Twelve month comparison of salmeterol and salbutamol as dry powder formulations in asthmatic patients. European Study Group.

BACKGROUND: Salmeterol is a potent selective beta 2 agonist that has been shown to have a duration of action in excess of 12 hours. In this study salmeterol and salbutamol were compared over a three month period with a further extension of nine months. METHODS: Three hundred and eighty eight patients with mild to moderate reversible airways obstruction (forced expiratory volume in one second (FEV1) > 50% predicted) were randomised to receive salmeterol (50 micrograms) twice daily or salbutamol (400 micrograms) four times daily, both by dry powder, in a double blind parallel group study. During the first three months detailed assessment of efficacy was made with recording of morning and evening peak expiratory flow rates (PEF), asthma symptoms, and bronchodilator use when necessary for the relief of symptoms. Patients continued in the study for a further nine months with the salbutamol dose reduced to 400 micrograms twice daily. Lung function was measured at the clinic and safety data were collected during this period. RESULTS: Salmeterol produced a significantly higher mean morning PEF (mean difference compared with salbutamol 21 (95% CI 12-31) l/min), and a significant reduction in mean diurnal variation in PEF (from 30 l/min at baseline to 11 34 l/min at baseline to 32 l/min during salbutamol treatment). Salmeterol also reduced day and night symptoms and use of rescue bronchodilator. FEV1 increased with both salmeterol and salbutamol treatment over the 12 month treatment period. For both treatments the number of patients reporting exacerbations of asthma and the frequency of these exacerbations remained constant during the study. Thirty six patients in the salmeterol and 49 in the salbutamol group withdrew during the 12 months of the study. CONCLUSIONS: In this study salmeterol (50 micrograms twice daily) was more effective than salbutamol (400 micrograms four times daily) in the control of asthma over three months, and more effective than salbutamol (400 micrograms twice daily) over a further nine months. Neither salmeterol nor salbutamol was associated with any worsening of control of asthma.

Ketanserin and capillary flow in Raynaud's phenomenon.

The serotonin (S2) antagonist ketanserin has been proposed as a useful therapy for Raynaud's phenomenon. The present study was designed to investigate the effects of 8 weeks therapy with oral Ketanserin (40 mg tds for the last 6 weeks) on finger nailfold capillary flow velocity at rest and following cold challenge and symptom score in 30 patients with Raynaud's in a double-blind, placebo-controlled, parallel design study. The ketanserin treated group reported a 16.7% improvement in symptom score (p less than 0.05) relative to the end of the run-in phase compared with a 2.4% (NS) improvement in the placebo group. Improvement in capillary flow was confined to a significant (p less than 0.02) rise in rest flow in the ketanserin treated group but no beneficial changes were observed following cold challenge. The disparity between the subjective and objective benefits demonstrated for this drug suggest the possibility of a central action rather than one that involves the correction of a local vascular fault.

Dynamic measurement of human capillary blood pressure.

1. Capillary blood pressure was measured in man using a dynamic servo-nulling system and direct micropuncture. This enabled assessments of the normal variations in pressure which influence fluid filtration and reabsorption. 2. Seventy-eight capillaries in 19 subjects were punctured in one of three positions around the capillary loop with the hand at the level of the sternal angle. Mean pressure around the loop fell from 37.7 +/- 3.7 mmHg (arteriolar limb, mean +/- SEM, n = 12) to 19.4 +/- 1.0 mmHg (apex, n = 25) to 14.6 +/- 0.5 mmHg (venular limb, n = 41) at skin temperatures of 18.7-33.1 degrees C. These values agree closely with Landis' original studies in 1930 [E. Landis (1930) Heart, 15, 209-228]. 3. The mean filtration/reabsorption state of any particular capillary limb was not static because of cardiac, vasomotor and respiratory fluctuations in capillary pressure. From a total of 38 capillaries in which recordings were analysed for 30 s, the fluctuations in pressure were such that 27 capillaries probably had periods of both filtration and reabsorption. 4. Computerized superimposition and coherent averaging of trains of capillary pulses enabled an accurate description of the pulse waveform to be made in three capillaries. This was remarkably similar to waveforms from the radial artery, albeit at reduced amplitude (average 3.6 +/- 3.4 mmHg, mean +/- SD overall). The time for the pulse to travel between the radial artery and the finger capillary was approximately 10 ms, which implies a propagation velocity of several metres per second.(ABSTRACT TRUNCATED AT 250 WORDS)