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Biomedical subjects

W E Ormerod

Publications and source records attributed to W E Ormerod.

14 recordsLinked to original sources

Hypothesis: the significance of Winterbottom's sign.

Swollen glands in the neck in African sleeping sickness is usually considered to be a sign of peripheral trypanosomiasis without cerebral involvement. Experimental evidence of connection between these glands and the ventricles of the brain is reviewed. The evidence suggests that Winterbottom's sign may indicate also a cerebral infection. It also suggests that trypanosomes may enter the brain via the lymphatic system.

Animals

Screening compounds for sleeping sickness therapy without relapse.

The finding of an intracellular stage of Trypanosoma brucei in ependymal cells of the choroid plexus (Abolarin et al., 1986) and of the lining of the ventricles (Ormerod and Hussein, 1986) has suggested a new technique for screening trypanocidal compounds against the failure of drugs to eliminate "occult" stages of the infection (Raseroka and Ormerod, 1986). A (donor) mouse, infected for 28 days, is dosed with a drug, or combination of drugs, and samples of blood, cerebral cortex, choroid plexus and lining of ventricle are injected into clean (recipient) mice. The response of recipient mice shows whether the part, under examination, of the donor mouse has been cleared of trypanosomes. Suramin clears the blood and cerebral cortex but not sites containing ependymal cells (i. e. choroid plexus and lining of ventricle). Melarsoprol is active in all sites but is not always effective. DFMO clears the ependymal cells but its action elsewhere is difficult to evaluate. Metronidazole (inactive on its own), when given with suramin is active at all sites. Bleomycin was the most effective single compound. Bleomycin, an anti-cancer agent registered for use in man, should receive clinical evaluation for sleeping sickness: there is evidence, however, of incompatibility with DFMO.

Animals

Filaments of Trypanosoma brucei: some notes on differences in origin and structure in two strains of Trypanosoma (Trypanozoon) brucei rhodesiense.

Filaments attached to trypanosomes of two strains of T. (T.) brucei were studied by electron microscopy and two distinct types identified: short-thick and long-thin. The former are associated with stumpy trypanosomes and are secretions, via the flagellar pocket, which originate in the area of the Golgi complex, during the infection of the host. They are referred to as 'secretory filaments'. Their diameter is 0.09 to 0.14 mum. The long-thin filaments are associated with slender forms of trypanosome in various artificial situations; those shown by negative staining are believed to be cytoplasmic extrusions from the anatomically weak extremities of the parasite and are referred to as 'plasmanemes'. Their diameter is 0.06 mum. Both types appear to maintain their structure without the aid of the normal type of unit membrane as myelin formations.

Animals

The fate of metronidazole and tis implications in chemotherapy.

1. [14C]Metronidazole was rapidly absorbed from the gastro-intestinal tract of rats giving maximum blood levels of radioactivity, equivalent to 6-4 and 6-7 mug metronidazole per ml blood, 1 h after oral dosing. 2. There was rapid equilibration between blood and most tissues, although radioactivity was concentrated in the liver, kidney, gastro-intestinal tract and vaginal secretions. 3. The half-life of clearance of radioactivity from the majority of tissues was between 3 and 4 h, although it was longer in the skin (8 h) and gastro-intestinal tract (14 h). 4. Fourteen radioactive excretion products were detected in rat urine and all the major products were identified. These all contained a nitro group and represented 97 degrees of the total radioactivity excreted in urine. 5. Unchanged metronidazole was secreted throughout the entire length of the gastro-intestinal tract and into the vagina of rats. 6. A hypothesis has been proposed to explain the high clinical efficacy of metronidazole in treating trichomonal and amoebic infections.

Administration, Oral