Diffusion through narrow pores: movement of ions, water and nonelectrolytes through track-etched PETP membranes.

The rates at which ions (86Rb+, [3H]-choline, 36Cl), 3H2O and nonelectrolytes ([14C]-urea, [14C]-glycerol, and [14C]-sugars) equilibrate across track-etched polyethyleneterephthalate (PETP) membranes (isotopic diffusion) have been measured by a 'static' and a 'dynamic' technique under conditions where no net flow takes place; the two techniques give essentially the same results. All tracers diffuse faster the longer the membranes are etched, consistent with an increase in pore size. Water and neutral solutes diffuse at rates that are relatively independent of ionic strength, pH or the presence of divalent cations. Diffusion of cations is decreased by high ionic strength, by reducing pH or by addition of divalent cations; diffusion of chloride is increased by these procedures. Treatment of the membrane with diazomethane to reduce the negative fixed charge decreases diffusion of cations and increases that of anions; diffusion of water and neutral solutes is unaffected by methylation except in the membranes with the narrowest pores (i.e., those etched for the shortest time), in which case diffusion is reduced. We conclude (1) that the special features of flow near a charged surface apply to ions but not to water or nonelectrolytes and (2) that calculation of absolute rates of diffusion leads to values for the radii of pores through track-etched PETP membranes that are in remarkably good agreement with measured values.

A comparison of the pharmacokinetics of theophylline in asthmatic children in the acute episode and in remission.

The pharmacokinetics of theophylline following a single intravenous dose of aminophylline were determined in 8 asthmatic patients in each of the acute, the recovery and the remission phase. The overall results for mean plasma theophylline clearance (78.6 +/- 33.3 ml/kg/h), plasma theophylline half-life (4.14 +/- 1.36 h) and apparent volume of distribution (0.41 +/- 0.066 l/kg) are in accordance with previously published values. There was no general statistically significant difference in any of the pharmacokinetic parameters when results from the acute and remission phases were compared. However, certain patients showed reductions in plasma theophylline clearance in the acute phase of the illness such that a dosage regimen standardised during remission may cause toxicity if continued in the acute episode. It is suggested that monitoring the plasma theophylline levels is desirable in all patients in the acute episode.

Enzymological diagnosis of a group of lysosomal storage diseases. Review of 5-year experience of 1600 patient-sample referrals.

Lysosomal acid hydrolase activities have been measured in extracts of peripheral blood leucocytes of approximately 1600 patients referred from throughout Australia, each of whom was suspected of having a neurolipidosis. Assays for 12 different lysosomal enzymes were performed on each patient as a routine; ten assay systems were based on commercially available substrates, and four used radiolabelled glycosphingolipids prepared in our own laboratory. Of the 85 patients with positive results, 81 were diagnosed as being homozygous-deficient for a particular lysosomal enzyme. These patients comprised nine with GM1-gangliosidosis, 12 with GM2-gangliosidosis (11 of Tay-Sachs' disease and one of Sandhoff's disease), 18 with trihexosylceramide lipidosis (Fabry's disease), eight with beta-galactosylceramide lipidosis (Krabbe's disease), 14 with beta-glucosylceramide lipidosis (Gaucher's disease), two with sphingomyelin lipidosis (Niemann-Pick disease), 13 with metachromatic leucodystrophy and five with alpha-mannosidosis. In addition, four patients were diagnosed as being affected with mucolipidosis Type II (I-cell disease), based on elevated plasma lysosomal enzyme activities, making a total of 85 homozygous-affected patients. Clinically the patients showed wide phenotypic variability within each of the enzyme-deficient states, which did not appear to correlate with the level of "residual" enzyme activity in their leucocyte extracts.

Serum cholesterol levels from birth to maturity.

Normal values for serum levels of total cholesterol, and of low-density and high-density lipoprotein cholesterol from a longitudinal study of children from birth to two years of age, and from cross-sectional studies of four-year-old children, schoolchildren aged from eight to 18 years, and the young adult parents of the two-year-old children are reported. These data will provide a reference range for the normal Australian youth population, and cut-off points in the identification of hypercholesterolaemia.

Evaluation of a state-wide neonatal screening programme.

A screening programme which was already established to detect phenylketonuria in the newborn period in South Australia was extended to include screening for galactosaemia, homocystinuria, hereditary tyrosinaemia, histidinaemia, maple syrup urine disease and severe alpha 1-antitrypsin deficiency for a trial period. Later, screening for hypothyroidism was introduced. Results suggest that screening for galactosaemia and hypothyroidism are useful additions to the programme. Screening for trrosinaemia and alpha 1-antitrypsin deficiency produced a high number of requests for repeat samples, causing anxiety and no positive benefit to patients. Homocystinuria, an eminently treatable condition, was not detected, nor was maple syrup urine disease, a much less readily treatable condition. Histidinaemia was detected only once. Screening for tyrosinaemia, alpha 1-antitrypsin deficiency, maple syrup urine disease and histidinaemia has been discontinued. Newborn screening in South Australia currently includes tests for phenylketonuria, hypothydroidism, galactosaemia and homocystinuria.

Management of phenylketonuria: South Australian experience of 13 cases.

The management and present status of 13 children with phenylketonuria detected on the fifth day of life, who have been treated by diet thereafter for five to eight years, are discussed. In all 10 cases in which there has been continuous adequate dietary control of blood phenylalanine levels, the physical, social and mental development of the children has been normal. In some of these cases there is an unexplained discrepancy between the verbal and performance IQ scores. The present policy is to continue restricting the diet indefinitely, relaxation being permitted conditionally only after the age of seven years.