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Biomedical subjects

A Seaton

Publications and source records attributed to A Seaton.

At least 37 records · Page 2Linked to original sources
PubMed2000

Structural studies on bioactive compounds. 32. Oxidation of tyrphostin protein tyrosine kinase inhibitors with hypervalent iodine reagents.

Hydroxylated styrenes (tyrphostins) undergo oxidation by hypervalent iodine oxidants such as [(diacetoxy)iodo]benzene (DAIB) to give a range of products depending on the structure of the phenolic substrate, the solvent, the oxidant stoichiometry, and the purification strategy. Conditions have been developed to modify the phenolic component of the tyrphostin without affecting the appended substituted-vinyl moiety. Novel products include: unstable 2-acyloxy-2-methoxy-4-(substituted-vinyl)cyclohexadienones and their rearrangement products 2-acyloxy-4-hydroxy-3-methoxy-1-(substituted-vinyl)benzenes; phenyliodoniophenolates and their rearrangement products iodophenoxytyrphostins; and 3,3'-dialkoxy-2,2'-dihydroxy-5, 5'-di(substituted-vinyl)biphenyls. None of these oxidation products displayed enhanced activity in vitro in the NCI 60-cell line panel or in a panel of human breast cancer cell lines, compared to their tyrphostin precursors. The inhibitory activity of three representative tyrphostins (3e,n, 28) was not modulated by aerobic/anaerobic conditions in MCF-7 and MDA 468 cells and was independent of EGFR status in clones of ZR75B cells transfected with this receptor. Basal growth of MCF-7 cells was unaffected by co-administration of the growth factors EGF, TGF-alpha, IGF-I, and IGF-II, and the new agents did not inhibit EGFR and c-erbB2 autophosphorylation in cell lysates from MDA 468 or SkBr3 cells, respectively, suggesting that receptor tyrosine kinases are not targets for these compounds. Growth stimulation by the tyrphostin 3n in the ER(+) breast cell lines MCF-7, T47D, and ZR75-1 was abolished by 1 microM tamoxifen, suggesting that this compound has estrogen agonist activity.

Acetates↗
PubMed2000

Diet, infection and wheezy illness: lessons from adults.

An increase in asthma and atopic disease has been recorded in many countries where society has become more prosperous. We have investigated two possible explanations: a reduction in childhood infections and a change in diet. In a cohort of people followed up since 1964, originally selected as a random sample of primary school children, we have investigated the relevance of family size and the common childhood infectious diseases to development of eczema, hay fever and asthma. Although membership of a large family reduced risks of hay fever and eczema (but not asthma), this was not explained by the infections the child had suffered. Indeed, the more infections the child had had, the greater the likelihood of asthma, although measles gave a modest measure of protection. We have investigated dietary factors in two separate studies. In the first, we have shown the risks of bronchial hyper-reactivity are increased seven-fold among those with the lowest intake of vitamin C, while the lowest intake of saturated fats gave a 10-fold protection. In the second, we have shown that the risk of adult-onset wheezy illness is increased five-fold by the lowest intake of vitamin E and doubled by the lowest intake of vitamin C. These results were supported by direct measurements of the vitamins and triglycerides in plasma. We have proposed that changes in the diet of pregnant women may have reflected those observed in the population as a whole and that these may have resulted in the birth of cohorts of children predisposed to atopy and asthma. The direct test of this is to study the diet and nutritional status of a large cohort of pregnant women and to follow their offspring forward. This is our current research.

Adult↗
PubMed2000

Neurological deficits in solvent-exposed painters: a syndrome including impaired colour vision, cognitive defects, tremor and loss of vibration sensation.

Five individuals are described who had participated in a study of former dockyard painters. All had worked between 16 years and 45 years as industrial painters, much of the time inside ships. All underwent structured neurological examination, colour vision testing (allowing calculation of a colour confusion index corrected for age and alcohol), and detailed psychometric testing. An occupational history sufficient to allow estimation of past exposure to solvents was taken. All gave a history of exposure to high concentrations of solvents at work, and several described episodes of acute narcosis. All showed neurological deficits and some had overt neurological disease, although in no case had this previously been linked to their work. The most striking features, sufficient to constitute a syndrome, were acquired blue-yellow colour vision deficits, coarse tremor, impaired vibration sensation in the legs and cognitive impairment. Their estimated cumulative exposures to solvents ranged between the equivalent of 13 and 37 calendar years working at the Occupational Exposure Standard concentration (OES years). This study for the first time gives an indication of the concentrations of solvents likely to lead to serious neurological disease in humans. It serves as a reminder to physicians to take an occupational history from patients with obscure neurological or psychological impairment.

Aged↗
PubMed2000

Impairment of colour vision in workers exposed to organic solvents.

OBJECTIVES: To investigate loss of colour vision related to exposure to solvents and the role of three enzyme polymorphisms in modifying the risk in exposed workers. METHODS: A sample was studied of 68 male dockyard workers and 42 male community controls with and without neuropsychological symptoms from a previous cross sectional study. Indices of cumulative and intensity based exposure to solvents were calculated for all subjects. Alcohol, drug, and smoking histories were obtained. Colour vision was tested by Lanthony D15d colour vision test. Genotype of glutathione S-transferase M1 and T1 and N-acetyltransferase 2 polymorphisms were determined. RESULTS: The relation between impairment of colour vision and exposure to solvents was investigated with multiple regression techniques. Increasing annual exposure to solvents was significantly associated with reduced colour vision (p=0.029). Impairment of colour vision was not associated with neuropsychological symptoms as measured by the Q16 solvent symptom questionnaire. No significant association was found between acquired impairment of colour vision and genetic polymorphisms when GSTM1, GSTT1 or NAT2 phenotypes were included in the analyses. CONCLUSIONS: Exposure to mixed solvents is associated with impairment in colour vision, the risk increases with increasing exposure. The risk of impairment of colour vision was not altered in this study by the presence of different GSTM1, GSTT1 or NAT2 polymorphisms.

Arylamine N-Acetyltransferase↗
PubMed2000

Diet and childhood asthma in a society in transition: a study in urban and rural Saudi Arabia.

BACKGROUND: The causes of the worldwide increases in asthma and allergic diseases in childhood, which seem to relate to increasing prosperity, are unknown. We have previously hypothesised that a reduction in the antioxidant component of the diet is an important factor. An investigation was undertaken of dietary and other risk factors for asthma in Saudi Arabia where major lifestyle differences and prevalences of allergic disease are found in different communities. METHODS: From a cross sectional study of 1444 children with a mean age of 12 (SD 1) years in Jeddah and a group of rural Saudi villages, we selected 114 cases with a history of asthma and wheeze in the last 12 months and 202 controls who had never complained of wheeze or asthma, as recorded on the ISAAC questionnaire. Risk factors for asthma and allergies (family history, social class, infections, immunisations, family size, and diet) were ascertained by questionnaire. Atopy was assessed by skin prick testing. RESULTS: In univariate analyses, family history, atopy, and eating at fast food outlets were significant risk factors for wheezy illness, as were the lowest intakes of milk and vegetables and of fibre, vitamin E, calcium, magnesium, sodium, and potassium. These differences were present also in the urban children considered separately. Sex, family size, social class, infections, and parental smoking showed no relationship to risk. In multiple logistic regression analysis, urban residence, positive skin tests, family history of allergic disease, and the lowest intakes of vitamin E, magnesium and sodium related significantly and independently to risk. The lowest tertile of intake of vitamin E was associated with a threefold (95% CI 1.38 to 6.50) increase in risk when adjusted for the other factors. Intake of milk and vegetables both showed inverse linear relationships to being a case. CONCLUSIONS: This study suggests that dietary factors during childhood are an important influence in determining the expression of wheezy illness, after allowing for urban/rural residence, sex, family history, and atopy. The findings are consistent with previous studies in adults and with the hypothesis that change in diet has been a determinant of the worldwide increases in asthma and allergies.

Analysis of Variance↗
PubMed1999

Bronchial hyperresponsiveness and adult onset wheeze: the influence of atopy.

The commonly held belief that adult onset wheezing illness is primarily nonatopic in nature suggests that the role of atopy in the pathophysiology of bronchial hyperresponsiveness (BHR) in adult onset wheeze may be minimal. This study examined risk factors for BHR (BHR: provocative dose causing a 20% fall in forced expiratory volume in one second PD20 < or =16.38 micromol methacholine) among 82 subjects with adult onset wheeze and among 191 subjects who had never wheezed. Subjects were identified from a cohort of subjects aged 39-45 yrs who were known to have had no childhood wheeze and who were involved in a 30 yr follow-up survey. Risk factors for BHR were examined among all subjects with BHR and among subjects with BHR stratified according to whether or not they had ever wheezed. The prevalence of BHR was 40% (33/82) among the subjects with adult onset wheeze and 11% (21/191) among the subjects who had never wheezed. Lower baseline lung function (odds ratio (OR) = 0.94; 95% confidence interval (CI) = 0.92-0.97 per unit forced expiratory volume (FEV1)% predicted) and atopy (OR = 7.23; CI = 2.53-20.64 for all three measures of atopic compared to nonatopic) were associated with BHR, while smoking and family history showed no statistically significant relation to BHR. This pattern was also apparent in analyses stratified by symptom status. A family history of atopy increased the risk that BHR was accompanied by wheezing symptoms (OR = 4.75; CI = 1.53-14.72 for more than one affected relative compared to no affected relatives). These findings suggest that atopy is associated with bronchial hyperresponsiveness in adults known to have had no childhood wheeze. A familial factor reflecting genetic influences and/or shared environmental factors may influence whether bronchial hyperresponsiveness is associated with symptoms.

Adolescent↗
PubMed1999

Health effects of solvent exposure among dockyard painters: mortality and neuropsychological symptoms.

OBJECTIVES: To study mortality and prevalence of neuropsychological symptoms among a cohort of painters known to have been heavily exposed to organic solvents. METHODS: A mortality study of 1292 male painters who had worked in a dockyard in Scotland for > or = 1 year between 1950 and 1992 comprised a nested cross sectional study of 953 surviving painters from the cohort and 953 male non-painters randomly selected from the local population and a case-control study of those with high symptom scores. Mortality, symptoms, and risks associated with painting, adjusting for age, education, smoking, alcohol, and personality were measured. RESULTS: The proportional mortality ratio for all cancers was not increased significantly (110 (95% confidence interval (95% CI) 84 to 143), except for a possible excess of deaths from ischaemic heart disease (132, 105 to 164). Standardised mortality ratios were not significantly increased. Among the 260 surviving painters and 539 community controls who responded to the questionnaire there was a significant excess of symptoms among painters; adjusted relative risk (RR) increased significantly with increasing symptom score. These RRs suggested an exposure-response relation; for a high score (12-22) for all symptoms RR was 2.27 (1.20 to 4.30) for 1-4 years of exposure, 2.42 (1.18 to 4.95) for 5-9 years, 2.89 (1.42 to 5.88) for 10-14 years, and 3.41 (1.82 to 6.36) for 15-41 years, compared with controls. In multivariate analyses, painting exposure, and aging were associated with high symptom scores and there was again an increased risk relative to time worked as a painter. CONCLUSION: This study supports the hypothesis that heavy and prolonged exposure to paint solvents leads to neuropsychological ill health.

Adult↗
PubMed1999

Neuropsychological symptoms in Chinese male and female painters: an epidemiological study in dockyard workers.

OBJECTIVES: To study the prevalences of neuropsychological symptoms in male and female dockyard painters in China and to compare them with those in British dockyard painters. METHODS: All 116 painters were identified, active and retired, who had been employed in two Chinese dockyards for at least 1 year together with a matched random sample of 263 dockyard non-painters. Neuropsychological and personality questionnaires that we had used previously in a study of United Kingdom dockyard painters were used, translated into Chinese. Neuropsychological symptoms in painters and controls were compared, adjusting for age, educational level, smoking, alcohol intake, and personality. RESULTS: The response rate was 94% for painters and 97% for controls. Highly significant excesses of symptoms were found in painters, suggestive of neuropsychological dysfunction. Both male and female painters showed higher relative risks than were found in similar tradespeople in the United Kingdom. The relative risk increased with increasing score of both neurological and psychological symptoms. Relative risk of having a high symptom score, compared with controls and adjusted for confounders, was 6.61 (95% confidence interval (95% CI) 2.36 to 18.50) for 2-15 years exposure, 14.88 (5.74 to 38.56) for 16-22 years and 9.42 (3.97 to 22.36) for > or = 22 years. CONCLUSION: These results indicate that neuropsychological symptoms are associated with heavy exposure to painting work in China, and that the phenomenon is likely to be found worldwide wherever there is such exposure to solvent based paints. The high response rate in this study answers a possible criticism of the earlier United Kingdom study.

Adolescent↗
PubMed1999

Particulate air pollution and the blood.

BACKGROUND: Particulate air pollution has been associated with excess deaths from, and increases in hospital admissions for, cardiovascular disease among older people. A study was undertaken to determine whether this may be a consequence of alterations in the blood, secondary to pulmonary inflammation caused by the action of fine particles on alveolar cells, by repeatedly measuring haematological factors in older people and relating them to measurements of exposure to airborne particles. METHODS: One hundred and twelve individuals aged 60+ years in two UK cities provided repeated blood samples over 18 months, 108 providing the maximum of 12 samples. Estimates of individual exposure to particles of less than 10 microm diameter (PM(10)), derived from a mathematical model based on activity diaries and comparative measurements of PM(10) at multiple sites and during a variety of activities, were made for each three day period prior to blood sampling. The relationships between blood values and estimates of both personal exposure and city centre measurements of PM(10) were investigated by analysis of covariance, adjusting for city, season, temperature, and repeated individual measurements. RESULTS: Estimated personal exposure to PM(10) over the previous three days showed negative correlations with haemoglobin concentration, packed cell volume (PCV), and red blood cell count (p<0.001), and with platelets and factor VII levels (p<0.05). The changes in red cell indices persisted after adjustment for plasma albumin in a sample of 60 of the subjects. City centre PM(10) measurements over three days also showed negative correlations with haemoglobin and red cell count (p<0.001) and with PCV and fibrinogen (p<0.05), the relationship with haemoglobin persisting after adjustment for albumin. C reactive protein levels showed a positive association with city centre measurements of PM(10) (p<0.01). Based on a linear relationship, the estimated change in haemoglobin associated with an alteration in particle concentration of 100 microg/m(3) is estimated to have been 0.44 g/dl (95% CI 0.62 to 0.26) for personal PM(10) and 0.73 g/dl (95% CI 1.11 to 0.36) for city centre PM(10) measurements. CONCLUSIONS: This investigation is the first to estimate personal exposures to PM(10) and to demonstrate associations between haematological indices and air pollution. The changes in haemoglobin adjusted for albumin suggest that inhalation of some component of PM(10) may cause sequestration of red cells in the circulation. We propose that an action of such particles either on lung endothelial cells or on erythrocytes themselves may be responsible for changing red cell adhesiveness. Peripheral sequestration of red cells offers an explanation for the observed cardiovascular effects of particulate air pollution.

Aged↗
PubMed1999

Antioxidant intake and adult-onset wheeze: a case-control study. Aberdeen WHEASE Study Group.

An increase in prevalence of wheezing illness in the UK has coincided with a reduction in the consumption of natural antioxidants, which may modulate the lung's response to oxidant stress, limiting the expression of airway inflammation and respiratory symptoms. The hypothesis that intakes and plasma levels of natural antioxidants would be determinants of adult-onset wheezing illness was tested. A nested case-control study was conducted in 94 cases with adult-onset wheeze and 203 controls aged 39-45 yrs identified in a 30-yr follow-up survey. Antioxidant intake was measured by a food frequency questionnaire, and plasma and red cell measurements of antioxidant status were obtained. Outcome measures were onset of wheeze since age 15 yrs (ever wheeze) and wheeze occurring in the past 12 months (current wheeze). After adjusting for the effects of smoking, socioeconomic status, atopy, family history of atopic disease and total energy intake, intakes of vitamin E (odds ratio (OR) = 4.02 for low compared to high tertile of intake) and plasma levels of ascorbate (OR = 0.98 per unit) and alpha-tocopherol:triglyceride ratio (OR = 0.34 per log(e) unit) were inversely related to adult-onset wheeze. In analyses stratified by social class and smoking, intakes of vitamin C and E and plasma levels of ascorbate and alpha-tocopherol:triglyceride ratio were inversely related to current wheeze in the manual social class and among current smokers. No independent associations of vitamin A, beta-carotene or total plasma antioxidant capacity were found. The results support the hypothesis that deficiencies of vitamins C and E are associated with wheezing symptoms. Smokers in the manual social class are particularly susceptible to these effects.

Adolescent↗
PubMed1998

A meta-analysis of painting exposure and cancer mortality.

To assess risks of cancer mortality among workers exposed to paints, published papers referring to painters and mortality with standardized mortality ratios (SMR) were meta-analyzed in fixed and random effect models. The SMR for all sites of cancer was significantly raised (111.4; 95% CI: 105.8-117.4). The highest risks of cancer death were from leukemia (187; 95% CI: 114.5-306.7) and from liver cancer (143.6; 95% CI: 117.6-175.4). The SMRs for esophagus and stomach cancer were 132.7 (95% CI: 112.1-157.2) and 120.3 (95% CI: 111.3-130.0), respectively. The risks of bladder cancer (130.4; 95% CI: 113.8-149.5) and lung cancer (129.1; 95% CI: 119.2-139.8) were also raised. The findings provide evidence of an association between work as a painter and risk of cancer, although the confounding effects of smoking and alcohol cannot be entirely excluded, especially with respect to liver cancer since deaths from cirrhosis were also increased. The excess deaths from leukemia could have been from exposure to benzene mixed with other organic solvents, while that from lung cancer may be from exposure to particles containing lead chromate and to asbestos in the paint trade. The high risks of cirrhosis and liver cancer need to be examined further as to possible interactions between organic solvents and alcohol.

Female↗
PubMed1998

Quartz exposures and severe silicosis: a role for the hilar nodes.

BACKGROUND: Two stonemasons working together in an environment with high concentrations of quartz pursued very different clinical courses; one died of rapidly progressive silicosis and the other developed hilar adenopathy and, later, early massive fibrosis. The exposures to quartz of these two men were investigated to allow comment on the pathogenesis of severe silicosis relative to concentrations of dust. METHODS: Estimates of exposure were based on previously taken personal dust samples, detailed lifetime occupational histories, and semiquantitative exposure modelling. RESULTS: One of the men who died had a 30 year exposure estimated to have averaged < 0.1 mg/m3, leading to hilar node fibrosis and calcification, followed by a five year exposure to about 2 mg/m3 which proved fatal. Estimates of exposure tallied with postmortem measurement of lung burden, suggesting retention of all dust deposited in the lungs over his final period of work. The younger man, working from the start of his apprenticeship alongside the older one, had a six year exposure to about 1.5 mg/m3, which caused hilar node enlargement and subsequent calcification but minimal lung involvement. CONCLUSIONS: Exposures to relatively low concentrations of quartz may be capable of causing hilar node fibrosis, impairing the clearance of any quartz inhaled subsequently. The findings support the concept that destruction of the hilar nodes by silicotic fibrosis, impairing lung clearance, has an important pathogenic role in the development of massive fibrosis, and in men subsequently exposed to very high concentrations of respirable quartz, rapidly progressive silicosis.

Adult↗