PATHOLOGICAL CHANGES IN SIX TREATED BABOON‐TO‐MAN RENAL HETEROTRANSPLANTS

Six baboon‐to‐man renal heterotransplants, each consisting of a pair of kidneys, were examined. Two had been removed from their recipients at forty‐nine and sixty days after transplantation because of the ever‐increasing doses of immunosuppressive drugs needed to control rejection; the other four pairs of kidneys were examined after death of the recipients at nineteen, twenty‐three, thirty‐five, and forty‐nine days. All the kidneys were enlarged. On the subcapsular surfaces of one pair there were petechias; four were mottled with irregular haemorrhages and infarcts; one pair had undergone almost complete hemorrhagic infarction. The transplants were heavily infiltrated with plasma cells, lymphocytes, large pyroninophilic lymphoid cells and eosinophils. Mitoses, “LE” cells and erythrophagocytosis were seen. Associated with this infiltration there was rupture of peritubular capillaries, interstitial cedema and widespread tubular damage. Fibrinoid necrosis of the walls of arterioles and interlobular arteries, with narrowing and obstruction of some vessels by fibrin and platelet deposits on the intima were common in all except one pair of kidneys. Associated with these vascular lesions there were focal infarcts and extensive interstitial haemorrhages. All the histological changes were more severe than those seen either in treated human renal homotransplants or in a comparable series of chimpanzee‐to‐man renal heterotransplants where cellular infiltration was slight and vascular lesions only present at the height of rejection. This work was aided by grants A‐6283, A‐6344, HE‐07735, AM‐07772, A1‐01452, and OG‐27 from the U.S. Public Health Service, and by a grant from the Medical Research Council. We would like to thank Drs D. Baitlon, J. Gordon, R. B. Hill, D. Lang, and D. E. Smith who performed the autopsies on these cases. We are particularly grateful to Dr D. T. Rowlands, who supervised most of the autopsies, for his helpful co‐operation throughout this study. Expert assistance in preparing the sections and photomicrographs was given by Miss Jane Rendall. © 1965 BJU International Compan

Cyclosporine Absorption Following Orthotopic Liver Transplantation

Blood concentrations of cyclosporine were determined in adult and pediatric patients following orthotopic liver transplantation to quantitate cyclosporine blood clearance and oral absorption. Seventeen bioavailability studies were performed following transplantation surgery in nine children and seven adults. The intravenous cyclosporine study was performed following an average dose of 2.1 mg/kg. The patients were again studied when they received the same intravenous dose plus an oral dose of cyclosporine of 8.6 mg/kg or an oral dose alone. Blood samples were collected and analyzed for cyclosporine using high-performance liquid chromatography. Cyclosporine blood clearance ranged from 29 to 203 mL/min (1.9–21.5 mL/min/kg) in children and from 253 to 680 mL/min (3.2–7.6 mL/min/kg) in adults. The mean cyclosporine clearance value was 9.3 mL/min/kg in the pediatric patients and 5.5 mL/min/kg in the adults. Cyclosporine bioavailability was less than 5% in six studies on five pediatric patients in the immediate postoperative period. The bioavailability varied from 8% to 60% in adult liver transplant patients (mean, 27%). We conclude that: (1) cyclosporine clearance is highly variable between patients, (2) pediatric patients clear the drug more rapidly than adults and therefore need a higher cyclosporine dose on a body weight basis, (3) cyclosporine is poorly and variably absorbed in liver transplant patients, and (4) cyclosporine blood concentration monitoring is essential following orthotopic liver transplantation

Fifteen years of clinical liver transplantation

Liver transplantation in humans was first attempted more than 15 yr ago. The 1-yr survival has slowly improved until it has now reached about 50%. In our experience, 46 patients have lived for at least 1 yr, with the longest survival being 9 yr. The high acute mortality in early trials was due in many cases to technical and management errors and to the use of damaged organs. With elimination of such factors, survival increased. Further improvements will depend upon better immunosuppression. Orthotopic liver transplantation (liver replacement) is the preferred operation in most cases, but placement of an extra liver (auxiliary transplantation) may have a role under special circumstances. © 1979

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Adult liver transplantation: An analysis of the early causes of death in 40 consecutive cases

One hundred twenty‐nine adult patients who received an orthotopic liver transplantation and survived at least 24 hr after surgery were evaluated. During the period of follow‐up, 48 of the 129 patients (37%) died. Only 40 of these 48 patients died at our institution and were included in this study. Seventeen of the 40 deaths (42.5%) occurred during the first month after orthotopic liver transplantation and 30 of the 40 deaths (75%) occurred during the first 60 days post‐orthotopic liver transplantation. Death was related to infection in 21 cases (52.5%), to multiorgan failure in 8 (20%) and to uncontrollable rejection in 3 (7.6%). The remaining eight deaths (20%) were attributed to a variety of other causes. Eleven of the 21 deaths related to infection (52%) occurred during the first month after orthotopic liver transplantation. Bacterial sepsis was the leading cause of death and accounted for 17 of the 21 deaths (81%) in which infection was present at the time of death. The most frequently isolated bacteria were Pseudomonas and other enteric Gram‐negative bacilli. Three patients had complete occlusion of the hepatic artery of the grafted liver. Six patients developed massive infarction of the liver despite patent vascular anastomoses. Histological signs of rejection were seen in 9 of the 31 patients autopsied (29%), but in only 3 of these (9.6%) was rejection the principal cause of death. The biliary anastomoses were patent in all 31 cases examined at autopsy. Copyright © 1986 American Association for the Study of Liver Disease

Murine liver allograft transplantation: Tolerance and donor cell chimerism

Nonarterialized orthotopic liver transplantation with no immunosuppression was performed in 13 mouse‐strain combinations. Two strain combinations with major histocompatibility complex class I and class II and minor histocompatibility complex disparity had 20% and 33% survival of more than 100 days, but the other 11 combinations, including four that were fully allogeneic and all with only class I, class II or minor disparities, yielded 45% to 100% survival of more than 100 days. Long‐living recipients permanently accepted donor‐strain heterotopic hearts transplanted on the same day or donor‐strain skin 3 mo after liver transplantation, in spite of detectable antidonor in vitro activity with mixed lymphocyte reaction and cellmediated lymphocytotoxicity testing (split tolerance). In further donor‐specific experiments, liver grafts were not rejected by presensitized major histocompatibility complex class I‐disparate recipients and they protected donor‐strain skin grafts from second set (or any) rejection. Less frequently, liver transplantation rescued rejecting skin grafts placed 1 wk earlier in major histocompatibility complex class I, class II and minor histocompatibility complex, class II or minor histocompatibility complex‐disparate strain combinations. Donor‐derived leukocyte migration to the central lymphoid organs occurred within 1 to 2 hr after liver transplantation in all animals examined, persisted in the surviving animals until they were killed (>375 days), and was demonstrated with double‐immunolabeling to be multilineage. The relation of these findings to so‐called hepatic tolerogenicity and to tolerance in general is discussed. (HEPATOLOGY 1994;19:916–924.) Copyright © 1994 American Association for the Study of Liver Disease

World's longest surviving liver-pancreas recipient

In July 1988, the liver and pancreas of a cadaveric donor were transplanted separately into a man with type 1 diabetes with end-stage chronic hepatitis B virus. Two features of the operation may help explain the patient's current status as the longest-lived liver-pancreas recipient. One was enteric drainage of pancreatic exocrine secretions. The other was delivery of the pancreas venous effluent to the host portal system and then directly to the hepatic allograft. © 2007 AASLD