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Biomedical subjects

S Pedersen

Publications and source records attributed to S Pedersen.

At least 55 records · Page 3Linked to original sources

Short-term knemometry and urine cortisol excretion in children treated with fluticasone propionate and budesonide: a dose response study.

Few thorough comparisons of the systemic effects of inhaled corticosteroids in children are available. The aim of this study was to compare the effect of budesonide and fluticasone propionate on short-term lower leg growth. Fluticasone propionate, budesonide and placebo were administered for 2 weeks in a randomized, double-blind, double-dummy, cross-over design. Twenty four children aged 6-12 yrs received 200 microg x day(-1) of each drug, or placebo. Another 24 children aged 6-12 years received 400 microg x day(-1) of each drug, or placebo. Dry powder inhalers were used. Lower leg length was measured by knemometry twice a week during all three treatment periods, and 24 h cortisol excretion in the urine was measured at the end of each period. In the low-dose group, lower leg growth rate was the same during treatment with placebo (0.35 mm x week(-1)), fluticasone propionate (0.38 mm x week(-1)) or budesonide (0.26 mm x week(-1)). No significant difference (p=0.39) in lower leg growth rate was found between treatment with 400 microg x day(-1) budesonide (0.30 mm x week(-1)) and 400 microg fluticasone propionate treatment (0.37 mm x week(-1)). Growth rate during treatment with budesonide, 400 microg x day(-1), was significantly lower than during placebo treatment (0.52 mm x week(-1)). Cortisol excretion in the urine during treatment with 200 microg x day(-1) fluticasone propionate was significantly reduced as compared with placebo (p=0.006), but not when compared with 200 microg x day(-1) budesonide (p=0.07). Budesonide 200 microg x day(-1) was not significantly different from placebo. Fluticasone propionate and budesonide, both at 400 microg x day(-1), resulted in a significant reduction in cortisol excretion in the urine as compared with placebo (p=0.001). It is concluded that, dose-for-dose, budesonide Turbuhaler and fluticasone propionate Diskhaler have similar systemic effects.

Administration, Inhalation

Knemometry, urine cortisol excretion, and measures of the insulin-like growth factor axis and collagen turnover in children treated with inhaled glucocorticosteroids.

Correlations between knemometric (lower leg length) growth rates and urine free cortisol excretion, respectively, and serum concentrations of IGF-I, IGF binding protein-3, osteocalcin, carboxy terminal propeptide of type I collagen (PICP), carboxy terminal pryridinoline cross-linked telopeptide of type I procollagen (ICTP), and amino terminal propeptide of type III procollagen (PIIINP) were investigated in 17 asthmatic children aged 7-14 y during treatment with fluticasone propionate, 200 micrograms, and beclomethasone dipropionate, 400 and 800 micrograms/d, taken from dry powder inhalers. The study was a double blind, crossover trial with three active treatment periods and two wash-out periods. All periods were 15 d long. Overnight urine free cortisol/ creatinine x 10(6) did not correlate with knemometric growth rates or any of the serum markers. Significant correlations (Pearson's correlation coefficient, P) between knemometric growth rates and IGF-I (0.41; 0.006), IGFBP-3 (0.35; 0.02), PICP (0.44; 0.003), ICTP (0.35; 0.001), and PIIINP (0.46; 0.002) were found. Compared with fluticasone propionate, 200 micrograms, beclomethasone dipropionate, 400 and 800 micrograms, caused significant suppression of lower leg growth rate (F = 12.41; p = 0.002, and F = 23.30; p = 0.0001, respectively) and of urine free cortisol/creatinine x 10(6) (F = 10.52; p = 0.003, and F = 13.74; p = 0.001). Beclomethasone, 800 micrograms, caused suppression of PICP compared with fluticasone propionate, 200 micrograms (F = 8.31; p = 0.008), and beclomethasone, 400 micrograms (F = 7.53; p = 0.01). Both low (F = 6.82; p = 0.02) and high (F = 23.35; p = 0.0001) doses of beclomethasone were associated with reduced concentrations of ICTP, the high dose being the most suppressive (F = 4.42; p = 0.05). Beclomethasone 400 (F = 9.75; p = 0.004) and 800 micrograms (F = 23.61; p = 0.0001) resulted in reduced levels of PIIINP. Reduced short-term knemometric growth rates in children treated with inhaled glucocorticosteroids reflect suppressive effects on type I and type III collagen turnover.

Administration, Inhalation

What are the goals of treating pediatric asthma?

For many years improvement in symptoms and normalization of lung function have been the main goals in treatment of pediatric asthma. Recently, other parameters, such as reductions in frequency and severity of exacerbations, reduced mortality, normalization of airway hyperresponsiveness, reduction in chronic inflammation of the airways and airway remodeling, normal development of lung function, and normal psychosocial development, are thought to be of similar, or possibly greater, importance. The present understanding of the effects of various drugs used for asthma control is at an early stage. For example, excellent control of one outcome measure may be achieved by a particular drug without any effect on other outcome measures, and the dose of drug needed to control one outcome measure may be quite different from the dose required to control others. Furthermore, the time course of the effect of a drug on the various parameters can differ for each parameter. Improvements in lung function and symptoms often precede, and even reach a plateau, before the maximum reduction in responsiveness is observed. This makes it difficult to determine whether all the goals have been achieved. Therefore, treatments and doses that have been shown in controlled trials to improve most outcome measures are preferred, but their side-effect profiles must also be considered. The majority of parameters seem to be related to the degree of airway inflammation. Unfortunately, at present, the tools of measure all aspects of airway inflammation in the day-to-day management of asthma are not available. Also, the degree to which the inflammatory process must be suppressed, or which aspects of inflammation need to be controlled, to influence the various parameters is not known.

Adolescent

[Prevalence of Chlamydia trachomatis among conscripts. A comparative study of urine samples and urethral swabs].

The purpose of the investigation was 1) to determine the prevalence of C. trachomatis among young men and women enrolled in military service, 2) to compare enzyme-immunoassay (EIA) of a urethral swab with a sample of first voided morning urine, 3) to determine frequency of earlier venereal diseases (VD) and actual symptoms of urethritis and cervicitis. EIA positive specimens were confirmed by immunofluorescent microscopy. The investigation comprised 831 men and 80 women (17-26 years). The prevalence was 5.7% (95% confidence limits 4.2-7.4%) and 15% (8-25%) for men and women, respectively (p < 0.005, chi 2). The agreement between the results of the urethral swab and the urine sample was low. Sensitivity and positive predictive value for urethral swab was better than for urine. The handling of urine specimens was more laborious and confirmation more difficult. The percentage of actual symptoms among Chlamydia positive men was 6. The frequency of earlier VD was 7.5% and 10% among men and women, respectively. Treatment with tetracycline was effective, which makes control of eradication unnecessary. We conclude that genital chlamydial infection among young asymptomatic people is common and screening would be desirable. We still recommend urethral swabbing as the routine method until simpler and/or more reliable assays for urine specimens are developed.

Adolescent

Absence of relation between sick leave caused by musculoskeletal disorders and exposure to magnetic fields in an aluminum plant.

This is a study of the relationship between occupational exposure to magnetic fields in pot rooms and occurrence of sick leave caused by musculoskeletal disorders. The average exposure to static magnetic fields was 8 mT in the pot rooms. Ripple fields were recorded as well. A cohort of 342 exposed workers and 222 unexposed workers from the same electrolysis plant was retrospectively followed for 5 years. The reference group had a type of work similar to the exposed group except for the exposure to magnetic fields. The occurrence of sick leave and the diagnoses causing the sick leave were obtained from the Occupational Health Care Unit: these data were stored in their computer files. The data were complete. No relationship between the occurrence of sick leave caused by musculoskeletal disorders and exposure to magnetic fields was found. This was the case for both the annual number of periods of sick leave and the total number of days with sick leave. The results must be interpreted with caution due to limitations in the design and available data. Also, static magnetic fields constituted the major exposure, and the results may be different when related to work in other types of magnetic-field exposure.

Adult

Indirect evidence for lipid-domain formation in the transition region of phospholipid bilayers by two-probe fluorescence energy transfer.

The fluorescence energy transfer between two lipid probes, N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1, 2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (donor) and N-(Lissamine rhodamine B sulfonyl)-1, 2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (acceptor), incorporated into 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine unilamellar and multilamellar lipid bilayers, is studied in the temperature region of the main phase transition. The two probes display different relative solubilities in the gel and fluid lipid-bilayer phases. A distinct maximum in the fluorescence intensity of the donor is observed in the transition region, indicating that the two probes are demixing and hence increasing their average separation. The observation is interpreted in terms of dynamic segregation of the two probes into coexisting gel and fluid lipid domains that are formed dynamically in the transition region due to strong density fluctuations. The interpretation of the experimental observations is supported by a detailed theoretical calculation using computer simulation of a microscopic model that takes full account of diffusion of the two probes and the fluctuations of gel and fluid lipid domains characteristic of the main phase transition.

Calorimetry, Differential Scanning

Inhalers and nebulizers: which to choose and why.

It is obvious that many factors should be considered when an inhaler is prescribed. Based upon the information discussed above, a rational inhaler strategy could be as follows: (1) Children < or = 5 years and elderly patients are prescribed a spacer with a valve system (and a face mask for the children) for the delivery of all drugs. When they are severely obstructed, some may need a nebulizer. If the patient cannot be taught the correct use of a spacer, a nebulizer should be prescribed. (2) Children > or = 5 years and adults are prescribed a spacer or a Turbuhaler for the administration of inhaled corticosteroids and a dry powder inhaler (preferably multiple dose) or a breath-actuated MDI for other drugs. If these alternatives are not available or the patient prefers, a conventional MDI can be used (preferably not for other corticosteroids than fluticasone propionate) provided that careful tuition is given. Fluticasone dipropionate may be given by DPI, Spacer or MDI. (3) Nebulizers are mainly reserved for severe acute attacks of bronchoconstriction. With this approach, most patients can be taught effective inhaler use with a minimum of instructional time. Finally, it must always be remembered to consider the patient's wish, since prescription of an inhaler which the physician likes but the patient does not is likely to reduce compliance.

Administration, Inhalation

The centromere-like parC locus of plasmid R1.

The parA partitioning system of plasmid R1 consists of three components: the cis-acting centromere-like parC locus, and two proteins, ParM and ParR. The parC locus contains two sets of five direct repeats (iterons) to which the ParR protein binds. The parA promoter is located in the core region between the two sets of iterons. Mini-R1 replicons carrying parC are stabilized by the simultaneous presence of ParM and ParR. The parC locus present on a co-resident plasmid leads to instability of the mini-R1 replicon (incompatibility). Here we present a genetic analysis of the stability and incompatibility phenotypes associated with parC. We show that all 10 iterons are required for maximum stabilization and incompatibility. Replacement of the core promoter region between the repeats by a foreign promoter region did not reduce stabilization. Thus, the only structural components in parC seem to be the two sets of iterons. The parA promoter, P parA, is repressed by ParR. We show that all 10 iterons are required for full repression of the promoter. The activity of the promoter was influenced by sequences located outside the core region. An A-rich region located upstream of the -35 element of PparA was found to increase promoter activity. The region encoding the parA mRNA leader region also strongly influenced the expression level of PparA- lacZ fusions. We show that this high expression (hex) element is a transcriptional antiterminator that prevents Rho-dependent termination.

Bacterial Proteins

Transient dystonia in non-handicapped low-birthweight infants and later neurodevelopment.

The aim of the present study was to evaluate the long-term prognostic significance of transient increase in muscle tone during infancy (dystonia) in very low-birthweight (VLBW) infants without cerebral palsy. Motor (Peabody Developmental Motor Scales), cognitive (Wechsler Preschool and Primary scale of Intelligence) and behavioural (Personality Inventory for Children, Yale Children's Inventory) development was assessed at 5 years of age. In a population-based sample of 50 VLBW children, transient dystonia was present in 14. In explorative analyses, transient dystonia was associated with low 1 min Apgar scores, neonatal bacterial infection, and lack of breast-milk in the neonatal period. Cognitive, neuromotor and behavioural development at 5 years of age was comparable in those with and without transient dystonia, although there was a statistically non-significant tendency towards more neuromotor problems in the dystonic children.

Apgar Score

Videoconferencing in psychiatry: a survey of use in northern Norway.

A survey of the use of videoconferencing in mental health care was carried out in northern Norway. A questionnaire was distributed to all user institutions in northern Norway at the same time that ISDN became available, in mid-1995. The questionnaire completion rate for locations recorded as participants in videoconferencing sessions was 62%. Within six months, a total of 1028 persons had participated in 140 videoconferencing sessions from 35 institutions. The purposes of videoconferencing included meetings (50%), supervision, training and teaching (31%), clinical consultations (14%) and tests or demonstrations (5%). The alternative forms of contact which videoconferencing replaced included travel (59%), no contact (25%), telephone (14%), and mail or fax (2%). No problems were reported in 55% of the sessions; in 19% there were audio problems, in 14% there were picture problems, in 5% attempts to connect failed and in 5% disconnection occurred. The majority of users (87%) reported that they were satisfied or very satisfied with the facility; 8% were uncertain and 5% were less satisfied or totally dissatisfied. Continued surveying will provide longitudinal data on the diffusion of telepsychiatry in northern Norway.

Attitude of Health Personnel

Rapid characterization of disease-causing mutations in the low density lipoprotein receptor (LDL-R) gene by overexpression in COS cells.

To characterize disease-causing mutations in the low density lipoprotein receptor (LDL-R) gene, COS cells are transfected with the mutant gene in an EBV-based expression vector and characterized by flow cytometry. Using antibodies against the LDL-receptor the amount of receptor protein on the cell surface is quantitated. The receptor activity is measured by incubating the cells with fluorescence labeled LDL (Dil-labelled LDL) at 37 degrees C and 4 degrees C. The transfected cells stained with anti-LDL-R antibodies can also be analysed by immunofluorescence microscopy allowing the study of the intracellular location of variants of the receptor. To evaluate these methods, we are analyzing four previously well-characterized LDL-R mutations, belonging to each of the classes 2 to 5. Preliminary data show that mutant genes belonging to class 3 and 4A give rise to receptor protein on the cell surface, but impaired LDL uptake, while mutant receptors belonging to class 2A and 5 can only be detected intracellularly. Expression of the class 2A mutation results in an ER staining pattern, whereas the class 5 mutation gives rise to an intracellular staining compatible with localization in the endosomal/lysosomal compartments. We conclude that this system is useful for a rapid functional analysis of newly discovered mutations in the LDL-R gene.

Cell Line

A flow cytometric competition technique for measuring interaction of LDL with cellular LDL-receptors applied to patients with mutant (Arg3500-->Gln) apolipoprotein B.

We report our experience with a method to evaluate binding and uptake in cells of low density lipoprotein (LDL) from heterozygous patients with familial defective apolipoprotein B-100 (FDB-LDL) and LDL from normolipidemic subjects (nonFDB-LDL). The method is based on competition for binding/uptake in Epstein-Barr Virus (EBV)-transformed lymphocytes or COS cells overexpressing an LDL-receptor transgene between fluorescently labeled LDL and the unlabeled LDL of interest, and measurements are by flow cytometry. With EBV-lymphoblasts, the ability of FDB-LDL to displace fluorescent LDL ("Dil"-LDL) from cells at 4 degrees C (binding) was reduced to approximately 1/3 of normal. Displacement of "Dil"-LDL by FDB-LDL from cells at 20 degrees C (binding/uptake) was reduced to less than 1/2 of normal. Similar results were obtained with COS cells. Freezing of serum to -80 degrees C for 24 hours did not affect results, and we could discriminate between binding/uptake of FDB-LDL and nonFDB-LDL prepared from serum that had been stored at -80 degrees C for three months.

Adult

Safety of treatment.

Data concerning safety of treatment in schoolchildren cannot be extrapolated to preschool children due to differences in growth velocity and metabolism. The safety issue in preschool children is further complicated by insufficient knowledge of the optimal dose, and the lung delivery from the devices available. Systemic activity has often been studied as a marker of adverse clinical effect. However, with improving technology, systemic activity can be detected within the range of the normal biological feedback system, where it is of no clinical importance. Therefore, systemic activity is not synonymous with clinically relevant side-effects. Side-effects should be assessed in specific clinical studies. Effect on growth velocity is a potential side-effect of major interest. Knemometry is a sensitive measure of short-term growth of the lower leg length in schoolchildren as well as in preschool children, which enables precise measurements of systemic activity, but it is not a measure of statural growth. The only clinically relevant outcome measure of human growth is the final height in relation to expected final height, allowing for gender and midparental height differences. In addition to effects on statural height, osteoperosis is an important potential side-effect. The importance of bone density during preschool age for final adult bone mineral density needs to be studied. Cataract formation is a side-effect associated with systemic steroid treatment and may be of special consideration during treatment with nebulized steroids, which may expose the eyes to high doses. Thrush, dysphonia and local skin atrophy in steroid-exposed areas are potential local side-effects, and yet the incidence in young children is unknown and dependent on the device used for delivery. When considering adverse effects of treatment, the risk of side-effects from undertreatment should always be observed.

Age Factors

Efficacy and safety of salmeterol in childhood asthma.

UNLABELLED: In children with asthma, twice daily administration of salmeterol 25 micrograms, salmeterol 50 micrograms and salbutamol 200 micrograms were compared in two, 3-month, double-blind, parallel group studies, one using metered dose inhalers (MDIs), the other using dry powder inhalers (Diskhaler, DPIs). Both studies were continued for a further 9 months during which time exacerbation rates, lung function at the clinic and adverse events were monitored. Similarities in design and methodology of the two studies justified a combined analysis. Eight hundred and forty-seven asthmatic children aged between 4 and 16 (mean 10.1) years, requiring inhaled beta 2-agonist treatment were randomised to treatment. After a 2 week run-in when all bronchodilator therapy was withdrawn, 279 patients received salmeterol 25 micrograms bd, 290 patients salmeterol 50 micrograms bd and 278 patients salbutamol 200 micrograms bd. After 3 months' treatment the change from baseline in daily morning and evening peak expiratory flow (PEF) was significantly greater with salmeterol 50 micrograms bd than with salbutamol 200 micrograms bd (P < 0.001). Salmeterol 50 micrograms bd was also significantly better than salmeterol 25 micrograms bd at improving mean morning PEF (P = 0.017) but both treatments had a similar effect on evening PEF. Analysis of variance showed an interaction between baseline PEF less than 100% predicted normal value and treatment outcome. Analysis of this sub-set of patients with lower lung function revealed similar results to the total population although the improvements in PEF from baseline were greater. Data from both studies, showed that the improvement in lung function was maintained throughout 12 months' treatment. Patients receiving salmeterol 50 micrograms bd had significantly more symptom-free nights (P < 0.01) and a higher percentage of rescue bronchodilator-free days (P = 0.01). The incidence of asthma exacerbations was evenly distributed between the three treatment groups and there was no evidence of any change in the rate of occurrence of exacerbations over the 12 month period. Adverse events were no different across treatment groups or across age groups and were primarily related to the patients' disease state. CONCLUSION: Salmeterol 50 micrograms bd is the appropriate dose for the treatment of children with mild to moderate asthma.

Administration, Inhalation

Telemedicine protocols and standards: development and implementation.

Telemedicine is likely to adopt rather than create most of its protocols and standards as it becomes an integral part of medical practice. To optimize this process, it will be necessary to understand how to use existing protocols and standards, and influence the development, evaluation, and modification of new ones. We have identified key participants in standards setting activities under the titles of international government, United States government, professional certifying organizations, and independent institutes. We have reviewed their roles in establishing standards for identification of patients and providers, content and structure of patient records, terminology and codes of medical information and records, and transfer of messages and data. We have addressed requirements for storing and viewing images, the impact of image resolution on accuracy of clinical interpretation, the choice of communications protocols to satisfy transmission requirements, the need to link images and text data, and the evaluation of telemedicine systems.

Computer Communication Networks