Search PubMed⌕ Search

Biomedical subjects

C R Stiller

Publications and source records attributed to C R Stiller.

At least 91 records · Page 5Linked to original sources
PubMed1983

Cyclosporin prevents diabetes in BB Wistar rats.

Cyclosporin (U.S.A.N. cyclosporine) was used prophylactically to suppress the development of insulin-dependent diabetes mellitus in BB Wistar rats. In this rat strain diabetes spontaneously develops between 60 and 120 days of age and this condition resembles human type 1 diabetes. In 30 (75%) out of 40 control rats glycosuria and hyperglycaemia developed and these rats became insulin-dependent. Their pancreases showed partial to complete destruction of the islets of Langerhans by lymphocytic infiltration. None of the 40 cyclosporin-treated rats became diabetic and their pancreases were histologically normal. Serum cyclosporin was monitored in a subgroup and the dosage was adjusted accordingly; neither hepatotoxicity nor nephrotoxicity was seen in the treated animals.

Animals↗
PubMed1983

The effects of intravenous anaesthetic agents on human neutrophil chemiluminescence.

Intact neutrophil function is essential for the defence against infection. Any alteration in neutrophil function, which decreases their ability to phagocytose and kill bacteria, might contribute to mortality and morbidity. We investigated the effects of clinical concentrations of thiopentone, Alfathesin, methohexitone, morphine, lidocaine and diazepam on the microbicidal oxidative function of human neutrophils. The oxidative activity was assessed utilizing the technique of chemiluminescence, which is a measure of free radical generation. Thiopentone and Alfathesin produced a significant dose dependent depression in chemiluminescence. There was a 27 per cent reduction in activity with thiopentone 5 micrograms X ml-1, a concentration equivalent to the free plasma concentration achieved following an anaesthetizing dose of thiopentone. There was a 55 per cent reduction in chemiluminescence at an alphaxolone concentration of 1.25 micrograms X ml-1, a concentration equivalent to the free plasma level obtained after induction of Alfathesin anaesthesia. The effect of thiopentone and Alfathesin was reversed by cell washing. Methohexitone, morphine, diazepam, and lidocaine caused no significant reduction in chemiluminescence over the dose ranges studied. These observations indicate that thiopentone and Alfathesin can adversely affect leucocyte function in vitro and, therefore, may contribute to impaired host resistance in the perioperative period and in the intensive care unit.

Alfaxalone Alfadolone Mixture↗
PubMed1983

Cyclosporine: action, pharmacokinetics, and effect in the BB rat model.

Cyclosporine (Cy) was given to BB rats in an attempt to prevent the onset of diabetes. A dose of 15 to 20 mg/kg/d given orally or subcutaneously was associated with high Cy trough serum levels and caused nephrotoxicity and severe weight loss. Ten mg/kg/d of Cy was tolerated well. Forty rats were treated with Cy starting at 34 days of age. No Cy-treated rats developed diabetes by day 121, compared with 70% of the control rats. Once Cy was discontinued on day 121, 38% of female and 13% of male rats developed diabetes by day 169. Transient, spontaneously remitting hyperglycemia developed in nine rats. This occurred both in control rats and in rats on Cy, but it was more common in females than in males. Thus, Cy prevents diabetes mellitus in the BB rat when trough Cy serum levels greater than 100 ng/mL are achieved. Diabetes occurs in some rats after Cy is discontinued. In all treatment subgroups, diabetes occurred more frequently in females than in males.

Animals↗
PubMed1983

Small bowel transplantation in the dog using cyclosporine.

The effect of the new immunosuppressant cyclosporine on survival after total small intestinal allotransplantation (TSIA) was studied in a canine model. Successful TSIA was performed in 34 dogs. Eleven dogs were treated with cyclosporine, 25 mg/kg/day i.m., starting the day before the operation and continuing for four weeks. Thereafter the same dose was given orally. Thirteen dogs were given oral cyclosporine only, 25 mg/kg/day from the day after transplantation. Ten dogs served as controls. The dogs treated with intramuscular and oral cyclosporine survived a mean of 103.8 +/- 39.4 days (mean +/- S.E.M.). The longest survivor died after 432 days. Survival in this group was significantly longer than that of the control dogs, which survived 12.5 +/- 4.6 days. The orally treated dogs survived 30.4 +/- 7.6 days. All control dogs, and seven of the orally treated dogs, but only two of the intramuscularly treated dogs, died of acute rejection. It is concluded that cyclosporine is effective in prolonging survival after TSIA in the dog and reduces the incidence of acute rejection.

Animals↗
PubMed1983

Renal allograft survival in the baboon using a pretreatment protocol with cyclosporine.

Cyclosporine extends kidney allograft survival in the chacma baboon, and this study explores various administration protocols to generate optimal serum concentrations of the drug, assessed by radioimmunoassay and by inhibition of lymphocyte transformation by phytohemagglutinin and allogeneic lymphocytes in culture. Serum levels commensurate with concentrations that have been shown to be immunosuppressive in humans (150-400 ng/ml) are reached after 14 days of pretreatment with 10 mg cyclosporine/kg, and after 7 days with 20 and 30 mg cyclosporine/kg. The 10-mg dose prolongs median graft survival from 11 to 21 days, which is the same as that obtained with 20 mg/kg administered after transplantation. Further increases in the pretreatment dose to 20 or 30 mg/kg result in survivals of 27 and 31 days, respectively. All the animals died from rejection during therapy and the T-cell-binding avidity, and absorptive or degradative processes may necessitate doses far in excess of those currently used in transplantation.

Absorption↗
PubMed1983

Simplified liquid-chromotographic analysis for cyclosporin A, and comparison with radioimmunoassay.

We describe a simplified isocratic "high-performance" liquid-chromatographic method for measuring a new immunosuppressive drug, cyclosporin A, in biological fluids with use of its analogs cyclosporin C and cyclosporin D as internal standards. The method is reproducible and accurate and appears to be specific for cyclosporin A; the detection limit is 31 micrograms/L. The chromatographic measurements of the concentration of cyclosporin A in serum of patients receiving the drug were invariably lower than those by radioimmunoassay and the difference became more pronounced the greater the period of time after dosing. Because measurements of cyclosporin A in serum standards were almost identical with both techniques, the differences between the two sets of results for patients' samples suggests that the radioimmunoassay is nonspecific and measures metabolites of cyclosporin A.

Adult↗
PubMed1983

CT findings in postpartum renal cortical necrosis.

A 34-year-old woman presented with postpartum renal cortical necrosis. Contrast-enhanced computerized tomography (CT) of her kidneys showed a narrow subcapsular band of increased density that was separated from the medulla by a distinct band of decreased density. This is analogous to the decreased cortical nephrogram seen on arteriography. The CT scan may be a useful, non-invasive diagnostic procedure in renal cortical necrosis.

Acute Kidney Injury↗
PubMed1982

Cyclosporin A: a powerful immunosuppressant.

Cyclosporin A (CyA) is a powerful immunosuppressive agent whose lack of myelotoxicity makes it unique among nonsteroidal drugs currently given for immunosuppression. It has been used with initial success in recipients of kidney, liver, bone marrow and pancreas transplants, and it may also have clinical application in the treatment of autoimmune disorders. In regard to its use in transplant recipients, there are many remaining questions about its mechanism of action, the optimum dose, whether it should be used alone or with other immunosuppressants, whether it can suppress chronic rejection and what its long-term side effects may be. These questions can only be answered by further careful laboratory investigation and controlled clinical trials. Until then, CyA should only be administered in centres experienced in its use.

Chemical Phenomena↗
PubMed1982

Immune response to transplanted pancreas in pigs.

Segmental allografts of the body and tail of the pancreas have been carried out in pigs using an open duct technique. Diabetes was induced by total pancreatectomy. Control animals on no immunosuppression survived an average of 17 days while animals receiving CyA survived 30 days. In the CyA group those with adequate serum levels of CyA survived 46 days while those with low levels survived 18 days. Once the animal became diabetic rejection was not reversible. In this model complement dependent cytotoxicity was more useful than lymphocyte mediated cytotoxicity in predicting rejection. However the rejected pancreas showed intensive mononuclear infiltration. Malabsorption resulting from total pancreatectomy used to induce diabetes may have contributed to the erratic CyA absorption. Prolonged and relatively normal pancreatic allograft function is possible, but adequate CyA levels must be achieved and maintained. Monitoring of serum levels is essential.

Animals↗