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Biomedical subjects

D E Sutherland

Publications and source records attributed to D E Sutherland.

At least 469 records · Page 26Linked to original sources

A single-center experience of renal transplantation in thirteen Jehovah's Witnesses.

The beneficial effects of pretransplant blood transfusions on the success rate of renal transplantation have been so overwhelmingly emphasized that there is virtually no information on the fate of grafts in nontransfused patients transplanted during the last decade. Since 1979, all patients who have undergone renal transplantation at the University of Minnesota have routinely received random blood transfusions except Jehovah's Witnesses. Jehovah's Witnesses refuse transfusions but will accept renal allografts. From 1979 to May 30, 1987, primary renal allografts were placed in thirteen nontransfused Jehovah's Witnesses; six patients received kidneys from mismatched living-related donors, two patients received HLA-identical sibling grafts, and five patients received cadaveric renal allografts. The range of follow-up of the thirteen patients was 3-93 months, with a mean of 45 months and a median of 50 months. The outcomes after renal transplantation in Jehovah's Witnesses were compared with those of a paired control group (n = 25) matched for age, date of transplant, donor source, and diabetic status. The overall three-year actuarial patient and graft survival rates of the Jehovah's Witnesses were 83 per cent and 66 per cent, versus 80 per cent and 77 per cent for the controls. Although the outcomes after renal transplantation in Jehovah's Witnesses were similar to those of the control group, the Jehovah's Witnesses had an increased susceptibility to rejection episodes. The cumulative percentage of incidence of primary rejection episodes was 77 per cent at three months in the Jehovah's Witnesses versus 44 per cent at 21 months in the matched control group. The consequence of early allograft dysfunction from rejection was particularly detrimental to Jehovah's Witnesses who developed severe anemia (hemoglobin (Hgb)* 4.5 g per cent)-two early deaths occurred in the subgroup with this combination of problems. The overall results suggest that renal transplantation can be safely and efficaciously applied to most Jehovah's Witnesses but those with anemia who undergo early rejection episodes are a high-risk group relative to other transplant patients.

Actuarial Analysis↗

Single-center 1-15-year results of renal transplantation in patients with systemic lupus erythematosus.

Initially, poor long-term prognosis in patients with SLE and fear of recurrent disease dissuaded renal transplantation in this group of patients. However, in 1975 the Advisory Committee to the Renal Transplant Registry reported satisfactory 1-2-year results in 56 patients with SLE from 36 institutions. Subsequently, renal transplantation for SLE patients with end-stage renal disease has become more accepted, though it has been recommended that transplantation be postponed for at least one year after initiating dialysis. Five cases of recurrent lupus nephritis have been reported in the literature. However, since the long-term outcome after transplantation in this group of patients is not well established, we have examined the long-term outcome in SLE patients who underwent renal transplantation at the University of Minnesota. Thirty-two SLE patients receiving 33 transplants between December 1969 and December 1987 were studied retrospectively and compared with controls matched for age, sex, donor source, HLA match, date of transplant, and diabetic status. A total of 69% (22/32) of patients underwent less than 1 year of dialysis prior to transplantation, and 50% (16/32) experienced biopsy-proved acute rejection, which was reversible in 67% (11/16). Actuarial graft function and patient survival rate in SLE patients were not significantly different from those in the matched control group. Duration of prior dialysis did not affect outcome. Surviving grafts have excellent function as measured by serum creatinine (1.3 +/- 0.4 mg/dl, means +/- SD). Causes of death were sepsis (5) and myocardial infarction (1). One patient lost the graft from rejection after withdrawal of immunosuppression because of a malignancy one month posttransplant. Three patients lost graft function due to chronic rejection. To date no patients have had evidence of recurrent SLE nephritis.

Follow-Up Studies↗

Monitoring urinary amylase and pH in pancreas transplantation with urinary drainage in rats.

Whole pancreas isografts or allografts (ACI donors, RT1a) with bladder drainage of exocrine secretions were performed in Lewis rats (RR1(1] with streptozotocin-induced diabetes. Urinary amylase, pH, and volume and serum glucose were measured daily. They were analyzed alone, or in combination, to determine patterns in deviations from normal values, from isograft control values, or from a posttransplant baseline in relation to rejection (defined as reversion of plasma glucose of greater than 200 mg/dl) in nonimmunosuppressed recipients. Also studied were the sensitivity and specificity by which such deviations predicted rejection. Functioning grafts were associated with increased urinary amylase and pH compared with normal or diabetic controls; urinary volume was less than that of diabetic rats, but greater than that of normal rats. In nonimmunosuppressed allograft recipients (n = 9), rejection occurred at a mean (+/- SD) of 7.78 +/- 0.44 days. Serum glucose rose to above normal (greater than 134 mg/dl) 1 day before rejection in 3 animals (sensitivity 33%, false negative rate 66%; false positive rate in 9 isograft recipients, 44%). Urinary volume dropped below 3 ml at a mean of 3.17 +/- 0.98 days (range 2-5 days) before rejection in 6 animals (sensitivity 66%, false negative rate 33%; false positive rate 0%). Urinary pH fell below 7.25 at a mean of 3.13 +/- 1.81 days (range 1-5 days) before rejection in 8 rats (sensitivity of 89%, false negative rate 11%; false positive rate 29%). Urinary amylase dropped from a posttransplant peak at a mean of 3.56 +/- 1.42 days (range 1-6 days) before rejection in 9 animals (sensitivity 100%, false negative rate 0%; false positive rate 43%), and dropped below 1500 units per 24 hr at a mean of 2.00 +/- 1.32 days (range 1-5 days) before rejection in 8 animals (sensitivity 89%, false negative rate 11%; false positive rate 0%). A drop in urinary amylase combined with a drop in urinary volume or pH occurred at a mean of 3.22 +/- 1.48 days (range 1-5 days) before rejection in 9 rats (sensitivity 100%, false negative rate 0%; false positive rate 0%). In a separate group of 10 allograft recipients, immunosuppression with prednisone and cyclosporine was begun concomitant with, or within 2 days of, the drop in urinary amylase from the peak value; rejection did not occur in 3 animals and was delayed to a mean of 12.0 +/- 5.0 days posttransplant in 7 animals (P less than .05 compared with the nonimmunosuppressed group).(ABSTRACT TRUNCATED AT 400 WORDS)

Amylases↗

Percutaneous aspiration and drainage of abdominal fluid collections after pancreatic transplantation.

Pancreatic transplantation, performed to avert or delay the long-term complications of insulin-dependent diabetes mellitus, is sometimes complicated by the development of intraabdominal fluid collections. We performed 33 sonographically guided and CT-guided percutaneous abdominal aspiration and drainage procedures in 22 transplant patients; 25 procedures were done with the pancreatic graft-in-situ, and eight were done after removal of the transplant. All 11 percutaneous aspirations performed in 10 patients were successful in obtaining microbiologic culture material, and there were no complications. Sixteen percutaneous catheter drainages were performed in 13 patients with the graft-in-situ. Subsequent surgical intervention was avoided after only five (31%) of these drainage procedures. However, further intervention was unnecessary after five (83%) of six percutaneous catheter drainages in five patients who had previously undergone transplant pancreatectomy. No significant short-term or long-term complications were identified. Guided percutaneous aspiration of abdominal fluid collections after pancreatic transplantation is a safe and effective means of obtaining diagnostic material, and guided catheter drainage is definitive treatment in approximately one-third of procedures with the graft-in-situ and in most procedures done after removal of the graft.

Adult↗

Long-term follow-up of polyneuropathy in diabetic kidney transplant recipients.

Nerve conduction and electromyography (EMG) of insulin-dependent (type 1) diabetic patients with end-stage nephropathy was studied before and up to 10 yr after kidney transplantation (KTx). A series of nondiabetic KTx patients served as a comparison group. Motor nerve conduction velocity (NCV) was measured in the ulnar, median, peroneal, and tibial nerves; sensory NCV was measured in the median nerve. EMG was performed in the first dorsal interosseus, flexor carpi radialis, anterior tibialis, and gastrocnemius muscles. In 68 pre-KTx diabetic patients, the mean NCV was below normal in all nerves, and the mean amplitudes of the evoked muscle action potential (MAP) were low normal in the upper extremity and below normal in the lower extremity. The values of the comparison group were within the normal range. At 1 (n = 57), 5 (n = 23), and 10 (n = 10) yr after KTx, the mean NCV of the diabetic patients remained essentially unchanged, but MAP amplitudes of all muscles had declined. EMG revealed progression of the denervation process, especially in muscles of the lower extremities. We conclude that diabetic neuropathy continues to progress by a progressive axonal loss after correction of uremia by KTx.

Action Potentials↗

Weight-corrected islet counts are predictive of outcome in the canine intrahepatic islet autograft model.

A combination of high-concentration collagenase digestion and density-gradient purification of canine pancreatic tissue made it possible to obtain relatively pure islets which could be quantified and the outcome of intrahepatic autotransplantation correlated with weight-corrected islet counts in the transplanted tissue. Of eleven dogs, seven achieved durable euglycaemia within 24 hours. All of these animals received islet doses of greater than 4,380 per kilogram of body weight. The remaining four animals became progressively hyperglycaemic necessitating sacrifice within one week; they all received islet doses of less than 4,380 per kilogram (p = 0.042). This model is therefore satisfactory for the investigation of preservation injury to islets and of allotransplantation because it identifies prospectively the transplants which ought to succeed, giving evidence for or against additional immune or ischaemic resistance to graft function.

Animals↗

Pancreas transplantation in nonuremic, type I diabetic recipients.

Between July 1978 and January 1988, 111 of 210 pancreas transplants were in nonuremic, nonkidney (NUNK) recipients in whom complications of diabetes were judged more serious than the potential side effects of antirejection therapy. In all NUNK cases, the 1-year patient survival rate (PSR) and graft survival rate (GSR) were 90% and 39%. Since November 1984, 1-year PSR and GSR for 62 NUNK recipients of pancreas transplants alone (PTA) were 93% and 48%, compared to 89% and 37% for 28 pancreas transplants after (PAK) and 89% and 73% for 20 simultaneous (SPK) with a kidney transplant. The 1-year GSR for 1984-88 technically successful (TS) PTA cases (n = 47) was 63%, versus 75% for PAK (n = 13) and 86% for SPK (n = 17) cases. The 1-year GSRs, by technique and source for 1984-88 PTA cases, were 58% for bladder-drained cadaver (n = 30), 51% for enteric-drained related (n = 32), and 29% for enteric-drained cadaver (n = 17) donor transplants, and 75% (n = 24), 77% (n = 16), and 38% (n = 13) for the corresponding TS cases. Of NUNK recipients, 35 have had grafts function for more than 1 year and all but 3 were treated with cyclosporine (CsA). In the CsA-treated recipients, serum creatinine increased and creatinine clearances decreased by a magnitude of 40% during the first 6 months but thereafter remained stable in all but 2 patients. In the patients with functioning grafts studied at 1 year, retinopathy remained stable in 59% and progressed in 41% of the eyes (n = 39). Motor nerve conduction velocities were significantly increased and muscle action potentials remained stable in 24 patients with functioning grafts studied at 1 year, while in 14 patients in whom transplants failed there was a significant decrease in evoked muscle action potentials. A sustained euglycemic, insulin-independent state can be established in nonuremic, nonkidney diabetic recipients of pancreas transplants alone, with a beneficial effect on neuropathy, lack of an immediate benefit on advanced retinopathy, and an effect on nephropathy compounded by the influence of CsA on renal function.

Cyclosporins↗

International Pancreas Transplant Registry report.

From December 1966 to December 1988, 1,830 pancreas transplants were reported to the International Pancreas Transplant Registry. Of these, 1,549 were reported as of June 30, 1988 and analyzed on July 13, 1988. One-year actuarial graft function (insulin-independent) and recipient survival rates for all cases were 42% and 80%, respectively. In an analysis by era of 1966 to 1977 (n = 64), 1978 to 1983 (n = 336), 1984 to 1985 (n = 387), and 1986 to 1988 (n = 762) cases, 1-year graft function rates were 5%, 25%, 41%, and 55% and recipient survival rates were 44%, 72%, 81%, and 88%, respectively (p less than or equal to 0.01 all comparisons). In an analysis of 1984 to 1988 cases only (n = 1,149), the overall 1-year graft function and patient survival rates were 49% and 85%, respectively. During this period, graft functional survival rates for the most common duct management methods were 53% for duct injection (n = 313), 45% for intestinal drainage (n = 257), and 51% for bladder drainage (n = 535) at 1 year (p less than 0.04 for intestinal vs bladder drainage). Graft function rates were similar for whole (n = 552) and segmental (n = 595) pancreas transplants (48% vs 50% at 1 year). Functional survival rates according to duration of preservation for grafts stored less than 6 hours (n = 706), 6-12 hours (n = 243), 12-24 hours (n = 95), and 12-24 hours (n = 9) were 50%, 47%, 43%, and 78% at 1 year, and none of the differences were significant. Graft functional survival rates for 1984 to 1988 cases were significantly higher (p less than 0.05) in recipients who received AZA and CsA in combination (n = 895) than in those who received CsA without AZA (n = 218) or AZA without CsA, (n = 27), with 1-year graft functional survival rates of 52%, 41%, and 33%, respectively. For technically successful grafts, the function survival rates were also significantly higher (p less than 0.05) in recipients treated with CsA + AZA (n = 708) than in those who received CsA without AZA (n = 156) or AZA without CsA (n = 19), with 1-year function rates of 66%, 56%, and 47%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Europe↗

A comparison of two cyclosporine protocols at the University of Minnesota.

1. There have been 1,426 renal transplants performed at the University of Minnesota from January 1, 1980 through August 31, 1988. CsA+P was used by 260 adult recipients, CsA+P+AZA(+ALG) by 536. 2. In general, there are no significant differences in actuarial graft or patient survival rates between the 2 CsA protocols. This is true for all adults, for all adult CAD recipients, and for a matched control group of adult CAD recipients. 3. Cox's proportional hazards regression model also indicates that there is no significant difference between the 2 CsA regimens. Donor type, number of transplants, and age at transplant influence graft survival in all adult recipients. The use of LRD is still indicated in the CsA era. Diabetic status, age at transplant, and number of transplants affect patient survival. The model fits the observed data quite well. 4. Actuarial analysis and Cox regression failed to document a beneficial effect of HLA-A, B, and DR matching in patients receiving either CsA protocol. Our data do not support the HLA matching point system currently used by UNOS or the Terasaki proposal to give points based on mismatching. 5. A matched control analysis of adult CAD recipients indicates that CsA+P+AZA+ALG has alleviated the problems of our CsA+P protocol without lowering the graft and patient survival rates. Thus, the sequential therapy group has equivalent graft and patient survival rates but shorter duration of ATN, lower serum creatinine levels at 1 year, and fewer patients who require modifications of protocol. Sequential therapy is our treatment of choice.

Adult↗

An update on pancreatic transplantation.

The number of pancreatic transplants and the success rate have continued to increase. Most pancreatic transplants have been placed in diabetic recipients of renal transplants with end-stage renal disease, but application to nonuremic patients not undergoing renal transplants is increasing. Drainage of the graft duct into the bladder allows direct assessment of exocrine function and leads to earlier diagnosis and treatment of rejection episodes. There has been an improvement in graft survival rates associated with the use of cyclosporine in combination with other immunosuppressants. The effect of successful pancreatic grafts on the specific complications of diabetes is just beginning to be discerned, but a salutary effect appears to occur if the transplant is performed sufficiently early in the course of the disease.

Animals↗