Recovery from neonatal myocardial dysfunction after treatment of acute hypertension.

Echocardiography showed gross cardiac dysfunction in a neonate with hypertension secondary to renal artery thrombosis. Cardiac recovery was dramatic after control of hypertension with captopril.

Gluconeogenesis in the suckling rat.

Gluconeogenesis from lactate was increased more than twofold in perfused livers and isolated hepatocytes from 10- and 15-day-old suckling rats compared with adult rats and was not increased by fasting. Glucagon (10(-19)-10(-7) M) induced minimal activation of gluconeogenesis in hepatocytes from such animals even though it promoted accumulation of cAMP. Suckling rats had low plasma insulin levels and high plasma glucagon levels. The presented very low insulin/glucagon ratios were associated with high liver cAMP levels. Contrary to the situation in adult rats, glucagon levels fell with fasting. Insulin levels fell proportionally further so that the insulin/glucagon ratios declined. On the basis of these findings, it is proposed that the high glucagon and low insulin levels in young suckling rats result in high liver cAMP levels with resultant maximal stimulation of hepatic gluconeogenesis so that it cannot be further increased by fasting or exogenous glucagon. It is also suggested that milk is an important stimulus to the hyperglucagonemia of suckling rats in view of its high protein and low carbohydrate content.

Pharmacokinetics of doxapram in idiopathic apnea of prematurity.

Pharmacokinetics of doxapram were determined in 13 infants with idiopathic apnea of prematurity uncontrolled by aminophylline and caffeine. Doxapram was maintained for 72-96 h at a constant infusion rate of 2-2.5 mg/kg/h. Plasma doxapram levels were measured by gas liquid chromatography. The infants studied had a birth weight of 1,247 +/- 240 g (mean +/- SD), a gestational age of 29.4 +/- 2 weeks and were 9.9 +/- 6 days old. Steady-state plasma doxapram levels reached by all infants averaged 5.8 +/- 1.8 mg/l. Half-life was 6.6 +/- 5.7 h, plasma clearance 0.44 +/- 0.1 litres/kg/h, and calculated volume of distribution 4 +/- 2.7 litres/kg. Doxapram controlled apnea successfully in 12 of 13 babies. A significant fall in PaCO2 and reduction in the rate of apnea was seen within 6-8 h with corresponding doxapram levels of 3.7 +/- 1.8 mg/l. The factors influencing the pharmacokinetics of doxapram in newborns are presently unknown.

[Chronic hyperammonemia with orotic aciduria: evidence of pyrimidine pathway stimulation (author's transl)]. / Hyperammoniémie chronique avec acidurie orotique: stimulation de la voie des pyrimidines

We have investigated a 3 year old girl with mental and physical retardation, chronic hyperammonemia and orotic aciduria. Plsma glutamine, alanine and proline concentrations were high. Alanine was present in her urine. She excreted only half the urea of control subjects on a similar protein intake. Raising protein intake induced NH4 intoxication with convulsion. Orotic aciduria was present (max: 693 mg/day) and was related to NH4 levels. Red blood cell orotate phosphoribosyl transferase and orotidine decarboxylase activieé were normal, eliminating congenital orotic aciduria, with induction of activity seen on repeated assay during protein load (form 1.37 to 7.5 nmole/109 RBC/hr). Blood ammonia rose with ornithine load, while ornithine levels were twice that of controls. Citrulline was normally metabolized. Although lacking liver assay, we have provided evidence of partial ornithine carbamyl transferase deficiency. The importance of orotic aciduria for ammonia detoxication in partial OCT deficiency is shown, and its possible effect on liver lipoprotein synthesis discussed. Our investigation also confirmed that OCT activity is not present in normal leukocytes rendering them useless for OCT deficiency diagnosis.

Total body digoxin clearance and steady-state concentrations in low birth weight infants.

Serial serum digoxin concentrations were measured over a 10-day period in 15 low birth weight infants requiring digoxin therapy. The calculated total body digoxin clearance (TBDC) was found to be highly dependent on gestational age and body weight, with dose-normalized, steady-state digoxin concentrations inversely related to the same factors. Because of the decreased TBDC in low birth weight infants, our data support the recent recommendations in the literature to reduce maintenance doses of digoxin in these infants. Our study has further demonstrated that the reduction should be proportional to both gestational age and body weight.