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Biomedical subjects

H Mosbech

Publications and source records attributed to H Mosbech.

At least 73 records · Page 4Linked to original sources

Immunotherapy with Hymenoptera venoms. Position paper of the Working Group on Immunotherapy of the European Academy of Allergy and Clinical Immunology.

Immunotherapy with Hymenoptera venoms is widely used throughout the world and is accepted as an effective treatment for most patients with Hymenoptera venom allergy. There are, however, still some unresolved problems with this form of treatment. At present there is no definite test which makes it possible to identify patients at risk - and thus candidates for immunotherapy - unequivocally. On the basis of prospective studies on the natural history of Hymenoptera allergy, venom immunotherapy is indicated in adults with severe systemic anaphylaxis. It is usually not necessary in patients with large local reactions only. Children with mild systemic reactions, e.g. urticaria, will need immunotherapy only in case of repeated reactions and/or a high risk of re-exposure. The selection of venoms for immunotherapy may lead to some confusion owing to common antigenic determinants shared by venoms of various Hymenoptera species. Many different regimens for immunotherapy have been proposed. At present, the three main are: rush, stepwise or clustered and classical. The maintenance dose of 100 micrograms usually protects from life-threatening reactions. However, in some patients 200 micrograms are necessary for complete protection. The usual interval between maintenance injections is 4 to 6 weeks. In many patients a strong increase of venom specific serum IgG-antibodies usually parallels clinical protection induced by venom immunotherapy, although many exceptions have been reported. Allergic side effects of venom immunotherapy are not rare, especially with honey bee venom and during the initial phase of dose increase. The question of the duration of venom immunotherapy is handled differently: although some authors recommend treatment for life, most suggest treating patients until skin tests and RAST become negative.

Adult↗

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↗

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↗

House dust mite-induced histamine release from washed blood cells. Evaluation of effect parameters.

In a selected group of 60 house dust mite allergic asthmatics, the correlation between the bronchial sensitivity to house dust mite and effect parameters of mite-induced histamine release from washed blood cells was evaluated. Using a sensitive glass microfibre-based method, a significant positive correlation (r = 0.60; P less than 0.001) was found between bronchial allergen sensitivity and basophil cell sensitivity expressed as the house dust mite concentration necessary to give half the maximum histamine release. No correlation was found between bronchial sensitivity and other parameters of the histamine release response. This way of determining the histamine release from washed blood cells is a simple and valuable alternative to bronchial allergen challenge.

Animals↗

Cell-mediated immunity assessed by skin testing (Multitest). I. Normal values in healthy Danish adults.

The Multitest CMI system consists of a disposable multiple puncture device that simultaneously applies seven standardized recall antigens for assessment of cell-mediated immunity (CMI). The seven antigens included were toxoid from Clostridium tetani and Corynebacterium diphtheriae, tuberculin, plus antigens from streptococcus (group C), Candida albicans, Trichophyton mentagrophytes, and Proteus mirabilis. A population of 352 healthy Danish adults, aged between 17 and 90 years, was tested to determine the incidence and size of delayed-type hypersensitivity (DTH) responses. All but six healthy adults (98%) responded to one or more antigens, the median number of positive responses being four in males and three in females. The incidence of positive responses ranged from 91% for tuberculin to 11% for trichophyton. The number of positive responses declined with age, being somewhat faster in females than males. Six of the seven antigen response rates were significantly lower in the over 65-years-olds, the only exception being trichophyton, and for four of the seven antigens significantly lower in females compared to males. When correlated to age and sex no major differences were found with regard to the size of response to the seven antigens except that the tuberculin response was larger in males. A scoring system based on both number and size of positive responses revealed significant age and sex related differences. The median "score" in 17-65-year-old males and females were, respectively, 17 mm and 14 mm compared to 13 mm and 8 mm in those over 65 years old (P less than 0.001 for both comparisons).

Adolescent↗

Insect allergy. Predictive value of diagnostic tests: a three-year follow-up study.

One hundred and six adults with various reactions to yellow jacket (YJ), honey bee (HB) or unidentified insects (UI) were tested for allergy to insect venoms. For various reasons none received immunotherapy. Individuals completed questionnaires annually for three consecutive years and described sting reactions within the previous season. Ninety subjects completed all the questionnaires and 77 of these were re-tested at the end of the period. Nine out of 25 patients reacted with a systemic reaction when re-stung. High IgE and low IgG venom-specific antibody levels indicated an unfavourable prognosis, since eight of 11 individuals who initially presented venom-specific IgE greater than RAST class 2 and venom-specific IgG below detection limit had systemic reactions at re-sting. No such reactions occurred in subjects with no specific IgE and only one out of six with specific IgE as well as IgG reacted systematically. Skin prick tests (SPT) of less than 3mm with YJ venom 1,000 micrograms/ml excluded later systemic symptoms to stings, whereas larger skin reactions gave an equal chance of systemic or local reactions at re-sting. In individuals not stung by UI, YJ and/or HB the decline in venom-specific IgG and IgE was significant, median values ranging from 41% to 75% over the 3-year period. The decline was unaffected by the type of sting reaction prior to the initial test. SPT results did not change significantly. The findings are relevant when testing patients several years after their last insect sting and the results might indicate that the antibody decline is accompanied by a decrease in clinical sensitivity.

Adult↗

Immunotherapy with yellow jacket venom. A comparative study including three different extracts, one adsorbed to aluminium hydroxide and two unmodified.

Thirty-two patients with previous systemic allergic reaction to yellow jacket stings were randomly allocated to three groups receiving immunotherapy with different preparations of yellow jacket venom: 1) extract adsorbed to aluminium hydroxide (Alutard-SQ), 2) Pharmalgen extract or 3) non-adsorbed extract from Allergologisk Laboratorium (ALK aq.). Regular examinations showed a decrease in skin prick test size in nearly all patients. Specific IgE-antibody (RAST and CRIE scores) showed a similar, but not significant tendency to decrease in all three groups. Specific IgG-antibody increased considerably in the Alutard group only; after 2 years, however, no difference could be detected between the three groups. During dose increase, patients treated with ALK aq. generally had smaller local reactions to injections than those treated with Pharmalgen. Few systemic reactions occurred in all three groups. Nineteen patients treated for 2 1/2-3 1/2 years were challenged in-hospital with stings from yellow jackets. No systemic and only minor local reactions occurred. Consequently, with the dose regimens applied all three extracts seem effective even though no common changes in either specific IgE or IgG could be demonstrated.

Adult↗

Collection of house dust for analysis of mite allergens. Allergen-reducing effect of a self-administered procedure.

To assess allergen-reducing effect of dust collection from mattresses, patients were asked to vacuum clean the entire surface of their mattresses for 5 min with their household cleaners at specified intervals ranging from 1-21 days. Ten patients performed four collections, nine patients only two. Amounts of dust, concentrations and amounts of major allergens from Dermatophagoides pteronyssinus (Dp42), Dermatophagoides microceras (Dm6), and Dermatophagoides farinae (Df6) were determined. The first sampling caused a statistically significant reduction in the absolute amounts of allergens in a following sample. The same tendency was seen in dust weight but not in concentrations of allergens. At intervals of 1 or 3 weeks no consistent changes could be registered. Differences were small and good reproducibility of the sampling and analysing procedure could be assumed. Since the self-administered procedure is much cheaper and easier to handle than sampling done by technicians with special equipment, it can be recommended for sequential analysis of allergen exposure.

Allergens↗

Effect of a mixture of pyridostigmine and atropine on forced expiratory volume (FEV1), and serum cholinesterase activity in normal subjects.

Pyridostigmine 0.143 mg kg-1 (maximum 10 mg) and atropine 0.0143 mg kg-1 (maximum 1 mg) were administered i.v. to six healthy male volunteers. Peripheral venous blood samples were drawn for measurement of serum cholinesterase activity. Maximum inhibition of the enzyme was found 5 min after injection with a decrease to 27 +/- 5% (mean +/- SEM) of the original activity. Forced expiratory volume in the first 1s (FEV1) was measured at fixed time intervals for 90 min. No decrease in FEV1 was observed; on the contrary, there was a small increase. We conclude that atropine effectively antagonizes the muscarinic side-effects of pyridostigmine on bronchial smooth muscle tone and bronchial secretions, when administered in clinical doses to normal human subjects.

Adult↗

Sensitive glass microfibre-based histamine analysis for allergy testing in washed blood cells. Results compared with conventional leukocyte histamine release assay.

The new microfibre method for allergy testing is based on basophil histamine release after challenge with suspected allergens in samples of 50 microliter washed blood cells. Released histamine is bound to microfibres and measured after removal of interfering substances by washing. The microfibre method was compared with the conventional leukocyte histamine release assay in 18 allergic patients tested with 10 different allergens. It was found that the same individuals responded with histamine release to the same allergens in both assays, and the number of responders was almost identical. Also the dose-response curves and the cell sensitivity were almost identical, which further substantiated identity between the results obtained by the new microfibre method and the conventional assay. A comparison between the microfibre method and in vivo provocation tests showed good agreement when comparing the number of positive and negative responses in these test. The new method overcomes the problems in allergy testing, where only small amounts of blood are available and many tests have to be carried out.

Allergens↗

HEP versus PNU standardization of allergen extracts in skin prick testing. A comparative randomized in vivo study.

During 1 year, all patients referred to an allergy outpatient clinic for adults were skin prick tested with a panel of standard allergen extracts from two manufacturers using different methods of standardization. One company referred to the histamine equivalent prick (HEP) and the other used the more traditional protein nitrogen units (PNU). Standard extracts and five-fold dilution were tested. The results indicate that the ratio of concentration between two extracts of the same allergen should be measured by the absolute difference of the wheal diameters. We found significant differences between corresponding extracts from the two manufacturers.

Adult↗

Inhibitory effect of cyclosporin A on histamine release from human leukocytes and rat mast cells.

The influence of cyclosporin A (CyA) on human basophil histamine release induced in vitro by specific antigen, anti-IgE, calcium ionophore A23187, or concanavalin A (Con A) was studied. CyA inhibited the release induced by these four stimulators. It is suggested that the drug acts directly on the target cell, since similar effect was obtained with isolated peritoneal rat mast cells. The basophil histamine release was not changed by a non-immunosuppressive cyclosporin derivate.

Animals↗