Seizures associated with oxamniquine therapy.

Three patients who were treated for schistosomiasis mansoni with oxamniquine suffered generalized seizures. We suggest that this side effect may be more common than previously reported. Specific ethnic groups may be particularly at risk.

Experimental induction of oral squamous cell carcinomas in mice with 4-nitroquinolone-1-oxide.

The oral mucosa of mice is resistant to the action of a variety of carcinogens. In this study, the water-soluble carcinogen 4-nitroquinoline-1-oxide (4NQO) was applied repeatedly to the palates of male CBA mice for 2, 4, 6, 8, 12, or 16 weeks, and the animals were observed for the remainder of the 50-week experimental period. Oral epithelial atypia and squamous cell carcinoma were observed with increasing prevalence as the period of carcinogen exposure was increased. Carcinomas developed by 50 weeks in all animals that received 4NQO for 16 weeks.

Safety and toxicity of oxamniquine in the treatment of Schistosoma mansoni infections, with particular reference to electroencephalographic abnormalities.

Thirty-seven patients infected with Schistosoma mansoni were treated with oxamniquine. All were cured. The only significant adverse reaction was the development of abnormal electroencephalographic (EEG) findings in 6 (17.6%) of 34 patients whose pretreatment EEG was normal. Management of patients, with particular reference to the EEG abnormalities, is discussed.

Seizures and electroencephalograph changes associated with oxamniquine therapy.

A Tanzanian man with a known seizure disorder was admitted to hospital for treatment of schistosomiasis mansoni. He suffered a grand mal seizure soon after the second dose of oxamniquine. This is the first recorded seizured associated with use of this drug. Two other cases are reported in which transient electroencephalograph changes occurred during oxamniquine therapy. The central nervous system effects of oxamniquine are reviewed with respect to its possible epileptogenic effects.

A study of chromosomes of schistosomiasis patients under oxaminiquine (UK 4271) treatment.

Blood samples from 24 patients infested with Schistosoma mansoni were drawn immediately before and 2 days after the administration of a single therapeutic dose of 12-15 mg/kg oral oxaminiquine. Two-day lymphocyte cultures were obtained and about 100 mitoses from each blood sample were analyzed for chromosome aberrations. No significant differences were observed between the "before" and "after" cultures in the frequencies of aberrations resulting from spindle, chromatidic, or chromosome events. It is concluded that there is no reason to fear harmful effects on the chromosomes of patients from treatment with oxaminiquine.

Long-term hepatocellular effects of hycanthone and of two other anti-Schistosomal drugs in mice infected with Schistosoma mansoni.

In confirmation of an earlier study, it was found that in mice infected with Schistosoma mansoni hepatocellular carcinomas are induced by hycanthone, an antischistosomal drug and potent frameshift mutagen. In addition, a high incidence 1) of micronodular hepatocellular whirling lesions with increased basophilia, 2) of other proliferative areas of altered cellularity and 3) of precancerous nodules was found in the livers of schistosome-infected mice treated with hycanthone. A dosage schedule of hycanthone which was too small to have any significant chemotherapeutic effect in mice (3 X 3 mg/kg) was sufficient to induce a statistically highly significant incidence of micronodular lesions and of precancerous nodules. Hence, the hepatic tissue proved more susceptible to low doses of this drug than the parasite. No significant hepatocarcinogenic effects or other hepatocellular changes were induced by chemotherapeutically effective doses of two related equipotent antischistosomal compounds, a chloroindazole analog of hycanthone, IA-4, and the tetrahydroquinoline derivative, oxamniquine.