RESUMO
The artemisinin-based combination therapies artemether-lumefantrine (AL) and amodiaquine (AQ) plus artesunate have been adopted for treatment of Plasmodium falciparum malaria in many African countries. Molecular markers of parasite resistance suitable for surveillance have not been established for any of the component drugs in either of these combinations. We assessed P. falciparum mdr1 (Pfmdr1) alleles present in 300 Tanzanian children presenting with uncomplicated falciparum malaria, who were enrolled in a clinical trial of antimalarial therapy. Pfmdr1 genotype analysis was also performed with isolates from 182 children who failed AQ monotherapy and 54 children who failed AL treatment. Pfmdr1 alleles 86Y, 184Y, and 1246Y were more common among treatment failures in the AQ group than among pretreatment infections. The converse was found in the AL-treated group. Children presenting with the 86Y/184Y/1246Y Pfmdr1 haplotype and treated with AQ were significantly more likely to retain this haplotype if they were parasite positive during posttreatment follow-up than were children treated with AL (odds ratio, 33.25; 95% confidence interval, 4.17 to 1441; P, <0.001). We conclude that AL and AQ exert opposite within-host selective effects on the Pfmdr1 gene of P. falciparum.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/efeitos dos fármacos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Amodiaquina/farmacologia , Antimaláricos/farmacologia , Artemisininas/farmacologia , Etanolaminas/farmacologia , Fluorenos/farmacologia , Malária Falciparum/parasitologia , Plasmodium falciparum/genética , Alelos , Animais , Artemeter , Pré-Escolar , Resistência a Medicamentos , Feminino , Ligação Genética/genética , Genótipo , Haplótipos , Humanos , Lactente , Lumefantrina , Malária Falciparum/tratamento farmacológico , Masculino , Polimorfismo Genético/genética , Polimorfismo de Nucleotídeo Único/genética , Tanzânia , Resultado do TratamentoRESUMO
Eighteen hypertensive Jamaicans underwent a double-blind cross-over trial of propranolol in order to prove or disprove the assertion that the drug is a relatively potent hypotensive agent. Though the dosage used was high there was no significant difference in effect between the drug and an inert placebo. It is suggested that this may have been so because the "tranquillizing" effect of the drug is unlikely to be of value in Jamaican hypertensive patients. We stress that our conclusions do not necessarily apply to European patients, in whom a properly controlled trial is urgently needed, preferably for longer periods of therapy to exclude any possible "carry-over" effect. Propranolol in high dosage is remarkably free from side-effects when given to carefully selected patients. (AU)
Assuntos
Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Hipertensão/tratamento farmacológico , Propranolol/uso terapêutico , Ensaios Clínicos como Assunto , Jamaica , PlacebosRESUMO
Another case of diffuse progessive interstitial fibrosis of the lung is described in a child. The diagnosis was made by lung biopsy and treatment with steroids instituted because of the extreme dyspnoea. There appeared to be considerable symptomatic inprovement but no significant changes occurred in the radiological appearance (AU)
Assuntos
Humanos , Criança , Fibrose Pulmonar/diagnóstico , Fibrose Pulmonar/tratamento farmacológicoRESUMO
Details of a family with this disorder are presented. It appears to be transmitted by means of an autosomal dominant gene. The changes include gingival hypertrophy, particularly in the maxilla, increase in the soft tissues of the palate, nose and ears, changes in the nails and digits, excessive joint mobility and pes cavus as well as splenomegaly (AU)
