Measures of systemic activity of inhaled glucocorticosteroids in children: a comparison of urine cortisol excretion and knemometry.
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Administration, Inhalation↗
Biomedical subjects
S Pedersen
Publications and source records attributed to S Pedersen.
Budesonide treatment of moderate and severe asthma in children: a dose-response study.
OBJECTIVE: The purpose of the study was to evaluate the dose-response relationships of the inhaled corticosteroid budesonide in a double blind crossover study in 19 children with moderate and severe asthma. METHODS: A 2-week placebo treatment period (run-in) was followed by three 4-week treatment periods during which 100, 200, and 400 micrograms of budesonide were given per day in randomized order. Urinary cortisol excretion, lung functions, and protection against exercise-induced asthma were assessed at the end of run-in and each treatment period. Furthermore, morning and evening peak expiratory flow rates, day and night symptoms, and use of rescue beta 2-agonists were recorded throughout the study. RESULTS: One hundred micrograms of budesonide per day markedly improved symptoms, morning and evening peak expiratory flow rates, and use of rescue beta 2-agonists (p < 0.01). No further improvement was seen in these parameters with increasing doses of budesonide. In contrast, a significant dose-response effect was found on lung functions measured at the hospital and fall in lung functions after exercise (p < 0.001); 200 micrograms was significantly better than 100 micrograms, and 400 micrograms was significantly better than 200 micrograms. About 53% of the maximum effect against exercise-induced asthma was achieved by the lowest budesonide dose (p < 0.001), and about 83% by the highest dose. No significant differences were seen in urinary cortisol excretion between run-in and the various budesonide doses. CONCLUSIONS: Low doses of budesonide, which are not associated with any systemic side effects, have a marked antiasthma effect in children. Protection against exercise-induced asthma requires higher doses than achievement of symptom control.
Adolescent↗
Tele-endoscopic otorhinolaryngological examination: preliminary study of patient satisfaction.
OBJECTIVE: Modern telecommunications and computer technologies enable the delivery of expert consultations and remote diagnoses that previously required transportation of patients or medical specialists. The purpose of this study was to determine whether patients are satisfied with one form of telemedicine consultation. METHODS: A general practitioner was trained to perform endoscopic otorhinolaryngological examinations. After the training period, he examined patients at a local health center in Alta, 250 km from Tromsø. Images from the endoscopic examination were transmitted to the otorhinolaryngologist at the University Hospital of Tromsø for real-time consultation. Twenty-six patients, on a randomly selected day, were asked to complete a questionnaire after the tele-endoscopic examination. The questionnaire was returned anonymously by 24 of the patients. RESULTS: Although patients interacted with the specialist only via videoconferencing, the results show that most (23/24) were satisfied with this type of consultation, and they reported more advantages than disadvantages. Twenty-one patients indicated that they would accept another tele-endoscopic consultation if they required examination by an otorhinolaryngologist in the future. CONCLUSION: Although the sample is limited, the results justify continued investigation of this and other types of telemedicine consultations.
Adult↗
Influence of budesonide on the response to inhaled terbutaline in children with mild asthma.
The aim of this study was to evaluate if continuous treatment with budesonide or salmeterol influences the bronchodilator response to terbutaline in children with asthma; 23 children, aged 7 to 16 years (mean = 11 years), with mild asthma were treated with inhaled budesonide 100 micrograms b.i.d. and placebo for three weeks in a randomized, double blind crossover study. These treatments were followed by treatment with inhaled salmeterol 50 micrograms b.i.d. for 3 weeks. On the last day of each period a cumulative dose-response experiment with terbutaline in the doses 50, 100, 250 and 500 micrograms (cumulative dose 900 micrograms) was performed. Lung function was measured before and 20 min after each terbutaline inhalation. Baseline pulmonary functions after budesonide treatment were significantly higher than the baseline measured after the two other treatments (p < 0.05). After budesonide treatment, the dose-response curve was shifted vertically upwards but otherwise parallel to the dose-response curve after placebo. The increase from baseline after the first cumulative dose of terbutaline was significantly lower after salmeterol treatment than after the two other treatments (p < 0.01). Maximal lung functions after 900 micrograms terbutaline also differed significantly between the three dose-response days; budesonide being significantly higher and salmeterol significantly lower than placebo (p = 0.02 and p < 0.001, respectively). It is concluded that budesonide treatment does not enhance the brochodilator response to terbutaline. Further studies are needed to assess if long-term continuous salmeterol treatment reduces the response to terbutaline.
Administration, Inhalation↗
The insulin-like growth factor axis and collagen turnover in asthmatic children treated with inhaled budesonide.
Serum concentrations of growth hormone-dependent insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3), the carboxy terminal propeptide of type I procollagen (PICP), the carboxy terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) and the amino terminal propeptide of type III procollagen (PIIINP) were studied in 14 prepubertal children with asthma (mean age 9.7 years) during treatment with inhaled budesonide. The study design was a randomized, crossover trial with two double-blind treatment periods (200 and 800 micrograms) and one open, non-randomized treatment period (400 micrograms). All periods were 18 days' duration. Budesonide treatment was associated with a dose-related suppressive trend in serum concentrations of PIIINP when the 400 micrograms period was included (p < 0.01; z = -2.7) and when it was excluded from the calculations (p < 0.01; z = -2.6), indicating reduced synthesis of type III collagen. A similar trend was observed in ICTP levels when the 400 micrograms period was excluded from the calculations (p = 0.05; z = -1.9). No other statistically significant variations were seen.
Administration, Inhalation↗
The cmk gene encoding cytidine monophosphate kinase is located in the rpsA operon and is required for normal replication rate in Escherichia coli.
A gene encoding a polypeptide of 25 kDa is located immediately upstream of the gene for ribosomal protein S1, rpsA. In high gene copy number, this gene, mssA, was previously found to suppress defects in smbA, which is now known to be identical to pyrH, encoding UMP kinase. We show here that the 25-kDa polypeptide comprises CMP kinase and propose that the gene be designated cmk. In a strain deleted for cmk, the pools of CMP and dCMP were elevated approximately 30-fold. We constructed a plasmid from which synthesis of CMP kinase was regulated by the lac promoter-operator and measured the synthesis rates for RNA and DNA after induction in the delta cmk/lacPO-cmk+ strain. A specific increase in the rate of DNA synthesis was observed. Further analyses showed that the replication elongation rate was halved in the delta cmk strain, most likely caused by the reductions of the dCTP and dTTP pools to 30 and 70%, respectively, of the levels in the parental strain, but that this was compensated for by a doubling in the frequency of initiation. The delta cmk strain is viable at 37 degrees C but cold sensitive. The cold sensitivity may be related to defects in the synthesis of phospholipids or lipopolysaccharides. In addition to the physiological studies, the region upstream of cmk was sequenced, and 120 codons with strong homology to an uncharacterized protein of the speB operon were identified.
Base Sequence↗
Symptoms of the musculoskeletal system and exposure to magnetic fields in an aluminium plant.
OBJECTIVE: The study was performed to examine the influence of the exposure to magnetic fields in the potrooms of an electrolysis plant on the occurrence of musculoskeletal symptoms among the employees. The study was performed after much discussion and worry in the aluminium industry about this issue. METHODS: A retrospective cohort study was performed at an aluminium plant. The occurrence of musculoskeletal symptoms registered at health controls performed by the occupational health care unit in 1986 and 1991 was assessed from employees exposed to magnetic fields in the potrooms (n = 342) and from a control group (n = 277). The data were collected before the discussion about the effects of magnetic fields started. The exposure to static magnetic fields was found to be 3-20 mT inside the potrooms. Ripple components (alternating currents (AC fields)) were registered as well. RESULTS: No difference between the exposed and unexposed groups was found for the reported musculoskeletal symptoms in 1986 or in 1991. CONCLUSIONS: There seems to be no relation between work in potrooms with exposure to static magnetic fields and the occurrence of musculoskeletal symptoms.
Adult↗
[Pseudocroup treated with inhaled steroid (budesonide). A double-blind placebo-controlled trial].
The aim of this prospective, randomised, double blind study was to evaluate whether inhaled nebulized corticosteroid is effective in the treatment of croup. Thirty-seven children (aged 0.4-4.9 years) admitted to hospital with moderate to severe croup were allocated to treatment with either 2 mg nebulized budesonide (20) or saline (17). Disease severity was assessed by a clinical croup score based on stridor, cough, retractions, dyspnoea and cyanosis, and the overall clinical assessment was scored on a visual log scale (0-100). Two hours after treatment there was a significant improvement in croup score in the group treated with budesonide (8 to 4.5), but not in the group treated with saline (8 to 8). Furthermore, the overall clinical assessment score decreased significantly (50 to 25) in the group treated with budesonide, whereas it remained constant in the placebo group (60 to 62). The results indicate that nebulised budesonide can be used as a safe and effective alternative treatment in children with moderate to severe croup.
Administration, Inhalation↗
[Telemedicine--a review].
Modern telecommunication technology enables medical information and images to be transmitted from the general practitioner to a hospital or between hospitals. This allows the specialist to interactively conduct and control the examination carried out by the GP via the two way sound and picture connection within radiology, pathology, dermatology, psychiatry, cardiology and otorhinolaryngology. The diagnostic quality of the technique is equal to that of an ordinary examination. The method gives the patients access to adequate medical expertise in their home environment, is highly effective and saves cost of transport. The patients are satisfied with being able to meet the experts this way.
Norway↗
[Clinical research, teaching and quality assurance in an electronic network].
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Computer Communication Networks↗
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↗
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↗
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↗
Primed in situ labeling (PRINS) and fluorescence in situ hybridization (FISH).
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Base Sequence↗
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↗
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↗
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↗
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↗