Biomedical subjects
U G Svendsen
Publications and source records attributed to U G Svendsen.
[Foot zone therapy and bronchial asthma--a controlled clinical trial].
Thirty patients with proved bronchial asthma receiving treatment with inhaled steroid in dosages of less than 1,000 micrograms daily were subdivided at random into two groups of 15 patients. One group received foot zone therapy and the other merely uniform clinical care but without "placebo foot zone therapy". The "active" group received a total of ten foot zone therapy sessions of one hour at intervals of one week. The asthmatic symptoms, consumption of medicine and the objective pulmonary function parameters were followed-up during the subsequent six months. Decrease in consumption of beta-2-agonists and increase in peak-flow levels were observed in the group which had received foot zone therapy, but the same changes were observed in the control group. The authors do not find that this investigation demonstrates that foot zone therapy is of effect on the disease bronchial asthma. They conclude, however, that the favourable effect in both of the groups are due to increased care and control which occurred in both patient groups.
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.
Comparison between two different assays for measurements of allergen-specific IgE and skin prick test in the diagnosis of insect venom allergy.
Forty-one patients stung by wasp and 29 by bee were evaluated by comparing the correlation between skin prick test (SPT), Phadebas radioallergosorbent test (P-RAST) and Magic Lite SQ Specific IgE assay (LIA). All patients had had a systemic reaction to insect sting. In the patients stung by bee we found agreement between SPT and P-RAST, and SPT and LIA. Similarly, there were no significant differences in sensitivity between P-RAST and LIA (p > 0.05). In patients stung by wasp, SPT was found to be more sensitive than P-RAST. There were no differences between SPT and LIA or between P-RAST and LIA.
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.
Comparison of loratadine and terfenadine in allergic seasonal rhinoconjunctivitis with emphasis on nasal stuffiness and peak flow.
Non-sedating antihistamines have been used in the treatment of allergic rhinoconjunctivitis. Recommended dosage of loratadine (CAS 79794-75-5) is 10 mg once daily, whereas terfenadine (CAS 50679-08-8) until recently has been recommended as 60 mg twice daily. 105 patients took part in this double-blind 3-week controlled study comparing loratadine 10 mg once daily to terfenadine 120 mg once daily. Patient's daily symptom score and physician's assessment of symptoms, treatment effect and anterior rhinoscopy were evaluated as well as an objective parameter, nasal peak flow. In addition nasal peak flow was compared to patient's symptom score of stuffiness. A significant treatment effect in both treatment groups was found but there was no statistically significant difference between the two groups. Correlation between patient's feeling of stuffiness and nasal peak flow was significant. It is concluded that loratadine 10 mg once daily is as effective as terfenadine 120 mg once daily in controlling allergic rhinoconjunctivitis, and that patients' feeling of stuffiness correlates well to nasal peak flow.
[Sodium-nedocromil. A new anti-inflammatory agent for the treatment of asthma].
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[Allergy to insect stings].
Components in the insect venom and probably also in their saliva may have direct toxic effects or may cause sensitization and may result in allergic reactions to subsequent stings. In Denmark, only the stings of honey bees and wasps (yellow jackets) are of clinical significance and it is important to be aware that these insects contain separate allergenic components. Clinical manifestations following stings are observed from all of the organ systems on the whole. The commonest are itching of the skin, urticaria, possibly angioedema and slight generalized symptoms with vertigo, headache and fatigue. Life-threatening reactions may also occur and one or two fatal cases are registered annually in Denmark. It may be difficult to decide whether an allergic or a toxic reaction is involved on the basis of the symptoms. Possible IgE-sensitization must therefore be assessed by means of a prick test and measurement of specific IgE. The main treatment in cases of acute systemic reactions is adrenaline which may possibly be supplemented with antihistamine and corticosteroid. In cases of massive local reactions and urticaria, antihistamines will, as a rule, prove sufficient. Hyposensitization with insect venom preparations eliminates the future risk for systemic insect sting reactions practically entirely and this must be recommended for patients with demonstrated IgE-sensitizing and generalized reactions. At present, treatment should be continued for three to five years and protection lasts for a series of years after cessation of treatment.
Purification and characterization of the major dog allergen, Can f I.
An important dog-hair and dander-specific allergen Ag13 has been purified by means of immunoaffinity chromatography utilizing rabbit antibody specific for Ag13. Purity was judged to be very high as detected by crossed immunoelectrophoresis and SDS-PAGE. The purified allergen was subjected to amino acid analyses. Molecular weight was about 22 kD in HPLC-gel filtration and 25 kD in SDS-PAGE with an additional band at 18 kD. In vitro IgE binding of the allergen was investigated by luminescence immunoassay (LIA) inhibition. Removal of Ag13 from dog hair and dander extract (DHD) removed 50 +/- 1.5% of the IgE binding capacity. The purified allergen inhibited up to 56.5% of the IgE activity to DHD as measured with a pool of serum from dog-allergic patients. Out of 26 dog-allergic patients, 24 had a positive skin-prick test to the allergen. Out of 23 dog-allergic patients, 16 reacted with the allergen in IgE immunoblotting. We suggest that Ag13 be termed Can f I. The allergen will be a marker allergen for environmental dog hair and dander exposure.
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)
Comparison of methods for intestinal histamine application: histamine in enterosoluble capsules or via a duodeno-jenunal tube. Influence of fast and histamine-restrictive diet.
The study was conducted to investigate whether introduction of histamine in enterosoluble capsules produced the same amount of urinary histamine metabolites as that found after application of histamine through a duodeno-jejunal tube. Secondly, to examine whether a histamine-restrictive or a fast diet affected the amount of urinary metabolites. Fifteen healthy subjects were challenged four times with 100 mg of histamine. Results were monitored by the urinary recovery of 1,4-methylimidazole acetic acid (MIAA) from 24 h before to 72 h after challenge. Urine was collected in 24-h samples except on the first day after challenge when separation into 0-2h-, 2-4 h- and 4-24 h-fractions was made. MIAA was measured by high performance liquid chromatography (HPLC). The results showed that during the first 2 h after challenge the recovery of MIAA was higher with tubes than with capsules. Measurements from all other intervals did not differ significantly between the two challenge regimens. Fast (water only) and histamine-restrictive diet versus non-restrictive diet did not affect the urinary MIAA. MIAA was significantly higher overall during the first 24 h after challenge than in any other fraction. We conclude that oral administration of enterosoluble capsules is an easy and appropriate method for intestinal histamine challenge. Fast and histamine-restrictive diets are not necessary, but subjects should record unexpected responses in a food and symptom diary.
House dust mite allergy and anti-mite measures in the indoor environment.
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Inhaled nedocromil sodium as additional treatment to high dose inhaled corticosteroids in the management of bronchial asthma.
Thirty five asthmatic patients were included in a randomized, double-blind, placebo-controlled, parallel group study of inhaled nedocromil sodium (4 x 4 mg daily) as an additional treatment to high dose (greater than or equal to 1,000 micrograms) inhaled corticosteroids in the management of bronchial asthma. Following a four week baseline, patients received nedocromil sodium (17) or placebo treatment (18) for eight weeks. Five patients (four in the group subsequently randomized to nedocromil sodium) used short course oral corticosteroid therapy during the baseline and four placebo treated patients used oral steroid therapy during treatment. Fifteen patients (11 nedocromil sodium) reported unusual symptoms. Two nedocromil sodium treated patients were withdrawn owing to treatment taste and vomiting. Statistically significant treatment differences in favour of nedocromil sodium were seen for daytime symptoms (p = 0.03) and morning peak expiratory flow (PEF) (p = 0.012) during weeks 5-8, and for clinician opinion (p = 0.02). Patient opinion (p = 0.053) and evening PEF (p = 0.08) failed to reach statistical significance. Eight out of fifteen and three out of seventeen patients considered nedocromil sodium and placebo, respectively, to be very or moderately effective. The results indicate that the addition of nedocromil sodium (4 mg four times daily) to moderate to severe asthmatics not fully controlled on a regimen of greater than or equal to 1,000 micrograms inhaled corticosteroids and inhaled bronchodilators can produce improvements in symptoms and pulmonary function.
[Lung transplantation].
Isolated lung transplantation or combined heart and lung transplantation provides a new therapeutic possibility for patients with certain benign terminal pulmonary diseases. This method of treatment makes great demands on not only the donors but also the recipients. Following operation, which is undertaken in selected centres, life-long clinical control with immune suppressive treatment is essential. The method of treatment is associated with a series of complications and long-term survival does not appear to be optimal yet. A series of Danish patients have received lung transplantation abroad and are now followed in Danish special departments in cooperation with their own general practitioners.
[The significance of incorrect spray technic on the consumption of terbutaline in patients with chronic obstructive lung disease].
A total of 140 patients with chronic obstructive pulmonary disease was included in this multicentre parallel group investigation with the object of assessing whether poor inhalation technique results in increased consumption of beta 2-agonist. On the basis of measurements of pulmonary function, the patients were stratified into two groups with good and poor inhalation techniques, respectively, and these were subdivided at random to inhalation of terbutaline via either a freon spray (aerosol) or Turbohaler (powder). During a period of four weeks the daily terbutaline consumption, the symptoms and pulmonary function were noted. Patients with poor inhalation technique did not have significantly increased terbutaline consumption. The consumption of terbutaline was independent of the method of administration. The Turbohaler was just as effective as the spray and the patients preferred this method, (p less than 0.05).
Hyposensitization in asthmatics with mPEG-modified and unmodified house dust mite extract. IV. Occurrence and prediction of side effects.
A double-blind study on hyposensitization (HS) with two extracts prepared from the house dust mite Dermatophagoides pteronyssinus (Dp) was performed on a group of asthmatics with bronchial sensitivity to Dp. In 18 patients, aluminium-hydroxide was added to the Dp-extract to give a depot effect (Dp-group). Nineteen patients were treated with a similar extract in which allergenicity had been reduced by coupling to monomethoxypolyethylene glycol (mPEG-Dp-group). This extract had previously been shown to have less effect on clinical symptoms and skin sensitivity compared to the Dp-extract. In the Dp- and mPEG-Dp-groups, 778 and 675 injections were administered. Fifteen and 12 patients in the Dp- and mPEG-Dp-groups had systemic reactions (P greater than 0.05). The frequency of injections giving systemic reactions was reduced in the mPEG-Dp-group: 5.1% compared to 9.0% in the Dp-group (P less than 0.01). In the mPEG-Dp-group, reactions were mild to moderate, mainly late-occurring asthma and urticaria, whereas two episodes of anaphylaxis and four of severe asthma occurred in the Dp-group. The reduction in side effects seems promising, but a further dose increase in the mPEG-Dp-group would be necessary to compare the side effects of doses with equal therapeutic effectiveness. High frequency of late local reactions made dose increase impossible with the present slightly modified extract. The systemic side effects occurred more frequently in patients highly skin test-sensitive to Dp prior to treatment. All patients skin test-positive to less than or equal to 100 BU had systemic reactions. Systemic side effects could not be predicted from the size of previous local reactions.
Methylprednisolone pulse therapy in acute severe asthma. A randomized, double-blind study.
Methylprednisolone pulse therapy (MPPT) has been shown to possess a long-lasting effect in other immune-inflammatory diseases without the well-known side effects caused by long-term treatment with glucocorticosteroids. In an attempt to reduce the long-term use of oral steroids in asthmatics, we conducted this double-blind, double-dummy study to compare the use of MPPT (1 g of methylprednisolone intravenously) (8 patients) with a short course of oral prednisolone (10 patients) in asthmatics presenting with acute severe asthma. Both treatments were effective in relieving the acute attack of asthma. The MPPT-treated patients did not show a faster resolution than did the orally treated group. No patients needed assisted ventilation, and no deaths occurred. One week after the treatment FEV1 tended to decrease in the methylprednisolone group compared with the oral prednisolone group (P = 0.06). The patients initially receiving MPPT needed supplementary prednisolone earlier and in higher doses than did the patients receiving oral prednisolone as initial treatment. At the end of the 12 weeks' study period, the groups reached identical FEV1. In conclusion, we did not find intravenous methylprednisolone superior to oral prednisolone in the treatment of acute attacks of severe asthma, but methylprednisolone pulse therapy had a shorter duration as regards protection against future asthma attacks.
[Diagnostic reliability of the CLA test and RAST in IgE-mediated allergy compared with anamnesis and the prick test].
The principle and mode of conduction of a non-isotope method, the DHS-CLA-allergy test, for in vitro diagnosis of allergic disease is described. The method has been tested and found easy to carry out without special laboratory facilities. Thirty-nine patients all of whom were suspected of allergy were tested for nine typical allergens with the prick test, Al-RAST (ALK) and the DHS-CLA-allergy test. Definite allergy was defined on the basis of definite history of allergy and the positive prick test and, from this, the nosological sensitivity was calculated. No history of allergy and negative prick test results were defined as no allergy, and the nosological specificity was calculated from this. The nosological sensitivity for all nine allergens: Al-RAST: 46.8%, DHS-CLA: 85.5%. Nosological specificity for all nine allergens: Al-RAST: 85.7%, DHS-CLA: 80.3%. The results for the individual allergens are apparent from the text.