Prevention of latex sensitization in guinea pigs by a bacterial and viral filter used in anaesthesia.

BACKGROUND: Preventing anaphylactic reactions as a result of natural rubber latex (NRL) proteins is an important concern in anaesthesia. The clinical relevance of a bacterial/viral filter (Pall BB25) in preventing sensitization to NRL by inhalation was tested in guinea pigs. METHODS: Guinea pigs (n=8-10 in each group) were exposed to aerosolized NRL-contaminated cornstarch powder or to NRL in saline for 1 h every day for 2 weeks. The experiments were repeated with a Pall BB25 filter placed over the aerosol system. Control groups were exposed to non-contaminated cornstarch or to saline alone. Three weeks after the last exposure, specific bronchial challenge was performed and thromboxane (Tx) B2 levels in bronchoalveolar lavage fluid were measured. RESULTS: After bronchial challenge, the animals exposed to NRL or NRL-contaminated cornstarch with the BB25 filter in place showed a level of bronchoconstriction (i.e. the variation of pulmonary insufflation pressure) not different from controls. Conversely, those exposed to NRL or NRL-contaminated cornstarch without the filter showed a higher level of bronchoconstriction (respectively, P<0.02 and P<0.001) than control. Elevated TxB2 levels were found in the lungs of the guinea pigs, which inhaled NRL or NRL-contaminated cornstarch in the absence of a filter. Animals treated with the filter showed comparable TxB2 levels with those of control. CONCLUSION: The Pall BB25 filter efficiently protected the guinea pigs from sensitization to NRL. This filter can be used as a complementary measure for avoidance of NRL contact during surgical procedures particularly if the mechanical ventilator apparatus contain NRL devices.

Inhaled cornstarch glove powder increases latex-induced airway hyper-sensitivity in guinea-pigs.

BACKGROUND: Breathing is one of the most important modes of sensitization to natural rubber latex (NRL) for health-care workers, a group most at risk. Cornstarch powder (CSp) from medical powdered NRL gloves is known to be an allergen carrier, and sensitization to NRL can occur by inhaling airborne particles from such gloves. OBJECTIVE: The aim of this study was to demonstrate, using an experimental model, which CSp may act as an adjuvant in NRL-induced airway hyper-responsiveness. METHODS: Guinea-pigs were exposed to aerosolized NRL-contaminated CSp or to NRL in saline solution for 1 h every day for 2 weeks. The control groups were exposed either to CSp or to saline alone. An additional group of guinea-pigs was exposed to aerosolized ovalbumin (OVA) in saline. Three weeks after the last exposure, specific bronchial challenges were performed. In addition, Specific IgG and IgG1 in sera and thromboxane (Tx) B(2) levels in bronchoalveolar lavage fluid (BALF) were measured. RESULTS: The NRL challenge caused significant bronchospasm in the animals that had been exposed to NRL compared with those in the control groups (P<0.02). Guinea-pigs exposed to OVA also demonstrated a significant bronchospasm after OVA challenge (P<0.001). The guinea-pigs that had inhaled NRL-contaminated CSp had a significantly higher bronchoconstriction level than those that had inhaled NRL alone (P<0.02). Specific IgG and IgG1 were undetectable in sera from all groups, whereas significant amounts of TxB(2) (P<0.001) were found in the lungs of the guinea-pigs exposed to NRL or OVA. CONCLUSION: Inhaling CSp increases the airway response to NRL. The fact that specific IgG and IgG1 were not detected might be the result of an immune response limited to the airways. This finding is supported by a significant increase of TxB(2) level in the BALF of sensitized guinea-pigs.

Immunoadjuvant properties of glove cornstarch powder in latex-induced hypersensitivity.

BACKGROUND: Cornstarch powder present in medical gloves plays an important role in latex-induced hypersensitivity as allergen carrier either, by the inhalation route, by skin contact or by direct contact with mucous membranes. OBJECTIVE: Our objective was to test the hypothesis that cornstarch could act as an immunoadjuvant in immediate type-I latex-induced hypersensitivity. METHODS: Guinea-pigs were sensitized by intraperitoneal route with two different antigens (latex proteins and ovalbumin) with or without cornstarch powder. Airway responsiveness after specific bronchial provocation was evaluated and specific IgG and IgG1 levels were determined by enzyme-linked immunosorbent assay (ELISA). Controls were treated with cornstarch powder or saline alone. RESULTS: Animals sensitized with latex proteins (n = 7 in each group) showed significant bronchoconstriction (P < 0.03) and higher anti-latex antibody levels than the controls (P < 0.005). Guinea-pigs sensitized with latex-contaminated cornstarch had higher levels of specific antibodies than those sensitized with latex alone (P < 0.05). Animals sensitized to latex mixed with cornstarch showed higher bronchospasm than those treated with latex alone (P < 0.003). Animals sensitized to ovalbumin mixed with cornstarch also showed higher antibody and bronchoconstriction levels (P < 0.05) than those immunized with ovalbumin alone but antibody titres were significantly lower than those of the animals treated with ovalbumin and Freund's complete adjuvant (P < 0.01; n = 5 in each group). CONCLUSION: Our findings show that cornstarch powder increases antigen-induced bronchoconstriction and antibody production. This role of immunoadjuvant is not antigen-specific. The cornstarch powder used as donning agent in latex gloves is an allergen carrier and it can enhance latex-induced hypersensitivity.

[Potential importance of antileukotrienes in the treatment of asthma and other inflammatory diseases: apropos of a new pharmacological class]. / Intérêt potentiel des antileucotriènes dans le traitement de l'asthme et autres pathologies inflammatoires: à propos d'une nouvelle classe pharmacologique.

OBJECTIVES: Among the mediators involved in the asthma bronchoconstriction and inflammation mechanisms, there is now substantial evidence that the sulfidopeptide leukotrienes (LTs) are important. Antagonists of their receptors and inhibitors of their synthesis have been developed. IMPORTANT POINTS: Antagonists of LTs, as well as inhibitors of their synthesis, reduce the LTs actions: bronchoconstriction, bronchial hyperresponsiveness, hypersecretion and inflammation. They produce an acute bronchodilating effect in mild asthma, reduce the hyperresponsiveness responses due to allergens, aspirin and cold and dry air, and also cutaneous and gastrointestinal reactions. Oral administrations tested during 4 or 6 weeks diminish the use of the beta-agonists, decrease the asthma symptom scores and other inflammatory signs. PERSPECTIVES AND PROJECTS: More studies for longer periods, double blind trials and comparisons with classical treatments will be necessary to define the real place of LTs antagonists in the treatment of asthma. So their efficacy has to be confirmed as well as their good tolerance profile (particularly for hepatic functions). CONCLUSION: Antagonists of receptors and synthesis inhibitors of LTs have known a recent and important development. They constitute a new therapeutic class: further studies are needed to better define the place of these new drugs in the treatment of asthma and other inflammatory diseases.

Effect of temafloxacin on the pharmacokinetics of theophylline.

A number of fluoroquinolones have been shown to interact adversely with theophylline. We studied the influence of coadministration of temafloxacin, a new fluoroquinolone antimicrobial agent, on steady-state theophylline pharmacokinetics. Twelve healthy subjects (8 males, 4 females; average age and weight 34 years and 62 kg, respectively) were given oral controlled-release theophylline in an individualized dosage to achieve a target plasma level of 10 mg/L. Once steady state was achieved, temafloxacin 600 mg given orally twice daily was concomitantly administered for 4-5 days. Serial blood samples were collected before and during simultaneous temafloxacin administration and plasma assayed for theophylline using a high-performance liquid chromatography technique. Theophylline pharmacokinetic parameters were determined noncompartmentally, and results of single and combined administration were compared. Theophylline plasma concentrations did not differ significantly with temafloxacin coadministration, and similar area-under-the-curve (AUC) values were observed. Theophylline oral clearance increased from 2.67 +/- 1.01 L/hour to 2.69 +/- 0.93 L/hour, when given alone and with temafloxacin, respectively (p = 0.92). Only 2 of 12 subjects showed an appreciable decrease in clearance when theophylline and temafloxacin were administered together, while 2 subjects demonstrated increases greater than 15% and 8 showed no change. We conclude that temafloxacin does not interact significantly with theophylline and that these agents can be safely administered together.

[The H1 and H2 histamine receptors]. / Les récepteurs H1 et H2 de l'histamine.

Histamine is a major mediator of the allergic reactions. Histamine have different actions: contraction of smooth muscles, vascular action, increase in gastric and adrenal medulla secretion. Effects on central or peripheral nervous system are discussed. The specific H1 or H2 activity explains the different configurations of histamine. The specificity of H1 receptors agonists is now well known: H1 activities have a positive charge on the side chain with an imidazole ring able to rotate around the axis of side chain. The contraction of smooth muscles is due to the action of H1 receptors agonists. Many doubts remain about the exact structures of the H2 receptors, and their agonists. Trough the H2 receptors occur dilatation of small arteries and capillaries, as well as an increase in gastric secretion. Subdivisions of H2 receptors have been, suggested. Recently H3 receptors have been described in the brain and in some peripheral tissues. Interrelations between H1 and H2 histamine receptors have been described as well as a feedback of synthesis and of histamine release.

Beta-2 adrenergic responses to tulobuterol in airway smooth muscle, vascular smooth muscle and adrenergic nerves.

Experiments were designed to determine the mechanism of action of the bronchodilator drug tulobuterol. Tissues were suspended in organ chambers for isometric tension recording. Tulobuterol caused concentration-dependent relaxations of guinea pig tracheae, canine saphenous veins and canine bronchi; the compound relaxed canine coronary arteries only at high concentrations and did not affect spontaneously beating guinea pig atria. A metabolite of tulobuterol, 4-hydroxytulobuterol, was more potent in relaxing guinea pig tracheae than tulobuterol, salbutamol and isoproterenol. Other metabolites (3-hydroxy-, 5-hydroxy- and 4,5-dihydroxytulobuterol) were less efficacious than 4-hydroxytulobuterol. Both tulobuterol and 4-hydroxytulobuterol acted as partial agonists. The effects of tulobuterol in the saphenous vein (but not in the coronary artery) were antagonized by the selective beta-2 adrenergic blocker ICI 118,551 but were not affected by the selective beta-1 adrenergic inhibitor metoprolol. In bronchi, removal of the epithelium reduced the relaxations caused by tulobuterol. The drug did not inhibit responses of canine bronchi to electrical stimulation of the cholinergic nerves more than those to exogenous acetylcholine. Tulobuterol caused a moderate augmentation of the evoked release of [3H]norepinephrine in canine saphenous veins previously incubated with the labeled transmitter. Thus, tulobuterol is a selective beta-2 adrenergic agonist with minimal nonselective inhibitory effect on airway and vascular smooth muscle. It also facilitates adrenergic neurotransmission, which may help to explain its bronchodilator effect in the intact organism. Tulobuterol does not activate beta-1 adrenoceptors and has no direct positive chronotropic effect. A metabolite of tulobuterol, 4-hydroxytulobuterol, is more active than the parent compound.

The effects of atropine on anaphylactic shock in the guinea-pig.

The effects of atropine, 2 mg/kg i.v., on anaphylactic shock were studied in guinea-pigs sensitized to ovalbumin. Atropine only moderately reduced (--31%) the increase in pulmonary resistance observed and slightly prolonged (+26%) the survival time in pretreated animals compared with controls. These effects, however, were no statistically significant. The drug temporarily improved ventilation but had no influence on haematosis. On the other hand, atropine significantly reduced the amount of histamine released (--60%) and of GMPc synthetized in the lung (--21%). The levels of AMPc and prostaglandins E1, E2 and F2 alpha remained comparable to those of control animals. These results suggest that the reflex-induced action of the cholinergic system during anaphylaxis primarily affects large-calibre airways and that the role of acetylcholine in severe reactions is moderate when compared with the direct action of other mediators.

The effects of metiamide and H1 receptor blocking agents on anaphylactic response in guinea-pigs.

The effects of metiamide and of four H1 receptor blocking agents (mepyramine, promethazine, clemastine and ketotifene) on anaphylactic reaction were studied in the guinea-pig. The H1 blockers conferred partial protection which shows that with the experimental protocol utilized (challenge injection with high doses of antigen), histamine plays a lesser role than other mediators released or synthesized. Metiamide (30.0 mg/kg i.v.) noticeably enhanced the increase in pulmonary resistance observed during anaphylactic reaction and reduced the protective effect of the H1 antagonists on this parameter and on histamine release. These effects might be explained by an inhibition - at least partial - of the negative feed-back mechanism through which histamine controls its own release, or by a specific action of metiamide in high doses. The transient tachycardia initially observed in anaphylactic shock is partly related to stimulation of cardiac H2 receptors by the histamine released, since it is suppressed by metiamide.

[Measurement of blood theophylline levels in the child: will this affect methods of prescription? (author's transl)]. / Le dosage de la théophyllinémie chez l'enfant va-t-il modifier notre mode de prescription?

Twelve children aged between 2 and 13 years received an oral dose of 5 mg/kg of pure theophylline, and 28 children aged between 2 and 15 years were given 10 mg/kg/day of the same drug in 3 or 4 divided doses for 3 days. In the first group blood theophylline levels were higher than 10 microgram/ml, after 1 or 3 hours, in only 3 children, two of whom were receiving erythromycin at the same time. Six hours and 12 hours later, none of the serum levels were higher than 10 microgram/ml. In the second group, estimations were performed on the 4th day. At 8 a.m., when the last dose had been given 12 hours previously, blood theophylline levels were all less than 10 microgram/ml (mean: 4.03 +/- 0,88 microgram/ml). Two hours and four hours after the usual morning dose, serum levels of greater than 10 microgram/ml were found in respectively 35 and 25% of the children only. Since the bronchodilator effect of theophylline is optimal for serum levels of greater than 10 microgram/ml, the dose currently recommended in France (10 mg/kg/day) would thus appear to be insufficient in most instances. However, increase in individual doses must be guided by serum estimations, which make it possible to avoid complications related to overdosage.

[Determination of theophylline blood level by high-pressure liquid chromatography (author's transl)]. / Détermination du taux sanguin de theophylline par une technique de chromatographie liquide à haute performance.

The authors describe an easy, rapid, selective and reproducible quantitative determination of theophylline using a high-pressure liquid chromatograph. Plasma theophylline determination is very useful to establish an efficaceous and non toxic posology for each patient.

Immunoglobulin E in human aqueous humor and corresponding serum. A physiopathological and clinical study.

The analysis of IgE in aqueous humor yielded an average concentration of 3.4 +/- 0.97 U/ml for 22 cataract patients and 5.5 +/- 3.42 U/ml for five uveitis patients. The IgE level in aqueous humor (IgEa.h.) of the cases examined is most probably, beside hematoocular diffusion of serum IgEs, the result of intra-ocular IgE production. In comparison with (mostly normal) IgEs levels, the IgEa.h. concentration appears relatively elevated, not only with uveitis patients, but also with cataract patients, above all when lenticular opacity is accompanied by other ophthalmic diseases (glaucoma, high myopia, diabetes). This "increase" of IgEa.h. concentration in very probably due to the radioimmunosorbent (RIST) technique employed, the most sensitive method available at the time of the present study. Thus, the calculated IgEa.h. value in the cataractous eyes should be regarded simply as approximate to the normal IgEa.h. concentration. These values are of clinical significance however, since a reference IgEa.h. mean-value is indispensable to the interpretation of pathologically high IgEa.h. levels and ethics do not permit of IgEa.h. determination in healthy eyes. The mean IgEa.h. levels of the delayed-type uveitis and cataract patients examined reveal no significant differences. IgEa.h. determination could make a contribution to the etiological clarification of, for example, immediate-type uveitis cases and intra-ocular parasitosis and serve as an appropriate model to study intra-ocular immunomechanisms.