Samuel M. Feinberg

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.

Asthma and rhinitis from insect allergens: I. Clinical importance

Abstract Insects and arthropods probably constitute a major cause of respiratory allergy. This is supported by the frequent reactions to insects on scratch tests, the inability to find other etiological factors to explain completely the symptoms in many of these patients, the probable prevalence of insect substances in the air, and the encouraging results obtained by desensitization. Preliminary findings on immunologic aspects are noted, but extensive work is needed to determine the antigenic relationship and chemical characteristics of the antigens.

A suggested quantitative evaluation of the degree of sensitivity of patients with ragweed pollinosis

Abstract 1.1. A quantitative method is presented whereby the response of the eye, nose, and bronchi to a specific antigen can be determined. 2.2. Twenty patients with ragweed pollinosis without desensitization therapy showed a greater sensitivity than that found in another group of 20 ragweed sensitive patients who had had more than one year of such treatment. 3.3. There was correlation between the history of clinical symptoms in a particular shock organ and the degree of sensitivity as shown by quantitative tests in the various tissues. 4.4. The methods, or future modifications of it, should be applicable to the study of various factors. Among these are variations in procedures in desensitization therapy, modified allergens, the effect of various nonspecific factors and nonspecific therapy and the establishment of safe levels at which to discontinue treatment.

Aspirin allergy; its relationship to chronic intractable asthma.

Excerpt For some time we have recognized a rather characteristic type of asthmatic patient whose symptoms are of unusual severity and chronicity, and who in addition presents a history of hypersens...

Atopy to simple chemical compounds—Sulfonechloramides

Abstract 1.1. Asthma and rhinitis due specifically to the inhalation of dust of the water disinfectants, chloramine-T and halazone, are reported in fourteen workers exposed to these chemicals. 2.2. These simple chemical substances of low molecular weight have been shown to behave as true atopens, by producing immediate whealing skin reactions by direct test and by passive transfer. 3.3. The experiences cited suggest a number of possibilities: (a) that such simple chemicals may act as complete antigens; (b) that simple chemical allergens, as yet of unidentified nature, may be present in food, drink, and air; and (c) that chemical irritants, hitherto regarded as acting in a nonspecific manner, may, on re-examination, exhibit specific allergenic behavior.

Delayed and immediate skin reactivity in man after the injection of antigen in emulsion: Cell transfer of the delayed sensitivity

Abstract In fifteen nonallergic subjects receiving ragweed in repository form, seven developed immediate skin reactivity, nine delayed reactivity, and three both. After six months all still react. In those developing delayed skin reactivity there was an inflammatory swelling of varying degree at the site of the repository injection, beginning several days later and lasting for several weeks. The delayed reactivity to ragweed was transferred locally and systemically by the injection of peripheral leukocytes from three subjects in whom delayed sensitivity had been induced by an injection of ragweed emulsion. Punch biopsy from the delayed reaction produced in the recipient showed histologic changes characteristic (but not pathognomonic) for a delayed hypersensitivity response. The findings point to the advisability of confining repository treatment to antigens to which the patient is known to be sensitive. This investigative model offers an opportunity for basic studies on delayed hypersensitivity and the relationship between the delayed and immediate type.

Leukocytes and hypersensitivity reactions: I. Eosinophil response in skin window to ragweed extract, histamine, and compound 4880 in atopic and nonatopic individuals

Abstract Eosinophil counts were made from coverslips obtained from skin windows after intradermal injections of buffered saline, histamine, compound 4880, and mixed ragweed extract in 17 atopic clinically sensitive, 7 skin reacting but clinically nonsensitive, and 11 nonatopic subjects. The concentration of challenging substance was selected on the basis of equal reactivity by titration and wheal size, but other concentrations were also tried. A challenging dose of a size individualized for the subject was necessary to produce the most effective response. When a potent reaginic serum and a proper dose of antigen are used, the eosinophil response in the passively sensitized site is not much different from that in the atopic individual. The response in the atopic, clinically nonsensitive persons appears to be less than the response in those with a history of pollinosis, although the number of subjects and their degree of sensitivity do not permit a final opinion. The eosinophil response to histamine and compound 4880 was found to be greater in atopic clinical than in atopic nonclinical or nonatopic subjects. The eosinophilia from these solutions is usually moderate, is absent at 45 minutes, begins at about 2 hours, is maximal at 6 hours, and is usually negligible at 24 hours. There is considerable variability and inconsistency in the cosinophil determination by this method, some of which is based on factors not yet recognized or corrected. However, it is concluded that conditions which constitute a minimal requirement are: accuracy of dose of challenging substance, a dose selected on basis of titration, repeated trials in the same subject, the counting of at least 1,000 leukocytes, and an averaging of representative areas on the same coverslip.

Relief of dermographism and other urticarias of histamine origin by a synthetic benzhydryl alkamine ether

Abstract The new histamine antagonist, β-dimethylaminoethyl benzhydryl ether hydrochloride, is an effective palliative remedy in dermographism and is particularly useful in the type of dermographism interfering with cutaneous testing for atopic manifestations.

The development of tolerance to antihistamines: A study of the quantitative inhibiting capacity of antihistamines on the skin and mucous membrane reaction to histamine and antigens

Abstract 1.1. The majority of a series of patients showed evidence of the development of tolerance to antihistaminic drugs as shown by the failure or diminished effectiveness of the drugs to reduce the wheal and flare response to histamine and ragweed extract. 2.2. The time necessary to develop tolerance was between 7 and 20 days of maintenance on therapeutic doses of the antihistamine. 3.3. Tolerance developed to one antihistamine extended to others, even though the chemical relationship was not close. 4.4. Return of pharmacologic response to an antihistamine after discontinuance of the drug takes from 3 to 14 days. 5.5. We believe that, clinically, the development of tolerance is only relative. Even though our data would imply complete clinical tolerance in the greater part of our cases, most patients continue to derive symptomatic relief on prolonged antihistaminic therapy. The evidence presented does suggest, however, that patients on prolonged antihistamine therapy may develop clinical tolerance. When this is suspected the dose should be increased or the drug discontinued for a short perior (3 to 14 days) before resuming therapy.

Repository antigen injections. Absorption studies by immunologic and radioactive methods.

Abstract 1.1. Methods employed to study the degree of immediate release of ragweed pollen antigen from emulsions have consisted of the ability of emulsified and injected antigens to produce reaction in passively sensitized sites, the reaction on scratch test in allergic subjects after titration with aqueous extracts, the radioactivity of the blood and urine shortly after the injection of radioiodinated emulsion, the local reaction of the emulsion in allergic persons, and the radioactivity release from the emulsion placed in an aqueous solution. 2.2. With the emulsions studied, such immediate release varies from about 1 to 3 per cent, depending on the method used and the batch of the emulsion. 3.3. Persistence of the antigen at the site of injection has been studied in relation to the persistence of radioactivity of radioiodinated pollen extract. Traces of the radioiodination can be shown to exist for as long as four weeks with the emulsion and three weeks with the aqueous preparation. It is possible that longer persistence might be shown with our use of more potent radioactivity. 4.4. By the method of reagin neutralization, it could not be proved that antigen is released from the emulsion in active form beyond the twenty-four-hour period. It is admitted that this is not final evidence that the antigen is unavailable. 5.5. The production of delayed hypersensitivity with the emulsified antigen in nonallergic subjects is of basic and clinical significance. 6.6. Further amplification of these and other studies is needed to perfect the antigenic preparation and to understand the immune mechanisms involved.