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The growing disparity between available organs for liver transplantation and the number of waiting recipients has prompted significant debate over organ allocation and distribution. In light of this debate, recipient selection and prediction of factors relating to outcome have become increasingly important. Current immunosuppressive regimens provide excellent short-and long-term survival for patients and grafts. Increasingly, efforts are being made to decrease or withdraw immunosuppression late after transplantation to minimize long-term side effects. Viral disease, particularly cytomegalovirus infection, results in significant morbidity and mortality in patients. However, strategies for targeting high-risk patients with prophylactic antiviral therapy have been successful in reducing the incidence of cytomegalovirus disease. Recurrent viral hepatitis following liver transplantation may limit long-term graft success. Lamivudine appears to limit recurrent infection with hepatitis B virus in a significant number of patients who develop this condition following liver transplantation and may represent a cost savings over hepatitis B immunoglobulin. Although the overall survival of patients with chronic hepatitis C virus infection after orthotopic liver transplantation is excellent, significant morbidity and mortality occur in the subset of patients with severe recurrent disease. Interferon may delay the onset of disease in patients infected with hepatitis C virus following orthotopic liver transplantation, and investigation continues into antiviral therapy in this group of patients.

Survival after liver transplantation has steadily improved, in part because of newer immunosuppression, which may offer decreased long-term side effects. Reduction of steroids early in the course of transplant continues to be a goal, with satisfactory results in terms of both risk of rejection and reduction of side effects. Dominating the literature and the press in 1999 was the controversy surrounding the way in which livers are allocated. Regulation by the federal government was proposed to change the way the United Network of Organ Sharing distributes and allocates livers. Prompted by the shortage of organs, living-donor liver transplantation has blossomed. Continued experience in pediatric patients has shown excellent survival rate and quality of life. In adults, further experience is being gained with respect to the use of right lobes for transplantation. Early data suggest that this is a potential alternative to cadaveric transplantation in adults, with acceptable risk to the donor. Despite advances made in improving the technical aspects of transplantation, recurrent disease remains a significant issue. Lamivudine appears to be a potent inhibitor of hepatitis B virus DNA replication after liver transplantation, although resistance remains a significant problem. Further review of transplantation for hepatitis C virus is encouraging, with excellent five-year survival rate. However, studies evaluating the evolution of fibrosis in these patients throw caution on those results, showing increased progression to cirrhosis over time. Further follow-up of these patients is needed to more accurately assess long-term impact of hepatitis C on morbidity and mortality rates after liver transplantation.

Several studies have indicated to us that certain amino acids may exhibit antiinflammatory activity. In the present study we attempted to evaluate the inhibitory effect of various amino acids on gelatin-induced abdominal inflammation in mice using peritoneal fluid cytology as the diagnostic tool. The L-amino acids tested were tryptophan, phenylalanine, alanine, cystine, hydroxyproline, tyrosine, citrulline, leucine, and valine. Hydrocortisone was used as an antiphlogistic steroid control. Tryptophan, phenylalanine, alanine, cystine, hydroxyproline, and tyrosine all significantly decreased the inflammation. Citrulline and valine, however, both exhibited strong antiiflammatory responses. Based on these results, three related dipeptides were also screened: L-valy-L-alanine, L-valyl-L-tryptophan, and L-tyrosl-L-valine. Valyl alanine was found to produce a strong antiinflammatory effect. In a final test, the combination of the steroid, hydrocortisone, and the amino acid, cystine, was screened for a synergistic effect. The combined treatment inhibited the gelatin-induced inflammation more than either the amino acid or the steroid administered alone.

Investigators have previously reported good retention, antifertility efficacy, and good retrievability with no adverse tissue reactions in rabbit oviducts occluded with silicone rubber for 55 days. The present study attempts to determine the long-term effects of this silicone polymer system installed into the oviducts of 12 New Zealand White rabbits for 7 months. 9 rabbits had both oviducts occluded while 3 had only one oviduct treated. All animals were visualized by X-rays and were mated an average of six times over the experimental period. Oviduct tissue was examined with light and scanning electron microscopy. There was no evidence of inflammation, distortion, or tissue irritation. Good retention and antifertility efficacy were exhibited.

Human retroviruses have recently been linked with T cell lymphoproliferative disorders and with the acquired immune deficiency syndrome. We investigated the mechanisms for acquired pure red cell aplasia and cutaneous anergy in a patient with the chronic T gamma-lymphoproliferative disease (T gamma-LPD) syndrome. Patient marrow erythroid progenitors (BFU-E) were 17 +/- 9% of control and were selectively increased to 88-102% of control after marrow T cell depletion. Patient Leu 2+ suppressor T cells spontaneously produced high titers of human gamma-interferon and resulted in a concentration-dependent selective inhibition (74-91%) of BFU-E when co-cultured with autologous or allogeneic marrow. Conditioned media (CM) derived from patient Leu 2+ T cells similarly inhibited growth of autologous or allogeneic marrow BFU-E. The inhibitory factor derived from patient CM was acid-labile (pH 2) and sensitive to trypsin; prior treatment of patient T cells with anti-HLA-DR monoclonal antibody plus complement abrogated the suppressive effect of T cell-derived CM. Patient peripheral blood mononuclear cells (PBMC) were unable to support growth of cultured interleukin 2 (IL 2)-dependent T cells, but responded to exogenous IL 2 in vitro with a 16-21-fold augmentation, relative to control, in mitogen-induced proliferation. Antibodies to HTLV-I core proteins p19 and p24 but not to HTLV-III proteins were detected in patient serum by Western blotting; patient cultured PBMC stained (7-11%) with antibodies to p19 and p24. Patient cultured PBMC demonstrated integrated HTLV-I genomic sequences by the Southern technique and expressed both specific HTLV-I genomic sequences by RNA dot blot plus reverse transcriptase activity. Utilizing a cloned DNA probe for the beta chain of the T cell receptor gene, patient PMBC demonstrated gene rearrangements providing presumptive evidence for clonality. The presence in serum of HTLV-I p19 and p24 antibodies, the expression of p19 and p24 core antigens on patient mononuclear cells, the evidence of HTLV-I proviral integration sequences and the expression of HTLV-I genomic sequences in patient cells, indicates infection with HTLV-I and raises the possibility of an etiologic link between human retrovirus infection and some instances of large granular lymphocytic leukemia (T gamma-LPD).