Max Samter

Concerning the nature of intolerance to aspirin

Abstract (1) Intolerance to aspirin is not uncommon in individuals near middle age who, as a rule, do not have a history of atopy. It is characterized by changes in the skin and respiratory mucous membranes—angioedema, perennial rhinitis, formation of nasal polyps, and bronchial asthma—which precede the development of intolerance to aspirin. (2) While reactions induced by aspirin simulate an immunological discase evidence for an allergy to acetylsalicylic acid per se or acetylsalicylic acid as an antigenic determinant is unconvincing. Attempts to demonstrate antibodies to acetylsalicylic acid have been generally unsuccessful. (3) If an immunological etiology can be ruled out, aspirin must induce its effects by a direct action on effector organs. (4) Acetylsalicylic acid can inhibit at least one mediator-induced reflex, i.e., the kinin-induced vasodilatation in the skin of man and the kinin-induced bronchoconstriction of the guinea pig. (5) Patients who have an intolerance to aspirin have a comparable intolerance to other minor analgesics, e.g., pyrazolones and indomethacin. Reactions to these structurally dissimilar compounds occur after first administration. It appears reasonable to assume that they exert their effect on the same receptors. (6) It is proposed that aspirin produces characteristic symptoms in aspirin-sensitive patients by activating peripheral chemoreceptors which have been altered by a pre-existing disease. (7) A possible mechanism by which peripheral chemoreceptors might participate in the pathogenesis of bronchial asthma has been outlined and reviewed in the light of what is known about reflexes which control the vascular bed of the skin and the functional state of the respiratory mucous membranes.

Charcot-Leyden crystals: A study of the conditions necessary for their formation☆

Abstract 1.1. Charcot-Leyden crystals found in the blood of patients with high absolute eosinophilia, originate in individual eosinophiles. Only a minority of the eosinophiles present develops Charcot-Leyden crystals. 2.2. Supravital staining of eosinophilic granules does not interfere with the development of Charcot-Leyden crystals which are of the same shape and color as in unstained preparations. Dilution prevents the formation of Charcot-Leyden crystals. 3.3. Concentrations of eosinophiles of various sources: blister fluid, nasal secretion, failed to produce Charcot-Leyden crystals. After separation of the cellular from the liquid fraction of blister fluid, a considerable number of Charcot-Leyden crystals were seen to develop in cellular material. 4.4. Addition of intact red blood cells obtained from C-L positive patients with high absolute eosinophilia increased both number and size of Charcot-Leyden crystals in C-L positive, centrifuged cellular material; it stimulated the formation of Charcot-Leyden crystals in several though few instances of previously C-L negative concentrations. Addition of intact red blood cells from C-L negative patients or of the stroma of red blood cells from either source did not substantially interfere with the development in Charcot-Leyden crystals in C-L positive material, but no stimulation of development of Charcot-Leyden crystals in previously C-L negative preparations was seen. 5.5. Addition of substances other than red blood cells, including serum, plasma, and solutions of breakdown products of red blood cells prevented the formation of Charcot-Leyden crystals in C-L positive material and had no influence on C-L negative preparations. 6.6. Significance and limitations of these findings are discussed.

Acth in ragweed pollinosis: A histologic, immunologic, and clinical study☆☆☆

Abstract 1.1. Nine of 26 ragweed-sensitive patients who received 60 mg. ACTH daily for 4 days showed clinical improvement. 2.2. None of the 8 patients who received placebo injections were improved. 3.3. Neither the reagin titer nor skin sensitivity to ragweed pollen were altered by treatment with ACTH for the indicated period. 4.4. Suggestive evidence was found that there is a correlation between the degree of skin sensitivity, the peripheral eosinophilia, and the tissue eosinophilia. 5.5. No change in histologic characteristics attributable to the use of ACTH could be demonstrated. Edema and eosinophils in various stages of disintegration were found in pretreatment, posttreatment, and control biopsies.

The Acetyl- in Aspirin

Excerpt A recent paper on structural changes in human serum albumin (HSA) induced by acetylsalicylic acid (1) raises additional questions about the differences between aspirin and other salicylates...

The effect of ACTH on the distribution of eosinophils in blood and peribronchial tissue of guinea pigs

Abstract 1.1. Guinea pigs are of limited usefulness for the study of the response of eosinophils to the injection of ACTH adrenal cortical stroids. 2.2. One single dose of ACTH failed to produce significant changes in the eosinophils in blood and peribronchial tissue of guinea pigs which have been sensitized and reinjected with a homologous antigen. 3.3. Repeated injection of ACTH in sensitized but not reinjected guinea pigs produced a marked depression of the peripheral eosinophil count without proportionate reduction of the number of eosinophils in the peribronchial tissue. 4.4. The production of anaphylactic shock in guinea pigs whose peripheral eosinophil count has been depressed by the administration of ACTH caused a return of eosinophils into the circulation. The distribution of eosinophils in the peribronchial tissue of these animals is similar to the distribution found in shocked animals which had not received ACTH.

On the rationale of treating allergic diseases with bacterial pyrogens

Abstract 1.1. Studies of the effect of Pyromen on sensitization and re-injection of guinea pigs with anaphylactic antigens failed to indicate that the compound produces a demonstrable decrease in formation of antibodies or in the results of antigen-antibody reactions. 2.2. The administration of Pyromen to 38 patients with allergic disease of the anaphylactic type (rhinitis, bronchial asthma, and urticaria) failed to indicate that the clinical effectiveness of the compound is superior to a placebo containing its solvent, 16 molar sodium r-lactate.

Fixed anaphylactic sensitization: Bromsulphalen Studies

Abstract 1.1. A case of fixed tissue sensitivity of the anaphylactic (immediate wheal) type is described. 2.2. Bromsulphalein injected paravascularly (subcutaneously) resulted in an area of inflammation. 3.3. Intravenous injection of bromsulphalein one month after the paravascular injection produced an immediate flare-up at the site of the previous inflammatory reaction, a generalized urticaria, and systemic symptoms resembling anaphylactic shock. Both local and systemic symptoms responded promptly to epinephrine and Benadryl. 4.4. The area of extravasation was found to be sensitive to bromsulphalein and a very closely related halogen analogue, giving immediate wheal reactions on intradermal testing. The whealing response could be inhibited by the prior administration of Pyribenzamine. 5.5. Studies to correlate chemical structure and skin reactivity were attempted. The tetrachloro analogue of bromsulphalein yielded exactly the same reactions, but a halogen-free analogue did not react. Compounds representing component parts of the bromsulphalein molecule also failed to elicit reactions.

Effect of the calcium ionophore A23187 and aspirin on histamine release in vitro from leukocytes of aspirin-intolerant donors.

In vitro histamine release from leukocytes of 10 aspirin-intolerant donors in response to the calcium ionophore A23187 and aspirin was compared to that of controls. Incubation with A23187 induced a concentration-dependent histamine release from leukocytes of all donors. At 0.1 and 0.2 micrograms/ml A23187, release from leukocytes of aspirin-intolerant donors was significantly less (p less than 0.01) than that of controls. Preincubation with aspirin failed to alter spontaneous or A23187-stimulated histamine release. Leukocytes of aspirin-intolerant donors do not demonstrate an enhanced sensitivity to histamine release stimulated by aspirin or A23187.

Allergy and immunology 1947-1987. A PGM retrospective.

(1987). Allergy and immunology 1947–1987. Postgraduate Medicine: Vol. 82, No. 5, pp. 147-150.

BRONCHIAL ASTHMA. INVENTORY AND OUTLOOK.

Increasing experience has modified our concepts of bronchial asthma; it is no longer considered a hopeless disease. Competent care of the asthmatic requires more than prescribing symptomatic medication. It is necessary to dissociate allergic from nonallergic components, to identify the antigen and establish the degree of sensitivity, to correlate positive skin reactions with clinical symptoms, to estimate respiratory defect by pulmonary function tests before and after bronchodilators, and to instruct the patient in the control of acute attacks as well as in a long-term program for normal living.