Tacrolimus-induced thrombotic microangiopathy in orthotopic liver transplant patients: case series of four patients.

Thrombotic microangiopathy (TMA) is a potentially fatal complication in solid organ and bone marrow transplant patients, with reported incidence of 0.5-3% and mortality of about 75%. To emphasise the importance of early diagnosis and prompt commencement of therapy results in improved clinical outcomes. A retrospective study of all patients who underwent orthotopic liver transplantation (OLTX) at the Western Australian Liver Transplantation Service from May 1994 to December 2010 was conducted to identify patients who developed tacrolimus-induced TMA. We identified four patients with tacrolimus-induced TMA post-OLTX, derived from a cohort of 104 patients treated with tacrolimus in our institution. The mean age at diagnosis was 40 years, and the mean time of onset was 63 ± 7.5 weeks after OLTX. The indications for OLTX in the four patients were fulminant hepatic failure in three (Wilson disease, paracetamol overdose and post-partum thrombotic thrombocytopenic purpura) and hepatitis C virus-related cirrhosis. All patients had tacrolimus post-OLTX. At diagnosis, tacrolimus was discontinued in all patients, and three of the four patients underwent plasma exchange and all patients improved clinically. Mean duration of follow up was 15 ± 7.5 months. There was no mortality 6 months post-TMA. Early diagnosis with immediate discontinuation or conversion of calcineurin inhibitors and plasma exchange should be offered to OLTX patients with TMA as it results in good outcomes.

Testicular growth and functional capability after 4-24 weeks of continuous exposure to 11 ATA He-O2.

A study of testicular developmental and functional capabilities was made of rats continuously exposed for 4, 8, 12, 16, 20, or 24 weeks to 1 ATA He-O2, 11 ATA He-O2, or ambient pressure air environmental conditions. Other groups of rats were exposed for 24 sequential weeks to the same three sets of environmental conditions with brief interruptions for decompression and recompression at the end of each 4 weeks. The rats were comfortably housed and adequately fed in accord with earlier investigations. Visual observations of the testes at the time of slaughter, dry matter content of the testes, and histological examinations--all revealed normal growth and active spermatid formation from healthy germinal epithelia in all semeniferous tubules. The stress of hyperbaria or of helium to 11 ATA did not inhibit or destroy male germinal epithelial functional capabilities.

Vitamins limiting for growth of subjects fed a normal diet under hyperbaric He-O2 conditions.

A growth study was conducted of rats continuously exposed for 4 weeks to ambient air, 1 ATA He-O2, or 11 ATA He-O2 conditions and fed one of 16 diets. The diets were the standard diet alone (adequate according to National Research Council standards); the standard diet with additional casein (50%), fat (25%), and all vitamins (25%); or the standard diet with all vitamins (25%), or all vitamins increased (25%) except one, which was supplied at the standard level. The standard diet was inadequate to support a normal rate of growth when fed under 11 ATA He-O2 conditions. Supplemental casein, fat, and vitamins or all vitamins alone adequately provided nutrients necessary for a normal rate of growth by hyperbaric exposed rats. The standard levels of thiamine, pantothenic acid, biotin, and vitamin K were inadequate and the standard levels of niacin, and vitamins A, D, and E were marginal in supporting growth when fed under hyperbaric conditions.