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J T Mayes

Publications and source records attributed to J T Mayes.

At least 19 recordsLinked to original sources
PubMed1992

Multiple pathways in the rejection of skin grafts.

We have analyzed the ability of CD4+ and CD8+ T cells to cause rejection of skin grafts in an Ir gene high responder strain. (DA.RT1u x DA.RT1c)F1 B rats (thymectomized, lethally irradiated, reconstituted with fetal liver cells) were grafted with ear skin of the recombinant strain, DA.RT1rl. The only allogeneic difference was a single class I MHC antigen. The B rats, which do not reject these grafts due to the absence of T cells, were reconstituted at various time intervals after skin grafting with either unsorted lymph node cells (LNCs), CD4+, CD8+ or CD4+ and CD8+ T cells. Unsorted LNCs given any time after graft placement always caused rejection (MST = 15d). CD4+ cells alone never caused rejection (MST greater than 60d, n = 8). CD8+ cells alone caused rejection if given within 3 weeks of graft placement. Thereafter, CD8+ cells alone lost their ability to cause rejection (MST greater than 60d, n = 6). B rats with grafts in place more than 3 weeks, when CD8+ cells alone were ineffective, rejected their skin grafts when given both CD8+ and CD4+ cells. These data suggest that there may be two T cell pathways in skin graft rejection. The first requires only CD8+ cells and causes rejection of a recently placed graft. The second pathway requires both CD4+ and CD8+ cells to reject long-standing grafts in which donor antigen-presenting cells have been putatively depleted and, therefore, may be dependent on host antigen-presenting cells.

Animals↗
PubMed1992

Withdrawal of steroids after renal transplantation--clinical predictors of outcome.

Withdrawal of steroid therapy in renal transplant recipients is associated with a risk of acute allograft rejection. To define clinical risk factors for rejection associated with steroid withdrawal, we analyzed the clinical characteristics of 107 patients with drawn from steroid therapy at various times after transplantation. Both univariate and multivariate analyses suggested that the timing of steroid withdrawal is an important predictor of steroid withdrawal failure. Withdrawal of steroids was successful in only 13 of 32 patients (41%) in whom prednisone was discontinued shortly after transplantation. In contrast, steroid withdrawal has been successful in 59 of 75 patients (79%) in whom prednisone was discontinued at least 6 months after transplantation. Black race and donor-recipient racial mismatch also were significant predictors of rejection associated with steroid withdrawal. In patients undergoing steroid withdrawal at least 6 months posttransplant, serum creatinine concentration also correlated independently with the risk of rejection. Neither age, sex, HLA match, pretransplant PRA, source of the allograft (cadaver vs. living relative), acute tubular necrosis, nor the presence of diabetes was predictive of the outcome of steroid withdrawal.

Adrenal Cortex Hormones↗
PubMed1992

Variable effects of steroid withdrawal on blood pressure reduction in cyclosporine-treated renal transplant recipients.

The effects of complete withdrawal of steroid therapy on blood pressure and other clinical variables were studied in 58 renal transplant recipients subsequently maintained on azathioprine and cyclosporine; 76% of the patients were hypertensive prior to withdrawal of steroids. Cessation of steroids was accompanied by a significant decrease in mean arterial blood pressure and by a reduction in the number of required antihypertensive medications; however, changes in blood pressure were variable among individual patients. Previously normotensive patients exhibited little further decline in blood pressure. Multivariate analysis of the entire cohort of patients showed that the reduction in blood pressure accompanying steroid withdrawal was directly related to the prior severity of hypertension and inversely related to the dose of cyclosporine. We conclude that steroids play an important role in the pathogenesis of posttransplant hypertension in the majority of renal transplant recipients. Withdrawal of steroids generally is accompanied by reduction in blood pressure, but the benefit is greatest in previously hypertensive patients receiving relatively low doses of cyclosporine.

Adult↗
PubMed1992

The effects of steroid withdrawal on the lipoprotein profiles of cyclosporine-treated kidney and kidney-pancreas transplant recipients.

Lipoprotein profiles were measured before and two months after complete withdrawal of prednisone in 34 kidney and 9 kidney-pancreas transplant recipients subsequently maintained on cyclosporine and azathioprine. Withdrawal of steroid therapy was accompanied by a 17% reduction in total serum cholesterol levels. However, there was a parallel reduction in all other measured lipoprotein concentrations, including an 18% reduction in high-density lipoprotein cholesterol levels. In diabetic recipients of a kidney or kidney-pancreas transplant, the ratio of total to high-density lipoprotein cholesterol was unchanged after steroid withdrawal. In nondiabetic kidney transplant recipients, this ratio actually increased significantly following withdrawal of prednisone. These observations suggest that it is premature to presume that withdrawal of steroid therapy will reduce the cardiovascular risk related to hyperlipidemia in cyclosporine-treated kidney or kidney-pancreas transplant recipients.

Adult↗
PubMed1991

Salvage of thrombosed forearm polytetrafluoroethylene vascular access grafts by reversal of flow direction and venous bypass grafting.

A technique is described for salvage of looped forearm polytetrafluoroethylene (PTFE) vascular access grafts that fail because of thrombosis due to cephalic vein outflow obstruction. It entails reversal of blood flow direction through the graft and construction of a new venous outflow in the medial upper arm. This procedure was performed in nine patients and, at the present time, has increased the graft life by an average of 6.2 months (range: 2 to 14 months) in eight. We conclude that this is a useful alternative to abandoning failed looped forearm PTFE grafts that have cephalic vein outflow obstruction.

Anastomosis, Surgical↗
PubMed1991

Independent effects of cyclosporine and prednisone on posttransplant hypercholesterolemia.

To clarify the relative influences of cyclosporine (CsA) therapy, corticosteroid therapy, and other clinical variables on posttransplant hypercholesterolemia, total serum cholesterol levels were measured in 107 renal transplant recipients receiving one of three immunosuppression regimens: CsA and azathioprine (AZA) (group I); CsA, AZA, and prednisone (group II); or AZA and prednisone (group III). Multivariate analysis demonstrated that prednisone therapy, CsA therapy, patient age, and pretransplant cholesterol levels correlated independently with posttransplant cholesterol levels at last follow-up (ranging from 13 to 84 months after transplantation). In 32 patients successfully withdrawn from corticosteroid therapy and maintained on AZA and stable doses of CsA, serum cholesterol decreased from 6.55 +/- 1.1 mmol/L (253.5 +/- 43.1 mg/dL) to 5.27 +/- 1.2 mmol/L (203.9 +/- 45.6 mg/dL). Results of this analysis indicate that prednisone and CsA are independent factors in the pathogenesis of posttransplant hypercholesterolemia. Complete withdrawal of corticosteroids partially corrects hypercholesterolemia in CsA-treated renal transplant recipients.

Adult↗
PubMed1991

Effects of steroid withdrawal on posttransplant diabetes mellitus in cyclosporine-treated renal transplant recipients.

Posttransplant diabetes mellitus (PTDM) traditionally has been attributed to therapy with steroids--however, several lines of evidence suggest that cyclosporine also is diabetogenic. A retrospective review revealed that PTDM developed in 9 of 70 previously nondiabetic kidney transplant recipients (12.9%) maintained on prednisone, azathioprine, and CsA compared with 8 of 83 nondiabetics (9.6%) maintained on azathioprine and prednisone alone in an earlier era (P = NS). Among patients maintained on triple-drug therapy, complete withdrawal of prednisone was attempted in 7 renal transplant recipients with PTDM and in 1 recipient of a combined kidney-pancreas transplant who exhibited evidence of type II diabetes mellitus. Seven of the 8 patients were able to discontinue insulin or oral hypoglycemic agents within 4 months of discontinuing steroids. Mean glycohemoglobin level declined from 10.6 +/- 3.6% prior to steroid withdrawal to 6.0 +/- 1.3% within 1 month of steroid cessation, while mean CsA dose and trough CsA blood levels remained unchanged. In 2 patients, mild rejection episodes prompted a return to steroid therapy. Although CsA may be diabetogenic, evidence from this study suggests that withdrawal of steroid therapy is a safe and effective approach to the management of PTDM in patients subsequently maintained on CsA and azathioprine.

Blood Glucose↗
PubMed1991

Treatment with OKT3 and cyclosporine for acute allograft rejection.

In summary, we believe that our experience with concomitant use of OKT3 and either reduced-dose CyA for treatment of renal allograft rejections or full-dose CyA therapy for treatment of liver allograft rejection is both safe and possibly more effective in reversing allograft rejection than use of the antibody alone. This strategy has also allowed us to use this MAb therapy without incurring the untoward consequence of the development of hightiter anti-OKT3 antibodies that could preclude its subsequent reuse.

Adult↗
PubMed1990

Combined kidney and pancreas transplantation. A safe and effective treatment for diabetic nephropathy.

Seventeen patients with type I diabetes and diabetic nephropathy underwent combined kidney and pancreas transplantation. Mean age was 32 +/- 6 years and average duration of diabetes was 21 +/- 6 years. Transplantation was performed through bilateral iliac fossa incisions, and graft duodenocystostomy was used to achieve exocrine pancreas drainage. The actuarial patient and kidney survival rate was 92% and the pancreas survival rate, 88% (follow-up of 3 to 28 months). One patient with functioning grafts died at 10 months owing to a cardiac arrhythmia and one pancreas was "lost" to early thrombosis. Major morbidity was due to pancreas wound infection (53%) that required reoperation, but all patients have had subsequent healing of their wounds. Rehabilitation with return to meaningful activity has been accomplished by 15 patients. This experience demonstrates that combined kidney and pancreas transplantation can be performed safely and successfully.

Adult↗
PubMed1990

A prospective randomized trial of prednisone versus no prednisone maintenance therapy in cyclosporine-treated and azathioprine-treated renal transplant patients.

The purpose of this study was to evaluate early (6-12 days) prednisone withdrawal in cyclosporine- and azathioprine-treated renal transplant recipients. Patients, including 8 recipients of live-related donor kidneys and 59 recipients of cadaver donor kidneys, were prospectively randomized to receive maintenance prednisone (PRED) therapy or not (NOPRED) in addition to antilymphocyte globulin, cyclosporine, and azathioprine. Rejection episodes were initially treated with methylprednisolone pulses, and OKT3 monoclonal antibody was used to treat steroid resistant rejections that were verified by biopsy. NOPRED patients were declared protocol failures and returned to PRED therapy if they sustained 2 steroid-sensitive rejection episodes in the first 3 months or an OKT3-treated rejection at any time. Patient and graft survival for the LRD patients in both treatment categories were 100% at 12 months. Patient and graft survival for CAD recipients at one year was 94% and 83% (PRED) and 88% and 77% (NOPRED), respectively. Rejection episodes were more frequent (26 of 32 NOPRED patients vs. 19 of 35 PRED patients P = 0.02) and occurred earlier (4.5 weeks in NOPRED vs. 7.7 weeks in PRED patients) in patients not taking maintenance steroids. Rejection severity was also greater in the NOPRED group, as 15 OKT3-treated rejections occurred in that group whereas only 7 OKT3-treated rejections were observed in the PRED group (P = less than 0.01). The incidence of serious infection was similar in each group. Finally, protocol failure occurred in 40% of the LRD patients and 59% of the CAD patients. These data indicate that initiating maintenance therapy without PRED is safe but is attended by a greater risk of developing rejection. Because of this increased incidence and severity of early rejection episodes in NOPRED patients, we do not advise use of this immunosuppressive strategy in renal transplantation.

Azathioprine↗
PubMed1990

Inhibition of anti-OKT3 antibody generation by cyclosporine--results of a prospective randomized trial.

To investigate the influence of therapy with cyclosporine on the generation of antibodies to OKT3, 51 renal transplant recipients previously maintained on CsA, azathioprine, and prednisone were allocated randomly either to receive 50% of their maintenance dose of CsA (group 1, n = 27) or to discontinue CsA (group 2, n = 24) during treatment with OKT3 for acute renal allograft rejection. In the month following therapy with OKT3, anti-OKT3 antibodies were detected in 11% of patients in group 1 and in 42% of patients in group 2 (P less than 0.02). No patient in group 1 developed antibody titers greater than 1:100, whereas 4 patients in group 2 developed titer greater than or equal to 1:1000. Rejection was reversed in 96% of patients in group 1 and in only 75% of patients in group 2 (P less than 0.03), suggesting that continued administration of reduced doses of CsA during therapy with OKT3 improves the short-term response to this monoclonal antibody. Results of this study suggest that concurrent administration of CsA during therapy with OKT3 inhibits the generation of anti-OKT3 antibodies and improves the response to this monoclonal antibody.

Acute Disease↗
PubMed1990

Kidney transplantation in patients aged sixty years and older.

Outcomes of renal transplantation were reviewed for 26 transplants performed in 25 patients 60 years of age or older between 1985 and 1989. Three grafts were from family donors and 23 were from cadaver donors. Twenty-one were first transplants and five were retransplants. Cyclosporine was used as primary immunosuppression and azathioprine and prednisone were administered to most patients. Overall patient and graft actuarial survival rates were 79% and 71%, respectively, at both 1 and 3 years. Patients (n = 14) free of both diabetes and cardiac disease (low risk) had 1- and 3-year patient and graft survival rates of 91% and 84%, respectively. Conversely, high-risk patients (n = 12) had patient and graft survival rates at 1 and 3 years of 67% and 58%, respectively. Early deaths (less than or equal to 6 months) were caused by sepsis (two patients) or cardiac events (three patients), and four of the five were in high-risk patients. Irreversible rejections and serious infectious complications were not as common as steroid-induced diabetes, which occurred in five patients. This experience suggests that kidney transplantation can be done safely and successfully in patients older than 60 years of age and should be the treatment of choice for low-risk patients in this category.

Aged↗