Prolongation of cardiac graft survival with anti-CD4Ig plus hCTLA4Ig in primates.

BACKGROUND: The aim of this study was to determine whether the use of combined immunotherapy with a brief course of humanized anti-CD4Ig and hCTLA4Ig would prolong heterotopic cardiac allograft survival in primates (rhesus monkeys). This model was based on work in "high responder" rats where a brief course of depletive anti-CD4mAb plus hCTLA4Ig was successful in inducing transplantation tolerance. METHODS: Heterotopic cardiac transplants were performed in rhesus recipients. Donor/recipient pairs between groups were confirmed to be reactive prior to transplantation by MLR matching. Humanized anti-CD4Ig, a recently developed anti-CD4mAb, was given at a dose of 20 mg/kg i.v. on days -3, -2, -1, and 0. hCTLA4Ig was administered at 6 mg/kg/dose i.v. on days 0 and 2 for the first recipient and days 0, 2, 4, and 6 for the second recipient. No further immunosuppression was administered. The treated (n = 2) or untreated (n = 5) recipients were followed for graft function by daily palpitation. RESULTS: Treatment with anti-CD4Ig plus hCTLA4Ig resulted in a significant prolongation of heart graft survival (42 days for the first recipient and 52 days for the second recipient) compared to untreated recipients (7 days x 4, 11 days x 1). FACS analysis demonstrated CD4 depletion of anti-CD4 treated animals to <2% on posttransplant day 1. The CD4+ T cells gradually repopulated to 50-70% pretransplant levels just prior to rejection. No adverse responses (fever, tachypnea, tachycardia, infections) were observed. CONCLUSIONS: These are the first results demonstrating that a brief course of combined specific induction immunotherapy with humanized anti-CD4Ig plus hCTLA4Ig, in the absence of adjuvant posttransplant immunosuppression, was well tolerated and resulted in marked prolongation of cardiac allograft survival in primates.

Cervicothoracic vascular injuries.

Arterial and venous trauma of the cervicothoracic region continues to present challenging problems for the surgeon, despite advances in vascular diagnostics and surgical technique. Whether due to penetrating or blunt mechanisms, overall incidence of these injuries is low, whereas morbidity and mortality remain high. Despite collective experience from busy trauma centers, there still remain controversies regarding diagnostic evaluation, operative approach, and surgical treatment of these potentially devastating injuries. Therefore, this article compares and contrasts recent literature and controversies surrounding the treatment of cervicothoracic trauma. Pros and cons of duplex ultrasonography and angiography in the diagnosis of carotid and vertebral artery injury are highlighted, and selective versus mandatory neck exploration for zone II penetrating injuries are discussed. Increasing awareness of blunt carotid artery injury is emphasized, including management dilemmas that frequently accompany this type of injury. In addition, we review interventional radiological techniques for the management of vertebral artery injury and surgical approaches for aortic arch branch vessel or major cervicothoracic vein injury.