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Biomedical subjects

A G Diethelm

Publications and source records attributed to A G Diethelm.

At least 37 records · Page 2Linked to original sources
PubMed1995

Risk factors affecting second renal transplant outcome, with special reference to primary allograft nephrectomy.

Removal of a failed primary renal allograft was found by some groups to adversely affect the outcome of a second kidney transplant. Recent data does not support this view and fail to show any such effect. Such data, however, are limited by small numbers or univariate analysis. The records of 192 patients receiving a primary and a subsequent kidney transplant between January 1980 and July 1992 were retrospectively reviewed. Immunosuppression initially included azathioprine and prednisone; cyclosporine was introduced in December 1983 with Minnesota antilymphocyte globulin (MALG) added for induction in May 1987. Regraft survival rates were 66% at one year and 60% at two years. Using Kaplan-Meier survival analysis patients having primary transplant nephrectomy had a worse second allograft outcome than patients who kept their failed grafts (P = 0.0003). Multivariate analysis showed a significant relationship between primary allograft survival and retransplant outcome. To eliminate this influence, patients whose first graft failed within six months of transplantation were excluded from the analysis. This resulted in 90 patients whose first graft functioned for more than 6 months. Graft survival was 80% at one year and 73% at 2 years in this select population. Patients with prior transplant nephrectomy still had a worse retransplant outcome than those who kept their failed grafts (P = 0.05). Multivariate analysis identified primary allograft nephrectomy, older donor age, longer interval from nephrectomy to retransplant, and lack of MALG at induction as negative risk factors. In conclusion, primary allograft nephrectomy may have a negative influence on second renal transplant outcome. This result may be improved by reducing donor age and the time interval from nephrectomy to retransplantation, and using MALG at induction.

Adult↗
PubMed1995

A rapid flow cytometry assay for HLA antibody detection using a pooled cell panel covering 14 serological crossreacting groups.

Many studies have demonstrated the usefulness of flow cytometry crossmatching (FC-XM) for selection of regraft recipients, and more recently this assay has been shown to correlate with allograft survival in primary cadaveric transplant patients. The need now exists for a practical antibody screening procedure which uses the same methodology. We describe here a simple and sensitive method to screen for HLA antibodies by FC using a pool of 6 cells selected to cover the 14 serological crossreacting groups defined by Rodey. Screenings of 367 sera (255 primary transplant sera, 112 regraft sera) received for monthly antibody testing were performed by both pooled cell FC and complement-dependent cytotoxicity (CDC) assays. Forty of these sera were also FC-screened using a panel of 16 individual cells for comparison with the pooled cell FC screenings. Analysis indicated a strong correlation between the pooled FC-PRA and the individual cell panel FC-PRA (P = .0001) with mean values of 60% and 73%, respectively. Only 2 of the 40 sera screened by both FC methods resulted in PRAs that differed by > 40%. The majority (82%) of the primary patients did not exhibit HLA antibodies by CDC--however, 22% of the CDC negative patients were positive by flow cytometry. Females were more likely to be positive by FC (35%) than males (16%) (P = .0001). Similarly, black patients were more likely to have FC-demonstrable antibodies (28%) than white candidates (14%) (P = .014). The regraft patients who tested positive by either or all methods had a mean PRA for CDC, pooled FC-PRA, and individual cell FC-PRA of 40, 75, and 85, respectively. FC-PRA proved to be a more sensitive technique in both primary and regraft patients.

Blood Grouping and Crossmatching↗
PubMed1995

Progress in renal transplantation. A single center study of 3359 patients over 25 years.

OBJECTIVE: The study analyzed 3359 consecutive renal transplant operations for patient and graft survival, including living related, cadaveric, and living unrelated patients. The analysis was separated into three groups according to immunosuppression and date of transplant. SUMMARY BACKGROUND DATA: Improvements in renal transplantation in the past 25 years have been the result of better immunosuppression, organ preservation, and patient selection. METHODS: A single transplant center's experience over a 25-year period was analyzed regarding patient and graft survival. Potential risk factors included patient demographics, tissue typing, donor characteristics, number of transplants, acute and chronic rejection, acute tubular necrosis, primary disease, and malignancy. RESULTS: The primary cause of graft loss was rejection. Improvement in cadaveric graft survival since 1987 with quadruple therapy was not apparent in living donor patients. Race continued to be a negative factor in graft survival. Avoiding previous mismatched antigens and the use of flow cytometry improved allograft survival. The leading cause of death in the past 7 years in cadaveric recipients was cardiac (52%). CONCLUSIONS: Improved graft survival in the past 25 years was related to 1) advances in immunosuppression, 2) better methods of cytotoxic antibody detection, and 3) human lymphocyte antigen match.

Adolescent↗
PubMed1994

Peripheral blood chimerism in renal allograft recipients transfused with donor bone marrow.

Experimental studies have shown that administration of antilymphocyte serum combined with donor bone marrow cells can induce tolerance to allograft tissue. We have initially reported application of these protocols in clinical studies of cadaveric renal allograft recipients who were treated with MALG and donor-specific bone marrow cells. To evaluate the effectiveness of the donor marrow cells in the production of chimerism, a detection method based on 32P-incorporated PCR was established. The 32P PCR was utilized with primers specific for the HLA class II, VNTR (D17S5 and D1S111), and/or Y-chromosome genes to detect the presence of allogeneic chimerism in the recipients. Immediately posttransplant, 26.4% of marrow recipients demonstrated the presence of allogeneic chimerism prior to the marrow transfusion as did 18% in the untransfused controls. In transfused patients, chimerism was detected most frequently during the 1-3-month interval after marrow transfusion (65%), and then diminished to 50-56% at 3-12 months posttransfusion. In the control group the frequency of allogeneic chimerism was gradually decreased and was undetectable in the majority of the patients beyond 3 months posttransplant while marrow-transfused recipients were more likely to have chimeric cells detected consistently beyond 3 months. Rejection episodes were significantly effected by the presence of chimerism in the recipients. Of the transfused patients, 91.3% who demonstrated allogeneic chimerism were rejection-free as compared with 8.7% who experienced at least one rejection episode (P = 0.01). While the presence of allogeneic chimerism in the control group was correlated with rejection-free graft survival, this difference did not reach statistical significance.

Base Sequence↗
PubMed1994

Erythropoiesis after withdrawal of enalapril in post-transplant erythrocytosis.

Enalapril effectively decreases hematocrits in patients with postrenal transplant erythrocytosis (PTE). We studied the effect of enalapril withdrawal on erythropoiesis in 18 patients with PTE who had been treated for 13 +/- 8 months. Hematocrit, reticulocyte count, plasma erythropoietin, and plasma insulin-like growth factor I were measured biweekly for six weeks. Red cell mass, plasma volume, transferrin saturation, and plasma angiotensin II were measured at withdrawal and six weeks later. Hematocrit increased by at least 0.04 in 13 patients ('responders') but changed by -0.08 to 0.01 in five patients ('nonresponders'). In the responder subgroup, hematocrit increased from 0.43 +/- 0.05 to 0.51 +/- 0.05 (P < 0.001), red cell mass increased from 25.4 +/- 5.9 to 28.9 +/- 5.9 ml/kg body weight (P < 0.001), and transferrin saturation decreased from 41 +/- 16 to 27 +/- 9 percent (P < 0.01). Reticulocyte count increased two weeks after withdrawal of enalapril. Plasma volume did not change significantly. No measurement changed in the nonresponder subgroup. Plasma levels of erythropoietin, total erythroid stimulating activity, insulin-like growth factor I, and angiotensin II did not change significantly in either subgroup. Enalaprilat did not inhibit erythropoiesis in cell culture. Thus, erythropoiesis increased in 13 of 18 patients after stopping enalapril and was independent of changes in circulating concentrations of several erythropoietic factors, including erythropoietin. The pathogenesis of PTE and mechanism underlying the beneficial effect of angiotensin converting enzyme inhibition remain undetermined.

Blood Proteins↗
PubMed1994

Review of 333 living donor nephrectomies.

We reviewed the operative complications in 333 living related donor nephrectomies done at our institution over the past 12 years. The overall complication rate was 17.1%; only three patients (0.9%) had major complications, and none died. The major complications were a delayed splenectomy because of bleeding, an adrenalectomy, and acute renal failure in one patient in the immediate postoperative period. We concluded that donor nephrectomy done through a flank incision results in minimal morbidity.

Adolescent↗
PubMed1994

The Ross operation--early echocardiographic comparison of different operative techniques.

Fifty-four consecutive patients underwent aortic valve replacement with a pulmonary autograft (Ross operation) over an 18-month period. It was inserted as an intra-aortic cylinder in 13 patients and as a total aortic root replacement in 41; unwrapped in 16, partially wrapped with autologous pericardium in 12 and completely wrapped with bovine pericardium in 13. There were two cardiac deaths, one death from mediastinitis, and two early reoperations to replace an incompetent autograft. Comparison of postoperative echocardiographic data showed a higher incidence of moderate and severe autograft incompetence in the intra-aortic cylinder group and also in the subset without previous operation which had a total root replacement without a complete wrap. Autograft function was best in the group which received a total root replacement with a complete wrap and in those with previous cardiac surgery who received an unwrapped autograft. This preliminary information with short follow up supports the use of complete wrapping of the autograft when it is used as a total root replacement particularly in older patients without previous cardiac surgery in whom future autograft growth is not desirable.

Adolescent↗
PubMed1994

Renal retransplantation: the role of race, quadruple immunosuppression, and the flow cytometry cross-match.

To assess the impact of quadruple immunosuppression in black and white recipients of cadaver kidney retransplants, we reviewed data from 178 second or subsequent renal allografts performed at our center between 1985 and 1991. Sixty-six black and 102 white recipients were divided into 3 groups: groups 1 and 2 consisted of patients with a negative complement-dependent cytotoxicity (CDC) T cell cross-match, receiving triple drug therapy (CsA-AZA-prednisone) and quadruple immunosuppressive therapy (quad therapy; Minnesota antilymphoblast globulin-CsA-AZA-prednisone), respectively. Group 3 patients also received quad therapy, but, in addition to a negative CDC cross-match, had a negative T cell flow cytometry cross-match (FCXM). Black and white patients in groups 1 and 2 experienced similar graft survival at 1 year, ranging from 47% to 63% (P = NS). In group 3, 1-year graft survival in whites, but not blacks, improved to 82%, with fewer grafts lost to immunologic causes in the first 90 days after transplant. A parametric analysis of potential risk factors identified a significant effect of better HLA-DR matching (P = 0.0005) on improved graft survival, with previous mismatched antigens (P = 0.04), female donor (P = 0.002), and short duration of previous graft (P = 0.05) as risk factors for graft loss. Race and immunosuppressive protocol did not affect graft survival. In group 3, blacks received fewer well-matched kidneys than whites (P = 0.05), which may have contributed to poorer outcomes for black recipients. Nine of 10 patients undergoing retransplantation with a negative CDC cross-match and a positive T cell FCXM suffered graft loss at a median of 26 days after transplant. Thus, quad therapy did not enhance graft survival for either black or white patients undergoing cadaveric retransplantation. Immunologic considerations, including HLA-DR matching and the FCXM, continue to exert a strong influence on outcomes in these high-risk recipients.

Adult↗
PubMed1993

Tapering or discontinuing cyclosporine for financial reasons--a single-center experience.

In patients with primary cadaveric renal transplants and stable allograft function, we assessed the impact of tapering or discontinuing cyclosporine A (CsA) for financial reasons. Forty-two patients whose CsA was discontinued ("no-dose") and 29 patients whose CsA was tapered to 100 to 150 mg/d ("low-dose"; mean, 1.7 mg/kg/d) were examined. Results were compared with 70 age- and race-matched control patients maintained on at least 200 mg/d of CsA (mean, 3.9 mg/kg/d). Follow-up time for all patients averaged 55 +/- 18 months. Late acute rejection episodes occurred more frequently in no-dose than in low-dose (P = 0.017) or control (P = 0.001) patients. In the no-dose group, blacks experienced a greater number of late acute rejections than whites. These late acute rejections often coincided with the discontinuation of CsA and contributed to an increased rate of allograft loss in blacks in the no-dose group compared with black and white controls (P = 0.011). In contrast, no increase in late acute rejection episodes occurred in blacks tapered to low doses of CsA. Black patients who remained on low doses of CsA also exhibited a trend toward allograft survival that was intermediate between that of control and no-dose patients. In those patients who retained functional allografts, mean serum creatinine concentration did not differ between the study groups at the beginning and end of the follow-up period. These findings support continuance of CsA in black primary cadaveric renal transplant patients, even if dosages must be reduced to 100 to 150 mg/d.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Experience with mycophenolate mofetil (RS61443) in renal transplantation at a single center.

OBJECTIVE: Mycophenolate mofetil (MM) is a new immunosuppressive agent that reversibly inhibits guanine nucleotide synthesis and DNA replication. Its activity is highly selective for T and B lymphocytes. Two open-label multicenter trials of MM in renal transplantation have been performed. This report summarizes the results from one center involved in these two trials. METHODS AND RESULTS: The initial trial of MM was an open-label dose-ranging trial in primary cadaveric renal transplantation. Mycophenolate mofetil was included in the maintenance immunosuppression regimen from the day after transplantation. Of the 21 patients enrolled in this trial, one (5%) was withdrawn for side effects. There was one graft loss due to recurrent renal disease and two patients were withdrawn for difficulty with follow-up. Mean follow-up is 26 months, and patient and graft survival at 2 years are 100 and 95% respectively. The second trial was designed to study the efficacy of mycophenolate in reversing refractory renal allograft rejection. Patients enrolled in the trial had biopsy-proven acute rejection and had previously received at least one course of high-dose corticosteroids and/or OKT3. Of the 26 patients enrolled in this trial, one (4%) was withdrawn for side effects. There were two deaths. Mean follow-up is 20 months, and patient and graft survival at 12 months was 91 and 54%. The incidence of infections in the two groups was 38% and there were no deaths in either group attributable to infection. CONCLUSIONS: The results of these two studies indicate that mycophenolate mofetil could be administered safely to renal allograft recipients for periods up to 2 years. It appears to be effective in reversing acute rejection in a high percentage of patients refractory to other forms of therapy.

Adrenal Cortex Hormones↗
PubMed1993

Pediatric renal transplantation at the University of Alabama at Birmingham, 1968 to 1993.

From May 5, 1968 through January 31, 1993, 272 renal allografts were performed in 233 children at the University of Alabama at Birmingham. Graft survival has improved since 1983 with the addition of cyclosporine. Acute and chronic rejections continue to be the major causes of graft failure. The use of living-related donor renal allografts optimizes long-term graft function, allows early transplantation, and minimizes potential long-term dialysis complications in children.

Academic Medical Centers↗
PubMed1992

RS-61443: successful rescue therapy in refractory renal rejection.

RS-61443, the morpholinoethyl ester of mycophenolic acid (mPA), is a potent, noncompetitive, reversible inhibitor of eucaryotic inosine monophosphate (IMP) dehydrogenases. Because of the importance of the guanosine and deoxyguanosine nucleotides in activating phosphoribosyl pyrophosphate (PRPP) synthesis and ribonucleotide reductase, respectively, it was postulated that depletion of GMP (and consequently GTP and GDP) would have antiproliferative effects on lymphocytes. Furthermore, since lymphocytes rely on de novo pruine synthesis whereas other cell types do not, antiproliferative effects produced in this way are more selective for lymphocytes than other cell types.

Adrenal Cortex Hormones↗