Recent evidence suggests the rise in urinary albumin excretion preceding diabetic nephropathy may represent a continuum. We therefore studied factors relating to albumin excretion rate in children with insulin-dependent diabetes. Normal overnight albumin excretion rate was determined in 690 healthy schoolchildren. The 95th centile was 7.2 micrograms min-1. Patients included 169 children with IDDM aged 12.4 +/- 3.1 years who performed 4.8 +/- 0.4 overnight collections during 15 +/- 0.5 months and were analysed cross sectionally. They were stratified accordingly to mean albumin excretion rate: normal < 7.2 micrograms min-1, borderline 7.2-20 micrograms min-1, microalbuminuria 20-200 micrograms min-1; 96/169 patients performed 6.4 +/- 0.2 overnight collections during 24 months follow-up and were analysed longitudinally. Cigarette smoking was determined by history and urine cotinine levels. Smoking correlated with albumin excretion rate, independent of age and other variables, in cross-sectional and longitudinal analysis (p < 0.003). Smoking was more prevalent in the borderline albuminuria and microalbuminuria groups (p < 0.004, p < 0.001). Mean HbA1c during follow-up and mean HbA1c since diagnosis were significantly higher in the microalbuminuric group, compared with the normal patient group. HbA1c since diagnosis, mean blood pressure, lipoprotein(a), and apolipoprotein B did not correlate with albumin excretion rate, after controlling for other variables. Our findings highlight the continuing need for strategies to prevent smoking in this age group.
The effect of Vitamin A supplementation on susceptibility to acute respiratory infections was investigated in a randomized controlled trial. One hundred and forty-seven preschool-age children with a history of frequent respiratory illness were randomized into Vitamin A supplemented (450 pg/day) and placebo groups. Respiratory symptoms were recorded on a daily basis over a period of 11 months. The children who received the supplement experienced 19% fewer episodes of respiratory symptomatology (Pt0.05) than their placebo counterparts, despite the fact that their plasma retinol levels did not change. Children with a prior history of lower respiratory illness or of allergy benefited most from supplementation. The plausibility of a role for Vitamin A in the aetiology of respiratory proneness is reviewed.
In order to extend our earlier observation that children who experience frequent respiratory episodes may benefit from Vitamin A supplementation, 206 children aged 2-7 years who had been hospitalized for bronchiolitis during infancy were randomized into a controlled trial of Vitamin A supplementation. Of these, 149 met the criteria of protocol compliance after 12 months of follow-up. Mean plasma retinol at baseline was 39.2 pgl100 ml (s.e.m. = 1.0) and did not increase after 12 months (mean = 36.0 pg/lOO ml, s.e.m. = 0.7) despite the older age of the cohort. The range observed (11.7-73.9 pg/lOO ml) included some children at risk of marginal Vitamin A deficiency. Mean plasma retinol levels were 20% lower than those of children experiencing frequent respiratory episodes recorded earlier. Oral supplementation did not change plasma retinol levels, nor did it affect respiratory morbidity.
SUMMARY.Recent interest in conditions associated with increased blood serotonin level has highlighted the need for consistency between assay methods to allow for more accurate delineation of serotinin variables. To this end, comparison was made between a spectrofluorimetric technique frequently used in the past and two potentially more specific high performance liquid chromatographic procedures. Normal ranges and diurnal variations for blood serotonin in adults, normal, autistic children and children with developmental dysphasia were also determined. No significant difference was found between serotonin level in blood drawn by simultaneous venepuncture and capillary (fingerprick) collection. Whilst there was no evidence of circadian rhythm, seasonal variation with mean blood serotonin levels significantly lower in summer than in two successive winters was suggested. Blood serotonin values in normal children tended to decline with increasing age. No similar maturational effect was apparent in autistic children. The mean level for autistic children in winter was significantly higher than that for normal children in the same 'Season; despite this there was considerable overlap of blood serotonin levels between normal and autistic groups. Serotonin levels determined by the three different methodologies showed a high correlation but differed significantly: caution should be exercised when comparing blood serotonin results where different methods are employed.
We have studied the pharmacokinetics of the anti-mycotic ketoconazole in seven patients who took it for 1-6 months at a dose of 200 mg daily. The mean elimination half-life of the drug was 3.3 h, and although the ketoconazole was given only once daily, a satisfactory clinical response was obtained in all seven individuals. Only a small fraction of the absorbed drug (mean 0.22%) was excreted unchanged in the urine, suggesting almost complete metabolism. Our results support the concept that anti-mycotic activity in the tissues continues after the plasma drug concentration has fallen below a critical level. Our results also support the concept of a change in pharmacokinetics with chronic dosing.
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