PubMed Health⌕ Search

Biomedical subjects

S J Fowler

Publications and source records attributed to S J Fowler.

At least 19 recordsLinked to original sources
PubMed2006

Nontuberculous mycobacteria in bronchiectasis: Prevalence and patient characteristics.

The aim of the current study was to investigate the prevalence and clinical associations of nontuberculous mycobacteria (NTM) in a well-characterised cohort of patients with adult-onset bronchiectasis. The sputum of all patients attending a tertiary referral bronchiectasis clinic between April 2002 and August 2003 was examined for mycobacteria as part of an extensive diagnostic work-up. NTM-positive patients subsequently had further sputa examined. A modified bronchiectasis scoring system was applied to all high-resolution computed tomography (HRCT) scans from NTM-positive patients, and a matched cohort without NTM. Out of 98 patients attending the clinic, 10 had NTM in their sputum on first culture; of those, eight provided multiple positive cultures. Three patients were treated for NTM infection. A higher proportion of NTM-positive than -negative patients were subsequently diagnosed with cystic fibrosis (two out of nine versus two out of 75). On HRCT scoring, more patients in the NTM-positive group had peripheral mucus plugging than in the NTM-negative group. In the current prospective study of a large cohort of patients with bronchiectasis, 10% cultured positive for nontuberculous mycobacteria in a random clinic sputum sample. Few clinical parameters were helpful in discriminating between groups, except for a higher prevalence of previously undiagnosed cystic fibrosis and of peripheral mucus plugging on high-resolution computed tomography in the nontuberculous mycobacteria group.

Aged↗
PubMed2005

Provision for major obstetric haemorrhage: an Australian and New Zealand survey and review.

Obstetric haemorrhage is a leading cause of maternal death and the most common contributor to serious obstetric morbidity. Maternal mortality audit data suggest that appropriate preparation and good emergency management leads to improved outcome. The aim of this study was to assess facilities relevant to major obstetric haemorrhage management in all units in Australia and New Zealand that offer operative obstetric services. The questionnaire was divided into ten sections: demographics, facilities, staffing, policies and guidelines, drugs, procedures, equipment, point of care testing, availability of O negative blood and free comments. Responses were received from 240 (76.4%) of the 314 hospitals surveyed (187 public and 53 private). One hundred and nine units (45%) had fewer than 500 deliveries per year Distances to referral facilities were frequently very large. Of the 90 hospitals (38.1%) without an onsite blood bank, 12 did not have a supply of blood for emergencies. Half of all units (n=121) had on-site intensive care or high dependency facilities and 72.9% (n=175) had an on-site cardiac arrest team. Only 58.8% of units (n=141) had a written haemorrhage protocol. Findings are presented in the context of other literature, including evidence-based guidelines. Haemorrhage responds well to appropriate treatment, although careful preparation and anticipation of problems is required. In our region geographical factors and different systems of healthcare complicate provision of obstetric services. Where facilities are limited, women should be offered antenatal transfer to a larger centre.

Anesthesia↗
PubMed2004

Recurrent atrial tachyarrhythmia triggered by percutaneous balloon rhizotomy of the trigeminal nerve.

Stimulation of sensory branches of the trigeminal nerve is known to cause sudden bradycardia (trigeminocardiac reflex). However we report a case where percutaneous balloon rhizotomy of the trigeminal ganglion provoked atrial tachyarrhythmias during two separate treatments. On both occasions the patient was treated with antiarrhythmic drugs and reverted to sinus rhythm within days. Our case demonstrates that surgery involving the trigeminal nerve may cause variable cardiovascular effects that are often clinically significant. Possible mechanisms and management of arrhythmias in this setting are discussed.

Aged↗
PubMed2003

Effects of mediator antagonism on mannitol and adenosine monophosphate challenges.

BACKGROUND: Airway hyper-responsiveness (AHR) to indirect stimuli is a useful non-invasive surrogate inflammatory marker in the evaluation of asthma, while histamine and cysteinyl leukotrienes are important inflammatory mediators. OBJECTIVE: To evaluate AHR to indirect bronchoconstrictor stimuli and time taken to recover following single doses of montelukast 10 mg and desloratadine 5 mg in combination, montelukast 10 mg alone and placebo. METHODS: Fifteen mild-to-moderate persistent asthmatics completed a randomized, double-blind, cross-over study. Patients received encapsulated montelukast 10 mg/desloratadine 5 mg combination, montelukast 10 mg alone and placebo, 10-14 h prior to challenge on two separate occasions. The mannitol threshold dose, AMP threshold concentration and recovery times after challenge were measured along with lung function. RESULTS: Compared to placebo, montelukast/desloratadine conferred improvements (P < 0.05) in adenosine monophosphate (AMP) threshold concentration and mannitol threshold dose: a 3.2-fold (95% CI 2.2-4.6) and 2.4-fold (95% CI 1.7-3.3) difference, respectively, while compared to montelukast this amounted to a 2.0-fold (95% CI 1.2-3.4) and 1.5-fold (95% CI 1.1-2.4) improvement, respectively. Montelukast was not significantly different from placebo. Both montelukast/desloratadine and montelukast compared to placebo, shortened recovery following both challenges (P < 0.05): a 27-min (95% CI 17-37) and 29-min (95% CI 20-36) reduction, respectively, for AMP, and a 27-min (95% CI 17-37) and 26-min (95% CI 17-35) reduction, respectively for mannitol. CONCLUSION: The dissociated effects of single doses of montelukast alone but not montelukast/desloratadine combination on AHR and recovery time, highlights the relative roles of histamine in initiating the bronchoconstrictor response and cysteinyl leukotrienes in sustaining it. Similar improvements in AHR and recovery time were observed following both indirect bronchoconstrictor stimuli.

Acetates↗
PubMed2002

Airway and systemic effects of hydrofluoroalkane fluticasone and beclomethasone in patients with asthma.

BACKGROUND: With the transition to hydrofluoroalkane-134a propellants in metered dose inhalers, it is important to consider the efficacy and safety profiles of formulations containing inhaled corticosteroids. We examined the airway and systemic effects of hydrofluoroalkane-134a fluticasone propionate (FLU-HFA) and beclomethasone dipropionate (BEC-HFA) at recommended labelled doses. METHODS: Twenty mild to moderate asthmatics were randomised in crossover fashion to receive 6 weeks of 500 micro g/day followed by 1000 micro g/day FLU-HFA and BEC-HFA. Measurements were made at baseline after placebo run in and washout, and after each randomised treatment. The primary airway outcome for benefit was the dose of methacholine provoking a fall in forced expiratory volume in 1 second (FEV(1)) of 20% or more (methacholine PD(20)) and for systemic adverse effects was overnight urinary cortisol/creatinine (OUCC). RESULTS: For mean responses, both doses of BEC-HFA and FLU-HFA produced significant improvements in PD(20) compared with baseline. The improvement was not significantly greater with 1000 micro g/day FLU-HFA versus BEC-HFA, a 1.69 fold difference (95% CI 0.94 to 3.04). Both doses of BEC-HFA but not FLU-HFA caused significant suppression of OUCC compared with baseline, with significantly (p<0.05) lower values at 1000 micro g/day for BEC-HFA versus FLU-HFA (1.97 fold difference (95% CI 1.28 to 3.02)). CONCLUSION: There was no difference in the airway and systemic effects in patients with mild to moderate asthma between FLU-HFA and BEC-HFA at a dose of 500 micro g/day. At 1000 micro g/day there was increased systemic bioactivity with BEC-HFA compared with FLU-HFA, without any gain in airway efficacy.

Adult↗
PubMed2001

Dose-response for adrenal suppression with hydrofluoroalkane formulations of fluticasone propionate and beclomethasone dipropionate.

AIMS: With the recent introduction of hydrofluoroalkane (HFA) inhalers it is important to know the relative systemic safety profiles of inhaled corticosteroids. We therefore decided to compare systemic bioavailability of HFA-beclomethasone dipropionate (BDP) vs HFA-fluticasone propionate (FP). METHODS: Sixteen healthy volunteers were randomised in placebo-controlled single blind cross-over fashion to receive 3 weeks with HFA-FP or HFA-BDP, given as 1 week cumulative doubling doses (nominal ex-valve) of 500, 1000 and 2000 microg day(-1), with a 1 week placebo run-in and wash-out. Overnight (22.00 h to 08.00 h) and early morning (08.00 h) urinary cortisol/creatinine excretion and 08.00 h serum cortisol were measured after each placebo and dosing period. All data were log-transformed to normalize their distribution. RESULTS: Urine and serum cortisol were suppressed by 2000 microg FP and BDP vs placebo and by 1000 microg BDP vs placebo for urinary cortisol/creatinine (P < 0.05). Overnight urinary cortisol/creatinine ratio (the primary endpoint) was suppressed more by 1000 microg BDP vs 1000 microg FP (P < 0.05), amounting to a geometric mean fold difference (95% CI) of 1.64 (1.04-2.56). There were also more individual low values less than 3 nmol mmol(-1) with BDP than FP at 1000 microg: n = 8/16 vs n = 2/16 (P < 0.05). CONCLUSIONS: There was dose-related suppression of corrected urinary cortisol/creatinine with the HFA formulations of BDP and FP. Suppression of overnight urinary cortisol/creatinine ratio was significantly greater with HFA-BDP than HFA-FP at 1000 microg. This suggests that the greater glucocorticoid potency of HFA-FP may be offset by the greater lung bioavailability of HFA-BDP.

Administration, Inhalation↗
PubMed2001

Pharmacokinetics and systemic beta2-adrenoceptor-mediated responses to inhaled salbutamol.

AIMS: To examine whether systemic beta2-adrenoceptor responses, such as tachycardia, tremor and hypokalaemia, can be used as a surrogate for the 20 min pharmacokinetic profile of inhaled salbutamol. METHODS: A retrospective analysis of eight separate published studies in healthy volunteers was performed, each with an identical protocol evaluating the early lung absorption profile of a nominal 1200 microg dose of salbutamol given by different inhaler devices. Peak postural finger tremor, plasma potassium and heart rate were assessed. RESULTS: We found the maximum (Cmax) and average (Cav) plasma concentrations of salbutamol to be correlated (P < 0.0001) to change in plasma potassium (Cmax r = 0.904; Cav r = 0.899) and tremor (Cmax r = 0.875; Cav r = 0.857). No significant correlations existed between change in heart rate and Cmax (r = 0.425) or Cav (r = 0.415). CONCLUSIONS: Systemic beta2-adrenoceptor responses, in particular hypokalaemia and tremor, but not heart rate, appear to be good surrogates for evaluating the lung delivery of inhaled salbutamol. Consequently it is suggested that potassium or tremor responses may be used to evaluate the relative lung delivery of salbutamol from different inhaler devices.

Administration, Inhalation↗
PubMed2001

Comparative in vivo lung delivery of hydrofluoroalkane-salbutamol formulation via metered-dose inhaler alone, with plastic spacer, or with cardboard tube.

STUDY OBJECTIVE: To compare the lung delivery of chlorofluorocarbon-free salbutamol via a pressurized metered-dose inhaler (pMDI) alone, a pMDI with a small-volume plastic spacer, and a pMDI with a cardboard tube. DESIGN: A randomized, single (investigator)-blind, three-way, crossover study. SETTING: The Asthma and Allergy Research Group, Ninewells Hospital, University of Dundee, Dundee, Scotland, UK. PARTICIPANTS: Twelve healthy volunteers aged 16 to 65 years. INTERVENTIONS: The subjects were administered 400 microg of salbutamol via a pMDI alone, via a pMDI plus a small-volume plastic spacer, or via a pMDI plus a cardboard tube. MEASUREMENTS AND RESULTS: Blood samples for plasma salbutamol concentrations were taken at 5 min, 10 min, and 20 min after inhalation, to measure lung bioavailability as a surrogate for relative lung dose. The addition of the plastic spacer resulted in a significantly higher maximal plasma salbutamol concentration (CMAX) and average plasma salbutamol concentration (CAV) than the pMDI used alone. This amounted to a 1.48-fold (32%) difference (95% confidence interval [CI], 1.03 to 2.13) for CMAX and a 1.42-fold (30%) difference (95% CI, 1.01 to 2.00) for CAV. There was no significant difference in the CMAX or CAV comparing the addition of the cardboard tube with the plastic spacer or the pMDI alone. CONCLUSIONS: Using a chlorofluorocarbon-free pMDI with a plastic spacer produced statistically, but not biologically, significant greater lung delivery of salbutamol. If a spacer is required for reasons other than increasing delivered drug dose, then the addition of a readily available cardboard tube will fulfill many of the required functions with no expense to the patient.

Administration, Inhalation↗
PubMed2001

Evaluation of the importance of head and probe stabilisation in acoustic rhinometry.

As yet there is no established procedure to ensure the repeatability of acoustic rhinometry measurements although anecdotal evidence suggests that instrument fixation improves repeatability. The aim of this study is to validate the methodology of acoustic rhinometry and determine whether instrument fixation and head stabilisation is necessary. Four methods were compared in fifteen healthy volunteers, after nasal decongestion: A) Patient holding the probe (patient-held), B) Probe fixed in a probe stand (probe-stand), C) Probe fixed in stand and head stabilised in head rest (head-rest), D) Examiner holding the probe (examiner-performed). The two minimum cross-sectional areas and volume between 0 and 5 cm were recorded. The examiner-performed and probe-stand methods were consistently less variable than the other methods. With examiner-performed method, this was significant (p < 0.05) versus head-rest and patient-held methods for both measures of minimum cross-sectional area. For nasal volume the examiner-performed method was significantly (p < 0.05) less variable than the head-rest method. In conclusion, examiner-performed acoustic rhinometry is more repeatable than combined head stabilisation and instrument fixation and therefore the use of a head-rest may be unnecessary. Instrument fixation or examiner performed test is also preferable to allowing the patient to position the probe. The repeatability of the probe-stand method was similar to the examiner-performed method.

Adult↗
PubMed2000

Characterization of hydra type IV collagen. Type IV collagen is essential for head regeneration and its expression is up-regulated upon exposure to glucose.

Hydra vulgaris mesoglea is a primitive basement membrane that also exhibits some features of an interstitial matrix. We have characterized cDNAs that encode the full-length hydra alpha1(IV) chain. The 5169-base pair transcript encodes a protein of 1723 amino acids, including an interrupted 1455-residue collagenous domain and a 228-residue C-terminal noncollagenous domain. N-terminal sequence analyses of collagen IV peptides suggest the molecule is homotrimeric. Denatured hydra type IV collagen protein occurs as dimers and higher order aggregates held together by nonreducible cross-links. Hydra collagen IV exhibits no functional evidence for the presence of a 7 S domain. Type IV collagen is expressed by the ectoderm along the entire longitudinal axis of the animal but is most intense at the base of the tentacles at the site of battery cell transdifferentiation. Antisense studies show that inhibition of collagen IV translation causes a blockage in head regeneration, indicating its importance in normal hydra development. Exposure of adult hydra to 15 mm glucose resulted in up-regulation of type IV collagen mRNA levels within 48 h and significant thickening of the mesoglea within 14 days, suggesting that basement membrane thickening seen in diabetes may be, in evolutionary terms, an ancient glucose-mediated response.

Amino Acid Sequence↗
PubMed2000

Screening for bronchial hyperresponsiveness using methacholine and adenosine monophosphate. Relationship to asthma severity and beta(2)-receptor genotype.

Bronchial hyperresponsiveness (BHR) is a key feature of asthma and may be measured by direct methacholine challenge or indirect adenosine monophosphate (AMP) challenge. We performed a retrospective analysis of our database (n = 487) of patients with asthma with the aim first, to compare methacholine and AMP challenge as screening tools, and second, to identify any relationships between BHR and disease severity markers or beta(2)-adrenoceptor genotype. Of these subjects, 258 had a methacholine challenge, 259 an AMP challenge and 185 both. Of subjects having both, 140 (76%) were methacholine responsive with PD(20) < 500 microgram (PC(20) < 5 mg/ml) and 92 (50%) were AMP responsive with PC(20) < 200 mg/ ml. For those who were AMP unresponsive 57% were methacholine responsive, whereas for the methacholine nonresponders 11% were AMP responsive. Methacholine (but not AMP)-responsive patients had a significantly (p < 0.05) lower % predicted FEV(1) and FEF(25-75) and higher inhaled corticosteroid dose than unresponsive patients. Finally, subjects with a glycine allele at codon 16 had significantly (p < 0.05) increased BHR to methacholine but not AMP. Our results suggest that methacholine is a more appropriate screening tool for BHR than AMP as it was more sensitive in our population and was also related to asthma severity. In addition, we have demonstrated an association between the glycine allele (codon 16) and increased BHR to methacholine.

Adenosine Monophosphate↗