Graft pretreatment with cyclosporin A. Long-term study including four trials in one and a half years.

Four trials were conducted to establish whether Cyclosporin A (Cy A) could be used as a graft pretreatment to prolong the graft function and animal survival of kidneys transplanted into bilaterally nephrectomized mongrel dogs. The first nonrandomized trial analyzed various parameters such as concentration, flush temperatures, effect of reflushing, and the need for subsequent minimal immunosuppression. By analyzing data from the ten groups in this trial, we established that 50 mg/l Cy A could be flushed successfully at either 4 C or 25 C without nephrotoxic effects. This concentration was found to prolong graft function and animal survival in some animals greater than 100 days. Reflushing the kidney after primary graft pretreatment with Cy A did not entirely remove the immunosuppressive effect of the drug as significant prolongation of survival also was observed in this group. In addition, minimal immunosuppression with azathioprine was necessary to observe a delay in the onset of rejection and prolongation of animal survival when Cy A was used for graft pretreatment. Trials 2 and 4 compared the efficacy of the original batch that was obtained later. The effects observed in Trial 1 and reproduced in Trial 3, which were randomized and double blinded using the original batch, were not seen in either Trials 2 or 4. This may have been related to the amount of time that the Cy A was dissolved in ethanol prior to its use or the batch of Cy A utilized. These preliminary results indicate that Cy A, when used for graft pretreatment under certain conditions, can delay the onset of rejection and prolong animal survival of transplanted renal allograft recipients.

T lymphocytes bearing complement receptors in a patient with chronic lymphocytic leukaemia.

A patient is described who presented with a disease clinically resembling chronic lymphocytic leukaemia, characterized by generalized lymphadenopathy, pleural and peritoneal effusions, a blood lymphocyte count of 700,000/mul and failure to respond to conventional therapy. At least 95% of these cells formed rosettes with sheep erythrocytes (E) and with erythrocytes coated with 19S antibodies and complement (EAC). All of these cells bound rabbit anti-human thymocyte serum; this serum bound to 0--22% of the lymphocytes from twenty other patients with chronic lymphocytic leukaemia. These unusual cells did not bear surface immunoglobulin detectable by immunofluorescence. The clinical and cellular features of this malignancy are compared to previously reported cases of T cell chronic lymphocytic leukaemia. As this case illustrates, T-cell chronic lymphocytic leukaemia may present without skin lesions and may be a more aggressive disease than the more common B-cell neoplasm.

Idiopathic polyneuropathy associated with cytotoxic anti-neuroblastoma serum. IgG and IgM immunoglobulin studies.

Serums from six patients with progressive idiopathic acute or chronic polyneuropathy possessed a cytolytic activity against transformed mouse cholinergic or noncholinergic neuroblasts but not against transformed rat astrocytes. This activity was not qualitatively nor quantitatively present in serums from normal controls or from patients with a variety of other motor system disorders and other neurologic disorders. Fluorescein conjugated goat antihuman IgG and IgM monospecific immunoglubulins were used to characterize further the cytotoxic activity from patient serums and these studies suggested the presence of immunoglobulin G (IgG) and immunoglobulin M (IgM) directed against a cell surface neuroblastoma antigen. Cold reactive immunoglobulins of the IgG and IgM type were present in the serums of all six patients. A bioassay is described that may be helpful in evaluating other patients with progressive idiopathic polyneuropathies.