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Biomedical subjects

B Weeke

Publications and source records attributed to B Weeke.

At least 109 records · Page 6Linked to original sources

Protective effect of a new anti-asthmatic agent (Minocromil) in bronchial allergen challenge tests.

Ten patients were included in a double-blind crossover trial, designed to compare the effects of a new anti-asthmatic agent Minocromil, an organic decarboxylic acid, and placebo on bronchial allergen challenge. The challenges were performed at weekly intervals. Significant differences in favour of Minocromil were found in the concentration of antigen reached at which FEV1 fell below 20% of baseline. This was confirmed by analysis of the decrease in FEV1 recorded at the highest concentrations of antigens, which showed statistically significant differences in favour of Minocromil.

Asthma↗

The predictive value of bronchial histamine challenge in the diagnosis of bronchial asthma.

A prospective survey aiming to study the predictive value of bronchial histamine challenge was performed on 151 patients with a forced expiratory volume1 (FEV1) above 60% of predicted. According to variations in peak expiratory flow rate (PEFR) and medical history the patients were classified as asthmatics (n = 97) or non-asthmatics (n = 54). The diagnostic properties of the challenge were calculated using the statement of Baye. Considering PC20 values below 4.00 mg/ml as positive, the predictive value of a positive test was about 0.80 and the predictive value of a negative about 0.76. When PC20 was below 0.125 mg/ml the predictive value of a positive test was 1.00, but an increase in PC20 in the range from 4.00 to 16 mg/ml did not increase the predictive value of a negative test. In this study the prevalence of asthma was about 0.6. We therefore conclude that bronchial histamine challenge is a valuable test for detection and exclusion of bronchial asthma, when the prevalence of the disease is high. In populations with a lower frequency of bronchial asthma the diagnostic value of a positive bronchial challenge will be negligible.

Adolescent↗

Long-term oral therapy of asthma with terbutaline and theophylline, alone and combined.

Bronchodilation and side effects of 28 days treatment with either a full therapeutic dose of theophylline slow-release preparation 500 mg twice daily (400-600 mg), a slow-release terbutaline preparation 10 mg twice daily or combinations of the 2 drugs in full or half doses were evaluated in 31 asthmatic outpatients in a double-blind, randomized crossover design. The combination of half doses of the 2 drugs produced slightly better bronchodilation than high-dose, single drug regimen and similar bronchodilation as a high-dose combination. Side effects during half dose combination were less than when theophylline alone or high dose combination treatment were administered. High-dose combination treatment produced slightly more ventricular ectopic beats and supra ventricular ectopic beats, and 3 patients developed cardiac arrhythmias. A combination of half the normally used doses of oral slow-release formulations of terbutaline and theophylline seems superior to a high-dose combination.

Administration, Oral↗

Short and long term reproducibility of responsiveness to inhaled histamine: Rt compared to FEV1 as measurement of response to challenge.

Repeatability (123 min) and reproducibility (65 days) of response to inhaled histamine were tested in a selected group of stable asthmatics and non-asthmatics by means of FEV1 and breathing resistance (Rt) determined by the interruptor method. Variation in prechallenge FEV1 and Rt was kept within a +/- 10% and +/- 40% range, respectively. We found the PC20-FEV1 highly repeatable after 123 min. The 95% confidence interval for a single determination was the measured value +/- 1.72 two-fold concentration differences. Reproducibility was significantly lower (p less than 0.05). Both repeatability and reproducibility of PC30-Rt were significantly lower than that of PC20-FEV1. Interruptor method determined PC30-Rt was found repeatable within 4 two-fold concentration differences which is not acceptable for clinical and research purposes. The poor repeatability of PC30-Rt could be due to changes in functional residual capacity during challenge.

Adolescent↗

Dose frequency in the treatment of asthmatics with inhaled topical steroids. Comparison between a twice daily and a once daily dosing regimen.

In 23 stable asthmatic patients sensitivity to inhaled beclomethasone dipropionate (BDP) was demonstrated during single blind gradual tapering off of BDP. After a 2 week stabilization period the patients were randomly allocated to receive either 4 puffs of 50 micrograms BDP twice daily (AM/PM) or 8 puffs of 50 micrograms once daily (AM). After 4 weeks the patients were crossed over. Fifteen patients preferred the twice daily regimen, 5 preferred once daily and 3 had no preference (p less than 0.05). During the once daily dosing regimen a decrease in morning and evening peak expiratory flow (p less than 0.05) and an increase in nighttime and daytime symptom score (p less than 0.05) was found, while the number of inhaled beta 2-agonist doses did not change significantly (p = 0.05). It is concluded that a twice daily regimen controls the asthmatic symptoms significantly better than a once daily regimen.

Administration, Topical↗

Comparison of oral enprofylline and theophylline in asthmatic patients.

The bronchodilator effect and side-effects of a single oral dose of enprofylline were compared with the corresponding actions of a therapeutic dose of theophylline in 20 asthmatic patients, in a randomized cross-over clinical trial. Enprofylline 4 mg/kg and theophylline 8 mg/kg produced mean maximum plasma levels of 4.40 +/- 0.91 micrograms/ml and 16.5 +/- 2.58 micrograms/ml and mean maximum increases in FEV1.0 of 38.5% and 34.8%, respectively. The degree of headache and nausea was estimated by a scoring system. Enprofylline produced significantly higher scores for headache than theophylline, and both drugs produced s light nausea. No other side-effects were seen. Enprofylline seems to have bronchodilating properties comparable to those of theophylline without producing severe side-effects.

Administration, Oral↗

A new method for detecting histamine release.

Glass microfibres have been found to bind histamine with high affinity and selectivity. A new test for measuring basophil histamine release has been developed using the glass microfibres as a solid phase. Glass microfibres are crushed and fixed to the bottom of microtitre plates with a water-soluble glue. Histamine release is performed in the glass microfibre -prepared microtitre plates by challenging 100 microliter washed blood with 20 microliter antigen per well for 90 min at 37 degrees C. Released histamine is bound with high affinity to the glass microfibres , since 90% of histamine in the solution is adsorbed to the fibres. After incubation the microtitre plate is washed with H2O to remove cells and interfering substances. Fibre-bound histamine is detected by the fluorometric o-phthaldialdehyde method. The sensitivity of the assay is 0.63 ng histamine, 2 HCl and the histamine standard curve is linear up to at least 5 ng histamine, 2 HCl. Optimal conditions for the new assay are described. After challenge with anti-Ige a comparison with the conventional histamine release from Ficoll-Hypaque-isolated leukocytes showed almost identical results.

Histamine↗

Maximally effective plasma concentrations of enprofylline and theophylline during constant infusion.

Bronchodilating effects produced by increasing intravenously administered doses of enprofylline and theophylline compared to placebo were evaluated in 20 asthmatic outpatients. Three mean plasma plateaux of enprofylline of 1.5, 2.9 and 4.0 micrograms/ml produced a mean increase in forced expiratory volume in the first second (FEV1.0) as a percentage of baseline, of 12.8%, 18.8% and 30.1%, respectively. Comparable plasma plateaux of theophylline i.e. 5.5, 10.8 and 15.2 micrograms/ml produced a mean increase of FEV1.0 in percent of basal values of 12.4%, 21.6% and 28.2%, respectively. Enprofylline at plasma concentrations above 2.9 micrograms/ml induced more headache and slightly more nausea than theophylline and placebo. Theophylline infusion produced more tremor (finger oscillation) than enprofylline and placebo. Intravenously administered enprofylline produces bronchodilation comparable to theophylline in a mean dose ratio of 3.8.

Adult↗

A reference allergen preparation of the house dust mite D. pteronyssinus, produced from whole mite culture--a part of the DAS 76 study. Comparison with allergen preparations from other raw materials.

A D. pteronyssinus whole culture allergen preparation contained 49 antigens as revealed by crossed immunoelectrophoresis (CIE), using polyspecific rabbit antibodies. Crossed radio-immunoelectrophoresis ( CRIE ) with sera from 30 patients revealed nine allergens, antigens 42, X, Y and 23 (in rank order) showing the most frequent and intense IgE-uptake. Nine antigens originated from the culture medium (human dander + yeast), but none of these gave rise to specific IgE-uptake. Extremely few and weak reactions were observed in radioallergosorbent (RAST) with 129 sera, using media extracts on the discs. Purified mite body extract (PMB) contained less ag 42 and more ag Y and ag 23 than whole mite culture extract ( WMC ), whereas an acetone-extracted mite excreta preparation (AML) contained 5 times more ag 42, but was devoid of ag Y and ag 23. Ag X was present in all preparations. The RAST-inhibitory potency of PMB was best correlated with the content of ag X. Preparations with properties similar to WMC and PMB were judged as suitable for clinical application.

Allergens↗

Isolation of patient-related antigens from allergen extracts by means of protein A-sepharose-patient IgG1,2,4 bio-affinity chromatography.

A method is described for bio-affinity purification of patient-specific IgG reactive antigens by using protein A-sepharose allergic patient serum and the corresponding antigen/allergen extract. The optimal conditions for each step have been determined and it is shown that the non-specific binding of both serum proteins and antigens can be kept at very low levels by a high ionic strength. The specificity of the reaction has been shown by biospecific elution of 125I-labelled antigens by non-labelled antigens and also by comparison of the amount of antigen bound by sera from hyposensitized patients with that from non-atopic individuals. It is suggested that the isolated antigen-IgG-immune complexes could be used for a specific and active immunotherapy.

Allergens↗

Cumulative dose response study comparing clinical effects of two doses of terbutaline sulphate administered via a 750 ml spacer to asthmatic patients.

Thirteen out-patients suffering from chronic reversible bronchial obstruction were treated on two separate days with two doses of terbutaline aerosol, administered with a 750 ml spacer interposed between the actuator and the mouth, in order to evaluate whether clinical responses showed a dose dependency during a 4-h period. On each day the two different doses (65 micrograms versus 250 micrograms) were inhaled three times at 15-min intervals. Fifteen minutes after the first dose there was a significant difference in FEV1 increase between the small dose and the normal dose, FEV1 being higher after 250 micrograms, but no significant differences in increase after the 2nd and 3rd inhalations. This study indicates that the bronchodilating effect of terbutaline administered via the spacer is dose-dependent at the first inhalation, and that succeeding inhalations show no dose-response effects.

Adult↗

A three-layer immunoradiometric assay for determination of IgG subclass antibodies in human sera ("IgG subclass RAST"). Validation of the subclass specificity, and establishment of equipotency.

We report the development of a three-layer immunoradiometric assay (TIRA) for measurement of IgG antibodies of all four subclasses in human sera. The first layer consists of diluted human serum, the second layer is monoclonal mouse antibodies to human IgG subclasses, and the third layer is 125I-labelled rabbit anti-mouse IgG. Monoclonal anti-IgG1, anti-IgG3 and anti-IgG4 reacted only with their complementary IgG subclass, whereas the anti-IgG2 showed slight cross-reactivity to immunoglobins of other subclasses and classes and to light chain proteins. The observed cross-reactivity was found to be without importance, when the TIRA was applied to measurement of IgG subclass antibodies. Equipotency was established by use of appropriate dilutions of the monoclonal antibodies, and the assay was calibrated by use of human reference serum. The TIRA therefore permits reliable inter-individual and intra-individual comparisons of the IgG antibody response in all four subclasses. Non-specific binding obtained with pooled normal human serum was below 0.33%. Inter-assay coefficient of variation was between 18 and 27%. The TIRA was applied to measurement of IgG subclass antibodies to timothy grass pollen in sera from grass pollen allergics undergoing immunotherapy.

Animals↗

A modified crossed radioimmunoelectrophoretic method for determination of allergen-specific IgG antibodies. Elimination of non-specific binding by use of F(ab')2-fragments of rabbit antibodies and 125I-labelled protein A.

A crossed radioimmunoelectrophoretic (CRIE) method for detection of specific IgG antibodies in patients' sera against horse hair and dander was developed. The unacceptably high non-specific binding encountered when substituting 125I-labelled antihuman IgG for 125I-labelled antihuman IgE in an ordinary CRIE was eliminated by the combined use of 125I-labelled Protein A as detector, and F(ab')2-fragments of the allergen-specific rabbit antibodies. The low background binding thus obtained makes the method useful for detection of specific IgG in sera where the ratio between specific and non-specific IgG is low. Therefore the method should also be applicable to other antigen/allergen systems.

Animals↗

Acupuncture and bronchial asthma.

Seventeen patients with stable bronchial asthma were randomly assigned to receive either correct acupuncture or placebo acupuncture. The study lasted 11 weeks and consisted of a pre-therapy, therapy, and post-therapy period. The patients received 10 treatments during a 5-week period. The effect of therapy on pulmonary function was assessed daily by the patients at home. Morning and evening peak expiratory flow rate, number of puffs beta 2-agonist aerosol needed, as well as subjective symptoms of asthma were recorded in a diary. The correctly treated group improved significantly throughout the study. Also, compared with the placebo group, a significant improvement was found in all assessed parameters 2 weeks after beginning therapy. Hereafter, no differences could be shown.

Acupuncture Therapy↗

Purification of patient-related allergens by means of bioaffinity chromatography on a sepharose anti-IgE patient IgE immunosorbent.

A method is described for bioaffinity chromatographic purification of patient-specific IgE reactive allergens by using sepharose coupled rabbit anti-human IgE antibodies, patient serum and an allergen extract. The conditions for this bioaffinity chromatographic procedure have been optimised, and it was shown that the nonspecific binding of serum proteins and antigens can be kept at very low levels by a high ionic strength. The specificity of the method has been determined by showing that allergens to which the patient did not react were not bound to the affinity matrix. We suggest that the isolated allergens could be used for more specific immunotherapy in the future.

Allergens↗

Characterization of IgG-subclass antibodies to individual allergens by crossed radioimmunoelectrophoresis.

A crossed radioimmunoelectrophoretic (CRIE) method for detection of human IgG subclass specificities against individual antigens is described. After crossed immunoelectrophoresis (CIE) of the antigens the immunoplates are incubated with serum, washed and incubated with mouse monoclonal anti-human IgG-subclass antibodies. After washing, the plates are finally incubated with the 125I-labelled detector protein, rabbit anti-mouse IgG, and washed. The plates are then placed on an X-ray film for autoradiography. The specificity of the method was tested by inhibition with antigens in the first layer and by inhibition with myeloma sera containing only one IgG subclass protein in the second layer. The specificity of the third layer was assured by affinity purification of the rabbit anti-mouse IgG antibodies. The method was shown to be sensitive and specific. The test systems were timothy (Phleum pratense) pollen antigens and house dust mite (Dermatophagoides pteronyssinus) antigens.

Allergens↗

Non-hydrolysed and hydrolysed soy protein. A human immunological study.

Daily consumption of soy protein has increased during recent years. Twelve healthy subjects and 12 atopic patients were given 30 g non-hydrolysed soy protein (NHS) or 30 g hydrolysed soy protein (HS) daily during a 3-month period. There were no changes in the following immunological parameters: IgE with specificity for NHS or HS, IgG with specificity for NHS, crossed radioimmunoelectrophoresis with NHS and skin prick test using NHS or HS. Hypertrophy of the pancreas in rats exposed to excessive peroral intake of soy flour has been reported. In our study the size of the pancreas was measured before dosing began and at the end of the study by means of ultrasound. No change in size was shown. Daily intake of 30 g NHS and 30 g HS gave rise to gastrointestinal discomfort, while 15 g of both soy protein preparations were usually accepted.

Adult↗