Origin of lymph node-derived lymphocytes in human hepatic allografts

Hepatic allograft-derived lymph nodes were examined in the post-transplant period on order to determine the origin of lymphocytes and structural elements of the lymph node. Histologic assessment and immunohistochemical studies verified that T-cell infiltration of donor lymph nodes by recipient-derived lymphocytes occurred early in the post-transplant period. These T cells bore T-cell activation markers, e.g. TAC receptor and HLA-DR antigens. In addition, functional analysis demonstrated alloreactive T cells in secondary proliferation assays. The pattern of alloreactivity in these assays was dependent upon the phenotypic make-up (and therefore origin) of the lymphocytes within the lymph node. A gradual shift in predominance of donor-derived lymphocytes to recipient-derived lymphocytes occurred, but even late in the post-transplant course the stromal elements and a residium of lymphocytes within the lymph nodes continued to bear donor HLA antigens. The possible role of these 'passenger' lymphocytes in allograft immunity is discussed

A dog model for acetaminophen-induced fulminant hepatic failure.

The development of a large animal model of fulminant hepatic failure produced with acetaminophen that should be useful in the development and evaluation of potential medical therapies for the important clinical problem of fulminant hepatic failure is described. Acetaminophen in dimethyl sulfoxide (600 mg/ml) given as three subcutaneous injections, with the first dose (750 mg/kg body wt) being given at noon, the second dose (200 mg/kg body wt) being given 9 h later, and the third dose (200 mg/kg body wt) being given 24 h after the initial dose consistently produces fulminant hepatic failure in dogs. The dimethyl sulfoxide vehicle, injected intramuscularly, does not influence either animal survival or hepatic function in control-treated dogs. No deaths occur within the first 36 h. By 72 h after initial drug administration, the mortality is 90%. Histopathological and biochemical investigations demonstrate a high degree of hepatocellular necrosis in nonsurviving animals without appreciable damage to the kidneys, lungs, or heart. The drug schedule and preparation outlined avoids the administration of large volumes of vehicle and results in prolonged high levels of acetaminophen in the blood sufficient to induce severe hepatic injury. Ranitidine (120 mg/kg body wt i.m.) given 30 min before each acetaminophen dose significantly reduces the mortality and hepatic necrosis produced using this model. This model satisfies all criteria established by Miller et al. for the production of a suitable large animal model of fulminant acute hepatic failure

One hundred ten consecutive primary orthotopic liver transplants under FK 506 in adults.

An account is given of the 6- to 12-month survival, and causes of failure in 110 consecutive patients who underwent primary liver transplantation under treatment from the outset with FK 506 and steroids. The patient survival is 92.7%, and the first graft survival is 87.3%. At a very high frequency, the patients achieved good graft function, and they had a relatively low morbidity that was partially ascribable to minimal use and early discontinuance (in 60% of cases) of steroids. Renal dysfunction and other adverse findings were largely confined to patients with poor initial graft function and consequent apparent alteration of the kinetics of FK 506 elimination, causing functional overdosage. Results compare very favorably with our past record using conventional immunosuppression, and support the belief that FK 506 is a superior immunosuppressive agent which is suitable for chronic administration