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Biomedical subjects

A L James

Publications and source records attributed to A L James.

At least 19 recordsLinked to original sources
PubMed2004

Management of bilateral choanal atresia in the neonate: an institutional review.

The endoscopic repair of bilateral choanal atresia using powered instrumentation has become a common procedure performed by many pediatric otolaryngologists. A 10-year retrospective review of the management of bilateral choanal atresia in the neonate was undertaken at the Hospital for Sick Children, a tertiary care pediatric institution in Toronto. Although many techniques were used for repair including the endoscopic technique, a simple puncture, dilation and stenting technique was used most frequently. Fifty-two patients were identified who underwent this technique. The modifications and refinements of this technique and post-operative care will be detailed. The results were as follows. All patients were successfully extubated within 24h of the operation. The average duration of nasal stenting was 3 months. Three patients required re-stenting, one of which had nasal stenting for the first year of life. This patient was born prematurely, had trisomy-21 and was stented weighing a mere 600g. One patient had a small septal perforation and only two patients required transpalatal repair later in life for persistent nasal symptoms. There were no CNS complications and no incidence of significant nasal hemorrhage or infection. All patients received topical antibiotics and steroid drops during the stenting period. Mitomycin C was not used. Granulation tissue was not a significant problem. Despite the advances in endoscopic technology, the puncture, dilation and stenting technique is still the senior author's preferred method of repair for neonatal bilateral choanal atresia.

Choanal Atresia↗
PubMed2002

Contralateral suppression of DPOAE measured in real time.

The aim of this study was to measure contralateral suppression of distortion product otoacoustic emissions (DPOAE) in real time. A total of 10 human subjects were studied with a novel device to record DPOAE without signal time averaging, using digital narrow band pass filtering. Real time DPOAE levels were recorded at 2f1-f2 using primary tone settings of f2/f1 = 1.22 and L1 = 70 dB SPL, L2 = 65 dB SPL, at five values of f2 between 2.2 and 7.7 kHz. An acoustic stimulus was applied intermittently to the contralateral ear to cause DPOAE suppression. Characteristic features of contralateral suppression were identified and distinguished from small spontaneous variations in the real time DPOAE signal. Magnitude of suppression increased with contralateral stimulus intensity. Onset latency of suppression was around 43 ms (31-95 ms). Potential clinical applications are discussed in the light of these findings, including a role in improving the specificity of neonatal hearing screening.

Acoustic Stimulation↗
PubMed2002

Increased mast cells and neutrophils in submucosal mucous glands and mucus plugging in patients with asthma.

BACKGROUND: Mucus plugging of the airways is invariably seen in cases of fatal asthma, mucus production is associated with asthma attacks, and the area of submucosal glands is increased in asthma. Mediators secreted from mast cells and neutrophils can stimulate mucous gland secretion. A study was undertaken to count the mast cells and neutrophils in submucosal glands and to relate cell numbers to the presence of mucus in the airway lumen. METHODS: Cartilaginous airways obtained at necropsy from cases of fatal asthma (n=8), non-fatal asthma (n=8), and control cases (n=8) were examined. Contiguous transverse sections were stained for mast cell tryptase and neutrophil elastase, and with Periodic Acid Schiff solution to identify mucus. Mucous gland area, lumen area, and the percentage of the relaxed lumen area occupied by mucus (mucus occupying ratio, MOR) were measured. Mast cells (intact and degranulated) and neutrophils per area of submucosal gland were calculated. RESULTS: Compared with controls, the cases of fatal asthma had increased mucous gland area, MOR, percentage of degranulated mast cells, and numbers of neutrophils in the submucosal glands (p<0.05). In cases of non-fatal asthma the MOR and the numbers of mast cells and neutrophils in the submucosal glands were increased (p<0.05). When all cases were pooled together, the MOR correlated with the total number of mast cells (r=0.55, p=0.005) and with the number of degranulated mast cells in the submucosal glands (r=0.51, p=0.013), but not with the number of neutrophils (r=0.21, p=0.121). CONCLUSION: These results show that mucous gland area, MOR, and mucous gland inflammation are increased in asthma and that degranulation of mast cells may contribute to secretion of mucus into the lumen in cases of fatal asthma.

Adult↗
PubMed2002

Distribution and degranulation of airway mast cells in normal and asthmatic subjects.

It was hypothesized that the distribution and activation of mast cells across the airway wall may reflect their function in asthma. The density of mast cells (intact and degranulated) within airway compartments in cartilaginous and membranous airways, obtained from autopsies on patients with fatal asthma, nonfatal asthma, and nonasthmatic control cases have been examined. In cartilaginous airways, the mean+/-SE density of mast cells in control cases was 27+/-9 cells x mm(-2). It was similar in nonfatal asthma (24+/-2 cells x mm(-2)) but reduced (p<0.05) in fatal asthma cases (16+/-2 cells x mm(-2)). In membranous airways, the density of mast cells in control cases was 155+/-21 cells x mm(-2) and was higher (p<0.05) in cases of nonfatal (270+/-51 cells x mm(-2)) and fatal asthma (219+/-26 cells x mm(-2)). Mast-cell density was greatest on the smooth muscle and mucous glands in cartilaginous airways and on the smooth muscle and outer airway wall in membranous airways. The percentage of degranulated mast cells was higher (p<0.05) in cases of asthma, related to disease severity, and was higher in cartilaginous than membranous airways. Degranulation was greatest on the smooth muscle in fatal asthma cases. Mast-cell distribution and degranulation varies between cartilaginous and membranous airways and across the airway wall. Degranulation of mast cells is related to asthma severity. The increased degranulation in proximal airways may reflect stimulation via the inhaled route.

Adolescent↗
PubMed2001

Betahistine for Menière's disease or syndrome.

BACKGROUND: Menière's disease is characterised by attacks of hearing loss, tinnitus and disabling vertigo. Betahistine is used by many people to reduce the frequency and severity of these attacks but there is conflicting evidence relating to its effects. OBJECTIVES: The objective of this review was to assess the effects of betahistine in people with Menière's disease. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (The Cochrane Library issue 4,1999), MEDLINE (January 1966 to December 1999), EMBASE (January 1985 to December 1999) and Index Medicus (1962 to 1966). We checked reference lists of articles and contacted pharmaceutical companies for further studies. SELECTION CRITERIA: Randomised controlled studies of betahistine versus placebo in Menière's disease. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for further information. MAIN RESULTS: Six trials involving 162 patients were included. No trial met the highest quality standard set by the review because of inadequate diagnostic criteria or methods, and none assessed the effect of betahistine on vertigo adequately. Most trials suggested a reduction of vertigo with betahistine and some suggested a reduction in tinnitus but all these effects may have been caused by bias in the methods. One trial with good methods showed no effect of betahistine on tinnitus compared with placebo in 35 patients. None of the trials showed any effect of betahistine on hearing loss. No adverse effects were found with betahistine. REVIEWER'S CONCLUSIONS: There is insufficient evidence to say whether betahistine has any effect on Menière's disease.

Betahistine↗
PubMed2001

Gibbs sampling-based segregation analysis of asthma-associated quantitative traits in a population-based sample of nuclear families.

Asthma is a common, complex human disease. Elevated serum immunoglobulin E (IgE) levels, elevated blood eosinophil counts, and increased airway responsiveness are physiological traits that are characteristic of asthma. Few studies have investigated major gene effects for these traits in a population-based sample. Further, it is not known if any putative major genes may be common to two or more of these traits. We investigated the existence and nature of major genes modulating asthma-associated quantitative traits in an Australian population-based sample of 210 Caucasian nuclear families. The sharing of these major genes was also investigated. Segregation analysis was based upon a Markov Chain Monte Carlo (Gibbs sampling) approach as implemented in the program BUGS v0.6. All models included adjustment for age, height, tobacco smoke exposure, and gender. The segregation of total IgE levels, blood eosinophil counts, and dose-response slope (DRS) of methacholine challenge were all consistent with major loci at which a recessive allele acted to increase or decrease the phenotype. The respective estimated frequencies of the recessive alleles were 68% (total IgE), 10% (blood eosinophil count), and 27% (DRS). Extensive modelling suggested that the major loci controlling total serum IgE levels, blood eosinophil counts, and airway responsiveness represent different genes. These data provide evidence, for the first time, of the existence of at least 3 distinct genetic pathways involving major gene effects on physiological traits closely associated with asthma. These results have implications for gene discovery programs.

Adolescent↗
PubMed2001

Synthesis and evaluation of novel fluorogenic substrates for the detection of bacterial beta-galactosidase.

AIMS: A widely used coumarin derivative is 7-hydroxy-4-methylcoumarin-beta-D-galactoside (4-methylumbelliferone-beta-D-galactoside; 4-MU-GAL). This galactoside is utilized as a substrate for the detection of the beta-galactosidase activity of coliform bacteria in water analysis. The intense fluorescence of coumarin-based molecules has enabled them to be incorporated into enzyme-based tests for the quantitative assay of indicator bacteria. The aim of this present study was to evaluate the potential of other coumarin derivatives, by synthesis of a selection of core coumarin molecules. METHODS AND RESULTS: Several coumarin derivatives were found to be more promising than 4-MU, with ethyl-7-hydroxycoumarin-3-carboxylate (EHC) giving a combination of greater fluorescence over a broad pH range and reduced growth inhibition with 12 representative coliform strains. On conversion to a beta-galactoside derivative, EHC-GAL generated a more rapid fluorescence than any other tested substrate. CONCLUSIONS: When tested in a broth assay format, based on most probable number (MPN), low numbers of coliforms were detected with EHC-GAL around 1 h earlier than with 4-MU-GAL. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study suggests that EHC-GAL should be evaluated as a substrate for the detection of coliforms in water analysis, due to a combination of the following favourable features: (i) reduced toxicity; (ii) increased fluorescence; (iii) pH stability of fluorescence; and (iv) rapid detection.

Bacteriological Techniques↗
PubMed2001

Fluorogenic substrates for the detection of microbial nitroreductases.

AIMS: To synthesize and evaluate fluorogenic substrates for the detection of microbial nitroreductases. These substrates, all based on 7-nitrocoumarin, may be reduced to form fluorescent aminocoumarins. METHODS AND RESULTS: Thirty pathogenic microbial strains, including both bacteria and yeasts, were examined for nitroreductase activity in a whole-cell assay. All strains readily reduced each of the seven substrates to generate fluorescence, suggesting the widespread presence of nitroreductase activity in pathogenic bacteria. CONCLUSIONS, SIGNIFICANCE AND IMPACT OF THE STUDY: These novel substrates facilitate the direct detection of nitroreductase activity and have potential as sensitive indicators of microbial growth.

Bacteria↗
PubMed2001

Tightening the net: children, community, and control.

The recent move to revitalize social democracy in the UK under the New Labour government, explored by Giddens as 'the Third Way', embraces many of Etzioni's ideas on communitarianism. The principles that emerge from these political philosophies, such as the involvement of local communities in policy consultations and implementation, have largely been welcomed as a reflection of the aim of revitalizing civic society in the context of a range of social policies. It is argued, however, that for children, contrary to this general trend, many of these policies represent attempts to increase the social control of children. Their effect has been to restrict children's agency and their rights, rather than to increase their participation as citizens, and thus,in spite of the requirements of the UN Convention on the Rights of the Child, children continue to be marginalized.

Adult↗
PubMed2001

Familial aggregation and heritability of adult lung function: results from the Busselton Health Study.

Decreased spirometric indices are characteristic of asthma and other respiratory diseases. The aim of this study was to investigate the genetic and environmental components of variance of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) measured in adulthood in an Australian population-based sample of 468 Caucasian nuclear families. The inter-relationships of the genetic determinants of these traits with asthma and atopic rhinitis were also investigated. Serial cross-sectional studies were conducted in the town of Busselton in Western Australia between 1966 and 1981 and follow-up of previous attendees was undertaken in 1995. Data from each subject included in this study were from a single survey in adulthood (25-60 yrs of age) when the subject was as close to age 45 yrs as possible. Multivariate analysis suggested that FEV1 and FVC levels were associated with age, sex, height, tobacco smoke exposure, asthma and atopic rhinitis. After adjustment for relevant covariates, FEV1 levels had a narrow-sense heritability (h2N) of 38.9% (SE 9.1%). FVC levels had an h2N of 40.6% (SE 8.9%). Extended modelling demonstrated little overlap in the genetic determinants of asthma or atopic rhinitis and either FEV1 or FVC levels. The results of this study were consistent with the existence of important genetic determinants of adult lung function that are independent of asthma or other atopic disease, cigarette smoking, height, age or sex.

Adult↗
PubMed2000

Familial aggregation and heritability of asthma-associated quantitative traits in a population-based sample of nuclear families.

Asthma is a common, genetically complex human disease. Elevated serum immunoglobulin E (IgE) levels, elevated blood eosinophil counts, variably reduced spirometric measures and increased airway responsiveness (AR) are physiological traits which are characteristic of asthma. We investigated the genetic and environmental components of variance of serum total and specific IgE levels, blood eosinophil counts, the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), and AR in an Australian population-based sample of 232 Caucasian nuclear families. With the exception of FVC levels, all traits were closely associated with clinical asthma in this population. Loge total serum IgE levels had a narrow-sense heritability (h2N) of 47.3% (SE = 10. 0%). Specific serum IgE levels against house dust mite and Timothy grass, measured as a RAST Index, had a h2N of 33.8% (SE = 7.3%). FEV1 levels had a h2N of 6.1% (SE = 11.6%), whilst FVC levels had a h2N of 30.6% (SE = 26.8%). AR, quantified by the loge dose-response slope to methacholine (DRS), had a h2N of 30.3% (SE = 12.3%). These data are consistent with the existence of important genetic determinants of the pathophysiological traits associated with asthma. Our study suggests that total and specific serum IgE levels, blood eosinophil counts and airways responsiveness to inhaled agonist are appropriate phenotypes for molecular investigations of the genetic susceptibility to asthma.

Adolescent↗
PubMed2000

Alizarin-beta-D-galactoside: a new substrate for the detection of bacterial beta-galactosidase.

We describe the synthesis of a new substrate for the detection of bacterial beta-galactosidase. This substrate, alizarin-beta-D-galactoside, is readily hydrolysed to release alizarin which complexes with various metal ions to form brightly coloured chelates. A total of 367 strains of Gram-negative bacteria were examined for their ability to hydrolyse three chromogenic substrates: alizarin-beta-D-galactoside (Aliz-gal), cyclohexenoesculetin-beta-D-galactoside (CHE-gal) and 5-bromo-4-chloro-3-indolyl-beta-D-galactoside (X-gal). A total of 182 strains (49.6%) were found to hydrolyse at least one of the three substrates. All of these 182 strains (100%) hydrolysed Aliz-gal whereas only 170 (93.4%) and 173 (95.1%) hydrolysed CHE-gal and X-gal, respectively. We conclude that alizarin-beta-D-galactoside is a highly sensitive substrate for the demonstration of beta-galactosidase.

Anthraquinones↗
PubMed2000

Evaluation of p-naphtholbenzein-beta-D-galactoside as a substrate for bacterial beta-galactosidase.

We describe the synthesis of a new substrate for the detection of beta-galactosidase and evaluate its performance in comparison with 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) and cyclohexenoesculetinbeta-D-galactoside (CHE-Gal). Of 206 Enterobacteriaceae strains able to hydrolyze X-Gal, 194 (94.2%) hydrolyzed CHE-Gal and 192 (93.2%) hydrolyzed p-naphtholbenzein-beta-D-galactoside (PNB-Gal). We conclude that PNB-Gal is an effective substrate for the detection of beta-galactosidase.

Chromogenic Compounds↗
PubMed2000

The airway longitudinal elastic fiber network and mucosal folding in patients with asthma.

A submucosal network of elastic fibers in a collagen and myofibroblast matrix form discrete longitudinal bundles (LB) in the bronchial tree. The LB may affect airway function by altering the mechanical properties of the airway wall or by changing the folding behavior of the airway mucosa. The area and number of LB were quantified from 12 cases each of fatal asthma (FA), nonfatal asthma (NF), and nonasthmatic (NA) control cases on elastic-trichrome stained airways. The effects of group, sex, age, and smoking were examined using multiple linear regression. The area fraction of LB increased (p < 0.05) approximately twofold in cases of FA compared with NA control cases in both large and small airways. The areas of LB were increased in smokers, older subjects, and men (p < 0.05). The number of mucosal folds was related to the number of longitudinal bundles in asthmatics and nonasthmatics and was not different between groups. Collagen and myofibroblasts were increased (p < 0.05) in LB of FA and NF cases compared with NA control cases. The increased size and altered composition of LB in asthma may influence airway function; however, excessive airway narrowing in asthma is not due to altered numbers of mucosal folds.

Adult↗
PubMed2000

Pulmonary vascular congestion selectively potentiates airway responsiveness in piglets.

The influence of pulmonary vascular congestion on the response of the airways and lung tissue to low doses of inhaled methacholine (MCh) was studied by inflating a balloon catheter in the left atrium of the heart in six piglets, with an additional five piglets serving as control animals. Congestion alone resulted in small increased in baseline airway (Raw) (14.6 +/- 3.7%) and tissue (Rti) resistance (8. 1 +/- 6.5%). Low-dose inhaled MCh (0.3 mg/ml) increased Raw and Rti in the control group by 10.8 +/- 10.3% and 42.2 +/- 29.5%, respectively. The increase in Raw with MCh in the presence of vascular engorgement was significantly greater (67.8 +/- 18.9%) but the increase in Rti (38.1 +/- 13.2%) was similar to that seen in the control group. Morphometric measurements were performed on transverse sections of large and small airways from nine additional piglets (three congested only, three MCh only, and three congestion plus MCh). The thickness of the inner airway wall was similar in all groups. Compared with MCh only piglets, the thickness of the outer airway wall (between the outer border of the smooth muscle and the surrounding lung parenchyma) was increased (p < 0.05) in engorged only and engorged plus MCh piglets. Compared with MCh only and engorgement only, the amount of airway smooth muscle shortening was greater (p < 0.05) in all airway size groups in piglets that underwent engorgement plus MCh challenge. The results of this study demonstrate that pulmonary vascular engorgement, induced by increased left atrial pressure, selectively enhances the airway, but not the parenchymal, response to inhaled MCh. These changes are associated with increased thickness of the outer airway wall in response to vascular congestion, suggesting that uncoupling of the mechanical interdependence between the airway smooth muscle and the lung parenchyma may have occurred. Mechanical uncoupling may reduce the load opposing smooth muscle shortening resulting in increased airway narrowing in response to low doses of inhaled methacholine.

Animals↗
PubMed2000

Independent inheritance of serum immunoglobulin E concentrations and airway responsiveness.

Elevated serum Immunoglobulin E (IgE) levels and increased airway responsiveness (AR) are correlated traits that are characteristic of asthma. It is not known to what extent these traits arise from distinct or shared genetic determinants. We investigated the genetic and environmental components of variance of serum total and specific IgE levels and AR in an Australian population-based sample of 232 Caucasian nuclear families. The inter-relationships of the genetic determinants of these traits were also investigated. Log(e) total serum IgE levels had a narrow-sense heritability (h(2)(N)) of 47.3% (SE = 10.0%). Specific serum IgE levels against house dust mite and timothy grass, measured as a RAST Index, ad a h(2)(N) of 33.8% (SE = 7.3%). AR, quantified by the log(e) dose-response slope to methacholine (DRS), had a h(2)(N) of 30.0% (SE = 12.3%). Extended modeling demonstrated an approximate 70% overlap in the genetic determinants of total and specific serum IgE levels. The genetic determinants of serum IgE levels and AR exhibited less than 30% sharing. These data are consistent with the existence of multiple genetic determinants of the pathophysiologic traits associated with asthma, and suggest that AR is genetically distinct from atopy. These results have implications for gene discovery programs.

Adolescent↗
PubMed1999

Lung function, respiratory symptoms, and mortality: results from the Busselton Health Study.

PURPOSE: This study examines the association between lung function [percentage predicted FEV, (forced expiratory volume in 1 s)] and respiratory symptoms (asthma, bronchitis, wheeze, dyspnea) and mortality from all causes; coronary heart disease, stroke, cancer, and respiratory disease in a cohort of 2,100 men and 2,177 women in the Busselton Health Study followed for 20-26 years for mortality. METHODS: A total of 840 men and 637 women died during the follow-up period, and Cox proportional hazards regression was used to assess the relationships between risk factors and mortality. RESULTS: Lung function was significantly and independently predictive of mortality from all causes, coronary heart disease, cancer, and respiratory disease in both men and women, and of mortality from stroke in women. There was evidence that, among men, the association was stronger in current and former smokers as compared to those who never smoked. After adjustment for age, smoking, lung function, coronary heart disease, blood pressure, treatment for hypertension, total cholesterol, body mass index, and alcohol consumption, dyspnea was significantly related to total mortality in men and women and to respiratory disease mortality in men, and asthma was significantly related to respiratory disease mortality in women. CONCLUSIONS: Lung function is associated with mortality from many diseases independent of smoking and respiratory symptoms. Although most respiratory symptoms are associated with smoking and lung function, after controlling for smoking and lung function, only dyspnea is associated with mortality from nonrespiratory causes.

Adult↗