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Biomedical subjects

D E Sutherland

Publications and source records attributed to D E Sutherland.

At least 487 records · Page 27Linked to original sources
PubMed1987

Pancreas transplantation.

The number of pancreas transplants being performed and the success rate have continued to increase. Most pancreas transplants have been placed in diabetic recipients of kidney transplants, but application to nonuremic, non-kidney transplant recipients without end-stage disease is increasing. Drainage of pancreatic graft duct into the bladder allows exocrine function to be assessed directly and has led to earlier diagnosis and treatment of rejection episodes. The improvement in graft survival rates has been associated with the use of cyclosporine in combination with other immunosuppressants. The effect that establishment of a euglycemic state by successful pancreas transplantation has on the specific complications of diabetes is just beginning to be discerned but appears to be favorable if the transplant is performed sufficiently early in the course of the disease.

Animals↗
PubMed1987

Recent advances in solid organ transplantation.

Advances in organ transplantation have come rapidly and consistently in recent years as the result of improved surgical techniques and immunosuppressive drug therapies. Experience gained in renal transplantation over the past 30 years has made this a standard therapeutic approach for treating chronic renal failure. This knowledge has been successfully applied to the transplantation of other organs to produce steadily increasing survival rates and improved quality of life. This article reviews the advances that have been made in solid organ transplantation and immunosuppressive drug therapy.

Heart Transplantation↗
PubMed1987

Hypercalcemia associated with pancreatitis and hyperamylasemia in renal transplant recipients. Data from the Minnesota randomized trial of cyclosporine versus antilymphoblast azathioprine.

The incidence and possible etiologic factors of acute pancreatitis and hyperamylasemia were statistically evaluated in renal transplant recipients. Two hundred twenty-four patients were randomized in a prospective trial of cyclosporine and antilymphoblast azathioprine immunosuppressive regimens. They had a median follow-up of 20 months. Pancreatitis developed in 8 patients and hyperamyl asemia developed in 20 patients. There were no statistical relationships between the incidences of pancreatitis and hyperamylasemia and the immunosuppressive drugs or viral infections. However, pancreatitis developed in 11 percent of the transplant patients with repeatedly elevated serum calcium levels (37 patients, p less than 0.01) and hyperamylasemia developed in 19 percent (p less than 0.025). Other etiologic factors, such as gallstones, alcoholism, and corticosteroids, played a minor role in this patient population. These results suggest that hypercalcemia is a major etiologic factor for pancreatitis in renal transplant recipients.

Acute Disease↗
PubMed1987

Pretransplant cytotoxic conditioning produces effects consistent with clonal deletion mechanisms.

A rat cardiac allograft model (ACl to Lewis) was used to investigate the clonal deletion theory. Twelve groups of Lewis recipients received various combinations of donor-specific blood transfusions (DSTs), immediate post-DST immunosuppression with azathioprine/prednisone, and low-dose cyclosporine (1 mg/kg/day) posttransplant. DSTs and cyclosporine together gave modest prolongation of graft survival (from 6.0 to 17 days). DSTs plus immediate post-DST immunosuppression followed by low-dose cyclosporine prolonged graft survival to an average of 45 days. Third-party transfusions alone and in combination with immunosuppression did not significantly prolong allograft survival. Postoperative cyclosporine was required for the expression of this effect suggesting that clonal depression rather than clonal deletion had occurred. Combining DSTs with brief but intense preoperative immunosuppression may be a more effective method of pretransplant conditioning than DSTs alone.

Animals↗
PubMed1987

Renal transplantation done safely without prior chronic dialysis therapy.

The complications, cost, and inconvenience associated with pretransplant hemodialysis and peritoneal dialysis would be minimized if transplantation were instituted without prior dialysis. That preuremic transplantation is safe and efficacious in patients with immanent end-stage renal disease has not been established. All 1742 consecutive primary renal transplants performed at the University of Minnesota during the 16.5 year period from January 1968 through July 1984 were reviewed to determine whether graft and patient survival were adversely affected by transplantation prior to dialytic therapy. In the overall group of primary renal transplants, no differences in actuarial graft or patient survival were noted with or without prior dialysis. Likewise, outcome was not affected by the pretransplant dialysis status in recipients of allografts from HLA-identical mismatched living-related donors. However, in cadaveric transplantation graft function appeared to be adversely affected by transplantation prior to dialysis, with 52% vs. 66% two-year graft function for nondialyzed vs. chronically dialyzed recipients, respectively (P = 0.15). Patient survival was significantly (P = .04) decreased in the nondialyzed group, with 66% vs. 80% two-year survival in the chronic dialysis group. However, nearly all of the nondialyzed, cadaveric recipients were diabetic. The outcome of transplantation was found to be identical in these patients, as compared with chronically dialyzed diabetic recipients of cadaveric grafts. Thus, the apparent detrimental effect of predialytic transplantation in the cadaver group was due to the preponderance of diabetics in the nondialyzed group. Since July 1984, a single-armed therapeutic trial of combination therapy with azathioprine, prednisone, antilymphoblast globulin (ALG), and cyclosporine has been undertaken, Since that time, 36 primary graft recipients were transplanted prior to dialysis. Of these 36, 35 currently have a functioning graft. Thus, transplantation prior to chronic dialysis is safe irrespective of donor source, or choice of immunosuppressive agents.

Azathioprine↗
PubMed1987

Experimental and clinical experience with urine amylase monitoring for early diagnosis of rejection in pancreas transplantation.

Pancreas allograft rejection in dogs with pancreaticocystostomy can be predicted in advance of hyperglycemia by monitoring the urinary amylase (UA) concentration (U/L): In initial experiments, UA values declined to less than 1000 1.3 +/- 0.2 days before hyperglycemia in nonimmunosuppressed dogs, 3.3 +/- 1.0 days in dogs treated with cyclosporine (CsA), and 9.3 +/- 0.7 days in dogs treated with CsA, azathioprine (Aza), and prednisone (triple therapy). Autotransplanted control dogs maintained high urine amylase concentrations indefinitely (mean 125,544 +/- 36,931). In a subsequent experiment, in 19 dogs with bladder-drained pancreas allografts on CsA only for prophylactic immunosuppression, a five-day course of antirejection treatment with Aza (5.0 mg/kg) and antilymphocyte globulin ALG (1 mg/kg) was started in group A (n = 10) when a raise in serum glucose was detected, and in group B (n = 9) when a drop of UA below 1000 was observed. The functional allograft survival rate was 9.2 +/- 0.5 days in group A (treatment started after hyperglycemia) and 29.0 +/- 5.7 days in group B (treatment started after drop in UA) (P = .002). The UA dropped in all dogs before hyperglycemia, at a mean of 2.7 days in group A and 20.8 days in group B. Clinically, 8 patients received a whole cadaver pancreas transplant with urinary drainage of the exocrine secretions. All were followed with UA monitoring. Three recipients lost the grafts for technical reasons. Three recipients lost the grafts for technical reasons. One had a primary non-function and UA was below 1000 U/24 hr; two developed abscesses and the grafts were removed while functioning with high UA values. Five grafts are currently functioning; 3 recipients had no rejection episodes and their UA values ranged from 30,000 to 100,000 U/24 hr during their entire postoperative course. The other two had rejection episodes. In both cases UA decreased to baseline levels 1 and 4 days in advance of the hyperglycemia. After antirejection treatment UA rose again to high values and plasma glucose levels declined. Both patients are currently insulin-independent, with UA values ranging from 10,000 to 200,000 U/24 hr. Both experimentally and clinically UA is an early predictor of pancreas allograft rejection. The institution of early treatment of rejection episodes in dogs, based on UA, significantly improved allograft survival. Urine amylase monitoring in pancreas transplant recipients could lead to an early treatment of rejection and improve graft survival.

Amylases↗
PubMed1987

Function of transplanted human pancreatic allografts after preservation in cold storage for 6 to 26 hours.

Preservation of cadaveric pancreas allografts has been a difficult problem in clinical pancreas transplantation; most institutions use Collins solution and limit preservation time to less than 6 hr. Longer preservation times have been used at the University of Minnesota. Between August 1983, and December 1985, 47 human cadaveric pancreas grafts were transplanted into Type I diabetic recipients after cold storage at 4 degrees C in a modified, hyperosmolar silica-gel filtered plasma (SGFP), a solution previously found to allow dog pancreas grafts to be successfully preserved for up to 48 hr. Ten grafts were preserved for 2-5 hr (group 1); 20 for 6-11 hr (group 2; 17 for 12-26 hr (group 3). Graft function and late outcome were compared between these groups and another group of 7 cadaveric grafts (group 4), which were transplanted immediately and without any preservation. Analysis of exocrine pancreatic function early after transplantation showed a maximum mean serum amylase (IU/L) of 557, 440, 429, and 307 in groups 1, 2, 3, and 4, respectively. Primary preservation failure rates of 0, 5%, 5.8%, and 0%, and endocrine graft function rates at 1 month of 80%, 80%, 76%, and 86% were obtained for groups 1, 2, 3, and 4, respectively (P = NS). Only patients who were insulin-independent were counted as having functioning grafts. Detailed functional studies at 1 month showed that mean plasma glucose levels during 24-hr metabolic profiles were in the normal range in 71%, 68%, 72%, and 50%, while oral glucose tolerance test results were within the normal range in 38%, 81%, 76%, and 66% of groups 1, 2, 3, and 4, respectively (P = NS). At 1 year, patient survival rates were 57%, 88%, 75%, and 100% (P = NS), and the graft functional survival rates were 0, 25%, 33%, and 29% (P = NS) in the respective groups. Five patients in group 2, and 6 in group 3 have currently functioning grafts at 4 to 37 months after transplantation. We conclude that cadaver pancreas grafts can be safely preserved for 12-24 hr in modified SGFP solution, thus making the sharing of these organs between different centers practical and the transplant operation less of an emergency procedure.

Adult↗
PubMed1987

The impact of cyclosporine and combination immunosuppression on the incidence of posttransplant diabetes in renal allograft recipients.

The incidence of posttransplant diabetes mellitus (PTDM) was compared in three groups of renal transplant recipients: nondiabetic patients who had been randomized between 1980 and 1983 to receive antilymphoblast globulin (ALG), azathioprine (AZA), and prednisone (P) (group 1) or cyclosporine (CsA) plus prednisone (group 2). Group 3 consisted of a more recent (1984-85) cohort who were given a combination of azathioprine, cyclosporine, and prednisone (+/- ALG). PTDM developed in 20 of 173 previously nondiabetic 18-55-year-old patients. Three of 47 patients (6.4%) in group 1, 4 of 58 patients (6.9%) in group 2, and 13 of 68 patients in group 3 (19.1%) developed PTDM. Thus in the two groups composing the concurrent prospective randomized trial (groups 1 and 2) the incidence of PTDM did not differ. The subsequent patients who were given a combination of ALG, azathioprine, cyclosporine, and prednisone developed a significantly greater incidence of PTDM even though the total dose of cyclosporine and prednisone were lower than in groups 1 and 2. PTDM usually occurred within two months of transplantation, and 11 of 17 patients who initially required insulin are still dependent upon exogenous insulin. The incidence of PTDM was not significantly affected by sex of the recipient, HLA-type, primary renal disease, rejection episodes, primary vs. secondary transplant, or prior splenectomy. The incidence of PTDM is greater in patients older than 45 (34.2% vs. 5.2%), and heavier than 70 kg (21.1% vs. 5.1%); in recipients of cadaveric allografts (15.7% vs. 4.6%); and in patients who were hospitalized for infections (22.4% vs. 4.7%). CsA levels tended to be higher in the group 2 and 3 patients who developed PTDM than in those who remained nondiabetic. One-year actuarial patient survival in those with PTDM was 83.3% vs. 98% (P less than .01) in the nondiabetic and graft survival was 77.1% vs. 87.1% (NS). The combination of Minnesota ALG, azathioprine, cyclosporine, and prednisone appears to predispose older, heavier recipients of cadaver allografts to the development of PTDM. The risk of PTDM must be weighed against the more usual results of improved patient and graft survival using this combination of immunosuppression.

Adult↗
PubMed1987

Thromboembolic complications in renal allograft recipients. A report from the prospective randomized study of cyclosporine versus azathioprine-antilymphocyte globulin.

The incidence of arterial and venous thromboembolic complications was compared in 224 renal allograft recipients who were prospectively randomized and stratified by risk to treatment with either cyclosporine-prednisone (CsA-P) (n = 117) or azathioprine-prednisone-antilymphocyte globulin (AZA-P-ALG) (n = 107). Thirteen CsA patients (11%) had 22 thromboembolic events, while 19 AZA patients (18%) had 24 events (P = 0.22). There was no significant difference between the 2 regimens in the number of patients with each type of venous or arterial event or in the number of patients with multiple or lethal events. The incidence of "minor" complications (all except myocardial infarction and stroke) in the related donor subgroup (n = 85) and the overall incidence of thromboembolism in the diabetic subgroup (n = 125) were both significantly higher in AZA-treated patients (P = 0.008 and 0.045, respectively). Thus, CsA immunosuppression does not appear to be a risk factor for thromboembolic disease, and it may in fact lower the incidence of thromboembolism in diabetic renal allograft recipients.

Adolescent↗
PubMed1987

Pancreas transplantation. An immunohistologic and histopathologic examination of 100 grafts.

The authors examined tissues obtained by biopsy, pancreatectomy, and autopsy from 100 pancreas grafts to determine the cause of dysfunction or failure of the graft. Immunohistologic examination of 42 tissues to determine the mononuclear cell phenotypes and Class I and II antigen expression was performed as well. Technical factors--infections, thrombosis, obstruction--accounted for a large number of graft losses, but immunologic-mediated mechanisms resulted in graft dysfunction and failure as well. Pleomorphic inflammatory infiltrates were present in grafts with acute rejection, as well as Silastic and Prolamine duct-obstructed grafts. Criteria useful in the identification of acute rejection from pancreatitis included a more intense, predominantly mononuclear cell infiltration of transformed lymphocytes in the exocrine pancreas and evidence of vascular rejection--endovasculitis or fibrinoid necrosis. Increased expression and/or induction of Class I and II antigens on pancreatic constituents occurred in grafts with evidence of acute rejection, but also with Silastic and prolamine duct-obstructed pancreatitis. An isletitis occurred in 25% of the grafts. Nine of the 25 grafts (36%) with isletitis also had selective loss of beta cells from the islets. Recurrent diabetes mellitus appeared to have developed in these cases, which accounted for loss of graft function.

Biopsy↗