Moral reasoning and consistency of belief and behavior: decisions about substance abuse.

In view of implications of Kohlberg's theory of moral development, two hypotheses were considered in two independent studies: a) individuals who consider the use of potentially harmful substances to be morally wrong will be less likely to use such substances than peers who view such activities as a personal choice; and b) compared to those who are less mature, more mature moral reasoners display more consistency between their expressed beliefs about the morality of drug use and their reports of actual drug use. Two samples of college students, 29 men and 59 women in Study 1 and 46 men and 100 women in Study 2, served as participants. All completed questionnaires about their use of tobacco, alcohol, and illicit drugs and their beliefs about the morality of using these substances. Participants in Study 2 also responded to the Defining Issues Test (DIT) to assess their level of moral thinking. Results from Study 1 supported hypothesis (a). Findings from Study 2 supported hypotheses (a) and (b).

Effects of angiotensin II on remodelling of the airway and the vasculature in the rat.

Airway remodelling occurs in chronic asthma. Angiotensin II promotes growth in cardiovascular remodelling. Since the renin-angiotensin system is activated in acute severe asthma, we hypothesized that angiotensin II has a role in airway remodelling. A total of 14 young male Wistar rats were randomly divided into two groups. All received 2-week infusions of bromodeoxyuridine, and the experimental group also received angiotensin II. Blood pressure rose in the angiotensin II-infused group [mean levels: pre-infusion, 134.9 (S.D. 14.7) mmHg; post-infusion, 197.1 (22.5) mmHg], and expression of renin mRNA in the renal juxtaglomerular cells was suppressed in these animals. The proportion of bromodeoxyuridine-positive cell nuclei was no different in the airways of control and angiotensin II-infused animals for smooth muscle [mean bromodeoxyuridine index: control, 8. 6% (S.E.M. 1.1%); angiotensin II, 9.3% (1.1%)], epithelium [control, 16.7% (2.3%); angiotensin II, 16.0% (2.2%)] and adventitia [control, 26.4% (2.2%); angiotensin II, 26.6% (2.4%)]. In the arteries, bromodeoxyuridine indices were higher in the angiotensin II-infused rats [18.4% (2.3%)] than in the control animals [9.4% (2.8%)], but no difference was found in the veins [12% (2.9%) and 11.4% (2.6%) respectively]. Morphometry of the airway wall and mesenteric vasculature was no different in the two groups. Therefore a 2-week infusion of angiotensin II increases blood pressure and DNA synthesis in the mesenteric arteries, but does not cause airway remodelling, in the rat.

Effect of acute alterations in inspired oxygen tension on methacholine induced bronchoconstriction in patients with asthma.

BACKGROUND: Recent in vitro and in vivo studies in animals have suggested that ambient oxygen tension may influence airway responsiveness to bronchoconstrictor stimuli. These observations may have relevance to the management of acute exacerbations of asthma. The present studies were designed to examine the influence of inspired oxygen tension (Fio2 1.0, 0.21, 0.15) on methacholine-induced broncho-constriction in patients with asthma. METHODS: In a dual study two groups of asthmatic patients performed methacholine inhalation challenges breathing either air (Fio2 0.21) or a hypoxic gas mixture (Fio2 0.15) in study 1 and air (Fio2 0.21) or hyperoxia (Fio2 1.0) in study 2. The gases were administered through a closed breathing circuit in a randomised double blind fashion. The PC20 values (dose of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) were calculated after each methacholine challenge by linear interpolation from the logarithmic dose response curve. Plasma catecholamine levels were measured before and after methacholine challenges as well as heart rate, oxygen saturation, and percentage end tidal carbon dioxide levels. RESULTS: The geometric mean PC20 value for methacholine was significantly lower on the hypoxic study day than on the normoxic day in study 1 (mean difference in PC20 values 2.88 mg/ml (95% CI 1.4 to 5.3); p < 0.05), but there was no significant difference in the geometric mean PC20 value for methacholine between the hyperoxic and normoxic study days in study 2 (mean difference in PC20 values 1.45 mg/ ml (95% CI 0.83 to 2.51)). CONCLUSIONS: Acute hypoxia potentiates methacholine induced bronchoconstriction and acute hyperoxia has no effect in mild to moderate patients with stable asthma.

Investigations on the renin-angiotensin system in acute severe asthma.

The renin-angiotensin system is activated in acute severe asthma. The precise mechanism of activation is at present unknown, but may involve, beta2-agonists, catecholamines or proteases released in airway inflammation. This study aims to identify potential factors involved in the activation of the renin-angiotensin system in acute asthma. Forty asthmatics with severe exacerbations of asthma, assessed by measurement of peak expiratory flow rate (mean (SD) 35 (18)% predicted), oxygen saturation (94 (4)%) and pulse rate (108 (16) beats x min(-1)) were recruited. Nineteen (48%) asthmatics had elevated plasma angiotensin II levels (median (interquartile range) 10.9 (4.3-23.5) pg x mL(-1) (normal range 3-12 pg x mL(-1))) and 10 (25%) had elevated plasma renin concentration (22.0 (10.0-50.0) microU x mL(-1) (normal range 9-50 microU x mL(-1))). Plasma renin and angiotensin II correlated strongly, implying renin-dependent angiotensin II formation. No correlation was found between plasma salbutamol, adrenaline, nor-adrenaline, endothelin-1, histamine, eosinophilic cationic protein, serum angio-tensin-converting enzyme (ACE) activity, total immunoglobulin E (IgE), urea and electrolytes, indicators of the severity of the attack, atopic status, blood pressure and renin or angiotensin II levels. We conclude that although a subpopulation of asthmatics appear to have raised renin and angiotensin II during attacks of acute, severe asthma, the mechanism of activation of the renin-angiotensin system remains unclear.

Effect of angiotensin II on histamine-induced bronchoconstriction in the human airway both in vitro and in vivo.

The renin-angiotensin system is activated in acute severe asthma. Angiotensin II causes bronchoconstriction in mild asthmatics and potentiates methacholine-evoked bronchoconstriction both in vitro and in vivo. To evaluate the effect of angiotensin II on histamine-induced bronchoconstriction, human bronchial rings (n = 6) were obtained from lung tissue at thoracotomy and were prepared in organ baths. Contractions were measured isometrically and cumulative concentration-response curves obtained to angiotensin II alone and to histamine in the presence and absence of threshold concentrations of angiotensin II. Eight asthmatic patients with bronchial hyper-reactivity to histamine were challenged with histamine during intravenous infusion of placebo, angiotensin II 1 ng kg-1 min-1 and angiotensin 2 ng kg-1 min-1 administered in a randomized, double-blind fashion, FEV1 was measured prior to, during the infusion and during the histamine challenge. Angiotensin II (3 x 10(-7)M and 10(-6)M) alone evoked small contractions (< 0.25 g) of human bronchi in vitro, but pre-incubation with threshold concentrations of angiotensin II (10(-7)M, 3 x 10(-7)M and 10(-6)M) had no effect on histamine-evoked contractions. In asthmatic patients, angiotensin II alone had no effect on baseline FEV1 at the low levels infused and did not affect the response to nebulized histamine as measured by the PC20 histamine: Geometric mean (range) PC20 histamine (mg ml-1) screening day 3.58 (1.26-7.75), placebo infusion 2.67 (0.89-9.57), angiotensin II 1 ng kg-1 min-1 2.45 (0.42-6.97) and angiotensin II 2 ng kg-1 3.09 (0.8-10.78). It is concluded that, in contrast to its potentiating effect on methacholine-induced bronchoconstriction, angiotensin II has no effect on histamine-evoked bronchoconstriction in human bronchi in vitro or in vivo.

Effect of acute hyperoxia on the bronchodilator response to salbutamol in stable asthmatic patients.

BACKGROUND: Recent animal studies have suggested that changes in oxygen tension may alter airway responses to bronchoconstrictor and bronchodilator stimuli. These effects may have relevance to the management of acute exacerbations of asthma but have not been well studied in man. This study was designed therefore to examine the effect of acute hyperoxia (Fio2 1.0) on the bronchodilator response to salbutamol in stable asthmatic patients. METHODS: Twelve stable adult asthmatic patients (three women) were studied using a randomised double blind placebo controlled crossover design. On two study days following baseline measurements patients breathed either air (Fio2 0.21) or oxygen (Fio2 1.0) for 10 minutes alone and then in combination with three incremental doses of nebulised salbutamol administered at 15 minute intervals. The same protocol was employed on two further study days using nebulised saline instead of salbutamol. RESULTS: The mean absolute change in forced expiratory volume in one second (FEV1) from baseline after salbutamol was similar on the normoxic and hyperoxic study days but significantly greater than the study days on which nebulised saline was administered. CONCLUSION: Acute hyperoxi does not potentiate the immediate bronchodilator response to salbutamol in stable asthmatic patients.