Search PubMed⌕ Search

Biomedical subjects

D C Dafoe

Publications and source records attributed to D C Dafoe.

At least 91 records · Page 5Linked to original sources
PubMed1990

Pancreatic and islet autotransplantation.

The techniques of segmental pancreatic autotransplantation and intraportal islet autografting have been reported to prevent diabetes after resection of the diseased pancreas. Unless total pancreatectomy is done, transplant function cannot be assessed without measuring insulin in the venous effluent. Islet infusion appears to be a more uncertain technique than segmental autotransplantation, probably because of technical difficulties in obtaining sufficient islets. Both methods have serious potential for morbidity and mortality, which must be balanced against the possible benefits of improved glucose homeostasis. In segmental autografts we recommend an intraperitoneal transplant site with iliac vessel anastomosis, and a lateral pancreaticojejunostomy to provide ductal drainage. For islet transplantation we recommend extreme caution and the use of only very pure islet preparations for portal vein infusions. There is insufficient long-term follow-up of patients with successful auto- or allotransplants to be certain that secondary complications of diabetes will be less than those of patients on insulin therapy. Further experience is necessary before the long-term functional survival of segmental or islet autografts will be known.

Adult↗
PubMed1990

Beneficial effects of fetal liver tissue on fetal pancreatic transplantation.

Recently, composite grafts of hepatocytes and islets have been shown to improve the survival of hepatocytes. The possibility of a reciprocal effect of hepatocytes on islet function was investigated. Diabetic Lewis rats were isografted with (1) fetal pancreas and fetal liver (FP/FL), (2) fetal pancreas alone (FP), and (3) fetal pancreas and fetal spleen (FP/FS). Grafts were transplanted to the small bowel subserosa. All (6/6) FP/FL recipients were cured (glucose less than 250 mg/dl for greater than 30 days), whereas only 72% (13/18) of FP alone and 60% (3/5) of FP/FS recipients were cured. The amount of time to normoglycemia for FP/FS recipients was less (26 +/- 15 days) compared with FP (50 +/- 29 days) or FP/FS recipients (71 +/- 40 days). Mean glucose levels at 6 weeks were 166 +/- 78 mg/dl, 237 +/- 97 mg/dl, and 355 +/- 81 mg/dl in cured FP/FL, FP, and FP/FS recipients, respectively. Glucose tolerance test results were not significantly different from those of nondiabetic control rats. In contrast to FP alone, FP/FL recipients had well-granulated hyperplastic islets and hepatocytes on histologic examination. When new isograft recipients were treated with cyclosporine, all FP recipients remained hyperglycemic; however, 75% (6/8) of FP/FL recipients were cured. In conclusion, FL in a composite graft with FP resulted in better engraftment, earlier isograft function, and protection from cyclosporine islet toxicity.

Animals↗
PubMed1989

Discriminating rejection from CMV infection in renal allograft recipients using flow cytometry.

The ability to distinguish among rejection, cytomegalovirus (CMV) infection, and cyclosporin toxicity in the symptomatic renal allograft recipient remains one of the major issues in clinical transplantation. The practical application of immunologic monitoring of peripheral blood lymphocytes through the use of fluorescently labeled monoclonal antibodies and single-color flow cytometry has been limited by the inability to demonstrate significant correlations between the levels of specific T-cell subset populations and the cause of impaired renal function. In the present study using two-color analysis, we monitored the expression of interleukin-2 receptor (IL-2R) and HLA-DR antigen on the T-cells of a group of 51 renal cadaveric allograft recipients receiving cyclosporin, azathioprine, and prednisone for an average of 4 months after transplantation. We found that the proportion of CD3+ cells coexpressing IL-2R increased above baseline during 12 out of 14 rejection episodes that took place during the course of the study (P less than 10(-6)). Alternatively, we found that the proportion of cells coexpressing HLA-DR antigen on CD2+ cells increased above baseline during 11 out of 11 CMV infections (P less than 10(-6)). There was no correlation between the level of IL-2R+CD3+ cells and CMV infection or between the level of CD2+DR+ cells and rejection. These relationships showed a high degree of sensitivity and specificity when used to discriminate among possible etiologies for decreased renal function in the symptomatic patient.

Adolescent↗
PubMed1989

No improvement of pancreas transplant endocrine function by exogenous insulin infusion (islet rest) in the postoperative period.

The concept of islet exhaustion maintains that exposure of pancreatic islets to hyperglycemia and other stresses leads to islet dysfunction and irreparable damage. The process of pancreatic transplantation places many stresses on islets (e.g., counter-regulatory hormones, steroids, cyclosporine toxicity). As practiced by some centers, it may be important to administer exogenous insulin in the postoperative period to provide islet rest. Using a porcine pancreas transplant model that simulates clinical transplantation, we studied 2 groups: 1 group (n = 8) received constant insulin infusion for 7 days after transplantation; the control group (n = 5) received vehicle only. The islets in the insulin infusion group were rested as evidenced by a significantly decreased mean C-peptide level (0.27 +/- 0.04 ng/ml) as compared to the control group (0.66 +/- 0.08 ng/ml) (P less than 0.05). After insulin infusion was discontinued, intravenous glucose tolerance testing found insulin, C-peptide and glucagon responses were not different between groups. Glucose clearance was also comparable; K values were -1.79 and -1.60 in the insulin infusion and control groups, respectively. In conclusion, islet rest by insulin infusion for 7 postoperative days did not improve subsequent pancreas transplant endocrine function.

Animals↗
PubMed1989

Pancreas transplantation: an immunohistochemical analysis of pancreatic hormones and HLA-DR expression.

The immunohistochemical features of pancreatic grafts in eight patients with pancreatic transplants were analyzed and compared with pancreases from five patients with chronic pancreatitis and with three pancreatic tissues without histological abnormalities. There was a significant increase in glucagon producing cells in patients with transplanted pancreases compared with those with chronic pancreatitis (P less than 0.05). A significant decline in insulin-producing cells was seen in the transplanted pancreases with rejection in comparison with normal pancreatic tissue. Immunohistochemical staining for HLA-DR (Ia) antigens revealed expression of HLA-DR by endothelial cells, mononuclear cells, and by some ductal epithelial cells, but not by the endocrine islet cells. These results suggest that significant changes in insulin and glucagon production occur in the transplanted pancreas with rejection and that HLA-DR is not expressed by islet cells during graft rejection or with chronic inflammation.

Adult↗
PubMed1988

Prophylaxis of serious cytomegalovirus infection in renal transplant candidates using live human cytomegalovirus vaccine. Interim results of a randomized controlled trial.

We report the interim results of a randomized, double-blind, placebo-controlled, clinical trial of prophylactic, live, attenuated cytomegalovirus (CMV) vaccination (Towne strain of CMV) of renal transplant candidates (RTCs). One hundred seventy-two RTCs were treated and subsequently underwent transplantation and followed up for at least one year and up to five years after transplantation. Eighty-eight RTCs received vaccine, and 84 received placebo. Results were analyzed according to the prevaccination serologic status (anti-CMV antibody titer) of the recipient (R- or R+) and the donor (D- or D+). The overall incidence of CMV disease was highest in the R-D+ group and almost absent in the R-D- group. There was no difference in the incidence of CMV infection or disease between vaccinated and respective placebo control recipients in either the R-D+, R+D+, R+D-, or R-D- groups. In contrast, the severity of CMV disease was significantly decreased in R-D+ vaccinees vs R-D+ placebo-treated recipients. Moreover, in the R-D+ group, one- and five-year cadaver renal allograft actuarial survival rates were 73% and 62%, respectively, for CMV vaccinees vs 40% and 25%, respectively, for control placebo patients. We conclude that seronegative cadaver RTCs may benefit from vaccination with live, attenuated, Towne strain CMV vaccine before transplantation.

Adult↗
PubMed1988

Preparation of islets of Langerhans from the hamster pancreas.

We describe a method for the preparation of viable islets from the pancreas of normal 8-week-old female Syrian golden hamster, based on the injection of the pancreatic duct with collagenase and on mechanical dissociation which liberates islets that maintain their normal morphological appearance and physiologic function. In a series of 11 animals, we examined the dose response of intraductal collagenase on islet yield. The mean number of isolated islets was 423 with a range from 130 to 873 per pancreas. Islet yield was most dependent on the concentration of collagenase solution used to inject the duct. The optimal concentration was determined to be 3.5 mg/ml when a total volume of 3.0 ml was injected. Islets responded to glucose stimulus in a normal biphasic pattern. Mesh filtration, rather than Ficoll, can be performed rapidly and results in a high yield of functional islets with minimal contamination by acinar tissue.

Animals↗
PubMed1988

Peripheral blood catalase in patients undergoing renal transplantation.

Oxygen free radicals are mediators of tissue injury and catalase is an enzyme which is involved in limiting this process. We examined peripheral blood catalase activity (PBCA) to assess its value as a marker in detecting tissue injury related to renal allograft rejection. Thirty-one consecutive recipients of kidney (n = 29) or simultaneous kidney/pancreas (n = 2) transplants and 10 normal volunteers were studied. Catalase activity, measured by the disk-flotation method, was expressed as Sigma units X 10(-3)/ml (SU/ml) of whole blood. Normal PBCA was determined to be greater than 76 SU/ml. Twenty-nine episodes of renal allograft rejection (diagnosed by clinical criteria +/- biopsy [79%]) were observed in 26 patients. PBCA (mean +/- SEM) was found to be low (64 +/- 1 SU/ml) in 28/29 episodes (chi 2 = 46.3, P less than 0.001), and the decrease (at least two consecutive daily catalase values less than 76 SU/ml) occurred 2 days prior to the clinical/biopsy diagnosis of rejection in 26/28 episodes. The sensitivity of PBCA as a discriminant of rejection was 97%, specificity was 96%, and test accuracy was 96%. PBCA less than 50 SU/ml on two or more occasions occurred in five cases and transplant nephrectomy was required in four of these because of uncontrollable rejection. Nine episodes of cyclosporine nephrotoxicity occurred in 7 patients and none of these episodes was associated with a decreased PBCA. Our data suggest that decreased PBCA is a sensitive and specific indicator of renal allograft rejection. PBCA remains normal during episodes of cyclosporine nephrotoxicity and therefore provides a rapid and inexpensive discriminant from allograft rejection.

Adolescent↗
PubMed1988

Extravesical ureteroneocystostomy in renal transplantation.

From October 1970 to January 1986, 808 patients underwent renal transplant ureteroneocystostomy by an extravesical technique. Complications related to the anastomosis and/or ureter were reviewed. There were 23 total complications, for an over-all urological complication rate of 2.8 per cent. Of these complications 17 were related to the ureteroneocystostomy, for an anastomotic complication rate of 2.1 per cent. Complications were almost universally repaired by another operation. Two patients died and 1 lost the allograft because of urological complications.

Anastomosis, Surgical↗
PubMed1988

MR diagnosis of pancreatic transplant rejection.

To determine the role of MR imaging in the assessment of pancreatic transplant rejection, we prospectively obtained 13 MR scans in nine transplant patients. The presence of rejection was verified pathologically by pancreatic transplant biopsies in five patients. In two additional patients, rejection was proved by concordant renal transplant biopsy as well as by compatible clinical and laboratory data. In the remaining two patients, in whom no biopsy was done, clinical and laboratory data showed no evidence of rejection. The mean T2 of the seven pancreata undergoing rejection was significantly elevated (86 msec) compared with the mean T2 of the two transplants not undergoing rejection (59 msec) (p less than .002). These preliminary results suggest that MR may be useful in the noninvasive diagnosis of pancreatic rejection.

Biopsy↗
PubMed1987

Quantitative scintigraphy with deconvolutional analysis for the dynamic measurement of hepatic function.

A mathematical technique known as deconvolutional analysis was used to provide a critical and previously missing element in the computations required to quantitate hepatic function scintigraphically. This computer-assisted technique allowed for the determination of the time required, in minutes, of a labeled bilirubin analog (99mTc-disofenin) to enter the liver via blood and exit via bile. This interval was referred to as the mean transit time (MTT). The critical process provided for by deconvolution is the mathematical simulation of a bolus injection of tracer directly into the afferent blood supply of the liver. The raw data required for this simulation are obtained from the intravenous injection of labeled disofenin, a member of the HIDA family of radiopharmaceuticals. In this study, we perform experiments which document that the simulation process itself is accurate. We then calculate the MTT under a variety of experimental conditions involving progressive hepatic ischemia/reperfusion injury and correlate these results with the results of simultaneously performed BSP determinations and hepatic histology. The experimental group with the most pronounced histologic findings (necrosis, vacuolization, disorganization of hepatic cords) also have the most prolonged MTT and BSP half-life. However, both quantitative imaging and BSP testing are able to identify milder degrees of hepatic ischemic injury not reflected in the histologic evaluation. Quantitative imaging with deconvolutional analysis is a technique easily adaptable to the standard nuclear medicine minicomputer. It provides rapid results and appears to be a sensitive monitor of hepatic functional disturbances resulting from ischemia and reperfusion.

Animals↗