Showing papers by "Glenfield Hospital published in 1999"

Eosinophilic Bronchitis Is an Important Cause of Chronic Cough

Abstract: Eosinophilic bronchitis presents with chronic cough and sputum eosinophilia, but without the abnormalities of airway function seen in asthma. It is important to know how commonly eosinophilic bronchitis causes cough, since in contrast to cough in patients without sputum eosinophilia, the cough responds to inhaled corticosteroids. We investigated patients referred over a 2-yr period with chronic cough, using a well-established protocol with the addition of induced sputum in selected cases. Eosinophilic bronchitis was diagnosed if patients had no symptoms suggesting variable airflow obstruction, and had normal spirometric values, normal peak expiratory flow variability, no airway hyperresponsiveness (provocative concentration of methacholine producing a 20% decrease in FEV(1) ([PC(20)] > 8 mg/ml), and sputum eosinophilia (> 3%). Ninety-one patients with chronic cough were identified among 856 referrals. The primary diagnosis was eosinophilic bronchitis in 12 patients, rhinitis in 20, asthma in 16, post-viral-infection status in 12, and gastroesophageal reflux in seven. In a further 18 patients a diagnosis was established. The cause of chronic cough remained unexplained in six patients. In all 12 patients with eosinophilic bronchitis, the cough improved after treatment with inhaled budesonide 400 micrograms twice daily, and in eight of these patients who had a follow-up sputum analysis, the eosinophil count decreased significantly, from 16.8% to 1.6%. We conclude that eosinophilic bronchitis is a common cause of chronic cough, and that sputum induction is important in the investigation of cough.

The endurance shuttle walk: a new field test for the assessment of endurance capacity in chronic obstructive pulmonary disease

Abstract: Background—The purpose of this study was to develop an externally controlled, constant paced field walking test to assess endurance capacity in patients with chronic obstructive pulmonary disease (COPD). There were four objectives: (1) to develop a protocol; (2) to compare treadmill and shuttle walk tests of endurance capacity; (3) to examine the repeatability of the endurance shuttle walk test; and (4) to compare the sensitivity to pulmonary rehabilitation of endurance and incremental shuttle walk tests. Methods—The test was designed to complement the incremental shuttle walk test (ISWT) using the same 10 m shuttle course and an audio signal to control pace. The intensity of the field endurance test was related to a percentage of each patient’s maximum field exercise performance assessed by the ISWT. A number of cassette tapes were prerecorded with a range of audio signal frequencies to dictate walking speeds between 1.80 and 6.00 km/h. In the first limb of the study 10 patients with COPD (mean (SD) forced expiratory volume in one second (FEV1) 1.0 (0.36) l, 35% predicted) performed three endurance shuttle walk tests (ESWTs) and three treadmill endurance tests. The walking speeds were calculated to elicit 75%, 85%, and 95% of each patient’s maximum ISWT performance for the field tests and measured peak oxygen consumption for the treadmill tests. In a separate group of patients the repeatability of the ESWT at an intensity of 85% of the ISWT performance was evaluated. Finally, the ESWT (at the 85% intensity) and the ISWT were

Transcatheter closure of atrial septal defect and interatrial communications with a new self expanding nitinol double disc device (Amplatzer septal occluder): multicentre UK experience

Abstract: OBJECTIVE To review the safety and efficacy of the Amplatzer septal occluder for transcatheter closure of interatrial communications (atrial septal defects (ASD), fenestrated Fontan (FF), patent foramen ovale (PFO)). DESIGN Prospective study following a common protocol for patient selection and technique of deployment in all participating centres. SETTING Multicentre study representing total United Kingdom experience. PATIENTS First 100 consecutive patients in whom an Amplatzer septal occluder was used to close a clinically significant ASD or interatrial communication. INTERVENTIONS All procedures performed under general anaesthesia with transoesophageal echocardiographic guidance. Interatrial communications were assessed by transoesophageal echocardiography with reference to size, position in the interatrial septum, proximity to surrounding structures, and adequacy of septal rim. Stretched diameter of the interatrial communications was determined by balloon sizing. Device selection was based on and matched to the stretched diameter of the communication. MAIN OUTCOME MEASURES Success defined as deployment of device in a stable position to occlude the interatrial communication without inducing functional abnormality or anatomical obstruction. Occlusion status determined by transoesophageal echocardiography during procedure and by transthoracic echocardiography on follow up. Clinical status and occlusion rates assessed at 24 hours, one month, and three months. RESULTS 101 procedures were performed in 100 patients (86 ASD, 7 FF, 7 PFO), age 1.7 to 64.3 years (mean (SD), 13.3 (13.9)), weight 9.2 to 100.0 kg (mean 32.5 (23.5)). Procedure time ranged from 30 to 180 minutes (mean 92.4 (29.0)) and fluoroscopy time from 6.0 to 49.0 minutes (mean 16.1 (8.0)). There were seven failures, all occurring in patients with ASD, and one embolisation requiring surgical removal. Immediate total occlusion rate was 20.4%, rising to 84.9% after 24 hours. Total occlusion rates at the one and three month follow up were 92.5% and 98.9%, respectively. Complications were: transient ST elevation (1), transient atrioventricular block (1), presumed deep vein thrombosis (1), presumed transient ischaemic attack (1). CONCLUSIONS It appears feasible to close interatrial communications and atrial septal defects up to 26 mm stretched diameter safely with the Amplatzer septal occluder. Short term results confirm an early high occlusion rate with no major complications. Careful selection of cases based on the echocardiographic morphology of the ASD and accurate assessment of their stretched diameter is of utmost importance. Further experience with the larger devices and longer term results are required before a firm conclusion regarding its use can be made.

Induced sputum eicosanoid concentrations in asthma.

Abstract: Further definition of the role of leukotrienes (LT) and prostaglandins (PG) in asthma would be helped by a noninvasive method for assessing airway production. The supernatant from sputum induced with hypertonic saline and dispersed using dithiotrietol has been successfully used to measure other molecular markers of airway inflammation and might be a useful method. We have measured induced sputum supernatant LTC(4)/D(4)/E(4) concentrations using enzyme immunoassay and PGE(2), PGD(2), TXB(2), and PGF(2alpha) using gas chromatography-negative ion chemical ionization-mass spectroscopy in 10 normal subjects and in 26 subjects with asthma of variable severity. Sputum cysteinyl-leukotrienes concentrations were significantly greater in subjects with asthma (median, 9.5 ng/ml) than in normal control subjects (6.4 ng/ml; p < 0.02) and greater in subjects with persistent asthma requiring inhaled corticosteroids (median, 11.4 ng/ml) or studied within 48 h of an acute severe exacerbation of asthma (13 ng/ml) than in subjects with episodic asthma treated with inhaled beta(2)-agonists only (7.2 ng/ml). There were no significant differences in the concentrations of other eicosanoids between groups, although there was a negative correlation between the percentage sputum eosinophil count and sputum PGE(2) concentration (r = -0.48; p < 0.01) in subjects with asthma. We conclude that induced sputum contains high concentrations of eicosanoids and that sputum LTC(4)/D(4)/E(4) concentrations are significantly greater in subjects with asthma than in normal subjects. The inverse relationship between eosinophilic airway inflammation and sputum PGE(2) concentration would be consistent, with the latter having an anti-inflammatory role.

Immunopathology and human mast cell cytokines

Abstract: The mast cell is a virtual pharmacopoeia of biological substances. It used to be believed that mast cell activation was all-or-nothing, with IgE cross-linking inducing symptoms of allergy and anaphylaxis. However, the activity of mast cells in health and disease is clearly much more complicated than this. The discovery that human mast cells secrete many pleiotropic cytokines suggested there may be many novel mast cell functions, and many of these are now being realised. The ubiquitous distribution of mast cells throughout connective tissues, along epithelial surfaces, and in close proximity to blood vessels, makes their products available to a large variety of cell types including fibroblasts, glandular epithelial cells, nerves, vascular endothelial cells, smooth muscle cells, and other cells of the immune system. This tissue distribution, and the vast array of lipid mediators, proteases, proteoglycans and cytokines identified as potential products of human mast cells, explains how this interesting cell has the potential to contribute to so many diverse biological events.

The inflammatory and coagulative response to prolonged extracorporeal membrane oxygenation

Abstract: Extracorporeal circulation is used therapeutically during renal dialysis, cardiopulmonary bypass (CPB), and extracorporeal membrane oxygenation (ECMO) All of these procedures result in activation of the body's natural defense mechanisms against "nonself" and foreign invasion The prolonged duration of ECMO compared with other applications and the absence of hypothermia, hemodilution, ischemia/reperfusion, and protamine administration make the host response to ECMO subtly distinct In this review, the host response to ECMO is discussed and contrasted to CPB The use of aprotinin and other response modifiers is also considered

Critical closing pressure explains cerebral hemodynamics during the Valsalva maneuver

Abstract: The Valsalva maneuver (VM), a voluntary increase in intrathoracic pressure of ∼40 mmHg, has been used to examine cerebral autoregulation (CA). During phase IV of the VM there are pronounced changes...

Orthostatic blood pressure changes and arterial baroreflex sensitivity in elderly subjects.

Abstract: Background: orthostatic hypotension in elderly people is often attributed to diminished afferent baroreflex sensitivity, but this has not been demonstrated. We examined the hypothesis that postural change in blood pressure is related to baroreflex sensitivity, independent of the confounding effect of baseline blood pressure. Methods: we studied 25 active, untreated elderly subjects free of postural symptoms (mean age 70 6 1 years): 16 with hypertension (clinic blood pressure 194 6 6/98 6 3 mmHg) and nine normotensive controls (clinic blood pressure 134 6 3/77 6 3 mmHg). We assessed baroreflex sensitivity from the heart rate and blood pressure responses to the Valsalva manoeuvre and a pressor and depressor stimulus (bolus phenylephrine injection or sodium nitroprusside infusion respectively). Subjects were then passively tilted to 608 and maximum changes in systolic blood pressure, heart rate, forearm blood flow and forearm vascular resistance recorded. Results: maximum change in systolic blood pressure with head-up tilt was correlated with supine systolic blood pressure (r = 0.60, P = 0.001). Maximum change in systolic blood pressure with orthostasis was greater in the hypertensive subjects (45 6 4 mmHg versus 29 6 6, P = 0.04) and the heart rate increment was less (16 6 2 bpm versus 24 6 4, P = 0.02). The increase in forearm vascular resistance with tilt was similar in the two groups (47 6 11 versus 38 6 7 units, P = 0.52). All three methods of assessing baroreflex sensitivity showed a reduction in the hypertensive subjects (all P # 0.02). Lower values of baroreflex sensitivity were related to greater falls in systolic blood pressure with tilt, after adjustment for the baseline level of systolic blood pressure. Conclusions: we found a relationship between baroreflex sensitivity and the systolic blood pressure fall with orthostasis, even after adjustment for prevailing systolic blood pressure. Despite equivalent changes in forearm vascular resistance with tilt, greater falls in systolic blood pressure were seen in hypertensive subjects than in normotensive controls, due in part to an inadequate baroreflex-mediated heart rate response. The postural fall in blood pressure often observed in elderly hypertensive subjects may be related to the reduced baroreflex sensitivity seen in this condition.

Development of irreversible airflow obstruction in a patient with eosinophilic bronchitis without asthma.

Abstract: Eosinophilic bronchitis is a recently described condition presenting with chronic cough and sputum eosinophilia without the abnormalities of airway function seen in asthma. The patient, a 48-yr-old male who had never smoked, presented with an isolated chronic cough. He had normal spirometric values, peak flow variability and airway responsiveness, but an induced sputum eosinophil count of 33% (normal <1%). Although his cough improved with inhaled corticosteroids the sputum eosinophilia persisted. Over 2 yrs he developed airflow obstruction, which did not improve following nebulized bronchodilators and a 2-week course of prednisolone 30 mg once daily sufficient to return the sputum eosinophilia to normal (0.5%). It is suggested that the progressive irreversible airflow obstruction was due to persistent structural change to the airway secondary to eosinophilic airway inflammation, and it is further speculated that eosinophilic bronchitis may be a prelude to chronic obstructive pulmonary disease in some patients.

Aortic obstruction caused by device occlusion of patent arterial duct

Abstract: A 2 year old girl is reported in whom deployment of the Amplatzer ductal occluder caused significant aortic obstruction, requiring surgical removal of the device. This case emphasises the need for careful echocardiographic and angiographic assessment of the position of the Amplatzer ductal occluder before and after detaching the device from its delivery system, with particular emphasis on the position of the aortic retention ring. Careful assessment of ductal anatomy must guide case selection.

The safety and success rate of sputum induction using a low output ultrasonic nebuliser

Abstract: Induced sputum differential cell counts have been advocated as a method of non-invasively assessing airway inflammation in asthma and other airway diseases. Since sputum induction usually involves delivering hypertonic saline via a high output ultrasonic nebulizer there have been concerns about its safety in asthma. There are relatively little data on the effects of sputum induction in large numbers of patients. We have examined the success rate and effect of sputum induction on forced expiratory volume in 1 sec (FEV1) in 100 inductions performed on 79 patients using a low output nebulizer. Thirty-seven patients had asthma, 29 had miscellaneous conditions (mainly chronic cough) and 13 were subjects without respiratory symptoms. Sputum was induced 10 min after 200 micrograms of inhaled salbutamol by sequential 5-min inhalations of 3, 4 and 5% saline delivered via a Fisoneb ultrasonic nebulizer and FEV1 was measured after each inhalation. Sputum induction resulted in a sample suitable for analysis in 92% of asthmatics, 90% of those with miscellaneous conditions and 100% of normal subjects. The mean (SEM) maximum per cent fall in FEV1 was 5.4% (0.1), 4.3%, (1.0) and 2.6% (1.1) in subjects with asthma, miscellaneous conditions and in asymptomatic subjects respectively. Only 13 inductions resulted in a > 10% fall in FEV1, and only three of these resulted in a > 20% fall. The maximum per cent fall in FEV1 did not correlate with baseline FEV1 % predicted (r = -0.17), the log sputum eosinophil count (r = -0.12), or the methacholine PC20 (r = -0.14). We conclude that sputum induction using a relatively low output ultrasonic nebulizer with premedication with salbutamol is successful and safe in the majority of patients with asthma and other airway conditions.

P- and L-selectin mediate binding of T cells to chronically inflamed human airway endothelium.

Abstract: The inflammatory process that underlies allergic diseases such as asthma is characterized by tissue infiltration of eosinophils and T cells. We have used the Stamper-Woodruff frozen-section assay to characterize the receptors involved in adhesion of human peripheral blood T cells to nasal polyp endothelium (NPE) as a model of T cell migration in allergic disease. T cells bound specifically to NPE in a temperature-, cell concentration- and shear stress-dependent fashion. Adhesion was inhibited by approximately 70% by antibodies against P-selectin and its counter-receptor P-selectin glycoprotein-1 (PSGL-1). In addition, a blocking monoclonal antibody (mAb) against L-selectin caused significant although lesser inhibition. Cells adhering to NPE were primarily of the CD45RO+ memory subset. Although only a minority subset of peripheral blood T cells expressed functional PSGL-1, as determined by binding of a P-selectin Fc chimera, the majority of the P-selectin chimera-binding cells were found to be CD45RO+. This is consistent with the observation that memory T cells bind to NPE via P-selectin. Using blocking mAb we also investigated which integrins and their counter-structures were involved in T cell binding. A combination of anti-beta1 and beta2 mAb was able to inhibit adhesion by almost 50%. An antibody against intercellular adhesion molecule (ICAM)-2 gave an inhibition similar to that by anti-CD18 mAb, suggesting ICAM-2 was the major counter-receptor involved for the beta2 integrin component. This study suggests that P-selectin, and to a lesser extent L-selectin, may be acting as specific homing receptors for the airway mucosa in the context of chronic allergic disease.

Video-assisted thoracoscopic surgery for spontaneous pneumothorax--a 7-year learning experience.

Abstract: OBJECTIVES: To determine the effect of increasing experience of video-assisted thoracoscopic surgery (VATS) in the treatment of spontaneous pneumothorax (SP) on clinical efficacy and surgical practice. PATIENTS AND METHODS: A prospective study of 180 consecutive operations in 173 patients who underwent VATS for SP by a single surgeon during a 7 year period. RESULTS: 118 patients, mean age 32.1 years (range 13-63 years), were treated for primary spontaneous pneumothorax (PSP) while 55 patients, mean age 65.9 years (range 28-92 years), were treated for secondary spontaneous pneumothorax (SSP). All patients had VAT parietal pleurectomy combined in 162 (90%) patients with stapled bullectomy. At a current median experience of 2.0 years (range 0.4-6.8 years), 12 (6.6%) patients required reoperation for treatment failures within 12 months of surgery--9 patients within 30 days of VATS and 3 for late recurrent pneumothorax. Two patients (both with SSP) died within 30 days of surgery. When compared with PSP, VATS in SSP is characterized by an elderly, male predominance, a longer postoperative stay, a higher mortality rate and a lower rate of late recurrence. With increasing experience of the technique, there has been a significant decrease in treatment failures. In the treatment of PSP, both operating time and postoperative stay have decreased significantly with experience whilst the use of staple cartridges per patient has increased significantly with experience in both PSP and SSP. CONCLUSION: There is a demonstrable 'learning curve' effect on the clinical efficacy and surgical practice of video assisted thoracoscopic surgery for spontaneous pneumothorax.

Increases in eotaxin-positive cells in induced sputum from atopic asthmatic subjects after inhalational allergen challenge.

Abstract: Background: Eosinophils are believed to be critical proinflammatory cells in airway mucosal damage in asthma. Eotaxin is a C-C chemokine with selective activity for eosinophils and basophils. Previous studies have shown increased expression of eotaxin in the airways of asthmatics at baseline. We aimed to investigate eotaxin expression during the late-phase reaction to allergen inhalation in atopic asthmatics. Methods: Sputum induction was performed before and 24 h after inhalational allergen challenge in atopic asthmatics, and eotaxin protein was detected immunocytochemically. Results: Thirteen patients with a mean decrease in forced expiratory volume in 1 s of 28% (±1.5) during the early asthmatic reaction, and 39% (±4.7) during the late asthmatic reaction produced sufficient sputum for study. The percentage of eosinophils in sputum was increased 24 h after allergen challenge (P<0.004), and eosinophil percentages in sputum after challenge correlated with the magnitude of the late-phase reaction (r=0.56, P=0.05). The percentage of eotaxin-positive cells increased from 12.6% (range 2–43.8) to 24.3% (8.1–47.1, P<0.005). Allergen-induced increases in eotaxin-positive cells correlated with increases in eosinophils (r=0.63, P<0.01). Conclusions: These findings suggest that eotaxin may contribute to allergen-induced recruitment of eosinophils to the airway in asthmatic subjects.

Objective quantitative analysis of eosinophils and bronchial epithelial cells in induced sputum by laser scanning cytometry.

Abstract: BACKGROUND Sputum induction is an important non-invasive technique for measuring airway inflammation in asthma. Cell numbers are often too low for flow cytometric analysis. Laser scanning cytometry (LSC) is a novel technique that allows objective multicolour fluorescence analysis of cells on a microscope slide. METHODS LSC was used to determine sputum eosinophil and bronchial epithelial cell counts. We first confirmed that we could measure eosinophil counts accurately in peripheral blood using α-major basic protein (MBP) immunofluorescent staining. Sputum induction was performed according to standard protocols. Sputum samples from eight normal controls and 12 asthmatic patients were analysed by LSC and manual counting by two independent observers. Octospot cytospins were fixed and stained with mouse-α-human-MBP monoclonal antibody or mouse-α-human-cytokeratin antibody and goat-α-mouse Oregon Green conjugated second antibody. RESULTS Sputum induction provided a mean (SE) of 0.99 (0.2) × 106 cells per donor. More than 3000 cells on three cytospins per slide were analysed per cell type. The intraclass correlation coefficient (R) and standard deviation (SD) of differences in eosinophils determined by manual counting and LSC were 0.9 and 2.1, respectively, and for bronchial epithelial cell counts they were 0.7 and 2.0. Selective detection of labelled cells was confirmed visually after relocation. CONCLUSION Eosinophils and bronchial epithelial cells can be accurately and reproducibly counted in an objective manner. LSC is therefore a potentially powerful new method for immunophenotyping leucocytes and epithelial cells objectively in induced sputum in patients with asthma.

Characterization of the integrin and activation steps mediating human eosinophil and neutrophil adhesion to chronically inflamed airway endothelium.

Abstract: We have used the Stamper–Woodruff frozen-section assay (FSA) to characterize the integrin and activation steps involved in adhesion of peripheral blood eosinophils and neutrophils to nasal polyp endothelium (NPE). Eosinophil and neutrophil adhesion was significantly inhibited by monoclonal antibodies (mAbs) against CD18 (β2) and CD11a-c. Eosinophil adhesion was also inhibited to a lesser extent by mAbs against CD29 (β1), CD49d (α4), and vascular cell adhesion molecule-1. The involvement of integrins raised the possibility of an activation step being involved in the adhesion process. Although stimulation of the cells with granulocyte macrophage colony-stimulating factor (GM-CSF) before the assay failed to modulate adhesion, binding was inhibited by up to 50% by treatment of the leukocytes with azide. In addition, neutrophil adhesion was completely abrogated by pertussis toxin (PT) and inhibited by about 50% by the platelet-activating factor antagonist WEB 2086 and antibodies against interleukin (IL)-8 and ...

Between-observer repeatability of sputum differential cell counts. Influence of cell viability and squamous cell contamination.

Abstract: Background Induced sputum differential cell counts have been advocated as a method of noninvasively assessing airway inflammation in asthma and other airway diseases. Relatively little is known about the between-observer repeatability of sputum differential cell counts and the factors that influence it. Objective To assess the between-observer variability of induced sputum cell counts. Methods Sputum was induced and processed using standard techniques. Forty-two slides from 38 patients (31 with asthma, seven normal subjects) were randomly selected. Slides were classified as good ( 50% viability; n = 24); low viability ( 20% squamous cells; n = 8). Two blinded observers counted between 200 and 400 nonsquamous cells and agreement was assessed by the intraclass correlation coefficient (ICC) and the standard deviation of between-observer differences ( sd). Results The overall ICC were 0.9, 0.89, 0.9 for eosinophils, neutrophils and macrophages and 0.29 and 0.69 for lymphocytes and epithelial cells. Repeatability was greater in slides classified as good compared with slides with low cell viability and particularly excess squamous cell contamination. Conclusions We have shown that the overall between-observer repeatability of the differential eosinophil, neutrophil and macrophage cell counts is good. Low cell viability and particularly excess squamous cell contamination reduce between-observer repeatability suggesting that techniques that ensure high cell viability and reduce squamous contamination would be an advantage.

The reproducibility of measurement of shoulder movement.

Abstract: To study the reproducibility of the measurement of shoulder movement, we have examined a series of 64 patients with and without shoulder problems, measuring active elevation, abduction, and external rotation in adduction using an inclinometer. The difference within which readings by different observers were expected to lie for 95% of the pairs of observations ranged from 24° to 33° for different movements in asymptomatic shoulders and from 24° to 41° in those with unilateral shoulder symptoms awaiting surgery.

Tubing failure during prolonged roller pump use: a laboratory study.

Abstract: Little is known about the mechanical forces acting on extracorporeal circuit tubing with prolonged roller pump use during extracorporeal membrane oxygenation (ECMO). We examined the time to tubing rupture of three different materials during actual roller pump use, mean and standard deviation (SD) (SD shown in parentheses): Tygon (control) 243.7 h (175.4); LVA 121 h (14.3); and SRT 6.6 h (2.1). Failure times for both LVA and SRT were significantly different from the control (paired t-test, p = 0.02 and p < 0.001, respectively). The minimum failure times for Tygon and LVA were 99 and 101 h, respectively. We then examined Tygon under conditions of pure compression, demonstrating that even after 3.67 million compression cycles at full occlusion crack formation did not occur. If the tubing was over-occluded, cracks appeared within 24 h. Scanning electron microscopy of Tygon, which has been used during clinical ECMO, and the failure pattern during destruction testing demonstrate that shear stress and compression coexist during clinical ECMO. Use of under-occlusive pump settings could improve tubing life.

As-required versus regular nebulized salbutamol for the treatment of acute severe asthma

Abstract: Current British guidelines for the administration of beta2-agonists in acute severe asthma recommend regular nebulized therapy in hospitalized patients, followed by as-required (p.r.n.) use via hand-held devices after discharge. Since beta2-agonists do not possess anti-inflammatory activity in vivo, and are thus unlikely to influence the rate of recovery from an asthma exacerbation, it was hypothesized that patients given the short-acting beta2-agonist salbutamol on an as-required basis after admission to hospital would recover as quickly as those on regular treatment, but with potential reductions in the total dose delivered. Forty-six patients with acute severe asthma were randomly assigned to either regular prescriptions of nebulized salbutamol or to usage on a p.r.n. basis, from 24 h after hospital admission. The primary outcome measures were length of hospital stay, time to recovery, and frequency of salbutamol nebulization from 24 h after admission to discharge. Secondary outcome measures were treatment side-effects (tremor, palpitations), and patient satisfaction. Length of hospital stay was reduced in those patients allocated to p.r.n. salbutamol (geometric mean (GM) 3.7 days) versus regular salbutamol (GM 4.7 days). Time taken for peak expiratory flow to reach 75% of recent best was the same in both groups. There was a highly significant reduction in the number of times nebulized therapy was delivered to the p.r.n. group (GM 7.0, range 1-30) compared with the regular treatment group (GM 14.0, range 4-57; p=0.003; 95% confidence interval for ratio of GMs 1.29-3.09). In addition, patients reported less tremor (p=0.062) and fewer palpitations (p=0.049) in the p.r.n. group. Of the patients in the p.r.n. group who had received regular nebulized therapy on previous admissions (n=12), all preferred the p.r.n. regimen. Prescribing beta2-agonists on a p.r.n. basis from 24 h after hospital admission is associated with reduced amount of drug delivered, incidence of side-effects, and possibly length of hospital stay. This has implications for the efficient use of healthcare resources.

The prediction of benefit from pulmonary rehabilitation: setting, training intensity and the effect of selection by disability

Abstract: This study tested the hypothesis that severity of respiratory disability may affect the outcome of pulmonary rehabilitation. In this randomized, controlled study, 126 patients with chronic obstructive pulmonary disease (COPD) were stratified for dyspnoea using the Medical Research Council (MRC) dyspnoea score into MRC3/4 (Moderate) (n=66) and MRC 5 (Severe) dyspnoeic (n=60) groups. The patients were randomly assigned to an eight week programme of either exercise plus education (Exercise group) or education (Control group). Education and exercise programmes for the moderately dyspnoeic patients were carried out in a hospital outpatient setting. Severely dyspnoeic patients were all treated at home. Those in the Exercise group received an individualized training programme. There was a significant improvement in shuttle walking distance in the moderate dyspnoeic group, who received exercise training; baseline (mean±SEM) 191±22 m, post-rehabilitation 279±22 m (p<0.001). There was no improvement in exercise performance in the severely dyspnoeic patients receiving exercise. Neither group of control patients improved. Health status, assessed by the Total Chronic Respiratory Disease Questionnaire score, increased in the moderately dyspnoeic patients receiving exercise from 80±18 to 95±17 (p<0.0001) after rehabilitation. Much smaller changes were seen in the other three groups. Improvement in exercise performance and health status in patients with chronic obstructive pulmonary disease after an exercise programme depends on the initial degree of dyspnoea. (Eur Respir J 1998; 12:363–9)

Measuring postural changes in blood pressure in the healthy elderly.

Abstract: BACKGROUND: Background The reproducibility of postural changes in blood pressure of a healthy elderly population determined using standard clinical measurements is not known. OBJECTIVE: To assess the differences in reproducibility of postural changes in blood pressure in healthy elderly subjects 1 and 3 min after standing within a day and between visits spaced 6 weeks apart. METHODS: Casual readings of blood pressures of supine and standing subjects were measured twice during the day by the same observer on two occasions 6 weeks apart using a semi-automatic syphgmomanometer. Twenty-two subjects with no known risk factors for orthostatic hypotension (13 men) aged 69+/-3 years (mean+/-SD) with a mean initial screening supine blood pressure of 153+/-19/88+/-11 mmHg were recruited. RESULTS: There were significant differences(P<0.001) between the postural changes both for systolic and for diastolic blood pressure between 1 and 3 min of standing, the largest falls occurring after 1 min of standing, though we found no variation between morning and afternoon measurements and between visits. The coefficients of reproducibility between visits for the postural changes in blood pressure after 1 and 3 min of standing were large both for systolic and for diastolic blood pressure, ranging from 9.8 to 29.3 mmHg. CONCLUSIONS:There was a consistent and significant difference between the postural changes in blood pressure after 1 and 3 min of standing for this healthy elderly population, but there was no significant difference between the postural changes in morning and afternoon measurements and between visits. This marked variability in the postural change in blood pressure with duration of standing must be taken into account when assessing the prevalence of orthostatic hypotension and the effects of treatment in patients with orthostatic falls in blood pressure.

What should we do about blood pressure and stroke

Abstract: As we draw towards the end of this millennium, it will become clear whether the aspirations raised by the Health of the Nation document will be realized with regard to the reduction in mortality from stroke. The target of a 40% decrease in stroke deaths by the year 2000 in those aged 65–74 years may initially have appeared optimistic without any specific new interventions, but mortality rates have been consistently falling in both the UK and most, but not all, Westernized countries over the past 2–3 decades.1 This decrease in mortality is probably due to a combination of decreased stroke incidence and stroke severity, as well as a reduction in death rate following the acute event. However, in the UK there are still over 120 000 strokes per annum, about 20% being due to a recurrence. Overall, 20% will die within the first few months of the event, and up to 35% of the survivors will still be dependent after a year.2 Primary stroke reduction must come from attacking the major risk factors, of which hypertension remains the primary treatable cause. This editorial deals primarily with the relation between ischaemic stroke and blood pressure (BP), and the benefits or otherwise of BP reduction in both primary and secondary prevention. Data from prospective observational studies have highlighted the strong association between increasing BP levels and stroke incidence for both cerebral haemorrhage and infarction. In the Prospective Studies Collaboration, a meta-analysis of 45 studies involving 450 000 subjects aged 15–99 years with a mean follow-up of 16 years, diastolic blood pressure (DBP) levels were closely related to stroke risk after adjustment for other potential confounding variables; for every 10 mmHg DBP increase, stroke risk rose by 80%.3 However the BP/stroke relation varies with age, the gradient being much steeper in younger …

Maximizing the contribution doctors make to NHS management.

Abstract: Management is an increasingly important issue for many doctors. If doctors wish to influence resource allocation, they must involve themselves in health service management. This article describes the results of an enquiry action learning project involving six doctors. As part of the project, clinical directors and their business managers were interviewed. In addition, the Police Force and BAA (formerly the British Airport Authority) were visited and their management structure, out-of-hours activities and planning for emergencies assessed. This article examines the reasons why many doctors do not involve themselves in management, such as increased time commitment and negative peer pressure, and suggests some solutions to these problems, including the need for a wider understanding of the role of clinical directors. It also considers how some organizations are already starting to address these issues, and how both doctors and hospitals can benefit from greater involvement of doctors in health service management.

Inappropriate admissions to hospital: the views of nursing and residential homes.

Abstract: Acute admissions of older people from residential and nursing homes are often seen as inappropriate by both residential and hospital nursing staff. In this survey, nursing staff from the primary care sector were asked their views on these admissions. Their comments indicate that with better staff education, role support and more effective communication between the two sectors, the continuity of care would be improved. This, in turn, would reduce the number of unnecessary hospital admissions, and improve overall quality of care.

Breast cancer: outcome audit of axillary management in 1991

Abstract: AimsTo audit the outcome of axillary treatment of patients diagnosed with invasive breast cancer in 1991, with particular reference to the incidence of regional recurrence and lymphoedema after limited axillary dissection.MethodsA review of records of patients identified prospectively.ResultsTwo per cent regional recurrence and 5.7% lymphoedema incidence at 5 years.ConclusionsThere is no indication from these results that axillary treatment, for our patient population, should be more aggressive.

Allergen immunotherapy and mast cells.

Abstract: After initial enthusiasm for the mast cell as an orchestrator of allergic responses, a lull followed with the observations that mast cell-‘stabilizing’ drugs such as the b-adrenoreceptor agonists and cromones have little impact on the course of many allergic diseases. However, interest in mast cell biology has been rekindled with the observation that mast cells are a source of many pleiotropic cytokines and proteases, with good evidence now that mast cells are involved in many diverse immunopathological events (reviewed in [1]). In fact, a month rarely passes without publication of a novel report on mast cell activity of relevance to human pathophysiology. This issue of Clinical and Experimental Allergy continues this theme, with the observation by Durham and colleagues that administering intradermal allergen immunotherapy to patients with severe hay fever induces a marked reduction in cutaneous mast cell numbers [2]. Interpretation of the mechanism behind this is speculative, so before discussing it further, I will provide a brief outline of the factors which control tissue mast cell numbers in health and disease.

Revised prognostic table to guide practitioners advising patients on adjuvant systematic therapy in early breast cancer.

Abstract: Two publications during 1998 from the Early Breast Cancer treatment, with the improved survival to be expected from the use of tamoxifen or polychemotherapy. The estimated Trialists Group have influenced the recommendations on benefit is taken from the relevant meta-analysis; for systemic treatment given to women newly diagnosed with polychemotherapy this depends on the patient’s age. breast cancer. These meta-analyses have been summarized Considering examples, adjuvant polychemotherapy has with the statement that all breast cancer patients should now long been considered appropriate for a pre-menopausal, be offered both adjuvant tamoxifen and polychemotherapy. node-positive woman. Accordingly, Table 1 shows that for This is, of course, an oversimplification. a woman with a 2.5-cm, moderately differentiated tumour Tamoxifen and, to a greater extent, chemotherapy have with involvement of two axillary nodes the 10-year survival side-effects which must be balanced against the expected without systemic treatment is in the region of 50%, benefits. The measured benefit from polychemotherapy improving to 64% with chemotherapy and further with diminishes with patient age and the tolerance of side-effects tamoxifen. However, if she were 65 years of age, her life decreases. Moreover, those with the earliest diagnosed breast expectancy would improve by only 4% with chemotherapy. cancer have an excellent prognosis, the same as age-matched She might be frail and unable to tolerate chemotherapy women who have never had breast cancer, which could not easily and one might then recommend reliance on tamoxifen be improved by adjuvant therapy. The data indicate that alone, if the tumour were oestrogen receptor positive, adjuvant tamoxifen does not improve survival in patients expecting a 13% improvement in projected survival. with tumours that have no detectable oestrogen receptors. Conversely, a fit 65-year-old with no detectable oestrogen However, in any patient, the 47% reduction in the incidence receptors in her tumour might be better offered of contralateral tumours can be considered a justification polychemotherapy despite the side-effects and might not for tamoxifen treatment. live to see the benefit in reduced risk of a second primary While the percentage reduction in the risk of death that that tamoxifen offers. Table 1 enables the benefits of can be achieved with systemic treatment now appears to be treatment for the individual woman to be estimated at a independent of the stage of the patient’s tumour at the time glance. of diagnosis, the absolute benefit to the individual depends Table 1 has been incorporated in the Leicestershire on her prognosis. With more data from larger numbers Guidelines for the Diagnosis and Management of Breast followed for longer after randomized controlled trials of Cancer and the text of this document gives further details. treatment, the range of patients in whom benefit has been For tamoxifen this includes the following: demonstrated is now wider and there are now groups in whom statistically significant benefit has been demonstrated, “Tamoxifen results in a 26% reduction in the risk of death but that benefit is small. at 10 years from diagnosis in patients of all ages and for It is necessary, therefore, for clinicians to be able to tell all tumours except those with no oestrogen receptor the individual patient what her estimated absolute benefit activity. Even in oestrogen-receptor negative tumours and might be. In the clinic this requires knowledge of the those with an excellent prognosis the 47% reduction in woman’s prognosis and the improvement to be gained from the incidence of contralateral tumours is a justification systemic treatment(s), which can then be discussed together for treatment. Therefore all patients should be offered with the likely side-effects. In order to do this I have adjuvant tamoxifen for 5 years unless side-effects prevent constructed a table (Table 1) which groups tumours into continuation. Younger women may have more the prognostic groups identified by Blamey et al. in the troublesome short-term side-effects than older women; construction of the Nottingham Prognostic Index, and tamoxifen should not be recommended in those who may become pregnant. Pregnancy cannot be reliably prevented then lists the 10-year survival without any systemic

Chronic haemoptysis as delayed complication of ventricular aneurysmectomy.

Abstract: Two patients developed a ventriculo-pulmonary fistula several years after original resection of a left ventricular aneurysm. Both presented with chronic mild haemoptysis. In the first case mild haemoptysis lasted nearly 19 months, and despite a battery of non invasive and invasive investigations, diagnosis was ultimately made via exploratory thoracotomy. In the second case mild haemoptysis lasted four months and finally manifested as a large haemoptysis. Diagnosis was made preoperatively using echocardiography. We recommend the use of echocardiography when haemoptysis occurs in a patient with a previous history of ventricular aneurysm repair.