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Biomedical subjects

C O'Callaghan

Publications and source records attributed to C O'Callaghan.

At least 19 recordsLinked to original sources
PubMed2006

Effect of oropharyngeal length in drug lung delivery via suspension pressurized metered dose inhalers.

PURPOSE: To determine the effect of the oropharyngeal length in adults on the lung dose of a suspension pressurized metered dose inhaler, and whether employing small volume spacers can alter this role. METHODS: Depositions of Ventolin Evohaler (100) microg in the oropharyngeal models of two healthy adult subjects with 17.1 cm (short cast) and 19.9 cm (long cast) centerline lengths via three small volume spacers [two spacers with 3 cm effective length but one with 6.5 cm2 (L3) and the other with 24.6 cm2 (L3W) cross sections, and the Optimiser] were studied. RESULTS: Without using spacers, lung dose of the long cast (19.52 +/- 2.32 microg, mean +/- standard deviation) was significantly larger than that for the short cast (8.08 +/- 1.01 microg, p < 0.006). However, using the L3 spacer with the short cast made the lung dose (18.59 +/- 3.33 microg) similar to that for the long cast alone. Lung doses of the short cast (20.43 +/- 1.42 microg) and the long cast (30.81 +/- 1.84 microg) with the L3W spacer were similar to those with the L3 spacer. However, using the Optimiser spacer increased the lung dose for the short cast (22.27 +/- 6.03 microg) and significantly for the long cast (35.61 +/- 2.19 microg, p < 0.006) compared to those for the L3 spacer. Using spacers increased drug deposition in the oropharynx part of the short cast, and this reduced the lung dose compared to that for the long cast. CONCLUSION: The oropharyngeal length in adults may affect the lung dose via the pMDIs, which may not be eliminated by using small volume spacers.

Administration, Inhalation↗
PubMed2006

Effect of sleeping position on nasal patency in newborns.

Sleeping posture has been implicated in the pathophysiology of sudden infant death syndrome. The effect of supine and lateral sleeping positions on nasal patency was investigated using acoustic rhinometry in 11 healthy newborns. The implications of the findings in sudden infant death syndrome are discussed.

Airway Resistance↗
PubMed2005

Suitability of the upper airway models obtained from MRI studies in simulating drug lung deposition from inhalers.

PURPOSE: In this study, the suitability of the upper airway models, obtained by applying a magnetic resonance imaging method, in simulating in vivo aerosol deposition data is determined. METHODS: Depositions of salbutamol sulfate from two nebulizers in two models, one with constriction at the oropharynx (the constricted cast) and another model without that constriction (the wide cast), were determined. RESULTS: For the Sidestream and Ventstream nebulizer, 76 +/- 3% (mean +/- standard deviation) and 81 +/- 2% of the emitted dose deposited in the constricted cast, whereas 51 +/- 2% and 49 +/- 3% of the emitted dose deposited in the wide cast, respectively. These values were in good agreement with in vivo data. Mostly, increasing nebulizer charge volume (by normal saline) from 2.5 ml to 5 ml increased significantly the lung dose. However, the lung doses from the Sidestream and Ventstream nebulizer with 2.5 ml charge volume via the wide cast were (1.37 +/- 0.06 and 1.38 +/- 0.05 mg) significantly larger than those for the constricted cast with 5 ml charge volume (0.87 +/- 0.15 and 0.86 +/- 0.21 mg, respectively) (p = 0.005). CONCLUSIONS: The upper airway models closely simulated the in vivo deposition data. Optimizing the upper airway posture during inhalation via the nebulizers would be more efficient in increasing drug lung delivery than diluting their contents.

Albuterol↗
PubMed2005

Recovery of the ciliated epithelium following acute bronchiolitis in infancy.

BACKGROUND: Little is known about the longitudinal changes in the ciliated respiratory epithelium of infants following viral bronchiolitis. A study was undertaken to investigate the time required for the ciliated epithelium to return to normal following bronchiolitis in infants treated with inhaled steroids or placebo. METHODS: Thirty one previously healthy term infants were studied as part of a clinical trial to determine the effect of 12 weeks of treatment with inhaled fluticasone (FP) or placebo via a spacer device (17 FP, 14 placebo). Nineteen healthy children aged 0-6 years previously studied in our department were used as controls. Nasal biopsy specimens were taken from infants with bronchiolitis and ciliary beat frequency (CBF) was measured before treatment and repeated 3, 6, 12, and 24 weeks later. The epithelial ultrastructure was examined by transmission electron microscopy and a normal errors mixed model based on normal controls was used to examine the time for cilia to return to normal in bronchiolitic infants. RESULTS: The mean CBF of infants with bronchiolitis (in Hz) at weeks 0, 3, 6, 12, and 24 were 0.5 (n = 4), 10.9 (n = 4), 12.0 (n = 9), 11.9 (n = 8), and 12.1 (n = 7) in the placebo group and 10.6 (n = 6), 11.4 (n = 9), 8.8 (n = 8), 10.9 (n = 4), and 13.2 (n = 7) in the FP group. The time for the epithelial ultrastructure to normalise was as follows: epithelial integrity score (13.1 weeks), % ciliated cells with loss of cilia (14.0 weeks), and % epithelial cells with abnormalities in projection (16.7 weeks) or mitochondria (15.9 weeks). Inhaled steroids had no significant effects on CBF or epithelial ultrastructure. CONCLUSION: Ciliary loss and epithelial abnormalities persist on average for 13-17 weeks following acute bronchiolitis in infancy.

Acute Disease↗
PubMed2005

Delivery of nebulized budesonide is affected by nebulizer type and breathing pattern.

The aim of this study was to determine the output in-vitro of budesonide from two different nebulizers under simulated breathing conditions. The BimboNeb and Nebula nebulizers were used to nebulize 2 mL of budesonide (500 microg) suspension. Particle size was determined by inertial impaction after a 5-min nebulization. Total outputs of the drug from both nebulizers were measured using a sinus flow pump to create simulated breathing conditions. Paediatric and adult breathing patterns were used, with drug output measured after 5 and 10 min nebulization. The mass median aerodynamic diameter of budesonide using the BimboNeb (4.5 microm) was significantly greater than that from the Nebula (3.4 microm) (P<0.01). With the simulated adult breathing pattern, the total drug output after 5 min with the BimboNeb (61.5 microg) was twice that from the Nebula (30.7 microg). For the paediatric breathing pattern, total outputs were very similar for both nebulizers. In all cases, nebulizing for 10 min produced greater drug outputs compared with those after 5 min, particularly for the paediatric breathing pattern. The amount of aerosolized drug available for inhalation needs to be assessed for each nebuliser used and the effect of the patient's breathing pattern should also be taken into account.

Administration, Inhalation↗
PubMed2004

What effect does isoflurane have upon ciliary beat pattern: an in vivo study.

The effect of anaesthetic gases given via laryngeal mask on nasal ciliary beat pattern and frequency has not been studied. Anaesthetic gases such as isoflurane, halothane and enflurane are known to reduce ciliary beat frequency, but it is unknown whether they also cause cilia to beat in a dyskinetic fashion. Brush biopsies of nasal mucosa were taken pre- and post-anaesthesia with isoflurane, given via a laryngeal mask, from patients undergoing nasal surgery. The samples were observed by light microscopy, and high-speed digital video recordings were made to determine ciliary beat frequency. Using slow-motion playback, the ciliary beat pattern was scored for dysmotility, and the proportion of immotile cilia in the sample was determined. We found that ciliary beat frequency decreased significantly (P < 0.01) after exposure to isoflurane (10.24 Hz compared to 9.20 Hz). However, isoflurane did not alter the ciliary beat pattern or the proportion of immotile cilia.

Adolescent↗
PubMed2004

A randomised crossover trial of facemask efficacy.

The efficacy of different facemasks that can be used in the delivery of aerosol medication to children with recurrent wheeze or asthma was investigated. The results showed a statistically significant difference between some of the masks used, which has important implications for current clinical practice

Administration, Inhalation↗
PubMed2003

The influence of inhaler selection on efficacy of asthma therapies.

Many different devices are available to aid inhalational drug delivery. Although each device is claimed to have advantages over its rivals, the evidence to support greater efficacy of a particular device is scanty. Most comparative studies are underpowered or flawed in their design. They may use inappropriate end-points, or involve healthy subjects, whose response may be very different from the patient with acute severe asthma. The dosage of drug used in a trial may be at the shallow part of the dose-response curve, masking differences in devices. Only in a few cases have clinical trials detected a significant difference between devices, and trials have rarely taken patient preference into account. The most efficacious device in practice is likely to be the one that the patient will use regularly and in accordance with a health care workers' recommendations.

Administration, Inhalation↗
PubMed2003

Functional analysis of cilia and ciliated epithelial ultrastructure in healthy children and young adults.

BACKGROUND: There are very few data on normal ciliary beat frequency, beat pattern, and ultrastructure in healthy children and adults. A study was undertaken to define ciliary structure, beat frequency and beat pattern in a healthy paediatric and young adult population. METHODS: Ciliated epithelial samples were obtained from 76 children and adult volunteers aged 6 months to 43 years by brushing the inferior nasal turbinate. Beating cilia were recorded using a digital high speed video camera which allowed analysis of ciliary beat pattern and beat frequency. Tissue was fixed for transmission electron microscopy. RESULTS: The mean ciliary beat frequency for the paediatric population (12.8 Hz (95% CI 12.3 to 13.3)) was higher than for the adult group (11.5 Hz (95% CI 10.3 to 12.7 Hz), p<0.01, t test); 10% (range 6-24%) of ciliated edges were found to have areas of dyskinetically beating cilia. All samples had evidence of mild epithelial damage. This reflected changes found in all measurements used for assessment of epithelial damage. Ciliary ultrastructural defects were found in less than 5% of cilia. CONCLUSION: Normal age related reference ranges have been established for ciliary structure and beat frequency. In a healthy population localised epithelial damage may be present causing areas of ciliary dyskinesia.

Adolescent↗
PubMed2001

Improved outcomes in stroke thrombolysis with pre-specified imaging criteria.

BACKGROUND: A 1995 National Institute of Neurological Disorders (NINDS) study found benefit for intravenous tissue plasminogen activator (tPA) in acute ischemic stroke (AIS). The symptomatic intracranial hemorrhage (SICH) rate in the NINDS study was 6.4%, which may be deterring some physicians from using this medication. METHODS: Starting December 1, 1998, patients with AIS in London, Ontario were treated according to NINDS criteria with one major exception; those with approximately greater than one-third involvement of the idealized middle cerebral artery (MCA) territory on neuroimaging were excluded from treatment. The method used to estimate involvement of one-third MCA territory involvement bears the acronym ICE and had a median kappa value of 0.80 among five physicians. Outcomes were compared to the NINDS study. RESULTS: Between December 1, 1998 and February 1, 2000, 30 patients were treated. Compared to the NINDS study, more London patients were treated after 90 minutes (p<0.00001) and tended to be older. No SICH was observed. Compared to the treated arm of the NINDS trial, fewer London patients were dead or severely disabled at three months (p=0.04). Compared to the placebo arm of the trial, more patients made a partial recovery at 24 hours (p=0.02), more had normal outcomes (p=0.03) and fewer were dead or severely disabled at three months (p=0.004). CONCLUSIONS: The results of the NINDS study were closely replicated and, in some instances, improved upon in this small series of Canadian patients, despite older are and later treatment. These findings suggest that imaging exclusion criteria may optimize the benefits of tPA.

Acute Disease↗
PubMed2001

The effects of coronavirus on human nasal ciliated respiratory epithelium.

Human coronavirus (HCoV) accounts for 15-30% of common colds, but only one case report has described the effect of a coronavirus infection, that was asymptomatic, on human respiratory epithelium. The authors examined the effects of infection with HCoV on ciliary structure and function in healthy volunteers infected by intranasal inoculation with HCoV 229E. A further four volunteers were sham infected with ultraviolet-inactivated virus. Immediately before inoculation (day 0) and 3 days later (day 3), ciliated epithelium was obtained by brushing the inferior nasal turbinate. Ciliary beat frequency was determined and beat pattern analysed for evidence of dyskinesia (0=normal, 3=severely dyskinetic) using digital high-speed video photography. Ciliary ultrastructure was examined by transmission electron microscopy. Symptom diaries were kept for the duration of the study. All subjects inoculated with HCoV, including the three who did not develop symptoms of an upper respiratory tract infection, had disruption of their respiratory epithelium on day 3. Although there was no difference in the mean ciliary beat frequency between day 0 (11.3 Hz (95% confidence interval (CI): 8.6-14.0) and day 3 (9.4 Hz (95% CI 7.2-11.6)), there was a significant increase (p<0.05) in the ciliary dyskinesia score between day 0 (0.2 (95% CI 0-0.5)) and day 3 (1.1 (95% CI 0.5-1.7). In sham-infected subjects, no differences in epithelial integrity, or ciliary structure and function were found between day 0 and day 3. Inoculation of healthy volunteers with human coronavirus caused disruption of the ciliated epithelium and ciliary dyskinesia. This is likely to impair mucociliary clearance. Damage to the respiratory epithelium, due to human coronavirus infection, may occur without overt clinical symptoms.

Adult↗
PubMed2001

Combining the anti-HER2 antibody trastuzumab with taxanes in breast cancer: results and trial considerations.

Overexpression of the p185/HER2 protein is seen in 20%-25% of primary breast cancers and is associated with poor prognosis. Recent phase II and III clinical trials demonstrate that trastuzumab is active against breast tumors, both as a single agent and in combination with chemotherapy. In patients with HER2-overexpressing metastatic breast cancer, use of trastuzumab in combination with chemotherapy is associated with a 20% reduction in relative risk of death and an increase in median survival from 20.3 to 25.1 months compared to chemotherapy alone. Side effects include fever and chills and an unexpected increase in doxorubicin/trastuzumab-associated cardiomyopathy. Clinical development is now focused on trastuzumab in combination with chemotherapy regimens that do not contain an anthracycline. Trastuzumab in combination with docetaxel is synergistic in vitro. Data from ongoing clinical trials are consistent with this finding. Preliminary data from 3 phase II studies suggest a 44%-63% response rate when the combination is used first or second line in HER2-overexpressing metastatic breast cancer. The combination of docetaxel with trastuzumab is well tolerated and has not been associated with significant cardiotoxicity. Given in vitro evidence that platinum salts act synergistically with trastuzumab and docetaxel, and phase II data suggesting clinical efficacy and good tolerability, the combination of platinum salt plus trastuzumab and docetaxel is now being assessed in adjuvant trials

Antibodies, Monoclonal↗
PubMed2001

Bringing music to life: a study of music therapy and palliative care experiences in a cancer hospital.

A music therapy research study aimed at understanding patients', visitors' and staff members' experiences of a music therapy program in a cancer hospital over a three-month period is described. Respondents' answers to brief open-ended questions, as well as the music therapist researcher's interpretations of the program's relevance, were examined using thematic analysis based on grounded theory. ATLAS.ti software supported data management and analysis. Themes encapsulating 128 patients' reflections about music therapy were delineated and substantiate how music therapy can support palliative care aims throughout the cancer illness trajectory.

Adolescent↗
PubMed2000

No objective benefit from steroids inhaled via a spacer in infants recovering from bronchiolitis.

A double-blind randomized placebo-controlled trial was conducted to investigate the efficacy of 3 months' inhaled steroids delivered via a spacer device with face mask attachment to infants recovering from bronchiolitis. Forty-eight previously healthy infants recovering from their first documented episode of acute bronchiolitis were randomized to receive 150 microg fluticasone propionate (FP) b.i.d. or placebo delivered via the Babyhaler spacer. Longitudinal assessments were performed on seven occasions over 1 yr based on symptom diaries and health records, clinical examinations, overnight cough recordings and oxygen saturation readings. Lung function was measured 6 months after hospital discharge. Forty-three infants completed the trial (FP 21, placebo 22). There were no significant differences in the three objective end-points measured, recorded night cough, oxygen saturation and lung function test results. Symptom scores were low in both the FP and placebo groups with the absence of (0) or mild (1) symptoms > or =90% of the trial days. No statistical differences in symptom frequency, use of rescue respiratory medications or hospital admissions between treatment groups were found throughout the trial or follow-up periods. In conclusion, the use of inhaled fluticasone propionate in infants recovering from acute bronchiolitis cannot be recommended.

Administration, Inhalation↗
PubMed2000

Local mucociliary defence mechanisms.

The lung is continually at risk of exposure to noxious environmental agents and respiratory pathogens. An elaborate series of defence mechanisms have been developed to protect the airways from these insults. The lower respiratory tract is protected by local mucociliary mechanisms that involve the integration of the ciliated epithelium, periciliary fluid and mucus. Mucus acts as a physical and chemical barrier onto which particles and organisms adhere. Cilia lining the respiratory tract propel the overlying mucus to the oropharynx where it is either swallowed or expectorated. Regulation of periciliary fluid is thought essential to maintenance of both mucociliary clearance and to produce an environment in which airway antimicrobial peptides and defensins are effective. Disruption of mucociliary clearance may be caused by diseases such as cystic fibrosis, primary ciliary dyskinesia and asthma or may be secondary to pollutant exposure and viral or bacterial infections.

Cilia↗