Combined inhibition of apoptosis and complement improves neural graft survival of embryonic rat and porcine mesencephalon in the rat brain.

To define potential mechanisms of cell death during neural cell transplantation, we investigated the role of intracellular caspase activation in combination with the activation of serum complement. We demonstrated that ventral mesencephalic (VM) cells are susceptible to complement-mediated cell lysis that can be blocked with an anti-C5 complement inhibitor (18A10). We also determined that incubating freshly isolated allogenic VM cells with the caspase inhibitor 1-3-Boc-aspartyl(Ome)-fluoromethyl ketone (BAF), followed by immediate striatal implantation, led to a 2.5-fold increase in tyrosine hydroxylase (TH) cell survival 12 weeks postimplantation (P < 0.05). In contrast, overnight incubation with BAF followed by striatal implantation led to a 2-fold reduction in TH cell survival at 12 weeks (P < 0.05). Using the optimal BAF treatment and complement inhibition, we tested the hypothesis that these treatments would lead to increased cell survival in both allogeneic and xenogeneic transplantation models. We transplanted cell suspensions of (a) rat E14 VM or VM treated with (b) BAF alone, (c) anti-C5, or (d) a combination of BAF and anti-C5. There was a significant increase in the relative number of TH-positive cells in the BAF/anti-C5 group versus control at 12 weeks posttransplantation. Similar results were achieved in a pig to rat xenotransplant paradigm. A neuronal xenograft marker (70-kDa neurofilament) also demonstrated relative increases in graft volume in the BAF/anti-C5 treatment group. These studies indicate that more than one mechanism can mediate cell death during neural cell transplantation and that a combined treatment using caspase and complement inhibition can significantly improve cell survival.

Vascular surgery in a small community hospital: review of 286 consecutive major procedures.

From August 1981 to August 1985, 286 major vascular procedures were performed in a small community hospital by one trained vascular surgeon. The procedures were performed in 272 patients, 174 (64%) of whom were men and 98 (36%) of whom were women, with a median age of 66.3 years. The average length of hospital stay was 9.3 days. Two hundred fifty-three (88%) of the cases were elective, and the other 33 (12%) were emergencies. The overall operative mortality was 1.9% (5 out of 253 patients) in the elective group and 27.0% (9 out of 33 patients) in the emergency group. The stroke and mortality rate was 1.2% for elective cerebrovascular procedures. Sixty infrainguinal bypasses were performed, with three early failures and one late failure resulting in major amputation. All failures occurred in the limb salvage group (who had infrapopliteal bypasses and profundoplasty). These data suggest that vascular surgery can be performed safely and adequately in a small community hospital, with results comparable to those of a university hospital, and that vascular surgeons may maintain an adequate level of competence even if they perform fewer than 100 cases per year.

Arsenic exposure followed by the development of dermatofibrosarcoma protuberans.

A case of documented significant arsenic exposure followed by the development of dermatofibrosarcoma protuberans is reported. Exposure to arsenic is associated with an increased chance of the subsequent development of a variety of neoplasms. It is possible that dermatofibrosarcoma protuberans may be one such tumor.