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Biomedical subjects

F Madsen

Publications and source records attributed to F Madsen.

At least 55 records · Page 3Linked to original sources

Challenge interval determines tachyphylaxis to aerosolized LTD4.

Leukotrienes (LK) play an important role in the inflammatory response found in the asthmatic airway and it is therefore of interest to explore the clinical value of agents which can either block the effect or inhibit the synthesis of leukotrienes. If tachyphylaxis does not develop, repeated LTD4 challenges can be used for dose ranging studies. Tachyphylaxis has been observed when LTD4 challenge intervals are kept below 1 h, but the effect of prolonging the interval is uncertain. The aim of this study was therefore to investigate the interval between LTD4 challenges necessary to avoid development of tachyphylaxis. Ten stable adult asthmatics with moderate asthma were challenged seven times: a screening day to secure responsiveness to LTD4, two challenges on three separate days with an interval of 2, 4 and 6 h, respectively. No significant differences between mean PC20-LTD4 values (P > 0.5) was found. It was concluded that tachyphylaxis to repeated LTD4 challenges of asthmatics does not develop when challenge intervals are prolonged above 2 h.

Administration, Inhalation↗

Chronic asthma and chiropractic spinal manipulation: a randomized clinical trial.

The purpose of this randomized patient- and observer-blinded cross-over trial was to evaluate the efficacy of chiropractic treatment in the management of chronic asthma when combined with pharmaceutical maintenance therapy. The trial was conducted at the National University Hospital's Out-patient Clinic in Copenhagen, Denmark. Thirty-one patients aged 18-44 years participated, all suffering from chronic asthma controlled by bronchodilators and/or inhaled steroids. Patients, or who had received chiropractic treatment for asthma within the last 5 years, who received oral steroids and immunotherapy, were not eligible. Patients were randomized to receive either active chiropractic spinal manipulative treatment or sham chiropractic spinal manipulative treatment twice weekly for 4 weeks, and then crossed over to the alternative treatment for another 4 weeks. Both phases were preceded and followed by a 2-week period without chiropractic treatment. The main outcome measurements were forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), daily use of inhaled bronchodilators, patient-rated asthma severity and non-specific bronchial reactivity (n-BR). Using the cross-over analysis, no clinically important or statistically significant differences were found between the active and sham chiropractic interventions on any of the main or secondary outcome measures. Objective lung function did not change during the study, but over the course of the study, non-specific bronchial hyperreactivity (n-BR) improved by 36% (P = 0.01) and patient-rated asthma severity decreased by 34% (P = 0.0002) compared with the baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Allergen skin test reactivity in an unselected Danish population. The Glostrup Allergy Study, Denmark.

The aim of this study was to assess the distribution of allergen skin test reactivity in an unselected Danish population. A total of 793 subjects, aged 15-69 years, were invited, and 599 (75.5%) attended. The skin prick test was performed with standardized allergen extracts of high potency. Skin reactivity occurred in 28.4% of the subjects. The frequency of skin reactivity to the specific allergens ranged from 1.5% (Cladosporium) to 12.5% (Dermatophagoides pteronyssinus), and the frequencies of skin reactivity to the allergen groups (pollen, animal dander, house-dust mites, and molds) were 17.6%, 8.7%, 14.0%, and 3.2%, respectively. Young women appeared to reflect the average skin reactivity. When compared with young women, skin reactivity to animal dander was more probable in young men (odds ratio (OR) value = 2.6; 95% confidence interval (CI) of odds ratio value = 1.1-6.1). Current smokers were less likely than nonsmokers to be skin-reactive to pollen (OR = 0.4; 95% CI = 0.3-0.7). In conclusion, allergen skin test reactivity was common, and was related to sex, age, smoking history, and probably genetic predisposition.

Adolescent↗

Food allergy and food intolerance--what is the difference?

The literature is contradictory concerning the use (and misuse) of the terms "food allergy" and "food intolerance." When using double-blind, placebo-controlled food challenge as the gold standard, the clinical picture characterizing both diseases is identical, ie, concomitant signs and symptoms from the skin, gastrointestinal-tract and respiratory system (classical allergic signs and symptoms). A distinction between food allergy and food intolerance thus depends on whether the involvement of the immune system can be verified. The basic problem with diagnostic tests such as skin prick test (SPT), measurement of specific IgE (RAST) or histamine release from basophils (HR) is that in contrast to inhalant allergens, no standardized extracts are commercially available. It is therefore often not possible to discriminate between the ability of a test per se in the diagnosis of food allergy and differences in allergen extract quality. This is probably the reason for the great variability in diagnostic sensitivity and specificity reported in the literature. Many cases of food allergy to proteins may be therefore misdiagnosed as food intolerance due to a low sensitivity of the tests (SPT, RAST, and HR) used.

Double-Blind Method↗

[High dose inhaled steroids in the treatment of bronchial asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial reactivity and adrenocortical function].

The effects of high-dose inhaled budesonide (800 micrograms twice daily) and those of inhaled beclomethasone dipropionate (750 micrograms twice daily) were compared with respect to lung function, symptoms, bronchial reactivity and adrenocortical function in a doubleblind, double-dummy cross-over study. The subjects were 40 adult patients suffering from either allergic or non-allergic asthma. The asthma was categorized as moderate to severe, and the asthma was insufficiently controlled on inhalational steroids given in doses of 300 to 500 micrograms daily. After a two week "run-in" period the patients were randomized to six weeks treatment with either budesonide or beclomethasone dipropionate, followed by six weeks treatment with the opposite drug. Both inhaled budesonide and inhaled beclomethasone dipropionate were able to improve objective measures of lung function and bronchial sensitivity to histamine. Neither drug affected adrenocortical function, and no serious side-effects were noted during the trial. It is concluded that budesonide and beclomethasone dipropionate are safe and effective drugs for the treatment of asthma in adults. The substances are equally effective taken microgram for microgram.

Administration, Inhalation↗

The protective effect of inhaled levomepromazine (Nozinan) on histamine-induced bronchial constriction.

The effect of inhaled levomepromazine (Nozinan, Veractil) on bronchial responsiveness to inhaled histamine was investigated in asthmatics. In a double blind, randomized controlled study, 12 asthmatics (FEV1% pred 52-96%, and PC20 histamine 1.01 mg/ml (geometric mean)) were challenged before and after inhalation of levomepromazine in three different doses. Before and after each inhalation of levomepromazine, PC20, FEV1, the continuous reaction time (CRT) and the subjective sedation score (VAS) were determined. A dose-dependent increase in PC20 was observed after inhalation of levomepromazine. PC20 was increased by up to 4.02 two-fold concentration differences (doubling), i.e. up to a 38-fold increase from the basic values. Inhalation of the two higher doses of levomepromazine had a small sedative effect evaluated from an increase in CRT and the VAS-score and corresponding to the plasma concentrations. We conclude that inhaled levomepromazine has a dose-dependent protective effect on histamine-induced bronchial hyperresponsiveness in asthmatics and that inhalation of levomepromazine was well tolerated. The mechanism by which levomepromazine acts on histamine-induced bronchial hyperresponsiveness is not known but it could be partly explained by the antihistaminic effect. In this respect levomepromazine bears comparison with the most potent second generation antihistamines. The plasma concentrations of levomepromazine measured corresponded to those seen after oral intake of 5-10 mg levomepromazine.

Administration, Inhalation↗

Can subjects with a positive allergen skin test be selected by a short questionnaire? The Glostrup Allergy Study, Denmark.

The objective was to evaluate a postal questionnaire screening procedure for selection of subjects with positive reactions to skin prick tests with common allergens. The project consisted of a screening, with subsequent skin prick test of two selected groups. The setting was the Glostrup Population Studies institute in Copenhagen, Denmark. Participants in the screening included 8000 subjects, aged 15-69 years. The subjects were randomly selected from the population of western Copenhagen County, Denmark. From the 6998 respondents (87.5%), 793 subjects were randomly selected (Random Group), and 788 subjects were chosen on the basis of their answers to the questionnaire (Symptom Group). Both groups were invited to take skin prick tests. Attendance rates were 75.5% (Random Group) and 80.6% (Symptom Group). The main outcome measures were responses (yes or no) to the specific questions and the subjects' skin reaction (positive or negative). The association between symptoms and skin reactivity, adjusted for the effects of sex and age, was summarized by odds ratios. Symptoms on exposure to allergens were highly associated with positive skin reactivity. In the Symptom Group the percentage of subjects with at least one positive skin reaction was 57.7%, which was twice as much (28.4%) as in the Random Group. The results show that it was possible to select a group with high skin reactivity on the basis of the symptoms reported in the screening. Questions about exposure to allergens were the most appropriate for selection of this group.

Adolescent↗

Importance of cerebral pan-angiography for detection of multiple aneurysms in patients with aneurysmal subarachnoid haemorrhage.

In the Danish Aneurysm Study 948 patients had a ruptured intracranial aneurysm (RA) revealed by cerebral angiography. Unilateral carotid angiography (UCA) with or without vertebral angiography (VA) demonstrated the RA in 206 patients, and 16 (7.8%) unruptured aneurysms (UA) were disclosed by UCA and 1 UA by VA. In 740 patients with at least bilateral carotid angiography (BCA) 164 UA (22.2%) were disclosed by BCA and 10 by VA. I.e. the number of UA demonstrated in patients with RA is not only doubled by BCA compared to ipsilateral UCA, but tripled demonstrating that an additional UA is more likely situated on the opposite side of the RA. Pan-angiography (or at least BCA) is therefore recommended in patients with RA.

Adolescent↗

The effect of specimen geometry on the mechanical behaviour of trabecular bone specimens.

The effect of specimen geometry on the mechanical behaviour of trabecular bone specimens was studied by non-destructive uniaxial compression to 0.4% strain using cylindrical specimens with different sizes and length-to-diameter ratios, and by comparing cubic and cylindrical specimens with the same cross-sectional area. Both the length and the cross-sectional area of the specimen had a highly significant influence on the mechanical behaviour (p less than 0.0001). Within the actual range of length (2.75-11.0 mm) the normalized stiffness (Young's modulus) was related nearly linearly to the specimen length. This dependency on specimen length is suggested to be caused mainly by structural disintegrity of the trabecular specimens near the surface. The normalized stiffness (Young's modulus) was also positively correlated to the cross-sectional area. This dependency on cross-sectional area is probably due to friction-induced stress inhomogeneity at the platen-specimen interface. A cube with side length 6.5 mm or a cylindrical specimen with 7.5 mm diameter and 6.5 mm length are suggested as standard specimens for comparative studies on trabecular bone mechanics.

Adult↗

Bronchial allergen challenge: dose versus concentration.

This study was designed to investigate if two equivalent doses of allergen administered by different dosing regimes--two breaths and 10 breaths of each concentration--would result in the same magnitude of the early and late asthmatic response. Fifteen patients with extrinsic allergic asthma were challenged twice with either two or 10 breaths of twofold increasing allergen concentrations. The challenge was continued until a 20% decrease in FEV1 had been achieved. A non-cumulative PC20FEV1 allergen was derived, and the cumulative dose of allergen given was similarly derived. In order to assess the reproducibility of the challenge, seven patients were challenged twice with two-breath regime. The mean value of allergen PC20 obtained by the two-breath regime was 4.1 fold (95% CI: 2.3-7.1 fold) greater than those obtained by the 10-breath regime (P less than 0.05), whereas the difference was 1.4 fold (95% CI: -3.3-0.5 fold) for the cumulative dose (P greater than 0.05). A statistically significant larger magnitude of the early asthmatic response, as determined by the maximum per cent fall in FEV1, and late asthmatic response determined by the maximum per cent fall in peak expiratory flow domiciliary recorded during the following 24 hr after challenge, was observed in favour of the 10-breath regime compared to the two-breath regime (mean difference 6%, 95% CI: 0.6-11%). The reproducibility of the provocation test was acceptable (+/- 1.8 two-fold concentration difference). These results confirm the 'equivalent dose hypothesis', and demonstrates that dosage rather than concentration appears to determine the early and late asthmatic response after bronchial allergen challenge.

Adolescent↗

Aeroallergen analyses and their clinical relevance. II. Sampling by high-volume airsampler with immunochemical quantification versus Burkard pollen trap sampling with morphologic quantification.

A comparison was made between the amount of airborne pollen collected by Burkard airsampler and the allergenic activity of particles trapped on glass fibre filters in an Accu-Vol high-volume airsampler. The comparison was made throughout the pollen seasons 1986 to 1989. Both airsamplers were operated 24 h a day. They were placed less than 5 m apart, and estimation of the pollen amount was made on a day-to-day basis during the pollen seasons, and on a weekly basis outside the seasons. The occurrence of the 3 clinically most important allergenic types of pollen, birch, grass, and mugwort, was analysed, and close correlations between the 2 sampling techniques were found (rs 0.5-0.8, p < 0.001). The detected range of counted pollens/m3 was: birch 0-1075, grass 0-156, and mugwort 0-44. By immunochemical analysis we found the corresponding amounts to be 0-80, 0-8, and 0-1 SQ-U/m3, respectively. Pollen counts and immunochemical estimation were compared with the symptom score recordings of allergic persons for birch season 1989 and for grass seasons 1986, 1988, and 1989. A close correlation was found for both sampling techniques for the grass seasons in 1986 and 1989 (rs 0.51-0.61, p < 0.001-0.0001), but a less significant correlation was found for the 1988 grass season, and for birch in 1989 (rs 0.24-0.34, p < 0.001-0.05).

Air Pollutants↗

High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function.

The efficacy of budesonide (800 micrograms b.d.) and beclomethasone dipropionate (750 micrograms b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV1, FVC, PEF or the histamine PC20. Asthma severity, symptom score and inhaled bronchodilator use showed the same results after both treatments. It is concluded that inhalations of budesonide and beclomethasone dipropionate in high doses are equally potent in the treatment of severe asthma. There is no significant influence on the adrenal function and no significant side effects during a period equal to that of the present study.

Administration, Inhalation↗

Airway calibre as a confounder in interpreting bronchial responsiveness in asthma.

BACKGROUND: The relation between airway responsiveness to constrictor agents and forced expiratory volume in one second (FEV1) is important when interpreting change in airway responsiveness after an intervention. The aim of the study was to analyse the relation between FEV1 as a percentage of predicted values (% predicted) and airway responsiveness between and within asthmatic subjects. METHODS: Results of non-specific bronchial challenge tests were pooled from two randomised crossover studies comparing the effect of a non-sedative antihistamine with placebo in 35 patients with moderate asthma. The design of the two studies was similar: the provocative concentration of either histamine (first study) or methacholine (second study) resulting in a 20% decrease in ventilatory capacity (PC20) was repeated at two week intervals while patients were treated with the antihistamine or placebo. The dose of inhaled corticosteroid was gradually reduced during the study. Data were analysed with PC20 as the dependent variable in a general linear model so that the influence on PC20 of inhaled corticosteroid dose, antihistamine, and choice of bronchoconstricting agent could be separated from the influence of FEV1% predicted. RESULTS: The correlation coefficient between mean PC20 and mean prechallenge FEV1 for each patient was 0.45. In the general linear model two thirds (65%) of the variation in PC20 was due to variation between subjects. One third of the within subject variation in PC20 could be explained by variation in prechallenge FEV1% predicted (a change in FEV1 of 27% predicted was associated with one doubling or halving of PC20). Treatment with the antihistamine had no influence on PC20, except when histamine was used as the bronchoconstricting agent. The dose of inhaled corticosteroid had a small but significant effect. CONCLUSIONS: The variation in a patient's PC20 over time (several months) is related to changes in FEV1% predicted. Variation in FEV1% predicted explains less of the variation in bronchial responsiveness between subjects where a patient specific factor, which is probably related to the pathogenesis of bronchial asthma, seems to dominate.

Adrenal Cortex Hormones↗

Immunological and physical properties of allergen solutions. Effects of nebulization.

Lyophilised birch pollen allergen extracts, reconstituted with different diluents (H2O, saline, Albumin diluent (AD] were investigated to determine whether the allergen activity and quality of the extracts deteriorated by nebulization with different nebulizers (Pari, Wright, and Sandoz). Allergen activity was measured by IgG4 RAST inhibition technique and allergen quality was analysed by crossed immunoelectrophoresis (CIE). The distribution of particle sizes of aerosols of different allergen solutions was determined by a TSI Aerodynamic Particle Sizer. A significant difference (P less than 0.05) in allergen activity was found between the AD and H2O diluents before and after using a Sandoz nebulizer and a Wright nebulizer equipped with a small chamber. This suggested greater allergen activity in AD-diluted solutions, and the pattern was repeated with the other two nebulizers, but was not statistically significant. The samples diluted with saline showed no significant differences in quality after nebulization except for the impacted aerosol in which one of the precipitates was slightly diminished. In the AD-diluted sample one of the precipitates disappeared from the impacted aerosol and from the nebulization chamber after 2 min nebulization. To elucidate whether the extract proteins had been bound by albumin, samples were submitted to CIE with rabbit anti-human albumin in an intermediate gel. By this procedure one precipitate was transformed to a precipitate in the intermediate gel, indicating that one or more proteins in the extracts may associate with albumin. No significant difference in output was observed between the nebulizers. The particle size distribution curves for each diluent (saline, AD) were identical for the Wright nebulizer with 99% of the dry particles distributed within 0.5-2.0 microns.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

Reproducibility of leukotriene D4 inhalation challenge in asthmatics. Effect of a novel leukotriene D4/E4-antagonist (SR 2640) on leukotriene D4-induced bronchoconstriction.

We have studied the reproducibility of a bronchial leukotriene (LT) provocation test in asthmatics, and the effect of prior treatment with an oral leukotriene D4/E4 antagonist (SR 2640) on LTD4-induced bronchoconstriction in nine asthmatics in a double-blind placebo-controlled randomized cross-over trial. The reproducibility of the bronchial leukotriene provocation test was high. For a specific patient, the replication variance is 0.2303, and the standard deviation is thus 0.4799, corresponding to 48%, i.e. one halving of the dose or half doubling of the dose. SR 2640 antagonised LTD4 induced bronchoconstriction causing a mean shift of 48% to the right of the dose-response curve as compared with placebo (95% confidence interval being 11-137%). This study demonstrates that bronchial LTD4 provocation test is a safe and reproducible method in asthmatics, and that the method can be used to detect LT-antagonism; furthermore that SR 2640 is a weak LTD4-antagonist in asthmatics.

Adult↗

Injuries in high-skilled and low-skilled soccer: a prospective study.

Fifty-five male soccer players organized in three teams, one high and two lower ranking, were followed prospectively during 1 year to register the rate, type and severity of injuries in highly skilled and low-skilled players. The injury rate of the low-skilled players was significantly higher than that of the better players. The reason for this is that low-skilled players play in more competitions. and this is where injuries tend to occur. When we stratified on game/practice, the low-skilled players' excess risk disappeared and no difference was found in the severity of injuries. Different ways of collecting data in epidemiological studies of soccer are discussed and it is concluded that the most precise and accurate collection of data can only be obtained by direct supervision and examination of soccer players in the field.

Adult↗