American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
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Corneal transplants normally enjoy a high percentage of survival, mainly because the eye is an immune-privileged site. When allograft failure occurs, it is most commonly due to rejection, an immune-mediated reaction that targets the corneal endothelium. While the exact mechanism by which the endothelium is targeted is still unknown, we postulate that corneal endothelial cell loss during allograft failure is mediated by apoptosis. ⋯ In a murine model of transplantation, TUNEL staining and confocal microscopy showed apoptosis of the graft endothelium occurring in rejecting corneas as early as 2 weeks posttransplantation. We found that bcl-xL protected cultured corneal endothelial cells from apoptosis and that lentiviral delivery of bcl-xL to the corneal endothelium of donor corneas significantly improved the survival of allografts. These studies suggest a novel approach to improve corneal allograft survival by preventing apoptosis of the endothelium.
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Randomized Controlled Trial
Tacrolimus monotherapy without steroids after liver transplantation--a prospective randomized double-blinded placebo-controlled trial.
Early steroid withdrawal after liver transplantation (LT) is desirable in order to reduce steroid side effects. Between February 2000 and August 2004, 110 patients after LT were included in this prospective, randomized, double-blind, placebo-controlled trial. Randomization was performed before LT. ⋯ Two patients in the placebo group but none in the steroid group experienced chronic rejection (p = 0.257). The rates of side effects were (placebo versus steroid, respectively): CMV infection 25% versus 33% (p = 0.336), post-transplant diabetes 30% versus 53% (p = 0.024), hypertension 39% versus 52% (p = 0.248), hypercholesterolemia 10% versus 41% (p = 0.002) and hypertriglyceridemia 32% versus 54% (p = 0.046). In conclusion, early steroid withdrawal after LT is feasible under tacrolimus monotherapy without increased rejection rates and with a lower rate of side effects.
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We compared the effects of hormone resuscitation (HR) with a norepinephrine-based protocol on cardiac function, hemodynamics and need for vasopressor support after brain death in a porcine model. Following brain death induction, animals were treated with norepinephrine and fluids for 3 h. In the following 3 h, they continued on norepinephrine and fluids (control) or received additional HR (triiodothyronine, methylprednisolone, vasopressin, insulin). ⋯ At 6.25 h, HR animals had higher stroke work (3540 +/- 1083 vs. 1536 +/- 702 mL.mmHg; p < 0.005), stroke volume (37.2 +/- 8.2 vs. 21.5 +/- 9.8 mL; p < 0.01) and cardiac output (5.8 +/- 1.4 vs. 3.2 +/- 1.2 L/min; p < 0.005). HR in a porcine model of brain death reduces norepinephrine requirements, and improves hemodynamics and cardiac function. These results support the use of HR in the management of the brain-dead donor.
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Clinical Trial
Clobetasol ameliorates aphthous ulceration in renal transplant patients on sirolimus.
Aphthous ulceration is a common side effect of sirolimus. These lesions of the oral mucous membranes are often painful and debilitating, leading to either dose reduction or discontinuation of sirolimus in a significant number of patients. We report that the direct application of clobetasol, a high potency topical steroid, led to prompt resolution of the aphthous ulcers that developed in our renal transplant patients on sirolimus-based immunosuppression.