The effect of sleep state on ventilation and the mechanics of breathing was studied in nine normal adolescents by use of a respiratory inductive plethysmograph and surface electromyogram electrodes. Minute ventilation was state dependent (P less than 0.01), decreasing by a mean of 8% from wakefulness to nonrapid-eye-movement (NREM) sleep and increasing 4% from NREM to rapid-eye-movement (REM) sleep. These changes were caused by changes in respiratory rate. Tidal volume (VT) was not affected by sleep state (P greater than 0.10). The pattern of breathing during wakefulness was similar to that of REM sleep. During NREM sleep intercostal and diaphragmatic muscle activity increased by a mean of 34% and 11%, respectively, as compared with wakefulness, indicating an increase in the respiratory work load. This was accompanied by a substantial increase in rib cage contribution to VT. REM sleep was associated with a marked decrease in intercostal muscle activity (P less than 0.05) and a diminished rib cage contribution; VT was maintained due to a mean increase of 34% in diaphragmatic muscle activity (P less than 0.05).

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Maximal inspiratory and expiratory mouth pressures (Plmax and PEmax) were measured over a wide age range using a cylindrical mouthpiece and a multiple trial procedure. Two hundred forty-three students and 30 adults were studied. In addition, a comparison of a cylindrical and a scuba-type mouthpiece was made in 16 subjects. Fifty percent of the subjects required five or more trials to achieve their maximal mouth pressures. Higher PEmax values were obtained using a cylindrical mouthpiece than with a scuba-type mouthpiece in 15 of the 16 subjects tested. Plmax was not affected by mouthpiece type. Males had higher Plmax and PEmax values than females except in the 8-10 years age group. Maximal mouth pressures correlated with age in boys only. Technical considerations, such as the number of trials and the type of mouthpiece used, are important determinants of maximal mouth pressure values.

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Maternal deprivation (MDep) of neonatal rats significantly influences the hypothalamic-pituitaryadrenal (HPA) axis. This study hypothesized that GR-mRNA modulation constituted an early, critical mechanism for the acute effects of MDep on neuroendocrine stress-responses. GR-mRNA hybridization signal in hippocampal CA1, hypothalamic paraventricular nucleus (PVN) and frontal cortex was significantly reduced immediately following 24 h MDep. In amygdala, cingulate cortex, PVN and CA1, apparent gender-dependent MDep effects on GR-mRNA expression were observed, without significant differences in absolute levels. Thus, rapid, regionspecific MDep effects on GR-mRNA expression in HPA-regulating areas are shown, consistent with involvement of GR-expression in mechanisms of MDep influence on HPA tone.

Fluticasone propionate is a synthetic steroid for use by the inhaled route. It's high topical potency and low systemic bioavailability make it suitable for use in asthmatic children. A total of 258 children were randomised in a double-blind study to receive fluticasone propionate (50 micrograms bd) as the dry powder formulation inhaled via a Diskhaler inhaler, or matched placebo (with current therapy) for 4 weeks throughout which time diary cards were completed. During clinic visits lung function and adrenal function were measured. Fluticasone propionate produced a significantly greater increase in morning peak expiratory flow rate (PEFR) (adjusted mean difference over days 1-28, 17 l/min (95% CI; 10, 24); P < 0.001) and evening PEFR (adjusted mean difference over days 1-28, 16 l/min (95% CI; 9, 23); P < 0.001). In addition, diary card symptom scores, beta 2-agonist rescue and clinic lung function improved significantly on fluticasone propionate. There were few adverse events and basal plasma cortisol remained within the normal range. In conclusion fluticasone propionate at 50 micrograms bd is superior to placebo (current therapy) in the treatment of childhood asthma with no evidence of adverse effects.

Early-life experiences, including maternal interaction, profoundly influence hormonal stress responses during adulthood. In rats, daily handling during a critical neonatal period leads to a significant and permanent modulation of key molecules that govern hormonal secretion in response to stress. Thus, hippocampal glucocorticoid receptor (GR) expression is increased, whereas hypothalamic CRH-messenger RNA (mRNA) levels and stress-induced glucocorticoid release are reduced in adult rats handled early in life. Recent studies have highlighted the role of augmented maternal sensory input to handled rats as a key determinant of these changes. However, the molecular mechanisms, and particularly the critical, early events leading from enhanced sensory experience to long-lasting modulation of GR and CRH gene expression, remain largely unresolved.To elucidate the critical primary genes governing this molecular cascade, we determined the sequence of changes in GR-mRNA levels and in hypothalamic and amygdala CRH-mRNA expression at three developmental ages, and the temporal relationship between each of these changes and the emergence of reduced hormonal stress-responses. Down-regulation of hypothalamic CRH-mRNA levels in daily-handled rats was evident already by postnatal day 9, and was sustained through postnatal days 23 and 45, i.e. beyond puberty. In contrast, handling-related up-regulation of hippocampal GR-mRNA expression emerged subsequent to the 23rd postnatal day, i.e. much later than changes in hypothalamic CRH expression. The hormonal stress response of handled rats was reduced starting before postnatal day 23. These findings indicate that early, rapid, and persistent changes of hypothalamic CRH gene expression may play a critical role in the mechanism(s) by which early-life experience influences the hormonal stress-response long-term.EARLY-LIFE EXPERIENCE influences both hormonal and behavioral responses to stress throughout life (1-5). In the human, early-life experiences may modulate stress-responses and coping, with long-term implications for emotional health and cognitive function (5). In rats, daily handling during a critical neonatal period leads to a significantly reduced stress response (compared with animals raised without any disturbance) that persists throughout