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D E Sutherland

Publications and source records attributed to D E Sutherland.

At least 451 records · Page 25Linked to original sources
PubMed1988

Progression of diabetic retinopathy after pancreas transplantation for insulin-dependent diabetes mellitus.

We studied the effect of successful pancreas transplantation and consequent normoglycemia (mean total hemoglobin A1, 7.0 percent; range, 5.8 to 8.3) on visual function and diabetic retinopathy in 22 patients with Type I diabetes mellitus (study group). Sixteen similar patients in whom pancreas transplantation had been unsuccessful (mean total hemoglobin A1, 12.0 percent; range, 8.0 to 18.0) served as a control group. The majority of patients in both groups had advanced proliferative retinopathy. At a mean follow-up of 24 months we found no significant difference between the groups in the rate of progression of retinopathy, expressed as a score. Success of the transplantation did not prevent progression of retinopathy across the range of retinopathy studied. Progressive retinopathy was observed more commonly in patients with low retinopathy scores (nonproliferative or mild proliferative retinopathy) at base line in both the study group (13 of 17 eyes, or 76 percent) and the control group (7 of 12 eyes, or 58 percent). Further analysis suggested the possibility that after three years of euglycemia, the study group had less deterioration than the control group, particularly in eyes with advanced retinopathy. We observed no difference in the rate of loss of vision between the two groups. This study provides evidence that pancreas transplantation and subsequent normoglycemia neither reverse nor prevent the progression of diabetic retinopathy.

Adolescent↗
PubMed1988

Prevalence of major depression, simple phobia, and other psychiatric disorders in patients with long-standing type I diabetes mellitus.

To examine the prevalence of psychiatric disorders in patients with long-standing type I diabetes mellitus, we assessed a series of candidates for pancreas transplantation. Using the Diagnostic Interview Schedule, six-month and lifetime prevalences of psychiatric disorders were established for the candidates and their potential donors (first-degree relatives). Excluding tobacco use disorder and psychosexual dysfunction, 38 diabetic subjects (51%) received one or more psychiatric diagnoses. The lifetime prevalence of major depression was comparable for female (11 of 48 [22.9%]) and male (seven of 27 [25.9%]) diabetics; both rates were significantly higher than rates in first-degree relatives and the general population. Among female diabetics, the six-month and lifetime prevalences of simple phobia were increased vs donors and the general population; among male diabetics, the lifetime prevalence of antisocial personality disorder was greater than that in the general population. None of these disorders was found to be related to the duration of diabetes or the presence of various complications. The data suggest that increased rates of psychiatric disorder in type I diabetics have both gender-independent and gender-related components.

Adolescent↗
PubMed1988

Pancreatitis and hyperparathyroidism.

Hypercalcaemia is considered to be a rare cause of pancreatitis but the true cause-and-effect relationship between hyperparathyroidism and pancreatic inflammatory disease remains controversial. Over 100 patients have been reported in whom both processes have occurred concurrently, but doubts have been expressed as to whether or not this association is due to chance. We report 10 new cases of hypercalcaemic hyperparathyroidism associated with different types of pancreatitis. Seven patients had primary hyperparathyroidism and three had hyperparathyroidism after renal transplantation. Two experienced acute pancreatitis after parathyroidectomy. Of the remaining eight patients, five had hypercalcaemia equal to or above 120 mg/l. The prevalence of pancreatitis in our series of 86 cases of primary hyperparathyroidism is 8 per cent. Acute and chronic calcifying types of pancreatitis were observed. Three patients died of the disease, two of them after renal transplantation. It is suggested that pancreatitis may complicate the clinical course of hyperparathyroidism, particularly when hypercalcaemia is moderate to severe and/or there are other risk factors such as treatment with steroids and azathioprine after renal transplantation.

Adult↗
PubMed1988

Time-dependent disposition of cyclosporine after pancreas transplantation, and application of chronopharmacokinetics to improve immunosuppression.

We studied the circadian influences on cyclosporine pharmacokinetics in five recipients of pancreatic allografts. Results from these patients demonstrate a slightly increased area under the concentration-time curve (p = 0.156) resulting from decreased apparent clearance during the resting (PM) versus activity (AM) period (p = 0.199). A significant delay in mean residence time was observed after the PM dose (p = 0.039), and the PM area under the moment curve was larger than the AM value (p = 0.063). We propose three chronopharmacokinetic dosing methods that alter either the PM dose administration time or redistribute the daily dose to produce equal exposure to cyclosporine during the active and resting periods. These trends and differences suggest that more sophisticated time-dependent cyclosporine dosing methods are needed to balance AM and PM drug exposure and thereby improve immunosuppression.

Administration, Oral↗
PubMed1988

Is HLA matching relevant in pancreas transplantation? A registry analysis.

The International Pancreas Transplant Registry data base was analyzed for the effect of HLA and mismatching on pancreas survival rate. Typing data was available for both donor and recipient at the A, B and DR loci in 524 of 855 cadaver cases reported since 1982 and in 37 related cases. For cadaver cases, the 1-year functional survival rates for grafts mismatched at less than or equal to 3 (N = 163) versus greater than or equal to 4 (N = 361) A, B and DR antigens were 49% versus 39% (P = 0.121); for technically successful (TS) cases the rates were 66% (N = 123) versus 54% (N = 257) (P = 0.038). An effect was seen at A, B and DR loci, but the differences were not significant when considered separately. THe analysis of TS related donor transplants showed a 1-year graft survival rate of 89% for HLA mismatched donors (N = 11) and of 80% for HLA identical donors (N = 11). The survival rate of the latter is significantly higher (P = 0.046) than that of the TS cadaver donor transplants (59% at 1 year, N = 361). The data suggest that the results of pancreas transplantation will be improved by minimizing HLA mismatches. However, a reanalysis with a more complete data base is needed before firm conclusions can be drawn.

Graft Survival↗
PubMed1988

Failure to prolong pancreatic islet allograft survival in rats with donor-specific blood transfusions and immunosuppression.

The effects on pancreatic islet allograft survival of donor-specific blood transfusions (DST) in combination with pre- and posttransplant immunosuppression were studied. A total of 12 groups of rats (n = 105) with chemically induced diabetes underwent islet allotransplantation. Multiple DST or third-party blood transfusions (TPT) were given prior to transplantation. Pretransplant immunosuppression consisted of azathioprine and prednisolone, and low-dose cyclosporin A was used for posttransplant immunosuppression. TPT, as well as separate or combined pre- and posttransplant immunosuppression without blood transfusions, did not prolong islet allograft survival. DST resulted in either primary nonfunction of the islet allografts or a markedly decreased islet allograft survival. These findings contrast with the beneficial effect of DST on whole-organ allograft survival in rats previously described by others.

Animals↗
PubMed1988

In vitro generated allospecific cytolytic T lymphocytes injure pancreatic islets.

The role of cytotoxic T lymphocytes in the rejection of pancreatic islet allografts remains poorly defined. The present study was designed to assess the ability of in vitro generated cytolytic T lymphocytes to produce allospecific functional and structural damage of mouse pancreatic islets. A mixed lymphocyte-islet coculture model (MLIC) has been developed, in which islets from DBA/2J mice (H-2d) stimulate the generation of allospecific cytolytic T lymphocytes (C57B1/6, H-2b), as measured by lysis of allospecific chromium-labeled tumor targets. Responder C57B1/6 splenocytes sensitized to DBA/2J islets were harvested from the MLIC on Day 5 and cocultured with either freshly isolated DBA/2J or B10.BR (H-2K) islets. Islet injury was determined by assessment of beta cell function after 8 hr (as measured by insulin release in response to a glucose challenge) and islet destruction after 24 hr of coculture with the sensitized splenocytes. Whereas coculture of third party B10.BR islets with MLIC-sensitized C57B1/6 anti-DBA splenocytes had no effect on insulin release or structure, incubation of allospecific DBA/2J islets with these splenocytes resulted in inhibition of insulin release after 8 hr and disintegration of the islets by 24 hr. The depletion of MLIC-sensitized C57B1/6 anti-DBA splenocytes with anti-Lyt2 monoclonal antibody, but not anti-L3T4 monoclonal antibody, prevented the allospecific destruction of fresh islets by the splenocytes in culture. This study suggests that allospecific, cytotoxic T lymphocytes may play an important role in the effector mechanism of pancreatic islet allograft destruction.

Animals↗
PubMed1988

Hyperuricemia after renal transplantation.

Hyperuricemia is common in cyclosporine-treated renal allograft recipients. An increased incidence of gout in patients receiving both diuretics and cyclosporine has been reported, but the effect of hyperuricemia on renal allograft function has not been studied. In a prospective, randomized trial of cyclosporine and prednisone versus azathioprine, prednisone, and antilymphocyte globulin for immunosuppression in renal allograft recipients, 105 of 131 cyclosporine and prednisone-treated patients (80 percent) experienced hyperuricemia (serum uric acid level above 8 mg/dl) and 13 of 131 (10 percent) were severely hyperuricemic (serum uric acid level above 14 mg/dl). In contrast, hyperuricemia developed in 63 of 115 patients (55 percent) treated with azathioprine, prednisone, and antilymphocyte globulin (p less than 0.002). Despite the frequent occurrence of hyperuricemia, gout was rare. Clinical gout developed in six patients in the cyclosporine and prednisone group and in 0 patients in the azathioprine, prednisone, and antilymphocyte globulin group between 1 and 43 months (median 22.5 months) after transplantation. Neither severe hyperuricemia nor diuretic therapy were associated with a significantly increased incidence of gout. The mean serum creatinine concentration of severely hyperuricemic patients (all on cyclosporine and prednisone) was similar to that of normouricemic cyclosporine and prednisone patients (1.8 mg/dl versus 1.6 mg/dl, p greater than 0.2), and the severely hyperuricemic patients had a 4-year graft survival rate of 90 percent. Asymptomatic hyperuricemia after renal transplantation does not adversely affect allograft function, requires no specific therapy, and is not a contraindication to use of diuretics.

Antilymphocyte Serum↗
PubMed1988

Incidence and treatment of candida esophagitis in patients undergoing renal transplantation. Data from the Minnesota prospective randomized trial of cyclosporine versus antilymphocyte globulin-azathioprine.

Of 224 consecutive renal transplant patients in a prospective, randomized immunosuppressive trial, candida esophagitis developed in 5 despite nystatin prophylaxis. No differences were noted between cyclosporine and antilymphocyte globulin-azathioprine immunosuppressive treatment. All patients were diabetic, and four were recipients of cadaver kidneys. Candida esophagitis occurred within 6 months after transplantation, and only one patient had recurrence. All patients responded to treatment consisting of 2 to 6 days of intravenous amphotericin B (0.2 to 2 mg/kg total dose). The prevalence of candida esophagitis was not related to rejection episodes. Three of five patients eventually died, one 2 weeks after resolution of candida esophagitis from a hypoglycemic episode, one from acute exacerbation of pulmonary failure and relapsing pancreatitis in association with candida esophagitis and therapy-resistant candidemia, and one 17 months after candida esophagitis from pulmonary edema. Our findings show that candida esophagitis by itself is an easily managed complication, but is also a sign of potentially increased morbidity in these patients.

Adult↗
PubMed1988

Exocrine function of the heterotopic transplanted pancreas segment: influence of denervation in dogs.

We investigated the effect of denervation after heterotopic segmental pancreas autotransplantation on the exocrine function of the graft. The weight of the pancreas segment was determined, and secretory volume, bicarbonate output, and amylase activity were measured before and after i.v. infusion of secretin and cholecystokinin (CCK)-8. The studies were performed in untreated normal dogs, at 2 months postoperatively in partially pancreatectomized dogs with an innervated segment left in situ, and in totally pancreatectomized recipients of denervated heterotopic autotransplanted segments (approximately 30% of whole pancreas). The weight of the pancreas segment was similar in innervated and denervated dogs. Basal pancreatic secretory volume, bicarbonate output, and amylase activity were largely independent of cholinergic control. The secretory volume and bicarbonate output response to i.v. gut hormones (mainly secretin) were slightly modulated by cholinergic activity, whereas amylase response to gut hormones (mainly CCK-8) was quite independent of cholinergic control. We conclude that, after pancreas transplants, the effect of denervation on graft exocrine function is negligible--a finding that is reassuring if preserving of the exocrine tissue is important for optimal endocrine function of the graft.

Amylases↗
PubMed1988

Factors necessary for successful 48-hour preservation of pancreas grafts.

Thirty-nine canine segmental pancreatic autografts were preserved at 4 degrees C for 48 hr prior to transplantation using five different preservation solutions: modified silica gel-filtered plasma (SGFP) (n = 10); modified PPF (n = 9); modified Collins' solution (n = 8); partially modified plasma protein fraction (PPF) (n = 6), and unmodified PPF (n = 6). These modifications were with respect to osmolality, pH, protein, and potassium content. Graft function was assessed by daily fasting blood sugar and serum amylase, and by intravenous glucose tolerance test (IVGTT) and insulin output at 14-21 days. Viable preservation was deemed successful if normoglycemia was maintained for at least 5 days. Modified SGFP was successful in 80% of the animals, modified PPF in 100%, partially modified PPF in 60%, unmodified PPF in 50% and modified Collins' solution in 37%. The difference between modified PPF and the latter three solutions was significant (P less than 0.05). The causes of graft failure were primary nonfunction, graft pancreatitis, and focal necrosis in some of the grafts preserved by Collins' solution. Graft function in the surviving animals, as determined by the IVGTT and K value, was similar regardless of the method of preservation and was comparable to that previously obtained with fresh and unpreserved segmental pancreatic autografts. It is concluded that modified PPF solution is as effective as modified SGFP in the preservation of pancreatic grafts for 48 hr. The essential elements in this modification appear to be high pH and high oncotic pressure in a hyperosmolar and moderately hyperkalemic solution. Since PPF is readily available and is much cheaper than SGFP, it may be the solution of choice for clinical preservation of pancreas allografts for periods of 24-48 hr.

Animals↗
PubMed1988

The effect of pancreas transplantation on diabetic polyneuropathy.

Neuromuscular function was evaluated in long-term type I diabetic patients who retained a functioning pancreas graft. A group of 34 patients was examined at 1 year and another group of 11 patients at 2 years after pancreas transplantation. In this report the clinical and electrophysiological course of motor features of polyneuropathy are described. Before pancreas transplantation, clinical evidence of polyneuropathy was present in all patients. The mean motor nerve conduction velocities (NCV) were below normal and the mean amplitude of the evoked muscle action potentials (MAP) were in the low normal range. The observed abnormalities of muscle strength and tendon reflexes had not progressed in these intervals. Motor NCV improved slightly and MAP amplitude was essentially unchanged. These preliminary results indicate that the progression of diabetic polyneuropathy may be halted by successful pancreas transplantation.

Adolescent↗
PubMed1988

A randomized trial comparing cyclosporine with antilymphoblast-globulin-azathioprine for renal allograft recipients. Results at 2 1/2-6 years.

Between September 1980 and June 1984, 246 splenectomized, transfused renal allograft recipients were stratified according to presence of diabetes and donor source, and randomized to treatment with either cyclosporine (CsA)-prednisone (pred) or antilymphoblast-globulin (ALG--azathioprine (AZA)--prednisone. As of August 1986, mean follow-up is 47 months. Over all, actuarial patient survival is 84% and 83%, respectively at 4 years. Corresponding graft survival is 70% and 63% for CsA-treated and ALG-AZA-treated patients (NS). Within the subgroup of diabetic recipients of cadaver grafts, graft survival is 70% for CsA-treated and 53% for ALG-AZA-treated recipients (P = .035). In the CsA group, 71% required either a significant reduction in CsA dosage with the addition of azathioprine or a complete switch to azathioprine, mainly because of CsA-associated nephrotoxicity. Of those CsA patients switched at a mean time of 21.3 +/- 16.4 months posttransplant with mean serum creatinine of 2.40 +/- .67, current serum creatinine is 1.79 +/- .63. Current mean serum creatinine values are significantly greater for patients randomized to CsA-pred (1.73 +/- .60) vs. ALG-AZA-pred (1.49 +/- .59), P = .014, even though most CsA-treated patients were eventually switched. The causes of graft loss are not different between CsA and ALG-AZA randomized patients. In nondiabetics, rejection is the most common cause of graft loss (17/33), whereas in diabetics loss due to complications from overimmunosuppression or death from cardiovascular events is significantly more common (27/44) than corresponding losses in nondiabetics (6/33, P less than .05). Switching does not seem to influence the incidence or cause of graft loss. Since most patients started on CsA-prednisone are ultimately switched to triple drug therapy, the latter is now the preferred initial treatment modality.

Adolescent↗