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Biomedical subjects

D E Sutherland

Publications and source records attributed to D E Sutherland.

At least 703 records · Page 39Linked to original sources
PubMed1980

Total or near total pancreatectomy and islet autotransplantation for treatment of chronic pancreatitis.

Total or near total pancreatectomy is the surest way to relieve the pain of chronic pancreatitis but is rarely applied because the metabolic consequences are so severe. For most patients drainage procedures are applicable, but pancreatectomy may be the only alternative for small duct disease or where procedures to improve duct drainage have failed. Preservation of endocrine function is a major problem in patients who require pancreatectomy. Experiments in pancreatectomized dogs have shown that intrasplenic or intraportal transplantation of unpurified pancreatic islet tissue dispersed by collagenase digestion can prevent diabetes. We have applied this technique to ten patients with chronic pancreatitis, small ducts, and intractable pain. The entire pancreas of > 95% of the pancrease was excised, minced, dispersed by collagenase digestion and infused into the portal vein < 2 1/2 hours after removal. Mean (+/- SD) rise in portal pressure was 17 +/- 8 cm of water. Liver function tests were altered minimally. All patients were relieved of pain. One patient died of a complication not related to the islet autotransplant; viable islets were identified in the liver at autopsy. Of the remaining nine patients, three have been insulin independent for 1, 9, and 38 months. One patient was insulin indpendent for 15 months and now takes 12 units of insulin daily. Three have nonketosis prone diabetes (tested by insulin withdrawal) and take 15--30 units of insulin per day. C-peptide studies in these patients show that functioning islets are present. Two patients are diabetic and require 35 and 60 units of insulin per day. In eight of nine patients tested serum insulin concentrations fell to undetectable levels during the interval between pancreatectomy and islet transplantation. Serum insulin levels during the first few hours after islet transplantation predicted success. In the insulin independent or in the patients with mild diabetes, insulin levels were persistently greater than or equal to 6 microU/ml. In the other two patients, the increase in insulin concentration was not sustained. Islet tissue preparation from a diseased pancreas is difficult. The surgeon and the patient must still be willing to accept diabetes for relief of pain when performing this operation. In some patients, however, islet autotransplantation can prevent or partially ameliorate diabetes after pancreatectomy, and preservation of endocrine function is worthwhile.

Adult↗
PubMed1980

Clinical segmental pancreas transplantation without duct anastomosis in diabetic renal allograft recipients.

Segmental pancreatic allografts with unligated ducts were transplanted intraperitoneally to five diabetic patients who had received renal allografts more than 2 yr earlier. One patient is alive with a functioning graft 10.5 mo later. Two patients rejected their grafts at approximately 2 and 3 mo but are alive 8--9 mo later after resumption of exogenous insulin therapy. In both patients, carbohydrate metabolism was nearly normal during the period of graft function. Two patients died of infectious complications between 1 and 2 mo after transplantation. The main hazard of pancreas transplantation relates to the immunosuppression necessary to prevent rejection, setting the stage for infectious complications. Technically, pancreas transplantation is a feasible and efficient procedure, and, if better methods are developed for preventing rejection, it should be applicable to patients prone to develop secondary complications of diabetes.

Adult↗
PubMed1980

Transplantation of dispersed pancreatic islet tissue in humans: autografts and allografts.

Islet transplantation is successful in animals and holds considerable promise as endocrine replacement therapy for patients with diabetes mellitus, but clinical application to diabetic patients has been difficult. We have shown the technical feasibility of human islet transplantation by autotransplantation of dispersed pancreatic islet tissue into the portal vein in three patients with chronic pancreatitis and incapacitating, intractable pain who underwent near-total (greater than 97%) pancreatectomy. In all three patients, the excised pancreas was dispersed by collagenase digestion, but no effort was made to purify the islets. Islet yield, as judged by tissue insulin content, ranged from 24 to 55%. The first patient, who never received insulin after the pancreatectomy and islet autotransplantation, had a normal oral glucose tolerance test by 3 wk and has remained normoglycemic for over 2 yr. In the second patient, viable islets were histologically identified in the liver parenchyma. The third patient was treated with hyperalimentation for 3 wk after the pancreatectomy and islet autotransplantation and, during this period, required insulin. After cessation of hyperalimentation and initiation of oral geedings, the patient was withdrawn from insulin. Although abnormalities of carbohydrate metabolism were present, the patient did not require insulin for more than 1 yr. Seven diabetic renal allograft recipients have received allografts of dispersed pancreatic islet tissue prepared in the same way. No patients were cured of diabetes, although transient evidence of islet function--increase in serum or urinary C-peptide levels or decrease in exogenous insulin requirements--occurred in some. Although rejection was probably responsible for most of the failures, transplantation of allogeneic human islet tissue as a free graft is metabolically inefficient. With the current state of immunosuppressive therapy, the primary role of islet transplantation may be in a situation where rejection cannot occur: as an autograft to obviate the occurrence of diabetes after extensive pancreatectomy for benign disease.

Adult↗
PubMed1980

Prolongation of heterotopic cardiac allografts in rats by cyclosporin A.

Cyclosporin A (CsA), an investigational immunosuppressive drug, was tested for its ability to prevent rejection of heterotopic rat heart allografts transplanted across a major histocompatibility barrier (ACI to Lewis). The relative efficacy of CsA was compared to a combination of azathioprine and prednisolone. Various dose-schedule combinations of CsA as a single drug were evaluated in regard to duration of grafts beating, recipient mortality rate, and histology of long-term functioning grafts. A daily dose of CsA of 10 mg/kg prevented rejection, but was associated with a 40% recipient mortality rate from infection. CsA in 5 mg/kg/day doses resulted in long-term graft function (> 100 days), but histological examination of these grafts showed mild rejection. A dose-schedule of CsA in 10 mg/kg/day for 7 to 35 days followed by a reduction to 5 mg/kg/day prolonged the survival rate of all grafts to longer than 100 days; no rats died from this treatment and there was no evidence of rejection on graft histology. In contrast, a combination of 4 mg/kg/day azathioprine and 4 mg/kg/day prednisolone did not prolong graft survival rates. Azathioprine in 30 mg/kg and prednisolone in 12 mg/kg prolonged allograft survival (50 to 60 days), but was associated with significant recipient morbidity (> 25% weight loss) and histological evidence of acute and chronic rejection. A nontoxic dose of CsA is superior to a combination of azathioprine and prednisolone in preventing the rejection of heterotopic rat heart allografts. The therapeutic index of cyclosporin A in rats can be increased by using a tapering dose schedule, as opposed to a fixed dose schedule. CsA has good potential for clinical application to organ transplantation.

Animals↗