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Biomedical subjects

A Tibell

Publications and source records attributed to A Tibell.

At least 91 records · Page 5Linked to original sources

Insulin secretion, insulin action and non-insulin-dependent glucose uptake in pancreas transplant recipients.

To assess individual factors responsible of overall glucose tolerance after successful pancreas transplantation, an i.v. glucose tolerance test, with frequent blood sampling and tolbutamide administration to elicit a second insulin response was used to estimate insulin sensitivity (SI) and glucose effectiveness (SG) with Bergman's minimal model. Insulin secretion was calculated from the combined insulin-C-peptide kinetics method. These parameters were quantified in identically immunosupressed transplants: ISPx, four segmental pancreas recipients with impaired glucose tolerance; TSPx, five segmental pancrease recipients with normal glucose tolerance; WPx, five whole pancreas recipients with normal glucose tolerance; and in two controls groups, Kx, eight nondiabetic kidney recipients, and Ns, eight normal subjects. All participants had normal fasting plasma glucose and normal glycosylated hemoglobin A1C levels. The glucose tolerance KG value was significantly reduced only in ISPx compared with Ns (P < 0.05). SI was reduced by 60% in ISPx, WPx, and Kx compared with normal subjects (P < 0.05), whereas SI was reduced by 30% in TSPx compared with normal controls (P = NS). The reduction in SG was the same in all pancreas transplanted groups, as compared to Kx and Ns (by 33% and 40%, respectively, P < 0.05). The first-phase insulin secretion (0-5 min) was markedly reduced in ISPx and TSPx compared with Ns (by 76% and 50%), to Kx (by 84% and 66%) and to WPx (by 73% and 45%), respectively (P < 0.05), but similar to Ns in WPx. The overall incremental insulin secretion was reduced in ISPx compared with Ns, WPx, and Kx (by 38%, 62%, and 73%, respectively, P < 0.05) and reduced in TSPx compared to WPx and Kx (by 47% and 67%, respectively, P < 0.05) Ns secreted 43% of the total amount of insulin during the first phase the corresponding value was only 13% in ISPx vs. 24% in TSPx, 24% in Kx, and 25% in WPx, respectively (P < 0.05). In conclusion, after pancreas transplantation, the overall glucose tolerance is determined by the net effect of reductions in insulin sensitivity and glucose effectiveness and in the adaptability of the beta-cells to ensure sufficient insulin secretion. beta-cell function was impaired in both the whole pancreas and segmental transplant recipients, and the failure to increase insulin secretion sufficiently leads to glucose intolerance.

Adult↗

Dissolving intravenous cyclosporin A in a fat emulsion carrier prevents acute renal side effects in the rat.

Cyclosporin A (CyA)-induced nephrotoxicity is still a serious clinical problem. The nephrotoxicity seems to be more pronounced when CyA (solubilized in water with Cremophore EL, as in Sandimmun) is given intravenously than when it is given orally. Using soybean oil in which CyA was dissolved, we prepared an intravenous fat emulsion without an artificial detergent, such as Cremophore EL. The renal effects of our new formula were compared with those of Sandimmun and Cremophore EL in a rat model. CyA in the fat emulsion did not significantly affect the glomerular filtration rate (GFR). Both Sandimmun and Cremophore EL significantly reduced the GFR. These results suggest that a change in the vehicle may obviate the acute nephrotoxic side effects caused by intravenous administration of CyA solubilized by Cremophore EL.

Animals↗

Ten years' experience of renal transplantation in children in the cyclosporine era.

Sixty renal transplantations were performed in 53 children, 0.4-16.0 years of age during the last 10 years. Fifty-five percent of the children were < or = 7 years at transplantation and 23% were < or = 2 years. Congenital nephropathies were the primary disease in 79%. Preemptive transplantation was performed in 24 first transplantations. Forty-two grafts came from living related donors and 18 came from cadaveric donors. The 1- and 5-year patient survival rates in the 0- to 7.0-year age group were 83% and 83%, respectively, and in the 7.1- to 16.0-year age group, 100% and 93%. The 1- and 5-year graft survival rates were 77% and 77% and 90% and 74% in the two groups, respectively. In children < or = 2 years old at transplantation, the 1- and 5-year patient and graft survival rates were the same, 86% and 86% in living related donors recipients, whereas they were 40% and 40% in cadaveric donors recipients. Six patients died, 3 with functioning grafts. An additional 7 grafts were lost in 6 patients, all of whom were subsequently retransplanted. The median height SD scores at transplantation was -2.98 SD in children with congenital diseases and -0.48 SD in children with acquired diseases. The median height SD scores of the 22 children followed for 3 years after transplantation was -1.06 SD. It is concluded that the survival rates obtained are satisfactory, despite the fact that the majority of the children were transplanted at a comparatively young age because of a high frequency of congenital renal disorders.

Adolescent↗

Renal transplantation in r-HuEPO-treated patients.

After sporadic reports of renal graft artery thromboses, prophylaxis against thrombosis (PAT) was given to all of our r-HuEPO-treated patients (n = 35) during a period of 2 years. No thromboembolic events (TEE) occurred in the r-HuEPO-treated group receiving PAT. However, the PAT-protocol (500 ml dextran on days 0, 1, 3 and 5, followed by low doses of aspirin, 160-250 mg daily) resulted in a 54.3% incidence of bleeding complications, of which 22.9% were major (i.e., necessitating multiple transfusions or invasive procedures). A group of renal graft recipients (n = 83), who were not treated with r-HuEPO and were not given PAT, showed a 10.8% incidence of bleeding complications of which 2.4% major. Two cases of TEE were noted in the untreated group. The difference in bleeding complications between the two groups was statistically significant (0.025 > P > 0.01). The difference in TEE between the groups was not significant. We found no difference between the groups with regard to early and late graft function and the incidence of acute rejections. In summary, r-HuEPO treatment did not influence the prognosis in renal graft recipients. The use of PAT in the r-HuEPO-treated group resulted in a high incidence of bleeding complications. In consequence, we have abandoned the routine use of PAT in this patient group.

Adult↗

Cyclosporine A in fat emulsion carrier: immunosuppressive effect in vitro.

We have recently shown in a rat model that the acute decrease in glomerular filtration rate caused by intravenous Sandimmun can be avoided if Cyclosporine A (CyA) is given in a fat emulsion carrier instead. The present study was undertaken to determine the immunosuppressive effect in vitro of this new formulation. The inhibitory effect on the lymphocyte responsiveness of CyA in fat emulsion carrier was compared with that of CyA dissolved in alcohol, using mitogens as well as alloantigens as stimuli. In the mixed lymphocyte culture and cell-mediated lympholysis tests and in the interleukin-2 assay, both formulations seemed equally effective. CyA in fat emulsion was somewhat less effective than CyA in alcohol in the mitogen tests. In clinical practice the fat emulsion would be rapidly metabolized, and to further evaluate our new formulation, studies in experimental organ transplantation are needed.

Cyclosporine↗