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D C Dafoe

Publications and source records attributed to D C Dafoe.

At least 73 records · Page 4Linked to original sources
PubMed1995

Clinical outcome of interval cadaveric renal transplantation in cardiac allograft recipients.

The introduction of cyclosporine into widespread clinical use has resulted in improved patient survival following cardiac transplantation. As a result of increased numbers of cardiac transplants, the inherent nephrotoxicity of cyclosporine, and prolonged patient survival, cardiac transplant recipients commonly present with renal dysfunction. In the subgroup who ultimately develop end-stage renal disease (ESRD), therapeutic options include renal transplantation. However, the clinical course associated with this treatment modality is unknown. From 1980 to 1993, 430 cardiac transplants were performed with cyclosporine-based immunosuppression at the Standard University Medical Center. Fourteen (3.3%) patients developed ESRD, requiring chronic dialysis or renal transplantation. The cause of ESRD was cyclosporine nephropathy (13/14; 93%) and glomerulonephritis (1/14; 7%). The average time interval to the development of ESRD was 82 +/- 42 months. Nine patients underwent renal transplantation. During the period of followup (38 +/- 27 months; range 6-89 months) after renal transplantation, cardiac function remained stable. There were no episodes of primary nonfunction of the renal allograft. Patient and renal allograft survival was 89% at both 1 and 3 years after renal transplant. Average serum creatinine was 1.3 +/- 0.6 mg/dl at 1 year and 1.6 +/- 0.8 mg/dl at 3 years post-transplant. The incidence of infectious complications was not statistically different when compared to that of the heart transplant controls and that of a group of cadaveric renal transplant controls (n = 20). Surprisingly, the incidence of renal allograft rejection in the heart transplant patients was 10-fold less than that of the renal transplant controls (0.006 +/- 0.02/patient-year vs. 0.062 +/- 0.05/patient-year; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The utility of retroperitoneal kidney placement in simultaneous kidney pancreas transplantation.

Simultaneous kidney-pancreas (SPK) transplantation has become an accepted therapeutic modality for patients with Type I diabetes mellitus-mediated end-stage renal disease (ESRD). However, the intraperitoneal placement of the renal allograft may pose technical problems when attempting percutaneous biopsy or Doppler ultrasound examination. Recently, the Stanford University Transplant Center adopted the technique of retroperitoneal placement of the renal allograft with intraperitoneal placement of the pancreas allograft (RETRO). From August 1993 to August 1994, a total of 12 patients underwent SPK with this new technique. Twelve patients who had received SPK with the standard technique served as historical controls (INTRA). Demographic data, follow-up, operative time, creatinine and amylase on discharge, length of stay, intraoperative fluid requirements, rejection episodes, thrombotic complications, infections, and number of open and closed renal biopsies were compared between the two groups. Average length of follow-up was greater in the INTRA group (29.3 +/- 1.7 vs. 15.9 +/- 1.1 months). In addition, the RETRO group had significantly fewer open renal biopsies (1/15) in comparison to the INTRA group (7/12) (p < 0.001). The two groups otherwise did not differ in any of the parameters studied. We conclude that retroperitoneal kidney and intraperitoneal pancreas allograft placement is associated with a significantly decreased requirement for open renal biopsy with its associated operating room and anesthetic costs. In addition, the option of transcystoscopic or percutaneous needle biopsy of the pancreas allograft is preserved. This technique should be considered as an alternative to intraperitoneal placement of both the pancreas and renal allografts.

Female↗
PubMed1994

Insulin-like growth factor-I promotes successful fetal pancreas transplantation in the intramuscular site.

BACKGROUND: Fetal pancreas (FP) has the capacity for exuberant proliferation and engrafts in the safe, accessible intramuscular site. These characteristics make FP transplantation an attractive approach to the treatment of diabetes mellitus. Insulin-like growth factor-I (IGF-I) is an important mediator of growth and maturation of many tissues and has been shown to induce fetal islet proliferation. METHODS: IGF-I was locally administered at a rate of 69 micrograms/kg/day to 0, 2, 4, 8, or 16 FP isografts placed into the thigh muscle of streptozotocin-induced diabetic Lewis rats (blood glucose > 350 mg/dl). RESULTS: Diabetes was reversed in eight of eight animals receiving 16 FP and treated with IGF-I. One of seven animals receiving 16 FP without IGF-I treatment became euglycemic (p = 0.003). Similar improved conversion rates were seen in groups of animals receiving either eight, four, or two FP and treated with IGF-I, compared to groups receiving eight, four, or two FP without IGF-I treatment. Euglycemic recipients had physiologic glucose tolerance. The interval to conversion increased inversely in proportion to the amount of FP tissue transplanted. CONCLUSIONS: These results show that local delivery of IGF-I has potent trophic effects on FP transplanted to the intramuscular site.

Animals↗
PubMed1992

Studies of composite grafts of fetal pancreas (FP) and fetal liver (FL) in the streptozotocin-induced diabetic rat.

A hepatotrophic effect of pancreatic islets on co-transplanted hepatocytes has been described recently by Ricordi et al. We investigated a possible reciprocal effect of co-transplanted fetal liver (FL) on fetal pancreas (FP) isografted into streptozotocin diabetic rats. FL was co-transplanted with FP in three sites: the new intramural small bowel (ISB) site, the conventional renal subcapsular (RSC) site, and the historically inhospitable intramuscular (IM) site. Overall, as compared to grafts of FP alone, composite FP/FL grafts consistently provided earlier restoration of normoglycemia in streptozotocin diabetic recipients (24 +/- 8 vs. 67 +/- 43 days P = 0.001). The proportion of recipients rendered normoglycemic and the clearance of glucose was site-dependent. For FP and FP/FL recipients respectively, the ISB site resulted in 100% normoglycemia in both groups (19/19 and 6/6), the RSC site resulted in 71% (5/7) and 40% (2/5) and the IM site resulted in 14% (1/7) and 67% (6/9). In normoglycemic recipients, glucose clearance was normal or supraphysiologic except for the RSC site. Composite isografts brought about normoglycemia in 75% (6/8) of recipients treated with beta-cell toxic doses of cyclosporine that prevented reversal of diabetes in recipients of FP alone. Co-transplantation of FL benefits FP through paracrine mechanisms mediated by unknown factor(s). Thus, as compared to grafts of FP alone, composite FP/FL grafts established normoglycemia more rapidly, mitigated cyclosporine toxicity and corrected diabetes when transplanted in the small bowel site. There are several mediators that may be responsible for these paracrine effects between the liver cells and the pancreas. IGF-1 elaborated by FL is the most likely trophic factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of cotransplanted fetal liver on fetal pancreas isografts.

Ricordi et al. described a hepatotrophic effect mediated by pancreatic islets on cotransplanted hepatocytes. We found a reciprocal salutary effect of fetal liver (FL) on fetal pancreas (FP) in the intramural small bowel (ISB) site. To further investigate this intriguing finding, composite FP/FL isografts were transplanted to the conventional renal subcapsular (RSC) site and the accessible but historically inhospitable intramuscular site in streptozotocin-diabetic Lewis rats. A comparison of recipients of FP/FL and FP alone found the proportion rendered normoglycemic was site dependent. All recipients of either composite FP/FL grafts or FP alone transplanted in the ISB site became normoglycemic. The proportion of normoglycemic recipients was lower in the RSC site (71% FP and 40% FP/FL) and the i.m. site (14% FP and 67% FP/FL). Importantly, regardless of site, normoglycemia was established with an accelerated time course in recipients of FP/FL versus FP alone (24 +/- 8 vs. 67 +/- 43 days; P = 0.001). Normal (or more rapid) glucose clearance after challenge was achieved in all normoglycemic recipients except those transplanted in the RSC site. On histological examination of excised FP/FL grafts, hepatocytes were present in association with islets. Cyclosporine-induced islet toxicity could not be overcome in 6 recipients of FP alone, but 6 of 8 recipients of FP/FL became normoglycemic (P less than 0.01). To assess the effect of FP on hepatocytes, allografts (Wistar donors) of FP or FP/FL were cotransplanted in the ISB of enzyme-deficient jaundiced Gunn rats. Immunosuppression consisted of rapamycin (0.8 mg/kg/day) infused intravenously for 4 weeks. In the FP/FL group (n = 4), the mean serum bilirubin level decreased from 8.6 to 4.9 mg/dl at 6 weeks after transplantation. This was a significant difference as compared with the increased mean serum bilirubin from 6.9 to 7.8 mg/dl (P less than 0.05; paired Student's t test) in recipients of FL alone (n = 4). In conclusion, we found a mutual paracrine effect on islets and hepatocytes transplanted as a composite FP/FL graft. FL hastened the establishment of normoglycemia following transplantation of FP in diabetic rats, and FP enhanced FL transplant function in Gunn rats.

Animals↗
PubMed1992

Normocalcemia thirteen years after successful parathyroid allografting in a recipient of a renal transplant.

Two months after receiving a cadaveric renal allograft, a 36-year-old woman received a parathyroid allograft from a living unrelated donor, who was haploidentical to the renal donor. Her preoperative 24-hour urinary excretion of calcium was 0.18 gm/24 hrs, and after operation it decreased to 0.004 gm/24 hrs, (normal, less than 0.20 gm/24 hrs). The C-terminal parathyroid hormone level increased from 155 pg/ml (normal, 275 to 675 pg/ml) to 327 pg/ml after operation. The N-terminal parathyroid hormone level in her grafted arm has varied between 2.5 to 10 times the level in her nongrafted arm. Thirteen years later, both allografts are functioning normally. To our knowledge, this is the longest functioning parathyroid allograft.

Calcium↗
PubMed1991

Arterial reconstruction of the pancreatic allograft for transplantation.

The shortage of organs is particularly acute in whole pancreas transplantation, because the liver and pancreas often share a common arterial supply, making combined procurement of both organs difficult. A previously described technique of simultaneous whole liver and pancreas procurement depended on "classic" hepatic arterial anatomy, which is present just over half the time. We describe herein our experience with three Y-reconstructions of the splenic and superior mesenteric arteries of the pancreatic allograft using donor allograft internal and external iliac arteries. In situ Doppler ultrasound examination of the pancreatic allograft after surgery demonstrated a patent reconstruction without evidence of stenosis or turbulent flow patterns. We believe this reconstruction is a safe, alternative method to provide arterial flow to the whole donor pancreas.

Humans↗
PubMed1991

Changes in causes of death after renal transplantation, 1966 to 1987.

This descriptive study was undertaken to examine survival and changes in cause of death after renal transplantation. One fourth (259) of the 1,022 patients who received a renal transplant between 1966 and 1987 at the University of Pennsylvania had died by January 1, 1988. Causes of death for 246 (96%) of the deceased patients were analyzed. Despite an increase in age and number of comorbid diseases before transplantation, posttransplant survival increased significantly over the study period. All-cause mortality rates at 1, 2, and 5 years decreased significantly. Infectious disease cumulative mortality rates at 1, 2, and 5 years also decreased between 1966 and 1985. No trend in the 1-, 2-, or 5-year cardiovascular disease cumulative mortality rates was detected. The decline in the rate of deaths due to infection led to a decrease in the proportion of infection-related deaths and an associated increase in the proportion of cardiovascular disease-related deaths. The reduction in mortality over the past 2 decades is associated with the simultaneous improvement in immunosuppression and treatment of infectious diseases.

Cause of Death↗
PubMed1991

Adrenal suppression and steroid supplementation in renal transplant recipients.

The use of increased dosages of glucocorticoids during periods of physiologic stress in allograft recipients represents a clinical dilemma in that the short-term exogenous therapy required may significantly impair wound healing and immunocompetence. To investigate whether "stress steroids" are actually necessary, a prospective study was conducted in 40 renal allograft recipients admitted with significant physiologic stress. Stress categories included sepsis, metabolic abnormalities, and surgery. These patients received only their baseline prednisone immunosuppression (5-10 mg/day) and no supraphysiologic or stress doses of glucocorticoids. The clinical course of the patients revealed no evidence of adrenal insufficiency. There was no mortality, increase in hospital stay, or eosinophilia. Five episodes of hyponatremia and seven instances of hypotension were attributed to primary disease processes and responded promptly to specific treatment without steroid supplementation. Biochemical evaluation during stress revealed suppression of ACTH levels in 74.5% of episodes, elevation of urinary free cortisol levels in 79.1% of episodes, and elevation of isolated serum cortisol levels in 55.9% of episodes. This suggested that these patients had physiologically adequate adrenal function. The cosyntropin stimulation test overestimated the incidence and degree of clinically significant adrenal dysfunction (63% of patients) and was not a useful indication of a requirement for additional glucocorticoids. We conclude that functional adrenal suppression is uncommon in renal allograft recipients receiving baseline prednisone immunosuppression (5-10 mg/day) and that the demands of physiologic stress are met by a combination of endogenous adrenal function plus exogenous, baseline, immunosuppressive doses of glucocorticoids. Supra-physiologic or high doses of so-called "stress steroids" are not required. The cosyntropin stimulation test has significant clinical limitations and did not serve to alter clinical care.

Adrenal Glands↗
PubMed1991

Renal transplantation despite a positive antiglobulin crossmatch with and without prophylactic OKT3.

The antiglobulin crossmatch (AGXM) is a sensitive technique employed by many transplant centers to enhance detection of preformed antibody to donor antigens that may cause hyperacute rejection. However, positive AGXM may detect irrelevant or very low titers of anti-HLA antibody precluding transplantation in suitable recipients. To investigate the significance of a positive AGXM, cadaveric renal transplantation was carried out despite a weakly positive AGXM (defined as cell killing above background but not greater than 20%) in 48 recipients. In an initial group (n = 10), maintained on triple therapy (cyclosporine, azathioprine, and prednisone), accelerated acute rejection occurred in 4 recipients and 3 grafts were lost. A subsequent group (n = 38) was treated with a prophylactic course of OKT3 then triple therapy. There were no episodes of accelerated acute rejection (P less than 0.01) although clinical hyperacute rejection claimed one graft and the incidence of delayed graft function was high (75%). The prophylactic OKT3 group had a reduced incidence of acute rejection (0.5 versus 1.0) per recipient and the onset of first episodes was delayed (mean onset: 13 versus 35 days after transplantation). One year actuarial primary graft survival was 88% in the prophylactic OKT3 group as compared with only 50% in the initial group. The outcome in the positive AGXM group was similar to a concurrent group (n = 32) with a negative AGXM and immediate graft function. On the other hand, the subset of positive AGXM regraft recipients treated with prophylactic OKT3 fared poorly, with a 36% (4/11) incidence of primary nonfunction. In summary, a positive AGXM, as defined in this report, is not a contraindication to primary renal transplantation--in fact, the use of the AGXM will identify recipients that would benefit from prophylactic OKT3.

Adult↗