Diethylcarbamazine in the treatment of patients with onchocerciasis.
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Biomedical subjects
Publications and source records attributed to H M Gilles.
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Ninety-two males, infected with Onchocerca volvulus, from an area of on-going transmission in the forest zone of southern Ghana were treated with albendazole. 31 patients received 800 mg daily x 3, 31 received 1200 mg daily x 3 and 30 others received 800 mg daily x 7. Albendazole was given as a single daily dose with a fatty breakfast. Detailed systemic, ocular and laboratory examinations were performed pretreatment and at intervals over one year. Nodules were extirpated on days 30 and 60 and examined by histopathology. All the dose regimes were well tolerated but were neither microfilaricidal nor macrofilaricidal. The main effect was embryotoxicity affecting all intra-uterine stages. The most encouraging results were obtained in the 800 mg daily x 3 group in which a prolonged suppression of skin microfilarial counts occurred. Controlled studies in combination with ivermectin are recommended to determine whether an additive effect of the two drugs would result in permanent sterilisation of the adult worms.
The antimalarial drug primaquine was analysed in plasma and urine by gas chromatography mass spectrometry, using a deuterated internal standard. After freeze-drying and extraction with trichloroethylene the sample plus internal standard was reacted with Tri Sil TBT (a 3:3:2 by volume mixture of trimethylsilylimidazole, N,O,-bis-(trimethylsilylacetamide and trimethylchlorosilane) and an aliquot injected into the gas chromatograph mass spectrometer. The gas chromatographic effluent was monitored at m/z 403 and m/z 406, the molecular ions of the bis-TMS ethers of primaquine and 6-trideuteromethoxy primaquine. Calibration curves were prepared from standards made up in plasma and urine. Data from the analysis of plasma and urine samples from a volunteer who ingested the equivalent of 45 mg primaquine are presented.
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No association was found between bacteriuria and Schistosoma haematobium infection in the Malumfashi area, and no male had a confirmed significant bacteriuria. The overall bacteriuria prevalence rate in a separate group of schoolgirls was 0.96%, while in females over the age of 20 it was 1.37%; there was an estimated prevalence of 3.2% in women over the age of 30. These figures for females agree with those from populations which have no experience of bilharzia. No urinary S. typhi carriers were found. The lack of association between urinary bacterial infection and schistosomiasis probably reflects the low intensity of S. haematobium infection in the Malumfashi area of northern Nigeria.
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Several substituted 8-aminoquinolines related to known antimalarial drugs have been studied by gas chromatography mass spectrometry. 5,6-Dihydroxy-8-aminoquinoline, a possible metabolite of Primaquine, can be detected by single ion monitoring after conversion to a trimethylsilyl ether derivative. The mass spectra obtained in this study indicate that there are certain ions which are characteristic of the trimethylsilyl ethers of hydroxylated 8-aminoquinolines and 5,6-dimethoxy-8-aminoquinolines. These compounds should thus be amenable to analysis if they were produced during in vivo metabolism studies. Using selected ion monitoring the derivatized compounds can be detected at submicrogram levels.
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Prior to longitudinal studies into the effects of malaria upon the immune response, nutritional status and haematological indices in young children in northern Nigeria, the degree of malarial endemicity in the area has been established. Field work was carried out in the wet seasons of 1976 and 1977 and the dry season of 1977 (April). Seasonal variation in transmission has been demonstrated. Age-specific parasite prevalence rates and splenic indices confirm previous studies that this northern part of the Guinea savannah belt of West Central Africa is an holoendemic area.
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