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Biomedical subjects

B Weeke

Publications and source records attributed to B Weeke.

At least 127 records · Page 7Linked to original sources

Continuous treatment of asthmatic patients with enprofylline and theophylline.

Twenty-five asthmatic outpatients were treated for 3 one-week periods with either enprofylline slowly eroding 300 mg tablets t.i.d., theophylline 300 mg tablets (Theo-Dur) t.i.d., or placebo in a double-blind, cross-over, randomized trial. Sixteen patients were able to complete 2 or 3 one-week periods. Evaluation of bronchodilating properties by home recordings of peak expiratory flow (PEF) and side effects suggested that enprofylline was an effective antiasthmatic xanthine derivative for continuous treatment, as it improved mean morning PEF significantly. Continuous treatment with the 2 xanthine derivatives resulted in mean steady state plasma levels within therapeutic range for theophylline, and 3-4 times lower mean plasma levels for enprofylline. Enprofylline induced headache in 13 of 16 patients, theophylline in 9 of 19 patients, and placebo in 2 of 18 patients. No serious side effects were seen.

Adult↗

A nylon ball solid-phase radioimmunoassay for specific antibodies in human sera. Application to measurement of IgG antibodies to pollen allergens.

The principle of the radioallergosorbent test (RAST) has been used to measure IgG antibodies to timothy grass pollen allergens in sera from desensitized allergic subjects. 125I-labeled goat anti-human IgG was used as detector protein. Non-specific binding was eliminated by use of a non-porous nylon ball an antigen carrier and by use of a special buffer with high ionic strength and pH, containing 1% bovine gamma globulin and 5% normal rabbit serum as 'balance proteins'. At dilution 1:80 non-specific binding was only 0.28% and the binding ratio for a high-liter serum was about 10. By inhibition experiments the assay was demonstrated to be specific for IgG antibodies to timothy grass pollen. The results obtained with this assay correlated statistically significantly with those found th a double -antibody method (rs equal 0.68, n equal 20, t equal 3.93, P less than 0.001). Serum dilution curves were parallel, indicating that the assay is in allergen excess. The within-assay coefficient of variation ranged from 3.9 to 7.6%; the between-assay coefficient of variation from 8.4 to 19.5%. The assay is very simple to perform, requiring no centrifugation. The allergen-coated balls are stable for at least 3 months. The assay should be applicable to measurement of IgG antibodies and IgG subclass antibodies to any protein antigen of interest.

Antibodies↗

Intravenous administration of enprofylline to asthmatic patients.

In 6 asthmatic patients, the possibility of obtaining a steady state plasma level of 5 mg/l of enprofylline by administration of two constant rate infusions was examined. The simulated plasma concentration curves, based on information from preassessment of individual pharmacokinetic parameters, were in good agreement with the plasma levels obtained. The side-effects and bronchodilatation produced by enprofylline were compared to those obtained with theophylline at a steady state level of 15 mg/l. Enprofylline and theophylline caused a mean maximal increase in FEV1.0 of 14% and 2.6% per mg/l in plasma, respectively. Side-effects, headache, nausea and vomiting, became pronounced in 2 patients in whom the plasma enprofylline level was about 6 mg/l. No other serious adverse reaction was seen. It is suggested that enprofylline should be further evaluated as a possible anti-asthmatic drug.

Adult↗

Specific IgE response toward allergenic molecules during perennial hyposensitization: a three-year prospective double-blind study.

Allergenic extracts are multicomponent systems containing a number of potentially allergenic molecules. In a 3 yr prospective double-blind study, sera from 40 patients hyposensitized with either a two-component timothy extract or a 20-component timothy extract were evaluated by means of crossed radioimmunoelectrophoresis. The patients exhibited specific IgE response toward individual allergenic molecules, and IgE with new specificities did not develop after hyposensitization. A high degree of clinical protection could generally be obtained on treatment with the 20-component timothy extract, but this was true only with the two-component timothy extract containing the allergenic molecules that matched the individual IgE response.

Adolescent↗

Enprofylline--effects of a new bronchodilating xanthine derivative in asthmatic patients.

The bronchodilating effect of two doses of peroral enprofylline was compared with placebo in 24 asthmatic patients. Enprofylline produced significantly greater bronchodilatation than placebo. A dose of 2 mg/kg b.wt. and 4 mg/kg b.wt. caused a mean maximal increase in FEV1 of 26% and 35%, respectively. The degree and the incidence of headache and nausea were estimated by means of a scoring system. Dose-related effects on both parameters were observed. Other side effects were negligible. In seven patients the mean plasma half-life of enprofylline was found to be 113 min. It is suggested that enprofylline should be studied further in patients suffering from obstructive lung disease.

Adult↗

An automated particle counting immunoassay (PACIA) for determination of blocking antibodies against timothy grass pollen in sera from desensitized allergics.

An automated particle counting immunoassay (PACIA) for measurement of blocking antibodies (antigen neutralizing capacity) against timothy grass pollen extract in sera from desensitized allergics is described. Latex particles coated with F(ab')2-anti-timothy are agglutinated by timothy. Serum containing anti-timothy antibodies inhibits the agglutination. Non-agglutinated particles are counted in a modified AutoCounter. Nineteen of 20 sera from timothy allergics who had undergone immunotherapy with purified timothy extract for 30 weeks, showed significant agglutination-inhibition. None of 42 normal human sera gave significant inhibition. The inhibiting antibody could be removed by absorption with protein A and was thus of non-IgE nature, i.e. blocking antibody. The results obtained correlated statistically significantly with those found with a double-antibody method (rS = 0.62, n = 20, t = 3.35, P less than 0.01) and with the cumulated dosage of timothy allergen extract administered to the individual patient (rS = 0.56, n = 20, t = 2.87, P less than 0.02). Between-assay coefficient of variation was from 6.4% to 18.3%. The capacity is 40 samples per hour. The method has also been applied to measurement of blocking antibodies to honey bee and wasp venom.

Animals↗

Bronchodilation of terbutaline in small doses from a 750 ml spacer. A cumulative dose-response study.

The influence on lung function of small cumulative doses (31 + 31 + 63 + 125 + 250 micrograms) of terbutaline inhalations from a pressurized aerosol with a 750 ml spacer was evaluated in 12 stable asthmatics. The trial was double-blind and cross-over, using the double-dummy method. Lung functions was recorded 5, 30, and 60 min after each inhalation. No significant differences in FEV1, FVC and FMF25-75% were found between the two devices. A very marked response, which was not a placebo effect, was noted after the subjects had inhaled the first 31 micrograms dose. The results suggest that the number of inhalations is more important for the response in lung function than the dose administered. The addition of a 750 ml spacer to the pressurized aerosol is not likely to be beneficial for adults who are able to handle an ordinary aerosol properly.

Adult↗

Orally administered grass pollen.

In 1900 it was claimed that oral administration of ragweed could be used for the hyposensitization of hay fever patients. Several uncontrolled trials have been published, all showing an effect of oral hyposensitization. Only one study was controlled and showed no effect of oral hyposensitization. It was decided to undertake controlled clinical trials to determine the safety and effectiveness of orally administered enteric-coated grass pollen tablets in patients with hay fever. The actual grass pollen dose in the first trial was 30 times the dose that is normally recommended for preseasonal oral pollen hyposensitization using pollen aqueous solution or pollen powder. The safety study will be described here. Twelve young adults with a history of grass pollen hay fever positive skin prick test and positive nasal provocation test with extracts of timothy grass pollen were randomly allocated to one of the treatment groups with four patients in each group taking enteric-coated Conjuvac Timothy tablets or enteric-coated Whole Timothy pollen tablets or enteric-coated placebo tablets. The study was double blind. Preseasonally, the patients received 342,500 PNU and in total they received 4,500,000 PNU during 6 months. The patients receiving active treatment did not have any side effects. No significant changes were shown in the skin and nasal reactivity to grass pollen during the study. Neither were there any changes in timothy-specific IgE, IgG, total IgE nor histamine liberation from basophils.

Administration, Oral↗

The use of particle counting immunoassay (PACIA) for the titration of specific antibodies. Application to sera from honeybee venom-desensitized patients.

Particle counting immunoassay (PACIA) is shown to be a suitable nonradioisotopic method for the titration of anti-phospholipase A2 antibodies in the sera from honeybee venom-desensitized patients. The sensitivity of the method is equal to the RAST-IgG with a correlation coefficient between the two methods of r = 0.94. Within-day and between-day precisions were 2.5 and 9.2%, respectively. The main advantages of PACIA are: (i) the use of easily prepared non-radioactive reagents having a shelf-life of at least 1 year at -20 degrees C: (ii) partial automation; (iii) calibration with antisera of animal origin, and (iv) the possibility of allergen standardization of honeybee venom extracts.

Agglutination↗

Long-term treatment with oral sustained-release theophylline.

The treatment of chronic asthma with a sustained-release theophylline preparation was evaluated in a placebo controlled, 2 X 4 week, randomised, double-blind study. The dose which would give serum theophylline levels in the range of 10-20 mcg/ml had been previously determined for each patient. This individualization of dosage resulted in 80% of the patients having serum concentrations within the 10-20 mcg/ml therapeutic range. The average daily dose taken by males was 998.55 mg (range 700-1175 mg) and by females 778.1 (range 500-1000 mg). Of the 33 patients who completed the study 28 had less asthma during the theophylline period, four did not respond and one did better during the placebo period. No serious side effects were reported. During theophylline therapy, patient's requirements for aerosol bronchodilators were significantly reduced.

Administration, Oral↗

Basophil histamine release and humoral changes during immunotherapy. Dissociation between basophil-bound specific IgE, serum value, and cell sensitivity.

An in vitro pilot study was performed to determine whether basophil cell-bound specific IgE was correlated to serum-specific IgE and to basophil cell sensitivity during immunotherapy with a well-documented treatment. The findings showed a clear dissociation between these three parameters, which is in contrast to the situation before hyposensitization and to our previous study in a comparable group of non-hyposensitized patients, where highly significant correlations were observed. Further investigations are in progress to clarify whether the dissociation is involved in the clinical improvement.

Allergens↗

Immunotherapy with grass pollen major allergens. Immunological results from a prospective 3-year double blind study.

Preseasonal hyposensitization stimulated an intercorrelated increase in both serum-specific IgE and allergen-specific IgG. Subsequent perennial treatment depressed the stimulated IgE response and the basophil cell sensitivity, whereas the allergen-specific IgG response showed further increase and persisted at a high level. Nasal IgE response was stimulated from the second pollen season and subsequently became depressed. One year after the end of hyposensitization the allergen-specific IgG response had fallen by 25-50%.

Allergens↗

The allergy pricker. Qualitative aspects of skin prick testing using a precision needle.

Skin prick test has advantages over other diagnostic tests in allergy, and attempts to increase the reproducibility are warranted. A standardised disposable precision needle with a needle point of 1.0 mm has recently become available. Based on 960 tests with histamine and grass pollen (Phleum pratense) the reproducibility of the skin prick weal area was calculated. Using histamine 10 mg/ml and grass pollen (1000 and 5000 PNU) a significantly lower coefficient of variation was found compared with a standard blood lancet with a point of 4 mm. The mean weal reaction is reduced to about 80% of the size obtained with the blood lancet. Testing with the precision needle resulted in a significantly reduced incidence of bleedings. The precision needle simplifies the skin test and does not require as much skill as other needles, and is recommended for both routine tests and the biological standardization of allergen extracts.

Adult↗

Isolation and partial characterisation of three major allergens in an extract from cow hair and dander.

Three 'major allergens' of an extract from cow hair and dander were isolated by means of anion-exchange chromatography and hydrophobic chromatography. Two of the isolated 'major allergens' were immunochemically pure and the third contained less than 1% impurities. The molecular weights were 2.0, 2.2 and 2.4 x 10(4) daltons, and pI was about 4.0. The amino acid content revealed no specific traits. The protein part of the major allergens constituted about 60% (w/w). The allergenic activity of the isolated allergens was verified in RAST-inhibition experiments and in prick tests.

Allergens↗