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Biomedical subjects

S Iwatsuki

Publications and source records attributed to S Iwatsuki.

At least 199 records · Page 11Linked to original sources

Long-term use of cyclosporine in liver recipients. Reduction of dosages in the first year to avoid nephrotoxicity.

Cyclosporine is a potent immunosuppressive drug, which has dose-related nephrotoxicity. In renal transplantation, the differentiation between rejection and toxicity is difficult and even with the aid of blood levels of the drug, it may be difficult to establish a chronic maintenance dose. Long-term survivors after liver transplantation can provide modes with which to establish maintenance doses, as these are dictated by nephrotoxicity in these patients. Twenty-nine liver transplant patients who survived one year or more were followed for changes in their cyclosporine doses. Daily oral cyclosporine dose, BUN, serum creatinine and bilirubin were monitored. The reductions in cyclosporine were dictated almost entirely by the findings of nephrotoxicity.

Adolescent↗

Cadaveric renal transplantation under cyclosporine-steroid therapy.

Ninety-seven cadaveric renal transplants were performed upon 96 patients during 1981. The one year patient mortality was 2.1 per cent. Seventy of the recipients were undergoing transplantation for the first time. Of these patients, 38 were treated with cyclosporine and steroids with a one year graft survival rate of 89.5 per cent. The other 32 primary recipients were treated with azathioprine and steroids with a one year graft survival rate of 50 per cent. The difference between the cyclosporine-steroid versus conventional therapy groups was significant. Cyclosporine and steroids also were used to treat 26 patients who underwent retransplantation with 27 cadaveric grafts. The one year graft survival time was 77.8 per cent; most of the graft losses were in presensitized patients. The results with retransplantation were twice as good as in historical control groups.

Adrenal Cortex Hormones↗

Liver and kidney transplantation in children receiving cyclosporin A and steroids.

The new immunosuppressive agent, cyclosporin A, was used with low doses of steroids to treat eight patients undergoing hepatic transplantation and three patients undergoing cadaveric renal transplantation. Seven of the eight liver recipients are well, including one who was given two livers. The three kidney recipients who had developed cytotoxic antibodies after previously rejecting grafts with conventional immunosuppressive therapy, have had good results despite conditions which usually preclude attempts at transplantation. The ability to control rejection effectively and safely without chronic high-dose steroid therapy may make the described therapeutic regimen valuable for pediatric recipients of whole organs.

Adolescent↗

99mTc-DTPA and 131I-hippuran findings in liver transplant recipients treated with cyclosporin A.

The effects of cyclosporin A (CyA), an immunosuppressive agent that is potentially nephrotoxic, on the kidneys of 9 liver transplant recipients were studied with serial 99mTc-DTPA and 131I-hippuran scans. In addition, renal function was determined by measuring serum creatinine levels during the second postoperative week in the 9 unselected CyA-treated patients and, retrospectively, in a control group of 29 liver transplant recipients who had not been treated with CyA and who were selected because they had survived for at least 3 months postoperatively. The early postoperative creatinine level was significantly greater in the CyA group. Eight of the 9 CyA patients showed imaging abnormalities in all preoperative and postoperative studies. Five of the 8 patients showed a pattern similar to that of acute tubular necrosis (relatively preserved perfusion) in at least one study. Lowering the dosage of CyA permitted the continuation of therapy, and all 9 patients are alive after 8 to 14 months.

Bilirubin↗

Variable convalescence and therapy after cadaveric renal transplantation under cyclosporin A and steroids.

The postoperative convalescence period was analyzed for 42 consecutive patients who had cadaveric renal transplantation under therapy with cyclosporin A and steroids. Twenty-two of the patients underwent transplantation for the first time, and the other 20 had retransplantation. None of the recipients has died. With follow-up period of two to eight months, the survival rate of grafts is 96 per cent after first transplantation and 85 per cent after retransplantation. Immunosuppression with a standard regimen was used for all patients at the outset. Early convalescence was highly variable, often necessitating adjustments of cyclosporin A and steroid dosage to accommodate the possibilities of rejection or cyclosporin A nephrotoxicity, or both, simultaneously. Management problems were more frequent and complex in patients undergoing retransplantation. From the results, a classification of convalescence patterns was evolved, with recommendations about how standardized initial therapy should be adjusted if the renal graft does not function promptly or deteriorates later.

Adolescent↗

Lymphapheresis in organ transplantation: preliminary report.

Reduction of lymphoid tissue by splenectomy and/or thymectomy has been used as a part of immunosuppression in organ transplantation (4). More recently Walker (7), Johnson (2), Franksson (1) and Starzl (5,6) and their associates have shown that chronic depletion of lymphocytes by thoracic duct drainage decreases the incidence of rejection and hence increases renal graft survival. Mechanical removal of lymphocytes from circulation peripheral blood should theoretically achieve the same or similar effect on the immunity as thoracic duct drainage. Since September, 1979, five organ transplant recipients have received multiple lymphocytapheresis by IBM 2997 Blood Cell Separator as a mechanical pretransplant immunosuppression. The changes in cellular and humoral immunity and the clinical outcome are presented in this report.

Adult↗

Nephrotoxicity of cyclosporin A in liver and kidney transplant patients.

In six of twelve orthotopic liver recipients nephrotoxicity was noted after 13-22 days of treatment with 16.3 + or - 2.9 (SEM) mg/kg per day of cyclosporin A (CyA). With a decrease in the daily CyA dose to 9.2 + or - 2.3 (SEM) mg/kg kidney function returned to normal. No hepatic rejections occurred on this lowered CyA dose. In 4 out of 66 kidney recipients a switch from a CyA dose of 5.2 - 10.7 mg/kg daily to azathioprine was done 4 - 8 months after transplant because of unsatisfactory kidney function, suspected to be due to nephrotoxicity. In three patients, this resulted in an improved graft function. A fourth transplant was lost to an irreversible rejection 13 days later. Thus CyA is nephrotoxic but this toxicity is easily reversed, even after many months of treatment, and the ease with which this complication can be managed suggests that nephrotoxicity should not diminish the high expectations that transplant surgeons have for CyA.

Cyclosporins↗

Past and future prospects of orthoptic liver transplantation.

The hopes for liver transplantation have been increased by experience with the new immunosuppressive drug cyclosporin A. Optimal therapy with cyclosporin A has required steroid therapy, but the amounts of prednisone used have been a small fraction of those used in the past.

Animals↗

Cyclosporin A hepatotoxicity in 66 renal allograft recipients.

Liver functional abnormalities were seen in 13 (19.7%) of 66 recipients of cadaveric renal homografts treated with cyclosporin A and prednisone. However, such presumed hepatotoxicity was a minor problem in the use of cyclosporin A. The complication was less frequent than that of nephrotoxicity, was as easily manageable with reductions in the cyclosporin A dosage, and generally did not cause clinical illness. In an occasional case, late hepatotoxicity can force a therapeutic change from cyclosporin A to azathioprine, but careful consideration should be given to the dangers of subsequent rejection.

Azathioprine↗

Cyclosporin A and steroid therapy in sixty-six cadaver kidney recipients.

From nine to 18 months ago, 66 patients were given 67 randomly matched cadaveric kidneys with cyclosporin A and steroid therapy. Nine of the recipients were undergoing retransplantation. The over-all kidney survival rate to date has been 77.6 per cent, and 78.8 per cent of the recipients are dialysis-free. The patient mortality in this learning phase was 13.3 per cent. Nephrotoxicity, hepatotoxicity and other side-effects of cyclosporin A could usually be dealt with by dosage adjustments, making feasible the chronic use of this agent. One B-cell immunoblastic sarcoma was encountered which was monoclonal. It was not responsible for death. Another patient had a perforation of the intestine from a lympho-proliferative reaction in which the B cells were polyclonal. After jejunal resection a year ago, there were no further complications. This lesion was not classified as a lymphoma. Both lympho-proliferative lesions were associated with a rise in antibody to viral capsid antigen of Epstein-Barr virus. Results of this study have verified the effectiveness and relative safety of cyclosporin A with steroids for immunosuppression in human recipients of cadaveric kidneys.

Adolescent↗

Late follow-up after thoracic duct drainage in cadaveric renal transplantation.

Thoracic duct drainage was added to conventional immunosuppression with azathioprine, prednisone and, sometimes, antilymphocyte globulin in 83 patients given cadaveric kidneys, including 65 primary graft recipients. The most effective use of thoracic duct drainage was for pretreatment. Optimal conditioning was at least four weeks duration, and when lymph drainage was this long, the incidence of rejection during the first three postoperative months was reduced to 4.5 per cent. Shorter pretreatment or institution of thoracic duct drainage contemporaneous with transplantation were less effective, but the one year results were still better than those with conventional immunosuppression alone. However, the advantage gained with thoracic duct drainage during the first year was diminished in all the treatment groups by graft losses in the second postoperative year. It was concluded that, without better maintenance therapy, the full value of temporary early lymphoid depletion procedures cannot be fully exploited.

Cadaver↗