Crohn's disease of the vulva.
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Biomedical subjects
Publications and source records attributed to D Millar.
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Niridazole, an antischistosomal agent, was given to renal transplant recipients in addition to azathioprine and prednisolone, as there is experimental evidence that this combination of drugs is highly immunosuppressive. Sera obtained from kidney-graft recipients during the first two weeks after transplantation were examined for their ability to inhibit the one-way mixed lymphocyte reaction (MLR). Sera from seven patients receiving azathioprine, prednisolone, and niridazole (triple-drug treatment), five patients receiving azathioprine and prednisolone, and two other patients treated with niridazole alone for schistosomiasis produced MLR inhibition by comparison with pretreatment (control) sera.A mean of 78% inhibition was observed with sera taken after one day's treatment with the three-drug combination, whereas this level of in-vitro immunosuppression occurred only after eight days of treatment with azathioprine and prednisolone. Niridazole alone produced an effect similar to azathioprine and prednisolone. Concentrated dialysate of urine from a patient receiving triple-drug treatment not only inhibited the MLR but also significantly prolonged the survival of heterotopic heart allografts in rats, whereas dialysate from the same patient after niridazole had been stopped gave less MLR inhibition and failed to prolong heart allograft survival.Since niridazole thus increased the in-vitro and in-vivo immunosuppressive action of azathioprine and prednisolone, we suggest that this triple-drug combination might be useful for preventing early acute kidney graft rejection.
The immunosuppressive properties of niridazole, an antihelminthic drug, have been investigated in rats. When given orally in a dose of 50 mg/kg, it extended the median survival of cardiac allografts from 7 to 20 days. The immunosuppressive effect was not increased by giving either azathioprine or prednisolone concurrently but when all three drugs were combined, immunosuppression was profound and only two of eight grafts were rejected. Drug combinations incorporating niridazole at a lower dosage or for a shorter period were less effective, and azathioprine and prednisolone on their own or used together prolonged graft survival only marginally in this model. It is concluded that niridazole is a powerful immunosuppressive drug in this species and a synergistic effect can be obtained by using it in combination with azathioprine and prednisolone.
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The immunosuppressive properties of niridazole, an antihelminthic drug, have been investigated in rats. When given orally at a dosage of 50 mg/kg it extended the median survival of cardiac allografts from 7 to 20 days. The immunosuppressive effect was not increased by giving either azathioprine or prednisolone concurrently, but when all three drugs were combined the immunosuppression was profound, and only 2 of 8 grafts were rejected. Drug combinations incorporating niridazole at a lower dosage or for a shorter period were less effective, and azathioprine and prednisolone on their own or together prolonged graft survival only marginally in this model.
The immune status of 35 patients with renal failure was studied shortly after they had commenced treatment by chronic haemodialysis to see if a group with poor immunological responses could be identified. Of 27 patients who were unimmunised to start with, only two developed lymphocytoxic antibodies after a year of treatment. The routine immunological tests that were carried out on these patients failed to predict which of them would develop antibodies, and the values that were obtained for the group of cytotoxic negative patients were no different from those obtained for the two patients who became immunised and six others who had previously rejected a kidney transplant. By using a new test that measured cellular immunity to rat antigens, eight patients could be identified as "poor responders." These individuals had in addition failed to develop cytotoxic antibodies during dialysis, had serum IgG levels that were significantly lower than normal, and were uniformly unresponsive to purified protein derivative. This group of patients might be a favoruable one to transplant.
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A test has been devised with the object of assaying immune responsiveness in normal and immunodepressed persons. It has been based on the graft-versus-host model of Ford et al. (Transplantation 10: 258, 1970) and employs rat antigens as the immunological stimuli. Peripheral blood lymphocytes were injected into the hind feet of young Wistar rats, and 7 days later the popliteal lymph nodes were removed and weighed. It was found that the unwanted host-versus-graft activity could be suppressed in the rats by total body irradiation. Inactivated lymphocytes were injected into the right hind foot as a control and the result was expressed as a ratio: weight of left node to weight of right node. Lymphocytes from 45 healthy individuals were examined in this way. The response was readily suppressed by administering daily injections of steroid or antilymphocyte globulin to the rats, but was not influenced by the presence or absence of antirat antibodies in these individuals.
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