Antibiotic use in early childhood and the development of asthma

BACKGROUND AND OBJECTIVE: Recent investigations have focused on the role of infections in infancy in promoting or protecting against the subsequent development of asthma. A related hypothesis concerns the possible role of medical responses to infections, including the widespread use of antibiotics. We chose children at Rudolf Steiner schools to test this latter hypothesis because a significant proportion of parents rejects the use of conventional treatments, including antibiotics. METHODS: Seventy-five per cent (n = 456) of parents of children aged 5-10 years attending Rudolf Steiner schools throughout New Zealand completed questionnaires which included questions on the use of antibiotics and a history of asthma and wheeze in their children. RESULTS: After controlling for potential confounders, antibiotic use was significantly associated with having a history of asthma (OR = 2.74, 95% CI: 1.10-6.85) or wheeze (OR = 1. 86, 95% CI: 1.06-3.26) but not with current wheeze (OR = 1.08, 95% CI: 0.54-2-16). The adjusted odds ratio for asthma was 4.05 (95% CI: 1.55-10.59) if antibiotics were used in the first year of life and 1. 64 (95% CI: 0.60-4.46) if antibiotics had been used only after the first year of life when compared with children who had never used antibiotics. The number of courses of antibiotics during the first year of life was also associated with increased odds ratios for asthma: 2.27 (95% CI: 1.14-4.51) for one to two courses and 4.02 (95% CI: 1.57-10.31) for three or more courses when compared with no antibiotic use in the first year of life. Although not significant, the association of antibiotics and hay fever (OR = 1.99 [95% CI: 0. 93-4.26]) was of a similar strength to the association of antibiotics with a history of wheeze. Antibiotics were not significantly associated with eczema (OR = 1.23 [95% CI: 0.71-2.13]). CONCLUSION: Antibiotic use in infancy may be associated with an increased risk of developing asthma. Further study is required to determine the reasons for this association.     

Dopamine and synaptic plasticity in the neostriatum

After the unilateral destruction of the dopamine input to the neostriatum there are enduring changes in rat behaviour. These have been ascribed to the loss of dopamine and the animals are often referred to as ‘hemiparkinsonian’. In the denervated neostriatum, we have shown that not only are the tyrosine hydroxylase positive boutons missing, but also the medium sized densely spiny output cells have fewer spines. Spines usually have asymmetric synapses on their heads. In a recent stereological study we were able to show that there is a loss of approximately 20% of asymmetric synapses in the lesioned neostriatum by 1 mo after the lesion. Current experiments are trying to establish the specificity of this loss. So far we have evidence suggesting that there is no obvious preferential loss of synapses from either D1 or D2 receptor immunostained dendrites in the neostriatum with damaged dopamine innervation. These experiments suggest that dopamine is somehow necessary for the maintenance of corticostriatal synapses in the neostriatum. In a different series of experiments slices of cortex and neostriatum were maintained in vitro in such a way as to preserve at least some of the corticostriatal connections. In this preparation we have been able to show that cortical stimulation results in robust excitatory postsynaptic potentials (EPSPs) recorded from inside striatal neurons. Using stimulation protocols derived from the experiments on hippocampal synaptic plasticity we have shown that the usual consequence of trains of high frequency stimulation of the cortex is the depression of the size of EPSPs in the striatal cell. In agreement with similar experiments by others, the effect seems to be influenced by NMDA receptors since the unblocking of these receptors with low Mg⁺⁺ concentrations in the perfusate uncovers a potentiation of the EPSPs after trains of stimulation. Dopamine applied in the perfusion fluid round the slices has no effect but pulsatile application of dopamine, close to the striatal cell being recorded from, and in temporal association with the cortical trains, leads to a similar LTP like effect. The reduction of K⁺ channel conductance in the bath with TEA also has the effect of making cortical trains induce potentiation of corticostriatal transmission. TEA applied only to the cell being recorded from has no similar effect; the cortical stimulation again depresses the EPSP amplitude, so the site of action of TEA may well be presynaptic to the striatal cell. The morphological and physiological experiments may not necessarily be related but it is tempting to suggest that dopamine protects some corticostriatal synapses by potentiating them but that in the absence of dopamine others simply disconnect and are no longer detectable on electron microscopy.     

A novel delivery system for continuous desferrioxamine infusion in transfusional iron overload

Fifteen iron-overloaded thalassaemia major (TM) patients and two homozygous sickle cell patients (SCD) were treated continuously for 7d each week with the novel 48h continuous subcutaneous (s.c.) desferrioxamine (DFX) delivery device (code C1083, Baxter) and 10 TM patients received the 24h continuous intravenous (i.v.) DFX delivery device (code C1071). The 27 patients had previously received conventional s.c. DFX for 8–10h on 5 or more days each week. The serum non-transferrin bound iron (NTBI) levels fell significantly in both groups within 12h of commencing the continuous infusion. In the s.c. group the mean level fell from 4.2 to 2.0μmol/l ( P =0.001), whereas in the i.v. group the mean level fell from 3.6 to 0.1μmol/l ( P =0.006) the initial levels being measured 12h after stopping conventional s.c. DFX. After 4 weeks there was a significant fall in serum ferritin in both groups ( P =0.009). The new DFX delivery device is effective at removing toxic-free iron from plasma and reducing body iron. Moreover, it is preferred by patients with much improved compliance compared to the conventional s.c. DFX pump.     

Determinants of house dust mite allergen in homes in Wellington, New Zealand

Objectives To measure levels of the major Dermatophagoides pteronyssinus allergen (Der p 1) in homes in Wellington, New Zealand, and to examine factors which affect these levels. Methods As part of a study of risk factors for asthma among 474 8–10-year-old children, standard procedures were used to collect reservoir dust and to measure Der p 1 levels on the living room floor and child's bedroom floor and bedding. Der p 1 levels were analysed both as geometric mean μg/g of fine dust and as μg/m². Questionnaires collected information about factors which might influence these levels, and an average relative humidity in the bed and on the bedroom floor was also measured. Results Similar geometric mean levels of Der p 1 were found at each floor site – 25.5μg/g (95% CI: 22.8–28.5) in the living room and 26.4 μg/g (95% CI: 23.7–29.3) on the child's bedroom floor. The geometric mean level of Der p 1 in the child's bed was 46.6 μg/g (95% CI: 42.3–51.3). After controlling for possible confounders, geometric mean living room and bedroom floor Der p 1 levels were significantly higher in households with older carpet than households with no carpets or newer carpets, and higher in the autumn. Households with three or more children had higher levels of Der p 1 than households with fewer children. Bedding levels were significantly higher in beds with kapok or inner sprung mattresses, or wool underlays and at relative humidities above the mean (51%). Conclusion The very high levels of house dust mite allergen (Der p 1) found in Wellington are likely to be due to a variety of life-style and climatic factors. However, the type and age of floor covering appears to be the single most important factor.