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Biomedical subjects

C O'Callaghan

Publications and source records attributed to C O'Callaghan.

At least 55 records · Page 3Linked to original sources
PubMed1997

Cough frequency and cough-receptor sensitivity are increased in man at altitude.

1. Travellers to high altitude often complain of paroxysmal cough, which has not been previously investigated. We recorded overnight cough frequency and cough-receptor sensitivity to inhaled citric acid in a group of climbers travelling to 5300 m or higher. 2. Cough frequency, monitored in ten subjects, increased from a median of 0 coughs at sea level (range 0-1) to 5 coughs at 5000 m (range 0-13) and to over 60 coughs in subjects ascending to 7000 m. Citric acid cough threshold, measured in 42 subjects, was unchanged on arrival at 5300 m compared with sea level (geometric mean difference 1.26, 95% confidence intervals 0.84-1.89, P = 0.25), but was significantly reduced after 6 days, or more, at altitude compared with sea level (geometric mean difference 2.2, 95% confidence intervals 1.54-3.15, P = 0.0002). Cough threshold was not related to symptoms of acute mountain sickness, oxygen saturation, carbon dioxide tension or lung function. 3. These results indicate an increase in cough and cough-receptor sensitivity after some days at altitude. This may be due to respiratory tract damage from breathing cold dry air at increased ventilatory rates. Other explanations, such as sub-clinical pulmonary oedema or an effect on the cough centre of acclimatization to altitude, cannot be excluded.

Altitude↗
PubMed1997

Nasal mucociliary transport is impaired at altitude.

There have been a number of anecdotal reports of rhinitis and nasal obstruction occurring at altitude. To quantify these reports, we investigated nasal obstruction and mucociliary transport in a group of healthy volunteers trekking to Mount Everest Base Camp, Nepal, altitude 5,300 m. Nasal obstruction was estimated by subjective scoring and mucociliary transport was determined by the saccharin method. Subjective assessment showed that nasal obstruction was increased on arrival at 5,300 m in 23 out of 54 subjects, unchanged in 24, and decreased in seven (McNemar's test: chi 2 = 7.5; p < 0.01). The median saccharin time at sea level was 11 min (95% confidence interval (95% CI) 8-17 min) and increased to 60 min (95% CI 27-60 min) on arrival at 5,300 m. Compared to sea level, the saccharin time was prolonged in 25 out of 33 subjects (McNemar's test: chi 2 = 14.7; p < 0.01), and remained prolonged after 2 weeks at altitude (median 60 min; 95% CI 38-60 min). These results confirm the subjective feelings of nasal obstruction and show that nasal mucociliary transport times are increased at altitude. The mechanisms of these findings are not clear, but nasal obstruction may impede breathing and adversely affect performance at altitude.

Adolescent↗
PubMed1997

In vitro comparison of the amount of salbutamol available for inhalation from different formulations used with different spacer devices.

Metered-dose inhalers (MDIs) are currently being reformulated to contain hydrofluoroalkanes (HFAs), which do not damage the Earth's ozone layer. As different formulations of inhaled drugs may behave differently when used with spacer devices, we wished to determine the amount of salbutamol available for inhalation from a conventional metered-dose inhaler (Ventolin) and a new HFA-containing formulation (Airomir), when used with two different spacers. A glass multistage liquid impinger was used to determine the amount of salbutamol delivered from the inhalers used with the Aerochamber and the Nebuhaler spacer devices. High speed video-recordings of inhaler actuation into air were made, and the speed of the aerosol and the aerosol cloud volume were measured. More salbutamol in small particles (<5 microm) was delivered from the Airomir MDI than the Ventolin MDI, when used with the Aerochamber (40.4 (95% confidence interval (95% CI) 31.2-49.6) versus 19.5 (19.0-20.0) microg) and the Nebuhaler (42.1 (36.3-47.9) versus 24.6 (23.3-25.8) microg). The aerosol cloud from the Airomir MDI was slower than the Ventolin aerosol, and 60 ms after actuation had travelled 186 mm, whereas the Ventolin aerosol had travelled 320 mm. At the same time, the Airomir aerosol occupied a smaller volume than the Ventolin MDI (251 (213-288) versus 695 (608-782) cm3). The hydrofluoroalkane formulation delivers more salbutamol than the conventional formulation when used either with the Aerochamber or Nebuhaler spacer. This may be because less drug is deposited in the spacer from the hydrofluoroalkane formulation, which is emitted from the metered-dose inhaler at a slower speed and occupies a smaller volume than the conventional formulation. The observed difference in drug delivery may be important for patients changing formulations, and in severe asthma, where high doses of salbutamol may be administered through a spacer.

Administration, Inhalation↗
PubMed1997

Delivery systems: the science.

Different delivery devices may be chosen and the prescribing physician requires information on those suitable for patients of different age, together with the reproducibility of the dose inhaled from the chosen device. A large number of different devices are currently available for inhalation therapy. Although the dose of a drug inhaled by a patient from a device may vary by up to 400%, such information is not usually available to the prescribing doctor. Spacer devices, with facemask attachments for younger children, are now the first choice device for delivery of anti-asthma aerosols to those 5 years of age or less. The dose that spacer devices deliver is governed by a variety of factors, including static charge, face mask design, spacer volume, the particular drug used, and the breathing pattern of the child. Nebulizers are generally prescribed for those not tolerating spacer devices. More recent designs, such as the open-vent nebulizer systems deliver the drug more rapidly to adults. The breath-enhanced open-vent systems have the advantage of delivering significantly more drug to older patients. These systems rely on the relatively large tidal volumes of older patients. As a result of their smaller tidal volumes, young children are unlikely to benefit as greatly from these devices. The open-vent system may result in some young children receiving less drug than from a conventional nebulizer.

Adolescent↗
PubMed1996

Effects of 3 MAC of halothane, enflurane and isoflurane on cilia beat frequency of human nasal epithelium in vitro.

We have measured the effects of three times the minimum alveolar concentration (MAC) of halothane, enflurane and isoflurane on cilia beat frequency of human nasal epithelial brushings from 18 healthy adult patients. Using the transmitted light technique and paired perfusion chambers, the cilia were exposed to 2.25% halothane, 5% enflurane or 3.6% isoflurane in air, or air alone, in a controlled and blinded manner. Over a 4-h observation period, cilia beat frequency of the samples exposed to inhalation anaesthetic agents demonstrated a significant reduction in frequency compared with controls exposed to air alone. Mean cilia beat frequency for the samples exposed to halothane was 9.3 (SEM 1.3) compared with its controls of 11.4 (1.0); for the samples exposed to enflurane, 10.9 (1.3) compared with its controls of 11.6 (1.2); and for the samples exposed to isoflurane, 10.8 (1.1) compared with its controls of 11.6 (1.2). There was a statistically significant difference between the samples exposed to all three volatile agents and their associated controls (halothane, P = 0.01; enflurane, P = 0.03; isoflurane, P = 0.01; nested repeated measures analysis of variance utilizing polynomial contrasts).

Adult↗
PubMed1996

Effects of upper respiratory tract infections in patients with cystic fibrosis.

BACKGROUND: The polymerase chain reaction has improved the detection of picornaviruses and rhinoviruses and our understanding of their role in reversible airways disease. The effects of colds on lower respiratory morbidity and bacterial colonisation in cystic fibrosis remain uncertain. METHODS: Children with cystic fibrosis were evaluated regularly in the clinic and the parents notified the investigators when their child developed a cold. Nasopharyngeal specimens were collected at the start of the infection for polymerase chain reaction, bacteriology was also undertaken and again three weeks later, and pulmonary function was measured in children aged > or = 6 years at four day intervals for three weeks. The effects of colds on rate of progression of cystic fibrosis were assessed by pulmonary function, Shwachman scores, and radiology. RESULTS: Thirty eight children suffered 147 colds over 17 months. Picornaviruses were detected in 51 (43%) of 119 nasopharyngeal specimens, and 21 of the 51 were further identified as rhinoviruses. Pulmonary dysfunction was similar following picornavirus and non-picornavirus infections; the mean change from baseline in forced expiratory volume in one second (FEV1) was -16.5% and -10.3% at 1-4 days and 21-24 days, respectively, after onset of a cold. Children who experienced more colds than average had evidence of disease progression with reduction in Shwachman score, increasing Chrispin-Norman score, and greater deterioration in FEV1 per annum. Ten of 12 new bacterial infections were associated with a cold. CONCLUSIONS: Picornavirus and non-picornavirus colds are associated with pulmonary function abnormalities and disease progression in patients with cystic fibrosis, and predispose to secondary bacterial infection and colonisation.

Adolescent↗
PubMed1996

Inhalational drug delivery from seven different spacer devices.

BACKGROUND: A study was performed to determine in vitro the difference in drug output of seven currently available spacer devices when used with different inhaled medications. METHODS: A glass multistage liquid impinger (MSLI) was used to determine the amount of disodium cromoglycate (DSCG, 5 mg), salbutamol (100 micrograms), or budesonide (200 micrograms) obtained in various particle size ranges from metered dose inhalers (MDIs) actuated directly into the MSLI or via one of seven different spacer devices; the Fisonair, Nebuhaler, Volumatic, Inspirease, Aerochamber, Aerosol Cloud Enhancer, and Dynahaler. RESULTS: In particles smaller than 5 microns in diameter the dose of DSCG recovered from the Fisonair and Nebuhaler was 118% and 124%, respectively, of that recovered using the MDI alone. The dose recovered from the smaller volume spacers was 90% (Inspirease), 36% (Aerochamber), 33% (Aerosol Cloud Enhancer), and 21% (Dynahaler) of that from the MDI alone. The Volumatic increased the amount of salbutamol in particles smaller than 5 microns to 117% of that from the MDI, and the Inspirease and Aerochamber spacers decreased it by nearly 50%. The amount of budesonide in small particles recovered after use of the Nebuhaler, Inspirease, and the Aerochamber was 92%, 101%, and 78%, respectively, of that from the MDI alone. CONCLUSIONS: Under the test conditions used, large volume spacers such as the Fisonair, Nebuhaler, and Volumatic delivered significantly more DSCG and salbutamol than the smaller spacers tested. The differences between spacers were less for budesonide than the other medications studied. This study shows that there are significant differences in the amount of drug available for inhalation when different spacers are used as inhalational aids with different drugs. Spacer devices need to be fully evaluated for each drug prescribed for them.

Administration, Inhalation↗
PubMed1995

The effect of delay, multiple actuations and spacer static charge on the in vitro delivery of budesonide from the Nebuhaler.

A multistage liquid impinger was used to determine the amount of budesonide available from the Nebuhaler spacer device following alteration of spacer static charge, delay in sampling from the spacer, and multiple actuations of the metered dose inhaler into the spacer prior to sampling. The mean amount of budesonide (s.d.) recovered per 200 micrograms actuation in particles smaller than 5 microns increased from 30.5 micrograms (8.8) to 69.3 micrograms (17.9) with a low static spacer. A 20 s delay between actuation and inhalation reduced the amount recovered to 10.9 micrograms (3.2), but no reduction was seen when using a low static spacer after the same delay. Multiple actuations into the spacer before sampling also reduced the recovery to 24.8 micrograms (3.4) after two actuations, and 13.5 micrograms (7.6) after five actuations. When using a Nebuhaler with budesonide metered dose inhalers, more respirable drug will be obtained if the aerosol is inhaled immediately after actuation, and multiple actuations into the spacer device are avoided. Low static spacers may also improve drug delivery. Attention to the details of spacer use may reduce the incidence of therapeutic failure and the cost of inhaled medications.

Administration, Inhalation↗
PubMed1995

Brain and respiratory cilia: the effect of temperature.

We have used a modified photodiode method to measure ciliary beat frequency of human neonatal cilia, and have developed techniques to allow similar measurements of rat brain cilial function. The effect of temperature change, within the physiological range, on neonatal human respiratory cilia and neonatal rat brain cilia was studied. The mean (SD) ciliary beat frequency of neonatal respiratory cilia at body temperature was 14 (1.1) Hz and that of rat brain cilia 18.9 (1.3) Hz. Respiratory cilial beat frequency decreased by 9.1% and brain cilia by 13% on cooling to 32 degrees C compared to normal body temperature. Beat frequency increased by 8.5% in respiratory samples and by 12% in brain samples on warming to 40 degrees C compared to the frequency at normal body temperature. The Q10 of human neonatal respiratory cilia was 1.2 and that of rat brain cilia 1.3.

Animals↗
PubMed1994

A single-dose comparison of the bioavailability of aluminium from two formulations of sucralphate in normal volunteers.

The oral bioavailability of aluminium was compared after administration of 1 g sucralphate as either a tablet or a suspension (1 g/5 ml) in a crossover study in 16 healthy volunteers. Aluminium levels were detectable in all subjects pre-dose (21.4 +/- 8.8 micrograms l-1 before tablet; 21.4 +/- 7.4 micrograms l-1 before suspension) and there was a measurable increase in the plasma concentrations of aluminium in all subjects after administration of the suspension, and in 14 of the subjects after administration of the tablet formulation, with Cmax reached within the first 8 h in most subjects. Plasma levels were still elevated 72 h after dosing. The variability in plasma levels of aluminium was significantly higher after administration of the suspension (CV 39-53%) than after administration of the tablet (CV 29-44%), reflecting greater absorption of aluminium from the suspension formulation in three subjects. Similarly, the variance of the Cmax, AUC(0-72 h), and AUC(0-infinity) (for both the raw data and the baseline adjusted data) were all higher for the suspension than for the tablet. A point estimate of the difference of the pharmacokinetic parameters (determined from the median of the arithmetic Walsh averages) indicated little or no difference in Cmax, Tmax, or AUC(0-infinity) in the two formulations. In summary, the performance of the suspension formulation of sucralphate is more variable than the tablet formulation in vivo and some patients may therefore have higher circulating levels of aluminium on therapy with the suspension formulation.

Administration, Oral↗
PubMed1994

Effect of halothane on cilia beat frequency of ciliated human respiratory epithelium in vitro.

The effect of halothane on human ciliated nasal epithelium was studied in vitro. Samples from 24 healthy adult volunteers were exposed to halothane in varying concentrations and cilia beat frequency was measured using the transmitted light technique. Mean cilia beat frequency was measured at 30-min intervals. There was a significant decrease in cilia beat frequency at 2 h in samples that were exposed to halothane (mean 8.4 (SD 2.5) Hz, 9.18 (2.6) Hz and 6.99 (4.9) Hz) compared with air (10.8 (2.7) Hz, 11.6 (2.1) Hz and 12.1 (2.3) Hz) (P < 0.01). The coefficient of variation of cilia beat frequency measurements increased after exposure to halothane. There was no change in the cilia beat frequency of controls exposed to air over a 3-h period.

Adult↗