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Biomedical subjects

S Pedersen

Publications and source records attributed to S Pedersen.

At least 217 records · Page 12Linked to original sources

How to use a rotahaler.

The bronchodilator response after five different modes of salbutamol inhalation by rotahaler was assessed in 15 asthmatic children in a double blind cross over study. Inspiratory flow rates lower than 50 litres/minute were associated with a significant reduction in response compared with flow rates higher than 60 litres/minute, but tilting the head back during inhalation and holding the breath for 10 seconds had no significant effect on bronchodilation. Peak inspiratory flow rates measured in 150 normal children and 13 asthmatic children with acute wheeze showed that many young children and many children with severe bronchoconstriction were unable to generate a sufficiently high inspiratory flow rate to obtain maximum benefit from rotahaler treatment. Children using a rotahaler should be taught to inhale as quickly as possible and not with a quiet deep breath as recommended in the instruction leaflets.

Acute Disease↗

Fenoterol powder inhaler technique in children: influence of inspiratory flow rate and breath-holding.

The bronchodilator response after three different modes of inhalation of 0.2 mg fenoterol from a fenoterol powder inhaler was assessed in ten asthmatic children in a double-blind, placebo-controlled, cross-over study. There was a small, but statistically significant increase in response when the children inhaled as fast as possible, compared with very slow inhalations (16-19 l/min), but a breath-holding pause of 10 s after the inhalation had no significant effect on bronchodilation. Peak inspiratory flow through the inhaler, measured in 150 normal children aged 3.5-15 years, showed that all the children studied were able to generate a sufficient inspiratory flow to benefit from treatment with this inhaler. It is concluded that children using a fenoterol powder inhaler should be taught to inhale as fast as possible. They need not hold their breath after the inhalation.

Adolescent↗

Comparison of Nebuhaler and nebulizer treatment of acute severe asthma in children.

In a double-blind, cross-over study, 21 children with acute severe asthma were treated with terbutaline (0.10 mg/kg) delivered by a pressurized aerosol with a 750 ml spacer (Nebuhaler) or as a nebulized solution by a Pari Inhalier Boy. A significant increase in FEV-1 was seen after both treatments. Furthermore, nebuhaler treatment resulted in significantly greater bronchodilation than treatment with the nebulizer (p less than 0.05). Irritation of mouth and throat and coughing were observed in 12 patients during nebuhaler treatment. These problems were not seen when the nebulizer was used. Eleven children preferred treatment with the nebuhaler, whereas only one child preferred the nebulizer. The main reason for preferring the nebuhaler was the shorter administration time.

Acute Disease↗

Time course of arrest of immunoglobulin expression in heterokaryons and early hybrids of human lymphoma cells and mouse fibroblasts. A study of transcriptional and translational events.

Early events in arrest of immunoglobulin expression were investigated at the levels of both translation and transcription in heterokaryons and early hybrids between human Daudi lymphoma cells and mouse cl. 1D cells. Large populations of 1s: 1s hybrids, isolated by fluorescence-activated cell sorting (FACS) a few hours after fusion, were grown for up to 5 days. A survey at the light-microscopical level of peroxidase-antiperoxidase-immunostained cell populations showed that arrest of expression of IgM heavy chain (mu) occurred in up to 98% of the cells. Furthermore, quantitation of mu chain contents, by using an ELISA technique, suggested that synthesis of IgM was blocked shortly after fusion. The levels of cytoplasmic mRNA specific for mu and kappa chains, respectively, decreased at rates similar to those induced in unfused Daudi cells by treatment with actinomycin D. It is concluded that arrest of immunoglobulin expression in these hybrids occurs immediately or very shortly after fusion by mechanisms that affect the levels of their cytoplasmic mRNAs.

Animals↗

Basal-cell subpopulations and cell-cycle kinetics in human epidermal explant cultures.

Cultured human epidermal cells were studied by cell sorting and autoradiography after different 3H-thymidine (3H-dThd)-labelling procedures and after labelling with DNA precursors that are incorporated via salvage or de novo pathways. It was shown that 3H-dThd incorporation was the best measure of the rate of DNA replication. Dose-response experiments with pulse and continuous labelling revealed that all S- and G2-phase cells were cycling, whereas some 20% of the cells stayed in G1-phase for long periods of time. Most, if not all of these cells were probably non-proliferating differentiated keratinocytes. At least two subpopulations of S-phase cells could be discriminated on the basis of the rate of incorporation of DNA precursors. The difference in precursor incorporation did not seem to be caused by differences in nucleotide metabolism but rather to reflect true differences in the rate of DNA replication. Continuous labelling experiments showed that these subpopulations also were apparent in the G1- and G2-phases. Studies of the grain-count distribution revealed that cells that appeared to move rapidly through the S-phase moved slowly through the G2-phase, and vice versa. Cells stained with acridine orange were subjected to a two-parameter analysis in the cell sorter by simultaneous measurement of the DNA and RNA fluorescence. Autoradiography of sorted cells revealed that, on average, cells with low RNA contents incorporated 3H-dThd at a higher rate than cells with high RNA contents.

Acridine Orange↗

DNA synthesis rate changes during the S phase in mouse epidermis.

The in vivo DNA synthesis rate throughout the S phase of mouse epidermal cells was investigated. Epidermal basal cells were isolated at various times of the day from normal animals injected with [3H]TdR 30 min before sacrifice, and from pulse-labelled animals with regenerating and growth-inhibited epidermis. The cells were analysed by DNA flow cytometry combined with cell sorting. Cells from successive fractions of the S phase were sorted on glass slides and subjected to quantitative [3H]TdR autoradiography. The results confirmed the presence of unlabelled (slowly replicating) cells in the S phase, the proportion of which was circadian stage-dependent with minimum values at midnight and in the early morning. The DNA synthesis rate throughout the S phase showed a general trend with high values in the mid-fractions, a pattern which was similar in normal and in growth perturbed epidermis. In the early morning the DNA synthesis rate pattern was bimodal with maxima both in the first and second half of the S phase, with a corresponding trough in mid-S. At this time of day the cell progression rate through S is at its maximum, indicating a relationship between the overall DNA synthesis rate and the rate distribution pattern through S.

Animals↗

Treatment of nocturnal asthma in children with a single dose of sustained-release theophylline taken after supper.

In a placebo-controlled, double-blind cross-over study of 2 X 3 weeks' duration, twenty-four children with stable asthma who were wheezing during the night, were treated with a single dose of sustained-release theophylline (SRT) taken after supper. The mean serum theophylline levels 4 and 12 hr after dosing were 7.7 and 11.2 mg/l, respectively. Few side-effects were seen. The mean morning peak expiratory flow (PEF) was significantly higher during SRT treatment (244 +/- 11 1/min) than during placebo treatment (207 +/- 121/min) (P less than 0.001). The mean difference between morning and evening PEF was reduced from 20.7 to 8.6% by treatment with SRT (P less than 0.001). Theophylline significantly reduced the severity of attacks of bronchoconstriction during the night as judged by PEF measurement and use of extra bronchodilator treatment per attack. The response to inhaled terbutaline was increased during SRT treatment compared with that in the placebo period, however pre-treatment PEF did differ significantly between the two periods. The number of acute asthma attacks during the night, the number of symptom-free nights and the use of extra bronchodilators during the night were all significantly improved by SRT treatment (P less than 0.001). Seventeen children correctly identified the SRT period whilst six children showed no preference for either period. A single dose of SRT taken after supper is an effective treatment for nocturnal asthma in children.

Adolescent↗

Influence of food on the absorption of theophylline from a sustained release formulation (Somophyllin).

The bioavailability and absorption pattern of theophylline from a sustained theophylline sprinkle product (Somophyllin) were investigated in ten healthy adult volunteers both in fasting conditions and after a standardized solid meal. Theophylline given intravenously was used as a reference. The only effect of the meal was a statistically significant reduction in the rate of absorption of theophylline during the first 2 hr after medication. After that time food had no effect upon the absorption characteristics of the preparation and the bioavailability was complete after both fasted and fed intake of the product (96.1% and 105.9% respectively).

Adult↗

Optimal use of tube spacer aerosols in asthmatic children.

In a double blind cross-over study the bronchodilator response after eight different modes of inhalation of terbutaline from a pressurized aerosol with a tube spacer was assessed in fifteen asthmatic children. Slow inspiratory flow rates (15-30 l/min) were found to be associated with a statistically significant increase in response when compared with flow rates higher than 70 l/min (P less than 0.01). Tilting the head back during the inhalations and a breath-holding pause of 10 sec after the inhalation had no significant effect upon bronchodilation. In addition, bronchodilation was the same whether the children inhaled from RV or FRC, and whether they inhaled as deeply possible or only to about half the maximum volume. The results suggest that efforts should be made to develop a new and more simple set of instructions for the use of tube spacer aerosols.

Adolescent↗

Treatment of acute bronchoconstriction in children with use of a tube spacer aerosol and a dry powder inhaler.

In a double blind cross-over study 24 children suffering from acute bronchoconstriction were treated with either placebo, or terbutaline delivered by a pressurized aerosol with a tube spacer (TS), or salbutamol from a dry powder inhaler (Rotahaler = RO). Both active treatments resulted in a significant increase in FEV1 as compared with placebo (P less than 0.001). Furthermore, TS treatment resulted in significantly greater improvement in FEV1 than treatment with the RO (P less than 0.05). Under the conditions of marked airways obstruction problems with correct handling of the RO (loading and breaking the capsule) were prevalent and many children were unable to empty the RO capsule. These difficulties seemed to account for the smaller bronchodilation after RO treatment and were not seen under quiet circumstances. It is recommended that inhalation therapy in children is supervised by an adult during periods of marked airways disease.

Adolescent↗

Persistent subcutaneous nodules in children hyposensitized with aluminium-containing allergen extracts.

A follow-up study of 202 children who had received hyposensitization with aluminium-containing allergens showed that 1-3 years after cessation of hyposensitization 13 children still had severely pruiginous treatment-resistant subcutaneous nodules in their forearms. Because of their long persistence the nodules of six children were studied in detail. Histologically, the nodules showed infiltration with lymphocytes (forming germinal centres), macrophages, plasma cells, mast cells and a few eosinophils. In five patients aluminium crystals were found scattered between the cells and, in addition, the phagosomes of the macrophages contained aluminium. Patch tests for aluminium were positive in four of the six patients. It is concluded that persisting nodules during hyposensitization with aluminium-containing allergens may indicate development of aluminium hypersensitivity, and if this is confirmed hyposensitization should be discontinued.

Adolescent↗

Escherichia coli ribosomes translate in vivo with variable rate.

The question of whether or not 'rare' codons are translated with the same rate as 'common' codons was investigated by measuring the translation time for two genes, lacI and bla, rich in rare codons, and comparing the results with the translation times measured on fus, tsf, tuf and rpsA which have very few rare codons. The rate of synthesis of the lac repressor was first measured with the up-promoter mutation lacIq1 present on the high copy number plasmid pBR322. In such a strain the average translation times for lacI and bla were 50% slower than the rate calculated from the translation time for the four ribosomal proteins. In a strain having lacIq1 on an F'lac episome this difference was much smaller, thus slow translation of genes rich in rare codons is exaggerated in strains with increased drain on the rare codon tRNAs. The data do not exclude that only a subset of the rare codons is translated more slowly. Translation times were also measured in cells growing in different media, and the translation chain growth rate was found to increase by approximately 40% going from acetate medium to a fully supplemented medium.

Codon↗

Transcriptional organization of the rpsA operon of Escherichia coli.

Three strong and two minor rpsA promoters were found by nuclease S1 mapping, promoter cloning and in vitro transcription. The longest transcript encodes a protein, located upstream from rpsA with a molecular weight of 25,000. The identity of this protein remains to be established. The other rpsA promoters are located within the gene for this 25 K protein. The rpsA leader region including the sequence of the 25 K protein and its promoter was DNA sequenced.

Base Sequence↗

Subpopulations of slowly cycling cells in S and G2 phase in mouse epidermis.

Evidence has been presented supporting the existence of heterogeneity in cell-cycle progression in mouse epidermis, The present study was undertaken to characterize this heterogeneity in more detail. Hairless mice were continuously labelled with tritiated thymidine every 4 hr for 4 days. Basal cell suspensions were prepared from slices of mouse skin at intervals during the experiment and subjected to DNA flow cytometry. Cell-cycle analysis was combined with sorting of cells from windows in G1, S and G2 phase, and the proportion of labelled cells within each window was determined in autoradiographs. Reanalysis and resorting to control the purity of of sorted fractions were performed. Computer simulations of the data were made using a mathematical model assuming different S and G2 phase characteristics. A good fit to the data was only obtained when heterogeneity in mouse epidermal cell-cycle progression was assumed, indicating the existence of slowly traversing, distinct subpopulations of cells in G2 and S phase. These cells are assumed to contribute to about 40% of all cells in S phase and to about 70% of all in G2 phase. The estimated residence times in the resting states were 38 and 32 hr in S and G2 phase, respectively. Two-parameter sorting based on DNA and light scatter indicated that slowly cycling cells were larger than the average. There is no evidence of significant subpopulations of permanently non-proliferating keratinocytes in any of the cell-cycle phases.

Animals↗