Faculty Bibliography

Although cyclosporine (CsA) is widely used as the primary agent for inhibiting the rejection of organ allografts in man, the ideal immunosuppressive regimen for utilizing this drug is still uncertain. To investigate this question, a concanavalin A (con A)-dependent cell-mediated cytotoxicity (CDCMC) assay was used to examine the development of intragraft and peripheral blood cytolytic T lymphocyte activity during CsA dose tapering. These studies were conducted in a canine single-lung transplantation model that facilitates serial examination of intragraft effector cells by bronchoalveolar lavage (BAL). A remarkable correlation of increased intragraft CDCMC and clinical evidence of lung allograft rejection was observed during CsA dose tapering in some recipients. In other recipients CDCMC remained low and evidence of rejection was not observed during drug tapering. In contrast, peripheral blood CDCMC did not correlate well with evidence of rejection. Rejection phenomena observed after termination of CsA therapy were reversed by resumption of CsA treatment but were not reversed by administration of methylprednisolone. Furthermore, the increased level of CDCMC was diminished by reinstitution of CsA therapy at the initial dosage. Following termination of CsA therapy, a prolonged period of unresponsiveness was observed in nearly two-thirds of the recipients, and 60% of these latter dogs had unlimited survival of their lung allografts (median greater than 496 days). Intragraft CDCMC remained low during the periods of unresponsiveness and increased upon onset of rejection. We conclude that measurement of intragraft CDCMC is a useful in vitro method of monitoring lung allograft rejection, and therefore provides a technique for adjusting CsA dosage schedules to achieve maximally effective immunosuppression. The use of this assay for monitoring rejection of other organ grafts requires further investigation

Of the 355 consecutive infrapopliteal bypasses for limb salvage performed over a 5 year period at our institution, 116 (Group I) were to noncalcified vessels, 203 (Group II) were to vessels of varying degrees of calcification (mild to moderate), and 36 (Group III) were to heavily and circumferentially calcified arteries. A new intraoperative fracture technique was used to overcome the rigidity of the arterial wall in the latter group. Three year cumulative patency rates for Groups I, II, and III were 45 percent, 58 percent, and 47 percent, respectively. Comparable limb salvage rates for Groups I, II, and III were 66 percent, 73 percent, and 75 percent. No significant difference in patency or limb salvage results could be elicited between the three groups by the log-rank test. These findings suggest that arterial calcification is an invalid predictor of failure in small vessel bypasses. Even circumferentially calcified arteries, which are generally thought to be surgically unapproachable, should not be a deterrent to limb salvage attempts

Cadaver kidneys remain a scarce resource, yet single pediatric donor kidneys are underutilized at some centers. Between 1967 and 1984, 133 single pediatric and 318 adult donor cadaver transplants were performed. Patient and graft survival, renal function, and complications in adult recipients grouped by donor age were compared. Recipient age for all groups was similar (34-36 years). Life table analysis revealed no difference in graft survival in recipients of kidneys from donors aged 2, 3, 4, 5-10, and 11-15 when compared with adult donors. Graft survival in these groups improved over time with current 1-year survival over 75%. Recipients from donors less than 24 months of age demonstrated significantly poorer results, with no kidney surviving greater than 2 months. Serum creatinine of grafts functioning greater than 6 months was similar in all groups. It is concluded that single pediatric kidneys from donors greater than 2 years of age can be successfully transplanted to adults with good long-term results

Over the past 20 years, many advances in surgical methods, transplantation immunology, donor organ procurement and preservation techniques, and postsurgical care regimens have influenced greatly the field of lung transplantation. The single remaining obstacle to widespread clinical success is donor lung availability. Improved methods of ex vivo lung preservation, organ donor maintenance, and donor lung retrieval after the completion of cardiac donation should help to ameliorate this problem

Fourteen patients with severely ischemic extremities but relatively minor degrees of pedal gangrene or ulceration were managed without surgery. Contraindications to direct arterial reconstruction included significant intercurrent illness or generally poor surgical risk, the need for reoperative or difficult distal reconstruction, or the favorable characteristics of the actual lesion. Management consisted of bed rest, simple saline soaks, occasional gentle debridement, and antibiotics when indicated. Seven patients had complete resolution of their lesions for 3 to 48 months, and seven had improvement or stabilization for 3 to 18 months. Only three of the 14 patients have eventually required surgery with limb salvage in one. Revascularization remains the method of choice for managing most severely ischemic extremities. However, the conservative approach described represents an alternative to early amputation, attempts at revascularization, or lumbar sympathectomy in some patients with advanced ischemia. Studies of sympathectomy and pharmacologic agents as effective treatment for ischemic ulcers or gangrene should include control groups treated with the conservative measures outlined herein