This report describes an age-related clinical study of detrusor muscle function using urodynamic data obtained from 1391 women and 324 men of different age groups who were free from overt neurological disease and diabetes. Isometric detrusor function during unstable activity was assessed by integrating the calculated force of unstable detrusor activity during filling of the bladder. Isotonic voiding activity was measured by calculating the velocity constant Q*, which reflects the speed of detrusor muscle shortening. In addition, the change in detrusor pressure on initiation of voiding and the post-micturition residual urine volume were recorded. Older patients of both sexes had higher residual urine volumes. Older women showed lower detrusor shortening velocities. There were no age-related differences in isometric detrusor function. Older women showed a tendency for the detrusor contraction to fail on initiation of voiding, whereas older men did not demonstrate this difference. Voiding dysfunction in late life was more marked amongst women and seemed to be related to a failure of isotonic detrusor function with no related changes in isometric function.

Inhaled frusemide protects against the bronchoconstrictor response to a wide range of stimuli that cause bronchoconstriction by indirect mechanisms. One possible explanation for this protection relates to the known ability of frusemide to enhance synthesis of prostaglandin E2 (PGE2). Studies in vitro suggest that PGE2 might protect against indirectly acting bronchoconstrictor challenges rather than those that act directly on airway smooth muscle, though little is known about the effects of PGE2 in vivo. The effect of inhaled PGE2 on the bronchoconstrictor response to inhaled sodium metabisulphite (a stimulus with an indirect action) and methacholine (which acts directly on airway smooth muscle) was studied in nine patients with asthma. Subjects were studied on four days, inhaling PGE2 (100 Mg) or placebo in a double blind fashion followed immediately by a cumulative dose challenge with sodium metabisulphite or methacholine. The response to the constrictor stimuli was measured as the provocative dose causing a 20% fall in FEV, (PD20). There was no significant change in FEV1 after inhaled PGE2 compared with placebo, nor any significant change in the response to methacholine; the geometric mean methacholine PD20 was 0 9 pmol after PGE2 and 0-56 pmol after placebo (mean difference 0 7 (95% confidence limits -0-1, 1 5) doubling doses). PGE2, however, protected against sodium metabisulphite, the geometric mean sodium metabisulphite PD20 being 118 pmol after PGE2 and 1-8 pmol after placebo (mean difference 2 5 (95% CL 1-9, 3-1) doubling doses). PGE2 conferred significantly greater protection against sodium metabisulphite than methacholine (mean difference 1-8 (95% CL 0-8, 2-8) doubling doses). This suggests that PGE2, like frusemide, has an inhibitory effect on pathways relevant to the bronchoconstriction induced by sodium metabisulphite, with little or no effect on those relevant to methacholine.The recent finding that inhaled frusemide protects subjects with asthma against the bronchoconstrictor response to stimuli that act indirectly but not directly on airway smooth muscle has aroused much interest. 1-5

It has been suggested that regular treatment with high doses of beta 2-agonists might result in poorer control of asthma and increased bronchial responsiveness. We have examined change in FEV1 (delta FEV1), bronchial reactivity, peak expiratory flow (PEF), and symptoms during and after 3 wk of regular treatment with a relatively low dose of albuterol and broxaterol, a new beta 2-agonist. Eleven subjects 18 to 50 yr of age with mild asthma inhaled albuterol (200 micrograms), broxaterol (400 micrograms), or placebo three times a day for 3 wk with a 2- to 4-wk run-in/washout period between treatments. Ipratropium bromide was allowed for symptomatic relief. The PD20 (dose of histamine causing a 20% fall in FEV1) was measured before and 11, 35, and 59 h after cessation of treatment and a bronchodilator dose-response study before and 83 h after cessation of treatment. Change from baseline after albuterol and broxaterol are compared with change after placebo. Diurnal change in PEF (amplitude % mean) increased during treatment with albuterol by 6.5% (95% CI, 1.7-12.3; p < 0.02) mainly because of a fall in morning PEF. Cessation of treatment with both beta 2-agonists was associated with a fall in FEV1 and PD20 compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Background -Pulmonary lymphangioleiomyomatosis is a rare progressive disease ofunknown aetiology affecting premenopausal women. Since the oral contraceptive pill has been implicated in its pathogenesis, a case control study was carried out to determine whether women with the disease were more likely to have taken the oral contraceptive pill, and whether the disease was associated with other conditions related to sex hormones including pregnancy, parity, and fibroids. Methods -All chest physicians in the UK were asked for details of all live patients with pulmonary lymphangioleiomyomatosis; the patient's family doctor was then asked for four age and sex matched control subjects from their patient register. Details of lifetime use of the oral contraceptive pill, pregnancy, parity, history of fibroids, and smoking were obtained from cases and controls. Relative odds of exposure to potential risk factors were estimated by conditional logistic regression. Results The aetiology of pulmonary lymphangioleiomyomatosis is unknown, but sex hormones have been assumed to be important since the disease develops exclusively in women and almost invariably women of reproductive age.'3"6 Treatment has usually invoved antioestrogen measures in the form of oophorectomy347 or treatment with tamoxifen,8-'0 medroxyprogesterone,8 '-and luteinising hormone releasing hormone analogues. 14 None of these treatments has been assessed in a controlled trial and their value is uncertain. 5 Reports of the disease occurring in women on the oral contraceptive pill2 16 -18 and of exacerbations of the disease during pregnancy8 have added to the suspicion that sex hormones are involved. We have therefore conducted a case control study to determine whether pulmonary lymphangioleiomyomatosis is associated with the use of the oral contraceptive pill or other conditions associated with sex hormones such as pregnancy, parity, and fibroids. Methods CASES AND CONTROLSChest physicians in the UK on the British Thoracic Society register were sent an explanation of the study and asked for details of all known live patients with pulmonary lymphangioleiomyomatosis. The physicians were asked to forward to such patients a written request asking them to participate in the study, plus a questionnaire and consent form which

There is a transient rebound increase in bronchial reactivity to histamine and methacholine following regular treatment with an inhaled beta 2-agonist. We set out to determine whether the response to allergen was increased after cessation of regular inhaled terbutaline and whether concomitant inhaled budesonide modifies this response. In a double-blind, double-dummy, parallel group design we studied 41 subjects (37 evaluable) with mild asthma who were allergic to Dermatophagoides pteronyssinus, grass pollen, or cat fur. Following a 2 wk run-in period, subjects underwent a fixed three-dose allergen challenge based on their previously determined provocative concentration of allergen producing a 20% fall in FEV1 (PC20) before starting terbutaline 1,000 micrograms or placebo three times daily and budesonide 800 micrograms or placebo twice daily for a period of 2 to 4 wk (mean 18 d). The same three-dose allergen challenge was repeated 33 h after stopping treatment. During treatment evening peak flow values were highest in the terbutaline plus budesonide group. Following regular terbutaline there was no rebound increase in bronchial reactivity to allergen. Following budesonide there was a significantly smaller response to allergen and an increased FEV1 compared with the other three groups, including the budesonide plus terbutaline group. The changes in median (95% CI) allergen PC20 after budesonide, terbutaline, budesonide plus terbutaline, and placebo were 0.79 (0.3, 2.3), 0.11 (-0.4, 0.6), 0.24 (-0.4, 0.5) and -0.47 (-1.5, 0.1) doubling doses (p < 0.01). The respective changes in mean FEV1 were 0.34, -0.16, -0.01, and 0.06 L (p < 0.005). Thus bronchial reactivity to allergen was not increased after regular inhaled terbutaline.(ABSTRACT TRUNCATED AT 250 WORDS)