No abstract

Twenty-three children, who were detected by neonatal PKU screening, were followed for 8-18 years in one paediatric centre. Dietary treatment was started if the blood phenylalanine level exceeded 0.72 mmol/l. All 23 infants were initially given a low phenylalanine diet. The growth and development rates of the children did not differ significantly from those in a reference population, although one child had mild mental retardation and another had a short attention span. Fourteen children were still on a strict phenylalanine-restricted diet on their last follow-up (at 8-18 years of age). In nine children who were initially put on a low phenylalanine diet, it was possible to normalize the diet between 1/2 and 10 years of age, while maintaining the blood phenylalanine levels between 0.25 and 0.72 mmol/l. It seems likely that those of our patients who markedly increased their phenylalanine tolerance during childhood had a regulatory mutation of the phenylalanine hydroxylase system. A continuous reevaluation of each child treated with a low phenylalanine diet reduces the use of unnecessarily restricted diets.

No abstract

The use of lidocaine as an oral antiarrhythmic drug is limited by its rapid disposition in the liver. In accordance with this we found that the drug was completely extracted during one passage through the perfused rat liver. The drug binds to rat liver microsomes with a type I spectral change of unusually high affinity. It is rapidly de‐ethylated by the microsomes with an apparent Vmax of about 15 nmol per mg protein × min. The apparent Km for this reaction is about 250 μM. The reaction occurres at about the same rate in isolated rat liver cells. We believe that the high affinity of lidocaine for the cytochrome P‐450 system, as indicated by its type I spectral change, as well as the rapid oxidation of the drug are the two main determinants for the marked liver extraction and first pass effect of the drug.