Isologous isolated islets of Langerhans were transplanted into the peritoneum and through the portal vein into the liver of diabetic rats. This resulted in the normalization of fasting blood glucose levels, with clear improvement of glucose tolerance tests. The results after intrahepatic implantation were better than after intraperitoneal implantation. Three months after implantation of islets into the peritoneum diabetes recurred and after one year only 2 of the 15 rats were alive, with high blood glucoe levels. In the group with intrahepatic islets the normalization of blood glucose was maintained over a period of one year. Immunohistochemical insulin proofs were positive in the peritoneum over a period of 3 months and in the liver up to one year after implantation. Glucagon proofs were positive in the intraperitoneal islets for 6 weeks and in intrahepatic ones for one year. Morphological examination of transplanted islets suggested that the liver is better suited for islet transplantation than the peritoneum.

Animals↗

PubMedDate not supplied

Pharmacokinetics of tacrolimus (FK506) in paediatric liver transplant recipients.

The pharmacokinetics of intravenous and oral tacrolimus was assessed in paediatric liver transplant patients at two centers in Europe. Sixteen patients, age 0.7 to 13 years, participated in the study; 12 patients were evaluable for intravenous pharmacokinetics, and 16 for oral. Intravenous tacrolimus was given as a continuous 24 h infusion (mean 0.037+/-0.013 mg/kg/day), and oral tacrolimus was given in 2 doses per day (mean 0.152+/-0.015 mg/kg). Whole blood samples for the intravenous pharmacokinetic profile were taken before initiation of the first infusion, 4, 8, 12 and 24 h post-infusion, and every 24 h thereafter until intravenous administration was discontinued. During the 12 h wash-out period between intravenous and oral administration, samples were taken every 3 h. Samples for the oral pharmacokinetic profile were taken immediately before the first oral dose and 0.5, 0.75, 1, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-administration. Non-compartmental procedures were used to characterise the pharmacokinetic parameters. Mean estimates for clearance and terminal half-life were 2.3+/-1.2 ml/min/kg and 11.5+/-3.8 h, respectively, following intravenous tacrolimus. The mean bioavailability of oral tacrolimus was 25+/-20%. A strong correlation was observed between AUC and trough whole blood levels of tacrolimus (r=0.90). The clearance was approximately 2-fold higher than that previously observed in adults; this could explain the higher dosage requirements in children.

Administration, Oral↗

PubMedDate not supplied

Sclerosing cholangitis associated to cryptosporidiosis in liver-transplanted children.

UNLABELLED: Three children of a series of 461 pediatric liver transplant recipients developed diffuse cholangitis associated with intestinal cryptosporidium carriage. All three received immunosuppression consisting of tacrolimus and prednisone. Cryprosporidium carriage was treated with paramomycin, while immunosuppression was decreased according to graft tolerance. No other infectious pathogens were found, and no vascular problems were detected. Bile duct anastomosis was reoperated in all three, but biliary cirrhosis developed in one patient, requiring retransplantation. All three patients are alive and well, and free of intestinal parasites on follow-up. CONCLUSION: Cryptosporidium intestinal infection may play a role in some cases of otherwise unexplained cholangiopathies in pediatric liver transplant recipients. This may lead to significant morbidity, including need for retransplantation.

Child↗

PubMedDate not supplied

Evaluation of a new immunoassay to measure sirolimus blood concentrations compared to a tandem mass-spectrometric chromatographic analysis.

A new immunoassay of sirolimus based on the microparticle enzyme immunoassay (MEIA) principle has been developed with collaboration of Abbott Diagnostics. Laboratories and Axis-Shield. Our laboratory evaluated this new assay on 153 whole blood samples (EDTA) drawn from a population of renal (n = 141) and hepatic (n = 12) transplant patients. Each blood sample was analyzed simultaneously by MEIA (Y) and by a reference method (X) used routinely in our laboratory, namely, liquid chromatography tandem mass spectrometry (LC-MS/MS). The statistical analysis of Passing-Bablok produced the following results: Spearman r value = 0.95, slope = 1.15 and intercept with the Y axis = +0.2 ng/mL. The observed global overestimation of 15% compared to the reference method could be explained by the cross-reactivity of sirolimus metabolites with the antibody. A complementary analysis taking into account the transplanted organ (kidney versus hepatic) did not show any significant difference between the populations, most likely owing to the low number of hepatic transplantation samples. The analytical performance of the MEIA method showed CV < or =10% and a limit of quantification of 1.5 ng/mL, which were acceptable for routine clinical monitoring. In conclusion, the MEIA method has shown robust, stable, reproducible, features with an excellent correlation with the reference LC-MS/MS method.

Chromatography, Liquid↗

PubMedDate not supplied

Adult hepatic retransplantation. UCL experience.

INTRODUCTION: Retransplantation is a rescue operation in orthotopic liver transplantation. Its appropriateness has been questioned on medical, economical and also on ethical grounds. MATERIAL AND METHODS: During the period february 1984-december 1997, 54 (14.5%) of 372 adult patients were retransplanted; three (0.8%) of them had two retransplantations. Indications were graft dysfunction [(primary non function (8x) and early dysfunction (14x in 13 patients)], immunological failure [acute (9x in 8 patients) and chronic (9x) rejection], technical failure [(hepatic artery thrombosis (5x in four patients), allograft decapsulation (1x), ischaemic biliary tract lesions (6x)] and recurrent viral allograft disease [HBV (4x) and HCV (1x)]. RESULTS: Five year actuarial patient survival after retransplantation was 70.8%, which was identical to this of non retransplanted patients (72%). Early (< 3 mo) mortality was significantly lower in elective procedures (9.1%--2/22 pat. vs 34.4%--11/32 pat. in urgent procedures--p < 0.05). Mortality was highest in the graft dysfunction (23.8%, 5/21 pat.) and immunological failure (41%, 7/17 pat.) groups. Five of six patients retransplanted for rejection, whilst being on renal support, and two of three patients retransplanted urgently twice died of infectious complications. All patients retransplanted because of recurrent allograft disease were long-term (> 3 mo) survivors. Both HBV-infected patients died of allograft reinfection 7 months later; the two HBV-Delta infected patients were, free of infection, 44 and 6 months after retransplantation under HBV-immunoprophylaxis. Length of hospitalisation after primary transplantation and retransplantation were identical (median of 16 days--range 11 to 40 vs 14 days (range 7 to 110). Economical study during the period 1990-1995 showed that costs of the first hospitalization of primary transplantation and of retransplantation could be equalized during the period 1994-1995 as a consequence of the more frequent use of elective retransplantation (median 1.3 million BF, range 720,988 to 8,887,145 vs 1.1 million BF, range 943,685 to 1,940,409). CONCLUSIONS: Hepatic retransplantation is a successful safety net for many liver transplant patients. Every effort should be made to do this intervention electively under minimal immunosuppression. In case of immunological graft failure and hepatic artery thrombosis retransplantation must be done early in order to avoid infectious complications; the same holds for ischaemic biliary tract lesions which cannot be cured by interventional radiology. Retransplantation for recurrent benign disease should be restricted to those diseases which can be effectively treated by (neo- and) adjuvant antiviral therapy.

Actuarial Analysis↗

PubMedDate not supplied

The pediatric liver transplant program at the Université Catholique de Louvain, Cliniques Saint-Luc, Brussels: overall results in 444 children (1984-1997).

Between 1984 and 1997, a total of 444 children (< 15 years) received an orthotopic liver transplant (OLT) at Saint-Luc University Clinics. Biliary atresia constituted the indication for OLT in 304 cases (68%). Median age (range) at OLT was 2.1 years (0.3-14.5). 177 children (40%) received a whole liver graft, 184 (41%) a reduced-size graft, 26 (6%) a split liver graft, whereas a living-related donor graft was used in 57 children (13%). Most grafts were ABO-identical or -compatible, in 395 cases (89%) and 40 (9%), respectively. Overall actuarial patient survivals at one and five years were 85% and 81%. The overall retransplantation rate was 19%. The results of uni- and multivariate statistical analyses showed a significant impact of year of transplantation (learning curve effect), with a 15% improvement of patient survival between the 1984-7 and the 1995-7 periods (p < 0.002). Results differed according to the indications for OLT, the best survivals being recorded for familial cholestasis, the worst for liver tumor (p = 0.004). Five year patient survival was significantly better after elective OLT (82%), when compared to highly urgent OLT (63%) (p < 0.001). Patient survivals were comparable in the children receiving primary cyclosporin-A microemulsion or tacrolimus immunosuppression, which were significantly higher than in the historical group treated with cyclosporin-A. No impact of the age at OLT, type of graft and ischemic time could be reported. In conclusion, this series illustrates the progressive improvements introduced in our pediatric liver transplant program between 1984 and 1997, including the technical variants allowing pediatric OLT using adult donors as well as the introduction of new immunosuppressive strategies.

Actuarial Analysis↗

PubMedDate not supplied

Paediatric orthotopic liver transplantation: lessons from a 532 transplant single centre experience with 532 transplants in 446 children.

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Belgium↗