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Biomedical subjects

D E Sutherland

Publications and source records attributed to D E Sutherland.

At least 181 records · Page 10Linked to original sources

Characterization and impact of wound infection after pancreas transplantation.

OBJECTIVE: To characterize the incidence, microbial pathogenesis, risk factors, and impact of wound infection after pancreas transplantation. DESIGN: Retrospective analysis. SETTING: A large university hospital. PATIENTS: From January 1, 1990, to September 30, 1993, 197 patients underwent 207 consecutive pancreas transplantation procedures. MAIN OUTCOME MEASURES: Wound infection and patient and allograft survival rates at 1 year. RESULTS: Sixty-nine patients (33%) suffered wound infections: 21 (10%) were superficial; 31 (15%), deep; and 17 (8%), combined. Most (74%) wound infections were monomicrobial. Staphylococcus epidermidis and Candida species were the most common pathogens. Prolonged operating time, older donors, and enteric drainage were associated with higher wound infection rates. Deep and combined wound infections led to allograft loss despite subsequent salvage procedures. Combined wound infection was associated with significantly higher mortality. CONCLUSIONS: A deep wound infection should be an indication for allograft removal. Antifungal prophylaxis, stringent donor criteria, and delayed primary wound closure should lower the incidence of wound infection.

Adult↗

Skewed T-cell receptor usage and junctional heterogeneity among isletitis alpha beta and gamma delta T-cells in human IDDM [corrected].

Because of anatomical limitations, molecular characterization of islet-inflammatory T-cells in human insulin-dependent diabetes mellitus (IDDM) has remained elusive. We have isolated isletitis T-cells from pancreas graft biopsies of two patients (syngeneic and allogeneic, respectively) shortly after onset of recurrent IDDM and have characterized their repertoire by sequencing T-cell receptor (TcR)-specific cDNAs. Histopathological analysis of the grafts revealed selective beta-cell loss and isletitis characteristic of recurrent disease with no evidence of chronic inflammation or rejection. Most of the in vivo-activated isletitis T-cells were CD8+TcR alpha beta+ and CD4-CD8-TcR gamma delta+ in both patients. Comparison of the different TcR alpha,beta,gamma, and delta sequences revealed V(D)J junctional heterogeneity but skewed TcR usage within patients. Eighth of 13 different isletitis TcR beta sequences (19 of 26 cDNAs) from the syngeneic graft of patient 1 were V beta 3+, as opposed to only 1 of 31 peripheral TcR beta sequences (1 of 31 cDNAs) (61.5 vs. 3.2%, P < 0.0001). Of the 19 different isletitis TcR alpha clonotypes of this patient (24 of 42 cDNAs), 5 were V alpha 14+. The isletitis TcR beta clonotypes of the human leukocyte antigen-identical allogeneic graft of patient 2 showed selective J beta, but not V beta, gene usage. Two of three predominant isletitis clonotypes of patient 2 were V alpha 22+ (19 of 28 cDNAs) and the other (5 of 28 cDNAs) was also V alpha 14+.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of 15-deoxyspergualin on immediate function and long-term survival of transplanted islets in murine recipients of a marginal islet mass.

15-Deoxyspergualin (DSG), a macrophage immunomodulatory agent, was used as a probe in a murine model of islet transplantation to examine 1) the significance of the nonspecific, macrophage-mediated effector arm of beta-cell injury in recipients of a marginal mass of isologous islets by analyzing the duration of temporary posttransplant hyperglycemia, a parameter of immediate beta-cell function; and 2) whether long-term (> 100 days) functional survival could be achieved in recipients of a marginal mass of allogeneic islets. A dose-response study of the number of islets required to ameliorate diabetes showed that 150 isologous islets per recipient resulted in a 75% incidence of cure at a mean of 39.2 +/- 5.8 days posttransplant. DSG-treated (0.625 mg.kg-1.day-1 intraperitoneally) recipients of isologous islets demonstrated a significant (P < 0.01) reduction in the duration of temporary posttransplant hyperglycemia (16.8 +/- 3.2 vs. 39.2 +/- 5.8 days), and DSG-treated recipients of allogeneic islets demonstrated a significant (P < 0.03) improvement in the rate of achieving long-term functional survival (75 vs. 22% in untreated control animals). Finally, identical rates of islet engraftment were found among control animals and DSG-treated animals by measurement of tissue insulin content in transplanted specimens. The results are consistent with the hypothesis that DSG alters the duration of temporary posttransplant hyperglycemia and extends long-term functional survival in murine recipients of a marginal mass of islets, not by affecting the efficiency of islet engraftment, but by suppression of the inhibitory effects on beta-cell function by nonspecific, macrophage mediators.

Animals↗

Pancreas transplant results in the United Network for Organ Sharing (UNOS) United States of America (USA) Registry compared with non-USA data in the International Registry.

As of 1994, more than 6,300 pancreas transplants were reported to the IPTR. More than 4,300 were performed in the USA, including more than 3,000 since the inception of the UNOS Registry in October 1987. The BD technique was used for 96% of USA cases but only for 64% of non-USA cases. In the overall analysis of USA BD cadaveric pancreas transplants reported to the registry by August 1994 (n = 3,000), patient survival and pancreas graft function survival rates were 91% and 72% at one year, 87% and 67% at 2 years, and 84% and 62% at 3 years, respectively. When the USA data for BD cases were analyzed according to the 3 major recipient categories: SPK, (n = 2584); PAK (n = 241); and PTA (n = 175)], patient survival rates were no different (91%, 91%, and 90% at one year, respectively), but pancreas graft survival rates were significantly higher in the SPK than in the PAK and PTA categories (76%, 47%, and 48%, at one year, respectively). In the SPK group, kidney graft survival rate at one year was 85%. Although the overall results were not as good for non-USA as for USA pancreas transplants, this was probably because the results with non-BD techniques were not as good as when BD was used, and in Europe, more than one-third of the cases were by techniques other than BD. The patient, pancreas, and kidney graft survival rates at one year for BD SPK transplants in Europe (n = 579) and other non-USA locations (n = 66) were similar to those in the USA; in Europe they were 92%, 78% and 84%, respectively. The graft survival rates for solitary pancreas transplants, however, were higher in the USA. Outcomes were also compared according to whether induction immunotherapy in USA recipients included ALG/ATG, OKT3, or neither. In the SPK category, there was no difference among the protocols, with one-year graft survival rates being 76% in the ALG/ATG (n = 1,130), 78% in the OKT3, (n = 927) but 69% in the Neither (n = 294) group (which had a significantly lower graft survival). In the PAK category, the use of OKT3 (n = 49) was associated with lower graft survival rates than when ALG/ATG (n = 154) or neither (n = 37) were given (33%, 51%, and 48% at one year, respectively). In the PTA category, the use of ALG/ATG (n = 109) was associated with significantly higher one-year graft survival rates than when OKT3 (n = 55) or neither (n = 8) were used (52%, 46%, and none, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗

Complications of ureterovesical anastomosis in kidney transplant patients: the Minnesota experience.

We reviewed urologic complications of 1183 consecutive primary or secondary renal transplants performed with bladder anastomoses at the University of Minnesota Hospital between 1985 and 1993. The Politano-Leadbetter (PL) technique of ureteroneocystostomy was used in 410 patients; the multistich (MS) extravesical technique modified from the methods of Witzel, Sampson, and Lich in 295; and the extravesical single-stitch (SS) technique in 478. Urologic complications occurred in 81 patients (6.8%). Of these complications, 68 (5.7%) were early (< 4 months) and 13 (1.1%) late; 32 (7.8%) were after PL, 17 (5.8%) after MS, and 32 (6.7%) after SS. A total of 13 patients had an anastomotic leak, 7 (1.7%) after PL, 4 (1.4%) after MS, and 2 (0.0004%) after SS; 49 patients had a ureterovesical obstruction, 16 (4.0%) after PL, 12 (4.0%) after MS, and 21 (4.2%) after SS; 5 patients had a ureteropelvic obstruction, 2 (0.5%) after PL, 2 (0.7%) after MS, and 1 (0.2%) after SS; and 14 patients had hematuria, 7 (1.7%) after PL, 1 (0.34%) after MS, and 6 (1.3%) after SS. Of the 81 patients with urologic complications, one (1%) resolved spontaneously; 30 (37%) were treated with temporary percutaneous nephrostomy, 17 (21%) with dilatation and stent; the 14 (17.3%) with hematuria were treated via cystoscopy; 19 (23%) required reoperation. Only 2 (2.5%) patients lost their graft. For both cadaver and living donor recipients, there was no difference between techniques for early and late complications of leakage, stricture, and hematuria. Each technique has certain advantages and each should be in every surgeon's repertoire.

Anastomosis, Surgical↗

Free intraperitoneal islet autografts in pancreatectomized dogs--impact of islet purity and posttransplantation exogenous insulin.

BACKGROUND: We compared the ability of impure, dispersed pancreatic islet tissue (DPIT) and purified islets to engraft in the peritoneal cavity of dogs. We also tested whether posttransplantation insulin therapy affects islet engraftment. METHODS: Thirty-two dogs underwent total pancreatectomy. DPIT was autotransplanted intraperitoneally in nine dogs. Purified islets were autotransplanted intraperitoneally in 13 dogs and intraportally in seven dogs. Dogs received comparable islet mass. One half of the recipients of intraperitoneal grafts received 12 days of posttransplantation exogenous insulin. Three dogs did not undergo transplantation. Intravenous glucose tolerance tests were done at 60 and 180 days. RESULTS: The long-term graft functional survival rate of intraperitoneal DPIT graft was significantly better than the rate of intraperitoneal purified islets (p < 0.01) and was as good as the rate of intraportal purified islets. Purified islets transplanted intraperitoneally failed early compared with other groups, with only 46% functioning at 3 weeks (p = 0.05); exogenous insulin reduced this early failure rate (p = 0.05). At 6 months 67% of intraperitoneal DPIT and 86% of intraportal purified grafts were functioning. Glucose disposal did not differ between groups. CONCLUSIONS: The peritoneal cavity is a safe, practical site for islet transplantation, particularly for high-volume DPIT grafts. DPIT may provide a larger, more viable beta-cell mass than purified islets, or the acinar-ductal tissue may have a positive effect on engraftment. Exogenous insulin may promote engraftment of transplanted islets with a marginal beta-cell mass.

Animals↗

Kidney transplant outcome with and without right renal vein extension.

Use of the vena cava to extend the right renal vein for cadaver transplantation is controversial. Right renal vein extension permits an easier anastomosis and possibly better positioning of the kidney, but may create a low flow or turbulent state. We studied whether use of a vein extension had an impact on outcome. Between January 1986 and April 1993, 305 cadaver transplant recipients received a right kidney. Of these, 76 received a graft with vein extension. None of the 76 experienced technical vascular complications versus 5 of the 229 (2.2%) without vein extension. There was no difference in 1- and 2-year graft survival for those with versus without extension. We conclude that there is no increased risk with use of the vena cava extension and recommend that the donor team routinely provide the right kidney with the vena cava attached. This allows the recipient team to determine whether an extension is appropriate for the particular recipient.

Anastomosis, Surgical↗