Suppression of allograft rejection with FK506. I. Prolonged cardiac and liver survival in rats following short-course therapy.

Heterotopic heart and orthotopic liver grafts from ACI donors were transplanted to Lewis rat recipients that were treated with a 3 (or 4) day course of FK506 IM that was started on postoperative day 0, 2, 3, 4, 5, or 6. Hearts, which rejected after a median of 6 days in untreated controls, always had prolonged survival (median 91 days) when treatment was started on postoperative day 4. The results were inferior when treatment was started earlier or later than this, but even when the first dose of FK506 was on postoperative day 5, one day before rejection was imminent in controls, the median survival was 50 days.

Liver transplantation in patients with previous portasystemic shunt.

Over a 9-year period, 58 patients who had previous portasystemic shunt procedures underwent orthotopic liver transplantation (OLTx) under a cyclosporine-steroid immunosuppressive regimen. The types of shunt used were distal splenorenal (18 patients), mesocaval (17 patients), end-to-side portacaval (11 patients), side-to-side portacaval (5 patients) and proximal splenorenal (7 patients). The mean interval between shunt and transplantation was 6 years.

Gamma linolenic acid alters the cytotoxic activity of anticancer drugs on cultured human neuroblastoma cells.

Gamma linolenic acid (GLA) by itself shows anti-tumor activity on various neoplastic cells in culture. We investigated the combined effect of GLA and anticancer drugs on two human neuroblastoma cell lines. The cytotoxic effect of Vinca alkaloids such as vincristine (VCR), vindesine (VDS) and vinblastine (VBL) was about 2-fold enhanced when GLA was added simultaneously to the growth medium.

Impaired natural killer activity and expression of interleukin-2 receptor antigen in familial erythrophagocytic lymphohistiocytosis.

A 1-month-old boy with familial erythrophagocytic lymphohistiocytosis (FEL) had a barely detectable natural killer (NK) activity of 0% to 7% (median, 0.5%) with an effector/target ratio of 20:1. The number of Leu7+ and Leu11+ cells was within normal range.

Hepatic artery reconstruction for hepatic artery thrombosis after orthotopic liver transplantation.

We evaluated the efficacy of reconstruction of the hepatic artery for intraoperative or postoperative thrombosis in orthotopic liver transplantation. Of 37 grafts with artery thrombosis, 13 (35.1%, 6 intraoperative and 7 postoperative) underwent reconstruction of the hepatic artery.

Liver transplantation for polycystic liver disease.

Four female patients with severe complications of polycystic liver disease were treated with liver replacement; two patients were also given kidneys from their liver donors. All four of the patients were suffering from extreme fatigue. Three of the recipients have survived for 8, 11, and 60 months with normal liver function and present good health.

The hepatotropic influence of cyclosporine.

The effect of cyclosporine on liver regeneration has been investigated in 25 dogs that underwent an end-to-side portacaval shunt (Eck fistula) followed by 4 days continuous infusion of the drug into the left branch of the portal vein. Three different cyclosporine infusion rates were used: 0.06, 0.

Treatment of upper abdominal malignancies with organ cluster procedures.

Upper abdominal exenteration for upper abdominal malignancies was carried out in 15 patients with removal of the liver, spleen, pancreas, duodendum, all or part of the stomach, proximal jejunum and ascending and transverse colon. Organ replacement was with the liver, pancreas and duodenum plus, in some cases, a short segment of jejunum. Eleven of the 15 patients survived for more than 4 months; 2 died, after 61/2 and 10 months, of recurrent tumor.

Analysis of surgical complications after 397 hepatic transplantations.

The results of 397 consecutive orthotopic hepatic transplantations in 333 recipients were reviewed. One or more surgical complications developed in 172 of 323 patients (55 per cent), excluding ten intraoperative deaths. The six month mortality rate among the patients with surgical complications (55 of 172; 32 per cent) was statistically higher than that among patients without such complications (16 of 151; 11 per cent) (p less than 0.

Liver transplantation in the treatment of primary liver cancer.

One hundred and fifteen patients underwent orthotopic liver transplantation (OLT) for primary liver malignancy. Overall survivals of these patients were significantly lower than those of patients with non-malignant diseases (5-year survival rates 37% and 65%, respectively). Hepatocellular carcinoma (HCC) was the most common malignancy among our patients (n = 80).

[Effects of mesna (2-mercaptoethane sodium sulfonate) in children with malignant disease receiving oxazaphosphorine chemotherapy].

We studied the efficacy of mesna as a protectant for urotoxicity in pediatric patients receiving chemotherapy including oxazaphosphorines. Nineteen patients with malignant diseases (5 neuroblastoma, 3 acute lymphocytic leukemia, 4 acute non-lymphocytic leukemia, 2 non-Hodgkin lymphoma, 3 osteosarcoma and 2 rhabdomyosarcoma) were treated with a total of 106 courses of therapy between June of 1986 and May of 1989. Of these, no gross hematuria were seen.

The use of FK-506 for small intestine allotransplantation. Inhibition of acute rejection and prevention of fatal graft-versus-host disease.

Small intestine allotransplantation in humans is not yet feasible due to the failure of the current methods of immunosuppression. FK-506, a powerful new immunosuppressive agent that is synergistic with cyclosporine, allows long-term survival of recipients of cardiac, renal, and hepatic allografts. This study compares the effects of FK-506 and cyclosporine on host survival, graft rejection, and graft-versus-host-disease in a rat small intestine transplantation model.

Liver transplantation in patients with situs inversus.

Two patients with situs inversus and biliary atresia were treated with hepatic transplantation, one with an auxiliary liver and the other with an orthotopic graft which was placed using a piggy-back technique. Both transplants functioned well initially. The auxiliary liver was rejected after 1 1/2 months, and the patient died after an attempt at retransplantation many months later.

Childbearing after liver transplantation.

Seventeen female patients who underwent orthotopic liver transplantation between June 1973 and June 1987 became pregnant 5 months to 11 years after transplantation. Immunosuppression was maintained with combinations of prednisone, cyclosporine, and azathioprine prior to and during pregnancy. One patient discontinued immunosuppression after knowledge of pregnancy, taking only azathioprine sporadically.

Induction of graft acceptance after dog kidney or liver transplantation.

We have reported that, a short delayed course of intramuscular FK 506 can induce a,donor strain-specific immunologic unresponsiveness to cardiac allograft in rats. Further studies have been performed to determine if this agent can induce graft acceptance after canine renal (KT) or hepatic (OLT) allotransplantation. Preliminary descriptions of these efforts have been published.