In an effort to establish diagnostic criteria for rejection and recurrent disease in transplanted pancreas, a comparative study was performed based on clinical diagnosis. Clinical rejection was diagnosed in patients who had decreased urinary amylase or increased blood glucose; they were treated for rejection and improved. A clinical diagnosis of recurrent diabetes was made in syngeneic transplant recipients with islet dysfunction. In addition, two control groups were used--nontransplant, nondiabetic pancreatitis patients and pretransplant normal biopsies from patients in the study. Morphologically, tissues were assessed for acinar inflammation, ductal changes, islet and nerve inflammation, and vascular changes. Immunohistochemical staining for insulin and glucagon was also performed to quantitate differences between the groups. Vascular changes (endothelialitis, vasculitis, obliterative endarteritis) were specific for rejection. Also, rejection was characterized by a lymphocytic or mixed infiltrate that involved the ducts. Recurrent diabetes was characterized by selective loss of beta cells with isletitis. Leukocyte common antigen and UCHL1 staining was helpful in identifying islet inflammation. An insulin/glucagon ratio of less than 1.0 appears to be specific for recurrent disease and in the absence of isletitis is a reasonable method for detecting recurrent disease at an early stage.

Adolescent↗

PubMed1990

Pancreas transplantation or insulin?

Explore the source record for details and available documents.

Diabetes Mellitus, Type 1↗

PubMed1990

Differential roles of Mac-1+ cells, and CD4+ and CD8+ T lymphocytes in primary nonfunction and classic rejection of islet allografts.

The high rate of persistent hyperglycemia, termed primary nonfunction, after islet allotransplantation in C57BL/6 mice recipients of B10.BR strain islets, as compared with B10.BR recipients of C57BL/6 islets, led to a series of experiments to determine whether islet allograft primary nonfunction was attributable to technical aspects of the transplant procedure or whether it was a consequence of alloimmunity. Primary nonfunction was prevented by systemic pharmacologic immunosuppression of the host with cyclosporine. Selective immunodepletion of host CD4+ and CD8+ T lymphocytes significantly extended the time of classic rejection but did not significantly affect the rate of primary nonfunction. However, modulation of macrophages by administration to the host of silica completely abolished primary nonfunction. These observations, in conjunction with the immunohistological findings of intense macrophage infiltration in islet allografts from recipients exhibiting persistent post-transplant hyperglycemia, support the hypothesis that primary nonfunction results from a cell-mediated host-immune response of rapid onset that is dependent on macrophages or macrophage byproducts as the main effectors.

Animals↗

PubMed1990

Effects of pancreatic transplantation on diabetic neuropathy.

Reestablishment of the euglycemic state by successful transplantation of the pancreas might halt or reverse diabetic neuropathy. To test this possibility we evaluated neurologic function by clinical examination, nerve conduction studies, and autonomic-function tests in patients with insulin-dependent (Type I) diabetes mellitus before and after successful pancreatic transplantation. Sixty-one patients were studied before and 12 months after transplantation, 27 again after 24 months, and 11 again after 42 months. A control group of patients with Type I diabetes treated with insulin underwent the same studies at similar intervals--48 patients before and after 12 months had elapsed, 21 again after 24 months, and 12 again after 42 months. In the control group, neuropathy tended to worsen during the follow-up period. The scores on the clinical examination indicated increased impairment after 12 months. Composite indexes of the degree of abnormality found on neurophysiologic testing of the function of peripheral motor, sensory, and autonomic nerves indicated decreased autonomic function after 12 months. The examination score and the three index values worsened slightly but not significantly in the patients followed for 24 and 42 months. In contrast, in the patients who had received pancreatic transplants, the neuropathy tended to improve. There was significant improvement in the motor and sensory indexes 12 months after transplantation and in the sensory index 24 months after transplantation. The other measures improved slightly but not significantly at these times, as did all four measures in the patients studied 42 months after transplantation. We conclude that the progression of diabetic polyneuropathy may be halted through the restoration of a euglycemic state by successful pancreatic transplantation.

Adult↗

PubMed1990

Effects of hemipancreatectomy on insulin secretion and glucose tolerance in healthy humans.

Pancreatic tissue obtained by hemipancreatectomy from healthy living related donors has been transplanted into recipients with Type I diabetes mellitus. To determine the metabolic consequences of this procedure for the donors, we carried out oral glucose-tolerance testing and 24-hour monitoring of serum glucose levels and urinary C-peptide excretion as a measure of insulin secretion in 28 donors, both before and one year after hemipancreatectomy. The mean fasting serum glucose level was significantly higher one year after the procedure (mean +/- SD, 5.4 +/- 0.9 vs. 4.9 +/- 0.5 mmol per liter; P less than 0.003), as was the serum glucose value two hours after the administration of glucose (8.7 +/- 2.9 vs. 6.5 +/- 1.0 mmol per liter; P less than 0.001). The fasting serum insulin level was significantly lower one year after hemipancreatectomy (33.0 +/- 21.6 vs. 38.4 +/- 21.6 pmol per liter; P less than 0.05), as was the area under the insulin curves during the oral glucose-tolerance test (52,554 +/- 22,320 vs. 76,230 +/- 33,354 pmol per liter per minute; P less than 0.04). The mean 24-hour serum glucose-profile value was higher at one year, and the 24-hour urinary C-peptide excretion was lower in the 17 donors who underwent these studies. Seven of the 28 donors had abnormal glucose tolerance one year after hemipancreatectomy; however, insulin secretion in these 7 donors was indistinguishable from that in the 21 donors who had normal glucose tolerance. All 28 donors had fasting serum glucose concentrations lower than 7.8 mmol per liter, and their mean 24-hour plasma glucose levels remained within the normal range. We conclude that in healthy donors hemipancreatectomy results in a deterioration of insulin secretion and glucose tolerance, as measured one year later. Further study is required to ascertain whether the development of clinical diabetes mellitus is a risk inherent in hemipancreatectomy.

Adult↗

PubMed1990

Prognostic risk factors for graft failure following pancreas transplantation: results of multivariate analysis of data from the International Pancreas Transplant Registry.

A multivariate analysis of prognostic factors for graft failure was performed on patients in the International Pancreas Transplant Registry. The analysis was restricted to the period January 1978 to June 1987 and included 764 patients. All patients had at least 1 year of follow-up. The following variables were studied: transplant year, continent (N. America, Europe, others), type of donor (cadaver, living related mismatched, living related HLA-identical), donor mismatch at the HLA A, B loci, donor mismatch at the DR loci, preservation time, kidney association (pancreas transplant alone, simultaneous pancreas and kidney transplant, pancreas after kidney transplant), whole versus segmental pancreatic transplant, graft duct management technique (polymer injection, enteric drainage, stomach drainage, bladder drainage), and immunosuppression. By stepwise, logistic regression analysis, we found that the following factors were predictive for 1-year graft function: donor mismatch at the DR loci (P = 0.0003), kidney association (P less than 0.0001), type of donor (P = 0.04), and immunosuppression (P = 0.0002). For donor mismatch at the DR loci, we found an odds ratio for success of 2.2 for 0 versus 2 mismatches. The odds for success were 2.9 for simultaneous pancreas and kidney transplant versus pancreas transplant alone. The best results--79% 1-year graft survival--were obtained for the combination of 0 mismatches at the DR loci, pancreas after kidney transplant, living related HLA-identical donor, and the immunosuppressive regimen consisting of cyclosporin, azathioprine, and prednisone. Patients receiving a pancreas transplant alone with 0 mismatches at the DR loci, living related HLA-identical donor, and triple immunosuppressive regimen had a predicted 1-year graft survival of 71%.

Graft Rejection↗

PubMed1990

En bloc simultaneous pancreas and kidney allotransplantation in the pig.

The pig is a large animal suitable for experimental pancreas transplantation due to its anatomy and transplant immunology, both of which are similar to humans. We established a model of en bloc simultaneous pancreas and kidney transplantation that decreases preservation time, operation time, and clamp time. The donor aorta--with celiac axis, superior mesenteric artery, and left renal artery--is anastomosed en bloc to the recipient's aorta in a side-to-oblique fashion. The portal vein is anastomosed end-to-side to the distal vena cava, and the left renal vein end-to-side to the left common iliac vein. The donor duodenum is anastomosed to the bladder to allow monitoring of the urinary amylase for rejection. En bloc transplantation is preferable for separating pancreas and kidney anastomoses in pigs. This technique could be used in humans, especially in adult uremic diabetic patients who receive a combined pancreas/kidney transplant from a pediatric cadaver donor.

Anastomosis, Surgical↗

PubMed1990

Influence of preservation time on outcome and metabolic function of bladder-drained pancreas transplants.

The influence of cold storage preservation time on graft survival and metabolic function of pancreatic transplants was studied in 130 recipients of bladder-drained grafts (47 simultaneous with, 33 after, and 50 without a kidney transplant) between October 1, 1984 and May 1, 1989. The recipients were divided into four groups according to the preservation time: less than 6 hr (n = 11), 6-12 hr (n = 24), 12-24 hr (n = 75), and greater than 24 hr (n = 20). Twenty-six grafts were procured by other transplant teams and sent to us. Silica gel fractionated plasma was used for preservation in 104 cases and the University of Wisconsin solution in 25 (1 in the less than 6 hr, 2 in the 6-12 hr, 16 in the 12-24 hr, and 6 in the greater than 24 hr groups). The technical failure rate at 1 month was 13% (17 grafts), 1 (9%) in the less than 6 hr, 5 (21%) in the 6-12 hr, 9 (12%) in the 12-24 hr, and 2 (10%) in the greater than 24 hr groups. At 1 month, 107 (82%) of the grafts were functioning, 10 (91%) in the less than 6 hr, 18 (75%) in the 6-12 hr, 62 (83%) in the 12-24 hr and 17 (85%) in the greater than 24 hr groups, the longest preserved for 30 hr. The respective 1-year graft survival rates were 51%, 50%, 57%, and 70%. Ninety patients (10 in the less than 6 hr, 16 in the 6-12 hr, 51 in the 12-24 hr, and 13 in the greater than 24 hr groups) had metabolic studies between 2 and 6 weeks postransplant. The results of 24-hour profiles (14 blood glucose determinations) were similar in each preservation time group; the means of the mean (+/- SD) profile glucose (mg/dl) values were 130 +/- 19, 126 +/- 31, 130 +/- 24, and 129 +/- 30, respectively (P greater than 0.6). Mean plasma glucose levels at 2 hr during OGTT were 141 +/- 32, 145 +/- 43. 163 +/- 49, and 184 +/- 100 in the respective preservation groups (P greater than or equal to 0.064). According to the National Diabetes Data Group classification, 75% of recipients in the less than 6 hr, 50% in the 6-12 hr, 44% in the 12-24 hr, and 33% in the greater than 24 hr groups had normal OGTT results.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Glucose↗

PubMed1990

An increased incidence of late acute rejection episodes in cadaver renal allograft recipients given azathioprine, cyclosporine, and prednisone.

We studied the incidence of biopsy-proven, acute rejection episodes occurring after 1 year posttransplant in cadaver renal allograft recipients. The 328 patients evaluated were given three immunosuppressive drug protocols. Group I (transplanted 9/80-6/84) (n = 75) received azathioprine, prednisone (P), and antilymphoblast globulin; group II (transplanted 9/80-6/84) (n = 83) received cyclosporine and P; group III (transplanted 7/84-12/86) (n = 170) received ALG, AZA, CsA, and P (sequential therapy). The incidence of first acute rejection episodes occurring up to 1 year posttransplant was 55% in group I and 35% in groups II and III. The incidence of late (greater than 1 year) acute rejection episodes was 6.5% in group I, 2.5% in group II, and 9.5% in group III (group II vs. III, P = 0.02). In group III, 50% of the late rejections were first, 44% second, and 6% third. The primary etiologies of this increased incidence of late acute rejection may have included subtherapeutic CsA levels and lower P doses. Sequential immunosuppressive therapy has been shown to be advantageous in the first posttransplant year. However, unless adequate immunosuppression is maintained, this approach can be associated with a significantly increased incidence of late acute rejection.

Adult↗