RESUMO
There are no recognized orally administered treatments for any of the leishmaniases. The 8-aminoquinoline WR6026 is an orally administered analog of primaquine that cured 50% of patients with kala-azar in Kenya at a dose of 1 mg/kg/day for 28 days. A further phase 2, open-label, dose-escalating safety and efficacy study was performed for kala-azar in Brazil. Cure rates for Brazilian patients treated for 28 days were as follows: 1 mg/kg/day: 0 of 4 (0%); 1.5 mg/kg/day: 1 of 6 (17%); 2.0 mg/kg/day: 4 of 6 (67%); 2.5 mg/kg/day: 1 of 5 (20%); and 3.25 mg/kg/day: 0 of 1 (0%). Nephrotoxicity that was not anticipated from preclinical animal studies or from phase 1 studies was seen at 2.5 mg/kg/day in 2 patients and in the single patient administered 3.25 mg/kg/day. WR6026 demonstrated the unusual clinical features of lack of increased efficacy against Brazilian kala-azar with increased dosing above 2 mg/kg/day and toxicity that was not present in previous investigations.
Assuntos
Aminoquinolinas/administração & dosagem , Antiprotozoários/administração & dosagem , Leishmaniose Visceral/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Aminoquinolinas/efeitos adversos , Aminoquinolinas/sangue , Animais , Antiprotozoários/efeitos adversos , Antiprotozoários/sangue , Criança , Relação Dose-Resposta a Droga , Feminino , Humanos , Nefropatias/induzido quimicamente , Leishmania/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Adolescents who have grand mal epilepsy and their parents were interviewed, and the adolescents were evaluated neurologically. Better seizure control and less neurologic disability were unexpectedly associated with less open communication between the adolescents and their families and friends, and with a poorer self-image and poorer expectations for the future. These findings were unrelated to IQ or school performance. This outcome is consistent with other studies of invisible defects and stigmatization, and suggests that youngsters who have relatively mild defects involving social disability may be more troubled than those with more apparent defects, for which denial may be operative. An incidental finding in the study was that a question more predictive of overall family, social, and academic function than the neurologic findings was simply whether or not the youngster was attending the appropriate grade in school for his or her age.