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[Anesthetics responsible for anaphylactic shock. A French multicenter study].

Combined allergological and anaesthetic consultations have been started in the last few years in eight French Teaching Hospitals so as to explore peranaesthetic anaphylactoid shocks. A survey was carried out in these centers in order to collect patients investigated with the same protocol, for the assessment of the incidence of anaphylaxis in France, as well as the involved drugs. Investigations were always carried out at least 6 to 8 weeks after the accident. The tests used to diagnose IgE-dependent anaphylaxis were skin tests (prick and intradermal tests, carried out in all eight centers), the radioimmunological assay of specific anti-quaternary ammonium IgE, together with an inhibition test with thiopentone and propofol (six centers), leukocyte histamine release (five centers) and human basophil degranulation tests (three centers) for those drugs for which no specific antibody assay exists. The collected data involved 1,240 patients, investigated within the last four years. Anaphylaxis was diagnosed in 821 patients (66.2%). Muscle relaxants were responsible in 668 cases (80% of cases of anaphylaxis). Suxamethonium was the main cause (54.3% of shocks due to muscle relaxants), followed by vecuronium (15.3%). General anaesthetics (hypnotics and benzodiazepines) were responsible for 9.2% of all cases of anaphylaxis opioids for 2.6%. There were only three cases of shock due to local anaesthetic agents. Latex and ethylene oxide are becoming increasingly involved. It would therefore seem mandatory to carry out after any anaphylactoid accident an assessment with sensitive and specific tests for anaphylaxis. Diagnosing anaphylaxis means that the involved drug should be used never again in that patient. Because muscle relaxants are by far the most involved drugs, anaesthetists should use them only when really required.

Analgesics, Opioid↗

The relation between degranulation and rapid metabolic responses in RBL-2H3 cells.

The relation between degranulation and rapid metabolic responses (acidification rate changes) in RBL-2H3 cells was studied using a cytosensor microphysiometer, a silicon-based biosensor system. The metabolic responses in RBL-2H3 cells by antigen stimulation were compared with those by inhibitors of Ca2+ -ATPase. The former resulted in a rapid transient increase in the acidification rate of RBL-2H3 cells while the latter resulted in gradual decreases. When RBL-2H3 cells were costimulated with the inhibitors of Ca2+ -ATPase and an activator (PMA, phorbol-12-myristoyl-13-acetate) of protein kinase C, the metabolic responses increased again in RBL-2H3 cells. This seems to indicate that degranulation in RBL-2H3 cells was accelerated by costimulation with the inhibitors and PMA. However, costimulation was not able to completely mimic the way antigen stimulated RBL-2H3 cells in degranulation and in rapid metabolic responses.

Animals↗

[Allergologic study of allergic asthma and therapeutic implications].

The diagnosis of allergic asthma is based on a number of clinical and paraclinical findings which should allow the appropriate therapeutic decisions to be taken. The following diagnostic procedures are available to the clinician: the clinical history which is always of prime importance, skin tests, second stage of diagnosis, total serum and specific IgE (RAST) concentrations demonstrate an IgE dependent mechanism, the human basophil degranulation test (HBDT) to assess cellular sensitivity, bronchial or nasal provocation tests which finally demonstrate the responsibility of the causative allergen. In practice, the clinical history, skin tests and the RAST are sufficient to establish the diagnosis of allergy and to take the appropriate therapeutic measures: eviction, antidegranulation therapy or specific immunotherapy.

Asthma↗

"In vitro" basophil degranulation by polymyxin B in asthmatic patients.

Polymyxin B is a potent mast cell degranulator. Inhalation of polymyxin B produces bronchoconstriction in atopic asthmatic patients. The study was undertaken to find the influence of polymyxin B on human basophils. Thirty atopic asthmatic patients and 10 healthy controls participated in the study. Preparation and counting of basophils taken from the whole venous blood was performed with the human basophils degranulation test (method by Benveniste). No significant degranulation was observed in the group of healthy subjects. Degranulation of basophils by polymyxin B was stated in 24 from 30 atopic asthmatic patients with dose-reaction dependency. Our results point out, that there exists "basophil releasability" to polymyxin B in atopic asthmatic patients.

Asthma↗

Anaphylaxis to latex during surgery.

Five young women, all of whom had anaphylactic responses in operating units, are described. Three of them worked in a hospital three showed immediate hypersensitivity to fruit and all had known urticaria to latex. Anaphylaxis appeared progressively 15 to 30 minutes after injection of anaesthetic drugs. Skin tests with these drugs were negative. Skin prick tests through gloves and with four different allergen preparations (saline which had been incubated with gloves and three kinds of latex) were positive. Human basophil degranulation tests with all four allergens were positive and radio allergo sorbent tests to latex were also positive. IgE-dependent allergy to latex may be investigated by questionnaire and if necessary by prick tests before each operation to prevent anaphylaxis due to surgical gloves.

Adult↗

[Apropos of drug allergy].

Immuno-biological diagnosis of allergies lo medicines can be carried out using a Flow Cytometer and by activating cells such as basophils and lymphocytes with membrane markers. A description is given of two cases of patients allergic to a myorelaxant: Rocuronium, who showed a correlation between the clinical history, skin tests and a positive basophil activation test, when compared to six negative controls.

Anaphylaxis↗

[Changes of airway responsiveness, and relative factors in asthmatics with remission at puberty].

OBJECTIVE: To study the airway responsiveness and relative factors in asthmatics with natural remission at puberty. METHOD: The airway responsiveness was evaluated by challenge of methacholine (PC20), blood sIL-2R, eosinophil count, basophil count and basophil releasability were detected in 18 asthmatics with remission at puberty (group I), in 20 asthmatics without remission at puberty (group II), and in 30 healthy controls (group III). RESULT: The mean value of PC20 in the group I was significantly lower than that of the group III (P < 0.01), but still higher than that of the group II (P < 0.01). The blood sIL-2R and eosinophil values were droped almost to those of the group III, significantly lower than those of the group II. The basophil value and positive rate of human basophil degranulation test stimulated by mannitol with hyperosmolarity were still abnormal, significantly higher than those of the group III, and the basophil level was significantly related to the airway responsiveness. CONCLUSION: The asthmatics with remission at puberty have a certain degree of airway hyperresponsivenes that is related to the abnormal of basophil.

Adult↗

[Comparative evaluation of efficiency of various immunologic reactions with Candida antigens in detecting immediate hypersensitivity].

In the dynamic survey of 577 persons having had contacts with yeast-like fungi of the genus Candida the effectiveness of tests for the diagnosis of mycogenic sensitization was made with the use of a number of immunological methods. The basophil degranulation test was shown to have higher sensitivity and specificity in the detection of hypersensitivity to microbial strains used in the production processes of microbiological synthesis, while the use of polysaccharide antigens is more expedient in immunological reactions, such as the precipitation test with the finished product obtained by these processes and with C. albicans. Some prevalence of the level of sensitization in the presence of Candida carriership was established in persons having had contacts with these fungi.

Adult↗

Changes in airway responsiveness and relative factors in asthma with remission at puberty.

OBJECTIVE: To elucidate the airway responsiveness and its relative factors in asthma with natural remission at puberty. METHOD: The airway responsiveness was evaluated by provocation of methacholine (PC20). Blood sIL-2R, IL-4 and IFN-gamma values in the cultural supernatant of mononuclear cells, eosinophil count, basophil count and basophil releasability were detected in 18 asthmatic cases with remission at puberty (group I), in 20 asthmatics without remission at puberty (group II), and in 30 healthy controls (group III). RESULT: The mean value of PC20 in group I was significantly lower than that in group III (P < 0.01), but still higher than that in group II (P < 0.01). The blood sIL-2R, and eosinophil counts dropped almost to those of group III, significantly lower than those of group II. IL-4 in the culture supernatant of mononuclear cells was similar to group III, but significantly lower than that in group II. However IFN-gamma was also similar to group III, significantly higher than that of group II. The basophil count and positive rate of human basophil degranulation test stimulated by mannitol with hyper-osmolarity were still abnormal, significantly higher than those of group III, and the basophil level was significantly related to the airway responsiveness. CONCLUSION: The asthmatics with remission at puberty have a certain degree of airway hyper-responsiveness that is related to the abnormality of basophil.

Adolescent↗

Detection of basophil sensitization by IgE antibodies to nuclear antigens in connective tissue diseases.

Responses of the IgE type to various nuclear antigens have been explored using the human basophil degranulation test (HBDT) to single (SS) and double-stranded (DS) deoxyribonucleic acid (DNA), nuclear ribonucleoprotein (nRNP), and Sm antigens. This study was conducted on systemic lupus erythematosus (SLE) patients as compared to rheumatoid arthritis (RA) polymyositis (PM), scleroderma (SCL) and mixed connective tissue disease (MCTD). SLE and MCTD patients showed a high level of basophil degranulation to the four antigens. Degranulation to nRNP protein was higher in MCTD than in SLE cases. HBDT to the four antigens were constantly negative in control donors and in RA, PM and SCL. Basophil degranulation to DS-DNA in SLE was blocked by previous exposure of the blood to anti-human-IgE antiserum. These results exemplify the specificity of the HBDT, making this simple and fast test a useful tool in the diagnosis of connective tissue diseases.

Antigens↗

Evidence of an immediate hypersensitivity mechanism in systemic lupus erythematosus.

In 30 patients with systemic lupus erythematosus the number of a circulating basophils was countered in different stages of activity. An inverse correlation was found between the absolute basophils count and anti-DNA antibodies and presumptive circulating immune complexes (as judged by polyethylene glycol precipitation of serum). A positive correlation was found between the absolute basophil count and C3 or C4 levels. IgE on the basophil surface was determined by radioimmunoassay in 7 patients. All of them showed a significantly higher surface IgE number. When the count of circulating basophils was roughly normal, 5 out of the 6 patients showed a positive basophil degranulation test with native DNA. These results suggest the existence of an anti-DNA specific IgE in lupus patients. Depression of the circulating basophil count may be a useful index of lupus activity.

Antibodies, Antinuclear↗

[Correlation between serum IgE level and human basophil degranulation by anti-IgE antibodies].

The human basophil degranulation test (HBDT) by anti-IgE antibodies was applied in 3 groups of subjects: 20 controls, 26 patients with helminthiasis and 28 allergic patients. Mean degranulation was higher in patients with helminthiasis than in the two other groups. A correlation was found between IgE serum level and HBDT results by anti-IgE (r = 0.373; p less than 0.02) with Spearman's rank correlation test. Therefore, degranulation with anti-IgE antibodies would appear to depend on the quantity of cell-bound IgE rather than on intrinsic basophil sensitivity.

Antibodies, Anti-Idiotypic↗

Automated measurement of human basophil degranulation.

Basophils disappear after challenge with specific antigen. A human basophil degranulation test has been carried out on a slide using an enriched cell suspension. On each slide, the same volume of cell suspension was deposited in wells with antigen diluted in buffer or with buffer only (control). The basophil count was made on an equal number of randomly distributed microscopic fields either by eye (optical) or by image analyser (automatic). In 33 subjects, the correlation coefficient between the numbers of non-degranulated basophils counted by eye and by image-analyser on control wells was found to be r-0.91, p less than 10-8. In 12 patients (6 with hydatidosis and 6 with schistosomiasis), the percentage of degranulation with three antigen dilutions was measured. The correlation between the results obtained by eye and by image-analyser reached 0.76 (p less than 10-7). The authors now use the automated measurement of human basophil degranulation routinely.

Autoanalysis↗

Two cases of autoimmune progesterone dermatitis. Immunohistochemical and serological studies.

Two cases of autoimmune progesterone dermatitis are reported. The patients developed recurrent pruritic erythematous and edematous eruptions on the extremities, trunk or face, with occasional vesicles on the palms and soles. The eruptions appeared 7 to 10 days prior to their menstruation and persisted for several days. They showed immediately positive skin tests with 0.1 mg/ml and 0.2 mg/ml of aqueous progesterone suspension, respectively. The patients had IgG serum factor which bound rat corpus luteum. Positive indirect basophil degranulation tests against progesterone were demonstrated in both patients. Circulating autoantibodies to patients' own progesterone may cause or modulate the intermittent eruptions of the disease.

Adult↗

[Cutaneous symptoms and diagnosis of drug hypersensitivity].

At the Department of Allergy, Clinic of Dermatovenerology, School of Medicine University of Zagreb, Clinical Hospital Centre Zagreb, patients with different clinical features of drug allergy during the period of two years (1990-1991) were analyzed. The research included 475 patients with positive history of drug allergy and typical clinical symptoms. The aim of the study was to correlate the clinical diagnosis and history with the results of diagnostic tests in vitro and in some cases in vivo. Positive history and clinical diagnosis were confirmed in 117 of the 475 patients (24.6 percent) by an indirect basophil degranulation test (Shelley's test) and in 59 of the 345 patients (17.1 percent) by means of a lymphoblast transformation test. Patients positive in tests in vitro (or on TTL or on Shelley's test) from unselected 56 patients in vivo (prick test, scratch test) showed positive results. We consider therefore that provocative tests are more precise and exact than in vitro tests in the diagnosis of drug allergy. The most common causes of drug allergy and 17 clinical types are presented.

Adolescent↗

Anaphylaxis due to succinylcholine. Immunoallergological study of thirteen cases.

The antigen non-specific release of histamine by synthetic neuromuscular blocking agents is well known, though our review of thirty-two cases reported in the literature of anaphylactoid reactions to succinylcholine, shows that there is insufficient evidence to determine whether the signs are due to anaphylactic or to anaphylactoid reactions. We have examined thirteen cases in whom evidence of anaphylactic sensitization was examined by direct skin tests (in eleven cases) Prausnitz--Küstner tests (in five), rabbit basophil degranulation, Shelley test (in twelve) and human basophil degranulation (in seven). These tests were done on two to four occasions, and the optimal period for the first test ascertained to be 6 to 12 weeks after the episode. All eleven patients examined by direct skin tests showed evidence of anaphylactic sensitivity, and in three of five cases the sensitivity could be transferred by the Prausnitz--Küstner procedure. In one of these P--K tests there was evidence of both IgE and of IgG S-TS antibodies (heat-stable antibody conferring sensitivity for 2 hr). Particular susceptibilities to adverse reactions of this drug appear to be prior drug allergy (in 50% of cases), several previous anaesthetics, and atopy.

Adolescent↗

Drugs and other agents involved in anaphylactic shock occurring during anaesthesia. A French multicenter epidemiological inquiry.

An epidemiological inquiry was carried out in departments of anaesthesia and immunology in French University and General Hospitals, as well as among those who were already known to have an allergo-anaesthesia outpatient clinic. This inquiry aimed to find out how many patients had undergone diagnostic investigations after as well as an anaphylactoid reaction during an anaesthetic in 1990 and 1991, as well as the demographic data, the kind of assessment, the accident mechanism and the drugs involved. Twenty-one French centres replied to the questionnaire and a series of 1,585 patients tested over a two-year period was thus collected. There were three female patients to one male. The reactions occurred mostly in the adult (80%), but 9% were observed in children. Allergological tests for IgE-dependent anaphylaxis were the skin tests (21 centres), combined with radioimmunological assays of specific serum antibodies to muscle relaxants (10 centres), propofol (9 centres), latex (5 centres), leukocyte histamine release (9 centres) and human basophil degranulation test (4 centres). The criteria for a positive result were the same for all centres. Among these 1,585 patients, 813 were recognized as having had a reaction of immunological origin (52%). The substances involved were identified in these 813 patients as being muscle relaxants (70%), latex (12.6%), hypnotics (3.6%), benzodiazepines (2.0%), opioids (1.7%), colloids (4.7%), and antibiotics (2.6%). Suxamethonium was responsible for 43% of the IgE-dependent reactions involving a muscle relaxant, vecuronium for 37%, pancuronium for 13%, alcuronium for 7.6%, atracurium for 6.8% and gallamine for 5.6%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗