Long-term effect of cyclosporine on renal function in children after liver transplantation.
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Although the precise link between the increased incidence of allograft rejection in female heart transplant recipients remains uncertain, various gender-specific characteristics may predispose women to earlier rejection episodes. Critical care practitioners must be cognizant of the underlying immunologic factors that indicate higher risk in these recipients. Until the ideal treatment for cardiac rejection is discovered, identifying pertinent immunologic factors, attending to subtle symptoms, obtaining serial endomyocardial biopsies and initiating prompt, additional aggressive immunosuppressive protocols remain paramount in rendering quality patient care. Research must continue to elicit more specific tissue-typing antigens and more selective immunosuppressive agents that will ultimately result in prolonged survival of all heart transplant recipients.
Since the initial report of the murine monoclonal antibody OKT3 for acute kidney rejection, a significant body of information has been collected regarding the efficacy of OKT3 in reversing acute allograft rejections in kidney, liver, and heart transplant recipients. The use of OKT3 therapy for the reversal of cardiac allograft rejection in patients in whom other therapeutic alternatives have failed or are contraindicated is described. Treatment with OKT3 reversed acute heart rejection in 102 of 113 patients (90%). Complete reversal was achieved in 63 patients, and partial reversal in 39 patients. At 2 years, graft and patient survival rate was 77% and 65%, respectively. No significant differences were noted in reversal rate and in 12-month graft and patient survival rates between those patients experiencing one rejection episode and those patients experiencing two or more rejection episodes. Comparable reversal rates and graft and patient survival rates were achieved in patients whether OKT3 was administered as the primary rejection therapy or as rescue therapy. Adverse events were common in the first 2 days of therapy, but they were well tolerated in most patients. Infectious complications occurred in 49% of patients in whom most infections were not serious. On the basis of this experience, OKT3 appears highly effective in reversing acute cardiac allograft rejection.
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We have recently shown that peripheral blood T cells of multiple myeloma (MM) patients are very susceptible to stimulation of the T-cell receptor/CD3 complex with anti-CD3 monoclonal antibodies (MoAbs). CD3 stimulation is currently under clinical investigation as a nonspecific approach to boost antitumor effector mechanisms. The aim of this study was to determine whether the hyperreactivity of MM T cells to CD3 stimulation could be exploited to generate antitumor activity. Bone marrow mononuclear cells (BMMCs) from 65 MM patients were stimulated with the anti-CD3 MoAb OKT3 and the effect of this stimulation on autologous T cells and plasma cells was evaluated. The number of CD3+ CD25+ cells on day 6 was significantly higher in MM than the controls (30 normal individuals) (P = .001). Kinetic studies showed that 3H-thymidine incorporation peaked on day 3 and that the T-cell expansion peaked on days 5 and 6. In MM, T-cell activation markedly affected the survival of autologous plasma cells; their number in OKT3-treated cultures was significantly lower than in unstimulated cultures (P < .0001). T-cell activation and plasma cell decrease were not observed when T cells were removed from BMMC preparations. MM produced significantly higher levels of interferon-gamma (P = .005) and tumor necrosis factor-beta (P = .001), but lower levels of tumor necrosis factor-alpha (P < .001) than normal individuals. Interferon-gamma only was partially involved in CD3-induced plasma cell killing. Transwell cultures showed that the main mechanism by which CD3+ CD25+ cells affected plasma cells was direct cell-to-cell contact rather than cytokines. In conclusion, T cells in MM BMMCs possess distinct features in terms of susceptibility to CD3 stimulation and cytokine production compared with normal bone marrow T cells that can be exploited to generate antiplasma cell activity.
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