Search PubMed⌕ Search

Biomedical subjects

D E Sutherland

Publications and source records attributed to D E Sutherland.

At least 595 records · Page 33Linked to original sources
PubMed1984

Recent experience with 89 pancreas transplants at a single institution.

Of 89 pancreas transplants performed in 77 diabetic patients (43 with and 34 without previous kidney transplants), 53 were from cadaver and 36 from related donors. To date, 64 patients (83%) are alive and 27 (35%) have functioning grafts (14 greater than 1 year), including 0 out of 3 duct-ligated, 3 out of 15 open-duct, 17 out of 32 enteric-drained, and 7 out of 39 duct-injected. Of technically successful allografts, 8 out of 16 (50%) in the azathioprine- and 17 out of 47 (36%) in the cyclosporin-treated recipients are functioning (eight cyclosporin patients also take azathioprine). Seven of the nine (78%) non-kidney-transplants recipients of technically successful pancreas allografts from HLA-identical siblings have functioning grafts. Causes of graft failure include allograft rejection, fibrosis secondary to duct injection, or selective beta-cell destruction independent of rejection. Of the 24 recipients who are currently insulin-dependent, 14 have normal or near-normal glucose tolerance test results, while 10 have abnormal results, even though they are otherwise euglycaemic. The patient population to whom pancreas transplantation is applied is gradually changing, and non-uraemic, non-kidney-transplant patients currently comprise the majority of our cases (17 out of 24 in 1983; nine of the 17 currently have functioning grafts). We now prefer the enteric drainage technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Rejection of established mouse pancreatic islet allografts by active immunization requires class I (H-2 K, D) antigen disparities.

In certain donor-recipient mouse strain combinations with class I (H-2 K, D, and K + D) or with classes I and II (H-2 D + I) disparities the incidence of islet allograft rejection is low. Furthermore pancreatic islet allografts transplanted between strains with class II (H-2 Ia) differences alone are rarely acutely rejected. In this experiment the ability of donor strain or third-party allogeneic splenocytes (active immunization) to induce rejection of established (greater than 100 days) islet allografts when the donor and recipient differed only for class I or class II antigens was tested. Class I disparate islet allografts are rejected if challenged with donor or third-party allogeneic splenocytes. The frequency of rejection is similar (80-89%) if the third-party splenocytes share the class I allele with the islet donor strain. In contrast, class II disparate islet allografts are not rejected after challenge with donor splenocytes or third-party splenocytes even when the third-party strain shares the class II disparity with the islet donor strain as well as class I antigens common to the donor and recipient. Furthermore, rejection of class II disparate islets did not occur following passive transfer of recipient strain splenocytes sensitized in vitro to donor strain lymphocytes. These results show that rejection of established islet allografts can only be induced if (1) the islet graft expresses H-2 K or H-2 D gene products that are different than the recipient strain, i.e., only class I antigens can serve as targets; and (2) challenging splenocytes also have class I disparities with the recipient.

Animals↗
PubMed1984

Factors effective in reducing rat mortality due to acute liver failure as induced by D-galactosamine poisoning.

Mortality from D-galactosamine hydrochloride (D-GalN)-induced acute liver failure (ALF) in rats can be reduced by (1) transplanting intact hepatocytes; (2) injecting cytosol from fractionated hepatocytes dispersed from a liver subjected to 70% hepatectomy 24 hr earlier (CYT-H); (3) injecting a cell-free supernate derived from cultured hepatocytes (SUP); or (4) injecting neuraminidase-treated plasma where the plasma is drawn 24 hr after donor rats are subjected to 70% hepatectomy (PHP-neu). These treatments are effective when administered 20-24 hr after D-GalN poisoning, but experiments to determine the alterations in mortality rates as a function of time of treatment in relation to poisoning have not been performed. Two experiments are reported here. In the first the survival of lethally poisoned rats was compared after intravenously injecting either SUP prepared from cultured hepatocytes of syngeneic adult or fetal rat sources, or CYT-H from syngeneic adult rats 20 hr after poisoning. Untreated rats, rats treated with culture media alone, or rats treated with CYT from a nonregenerating source had an 88-100% mortality, with all deaths occurring within 72 hr following poisoning. Improved survival followed all other treatments: 55% of the rats receiving adult SUP, 70% of the rats receiving fetal SUP, and 80% of the rats receiving CYT-H survived. In the second experiment the survival of poisoned rats was compared after injecting them with PHP-neu, PHP not treated with neuraminidase (PHP without neu), and neuraminidase-treated plasma from sham-operated rats (SP-neu) or normal, nonoperated rats (NP-neu) 20 hr after poisoning.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1984

The postoperative course and quantitative aspects of rat islet and segmental pancreas isografts.

Duct-ligated segmental pancreas transplants with systemic venous drainage were compared to intrahepatic islet grafts for beta-cell mass (proportional to tissue insulin content) and function in diabetic Lewis rats. Rats were serially killed to measure insulin in the segmental pancreas grafts and in the liver of the islet recipients. Segmental pancreas weight was maximum and insulin concentration and content lowest (P less than 0.05) on Day 3 when acute inflammation was present. At 21 days, there was no inflammation, and graft weight had decreased, but not to Day 0 level because of normal growth; insulin concentration was similar on Days 21 and 0. At 3 months, moderate fibrosis of the graft was present, but both total insulin and insulin concentration had increased (P less than 0.05). In the recipients of islet grafts, total insulin in the liver on Day 1 was only 43% of that contained in the original islet preparation, but by 3 months the insulin content in the liver had increased to that transplanted. IVGTT K values were similar in normal rats (-3.5 +/- 0.7%) and in recipients of segmental pancreas (-4.5 +/- 1.6%) and islet (-4.0 +/- 1.5%) grafts at 3 months post transplant. Acute segmental graft pancreatitis resolved, followed by an increase in beta-cell mass. Islet cell damage during transplantation is either reversible or residual viable islets proliferate, and provide metabolic control equivalent to segmental pancreas transplants, even though the final beta-cell mass is less.

Animals↗
PubMed1984

Alterations in immunological function in streptozotocin-induced murine diabetes mellitus: correction by islet cell transplantation.

Cell-mediated and humoral immune responses of streptozotocin-induced diabetic mice were evaluated using in vivo and in vitro immunological assays. C57BL/6 mice were rendered diabetic by a single intraperitoneal injection of 125-200 mg/kg of streptozotocin. Immunological studies were performed after the mice were diabetic (mean +/- SEM serum glucose 537 +/- 14 mg/dl) for a minimum of 4 weeks. Spleen cells from streptozotocin-induced diabetic mice exhibited significantly diminished direct IgM plaque-forming cell (PFC) responses following either in vivo or in vitro immunization with sheep erythrocytes, markedly impaired cytotoxic cell responses following in vivo or in vitro allogeneic stimulation, and diminished blastogenic response to the T-cell mitogens phytohemagglutinin and concanavalin A. In contrast the blastogenic response of diabetic spleen cells to lipopolysaccharide, a B-cell mitogen, was normal. The defects in in vivo PFC responses and in vivo cytotoxic cell responses were corrected by islet cell transplantation, suggesting that the abnormalities in immunological function of streptozotocin-induced diabetic mice are a consequence of the diabetic state and not of direct streptozotocin toxicity to lymphoid cells.

Animals↗
PubMed1984

Pancreas transplantation.

Clinical pancreas transplantation is a procedure being applied with increasing effectiveness for the treatment of diabetes. The authors examine, through the Pancreas Transplant Registry, all known cases of islet transplantation since 1970 and all pancreas transplantation since 1977 and then summarize their own work on pancreas transplants at the University of Minnesota.

Diabetes Mellitus↗
PubMed1984

Renal allograft survival in patients with positive B cell crossmatch to their donor.

B cell crossmatches were performed at cold (4 C) and warm (22 C and 37 C) temperatures on 193 renal allograft recipients with negative T cell crossmatches to their donor; 152 of the patients were also tested for autoantibody to autologous B cells. Fifty-six (29%) had a positive B cell crossmatch (21 cold, 35 warm); 14 were autoantibody positive, 23 autoantibody negative, and 19 were not tested for autoantibody. There were no differences in HLA-A, B, C, or DR antigen disparity between the B cell positive (14, 0 DR mismatch; 25, 1 DR mismatch; 9, 0 DR mismatch) and the B cell negative group (40, 0 DR mismatch; 57, 1 DR mismatch; 13, 2 DR mismatch). Similarly, age, diabetic status, and number and type of pretransplant blood transfusions were comparable between B cell positive and negative groups. Although there were no hyperacute rejections, 2-year actuarial graft survival was significantly lower in the B cell positive group, regardless of donor source, graft number, or temperature of reaction. Patients with a positive B cell crossmatch, presumably due to demonstrable autoantibody, may have better graft survival rates than patients with a positive B cell crossmatch and no autoantibody.

Adult↗
PubMed1984

One hundred pancreas transplants at a single institution.

Clinical pancreas transplantation at the University of Minnesota began in 1966. An initial series of 14 whole pancreas grafts was reported in part to the American Surgical Association in 1970. Only one patient survived for more than 1 year with a functioning graft. Twenty attempts at islet allotransplantation in the mid-1970s were unsuccessful. In 1978 we resumed performing pancreas transplants by the segmental technique, allowing the use of related donors. The current series (July 25, 1978 to December 20, 1983) includes 86 pancreas transplants (51 cadaver, 35 related) in 75 patients (41 with and 34 without previous kidney grafts). Variations in management of the pancreatic duct include three ligated, 15 duct-open, 39 duct-injected, and 29 pancreaticojejunostomies. The latter technique is currently preferred. Currently (April 1984) 61 patients are alive (81%), 24 have functioning grafts (32%), and 21 are insulin-independent (28%), three with open-duct grafts for 4.4 to 5.7 years, seven with silicone-injected grafts from 10 to 39 months, and 14 with pancreaticojejunostomies for 3 to 31 months; 15 of the grafts have functioned for greater than 1 year. Twenty-two of the grafts (25%) failed for technical reasons (thrombosis, infection, or ascites); 35 grafts functioned for 1 to 13 months before totally failing from either rejection, fibrosis, or recurrent disease; five patients died with functioning grafts. The graft survival rate has been higher for pancreases from related (15/35, 43% functioning) than from cadaver (9/51, 18% functioning) donors. The success rate has increased, e.g., 11/22 recipients of pancreas transplants in 1983 currently have functioning grafts (50%). Metabolic studies show most patients with functioning grafts to be euglycemic; however, three of 24 have chronic hyperglycemia unless supplemented with insulin, but they are no longer ketosis-prone. Glucose tolerance test results are normal or nearly normal in 12 and abnormal in 12 of the recipients with currently functioning grafts. Regression of diabetic nephropathy has been documented in two long-term recipients. Pancreas transplantation is currently applicable as treatment for selected diabetics who have demonstrated their propensity to develop serious secondary complications.

Adult↗
PubMed1984

Long-term effect of splenectomy versus no splenectomy in renal transplant patients. Reanalysis of a randomized prospective study.

In 1980 we determined the patient and renal allograft survival in 299 kidney transplants recipients who, between 1976 and 1979, were randomized to splenectomy (n = 146) versus nonsplenectomy (n = 152), and who were treated with antilymphocyte globulin-azathioprine-prednisone for immunosuppression. The preliminary analysis showed significantly (P less than .05) better (10% overall, 12% for cadaver, 14% for nonidentical-related) graft survival rates at two years in splenectomized recipients. The splenectomized patients had higher white blood counts and received more azathioprine and less prednisone. We concluded that splenectomy had a beneficial effect for at least the first two years posttransplant without a detrimental effect on patient survival. Splenectomy, however, remains controversial. Thus, we reanalyzed the original cohort 7 years after the study began and 4 years after the last patient was entered. The reanalysis showed that the differences in graft survival rates between splenectomized and nonsplenectomized recipients were no longer significant. There were more late deaths from sepsis in the splenectomized group, although the overall patient survival rates were similar in splenectomized and nonsplenectomized recipients. Splenectomy modestly improved graft survival for the first few years, but the eventual fate of the graft was determined by other factors. The dominant influence on graft survival rates was the source of the kidney (at 6 years in splenectomized recipients the functional survival rate of grafts from HLA-identical siblings was 24% higher than that of grafts from HLA-mismatched relatives, which in turn was 24% higher than that of grafts from cadaver donors; in nonsplenectomized recipients the difference in 6-year function rates between HLA-identical and mismatched related grafts was 34%, and between mismatched related and cadaver grafts was 16%. Between 1979 and 1983, we performed pretransplant splenectomies in all recipients of renal allografts from HLA-mismatched related or cadaver donors. Two-year graft survival rates were 81% and 68%, respectively, in azathioprine-treated recipients, 7% and 12% higher than in the splenectomized patients in the randomized trial. (ABSTRACT TRUNCATED AT 400 WORDS)

Azathioprine↗
PubMed1984

Pancreas transplants from related donors.

Of 89 pancreas transplants performed at the University of Minnesota between July 1978, and March 1983, 36 have been segmental grafts from living-related donors (17 HLA-identical siblings, 6 identical twins, 13 HLA-mismatched relatives). All recipients had been diabetic for at least 10 years and all donors were at least 10 years older than the ages of onset of diabetes in the recipients; in the case of sibling donors, no other siblings or family members other than the recipient were diabetic. Changes in plasma glucose and serum insulin levels occurred in most donors postoperatively, but glucose tolerance tests usually remained normal. Of the 36 grafts from related donors, 16 are currently functioning (12 were technical failures), as compared with 10 of 53 from cadaver donors (10 were technical failures). The pancreatic ducts were left open, injected with synthetic polymers, or anastomosed to a Roux-en-Y limb of recipient jejunum. All techniques have been associated with successes and failures, but we currently prefer the enteric-drainage technique. The patient survival rates for recipients of transplants from related versus cadaver donors were 94% versus 78% (P less than .013); the respective graft survival rates were 43% versus 20% (P = .25). When only technically successful grafts were considered, the one-year function rates were 65% for pancreas grafts from related donors (n = 29) versus 25% for those from cadaver donors (n = 43) (P = .005). The highest success rate has been in azathioprine-treated recipients of technically successful pancreas transplants from related donors of a previous kidney (3 of 3 grafts from HLA-identical siblings and 3 of 3 from HLA-mismatched relatives are functioning). However, 7 of 9 technically successful grafts from HLA-identical siblings in nonuremic, non-kidney-transplant recipients treated with cyclosporine are also functioning (one-year graft survival rate of 76%). The results in nonuremic, non-kidney-transplant recipients of mismatched related grafts have not been so good, and only one of 5 technically successful grafts in this category is currently functioning. However, this patient has been treated with cyclosporine, azathioprine, and prednisone (triple therapy)--an immunosuppressive regimen we have recently applied with success in nonuremic, non-kidney-transplant recipients of cadaveric grafts.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Glucose↗
PubMed1984

Similar renal allograft functional survival rates for kidneys from sibling donors matched for zero-versus-one haplotype with the recipient.

From January 1968 to December 1983, 536 primary renal transplants from siblings donors were performed at a single institution; of the donor-recipient pairs, 246 were matched for two, 205 for one, and 43 for zero HLA haplotypes. Renal allograft functional survival rates at two years were 93%, 75%, and 83% for the 2, 1, and 0-haplotype matched pairs. Corresponding patient survival rates were 95%, 85%, and 93%. The functional survival rate of grafts from the HLA-identical sibling donors was significantly better than the rates in both mismatched donor groups (P = .004), but the difference between the one-haplotype and the zero-haplotype matched pairs was not significant. Most transplant units do not perform transplants between siblings mismatched for both haplotypes because it is assumed that the graft survival rates will be inferior to what can be achieved with a one-haplotype match, and that the outcome will be no better than with cadaveric transplantation. Our results do not support that presumption. Although HLA-identical siblings are the best donors, a sibling should not be excluded as a donor simply because he or she is a complete mismatch. The graft survival rate (83%) is still superior to that achieved with cadaveric transplants (64% at two years, n = 618), and is at least as good as that achieved with transplants from siblings matched for one HLA haplotype. The advent of donor-specific blood transfusion has resulted in liberalization of criteria for acceptance of related donors, but the results of our analysis suggest that a liberal policy, at least in regard to haplotype matching, has always been justified--and certainly at this time the recipient with a willing living donor, regardless of match, should not be relegated to receive a cadaver graft (a scarce resource) that could otherwise be transplanted to someone else who does not have a related donor.

Graft Survival↗
PubMed1984

Structural-functional relationships in diabetic nephropathy.

Renal biopsies in 45 patients with insulin-dependent diabetes mellitus (IDDM) were examined by semiquantitative light microscopy and quantitative electron microscopic stereologic morphometry. In these 14 males and 31 females, aged 13-52 yr, who had had IDDM for 2.5-29 yr there was no strong relationship between either glomerular basement membrane (GBM) thickness or mesangial expansion and duration of IDDM. There was only a weak relationship between the thickness of the GBM and expansion of the mesangium. Thus, GBM thickening and mesangial expansion in IDDM occur at rates that often differ from one another and that vary greatly among patients. The clinical manifestations of diabetic nephropathy, albuminuria, hypertension, and decreased glomerular filtration rate related poorly or not at all to GBM thickening. In contrast, all light and electron microscopic measures of mesangial expansion were strongly related to the clinical manifestations of diabetic nephropathy, although in the absence of these clinical findings, it was not possible to predict the severity of any of the diabetic glomerular lesions. Mesangial expansion had strong inverse correlations with capillary filtering surface area density. It is hypothesized that mesangial expansion could lead to glomerular functional deterioration in IDDM by restricting the glomerular capillary vasculature and its filtering surface. However, capillary closure, glomerular sclerosis, and interstitial fibrosis could also contribute to the clinical manifestations of this disorder.

Adolescent↗