Costimulation blockade of CD40 and CD28 pathways in limb transplantation.

Costimulation blockade remains a promising experimental regimen for the induction of transplantation tolerance. The simultaneous blockade of both the CD40 and CD28 pathways has been synergistic in prolonging organ allograft survival but has not previously been investigated in a model of limb allotransplantation. This study determined the efficacy of this combination in the murine limb allograft model. C57B1/6 (H-2K(b)) female mice were recipients of heterotopic vascularized limb allografts from Balb/c (H-2K(d)) male donors. Experimental groups received treatment with a short course of MR1 (hamster anti-mouse anti-CD40 ligand antibody) alone or in combination with CTLA4-Ig, a fusion protein that blocks the B7/CD28 pathway. Untreated recipients rejected limb allografts at a mean of 9.6 +/- 1.1 (standard error of the mean) days postoperatively. Recipients of a prolonged course of MR1 rejected limb allografts at 75 +/- 25 days. When both MR1 and CTLA4-Ig were used, limb allograft survival of >120 days was observed despite a much shorter course of therapy. Rejection in both treatment groups was consistent with a chronic antibody-mediated process. Donor antigen rechallenge in these recipients by in vitro assay and skin allograft demonstrated a hyperacute response consistent with presensitization. Long-term limb allograft survival is produced by the synergistic effect of blocking both the CD40 and CD28 costimulatory pathways. However, permanent acceptance was not achieved, and allografts eventually succumbed to what appeared to be antibody-mediated rejection. The additional use of newer agents that block more recently described costimulatory pathways may be essential for the induction of tolerance by costimulation blockade.

Patient outcome following a thoracodorsal to musculocutaneous nerve transfer for reconstruction of elbow flexion.

This study reports patient outcome following a thoracodorsal to musculocutaneous nerve transfer. We retrospectively reviewed the charts of six patients who had undergone transfer of the thoracodorsal nerve to the musculocutaneous nerve for reconstruction of elbow flexion. The mean age was 47 years (standard deviation: 24 years; range: 17-72 years). The mean time from injury to surgery was 3 months (standard deviation: 2 months; range: 1-5 months). In all cases, the biceps muscle was successfully reinnervated; in one case the Medical Research Council (MRC) muscle grade was grade 5, in four cases it was grade 4, and in one case it was grade 2. No patients complained of functional weakness with shoulder adduction and/or internal rotation. In the majority of cases, transfer of the thoracodorsal nerve to the musculocutaneous nerve provides excellent recovery of elbow flexion.