Alex S. Friedlaender

The effect of pituitary adrenocorticotrophic hormone (ACTH) on histamine intoxication and anaphylaxis in the guinea pig

Abstract 1.1. Observations were made on the effect of pituitary adrenocorticotrophic hormone (ACTH) on histamine intoxication and anaphylaxis in the guinea pig. 2.2. The time required for guinea pigs to develop bronchospasm when exposed to aerosolized histamine was approximately the same before or after the administration of a single dose of ACTH. 3.3. Guinea pigs actively sensitized to horse serum 14 to 18 days previously, and who were given ACTH 4 hours before the second dose of horse serum, developed anaphylactic reactions comparable to those displayed by sensitized controls who had received no prior treatment with ACTH.

Oral cortisone therapy in allergic diseases

Abstract 1.1. Orally administered cortisone is readily absorbed from the gastrointestinal tract, and in comparable dosage affects allergic diseases in much the same manner as the saline suspension of cortisone given by intramuscular injection. 2.2. A moderate depression in blood eosinophiles is apparent 4 hours after a single 25 to 50 mg. dose of oral cortisone. Maximum depressions are usually attained during the second to fourth day of therapy. 3.3. Symptoms of hay fever, asthma, urticaria, atopic dermatitis and contact dermatitis are often completely relieved during oral cortisone therapy. The onset of such improvement appears to be more rapid than with cortisone suspension administered by injection, but the therapeutic effect of each dose of the oral material is dissipated more rapidly. 4.4. The effects of oral cortisone, although striking in many cases, are of relatively brief duration, and chronic symptoms recur shortly after withdrawal of the hormone. Close supervision of the patient is necessary to avoid the known side effects of adrenal hormone therapy.

Topical use of hydrocortisone and hydrocortisoneneomycin ointments in allergic dermatoses

T HE present, study summarizes observations made during the past year on the use of topically applied hydrocortisone, or compound F, in a fairly large group of patients with representative allergic skin eruptions. There is considerable experimental as well. as clinical evidence indicating that hydrocortisone differs from cortisone, at least quantitatively, in its local effect OH tissues1 While it is well known that cortisone is capable of influencing the course of many types of allergic dermatoses when administered by oral or parenteral routes, very little, if any, response is evident when it is applied directly to cutaneous lesions,‘, -* although it is highly effective on local application in certain diseases of the eye.5 Hydrocortisone appears even more effective than cortisone in the local treatment of similar ocular condition@; in its direct action on inflamed joints7; and in its local effect on certain inflammatory cutaneous lesions.*. 9 Its value in the clinical management of atopic dermatitis and certain other eczematous eruptions has also been reported.“, 4 Our own clinical trials of suitable prepa,rations of hydrocortisone in ointment form indicated a marked influence on eczematous and some papulosquamous lesions, and little or no effect on urticarial t,ype of eruptions. The cases included in the present summary a,re those of atopic and contact dermatitis, as well as certain other possible allergic eruptions, and a small number of nonallergic dermatoses. It must of course be emphasized that any favorable effect which n1a.y ensue from the use of locally applied hormones in allergic dermatoses is ent,irely symptomatic in nature, and does not influence the underlying etiologic mechanism involved. Such relief, however, though temporary in nature, is a valuable adjunct in the mana,gement of these conditions, at least until a more adequate solution of the problem can be attained through the control or correction of basic underlying mechanisms. In addition, the advantages of successful local steroid therapy are considerable when the attenda,nt side effects of systemic hormonad treatment are considered.

Clinical effects of ragweed antigen emulsion: A double-blind study

Abstract 1. A double-blind study was carried out in 33 patients with ragweed pollinosis to evaluate the effects of a single injection of emulsified ragweed antigen. The group consisted of 18 patients sensitive to ragweed who were treated with emulsion antigen the previous year, and 15 patients who had never before been treated. Seventeen patients received from 1,250 to 5,000 pollen units of emulsified ragweed antigen in a single day. The remaining patients were given a placebo emulsion containing no ragweed. 2. Immediate local reactions occurred in 8 patients in the groups treated with ragweed emulsion and in one patient in the placebo group. Mild constitutional reactions occurred in 2 patients who received ragweed emulsion. 3. Clinical results were determined by assigning a daily score to each patient, based on the severity of symptoms and the amount of medication used each day. A total seasonal score for each patient and a mean seasonal score for each group of patients was calculated. While the total scores of groups treated with ragweed emulsion (both previously treated and previously untreated) were more favorable than those of the corresponding placebo-treated groups, the statistical differences between them were small and were significant at the 5 per cent level only when all antigen-treated groups were combined and compared with placebo-treated groups. 4. It is pointed out that this type of study does not allow evaluation of many variables which may influence results of treatment.

OBSERVATIONS ON BASOPHIL DEGRANULATION AS AN INDICATOR OF ANTIGEN-ANTIBODY REACTION.

Abstract These observations involve the study of basophil degranulation induced by the addition of antigen to the sera of patients or animals known to be sensitive to ragweed pollen and in subjects with good histories of allergic reactions to penicillin. An indirect technique described by Shelley was used, wherein basophils obtained from buffy coat of rabbit blood are used as indicator cells. Although nonspecific alteration of basophils was frequent from antigen or serum alone, the incidence of positive basophil degranulation from human ragweed-sensitive sera was 76 per cent, compared to 36 per cent in sera from nonsensitive controls. A greater percentage of positive reactions was noted with purified ragweed fraction, pool C, over whole ragweed antigen. Limited observations with an antiragweed rabbit serum and its homologous antigen showed positive responses only with a high concentration of antigen. In 36 patients with histories of previous penicillin reaction, the basophil response was positive in 36 per cent. In a group of 24 patients, in 44 per cent of whom penicilloyl-polylysine skin tests were positive, the incidence of positive basophil degranulation was 38 per cent. In the present study, nonspecific alterations in basophils interfered with efforts to quantitate the basophil response. While the results with ragweed-sensitive sera suggest a possible specificity directed toward a fraction of the ragweed antigen, total correlation with clinical sensitivity and reaginic antibody was not found. Many technical and theoretical problems require solution before the specificity of the basophil degranulation phenomenon can be confidently related to antigen-antibody reaction.

Spectral absorption characteristics of antihistaminic drugs; relationship to ultraviolet erythema.

Abstract 1.1. The ultraviolet absorption spectra were determined for the following antihistaminic drugs: Benadryl, Pyribenzamine, Neo-Antergan, Neohetramine, Decapryn, Pyrrolazote, Antistine, Trimeton, Thenylene, Tagathen, Thephorin, AH-853 (Parke, Davis), and C-5581H (Bristol). These data obtained with the Beckman Quartz Spectrophotometer show that Pyribenzamine, Thenylene, Neo-Antergan, Pyrrolazote, Tagathen, Neohetramine, and Antistine possess absorption bands within the active portion of the ultraviolet spectrum (2950 to 3150 A.). The remaining compounds tested do not significantly absorb the erythema-producing rays. 2.2. Clinical studies in normal skin with ointment preparations of these drugs parallel the spectrophotometric findings. Those which possess an absorption band in the 2950 to 3150 A. region prevent erythema ordinarily produced by exposure to the radiations of the quartz mercury arc lamp. This action is demonstrable when the ointments are applied either directly to the skin or when placed on a square of quartz overlying the skin. The drugs without absorption characteristics in this zone of the spectrum do not appreciably affect the erythema response. This would indicate that the inhibitory action shown by some of these drugs is related to their spectral absorption characteristics. 3.3. The oral ingestion of antihistaminic drugs before exposure to the mercury are radiations and at regular intervals for a period of twenty-four hours afterwards failed to affect the development of the erythema reaction. This did not differ when either an absorbing or nonabsorbing drug was used. 4.4. Introduction of antihistaminic drugs beneath the superficial layers of the skin failed to affect the development of ultraviolet erythema. This is in marked contrast to the inhibition displayed when similar concentrations of the absorbing drug are applied to the skins surface. 5.5. Surface application of absorbing and nonabsorbing drugs to normal skin already exposed to ultraviolet radiations failed to impair the development of the erythema response. 6.6. Preliminary clinical studies indicate that antihistaminic drugs which absorb the active part of the ultraviolet spectrum may be employed effectively as sunburn preventives. 7.7. The results of these studies fail to support the concept that histamine release in the tissues is the principal factor involved in the production of ultraviolet erythema.