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Biomedical subjects

N M Anstey

Publications and source records attributed to N M Anstey.

39 records · Page 3Linked to original sources

Increased nitric oxide production in acute diarrhoea is associated with abnormal gut permeability, hypokalaemia and malnutrition in tropical Australian aboriginal children.

Australian Aboriginal children hospitalized with diarrhoeal disease have severe manifestations with acidosis, hypokalaemia, osmotic diarrhoea and abnormal small bowel permeability. Nitric oxide (NO) production is increased in diarrhoeal disease, but its relationship to mucosal function and diarrhoeal complications is not known. We examined the relationship between NO production and complications of acute diarrhoea in Aboriginal and non-Aboriginal children between February 1998 and February 2000. We enrolled 318 children admitted to Royal Darwin Hospital into one of three groups: acute diarrhoea, non-diarrhoeal controls with no inflammatory illness, and non-diarrhoeal controls with inflammatory illness. Nitric oxide production was measured by urine nitrate-creatinine (NOx/Cr) excretion on a low nitrate diet. Small bowel intestinal permeability was measured by the lactulose-rhamnose (L/R) ratio on a timed blood specimen. The NOx/Cr ratios were markedly elevated in Aboriginal diarrhoeal cases (geometric mean [GM] = 1.23, 95% confidence interval [95% CI] 1.07-1.44), lowest in non-Aboriginal non-inflammatory controls (GM = 0.13, 95% CI 0.10-0.16) and intermediate in all other groups (GM = 0.35, 95% CI 0.28-0.43). Convalescent levels (day 5) in the Aboriginal diarrhoeal group (GM = 1.02, 95% CI 0.82-1.28) were slower to fall than L/R ratios. Multivariate analysis in the diarrhoeal group indicated that high NO production was associated with abnormal permeability, hypokalaemia and malnutrition, but not with the severity of diarrhoea, acidosis or osmotic diarrhoea. We concluded that increased NO production may contribute to impaired mucosal barrier function and hypokalaemia in acute gastroenteritis, which may be the cost of the known gut-protective and antimicrobial effects mediated by NO in acute intestinal inflammation.

Acute Disease↗

Elevated levels of methaemoglobin in Tanzanian children with severe and uncomplicated malaria.

Elevated levels of methaemoglobin, the ferric form of haemoglobin incapable of oxygen transport, have been previously found during Plasmodium vivax infections and in acidotic infants. We measured methaemoglobin in the following 5 groups of children with P. falciparum malaria admitted to Muhimbili Medical Centre, Dar es Salaam, Tanzania. (i) Cerebral malaria (CM) with unrousable coma (n = 50), including 32 with complete recovery (CMCR) and 18 with death or neurological sequelae (CMDS); (ii) malaria with severe anaemia but without severe respiratory distress (SA; n = 6); (iii) uncomplicated malaria (UM; n = 37); (iv) asymptomatic parasitaemia (AP; n = 5); and (v) healthy controls (HC; n = 34). Mean methaemoglobin levels were elevated in all groups with malaria, forming up to 16.4% of circulating haemoglobin. The degree of methaemoglobinaemia correlated with disease severity and severity of anaemia. Mean methaemoglobin levels in children with AP, UM, SA, CMCR and CMDS were 3.3%, 4.1%, 5.6%, 4.7% and 5.8% respectively; the mean levels in those with clinical disease were significantly higher than those in healthy controls (2.0%). Methaemoglobinaemia > 10% was found in 5.4%, 16.7%, 12.5%, and 22.2% of those with UM, SA, CMCR and CMDS, respectively. In the presence of parasite sequestration, impaired tissue perfusion, and a reduction in oxygen carrying capacity of blood due to anaemia, a further reduction in oxygen carrying capacity from even a modest concentration of methaemoglobin is likely to exacerbate tissue hypoxia, perhaps critically so in a minority of anaemic and acidotic patients with severe falciparum malaria.

Antimalarials↗