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Biomedical subjects

N P Keaney

Publications and source records attributed to N P Keaney.

At least 19 recordsLinked to original sources
PubMed1998

Asthma in the elderly: underperceived, underdiagnosed and undertreated; a community survey.

Bronchial asthma is now increasingly recognized in the elderly and is associated with significant morbidity and mortality. The aims of this study were two-fold: first, to assess the prevalence and, second, to evaluate diagnostic awareness, therapeutic management and patient perception of bronchial asthma among elderly patients in the community. From the age-sex register of an urban general practice in NE England, 2004 patients aged > 65 years were eligible for inclusion. Response to an initial screening questionnaire on respiratory symptomatology was 68% (n = 1362). Of these, 869 patients had respiratory symptoms: 390 voluntarily agreed to be evaluated further including assessment of airway physiology. In this group 369/390 had obstructive spirometry and, of these, 95 patients fulfilled clinical and physiological criteria of bronchial asthma. Prevalence of asthma within this age cohort was minimally and rather crudely assigned at 4.5% (95/2004). Among the 95 patients so-defined patients with asthma [age 70 +/- 8 years (mean +/- SD), FEV1 = 0.96 +/- 0.41, 33 male, 75 life-long non-smokers], subjective awareness, perception and attribution of pulmonary symptoms were poor. Further, despite tangible evidence of reversible and significant airflow limitation, only 21 were receiving inhaled glucocorticoid therapy (median daily dose 400 micrograms). Asthma in the elderly remains poorly perceived, poorly recognized and suboptimally treated. These findings are particularly apposite in the light of current epidemiological trends in asthma mortality and morbidity in elderly age cohorts.

Aged↗
PubMed1995

Association of HLA-DR4, protease inhibitor phenotypes and keratoconjunctivitis sicca with pulmonary abnormalities in rheumatoid arthritis.

One-hundred rheumatoid arthritis (RA) patients were assessed for the association of HLA-DR4, protease inhibitor (Pi) phenotype and keratoconjunctivitis sicca (KCS) with a variety of clinical features, airflow obstruction and bronchial reactivity. Spirometry, lung volume and gas transfer factor measurements were performed to detect airflow obstruction. Bronchial reactivity to inhaled methacholine was assessed by measuring the provocative dose of methacholine causing a 20% fall in FEV1 from the baseline (PD20). Sixty-two patients were HLA-DR4 positive, 87 had Pi MM and 13 MS phenotypes and 37 had positive Schirmer's tear tests. Patients with KCS had a significantly increased history of wheeze (11/37 vs 7/63, P = 0.03, relative risk (RR) 1.8 [95% CI 1.04, 3.1]), those with HLA-DR4 had a significantly decreased atopy on skin-prick testing [3/62 vs 7/38, were significantly higher in the Pi MS group compared to Pi MM group. There was no significant association of HLA-DR4, Pi phenotype and KCS with bronchial reactivity. We conclude that there is no overall significant association of HLA-DR4, Pi phenotype and KCS with airflow obstruction and bronchial reactivity in RA.

Adult↗
PubMed1995

High resolution computed tomography of the lung in lifelong non-smoking patients with rheumatoid arthritis.

OBJECTIVES: To define pulmonary involvement on high resolution computed tomography (HRCT) of the thorax in lifelong non-smoking rheumatoid arthritis patients and to relate the results to pulmonary function, bronchial reactivity, and a variety of clinical and serological factors. METHODS: Twenty lifelong non-smoking RA patients (mean age 59 years (range 44-72; 18 females) were studied. Detailed medical and drug histories were taken. Protease inhibitor phenotype (Pi) and HLA-DR4 status were assessed. Schirmer's tear tests were performed to detect keratoconjunctivitis sicca (KCS). Spirometry, flow volume loops, and gas transfer factor measurement were recorded. The degree of bronchial reactivity (PC20 FEV1) was measured by a methacholine inhalation test. Chest and hand radiographs and HRCT of the lung were performed in all patients. RESULTS: Thirteen patients were HLA-DR4 positive. Eighteen had the Pi MM and two the Pi MS phenotype. Eight patients had evidence of KCS on Schirmer's tear testing. Ten patients achieved PC20 FEV1 in the methacholine inhalation test. All the patients had normal chest radiographs and all showed evidence of erosive arthropathy on hand radiographs. Five patients (25%) showed basal bronchiectasis and one mild interstitial lung disease on HRCT. All five patients with bronchiectasis had the Pi MM phenotype, four had HLA-DR4, four had KCS and three achieved PC20 FEV1; these values were not significantly different (p > 0.05) from those in patients without bronchiectasis. CONCLUSION: Using the highly sensitive technique of HRCT, we found evidence to suggest that the incidence of bronchiectasis in lifelong non-smoking RA patients may be much higher than previously reported.

Adult↗
PubMed1994

Glutaraldehyde, asthma and work--a cautionary tale.

A 46-year-old endoscopy nurse developed symptoms suggestive of occupational asthma after seven years of exposure to glutaraldehyde. An initial inhalation challenge test at the endoscopy suite caused a very dramatic immediate fall in FEV1 from 3.6 to 1.5 litres. To further evaluate the case and establish a threshold for the response, a technique was devised to allow a series of double-blind inhalation challenges with activated glutaraldehyde vapour at exposure levels of 0.01-0.32 ppm. The results suggested marked dual asthmatic reactions following challenges with 0.032 ppm glutaraldehyde; however, similar 'reactions' were observed on control days. These were associated with an increase in airway responsiveness to methacholine, with the PD20FEV1 falling from > 6400 micrograms to 135 micrograms. The interpretation of these results was potentially confounded by an intercurrent respiratory tract infection and by technically poor FEV1 recordings, so the challenge series was repeated three weeks later. The second series of double-blind inhalation challenges with carefully controlled exposures to glutaraldehyde (up to 0.32 ppm for 10 min) gave rise to no obvious asthmatic reactions, in marked contrast to the results of the unblinded workplace challenge. There was a slight increase in airway responsiveness, with the PD20FEV1 falling from > 6400 micrograms to 1850 micrograms. These results illustrate the potential for misdiagnosis of occupational asthma when unblinded challenge tests are used and show that, even with sophisticated investigatory techniques, a clear-cut diagnostic result may be elusive.

Asthma↗
PubMed1994

Bronchial reactivity and airflow obstruction in rheumatoid arthritis.

OBJECTIVES: To investigate the prevalence of airways obstruction and bronchial reactivity to inhaled methacholine in rheumatoid arthritis patients and unselected controls. The control population consisted of patients attending the rheumatology department for minor degenerative joint problems. METHODS: One hundred patients with rheumatoid arthritis (RA) [72 (72%) women, 28 (28%) men; mean (SD) age 58 (10) years] and fifty controls [30 (60%) women, 20 (40%) men; mean (SD) age 56 (9) years] were studied. Detailed medical, smoking and drug histories were taken; skin prick tests were performed to assess atopy and chest and hand radiographs were performed. Spirometry, flow volume loops and gas transfer factor measurement were performed to detect airflow obstruction and methacholine inhalation tests were carried out to assess bronchial reactivity. RESULTS: There was no significant difference between rheumatoid arthritis patients and the controls in age, sex, smoking status and atopy on skin prick testing (p < 0.05). A significantly higher number of patients with RA had a history of wheeze compared with the controls (18% v 4%, p < 0.05). FEV1, FVC, FEV1/FVC, FEF25-75%, FEF25%, FEF50% and FEF75% were all significantly lower in the rheumatoid arthritis group (p < 0.05). A significantly higher number of patients with RA compared with controls showed bronchial reactivity to inhaled methacholine [55 (55%) v 8 (16%), p < 0.05]. FEV1, FVC, FEV1/FVC, FEF25-75%, FEF25%, FEF50% and FEF75% were all significantly lower among the patients with RA achieving PD20 FEV1 to inhaled methacholine (p < 0.05). CONCLUSION: In unselected rheumatoid arthritis patients both airflow obstruction and bronchial reactivity are significantly increased compared with controls.

Adult↗
PubMed1991

Bilateral thoracic empyema complicating adult epiglottitis.

Haemophilus influenzae is a common cause of epiglottitis and meningitis in children and exacerbation of chronic bronchitis in adults. However, the ability of this organism to cause serious infections in adults is less well recognized. We report a case of a 34-year-old previously healthy female who presented with epiglottitis and later developed bilateral empyema; both blood and pleural fluid grew Haemophilus influenzae.

Acute Disease↗
PubMed1989

Nedocromil sodium in adults with asthma dependent on inhaled corticosteroids: a double blind, placebo controlled study.

Eighty nine adults with asthma who were receiving inhaled corticosteroid and bronchodilator treatment took part in a double blind, randomised, placebo controlled trial of nedocromil sodium, 4 mg four times daily by inhalation. During a run in period of two to four weeks corticosteroid treatment was reduced when possible to produce a comparable level of symptoms across the trial population. The test treatment was then taken for four weeks, with the severity of asthma recorded daily by patients and assessed at two weekly hospital visits. There was an improvement in symptoms in the patients taking nedocromil sodium by comparison with those having the placebo, the differences being significant for diary card PEF readings, asthma symptom scores, and bronchodilator usage at night. The mean difference between the two groups was 18 l/min for PEF, 0.42 for daytime asthma score, and 1.73 puffs in 24 hours for bronchodilator usage. These results suggest that asthmatic patients who require inhaled steroids show better control of their asthma with the addition of nedocromil sodium than of placebo over a four week period after reduction of the dosage of their inhaled steroids.

Adolescent↗
PubMed1983

Dose-response comparison of ipratropium bromide from a metered-dose inhaler and by jet nebulisation.

The dose-response relationships of the anticholinergic bronchodilator drug ipratropium bromide were studied. Cumulative doses totalling 288 micrograms ipratropium were given by inhalation of a liquid aerosol from a Wright nebuliser to each of 10 patients with stable, moderately severe airflow obstruction. Up to 80% of the maximum achievable bronchodilator response, as assessed by a rise in the patients' mean forced expiratory volume in one second (FEV1), was obtained with a cumulative total dose of 72 micrograms; with additional doses beyond 72 micrograms there was no significant further improvement. In the same patients the effects of administration of cumulative doses of ipratropium to a total of 72 micrograms from a Wright nebuliser were compared with those achieved with a metered-dose inhaler. Bronchodilatation was assessed by measurement of peak expiratory flow rate, FEV1, forced vital capacity, thoracic gas volume and specific airways conductance (sGaw). No significant difference was observed in the response at any dose level between the wet and the dry aerosols. By fitting a curve to the mean values of FEV1 and sGaw an estimate was made of the dose of ipratropium bromide required to produce 99% of the achievable bronchodilator response. For FEV1 this dose was 78 micrograms when ipratropium was inhaled as a nebulised solution from the Wright nebuliser and 82 micrograms when it was inhaled from the metered-dose inhaler; for sGaw the respective values were 54 and 58 micrograms. In these patients with stable airflow obstruction there was no therapeutic advantage in the use of ipratropium bromide as a wet aerosol.

Adult↗
PubMed1980

Effect of an extension tube on the bronchodilator efficacy of terbutaline delivered from a metered dose inhaler.

A double-blind within-patient investigation was performed to determine whether the interposition of an extension tube (10 cm length X 3.2 cm diameter) between a metered dose inhaler and the mouth alters the bronchodilator efficacy of terbutaline sulphate. On two consecutive study days 14 adult patients with stable reversible airways obstruction inhaled a cumulative dose of 500 micrograms of terbutaline which was delivered from a metered dose inhaler with or without the extension tube attached and received placebo in a similar manner. The drug was inhaled in doses of 125, 125, and 250 micrograms at 20 minutes intervals. The following measurements were made: forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR), thoracic gas volume (TGV), and specific airways conductance (sGaw). These were done immediately before and at five and 15 minute intervals after each dose, and were repeated 90, 120, 180, 240, and 300 minutes after the first inhalation of terbutaline. Administration of terbutaline with and without an extension tube achieved significant bronchodilation at all dose levels in all respiratory variables (p < 0.001). There was no statistically significant difference in FEV1, FVC, PEFR, and sGaw values at any time or dose level with either method of administration. The use of the extension tube did not impair the efficacy or duration of action of inhaled terbutaline.

Adult↗
PubMed1978

Control of cerebral vascular smooth muscle during general anaesthesia.

The effects of some general anaesthetics, for example thiopentone, Althesin (alphaxalone + alphadolone) and ketamine, on cerebral vascular smooth muscle are those which would be expected from their metabolic actions. With other anaesthetics, mainly those administered by inhalation, and especially the volatile agents, cerebral blood flow increases in excess of the metabolic activity, which is usually depressed to varying degrees. During general anaesthesia with any of these agents, responses to changes in arterial Pco2 or blood pressure are maintained. Furthermore, when seizure activity occurs during enflurane administration, there is a flow response to the associated metabolic stimulation. The time course of the flow response to the metabolically depressant drug Althesin has been measured in baboons and shown to be very rapid. Wtih this drug cerebrovascular resistance begins to increase within 2 s of its arrival in the brain. This rapid flow change occurs also after sympathetic denervation. Extracellular fluid pH of the cortex does not alter until after the initiation of the vascular smooth muscle response.

Alfaxalone Alfadolone Mixture↗
PubMed1978

Time course of the cerebral circulatory response to metabolic depression.

Baboons anesthetized with halothane and N2O/O2 were given an intravenous steroid anesthetic (Althesin; Glaxo Laboratories Ltd., U.K.). The drug bolus was labeled with 99mTc, and the time from central venous injection to peak radioactivity in the brain was designated drug brain arrival (DBA-peak). The electroencephalogram slowed 1.2 +/- 0.9 s after DBA-peak (P greater than 0.2), and approximately 2 s after DBA-peak, internal carotid blood flow (ICarBF) decreased and calculated internal carotid vascular resistance (ICarVR) rose. During this 2-s delay in the cerebrovascular response to the arrival of a cerebral metabolic depressant in the brain, the decrease in mean cortical Pco2 was calculated to be less than 0.26 mmHg from cortical CO2 solubility, and less than 0.32 mmHg from cortical CO2 diffusivity, which indicated that mean cortical Pco2 changes do not control cerebral blood flow (CBF). The unaltered time course of the changes in EEG, ICarBF, and ICarVR after acute cervical sympathectomy and alpha-adrenergic receptor blockade excluded the involvement of the sympathetic nervous system in the vasoconstrictor response. Intracarotid Althesin showed that the cerebral vasoconstriction was not a direct effect of the drug. The postulated link between the effects of Althesin on CBF and cerebral metabolism remains to be elucidated but is probably indirect, involving the brainstem.

Adrenergic alpha-Antagonists↗