Saul Malkiel

Acth and cortisone in allergic manifestations: Therapeutic results and studies on immunological and tissue reactivity

Abstract 1.1. Adrenocorticotrophic hormone and cortisone are of appreciable value in the temporary treatment of certain types and phases of allergic syndromes. They are most helpful in intractable asthma, in acute status asthmaticus, and in severe drug reactions. 2.2. These hormones have a number of limitations in their usefulness. The length of remissions after a single course of treatment varies from a few days to a few months, the necessity for frequent injections is a handicap, and some types of allergy do not respond. 3.3. ACTH and cortisone are not substitutes for more basic allergic management. 4.4. The dangers and hazards from continuous and sometimes from temporary use of these drugs are numerous, and the hormones must not be employed without a full understanding of their many actions. 5.5. In patients treated with ACTH or cortisone the skin reactions to antigens and histamine remained unchanged. 6.6. Quantitative studies of the ophthalmic and nasal reactions in those who have nasal and conjunctival allergy show them not to be significantly altered. 7.7. Sensitizing antibodies have remained unaffected after ACTH or cortisone therapy. 8.8. It is possible that the simple titration tests do not simulate the conditions of chronic allergy and that tests devised to resemble more closely continuous allergic stimulation might show a more decisive influence of these hormones on allergic reactivity.

Anaphylactic shock in the pertussis-vaccinated mouse☆

Abstract 1.1. It has been confirmed that H. pertussis vaccination of white mice produces a fiftyfold increase in histamine sensitivity. 2.2. Brucella abortus vaccine enhanced histamine sensitivity to a much less but significant degree. 3.3. Mice immunized by an intraperitoneal injection of a mixture of H. pertussis vaccine and horse serum become markedly anaphylactically sensitive to the serum. Brucella abortus vaccine has a somewhat similar effect on anaphylaxis. 4.4. The results of further experimentation seem to substantiate the impression that histamine plays a minor role in anaphylaxis in the mouse even when the mouse has been made markedly histamine sensitive. 5.5. The possible relationship between the enhancement of experimental anaphylaxis by H. pertussis vaccine and the questionable observation of the production of the clinical syndrome of paralysis following vaccination is discussed.

Anaphylactic shock in the pertussis vaccinated mouse.

Summary 1. It has been confirmed that H. pertussis vaccination of white mice produces a 50-fold increase in histamine sensitivity. 2. Mice immunized by an intraperitoneal injection of a mixture of H. pertussis vaccine and horse serum become markedly anaphylac-togenic to a challenging dose of the serum. Brucella abortus vaccine has a somewhat similar effect on anaphylaxis.

The effect of stress factors on asthma induced in guinea pigs by aerosolized antigens

Abstract 1.1. Asthma of controllable degree has been produced in passively sensitized guinea pigs by the inhalation of aerosolized crystalline ovalbumin. 2.2. Using this aerosol-induced asthma as an indicator it has been shown that a protective effect can be demonstrated by pretreatment of these animals with any of the following procedures: Pyribenzamine, cortisone, ACTH, localized chemical inflammation, yeast suspension, sodium nucleate, and human serum. 3.3. A pyrogenic bacterial polysaccharide, Piromen, failed to produce significant protection. 4.4. The method described and possible future modifications of it may be used advantageously in the study of basic factors in the production and alteration of hypersensitivity.

Histamine Sensitivity and Anaphylaxis in the Pertussis-Vaccinated Rat.

Summary Inoculation of the white rat with Hemophilus pertussis increases its sensitivity to histamine. Pertussis mixed with horse serum markedly enhances the ability of the antigen to produce anaphylactic sensitivity.

Protective effect of cortisone on induced asthma in the guinea pig.

Summary In a significant percentage of sensitized guinea pigs cortisone was found to be effective in inhibiting or delaying the symptoms of asthma induced by an aerosolized antigen.

Aspirin sensitivity—Experimental studies

Abstract 1.1. Guinea pigs were sensitized to aspirin by the use of aspirin-protein conjugates. Uncombined aspirin even when incorporated with various adjuncts failed to produce this sensitivity. 2.2. Rabbits showed precipitating antibodies to aspirin when immunized with aspirin-protein conjugates. 3.3. The sera of aspirin-sensitive human beings as well as that of immune rabbits and guinea pigs failed to show an increase in the amount of salicylate normally bound, as determined by our technique. 4.4. Guinea pigs passively sensitized by serum from aspirin-sensitive patients gave distinct though mild anaphylactic reactions when challenged with heterologous aspirin-protein conjugate.

The antigenic relationship of the pollen, seed, and leaves of giant ragweed

Abstract Fractions of the giant ragweed pollen, seed, and leaves were prepared in a purified form. The antigenic relationships of these preparations were compared by direct skin tests in ragweed-sensitive patients, by cross testing of reagin sites exhausted with a related antigen, by anaphylaxis and by precipitin tests. The results showed that: 1.1. There exists an antigenic relationship of the three investigated giant ragweed tissues. 2.2. Comparative titrations suggest a difference in potency decreasing from pollen through leaves to seed. 3.3. There seems to be a very close relationship between the leaf and pollen antigen. The seed does not contain an antigen present in the pollen in that it is not capable of exhausting sites inoculated with human reagin. The restricted number of tested subjects, however, does not allow final conclusions to be drawn on this point. 4.4. Quantitative titrations and other investigations showed that ammonium sulfate fractionation results in the most potent preparations for leaves and pollen, but acetone fractionation is apparently required to produce potent seed preparations, especially as observed by its anaphylactic properties in sensitized guinea pigs. 5.5. The relatively small amount of pollen antigen in the leaves and seed would speak against the use of these plant tissues as a practical source of the antigen for diagnostic and therapeutic purposes. 6.6. The results suggest that the plant debris may serve as a natural source of allergy to the pollen-sensitive patient. Further work would have to be done before this can be accepted as a final opinion.

Cortisone in the treatment of patients with ragweed pollinosis. Determination of changes in sensitivity of the mucosa produced by pre- and co-seasonal cortisone administration

Abstract 1.1. Fourteen patients having hay fever or a combination of hay fever and asthma due to ragweed were given oral cortisone. The hormone was administered for a short time several months before the ragweed season and again during the pollinating season. Changes in the mucous membrane sensitivity of the eye, nose, and bronchi were determined quantitatively during both periods. 2.2. Symptoms of hay fever were more difficult to control than were those of asthma. 3.3. Ten patients developed untoward reactions. Cortisone had to be discontinued in 3 patients because of severe complications. Reasons for this high rate of side reactions are suggested. 4.4. Cortisone given out of season decreased the sensitivity of the mucosa to ragweed extract. The greatest change occurred in the organs primarily affected. 5.5. After obtaining relief from cortisone administered during the pollinating season, a dilution of pollen weaker than that required prior to the season produced a reaction of the mucosa. 6.6. The time of disappearance of intracutaneously injected saline or histamine was somewhat lengthened by cortisone. The disappearance time of hyaluronidase was markedly prolonged. The altered reaction to hyaluronidase is discussed. 7.7. There was no detectable change in the titers of the skin sensitizing antibody or the thermostable antibody in the patients treated with cortisone.

Effect of slowly absorbing antigen (ragweed) on neutralizing antibody titer

Abstract 1.1. A sesame oil-aluminum monostearate preparation of ragweed extract has been shown to prolong the absorption of the allergen. 2.2. Therapy with this preparation results in an increased titer of neutralizing antibody. 3.3. The results are insufficient to draw any conclusions regarding the relationship between neutralizing antibody and clinical results.