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Biomedical subjects

B Weeke

Publications and source records attributed to B Weeke.

At least 37 records · Page 2Linked to original sources
PubMed1989

Specific IgE, IgG, and IgA antibody response to oral immunotherapy in birch pollinosis.

Thirty-nine patients with birch pollinosis participated in a double-blind, placebo-controlled trial of oral immunotherapy (OIT) for 18 months. They were treated with increasing doses of freeze-dried birch-pollen antigens for 16 months, reaching a cumulative dose of 280 x 10(6) biologic units. This is about 200 times more than the dose used in conventional subcutaneous immunotherapy (IT). In the placebo-treated group, but not in the actively treated group, there was a rise in postseasonal birch-specific IgE antibody levels. A significant decline in postseasonal values after 1 year of treatment was recorded in the actively treated, but not in the placebo-treated, group. Compared to the placebo treatment, there was a significant rise in birch-specific IgG antibodies in patients administered active treatment; however, the rise was less than that usually observed during subcutaneous IT. No significant change in birch-specific serum IgA was found in either group. The changes in IgE and IgG antibody levels demonstrate that OIT affects the immune system. This supports our recent findings that OIT demonstrates a beneficial effect in the treatment of birch pollinosis in adults. But, as with subcutaneous IT, there was no clear relationship between antibody response and clinical findings in the patients. The underlying mechanisms responsible for the relief of symptoms thus remain unknown.

Administration, Oral↗
PubMed1989

Distribution of enprofylline and theophylline between plasma and cerebrospinal fluid.

Six patients undergoing diagnostic lumbar myelography were studied with respect to plasma and cerebrospinal fluid (CSF) concentrations of two xanthine drugs--enprofylline and theophylline. Three patients received enprofylline and three patients received theophylline, 200 mg t.i.d., and plasma and CSF were sampled on the morning of the third day of treatment. CSF plasma ratios averaged 0.095 with enprofylline (range of 0.094-0.097) and 0.36 with theophylline (range of 0.35-0.37). The different ratios of the two drugs contrast to their similar plasma protein binding, about 50%. Different lipophilicity or differences with regard to transport out of the CSF may explain the discrepancy.

Adult↗
PubMed1989

Beclomethasone dipropionate versus flunisolide as topical steroid treatment in patients with perennial rhinitis.

After a 2-week run-in period 23 atopics and non-atopics with perennial rhinitis were treated with intranasally nebulized aqueous flunisolide or aqueous beclomethasone dipropionate in a randomized, double-blind cross-over study, each treatment period being 4 weeks. Before and after each treatment period daily rhinitis symptoms were recorded, and additional determination of nasal airway resistance was performed by posterior rhinomanometry. No statistically significant difference between drugs was observed for any effect parameter recorded, and furthermore no difference in patient preference for either drug was found. It is concluded that both steroids are effective for the improvement of nasal airway in patients with perennial, atopic and non-atopic rhinitis.

Administration, Intranasal↗
PubMed1989

Immunochemical estimations of allergenic activities from outdoor aero-allergens, collected by a high-volume air sampler.

To quantify airborne allergens in amorphus and morphological particles, a survey with collection of aero-allergens on glass fibre filters by means of a high-volume air-sampler (HIVOL) was conducted. In preliminary laboratory experiments we compared various filter elution techniques, and the pulverizing elution technique was found to be optimal with regard to yield and convenience. When a surfactant, Tween 20 (0.5% v/v), was added to the elution buffer, a recovery of 80% could be obtained. Allergens in eluates were analysed by means of an IgG-subclass RAST inhibition assay. This immunochemical method for quantification of airborne allergens was validated, as a high recovery of timothy grass pollen allergens was eluted from air filters, and eluates were shown specific by RAST inhibition. The amount of immunochemically measured airborne timothy and birch allergens collected by means of the HIVOL sampler was highly correlated with pollen counts obtained with a Burkard sampler (pollen trap) situated in the same place.

Air Pollutants↗
PubMed1989

Allergen-containing immune complexes used for immunotherapy of allergic asthma. Preparation of complexes and evaluation of their clinical performance in guinea pigs.

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 between antigen and specific IgG) IT were compared with placebo. The bronchial reactivity of the animals to the antigen was monitored regularly before, during (35 weeks) and after IT (20 weeks). Animals treated with passive IT did not improve clinically. Active and combined IT abolished most symptoms within 7 weeks of treatment. During the post-treatment period, animals from both groups surprisingly recovered their original sensitivity to inhalation of the antigen.

Allergens↗
PubMed1989

Maxisorp RAST. A sensitive method for detection of antigen-specific human IgE in culture fluids.

For determination of allergen-specific IgE in cell culture supernatants and other highly diluted IgE preparations a radioallergosorbent test (RAST) based on high adsorption polystyrene test tubes has been developed ("Maxisorp RAST"). Cladosporium herbarum extract was used as a model allergen but timothy grass pollen, house dust mite and dog dander showed similar results. The test showed specificities of both allergen and immunoglobulin isotype and significant correlations (r = 0.67-0.88) with established RAST procedures were found. Based on immunosorbent-purified allergen-specific IgE the estimated sensitivity was within the order of 150-300 pg allergen-specific IgE per ml. The within-assay variation was 4-9% and the inter-assay-variation 17-29%. The Maxisorp RAST is useful as an inhibition assay for quantitating allergenic activity down to 0.1 biological units/ml of allergen extracts.

Allergens↗
PubMed1989

Hyposensitization in asthmatics with mPEG modified and unmodified house dust mite extract. I. Clinical effect evaluated by diary cards and a retrospective assessment.

Forty-six asthmatics with verified allergy to the house dust mite, D. pteronyssinus (Dp), participated in a double-blind study comparing the effect of 2 years' hyposensitization with two different Dp extracts. Two groups received either monomethoxypolyethylene glycol modified (mPEG) Dp extract or the corresponding non-modified extract, and a third group acted as controls receiving no injections. Medicine consumption, symptom scores, and peak expiratory flow (PEF) were recorded daily from September to December prior to and after 6 and 18 months of treatment. Changes were calculated choosing changes greater than or equal to 10% as relevant. In addition, patients were asked to give their direct assessment of the clinical effect at the end of the study. After 6 months, there was an improvement in symptoms + medication in 11/14 of Dp-treated, 6/17 of the mPEG-Dp group (P greater than 0.05) and 3/15 of openly treated controls. Few patients had changed in PEF. During the second year, several Dp-treated relapsed and some controls improved. At the end of the study the same improvement rate was seen in all groups. Similarly, the retrospective questionnaire data did not disclose any significant differences between groups after 2 years. In conclusion, hyposensitization with unmodified Dp extract seemed to have a favourable short-term effect on bronchial symptoms + medication in the majority of patients. When mainly on maintenance dose, the beneficial effect was reduced. The mPEG modification of the extract had reduced not only allergenicity but also the clinical effect of equal doses. Changes in medicine and symptom scores only partly correlated to retrospective assessment, thus stressing the problems in this kind of evaluation.

Animals↗
PubMed1989

Hyposensitization in asthmatics with mPEG modified and unmodified house dust mite extract. II. Effect evaluated by challenges with allergen and histamine.

In a 2-year study, 46 asthmatics with verified allergy to the house dust mite D. pteronyssinus (Dp) were included either as controls (Ctls) or receiving hyposensitization (HS) with unmodified or monomethoxypolyethylene glycol (mPEG) modified Dp-extract. Patients were monitored by annual challenges with histamine in bronchi, and Dp allergen in bronchi, nose and conjunctiva. mPEG-modified extract was not inferior to unmodified Dp-extract; both were to some extent able to improve tolerance to Dp and histamine in bronchi and to Dp in nose and eyes. During the 1st year, the bronchial sensitivity to Dp decreased significantly in the HS groups but not in the Ctls. During the 2nd year, improvement was more pronounced in the Ctl group. The relative increase in Dp or histamine tolerance did not differ significantly between groups after either 1 or 2 years; the only exception was conjunctival sensitivity, which in the Ctl group was unchanged, and a 10-fold increase in tolerance in the HS groups. No direct benefit was seen on late-phase bronchial reactions. In patients with improved pulmonary symptoms a tendency was seen towards reduced sensitivity to histamine and Dp. Variation within groups was extensive.

Animals↗
PubMed1989

Effect of a non-sedative antihistaminic (loratadine) in moderate asthma. A double-blind controlled clinical crossover-trial.

Seventeen patients with perennial asthma, stable on a moderate dose of inhaled steroid, participated in a crossover study comparing the clinical effect of a non-sedative, potent and highly selective H1 antagonist (loratadine 10 mg) with placebo. Each treatment period began with 2 weeks run-in followed by 8 weeks on either antihistamine or placebo. During the 8-week periods inhaled steroid was gradually tapered according to a fixed scheme. One patient was withdrawn from active treatment and three from placebo periods because of decreasing lung function (P greater than 0.1). Among the remaining 13 patients there was a threefold (1.8-4.8) decrease in the bronchial sensitivity to histamine during treatment with antihistamine compared to placebo (P less than 0.01). There was a trend in favour of active treatment with regard to changes in all symptom scores, lung function and use of escape medication, but these differences were not statistically significant. The increase in FEV1 was less than 5% of predicted normal (P less than 0.05). We concluded that the bronchial response to histamine can be attenuated by loratadine, an oral H1 receptor antagonist, but further studies are necessary to assess the clinical usefulness and place of loratadine in the therapy of asthma.

Adult↗
PubMed1988

Comparison between steady state pharmacokinetics and effects of two once-daily, slow-release theophylline formulations in nocturnal asthma.

The effects on bronchoconstriction, on non-specific bronchial hyperreactivity (nBH), and the pharmacokinetics at steady state of two theophylline preparations, controlled release (CR) capsules (Riker Pharmaceuticals) and UnixanR tablets (Pharmacia) were compared in patients with nocturnal asthma. Doses were individualised with the intention of achieving plasma trough concentrations greater than 8 micrograms/ml with CR-capsules. The same dose of the two formulations was taken in the morning during two 2-week periods in a randomised, double-blind, cross-over design. During a 24 h hospital study day at the end of the two periods, pulmonary function tests, blood samples, and bronchial histamine challenges were performed. Eleven patients completed the study. Doses were median 15 mg/kg (range 10-20). FEV1 and PEF were statistically significantly better (p less than 0.05) 24 h after dosing (08:00) with CR-capsules. No statistically significant changes in nBH were demonstrated. Despite no significant differences in extents of absorption, the plasma theophylline concentration fluctuations were significantly less (p less than 0.001) during treatment with CR-capsules. We found CR-capsules superior to Unixan in pharmacodynamics 24 h after dosing and in pharmacokinetics with equal bioavailability. In nocturnal asthma the pharmacodynamic differences may be eliminated with evening dosing. No statistically significant changes in nBH were observed.

Adult↗
PubMed1988

Transfer of enprofylline into breast milk.

Enprofylline concentrations were measured on 3 consecutive days in milk and plasma from six nursing mothers who were treated twice daily with 150-mg enprofylline slow-release tablets. The mean plasma concentration was 0.89 mg/L and the mean milk concentration was 0.71 mg/L, the average milk/plasma ratio being 0.80. The mean milk/plasma ratio ranged from 0.67 to 0.98 in the six mothers. It was estimated that a maximum of approximately 10% of an adult dose of enprofylline, on a per-kilogram body-weight basis, may be transferred to the suckling infant.

Adult↗
PubMed1988

Fiberoptic bronchoscopy and bronchial mucosal biopsies in asthmatics undergoing long-term high-dose budesonide aerosol treatment.

Mucosal biopsies from the pharynx, right main stem bronchus and right lower lobe were obtained during flexible fiberoptic bronchoscopy and were examined with light microscopy (LM) and electron microscopy (EM) in 10 asthmatics after 11 months' (range 7-15 months) treatment with high doses of inhaled budesonide via the Nebuhaler, i.e. 1600 micrograms daily. Results were compared with biopsies from 10 controls suspected of having focal, malignant lung diseases. Visual inspection of the tracheobronchial tree showed no signs of atrophy, ulcerations or thrush patches, and LM and EM showed no specific signs of mucosa and connective tissue atrophy; however, epithelial desquamation was seen in the asthmatics. No complications were observed.

Adolescent↗
PubMed1988

Stability of histamine dihydrochloride in solution.

Histamine dihydrochloride (HC) is one of the bronchoconstrictors used for bronchial challenge. Information on the activity of HC dilutions during storage is desirable (4). Activity, bacterial, and fungal contamination of stored HC dilutions were tested after storage at 20 degrees, 4 degrees, and -18 degrees C. HC dilutions with a concentration of and below 0.25 mg/ml have a significantly reduced activity after 1 month's storage at 20 degrees C and should at present be used within 1 week to ensure the presence of the expected activity. The activity of HC dilutions stored at 4 degrees C or -18 degrees C was stable for at least 6 months. Upon delivery from a pharmacy we detected no bacterial or fungal contamination of HC dilutions by means of the method used. Before 3 months' storage, and independently of storage temperature, bacterial contamination was not found. After 3 months' storage, bacterial contamination was found in HC dilutions with a concentration below 0.5 mg/ml. No fungi were isolated. HC dilutions with a concentration of 0.25 mg/ml and below should not be stored for more than 1 month and should be used within 1 week of opening.

Cold Temperature↗
PubMed1988

Preparation of patient-related allergens for hyposensitization. Qualitative aspects.

An affinity chromatography method for preparation of patient-related antigens from commercially available allergen extracts has been investigated. IgG1,2,4 from a patient previously hyposensitized with dog hair and dandruff allergen was bound to protein A-sepharose. Secondly, commercial allergen extract was applied to the immunosorbent, and patient-related antigens were selectively absorbed by the specific antibodies from the patient serum. Finally, immune complexes containing antigen and IgG were eluted. Alternatively, the antigens alone were purified by retaining the IgG on the column by means of a covalent reinforcement of the protein A-IgG-binding. Purified, patient-related antigens were investigated in crossed immunoelectrophoresis and identity to IgG- and IgE-binding antigens (as determined by the CRIE-technique) was suggested. The affinity purified IgG was unaltered with regard to protein A-binding, binding of antigen and affinity for monoclonal antibody to human IgG-subclasses. Further, it was demonstrated that the antigen-binding capacity of IgG in the immune complexes was intact as evidenced by strong affinity to antigens even at low pH. The antigens eluted together with IgG were predominantly found in immune complexes with a molecular weight of greater than 300 kdalton equivalent to 2 or more molecules of IgG. The possibility of employing a similar method with IgE instead of IgG for preparation of patient-related allergens instead of antigens, is discussed.

Allergens↗
PubMed1988

Bambuterol: clinical effects of three doses of bambuterol once daily in asthmatic patients.

Twenty-two asthmatics received bambuterol solution, a terbutaline pro-drug, once every evening. The following doses were each given orally for 7 days in a double-blind cross-over study: 0.185, 0.270 and 0.400 mg/kg. Bambuterol 0.270 mg/kg was preferable regarding clinical effects and side effects. The plasma concentration of generated terbutaline showed a slow linear decrease at all doses. Tests of two methods for objective measurements of tremor in five patients did not add any new data compared with the subjective recordings.

Adult↗
PubMed1988

Bambuterol: clinical effects of different doses of a long-acting bronchodilator prodrug.

Sixty-eight asthmatics participated in a dose-finding study on bambuterol, a terbutaline prodrug, administered once every evening. Bambuterol administrations of 0.185, 0.270 and 0.400 mg/kg gave effective and long-lasting bronchodilation, for at least 24 h, with the two higher doses probably close to the maximal effect of the drug. Bambuterol 0.400 mg/kg was associated with more adverse effects than bambuterol 0.185 mg/kg. The side effects were those expected in oral beta 2-agonist treatment and mainly experienced by patients who had not been on oral beta 2-agonists before. The most favourable of the investigated doses was found to be 0.270 mg/kg. It can not be excluded, however, that a somewhat lower dose may still be as beneficial. This will be investigated in forthcoming studies.

Adult↗
PubMed1988

Modification of house dust mite allergens by monomethoxypolyethylene glycol. Allergenicity measured by in vitro and in vivo methods.

In animal models, allergen modification by coupling to monomethoxypolyethylene glycol (mPEG) molecules can reduce allergenicity of the extract and makes the allergen capable of suppressing boosted IgE response. To investigate in a human system the degree of attenuation implied by a mPEG modification of a house dust mite (Dermatophagoides pteronyssinus) extract, 55 adults with asthma caused by house dust mites were tested by skin prick test (SPT) and histamine release assay (HR). RAST inhibition was performed on sera from 6 additional patients. Modified extract containing 0.42 mmol mPEG/g protein was used for the analyses. In order to get the same response of the two extracts when assessed by HR and SPT, a median increase in concentration of 10-fold of the mPEG-modified extract compared to the unmodified extract was needed. Interindividual variation was limited. Sixty-four to 72% needed a dose increase within +/- half a decade from this value. In 42-49% of the patients, results from SPT and HR deviated less than half a decade. The relative potency of the modified extract as measured by RAST inhibition was reduced to 17-78% (mean 39%). Reduced allergenicity would by itself mean less side effects in immunotherapy. When planning such therapy it is important to know that mPEG modification reduces the allergenicity to a similar extent in a majority of patients.

Allergens↗