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Biomedical subjects

B Smit

Publications and source records attributed to B Smit.

44 records · Page 3Linked to original sources

Endocrine function after immunosuppression of pancreatic allograft by ionizing irradiation in the primate.

The object of this preliminary study was to evaluate the endocrine function after heterotopic intraperitoneal segmental pancreatic allotransplantation with unligated duct in irradiated, totally pancreatectomized primates. All allograft recipients received, pre- and peroperative donor-specific blood transfusions and peroperative external irradiation from a linear accelerator; 200 rads was administered weekly and increased to a total dose of 1,500 rads. Pancreatic transplantation was performed between 2 and 6 weeks after completion of irradiation and preoperative blood transfusions. As previously reported, only minimal pancreatic allograft survival was achieved following preoperative irradiation. One recipient remained normoglycaemic for greater than 100 days after transplantation, the longest surviving pancreatic allograft recipient reported from this laboratory. Intravenous glucose tolerance test results in this recipient revealed normoglycaemia, reduced K-value, hypoinsulinaemia, normal glucagon response, reduced C-peptide values, and moderate glucose intolerance. Aortography and electron-microscopic examination of allograft biopsy tissue confirmed the presence of a functioning allograft.

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Segmental pancreatic allograft survival in baboons treated with combined irradiation and cyclosporine: a preliminary report.

The present study was undertaken to evaluate the effectiveness of cyclosporine (CS) alone, total lymphoid irradiation (TLI) alone, and CS in combination with total body irradiation (TBI) in suppressing segmental pancreatic allograft rejection in totally pancreatectomized outbred chacma baboons. The administration of CS 25 mg/kg/day and 50 mg/kg/day resulted in mean graft survival of 21.5 days and 24.5 days, respectively. CS 85 mg/kg/day resulted in median graft survival of 9 days. There was a wide daily fluctuation of CS serum trough levels exhibited between primates receiving the same oral dose. TBI in excess of 300 rads resulted in irreversible bone marrow suppression. Modest results were achieved in recipients of TBI-76 rads (38 X 2 rads), with median graft survival of 21 days, results not different from recipients treated with CS. TLI recipients of 600 rads (150 X 4 rads) resulted in median pancreatic graft survival of 16 days. TBI together with oral CS administration exhibited no synergistic or additive effect and a single peroperative donor-specific blood transfusion did not enhance pancreatic allograft survival in this model. However, of 10 primates receiving TBI 100 rads (50 X 2 rads) and CS 25 mg/kg/day administered orally indefinitely, four remained normoglycemic for more than 60 days. TBI 100 rads (50 X 2 rads) together with oral and parenteral CS resulted in necrotizing enterocolitis in four of six recipients. Some immunosuppressive regimens gave modest graft survival, none resulted in indefinite graft survival, and there was considerable toxicity with many of the regimens. Although CS administration alone or in combination with irradiation resulted in modest pancreatic allograft survival in this model, the place of CS combined with TBI or TLI or other chemical immunosuppressive agents remains to be defined.

Animals↗