Justin F Doherty

Is there an acute-phase response in steady-state sickle cell disease?

Metabolic and serum changes during steady-state homozygous sickle cell (SS) disease are consistent with an acute-phase response and raise the possibility that inflammation occurs in SS disease even during the steady state. To test this hypothesis, we measured concentrations of acute phase reactants in patients with SS disease, in patients with sickle cell haemoglobin C (SC) disease, and in normal (AA) control subjects. The concentrations of C-reactive protein and serum amyloid A were increased above 10 mg/L and 5 mg/L, respectively (our definition of an acute-phase response) in 18% (26/143) of subjects with SS disease even when they were symptom free, in 17% (6/35) of subjects with SC disease, and in 1% (1/80) of AA controls (p < 0.001). We suggest that subclinical vaso-occlusion may generate a covert inflammatory response and that the cytokine mediators of this response may contribute to the metabolic abnormalities and growth failure in sickle cell disease.

The effect of the level of dietary protein, carbohydrate and fat on urea kinetics in young children during rapid catch-up weight gain

The kinetics of urea metabolism were measured in children recovering from severe malnutrition. For a period of up to 10 d they received one of four diets which provided 711 kJ (170 kcal)/kg per d. Two groups received a diet with a high protein:energy (P:E) ratio of 10-6% (HP), enriched with either fat (HP/F) or maize starch and sucrose (HP/C). Two groups received a diet with a low P:E ratio of 8.8% (LP), enriched with either fat (LP/F) or maize starch and sucrose (LP/C). The rate of weight gain on the HP diets was significantly greater than on the LP diets. There was no difference in urea production between any of the four diets: HP/F 1.23 (SE 0.12), HP/C 1.37 (SE 0.14), LP/F 1.64 (SE 0.22), LP/C 1.15 (SE 0.15) mmol nitrogen/kg per h. On the HP diets urea excretion was 0.77 (SE 0.07) mmol N/kg per h, 61% of production. There was significantly less urea excreted in the urine on diet LP/C than on LP/F (0.36 (SE 0.05) and 0.64 (SE 0.04) mmol N/kg per h respectively). A significantly greater percentage of the urea production was hydrolysed on the LP diets (61%) compared with the HP diets (39%), with the consequence that 50% of urea-N produced was available for synthetic activity on the LP diets compared with 30% on the HP diets. The increase in the urea hydrolysed on the LP diets was equivalent in magnitude to the decreased intake of N, so that overall intake plus hydrolysis did not differ between the LP and the HP diets. Crude N balance was similar on diets HP/F, HP/C and LP/C, but was significantly reduced on diet LP/F. These results show that there is an accommodation in urea kinetics during rapid catch-up weight gain, which becomes evident when the P:E ratio of the diet falls to 8.8%. It is proposed that, for a P:E ratio of 8.8%, protein is limiting for catch-up growth. When the intake has a P:E ratio of 8.8% the pattern of urea kinetics can be modified by the relative proportions of fat and carbohydrate in the diet. The measurement of urea kinetics provides a useful approach to the definition of the adequacy of the protein in the diet.

Ultrasonographic assessment of the extent of hepatic steatosis in severe malnutrition.

Ultrasonographic, blinded assessment was made of the extent of hepatic steatosis in 55 children with severe malnutrition: undernutrition (n = 6), marasmus (n = 18), marasmickwashiorkor (n = 17), and kwashiorkor (n = 14). The children were examined on admission, in early recovery (considered as baseline), and again at discharge. Eleven healthy control children and eight of the previously malnourished children were studied as comparison groups. Both oedematous and non-oedematous malnourished children had significantly more steatosis than the comparison groups at each time. Children with oedematous malnutrition had significantly greater steatosis than non-oedematous children at admission. Half of the non-oedematous malnourished children had appreciable hepatic steatosis at both admission and at baseline. Hepatic fat was only slowly mobilised. The rate constant was 1.4 +/- 0.3%/day. One quarter of the children did not change steatosis grades during the period they were in hospital. There was no overall correlation between the extent of steatosis and liver size. Hepatic steatosis in childhood malnutrition is not confined to oedematous children: it is frequently present in marasmic and undernourished children. Its extent is not necessarily related to the degree of hepatomegaly and accumulated lipid is only slowly mobilised.

The effect of dietary pectin on rapid catch‐up weight gain and urea kinetics in children recovering from severe undernutrition

The rates of weight gain and urea kinetics were measured in 12 children receiving one of two energy dense, isonitrogenous formulae (711 kJ/kg/day, 170 kcal/kg/day) during recovery from severe undernutrition. Both formulations contained added arachis oil but in one a source of complex carbohydrate was added in the form of pectin (3.4% of total energy). The children taking the pectin diet had a rate of weight gain which was highly significantly less (7 g/kg/day) than the children not receiving pectin (14 g/kg/day). Urea production was significantly less on the pectin diet (0.37 ± 0.07 vs 0.55 ± 0.18 gN/kg/day). On the pectin diet there was a reduction in the rate of excretion of urea in urine and in the rate at which urea nitrogen was salvaged by the lower bowel, but these differences failed to reach statistical significance.