Proximal renal tubular acidosis secondary to FK506 in pediatric liver transplant patients.

We hereby report our experience with an index case of a pediatric liver transplant patient in whom FK506 administration was associated with the development of proximal renal tubular acidosis (RTA), as well the prevalence of acidosis and renal dysfunction in all pediatric liver transplant patients in our institution followed long term during a 6-year period. Data were grouped according to immunosuppressant regime: cyclosporine (CsA) only, FK506 only, or CsA with conversion to FK506. A 23-month-old female treated with FK506 after orthotopic liver transplantation (OLT) performed 15 months earlier presented with a 1-wk history of fever, watery diarrhea and metabolic acidosis. Although the acidosis did not improve following correction of her hydration status, administration of oral bicarbonate was effective. Discontinuation of this therapy resulted in acidosis. Since other indirect measurements of renal tubular function were normal, the patient was judged to have an isolated proximal RTA. In our group of pediatric liver transplant patients converted from CsA to FK506, FK506 administration was associated with a decline in serum bicarbonate (19 +/- 1 vs. 16 +/- 1 mEq/l, p < 0.02); neither blood urea nitrogen nor serum creatinine differed between the two groups. The number of rejection episodes/patient/month was comparable, allowing clinically relevant comparison of relative drug nephrotoxicities. We conclude that proximal RTA may be a relatively common treatable complication of FK506 administration in children.

Prevalence and characteristics of Blastocystis hominis infection in children.

Blastocystis hominis, a protozoan whose pathogenicity has been questioned, is sometimes found in the human gastrointestinal tract. We sought to determine the prevalence of Blastocystis in stool and to characterize clinical features of infection with Blastocystis in children. Forty-six (3%) of 1,736 patients undergoing fecal microscopy at Children's Hospital of Pittsburgh between January 1, 1985, and December 31, 1988, harbored Blastocystis. Of these 46 children, 75% had exposure to well water or had been in developing countries. Thirty-nine of the 46 (85%) experienced gastrointestinal symptoms, such as abdominal pain, diarrhea, vomiting, and weight loss. Blastocystis was the only parasite found in 35 of those 39 symptomatic children. Symptoms resolved within one month in 90% of patients receiving antiparasitic pharmacotherapy, but in only 58% (P < .04) of those receiving no therapy. We conclude that children infected with Blastocystis often experience gastrointestinal symptoms and that treatment increases the rate of symptomatic improvement. We speculate that Blastocystis is a human pathogen.

Albendazole therapy in alveolar hydatid disease: a report of favorable results in two patients after short-term therapy.

Albendazole was administered preoperatively to two patients with active alveolar hydatid disease for 58 and 84 days. Vesicles of larval Echinococcus multilocularis obtained from surgical tissues were inoculated into red-backed voles for in vivo testing viability. No proliferation of the larval cestode had occurred when the animals were dissected three months post-inoculation. These findings suggest that short-term therapy with albendazole was effective in killing the larval cestode in these two cases. Albendazole was found to be hepatotoxic but resulting transaminase abnormalities have been reversible. Close monitoring of liver function and hematology is essential in patients under albendazole therapy.

Consequences of continuous mebendazole therapy in alveolar hydatid disease--with a summary of a ten-year clinical trial.

The assessment of a ten-year clinical trial of continuous therapy in eight patients revealed further evidence of a significant therapeutic effect of mebendazole on alveolar hydatid disease. Life-expectancy was increased when compared to untreated historical controls, especially in the patients over 55 years of age. All symptomatic patients showed subjective improvement. In four patients, three had a 50% or greater reduction in the diameter of massive hepatic lesions, and in the fourth, progressively enlarging metastases were arrested. Fall in the IHA titre suggested that the causative organism had been destroyed in two additional patients. Of greater significance was the absence of progression of the disease process as measured by changes in the size of the hepatic lesion or lack of development of distant metastases in patients under therapy. In contrast, progressive enlargement of hepatic lesions or the appearance of distant metastases were cardinal features of untreated cases (15 of the 16 cases followed). In vivo determination of viability of tissues of the larval Echinococcus multilocularis from patients receiving long-term therapy was considered important in evaluating efficacy of the drug. Such tissues, obtained by autopsy from two patients under continuous therapy for four and ten years, failed to proliferate when inoculated into rodents (red-backed voles), whereas similar inoculations from untreated patients or those receiving 15 months' or less of therapy brought about production of vesicles in rodents in eight of 11 tests (73%). These two deaths, unrelated to therapy, resulted from late fibrotic constriction of end-stage parasitic lesions about the portal vein and major bile ducts. The clinical findings in combination with negative in vivo tests and other data indicate that the mebendazole therapy significantly alters the clinical course of alveolar hydatid disease. The evidence strongly indicates that long-term therapy may eventually have a lethal effect on the larval cestode in advanced disease.