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Immunotherapy: rationale and mechanisms.

Immunotherapy is defined as the controlled exposure to known allergens to reduce the severity of the allergic response. Although available since 1910, its exact mechanisms of action is not known but may involve an increase in allergen-specific IgG antibodies, a decrease in IgE synthesis, and alteration in T-lymphocyte activity. Immunotherapy is indicated in patients with proven allergy who have significant symptoms. It may be used together with pharmacologic measures but is relatively contraindicated in patients receiving beta-blocker therapy. Immunotherapy may be continued during pregnancy and should not be initiated in patients with autoimmune diseases or in human immunodeficiency virus-positive patients. Selection of appropriate diagnostic tests is important. Before immunotherapy is considered, there are two recommended in vivo tests (combined prick and intradermal skin test, and skin end point titration) and two recommended in vitro tests (radioallergosorbent test [RAST] and enzyme-linked immunosorbent assays [ELISA]), all equally safe and sensitive. After appropriate test interpretation, treatment is initiated with slowly escalating doses of allergen. Effects are often apparent in 3 to 6 months and, after continuation for 3 to 5 years, patients usually achieve lasting benefit.

Contraindications↗

Standardization of allergenic extracts: a manufacturer's perspective.

The current procedure for standardizing allergenic extracts utilizes quantitative skin testing techniques and in vitro techniques. A reference preparation is selected and tested using a sensitive intradermal skin test technique to determine allergy units. Subsequent batches of standardized extracts are compared to the reference preparation using in vitro techniques. The standardization program has accelerated over the past few years and all indications are that it will continue to do so in the future.

Allergens↗

Studies on the drug binding of certain novel potential local anaesthetics.

One of the many factors affecting the response of an individual to a drug is the modification of its action by tissue and plasma proteins. Plasma proteins can be divided into three categories, viz., fibrinogen, globulins and albumin. Fibrinogen exhibits little reactivity with respect to drugs, being concerned solely with blood clotting, whereas globulins may have affinity for various endogenous compounds. Albumin, which constitutes around 4% of human serum, has the capability to bind reversibly or irreversibly to a wide range of substances. Generally, it has been found that albumins are particularly responsible for binding of local anaesthetics in plasma, but another binding factor may be lipoproteins present in blood cell membranes. Moreover, the transport of local anaesthetics to the site of action in the nerve membrane is influenced by their affinity for proteins present in extracellular fluids either at the site of injection, or surrounding the nerve fibres. Accordingly, systematic investigations on the protein binding characteristics of certain novel potential local anaesthetics was initiated with a view to ascertaining whether the duration of action of local anaesthetics could be correlated with their affinity for protein. The technique of equilibrium dialysis was used for measurements of drug-protein binding. This consists basically of two compartments separated by a semi-permeable cellulose membrane through which only free, unbound drug molecules can diffuse. The results indicate that there is no significant relationship between the extent of drug-protein binding and duration of local anaesthesia produced by these test compounds in the intradermal wheal test on the guinea-pig.

Anesthetics, Local↗

[Quantitative skin test and inhalation provocation test in asthma using platinum salts].

In this article, the in vivo test results obtained from workers of two platinum separating plants are described. A total of 30 out of 102 workers in two platinum separating plants and 0/40 control subjects showed a positive skin reaction on being provoked with platinum compounds. Twelve out of 15 workers and none of 5 control subjects showed a positive reaction to the bronchial provocation test; this indicates that both tests are highly specific. Three workers with negative skin test reactions showed a clearly positive immediate reaction to the bronchial provocation test with platinum compounds.

Bronchial Provocation Tests↗

The immunodiagnosis of Schistosoma mansoni infection in the different clinico-parasitological stages.

A total of 52 bilharzial mansoni patients were examined, 20 patients with early intestinal infection with living ova in stools, 20 patients with hepatosplenomegaly but without ascites, also with viable ova in stools, and 12 patients with hepatosplenomegaly and ascites without ova in stools; but in the rectal snip. Also 20 normal persons were examined. An IDT test was performed by S. mansoni adult worm antigen. S. mansoni adult worm and egg antigen extracts were used for performing CIEP, IHAT and ELISA tests showed statistically the same high sensitivity. In cases with hepatosplenomegaly whatever the clinical (with or without ascites) or the parasitological status (passing or not passing ova in stools) of the patients, the ELISA test with egg antigen is found to be a highly sensitive and a specific test.

Animals↗

[Significance of inhaled environmental allergens].

Whereas the importance of pollen as inhalative allergens has been largely investigated and is generally known, the experience in the frequency and the role of the sensibilization with air-borne fungi is relatively limited. In 720 patients with Asthma bronchiale the degree of sensitization has been tested with various extracts of air-borne fungi of SSW Dresden (mould mixture, aspergillin, mucor, cladosporium and penicillium and alternaria). The most frequent and also the strongest reactions were found with alternaria and the smallest part of positive skin reactions with penicillium. An isolated sensitization with mould has been demonstrated in 20 per cent of the cases. In 60 per cent of the tested patients a manifest mould allergy was shown by means of the Inhalative Allergen Test, the most favourable correlation between Intracutaneous Test (ICT) and Inhalative Test (IAT) was found with alternaria (76%). A conformance between ICT and basophils degranulation test (BDT) was stated in 69% of the cases. The aim should be comparable tests with allergen extracts without irritative effects and qualitative measurements of air-borne fungi.

Air Pollution↗

[Indications for the inhalation provocation test].

For proper performance of BPT certain medicaments must be set off. Kind and duration of inhalation, the time-frequency relation and the dosage of allergens are necessary parameters in evaluation of BPT-results. The BPT is necessary when the history is characteristic without positive skin reaction, when the skin reaction is positive without characteristic history and when several positive skin reactions have been obtained and cannot be excluded as specific for the complaints from the patient history. BPT is the main test in allergic airway diseases to prove an actual clinical allergy together with history and skin tests. RAST correlates differently with BPT with different allergens and does not help much in the house dust group--and mould allergies.

Allergens↗

Cutaneous histamine reactivity, histamine content of commercial allergens, and potential for false-positive skin test reactions in dogs.

The cutaneous reactivity of normal and atopic dogs to intradermal injections of histamine phosphate was evaluated. Significant differences were not found in the mean wheal diameters of either group. Commercial allergens used for intradermal skin testing and immunotherapy were determined to contain histamine. To determine whether allergen histamine content was sufficient to cause false-positive skin test results, the cutaneous response of Johnson grass allergic dogs was compared, using commercial Johnson grass allergen and commercial Johnson grass allergen with histamine removed. Significant differences were not noticed between Johnson grass and dehistaminized Johnson grass. Therefore, the histamine content of commercial Johnson grass allergen did not appear to cause false-positive skin test results for this group of Johnson grass allergic dogs.

Allergens↗

Automated histamine analysis for in vitro allergy testing. II. Correlation of skin test results with in vitro whole blood histamine release in 82 patients.

The recently developed sensitive, automated histamine assay system was applied for in vitro allergy testing. The simplified method for histamine release from whole heparinized blood was used. Aliquots of blood and allergen were incubated for one hour at 37 degrees C, and each supernatant was then analyzed for histamine release. Nine common pollen and environmental allergens were used at three 10-fold dilutions for in vitro testing with the use of 20 ml of blood. Intradermal skin tests were correlated with the whole blood histamine release in 82 patients who had received no immunotherapy. A scoring system for the histamine results was developed to take into consideration the results with multiple allergen concentrations. When the skin test was strongly positive (greater than or equal to 3 + at 100 protein nitrogen units [PNU]/ml), the whole blood histamine release was positive in 89% of the tests. In contrast, when the skin test was negative ( less than 1 + at 100 PNU/ml), the histamine release was also negative in 99.8% of the cases. When the skin test was 1 +, the histamine release from whole blood was positive in 6% of the tests; and when the skin test was 2+, the whole blood results were positive in 32%. The accuracy, precision, and sensitivity of the automated histamine assay allow its application for the clinical study of allergic patients.

Allergens↗

Skin tests in childhood lymphoma and neuroblastoma.

Intradermal skin test antigen (Varidase, Mumps, Candidine) and contact sensitization with 2,4-dinitrochlorobenzene (DNCB) were employed in 35 previously untreated children with neuroblastoma and malignant lymphoma, to evaluate delayed cutaneous hypersensitivity. Cutaneous responses were correlated to stage of disease and survival. The limited number of patients prevents any definitive conclusion. It is apparent, however, that in childhood non-Hodgkin's lymphoma anergy to DNCB is correlated to advanced stages with rapid progressive disease. In neuroblastoma and Hodgkin's disease patients skin test sensitization seems to be of questionable clinical value.

Adolescent↗