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Biomedical subjects

H Booth

Publications and source records attributed to H Booth.

At least 19 recordsLinked to original sources
PubMed2005

Deletion of the nuclear receptor Nr2e1 impairs synaptic plasticity and dendritic structure in the mouse dentate gyrus.

The spontaneous or targeted deletion of the nuclear receptor transcription factor Nr2e1 produces a mouse that shows hypoplasia of the hippocampal formation and reduced neurogenesis in adult mice. In these studies we show that hippocampal synaptic transmission appears normal in the dentate gyrus and cornu ammonis 1 subfields of adult mice that lack Nr2e1 (Nr2e1-/-), and that fEPSP shape, paired-pulse responses, and short-term plasticity are not substantially altered in either subfield. In contrast, the expression of long-term potentiation is selectively impaired in the dentate gyrus, and not in the cornu ammonis 1 subfield. Golgi analysis revealed that there was a significant reduction in both dendritic branching and dendritic length that was specific to dentate gyrus granule cells in the Nr2e1-/- mice. These results indicate that Nr2e1 deletion can significantly alter both synaptic plasticity and dendritic structure in the dentate gyrus.

Animals↗
PubMed2005

Hearing half the message? A re-audit of the care of patients with acute asthma by emergency ambulance crews in London.

PROBLEM: An initial audit of the care provided to emergency asthma patients by the ambulance service was carried out in 1996. Some under-recognition and under-treatment of severe asthma was found as well as a lack of documentation of patient condition on scene. A re-audit was undertaken in 1999. DESIGN: A multidisciplinary advisory group was reconvened. The same method was adopted as for the first audit. Patients included were those administered nebulised salbutamol by crews in the catchment areas of four hospitals and those diagnosed with asthma at the Accident & Emergency (A&E) departments of those hospitals between January and March 1999. SETTING: London Ambulance Service. KEY MEASURES FOR IMPROVEMENT: (1) Accuracy of diagnosis and appropriateness of treatment, and (2) adherence to protocol. STRATEGIES FOR CHANGE: Following the first audit, treatment protocols were widened and brought into line with the British Thoracic Society guidelines for care of acute asthma patients. The results were widely disseminated within the service and training was initiated for all operational staff. EFFECTS OF CHANGE: The number of patients included in the re-audit more than doubled (audit 1: n = 252, audit 2: n = 532). The increase occurred exclusively in those administered nebulised salbutamol by ambulance crews but diagnosed with conditions other than asthma in A&E (audit 1: n = 15, audit 2: n = 161). The proportion of patients diagnosed with asthma in A&E who were administered nebulised salbutamol by their attending crew rose from 58% to 75%. However, 43 asthma patients were not treated; several of these were not recognised as suffering from asthma and others fell within the changed protocols for treatment. Adherence to protocol for administration of salbutamol remained high. Pre-hospital documentation of key observations did not improve. LESSONS LEARNT: Messages from the first audit seem to have been acted upon selectively. Implementing change is complex, and re-audit is necessary to understand the effects of the changes made.

Acute Disease↗
PubMed2001

Cyclooxygenase-2 deficiency results in a loss of the anti-proliferative response to transforming growth factor-beta in human fibrotic lung fibroblasts and promotes bleomycin-induced pulmonary fibrosis in mice.

Prostaglandin E(2) (PGE(2)) inhibits fibroblast proliferation and collagen production. Its synthesis by fibroblasts is induced by profibrotic mediators including transforming growth factor (TGF)-beta(1). However, in patients with pulmonary fibrosis, PGE(2) levels are decreased. In this study we examined the effect of TGF-beta(1) on PGE(2) synthesis, proliferation, collagen production, and cyclooxygenase (COX) mRNA levels in fibroblasts derived from fibrotic and nonfibrotic human lung. In addition, we examined the effect of bleomycin-induced pulmonary fibrosis in COX-2-deficient mice. We demonstrate that basal and TGF-beta(1)-induced PGE(2) synthesis is limited in fibroblasts from fibrotic lung. Functionally, this correlates with a loss of the anti-proliferative response to TGF-beta(1). This failure to induce PGE(2) synthesis is because of an inability to up-regulate COX-2 mRNA levels in these fibroblasts. Furthermore, mice deficient in COX-2 exhibit an enhanced response to bleomycin. We conclude that a decreased capacity to up-regulate COX-2 expression and COX-2-derived PGE(2) synthesis in the presence of increasing levels of profibrotic mediators such as TGF-beta(1) may lead to unopposed fibroblast proliferation and collagen synthesis and contribute to the pathogenesis of pulmonary fibrosis.

Bleomycin↗
PubMed2000

Sociodemographic determinants of energy, fat and dietary fibre intake in Australian adults.

OBJECTIVE: To examine the relationship between sociodemographic factors (sex, age, education, occupation and region of birth) and absolute levels of energy, fat and fibre intake in adults at the national level. DESIGN, SETTING AND SUBJECTS: The 1983 National Dietary Survey of Adults (NDSA), covering six Australian capital cities, collected food and nutrient intake data using the 24-hour recall method, from subjects aged 25-64 years (n=6255). RESULTS: Interactions of variables occurred, especially for males. The greatest effect on male intake of all three dietary components was a combination of age and education. For females, the main explanatory variable for fat and energy intake was age, but that for fibre was a combination of region of birth and education. Both education (alone or in combination) and region of birth (alone or in combination) had a greater effect than occupation (alone or in combination). CONCLUSIONS: Energy, fat and fibre intakes vary considerably between sociodemographic groups. Such variability must be taken into account in formulating policy and planning decisions and in assessing temporal change.

Adult↗
PubMed1999

Pacific Island suicide in comparative perspective.

All available data for thirteen Pacific Island nations are used in a comparative analysis of suicide levels and characteristics. Age, sex and method of suicide are examined in detail. Global comparison shows Pacific rates are amongst the highest reported. Female youth rates exceed male rates in Western Samoa and amongst Fiji Indians. Method of suicide (paraquat ingestion) is instrumental in determining high rates in Western Samoa, especially in females. The broad causal theme is societal transition. Commonality and diversity are discussed.

Adolescent↗
PubMed1999

Detection of antibacterial agents in warm water prawns.

Samples of cooked and raw prawns intended for human consumption were collected by officers at Southampton Port Health Authority, and tested for the presence of antimicrobial agents. Antimicrobial activity was detected in 23 out of 98 cooked prawn samples but in none of the 20 raw samples collected. Samples that showed antimicrobial activity were analysed using high performance liquid chromatography and immunoassay, resulting in the presumptive identification of trimethoprim in 15 samples, and low levels of gentamicin in three samples. Prawns in which trimethoprim was putatively detected contained bacteria with significantly greater resistance to this antibiotic than samples in which no trimethoprim was found. This suggests that the presence of antibiotics in prawn samples may be correlated with increased resistance to these drugs in the associated microflora. There are currently no guidelines regarding acceptable levels of antibiotics in seafood products. These results indicate that the use of these drugs by prawn farmers may be widespread, and may be an issue that requires further attention in the future.

Animals↗
PubMed1997

Albumin is not suitable as a marker of bronchoalveolar lavage dilution in interstitial lung disease.

We have investigated the origin of raised bronchoalveolar lavage (BAL) albumin levels in interstitial lung diseases (ILDs), and the hypothesis that acute flux during BAL might contribute to the elevated levels of albumin in samples from ILD patients. Total albumin concentrations were measured in three separately aspirated 60 mL aliquots of BAL in 12 ILD patients and seven control subjects, and previous work indicating that BAL albumin levels may be raised in ILD was confirmed. In addition, the extent of acute flux from the circulation was investigated using 1.48 MBq of 125I-radiolabelled human serum albumin injected intravenously shortly before the procedure. It was found that acute albumin flux occurred in only a minority of the ILD patients (4 out of 12) and control subjects (3 out of 7). These results indicate that the elevated levels of plasma proteins, such as albumin, documented in BAL aspirates from ILD patients are not an artefact of the BAL procedure related to increased vascular permeability, and that this finding is more likely to be related to the effects of chronic inflammatory changes in the lung due to the underlying disease. The work confirms that albumin is unsuitable as a denominator for the normalization of bronchoalveolar lavage solute results, since levels can vary, both as a result of acute flux and, more frequently, because of disease activity.

Adult↗
PubMed1996

Cognitive performance and regional brain volume in human immunodeficiency virus type 1 infection.

BACKGROUND: Brain atrophy has been reported to occur in advancing human immunodeficiency virus (HIV) infection, particularly in patients with HIV-related dementia. Atrophy of the caudate region, as assessed by magnetic resonance imaging measures, has been reported to correlate with cognitive impairment in patients with HIV infection; however, differences in the severity of HIV-induced immunosuppression may have contributed to these findings. OBJECTIVE: To determine the relationship between regional brain volumes and cognitive performance in individuals with HIV infection. PATIENTS AND METHODS: We evaluated 11 patients with advanced HIV disease by using neuropsychologic tests and quantitative magnetic resonance imaging volume analysis. SETTING: University hospital, involving patients from a clinical trial. RESULTS: Caudate volume, expressed as a ratio of total intracranial volume, correlated with performance on the Trails A and Grooved Pegboard tests, but not with other tests of memory, motor speed, or mood (adjusted for age and education). Hippocampal volume did not correlate with any of the neuropsychologic tests. CONCLUSIONS: Caudate volume in patients with advanced HIV disease is associated with poor performance on neuropsychologic tests of complex motor and sequencing skills. Hippocampal volume does not appear to be related to impairment on neuropsychologic tests. These findings are independent of the degree of immunosuppression and the overall extent of brain atrophy; however, these results must be interpreted with some caution, given the limited sample size.

Adult↗
PubMed1996

Salmeterol tachyphylaxis in steroid treated asthmatic subjects.

BACKGROUND: Tachyphylaxis to the protection afforded by salmeterol to broncho-constrictor stimuli after regular use has been described in patients with mild asthma not receiving inhaled corticosteroids. The present study was performed to investigate whether airway tachyphylaxis occurs in symptomatic asthmatic subjects receiving inhaled corticosteroids, the group for whom salmeterol is recommended in clinical practice. METHODS: Thirty one adult patients with symptomatic chronic asthma who were receiving inhaled corticosteroids were randomised in a double blind manner and on a 2:1 basis to receive salmeterol 50 micrograms (n = 22) or placebo (n = 9) twice daily. Baseline forced expiratory volume in one second (FEV1) was measured during the run-in period, on day 0, and after four and eight weeks of regular treatment (following a 36 hour test drug washout period). Airway responsiveness to methacholine was measured one hour after administration of the test drug on these occasions. Diary cards were kept throughout the study and for a two week follow up period. RESULTS: Baseline FEV1 was not significantly different between the treatment groups or between visits. There was significant bronchodilatation one hour after salmeterol administration at 0, four, and eight weeks. No significant tachyphylaxis of the bronchodilator action of salmeterol was seen. Protection against methacholine induced bronchoconstriction reduced from 3.3 doubling dilutions after the first dose of salmeterol to two doubling dilutions after four and eight weeks of regular treatment. Symptom scores and "rescue" salbutamol use were significantly reduced during salmeterol treatment and daytime improvements were maintained into the follow up period. CONCLUSIONS: Inhaled corticosteroids did not prevent tachyphylaxis to the protection afforded by salmeterol to methacholine induced bronchoconstriction. The clinical significance, if any, of these findings remains to be defined.

Administration, Topical↗
PubMed1996

Intrasubject variability in airway inflammation in biopsies in mild to moderate stable asthma.

We have studied intrasubject variability with respect to counts of immunostained inflammatory cells in snap frozen endobronchial biopsies from a group of patients with clinically mild to moderate stable asthma. Fiberoptic bronchoscopy was used to obtain endobronchial biopsies from the upper and lower lobes in 12 volunteer subjects with asthma on two separate occasions 1 mo apart. During this period there was no significant change in asthma treatment, symptom scores, pulmonary function, or airway hyperresponsiveness. With the aid of immunohistochemistry and interactive image analysis, subepithelial counts for T lymphocytes, T-lymphocyte subsets, and eosinophils were made. There was wide intrasubject variability between anatomic site and with time for all the inflammatory cell counts. In each case the intrasubject variability with time was greater than lobar differences. Power calculations were made to establish the optimal sample size required for each marker. We conclude that even in stable asthma considerable biologic variability compounds sampling variability. Such sources of variability need to be borne in mind when calculating the likely power of intervention studies using biopsy data as end points. Power calculations suggest that approximately 15 subjects would be an optimal number with little advantage in increasing beyond this.

Adolescent↗
PubMed1995

Differences in aerosol output and airways responsiveness between the DeVilbiss 40 and 45 hand held nebulisers.

BACKGROUND: The DeVilbiss 40 glass hand held nebulisers have been widely used for airways responsiveness testing in epidemiological surveys of asthma. These nebulisers have been superseded in some recent studies by the DeVilbiss 45 plastic hand held nebulisers with the assumption that they are interchangeable. This study compared the aerosol outputs of the DeVilbiss 40 and DeVilbiss 45 nebulisers and investigated whether there was any difference in the in vivo measurements of airways responsiveness when using the two nebuliser types. METHODS: The aerosol output of six DeVilbiss 40 and six DeVilbiss 45 nebulisers was calculated by weight loss per actuation, the usual method of calibrating nebuliser output, and compared with the true amount of aerosol obtained measured by a flouride tracer technique. Airways responsiveness was measured twice in 13 asthmatic patients under identical conditions by the Yan protocol using DeVilbiss 40 and 45 nebulisers in random order. RESULTS: Weight loss overestimated the true aerosol output of both types of nebulisers. Weight loss was similar for the DeVilbiss 40 and 45 nebulisers but the true aerosol output of the DeVilbiss 45 was nearly twice that of the DeVilbiss 40 nebuliser. The geometric mean PD20 values with the DeVilbiss 40 nebuliser was a mean 1.7 doubling doses of histamine higher than that obtained with the DeVilbiss 45 nebuliser. CONCLUSIONS: The DeVilbiss 40 and 45 nebulisers should not be used interchangeably for airways responsiveness testing merely because their outputs based on weight loss are similar. Artefactual differences in the prevalence rates of airways responsiveness could occur in longitudinal studies if a change was inadvertently made from using DeVilbiss 40 to DeVilbiss 45 nebulisers.

Adult↗
PubMed1995

Effect of high dose inhaled fluticasone propionate on airway inflammation in asthma.

Inhaled corticosteroids are now first-line therapy for most patients with asthma. However, it has been shown that there is ongoing airway inflammation and airway hyperresponsiveness even in the presence of low dose inhaled corticosteroids. To ensure a maximal therapeutic potential we investigated the effect of 3 mo of a very high dose of a new inhaled corticosteroid, fluticasone propionate (FP) (equivalent to 4,000 micrograms daily of beclomethasone dipropionate [BDP]. Twenty asthmatics with mild-to-moderate disease were recruited into this single-blind study. Baseline data were compared with those from 26 normal subjects. Differences in inflammatory indices between asthmatics and normal subjects were detected in both BAL and endobronchial biopsies. After the FP treatment period there was a significant improvement in symptom scores, lung function, and airway responsiveness by a mean 2.8 doubling dilutions of methacholine. Reduction in the airway lymphocyte load and lymphocyte activation was demonstrated and is likely to be an important mechanism mediating the effects of inhaled corticosteroids. Decreased mast cell numbers and activity in atopic asthma suggest that corticosteroids may have additional targets in different types of asthma. Reduced lymphocyte and mast cell activity was found with high dose FP even in those receiving low dose maintenance BDP prior to the study, suggesting a dose-response effect of inhaled corticosteroids on airway inflammation. BAL eosinophilia was still present after FP, indicative of a component of asthmatic airway inflammation that is relatively resistant to corticosteroid therapy.

Administration, Inhalation↗
PubMed1995

Intrasubject variability in airway inflammation sampled by bronchoalveolar lavage in stable asthmatics.

Despite the increasing complexity of bronchoalveolar lavage (BAL) studies in asthmatics there are few published data concerning the variability of inflammatory parameters measured using this technique. We studied the intrasubject variability of cellular and solute parameters in 20 clinically stable, symptomatic, mild-to-moderate asthmatics, in repeat 180 mL BAL procedures performed 1 month apart. During the study, there was no change in disease activity or medication. Mean (SD) forced expiratory volume in one second (FEV1) was 3.2 (1.09) L at the first BAL and 3.05 (0.98) L at the second. The geometric mean dose of methacholine provoking a 20% decrease in FEV1 (PD20) was 23 micrograms (range 2-1,170 micrograms) at the first BAL and 28 micrograms (range 2-400 micrograms) at the second. There was considerable variability in the BAL cellular and solute parameters measured over the two procedures. Estimates of power calculated for subsequent studies involving this type of subject group were made from the observed variability. Sample sizes of less than 15 mean that differences have to be large in order to be detected in repeat BAL samples. However, there is little improvement in the power of BAL studies for sample sizes greater than 20, indicating that there is little gain in recruiting more than this number of subjects. Thus, our study indicates that although studies of the pathophysiology underlying asthma using BAL require considerable commitment, they are practicable.

Adolescent↗
PubMed1995

Effect of a microaerosol barrier filter on the measurement of lung function.

STUDY OBJECTIVE: A disposable barrier filter (Pall Biomedical, United Kingdom) was developed to prevent the contamination of lung function equipment in clinical use. The aims of this study were to examine its resistance characteristics and to determine the effect of the filter on clinical measurements of lung function. MEASUREMENTS: Twenty-one randomly selected patients and four normal subjects had lung function measured with and without the filter between the mouth and measuring equipment. Measurements of ventilatory function were made with a pneumotachograph (Lilly; Hoechberg, Germany), total lung capacity and airway resistance by constant volume plethysmography, and diffusing capacity for carbon monoxide by the single breath method. Resistance was determined in five unused filters over the flow range 1 to 12 L/s and at a single flow rate (12 L/s) just after a normal subject expired 20 forced vital capacity (FVC) breaths through each of them. RESULTS: The resistance (mean +/- SD) of unused filters was 0.19 +/- 0.02 cm H2O/L/s at 1 L/s and increased linearly to 0.56 +/- 0.02 cm H2O/L/s at 12 L/s. There was no significant increase in resistance after use. The addition of the filter to the breathing circuit caused statistically significant decreases in forced expiratory volume in 1 s (FEV1) (0.044 +/- 0.08 L, p = 0.014) and peak expiratory flow rate (PEFR) (0.47 +/- 0.073 L/s, p = 0.004). The filter did not affect other indices of lung function. CONCLUSION: The filter caused a statistically significant reduction in FEV1 and PEFR; however, this difference was believed not to affect the clinical utility of routine lung function testing.

Adult↗