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D E Sutherland

Publications and source records attributed to D E Sutherland.

At least 127 records · Page 7Linked to original sources
PubMed1996

A novel dextran 40-based preservation solution.

Although the University of Wisconsin (UW) solution has become the standard solution for the preservation of kidneys for transplantation, the importance of the colloid hydroxyethylstarch (HES), one of the key compounds of the UW solution, has been questioned repeatedly. It is now established that HES is not necessary for routine kidney preservation. However, colloids may still be advantageous in UW like solutions for the purpose of multiorgan procurements and the preservation of organs from marginal donors. It has been shown in various experimental models that dextran 40 may successfully substitute for HES. Dextran 40 is not only cheaper but also has a variety of biological effects that may be beneficial during the graft reperfusion phase. The aim of this clinical study was to examine the efficacy of a dextran 40-based preservation solution (Dex-PS) for its use in human kidney graft preservation and to compare the transplantation results with kidneys preserved with UW solution. A total of 87 kidneys were preserved with Dex-PS and matched with 87 kidneys preserved with UW solution. Both groups were comparable in terms of donor and recipient characteristics and both had a high proportion of kidneys from nonheart-beating donors. Patient survival and graft survival after 1 year were 95% and 86% for the Dex-PS group and 94% and 90% for the UW group, respectively (P = NS). Primary nonfunction, delayed graft function, postoperative need for dialysis, and follow-up of serum creatinine were statistically comparable between these two groups. We conclude that dextran 40 can safely replace HES in UW solution for the purpose of clinical kidney preservation. There were no statistically detectable differences in graft performance between the kidneys preserved with UW and those preserved with Dex-PS.

Adenosine↗
PubMed1996

Islet Autotransplantation after total pancreatectomy in a child.

Islet autotransplantation can prevent surgically induced diabetes after total pancreatectomy in adults; however, the efficacy of this procedure has not been established in children. The authors report the case of a 12-year-old boy who underwent total pancreatectomy and islet autotransplantation for intractable pain caused by idiopathic chronic pancreatitis. Islets were prepared from the excised pancreas by collagenase digestion and mechanical dispersion. The resultant preparation, containing 109,500 islets, was injected into the recipient's liver via the portal vein. No complication from the pancreatectomy or transplant occurred. Postoperatively, the patient had complete relief of abdominal pain. He remained insulin-independent, with normal fasting blood glucose and hemoglobin A1c levels, for 21/2 years. Preoperatively, the acute insulin response and the rate of glucose disappearance (Kg) were 213 microU/mL and 2.14% (respectively) after intravenous administration of 20 g of glucose. Although lower than pretransplantation values, both insulin response and Kg remained normal at 4 months (88 microU/mL; Kg, 1.01%); however, these decreased further, to below normal, by 2 years posttransplantation (10 microU/mL; Kg, 0.67%). Two-and-a-half years after transplantation, fasting hyperglycemia (> 200 mg/dL) was evident, and the patient was begun on exogenous insulin. Five years posttransplantation he remains insulin-dependent with a fasting serum C-peptide level of 0.20 ng/mL, which increased to 0.35 ng/mL in response to intravenous arginine, indicating sustained islet function. During the documented decreases in insulin secretion and Kg posttransplantation, the patient's body weight increased by 65% (from 34 to 56 kg) as a result of normal growth; the number of transplanted islets relative to body mass decreased accordingly, from 3,200 to 1,950 islets per kilogram of body weight. In this case, the number of islets transplanted likely could not meet the increased insulin demands of the larger body mass. Thus, exogenous insulin supplementation was needed to prevent hyperglycemia. In conclusion, insulin independence was initially established in a child by islet autotransplantation after total pancreatectomy. The failure of the islets to maintain normoglycemia long-term suggests that a sufficient number must be transplanted (to meet the demands of normal growth and development) for sustained insulin independence.

Blood Glucose↗
PubMed1996

Prostaglandin E2 potentiates interleukin-1 beta induced interleukin-6 production by human gingival fibroblasts.

Increased levels of cytokines and prostanoids have been detected in inflamed gingival tissue and may play an important role in periodontal pathogenesis. Recent studies suggest that monocytic products, such as interleukin (IL)-1 beta, could stimulate IL-6 production by human gingival fibroblasts (HGF). In this context, the production of local cytokines and inflammatory mediators could regulate the secretory capacity of resident gingival fibroblasts. Therefore, the purpose of this study was to determine if PGE2 induced by IL-1 beta could potentiate the IL-6 response by HGF. Utilizing an ELISA, it was determined that maximal IL-6 occurred when HGF were stimulated with 0.10-10 nM IL-1 beta. These concentrations of IL-1 beta also induced a small, but significant increase in PGE2 production by HGF. Interestingly, the combination of IL gamma beta and PGE2 induced a synergistic rise in IL-6 production by HGF. Moreover, inclusion of indomethacin caused a 20% reduction in IL-6 production and totally eliminated PGE2 production. These findings provide additional rationale for the clinical use of NSAIDs in the management of periodontal disease due to their ability to attenuate production of both PGE2, and IL-6. These results suggest the endogenous PGE2 induced by IL-1 beta plays an important regulatory role in IL 6 production by HGF. Moreover, they support the concept that elevated PGE2induced during inflammation can regulate HGF secretory function.

Analysis of Variance↗
PubMed1996

Vascular graft thrombosis after pancreatic transplantation: univariate and multivariate operative and nonoperative risk factor analysis.

BACKGROUND: Vascular thrombosis is still the leading cause of nonimmunologic, technical pancreatic transplant graft failures. The paucity of published data--coupled with our large institutional experience with pancreatic transplantation in all recipient and transplant categories, using a wide spectrum of surgical techniques--provided the impetus for a retrospective study of graft thrombosis risk factors. STUDY DESIGN: Four hundred thirty-eight patients with pancreatic transplants (45 percent simultaneous pancreas-kidney [SPK], 23 percent pancreas-after-kidney [PAK], and 32 percent pancreatic transplants alone [PTA] and with Type I insulin-dependent diabetes mellitus were studied retrospectively. Of 438 pancreatic transplants, 90 percent were bladder-drained and 10 percent were enteric-drained. Ninety-three percent were from cadaver donors, 90 percent were whole-organ grafts, and 20 percent were retransplantations. Quadruple immunosuppression was given. For bladder-drained, whole-organ transplantations (n=378), we performed Cox regression analyses to study the impact on pancreatic graft thrombosis of donor, recipient, mode of preservation, and surgical variables. RESULTS: The overall thrombosis rate was 12 percent (5 percent arterial, 7 percent venous). For cadaver, bladder-drained, whole-organ pancreatic transplants, the thrombosis incidence was highest in PAK recipients (20 percent). The PAK category was also found to be an independent risk factor for thrombosis by stepwise Cox regression analysis. In separate stepwise Cox regression analyses for each category, other identified risk factors for thrombosis included the following: donor age (PAK, PTA); cardiocerebrovascular cause of donor death (SPK, PAK); the use of an aortic Carrel patch (SPK); arterial pancreatic graft reconstruction using a splenic artery to superior mesenteric artery anastomosis (SPK, PTA) or an interposition graft between the splenic artery and the superior mesenteric artery (PTA); portal vein extension graft (PAK); left-sided implantation into the recipient (PAK); and graft pancreatitis (defined as hyperamylasemia exceeding five days post-transplant [PAK, PTA]). CONCLUSIONS: Older donors or those who died of cardiocerebrovascular disease should not be considered for any recipient category. Preservation time needs to be minimized and strategies need to be developed to decrease graft pancreatitis. Surgically, left-sided implantation and arterial reconstructions other than the Y-graft also increase risk, as do portal vein extensions. Renal transplants alone in prospective PAK recipients with Type I diabetes mellitus should, therefore, always be implanted left-sided to allow for right-sided pancreatic graft placement.

Adult↗
PubMed1996

Does re-exposure to mismatched HLA antigens decrease renal re-transplant allograft survival?

UNLABELLED: We analyzed 420 kidney retransplants at the University of Minnesota, 87 of which did and 333 which did not share HLA mismatches with the previous transplant. There was no difference in outcome. We conclude that exceptions to routine HLA matching policies do not have to be made for kidney retransplants. OBJECTIVE: To determine if the kidney graft functional survival rate for retransplants is influenced by presence of HLA mismatches in common with the previous (failed) transplant. SUMMARY BACKGROUND DATA: Kidney retransplants have a lower function rate than primary grafts. An anamnestic response to HLA antigens shared with the previous donor could be one factor responsible, but reports in the literature are conflicting. METHODS: Of 420 kidney retransplants with HLA information done at the University of Minnesota, 87 shared > or = 1 HLA antigens specifically mismatched with the previous donor (63 cadaver and 24 living donor retransplants), while 333 did not (247 cadaver, 86 living donor). Patient and graft survival rates were calculated by life-table analysis for recipients with vs. without repeat mismatches, with the significance of differences determined by the Lee-Desu statistic. RESULTS: Patient and kidney graft retransplant survival rate curves were not significantly different (p > or = 0.41) for those exposed or not exposed to the same HLA mismatches as before. At 2 years, 70% vs. 61%, respectively, of cadaver grafts and 71% vs. 78%, respectively, of living donor grafts were functioning. CONCLUSIONS: The probability of a successful outcome with a kidney retransplant is no different for patients who do than for those who do not receive an organ sharing HLA mismatches with the previous donor. Exceptions to routine HLA matching policies do not need to be made for kidney retransplants.

Cadaver↗
PubMed1996

Pancreas and islet cell transplantation: now and then.

Pancreas transplantation currently can be offered with the same probability of success as other solid organ transplants. In diabetic uremic recipients of kidney transplants, the addition of a pancreas is routine in many centers. For selected patients with labile diabetes and hypoglycemia unawareness, a successful pancreas transplant can dramatically improve quality of life. Islet transplantation is an alternative to pancreas transplantation that can reduce surgical morbidity, but is much less successful at the moment. The theoretical, immunological advantages of islet transplantation have not yet been realized. Part of the problem lies in the reduced beta cell mass that occurs with organ dispersal and islet purification. Diabetogenic immunosuppressants need to be eliminated in order to allow optimal function of what is engrafted. The immunosuppressants (eg, mycophenolate mofetil, rapamycin) give this possibility. Whether islet transplantation will replace pancreas transplantation remains problematic. Ultimately, and neither should be needed for Type I diabetes, since autoimmune diseases should be preventable by appropriate manipulation of the immune system in those identified at risk. Our personal goals as transplanters should be obsolescence.

Animals↗
PubMed1996

The case for pancreas transplantation.

More than 6,000 pancreas transplants had been performed by the end of 1994. Insulin-independence currently persists for more than one year in over 75% of diabetic recipients of simultaneous pancreas-kidney transplants, and in approximately 50% of recipients of a pancreas transplant alone. As kidney recipients are obligated to undergo immunosuppression in conjunction with this operation, the addition of a pancreas transplant entails only extra surgery. For non-uremic recipients of a pancreas transplant alone, immunosuppression itself is the trade-off for correction of diabetes. The problems of diabetes must be of a magnitude to justify the use of anti-rejection drugs. Thus, the main pancreas transplant applications have been in patients who are extremely labile or experience hypoglycaemic unawareness syndrome. Application to non-uremic patients without current problems would require randomisation to determine whether the probability of freedom from problems or the occurrence of complications differs over years of follow-up between a non-diabetic condition on immunosuppression and a diabetic status off immunosuppression. In the meantime, pancreas transplantation should be applied routinely to diabetic recipients of a kidney transplant or those whose quality of life is poor because of lability.

Diabetes Mellitus, Type 1↗
PubMed1996

Intra-abdominal fungal infections after pancreatic transplantation: incidence, treatment, and outcome.

BACKGROUND: Intra-abdominal infections account for 15 percent of technical failures after pancreatic transplantation. Although some data are available about intra-abdominal bacterial infections, no study has analyzed the incidence, treatment, and outcome of intra-abdominal fungal infections. STUDY DESIGN: We retrospectively studied 445 consecutive pancreatic transplantations--45 percent were simultaneous pancreatic and renal, 24 percent pancreatic after renal, and 31 percent pancreatic transplantations alone--in patients with Type I diabetes mellitus. Donors were cadavers in 92 percent and living relatives in 8 percent. Primary transplantations were done in 80 percent and retransplantation in 20 percent. Of these 445 pancreatic transplantations, 90 percent were bladder-drained, 9 percent enteric-drained, and 1 percent duct-injected. Only symptomatic patients with documented culture-positive intra-abdominal fungal infections were included. RESULTS: Intra-abdominal fungal infections occurred after pancreatic transplantation in 41 (9.2 percent) of 445 patients. Donor age, but not recipient age, was a significant risk factor. The rate of infections was higher for enteric-drained (21 percent) than for bladder-drained (10 percent) transplantations; for organs donated by living relatives (16 percent) than for those from cadavers (9 percent); and for pancreatic after renal (12 percent) and simultaneous pancreatic-renal (11 percent) than for pancreatic-only (5 percent) recipients. The rate of intra-abdominal fungal infections was 6 percent for recipients who were given antifungal prophylaxis (fluconazole, 400 mg/day for seven days after transplantation) compared with 10 percent for those without prophylaxis. The one-year graft survival rate for recipients with infection was 17 percent compared with 65 percent for those without (p = 0.0001); the survival rate was 70 percent compared with 92 percent for patients with and without infection, respectively (p = 0.0007). In 22 percent of recipients, the infection resolved and graft function persisted; in 58 percent, the infection resolved after transplant pancreatectomy; and in 20 percent, death occurred despite transplant pancreatectomy. Recipients with sole fungal or fungal and bacterial infection (n = 41) were 50 percent less likely to recover with a functioning graft and had a risk of death that was three times higher (p < or = 0.05) than those with sole bacterial infection (n = 48). CONCLUSIONS: Intra-abdominal fungal infections after pancreatic transplants are associated with high morbidity and mortality rates, significantly higher than for sole bacterial infections. In addition to aggressive treatment, including transplant pancreatectomy and reduction of immunosuppression, efforts must be made toward better prevention of intra-abdominal fungal infections.

Adult↗
PubMed1996

[Technical options of renal transplant in the absence of a viable ilio-caval venous circuit. Presentation of a case and review of the literature].

Congenital absence of useful ilio-caval venous segment is a very infrequent congenital anomaly and makes unfit grafting of a kidney transplant in iliac fossa. We report the case of a 18 years old male affected by this abnormality who was transplanted in intraabdominal situation. We review technical alternatives offered by the literature.

Adolescent↗
PubMed1996

A third kidney transplant: cost-effective treatment for end-stage renal disease?

Given the organ donor shortage, some question whether a third kidney transplant can be justified. We studied the outcome of 51 third transplants (mean age 28 +/- 2 yr) done between 1 January 1985 and 31 December 1994. We compared hospital stay (mean +/- S.E.), cost, readmissions, readmission days, and outcome of third (vs. first and second) transplants. We found that patient survival for third transplants was equivalent to first and second transplants; graft survival was not as good. However, when third transplant recipients with recurrent disease (specifically, hemolytic uremic syndrome and focal sclerosis) were excluded from our analysis, we found no difference in 5-yr graft survival (vs. first or second transplant recipients). Of the 51 third transplant recipients, 41 had a cadaver donor transplant. Third cadaver transplant recipients tended to have a longer hospital stay (p = NS) than first cadaver transplant recipients but had no more readmissions or readmission days than first and second cadaver transplant recipients. Employment data are available for 28 third transplant recipients; 16 (57%) are currently working or going to school. Of the 21 recipients who responded to quality of life questionnaires, 17 (81%) reported being healthy and all 21 (100%) said transplantation was not a drawback to their health. We conclude that third transplants should be considered for selected patients with renal failure whose first and second transplants have failed. Such patients can often be successfully transplanted.

Actuarial Analysis↗
PubMed1996

Metabolic characterization of long-term successful pancreas transplants in type I diabetes.

BACKGROUND: The encouraging results of the Diabetes Control and Complications Trial emphasize the need for improved methods of glycemic control to prevent the potentially devastating complications of Type I diabetes mellitus. However, current conventional approaches have failed to consistently achieve normal HbAlc levels and increase the risk of hypoglycemia. Pancreas transplantation is a consistently reliable method of achieving postoperative normal glucose levels, but no extensive assessment has been made of the long-term stability of its metabolic benefits. METHODS: To ascertain long-term stability of metabolic function of pancreas transplants in Type I diabetic patients, we studied fasting glucose levels, glucose disposal after intravenous glucose challenge, HbAlc levels, and pancreatic islet beta and alpha cell responsiveness in a series of 96 successfully transplanted recipients. Patients were studied cross-sectionally and, when possible, longitudinally for up to five years post-transplantation. Special emphasis was given to the longitudinal analysis to determine whether initial metabolic benefits maintain stability or undergo deterioration during the first five postoperative years. RESULTS: Pancreas transplantation was accompanied by normal or nearly normal fasting plasma glucose levels, intravenous glucose disappearance rates, and HbAlc levels. Beta cell function assessed by acute insulin responses and acute C-peptide responses to intravenous glucose injections revealed no deterioration in the magnitude of these responses. Analysis of acute insulin and C-peptide responses to intravenous arginine provided similar results. Alpha cell function, assessed by measuring acute glucagon responses to intravenous arginine, were significantly (p > .001) greater than preoperative responses and remained stable over the ensuing five-year period. In grafts that maintained function, none of these metabolic measures showed deterioration during the five-year postoperative period. CONCLUSIONS: Successful pancreas transplantation provides pancreatic islet function that results in normal or near normal glycemic control for up to five years postoperatively in Type I diabetic recipients receiving no exogenous insulin or oral hypoglycemic agent therapy.

Blood Glucose↗
PubMed1996

Pancreas transplantation in the United States (US) and non-US as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR).

As of November 1996, more than 8,800 pancreas transplants had been reported to the IPTR. There were 6,500 performed in the US, including more than 5,800 since the inception of the UNOS Registry in October 1987, and more than 1,000 in 1995. In Europe, more than 2,100 cases were reported to the IPTR, while fewer than 200 have been done in other locations. This report analyzes cases reported since 1987. In the US, BD has been used for the majority (92%). However, ED has recently increased in popularity, and for 1995, 15% of US cases were done by this method. In the SPK category results for 1994-1996 BD (n = 1,510) and ED (n = 221) were comparable, with one-year GSRs of 62% and 77%, respectively. When the 1987-1996 US data for BD cases were analyzed according to the 3 major recipient categories, SPK transplants (n = 3,989); PAK transplants (n = 375) and PAK transplants (n = 229), patient survival rates were no different (92%, 92% and 91%, respectively at one year). But one-year pancreas GSRs were significantly higher (p = 0.0001) in the SPK than in the PAK and PTA categories (79%, 60% and 57%, respectively). In the SPK group, the one-year kidney GSR was 88%. Retransplants and primary transplants fared similarly in the SPK category, with one-year GSRs of 79% (n = 3,947) and 77% (n = 42), respectively. But in the PAK category, primary transplants did better, 62% (n = 275) versus 47% (n = 100) functioning at one year. The PTA category outcome was also better for primary than retransplants, with GSRs of 57% (n = 191) and 51% (n = 38) at one year. An improvement in GSRs could be shown over the analyzed time period for all categories; for 1994-1996 cases in the SPK (n = 1,516), PAK (n = 141) and PTA (n = 64) categories, one-year pancreas GSRs were 81%, 71% and 64%, respectively (p = 0.004). The kidney GSR for 1994-96 SPK cases was 88% at one year. Preservation had minimal impact on outcome. In the SPK category, one-year GSRs for pancreases stored less than 12 (n = 1,400), 12-24 (n = 2,256) and more than 24 (n = 195) hours were 78%, 80% and 76%, respectively. The impact of FK506 immunosuppression on pancreas transplant survival was also analyzed for 1994-1996 cases. The results were comparable to those with CsA. For SPK cases, one-year GSRs were 82% with CsA (n = 1,247) and 81% with FK506 (n = 257). The one-year immunological loss rates were 2% and 3%, respectively. For PAK cases, one-year GSRs were 84% for FK506- (n = 42) and 65% for CsA- (n = 97) treated recipients (p < 0.04), and the immunological loss rates at one year were 11% and 7%, respectively. In PTA cases, the one-year GSRs were 66% with CsA (n = 37) and 64% with FK506 (n = 26) with immunological loss rates of 9% and 0%, respectively (p > 0.2). Outcomes were also compared according to whether recipients underwent induction immunotherapy with ALG/ATG/ATS, OKT3, or neither. In the SPK category, GSRs were 81% with OKT3 (n = 1,600), 75% with ALG/ATG/ATS (n = 1,715) and 75% with neither (n = 45) (p < 0.001). In the PAK category, the use of OKT3 (n = 81) was associated with lower graft survival rates than when ALG/ATG/ATS (n = 220) or neither (n = 49) was given (43%, 62%, and 54% at one year, respectively). In the PTA category the use of ALG/ ATG/ATS (n = 132) or OKT3 (n = 76) was associated with significantly higher graft survival (59% and 57%, respectively) than when neither (n = 13) was used (26% at one year). The effect of HLA-A,-B and -DR mismatching on outcome for US cases was determined on both overall graft survival rates and on risks for immunological loss. For SPK cases, the pancreas GSRs were significantly higher (p < 0.04) with zero-mismatched grafts (n = 30) than with higher degrees of mismatches (85% at one year versus 69%, 76% and 79% with one [n = 67], 2-3 [n = 925] and 4-6 [n = 2,836] mismatches, respectively). For PAK cases GSRs were progressively higher with decreasing numbers of mismatches (100%, 75%, 58% and 53% at one year with zero [n = 7], one [n = 35], 2-3 [

Adult↗
PubMed1995

Cystoscopic biopsies in pancreaticoduodenal transplantation. Are duodenal biopsies indicative of pancreas dysfunction?

Tissue diagnosis of pancreas graft dysfunction is desirable. Bladder-drained pancreaticoduodenal transplants allow tissue diagnosis by cytoscopic biopsy procedures of the pancreas and duodenum. To assess the diagnostic utility of duodenal biopsies, we reviewed all cystoscopically obtained pancreas and duodenal biopsy tissues at our institution (July 1, 1989 through September 30, 1993). Adequate tissue for histologic examination was obtained from 75 biopsies in 58 recipients. Indications for cytoscopic biopsies were relative hypoamylasuria in 85%, hematuria in 6%, hyperamylasemia in 3%, and other causes in 6%. Duodenal specimens were available from 52 biopsies (25 with, and 27 without, concurrent pancreas biopsies). Of the 27 duodenal biopsies alone, 3 were diagnostic of rejection, 15 had features consistent with rejection, 6 were normal, 1 showed fibrosis, 1 showed necrosis, and 1 was ulcerated. Thus, two-thirds of the duodenal biopsies alone yielded clinically relevant information resulting in antirejection treatment. In 25 of the duodenal biopsies, pancreas tissue was also available (11 simultaneous pancreas-kidney, 9 pancreas transplant alone, and 5 pancreas after kidney recipients). Findings in both organs completely agreed in 9 (36%) of the biopsies. In 7 (28%), rejection was suggested or diagnosed in both organs, although the organs were discrepant with regard to the presence of vascular rejection (6 pancreas, 1 duodenum). In 2 (11%), minor nonrejection discrepant findings were present. Therefore, in 18 of 25 (72%) pancreas-duodenal biopsies, treatment would not have been different if only one graft had been biopsied. But in the other 7 (28%), treatment would have been different if only the organ with negative findings had been biopsied. In 6 cases (4 duodenal, 2 pancreas), rejection was seen in one organ but not the other. In 1 case, cytomegalovirus (CMV) inclusions were present in the duodenum, but the pancreas was normal. We conclude that (1) the duodenum and pancreas can reject independently of each other, and a negative biopsy does not preclude rejection of the other organ; (2) duodenal biopsies determined therapeutic decisions one-fifth of the time when both tissues were available for examination, and two-thirds of the time when only duodenal tissue was available; and (3) since cystoscopy allows easy access to the duodenum, both the pancreas and duodenum should be biopsied whenever possible; tissue samples of one organ alone are sufficient only with positive findings.

Adult↗