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Biomedical subjects

S Pedersen

Publications and source records attributed to S Pedersen.

At least 73 records · Page 4Linked to original sources
PubMed1998

Measuring efficacy and safety of different inhaled corticosteroid preparations.

Inhaled corticosteroids are the mainstay of treatment for persistent asthma because of their proven efficacy, which is better than any other class of antiasthma therapy. Concerns about unwanted systemic effects with long-term use has, however, limited their use. Efforts have been made to develop inhaled corticosteroids with less systemic activity for a given clinical effect, thereby improving their therapeutic index. Many different study designs and outcome variables have been used to compare different inhaled corticosteroids. Differences in pharmacologic properties between drugs are most easily and accurately measured and quantified by measures of systemic effects. However, these differences should always be related to differences in clinical effects. It is difficult to draw firm conclusions with respect to the therapeutic index of different inhaled corticosteroids because no direct placebo-controlled, dose-response comparisons of clinical effects have been made. Despite this caveat, the available studies suggest that microgram for microgram, when delivered by a pressurized metered-dose inhaler (pMDI), fluticasone propionate (FP) is more effective than beclomethasone dipropionate (BDP), triamcinolone acetonide (TAA), or budesonide; however, the efficacy of budesonide delivered by Turbuhaler is equipotent to that of FP delivered by pMDI or Diskhaler and more effective than that of BDP. When comparative safety is considered, budesonide or TAA delivered by pMDI have less systemic activity than FP delivered by pMDI, whereas BDP and FP delivered by pMDI appear to be equivalent. Also, budesonide delivered by Turbuhaler has less systemic activity than FP delivered by Diskhaler.

Administration, Inhalation↗
PubMed1998

Importance of training for correct Turbuhaler use in preschool children.

AIM: To study the impact of both audiovisual information and nurse-training on the use of budesonide Turbuhaler in preschool children who had never used a dry powder inhaler. DESIGN: A single-blind, randomized, parallel-group trial studied 72 children aged 3-5 y. All children and their parents were shown an instructional video and given written instruction. After this, peak inspiratory flow (PIF1) through Turbuhaler was measured. Children in group A (n = 36) then received individual training by a nurse while those in Group B (n = 36) did not and PIF2 was measured. Afterwards, Group B received similar individual training while Group A received no additional training, and PIF3 was measured. Group A was given a placebo Turbuhaler and encouraged to practice at home. Two weeks later, both groups returned to the clinic where PIF4 was measured. RESULTS: The number of children who were able to correctly perform PIF1, PIF2 and PIF4 in Group A was 27, 34 and 36, respectively. The corresponding numbers for Group B were 30, 29, and 29. No effect of training was seen in 3-y-old children. Individual training by a nurse was associated with a statistically significant increase in PIF2 (10 l/min; p = 0.014). Moreover, 2 weeks of home training was associated with an additional increase in PIF of 8 l/min compared with Group B (p < 0.015). After individual instruction and home training, mean PIF in children aged 4 and 5 was 56 (42-72) and 55 (41-66) l/min, respectively. CONCLUSION: After individual instruction and training at home, the vast majority of children aged 4 and 5 y can use Turbuhaler correctly. Audiovisual information and individual instruction is not sufficient in the majority of these children. Few 3-y-old children can learn the correct use of Turbuhaler.

Analysis of Variance↗
PubMed1998

Bone mineral density in children with asthma receiving long-term treatment with inhaled budesonide.

The aim of our study was to assess the effects of long-term treatment with inhaled budesonide (BUD) on total body bone mineral density (BMD), total body bone mineral capacity (BMC), total bone calcium (TBC), and body composition in children with asthma. Dual energy X-ray absorptiometry (DEXA scan) was performed in 157 asthmatic children treated with inhaled BUD at a mean daily dose of 504 microg (range, 189 to 1,322 microg) for 3 to 6 yr (mean, 4.5 yr). Measurements were compared with those of 111 age-matched children also suffering from asthma but who had never been treated with exogenous corticosteroids for more than 14 d (control group). There were no statistically significant differences between the two groups in BMD (BUD = 0.915 g/cm2, controls = 0.917 g/cm2), BMC (BUD = 1,378 g, controls = 1,367 g), TBC (BUD = 524 g, controls = 519 g), or body composition (lean body weight = 27,600 g [BUD] and 26,923 g [control], % body fat = 20.1% [BUD] and 20.3% [control]). Furthermore, there was no correlation between any of these parameters and duration of treatment, accumulated or current dose of budesonide. Three to six years of treatment with inhaled budesonide at an average daily dose of 504 microg has no adverse effect on total BMD, total BMC, TBC, or body composition in children with chronic asthma.

Absorptiometry, Photon↗
PubMed1998

Posterior subcapsular cataracts, bruises and hoarseness in children with asthma receiving long-term treatment with inhaled budesonide.

We assessed the effect of long-term treatment with inhaled budesonide (BUD) on the occurrence of posterior subcapsular cataracts (PSC), bruises and hoarseness in children with asthma. Slit lamp examinations were performed in 157 asthmatic children treated with inhaled BUD at a mean daily dose of 504 microg (range 189-1,322 microg) for 3-6 yrs (mean 4.4 yrs). Measurements were compared with 111 age-matched children with asthma, who had never received treatment of exogenous corticosteroids (control group). The children were examined for bruises, their tendency to bruise and occurrence of voice changes. No incidents of PSC ascribable to BUD treatment were seen. One patient in the BUD group had been diagnosed with PSC before the study and this was still present. There were no statistically significant differences in number of bruises between the two groups (BUD=33, controls=3.2; p=0.70), area covered by bruises (BUD=10 cm2, controls=10.1 cm2; p=0.97), tendency to bruise (BUD=5/10, controls=5/10) or occurrence of hoarseness (BUD=20%, controls=21%; p=0.92). Furthermore, there was no correlation between the occurrence of bruises or tendency to bruise and duration of treatment, accumulated or current dose of BUD. A 3-6 yr treatment of children with inhaled budesonide at an average daily dose of about 500 microg is not associated with an increased occurrence of posterior subcapsular cataract, bruises, tendency to bruise, hoarseness or other noticeable voice changes.

Administration, Inhalation↗
PubMed1998

[Dust reduction in pig houses].

Airborne dust in pig houses causes health problems for humans with full-time employment in pig houses. Many attempts have been made to reduce the dust burdens, but often without sufficient results. At Research Centre Bygholm ten different possibilities for dust reduction have been tested in the test section, and the results are evaluated on the basis of results obtained simultaneously in an identical control section. Until now, the two most efficient methods are addition of fat to the pigs' diet and spraying a thin layer of rape seed oil in the animal house. By adding 4% of fat to the diet, a reduction of 50% can be seen, and by spraying 5 g of rape seed oil daily per pig place, the aerial dust concentration can be reduced to about 75%. The costs are about 1 DM/pig at a price of rape seed oil of 2 DM/l.

Animal Husbandry↗
PubMed1998

Pharmacological interventions. Childhood asthma.

Airway inflammation is present in early asthma. Chronic inflammation seems to be associated with airway remodelling and reduced growth of lung function. An inverse relationship between lung function and duration of asthma or an increase in bronchial reactivity with asthma duration has been reported in many studies. Several trials have found that late use of inhaled corticosteroids is associated with a smaller effect on bronchial hyperreactivity and lung function compared with early use. Furthermore, it has been suggested that early anti-inflammatory treatment may also influence long-term outcome. These findings have elicited the hope that it might be possible to cause disease resolution or modify the natural course of the disease. It has been hypothesized that there may be a window of opportunity in relation to the treatment of asthma after which remodelling and changes in lung function occur which cannot be reversed. However, just when this window of opportunity presents in the progression of the disease, or at what stage early intervention should be initiated, has not been clearly defined. Early pharmacological intervention in children <3 yrs of age is complicated by the fact that treatment will be given to a large number of children who will never develop persistent asthma. This must be considered when designing the studies addressing the various research questions about early pharmacological intervention. Studies in young children should probably be conducted in both high- and low-risk patients. Older patients with apparently mild disease are the main candidates for placebo-controlled trials. Patients with a greater disease severity are more suitable for studies comparing intervention with different drugs or different doses of drug.

Administration, Inhalation↗
PubMed1997

Distinct repression of translation by wortmannin and rapamycin.

The role of phosphatidylinositol 3-kinase and FK506-binding protein rapamycin-associated protein (FRAP) in translational control has been examined by treating RD-rhabdomyosarcoma cells with wortmannin and rapamycin and studying the effects on cell-growth, translation initiation, and protein synthesis. Whereas wortmannin and rapamycin exhibit subtle effects on global translation, examination of individual mRNAs in sucrose gradients and of individual proteins in two-dimensional polyacrylamide gels reveals that wortmannin and rapamycin exhibit distinct effects on the translation of individual mRNAs. Wortmannin represses the synthesis of a third of cellular proteins, whereas rapamycin affects a subset of these proteins. Since ribosomal protein S6 was rapidly dephosphorylated following wortmannin and rapamycin treatment, and the phosphorylation status of the eukaryotic initiation factor 4E was unchanged, our data imply that the p70 signalling pathway has at least one branch-point upstream of FRAP leading to an additional route of translational control.

Androstadienes↗
PubMed1997

[Counting of axillary lymph nodes during surgery of breast cancer. A comparison between radiographic examination and pathological assessment].

Proper breast cancer surgery should include removal of at least ten axillary lymph nodes according to recommendations given by DBCG (The Danish Breast Cancer Group). The present study evaluated the results of counting the lymph nodes peroperatively on radiographs of the axillary tissue compared to the final pathological examination, the latter being considered the "gold standard". Since agreement between the two methods was found in only 66 out of 90 patients (Kappa value 0.279), we consider the peroperative radiological examination of the axillary fat to be of no practical value.

Axilla↗
PubMed1997

Leukotriene D4-induced Ca2+ mobilization in Ehrlich ascites tumor cells.

Stimulation of Ehrlich ascites tumor cells with leukotriene D4 (LTD4) within the concentration range 1-100 nm leads to a concentration-dependent, transient increase in the intracellular, free Ca2+ concentration, [Ca2+]i. The Ca2+ peak time, i.e., the time between addition of LTD4 and the highest measured [Ca2+]i value, is in the range 0.20 to 0.21 min in ten out of fourteen independent experiments. After addition of a saturating concentration of LTD4 (100 nm), the highest measured increase in [Ca2+]i in Ehrlich cells suspended in Ca2+-containing medium is 260 +/- 14 nm and the EC50 value for LTD4-induced Ca2+ mobilization is estimated at 10 nM. Neither the peptido-leukotrienes LTC4 and LTE4 nor LTB4 are able to mimic or block the LTD4-induced Ca2+ mobilization, hence the receptor is specific for LTD4. Removal of Ca2+ from the experimental buffer significantly reduces the size of the LTD4-induced increase in [Ca2+]i. Furthermore, depletion of the intracellular Ins(1,4,5)P3-sensitive Ca2+ stores by addition of the ER-Ca2+-ATPase inhibitor thapsigargin also reduces the size of the LTD4-induced increase in [Ca2+]i in Ehrlich cells suspended in Ca2+-containing medium, and completely abolishes the LTD4-induced increase in [Ca2+]i in Ehrlich cells suspended in Ca2+-free medium containing EGTA. Thus, the LTD4-induced increase in [Ca2+]i in Ehrlich cells involves an influx of Ca2+ from the extracellular compartment as well as a release of Ca2+ from intracellular Ins(1,4,5)P3-sensitive stores. The Ca2+ peak times for the LTD4-induced Ca2+ influx and for the LTD4-induced Ca2+ release are recorded in the time range 0.20 to 0.21 min in four out of five experiments and in the time range 0.34 to 0.35 min in six out of eight experiments, respectively. Stimulation with LTD4 also induces a transient increase in Ins(1,4, 5)P3 generation in the Ehrlich cells, and the Ins(1,4,5)P3 peak time is recorded in the time range 0.27 to 0.30 min. Thus, the Ins(1,4, 5)P3 content seems to increase before the LTD4-induced Ca2+ release from the intracellular stores but after the LTD4-induced Ca2+ influx. Inhibition of phospholipase C by preincubation with U73122 abolishes the LTD4-induced increase in Ins(1,4,5)P3 as well as the LTD4-induced increase in [Ca2+]i, indicating that a U73122-sensitivity phospholipase C is involved in the LTD4-induced Ca2+ mobilization in Ehrlich cells. The LTD4-induced Ca2+ influx is insensitive to verapamil, gadolinium and SK&F 96365, suggesting that the LTD4-activated Ca2+ channel in Ehrlich cells is neither voltage gated nor stretch activated and most probably not receptor operated. In conclusion, LTD4 acts in the Ehrlich cells via a specific receptor for LTD4, which upon stimulation initiates an influx of Ca2+, through yet unidentified Ca2+ channels, and an activation of a U73122-sensitive phospholipase C, Ins(1,4,5)P3 formation and finally release of Ca2+ from the intracellular Ins(1,4,5)P3-sensitive stores.

Animals↗
PubMed1997

Dose titration of nebulized budesonide in young children.

We compared the clinical effect of the glucocorticoid budesonide delivered from two nebulizers Aiolos and Pari LL in 38 children less than 4 years of age (mean age, 20.2 months) with chronic wheeze. The design was a controlled, single-blind, randomized, cross-over, dose titration study. After a 1-week run-in, patients were randomized to treatment with 1 mg budesonide b.i.d. for 2 weeks from either an Aiolos or a Pari LL nebulizer. This was followed by a gradual dose reduction period during which the budesonide dose was reduced at 2-week intervals until unacceptable asthma symptoms appeared or the placebo level was reached. The patient was then switched to budesonide 1 mg b.i.d. from the other nebulizer for 2 weeks, after which the dose was reduced at 2-week intervals as described for the first period. Patients who completed the study on placebo for 2 weeks without deterioration of their asthma were not included in the statistical analysis. During Period #1 the minimum effective dose of budesonide was 2 mg/day in 9 patients, 1 mg/day in 10 patients, and 0.5 mg/day in 13 patients. In Period #2 the corresponding figures were 14, 5, and 13 patients. Six patients were excluded after the first period because their asthma control did not deteriorate during dose reduction and when finishing on placebo for 2 weeks. For both nebulizers the reduction in budesonide dose was associated with a small increase in symptoms and use of rescue terbutaline. The mean dose of budesonide delivered to the patient by the Aiolos was twice as large as that delivered by the Pari LL: 26% vs. 13% of the nominal dose assessed by the filter method. Nevertheless, no statistically significant difference in clinical effect or mean minimal effective dose (1.1 mg for Aiolos and 1.2 mg for Pari LL) could be detected between the two nebulizers. No serious adverse events were observed. We conclude that the minimal effective dose of nebulized budesonide varies from 0.5 to 2.0 mg/day in young children with asthma. A higher drug delivery, as assessed by the filter method, does not necessarily result in better clinical control or lower minimal effective dose. Further studies are needed to assess whether this is due to insufficient sensitivity of the study design in detecting a difference in clinical effect, or whether measurements of drug delivery by the filter method do not reflect lung deposition or clinical effect in young children with wheezing.

Asthma↗
PubMed1997

The effects of ethylene oxide containing lipopolymers and tri-block copolymers on lipid bilayers of dipalmitoylphosphatidylcholine.

A comparative study is conducted on the influence of two types of polymeric compounds on the phase behavior of 1,2-dihexadecanoyl-s,n-glycero-3-phosphotidylcholine (DC16PC) lipid bilayers. The first polymeric compound is a lipopolymer, with two different lengths of a hydrophilic polyethylene oxide moity, anchored to the bilayer by a 1,2-dioctadecanoyl-s,n-glycero-3-phosphoethanolamine (DC18PE) lipid. The second type, which is a novel type of membrane-spanning object, is an amphiphilic tri-block copolymer composed of two hydrophilic stretches of polyethylene oxide separated by a hydrophobic stretch of polystyrene. Hence the tri-block copolymer may act as a membrane-spanning macromolecule mimicking an amphiphilic protein or polypeptide. Differential scanning calorimetry is used to determine a partial phase diagram for the lipopolymer systems and to assess the amount of lipopolymer that can be loaded into DC16PC lipid bilayers before micellization takes place. Unilamellar and micellar phase structures are investigated by fluorescence quenching using bilayer permeating dithionite. The chain length-dependent critical lipopolymer concentration, denoting the lamellar-to-micellar phase transition, compares favorably with a theoretical prediction based on free-energy considerations involving bilayer cohesion and lateral pressure exerted by the polymer chains.

1,2-Dipalmitoylphosphatidylcholine↗