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Biomedical subjects

F Leynadier

Publications and source records attributed to F Leynadier.

At least 91 records · Page 5Linked to original sources

[Intolerance to sulfonamides in HIV infected subjects. Toxic and allergic origin].

Intolerance to sulfonamides is very frequent in HIV-infected subjects and 10 times more common than in the general population. There are 2 types of intolerance to sulfonamides: early reactions with urticaria or angioedema, which are IgE-dependent, and late reactions with febrile rash, which occur between the 6th and 12th days of treatment and represent the vast majority of allergic manifestations in HIV-infected subjects. Clinically, these reactions resemble serum sickness, but all physiopathological hypotheses point to toxic process. The degradation of sulfonamides has two different pathways: the N-acetylation pathway which is genetically determined and saturable, and the cytochrome P450 pathway which produces toxic hydroxylamine metabolites "detoxified" by glutathione. In HIV-infected subjects detoxication is thought to be incomplete due to an acquired deficiency of glutathione and probably increased in the presence of a slow acetylation profile.

AIDS-Related Opportunistic Infections↗

Purification of human IgG4 subclass with allergen-specific blocking activity.

Blocking antibodies (bAb) induced by allergen immunotherapy are restricted to the IgG1 and IgG4 subclasses, with IgG1 predominating early and IgG4 coming later. Study of IgG4 bAb has been limited, in part, by the absence of a method to purify IgG4. We describe a rapid immunoaffinity chromatographic method for the purification of that subclass from whole serum. Starting serum (TR) contained 90 micrograms/ml Dactylis glomerata (orchard grass) pollen (DGP)-specific IgG4, measured by indirect ELISA. The blocking activity of TR was assayed in vitro on IgE-sensitized human basophils. Immunoadsorption on a strong-binding anti-IgG4 monoclonal antibody (mAb) removed about 90% of the total and allergen-specific IgG4 and nearly all of the blocking activity from TR. An IgG4-rich fraction was then obtained by absorption of several small volumes of TR on a weak-binding anti-IgG4 mAb column at neutral pH followed by elution with glycine-HCl buffer. The pooled eluates contained 82% IgG4, amounting to a 65-fold purification of the serum IgG4; the yield was approximately 30%. Nearly all the DGP-specific antibody was in the IgG4 component of the eluate. The blocking activity of the eluate was approximately equal to that of TR. Immunoblot patterns with the eluate and with TR on SDS-PAGE of DGP were nearly identical. This method thus provides a fully active, relatively pure IgG4 blocking antibody. Moreover, the results reinforce the importance of using a well-chosen mAb when purifying proteins by immunoaffinity chromatography.

Adult↗

Flow cytometric evaluation of human basophils.

The expression of CD45 and IgE cell surface antigens on human leucocytes was studied by flow cytometry. More than 80% of sorted cells that expressed low CD45 (CD45dim) and high IgE (IgEbright) antigen site density were identified as basophils. Immunomagnetic depletion of the CD45dim-IgEbright cell subset by a biotin-coupled anti-IgE antibody and streptavidin-coated magnetic beads was greater than 90%, and more than 80% of cells binding significant numbers of beads exhibited the morphological characteristics of basophils. Interestingly, when the cell staining was performed in the presence of calcium and magnesium, we observed a significant increase of CD45 and an equivalent decrease of IgE cell surface expression, as well as an IgE concentration dependent diminution of the number of CD45dim-IgEbright cells.

Antibodies, Anti-Idiotypic↗

[Spontaneous ecchymosis disclosing acquired factor VIII inhibitor].

An 81-year old woman suddenly developed extensive ecchymosis. A factor VIII:c inhibitor was detected. She received porcine factor VIII, corticosteroids, intravenous immunoglobulins and cyclophosphamide. Normalization of factor VIII level was achieved in 1 month. The patient died, 3 months later, of congestive heart failure. Spontaneous development of factor VIII inhibitors is an extremely rare event which usually occurs in dramatic bleeding. Many associated diseases have been reported. Patients with serious bleeding should be given porcine factor VIII. Immunosuppressive therapy consists of corticosteroids, cyclophosphamide and intravenous immunoglobulins.

Aged↗

The house dust mite Dermatophagoides pteronyssinus is the most important allergen on the island of Mauritius.

To determine the relative importance of mites as a cause of allergic sensitivity and asthma on the western Indian Ocean island of Mauritius, we measured specific IgE antibodies to common inhalant allergens in sera from Mauritians claiming to have allergic symptoms and we examined house dust samples for evidence of mites and their allergens. Seventy-two of the 110 sera tested (65%) contained detectable IgE antibody to at least one mite, mould or pollen allergenic extract. By far the most prevalent was antibody to one or both of the common house dust mites, Dermatophagoides pteronyssinus and Dermatophagoides farinae, being present in 67 (61%) of the 110 sera. Allergy to pollens, including the locally prevalent Bermuda grass and sugar cane, was infrequent. Antibody to a limited number of moulds was detected in 22% of the sera tested. Of 81 subjects whose clinical history was known, 60 were asthmatic, and 75% of these asthmatic individuals had IgE antibody to mites. In contrast, only 35% of the subjects with rhinitis without asthma were sensitive to mites. Different mite species, including D. pteronyssinus but not D. farinae, were identified microscopically in samples of local house dust. Mite antigen Der p I but not antigen Der f I was detected with specific monoclonal antibodies in extracts of these dust samples. On the bases of this serological and environmental survey, we conclude that our data support the hypothesis that the house dust mite D. pteronyssinus is the principal cause of allergic sensitivity and asthma in that tropical environment.

Adolescent↗

Allergy to latex.

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Allergens↗

Study of the allergenic fractions of latex.

Two latex (Hevea brasiliensis) raw materials, one from the cytosolic fraction, the other from the total natural latex have been characterised by immunoblotting techniques. The two latex fractions A and B were studied by immunoprints using eight sera from patients who were allergic to latex. They gave different profiles though there were also allergens of common molecular weights (60, 35, 30, 25, 20, 18, 15, and 10 kD). This study confirms the importance of allergic reactions to latex, that may in some patients cause anaphylactic shock.

Adolescent↗

Allergenicity suppression in natural latex surgical gloves.

By a revised manufacturing process we aimed to obtain latex surgical gloves without immediate allergenicity, and also to determine a simple physical technique by which to estimate this allergenicity. Five glove samples were evaluated for allergenicity by physical and biochemical methods and by skin tests at the University Allergy Centre. Three groups of allergic patients with documented anaphylaxis to surgical gloves, positive skin tests to latex extract and specific IgE to latex (RAST Pharmacia greater than or equal to class II), volunteered for the study. The protein content, the in vitro allergenic potency of glove supernatants (RAST inhibition) and the skin test results with glove supernatants were lower in washed gloves than in non-washed samples (P less than 0.02 to P less than 0.009). The supplementary effect of glove sterilization at 120 degrees C (for 1 h in saturated steam) was obvious. The protein content became undetectable in four of the five glove supernatants, and skin tests results with sample supernatants were decreased (M +/- SEM = 0.68 +/- 0.29 mm vs 3.06 +/- 0.61 mm with non-sterilized gloves), P less than 0.009 by Wilcoxon test. With the Spearman test there was a significant correlation (P = 0.029) between the mean wheal size, obtained with supernatants (Groups 1 and 2) and electrical conductivity. Skin tests through pieces of gloves randomly distributed and coded were decreased by sterilization: 0.66 +/- 0.25 mm vs 2.86 +/- 0.45 mm, P less than 0.0001. Thus, it is possible to decrease glove allergenicity by washing them after mould forming and then sterilizing with steam. Electrical conductivity may be a simple parameter for revealing allergenicity.

Adult↗

Anaphylaxis to muscle-relaxant drugs: study of cross-reactivity by skin tests.

Intradermal skin tests (two dilutions) carried out systematically with 5 muscle-relaxant drugs were used to study the cross-reactivity between these drugs in 131 patients who had suffered from anaphylaxis. The skin tests were positive for at least 2 drugs in 65.6% of the cases. We observed a significant concordance (positive-positive or negative-negative skin tests) between pancuronium and vecuronium (p less than 0.01) and a significant correlation between the skin test diameters obtained with these 2 drugs (p less than 0.02 for wheals and p less than 0.01 for flares). Conversely, the lack of concordance between pancuronium and suxamethonium was significant (p less than 0.05). When comparing all the concordances obtained with each pair of drugs, it appeared that the concordance between pancuronium and vecuronium was significantly higher than all others. For other concordances, 2 main factors seemed to play a role: the N+ of the ammonium ions included in a ring as in pancuronium and the presence of a 'choline-like' side chain as in suxamethonium. But there was no significant correlation between skin test diameters. Altogether, these results suggest that in vivo there is no 'true' cross-reactivity between the drugs except frequently between pancuronium and vecuronium. In all other cases, the patients have probably specific IgE antibodies for each drug, all these antibodies being able to recognize the ammonium determinant; this common property may be insufficient to induce a clinical allergy.

Adolescent↗

Systemic allergic reactions to corticosteroids.

Allergic anaphylactic (type I) reactions to corticosteroid medications are uncommon; however, a number of well-documented cases have been reported. We present a review of the literature, and report on two patients who suffered anaphylaxis after injections of corticosteroids. The first patient, a registered nurse, was finally found to be sensitive to all corticosteroid preparations containing carboxymethylcellulose, as well as the pure carboxymethylcellulose. The second patient had positive skin tests to hydrocortisone, hydrocortisone sodium succinate, methylprednisolone sodium succinate, and suxamethonium. Both patients were tested on two occasions; four normal subjects were tested in parallel, and did not elicit any positive skin reaction. In patients with systemic severe reactions to injectable corticosteroids, we recommend careful and comprehensive skin testing with most available corticosteroids, as well as the components of the injectables.

Adult↗