Biomedical subjects
Publications and source records attributed to L Roels.
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A total of 20 renal transplant patients with end-stage diabetic nephropathy entered a randomized controlled trial comparing preoperative, fractionated total lymphoid irradiation (TLI) (radiation dose, 20-30 Gy) with postoperative cyclosporin A (CsA). Both groups received postoperative low-dose methylprednisolone maintenance therapy. The 3-year patient and graft survival was similar for both groups (100% and 71% in the TLI and 75% and 75% in the CsA group, respectively). Rejection crises occurred significantly more frequently (P less than 0.01) in the TLI-treated recipients. The incidence of infectious or diabetic complications was not significantly different in both groups. It is concluded that TLI and CsA are both effective treatment modalities for cadaveric renal transplantation in diabetics; CsA, however, is superior in preventing rejection crises.
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.
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.
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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.
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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.