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Biomedical subjects

K E Harris

Publications and source records attributed to K E Harris.

At least 109 records · Page 6Linked to original sources

Clinical and immunologic criteria for the diagnosis of allergic bronchopulmonary aspergillosis.

Clinical and immunologic characteristics are reported in a series of 20 patients with allergic bronchopulmonary aspergillosis seen by physicians in one consulting service during a period of 9 years. Seventeen of these patients have been identified in the past 2 years, reflecting the increasing recognition of the entity. Fifteen of the 20 patients are believed to have proven diagnoses; the other five are strongly suspected. Asthma, pulmonary infiltrates, and eosinophilia are the usual presenting symptoms. Serum immunoglobulin E was markedly elevated in all patients, and serum immunoglobulin D was normal in four out of five patients sampled. Bronchograms were abnormal in all cases in which they could be done. Lymphocyte transformation may be present in some cases but is not a diagnostic feature. The average age at time of diagnosis was 25.5 years, and seven of the 15 proven patients were 20 or younger.

Adolescent↗

Effect of PGE1 on immediate-type immunologic and pharmacologic respiratory responses of the rhesus monkey.

The effect of prostaglandin (PG)E1 on the acute, immediate-type airway response to antigen, carbocholine, PGF2alpha, histamine, and physostigmine was studied. In contrast to isoproterenol, which affects all abnormalities of pulmonary function, PGE1 selectively reversed only abnormalities of pulmonary resistance and dynamic compliance. Prior exposure to PGE1 minimally inhibited airway responses but when given simultaneously with antigen, it either selectively inhibited some or dampened all pulmonary function abnormalities. It is suggested that PGE1 acts on receptor sites to produce transient bronchodilation primarily in large central airways in contrast to isoproterenol, which produces bronchodilation in all airways. These results may be consistent with the stimulation of different adenylate cyclase systems in the respiratory tract analogous to those suggested for the gastric mucosa.

Aerosols↗

Immediate-type hypersensitivity to keyhole limpet haemocyanin in the dog.

A model of immediate-type hypersensitivity (ITH) in the dog using keyhole limpet haemocyanin (KLH) as the antigen was studied. Long-lasting ITH was induced in fifteen of sixteen dogs by the i.v. (Kepron & Tse, 1975), intradermal (Rockey, Schwartzmann & Halliwell, 1971), inhalation (Patterson & Kelley, 1974) and i.d. plus inhalation (Rockey et al., 1971) routes. This ITH was demonstrated by direct skin reactivity, acute respiratory reactions and peripheral blood leucocyte and respiratory cell histamine release. The reaginic antibodies considered to mediate these reactions were larger than canine IgG, heat labile, 2-mercaptoethanol sensitive, and are probably canine IgE. In addition to cutaneous and respiratory reactions, these reagins were shown to mediate systemic reactions. In the course of these studies, an unexpected finding was the occurrence of ITH to KLH in three dogs which had had no prior experimental exposure to KLH. This ITH was of sufficient intensity to be associated with acute airway reactions to the inhaled antigen.

Animals↗

Reagin-mediated asthma in rhesus monkeys and relation to bronchial cell histamine release and airway reactivity to carbocholine.

Rhesus monkeys with persistent immediate-type cutaneous and respiratory responses (RR) to ascaris antigen (AA) were compared with rhesus monkeys with skin reactivity and no respiratory responses, and animals with no skin reactivity and no respiratory responses to inhaled antigen (NR). The RR group could not be distinguished from the nonresponding (NR) group by the cutaneous skin test titers, serum, or respiratory secretion IgE concentration. Leukocyte histamine (H) release due to anti-IgE was similar with peripheral blood leukocytes and bronchial lumen mast cells (MC) from RR and NR animals. The RR group of animals could be distinguished from the NR group by their degree of sensitivity to inhaled carbocholine and H release from respiratory MC exposed to AA. The RR group demonstrates consistent, persistent respiratory responses suitable for immunologic, pharmacologic, and physiologic studies. Finally, it was found that the IgE concentration in respiratory secretions of rhesus monkeys was comparatively higher than in serum, evidence for IgE as a secretory Ig in the respiratory tract of this species.

Aerosols↗

The effect of cholinergic and anticholinergic agents on the primate model of allergic asthma.

Rhesus monkeys with reagin-mediated, immediate-type respiratory responses to ascaris antigen were used for comparison with the type of responses that occur from certain pharmacologic agents. Carbacholine produces a respiratory response that is the same type as an antigen-induced respiratory response and will sensitize an animal's airway so that a dose of antigen not reactive alone will stimulate a response. Antigen and histamine will sensitize the airway so that a subthreshold dose of carbacholine will produce a respiratory response. Atropine completely inhibited the carbacholine response and reversed the increased sensitivity to carbacholine that occurs after an antigen response. Atropine did not block the antigen-induced respiratory response or the respiratory response to prostagladin F2alpha. Partial inhibition of these responses may have occurred but was not detected in the systems used in these studies. A double-antigen challenge system in the rhesus model of asthma provides a useful technique for evaluating the effect of pharmacologic agents on the reagin-mediated respiratory response.

Airway Resistance↗

A comparison of immunologic asthma to two types of cholinergic respiratory responses in the rhesus monkey.

Rhesus monkeys were used to characterize the respiratory response (RR) to aerosolized physostigmine (Phy) and compare the response to the acute, reagin-mediated RR and the carbachol response. In the latter two responses, there are characteristic increases in frequency of respiration (f), pulmonary resistance (PR), and decreases in peak expiratory flow rate (PEFR), tidal volume (TV), and dynamic compliance (C). In contrast, a Phy RR characteristically shows no change in TV and f. The Phy RR is inhibited by atropine and lidocaine. The carbachol RR is inhibited by atropine but not lidocaine. The Phy RR mimics a vagally induced RR more closely than carbachol because it is inhibited by pharmacologic and physiologic vagal blockade produced by atropine and lidocaine, respectively, whereas the carbachol RR is blocked by atropine but not lidocaine. The carbachol block by atropine is primarily not a block of vagal action, but a general pharmacologic block of cholinergic action. The reagin-mediated RR is not inhibited by pharmacologic or physiologic vagal blockade. We conclude that a Phy-induced vagomimetic RR differs from a reagin-mediated, immediate-type RR. Although a minor portion, at most, of a reagin-mediated, immediate-type RR may be mediated via the vagus nerve, the major portion of a reagin-mediated RR occurs independent of the influences of the parasympathetic innervation of the lung.

Acetylcholine↗

Potentiating effect of D-2-O on the ascaris-induced, reagin-mediated model of asthma in the Rhesus monkey studied with a double aerosolized antigen challenge technique.

Rhesus monkeys with IgE-mediated sensitivity have respiratory reactions following aerosol challenge with antigen. Studies of agents affecting this response have previously been limited by variations in animal responsiveness at different times. A method for avoiding this variability was tested in these experiments by comparing the degree of response to two antigen challenges during the same experiment and subsequently repeating the experiment with antigen dissolved in a mixture of H-2-O and D-2-O. D-2-O was selected for testing because it should theoretically potentiate histamine-mediated respiratory responses. The results of the studies indicated that there is a potentiating effect of D-2-O on the antigen-induced respiratory response in rhesus monkeys. The double antigen challenge system described should have potential use for study of a variety of inhibiting or potentiating agents on the rhesus model of asthma.

Aerosols↗

Arterial and muscle oxygen tension in experimental models of asthma. Experimental models of asthma.

The immediate-type airway response in anesthetized dogs and rhesus monkeys to two antigens (ascaris and keyhole limpet hemocyanin) and pharmacologic agents (histamine, methacholine and prostaglandin F2alpha) were studied. The pulmonary function abnormalities demonstrated by changes in breathing frequency, peak expiratory flow rate, pulmonary resistance, expiratory-inspiratory time ratio, tidal volume, and dynamic compliance were compared with simultaneous determinations of arterial pO2, muscle pO2 or both, using indwelling electrodes. The results demonstrate that the O2 determinations provide an additional parameter of study of these experimental models of asthma, and that it may be one of the more sensitive indicators of an induced airway response of the immediate-type. The hypoxia parallels the degree of severity of the respiratory response and demonstrates a further similarity of this model to human asthma.

Animals↗

Potentiation of IgE-mediated cutaneous reactivity and blood leucocyte histamine release by deuterium oxide.

A previous study (Gillespie & Lichtenstein, 1972) demonstrated that there was potentiation of histamine release from human peripheral blood leucocytes following exposure to antigin or anti-IgE in deuterium oxide (D2O). The current study confirms the results with human leucocytes and indicates that the degree of histamine release due to anti-IgE or its potentiation by D2O appeared independent of the serum IgE concentration of the cell donor. Further studies demonstrated that the peripheral blood leucocytes from monkeys with a sufficient degree of IgE-mediated reactivity to Ascaris antigen-released histamine following exposure to that antigen. This leucocyte histamine release occurs in animals with immediate-type cutaneous and respiratory reactivity following challenge with this antigen. Peripheral blood leucocytes from certain monkeys release histamine following exposure to anti-human IgE. Both of these Rhesus leucocyte responses are potentiated by D2O. This potentiation of histamine release in vitro in two species by D2O was compared with the potentiation of cutaneous reactivity in IgE-mediated cutaneous reactions in two species. The addition of D2O to Ascaris antigen or anti-IgE increased the end-point cutaneous titres to these stimuli in Rhesus monkeys and the addition of D2O to Ascaris or ragweed antigen increased the end point cutaneous titre to these reactants in allergic dogs. D2O did not potentiate cutaneous reactivity to histamine in either dog or Rhesus monkey.

Animals↗

Emergency medical recognition and management of idiopathic anaphylaxis.

Idiopathic anaphylaxis (IA) is a diagnosis of exclusion that is made when no identifiable causative factors can be found for an episode of anaphylaxis. IA is a potentially life-threatening disease that is the result of a nonimmunologic mast cell activation syndrome. Acute presentation and treatment of these patients is most often in the emergency department and is clinically the same as anaphylaxis from allergens. Since these episodes are unpredictable and often recurrent, these patients are at risk of death if not identified on acute presentation and managed appropriately. As an increasing number of patients are being diagnosed with IA, they will be presenting to emergency departments with initial and recurrent episodes of IA. Therefore, increased awareness of IA and coordinated care is needed so that the morbidity and mortality of this potentially fatal disease can be kept at a minimum.

Acute Disease↗

Idiopathic anaphylaxis: variants as diagnostic and therapeutic problems.

Idiopathic anaphylaxis presents a problem requiring rapid diagnosis and initiation of therapy. Some cases are complex and difficult to assess. We present four cases of unusual complexity to illustrate diagnostic and therapeutic problems. Two cases were found not to be idiopathic anaphylaxis, one being undifferentiated somatoform idiopathic anaphylaxis and the other very severe urticaria. Various conditions can be or mimic idiopathic anaphylaxis, and patience and observation can result in reasonable outcomes.

Adult↗

A cross-sectional survey of 46 employees exposed to trimellitic anhydride.

This is a report of 46 employees exposed to trimellitic anhydride (TMA). The evaluation consisted primarily of periodic serum antibody studies and a questionnaire that identified symptoms compatible with allergic asthma and/or rhinitis, late respiratory systemic syndrome (LRSS), or pulmonary disease anemia (PDA) syndrome. Industrial hygiene data from the plant in 1989 reported exposures that were lower than levels in 1979. Seven employees had positive IgE antibody against trimellityl-human serum albumin (TM-HSA); one had TMA rhinitis, and another possibly had TMA asthma/rhinitis. Fourteen employees had positive IgG antibody against TM-HSA of whom only three had titers high enough to cause disease, and none of them had symptoms compatible with LRSS or PDA. At most, two workers had asthma or rhinitis during the 1990 evaluation. In summary, in this employee population with low level TMA exposure there is a low incidence of immunologically mediated disease due to TMA.

Adult↗

Idiopathic anaphylaxis: total experience with 225 patients.

Idiopathic anaphylaxis (IA) is defined as anaphylaxis with no identifiable precipitating agent or event. Episodes of IA can be life threatening, and onset of episodes is unpredictable and usually recurrent. The epidemiologic features and clinical course of 225 patients diagnosed with IA and managed according to the described protocol with prednisone, H1 antagonists, and beta adrenergic agents were evaluated. There were no fatalities from IA in our series. There was a sevenfold reduction in the average rate of episodes requiring emergency care after initiation of pharmacologic management. Ninety five of 147 patients being observed are in remission, defined as absence of episodes for 1 year without corticosteroid therapy. During 636 patient years of observation, no inciting cause of anaphylaxis or alternative organic disease was defined. The diagnosis of IA was highly reliable in this series. Long-term prognosis is good, with the majority of patients experiencing remission.

Adolescent↗