SUMMARY1. In the chronically catheterized fetal lamb, intravenous infusion of adrenaline at 0 5 jug/min produced slowing of the secretion of lung liquid or its absorption, an effect which increased exponentially with advancing gestation. Between 120 and 130 days, the characteristic response was slowing of secretion, whereas after 130 days it was absorption.2. Stimulus-response curves, relating secretion or absorption rate to plasma adrenaline concentration, were obtained by infusing adrenaline into the fetus intravenously at rates between 0-1 and 1.0 #sg/min (0-55-5 5 nmol/min). These curves allowed estimation of the minimum concentration of adrenaline required to inhibit secretion ([Ai]) and this was found to decrease from 0-43 ng/ml. (2-35 nM) at 132-4 days' gestation to 0-029 ng/ml. (0 16 nM) at gestations above 140 days.3. During spontaneous labour there was a slowing of lung liquid secretion in the early stages followed by absorption during the last 50-150 min. The mean concentration of adrenaline in plasma increased from 0-087 ng/ml. (048 nM) in early labour to 6-86 ng/ml. (37 5 nM) in the last 50 min and to 7-17 ng/ml. (39-2 nM) in the early post-natal period. Mean noradrenaline levels at the same times were 1-71 ng/ml.(10-1 nM), 12-14 ng/ml. (71'8 nM) and 9-10 ng/ml. (53 9 nM). The relationship between the plasma adrenaline concentration and the rate of absorption during labour was similar to that found when adrenaline was infused at various rates into the non-labouring fetus of comparable gestational age.4. The upper airway of the fetus was shown to be capable of acting as a one-way valve allowing outflow but not inflow of liquid. Thus withdrawal of liquid at 5-20 ml./hr from the fetal trachea below the larynx caused closure of the upper airway and this result was obtained both when the recurrent laryngeal nerves were intact and when they were divided.

SUMMARY1. Adrenaline was infused intravenously at rates of 0 1-10 tg/min into chronically catheterized fetal lambs (125-141 days gestation) to induce slowing of secretion or reabsorption of lung liquid.2. There was an electrical potential difference (p.d.) of -0 3 to -9-5 mV (mean -3.4 mV) between lung liquid and plasma (lung liquid negative) during control lung liquid secretion. In response to adrenaline infusion, the p.d. increased (lung lumen more negative) and this change was greatest (1-8+0±3 mV) in experiments in which reabsorption occurred.3. Measurements were made of bidirectional fluxes of Na+ and Cl-across the pulmonary epithelium during control lung liquid secretion and during adrenaline infusion. Adrenaline-induced reabsorption of lung liquid was associated with an increase in Na+ flux from lung lumen to plasma. Similar but smaller changes occurred when the adrenaline response was slowing of secretion.

Molybdenum cofactor deficiency (MoCD) is a rare metabolic disorder characterized by severe and rapidly progressive neurologic damage caused by the functional loss of sulfite oxidase, 1 of 4 molybdenum-dependent enzymes. To date, no effective therapy is available for MoCD, and death in early infancy has been the usual outcome. We report here the case of a patient who was diagnosed with MoCD at the age of 6 days. Substitution therapy with purified cyclic pyranopterin monophosphate (cPMP) was started on day 36 by daily intravenous administration of 80 to 160 microg of cPMP/kg of body weight. Within 1 to 2 weeks, all urinary markers of sulfite oxidase (sulfite, S-sulfocysteine, thiosulfate) and xanthine oxidase deficiency (xanthine, uric acid) returned to almost normal readings and stayed constant (>450 days of treatment). Clinically, the infant became more alert, convulsions and twitching disappeared within the first 2 weeks, and an electroencephalogram showed the return of rhythmic elements and markedly reduced epileptiform discharges. Substitution of cPMP represents the first causative therapy available for patients with MoCD. We demonstrate efficient uptake of cPMP and restoration of molybdenum cofactor-dependent enzyme activities. Further neurodegeneration by toxic metabolites was stopped in the reported patient. We also demonstrated the feasibility to detect MoCD in newborn-screening cards to enable early diagnosis.