Rosenberg L

Progression of Diabetic Retionopathy after Pancreas Transplantation

The progression of diabetic retinopathy after combined pancreatic and kidney transplantation was studied in eight patients for 12 to 49 months. Four patients who had rapid pancreatic graft failure constituted a control group for comparison with four patients who retained functioning grafts. Using Fishers exact probability test, the authors found no posttransplantation difference between the two groups in visual acuity lost, severity of diabetic macular edema, extent of capillary closure, progression of preretinal gliosis, development of disc or preretinal neovascularization, or worsening of the severity of the retinopathy. Achievement of normoglycemia by pancreatic transplantation is not effective in halting the progression of diabetic retinopathy in patients who already have severe diabetic microangiopathy joined the current follow-up.

No improvement of pancreas transplant endocrine function by exogenous insulin infusion (islet rest) in the postoperative period

The concept of islet exhaustion maintains that exposure of pancreatic islets to hyperglycemia and other stresses leads to islet dysfunction and irreparable damage. The process of pancreatic transplantation places many stresses on islets (e.g., counter-regulatory hormones, steroids, cyclosporine toxicity). As practiced by some centers, it may be important to administer exogenous insulin in the postoperative period to provide islet rest. Using a porcine pancreas transplant model that simulates clinical transplantation, we studied 2 groups: 1 group (n=8) received constant insulin infusion for 7 days after transplantation; the control group (n=5) received vehicle only. The islets in the insulin infusion group were rested as evidenced by a significantly decreased mean C-peptide level (0.27±0.04 ng/ml) as compared to the control group (0.66±0.08 ng/ml) (P<0.05). After insulin infusion was discontinued, intravenous glucose tolerance testing found insulin, C-peptide and glucagon responses were not different between groups. Glucose clearance was also comparable; K values were −1.79 and −1.60 in the insulin infusion and control groups, respectively. In conclusion, islet rest by insulin infusion for 7 postoperative days did not improve subsequent pancreas transplant endocrine function.

Peripheral blood catalase in patients undergoing renal transplantation

Oxygen free radicals are mediators of tissue injury and catalase is an enzyme which is involved in limiting this process. We examined peripheral blood catalase activity (PBCA) to assess its value as a marker in detecting tissue injury related to renal allograft rejection. Thirty-one consecutive recipients of kidney (n = 29) or simultaneous kidney/pancreas (n = 2) transplants and 10 normal volunteers were studied. Catalase activity, measured by the disk-flotation method, was expressed as Sigma units X 10(-3)/ml (SU/ml) of whole blood. Normal PBCA was determined to be greater than 76 SU/ml. Twenty-nine episodes of renal allograft rejection (diagnosed by clinical criteria +/- biopsy [79%]) were observed in 26 patients. PBCA (mean +/- SEM) was found to be low (64 +/- 1 SU/ml) in 28/29 episodes (chi 2 = 46.3, P less than 0.001), and the decrease (at least two consecutive daily catalase values less than 76 SU/ml) occurred 2 days prior to the clinical/biopsy diagnosis of rejection in 26/28 episodes. The sensitivity of PBCA as a discriminant of rejection was 97%, specificity was 96%, and test accuracy was 96%. PBCA less than 50 SU/ml on two or more occasions occurred in five cases and transplant nephrectomy was required in four of these because of uncontrollable rejection. Nine episodes of cyclosporine nephrotoxicity occurred in 7 patients and none of these episodes was associated with a decreased PBCA. Our data suggest that decreased PBCA is a sensitive and specific indicator of renal allograft rejection. PBCA remains normal during episodes of cyclosporine nephrotoxicity and therefore provides a rapid and inexpensive discriminant from allograft rejection.

Preparation of islets of Langerhans from the hamster pancreas

We describe a method for the preparation of viable islets from the pancreas of normal 8-week-old female Syrian golden hamster, based on the injection of the pancreatic duct with collagenase and on mechanical dissociation which liberates islets that maintain their normal morphological appearance and physiologic function. In a series of 11 animals, we examined the dose response of intraductal collagenase on islet yield. The mean number of isolated islets was 423 with a range from 130 to 873 per pancreas. Islet yield was most dependent on the concentration of collagenase solution used to inject the duct. The optimal concentration was determined to be 3.5 mg/ml when a total volume of 3.0 ml was injected. Islets responded to glucose stimulus in a normal biphasic pattern. Mesh filtration, rather than Ficoll, can be performed rapidly and results in a high yield of functional islets with minimal contamination by acinar tissue.

Pancreas transplant experience of individual institutions Experience of the University of Michigan Medical School, Ann Arbor, Michigan, USA

At the University of Michigan, 18 pancreas transplants have been carried out between March 1984 and October 1986. At our Center and other centers, the surgical technique, immunosuppressive regimen and candidate criteria have continued to evolve during this period. The impetus for constant re-evaluation and change has been dissatisfaction with historically low graft survival rates and the significant morbidity and mortality associated with pancreatic transplantation [1]. However, this process has produced several incremental advances which have resulted in improved success rates.