Orthotopic liver transplantation in U.S. veterans under primary tacrolimus immunosupression.

The evolution and refinement of surgical techniques, per ioperative patient care, and immunosuppression hav~ estab~ished orthoto~ic li~er transplantation (OLTX) as a ~ighly successful therapeutic modality for patients wrth end-stage hver disease. In February 1989,Tacrohmus (Prograf®, formerly FK 506)was first used successfully at the University of Pittsburgh Medical Center to treat patients with rejection refractory to cyclosporine-based immunosuppression." Clinical trials utilizing Tacrolimus in solid organ transplantation followed, and in April of 1994 it was approved for use by the Food and Drug Administration

Human liver xenotransplantation

During the past 30 years orthotopic liver transplantation has become a highly successful form of surgical treatments. The significant advances achieved in this field have led to an increased demand for organs and created a wide gap between organ availability and organ supply. A wider availability of organs for transplantation would allow an expansions rather than a contraction of the indications for transplantation, and, at the same time a relaxation of the patient selection criteria. All these facts clearly justify the renewed interest observed in the last decade in xenotransplantation. The original concept of xenografting, meaning the transplantation of cells, tissues, or organs between different species, is so ancient that it is easily recognizable in Greek and Roman mythology. The centaur Chiron, the teacher of Esculapius, and the Chimera are legendary examples of discordant xenogeneic creatures. However, it is only during this century that scientists have been able to bring this idea into the clinical arena. The early efforts were prompted by the shortage of humans organs at a time when there were few alternatives for treating end-stage organ failure

Orthopedic liver transplantation in high-risk patients

Background. One of the most controversial area in patients selection and donor allocation in the high-risk patient. Risk factors for mortality and major infectious morbidity were prospectively analyzed in consecutive United States veterans undergoing the liver transplantation under primary tacrolimus-based immunosuppression. Methods. Twenty-eight pro-liver transplant, operative and posttransplant risk factors were examined univariately and multivariately in 140 consecutive liver transplant in 1130 veterans (98% male); mean age 47.3 years) Results. Eighty-two percent of the patients had postnecrotic cirrhosis due to viral hepatitis or ethanol (20% ethanol alone), and only 12% had cholestatic liver disease. Ninety-eight percent of the patients were hospitalized at the time of transplantation (66% Unites Network for Network for Organ Sharing [UNOS] 2, 32% UNOS 1). Major bacterial infection, posttransplant dialysis, additional immunosuppression, readmission to intensive care unit (p=0.0001 for all), major fungal infection, posttransplant abdominal surgery, posttransplant intensive care unit stay length of stay (p<0.005 for all), donor age, pretransplant dialysis, and creatinine (P<0.05 for all) were significantly associated with morality by univariate analysis. Underlying liver disease cytomegalovirus infection and disease, portal vein thrombosis, UNOS status, Childs-Pugh score, patient age, pretransplant bilirubin, bilirubin time, and operative blood loss were not significant predictors of mortality. Patients with hepatitis C (HCV) and recurrent HCV a trend toward higher mortality (P=0.18). By multivariate analysis, donor age, any major infection, additional immunosuppresion, post-transplant dialysis, and subsequent transplantation were significant independent predictors of mortality (P<0.05). Major infectious morbidity was associated with HCV recurrence (P=0.003), posttransplant dialysis (P=0.0001), pretransplant creatine, donor age, median blood loss, intensive care unit length of stay, additional immunosuppression, and biopsy-proven rejection (P<0.05 for all). By multivariate analysis, intensive care unit length of stay and additional immunosuppression were significant independent predictors of infectious morbidity (P<0.03). HCV recurence was of borderline significance (P=0.07). Conclusions. Biologic and physiologic parameters appear to be more powerful predictors of mortality and morbidity after liver transplantation. Both donor and recipient variables need to be considered for early and late outcome analysis and risk assessment modeling

Chloroplast microsatellites: measures of genetic diversity and the effect of homoplasy

Chloroplast microsatellites have been widely used in population genetic studies of conifers in recent years. However, their haplotype configurations suggest that they could have high levels of homoplasy, thus limiting the power of these molecular markers. A coalescent-based computer simulation was used to explore the influence of homoplasy on measures of genetic diversity based on chloroplast microsatellites. The conditions of the simulation were defined to fit isolated populations originating from the colonization of one single haplotype into an area left available after a glacial retreat. Simulated data were compared with empirical data available from the literature for a species of Pinus that has expanded north after the Last Glacial Maximum. In the evaluation of genetic diversity, homoplasy was found to have little influence on Nei's unbiased haplotype diversity (H(E)) while Goldstein's genetic distance estimates (D2sh) were much more affected. The effect of the number of chloroplast microsatellite loci for evaluation of genetic diversity is also discussed