[Inhaled steroids and growth inhibition].
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Administration, Inhalation↗
Biomedical subjects
S Pedersen
Publications and source records attributed to S Pedersen.
Short term linear growth in asthmatic children during treatment with prednisolone.
OBJECTIVE: To see whether small daily doses of prednisolone have any adverse effect on short term linear growth in children with mild asthma. DESIGN: Double blind, random order crossover trial of two dosages of prednisolone. During run in and washout periods patients were given placebo. All treatment periods were of two weeks' duration. SETTING: Outpatient clinic referrals in a secondary referral centre. PATIENTS: 14 Children (10 boys) aged 7-11 years with normal growth velocity during the previous year, no signs of puberty, and no history of receiving systemic or topical steroids during the two months before the study. One child was excluded because his pulmonary function deteriorated and another was withdrawn because of varicella. INTERVENTIONS: 2.5 and 5.0 mg prednisolone daily given in divided dosage in the morning and evening. MAIN OUTCOME MEASURE: Growth of the lower leg as measured twice a week by knemometry. RESULTS: A significant reduction in mean growth velocity of the lower leg occurred in both prednisolone treatment periods. The mean difference between the run in period and the treatment period with 2.5 mg prednisolone daily was 0.63 mm/week (95% confidence interval 0.47 to 0.80 mm/week) and between the run in period and the treatment period with 5.0 mg prednisolone daily 0.57 mm/week (0.38 to 0.77 mm/week). CONCLUSION: Small daily doses of prednisolone suppress short term linear growth in children with mild asthma. The clinical relevance of this finding needs further study.
Adolescent↗
Extinction of an immunoglobulin kappa promoter in cell hybrids is mediated by the octamer motif and correlates with suppression of Oct-2 expression.
When immunoglobulin-expressing B cells are fused with fibroblasts, immunoglobulin expression is rapidly and selectively suppressed. here we demonstrate that the conserved octamer motif of a kappa light chain gene promoter plays a crucial role in mediating this "extinction" phenomenon. Replacement of this octamer site by an Sp1 or NF1 binding site is sufficient to bypass extinction. Furthermore, in early cell hybrids, immunoglobulin suppression is correlated with absence of the cell-specific transcription factor Oct-2 and its transcripts. Such hybrids cannot support transcription of a transiently introduced reporter plasmid, driven by an octamer-containing promoter, unless an expression vector encoding Oct-2 is cotransfected. Transfection of the same Oct-2 expression vector into hybrid cells is also sufficient to "reactivate" an integrated kappa promoter construct. Thus, our data further establish the role of Oct-2 for immunoglobulin transcription and show that in B cell x fibroblast hybrids, the lack of a necessary cell-specific transcription factor is involved in the extinction of immunoglobulin expression.
Animals↗
Use of different inhalation devices in children.
Many studies in which patient's inhaler use technique has been studied have shown that one of the major problems patients have, in using an inhaler correctly, is that of poor coordination of inhaler actuation with inspiration. We have studied a new breath-actuated inhaler ("Autohaler" 3M Riker) which is designed to ensure correct coordination automatically. This study involves 100 children (aged 3-10 years) and includes both normal children and asthmatic patients. None of these children have previous experience using any type of inhaler. Each child is taught to use the "Autohaler" containing a placebo only. A video film is employed in order to standardize the teaching technique. Once the child is able to operate the new inhaler correctly, he or she inspires through an "Autohaler" unit specially modified so that the inspiratory flow rate and the volume of air inhaled is measured by a pneumotachograph in series with the inhaler. The time point, within the inspiratory cycle, at which the inhaler is triggered is also recorded. The majority of children older than 7 years were able to use the "Autohaler" after a few minutes instruction. Therefore, this is a valuable alternative in this age group.
Asthma↗
Late muscular responses to transcranial cortical stimulation in man.
Transcranial cortical stimulation was performed in healthy human subjects. Electrical and magnetic stimuli were applied over the motor areas of the hand and the leg. Surface EMGs were recorded from the antagonistic extensor and flexor carpi radialis and the anterior tibial and triceps surae muscles. Except for the well known early (primary) responses several secondary responses have been recorded. (1) A response with a latency of approximately 100 msec and with higher threshold than the primary response. It was found in approximately half of the muscles recorded from except for the anterior tibial where it was comparatively rare. It could appear both contra- and ipsilaterally and increased in amplitude with preactivation of the target muscle. It is probably not of startle origin but its appearance may be influenced by an approximately simultaneous startle effect from the scalp stimulus. (2) In some subjects a response with a latency of 50-60 msec was recorded. Sometimes it was easily separated from the primary response and from S 100 but sometimes the differentiation was difficult. (3) It was found that the known inhibitory period which follows the primary response was contralateral and increased in duration with increasing stimulus strength. The increase in duration may be due to inhibitory feedback from receptors activated by the simultaneously increasing primary muscle twitch. (4) In relaxed muscle we also observed a contralateral response with a latency exceeding 150 msec. The latency increased with increasing stimulus strength. This increase seems to be related to discontinuance of the inhibitory period.
Cerebral Cortex↗
Immunocytochemical identification of the human alpha 2-macroglobulin receptor in monocytes and fibroblasts: monoclonal antibodies define the receptor as a monocyte differentiation antigen.
The alpha 2-macroglobulin receptor was recently purified from rat liver and human placenta. Three different monoclonal antibodies have now been raised against the human receptor and expression of the 440-kDa receptor protein is demonstrated in human placenta, fibroblasts, liver, and monocytes by immunoblot analysis. Flow cytometric studies showed that anti-alpha 2-macroglobulin receptor monoclonal antibodies bind to 90-100% of the blood monocyte population and not to other blood cells. This defines the alpha 2-macroglobulin receptor as a monocyte differentiation antigen, different from any of the classified leucocyte cluster determinants. Electron microscopic gold immunocytochemistry revealed the subcellular distribution of the receptor in human cultured monocytes and fibroblasts. In these cells, 18-33% of the gold particles were found on the outside of the plasma membrane, and in fibroblasts, especially, in coated invaginations. The intracellular receptors were mainly distributed in vesicles and tubular structures.
Antibodies, Monoclonal↗
Metabolic growth rate control in Escherichia coli may be a consequence of subsaturation of the macromolecular biosynthetic apparatus with substrates and catalytic components.
In this paper, the Escherichia coli cell is considered as a system designed for rapid growth, but limited by the medium. We propose that this very design causes the cell to become subsaturated with precursors and catalytic components at all levels of macromolecular biosynthesis and leads to a molecular sharing economy at a high level of competition inside the cell. Thus, the promoters compete with each other in the binding of a limited amount of free RNA polymerase and the ribosome binding sites on the mRNA chains compete with each other for the free ribosomes. The macromolecular chain elongation reactions sequester a considerable proportion of the total amount of RNA polymerase and ribosomes in the cells. We propose that the degree of subsaturation of the macromolecular biosynthetic apparatus renders a variable fraction of RNA polymerase and ribosomes unavailable for the initiation of new chain synthesis and that this, at least in part, determines the composition of the cell as a function of the growth rate. Thus, at rapid growth, the high speed of the elongation reactions enables the cell to increase the concentrations of free RNA polymerase and ribosomes for initiation purposes. Furthermore, it is proposed that the speed of RNA polymerase movement is adjusted to the performance speed of the ribosomes. Mechanistically, this adjustment of the coupling between transcription and translation involves transcriptional pause sites along the RNA chains, the adjustment of the saturation level of RNA polymerase with the nucleoside triphosphate substrates, and the concentration of ppGpp, which is known to inhibit RNA chain elongation. This model is able to explain the stringent response and the control of stable RNA and of ribosome synthesis in steady states and in shifts, as well as the rate of overall protein synthesis as a function of the growth rate.
Bacterial Proteins↗
Influence of inspiratory flow rate upon the effect of a Turbuhaler.
The effect of a new breath actuated dry powder inhaler, the Turbuhaler, was found to be reduced at inhalations slower than 28 1/minute. This flow rate could be generated by virtually all children aged greater than or equal to 6 years, by 42 of 57 children less than 6 years (74%), and by six of 15 preschool children with acute wheeze (40%).
Adolescent↗
Codon usage determines translation rate in Escherichia coli.
We wish to determine whether differences in translation rate are correlated with differences in codon usage or with differences in mRNA secondary structure. We therefore inserted a small DNA fragment in the lacZ gene either directly or flanked by a few frame-shifting bases, leaving the reading frame of the lacZ gene unchanged. The fragment was chosen to have "infrequent" codons in one reading frame and "common" codons in the other. The insert in these constructs does not seem to give mRNAs that are able to form extensive secondary structures. The translation time for these modified lacZ mRNAs was measured with a reproducibility better than plus or minus one second. We found that the mRNA with infrequent codons inserted has an approximately three-seconds longer translation time than the one with common codons. In another set of experiments we constructed two almost identical lacZ genes in which the lacZ mRNAs have the potential to generate stem structures with stabilities of about -75 kcal/mol. In this way we could investigate the influence of mRNA structure on translation rate. This type of modified gene was generated in two reading frames with either common or infrequent codons similar to our first experiments. We find that the yield of protein from these mRNAs is reduced, probably due to the action in vivo of an RNase. Nevertheless, the data do not indicate that there is any effect of mRNA secondary structure on translation rate. In contrast, our data persuade us that there is a difference in translation rate between infrequent codons and common codons that is of the order of sixfold.
Bacterial Proteins↗
Comparison of a new multidose powder inhaler with a pressurized aerosol in children with asthma.
Thirteen children with asthma were treated with cumulative doses of terbutaline delivered as a pressurized aerosol and from a new multidose powder inhaler (Turbuhaler) in a randomized cross-over dose-response study. The cumulative dose of terbutaline was 2 mg on each study day. All children used a correct aerosol inhalation technique. At no time was there any difference in forced expiratory volume in 1 s (FEV1), forced midexpiratory flow, forced vital capacity, peak expiratory flow rate, or percent increase in these parameters between the two inhalers. The mean total increases in FEV1 after 2 mg terbutaline were 60% (aerosol) and 62% (Turbuhaler); 90% of these increases were measured after a cumulative dose of 0.5 mg terbutaline. One milligram of terbutaline inhaled from a Nebuhaler at the end of each study day did not result in additional increase of pulmonary functions, indicating that maximal bronchodilation had been achieved with both inhalers. After a cumulative dose of 2 mg terbutaline from the aerosol seven children complained of tremor and one of restlessness. No side effects were reported when the Turbuhaler was used (P less than 0.02). 1989; 7:00-00.
Administration, Inhalation↗
Dose-response relationships of intravenously administered terbutaline in children with asthma.
The bronchodilator effect of three successive stable plasma terbutaline levels was studied in 10 children with asthma. Each terbutaline plateau was achieved by giving a rapid intravenous infusion of terbutaline, 0.9 microgram/kg, followed by a continuous infusion for 2 hours. Mean plasma terbutaline concentrations (18, 36, and 53 nmol/L at the three plateaus) were found to correlate linearly with the maintenance dose of terbutaline (2.4, 4.5, and 6.3 micrograms/kg/hr, respectively). Mean forced expiratory volume in 1 second increased from 65% to 96%, and mean forced mid-expiratory flow from 32% to 71% of the predicted normal value during the study (p less than 0.01); maximum bronchodilation was obtained at mean terbutaline levels of about 30 nmol/L (range 20 to 60). Effective plasma terbutaline levels were associated with side effects such as headache and tremor in all patients. In addition, heart rate increased from 84 to 116 beats/min, systolic blood pressure rose from 115 to 129 mm Hg, and diastolic blood pressure dropped from 72 to 61 mm Hg during the study. We conclude that a loading dose of 2 micrograms terbutaline per kilogram of body weight over 5 minutes, followed by a continuous infusion of 4.5 micrograms terbutaline per kilogram per hour, is suitable for treatment of severe bronchoconstriction in children. Because of interindividual variations in drug metabolism and clinical effect, dose adjustment should be evaluated at regular intervals.
Adolescent↗
Regulation of urokinase receptors in monocytelike U937 cells by phorbol ester phorbol myristate acetate.
A specific surface receptor for urokinase plasminogen activator (uPA) recognizes the amino-terminal growth factor-like sequence of uPA, a region independent from and not required for the catalytic activity of this enzyme. The properties of the uPA receptor (uPAR) and the localization and distribution of uPA in tumor cells and tissues suggest that the uPA/uPAR interaction may be important in regulating extracellular proteolysis-dependent processes (e.g., invasion, tissue destruction). Phorbol myristate acetate (PMA), an inducer of U937 cell differentiation to macrophage-like cells, elicits a time- and concentration-dependent increase in the number of uPAR molecules as shown by binding, cross-linking, and immunoprecipitation studies. The effect of PMA is blocked by cycloheximide. Overall, the data indicate that PMA increases the synthesis of uPA. PMA treatment also causes a decrease in the affinity of the uPAR for uPA, thus uncovering another way of regulating the interaction between uPA and uPAR. In addition, the PMA treatment causes a modification of migration of the cross-linked receptor in mono- and bidimensional gel electrophoresis.
Cell Count↗
Management of asthma: a consensus statement.
In developing these international guidelines there were several unifying themes in the diagnosis and simple management of childhood asthma. For the purposes of the meeting, asthma was operationally defined as 'episodic wheeze and/or cough in a clinical setting where asthma is likely and other rarer conditions have been excluded'. In making a diagnosis of asthma, a full history is a prerequisite. Additional tests are only used to support clinical impression and to provide objective evidence for therapeutic recommendations. General features of a multidisciplinary approach include an appreciation of the importance of psychosocial factors, counselling, and education. Drugs should be prescribed in a rational sequence: beta 2-stimulants for mild episodic wheeze; sodium cromoglycate for mild to moderate asthma; inhaled steroids for moderate to severe asthma; with xanthines, ipratropium bromide, and oral steroids having their place in more persistent and severe cases. Children and their parents should be reassured that if asthma is properly controlled there is no reason why the child should not lead a normal and physically active life. The management of asthma is rewarding and return to 'normal' lifestyle is nearly always possible with active participation in sporting activities.
Acute Disease↗
Audiometric results of TORP and PORP middle ear reconstruction.
The results of 70 middle ear reconstructions using either total or partial ossicular replacement prostheses are presented, the mean observation period being 45 months. Twenty-seven of the prostheses (39%) were extruded, this occurring as late as 72 months after surgery, and four (6%) were removed at reoperation. The surgical results when assessed by the magnitude of the air-bone gap are comparable to those of other series in the literature. However, postoperative air conduction thresholds remained high, and 23% of the patients are using hearing aids. The average air-bone gap for the frequencies 0.5, 1, and 2 kHz does not provide information on patients' everyday hearing level, and should no longer be employed as an index for assessing the functional results of middle ear surgery.
Audiometry↗
Optimal inhalation technique with terbutaline Turbuhaler.
The bronchodilator response after four different modes of inhalation of 0.25 mg terbutaline from a Turbuhaler was assessed, in a double-blind cross-over study, of 14 asthmatic children aged 8-14 yrs (mean 11.6 yrs). The children inhaled as fast as possible (mean peak inspiratory flow rate = 53 l.min-1), because fast inhalations have been found to be more efficient than slow inhalations when the Turbuhaler is used. Tilting the head back during inhalation and a breath-holding pause of 10 s after the inhalation had no significant effect upon bronchodilation. Furthermore, the response was the same whether the children inhaled from residual volume (RV) or functional residual capacity (FRC). These results suggest that this new inhaler can be used with a very simple inhalation technique without any loss of effect. A simple inhalation technique is likely to facilitate teaching and improve compliance.
Administration, Inhalation↗
[The contract-free period at a Danish general practice from 1 October 1984 to 6 January 1985].
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Denmark↗
[Examination for dislocation of the hip in the neonatal period].
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Clinical Competence↗
[Atypical Mycobacterium infections of the neck].
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Adolescent↗