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Biomedical subjects

S Dreborg

Publications and source records attributed to S Dreborg.

At least 55 records · Page 3Linked to original sources

The batch-to-batch variation of the potency of dog- and cat-allergen-coated lancets. Evaluation by skin prick testing.

In clinical work I formed the impression that the potency of Phazet lancets, for cat and dog allergens, was lower than earlier and too low to diagnose all clinically sensitive children with cat and dog allergy. Therefore, I decided to investigate the potency of newly produced and several years old Phazet lancets coated with dog and cat allergens. Twenty-six adults with case histories of cat and/or dog allergy and skin reactive to extracts of either dog dander or cat epithelium were skin prick tested in duplicate with one old batch and one newly produced batch of Phazet dog and/or cat lancets as well as the in-house reference of cat and/or dog allergen, 100,000 BU/ml. The potency of Phazet lancets in relation to the standard was evaluated by the median slope of the allergen dose-response relationship. The potency of the old dog lancets (mean 48,900 BU/ml) was higher (NS) than that of the newly produced lancets (mean 28,000 BU/ml), and the potency of both types of lancets was significantly less (P < 0.001) than that of the dog allergen in-house standard. On the other hand, the potency of newly produced (123,000 BU/ml), but not old (108,000), cat-allergen-coated Phazet lancets was higher than that of the cat allergen in-house reference extract (P = 0.048). There was a marked variation in potency between patients. Most of this variation was due to factors varying between patients, not between lancets, indicating that the composition of the allergen on the lancets was partly different from that of the standard.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Precision of biological standardization of allergenic preparations.

Biological standardization (BS) aims at equilibration of the activity of allergen preparations from different types of allergen source materials. The biological unit (BU), proposed in the Nordic guidelines for 20 patients, has been found reproducible among different countries in Europe, but to be relatively imprecise, with a 95% confidence interval of about one power of 10. A more precise estimate of the biological activity of allergens or difference in sensitivity between populations would be of value. We used Ch, i.e. the concentration of allergen eliciting a wheal of the same size as histamine in the individual patient, estimated by regression line analysis. The Ch of 36 patients included in a BS trial was used. One of the 36 Ch-values was drawn randomly, and then sent back to the sample. This procedure was repeated 10, 20, 30, 40 and 60 times to create "samples" of different sizes. Ten samples of each size were produced. With 60 "individuals", the 95% confidence interval of the sample and the confidence interval of the medians were reduced to less than a factor of 2, i.e. to 74 to 128% of the median of the medians.

Allergens↗

The major allergen content of allergenic preparations reflect their biological activity.

The content of major allergens in biologically standardized allergenic preparations of birch, mite (Der p), cat, Alternaria (Alt a) and ragweed (Amb e) was determined. It was found fairly constant between species, i.e. varied within a factor of 2, with the exception of Alt a 1 in Alternaria alternata extract. This variation is allowed by authorities between different batches prepared from the same species of allergen. The method for biological standardization (BS) prescribed in the Nordic Guidelines has, for common inhalant allergens, been shown to give reproducible results between regions of Europe. However, it is difficult to define patients suitable for BS of most food allergens as well as less common inhalant allergens. Therefore we propose that, in the future, BS is replaced by determination of well-established major allergens and that 1 ng of major allergen is given the value of 1 Biological Unit.

Adult↗

Monitoring of mite Dermatophagoides farinae allergen-specific IgG and IgG subclass distribution in patients on immunotherapy.

House dust mite D. farinae and Der f II-specific IgG and IgG subclass responses were evaluated in 32 adults with perennial rhinitis undergoing immunotherapy for 1 year by means of IgG-RAST and ELISA. The ELISA method, which is based on subclass-specific monoclonal antibodies, could detect 0.5-1.5 ng/ml of specific antibodies. D. farinae and Der f II-specific IgG4 antibodies increased continuously as immunotherapy proceeded, while total IgG and IgG1 antibodies reached a plateau value 6 months after the start of immunotherapy, followed by a slow decrease during maintenance therapy. During the early phase of treatment the concentration of IgG1 and IgG4 antibodies rose, even though the increase of IgG4 antibodies dominated. The positive clinical outcome as measured by the decrease in conjunctival sensitivity was associated with an increased ratio of specific IgG4/IgG1 antibodies as well as the magnitude of the IgG4 subclass response. Quantitation of IgG subclass antibodies in patients undergoing immunotherapy may be of some clinical value, but the clinical usefulness needs to be demonstrated for each type of allergen and possibly also for each assay system.

Adult↗

Standardization of mPEG-modified allergens.

Standardization of mPEG-modified allergens can be achieved by: standardization of allergens according to established principles; production of mPEG-modified allergens by a reproducible method; control of the batch-to-batch consistency by estimation of the allergenicity and the protein content in relation to the corresponding IHR and by determination of the degree of modification by estimation of the amount of PEG per unit allergen in the modified product. Standardization of mPEG-modified allergens should be looked upon only as a model for standardization of modified allergens. I hope that the authorities in Europe will set up strict and relevant criteria for the registration of similar products and also criteria for prolonging the registration of the older products without relevant standardization and documentation of safety and efficacy.

Allergens↗

Two-year double-blind trial of a monomethoxy polyethylene glycol (mPEG) modified grass pollen extract at different dose levels.

The aim of this study was to compare the efficacy and safety of a monomethoxypolyethylene glycol (mPEG) modified grass pollen mix allergen preparation (mPEG-gm) and a partly purified grass pollen mix allergen preparation (gm) in hyposensitization (HS), evaluating both products at two dose levels. Thirty adult patients with allergic rhinoconjunctivitis were allocated into two treatment groups based on their sensitivity to conjunctival provocation tests (CPT). Treatment was given in a double-blind manner. The starting dose was 20 BU and was approximately doubled weekly up to 20,000 BU the first year and 120,000 BU the second year. Skin testing and CPT were performed before treatment and at each dose level. All patients reached 20,000 BU the first year. Twenty-five patients continued the second year. Twenty-one of those reached 120,000 BU (9/12 on mPEG-gm and 12/13 on gm). The frequency of general side effects was reduced by about 50% with the mPEG grass mix compared with native grass mix. A significant improvement in the conjunctival sensitivity was found in both treatment groups the second year (120,000 BU) but not the first year (20,000 BU). Seventy-eight percent of the patients in the gm group and 50% in the mPEG-gm group improved by CPT (not statistically significant). The skin sensitivity was reduced after 1 year at low dose in 69% of the gm-treated patients and 33% of the mPEG treated patients. After the second year at high dose levels, the skin sensitivity decreased in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Precision of skin prick and puncture tests with nine methods.

New devices for puncture tests have been proposed recently, but their precision by comparison to the prick test method is poorly known. Seven puncture tests (Allerprick, Morrow Brown standardized needle, Phazer, Pricker, Stallerpointe, Stallerkit, and Wyeth bifucated needle) were compared with the modified prick test performed with hypodermic or intradermal needles in eight carefully selected normal volunteers. Skin tests with histamine hydrochloride (10 mg/ml) were only performed when there was no factor that might interfere with their interpretation. The site of skin tests on the forearm was demonstrated not to significantly influence the reaction size. The coefficient of variation of the tests ranged from 8.4% to 21.7%. Modified skin prick tests are satisfactory since they are highly reproducible (coefficient of variation: 13.4% and 16.5%) and there is no subject effect. Phazet was found to be more reproducible without subject effect. Pricker is satisfactory since it has no subject effect and a reproducibility similar to that of modified prick tests. Other tests are less reproducible (Stallerkit or Morrow Brown) or vary between subjects (Allerkit, Stallerkit, Stallerpointe, and Wyeth Needle).

Adult↗

Emergency treatment of allergic reactions to Hymenoptera stings.

Allergic reactions to Hymenoptera stings are frequently observed all over Europe. Rarely they may induce long-standing morbidity or even be fatal. Several investigations have shown that the emergency treatment given to these patients is often inadequate. Cutaneous symptoms respond well to antihistamines and also to adrenaline. Adrenaline is the mainstay for outside hospital treatment of more severe reactions involving the respiratory tract (bronchial asthma, laryngeal oedema) and the cardiovascular system (anaphylactic shock). Inhaled adrenaline is especially useful in respiratory symptoms, while parenteral application of adrenaline is prefered for shock treatment. All patients with severe respiratory or cardiovascular reactions must be hospitalized, treated under intensive care conditions and observed for at least 24 hr. Emergency medications including adrenaline for inhalation or for self-injection must be given to all patients with a history of systemic allergic reactions to hymenoptera stings. These patients must also get instructions for safety measures to avoid further stings. They should be referred to an allergist in order to evaluate the indication for venom immunotherapy.

Anaphylaxis↗

Aspergillus fumigatus specific IgE and IgG antibodies for diagnosis of Aspergillus-related lung diseases.

IgE and IgG antibodies against Aspergillus fumigatus were detected by crossed radio immunoelectrophoresis (CRIE) on the sera of seven patients with aspergilloma, six patients with allergic broncho-pulmonary aspergillosis (ABPA) and 25 patients with extrinsic asthma with Aspergillus allergy. IgE-CRIE analysis indicated the presence of A. fumigatus-specific IgE in sera of patients with ABPA and Aspergillus asthma but not of aspergilloma patients. IgG-CRIE showed that both aspergilloma and ABPA patient sera contained high levels of circulating specific IgG antibodies in contrast to sera of Aspergillus asthma patients, which did not show detectable amounts of Aspergillus-specific IgG antibodies. Specific IgE binding could be demonstrated for the major allergens Ag-10 and AG-40 in all ABPA patients, in 80% of Aspergillus asthma patients but not in sera from aspergilloma patients. Specific IgG antibodies directed towards the major allergens could be detected in most of the aspergilloma patients, between 30-70% of the ABPA patients but not in sera from patients with Aspergillus asthma.

Aspergillosis↗

Hyposensitization in asthmatics with mPEG-modified and unmodified house dust mite extract. III. Effect on mite-specific immunological parameters and correlation to changes in mite-sensitivity and symptoms.

Forty-six adult asthmatics allergic to D. pteronyssinus (Dp) participated in a 2-year study. Thirty-one underwent hyposensitization (HS-group). Fifteen were treated with Dp-extract (Dp-group), and 16 with a similar extract modified by monomethoxypolyethylene glycol with reduced allergenicity (mPEG-Dp-group). Fifteen patients served as controls. Dp-specific antibodies and histamine release from blood basophils were determined and compared with Dp-sensitivity in lungs and skin. In addition, IgG and IgE against the major allergen Der p I were followed in a subgroup. Dp-specific IgG, IgG1, and IgG4 increased significantly in both HS-treated groups after 1 and 2 years (median: 2.5- to 11.6-fold). IgG4 was not induced if maintenance dose during the first year was less than 20,000 BU. Median skin sensitivity decreased 4.4- to 8.2-fold after 1 year and 7.4- to 21.4-fold after 2 years. Der p I specific IgG response was unrelated to the occurrence or change in IgE with the same specificity. The mPEG-Dp-extract tended to have less effect on skin sensitivity and immunological parameters, differences reaching statistical significance for skin sensitivity only. In the HS-group, the decrease in bronchial sensitivity was significantly correlated to a decrease in IgE (r = 0.36), IgG1/IgG4 (r = 0.49), Dp-specific histamine release (r = 0.58), and to an increase in Dp-specific IgG4 (r = -0.36) and IgG4/IgE (r = -0.48). In patients improving clinically, Dp-specific IgG4/IgE increased, and median Dp-specific IgE was reduced to 80% compared with an increase to 150-160% seen in the unchanged or deteriorated group (P less than 0.05). Findings indicate an improvement of effect, if the allergen dose is sufficient to reduce specific IgE and/or induce an IgG and especially IgG4 response.

Adult↗

Hyposensitization in asthmatics with mPEG-modified and unmodified house dust mite extract. IV. Occurrence and prediction of side effects.

A double-blind study on hyposensitization (HS) with two extracts prepared from the house dust mite Dermatophagoides pteronyssinus (Dp) was performed on a group of asthmatics with bronchial sensitivity to Dp. In 18 patients, aluminium-hydroxide was added to the Dp-extract to give a depot effect (Dp-group). Nineteen patients were treated with a similar extract in which allergenicity had been reduced by coupling to monomethoxypolyethylene glycol (mPEG-Dp-group). This extract had previously been shown to have less effect on clinical symptoms and skin sensitivity compared to the Dp-extract. In the Dp- and mPEG-Dp-groups, 778 and 675 injections were administered. Fifteen and 12 patients in the Dp- and mPEG-Dp-groups had systemic reactions (P greater than 0.05). The frequency of injections giving systemic reactions was reduced in the mPEG-Dp-group: 5.1% compared to 9.0% in the Dp-group (P less than 0.01). In the mPEG-Dp-group, reactions were mild to moderate, mainly late-occurring asthma and urticaria, whereas two episodes of anaphylaxis and four of severe asthma occurred in the Dp-group. The reduction in side effects seems promising, but a further dose increase in the mPEG-Dp-group would be necessary to compare the side effects of doses with equal therapeutic effectiveness. High frequency of late local reactions made dose increase impossible with the present slightly modified extract. The systemic side effects occurred more frequently in patients highly skin test-sensitive to Dp prior to treatment. All patients skin test-positive to less than or equal to 100 BU had systemic reactions. Systemic side effects could not be predicted from the size of previous local reactions.

Animals↗

Effects of one-year hyposensitization in allergic rhinitis. Comparison of two house dust mite extracts.

In an open study, 21 patients suffering from chronic non-seasonal rhinitis and allergic to house mites (HDM) have been treated for 1 year with either a new extract (Pharmalagen; n = 10) or an allergoid, pyridine denatured, extract (Alavac; n = 11), both precipitated with AlOH3 (depot). The following investigations were performed before and after therapy: clinical scoring (for 4 weeks), quantified skin prick tests (SPT) and nasal provocation tests (NPT) with HDM, and determination in serum of HDM-specific IgE and IgG. Both groups were compared with six patients who remained untreated and underwent the same investigations. Hyposensitization with either extract induced an improvement in clinical scores (P less than 0.05), a decrease in SPT reactivity (Pharmalgen: P less than 0.001; Alavac: P less than 0.01), a marked increase in the nasal tolerance to HDM (P less than 0.001) and in HDM-specific IgG (P less than 0.001). In the group of untreated patients, all these parameters remained unchanged. Compared with the Alavac extract, the Pharmalgen extract was more active in decreasing SPT reactions (P less than 0.05) and inducing a HDM-specific IgG rise (P less than 0.05). Although both extracts induced some untoward allergic reactions, no adrenaline was used at any time during the study. These data suggest that hyposensitization with depot extracts of HDM can be considered a safe and active adjunct to the treatment of allergic rhinitis.

Adolescent↗