Effect of RG 12525, a new leukotriene antagonist, on pulmonary function of asthmatic adults.

RG 12525 is a new oral leukotriene D4 (LTD4) antagonist with proven activity in animal and human models of leukotriene-induced bronchoconstriction. In this randomized, double-blind, parallel-group, placebo-controlled study the bronchodilator effects of single oral doses of RG 12525 of 25 and 200 mg or placebo were evaluated in 62 adult asthmatic patients. All patients had previously demonstrated 20% reversibility of FEV1 with an inhaled beta-agonist. They had an unmedicated FEV1 less than 80% of predicted value at the time of the study. Bronchodilator activity was assessed by spirometry before and at multiple time points after dosing for eight hours. A single 200-mg dose of RG 12525 of mg resulted in statistically significantly greater increases in mean maximum change above baseline for FEV1 and FEF25-75% than placebo. The peak effect was observed four to five hours after dosing. The RG 12525 dose of 25 mg dose induced better bronchodilation than placebo but the differences were not significant. Adverse clinical experiences or laboratory abnormalities were not noted.

Fluticasone propionate given once daily is as effective for seasonal allergic rhinitis as beclomethasone dipropionate given twice daily.

Fluticasone propionate was compared with beclomethasone dipropionate for the treatment of allergic rhinitis in a multicenter, double-blind, randomized, placebo-controlled study during the mountain cedar (Juniperus ashei) pollination season in central Texas. Adults (n = 313) with moderate to severe symptoms were treated with fluticasone propionate aqueous nasal spray 200 micrograms once a day or beclomethasone dipropionate aqueous nasal spray 168 micrograms twice a day or placebo for 2 weeks. Fluticasone propionate administered once daily and beclomethasone dipropionate administered twice daily were equally effective as assessed by clinician- and patient-rated scores for nasal obstruction, rhinorrhea, sneezing, and nasal itching throughout the treatment and follow-up periods. Both regimens were more effective than placebo. Adverse events were related to topical administration and were similar in frequency and nature in all three treatment groups. Fluticasone propionate and beclomethasone dipropionate displayed a similar safety profile that did not differ from placebo. We conclude that fluticasone propionate aqueous nasal spray administered as 200 micrograms once daily in the morning is as safe and effective as beclomethasone dipropionate aqueous nasal spray administered as 168 micrograms twice daily for seasonal allergic rhinitis.

Imported fire ant allergy. Perspectives on diagnosis and treatment.

As the imported fire ant relentlessly expands its territory, more and more people are at risk of the insects' discomforting and sometimes dangerous stings. Thus, all primary care physicians in fire ant-infested areas should be familiar with diagnosis and treatment of fire ant stings and of allergic reactions to the stings. Fire ant venom is unique when compared with other Hymenoptera venoms, as it consists mainly of nonallergenic alkaloids that are of small molecular weight with only a small percentage of allergenic proteins. Fire ant wholebody extract, unlike other Hymenoptera wholebody extracts, retains its allergenic activity and is an adequate material for use in diagnostic testing and immunotherapy. Diagnosis of fire ant allergy can be readily made by the radioallergosorbent test (RAST) or by skin testing using fire ant wholebody extract. Immunotherapy with fire ant whole-body extract in allergic individuals can prevent serious recurrent systemic reactions.

Fire ant venom hypersensitivity. I. Comparison of fire ant venom and whole body extract in the diagnosis of fire ant allergy.

Levels of IgE antibody to fire ant whole body extract (FA-WBE) and fire ant venom (FAV) were evaluated in 60 patients with clinical histories of fire ant sting hypersensitivity and 11 frequently stung individuals without significant clinical reactivity to fire ant. An overlap of levels of IgE antibody to FA-WBE and FAV was seen between groups of patients with increasingly severe clinical reactivity; however, the group mean IgE antibody level of patients without significant clinical reactivity differed markedly from the group means of patients with more severe clinical reactivity (p less than 0.001). In 31 patients a good correlation (r = 0.6935) was found comparing FA-WBE IgE antibody level with FA-WBE skin tests, and in 26 patients a good correlation (r = 0.8564) was obtained comparing FAV IgE antibody levels with FAV skin tests. An excellent Spearman rank correlation coefficient (r = 0.9197) was found on comparison of FAV and FA-WBE IgE antibody levels in 71 individuals. Cross-reactivity of FAV and FA-WBE was demonstrated by the ability of these reagents to competitively inhibit the binding of IgE antibody to solid-phase FA-WBE and FAV in the radioallergosorbent test (RAST). From these results we conclude that FAV and FA-WBE both contain relevant allergens important in fire ant-allergic individuals and that skin tests and RAST are both valid as diagnostic tests for fire ant allergy. Finally, there is a good correlation between RAST and skin tests using FA-WBE or FAV as test reagents, since these reagents are highly cross-reactive as demonstrated by their ability to inhibit each other in the RAST.

Structure and activity of ragweed antigen E. II. Allergenic crossreactivity of the subunits.

Recently we have reported the isolation of the two subunits (alpha and beta) of ragweed antigen E (AgE) in their active form. In the present work we have compared the allergenic activity of the two subunits with native AgE by the radioallergosorbent test (RAST) and by inhibition of the RAST. Also, the amounts of IgE antibodies in 30 ragweed-sensitive sera bound to alpha and beta subunits as well as native AgE were measured by RAST. In all individuals the percentage of RAST binding was greatest to native AgE; however, varying patterns of reactivity to alpha and beta subunits were noted. In RAST inhibition experiments, free beta subunit was equally effective in inhibiting the binding of IgE antibody (from a pooled ragweed-sensitive sera) to immoblized alpha or beta subunit. Similarly, fluid-phase alpha subunit inhibited in a comparable manner the binding of IgE antibody to solid-phase alpha or beta subunits. In further RAST inhibition experiments 7 x 10(-13) moles of fluid-phase native AgE was required for 50% inhibition of the binding of IgE antibody to solid-phase native AgE. Larger molar amounts of fluid phase beta (3.5 x 10(-11) and alpha (3 x 10(-10) were needed for 50% inhibition of the binding of IgE antibody to solid-phase native AgE. AgE allergenicity as measured by RAST could not be totally reconstituted by recombination of equimolar quantities of alpha and beta subunits. Less than 1 x 10(-12) moles of fluid-phase native AgE inhibited the binding of IgE antibody to solid-phase alpha or beta, greater than 50%. Finally, the isolated chains are bioligcally active as demonstrated by their ability to provoke wheal-and-flare skin reactions in subjects allergic to ragweed pollen, and the activities of the chains were approximately equivalent on a weight basis to native AgE.

Melittin: an allergen of honeybee venom.

The presence of serum IgE antibodies to melittin was tested by the radioallergosorbent test (RAST). Melittin, the principal protein of honeybee venom, was isolated by gel filtration on Sephadex G-75 and covalently bound to cyanogen bromide-activated microcrystalline cellulose. The melittin preparation was homogenous by immunoelectrophoresis with the use of rabbit antiserum to whole honeybee venom and by polyacrylamide electrophoresis in gels containing 1% sodium dodecyl sulfate. Elevated serum IgE antibodies to melittin (three times greater than binding by normal sera) were found in 7 of 24 honeybee venom-sensitive persons and in 5 of 20 nonsensitive beekeepers. In one venom-sensitive patient a particularly high titer of IgE antibody was found. The reaction between solid-phase melittin and IgE antibody could be inhibited by fluid-phase melittin but not by phospholipase A (PLA). Similarly, the reaction of IgE antibody with solid-phase PLA was inhibited by PLA but not by melittin. In passive transfer skin tests with the sensitive patient's serum, positive wheal-and-flare reactions were obtained in 3 nonallergic recipients following melittin challenge; appropriate controls were negative. These results indicate that melittin is an allergen in some honeybee venom-sensitive patients and in an occasional patient melittin may be a major allergen.

Thyroid imaging in lymphocytic throiditis.

The thyroid radionuclide images of 51 adult patients with a histological diagnosis of either Hashimoto's thyroiditis (HT) or chronic lymphocytic thyroiditis (CLT) were reviewed. The findings were variable but similar in the two groups, the most common being a multinodular pattern and the presence of hypofunctional nodules. Thyroid carcinoma was found in 2 of 41 patients with CLT and in 4 of 10 with HT. In a patient with clinical or laboratory evidence of HT and the radionuclide image finding of a cold nodule, thyroid carcinoma should be excluded by surgical biopsy.