Comparison of asthma treatment given in addition to inhaled corticosteroids on airway inflammation and responsiveness.

There is increasing evidence that the assessment of eosinophilic airway inflammation using induced sputum and measurement of airway hyperresponsiveness provides additional, clinically important information concerning asthma control. The aim of this study was to directly compare the effects of different treatments on these markers in patients with asthma and persistent symptoms, despite the use of low-dose inhaled corticosteroids. A double-blind four-way crossover study was performed, which compared a 1-month treatment with budesonide 400 mug b.i.d., additional formoterol, additional montelukast and placebo in 49 patients with uncontrolled asthma despite budesonide 100 mug b.i.d., with each treatment separated by a 4-week washout period. The change in sputum eosinophil count with formoterol (2.4 to 3.8% change, 0.6-fold reduction, 95% confidence interval (CI) 0.5-0.9) differed significantly from placebo (2.8 to 2.5% change, 1.1-fold reduction, 95% CI 0.7-1.6) and high-dose budesonide (2.7 to 1.6% change, 1.6-fold reduction, 95% CI 1.2-2.2). The effects of montelukast did not differ from placebo. The changes in methacholine airway responsiveness were small and did not differ between treatments. High-dose budesonide had the broadest range of beneficial effects on other outcomes, including symptom scores, morning peak expiratory flow and forced expiratory volume in one second. In conclusion, treatment given in addition to low-dose inhaled corticosteroids results in modest benefits. Formoterol and high-dose budesonide have contrasting effects on eosinophilic airway inflammation.     

Relatedness of structures of a major immunogen in Trichomonas vaginalis isolates.

Solubilization of live Trichomonas vaginalis organisms with detergent caused the release of cysteine proteinases in the detergent extract which were inhibitable with N-alpha-p-tosyl-L-lysine chloromethyl ketone. The detergent extracts of all isolates tested possessed similar cysteine proteinase activities. These parasite proteinases rapidly degraded a prominent immunogen whose surface disposition undergoes phenotypic variation in some isolates. The relatedness of the forms of this immunogen among all isolates tested was confirmed by identical immunoblot patterns of autolysed immunogen, and data suggest the presence of repeating units or at least equidistant sites for proteinase cleavage within the immunogen molecule.     

Triggers or aggravators of symptoms?

This study attempts to replicate and extend the associations reported by Verbrugge among negative events, bad mood and symptoms. Employing the same symptomatology measure used in that study, but with more comprehensive event and mood questionnaires, we essentially replicated the same-day and lagged relationships reported by Verbrugge. One difference, however, was that undesirable events were a stronger predictor of symptom days than negative mood, whereas the opposite was true in Verbrugge's study. To further investigate the causal role of events and mood on symptoms, analyses were performed looking only at onset days of symptom episodes. This procedure greatly reduced same day event-symptom associations and eliminated event and mood's lagged relationships with symptoms. Our results do not, then, corroborate the triggering effect of events and mood for the onset of symptoms, although these variables may have a role in maintaining the duration of symptom episodes.     

The effects of age,sex, and genotype on self-report drunkenness following a challenge dose of alcohol

Age is a potential source of variation that contributes to differences between, but not within, twin pairs. In most genetic analyses of twin data, linear and other functions of age are usually removed prior to model fitting. This correction is typically applied only within twin groups of the same sex and zygosity, and no heterogeneity test of age regressions is performed. Here we include age as a variable in the model-fitting procedure and allow for tests of heterogeneity of age regressions across sex and zygosity groups. The LISREL formulation of the approach is illustrated with data collected from Australian twins on subjective impressions of drunkenness following alcohol consumption. The results indicate significant negative covariation of impressions of drunkenness with age. The data support a simple model of additive genetic and unique environmental variation. No evidence was found for sex differences in genetic or environmental components of variation.The theoretical work and data analysis described in this paper were made possible by NATO Grant 86/0823 and grants from the Belgian National Research Fund, the State University of Gent, and the Catholic University of Leuven. We are also grateful to Drs. R. Vlietinck and R. Derom for excellent organization of the successful workshop. Data collection was made possible by a grant from the Australian Associated Brewers to N.G.M. and Drs. J. G. Oakeshott, J. B. Gibson, and G. A. Starmer and by grants from the Australian National Health and Medical Research Council. The authors were supported by NIH Grants MH-40828 and AA-06781.     

Structural relationships in the inhibition of [3H]tryptamine binding to rat brain membranes in vitro by phenylalkylamines

The ability of various phenylalkylamines to inhibit the binding of [3H]tryptamine to rat frontal/parietal cortical membranes was examined in vitro. Affinity for [3H]tryptamine binding sites improved as the alkyl side chain was extended to include four carbons or when a methoxy group was added at the para position of the ring. One compound, p-methoxyphenylpropylamine (IC50 = 3.6 nM), was as potent as unlabelled tryptamine as a displacing agent. Based on the unique structure-activity relationship obtained, it appears that [3H]tryptamine binding sites do not mediate the actions of phenethylamines on serotonin uptake or release.     

Dose duration of nebulized nedocromil sodium in exercise-induced asthma.

The dose-duration effect of nebulized nedocromil sodium was studied in ten patients with exercise-induced asthma (7 males mean (SEM) age 30.1 (3.5) yrs and predicted forced expiratory volume in one second (FEV1) 102%). All of these patients showed > 40% protection of their exercise asthma with 4 mg of nedocromil sodium delivered via metered dose inhaler. Three concentrations of nedocromil sodium (0.5, 2.5 and 10 mg.ml-1) and placebo were administered in double-blind, randomized manner. One ml of each solution was nebulized via a Wright nebulizer. Effects were assessed from the mean maximal percentage fall in FEV1 after 6-8 min treadmill exercise at 15, 135 and 255 min following each treatment and expressed as percentage protection. The mean baseline FEV1 values before and after treatments were comparable on four days of testing. Nedocromil sodium inhibited exercise-induced fall in FEV1 at all concentrations (p < 0.001) and the inhibitory effect was still present at 255 min. No differences were observed between active treatments.     

The genetic epidemiology of phobias in women. The interrelationship of agoraphobia, social phobia, situational phobia, and simple phobia.

In 2163 personally interviewed female twins from a population-based registry, the pattern of age at onset and comorbidity of the simple phobias (animal and situational)--early onset and low rates of comorbidity--differed significantly from that of agoraphobia--later onset and high rates of comorbidity. Consistent with an inherited "phobia proneness" but not a "social learning" model of phobias, the familial aggregation of any phobia, agoraphobia, social phobia, and animal phobia appeared to result from genetic and not from familial-environmental factors, with estimates of heritability of liability ranging from 30% to 40%. The best-fitting multivariate genetic model indicated the existence of genetic and individual-specific environmental etiologic factors common to all four phobia subtypes and others specific for each of the individual subtypes. This model suggested that (1) environmental experiences that predisposed to all phobias were most important for agoraphobia and social phobia and relatively unimportant for the simple phobias, (2) environmental experiences that uniquely predisposed to only one phobia subtype had a major impact on simple phobias, had a modest impact on social phobia, and were unimportant for agoraphobia, and (3) genetic factors that predisposed to all phobias were most important for animal phobia and least important for agoraphobia. Simple phobias appear to arise from the joint effect of a modest genetic vulnerability and phobia-specific traumatic events in childhood, while agoraphobia and, to a somewhat lesser extent, social phobia result from the combined effect of a slightly stronger genetic influence and nonspecific environmental experiences.