PubMed Health⌕ Search

Biomedical subjects

S Pedersen

Publications and source records attributed to S Pedersen.

At least 127 records · Page 7Linked to original sources
PubMed1994

High concentrations of ppGpp decrease the RNA chain growth rate. Implications for protein synthesis and translational fidelity during amino acid starvation in Escherichia coli.

We show that the RNA chain growth rate on lacZ is reduced by an elevated ppGpp level even in the absence of starvation. Under these conditions the polypeptide chain elongation rate is affected little, if at all. These results lead us to re-examine the role of ppGpp in the reduction of protein synthesis and translational fidelity during amino acid starvation. We find that ppGpp has little or no direct effect on translation rate or fidelity. Rather, the effects of ppGpp on translation are indirectly caused by the fact that ppGpp inhibits mRNA synthesis, making mRNA limiting for translation during amino acid starvation. The reduced level of mRNA thereby reduces the severity of the aminoacyl-tRNA limitation and, in turn, decreases mistranslation. Mistranslation in the starved relA strain therefore results from an increased severity of aminoacyl-tRNA limitation due to the failure of this strain to reduce mRNA levels by increasing the level of ppGpp. Finally, the initial rise of the ppGpp level in the starved stringent strain, followed by a characteristic reduction to a steady poststarved level, can now be explained by the initially high, and then decreasing number of "hungry" codons adjusted through the mRNA pool.

Amino Acids↗
PubMed1994

Teleconsultation of patients with otorhinolaryngologic conditions. A telendoscopic pilot study.

OBJECTIVE: We have integrated endoscopic equipment with a network of video conference studios to develop a remote consultation service for diagnoses of patients with otorhinolaryngologic conditions. DESIGN: The study was performed as a diagnostic test in three phases. During the first phase, a general practitioner was instructed in otorhinolaryngologic examination techniques. In the second phase, remote endoscopic examinations were simulated and the diagnostic results were compared with results from a standard examination. In the third phase, the general practitioner made real telendoscopic examinations. SETTING: Signals from a video camera attached to the endoscope are transmitted from the primary care center to the otorhinolaryngologist who is 180 km away via a 2-million-bits-per-second circuit. The specialist observes the endoscopic examination on a monitor and influences the control and movement of the endoscope by communicating over a two-way sound-and-picture connection with the general practitioner. PATIENTS: A convenience sample of 24 patients was examined in the last two phases. RESULTS: Although the video image is compressed before transmission over the telecommunications network, our results show that the quality of the transmitted images was equivalent to the quality of the images from a standard endoscopic examination. CONCLUSIONS: Our study has shown that this method of consultation may be used in the clinic with the same degree of reproducibility as in a conventional consultation situation. This enables us to give patients in remote locations better service at a lower cost.

Adolescent↗
PubMed1994

Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children.

In a controlled prospective study we have measured growth and pulmonary function in children with asthma during long-term treatment with inhaled budesonide and compared these findings with those obtained from children not treated with corticosteroids. Two hundred and sixteen children were followed at 6 monthly intervals for 1-2 years without inhaled budesonide and then for 3-6 years on inhaled budesonide. Sixty-two children treated with theophylline, beta 2-agonists and sodium-cromoglycate but not with inhaled steroids were also followed for 3-7 years (controls). During the period of budesonide therapy the mean daily dose decreased from 710 to 430 micrograms (P < 0.01) and no signs of tachyphylaxis to the treatment were seen. Budesonide treatment was associated with a significant reduction in the number of annual hospital admissions due to acute severe asthma (from 0.03 to 0.004 per child, P < 0.001). In patients not treated with budesonide an annual decrease in % predicted FEV1 of 1-3% was seen. In contrast FEV1 improved significantly with time during budesonide treatment, both compared with the run-in period and with the control group (P < 0.01). Furthermore, there was a significant (P = 0.01) relationship between the duration of asthma at the start of budesonide and the annual increase in FEV1 during budesonide therapy. After 3 years of treatment with budesonide, children who started this therapy later than 5 years after the onset of asthma had significantly lower FEV1 (96%) than the children who received budesonide within the first 2 years after the onset of asthma (101%) (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1994

Inspiratory capacity through the Turbuhaler in various patient groups.

The effect of the Turbuhaler depends upon the inspiratory flow rate generated by the patient during the inhalation. In children both the peak inspiratory flow rate and the volume of air inhaled at that inspiratory flow rate are important. An inspiratory flow rate greater than 30L/min is usually considered sufficient to achieve an optimal effect. The exact volume which should be inhaled at flow rates above that level is not known. It is probably low (around 0.1-0.2L). In our clinic, virtually all children older than 5 years can inhale a sufficient volume at an inspiratory flow rate greater than 30L/min after careful tuition. With decreasing age an increasing proportion of children will be unable to inhale a sufficient volume at a flow rate greater than 30L/min, and generally children younger than 5 years should not be prescribed Turbuhaler treatment unless they have shown they are able to use it optimally. Both inspiratory flow rate and inhaled volume are decreased during episodes of acute wheeze. In clinical practice this is only important in the young age groups. The vast majority of school children will still be able to benefit optimally from Turbuhaler treatment during episodes of acute wheeze. Although there is a correlation between expiratory pulmonary function and peak inspiratory flow rate, measurement of expiratory pulmonary function cannot be used to predict whether an individual child can use the Turbuhaler optimally.

Administration, Inhalation↗
PubMed1994

Clinical efficacy and safety of budesonide Turbuhaler as compared to MDIs in children.

Pharmacokinetic studies in children indicate that budesonide by Turbuhaler results in higher intrabronchial deposition of drug but a higher systemic activity than the same dose of budesonide inhaled from a Nebuhaler. Furthermore, around 85% of the total systemic activity is caused by drug absorbed from the lungs. Therefore, subsequent studies have been performed to compare the clinical and/or systemic effect of these two inhalers. The findings in all these studies were in agreement with the findings of the pharmacokinetic studies: (1) In a double-blind crossover study, urinary cortisol excretion was reduced during Turbuhaler but not during Nebuhaler treatment. At the same time the Turbuhaler seemed clinically more effective than the Nebuhaler. (2) A double-blind parallel-group study on 126 children showed no deterioration in asthma control when the dose of budesonide was reduced by 50% when the children used the Turbuhaler. When the Nebuhaler was used a dose reduction resulted in deterioration of asthma control. (3) When the dose of budesonide delivered to the patient was measured by analysing the amount of drug deposited on a filter inserted between the patient's lips during inhalation, it was found that twice as much budesonide was deposited after Turbuhaler as after Nebuhaler treatment. (4) When the dose of budesonide required by 224 children followed in our outpatient clinic was recorded, we found that the mean daily dose in children using the Turbuhaler was 50% lower than the dose required by children using the Nebuhaler.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1994

Knemometric assessment of systemic activity of once daily intranasal dry-powder budesonide in children.

Systemic activity of the intranasal glucocorticosteroid budesonide administered once daily from a dry-powder inhaler (Turbuhaler) was assessed by knemometry. Lower leg length was measured weekly in 38 children aged 7-15 (mean 11.3) years with allergic or perennial rhinitis. The design was a randomized, double-blind, parallel-group study. After 4 weeks' run-in, the children were allocated to 4 weeks' treatment with either budesonide 200 or 400 micrograms or placebo. Fourteen children in the budesonide 200-micrograms group, 13 in the 400-micrograms group, and 10 in the placebo group completed the study. In the placebo and budesonide 200-micrograms groups, growth velocities during run-in (0.36 and 0.28 mm/week, respectively) and treatment periods (0.34 and 0.27 mm/week, respectively) were almost identical. In the budesonide 400-micrograms group (run-in: 0.40 mm/week), a nonsignificant reduction in mean growth velocity of 0.18 mm/week was seen (P = 0.11). There were no statistically significant differences among the run-in mean lower leg growth velocities (F = 1.12; P = 0.34), among growth velocities during treatment (F = 1.10; P = 0.34), or among the run-in and treatment growth velocities in the three groups (F = 1.19; P = 0.32). These results provide good evidence that systemic activity is low in children with allergic or perennial rhinitis treated with once daily budesonide in doses of 200- and 400-micrograms administered intranasally from a dry-powder inhaler.

Administration, Inhalation↗
PubMed1994

Concentrations of 4.5S RNA and Ffh protein in Escherichia coli: the stability of Ffh protein is dependent on the concentration of 4.5S RNA.

We measured the concentrations of both 4.5S RNA and Ffh protein under a variety of growth conditions and found that there were 400 molecules of 4.5S RNA per 10,000 ribosomes in wild-type cells and that the concentration of Ffh protein was one-fourth of that. This difference in concentration is 1 order of magnitude less than that previously reported but still significant. Pulse-chase labeling experiments indicated that Ffh protein is unstable in cells carrying ffh on high-copy-number plasmids and that simultaneous overproduction of 4.5S RNA stabilizes Ffh protein. Our analyses show that free Ffh protein is degraded with a half-life of approximately 20 min. We also tested whether three previously isolated suppressors of 4.5S RNA deficiency could reduce the requirement for Ffh protein. Since the two sffE suppressors do not suppress the Ffh requirement, we suggest that 4.5S RNA either acts in a sequential reaction with Ffh or has two functions.

Acetates↗
PubMed1994

Effect of 4.5S RNA depletion on Escherichia coli protein synthesis and secretion.

We examined the synthesis of individual proteins following depletion of 4.5S RNA by using a strain deficient in the induction of heat shock proteins. We found that initially the synthesis of all proteins was equally affected, and the peptide elongation rate was reduced by approximately 10%. For up to 1 generation time after the onset of inhibition of total protein synthesis, the processing of secreted proteins was unaffected. After further depletion of 4.5S RNA, accumulation of precursors of secreted proteins was observed under some growth conditions.

Bacterial Proteins↗
PubMed1994

Influence of spacer device on drug delivery to young children with asthma.

The budesonide dose delivered to the patient from three different spacer devices (Nebuhaler = 750 ml, Aerochamber = 140 ml, and Babyspacer = 260 ml) was assessed by measuring the budesonide dose deposited on a filter inserted between the spacer outlet and the mouth of the patient. Twenty children aged 10-25 months were given a single dose of 200 micrograms budesonide from each spacer device in a randomised crossover study. All spacers had a facemask attached and a one way valve system. The children breathed through the inhalation system for 30 seconds. Furthermore, the minute ventilation of the children through a tightly fitting facemask was measured. The filter dose of budesonide was significantly lower after Aerochamber treatment (39.4 micrograms, range 19-67 micrograms) than after Nebuhaler (53.5 micrograms, range 34-88 micrograms) and Babyspacer (55.5 micrograms, range 39-76 micrograms) treatment. The minute ventilation of the children varied from 1.4 l/min to 7.0 l/min (mean 5.0 l/min). This was sufficient to empty all spacers within the 30 seconds of inhalation. It is concluded that spacer volume does not seem to be so important for children aged 10-25 months as long as spacers with a volume lower than 750 ml are used.

Administration, Topical↗
PubMed1994

The insulin-like growth factor axis and collagen turnover during prednisolone treatment.

Serum concentrations of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3), the carboxyterminal propeptide of type I collagen (PICP), the carboxyterminal pyridinoline crosslinked telopeptide of type I collagen (ICTP), and the aminoterminal propeptide of type III procollagen (PIIINP) were studied in 10 prepubertal children with asthma (mean age 9.0 years). The children were treated with 2.5 and 5.0 mg/day prednisolone in a randomised double blind crossover trial with run in, treatment, and washout periods of two weeks. No statistically significant effects on serum concentrations of IGF-I and IGFBP-3 were found. Dose related reductions of PICP, ICTP, and PIIINP were observed: the mean (SEM) reduction in PICP was 33.4 (26.3) and 68.4 (20.6) micrograms/l, in ICTP 2.5 (0.5) and 2.9 (0.6) micrograms/l, and in PIIINP 2.1 (0.7) and 3.1 (1.8) micrograms/l during the 2.5 and 5.0 mg prednisolone periods respectively. Short term treatment with low daily doses of prednisolone is associated with suppression of serum markers of type I and III collagen turnover in children with asthma. Intermediate and long term effects remain to be studied.

Asthma↗
PubMed1994

Pseudodicentric chromosome 18 diagnosed by chromosome painting and primed in situ labelling (PRINS).

We report on a newborn white male infant with marked dysmorphic features and various congenital malformations. The initial clinical evaluation showed Crouzon-like features as well as some features of trisomy 18 syndrome and trisomy 13 syndrome. The results from conventional cytogenetic analysis showed a structurally abnormal chromosome replacing one normal chromosome 18, but only by applying molecular cytogenetic methods could the architecture of this abnormal chromosome be characterised clearly. The primed in situ labelling (PRINS) technique, using a newly synthesised alpha 18 oligonucleotide, showed the dicentric pattern and direct chromosome painting established the origin to be from chromosome 18. The combination of conventional cytogenetics and molecular cytogenetics showed the karyotype in the proband to be 45,XY,-14,-18,-21,+t(14;21),+psu dic(18) (qter-->cen-->p11.3: :p11.3-->psu cen-->qter). This was supported by molecular analysis using chromosome 18 specific DNA markers, which showed the paternal origin of the abnormal chromosome.

Abnormalities, Multiple↗
PubMed1994

Value of chromosome painting in determining the chromosomal outcome in offspring of a 12;16 translocation carrier.

We currently use direct and reverse chromosome painting in prenatal diagnosis. In a family with a subtle 12;16 translocation, adjacent 1 segregation was diagnosed in the first child, a boy, in whom symptoms compatible with partial trisomy 16p and partial monosomy 12q were seen. In the next pregnancy, a chorionic villus biopsy was tested using chromosome painting. Only by supplementing conventional cytogenetic methods with molecular cytogenetic techniques could the true karyotype be unequivocally determined. Reverse painting, using DOP-PCR amplified, flow sorted paternal derivative chromosomes as a DNA library to paint the chorionic villus cells, was especially informative.

Abnormalities, Multiple↗
PubMed1994

Use of budesonide Turbuhaler in young children suspected of asthma.

The question addressed in this study was the ability of young children to use a dry-powder inhaler, Turbuhaler. One hundred and sixty five children suspected of asthma, equally distributed in one year age-groups from 6 months to 8 yrs, inhaled from a Pulmicort Turbuhaler, 200 micrograms budesonide-dose-1, through a filter. The amount of drug trapped by the filter was used as a measure of drug released to the patient. None of the children had prior experience in the use of a Turbuhaler, but they were instructed carefully, together with their parents, in the clinic. The median dose released revealed an age-dependent increase, with a considerable scatter. Accordingly, the dose delivered could not be predicted in these young children. The limitation to effective use in young children appeared to be lack of sufficient co-operation, rather than physical limitations, as even some very young children appeared to obtain a sufficient activation of the device. It is likely that repeated training at home may improve these findings. In conclusion, our results indicate that dry-powder inhalers are not reliable in all circumstances for treatment of young children, and that careful and repeated tuition is required if such devices are to be used.

Asthma↗
PubMed1993

Synthesis of proteins in Escherichia coli is limited by the concentration of free ribosomes. Expression from reporter genes does not always reflect functional mRNA levels.

Induction of beta-galactosidase from high copy-number plasmids was found to reduce the synthesis of other cellular proteins in Escherichia coli. The reduction depends on the protein in question and on the induction level of the beta-galactosidase. It could be observed transiently within one minute after induction and in some cases also during steady-state induction. Our interpretation is that the concentration of the free ribosomal subunits decreases after induction, leading to an increased competition among the individual ribosome binding sites for ribosomes. The immediate reduction in the synthesis individual proteins after induction of beta-galactosidase was used as an assay to measure in vivo the efficiency of a ribosome binding site. These efficiencies were compared to the calculated affinities between the ribosome binding site of specific mRNA species and the 3' end of 16 S RNA. For several mRNAs with similar Shine-Dalgarno sequences, the sensitivity to competition differed twofold. Our results show, that both transiently during induction of lacZ and also at very high steady-state expression levels, the expression from reporter genes, including the lacZ gene itself, does not reflect the levels of the mRNAs in a simple way.

Bacterial Proteins↗
PubMed1993

Bone turnover in asthmatic children treated with oral prednisolone or inhaled budesonide.

Biochemical markers of bone turnover were studied in prepubertal school children with asthma in two randomized double-blind crossover trials with run-in, treatment, and wash-out periods of 2 weeks. One group (n = 11) was treated with 2.5 and 5.0 mg prednisolone, the other (n = 14) with 200 and 800 micrograms inhaled budesonide per day. Serum osteocalcin, serum total alkaline phosphatase, fasting urinary excretion of hydroxyproline and calcium, serum 25-hydroxyvitamin D, and 1,25 dihydroxyvitamin D were assessed. A dose-related reduction of serum osteocalcin (Page's test for trend: P = 0.04; z = -2.3) and of the fasting urinary hydroxyproline:creatinine ratio (Page's test for trend: P = 0.05; z = -2.0) was found in the children who were treated with prednisolone. Inhaled budesonide was not associated with statistically significant effects on any of the biochemical markers. Short-term treatment with low daily doses of prednisolone may cause a suppression of bone turnover in children with asthma. To reduce the risk of adverse effects on bone turnover, doses of inhaled budesonide up to 800 micrograms daily may be preferable to low doses of prednisolone. Bone turnover remains to be evaluated during long-term treatment.

25-Hydroxyvitamin D 2↗