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Biomedical subjects

S Pedersen

Publications and source records attributed to S Pedersen.

At least 235 records · Page 13Linked to original sources

Erratic absorption of a slow-release theophylline sprinkle product.

The bioavailability and absorption pattern of theophylline from a slow-release theophylline sprinkle preparation were investigated in 12 asthmatic children both in fasting conditions and after a standardized meal. Theophylline given intravenously was used as a reference. Theophylline from the slow-release theophylline product was well absorbed under fasting conditions, but both absorption pattern and bioavailability were severely affected by concomitant food intake: a delay in absorption was found and the bioavailability was reduced from 91% (fasting) to 44% (P less than .001). The erratic absorption of theophylline after food intake complicates safe therapy with the preparation and calls attention to the fact that it is not sufficient to investigate the absorption characteristics of slow-release theophylline preparations under fasting conditions only.

Absorption↗

Treatment of acute asthma in children with rectal administration of aminophylline solution.

In a double-blind cross-over study, 20 children suffering from acute bronchoconstriction were treated with an interval of 90 min with placebo and 9.0 mg theophylline per kg given rectally in aqueous solution. Each child took part on 2 occasions. Fifteen min after both administrations of theophylline there was a significant increase in peak flow (PEF) as compared with placebo treatment (p less than 0.05). The increase in PEF was related to the serum level of theophylline, a significant bronchodilating effect was observed at about 7 mg/l. Substantial inter- and intrapatient variations were found in the improvement of PEF. The absorption of theophylline was rapid. The measured peak serum levels varied from 7.3 to 16.0 mg/l and occurred within 60 min in most patients. The intra-subject variations in the dose-to-dose absorption profiles were generally small and within a range acceptable for clinical use. The solutions allowed an accurate dosage calculation, did not initiate the urge to defecate, and were retained well.

Acute Disease↗

Aerosol treatment of bronchoconstriction in children, with or without a tube spacer.

To assess whether an extension tube between the aerosol source and the patient improves drug-inhalation therapy in children with acute bronchoconstriction, we treated 20 children under double-blind conditions with placebo or terbutaline delivered by a conventional aerosol or an aerosol with a tube spacer. Both terbutaline treatments resulted in a significant increase in forced expiratory volume in one second, as compared with placebo (P less than 0.001), but treatment with the tube-spacer aerosol produced significantly more improvement than did treatment with the conventional aerosol (P less than 0.01). The number of errors in inhalation technique was reduced when the spacer aerosol was used, and this reduction may account for the greater improvement in the children treated with the spacer.

Aerosols↗

Morphological and functional differentiation in epithelial cultures obtained from human skin explants.

The present study was undertaken to characterize primary epithelial cultures obtained from human skin explants as experimental systems for studies of the differentiation process. When human skin explants were incubated at 34-35 degrees C, fibroblastic growth was strongly inhibited, whereas the epithelial growth proceeded unchanged. The lateral growth of the epithelial cells could be divided into two phases - a migratory and a proliferative one. Only cultures incubated at 35 degrees C or below completed the morphological differentiation process before sloughing, whereas no qualitative difference in protein synthesis was observed between cultures incubated at temperatures from 33-37 degrees C. Cultured epidermal cells were labelled with 3H-thymidine and analysed by flow cytometry and cell sorting. Cells sorted from the S- and G2-phase populations were further analysed by autoradiography and a considerable heterogeneity as to the nuclear labelling was disclosed. A large fraction of S-phase cells were found to be totally unlabelled. The grain count distributions revealed similar cell cycle subpopulations as have been shown to occur in vivo. The relationship of these subpopulations to the differentiation process is discussed.

Autoradiography↗

DNA synthesis in mouse epidermis: S phase cells that remain unlabeled after pulse labeling with DNA precursors progress slowly through S.

Epidermal basal cells from hairless mice were isolated after pulse labeling with tritiated DNA precursors and subjected to DNA flow cytometry combined with cell sorting. Cells were sorted from a window in the middle of the S phase, collected on glass slides, and subjected to autoradiography. Unlabeled cells in the middle of the S phase were found in normal mouse epidermis after optimal pulse labeling with tritiated thymidine [( 3H]dThd), in accordance with previous results. The proportion of unlabeled S phase cells was considerably increased among basal cells from mice treated with growth-inhibitory epidermal extracts. Reanalysis and re-sorting of cells previously sorted from mid S showed that unlabeled cells could not be accounted for by G1 contamination. Furthermore, labeling with precursors incorporated into DNA by "de novo" metabolic pathway [( 3H]Urd) did not reduce the proportion of unlabeled S phase cells, either when given alone or when given in combination with the precursor for DNA incorporated by the "salvage" pathway [( 3H]dThd). This strongly indicates that the unlabeled S phase cells do not synthesize DNA continuously, or are synthesizing DNA at a rate below the level of detection. A reduced proportion of unlabeled S phase cells was found in regenerating epidermis. This may be explained by a dilution effect caused by the 3-fold increase in the total number of cells within S phase at this condition. The observation that essentially all cells in mid S phase were labeled during 4 days of continuous labeling with [3H]dThd, indicates that cells in S phase that remain unlabeled after optimal pulse labeling are cycling, albeit slowly. Two-parameter sorting based on DNA and light scatter indicated that slowly cycling cells are larger than the average. These cells may represent a subpopulation of basal cells going through their last division cycle before differentiation.

Animals↗

Nasal inhalation as a cause of inefficient pulmonal aerosol inhalation technique in children.

In order to evaluate whether children can be taught the efficient use of a pressurized terbutaline aerosol with a tube spacer 71 children were given careful instruction in aerosol inhalation technique according to the manufacturer's instructions. Inhalation technique was assessed as being efficient when a child achieved an increase of more than 19% in FEV1 10 min after taking two puffs of terbutaline (each puff = 0.25 mg). After instruction about 37% of children aged 5-7 years and about 80% of children over 7 years were efficient in inhalation technique. Inhalation through the nose after actuation into the mouth accounted for about 50% of treatment failures, with the problem being more frequent in the younger age group. When this error was corrected about 83% of the children were efficient in the technique. Coordination problems and too rapid inspiration after actuation were also common errors. The findings stress the importance of checking all children's inhalation technique before prescribing inhalation therapy. Careful instruction was not enough. The possibility of nasal inhaling should be borne in mind when looking for causes of treatment failure.

Administration, Intranasal↗

Long-term treatment of children with sustained-release theophylline.

After one year of sustained-release theophylline (SRT) treatment, 19 children with severe perennial asthma participated in a 6-week, placebo-controlled, randomized, double-blind cross-over study. The severity of their asthma was evaluated before SRT-treatment (pre-period) and one year later, both during the theophylline period and the placebo period of the double-blind study. Compared with the pre-period, all observed parameters, except the number of extra bronchodilators required, were statistically significantly improved in the placebo period of the double-blind trial performed after one year. In addition, except for peak expiratory flow measured at home and the number of acute attacks, all parameters were significantly improved during the theophylline period when compared with placebo treatment. During this study, mean serum theophylline level was 13.3 mg/l (range 7.8-19.4 mg/l). The results show that theophylline remains efficient after one year's administration. The much better control of the children's asthma following one year of treatment emphasizes the need for regular re-evaluation of children receiving continuous prophylactic treatment.

Asthma↗

Pharmacokinetics of a new theophylline liquid in asthmatic children.

Eleven children suffering from an acute asthma attack were treated with 6 mg theophylline/kg given as a single dose of a new theophylline liquid (Nuelin Liquid, Riker) (day 1). After the initial treatment, 6 mg theophylline per kg body weight was given to the children on an 8-hourly dosage schedule for 3 days. Multiple serum theophylline measurements were made after the initial treatment and again during a steady-state, dose interval (day 5). The mean peak serum theophylline concentration of 58.9 +/- 4.5 mumol/1 on day 1 showed that the initial loading dose should be increased to about 7 mg theophylline per kg when the liquid is used in acute treatment. Peak serum levels were achieved in 96 +/- 7.5 min (day 1) and 71 +/- 5.5 min (day 5). Under steady-state conditions, serum theophylline levels could be maintained continuously within the therapeutic range during the 8-hourly dosage interval in many children. However, the observed peak-to-trough differences indicated that it may be necessary to use 6-hourly dosages. On day 1 no side-effects were observed but five children suffered from minor side-effects during the steady-state treatment.

Adolescent↗

Cathodic trypsin-like immunoreactivity in serum: influence of sex, age, renal function, food and diurnal variation.

Radioimmunologically determined cathodic trypsin-like immunoreactivity (TLI) in serum was positively correlated with age (Spearman's rho = 0.40, p less than 0.001) and negatively correlated with estimated creatinine clearance (Spearman's rho = -0.31, p less than 0.01) in healthy adults (37 women, 27 men) under standard conditions. Women had higher TLI concentrations than men (median value 358 micrograms trypsin standard/l compared with 283 micrograms trypsin standard/l, p less than 0.02). A clinically significant uptake of cathodic trypsin from the intestine to the blood is not likely because no change was found in serum concentrations of TLI and the two major protease inhibitors (alpha 1-antitrypsin and alpha 2-macroglobulin) one hour after a standard meal. No diurnal variation of TLI in serum was found in a group of 12 healthy subjects. The results indicate that due consideration must be given to sex, age and renal function of the persons used in reference groups for TLI determination.

Adult↗

Treatment of children with a single dose a day of sustained release theophylline.

Six children were given a single dose of theophylline (Nuelin Retard) (median dose 13.2 mg/kg) after a large breakfast, rich in carbohydrates, for 4 days. On 5 serum levels of theophylline were measured over the following 24 h. Absorption of theophylline was slow and acceptable peak to trough differences were demonstrated. However subtherapeutic serum levels of theophylline were recorded in all children at some time during the dose interval.

Adolescent↗

Influence of food on the absorption rate and bioavailability of a sustained release theophylline preparation.

Six children and six adults were given a single dose of a sustained release theophylline preparation (Nuelin Retard) after an overnight fast and later after a standardized breakfast. Food significantly reduced the absorption rate of theophylline whereas the extent of absorption of theophylline was unaffected by food. Under steady state treatment the fluctuations in the serum levels of theophylline were small when the tablets were taken after meals twice a day showing that this dose regimen was sufficient. No characteristic absorption or elimination phases were seen during the steady state dose interval, and the time to peak serum theophylline level showed great variation. Serum theophylline control about 4 h after fasting intake of the tablet is recommended.

Adult↗