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Biomedical subjects

D E Sutherland

Publications and source records attributed to D E Sutherland.

At least 505 records · Page 28Linked to original sources

Canine islet autografts with and without administration of cyclosporine.

Cyclosporine administration prolongs the survival of immediately vascularized allografts. However, its role in the prevention of rejection of dispersed pancreatic islet allografts is uncertain, and some studies have suggested that it may be harmful. We performed total pancreatectomies in 21 mongrel dogs, followed by intrasplenic autotransplantation of islet-enriched, dispersed pancreatic tissue prepared by means of ductal perfusion and collagenase digestion. Ten dogs received no other therapy (controls) and 11 received orally administered cyclosporine from the day before to 30 days after transplantation. Therapeutic blood levels of cyclosporine were documented by means of high-pressure liquid chromatography. There was no difference in engraftment in six of 10 controls, and eight of 11 cyclosporine-treated dogs remained normoglycemic for more than 30 days. Intravenous glucose tolerance test results (K values), fasting serum insulin levels, and insulin secretion in response to a glucose challenge were similar in the two groups. There were two late treatment failures in the control group and one in the cyclosporine-treated group. We were unable to detect an adverse effect of cyclosporine on the engraftment or function of canine islet autografts. We conclude that cyclosporine remains a promising drug for use in studies of islet transplantation in human beings.

Administration, Oral↗

Pancreas transplant protocols at the University of Minnesota: recipient and donor selection, operative and postoperative management, and outcome.

In summary, at the University of Minnesota we perform pancreas transplants from both living-related and cadaver donors. Living-related donors must meet strict criteria indicating that they are not at risk for diabetes. Segmental grafts are procured from living-related donors. We currently procure whole pancreas grafts from most cadaver donors, including those in whom a liver is procured. We will accept preservation times up to 24 hours using hyperosmolar silica-gel-filtered plasma as the preservation solution. In regard to recipient selection, we have several categories of patients, including nonuremic individuals with early secondary lesions of diabetes affecting the eyes, nerves, and kidneys. Pancreas transplants are also performed in patients with end-stage diabetic nephropathy, either simultaneous with or after a kidney transplant. The potential benefit from pancreas transplantation is greatest in patients who have early diabetic complications which in the absence of this intervention would progress to a severity more serious than the possible side effects of chronic immunosuppression. A careful pretransplant evaluation is necessary in order to select nonuremic, nonkidney recipients in whom pancreas transplantation is appropriate. The selection process is much easier in kidney transplant recipients; virtually any person who can withstand the additional surgery is a candidate, the risks associated with immunosuppression having already been accepted in lieu of the unsatisfactory alternative of chronic dialysis. The results we have obtained in the 3 categories of recipients since November 1984 in patients managed by our currently preferred surgical techniques and immunosuppressive protocols are shown in Figure 6. One-year pancreas survival rates in nonuremic, nonkidney transplant recipients are 63%, in recipients of a previous kidney 46%, and in recipients of simultaneous kidneys 75%. With respect to surgical technique, our current preference is the bladder drainage method because the ability to monitor exocrine function leads to earlier diagnosis and treatment of rejection episodes. With related donor transplant, we have continued to use enteric drainage. Because the rejection rate is much lower than with cadaver donors, the one-year functional survival rate has been relatively high for technically successful enteric-drained related donor grafts. Nevertheless, rejection does occur, and related donor segmental grafts are being performed with bladder drainage. Our current immunosuppressive protocol of quadruple drug therapy has been associated with the highest graft survival rates, particularly in the bladder-drained group where early diagnosis and treatment of rejection has been facilitated. In our experience, UAA monitoring results have had a high correlation with rejection episodes, and we have never seen loss of endocrine function with retention of high UAA levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical Protocols↗

Renal transplantation at the University of Minnesota during the 1980s.

1. There have been 1,225 renal allografts performed at the University of Minnesota between January 1, 1980 and May 31, 1987. Significant risk factors for graft survival include donor type, retransplantation, and age at time of transplant. In addition, diabetes is a significant risk factor in patient survival. 2. Three immunosuppressive regimens have been used during this time period: AZA + P + ALG, CsA + P, and CsA + AZA + P (+ ALG for CAD grafts). The 3 protocols have been received by 411, 205, and 356 primary renal allograft recipients, respectively. No overall differences between the therapies exist with respect to graft or patient survival. However, females, recipients of CAD organs (especially the recipient with diabetes), and patients 18-50 years of age at transplant have improved graft survival results using CsA + AZA + P (+ ALG). Females and the 18-50-year-old recipients also have improved results with respect to patient survival. 3. The 3 protocols [AZA + P + ALG; CsA + P; and CsA + AZA + P + ALG] have been used for 125, 112, and 174 primary recipients of CAD organs, respectively. Recipients of CsA + AZA + P + ALG have significantly better graft survival overall in the diabetic and poorly matched subgroups. Other high-risk (but small sample size) subgroups show statistically nonsignificant, but clinically important, improvements. These groups include patients over 50 years of age, patients with preformed antibodies, as well as those with compatible ABO blood types. Similar trends exist with respect to patient survival. 4. Risk factor analysis of all patients receiving CsA + AZA + P (+ ALG) indicates that donor type, retransplantation, and age at the time of transplant are still serious risk factors for graft survival. Only age at transplant influences patient survival significantly. 5. The failure to find any significant risk factors in primary recipients of CAD organs in the CsA + AZA + P(+ ALG) era, combined with the generally consistent good graft and patient survival rates, suggest that the traditionally high-risk patient can be successfully transplanted with excellent results. 6. Pediatric patients can be successfully transplanted with results equivalent to 18-50-year-old patients and better than those recipients over 50 years of age at the time of transplant. Random transfusions and combination therapy are at least as good as DST and AZA + P + ALG.

Adolescent↗