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Biomedical subjects

A G Diethelm

Publications and source records attributed to A G Diethelm.

At least 55 records · Page 3Linked to original sources
PubMed1992

Benefits of quadruple immunosuppressive therapy in recipients of living related donor kidneys. A review of 855 operations.

Eight hundred fifty-five living related donor transplant recipients were analyzed according to 15 potential risk factors with regard to patient and graft survival according to immunosuppression. Group I, 1968 to 1983, (n = 440 patients) received azathioprine and prednisone; group II, 1984 to 1987, (n = 229 patients) received triple therapy--azathioprine, prednisone, and cyclosporine; and group III, 1988-1991, (n = 186 patients), quadruple therapy--azathioprine, prednisone, cyclosporine, and Minnesota antilymphocyte globulin. Three important risk factors included immunosuppression, tissue typing, and race. Groups II and III had improved allograft survival over group I (p = 0.03). Patients with two haplotype matches had similar survival in all three groups. Kidney survival in one-haplotype-matched recipients improved in group II and was equal to that of the two-haplotype-matched patients in group III. Cyclosporine improved allograft survival in both races when combined with azathioprine and prednisone. Quadruple therapy improved early survival in one-haplotype black patients, even though long-term results remained better in whites. Cyclosporine did not improve graft survival in two-haplotype recipients. The addition of cyclosporine and quadruple therapy did not increase morbidity and mortality rates.

Adolescent↗
PubMed1992

RS-61443 (mycophenolate mofetil). A multicenter study for refractory kidney transplant rejection.

RS-61443 (mycophenolate mofetil) inhibits a key enzyme of the de novo synthesis of purine nucleotides in T and B lymphocytes. The purpose of this study was to evaluate the efficacy of RS-61443 in patients with refractory renal allograft rejection. Patients eligible for the study had previously undergone anti-rejection therapy with high-dose steroids or OKT3 monoclonal antibody. All rejection episodes were proven by renal biopsy. Successful rescue was achieved in 52 (69%) patients. Rescue was more successful when patients were entered with a creatinine of 4 mg/dL or lower (79%), versus a 52% rescue rate in patients entered with a creatinine of 4 mg/dL or above. Major side effects were predominantly gastrointestinal, but there was no overt nephrotoxicity, hepatotoxicity, or bone marrow suppression. The overall infection rate was 40%, with the spectrum of infections characteristic for the highly immunocompromised patient. The conclude that this pilot study suggests that RS-61443 is effective in refractory kidney allograft rejection. Based on this study, prospectively randomized multi-center trails have been planned and are in progress.

Adolescent↗
PubMed1992

Improved survival of primary cadaveric renal allografts in blacks with quadruple immunosuppression.

Black recipients of cadaveric kidneys have been shown to have a lower rate of allograft survival than whites. Data were reviewed from 642 primary cadaveric transplants: results in 276 patients (163 white and 113 black) (group 1) who had received triple therapy (azathioprine-CsA-prednisone, 1985-87) were compared with those in 366 patients (180 white and 186 black) (group 2) receiving quadruple immunosuppression (MALG-azathioprine-CsA-prednisone, 1987-90). Blacks in group 2 had better patient (97% vs. 91%, P = 0.03) and graft (77% vs. 55%, P = 0.0002) survival at 1 year than in group 1. There was no difference in these parameters among whites in either group. Racial differences in graft survival noted in group 1 disappeared in group 2. While HLA BDR matching improved in group 2 patients (P = 0.0001), whites received better matched kidneys than blacks in both groups (P = 0.001). HLA matching was associated with improved graft survival only in white recipients of 4 BDR-matched kidneys. In group 1, more blacks than whites had at least one episode of acute rejection (76% vs. 57%, P = 0.001); blacks also lost more grafts to acute and chronic rejection. In group 2, there were no racial differences in the number of rejection episodes or immunologic graft losses. Of 14 potential variables examined by parametric analysis, only quadruple therapy significantly reduced risk of graft loss in blacks. Quadruple immunosuppression improved primary cadaveric renal allograft survival in black recipients, abrogating previously noted racial differences.

Adult↗
PubMed1992

The effect of erythropoietin and blood transfusions on highly sensitized patients on a single cadaver renal allograft waiting list.

The effects of EPO on transfusion requirements and HLA allosensitization were studied in a group of 145 sensitized patients on a single cadaveric renal allograft waiting list. All patients included in the study had PRA levels greater than 40% and at least six months of follow-up after the general availability of EPO. A total of 108 (74%) of these patients received EPO during the study period while 37 (26%) did not. The EPO patients had a much higher incidence of prior transfusions than the non-EPO patients (64% vs. 39% P less than 0.05). During the follow-up period, there was a marked reduction in transfusion incidence in the patients who received EPO from 64% to 14% (P less than 0.05). A lesser and nonsignificant reduction in incidence of transfusions was seen in the non-EPO-EPO patients. Analysis of PRA levels in the EPO and non-EPO groups demonstrated a reduction in PRA levels over time but there was no difference between the two groups. When the patients were divided by the need for transfusions in the follow-up period, a comparison of these two groups demonstrated significant differences. At the six-month follow-up point, patients in the nontransfused group had a significantly lower mean PRA than the transfused patients (49% vs. 62%, respectively, P less than 0.05). Furthermore, a greater number of patients in the nontransfused group had PRA declines greater than or equal to 15% compared with the nontransfused group (56/46% vs. 4/15%, respectively; P = .007). Stepwise logistic regression analysis of possible risk factors for persistent high PRA levels demonstrated that continued transfusion was the only significant factor. This study suggests that the institution of EPO therapy in sensitized patients on a single cadaveric waiting list can result in substantial reduction in the need for on-going transfusions. However, the decline in PRA levels appears to be more closely tied to the avoidance of transfusion rather than to the specific institution of EPO therapy.

Adolescent↗
PubMed1992

RS-61443--a phase I clinical trial and pilot rescue study.

RS-61443, a morpholinoethyl ester of mycophenolic acid, inhibits the synthesis of guanosine monophosphate, which plays a pivotal role in lymphocyte metabolism. The drug blocks proliferative responses of T and B lymphocytes, and inhibits antibody formation and the generation of cytotoxic T cells. In vivo, RS-61443 prolongs the survival of islet allografts in mice, heart allografts in rats, and kidney allografts in dogs. Reversal of ongoing acute rejection was demonstrated in rat heart allografts and kidney allografts in dogs. Preliminary evidence suggests that the drug prevents chronic rejection. The purpose of this study was to test the safety and tolerance in patients receiving primary cadaver kidneys. RS-61443 in doses from 100 mg/day p.o. to 3500 mg/day p.o. was given to patients in combination with cyclosporine and prednisone. Further study goals were to evaluate the pharmacokinetics of RS-61443, watch for the occurrence of opportunistic infections and acute rejection, and establish dosages for further clinical trials. Forty-eight patients were entered, with six patients in each dose group. RS-61443 was well tolerated in all dose groups, with only one adverse event possibly related to the drug (hemorrhagic gastritis). There was a statistically significant correlation between rejection episodes and dose (P = 0.022), patients with rejection episodes versus dose (P = 0.038), and number of OKT3/prednisone courses versus dose (P = 0.008). There was no overt nephrotoxicity or hepatotoxicity. Preliminary results of a rescue trial in 20 patients with kidney transplants will also be presented.

Adult↗
PubMed1992

Renal transplant hypertension caused by iliac artery stenosis.

A captopril renal study performed with both radiohippuran and 99mTc-MAG3 demonstrated the typical changes of a hemodynamically significant renal artery stenosis in a hypertensive renal allograft recipient. Arteriography demonstrated high grade stenosis not of the renal artery but of the iliac artery. After successful angioplasty, the patient's hypertension resolved.

Captopril↗
PubMed1991

Renal transplantation in children with posterior urethral valves.

We compared retrospectively the outcome of renal transplantation in 18 children with a diagnosis of posterior urethral valves to 18 matched children with nonobstructed renal failure to identify the disadvantages of renal transplantation into the valve bladder. There was no statistical difference in patient survival. The 5-year graft survival rate was 62.3% in children with posterior urethral valves and 48% in the control group. The difference was not statistically significant (p = 0.32). A statistically significant increase in serum creatinine from 1.2 to 2.2 mg./dl. was noted in the patients with posterior urethral valves, which was not seen in the control group (p = 0.0009). The clinical significance of this finding is unknown. Renal transplantation can be performed successfully in patients with posterior urethral valves. A prospective study is required to determine the benefits of preoperative lower urinary tract urodynamic assessment and the true effect of the valve bladder.

Adolescent↗
PubMed1991

OKT3 first-dose reaction: association with T cell subsets and cytokine release.

Use of the monoclonal antibody OKT3 to prevent or treat allograft rejection has become commonplace. Its administration is often complicated by serious side effects, usually occurring within one to two hours after OKT3 is given, and is termed first-dose reaction. The mechanism underlying these signs and symptoms is poorly defined, but may be related to cytokine release. Twenty-three kidney or kidney/pancreas transplant recipients received OKT3 as treatment of acute rejection. Signs and symptoms occurring after the first dose were observed and quantitated prospectively, and a reaction score was calculated. Blood was drawn immediately before, and at 2 and 24 hours after the first dose of OKT3 for determination of interleukin-2 (IL2), interferon-gamma (IFN gamma), and tumor necrosis factor-alpha (TNF alpha) levels, and flow cytometric analysis of T cell subsets. Two groups were defined based on severity of first-dose reaction. Group 1 patients (N = 11) had very mild reactions (reaction score less than or equal to 3); Group 2 patients (N = 12) had more severe reactions (score greater than or equal to 5). All patients demonstrated a significant rise in serum TNF alpha from baseline to two hours after OKT3 (9 +/- 3 pg/ml to 378 +/- 54 pg/ml, P less than 0.0001), and there was significant correlation between reaction scores and two-hour TNF alpha levels (P = 0.005). Group 2 patients had higher TNF alpha levels at two hours than did Group 1 patients (484 +/- 75 pg/ml vs. 263 +/- 62 pg/ml, P = 0.04). Levels of IL2 and IFN gamma were not elevated at any sampling time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Long-term results of a controlled prospective study with transfusion of donor-specific bone marrow in 57 cadaveric renal allograft recipients.

Experimental studies have shown that antilymphocyte globulin combined with transfusion of donor-specific bone marrow cells can induce partial tolerance to allograft tissue. We have adapted these protocols to clinical use and present the results of 57 cadaveric renal allograft recipients who received Minnesota ALG followed by the transfusion of cryopreserved donor-specific bone marrow. A group of 54 patients received the contralateral kidney and similar immunosuppression without the marrow transfusion and serve as controls. Both groups received quadruple immunosuppression with MALG, cyclosporin, azathioprine, and prednisone. In the bone marrow group, after a 10-14 day induction course of ALG, cryopreserved marrow was transfused on the seventh day after the last dose of ALG. The median follow-up in both groups is 16 months, (range 2.5-33 months). Six grafts have been lost in the bone marrow group, (three rejections, 2 deaths [Cr 2.0, 2.3], 1 recurrent disease). In the control group 16 grafts have been lost (13 rejections, 3 deaths [Cr 1.7, 2.5, 3.0]). Five patients in the control group have biopsy-proved chronic rejection compared to one in the bone marrow group. 17 patients in the bone marrow group have been tapered off the prednisone, and three of these patients have had mild late rejection episodes without graft loss. The two groups were compared for differences in the number of rejection episodes, estimated renal plasma flow, glomerular filtration rate, and urine protein. No differences were found. The allograft survival of the bone marrow group was significantly greater (P less than .01) than the control group. The graft survival rates for the bone marrow group at 12 and 18 months were 90% (confidence limits [CL] 85-94) and 85% (CL 78-90), respectively. In the the control group the 12 and 18 month allograft survival rates were 71% (CL 63-78) and 67% (CL 58-74), respectively. The survival in the control group was similar to our overall transplant experience with quadruple therapy. Mixed lymphocyte culture analysis shows a trend to diminished donor-specific responsiveness in the bone marrow group. The use of cryopreserved donor-specific bone marrow is associated with improved allograft survival in cadaveric kidney allograft recipients. However, a more effective induction protocol is needed to reduce the overall number of rejection episodes.

Antilymphocyte Serum↗
PubMed1991

Analysis of 22 years experience in living-related transplantation at the University of Alabama in Birmingham.

Over the 22 years comprising this review of living-related renal allografts, 3 distinct eras of immunosuppression protocols were used; Era I-aziathioprine and prednisone, Era II-cyclosporine, azathioprine, and prednisone; and Era III-Minnesota antilymphocyte globulin, cyclosporine, azathioprine, and prednisone. We analyzed both recipient and donor populations for graft and patient survival related to race, haplotype matching, diabetes, and immunosuppressive agents. Graft and patient survival have remained unchanged in 2-haplotype-matched recipients throughout the differing immunosuppression eras. The addition of cyclosporine, however, improved graft survival in the 1-haplotype living-related recipient. During the cyclosporine era, 1-haplotype White living-related recipient graft survival was significantly greater than 1-haplotype Black living-related recipient survivals. The reason for this disparity in graft survival does not appear to be related to noncompliance. The parametric hazard function analysis of the constant phase did not identify cyclosporine as a risk factor for late graft loss, suggesting that long-term cyclosporine usage may decrease the risk of graft loss. However, diabetes was demonstrated to be a risk factor for late graft loss. In diabetics, late graft loss is most likely secondary to death (usually cardiovascular) with a functioning graft. The organ donor pool is being expanded through the utilization of both older donors and living-unrelated donors. Graft survival in the living-unrelated group has been comparable to that of 1- and 2-haplotype-matched recipients. Results with older donors reveal donor age as a risk factor for late graft loss. The issue of living-unrelated transplantation remains controversial. In over 20 years of follow-up on our living-related donor population, we were unable to demonstrate any adverse long-term effects on renal function. Results of our analysis indicate that living-related renal donation continues to be a safe and valuable avenue for kidney transplantation.

Adolescent↗
PubMed1990

Cyclosporine-induced changes in glomerular filtration rate and urea excretion.

PURPOSE: Cyclosporine is the mainstay of many immunosuppressant protocols, but confers a significant risk of nephrotoxicity. We sought to clarify the effects of cyclosporine on renal function in renal transplant recipients after induction of mild intravascular volume depletion. PATIENTS AND METHODS: Two groups of renal transplant patients with normal allograft function at least 6 months after transplantation whose immunosuppressive regimens differed only by the presence or absence of cyclosporine usage were enrolled in a 10-day in-hospital protocol. After a 3-day control period, intravascular volume depletion was produced by dietary restriction of sodium chloride for 4 days and the administration of furosemide. Creatinine and urea clearances, true glomerular filtration rate (GFR) (by radioisotope technique), and the fractional excretion of sodium were measured. The patients were subsequently given a high amount of sodium chloride by intravenous infusion (3.8 mEq/kg body weight/day) for 3 days and the studies were repeated. RESULTS: Ten patients treated with azathioprine and prednisone (azathioprine-treated) and nine patients treated with cyclosporine, azathioprine, and prednisone (cyclosporine-treated) were enrolled. The two groups developed a similar degree of intravascular volume depletion; blood pressure did not change and urine flow rates did not differ between the groups throughout the protocol. The cyclosporine-treated patients showed significant decreases in GFR, creatinine clearance, and urea clearance, and increases in blood urea nitrogen (BUN) and percent urea reabsorption after intravascular volume depletion; these findings resolved after challenge with the sodium chloride load. In contrast, the azathioprine-treated patients' BUN, urea clearance, GFR, and creatinine clearance did not significantly change throughout the protocol. The decrease in the fractional excretion of sodium after intravascular volume depletion was significantly greater in the cyclosporine-treated patients. CONCLUSION: Cyclosporine predisposes to acute reversible nephrotoxicity by compromising the renal compensatory mechanisms. Proximal tubular function, as manifested by urea and sodium reabsorption, remains intact.

Adult↗
PubMed1990

International air medical transport. Part I: Methods and logistics.

International air medical transport requires reliable equipment, skilled personnel and precise planning. A report is presented of an experience with 29 international transports. Details concerning equipment, personnel and logistics are presented. Results and problem areas are discussed. This early experience demonstrates the capability for the repatriation of critically ill patients, and the evacuation of patients who require access to a level of care which may be unavailable outside the United States.

Aircraft↗
PubMed1990

International air medical transport. Part II: Results and discussion.

International air medical transport requires reliable equipment, skilled personnel and precise planning. A report is presented of an experience with 31 international transports. Details concerning equipment, personnel and logistics are presented. Results and problem areas are discussed. This early experience demonstrates the capability for the repatriation of critically ill patients, and the evacuation of patients who require access to a level of care which may be unavailable outside the United States.

Aircraft↗