Search PubMed⌕ Search

Biomedical subjects

D E Sutherland

Publications and source records attributed to D E Sutherland.

At least 325 records · Page 18Linked to original sources
PubMed1991

Long-term metabolic function of pancreas transplants and influence of rejection episodes.

Pancreas grafts, when not rejected, can sustain an insulin-independent state in type I diabetic recipients for indefinite periods. To what extent the metabolic control achieved approaches that of normal individuals, the relationships between graft endocrine and exocrine function, the effect of reversible rejection episodes on subsequent graft function, and the correlation between the results of serial tests of graft function were determined by studies at 1 month, 1 year, and 2 years in a cohort of 39 recipients (29 females, 10 males; mean age (+/- SD), 33 +/- 5 years; mean duration of diabetes, 22 +/- 6 years) of bladder-drained pancreas transplants performed between November 1984 and December 1988. Fifteen patients received a pancreas transplant alone, 8 a pancreas after a kidney, and 16 a simultaneous pancreas/kidney transplant. Graft endocrine function was tested by a 24-hr metabolic profile of blood glucose levels before meals, at 1 and 2 hr after meals, and during the night (14 values in all), by intravenous and oral blood glucose tolerance tests, and by glycosylated hemoglobin levels (HA1 and HA1c). Graft exocrine function was assessed by urine amylase activity (U/hr). The results of the tests in the recipients were subjected to paired comparisons between timepoints and at each timepoint to the results of the same tests in 55 normal nondiabetic control individuals. The means of the mean 24-hr profile glucose (mg/dl) values were significantly lower (P less than 0.05) at 1 and 2 years posttransplant (116 +/- 27 and 115 +/- 15, respectively) than at 1 month (128 +/- 31) in the recipients, but the mean of the mean values in the normal controls (100 +/- 7) was even lower (P less than 0.05). Mean values of individual timepoints during the profile were significantly lower for 6 of the 14 values in the controls than in the recipients. The mean IVGTT K value of the normal controls (-1.9 +/- 0.4%) was significantly lower than the 1-month and 2-year values of the recipients (-1.5 +/- 0.5% and -1.3 +/- 0.6%, respectively), but the comparison with the 1-year value (-1.6 +/- 0.6%) was not significant. The mean glucose levels at zero minutes and between 120 and 300 min of the OGTTs were significantly lower at both 1 and 2 years than at 1 month in the recipients, and the values in the control group were also significantly lower than in the recipients at 1 month but not at 1 and 2 years.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Glucose↗
PubMed1991

Assessment of renal function in type I diabetic patients after kidney, pancreas, or combined kidney-pancreas transplantation.

The long-term kidney function (KF) in the three categories of diabetic type 1 pancreas (P) transplant recipients (simultaneous P and kidney [SPK]; P after K [PAK]; PTx alone [PTA] was studied sequentially over a 2-year period in 62 patients who received a bladder-drained allograft that functioned for at least 1 year. Fifty-three (85%) patients were analyzed at 1 month, 42 (68%) at 1 year, and 16 (26%) at 2 years posttransplant. Comparison of KF was made within each recipient category and between categories. In addition, the KF in the SPK and PAK patients was compared to a matched group of diabetic type 1 recipients of KTx alone (functioning at least 1 year). In the SPK group, KF was stable over time: the mean +/- SD serum creatinine (mg/dl) was 1.5 +/- 0.5 at 1 month, 1.8 +/- 1.0 at 1 year, and 1.7 +/- 0.5 at 2 years. In the PAK category, the pre-PTx serum creatinine value was 1.4 +/- 0.5, and then remained stable after the PTx (1.3 +/- 0.2 at 1 month, 1.3 +/- 0.4 at 1 year, and 1.2 +/- 0.4 at 2 years). In the recipients of a PTA, the values at 1 month (1.1 +/- 0.4), 1 year (1.4 +/- 0.5), and 2 years (1.3 +/- 0.5) were significantly higher (P less than or equal to 0.03) than the pre-PTx value (0.9 +/- 0.2); and results at 1 month and 2 years were lower than those at 1 year, a significant difference compared to the 1-month value (P = 0.01). Comparisons between the categories of PTx recipients demonstrated that the pre-PTx value in the PTA group (0.9 +/- 0.2) was significantly lower (P = 0.01) than in the PAK group (1.4 +/- 0.5). At 1 month the serum creatinine value in the PTA category (1.1 +/- 0.4) was significantly lower (P = 0.02) than in the SPK category (1.5 +/- 0.5), but thereafter (1 and 2 years) the difference was not significant (P greater than 0.1). KF in recipients of KTx alone was similar at each post-Tx time point when compared to the SPK and PAK categories. We concluded that a PTx can be performed in diabetics without a detrimental effect on a simultaneously or a previously transplanted kidney and that a statistically significant, albeit minimal to moderate, initial but not progressive deterioration in native KF occurs in recipients of a PTx alone.

Creatinine↗
PubMed1991

Total pancreatectomy in the pig for islet transplantation. Technical alternatives.

Pigs appear to be a suitable biological and logistical animal donor of islets for xenotransplantation in human diabetic type I recipients. To improve the islet isolation technique in this species, to evaluate the islet function in vivo, and to assess the toxic effects of various immunosuppressive regiments on transplanted islets will necessitate a model of the pancreatectomized pig suitable for islet autotransplantation. We describe three techniques of total pancreatectomy in pigs. The first removed the pancreas in order to study postoperative management and pig survival; no attempt was made to preserve the pancreas for islet isolation. The second consisted of a pancreatectomy in a surviving pig, with careful preservation of the whole pancreas for subsequent islet isolation. The third was rapid en bloc procurement of the pancreas and duodenum, to obtain a pancreas solely for the purpose of islet isolation. We conclude that pigs tolerate and survive a total pancreatectomy--they are suitable animals for islet isolation and possible autotransplantation. The result of islet isolation does not appear related to the pancreas procurement technique; however, the islet yield must be improved before autotransplantation can be functionally successful.

Animals↗
PubMed1991

Evidence for direct and indirect pathways in the generation of the alloimmune response against pancreatic islets.

The role of the direct and indirect pathways of alloantigen presentation in the generation of the alloimmune response was dissected using the murine mixed lymphocyte-islet coculture system (MLIC). Stimulator DBA/2J (H-2d) pancreatic islet populations consisted of whole islets (MHC class I+, II+) or FACS-purified beta cells (MHC class I+, II-). Responding C57Bl/6 (H-2b) splenocyte populations were either: (1) untreated; (2) depleted of helper T cells with anti-L3T4 monoclonal antibody plus complement; (3) depleted of cytotoxic T lymphocytes with anti-Lyt2 mAb plus complement; or (4) depleted of antigen-presenting cells by passage through a Sephadex G-10 column. Whole islets were capable of stimulating a significant C57Bl/6 anti-DBA cytotoxic T cell response if the responding population was untreated or treated with complement alone. Depletion of responding splenocytes with either anti-Lyt2 or anti-L3T4 mAb plus complement abrogated the generation of allospecific CTL. If the responding splenocyte population was depleted of APCs, the allo-CTL response against whole islets was decreased, but still significant. If, however, the stimulator population consisted of FACS-purified DBA 2J beta cells, APC-depleted C57Bl 6 splenocytes were incapable of generating any CTL response. Adding responder type (C57Bl/6) APCs back to the microwells restored the capacity for both whole islets and purified beta cells to stimulate a strong allo-CTL response. These data demonstrate that both indirect and direct pathways of alloantigen presentation function in the MLIC.

Animals↗
PubMed1991

Results of pancreas transplantation in the United States for 1987-90 from the United Network for Organ Sharing (UNOS) Registry with comparison to 1984-87 results.

An outcome analysis was performed on pancreas transplants in the United States reported to the United Network for Organ Sharing (UNOS) Registry from its inception on 1 October 1987 to 21 October 1990 (n=1021). These cases comprise nearly one-third of the 3082 pancreas transplants reported to the International Pancreas Transplant Registry (1819 U.S., 1263 non-U.S.) from 1 December 1966 to 31 December 1990, including 619 in 1990 (528 U.S., 91 non-U.S.). Nearly all pancreas transplants in the U.S. during the 1987-90 period were by the bladder-drainage (BD) technique (92%). The overall patient and pancreas graft actuarial survival rates were 92% and 72% at 1 year. Patient survival rates were similar in all recipient categories, but pancreas graft survival rates were significantly higher (p less than 0.001) in recipients of a simultaneous pancreas and kidney (SPK) transplant (n=883) than in recipients of a pancreas after a kidney (PAK, n=112) or a pancreas transplant alone (PTA, n=71), being 77%, 52%, and 54%, respectively, at 1 yr. Kidney graft survival at 1 yr in U.S. SPK recipients was 86%. Most grafts (81%) were preserved in University of Wisconsin (UW) solution, and more than half were stored greater than 12 hours, with no difference in outcome with increasing duration of storage. At 1 yr, functional survival rates were 72% for U.S. pancreas grafts stored for either less than 12 (n=439), 12-24 (n=422), or 24-30 h (n=42). For grafts stored greater than 30 h (n=8), the 1-yr functional survival rate was 50% (p=ns versus the other storage times). On univariate analysis, no effect of HLA antigen mismatching on outcome for 1987-90 U.S. cases could be discerned. The results in the UNOS Registry were compared to the results for U.S. cases in the International Pancreas Transplant Registry performed between 1 January 1984 and 30 September 1987. In all recipient categories the pancreas graft functional survival rates were significantly higher in the 1987-90 (UNOS) than in the 1984-87 (pre-UNOS) era. A Cox multivariate analysis of 1984-90 cases showed the relative risk for pancreas graft loss to be significantly less (p less than 0.05) with bladder-drainage, with simultaneous transplantation of the kidney, with use of UW solution for preservation, and with 0-1 HLA-A, B, DR or 0 HLA-DR mismatches.(ABSTRACT TRUNCATED AT 400 WORDS)

Graft Survival↗
PubMed1991

Examination of the role of the colloids hydroxyethylstarch, dextran, human albumin, and plasma proteins in a modified UW solution.

The delayed contralateral nephrectomy procedure (three-step) produced inconsistent results, indicating that the preserved autotransplanted kidney tends to remain unfunctional and to regenerate incompletely unless the demand for work is placed upon it. Omission of HES in UW (UW-plain) did not affect preservation success, but resulted in increased graft edema. Substitution of HES in UW with plasma (SGF-V) or albumin (MAlb) gave significantly worse results than UW-like solutions with or without synthetic colloids. Replacement of HES in UW with UMdex-70 or UMdex-500 gave nonsignificantly worse results than UW-like solutions with or without synthetic colloids. The use of UMdex-40 as the main colloid in UW cheapened the solution, equalled the preservation success of UW and UW-plain but surpassed UW-plain in edema prevention, and exceeded UW concerning recovery of graft microcirculation.

Adenosine↗
PubMed1991

A single institution's experience with solitary pancreas transplantation: a multivariate analysis of factors leading to improved outcome.

The results of cadaveric donor pancreas transplantation at a single institution using the bladder drainage technique have been analyzed according to several factors that may impinge on outcome. Both multivariate and univariate statistical methods were used, with emphasis on solitary (pancreas after kidney and pancreas transplant alone) as opposed to simultaneous pancreas/kidney transplants. Of the 444 pancreas transplants performed at our institution from December 1966 through December 1991, we analyzed 249 bladder-drained cadaver donor pancreas transplants from November 1984 through August 1991. The factors that had a significant impact on outcome in the Cox multivariate analysis included retransplantation, age, preservation time, and degree of HLA mismatching. The results of solitary pancreas transplants improved with time as the factors that have an impact on graft survival rates were deliberately manipulated. During the 1988 to 1991 era, pancreas graft functional survival (insulin-independent) rates were not significantly different among the 3 recipient categories. Solitary pancreas transplant recipients less than 45 years old receiving primary grafts had a 1-year function rate of 61% in the pancreas transplant alone group (n = 32) and 74% in the pancreas after kidney group (n = 24). By placing emphasis on minimizing HLA mismatches, by giving adequate immunosuppression, and by detecting and treating rejection episodes early based on a decline in urine amylase, the results with solitary pancreas transplantation can be as good as those with simultaneous pancreas kidney transplantation. There are limitations to the interpretations that can be given to retrospective studies using inhomogeneous factors, as is the case in the analyses presented here. We cannot identify risk factors with certainty because the protocols changed over time, eg, immunosuppressive regimens, policies on HLA matching, and choice of duct-management techniques. Thus, in the analysis of all cases, not only was there a higher proportion by the bladder-drainage techniques in the later period, but the proportion of cases with good HLA matches was also higher: yet the earlier cases (more poorly matched, performed by the other techniques, and with worse results), were in the model. Retransplantation is also a problem for the analysis. The number performed was proportionately greater in the later period, and the possibility of retransplantation differed according to the patient's age. Over such a long time, we cannot evaluate our gain in experience statistically.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Report on results of pancreas transplantation in the United States October 1987 to October 1991 from the United Network for Organ Sharing Registry.

More than 3,600 pancreas transplants were reported to the International Pancreas Transplant Registry by the end of 1991. More than 2,200 of the transplants were performed in the United States, including more than 1,600 that had been reported to the UNOS Registry since October 1, 1987. Of these, more than 1,400 have been entered into a computerized data base, and in more than 1,300 there was sufficient information for actuarial patient survival and graft functional (insulin-independent) survival rates to be calculated. Overall patient (n = 1,362) survival and pancreas graft (n = 1,340) functional survival rates were 91% and 72%, respectively at 1 year; the patient and graft survival rates were 86% and 65%, respectively, at 2 years; and 80% and 57%, respectively, at 3 years posttransplant. In the 3 major recipient categories, simultaneous pancreas/kidney (SPK) transplants (n = 1,149), pancreas after kidney (PAK) transplants (n = 131), and pancreas transplants alone (PTA) cases (n = 82), the 1-year patient survival rates were 90%, 92%, and 92%, with the corresponding survival rates at 2 years being 87%, 89%, and 89%, and at 3 years being 80%, 83%, and 83% (p = NS). The corresponding pancreas graft functional survival rates at 1 year in the 3 recipient categories were 76% for SPK (n = 1,131), 54% for PAK (n = 127), and 47% for PTA (n = 82).(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 1↗
PubMed1991

Autotransplantation of dispersed pancreatic islet tissue combined with total or near-total pancreatectomy for treatment of chronic pancreatitis.

Chronic pancreatitis is difficult to treat in patients with a nondilated duct. Patients experiencing intractable pain unresponsive to or judged untreatable by lesser procedures must decide between total pancreatectomy and resultant diabetes or a continuation of their pancreatitis. From 1977 through 1990, 26 patients underwent extensive pancreatectomy and dispersed pancreatic islet tissue autotransplantation for treatment of chronic pancreatitis pain and prophylaxis of surgical diabetes. Of these 26 patients, total (Whipple) or near-total (greater than 95%) pancreatectomy was performed in 24 patients. Of these 24 patients, pain relief could be assessed in 21 patients at 5 to 155 months (mean, 5.7 years), and 19 patients (90%) reported partial or complete remission. Of the patients who underwent total or near-total pancreatectomy, islets were injected intraportally in 22 patients and into the renal subcapsule in two patients. The latter two patients have required insulin since surgery. Of the other 22, one patient died from a complication of the pancreatectomy. Nine of the 21 evaluable recipients of intraportal islet autografts were insulin independent for at least several months after surgery. Five patients are currently insulin independent at 6 years, 4 years, 1.5 years, 9 months, and 5 months after surgery. Of the other four patients, one patient died insulin independent at 6 years, and three patients required insulin beginning 8 to 18 months after surgery. Insulin independence correlated with the number of islets recovered, which in turn correlated inversely with the degree of pancreatic fibrosis. Of our four most recent patients, three patients had mildly to moderately fibrotic glands, and higher numbers of islets were obtained. After total (Whipple) pancreatectomy, these three patients are insulin independent. A liver biopsy was performed in one patient 8 months after total pancreatectomy and islet autotransplantation; numerous clusters of islet cells staining strongly for insulin and glucagon were detected within portal triads on both wedge and needle biopsy specimens. Morbidity related to the intraportal-dispersed pancreatic islet tissue transplantation was low (no disseminated intravascular coagulation, significant portal hypertension, or hepatic dysfunction). Islet autotransplantation can be an effective and safe adjunct to extensive pancreatic resection for those patients who risk surgical diabetes for relief of their chronic pancreatitis pain.

Abdominal Pain↗