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Amiodarone-induced pulmonary toxicity. Immunoallergologic tests and bronchoalveolar lavage phospholipid content.

Amiodarone (A) is a widely-used antiarrhythmic drug. Pulmonary toxicity is the most serious adverse effect with an estimated mortality of 1 to 33 percent. In order to determine an element helpful for diagnosis, we examined four patients with amiodarone-induced pulmonary toxicity, three patients treated with A, without evidence of pulmonary toxicity but with a main underlying pulmonary disease, and four healthy volunteers. Daily and cumulative doses or duration of treatment were similar in the first two groups. Pulmonary function tests (spirometry, CO-diffusing capacity, arterial blood gases), roentgenographic examinations, pulmonary biopsies or immunoallergologic tests (skin reaction, lymphoblastic transformation test and human basophile degranulation test) did not provide any discriminatory element. In APT+, we observed an increased cellularity of the bronchoalveolar lavage. Neither the differential cell count nor the presence of foamy macrophages were distinguishable between APT+ and APT-. The phospholipid composition of BAL fluid showed a decreased total phospholipid and phospholipid/protein ratio in all patients compared to normal subjects. These changes reflect more the severity of pulmonary disease than the specificity of the causative agent. However, we observed that the unique PL which decreases in APT- and remains normal in APT+ is phosphatidyl-serine + phosphatidylinositol (PS + PI). This has to be confirmed and should be evaluated at different stages of the disease to determine an eventual specific element. We conclude that there are no data currently available to establish the diagnosis of APT except perhaps for the analysis of BAL PL content.

Aged↗

[The state of the art in immuno-allergology: histamine releasing factors (HRF)].

The present concepts on histamine releasing factors are discussed, their cellular origins, their effect on the target cells and its importance in asthma immunopathology. Personal results on the production of HRF by alveolar macrophages stimulated by allergen and its action on non atopic basophils are presented. Alveolar macrophages from atopic asthmatics release HRF in presence of allergen. Macrophage from non atopic do not. HRF has been tested in a Human Basophil Degranulation Test (HBDT) preparation, a significant degranulation induced by HRF from atopic patient being only observed when atopic basophils are used in HBDT. These results confirm that allergen could induce HRF production from alveolar macrophages and that this HRF could degranulate basophils in atopic and induce mediators release.

Basophil Degranulation Test↗

Clinical and pathophysiological aspects of hydroxyethyl starch-induced pruritus: evaluation of 96 cases.

BACKGROUND: It has been recently recognized that long-term infusions of hydroxyethyl starch (HES) as a substitute of human plasma may lead to deposits within the human skin and clinically induces severe pruritus in approximately one-third of the patients treated. OBJECTIVE: To analyze the clinical features and pathophysiology of HES-induced itching. METHODS: Clinical data of 86 patients were analyzed retrospectively. Furthermore, 10 patients were followed prospectively, in whom we also performed routine laboratory tests, skin biopsies, allergological investigations (skin prick, basophil degranulation test), and substance P measurements in stimulated macrophages. RESULTS: Special features of HES-induced pruritus included long latency of onset and persistence. Noteworthy, itching is not always generalized. 30% of patients present with localized pruritus. Symptoms were not relieved by antihistaminics. Accordingly, the basophil degranulation test after HES exposure was negative. Also, substance P release from macrophages was not increased following HES stimulation. Deposits were found mainly in macrophages and endothelial cells. CONCLUSIONS: Our findings indicate that pruritus in HES-infused patients is most likely not triggered by pruritogenic mediators. We support data from the recent literature, suggesting a direct stimulation of cutaneous nerves by HES deposits. In patients suffering from long-standing itching it seems important to consider previous HES exposure as a possible cause not only in generalized pruritus but also in localized symptoms.

Biopsy, Needle↗

[State of the art in immuno-allergology: histamine-releasing factors (HRF)].

The present concepts on histamina releasing factors are discussed, their cellular origins, their effect on the target cells and its importance in asthma immunopathology. Personal results on the production of HRF by alveolar macrophages stimulated by allergen and its action on non atopic basophils are presented. Alveolar macrophages from atopic asthmatics release HRF in presence of allergen. Macrophage from non atopic do not. HRF has been tested in a Human Basophil Degranulation Test (HBDT) preparation, a significant degranulation induced by HRF from atopic patient being only observed when atopic basofils are used in HBDT. These results confirm that allergen could induce HRF production from alveolar macrophages and that this HRF could degranulate basophils in atopic and induce mediators release.

Basophil Degranulation Test↗

[Study on basophil releasability induced by anti-IgE in allergic rhinitis].

We have investigated the basophil releasability induced by anti-IgE in allergic rhinitis patients and normal subjects by reverse human basophil degranulation tests. The results showed that anti-IgE-mediated basophil releasability and total serum IgE were significantly higher in allergic rhinitis patients than that in normal subjects. However, anti-IgE-mediated basophil releasability, total serum IgE and blood eosinophil count were not closely correlated with each other.

Basophil Degranulation Test↗

Basophil activation in idiopathic mixed cryoglobulinemia.

We studied basophil activation in patients affected by idiopathic mixed cryoglobulinemia in order to investigate the role of the basophil cell in the pathogenesis of the vasculitis typical of this disease. We selected 13 patients and we performed the in vitro basophil degranulation test with cryoprecipitate; in 5 cases the test was positive when it was performed in whole blood, while it was negative when it was performed with cells washed and resuspended in Tyrode's buffer. In 6 subjects it was not possible to perform the test because of the very low number of circulating basophil cells. Finally, in 2 subjects the in vitro basophil degranulation test with cryoprecipitate was negative; this result may be related to the very low levels of complement factors in the sera of these subjects. These findings suggest that the pathogenetic mechanism of vasculitis in idiopathic mixed cryoglobulinemia could be started by basophil activation.

Adult↗

Allergic contact dermatitis in the dog. Principles and diagnosis.

Allergic contact dermatitis is a rare hypersensitivity disorder in the dog. Clinical diagnosis is not easy. Primary lesions are transient. Secondary lesions caused by chronic inflammation and self-trauma are commonly present on typical areas, especially in sparsely haired regions and on the feet. A presumptive diagnosis can be made based on the history, clinical signs, and positive standardized closed patch testing. Histopathology and basophil degranulation testing may also be helpful in supporting the diagnosis and in identifying the offending allergens. However, a definitive diagnosis can be made only after restriction-provocation testing. With better understanding of the pathogenesis and clinical signs, and with increased availability of diagnostic tests (especially a standardized closed patch test), increased recognition of this dermatosis is expected.

Animals↗

[Anaphylaxis to muscle relaxants. Predictive value of intradermal tests and study of crossed anaphylaxis].

37 patients were studied, all of whom presented with anaphylaxis to a muscle relaxant. The diagnosis was made after simultaneous intradermal testing (IDT), human basophil degranulation tests (HBDT) and Prausnitz-Küstner tests (PK) of passive cutaneous anaphylaxis. Three tests were positive in 6 patients, both IDT and PK in 9, and both IDT and HBDT in 8. In 14 patients, the IDT, repeated twice, were positive both times. A search for crossed anaphylaxis to the other muscle relaxants was carried out in all the patients during a second series of tests, a few months to years after the first one. The drugs tested, at dilutions of the pharmaceutical preparation of 10(-3) or more, were: suxamethonium, gallamine, alcuronium, pancuronium, vecuronium, d-tubocurarine. The reliability of IDT in the diagnosis of anaphylaxis is discussed in terms of the small reactive concentration, the producibility of the tests, the one HBDT that did become positive later, and in one case the occurrence of shock by crossed anaphylaxis. Skin reactivity seemed to remain constant with time, so allowing the use of IDT as a diagnostic tool, in cases of old anaphylactoid shocks, occurring during general anaesthetics. The frequency of crossed anaphylaxis was assessed to be about 84%. The sensitivity to one or other drugs varied with each patient. Pancuronium and vecuronium appeared to be the least likely drugs to cause crossed anaphylaxis. The predictive use of these tests is discussed. It is also suggested that muscle relaxants with only one quaternary ammonium group should be used, this chemical characteristic probably reducing the risks of sensitization.

Adolescent↗

[Radioimmunoassay method for the detection of IgE antibodies specific to alcuronium].

A radio-immunoassay (RIA) was used to screen for specific IgE to myorelaxants. Alcuronium was coupled to epoxy-activated Sepharose. Sixteen patients with anaphylaxis to alcuronium (n = 2), gallamine (n = 2) or suxamethonium (n = 12) were studied. The diagnosis was established by intradermal tests (ID), passive cutaneous anaphylaxis tests and human basophil degranulation tests. The amount of non specific label retained by Sepharose-ethanolamine (with sera of patients) and Sepharose-alcuronium (with sera of 11 control subjects) was estimated. The RIA was positive 10/16 (8/14 patients having reacted to a muscle relaxant other than alcuronium). The RIA seemed to be useful in the diagnosis of anaphylaxis to muscle relaxants. Drug-reactive antibodies were specific of the quaternary ammonium radical, which was the common allergenic determinant of all molecules of muscle relaxants. This test accounted for in vitro cross-reactivity, but had no predictive value for the clinical risk of crossed-anaphylaxis. This risk was best assessed by ID; it was positive in three cases. Although it was not possible to compare ID and RIA, the interpretation of which was different, both tests should be recommended for the detection of sensitivity to muscle relaxants.

Adolescent↗

Coronary artery spasm and acute myocardial infarction in naproxen-associated anaphylactic reaction.

We present the case of a 43-year-old man who suffered an acute myocardial infarction after oral administration of 250 mg of naproxen, prescribed as antiinflammatory-analgesic agent after tooth extraction. Both intradermal skin test and human basophil degranulation test were positive to naproxen. These findings suggest a naproxen-associated anaphylactic reaction with concomitant coronary artery spasm and posteroinferior infarction, a clinical event previously not reported with the use of this drug.

Adult↗

[Effects of desensitization and immunologic changes in patients with allergic asthma].

The allergic dermal tests were carried out in 122 patients who were treated from June 1987 to August 1988. The positive rates for mycomutacapitis, myco-root-black, dust mite and artemisia pollemo were 37.5%, 34.5%, 34.2% and 21.88% respectively in inhaled antigens used for skin test. The positive rates for sesame, peanut, allium and garlic were rather high in food antigens used for skin test. The serum IgE and the total IgE tested by BA-ELISA and human basophil degranulation test (HBDT) were observed in 68 patients with allergic asthma and 52 healthy persons. It was found that the positive rate of BA-ELISA (82.35%) and HBDT (84.70%) coincided well with the dermal test. There was significant changes in serum level of the specific IgE and the total IgE before and after desensitizing therapy with the dust mite dermotaphagoides for 6 months (P less than 0.001).

Allergens↗

[Severe local reactions to mosquito bites. Apropos of 20 cases].

We relate 21 observations of children who present major local reactions, immediate and delayed after mosquito bites. An associated reagin mechanism is obvious in 8 patients: five positive cutaneous or RAST tests and three a basophil degranulation tests. They are mostly young children (14/21 an less 5 years old). After some difficult years, the evolution is finally favourable with a specific hyposensitization or under antihistaminic protection (ketotifen) during summer.

Animals↗

A novel human immunoglobulin Fc gamma Fc epsilon bifunctional fusion protein inhibits Fc epsilon RI-mediated degranulation.

Human mast cells and basophils that express the high-affinity immunoglobulin E (IgE) receptor, Fc epsilon receptor 1 (Fc epsilon RI), have key roles in allergic diseases. Fc epsilon RI cross-linking stimulates the release of allergic mediators. Mast cells and basophils co-express Fc gamma RIIb, a low affinity receptor containing an immunoreceptor tyrosine-based inhibitory motif and whose co-aggregation with Fc epsilon RI can block Fc epsilon RI-mediated reactivity. Here we designed, expressed and tested the human basophil and mast-cell inhibitory function of a novel chimeric fusion protein, whose structure is gamma Hinge-CH gamma 2-CH gamma 3-15aa linker-CH epsilon 2-CH epsilon 3-CH epsilon 4. This Fc gamma Fc epsilon fusion protein was expressed as the predicted 140-kappa D dimer that reacted with anti-human epsilon- and gamma-chain specific antibodies. Fc gamma Fc epsilon bound to both human Fc epsilon RI and Fc gamma RII. It also showed dose- and time-dependent inhibition of antigen-driven IgE-mediated histamine release from fresh human basophils sensitized with IgE directed against NIP (4-hydroxy-3-iodo-5-nitrophenylacetyl). This was associated with altered Syk signaling. The fusion protein also showed increased inhibition of human anti-NP (4-hydroxy-3-nitrophenylacetyl) and anti-dansyl IgE-mediated passive cutaneous anaphylaxis in transgenic mice expressing human Fc epsilon RI alpha. Our results show that this chimeric protein is able to form complexes with both Fc epsilon RI and Fc gamma RII, and inhibit mast-cell and basophil function. This approach, using a Fc gamma Fc epsilon fusion protein to co-aggregate Fc epsilon RI with a receptor containing an immunoreceptor tyrosine-based inhibition motif, has therapeutic potential in IgE- and Fc epsilon RI-mediated diseases.

Animals↗

[Respiratory allergy to house dust. A comparison between clinical reactions and the results of some diagnostic tests. 54 cases (author's transl)].

Fifty-four cases of respiratory allergy to house dust were studied by observing clinical reactions and, simultaneously, the results of skin tests, respiratory function tests, radio-allergo-sorbent test (RAST) and human basophil degranulation test (HBDT). The standard skin tests matched clinical reactions and correlated better with the results of HBDT (89.5%) than with those of RAST (50%). This would suggest that HBDT is a more reliable test to explore immediate hypersensitivity to heterogenous allergens.

Adolescent↗

Food allergy and atopic dermatitis in children: treatment with oral sodium cromoglycate.

Thirty-five children with atopic dermatitis were proven to be allergic to various foods by dietary elimination and challenge, radio-allergosorbent test (RAST) and human basophil degranulation test (HBDT). Oral sodium cromoglycate improved skin lesions in these patients and protected them from the effects of challenge with food allergens. This protective effect of oral sodium cromoglycate may be explained by the blocking of the immune response in the gut wall and of antigen entry.

Administration, Oral↗