Search

Aims: To define, in a prospective study, the risk of hypoglycaemia-defined as blood glucose concentration < 1.8 mmol/l-in term infants exposed in utero to valproate and to describe the withdrawal symptoms., Methods: Twenty epileptic women were treated with valproate only during pregnancy and two were treated with valproate and carbamazepine. In the first trimester, the daily median dose of valproate was 1.0 g (range 0.3-4.2) and in the third trimester 1.2 g (range 0.3-4.8)., Results: Thirteen of the 22 infants became hypoglycaemic. One infant had eight episodes of hypoglycaemia, one had three episodes, two had two episodes, and nine had one episode each. The lowest blood glucose concentration was 1.0 mmol/l. All episodes were asymptomatic. The maternal mean plasma concentration of total valproate during the third trimester correlated negatively with blood glucose concentration one hour after delivery (p < 0.0003) and with the development of hypoglycaemia (p < 0.0001). There was no evidence for hyperinsulinaemia as the cause of hypoglycaemia. Ten infants developed withdrawal symptoms, which correlated positively with the mean dose of valproate in the third trimester and the concentration of the free fraction of valproate in maternal plasma at delivery (p < 0.02)., Conclusions: Infants exposed to valproate in utero had a significantly elevated risk of hypoglycaemia, and withdrawal symptoms were often observed.

In a multicentre, double-blind, randomized, parallel study, 426 asthmatic children aged 5-15 years old received salmeterol 50 micrograms b.i.d. or placebo b.i.d. via the Diskhaler. All patients had access to inhaled salbutamol to be used on an 'as required' (p.r.n.) basis for symptomatic relief. The study design comprised a 2-week baseline, a 12-month treatment period incorporating a 2-week 'off treatment' after 6 months, and a 2-week follow-up period at the end of the trial. At the end of 12 months of treatment with salmeterol, the adjusted change from baseline for morning and evening peak expiratory flow rate (PEF) was 56 and 47 l min-1, respectively, and this was significantly greater than placebo (P < 0.01; P < 0.05). Exacerbation rates did not differ between groups and results were not dependent upon concurrent inhaled steroid use. Neither treatment caused a change of > or = 1 doubling dose in PC20/PD20 either during or on stopping treatment. Treatment with regular salmeterol 50 micrograms b.i.d. over a 12-month treatment period provides a significant, rapid and well-maintained improvement in lung function without increasing bronchial reactivity or asthma exacerbation rates compared to p.r.n. salbutamol.

Of thirty-eight children, who were immunized with mould extracts, seven (19%) were withdrawn from hyposensitization due to serious side-effects clinically consistent with a type III reaction. These seven children exhibited a two- to four-fold increase in circulating precipitating-antibodies to the injected extracts, and had shown a slight increase in precipitating antibodies to the mould extracts used before hyposensitization. A further fourteen patients, also hyposensitized with mould extracts but without side effects did not develop precipitating antibodies. It is suggested that hyposensitization with mould extracts may be hazardous in children who may have a primary "immune imbalance' with a risk of provoking type III reactions.

One hundred and six of 503 (21%) consecutive children with asthma, who from 1979 to 1983 commenced hyposensitization therapy, were prospectively studied on the safety of immunotherapy. More than 80% of the patients completed therapy without side effects. Thirteen patients were withdrawn from hyposensitization due to moderate and predictable, but intolerable, side effects such as asthma/rhinitis, urticaria and subcutaneous nodules and hypersensitivity to aluminium. However, more alarming was the outcome in six children, who after an uneventful course of immunotherapy and after several months on maintenance therapy, suddenly, 5 to 20 min (mean 10 min) following an earlier tolerable allergen injection, developed severe, anaphylactic reactions, in three of them nearly fatal. Mould extracts were responsible for the most frequent and serious side effects (Alternaria iridis/alternata, 3 patients, Cladosporium herbarum, 8 patients). Furthermore, serious, but not immediately life-threatening, anaphylactic reactions occurred in two children treated with Phleum pratense. On the other hand, hyposensitization with Dermatophagoides pteronyssinus was very well tolerated.

Eight children with Cushing's disease aged 6-18 years were treated with external radiation to the pituitary gland using 60Co gamma radiation given with stereotactic technique. The dose given varied between 50 and 70 Gy. The observation time was 2.6 to 6.75 years. Seven children had a clinical remission with normal urinary cortisol excretion. One child had insufficient effect of two irradiations and underwent bilateral adrenalectomy. In the patients in remission the growth velocity increased during the first year after treatment but growth retardation occurred again during the second year. Insufficient growth hormone secretion was demonstrated in all subjects. Two patients were given thyroxine substitution and three showed evidence for secondary hypogonadism. In conclusion, stereotactic pituitary irradiation was effective in normalizing the excessive glucocorticoid production in children with Cushing's disease. However, with the doses used, it was not possible to maintain a normal anterior pituitary function.