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Biomedical subjects

L Laker

Publications and source records attributed to L Laker.

25 records · Page 2Linked to original sources
PubMed1984

Prolongation of intraperitoneal segmental pancreatic allografts in primates receiving cyclosporin A.

In this study the efficacy of the new immunosuppressive agent, cyclosporin A (CYA), was examined in a model of segmental, intraperitoneal pancreatic allotransplantation with free duct drainage in totally pancreatectomized, outbred Chacma baboons. CYA, in doses of 25 to 50 mg/kg/day administered to recipients of heterotopic segmental (tail) allografts, produced a slight but significant prolongation of graft survival. CYA (25 to 85 mg/kg/day), administered orally after pancreatic transplantation gave daily serum trough levels of CYA that ranged from 300 to 600 ng/ml. Mean serum trough levels on the first postoperative day in recipients of 50 mg/kg/day were 121.1 +/- 61.6 ng/ml. There was a wide variation in daily serum trough levels exhibited between primates on the same daily oral dose, and there was no correlation between absolute serum trough levels of CYA and rejection. It is postulated that adequate serum CYA levels were not achieved by the oral administration of the drug to ensure allograft survival beyond 60 days in pancreatectomized recipients. Adverse effects occurred frequently and included anorexia, diarrhea, and tremors and were in direct proportion to the quantity of CYA required to prolong graft survival. Free duct drainage into the abdominal cavity frequently resulted in pancreatic ascites, which necessitated paracentesis, indicating that this method of duct drainage has limited clinical application. Although heterotopic autotransplantation or allotransplantation of the tail of the pancreas in the baboon was capable of maintaining normoglycemia in pancreatectomized baboons, glucose intolerance, reduced K values, and hypoinsulinemia were consistent findings during glucose tolerance tests, suggesting that an insufficient islet cell mass had been transplanted.

Animals↗
PubMed1983

Intraperitoneal transplantation of vascularized segmental pancreatic autografts without duct ligation in the primate.

The aim of this study was to determine whether diabetes could be ameliorated in totally pancreatectomized baboons by heterotopic intraperitoneal autotransplantation of the tail of the pancreas with the duct unligated. Twenty-five baboons were made diabetic by total pancreatectomy. Six untreated pancreatectomized animals survived a median of 5 days with mean (+/- SE) plasma glucose levels of 18 +/- 1.37 mmol/L and mean (+/- SE) potassium (K) values of 0.36 +/- 0.02% before death. Successful autotransplantation of the tail of the pancreas rendered pancreatectomized baboons consistently normoglycemic. Intravenous glucose tolerance tests performed 6 weeks after transplantation in 12 autograft recipients showed glucose intolerance in 12 of 14 recipients, and K values were significantly reduced to 1.03 +/- 0.015% (P less than 0.05). The K value of 40 normal baboons was 2.18 +/- 0.15. Histologic examination of successfully transplanted autografts of 12 animals at 6 weeks showed islets with intact beta and alpha cells, atrophy of the exocrine pancreas, graft fibrosis, and a cellular infiltration of the mononuclear type. The addition of a distal arteriovenous fistula to the graft did not reduce the incidence of graft vessel thrombosis, and all five animals died of hemorrhagic pancreatitis and venous thrombosis within 24 hours of transplantation.

Animals↗
PubMed1982

The effect of corticosteroid therapy on lysosomal enzymes and protein and lipid metabolism in rabbit lung after administration of Freund's adjuvant.

The effect of corticosteroid therapy on the broncho-alveolar cell response, the changes in activity of some lysosomal enzymes and the protein and lipid biosynthesis rates in lung tissue of normal rabbits and of rabbits after induction of an acute inflammation by the intravenous injection of complete Freund's adjuvant (CFA) 0,2 ml/kg body weight was investigated. Three intramuscular injections of methylprednisolone acetate (Depo-Medrol) 1,2 mg/kg over a period of 8 days reduced the mean total broncho-alveolar free cell yields significantly. The percentages of lymphocytes and granulocytes were decreased. The increase in the macrophage percentage was associated with a significant increase in the acid phosphatase activity of the broncho-alveolar cells. The beta-glucuronidase activity, on the other hand, was lowered in alveolar cells and even significantly suppressed in lung tissue. Protein and lipid biosynthesis was significantly retarded in lung tissue 8 days after the start of therapy. Administration of a single dose of CFA 0,2 ml/kg evoked an acute lung inflammation and a significant increase in total alveolar free cell yields. The macrophage percentage was reduced and the lymphocyte numbers doubled, whereas the granulocyte percentage increased more than sevenfold. The change in the percentage distribution of granulocytes may be associated with the marked increase in beta-glucuronidase activity of the cells as well as of the lung tissue. In the inflammatory phase, protein biosynthesis was significantly increased but lipid synthesis was not affected. Corticosteroid therapy in animals treated with adjuvant reversed all the effects of CFA. It has very pronounced anti-inflammatory action and a catabolic effect on protein and lipid metabolism.

Acid Phosphatase↗