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C J Cardella

Publications and source records attributed to C J Cardella.

At least 19 recordsLinked to original sources
PubMed1995

Lack of enhanced T-helper cell function in uremic patients with circulating alloreactive antibodies.

Some uremic patients with a history of blood transfusion, pregnancy, and previous transplantation maintain high levels of alloreactive cytotoxic antibodies in the absence of continuous exogenous allogenic stimuli and are thus considered sensitized to the major histocompatibility proteins. To differentiate into antibody-producing cells, B lymphocytes must interact with T-helper (CD4+) cells. Whether ongoing help from these cells is necessary for the B cells to continue producing cytotoxic alloreactive antibodies in these sensitized uremic patients is unknown. To gain insight into the cellular mechanisms that are associated with sustained alloantibody production, T cell activation markers were measured and specific and nonspecific T-helper cell function was studied in three uremic groups with different levels of panel reactive antibodies: 10 patients whose sera reacted to more than 80% of a panel of normal lymphocytes for at least 6 months before the study were highly sensitized, 20 patients whose sera reacted to less than 80% of the panel were moderately sensitized, and 10 nonsensitized patients whose sera did not react to any cell on the panel. The number of total and activated T-helper cells was similar in the highly sensitized and nonsensitized patients. Peripheral blood lymphocyte proliferation in response to plant lectins, soluble OKT3, or alloantigens was similar in the three uremic groups. The spontaneous proliferation of pure T-helper cells and proliferative responses to immobilized OKT3 or alloantigens were also similar in highly sensitized and nonsensitized patients. Alloreactive interleukin-2-producing cell frequencies with pure CD4+ cells as responding cells were 771 +/- 77.9/10(6) cells in highly sensitized, 945 +/- 252/10(6) cells in nonsensitized, and 973 +/- 114/10(6) cells in controls (P = not significant). Panel reactive antibody levels did not correlate with any of the measures of T helper responses. There was a significant decrease of peripheral blood lymphocyte responses to alloantigens and anti-CD3 antibody in all uremic patients as compared with normals, suggesting a dysfunction in accessory cells that was quantitatively similar in sensitized and nonsensitized patients. In spite of the continuous production of alloantibodies by B cells, there is no evidence of either specific or nonspecific enhancement of T-helper cell function in sensitized patients. The absence of T cell immunity to alloantigens suggests that sustained activation of T-helper cells with subsequent interleukin-2 production is not necessary to maintain alloreactive B cell function.

Adult↗
PubMed1992

Analyzing the number of "rejection episodes" in renal transplant studies.

Transplantation has become the treatment of choice for many chronic and debilitating diseases. Generally, the primary endpoints in evaluating therapy are graft and patient survival time. However, an important secondary outcome is the number of "rejection episodes" experienced by study patients. This response has a distinctive statistical character. That is, it is a categorical variable since it assumes only a small number of integer values, but it is measured on a ratio-level scale since the ratio of any two values is scientifically meaningful. Historical methods for analyzing this endpoint, for example, t tests, logistic regression and Kaplan-Meier analysis, have failed to take these characteristics into account. In this study, we investigated statistical procedures for analyzing the number of rejection episodes arising during the first three months posttransplant. Data compiled by the Multiple Organ Retrieval and Exchange (MORE) of the Province of Ontario were used for this purpose. It was found that assumptions underlying normal distributional techniques were not satisfied by these data. An alternative model based on Poisson regression models was considered and was shown to provide an adequate fit.

Graft Rejection↗
PubMed1991

The use of the kidney with an historical positive, and current negative crossmatch.

Until recently, most transplant units required that a negative crossmatch using all available sera was an essential criterion which would ensure the best use of a donor kidney. This policy was accepted without clinical trial until 1982 when it was suggested that a donor kidney will function successfully in the majority of recipients with a negative crossmatch using current sera and a positive crossmatch with one or more non-current sera, i.e., sera taken 3 or more months prior to the time of the transplant. In the 14 reported series addressing this question, the average 1-year graft survival ranges between 53% and 100% in these highly sensitized patients who receive a primary graft, and between 0% and 100% in those who receive a secondary graft. Controversy does exist as to whether a positive crossmatch in non-current sera is an additional risk factor, i.e., that it decreases graft survival significantly when compared with a similar group of highly sensitized patients who were transplanted with a negative crossmatch on all available pre-transplant sera. Of the published studies on this subject, the majority, but not all, find that there is no difference between controls and positive crossmatch patients who receive a primary graft, but those that receive a secondary graft may be at increased risk. The reasons for the different results from these studies may be related to differences in the many variables which influence graft outcome between various study groups.

Adult↗
PubMed1991

Blood pressure and left ventricular anatomy and function after heart transplantation.

To determine whether hypertension occurring after heart transplant causes the development of cardiac hypertrophy, changes in pressure load (N = 13) and left ventricular anatomy (N = 11) were evaluated up to 1 year after heart transplant in a prospective longitudinal study. Pressure load was evaluated by 24-hour ambulatory blood pressure monitoring, and left ventricular anatomy and function were assessed by M-mode echocardiography under two-dimensional guidance. Body weight increased by 11 to 12 kg. Blood pressure showed a gradual increase during the first few months after transplant: diastolic pressure by 15 to 18 mm Hg and systolic pressure by 12 to 15 mm Hg, with hypertension persisting during the night. Nearly all patients required treatment with one or two antihypertensive drugs. The increase in blood pressure was related to increased total peripheral resistance with minor decreases in cardiac output. Both septal and posterior wall thickness and left ventricular mass (by 25 to 30 gm/m2) decreased during the initial months after transplant and subsequently remained at "normal" levels (100 gm/m2). The persistence of normal left ventricular mass may indicate either that the increases in daily pressure load and body weight were not sufficient to induce myocardial growth or that the latter was prevented by, for example, absence of cardiac sympathetic nerve activity.

Adult↗
PubMed1990

The role of cold ischemia in a provincial organ-sharing program in the cyclosporine era.

Prolonged cold ischemia has been associated with impaired early cadaver renal allograft function. The role of CsA in potentiating these effects is not well understood, but CsA has been implicated in promoting delayed graft function and potentiating renal ischemic injury. In order to establish whether CsA is safely tolerated by kidneys subjected to protracted cold ischemia, we examined patient and graft outcome in a series of 1081 patients receiving cadaver-kidney transplants over an 8-year period (1981-1988). All patients received a standard immunosuppressive regimen that included CsA. Overall actuarial 1-year patient and graft survival rates were 96% and 80%, respectively. Renal preservation was achieved either by pulsatile perfusion (n = 261, 24%) or simple cold storage (n = 820, 76%). Results were analyzed according to total cold ischemic time as follows: 0-23 hr (n = 512; range, 0-23.9 hr); 24-35 hr (n = 380; range, 24.0-35.9 hr); 36-47 hr (n = 161; range, 36.0-47.7 hr); greater than or equal to 48 hr (n = 28; range, 48.0-70.6 hr). These groups did not differ significantly in recipient age, sex, incidence of diabetes, number of pretransplant blood transfusions, level of presensitization, or HLA match. There were no differences in overall actuarial 1-year patient or graft survival rates, incidence of rejection, or renal function at 1 year. There was a higher incidence of impaired early graft function for kidneys preserved greater than or equal to 48 hr, but eventual graft outcome, including serum creatinine at 1 year, was unchanged. Delayed introduction of CsA resulted in improved 1-year graft survival (84.4% vs. 74.7%, P less than 0.05) compared to CsA treatment begun at the time of transplantation ("initial CsA"). This improvement was present regardless of total cold ischemia time. The incidence of permanent graft nonfunction, which has been previously reported to increase with CsA therapy, was influenced by the timing of CsA therapy (initial: 12%; delayed: 3%, P less than 0.05) but was not affected by duration of cold ischemia. Thus, safe preservation of cadaver kidneys for up to 70 h can be achieved by standard techniques even when CsA is incorporated into the immunosuppressive regimen. The most important determinants of graft survival in these patients are the timing of CsA therapy and the presence of early graft function, not the duration of renal preservation.

Blood Group Incompatibility↗
PubMed1990

Low dose ciclosporin from the early postoperative period yields potent immunosuppression after renal transplantation.

This study sought to determine if low doses of ciclosporin (CS) designed to give fasting serum levels of 50-100 ng/ml achieve effective immunosuppression when used from the early postoperative period after renal transplantation. Ninety-four primary renal transplant recipients were studied. Group 1 patients were treated with CS 100 ng/ml and prednisone (0.15 mg/kg/day). Group 2 patients received CS 50 ng/ml, prednisone (0.15 mg/kg/day) and azathioprine (1 mg/kg/day). These patients were compared to a control group of 26 patients (group 3) maintained on only prednisone and azathioprine. CS-treated patients suffered significantly fewer rejection episodes than control subjects (rejection episodes per patient in first year: group 1: 0.3 +/- SD 0.6; group 2: 0.7 +/- SD 0.7; group 3: 1.3 +/- SD 1.1, p less than 0.005). In addition, a greater number of CS-treated patients were completely free of rejection episodes during the first year posttransplant (group 1: 63%; group 2: 64%; group 3: 19%, p less than 0.005). Patient and graft survival were similar in all groups after 1 year (group 1: 92 and 92% respectively; group 2: 95 and 87% respectively; group 3: 96 and 85% respectively). These data suggest that the dose of CS required for effective immunosuppression in vivo is lower than has been previously thought.

Adult↗
PubMed1989

Percutaneous needle biopsy of the transplanted kidney: technique and complications.

Over 11 1/2 years, 420 percutaneous needle biopsies were obtained from the transplanted kidneys of 205 patients at one institution. The procedure was performed by one nephrologist and 55 nephrology trainees. No limit was placed on the number of biopsies performed on one kidney, and the highest number was seven. The complications were macroscopic hematuria in 28 biopsies, prolonged hematuria (greater than 24 hours) in eight, transient anuria in five, and prolonged anuria requiring surgical intervention in one. Perinephric hematoma occurred in three patients; retroperitoneal hematoma led to compression of the iliac vein in one. None of these complications led to loss of the transplant. It is suggested that the freedom from serious complication is related to the safety of the technique and the precautions applied to preparation of the patient. These are described in detail.

Adolescent↗
PubMed1989

The effect of exogenous lymphokines on immunoglobulin production and lymphocyte proliferation in renal transplant patients.

Peripheral blood mononuclear cells from stable long-term kidney transplant patients were activated in vitro by Staphylococcus Aureus Cowan I (SAC) (a B cell mitogen). The effect of exogenous interleukin 2 and/or B cell growth factor (BCGF) on these cells was measured by 3H-thymidine incorporation and immunoglobulin production. Both proliferation and Ig production were lower in SAC-activated cells from transplanted patients compared to controls (P less than 0.01). BCGF significantly enhanced blastogenesis (P less than 0.01) and Ig production (P less than 0.01) in SAC-treated cells from either patients or controls; however, the SAC- and BCGF-treated cells of transplant patients did not reach normal proliferation or immunoglobulin production values (P less than 0.001, P less than 0.01, respectively). The addition of IL-2 to SAC-activated cells also increased proliferation and Ig production both in controls (P less than 0.05) and patients (P less than 0.005). However, cells from transplant patients treated with SAC and IL-2 did not reach the normal levels of proliferation or immunoglobulin production (P less than 0.05 for both). IL-2 did not enhance the increase of immunoglobulin production brought about by BCGF. SAC-activated B cells from transplant patients do not proliferate normally and do not produce normal amounts of Ig. The addition of IL-2 and BCGF results in a partial but subnormal improvement in both proliferation and Ig production. We conclude that the B cell abnormality in transplant patients may be due to lack of T cell lymphokines and an intrinsic B cell defect. These results suggest that the administration of exogenous lymphokines to transplant patients with B cell dysfunction may be clinically useful.

Adult↗