The popliteal lymph node assay in mice to screen for the immune disregulating potential of chemicals--a preliminary study.

Low mol. wt compounds were tested in the popliteal lymph node (PLN) assay to study whether PLN reactivity could be related to the ability of the compounds to induce autoimmune disorders in man. PLN reactions were measured 7 days after a single subcutaneous (s.c.) injection of dissolved compounds in amounts of 0.3-2.0 mg into one hind footpad of mice and assessed as the weight increase of the draining PLN relative to the PLN weight of the untreated contralateral paw. Hydralazine, chlorpromazine, diphenylhydantoin, carbamazepine, phenylbutazone and nitrofurantoin, all being drugs with a documented potential to induce systemic immunological disorders in man, caused marked PLN reactions. False negative PLN responses were observed following injection of procainamide and isoniazid. Among systemic drugs without known potential to induce autoimmune reactions in humans, quinacrine, denzimol and niridazole significantly increased PLN weights, while phenobarbital, levamisole and disulfiram had no effect. Chemicals with a well-known capacity to induce contact dermatitis in man like 2,4-dinitro-1-chlorobenzene, alpha-methylene-gamma-butyrolactone, p-phenylenediamine, 5-nitro-2-furaldehyde semicarbazone, 2-mercapto-benzothiazol and 1,3-dibutyl-2-thiourea caused marked PLN reactions, while the non-sensitizer 2,4-dichloro-1-nitrobenzene failed to do so. It is concluded that the PLN assay as applied in this study may give a rapid first indication of immunomodulating potential of low mol. wt compounds, but it does not discriminate as to the kind of immunomodulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiology of contact allergy in Singapore.

The prevalence of contact allergy in 2471 patients patch tested in Singapore was 49.2% (571/1160) in women and 49.8% (653/1311) in men (sex difference not significant). The rate appeared to increase with age (43.7% in those less than 20 years, 50.6% between 20 and 49 years, and 63.1% in those greater than 49 years). There was no significant difference in the prevalence of contact allergy among the major races (Chinese, Malay, and Indian) of Singapore. Contact allergies in 16.8% (96/571) of women and 38.9% (254/653) of men (p less than 0.001) were occupational. Nickel, fragrance mix, proflavine, and chromate were common sensitizers. The male:female prevalence of nickel allergy was 1:2 (sex difference p less than 0.001) and for chromate was 7:1 (sex difference p less than 0.001). Chromate sensitivity was occupational in 87.7% (121/138) of men and 47.1% (8/17) of women (sex difference p less than 0.001). Proflavine, neomycin, and clioquinol were the more common medicament sensitizers.

Assessment of the ability of mice fed on vitamin A supplemented diet to respond to a variety of potential contact sensitizers.

The contact sensitizing potential of various compounds was tested in mice maintained on a diet supplemented with vitamin A acetate. Substances were applied epicutaneously. After challenge, increases in ear thickness were measured and the differences in response between control and treated groups determined by the Mann Whitney test. A number of sensitizers, including Dowicil 200, cinnamaldehyde, hydroxycitronellal and Kathon CG gave positive sensitivity responses.

Drug-induced thrombocytopenia.

A variety of drugs may cause thrombocytopenia. Although it occurs more often than drug-induced anemia it is less well understood because techniques for studying drug-platelet-immune interactions have been unavailable until recently. The mechanisms by which drugs cause thrombocytopenia are varied. Bone marrow suppression or increased peripheral destruction of platelets could be involved. Nonimmunologic as well as immunologic mechanisms may also occur. These different mechanisms of drug-induced thrombocytopenia are reviewed. Diagnostic methods and treatment are also summarized.

The diagnosis of drug allergies. Utilizing in vitro mast cell test and IgE inhibition test.

With the ever-increasing use of pharmaceuticals and the relatively high risk of developing drug allergies, particularly for patients in hospitals and for ambulatory patients with a history of drug allergy, the need to develop in vitro assays for drug allergy is great. In the early 1970's a mast cell technique was developed for diagnosis of drug allergies. A PRIST inhibition assay has also recently been developed to detect IgE antibodies to drug allergens. This test has also been referred to as the Total IgE Inhibition Test by Specific Drug Allergen, and is a variant of the in vitro RAST Test. In vitro mast cell and IgE inhibition tests are applied for identification of drug and chemical allergens and for their cautious clinical trial to prevent future drug and chemical reactions. Over the last eight years, over 1,300 patients were examined utilizing the mast cell technique. Over 100 drugs were tested, with penicillin, barbiturates, "caine" derivatives and sulfonamides most frequently employed. Of 270 patients with well-defined drug reactions, 190 (70 per cent) gave a positive response to the mast cell test. Eighty-five per cent of sera tested with Type I reactions gave a mast cell response. Of these, a group of 30 patients was studied with PRIST inhibition as well. Procedures for comparative testing of necessary drugs and/or chemicals in cases of high anaphylaxis risk of reaction in the clinical setting, hospital or office are included in the study as well as individual case reports. Mast cell assay coupled with IgE inhibition has been successfully used to diagnose drug and chemical allergic reactions. The incidence of positivity is high when the offending drug causes a Type I allergic reaction. The cases reported indicate that both the Mast Cell and the PRIST inhibition assays are useful for diagnosing and setting the clinical treatment and clinical course of the patient. The mast cell assay would be potentially employed for patient use in hospitals where the incidence of drug allergy is highest and for occupational health in the chemical industry. The greatest potential would be in outpatient care applied to patients with multiple drug allergies in the selection of safe drugs (test negative by both methods, and other clinical studies) for future drug usage.

Drug-specific antibodies in human serum?

In view of the fact that all drugs possess the potential to stimulate an immunological response when administered to man, it was proposed that certain individuals in the general population may have developed high antibody titres to certain commonly used drugs. Human serum samples were incubated with radioactively-labelled drugs and the amount of IgG antibody present was determined by coprecipitation. Using the method outlined, we were unable to detect any antibodies specific for acetylsalicylic acid, ampicillin, erythromycin, lidocaine, penicillin, procainamide or tetracycline, and conclude that drug-specific immunoglobulins are not one of the major factors involved in the equilibrium between the free and bound drug forms.

[Immune and autoimmune reactions in the mechanism of action of drug substances, their detoxication and the development of habituation to them]. / Immunnye i autoimmunnye reaktsii v mekhanizme deistviia lekarstvennykh veshchestv, ikh detoksikatsii i razvitiia pyrivykaniia k nim.

It has been shown that rausedyl administration is followed by enhanced synthesis of autoantibodies to serotonine and adrenaline. Meanwhile bucarban enhances the synthesis of autoantibodies to endogenous insulin and ACTH to hydrocortisone and testosterone. Activation of the autoimmune system of regulating the balance of endogenous compounds was shown by an increased number of specific antibody-producing cells in the organs and tissues and by the growth of the titer of circulating antibodies in the blood.