (TLI, 17 daily fractions of 2 Gy, 70% survival at 20 wks). All surviving animals in both groups showed remission of the nephrotic range proteinuria. In all treated mice, light microscopy examination of the kidneys revealed a decrease of inflammation and a stabilization of proliferation and sclerosis, yet immunofluorescence for IgM, IgG and C3 was not significantly altered. The better survival of the TLI- as compared to the CY-treated mice (P less than 0.001) was due to a lower incidence of lymphomas or viral infections. IgG anti-DNA auto-antibodies were significantly lowered by CY but not by TLI treatment. It is concluded that CY pulse therapy and TLI are both efficient treatment modalities for high grade lupus like NZB/W disease. In this model TLI is safer than CY when used in a dose regimen of 25 mg/kg/wk and interferes with the course of the disease without lowering the IgG anti-DNA antibodies.

Animals↗
PubMed1988

Shortage of kidneys, a solvable problem? The Leuven experience. Leuven Collaborative Group for Transplantation.

Our 10-year experience with the LCGT indicates that close collaboration of nephrologists from peripheral centers for the long-term follow-up of transplanted patients presented no obstacles to excellent patient and graft survival rates. At the same time, "decentralization" greatly increased the motivation of collaborating centers to participate in organ procurement. In addition, the introduction of an "opting out" law provided spectacular stimulation for collaborating center participation. For the first time in many years, the number of transplants was higher than the number of new candidates registered on the waiting list.

Actuarial Analysis↗
PubMed1987

Immunological and clinical observations in diabetic kidney graft recipients pretreated with total-lymphoid irradiation.

In a feasibility study, twenty patients with end-stage diabetic nephropathy were treated with fractionated total-lymphoid irradiation (TLI, mean dose 25 Gy), before transplantation of a first cadaveric kidney. During radiotherapy, only one patient had a serious side effect (bone marrow depression). After transplantation four patients died (one of a myocardial infarction, one of ketoacidosis, and two of infections occurring during treatment of rejection crises). One graft was lost because of chronic rejection. The other 15 patients have a functioning graft (mean follow-up 24 months) and receive low-dose prednisone alone (less than 10 mg/day, n = 11) or in conjunction with cyclosporine (n = 4) as maintenance immunosuppressive therapy. A favorable clinical outcome after TLI (no, or only one, steroid-sensitive rejection crisis) was significantly correlated with a high pre-TLI helper/suppressor lymphocyte ratio, a short interval between TLI and the time of transplantation, and the occurrence of functional suppressor cells early after TLI. The most striking immunological changes provoked by TLI consisted of a long-term depression of the mixed lymphocyte reaction and of the phytohemagglutinin, and Concanavalin A or pokeweed-mitogen-induced blastogenesis. A rapid and complete recovery of the natural killer cell activity was observed after TLI. A permanent inversion of the OKT4+ (T helper/inducer) over OKT8+ (T suppressor/cytotoxic) lymphocyte ratio was provoked by a decrease of the OTK4+ subpopulation, together with a supranormal recovery of the OKT8+ lymphocytes. A majority of the latter lymphocytes did also express the Leu 7 and the Leu 15 phenotype.

Adult↗
PubMed1986

Identification of a major Leu 7/OKT 8 positive T-lymphocyte subpopulation in renal transplant patients pre-treated with total lymphoid irradiation.

When pretreated with total lymphoid irradiation, renal allograft recipients have an increased percentage of OKT 8 positive (cytotoxic/suppressor) T cells among their peripheral blood T lymphocytes (PBL) (56 +/- 21%) and also of Leu 7 PBL (47 +/- 18%). In contrast, transplant patients treated with azathioprine or cyclosporine A have percentages of OKT 8 and Leu 7 positive PBL, similar to control persons (respectively 29 +/- 13, 33 +/- 10, 30 +/- 10 for the OKT 8+ cells and 8 +/- 7, 11 +/- 6 and 15 +/- 9 for the Leu 7+ cells). After purification, about two thirds (70%) of the OKT 8 positive, OKT 3 positive, T lymphocytes of TLI patients were shown to co-express the Leu 7 antigen. It is concluded that after TLI, an increase of OKT 3+, OKT 8+ and Leu 7+ lymphocytes takes place, a subset previously described to be present in low numbers in control persons and whose function is still unclear. This expansion after TLI should allow functional identification of this subset and might contribute to the understanding of the immunosuppressive effects of TLI.

Antibodies, Monoclonal↗
PubMed1985

Thromboembolic complications and haemostatic changes in cyclosporin-treated cadaveric kidney allograft recipients.

The incidence of thromboembolic complications was compared retrospectively in 90 cadaveric kidney allograft recipients treated with cyclosporin and low-dose steroids and the same number of cadaveric kidney allograft recipients treated with azathioprine, antilymphocyte globulin, and high-dose steroids. In the cyclosporin group, 17 thromboembolic complications occurred in 13 patients: 10 pulmonary emboli, 1 renal vein thrombosis, 3 deep vein thromboses, and 3 haemorrhoidal thromboses. In the azathioprine group, the only thromboembolic complication was 1 episode of superficial thrombophlebitis. Haemostatic tests in cyclosporin-treated and azathioprine-treated patients and normal subjects (10 in each group) showed increased concentrations of factor VIII C, fibrinogen, antithrombin III, and protein C in the cyclosporin-treated patients. Adenosine-5'-diphosphate-induced platelet aggregation was also significantly enhanced in the cyclosporin group. The effect of cyclosporin on haemostasis may predispose to thromboembolic complications.

Azathioprine↗
PubMed1985

Kidney allograft tolerance in diabetic patients after total lymphoid irradiation (TLI).

The value of total lymphoid irradiation (TLI) combined with low dose prednisone as sole immunosuppressive regimen in renal allograft transplantation in humans has been investigated. Seventeen patients with end-stage diabetic nephropathy received TLI to a cumulative dose of 20-30 Gy in fractions of 1 Gy. Cadaver kidneys were grafted as soon as they were available after completion of TLI. Low dose prednisone was given after transplantation. Profound and long-term immunosuppression has been achieved in all patients. Six patients live already more than one year (greater than 2 years in 3 of them) and 7 for less than one year with a functioning kidney graft. Two out of these 13 patients had repeated rejection episodes necessitating a supplementary immunosuppressive treatment with cyclosporine A. One patient returned to chronic hemodialysis 11 months after transplantation and died of pericardial tamponade one month later. One patient had severe acute rejection for which cyclosporine A was administered; he died of septic shock as a consequence of immune deficiency a month later. The other two patients succumbed to other causes (myocardial infarction and hyperglycemia). The amount of steroids and azathioprine administered to these patients was substantially lower than in the case of conventional immunosuppression. The preliminary results are thus encouraging. However, the treatment schedule as used in the present study can not yet be considered as optimal since the majority of patients still had one or more rejection episodes. Further investigations are warranted. The optimal dose of radiation, the importance of the interval between TLI and organ transplantation, the influence of splenectomy on the immunity, etc., are still to be assessed.

Adult↗