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Biomedical subjects

B Weeke

Publications and source records attributed to B Weeke.

At least 19 recordsLinked to original sources

Evidence of a common regulation of IgE and IgG-subclass antibodies in humans during immunotherapy.

Based on a 3-year prospective study of 20 pollen-allergic patients, where a detailed analysis of the IgE, IgG1 and IgG4 immune response was performed, we propose that a common regulatory mechanism exists between the IgE and IgG1 synthesis and between IgE and IgG4 synthesis during immunotherapy. It was found that the IgE immune response to a number of antigens was quantitatively diminished during the period of immunotherapy when IgG1 was present early (week 12), and for other antigens there was a rise in IgE without an early IgG1 antibody response. Additionally, it was found that for some antigens a rise in IgE antibodies was contrasted by a fall in the IgG4 antibody response and for other antigens the opposite was true, indicating a regulatory mechanism between the IgE and the IgG4 synthesis. A statistical analysis showed that these findings were statistically significant at the 0.01% level for the IgE/IgG1 relationship and at the 0.05% level for the IgE/IgG4 relationship. These findings could have implications for future immunotherapy regimens.

Desensitization, Immunologic

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

A computational approach to the description of individual immune responses. IgE and IgG-subclass allergen-specific antibodies formed during immunotherapy.

Detailed evaluation of the IgE and IgG-subclass immune response during immunotherapy can now be performed by crossed radio immunoelectrophoresis (CRIE). Some new concepts are introduced facilitating the handling of the vast amount of data obtained by quantitating the immune response. These concepts are "distance" between antibody responses and "immune response width". The 20 patients included in this study were pollen-allergic patients who underwent specific immunotherapy in a 3-year prospective study. It was found that the immune response during immunotherapy was restricted to IgG1 and IgG4 antibodies. The semi-quantitative CRIE analysis correlated with the RAST analysis for the IgE samples before start of immunotherapy, for the IgG1 samples at week 12, and for all the IgG4 samples. During immunotherapy the number of IgG1 antibodies directed to the different antigens increased towards 11 antigens and decreased towards six. For the IgG4 antibodies the number of reactions increased towards 15 antigens and decreased towards four. The increase is generally paralleled by an increase in quantitative immune response as well. For some of the antigens a rise in the IgE antibodies is contrasted by a fall in the IgG4 antibody response, and for other antigens the opposite was true, indicating a regulatory mechanism between the IgE and the IgG4 synthesis. The IgE immune response to a number of antigens, including the major allergens before the start of immunotherapy, was quantitatively diminished during the period of immunotherapy when IgG1 was present early (week 12) in the period, and for other antigens there was a rise in IgE without an early IgG1 antibody response. This suggests that IgG1 can have a regulating influence on the IgE synthesis. Finally, we have found that IgE antibodies with specificities not present in the samples taken before immunotherapy were formed during immunotherapy. These new IgE antibodies do not, however, seem to impair the outcome of treatment.

Antigens

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.

Adolescent

Allergen-containing immune complexes used for immunotherapy of allergic asthma. II. IgE and IgG immune response during and after hyposensitization of sensitized guinea pigs.

In a previous study guinea pigs inbred for their ability to develop respiratory anaphylaxis to experimental antigens have been used for comparison of different forms of immunotherapy (IT). Passive, active and combined (immune complexes prepared from antigen and specific IgG) IT was compared with placebo. In the present study methods were evaluated for determination of the allergen-specific IgE and IgG. IgE was determined by the passive cutaneous anaphylactic test (PCA) and the variability of this test on different strains of the recipient guinea pig was investigated. The same strain as used for the IT study was found to produce the most potent response. Radioimmunometric assays (RIA) were developed and validated for determination of specific IgG1 and IgG2. The IgE and IgG immune response in animals from the IT study were then evaluated by means of PCA and RIA. Animals from all four treatment groups were sensitized during the first part of the IT study, and responded with a marked IgE synthesis which later stabilized on a more moderate level. In spite of notably reduced symptoms in groups treated with active and combined IT, no difference in the IgE level was found between the four groups. In contrast to IgE, mean group titers of IgG1 and IgG2 in the groups receiving active or combined IT rose drastically during the first part of therapy and closely paralleled the clinical response during the rest of the study period. However, in the individual animals, no correlations were found between immune response and clinical symptoms. Thus, the strong IgG response during immunotherapy may not be causally related to the outcome of treatment.

Animals

Single-dose inhaled budesonide in subjects with chronic asthma.

In 30 stable asthmatics, a comparison was made between the changes in pulmonary function (FEV1, FVC, PEF, MEF75, MEF50 and MEF25) hourly for 9 h after a single dose of inhaled budesonide 1,600 micrograms, and placebo. All subjects used inhaled steroids daily; this medication was, however, withheld 8 days prior to the study. For all parameters of pulmonary function, a significant difference in favour of budesonide was demonstrated. The effect tended to decrease after 9 h, and had abated within 24 h. FEV1 age, sex, smoking habits, or results of an inhaled beta 2-agonist reversibility test could not be demonstrated as predictors of those subjects to react with the most pronounced responses to budesonide. In conclusion, our results demonstrate an effect 3 h after administration of an inhaled glucocorticosteroid in adult outpatients with chronic asthma. These results parallel previous findings in highly selected asthmatics and after systemic administration of glucocorticosteroids. Single-dose administration and subsequent monitoring for 8-9 h may therefore prove valuable in evaluating new prophylactic agents for the treatment of asthma.

Administration, Inhalation

Oral allergy syndrome: the effect of astemizole.

The effect of treatment with astemizole (Hismanal) on symptoms elicited by ingestion of hazelnuts in birch pollen-allergic patients (the oral allergy syndrome) was investigated. Thirty patients with a well-documented allergy to silver birch, experiencing symptoms when ingesting hazelnuts, were included in the study. All had a positive skin prick test (SPT) to birch, whereas 29 and 27, respectively, showed a positive RAST and basophil histamine release test (HR) to birch. In contrast, only 15 patients had a positive SPT to hazelnut, 13 had a positive RAST, whereas 24 had a positive HR. After two oral provocations with hazelnuts the patients were randomized to receive either 10 mg of astemizole or placebo daily for 2 weeks in a double blind protocol followed by two oral provocations. Treatment with astemizole significantly reduced the symptoms compared with placebo (P = 0.004); however, without completely abolishing the symptoms.

Astemizole

Immunotherapy of extrinsic asthma.

It is an elegant treatment of IgE allergic inflammation in the airways. It must be started very early in the allergic disease together with allergen avoidance, prevention, optimal symptomatic and antiinflammatory treatment and general health care.

Allergens

Analysis of antigens in a commercial house-dust extract by means of quantitative immunoelectrophoresis.

Crossed immunoelectrophoresis (CIE) of a commercial house-dust extract revealed 43 immunoprecipitates. Rocket immunoelectrophoresis with 106 different allergen extracts from animal hair and dander, feathers, fungi, pollen, foodstuffs, textiles and house-dust mites showed the presence of precipitating antibodies in the rabbit anti-house-dust serum against antigens from 34 of the extracts. Crossed immunoelectrophoresis with the addition of antigen, and crossed line immunoelectrophoresis (CLIE) with these 34 allergen extracts, as well as crossed immunoelectrophoresis with intermediate gel containing rabbit antibodies against nine human serum proteins, allowed the identification of 14 antigens in the house-dust extract. These antigens were shown to originate from house-dust mites, hair and dander from various animals, fungi, feathers, human hair and dander, and human serum proteins.

Allergens

Specific diagnosis of exogenous bronchial asthma in adults. Comparison between case history, intracutaneous test, RAST, histamine release from basophil leucocytes, and bronchial provocation.

Twenty-two adults with extrinsic bronchial asthma were examined with 26 different allergens from five groups: house dust + mite (30 BP), animal dandruff (30 BP), pollen (12 BP), mould fungi (11 BP), and feather + cotton (10 BP). The same allergen batch was used for each allergen extract in all analyses. Based on the results of the single analyses: case history (CH), intracutaneous test (ST), RAST, histamine release from basophil leucocytes (HR), and the results of the analysis combinations and the "true diagnosis" bronchial provocation (BP), the sensitivity and specificity (SE and SP) were calculated and shown graphically. An evaluation of the diagnostic reliability of the single analyses and analysis combination was then possible. Generally, HR was the best individual analysis with very few false positive values and false negative values, followed by RAST, ST, and CH. None of them was able to predict allergy for feather + cotton. Otherwise, BP was positive when HR and rast reached scores 2 and 3 with the exception of RAST for animal dandruff. As regards ST, we had to reach score 3 in order to predict positive BP. CH would only provide the diagnosis with a maximum score in the pollen group. BP was positive in any analysis combination resulting in score 6 or more. ST appeared to be the most sensitive of the individual analyses. All the patients with ST score 0 showed negative BP for all allergen groups, whereas a corresponding sensitivity for HR score 0 was only achieved with animal dandruff, and for RAST score 0 for pollen only. In spite of the new analyses, BP is in many cases necessary if a definite diagnosis is required.

Adolescent

Influence of small atmospheric ions on the airways in patients with bronchial asthma.

The influence of artificially generated atmospheric ions is studied in 15 patients with bronchial asthma. A slight but significant (at 5% level) improvement in the lung function was demonstrated in nine patients during positive as well as negative ion exposure, but the patients' subjective votings of the air quality did not show any changes due to ion exposure. No change in the histamine threshold of the airways in six patients with bronchial asthma was demonstrated during exposure to ions. Further controlled studies with electro-aerosols are needed.

Adolescent

A new lancet for skin prick testing.

A new lancet with a point length of 1.0 mm suitable for skin prick testing is described. The weal reactions appearing after the use of histamine chloride 1 mg/ml and an extract of Phleum pratense in a 1 HEP concentration (1 histamine equivalent prick) prove suitable as regards size and reproducibility compared with the reactions produced by a more conventional prick test method. The new lancet simplifies the prick test procedure and does not require as much experience as do needles and longer lancets.

Adult

3H-histamine release from human leukocytes. A new method for detecting type I allergy compared with basophil histamine release technique.

A rapid, simple, and inexpensive method for large scale screening of patients suspected of type I allergy has been developed. The method is based on in vitro incorporation of 3H-histamine in the leukocytes of the patient, whereafter release of labelled histamine is measured after provocation of the cells with the suspected allergen. The new method was compared with the conventional basophil histamine release technique by in vitro provocation of six asthmatic patients under suspicion of type I allergy against animal dander, house dust, and mite, and an almost identical release of histamine was observed in both assays.

Allergens

[Allergology].

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Allergens

Perennial rhinitis: an analysis of skin testing, serum IgE, and blood and smear eosinophilia in 201 patients.

Allergen skin testing, eosinophil counting in blood and nasal smear and serum IgE determination were performed in patients with simple perennial rhinitis, and in patients with rhinitis and asthma. The results were compared with those obtained in normal controls. As a positive skin test was demonstrated in 40% of patients with simple rhinitis and in 88% of patients with rhinitis and asthma, skin testing is considered relevant in all patients with perennial rhinitis. While blood eosinophil count and serum IgE level were elevated in a fair proportion of asthmatic patients, only a few subjects with simple perennial rhinitis had an elevated level, and the diagnostic values of these tests is questionable. On the other hand, examination of a nasal smear for eosinophils could usually separate the patients from the controls. The study emphasizes the importance of making a distinction between simple perennial rhinitis and perennial rhinitis associated with other symptoms and diseases.

Adolescent

Demonstration isolation and identification of culturable microfungi and bacteria in horse hair and dandruff. Immunochemical comparison with allergic components.

Horse hiar and dandruff have been investigated for their content of microfungi and bacteria. Inoculation and incubation on V-8 agar containing penicillin and streptomycin, with subsequent colony counting and identification, revealed more than nine and five different genera of microfungi and bacteria respectively, in horse hair and dandruff. Isolation and cultivation of the quantitatively dominating species, and preparation of an extract of these were performed, followed by immunochemical comparison with extract of the horse hair and dandruff using crossed-line immuno-electrophoresis. As no immunochemical identity was demonstrated it was concluded that the identified microorganisms might serve as a guideline to suspected sensitizing substances when patients with a typical case history of horse allergy do not react to extracts of horse hair and dandruff.

Allergens