Manipulation of alcohol drinking by liver transplantation.

The procedure of liver transplantation in alcoholic liver disease raises the question whether it would be possible to regulate the recipient's future drinking by the choice of donor liver. To address this question, we conducted transplantations with rat lines selected for high (AA) and low (ANA) alcohol preference. AA recipients having alcohol experience before the operation remained heavy drinkers regardless of whether the graft came from an AA or ANA donor. However, in these AA recipients who started drinking only after the operation, differences emerged, with AA grafts creating heavy drinking and ANA donor livers resulting in very low drinking. An overall increase in the acetaldehyde levels was introduced by the ANA livers, thus reflecting the original line differences. Similarly, in subsequent experiments, it was observed that when the aldehyde dehydrogenase inhibitor calcium carbimide was introduced in different amounts to the diet, alcohol drinking was reduced more in animals not used to drinking. The magnitude of this effect, especially in situations with established heavy drinking, is of relevance in future contemplations about liver transplantations between humans with different aldehyde dehydrogenase genotypes.

The essential roles of parenchymal tissues and passenger leukocytes in the tolerance induced by liver grafting in rats.

Liver allografts in pigs and rodents are uniquely capable of inducing tolerance to themselves and to other grafts of donor tissues, instead of succumbing to the acute rejection that follows transplantation of other allogeneic tissues. We demonstrate here, using normal and chimaeric rat liver grafts, that both the allogeneic liver parenchyma and the intrahepatic leukocytes of donor type contribute to the establishment of long-term tolerance, each component being essential and complementary. The essential role of hepatic parenchyma may be related to its continuous release of soluble transplantation antigens that facilitate tolerogenesis. We suggest that clinical attempts at tolerance induction by the infusion of donor bone marrow-derived leukocytes may likewise be facilitated by the coadministration of soluble transplantation antigens of donor type.

Tolerance of porcine renal allografts induced by donor spleen cells and seven days' treatment with cyclosporine.

Liver allografts in pigs and in rats elicit a substantial cellular immune response that can resolve spontaneously with the induction of donor-specific systemic tolerance. Self-limiting interactions between host and donor (graft)-derived leukocytes may be the basis for tolerogenesis. We have attempted to reproduce this effect of liver grafting in pigs by peroperative infusion of donor leukocytes into kidney graft recipients given an interrupted short course of CsA designed to promote donor leukocyte survival and interaction with host cells. This protocol can secure long-term kidney graft survival resistant to challenge by donor skin grafting. Donor skin is, however, rejected, but more slowly than third-party skin, indicating a degree of systemic specific unresponsiveness in these long-term kidney graft recipients.

Incidence of malignancy in peripheral lymph node biopsy.

A review was made of 62 lymph node biopsy procedures during a 12-month period, from January 1, 1982, to December 31, 1982. The overall diagnostic yield was 56.5 per cent. Malignant lymph nodes were found in 53.2 per cent of cases. Seventy-two and two-tenths per cent (72.2%) of all malignant lymph nodes were metastatic carcinoma, including 6.1 per cent of metastatic lymph nodes with unknown primary. Twenty-seven and three-tenths per cent (27.3%) of all malignant lymph nodes belonged to the lymphoma-leukemia group. Among all the superficial lymph node regions, enlarged supraclavicular lymph nodes are associated with the highest incidence (75%) of malignancy. Clinical features associated with high incidence malignancy were: age greater than 55 years (75.8%), duration of less than 1 month (66.6%)--particularly, with a history of previous malignancy (91.7%). The anatomic knowledge of regional lymphatic drainage is essential in localizing the primary lesion of a metastatic lymph node.