Enterocytic CYP3A4 in a paediatric population: developmental changes and the effect of coeliac disease and cystic fibrosis

AIMS: To investigate the effects of age and disease states on the expression and activity of intestinal CYP3A4 in a paediatric population. METHODS: Duodenal biopsies and surgical sections were collected from 104 paediatric patients (age range 2 weeks to 17 years) and from 11 foetuses. An S9 fraction was prepared in each case. CYP3A4 expression was assessed by Western blotting and by immunohistochemistry; activity was measured by the rate of formation of 6beta-hydroxytestosterone from testosterone. Villin expression was used as a marker of enterocyte harvest to normalize CYP3A4 expression and activity data. RESULTS: In the 74 histologically normal paediatric biopsies there were statistically significant increases in CYP3A4 expression (r2 = 0.19, P = 0.001) and activity (r2 = 0.17, P = 0.02) with age. CYP3A4 was practically absent in fetal duodenum and was expressed at relatively low levels in neonates (P < 0.05 between neonates and children > 5 years). Active coeliac disease resulted in significant (P < 0.001) decreases in CYP3A4 expression and activity. CONCLUSIONS: Duodenal CYP3A4 is present at significantly lower levels in neonates and in patients with active coeliac disease. This may have clinical significance with respect to the oral bioavailability of CYP3A4 substrates.     

A double-blind controlled trial of metronidazole suppositories in children undergoing appendicectomy

Summary

A total of 133 children, aged 16 months to 15 years (mean 6.7 years), with presumptive acute appendicitis, was included in a double-blind, placebo-controlled trial of the short-term (72 hour) use of metronidazole suppositories as prophylaxis against post-operative infection. There was no significant difference in the incidence or severity of wound infection or post-operative intra-abdominal sepsis between the metronidazole-treated and placebo groups. It is suggested that intra-rectal metronidazole, when used exclusively, is not sufficient for effective prophylaxis for appendicitis in childhood.     

Peripheral and local anaesthetic techniques for paediatric surgery

Peripheral nerve blocks (PNBs) in paediatric patients are usually used as an adjunct to general anaesthesia, providing intra- and postoperative analgesia. These blocks provide good-quality analgesia preventing morbidity related to pain and reducing adverse effects from systemic analgesics. PNBs aid early patient recovery and discharge, which is essential in day-case surgery. Like all invasive techniques, PNBs are associated with complications and adverse effects. They should therefore be performed only after careful analysis of the risk:benefit ratio for each child. This article discusses a general approach to PNBs in children. It covers a small selection of limb and trunk blocks, and discusses the benefit of ultrasound guidance.     

Respiratory support in children

Respiratory failure is defined by the inability of the respiratory system to adequately deliver oxygen or remove carbon dioxide from the pulmonary circulation resulting in hypoxemia, hypercapnia or both. A wide variety of disease processes can lead to respiratory failure in children. Multiple interventions can support the paediatric patient with respiratory failure, from simple oxygen delivery devices to high frequency oscillatory ventilation and extracorporeal membrane oxygenation. This article will review available devices to improve oxygenation and ventilation, their advantages and disadvantages, and help guide physicians in the management of children with respiratory failure.     

Serum vitamin D levels are lower in Australian children and adolescents with type 1 diabetes than in children without diabetes

Vitamin D is synthesised in the skin through the action of UVB radiation (sunlight), and 25‐hydroxy vitamin D (25OHD) measured in serum as a marker of vitamin D status. Several studies, mostly conducted in high latitudes, have shown an association between type 1 diabetes mellitus (T1DM) and low serum 25OHD. We conducted a case–control study to determine whether, in a sub‐tropical environment with abundant sunlight (latitude 27.5°S), children with T1DM have lower serum vitamin D than children without diabetes. Fifty‐six children with T1DM (14 newly diagnosed) and 46 unrelated control children participated in the study. Serum 25OHD, 1,25‐dihydroxy vitamin D (1,25(OH)₂D) and selected biochemical indices were measured. Vitamin D receptor (VDR) polymorphisms Taq1, Fok1, and Apa1 were genotyped. Fitzpatrick skin classification, self‐reported daily hours of outdoor exposure, and mean UV index over the 35 d prior to blood collection were recorded. Serum 25OHD was lower in children with T1DM (n = 56) than in controls (n = 46) [mean (95%CI) = 78.7 (71.8–85.6) nmol/L vs. 91.4 (83.5–98.7) nmol/L, p = 0.02]. T1DM children had lower self‐reported outdoor exposure and mean UV exposure, but no significant difference in distribution of VDR polymorphisms. 25OHD remained lower in children with T1DM after covariate adjustment. Children newly diagnosed with T1DM had lower 1,25(OH)₂D [median (IQR) = 89 (68–122) pmol/L] than controls [121 (108–159) pmol/L, p = 0.03], or children with established diabetes [137 (113–153) pmol/L, p = 0.01]. Children with T1DM have lower 25OHD than controls, even in an environment of abundant sunlight. Whether low vitamin D is a risk factor or consequence of T1DM is unknown.     

Micronutrients

Micronutrients are essential dietary components and play a fundamental role in the prevention of disease. 30 are essential and cannot be synthesized by the body on a daily basis, making dietary sources critical. Micronutrients have an array of biochemical functions which are fundamental in the homoeostatic regulation of body function. It is at any point in a metabolic pathway that the chemical reaction may be unable to continue along its nature cascading pathway because the essential micronutrient is lacking. The normal metabolic regulation of the body will have been disturbed and ill health may occur due to the absence of a specific micronutrients. Several population groups with specific nutritional requirements, complex social, environmental and economic circumstances may be at risk of inadequate micronutrient intakes due to poor consumption or excessive losses, and hence maybe unable to meet their recommended requirements of micronutrients. This group may benefit from micronutrient supplements. Infants/children are a specific population group who are at risk of micronutrient deficiency states making adequate intakes essential to ensure normal growth and development. The paediatric group will be discussed here, with reference to current recommendations for their micronutrient and supplementation requirements based on current evidence available to advisory groups.