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Donald C Dafoe

Publications and source records attributed to Donald C Dafoe.

7 recordsLinked to original sources
PubMed2006

Osteopontin protects the islets and beta-cells from interleukin-1 beta-mediated cytotoxicity through negative feedback regulation of nitric oxide.

Osteopontin (OPN), a phosphorylated glycoprotein that binds to an integrin-binding motif, has been shown to regulate nitric oxide (NO) production via inhibition of induced NO synthase (iNOS) synthesis. In the transplanted islets, iNOS and toxic amounts of NO are produced as a result of islets infiltration with inflammatory cells and production of proinflammatory cytokines. Here, we demonstrate that addition of OPN before IL-1beta in freshly isolated rat islets improved their glucose stimulated insulin secretion dose-dependently and inhibited IL-1beta-induced NO production in an arginine-glycine-aspartate-dependent manner. Transient transfection of OPN gene in RINm5F beta-cells fully prevented the toxic effect of IL-1beta at concentrations that reduced the viability by 50% over 3 d. OPN prevention of IL-1beta-induced toxicity was accompanied by inhibited transcription of iNOS by 80%, resulting in 50% decreased formation of the toxic NO. In OPN-transfected cells, the IL-1beta-induced nuclear factor-kappaB activity was significantly reduced. Islets exposed to IL-1beta revealed a naturally occurring early up-regulated OPN transcription. OPN promoter activity was increased in the presence of IL-1beta, IL-1beta-induced NO, and an inducer of NO synthesis. These data suggest the presence of a cross talk between the IL-1beta and OPN pathways and a unique trans-regulatory mechanism in which IL-1beta-induced NO synthesis feedback regulates itself through up-regulation of OPN gene transcription. Our data also suggest that influencing OPN expression represents an approach for affecting cytokine-induced signal transduction to prevent or reduce activation of the cascade of downstream devastating effects after islet transplantation.

Animals↗
PubMed2005

Patterns of volunteerism, testing, and exclusion among potential living kidney donors.

We found that in kidney transplantation, more females donate. We analyzed transplant recipients for patterns of potential donor exclusion and found that equal proportions of male and female potential donors existed among first-degree biological relatives. More male recipients were married and therefore had more spousal potential donors. Among friends and non-first-degree relatives, significantly fewer males offered to donate to females. Equal proportions of female and male potential donors were excluded from donating for medical comorbidities, blood type incompatibility, recipient refusal, and potential donor reluctance. We concluded that female transplant candidates had fewer potential donors among spouses and opposite sex volunteers from friends and non-first-degree relatives.

Adult↗
PubMed2005

Pancreatico-renal composite transplant: a new technique designed to decrease pancreatic graft thrombosis.

Pancreas graft thrombosis continues to be a major cause of graft loss. The removal of the donor spleen is accompanied by a significant reduction in pancreas graft blood flow. It is likely that reduced blood flow contributes to thrombosis in concert with other factors. We present a case of simultaneous pancreas and dual kidney transplantation wherein one donor kidney was anastomosed to the splenic vessels of the pancreas graft. The portal venous drainage of the pancreas graft was into the vena cava and duodenal segment was drained into the recipient's jejunum. Intraoperative blood flow determinations using an ultrasonic flow probe around the graft portal vein showed that the placement of the renal graft in the position of the donor spleen improved flow by approximately one-third (e.g. at 15 min after transplantation, 800 cc/min vs. 550 cc/min with the composite vascular pedicle clamped). The perfusion phase of a radionuclide scan on postoperative day 3 showed both transplanted kidneys had brisk and comparable visualization. The patient had an uneventful recovery and was discharged on the seventh postoperative day with normal blood glucose values and a serum creatinine of 1.2 mg/mL. A pancreatico-renal composite graft may decrease the incidence of thrombosis by improving pancreatic graft blood flow.

Adult↗
PubMed2004

Dual-kidney transplantation with organs from expanded criteria donors: a long-term follow-up.

BACKGROUND: Since 1995, dual-kidney transplantation using organs from marginal donors has been used at our center to expand the organ donor pool and decrease the waiting time for deceased donor kidney transplantation. This approach has allowed for a shorter waiting period without compromising outcome in the early posttransplant period. We now have 8-year follow-up in the first recipients. Older individuals were offered this option preferentially, because we reasoned that they would stand to benefit most from the shorter waiting period. METHODS: Patients aged 55 years or more who underwent either dual-kidney transplantation with expanded criteria donors or single-kidney transplantation with standard donors were included in this study. All expanded criteria donor organs were those that were refused by all other local transplant centers. The primary endpoints were recipient death and graft failure. RESULTS: Waiting time for dual-kidney transplantation was 440 +/- 38 days versus 664 +/- 51 days for single-kidney transplantation (P<0.01). The 8-year actuarial patient survivals for the single- and dual-kidney transplants were 74.1% and 82.1%, respectively. The 8-year actuarial graft survivals for the single- and dual-kidney transplants were 59.4% and 69.7%, respectively. CONCLUSIONS: Eight-year actuarial patient and graft survivals in older individuals who underwent dual-kidney transplantation are equivalent to those who underwent standard single-kidney transplantation. With the continuing organ shortage and increasing waiting times for cadaver kidney transplantation, dual-kidney transplantation using organs that would otherwise be discarded offers a good option for older individuals who may not withstand a long waiting period.

Actuarial Analysis↗
PubMed2004

Successful living donor renal transplantation despite ABO incompatibility and a positive crossmatch.

Potential live kidney donors have been rejected when the prospective recipients are blood type or crossmatch incompatible. By utilizing plasmapheresis combined with intravenous immune globulin (PP/IVIg) prior to surgery, donor-specific antibodies against blood group or human leukocyte antigens (HLA) have been removed, thereby allowing successful renal transplantation. A 26-yr-old male with a panel reactive antibody level of 100% and repeated positive crossmatches against deceased donor kidney offers, including zero HLA mismatched donors, successfully underwent ABO-incompatible kidney transplantation from his HLA-identical but nevertheless crossmatch-incompatible sister. The initial anti-A blood group isoagglutinin titers were 128, 256, and 1024 at room temperature, 37 degrees C, and 37 degrees C anti-IgG enhanced, respectively. With an individualized PP/IVIg regimen based on donor-specific antibody titer, however, the relevant antibodies were adequately reduced and hyperacute rejection avoided. Subsequent antibody-mediated rejection, likely directed against a minor histocompatibility antigen, was diagnosed on postoperative day 7 and successfully treated. Neither ABO, or crossmatch incompatibility, or both in combination prohibit kidney transplantation.

ABO Blood-Group System↗
PubMedDate not supplied

Validation of a screening protocol for identifying low-risk candidates with type 1 diabetes mellitus for kidney with or without pancreas transplantation.

BACKGROUND: Certain clinical risk factors are associated with significant coronary artery disease in kidney transplant candidates with diabetes mellitus. We sought to validate the use of a clinical algorithm in predicting post-transplantation mortality in patients with type 1 diabetes. We also examined the prevalence of significant coronary lesions in high-risk transplant candidates. METHODS: All patients with type 1 diabetes evaluated between 1991 and 2001 for kidney with/without pancreas transplantation were classified as high-risk based on the presence of any of the following risk factors: age >or=45 yr, smoking history >or=5 pack years, diabetes duration >or=25 yr or any ST-T segment abnormalities on electrocardiogram. Remaining patients were considered low risk. All high-risk candidates were advised to undergo coronary angiography. The primary outcome of interest was all-cause mortality post-transplantation. RESULTS: Eighty-four high-risk and 42 low-risk patients were identified. Significant coronary artery stenosis was detected in 31 high-risk candidates. Mean arterial pressure was a significant predictor of coronary stenosis (odds ratio 1.68; 95% confidence interval 1.14-2.46), adjusted for age, sex and duration of diabetes. In 75 candidates who underwent transplantation with median follow-up of 47 months, the use of clinical risk factors predicted all eight deaths. No deaths occurred in low-risk patients. A significant mortality difference was noted between the two risk groups (p = 0.03). CONCLUSIONS: This clinical algorithm can identify patients with type 1 diabetes at risk for mortality after kidney with/without pancreas transplant. Patients without clinical risk factors can safely undergo transplantation without further cardiac evaluation.

Age of Onset↗