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No abstract is provided for this article.
AbstractRecently there has been a much greater understanding of the molecular mechanisms involved in the actions of antiasthma therapy, β2-agonists are the most effective bronchodilators and act predominantly on airway smooth muscle. Recent evidence suggests that β2-receptors in airway smooth muscle are coupled directly to maxi-K channels and may thereby bronchodilate without an increase in cyclic AMP. The issue of β-receptor tolerance has been reawakened by the recognition that the protective effects of β2-agonists against bronchoconstrictor stimuli may become tolerant.Inhaled glucocorticoids are the mainstay of treatment in patients with chronic asthma. They suppress asthmatic inflammation predominantly by reducing transcription of genes coding for inflammatory mediators (particularly cytokines) and enzymes (inducible NO synthase, inducible cyclo-oxygenase). The inhibition of gene transcription is mediated predominantly by inhibition of transcription factors, such as activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB). There may be an abnormal activation of AP-1 in steroid-resistant asthma, and high concentrations of β2-agonists may induce a secondary resistance by an interaction between the transcription factor CREB and the glucocorticoid receptor.Theophylline may have immunomodulatory effects that are more important than its bronchodilator action. Some effects of theophylline are mediated via inhibition of phosphodiesterases and several PDE IV inhibitors are currently undergoing evaluation in asthma.Key Words: β-adrenergic agonistsbronchodilatorsglucocorticoidstranscription factorstheophyllinephosphodiesterase
No abstract is provided for this article.
Three successive time periods were compared to study the impact of evolving techniques and new equipment on the immediate results of single‐vessel percutaneous transluminal coronary angioplasty (PTCA), the initial success rate and major complication rate (death, myocardial infarction, and urgent surgery). The three periods were selected on the basis of a significant advance in either PTCA technique or equipment. In period I from 1980 to 1983 a nonsteerable catheter system was used. In period II from 1983 to 1986 a steer‐able catheter was used. In period HI from 1986 to 1987 the long guidewire technique and/or monorail system was used. A total of 1,371 successive patients underwent single‐vessel dilatation for stable angina (848 patients) or for unstable angina (523 patients). Initial success was defined as a reduction of the stenosis to less than 50% with no major complications (myocardial infarction or death, or the necessity of proceeding to coronary artery bypass surgery). The initial success rate increased from 68% (period I) to 88% (period II) and to 91% (period III) for all attempts. When attempts of dilatation of totally occluded vessels were excluded these figures were 71%, 91%, and 95%, respectively. The overall major complication rate decreased from 16% (period I) to 8% (period II) to 3.5% (period III). Thus, increase in investigator experience, technical improvements of balloon catheter systems, and introduction of new PTCA techniques have resulted in an increase in success and safety of PTCA procedures. (J Inter‐ven Cardiol 1988:1:1)
Bombesin is a potent bronchoconstrictor in guinea pigs in vivo, but the mechanisms of its effect are not certain. In vivo increases in tracheal pressure induced by bombesin were measured as an index of airway caliber. Bombesin (0.3-10 micrograms/kg) produced a dose-related bronchoconstrictor response in vivo which was not inhibited by indomethacin (5 mg/kg), BW A4C (50 mg/kg, a lipoxygenase inhibitor), WEB 2086 (10 micrograms/kg, a platelet-activating factor antagonist) or mepyramine (10 mg/kg, a histamine H1-receptor antagonist). Capsaicin pretreatment (50 mg/kg), which depletes neuropeptides from sensory nerve endings, similarly failed to inhibit the action of bombesin. Propranolol (1 mg/kg) produced a small shift to the left and atropine (1 mg/kg) and the serotonin antagonist, methysergide (1 mg/kg), produced a small shift to the right in the bombesin dose-response curve. The bombesin receptor antagonist, BIM 26159 (50 micrograms/kg), transiently inhibited bombesin-induced bronchoconstriction. Isoproterenol (0.1-10 micrograms/kg) reversed the increase in tracheal pressure induced by bombesin, suggesting that contraction of airway smooth muscle was involved. Bombesin (10(-10)-3 x 10(-5) M) failed to produce contraction in trachea or main bronchi either denuded of epithelium or in tissues pretreated with phosphoramidon, captopril or indomethacin (all 10(-5) M) and was inactive in peripheral lung strip preparations. Thus, bombesin is a potent constrictor of guinea pig airways in vivo. The inability of bombesin to contract airway smooth muscle in vitro suggests that the bronchoconstrictor action of bombesin is largely due to the release of an unidentified spasmogenic substance.
The usefulness of performing real time cross-sectional echo contrast studies, using peripheral venous injections ofdextrose 5 per cent in water, for the detection and localisation of atrial and ventricular right-to-left shunts was evaluated in 70 adult patients.Based on their catheterisation data, 20 patients had a shunt at atrial level (group 1) and 14 patients a ventricular septal defect (group 2).Thirty-six patients without a shunt by oximetry served as controls.Echo contrast could not be detected in the left-sided cardiac cavities in any of the control patients.In 11 of the 15 patients with an uncomplicated atrial septal defect of the secundum type, echo contrast appeared at the left side of the heart and this small right-to-left shunting occurred in systole.Left-sided echo contrast was demonstrated in the 5 patients in whom a bidirectional atrial shunt was found by oximetry.Of the 14 patients with a ventricular septal defect, 7 had a ratio of right-to-left ventricular pressure exceeding 50 per cent and early diastolic right-to-left shunting of echo contrast was observed in all.This was not seen in any of the patients with an uncomplicated ventricular septal defect.Diagnostic real time ultrasonic cross-sectional contrast studies can thus be performed in adults using peripheral venous injections of dextrose 5 per cent in water.The presence and timing of intracardiac right-to-left shunts, even when small, are greatly facilitated.The concept of contrast echocardiography was introduced in the late sixties by Gramiak and his group, primarily to identify intracardiac structures (Gramiak and Shah, 1968; Gramiak et al., 1969; Feigenbaum et al., 1970).Subsequently, intra- cardiac injections of echo contrast material were found useful in the assessment of congenital heart disease, as a complementary technique to conven- tional catheterisation methods (Pieroni et al., 1973; Kerber et al., 1974; Seward et al.,, 1975).Contrast echocardiography found rapid acceptance in the echocardiography laboratory after it was shown by Valdes-Cruz et al. (1976) that peripheral vein injection of a Cardiogreen solution produced sufficient ultrasonic contrast to define intracardiac shunts.
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