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Biomedical subjects

J Britton

Publications and source records attributed to J Britton.

At least 73 records · Page 4Linked to original sources
PubMed2000

Risk of cryptogenic fibrosing alveolitis in metal workers.

We report increased proportional mortality from cryptogenic fibrosing alveolitis in the workforce of a major UK engineering company. Measures of metal exposure from unbiased historical occupational records showed that among employees who have worked with metal, the risk of death from or with cryptogenic fibrosing alveolitis increased in relation to the duration of metal-working.

Aged↗
PubMed2000

Exposure to antidepressants and the risk of cryptogenic fibrosing alveolitis: a case-control study.

The explanations for the emergence of cryptogenic fibrosing alveolitis as a new clinical entity during the second half of the 20th century are unclear. The authors have previously reported evidence of an increased risk of cryptogenic fibrosing alveolitis in relation to the use of antidepressant drugs. The authors have now tested this hypothesis a priori in an analysis of computerized general practice records for 890 cases of cryptogenic fibrosing alveolitis and 5,884 matched controls drawn from the UK General Practice Research Database. Exposure to antidepressants at the time of diagnosis was increased in cases compared to controls (odds ratio (OR) 1.52, 95% confidence interval (95% CI) 1.24-1.86), and this increase remained if the analysis was restricted to exposures 4 yrs prior to diagnosis (OR 1.50, 95% CI 0.98-2.30). However this increased prescribing was not specific to any particular class of antidepressant or individual drug, and there was no evidence of a dose-response relationship between exposure to amitriptyline (the most commonly prescribed antidepressant) and disease. The presented data do not allow any firm conclusion to be made as to whether there is a causal relationship between antidepressant exposure and cryptogenic fibrosing alveolitis, but it seems unlikely that exposure to tricyclic antidepressants shortly before diagnosis is a strong risk factor for cryptogenic fibrosing alveolitis.

Aged↗
PubMed2000

Evidence for a role of HLA DRB1 alleles in the control of IgE levels, strengthened by interacting TCR A/D marker alleles.

BACKGROUND: MHC class II alleles at human chromosome 6p21.1 and alleles in the TCR A/D locus at human chromosome 14q11.2 have been implicated in susceptibility to specific allergies and the modulation of total serum IgE. It has also been hypothesized that HLA and TCR allelic interactions may have a strong influence on predisposition to allergic disease. OBJECTIVE: This study was performed to investigate the influence of HLA-DRB and DQB1 alleles and D14S50 alleles (adjacent to TCR A/D locus on 14q11.2), individually and in-combination, on total serum IgE levels, and on the development of specific allergies. METHODS: We performed an association study between HLA-DRB, HLA-DQB1 polymorphisms, D14S50 alleles, total serum IgE expression and specific allergies to house dust mite, grass pollens and cat fur. A sample of 181 individuals was drawn from a larger set of 2415 adults, sampled at random from a district in Nottingham. RESULTS: Strong association was observed between HLA-DRB1*0701 allele and high total serum IgE expression (P < 0.001). D14S50 alleles alone showed no evidence for independent association. However, there was a significant interaction between DRB1*0701 and D14S50 allele 170 such that, when both were present, there was a further increase in total serum IgE levels. CONCLUSION: This study suggests that DRB1*0701 allele is involved in the modulation of total serum IgE, and that there is an interaction between DRB1*0701 and a marker adjacent to TCR A/D in the control of IgE expression.

Adolescent↗
PubMed2000

Recent advances in the aetiology of cryptogenic fibrosing alveolitis.

Crytogenic fibrosing alveolitis is the commonest intersititial lung disease but, until recently, very little has been known about its aetiology. The histopathologist usually sees this disease at transbronchial biopsy or at autopsy. This article reviews the current knowledge of the aetiology of cryptogenic fibrosing alveolitis looking at possible infective, occupational, drug-related, smoking-associated, genetic and dietary factors. Knowledge of the possible roles of these factors in the disease process informs histopathologists when they are reporting these biopsies and enables them to make a larger contribution to defining the pathogenetic mechanisms.

Feeding Behavior↗
PubMed2000

Nutritional issues and asthma.

The effect of diet in determining the etiology and clinical severity of asthma is uncertain. Epidemiologic studies suggest that antioxidants, magnesium, and fat consumption may have an important role in etiology, though the relative importance of these individual nutrients is unclear. Interventional studies are beginning to help clarify the importance of diet in patients with asthma, and early studies suggest that antioxidants in particular may be beneficial.

Antioxidants↗
PubMed2000

Local road traffic activity and the prevalence, severity, and persistence of wheeze in school children: combined cross sectional and longitudinal study.

OBJECTIVES: To investigate the relation between local road traffic activity and the occurrence, severity, and persistence of wheeze in children. METHODS: Data on wheeze and asthma were collected in a cross sectional questionnaire survey of 22,968 primary school children (age 4-11) and 27,826 secondary school children (age 11-16) in the Nottingham area. Direct measures of road traffic flow were made in the locality of each school and combined with Local Authority traffic data for major roads to estimate local traffic activity in vehicle metres/day/km2. Assessment of the effects of potential confounders was performed in nested case-control groups of 6576 primary and 5936 secondary children. Data on frequency of wheeze were collected for the cases to study disease severity. Longitudinal data on a historical cohort of 883 children who reported wheeze when aged 4-11 in 1988 were used to study the persistence of wheeze into adolescence. RESULTS: Unadjusted prevalence of wheeze in the past year within schools varied widely but was not associated with traffic activity in the school locality (weighted regression coefficient beta = -0.01, p = 0.93 for primary schools, beta = -0.18, p = 0.26 for secondary schools). The risk of wheeze in individual primary school children was not associated with traffic activity analysed as a continuous variable, although there was some suggestion of a weak, non-linear plateau effect. Similar effects were found for diagnosed asthma and recent cough. There was no evidence of any relation between traffic activity and risk of wheeze in secondary school children. There were positive but non-significant dose related effects of traffic activity on wheeze severity in primary and secondary children and on persistence of wheeze in the longitudinal cohort. CONCLUSIONS: Traffic activity in the school locality is not a major determinant of wheeze in children.

Adolescent↗
PubMed2000

Lung cancer and cryptogenic fibrosing alveolitis. A population-based cohort study.

Cryptogenic fibrosing alveolitis has been reported to be associated with an increased risk of lung cancer. However, it has recently become apparent that cigarette smoking may be a risk factor for cryptogenic fibrosing alveolitis as well as for lung cancer, and so may confound the association between these conditions. We have therefore estimated the independent increase in lung cancer incidence in patients with cryptogenic fibrosing alveolitis compared with the general population in a population-based cohort study involving 890 subjects with cryptogenic fibrosing alveolitis and 5, 884 control subjects drawn from the United Kingdom General Practice Research Database. The incidence of lung cancer was markedly increased among patients with cryptogenic fibrosing alveolitis (rate ratio [RR] 7.31, 95% confidence interval [95% CI] 4.47 to 11.93, p < 0.001), and adjustment for previous smoking history had little effect on this odds ratio (adjusted RR: 8.25, 95% CI 4.70 to 11.48, p < 0.001). This increase in lung cancer incidence remained when the analysis was restricted to current smokers (RR 7.36, 95% CI 1.54 to 35.19, p = 0.012). This study provides clear evidence that the incidence of lung cancer is increased in patients with cryptogenic fibrosing alveolitis, and that this effect is independent of the effect of cigarette smoking.

Aged↗
PubMed2000

Increased risk of fibrosing alveolitis associated with interleukin-1 receptor antagonist and tumor necrosis factor-alpha gene polymorphisms.

Fibrosing alveolitis (FA) is characterized by persistent inflammation and elevated production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and interleukin-1 receptor antagonist (IL-1ra) in the lung. Single base variations at position +2018 in the IL-1ra gene (IL-1RN) and position -308 in the TNF-alpha gene (TNF-A) are overrepresented in other chronic inflammatory disease populations. We have tested the hypothesis that predisposition to FA may also be influenced by these polymorphisms by genotyping 88 cases and matched controls from England and 61 cases and 103 unmatched controls from Italy. The rarer allele for IL-1RN and TNF-A was designated allele 2 in each case. For IL-1RN allele 2, in the English group, the relative odds of FA were increased in homozygous subjects by an odds ratio (OR) of 10.2 (95% confidence intervals [CI], 1.26 to 81.4; p = 0.03) and for carriers by an OR of 1.85 (95% CI, 0.94 to 3.63; p = 0.075). In the Italian population, the risk of FA was increased, in IL-1RN allele 2 homozygotes (OR, 2.54; 95% CI, 0.68 to 9.50; p = 0.2) and in carriers (OR 2.40; 95% CI, 1.26 to 4.60; p = 0.008). Carriage of TNF-A allele 2 was also associated with increased risk of FA in the English (OR, 1.85; 95% CI, 0.94 to 3.63; p = 0.075) and Italian (OR, 2.50; 95% CI, 1.14 to 5.47; p = 0.022) populations. These data suggest IL-1RN (+2018) allele 2 and TNF-A (-308) allele 2 confer increased risk of developing FA and, therefore, that unopposed IL-1beta and/or excessive TNF-alpha may play a pathophysiologic role in this condition.

Aged↗
PubMed2000

International comparison of median age at death from cystic fibrosis.

STUDY OBJECTIVES: To compare international trends in mortality from cystic fibrosis. DESIGN: Comparison of trends in median age at death using national mortality data. SETTING: Data from 10 countries in North America, Europe, and Australasia. PARTICIPANTS: All persons registered as having died of cystic fibrosis in specified years from 1980 to 1994. INTERVENTIONS: Comparison of relative odds of death at the international median age at death for the year of death between countries for two periods of time; from 1980 to 1987 (10 countries) and from 1980 to 1994 (7 countries). MEASUREMENTS AND RESULTS: The international median age at death increased from 8 years in 1974 to 21 years in 1994. Median age at death also increased within all countries, was consistently highest in the United States, and varied significantly by a factor of > twofold between countries. Women were significantly more likely to die at a younger age than the median age at death than men. CONCLUSIONS: Median age at death from cystic fibrosis is increasing, but our findings imply that clinically significant differences in survival with cystic fibrosis persist between countries.

Adolescent↗
PubMed1999

Modifying radical radiotherapy in high grade gliomas; shortening the treatment time through acceleration.

PURPOSE: To evaluate the efficacy and toxicity of accelerated radiotherapy in patients with primary high grade glioma, where acceleration is used as a means of delivering a shortened course of radical radiotherapy. PATIENTS AND METHODS: Two-hundred and eleven patients with primary high grade glioma were treated at the Royal Marsden NHS Trust between 1987 and 1997 with accelerated radiotherapy (55 Gy in 34 fractions twice daily), to planning target volume (PTV) defined as enhancing tumour and a 3 cm margin. All had histologically confirmed high grade glioma (53 anaplastic astrocytoma, 137 glioblastoma multiforme, 4 gliosarcoma, 5 gemistocytic astrocytoma, 12 high grade astrocytoma not otherwise specified). The mean Karnofsky performance status (KPS) was 90 and median age was 54 years (range 19-77). RESULTS: Of 211 patients entered, 201 were able to complete radiotherapy; 39 patients (19%) had deterioration in KPS during radiotherapy and this was transient in 11. Median survival of 211 patients was 10 months with 1 year, 2 year, and 3 year survival probabilities of 38%, 14%, and 8% respectively. Age and extent of excision were independent prognostic factors for survival. Previous comparison to matched cohort receiving 60 Gy in 30 daily fractions did not demonstrate significant survival difference. CONCLUSION: Accelerated radiotherapy is a feasible treatment approach for patients with high grade glioma. The survival and functional outcome are comparable to conventional radiotherapy and the treatment is without serious acute toxicity. While acceleration of conventional dose irradiation could be tested in randomised studies, it is unlikely this approach would result in a clinically meaningful survival benefit. Accelerated radiotherapy therefore remains one of the ways of delivering radical irradiation in patients with high grade glioma. However, it adds complexity to what is a palliative treatment regimen and the rationale and advisability should be re-examined, particularly in terms of impact on quality of life, true patient preference, and health economic considerations.

Adult↗