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Biomedical subjects

D E Sutherland

Publications and source records attributed to D E Sutherland.

At least 685 records · Page 38Linked to original sources
PubMed1981

Pancreas and islet transplantation. II. Clinical trials.

Clinical islet allotransplantation has been a safe, but largely unsuccessful enterprise. It has been difficult to apply techniques that might overcome the islet yield and allograft rejection problems encountered in animal experiments. Over the past decade only 4 of 74 attempts at islet transplantation have been followed by long term withdrawal of exogenous insulin therapy, and there are problems with intrepretation of the outcome in each of theses cases, as discussed in the preceding section. In the islet allograft situation, the failures may have been for technical or for immunological reasons. In the autograft situation, rejection could not occur and the failures were clearly technical. The success rate with islet autografts gives some indication as to what might be achieved with islet allotransplantation if rejection could be prevented in the latter situation. The islet autotransplant experience is not entirely predictative, however, for two reasons: 1) the uncertainty over the contribution of the pancreatic remnant to carbohydrate metabolism when less than the total pancreatectomy is done; 2) the increased difficulty with liberating islets from diseased, fibrotic pancreases. For both islet allo- and autotransplantation, the success rate will probably remain low until more effective techniques are developed for preparation of islets from adult pancreases. For the allograft situation, additional advances will be needed in immunosuppression or in techniques to alter islet graft immunogenicity in order to overcome the rejection phenomenon.

Clinical Trials as Topic↗
PubMed1981

Colon ulceration in lethal cytomegalovirus infection.

Six renal transplant recipients with severe cytomegalovirus (CMV) infection developed colonic ulceration and lower gastrointestinal bleeding. All patients died between four and 84 days following onset of bleeding. Four patients required colon resection to control blood loss. In the remaining two cases, there was complete autopsy examination with thorough tissue sampling of the colon. In addition to routine light microscopic examination, all cases were studied with an immunoperoxidase technic for identification of CMV. Electron microscopic examination of the colon was performed on two cases. In this select group of patents, CMV plays an active role in damaging colonic mucosa, primarily as a result of CMC vasculitis. Clinical and pathologic features of our cases are compared to published reports of CMV infection of the colon.

Adult↗
PubMed1981

Kidney allograft survival in dogs treated with total lymphoid irradiation.

Total lymphoid irradiation (TLI) is immunosuppressive and, in rodent, can induce a state where transplantation of allogeneic bone marrow results in chimerism and permanent acceptance of organ allografts from the donor strain. We attempted to apply this treatment to a large animal model. Twelve splenectomized dogs were treated with TLI (150 rads per fraction, total dose 1950-3000 rads) before bilateral nephrectomy and renal allotransplantation. Eight dogs received bone marrow from the kidney donor. In 13 untreated control dogs renal allografts functioned (serum creatinine level less than 2.0 mg/dl) for a mean +/- (SE) of 4.7 +/- 0.3 days. In the four TLI treated dogs who did not receive bone marrow the renal allografts functioned for 15-76 days (two dogs died with functioning grafts). In the eight TLI treated dogs who received donor bone marrow, two died immediately after transplantation, two rejected at 3 and 13 days, one died at 13 days with a functioning graft, and two have had the grafts function for longer than 500 days. Chimerism was not detected in the one dog tested. The response of peripheral blood lymphocytes to stimulation with phytohemagglutinin and in mixed lymphocyte culture was suppressed for at least on month after TLI. The results confirm the immunosuppressive effect of TLI. The absence of kidney rejection in two recipients of donor bone marrow show the potential of this approach to induce long-term immunologic unresponsiveness as to an organ allograft, but the outcome is unpredictable and further experiments are needed to define the optimal conditions for administration of TLI and bone marrow to the recipients.

Animals↗
PubMed1981

Patient and graft survival in amputated versus nonamputated diabetic primary renal allograft recipients.

Between September 23, 1968 and March 22, 1980, primary renal allografts were performed in 373 uremic patients with insulin-dependent diabetes. After transplantation 65 of the diabetic patients (17%) underwent 151 amputations involving at least a digit or a limb. The lower extremity was involved in 72% of the amputations. Twenty-four patients had only one procedure, while 41 required multiple procedures. Mean interval from transplantation to first amputation was 25.2 +/- 2.4 (SE) months. Patient and graft loss (perioperative risk) in the first 3 months after amputation was 13%. Diabetic renal allograft recipients living long enough to require amputation have more severe manifestations of vascular disease. These amputees display both an 11% lower patient and graft survival after the first year following transplantation, as well as an accelerated rate of graft loss following amputation. Those diabetics requiring an amputation do significantly more poorly than nonamputees of the corresponding demographic category if diabetes onset occurred at age 10 to 20 years, diabetes duration prior to transplant was less than 20 years, age at transplant was less than 30 years, dialysis duration was less than 4 months, and donor type was HLA-nonidentical related. Nevertheless, more than 50% of the diabetics undergoing amputation will be alive with functioning allografts 4 years after amputation. On the other hand, diabetics not requiring amputation do particularly well if they survive 1 year, with more than 80% chance that they will be alive with a functioning graft 4 years after transplantation.

Adult↗
PubMed1981

Hormonal and metabolic effects of a pancreatic endocrine graft. Vascularized segmental transplantation in insulin-dependent diabetic patients.

A new modification of pancreas transplant technique, the vascularized segmental intraperitoneal graft without duct ligation, has provided reversal of insulin-dependent (type I) diabetes mellitus for as long as 2 years of comfortable life. Although the risks associated with immunosuppression remain high (two of the 12 patients have died of early postoperative infection), selected data are presented from six cases to show the following striking hormonal and metabolic results after transplantation and withdrawal of insulin: restoration of normal beta cell function as shown by 24-hour urine C-peptide excretion and acutely responsive serum insulin, restoration of normal suppressibility of plasma glucagon, elimination of ketosis and negative nitrogen balance, normal fasting plasma glucose and glycosylated hemoglobin, and normal or near-normal glucose tolerance. These results provide a standard for current explorations of new ways of treating insulin-dependent diabetes.

3-Hydroxybutyric Acid↗
PubMed1981

[Transplantation register for pancreas and island of Langerhans].

A new registry for human pancreas and islet transplantation has been established (D. E. R. Sutherland). Between 17 December 1966 and 31 December 1980, 108 pancreas transplantations were performed. Six patients had grafts that functioned for more than 12 months. In most of the 68 islet allotransplants performed, little or no evidence of islet function has been obtained. Three diabetic patients were dependent on insulin for 2.5 to 8 months after the operation. One of these, however, still has a functioning graft. Autotransplants of dispersed pancreatic islet tissue have been performed on 59 patients after total or partial pancreatectomy for benign disease. The 28 patients who had 90% pancreatectomies did not require insulin. Information from the registry should be helpful to the various transplant teams attempting clinical application of these procedures.

Diabetes Mellitus↗
PubMed1981

Segmental pancreas transplantation from living related and cadaver donors: a clinical experience.

Between July 25, 1978, and January 25, 1981, 20 segmental pancreas transplants from 14 cadaver (cad) and six related (rel) donors were performed. All but two recipients had previously received renal allografts for treatment of end-sage diabetic nephropathy. The grafts were placed intraperitoneally-13 with open ducts, 4 with prolamine-injected ducts, and 3 with silicone rubber-injected ducts. At this writing six patients have functioning grafts (3 silicone, 3 open duct) at less than 1 (cad), 2 (cad), 3 (rel), 15 (cad), 20 (rel), and 31 (cad) months. Five open-duct grafts failed for technical reasons. Two prolamine-injected grafts lost function between 1 and 3 months; biopsy specimens showed severe fibrosis. The others lost function between 2 and 4 months. Three patients died 1 to 3 months after transplantation. Metabolic test results were normal or nearly normal in most recipients with functioning grafts. Splenectomy was required in one related donor; there were no other complications of donation. Technical problems and rejection are impediments to application of pancreas transplantation, but a sustained correction of the metabolic defect has been achieved in a few patients, and the effect on secondary complications are studied.

Adolescent↗