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Biomedical subjects

A Seaton

Publications and source records attributed to A Seaton.

At least 19 recordsLinked to original sources

Family size, childhood infections and atopic diseases. The Aberdeen WHEASE Group.

BACKGROUND: This study addresses the causes of the increases in childhood asthma and allergic disease. On the basis of an observed inverse relationship between family size and allergic disease or atopy, it has been proposed that a fall in common childhood infections may have been responsible for the rise in asthma. This study was undertaken to investigate the relationships between family size and reported allergic disease and to test the hypothesis that an inverse relationship between the two is a consequence of childhood infections. METHODS: Data had been obtained in a 1964 cross sectional survey of a random sample of Aberdeen schoolchildren aged between 10 and 14 in that year. Records of the presence or absence of asthma, eczema, or hay fever at the time of the survey and a history of measles, pertussis, varicella, rubella, and mumps before and after the age of three years were available for 2111 subjects. RESULTS: The risks of hay fever (odds ratio 0.2, 95% CI 0.1 to 0.8) and eczema (OR 0.3, CI 0.1 to 0.7) were inversely related to having had three or more older siblings, whilst the risk of asthma (OR 0.4, CI 0.1 to 0.9) was inversely related to having had three or more younger siblings. Increasing total numbers of siblings showed a significant trend in protection against both eczema and hay fever. A weak protective effect against asthma was found for measles after the age of three (OR 0.5, CI 0.3 to 0.9) and slight increases in the risk of eczema were associated with having had rubella or pertussis and of asthma with having had varicella. The number of infections before the age of three was associated with a significant trend in the odds ratios towards increased risk of asthma (p = 0.025). There were significant trends in the odds ratios towards greater risk of eczema and hay fever with increasing exposure to rubella, mumps, and varicella. These relations between infection and atopic diseases were independent of the potential confounding factors age, sex, father's social class, and total number of siblings. CONCLUSIONS: These data add to the accumulating evidence that membership of a large sibship confers some protection against atopic disease. This does not appear to be explained by the common childhood infections which show conflicting relationships with atopic disease, in that measles may have some protective effect against asthma but the more infections a child has had, the more likely he or she is to have atopic disease. The explanation of the sibship effect is likely to lie elsewhere and the fall in common childhood infections is unlikely to explain the rise in atopic disease.

Adolescent

Pregnancy following intracytoplasmic sperm injection treatment with dead husband's spermatozoa: ethical and policy considerations.

This paper describes the first pregnancy in a childless widow after intracytoplasmic sperm injection (ICSI) treatment with her deceased husband's spermatozoa which had been stored for nearly 3 years before use. Before his death the husband had received treatment for testicular cancer and he had given the appropriate written consent for the future use of his spermatozoa. Of the 10 eggs injected, six resulted in normal embryos. Three embryos were transferred and the remaining three embryos are currently stored for possible future use. The treatment resulted in a continuing singleton pregnancy. The case demonstrated the suitability of ICSI in those difficult cases where the sperm quality is extremely poor. This success is also compared with a widely debated case of another widow who was refused permission to use her deceased husband's spermatozoa. It is concluded that in the case of posthumous use of frozen spermatozoa, the current laws are conveniently applicable in a chronic illness but not so in an acute illness leading to death. In the light of the wide public debate on the issues raised by this legal case, the UK Government has also decided to conduct a review of consent procedures involving the storage and use of genetic material.

Cryopreservation

Episode of toxic gas exposure in sewer workers.

OBJECTIVES: Sewer workers are used to unpleasant smells, but may be required to investigate unusual ones. Twenty six men were involved in investigation of episodes of such a smell after neighbourhood complaints over several weeks. METHODS: Workers exposed to the smell were investigated by clinical follow up, lung function tests, and measurement of pituitary function. RESULTS: 14 of the 26 developed subacute symptoms including sore throat, cough, chest tightness, breathlessness, thirst, sweating, irritability, and loss of libido. Severity of symptoms seemed to be dose related. Minor symptoms resolved over several weeks but those more seriously affected have shown deteriorating respiratory symptoms and lung function and remain unable to work a year after the incident. In one, evidence of mild cranial diabetes insipidus was found. Analysis of gas from the sewer showed the presence of a mixture of thiols and sulphides, known to be highly odorous and not normally found in sewers. The source remains unknown. CONCLUSIONS: Several of these men seem to have developed delayed airways disease and disturbances of hypothalamic function. Such an outcome has not to our knowledge been described before. Despite the presence of the smell, standard safety gas detection equipment used to ensure the sewer was safe to enter failed to indicate the presence of a hazard. Protection against such incidents can only be provided by the use of positive pressure breathing apparatus.

Adult

Bronchial reactivity and dietary antioxidants.

BACKGROUND: It has been postulated that dietary antioxidants may influence the expression of allergic diseases and asthma. To test this hypothesis a case-control study was performed, nested in a cross sectional study of a random sample of adults, to investigate the relationship between allergic disease and dietary antioxidants. METHODS: The study was performed in rural general practices in Grampian, Scotland. A validated dietary questionnaire was used to measure food intake of cases, defined, firstly, as people with seasonal allergic-type symptoms and, secondly, those with bronchial hyperreactivity confirmed by methacholine challenge, and of controls without allergic symptoms or bronchial reactivity. RESULTS: Cases with seasonal symptoms did not differ from controls except with respect to the presence of atopy and an increased risk of symptoms associated with the lowest intake of zinc. The lowest intakes of vitamin C and manganese were associated with more than fivefold increased risks of bronchial reactivity. Decreasing intakes of magnesium were also significantly associated with an increased risk of hyperreactivity. CONCLUSIONS: This study provides evidence that diet may have a modulatory effect on bronchial reactivity, and is consistent with the hypothesis that the observed reduction in antioxidant intake in the British diet over the last 25 years has been a factor in the increase in the prevalence of asthma over this period.

Adult

A meta-analysis of mortality among workers exposed to organic solvents.

It has been suggested that organic solvent exposure may contribute to an increased risk of blood disorders, neurological, liver and renal disease, and cancer. A meta-analysis has been performed of 55 published mortality studies which involved solvent exposure and provided standardised mortality ratios (SMR) or relative risk (RR). The combined results showed the overall SMR to be 86.7 (95% confidence interval [Cl] = 83.7-89.9), while that for all sites of cancer was 92.3 (Cl = 87.5-97.4). Risk of death from leukaemia was increased (SMR = 112.2, Cl = 101.6-146.9) as was that from cancer of liver and biliary passages (SMR = 119.7, Cl = 104.4-137.2), even though the risk of death from cirrhosis was reduced (SMR = 81.5, Cl = 68.1-97.4). No excess risk of death from other diseases has been found. The favourable mortality might be from a "healthy worker effect', but the increase in death from liver cancer in the absence of excess deaths from cirrhosis is biologically plausible and justifies further investigation. The increase in mortality from leukaemia is likely to have been associated with exposure to benzene.

Chemical Industry

The influence of study characteristics on the healthy worker effect: a multiple regression analysis.

The so-called 'healthy worker effect' (HWE) describes a reduced mortality rate in occupational populations. From 85 occupational cohorts of workers exposed to organic solvents, we have previously found a low weighted standardized mortality ratio (SMR) for all causes (SMR = 89.5, 95 per cent confidence interval [Cl] = 89.0-90.2). Characteristics of the cohorts were examined for association with the HWE. A multiple regression analysis revealed that, for overall deaths, the closer the comparison group, the smaller the HWE (p = 0.001); the more hazardous the potential exposures, the higher the SMR (p = 0.02); the higher the social class, the greater the HWE (p = 0.02); and the higher the rates of loss to follow up, the greater the HWE (p = 0.04). These results have shown that, in addition to time-related modifiers, the comparison group, type of occupational exposure, social class and rates of loss to follow-up significantly influence the size of the so-called HWE. Differences in the HWE related to gender and race were probably attributable to different rates of loss to follow-up.

Cohort Studies

Egg-sharing in assisted conception: ethical and practical considerations.

The present acute shortage of eggs for donation cannot be overcome unless adequate guidelines are set to alleviate the anxieties regarding payments, in cash or kind, to donors. The current Human Fertilisation and Embryology Authority (HFEA) guidelines do not allow direct payment to donors but accept the provision of lower cost or free in vitro fertilization (IVF) treatment to women in recognition of oocyte donation to anonymous recipients. Egg-sharing achieved in this way enables two infertile couples to benefit from a single surgical procedure. However, the practical guidelines related to this approach are ill-defined at the present time leading to some justifiable uncertainty. A pilot study was therefore undertaken in order to establish the place of egg-sharing in an assisted conception programme. The current HFEA guidelines on medical screening of patients, counselling, age and rigid anonymity between the donor and recipient were followed. The study involved 55 women (25 donors and 30 recipients) in 73 treatment cycles involving fresh and frozen-thawed embryos. Donors were previous IVF patients who, regardless of their ability to pay, shared their eggs equally with matched anonymous recipients. They paid only for their consultations and tests right up to the point of being matched with a recipient. The sole recipient paid the cost applicable in egg donation of a single egg collection, although both received embryo transfers. The results indicate that although the recipients were older than the donors (41.4 +/- 0.9 versus 31.6 +/- 0.5 years), and there was no difference in the mean number of eggs allocated, the percentage fertilization rates, or the mean number of embryos transferred, there were more births per patient amongst recipients than amongst donors (30 versus 20%). We conclude that providing the donors are selected carefully, this scheme whereby a sub-fertile donor helps a sub-fertile recipient is a very constructive way of solving the problem of the shortage of eggs for donation. There are also the advantages of including a group of women who would otherwise be denied treatment. Problems related to 'patient coercion' can, in our view, be fully overcome by the application of strict common-sense safeguards. The ideal of pure altruism is not without its medical and moral risk. The success of egg-sharing depends on shared interests and a degree of altruism between the donor, the recipient and the centre. The current HFEA guidelines should be applauded for enabling a highly effective concept of mutual help to develop.

Adult

The increase in hay fever: pollen, particulate matter and SO2 in ambient air.

To investigate whether the rise in allergic disease is explicable on the basis of an increase in the concentrations of allergen and urban air pollutants to which the population has been exposed, we compared the concentrations of grass pollen, sulphur dioxide and black smoke to which two samples of children with previously measured prevalences of hay fever had been exposed, in Cardiff, South Glamorgan. In these studies there had been a 59% increase in the prevalence of hay fever among 12 year old school children between 1973 and 1988. Exposures to grass pollen of the two populations had been no different, but the earlier sample, with the lower prevalence of hay fever, had been exposed to substantially higher concentrations of ambient particulate matter and sulphur dioxide. The rise in prevalence of hay fever, occurring without a rise in grass pollen concentrations, supports the hypothesis that the population has become more susceptible to airborne allergen. This increased susceptibility is unlikely to be a consequence of concomitant exposure to sulphur dioxide and particulate air pollution.

Air Pollutants

Inhibition of the alveolar macrophage oxidative burst by a diffusible component from the surface of the spores of the fungus Aspergillus fumigatus.

BACKGROUND: Aspergillus fumigatus is a fungus that grows on dead and decaying organic matter in the environment and whose spores are present ubiquitously in the air. The fungus causes a range of diseases in the human lung. A study was undertaken to demonstrate and partially characterise an inhibitor of the macrophage respiratory burst from the surface of A fumigatus spores that could be an important factor in allowing the fungus to colonise the lung. METHODS: The spore-derived inhibitor of the respiratory burst of rat alveolar macrophages, as measured by generation of superoxide anion, was demonstrated in Hank's balanced salt solution extracts of four clinical isolates and an environmental isolate of A fumigatus. The time course of the release of the inhibitor into aqueous solution was assessed and the cytotoxic potential of the spore-derived inhibitor towards macrophages was tested using the propidium iodide method. An oxygen electrode was used to confirm the superoxide anion measurements. Molecular weight cutoff filters were used to determine the size of the inhibitor as assessed in the respiratory burst assay and also by its ability to inhibit macrophage spreading on glass. The crude diffusate from the spore surface was fractionated by reversed phase high pressure liquid chromatography (HPLC) and the fractions analysed for inhibitory activity, protein, and carbohydrate content. RESULTS: A small molecular weight (< 10 kD) heat stable toxin was released from the spores of clinical and environmental isolates of A fumigatus within minutes of deposition in aqueous solution. The key effect of the toxin demonstrated here was its ability to inhibit the oxidative burst of macrophages as measured by superoxide anion release. The inhibition was not due to cell death or detectable loss of membrane integrity as measured by permeability to propidium iodide. The toxin was not a scavenger of superoxide anion. Oxygen electrode studies suggested indirectly that the inhibitor acted to inhibit the assembly of the macrophage NADPH-oxidase complex. Fractions of < 10 kD also inhibited the spreading of alveolar macrophages, confirming that the toxin had an additional effect on macrophages that leads to loss of adherence or impairment of cytoskeletal function. In reversed phase HPLC fractions the inhibitory activity eluted with an associated carbohydrate, although the exact chemical nature of the toxin remains to be elucidated. CONCLUSIONS: This spore toxin may, through its ability to diffuse rapidly into lung lining fluid, diminish the macrophage respiratory burst and play a part in allowing A fumigatus to persist in the lung and manifest its well known pathogenic effects. Future research will be focused on further molecular characterisation of the toxin and elaboration of the effect of the toxin on intracellular signalling pathways involved in the activation of alveolar macrophages.

Animals

[Asbestos: past, present and future].

Owing to its particular properties asbestos has been widely used for the production of insulating material, for fire proofing, and for strengthening to other materials such as cements and plastics, and thus the story of this mineral was one of progressive commercial success until the middle of this century. However, serious health hazards were realized early: around the turn of the century a progressive form of diffuse fibrosis (asbestosis) in asbestos workers was observed and in 1950 an excess risk of lung cancer, while in 1960 the causal relationship between asbestos and mesothelioma were confirmed. In view of the known potential risks of asbestos and its widespread use in the building industry, more recently asbestos has caused considerable public concern and anxiety. Based on numerous experimental and epidemiological observations, present knowledge of the pathogenic effects of asbestos is sufficient for a number of broad conclusions to be drawn. (1) The amphibole types of asbestos are too dangerous for use as industrial material, and should be banned. (2) Chrysotile can probably be used safely if there is strict control of the workers' dust exposure. (3) It is very unlikely that the general public is at any measurable risk from asbestos in buildings. Exceptions are people working regularly on maintenance tasks involving removing or cutting of asbestos in buildings; such people are properly classified as asbestos workers and should be protected accordingly.(ABSTRACT TRUNCATED AT 250 WORDS)

Asbestos

Particulate air pollution and acute health effects.

Epidemiological studies have consistently shown an association between particulate air pollution and not only exacerbations of illness in people with respiratory disease but also rises in the numbers of deaths from cardiovascular and respiratory disease among older people. Meta-analyses of these studies indicate that the associations are unlikely to be explained by any confounder, and suggest that they represent cause and effect. We propose that the explanation lies in the nature of the urban particulate cloud, which may contain up to 100000 nanometer-sized particles per mL, in what may be a gravimetric concentration of only 100-200 micrograms/m3 of pollutant. We suggest that such ultra-fine particles are able to provoke alveolar inflammation, with release of mediators capable, in susceptible individuals, of causing exacerbations of lung disease and of increasing blood coagulability, thus also explaining the observed increases in cardiovascular deaths associated with urban pollution episodes. This hypothesis is testable both experimentally and epidemiologically.

Air Pollutants

Audit of sickness absence and fitness-for-work referrals.

Since referrals in relation to sickness absence and fitness to continue work constitute an important part of occupational physicians' workloads, a study was carried out to audit this activity. Randomly selected referrals (u = 162) were audited by external peer review in relation to the information provided in the referral request, the consultation records and responses of the occupational physicians, and the response times linking the referral, the consultation and the response. The study showed that the referral record was adequate when specifying or quantifying long-term absences (90% and 84% of relevant cases, respectively) but questions or information regarding other relevant issues were much less frequent, eg only 12% of the referral records provided a description of the job or task. The physicians' response rate was high in relation to likely date of return to work (96%) but lower for other relevant items. In all the issues audited, the frequency of the physicians' responses was higher than the frequency with which the relevant questions were posed to them, thus suggesting 'added value' in the formulation of the problem by the physicians. The response times (often interpreted as a measure of health care quality) did not correlate usefully with the completeness of the responses as determined by peer review audit. Occupational physicians should aspire to achieve a validated standard of assessment and communication which can be audited.

Absenteeism