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Biomedical subjects

B Weeke

Publications and source records attributed to B Weeke.

At least 55 records · Page 3Linked to original sources
PubMed1988

Role of IgG4 in histamine release from human basophil leucocytes. I. Sensitization of cells from normal donors.

Several conflicting reports on the ability of IgG4 to mediate type I allergic reactions have appeared lately. We have developed a model system for testing this possibility, using passive sensitization of basophil leucocytes from normal individuals. At first, the system was optimized with regard to donor cells and anti-IgG4 antibody: among 3 normal individuals with cells showing high, medium and low responses to anti-IgE, only the high responder showed a reproducible, but low response to anti-IgG4. This response was consistent when testing anti-IgG4 from different sources, and could be potentiated by a phorbol ester TPA, although not up to the level of anti-IgE. The cells from the high responding donor and a monoclonal anti-IgG4 were selected for further studies. Serum pools from patients allergic to house dust mite (Dermatophagoides pteronyssinus) were used for passive sensitization. The pools contained allergen-specific IgE with or without concomitant IgG4 of the same specificity. The sensitized basophils reacted to anti-IgE and allergen, but to anti-IgG4 only to a small extent. However, when these serum pools were fractionated by affinity chromatography, only the IgE fractions and not the IgG4 fractions made the cells reactive towards specific allergen. It was still possible to elicit a reaction by triggering IgE with anti-IgE, whereas only a small reaction was seen, when IgG4-sensitized basophils were provoked with anti-IgG4. We conclude that IgG4 does not sensitize normal basophils.

Basophils↗
PubMed1988

IgG subclass concentrations in sera from 200 normal adults and IgG subclass determination of 106 myeloma proteins: an interlaboratory study.

The IgG subclass protein concentrations in sera from 200 normal subjects were determined independently in two laboratories, using the same technique (radial immunodiffusion), the same subclass-specific antibodies and the same calibrator. The coefficients of correlation (rs) between IgG subclass concentrations determined in the two laboratories were 0.487, 0.883, 0.928 and 0.926 for IgG1, IgG2, IgG3 and IgG4, respectively (p less than 0.0005 in all four cases). By the chi-square test for goodness of fit, the frequency distributions observed in the two laboratories were found to differ significantly for all four subclasses (p less than 0.01). In one laboratory, the distributions of IgG1 and IgG2 were not significantly different from normal distributions, whereas the distributions of IgG3 and IgG4 deviated significantly. In the other laboratory, all four subclass distributions were significantly different from normal distributions. In the first laboratory, the IgG2 concentrations were log-normal distributed, whereas in the second, IgG1, IgG2 and IgG4 concentrations were log-normal distributed. We conclude that use of identical reagents does not ensure identical frequency distributions. This finding emphasizes the need for standardization of the measurement technique too. Furthermore, we argue that at present, intralaboratory reference intervals for IgG subclass protein concentrations are necessary. The reference intervals should be based on non-parametric statistics. The subclass of 106 monoclonal IgG proteins, which were demonstrated by agarose gel electrophoresis, was identified by RID for 89 samples. The subclass of the remaining 16 M-components was readily determined by qualitative immunoelectrophoretic analysis using the same subclass-specific antibodies.

Adult↗
PubMed1988

A multicentric study of loratadine, terfenadine and placebo in patients with seasonal allergic rhinitis.

This multicentric study compared 14-day treatment with loratadine (Clarityne) 10 mg once daily, terfenadine 60 mg twice daily and placebo in outpatients with seasonal allergic rhinitis. Of 275 patients enrolled, 256 (87 in the loratadine group, 89 in the terfenadine group and 80 in the placebo group) were evaluable for efficacy and 266 (90, 91 and 85 in respective groups) were evaluable for safety. Investigators graded the severity of 4 nasal and 4 nonnasal signs/symptoms and investigators and patients rated overall disease condition and therapeutic response on treatment days 3, 7 and 14; patients recorded when signs/symptoms of rhinitis were relieved, as well. Hematology and blood chemistry tests were conducted before and after therapy, and patients were questioned throughout the study about possible adverse experiences. At all visits, loratadine and terfenadine were significantly superior to placebo (p less than or equal to 0.004), and the two active medications were statistically comparable, based on mean totals of sign/symptom severity scores and ratings of overall disease condition and therapeutic response. By patients' last valid visit, mean totals of sign/symptoms severity scores improved by 56% and 53% for loratadine and terfenadine groups, respectively, but exacerbated by 5% for the placebo group. Moreover, an excellent or a good therapeutic response was observed in 58/87 (67%) loratadine-treated patients and 58/89 (65%) terfenadine-treated patients, as compared to 13/80 (16%) placebo-treated patients (p less than 0.01). A total of 61/76 (30%) patients in the loratadine group and 57/78 (73%) in the terfenadine group versus 22/71 (31%) in the placebo group experienced relief within the first 3 days of therapy (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Impaired basophil histamine release from allergic patients.

A few patients (6-7%) with a verified type I allergic reaction do not respond with histamine release after challenge of their basophils with specific antigen (non-responding basophils from allergic patients). Sera from these non-responding patients were used for passive sensitization of responding cells from healthy controls. When these sensitized cells were challenged with specific antigen, histamine release was observed indicating that the non-responding allergic patients have circulating antigen-specific IgE capable of binding to Fc-receptors on the basophils. These findings suggest the possibility that non-responding basophils have impaired cell functions. We therefore examined the influence of enhanced IgE receptor stimulation on histamine release in non-responding basophils. This was made by stimulating protein kinase C activity by a phorbol ester (phorbol 12-myristate 13-acetate). When the non-responding cells were incubated with the phorbol ester and challenged with either anti-IgE or specific antigen, the cells released histamine. These findings support the hypothesis that the unresponsiveness of basophils in some allergic patients is associated with impaired IgE receptor complex activation or subcellular functioning and not with a lack of cell-bound IgE.

Asthma↗
PubMed1987

Oral immunotherapy in birch pollen hay fever.

Previous controlled trials with oral administration of allergen have not demonstrated any treatment effect in patients with allergic rhinoconjunctivitis or asthma. In the present double-blind, placebo-controlled trial, we have tested the effect of oral immunotherapy in adult patients with birch pollinosis. Thirty-nine patients completed this 18-month study comprising two birch pollen seasons. The patients received enterosoluble capsules daily, and the actively treated patients reached a cumulated dose of 280 times 10(6) biologic units of birch pollen extract, which is about 200 times higher than the dose used in conventional subcutaneous immunotherapy. We found a significant decrease in eye symptom scores and conjunctival sensitivity to birch pollen, as determined by conjunctival provocation test, as well as a numerical but nonsignificant decrease in nasal symptom scores, nasal sensitivity as determined by nasal provocation test, and antiallergic medication. The treatment was safe, and only a few slight side effects were observed. We thus conclude that our study demonstrates a clinical effect of oral immunotherapy in birch pollinosis.

Administration, Oral↗
PubMed1987

A comparison of the effects of sodium cromoglycate and beclomethasone dipropionate on pulmonary function and bronchial hyperreactivity in subjects with asthma.

After a run-in period of 2 weeks, receiving a regimen of inhaled beta 2-agonists and/or theophyllines, 38 atopic patients with asthma with perennial symptoms were randomly allocated to receive an 8-week treatment of additional inhalation treatment with either sodium cromoglycate (SCG), 2 mg four times daily, and placebo beclomethasone dipropionate (BDP), or BDP, 200 micrograms twice daily, and placebo SCG. After crossover, each group received the opposite treatment for the final 8 weeks. FEV1, FVC, and provocation concentration of histamine causing a 20% fall in FEV1 (PC20) were determined monthly and peak expiratory flow (PEF) daily throughout the study. A significant increase in FEV1, FVC, and PEF (p less than 0.01) was observed after BDP treatment was started, and likewise, in the second period, an increase in both FEV1 and PEF (p less than 0.05) was observed. The total effect on logarithm-natural (Ln) (PC20), i.e., the mean effects of the two periods, was also significant (p less than 0.01). SCG, however, was most effective when it was used as the first drug, indicated by a significant increase in FVC in the first period (p less than 0.05). Neither in the first nor in the second period did SCG treatment influence the Ln (PC20) value positively, and the SCG treatment administered in the second period could not maintain the improvement in the pulmonary function (i.e., FEV1, FVC, and PEF) obtained initially with the BDP treatment. When the effect of BDP on FEV1, FVC, PEF, and Ln (PC20) was compared to the effect of SCG in the first 8-week treatment period, no significant difference was observed (p greater than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Reproducibility of responsiveness to a standardized bronchial allergen provocation-Rt compared to FEV1 as measurement of response to provocation.

Standardized bronchial allergen provocation was performed twice in nineteen extrinsic, well defined, stable asthmatic patients, with an interval of median 15 days (range 14-19) to study the reproducibility of the bronchial response. Smoking and medications were withheld prior to the provocation after a rigid scheme. Ten-fold increasing concentrations of allergen solution 0.9 ml were inhaled by tidal volume breathing for 5 min with intervals of 10 min. The bronchial response to inhaled allergen was determined by forced expiratory volume in the first sec (FEV1) and by total resistance to breathing (Rt) determined by an opening interrupter method. The provocation was continued until an allergen concentration causing at least 20%, decrease of the postsaline FEV1 or a 40% increase in Rt was reached. A PC20-FEV1 and a PC40-Rt was calculated by interpolation on the log-dose-response curve. The reproducibility of PC20-FEV1 allergen was high with a 95% confidence interval (CI) for a single determination being the observed value +/- 0.83, ten-fold concentration difference, the intraclass correlation (IC) was 0.99 and the coefficient of variation 8.46%. Concerning PC40-Rt a 95% CI for a single determination was calculated being the observed value +/- 0.58, ten-fold concentration difference, IC was 0.99 and the coefficient of variation was 5.79%. No significant correlation was found between differences in pre-challenge FEV1 and Rt values and the corresponding PC20-FEV1 and PC40-Rt values. Least square regression between PC20-FEV1 and PC40-Rt was performed for the first and the second provocation (P less than 0.05). We conclude that bronchial allergen challenge performed in stable asthmatics is highly reproducible and as such a valuable test in the diagnosis of allergic asthma when connected with anamnesis, skin-prick test and the level of specific immunoglobulin E in peripheral blood.

Adolescent↗
PubMed1987

Bronchial allergen challenge: comparison between two different methods of provocation.

Bronchial allergen challenge was performed twice in ten well-defined stable asthmatic patients. On each provocation day the allergen was administered either by a standard method at tidal volume breathing or by a dosimeter method. Ten-fold increasing concentrations of allergen were administered with an interval of 10 min. Total amount of allergen of 9, 90, 900, 9000 and 90,000 SQ units using the standard method, whereas the corresponding amount by the dosimeter method was 0.5, 5, 50, 500, and 5000 SQ units. The bronchial response was determined by forced expiratory volume in the first second (FEV1) and by total resistance to breathing (Rt) measured by an opening interrupter method. The provocation was stopped when a decrease of at least 20% of the post-saline FEV1 and a 40% increase in post-saline Rt was observed. A PC20-FEV1 and a PC40-Rt was calculated by interpolation on the log dose-response curve. The late reaction was recorded and defined as a 20% reduction in peak expiratory flow (PEF) occurring during the 24-hr period after challenge. The comparability of PC20-FEV1 and PC40-Rt obtained with the standard method and with the dosimeter was high, r = 0.89 and r = 0.88. Furthermore, no significant difference was found by comparing delta FEV1 and delta Rt during provocation by either method as well as the occurrence and magnitude of the late reaction. We conclude that there exists a high comparability of the bronchial response to an allergen challenge performed either by a standard method at tidal volume breathing by continuous inhalation of the allergen aerosol or by a dosimeter method of inhalation despite the difference in the total allergen doses inhaled.

Administration, Inhalation↗
PubMed1987

High dose grass pollen tablets used for hyposensitization in hay fever patients. A one-year double blind placebo-controlled study.

Previous, placebo-controlled clinical trials with oral hyposensitization in grass pollinosis have been disappointing. Since the results possibly could be explained by too low doses of ingested allergens, the present study was initiated to evaluate the effect of high doses of allergens. Forty-two adults with symptoms in the grass pollen season and with grass pollen sensitivity demonstrated by skin prick test and conjunctival provocation test were included. Enterosoluble tablets were administered daily for 1 year. Twenty-two patients, who completed the study, received placebo and 17 mixed grass pollen allergens from rye grass, timothy grass, cultivated rye and velvet grass. Evaluated either by self-assessment or by symptom and medicine score before and after treatment, the group receiving pollens did not improve clinically compared the controls. During the study, conjunctival sensitivity decreased equally in the two groups, and changes in specific IgE, allergen-induced histamine release from blood cells and skin prick test were insignificant and with no difference between groups. Five patients, who received pollen allergens, had episodes of urticaria or angioedema, and a further three patients on the same treatment had slight gastrointestinal side effects. In conclusion, enterosoluble grass pollen allergens in contrast to birch pollens did not have any therapeutic effect, even in doses more than 4,000 times higher than those used for subcutaneous hypersensitization. The reason may be degradation of allergens before the immune system is reached.

Adolescent↗
PubMed1987

House dust mite asthma. Correlation between allergen sensitivity in various organs.

Fifty asthmatics, candidates for hyposensitization with the house dust mite Dermatophagoides pteronyssinus (Dp), went through a series of allergy tests to evaluate the sensitivity of different organs to Dp. All patients were exposed to bronchial challenge with histamine and bronchial, nasal and conjunctival challenge with Dp, skin prick test (SPT) with Dp, analyses for Dp-specific histamine release from blood cells (HR) and for anti-Dp-IgE in serum (RAST). Results from 40 patients reacting positively in all tests were further analysed. Sensitivity to Dp in the various organs did not parallel, but a fair correlation was demonstrated between pulmonary allergen sensitivity and HR (r = 0.65, P less than 0.001), and between pulmonary sensitivity to allergen and to histamine (r = 0.47, P less than 0.001). Combined variations in HR and in (unspecific) bronchial sensitivity to histamine explained 53% of the variation in bronchial sensitivity to the allergen. This parameter showed less correlation to RAST and SPT (r = 0.31 and r = 0.35, P greater than 0.05). The results indicate that bronchial allergen challenge cannot be replaced by similar challenge of other organs, since the sensitivity of the mucosa in different organs of the same patient seems unrelated. Diagnosis should therefore be based on challenge of the organ with dominating clinical importance. In our selected group of patients, however, it was indicated that a substitution of the result of bronchial allergen challenge by measurement of unspecific bronchial reactivity, together with information on the general allergen sensitivity on a cellular level, might be possible. The unpleasant symptoms of the immediate and late bronchial reactions to allergen challenge could thereby be avoided.

Allergens↗
PubMed1987

Fixed ventilation during tidal volume breathing bronchial challenge may improve repeatability.

Tidal breathing during bronchial challenge shows both between- and within-subject variation. A challenge protocol permitting controlled ventilation was designed in order to improve repeatability of the method. Twenty-five patients were challenged twice with an interval of 2 h. The 2 min ventilation was kept constant at each concentration administered. During the 2 min inhalation of aerosol all expired air (VE) was led through a dry gas meter and respiratory frequency was counted concomitantly. The patients were instructed to achieve the same 2 min ventilation at each dosage. All patients accomplished the two challenges without problems. A PC20 was determined by interpolation on the log dose-response curve. Repeatability was improved compared to what has been found in previous studies on adults, although statistically non-significant when compared to one study. The 95% confidence interval for PC20 based on a single determination was rather narrow, being the observed value +/- 0.58 two-fold concentration differences.

Adult↗
PubMed1987

Intramuscular betamethasone dipropionate vs. oral prednisolone in hay fever patients.

In a double-blind group comparative study, 36 adult, birch pollen-allergic outpatients with seasonal rhinoconjunctivitis, were treated with either oral prednisolone 7.5 mg daily for 3 weeks or an injection with 2 ml suspension of betamethasone dipropionate and betamethasone disodium phosphate (Diprospan) immediately prior to the birch pollen season. Both treatments were able to prevent an increase in symptoms from the nose and the eyes during the 3-week birch pollen season. There was no significant difference in symptom score or nasal peak flow between the two treatments. However, there was a significant suppression of adrenal gland function after oral prednisolone treatment in contrast to Diprospan treatment. Unless there are contraindications for treatment with depot steroid injections (children, pregnant women, patients suffering from peptic ulcer, tuberculosis, eye disease, herpes, hypertension or diabetes) it seems to be a reasonable alternative to oral prednisolone in hay fever patients.

Administration, Oral↗
PubMed1987

Diagnosis and immunotherapy of mould allergy. VI. IgE-mediated parameters during a one-year placebo-controlled study of immunotherapy with Cladosporium.

The IgE-response was evaluated by skin prick test, bronchial provocation test and RAST in a 1-year placebo-controlled double-blind immunotherapy study. Eleven adult asthmatics were treated with a Cladosporium allergen preparation and 11 comparable patients received histamine placebo. The bronchial sensitivity (PC20) decrease greater than 0.5 log step in 8/11 (73%) Cladosporium-treated versus 3/11 (27%) in the placebo group. Corresponding figures for skin prick test sensitivity was 10/11 (91%) and 1/11 (9%) respectively. Circulating IgE showed a temporary boost in the Cladosporium group and then values approaching the pretreatment value. Only minimal and insignificant changes were found in the placebo-treated patients. Changes in IgE-reactivity were not related to allergen dose, clinical efficacy or to the occurrence of side effects. Some interrelation between changes in skin prick test, bronchial provocation test and RAST was found indicating a differentiated effect of immunotherapy on various IgE compartments. In spite of the pathogenetic role of IgE in allergic diseases, changes in IgE-reactivity do not seem directly involved in the mechanisms underlying the clinical efficacy of immunotherapy but might be of importance in a complex interaction with other immunological parameters.

Adult↗
PubMed1987

Methylprednisolone pulse therapy in severe acute asthma.

In a group comparative double blind pilot study six asthmatic patients with an acute exacerbation of their disease were randomly treated with either methylprednisolone pulse therapy (MPPT) (1000 mg daily for 3 days) (n = 2) followed by placebo tablets, or standard doses of methylprednisolone (MP) (50 mg daily gradually decreased to zero over 3 weeks) (n = 4). The results showed that the effect of MPPT did not differ from that of standard doses of MP. MPPT has, however, the potential of being preferable to standard treatment with MP, because of easy administration and optimal patient compliance.

Adult↗
PubMed1987

Reproducibility of challenge tests at different times.

Bronchial challenge for determination of bronchial reactivity is widely used in the diagnosis of asthma, the grading of severity, and evaluation of effect of treatment with new antiasthmatic drugs. Allergen challenge is also used for diagnosis of specific IgE-mediated asthma and evaluation of the effect of immunotherapy. A number of factors influence the result of the challenge test including the selection of patients, criteria for carrying out the challenge test, a number of technical factors concerning the challenge, the dosing schedule, pulmonary function tests carried out and analysis of the data. All these factors have to be taken into consideration before reproducible challenge tests can be performed. Detailed description of the equipment and procedures used and inclusion criteria for the patients should be included in all publications concerning challenge tests in order to be able to compare results from different laboratories. Each clinic or laboratory needs to perform reproducibility studies on bronchial challenge testing procedures and equipment used in their clinic.

Aerosols↗
PubMed1986

A sensitive and reproducible method for the determination of subnanogram quantities of immunoglobulin E (IgE).

An immunoradiometric assay for immunoglobulin E (IgE) using high adsorption polystyrene test tubes as the solid phase (the 'Maxisorp' assay) is described. The sensitivity of the method was found to be 50 pg IgE/ml and the within-assay reproducibility was 3-7%. The accuracy was estimated by means of a comparison between the Maxisorp assay and paper radioimmunosorbent test (PRIST) and a correlation coefficient of 0.98 (P less than 0.001) was obtained. We conclude that the Maxisorp assay is a fast and reliable assay for IgE determination in cord blood, cell culture supernatants and other highly diluted IgE preparations.

Antibody Specificity↗