PubMed Health⌕ Search

Biomedical subjects

P F Gores

Publications and source records attributed to P F Gores.

At least 19 recordsLinked to original sources
PubMed1994

The role of nitric oxide in IL-1 beta-mediated dysfunction of rodent islets of Langerhans. Implications for the function of intrahepatic islet grafts.

Products of inflammation, such as interleukin-1 beta (IL-1 beta) and nitric oxide (NO), may impair early function of pancreatic islet grafts. In in vitro studies, freshly isolated rat islets of Langerhans cultured for 24 hr (10 islets/well) in the presence of 20 IU/ml of IL-1 beta released 57% less insulin (mean +/- S.E. of 151 +/- 61 microU) on the average than control (385 +/- 89 microU) cultures (n = 9, P = 0.08). Nitrite levels in the medium (indirect measure of NO) after islets were cultured for a 24-hr period were nearly 3-fold greater in IL-1 beta-exposed islets than control islet cultures (5.8 +/- 1.0 microM vs. 2.2 +/- 0.3 microM, P = 0.03). Production of nitrite by islet cells in the presence of IL-1 beta was inhibited in cultures also containing 2 mM L-NG-monomethyl-Arginine (L-NMMA) (3.4 +/- 0.4 microM, n = 9, P = 0.09 vs. control). When islets were maintained for 1 hr in 30 mg/dl glucose followed by 300 mg/dl for 1 hr, insulin release (stimulated) increased 6-fold (from 7 +/- 2 to 45 +/- 11 microU) in control cultures but only 3-fold (from 4 +/- 2 to 12 +/- 4 microU) in IL-1 beta-exposed cultures (n = 9, P = .01). Addition of 2 mM L-NMMA to islet cultures in the presence of IL-1 beta (20 IU/ml) (n = 9) restored insulin release to normal (from 6 +/- 2 to 38 +/- 9 microU, P > or = 0.6), suggesting that NO mediates the inhibitory effect of IL-1 beta on beta-cell function. In in vivo studies, rats with streptozotocin-induced diabetes (blood glucose > 400 mg/dl) received minimal (750 hand-picked islets) intraportal beta cell mass isografts with (n = 5) or without (n = 9) treatment with 100 mg/7 days of L-NMMA from 3 days before transplantation to 4 days after transplantation (POD -3 to +4). L-NMMA-treated rats became euglycemic (glucose < 200 mg/dl) earlier than nontreated rats (mean +/- SD of 6.4 +/- 2.5 vs. 16.7 +/- 4.7 days posttransplant, P = 0.001). These findings support the hypothesis that NO is a mediator of beta cell dysfunction after intraportal transplantation of freshly isolated islets of Langerhans.

Animals↗
PubMed1994

A prospective randomized study of acyclovir versus ganciclovir plus human immune globulin prophylaxis of cytomegalovirus infection after solid organ transplantation.

Cytomegalovirus disease occurs frequently after solid organ transplantation and has been associated with decreased patient and allograft survival. We hypothesized that CMV transmission or reactivation begins immediately or soon after transplantation, and that a short-duration ganciclovir (GCV)-based regimen would obviate the need for long-term antiviral agent administration, perhaps serving to interdict CMV infection and disease as well as, or perhaps even more effectively than, a more prolonged, oral acyclovir (ACV)-based form of prophylaxis. A total of 311 patients were stratified according to allograft type, age, and presence or absence or diabetes mellitus, and were then randomized to receive either long-duration ACV prophylaxis (800 mg orally or 400 mg i.v. q.i.d. for 12 weeks after transplantation or 6 weeks after any antirejection therapy) versus short-duration GCV (5 mg/kg/12 hr i.v. for 7 days after transplant or after any antirejection therapy) plus human immune globulin (HIg; Sandoglobulin or Minnesota CMV immune globulin) 100 mg/kg i.v. administered on days 1, 4, and 7 after transplant or after any antirejection therapy. A total of 266 patients (ACV, n = 133; GCV+HIg, n = 133) completed the protocol and were available for follow-up. CMV disease occurred in fewer patients (n = 28, 21.0%) in the ACV group, while significantly more patients (n = 42, 31.6%) in the GCV + HIg group developed group developed CMV disease slightly later (2.83 +/- 0.70 months) than those who received GCV/HIg (2.15 +/- 0.21 months, P > 0.01). Multivariate analysis demonstrated (2.15 +/- 0.21 months, P > 0.1). Multivariate analysis demonstrated that receiving antirejection therapy, a liver transplant, or a donor organ from a CMV-seropositive individual if the recipient was CMV seronegative were major risk factors for the development of CMV disease (P < 0.001), while the difference between ACV versus GCV + HIg prophylaxis was also significant (P = 0.054). No differences in actuarial patient or allograft survival, however, were noted between the 2 prophylaxis groups. Overall, ACV prophylaxis appeared to be more effective in reducing the incidence of posttransplant CMV disease, although this effect was diminished in high-risk groups of patients. Our findings indicate that CMV transmission or reactivation may best be prevented by long-term antiviral agent administration, and that the primary morbidity of CMV disease is the need for rehospitalization when either prolonged ACV or short-duration GCV + HIg prophylaxis is used in this patient population.

Acyclovir↗
PubMed1994

Successful long-term outcome with 0-haplotype-matched living-related kidney donors.

The waiting list for cadaver kidney transplantation continues to grow. Yet there has been little increase in the number of living-donor transplants. At many centers, willing relatives are turned down as potential donors because of poor HLA ABDR matching with the recipient. It has been our policy to accept the 0-haplotype-match (0-HTM) living-related donor. We studied long-term (6-year) outcome of 0-HTM transplants compared with the outcome of transplants from 1- and 2-HTM recipients and from cadaver donors. Since 1984, 352 adults have received primary living-related renal transplants, and had a minimum of 1 year of follow-up: 92 2-HTM, 216 1-HTM, and 44 0-HTM. In the same period and with the same follow-up, 362 adults have received primary cadaver (CAD) renal transplants. Immunosuppression consisted of cyclosporine, azathioprine, and prednisone (triple therapy) for living-donor and sequential therapy for CAD recipients. ABDR match (mean +/- SD) for 0 HTM was 1.3 +/- 8; CAD, 2.0 +/- 1.6; % peak panel-reactive antibodies (PRA) for 0 HTM was 1.2 +/- 5.3; 1 HTM, 6.7 +/- 20; 2 HTM, 7.5 +/- 21; CAD, 15.5 +/- 30. The percentage of PRA at the time of transplant for 0 HTM was .7 +/- 4.4; 1 HTM, 4.1 +/- 1.6; 2 HTM, 6 +/- 18; CAD, 7.2 +/- 20. While the number of ABDR matches was significantly fewer for 0 HTM than for the other groups, the % PRA at transplant and the peak % PRA were less in the 0-HTM group. Other demographics were not significantly different. Patient survival was significantly lower in the CAD group vs. 2-HTM recipients (P < .05). The living-related grafts had significantly greater survival than the CAD grafts (P < .05), but there was no significant difference between 0-, 1-, and 2-HTM graft survival. The most common causes of graft loss in all groups were death and chronic rejection. In our experience, the long-term graft survivals of 0-HTM and 1-HTM transplants are the same, and both are superior to CAD results, using 0-HTM living-related donor transplants should be continued and encouraged.

Adult↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗