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Biomedical subjects

D E Sutherland

Publications and source records attributed to D E Sutherland.

At least 541 records · Page 30Linked to original sources
PubMed1987

Pancreas transplantation: clinical considerations.

The number of pancreas transplants performed and the success rate have increased significantly since the first segmental pancreas transplant was performed in 1966. Since 1977, 716 pancreas transplants have been performed in 670 patients at 69 institutions. Currently 230 grafts (32 per cent) are listed as functioning (insulin independent). The present 1-year actuarial graft and survival rates at the University of Minnesota are 43 and 88 per cent, respectively. The indications for pancreas transplantation and the selection of recipients have undergone modification, and more nonuremic nonkidney transplant patients are now receiving pancreas allografts. A variety of techniques have been used for pancreas transplantation. Whole or segmental pancreas grafts have been used. Most centers drain the graft exocrine secretions into the gastrointestinal tract as a Roux-en-Y pancreaticojejunostomy or into the bladder as a pancreaticocystostomy. The most common complications requiring radiologic evaluation and treatment include vascular thromboses utilizing technetium flow studies and arteriography and intra-abdominal fluid collections and infections requiring ultrasonography and CT scans. Percutaneous aspiration of intra-abdominal fluid collections is important for diagnosis but has not been successful therapeutically. Intra-abdominal infections are most common in patients with enteric drainage of the pancreas graft, which carries a high risk of contamination at the site of anastomosis. Most intra-abdominal infections require surgical drainage and removal of the graft.

Cadaver↗
PubMed1987

Ultrasound and computed tomography in the evaluation of pancreatic transplantation.

Both ultrasound and computed tomography are useful imaging modalities in the evaluation of pancreatic transplants and their complications. Ultrasound and computed tomography are most valuable in the detection of peripancreatic fluid collections, although some parenchymal abnormalities can occasionally be detected. Directed diagnostic aspiration is useful in determining the etiology of peripancreatic and other peritoneal fluid collections. The role of percutaneous catheter drainage in the management of these complex patients is not yet clearly defined.

Humans↗
PubMed1986

Depletion of donor Ia+ cells before transplantation does not prolong islet allograft survival.

Culture of pancreatic islets reduces their immunogenicity and results in prolonged graft survival after allotransplantation. The mechanism by which immunogenicity is reduced by culture is not known, but it has been suggested that prolonged graft survival is the result of the depletion of Ia+ cells from the graft. We studied the effect of eliminating Ia+ cells from islets before allotransplantation. Freshly isolated islets were incubated with anti-Ia serum plus complement or with monoclonal antibody to IAk plus complement or were left untreated before transplantation beneath the renal capsule of diabetic recipients. Incubation with anti-Ia serum plus complement eliminated intra-islet IA+ cells as demonstrated by indirect immunofluorescence staining. Incubation with monoclonal antibody to IAk plus complement significantly reduced but did not eliminate IA+ cells. Neither pretreatment regimen influenced survival of islet allografts placed beneath the renal capsule. However, untreated islets injected into the portal circulation were rejected in a low percentage of cases. We conclude that decreased immunogenicity observed after culture is not due solely to the depletion of Ia+ cells and that the site of engraftment has an important impact on graft survival.

Animals↗
PubMed1986

Pulmonary infections. The Minnesota randomized prospective trial of cyclosporine vs azathioprine-antilymphocyte globulin for immunosuppression in renal allograft recipients.

Nineteen of 224 renal allograft recipients who were prospectively randomized to receive either cyclosporine (n = 117) or azathioprine sodium-antilymphocyte globulin (n = 107) for immunosuppression suffered from one period of pneumonia (14 azathioprine and five cyclosporine recipients); two recipients of azathioprine had two episodes. Four patients in the azathioprine group and one in the cyclosporine group died, for mortalities of 3.7% and 0.85%, respectively. The percentage of pneumonia-free patients at one year was 96.3% in the cyclosporine group while it was 90.8% in the azathioprine group. Nondiabetics, women, and recipients of grafts from living related donors were at a statistically lower risk of developing pneumonia when treated with cyclosporine. Viral (cytomegalovirus), fungal (Candida, Aspergillus), and multibacterial causes of pneumonia each occurred with a similar incidence.

Adult↗
PubMed1986

Definition of normothermic ischemia limits for kidney and pancreas grafts.

Normothermic ischemia tolerance is an important aspect of organ procurement and transplantation. The function of pancreas and kidney autografts was investigated in totally pancreatectomized or nephrectomized canine recipients. In 30 dogs the left limb (tail) of the pancreas was removed but left in the abdominal cavity after cessation of blood flow to produce warm ischemia for 30, 60, and 120 min (10 dogs at each time point), and then was flushed with cold Ringers' lactate and transplanted to the iliac vessels. Twenty dogs with fresh pancreatic transplants were controls. The success rate of pancreas transplants with warm ischemia of 1/2 and 1 hr was the same as that of controls (80%); however, after 1 hr normothermia 5/10 dogs had episodes of hyperglycemia for 1 week before glucose levels came back to normal. All but one graft with 2 hr warm ischemia failed. Intravenous glucose tolerance test (IVGTT) mean (+/- SEM) K values were not different in the successful groups, i.e., no warm ischemia: -1.55 +/- 0.15%; 1/2 hr warm ischemia: -1.81 +/- 0.18%; 1 hr warm ischemia: -1.64 +/- 0.09%. Amylase levels increased after transplant with maximum values at Day 2, then returned to normal, but the levels remained elevated in recipients of grafts subjected to longer normothermia with evidence of pancreatitis after 1 hr warm ischemia. Fifteen kidney grafts were treated similarly with warm ischemia exposure of 1/2 hr (n = 9) and 1 hr (n = 6) before being flushed and autotransplanted, and were compared to 16 fresh kidney transplants. After 1/2 hr warm ischemia none of the kidney grafts failed but 78% of the recipients had elevated serum creatinine and urea nitrogen levels which returned slowly to normal after 3 to 4 weeks. There was only one long-term survivor after 1 hr warm ischemia. Thus the pancreas seems to be more resistant to warm ischemia damage than is the kidney. This difference should be taken into consideration in regard to organ procurement for clinical transplantation.

Amylases↗
PubMed1986

Urinary amylase monitoring for early diagnosis of pancreas allograft rejection in dogs.

The diagnosis of pancreas allograft rejection is usually made on the basis of blood glucose concentration, a late indicator of rejection. We performed segmental pancreas transplants in totally pancreatectomized dogs with the exocrine secretions drained into the bladder (ductocystostomy). We directly measured exocrine pancreatic secretions (urinary amylase), in an attempt to find a sensitive indicator for early rejection. Five groups were studied: (I) autografts; (II) autografts immunosuppressed with cyclosporine (CsA), azathioprine and prednisone; (III) allografts without immunosuppression; (IV) allografts immunosuppressed with CsA alone; (V) allografts immunosuppressed with CsA, azathioprine, and prednisone. The control groups (I, II) maintained high urine amylase concentrations indefinitely (mean +/- SE of 125,544 +/- 36,931 u/liter). Rejection, as diagnosed by rise of serum glucose to greater than 150 mg/dl, occurred at a mean (+/- SE) of 9.0 +/- 0.2 days in nonimmunosuppressed recipients of Group III, at 9.3 +/- 0.7 days in cyclosporine-treated dogs of Group IV, and at 28.0 +/- 8.3 days after transplantation in dogs immunosuppressed with triple therapy of Group V. In all allograft recipients, urine amylase declined precipitously (less than 1000 u/liter) before the onset of hyperglycemia, by 1.3 +/- 0.2 days in Group III, 3.3 +/- 1.0 days in Group IV, and 9.4 +/- 2.8 days in Group V. In a further experiment, nine dogs with pancreas allografts received cyclosporine for prophylactic immunosuppression; further antirejection therapy with azathioprine and antilymphocyte globulin was given for 5 days beginning the first day that rejection was diagnosed. In five dogs (Group A) rejection was diagnosed when serum glucose rose to greater than 150 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗
PubMed1986

Pancreas transplantation.

The data on vascularized pancreas transplant cases reported to the old American College of Surgeons/National Institutes of Health Organ Transplant Registry from December 17, 1966, through December 31, 1984, are summarized in this article. Also described is the experience at the University of Minnesota, where more than one fifth of the transplants have been performed. The authors conclude that pancreas transplantation is now an effective treatment for human diabetes.

Diabetes Mellitus↗
PubMed1986

Glomerular filtration surface in type I diabetes mellitus.

Previously we have shown that relative glomerular mesangial expansion was an important correlate of renal dysfunction in diabetes. To extend the understanding of structural functional relationships, 37 patients with type I diabetes mellitus for 5 to 33 years were studied with multiple creatinine clearance (Ccr), urinary albumin excretion, and blood pressure measurements, and percutaneous renal biopsies. Glomerular volume and percent sclerosed glomeruli were determined; quantitative stereology was performed to determine relative glomerular structural parameters. Per glomerulus we calculated mesangial volume and capillary filtration surface and per patient we estimated capillary filtration surface. Capillary filtration surface per glomerulus or per patient were highly predictive of Ccr (r = +0.78, r = +0.79, P less than 0.001). There was a significant but weak relationship between Ccr and mesangial volume. However, mesangial volume and glomerular volume together were highly predictive of both Ccr and filtration surface. Mesangial volume was increased and filtration surface decreased in the hypertensive patients and the patients with urinary albumin excretion less than 250 mg/24 hr. Thus, it appears that mesangial expansion within a relatively large glomerulus has less influence on filtration than does a similar increase in mesangial volume within a smaller glomerulus. There is a striking relationship between glomerular filtration rate and filtration surface in diabetes throughout the range from hyperfiltration to significant hypofiltration.

Adolescent↗
PubMed1986

Intra-abdominal infections in pancreas transplant recipients.

During a 7-year period, 116 pancreas transplants were performed in 98 diabetic patients (49 with and 49 without previous kidney transplants) at the University of Minnesota. The posttransplant clinical course of 26 recipients (22%) was complicated by an intra-abdominal infection (8 with and 18 without previous kidney transplants). Infections occurred in 19/57 cases (33%) in which exocrine secretions were managed by enteric drainage, in 5/15 cases (33%) managed by free drainage into the peritoneal cavity, in 1/39 cases (3%) in which the duct was injected with a synthetic polymer, and in 1/2 cases (50%) in which a pancreaticocystostomy was performed. The organisms Escherichia coli, enterococci, bacteroides, and several anaerobes were cultured from the patients with enteric drainage, while staphylococci were associated with the open duct drainage. Fungal infections with Candida were found with all techniques. Surgical and percutaneous drainage was performed in all patients. In 14 patients, functioning and, in four patients, nonfunctioning grafts were removed. In five patients, the infection resolved while the grafts were functioning, and these patients are currently alive and well. Seven of the 26 patients with infections died (27% mortality rate), five after graft removal and two with the graft still in place (1 with and 1 without function), five in the open-duct, and one each in the enteric and urinary drainage categories. In the 90 cases without intra-abdominal infection, only six patients died (4 cardiovascular, 1 anaphylaxis, 1 cytomegalovirus infection), for a mortality rate of 7%.

Abdomen↗
PubMed1986

The outcome of 304 primary renal transplants in children (1968-1985).

Of 304 children who received primary renal transplants at the University of Minnesota between January 1, 1968, and December 31, 1985, 48 (16%) were under the age of 24 months, 60 (20%) were 2-5 years old, and 196 (64%) were 6-17 years old at transplantation. Currently, 254 (84%) are alive at 2 months to 18 years following their first transplants, 77% with functioning grafts (188 first, 45 retransplants) and 7% on dialysis. Overall, patient and graft survival were not significantly different from the primary graft outcome of nondiabetic adults. The actuarial primary graft function rates at 1, 5, and 10 years were 100, 100, and 90% in 16 HLA-identical sibling kidneys; 84, 64, and 52% in 210 mismatched related kidneys; and 72, 54, and 47% in 78 cadaver kidneys (p less than 0.002). The 1-year patient survival and primary graft function rates in 44 mismatched related recipients under the age of 24 months were 92 and 88%. The use of deliberate, pretransplant random blood transfusion since 1979 has been associated with a decreased rejection rate. Primary graft function of mismatched related kidneys in children receiving standard immunosuppression has significantly improved from 78% at 1 year in the pretransfusion era to 91% (p less than 0.01) in the transfusion era. The overall primary cadaver graft function rate, however, did not improve in the transfusion era. Whether cyclosporine use will improve the cadaver renal allograft function in very young recipients remains to be established. However, with the use of related donors, even very young children can be transplanted safely and with excellent results.

Adolescent↗
PubMed1986

The effects of delayed function on recipients of cadaver renal allografts. A study of 158 patients randomized to cyclosporine or ALG-azathioprine.

We randomized 158 recipients of cadaver renal allografts to cyclosporine-prednisone (83) or antilymphocyte globulin-azathioprine-prednisone (75) to evaluate: the effects of immunosuppression and pretransplant risk factors on the incidence of delayed graft function, the effects of immunosuppression on the resolution of delayed graft function, and the effects of delayed graft function and pretransplanted risk factors on patient and graft survival. Cyclosporine did not increase the incidence of delayed graft function, compared with ALG-azathioprine-treated patients (33% versus 27%, P = 0.550) but doubled the mean (+/- SD) duration of oliguria (11.8 +/- 11.0 versus 5.9 +/- 3.2 days, P = 0.002) and the number of required dialyses (6.6 +/- 7.6 versus 3.2 +/- 1.3, P = 0.031). Retransplanted patients had a higher incidence of delayed graft function that recipients of primary grafts in both the cyclosporine (82% versus 25%, P = 0.001) and ALG-azathioprine (55% versus 22%, P = 0.025) treatment groups. The presence of delayed function reduced one-year graft survival from 89% in all patients without delayed function to 72% (P = 0.011) in all patients with delayed function. Cyclosporine-treated patients had a slightly, but not significantly better one-year graft survival rate than ALG-azathioprine treated patients both with (73% versus 68%, P = 0.750) and without (92% versus 82%, P = 0.069) delayed graft function. A preservation time longer than 24 hr did not increase the incidence of delayed graft function in cyclosporine-treated patients (34% versus 32%, P = 0.811) or ALG-azathioprine-treated patients (27% versus 27%, P = 0.902). Cyclosporine-treated patients given kidneys with greater than 24 hr of preservation time had reduced graft survival only when delayed graft function occurred (67% versus 92%, P = 0.009). In conclusion, (1) cyclosporine did not increase the incidence of delayed graft function over ALG-azathioprine treatment; (2) cyclosporine did significantly slow recovery of kidneys with delayed function; (3) delayed graft function correlated with poorer graft survival rate in both treatment groups; but (4) prolonged preservation time did not increase the incidence of delayed graft function or reduce graft survival.

Actuarial Analysis↗