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Biomedical subjects

M F Muers

Publications and source records attributed to M F Muers.

14 recordsLinked to original sources

Response to nebulized ipratropium bromide and terbutaline in acute severe asthma.

Outpatient studies on asthmatics have shown that inhaled anti-cholinergic agents decrease in efficacy as FEV1 falls. To determine whether there are changes in response to inhaled anti-cholinergics during acute bronchoconstriction we have examined the effects of nebulized ipratropium and terbutaline in nine hospitalized patients recovering from acute severe asthma. At 6 a.m. each day throughout the admission, baseline PEFR was recorded. Ipratropium bromide, 1 mg, was nebulized and PEFR measured again 1 h later. Following this, terbutaline, 5 mg, was nebulized with further measurement of PEFR 15 min after nebulization. Results were analysed by paired t-tests. Mean baseline PEFR rose from 157 l m-1 on patients worst day to 300 l m-1 on their best day (P less than 0.01). Ipratropium improved mean PEFR by 55 l m-1 and 42 l m-1 on patients worst and best days respectively (P less than 0.01). Subsequent terbutaline improved mean PEFR on patients worst day by 23 l m-1 (P less than 0.01) but only by a non-significant 4 l m-1 on their best day (P = 0.09). Hence, ipratropium produced 96% of total bronchodilatation when baseline was highest, but achieved only 71% of total response when baseline was lowest, a highly significant change in response (P less than 0.01). We conclude that in acute severe asthma as baseline PEFR rises response to inhaled ipratropium improves, compared with total response to combined ipratropium followed by terbutaline.

Acute Disease

Simplifying the assessment of patients with chronic airflow limitation for home nebulizer therapy.

One-hundred nebulizer trials were performed in 98 adult patients with chronic airflow limitation who had remained symptomatic despite regular use of bronchodilators by metered dose or dry powder inhalation. Mean baseline FEV1 was 0.9 (SD = 0.41) 1, FVC -2.0 (0.74) 1 and PEFR 169 (77) 1 min-1. After laboratory measurements of reversibility to inhaled salbutamol (5 mg) and ipratropium bromide (0.5 mg), patients were supplied with a compressor and a peak flow meter to make twice daily measurements at home for 3 weeks. They nebulized normal saline, salbutamol (5 mg) and salbutamol (5 mg) ipratropium (0.5 mg) mixture 6-hourly, each for 1 week. A positive nebulizer trial was defined as a 15% increase in mean PEFR over a week on an active treatment compared to the week on saline. Twenty-eight patients had positive trials based on these criteria. Of these nine responded to both active treatments and 16 to the salbutamol/ipratropium mixture. Although no laboratory measurements predicted a positive domiciliary trial, the patients' subjective assessment of benefit had a 93% sensitivity and 87% negative predictive value. We conclude that an appropriate protocol for assessing the value of long-term nebulized bronchodilators is for patients to measure their PEFR during a week of nebulized saline and a week of nebulized beta-agonist/ipratropium mixture. Those with an increase of 15% in mean PEFR in the week on active treatment and who experienced subjective benefit should be supplied with a compressor. Had we conducted our 100 trials in this way we would have started 25 of our 98 patients on long-term home nebulized bronchodilators.

Adult

Comparisons between basal metabolic rate and diet-induced thermogenesis in different types of chronic obstructive pulmonary disease.

1. Some patients with the emphysematous type of tobacco-related chronic obstructive pulmonary disease are hypermetabolic. Since the likely mechanism is the increased work of breathing, other groups of patients with chronic obstructive pulmonary disease should be similar. We have now measured basal metabolic rate and diet-induced thermogenesis in six patients with chronic obstructive pulmonary disease with an arterial partial pressure of CO2 of less than 5 kPa (emphysematous), nine patients with chronic obstructive pulmonary disease with an arterial partial pressure of CO2 of greater than 6 kPa (bronchitic), eight patients with chronic obstructive pulmonary disease due to chronic asthma and seven control subjects. Diet-induced thermogenesis was measured for 4h after a meal of 87% carbohydrate, 11% protein and 2% fat as energy, with a total energy content of 40% of basal metabolic rate. 2. There was no difference between measured and predicted basal metabolic rate in the control (5541 +/- 272 versus 5881 +/- 245 kJ/24h) or emphysematous (5552 +/- 370 versus 6239 +/- 197 kJ/24h) groups, but measured basal metabolic rate was significantly higher than predicted in the bronchitic (6126 +/- 387 versus 5405 +/- 250 kJ/24h) and asthmatic (6293 +/- 197 versus 5701 + 245, mean +/- SEM, P less than 0.01) groups. All the control subjects had measured basal metabolic rates within 10% of predicted, whereas two out of six emphysematous patients, four out of nine bronchitic patients and five out of eight asthmatic patients were hypermetabolic. The contributions of fat, carbohydrate and protein oxidation rates to the overall basal metabolic rate were similar between groups. 3. Diet-induced thermogenesis was similar between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Anthropometry

Assessing physiological benefit from domiciliary nebulized bronchodilators in severe airflow limitation.

In steroid resistant chronic obstructive pulmonary disease (COPD) we assessed the effect of q.i.d. domiciliary nebulized fenoterol (F) 1.25 mg and ipratropium (I) 0.5 mg for three weeks in a placebo-controlled, randomized, double-blind, crossover study. The twenty patients studied (mean forced expiratory volume in one second (FEV1) 0.8 l) all showed less than 20% increase in FEV1 to 200 micrograms inhaled salbutamol (S) and less than 20% increase in peak expiratory flow rate (PEFR) after 2 weeks prednisolone therapy. Respiratory function tests, 5 min walking distance (5 MWD), visual analogue scales (VAS) for breathlessness, oxygen cost diagrams and reversibilities were performed weekly for three weeks with patients on their usual therapy, after three weeks domiciliary F+I, after three weeks saline and, finally, after a further three weeks on usual therapy again. Primary end-points, selected prior to unblinding, were mean home twice daily PEFR, trapped gas volume, FEV1 and 5 MWD. Home PEFR rose from 164 l.min-1 on saline to 196 l.min-1 on F+I (p = 0.0001). Secondary end-point analysis revealed a fall in home inhaler usage and a rise in VAS. Using the criterion of +15% and greater than 20 l.min-1 increase in home PEFR, 11 out of 20 patients had a "positive" trial. We suggest that such patients, but not others, benefit from long-term, nebulized beta 2-agonist and ipratropium. Trials using home PEFR recordings should be used to identify them.

Aged

Reversibility tests in chronic obstructive airways disease: their predictive value with reference to benefit from domiciliary nebuliser therapy.

The role of short-term tests of reversibility in selecting patients with COAD for long-term nebuliser therapy is uncertain. In a double-blind placebo-controlled crossover study we have examined the correlation between short-term reversibility and response to a home nebuliser. We studied 20 patients with severe COAD (mean age 66, mean FEV1 0.81 l) and little reversibility (less than 20% increase in FEV1 post-inhaled salbutamol 200 micrograms and less than 25% increase in peak expiratory flow rate, PEFR, on oral steroids). PEFR, spirometry, lung volumes and airways conductance were recorded before and 1 h after a mixture of nebulised ipratropium 0.5 mg and fenoterol 1.25 mg. Patients then recorded twice-daily PEFR at home while they received nebulised ipratropium plus fenoterol, or saline placebo, four times a day for three week blocks using a double-blind cross over protocol. Mean PEFR on home nebuliser rose from 164 l m-1 (placebo) to 196 l m-1 (ipratropium plus fenoterol), paired t-test P = 0.0001. Correlation coefficients between short-term response for PEFR, spirometry and lung volumes, and improvement in home PEFR on nebulised ipratropium plus fenoterol, were all poor (R = -0.37-0.35, P = 0.83-0.11). We conclude that in severe COAD, reversibility tests of PEFR, spirometry and lung volumes do not correlate with response to a home nebuliser. Home measurements of PEFR are probably the best objective method of assessing response to a home nebuliser in such patients.

Aged

The thermic effect of food in underweight patients with emphysematous chronic obstructive pulmonary disease.

Malnutrition and weight loss commonly occur in patients with the emphysematous type of chronic obstructive pulmonary disease (COPD), despite normal energy intakes. The present study was designed to assess energy expenditure, basal metabolic rate (BMR) and diet-induced thermogenesis (DIT) in ten patients with COPD, together with the oxidation rates of carbohydrate, protein and fat. The BMR was elevated when tested against the Harris-Benedict equation (p less than 0.001) or when compared with six age- and sex-matched controls (11.11 +/- 2.52 vs 8.12 +/- 1.31 kJ.h-1.kg muscle-1, p less than 0.05). The main difference in fuel oxidation rate was an elevated fasting fat oxidation rate in the patients compared with controls (8.31 +/- 3.09 vs 4.76 +/- 2.53 kJ.h-1.kg muscle-1, p less than 0.05). The overall thermic response to food (41.2 kJ.kg-1 liquid meal) as a percentage of energy intake was greater in the patients (49.5 +/- 6.3 vs 39.8 +/- 2.9%, p less than 0.01). The patients also displayed a greater post-prandial rate of protein oxidation as a percentage of protein intake than controls (56.9 +/- 18.5 vs 34.1 +/- 6.5%, p less than 0.05). These data suggest an increased energy cost of feeding and fasting in patients with the emphysematous type of COPD.

Aged

Investigation, treatment and prognosis of bronchial carcinoma in the Yorkshire Region of England 1976-1983.

We studied all cases presenting during life with carcinoma of the bronchus and registered at the Yorkshire Regional Cancer Registry 1976-1983. During this period fibreoptic bronchoscopy became more widely available in the region, and multiple drug chemotherapy became first line treatment for small cell carcinoma. Although there was little change in the overall incidence of lung cancer during the study period, the proportion of females increased by 4.8% and the mean age at presentation rose by 2.3 years. The histological confirmation rate rose by 29% from 45% to 58%. The proportion of patients with small cell carcinoma treated by chemotherapy increased from 17% to 39%. With this exception therapeutic intervention rates were unaltered. The prognosis of patients with small cell carcinoma treated by chemotherapy improved, particularly so for those less than 60 years. There was a consistent trend for an overall improvement in survival in other groups, and this was significant for those aged 70 and over where it appeared to be related to more appropriate management of squamous cell carcinoma. We conclude from this regional study that increased diagnostic activity in District General Hospitals has allowed an improvement in prognosis both for patients with small cell carcinoma treated by chemotherapy, and in patients over 70 with non-small cell cancer. These trends can be expected to continue over the next few years.

Aged

Profiles of non-compliance with antituberculous therapy.

Treatment compliance was assessed by testing multiple urine samples for rifampicin in 113 consecutive patients taking a rifampicin containing regimen for tuberculosis. Nineteen (16.8%) patients had at least one negative urine sample after chromatographic analysis and these patients were more likely to be from social classes IV and V, to be Asian, and to have defaulted from at least one clinic appointment without good reason. A questionnaire was completed by 70 of the patients and four (6%) admitted to having omitted at least one treatment weekly; two of these also had at least one negative urine test. Physicians were only partly successful in identifying non-compliers. The relevance of these findings is discussed.

Adolescent

Reproducibility of walking test results in chronic obstructive airways disease.

Thirty six patients with chronic airflow obstruction were studied to examine (1) the reproducibility and order effect of repeated walking tests when performed over consecutive days or consecutive weeks; (2) the correlation between walking distance and spirometric measurements; and (3) the effect of static visual clues on performance. In study 1, where 12 patients performed 12 walks over three consecutive days, five minute walking distance increased by 33% between walks 1 and 12, half of the increase occurring after the first three walks. In study 2, where 24 patients performed 12 walks over four consecutive weeks, five minute walking distance increased by 8.5% between walks 1 and 12. A learning effect was seen over the first nine walks. Static visual clues to performance did not affect the distance walked. Spirometric measurements showed no order effect in either study. Although walking distance correlated significantly with FEV1, forced vital capacity, and peak expiratory flow, these measurements were poor predictors of exercise performance. The learning effects seen on repeated performance of walking tests over short intervals should be considered when an individual's response to treatment is being interpreted. When walking tests are used in clinical trials a placebo group or randomised crossover design is essential.

Aged

Evaluation of a radioimmunoassay for neuron specific enolase in small cell lung cancer.

A radioimmunoassay for neuron specific enolase (NSE), a marker of neuroendocrine differentiation, has been evaluated in small cell lung cancer (SCLC). In untreated patients 25/38 (68%) with localized SCLC had raised blood levels of NSE (greater than 13 ng ml-1), in extensive disease 34/39 (87%) patients had raised NSE levels. In patients with non-small cell lung cancer (NSCLC) the serum levels were raised in 16/94 (17%). In extensive tumours of non-pulmonary origin NSE levels were increased in 24/116 (20%) patients. Longitudinal studies indicated a good correlation between the response to chemotherapy and fall of NSE levels. Tumour progression was accompanied by a rising NSE in 25/29 patients, with doubling times of 7-90 days. In patients with progression with a normal NSE the recurrence was a NSCLC. Cerebral metastases occurring as the only recurrence during clinical complete remission were not accompanied by a rise of NSE. Serum NSE levels provides a valuable monitor for SCLC during and after chemotherapy.

Carcinoma, Small Cell