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Biomedical subjects

T Fletcher

Publications and source records attributed to T Fletcher.

At least 19 recordsLinked to original sources

NO2 and children's respiratory symptoms in the PATY study.

OBJECTIVES: NO2)is a major urban air pollutant. Previously reported associations between ambient NO2)and children's respiratory health have been inconsistent, and independent effects of correlated pollutants hard to assess. The authors examined effects of NO2 on a spectrum of 11 respiratory symptoms, controlling for PM10 and SO2, using a large pooled dataset. METHODS: Cross sectional studies were conducted in Russia, Austria, Italy, Switzerland, and the Netherlands, during 1993-99, contributing in total 23 955 children. Study-specific odds ratios for associations with ambient NO2 are estimated using logistic regressions with area-level random effects. Heterogeneity between study-specific results, and mean estimates (allowing for heterogeneity) are calculated. RESULTS: Long term average NO2 concentrations were unrelated to prevalences of bronchitis or asthma. Associations were found for sensitivity to inhaled allergens and allergy to pets, with mean odds ratios around 1.14 per 10 microg/m3 NO2. SO2 had little confounding effect, but an initial association between NO2 and morning cough was reduced after controlling for PM10. Associations with reported allergy were not reduced by adjustment for the other pollutants. Odds ratios for allergic symptoms tended to be higher for the 9-12 year old children compared with the 6-8 year old children. CONCLUSIONS: Evidence for associations between NO2 and respiratory symptoms was robust only for inhalation allergies. NO2 most likely is acting as an indicator of traffic related air pollutants, though its direct effect cannot be ruled out. This remains important, as policies to reduce traffic related air pollution will not result in rapid reductions.

Air Pollutants↗

Parental education and children's respiratory and allergic symptoms in the Pollution and the Young (PATY) study.

Inequalities in health between socio-economic groups are a major public health concern. The current authors studied associations between parental socio-economic status (SES) and children's respiratory and allergic symptoms in 13 diverse countries, including the Russian Federation, North America (Canada and the USA), and countries across Eastern and Western Europe. Data of 57,000 children aged 6-12 yrs, originating from eight cross-sectional studies, were analysed. SES was defined by parental education. Respiratory and allergic symptoms were defined by parental questionnaire reports. Multiple logistic regressions showed that low parental education was associated with a decreased risk of inhalant allergy and itchy rash in school children. Furthermore, low parental education was associated with an increased prevalence of wheeze and nocturnal dry cough. No clear association was found between parental education and prevalence of doctor-diagnosed asthma and bronchitis. Part of the difference between socio-economic groups with regard to their children's symptoms was explained by established risk factors, such as parental allergy, smoking during pregnancy, pet ownership, crowding, mould/moisture in the home, use of gas for cooking, and air pollution (particulate matter with a diameter of <10 microm). However, differences remained after adjusting for these variables. Children's health was associated with parental education. The association could not fully be explained by established risk factors.

Asthma↗

The management of patients with ischaemic heart disease undergoing non-cardiac elective surgery: a survey of Australian and New Zealand clinical practice.

Improvements in patient risk stratification and peri-operative beta-blockade have been suggested as methods which can reduce cardiovascular risk in patients with known cardiac risk factors. A postal questionnaire was sent to all Australian and New Zealand teaching hospitals to identify patterns of pre-operative cardiac risk evaluation and methods of peri-operative beta-blocker use. In all, 67 replies were evaluated (64% response rate). Specialist anaesthetists are present in the majority of pre-admission clinics (78%), with a designated peri-operative physician in 9%. Further cardiological referral was possible in almost all institutions (96%), and specific peri-operative physician referral in 54%. Waiting times for specialist consultation were < 7 days in the majority of cases. Whilst 79% of institutions used peri-operative beta-blockade, specific protocols were available in only 10%. In 60% of institutions, beta-blockers were administered to high-risk patients, and in 25% they were given to intermediate risk group patients. There was a wide range in the duration of pre- and postoperative beta-blocker administration. Whilst peri-operative risk assessment appears to be consistent, the pattern of beta-blockade, a known beneficial intervention, is variable. Reasons need to be identified, protocols developed and consistent administration targeted for further improvements to be made.

Adrenergic beta-Antagonists↗

Nutrition and respiratory health in children in six Central and Eastern European countries.

BACKGROUND: The results of studies on the effect of nutrition on respiratory diseases are inconsistent. The role of nutrition in children's respiratory health was therefore analysed within the cross sectional Central European Study on Air Pollution and Respiratory Health (CESAR). METHOD: A total of 20 271 children aged 7-11 were surveyed in six European countries. Respiratory health and food intake were assessed using questionnaires. Associations between four symptoms and nutritional factors were evaluated using logistic regression, controlling for area plus other potential confounders. RESULTS: All symptoms showed initial associations with nutritional factors. Low consumption of fish and of summer and winter fruit were the most consistent predictors. In a fully adjusted model low fish intake remained a significant independent predictor of persistent cough (OR=1.18; 95% CI 1.04 to 1.34), wheeze ever (OR=1.14; 95% CI 1.03 to 1.25) and current wheeze (OR=1.21; 95% CI 1.06 to 1.39) and a weaker predictor of winter cough (OR=1.10; 95% CI 0.99 to 1.23). Low summer fruit intake was a predictor of winter cough (OR=1.40; 95% CI 1.10 to 1.79) and persistent cough (OR=1.35; 95% CI 1.01 to 1.82). Low winter fruit intake was associated with winter cough (OR=1.28; 95% CI 1.09 to 1.51). Associations between symptoms and vegetable intake were inconsistent. Low summer intake was significantly associated with winter cough (OR=1.23; 95% CI 1.03 to 1.47) but, overall, winter intake had inverse associations with both coughs. Associations between winter vegetable intake and wheeze varied considerably between countries. CONCLUSION: A number of associations were found between respiratory symptoms and low intake of fish, fruit and vegetables in children. Low fish intake was the most consistent predictor of poor respiratory health. Fruit and vegetable intake showed stronger associations with cough than with wheeze.

Child↗

Perceptual differences regarding health and environmental problems and their remedies in two states of the former Czechoslovakia.

In the framework of the Central European Study on Air pollution and Respiratory Health (CESAR), a risk perception and risk communication study was carried out in a total of 25 areas in Bulgaria, the Czech Republic, Hungary, Poland, Romania and the Slovak Republic. This paper is focused on the differences of perception between the Czech (CR) and the Slovak Republic (SR), and the other involved countries. The analysis is based on the data of a structured risk perception questionnaire survey of a random population sample. 6,043 completed questionnaires were collected from the total number of 14,400 distributed ones in 25 areas of the 6 countries. The risk perception was different in the CR and the SR, mainly concerning local environment and health of children in the CR and drug abuse including alcohol consumption and AIDS in the SR. In both countries environmental and health problems were seen as important, but the perceived responsibility for finding a solution was placed with different kinds of institutions.

Adult↗

Personality testing and profiling for anaesthetic job recruitment: attitudes of anaesthetic specialists/consultants in New Zealand and Scotland.

Specialist/consultant anaesthetists based in New Zealand and Scotland were sent a reply paid postal questionnaire asking about their attitudes to personality testing and personality types in the recruitment process for registrars and specialists. The questionnaire consisted of nine Likert-style questions and 14 visual analogue questions. The overall response rate was 65% (523/808). The responses to all the questions were broadly similar in the two countries. Personality testing was deemed of use in recruiting trainees and specialists, with a slightly greater proportion considering personality traits more important than academic achievement. An overwhelming majority believed the presence of an adverse personality trait would influence an appointment process, but few believed that the personality makeup of anaesthetists influenced the way in which they react to stressful situations. A slight majority considered the interview process a poor predictor of personality. New Zealand anaesthetists rated independence, orderliness, compassion, empathy, reflectiveness and patience higher than did anaesthetists in Scotland. In contrast, anaesthetists in Scotland rated pragmatism, as opposed to perfection, as a more important characteristic than did the New Zealand specialists. Personality assessment, although not effective as the sole tool for candidate selection, may have a role in the process of anaesthetic job recruitment and warrants further investigation.

Anesthesiology↗

Respiratory symptoms, bronchitis and asthma in children of Central and Eastern Europe.

The multicentre Central European Study of Air Pollution and Respiratory Health (CESAR) aimed to measure the respiratory health of schoolchildren using a standardised questionnaire in six countries of Central and Eastern Europe (CEE), allowing comparisons within this region and with other European countries. A cross-sectional study was conducted in 25 urban areas of Bulgaria, Czech Republic, Hungary, Poland, Romania, and Slovakia in 1996. Parents of 21,743 schoolchildren of age 7-11 yrs completed a questionnaire based on items from the World Health Organization and International Study of Asthma and Allergies in Childhood questions on cough and wheeze symptoms, as well as on diagnoses by doctors. Life-time prevalence of bronchitis was 55.9%, asthma 3.9%, and asthmatic, spastic or obstructive bronchitis 12.3%. In CEE countries the prevalence of bronchitis is higher and prevalence of asthma appears lower than in Western Europe. However, if asthma is defined as a diagnosis of either asthma or asthmatic, spastic or obstructive bronchitis, then its prevalence is comparable to Western Europe, or higher. In this region, within-country variation for most respiratory parameters is less than between-country variation. Between-country comparisons in doctors' diagnoses appear dependent on the choice of definition of asthma. Europe-wide comparisons in prevalence of respiratory symptoms and diagnosis are reported in this study. Some of the East-West difference in asthma prevalence may be attributable to differences in diagnostic practice.

Acute Disease↗

Time series analysis of air pollution and mortality: effects by cause, age and socioeconomic status.

OBJECTIVE: To investigate the association between outdoor air pollution and mortality in São Paulo, Brazil. DESIGN: Time series study METHODS: All causes, respiratory and cardiovascular mortality were analysed and the role of age and socioeconomic status in modifying associations between mortality and air pollution were investigated. Models used Poisson regression and included terms for temporal patterns, meteorology, and autocorrelation. MAIN RESULTS: All causes all ages mortality showed much smaller associations with air pollution than mortality for specific causes and age groups. In the elderly, a 3-4% increase in daily deaths for all causes and for cardiovascular diseases was associated with an increase in fine particulate matter and in sulphur dioxide from the 10th to the 90th percentile. For respiratory deaths the increase in mortality was higher (6%). Cardiovascular deaths were additionally associated with levels of carbon monoxide (4% increase in daily deaths). The associations between air pollutants and mortality in children under 5 years of age were not statistically significant. There was a significant trend of increasing risk of death according to age with effects most evident for subjects over 65 years old. The effect of air pollution was also larger in areas of higher socioeconomic level. CONCLUSIONS: These results show further evidence of an association between air pollution and mortality but of smaller magnitude than found in other similar studies. In addition, it seems that older age groups are at a higher risk of mortality associated with air pollution. Such complexity should be taken into account in health risk assessment based on time series studies.

Adolescent↗

Respiratory diseases in children and outdoor air pollution in São Paulo, Brazil: a time series analysis.

OBJECTIVES: To investigate the short term effects of air pollution on the respiratory morbidity of children living in São Paulo, Brazil, one of the largest cities in the developing world. METHODS: Daily counts of hospital admissions due to respiratory diseases along with daily levels of meteorological variables and air pollutants (PM(10), SO(2), NO(2), O(3), and CO) were analysed with Poisson regression. Final models were adjusted for the effects of time trends, seasonal patterns, weekdays, holidays, meteorological factors, and serial correlation. RESULTS: Daily admissions of children to hospital for total respiratory disease and pneumonia showed significant increases associated with O(3) (5-8%), NO(2) (9%), and with PM(10) (9%) (results are for an increase from the 10th to the 90th percentile of pollution measurements). Consistently, effects for pneumonia were greater than for all respiratory diseases combined. Also, effects on infants (children <1 year old) presented higher estimates. Similar associations were found for asthma admissions. Point estimates for most pollutants were higher for asthma than for other diagnosed admissions. However, these associations were not significant. CONCLUSIONS: These results agree with the limited publications on this subject but indicate a rather smaller magnitude of effects. Nevertheless, given the present concentrations of air pollution in São Paulo and the large population potentially exposed attention should be directed to minimise such effects.

Air Pollutants↗

Immune biomarkers in relation to exposure to particulate matter: a cross-sectional survey in 17 cities of Central Europe.

Human population data on air pollution and its effects on the immune system are scarce. A survey was conducted within the framework of the Central European Study of Air Quality and Respiratory Health (CESAR) to measure a panel of immune biomarkers in children of Bulgaria, Czech Republic, Hungary, Poland, Romania, and Slovakia. Seventeen cities were chosen to represent a wide range of exposure to outdoor air pollution. In each, ambient particulate matter of less than 10 microns diameter and less than 2.5 microns diameter (PM10 and PM2.5) were measured with a Harvard impactor. Blood was collected from 366 school children aged 9 to 11 yr between 11 April and 10 May 1996. The percentage of B, total T, CD4+, CD8+, and natural killer (NK) lymphocytes was determined by flow cytometry (Becton Dickinson); total immunoglobulins of class G, M, A and E (IgG, IgM, IgA, and IgE) were measured in serum using nephelometry (Behring). Associations between PM and each log-transformed biomarker concentration were studied by linear regression, in a two-stage model. The yearly average concentrations varied from 41 to 96 micrograms/m3 for PM10 across the 17 study areas, from 29 to 67 micrograms/m3 for PM2.5, and from 12 to 38 micrograms/m3 for PM10-2.5 (coarse). Number of B, CD4+, CD8+, and NK lymphocytes increased with increasing concentration of PM, having adjusted for age, gender, parental smoking, laboratory of analysis, and recent respiratory illness. Differences in lymphocyte number were larger and statistically significant for exposure to PM2.5. Similar results were found when we examined the association between PM and lymphocyte number separately for each laboratory. Total IgG was increased with increasing concentration of PM, significantly in the case of PM2.5. When we repeated the analyses with two other statistical approaches the results did not differ from those reported here. The effect of coarse PM on lymphocyte numbers appears small in comparison to PM2.5. One possible interpretation of our findings is that long-term exposure to airborne particulates leads to inflammation of the airways and activation of the cellular and humoral immune system.

Air Pollutants↗

Parental agricultural work and selected congenital malformations.

The authors conducted a case-control study in Comunidad Valenciana, Spain, to assess the relation between occupational exposure to pesticides, mainly as a result of agricultural work, and the prevalence of congenital malformations. A total of 261 cases and 261 controls were selected from those infants born in eight public hospitals during 1993-1994. The cases were those who were diagnosed with selected defects (nervous system, cardiovascular, oral clefts, hypospadias/epispadias, musculoskeletal, and unspecified anomalies) during their first year of life. Information on occupational exposures and potential confounding variables was collected from the parents. For the mothers who were involved in agricultural activities during the month before conception and the first trimester of pregnancy, the adjusted odds ratio was 3.16 (95% confidence interval 1.11-9.01) primarily due to an increased risk for nervous system defects, oral clefts, and multiple anomalies. Paternal agricultural work did not increase the risk, although fathers who reported ever handling pesticides had an adjusted odds ratio of 1.49 (95% confidence interval 0.94-2.35) mainly related to an increased risk for nervous system and musculoskeletal defects. Although the power of this study regarding some associations is limited, the results justify further attention to maternal agricultural work and paternal pesticide exposure.

Adult↗

Maternal occupation in the leather industry and selected congenital malformations.

OBJECTIVES: Data from a hospital based case-control study were analysed to assess the relation between maternal occupation in the leather industry and several groups of congenital defects (nervous system, cardiac defects of closure, oral cleft, epispadia or hypospadia, and multiple anomalies). METHODS: Cases and controls were selected from eight public hospitals in Comunidad Valenciana, Spain, in 1993 and 1994. Cases were located from the hospital discharge records, including children born and diagnosed in some of the selected hospitals during their first year of life. Controls were selected from births without congenital defects in the same hospitals and dates of the cases (ratio 1:1). Both parents of selected children were interviewed (mainly by phone) and information about potential confounding variables and occupational history during the three years before the birth was collected in structured questionnaires. RESULTS: A total of 261 cases and the same number of controls were included in the study. Adjusted odds ratios (ORs) were estimated for maternal occupation in the leather industry in the period between three months before the conception and the birth of the child (n = 22), and each selected group of congenital malformations: nervous system defects (OR 1.02, 95% confidence interval (95% CI) 0.12 to 8.51), cardiac defects of closure (OR 1.78, 95% CI 0.44 to 7.17), oral clefts (OR 6.18, 95% CI 1.48 to 25.69), for epispadia or hypospadia (OR 4.05, 95% CI 0.77 to 21.44), and multiple anomalies (OR 3.14, 95% CI 0.82 to 12.00). CONCLUSION: These data are compatible with an increased risk for oral clefts in the offspring of women working in the leather industry. Some other categories of defect could have an increased risk as well, although for these our data cannot exclude random error as an explanation. Given these results and previous findings in similar studies, some precautionary recommendations regarding maternal exposure in leather industries, probably in relation to solvents, would be justified.

Case-Control Studies↗

Paternal exposure to pesticides and congenital malformations.

OBJECTIVES: A case-referent study with 261 matched pairs was carried out in 8 hospitals of Comunidad Valenciana, Spain, to assess the relation between occupational exposure to pesticides and selected congenital malformations. In this paper, the results concerning paternal exposure are presented. METHODS: The parents of the case patients and the referents were interviewed to collect information about exposure to pesticides and potential confounding variables. Detailed information on direct involvement in the handling of pesticides was collected for the interviewees involved in agricultural activities during a previously defined period in relation to conception and pregnancy. Exposure data were reviewed by 2 experts who assigned ordinal scores for the probability and intensity of exposure to pesticide classes and active ingredients. RESULTS: The dichotomous analysis of exposure (absent, present) yielded some increased risks, although not statistically significant, for aliphatic hydrocarbons [adjusted odds ratio (adjusted OR) 2.05, 95% confidence interval (95% CI) 0.62-6.80], inorganic compounds (adjusted OR 2.02, 95% CI 0.53-7.72), and glufosinate (adjusted OR 2.45, 95% CI 0.78-7.70), and a significant association for pyridil derivatives (adjusted OR 2.77, 95% CI 1.19-6.44). The analysis based on the experts' scores (2 levels of exposure) showed some consistent associations for these compounds. CONCLUSIONS: This research indicates a possible risk of congenital malformations for paternal exposure to some pesticides, notably, pyridils, aliphatic hydrocarbons, inorganic compounds, and glufosinate. It did not find an increased risk for paternal exposure to pesticides in the classes of organophosphates, carbamates, organochlorines, chloroalkylthio fungicides and organosulfurs. These findings warrant further investigation.

Agriculture↗

CVT-124, a novel adenosine A1 receptor antagonist with unique diuretic activity.

Administration of the selective adenosine A1 receptor antagonist, CVT-124, to conscious chronically instrumented rats resulted in significant increases in urine flow rate and sodium excretion without affecting potassium excretion or renal hemodynamics. Its maximum effect was twice that of hydrochlorothiazide which was associated with a significant kaliuresis. The diuretic effect of CVT-124 was less than that observed with furosemide; however, furosemide administration was associated with a large increase in potassium excretion as well as a reduction in glomerular filtration rate. When given at equinatriuretic doses, CVT-124 enhanced the diuretic and natriuretic activity of furosemide without further increasing potassium excretion. In contrast, the combination of hydrochlorothiazide and furosemide resulted in a 3-fold increase in potassium excretion. These data suggest that CVT-124 possesses unique diuretic activity and, as such, it represents a potential new therapeutic in fluid retaining disorders. In addition, its unique mechanism of action suggests that CVT-124 would be effective in otherwise diuretic-resistant patients.

Animals↗

Contribution of endogenous endothelin-1 to the maintenance of vascular tone: role of nitric oxide.

Studies were designed to compare the effect of the nitric oxide inhibitor, N omega-nitro-L-arginine (L-NNA), and the novel ETB receptor antagonist, RES-701-1, on changes in blood pressure and renal blood flow induced by exogenous endothelin receptor agonists and to determine the effect of L-NNA on basal hemodynamics in conscious, chronically instrumented rats. Infusion of low (nonpressor) doses of L-NNA or RES-701-1 potentiated systemic and renal vasoconstriction induced by bolus injections of endothelin-1 or sarafotoxin 6c. Bolus intravenous injection or sustained infusion of L-NNA alone resulted in dose-dependent increases in blood pressure and decreases in renal blood flow, similar to our recently reported results with RES-701-1. Vasoconstriction induced by inhibition of nitric oxide was attenuated by SB 209670, a mixed ETA/B receptor antagonist, but not by BQ123, an ETA receptor antagonist; neither antagonist altered basal hemodynamics. Collectively, the results indicate that: (1) endothelin plays an important role in the control of basal vascular tone by mediating both vasodilation and vasoconstriction; (2) these effects are mediated by different ETB receptor subtypes in the rat, one located on the endothelium that mediates vasodilation via the nitric oxide pathway, the other located on the vascular smooth muscle that mediates contraction.

Animals↗

Evidence for the existence of endothelin-B receptor subtypes and their physiological roles in the rat.

The physiological roles of endothelin-B (ETB) receptor subtypes in systemic and renal hemodynamics were assessed in conscious Sprague-Dawley rats. Mean arterial pressure, hindlimb flow, and renal blood flow were measured via an implanted catheter and pulsed Doppler flow probes. Bolus intravenous injections of sarafotoxin 6c (S6c), a selective ETB agonist, elicited transient dose-dependent vasodilation, followed by sustained vasoconstriction in the systemic bed, but only vasoconstriction in the renal bed. RES-701-1, a selective ETB antagonist, blocked the dilator and potentiated the constrictor effect; SB-209670, a mixed ET receptor antagonist, attenuated both responses to S6c. In follow-up studies, the role of endogenous ET was assessed by administration of the antagonists alone: RES-701-1, SB-209670, and the ETA-selective antagonist BQ-123. RES-701-1 unmasked a significant systemic and renal vasoconstriction, which was attenuated by SB-209670 but not by BQ-123. SB-209670 and BQ-123 had no effect on basal hemodynamic parameters. Data from radioligand binding experiments showed that RES-701-1 binds with high affinity to the cloned human ETB receptor but poorly to the ETB receptor predominant in the rat kidney. Collectively, the results indicate that 1) the vascular effects of ET in the rat are mediated by two ETB receptor subtypes: an RES-701-1-sensitive subtype, mediating vasodilation, and an RES-701-1-insensitive subtype, mediating vasoconstriction; 2) the predominant role of endogenous ET is vasodilation; and 3) the ETA receptor plays a negligible role in the control of vascular tone in the rat.

Animals↗

Mortality study of construction workers in the UK.

BACKGROUND: Construction is one of the most dangerous industries in the world. However, there has been little literature on occupational epidemiology in this field. A study of the mortality experience over a 13-year period among construction workers in the UK was carried out. METHOD: This was based on 15,007 death certificates of members of the Building and Civil Engineering Holiday and Benefit Scheme, who had died during 1975 to 1987 aged 20-64 years. Proportional mortality ratio (PMR) and mortality odds ratio techniques were used. RESULTS: Significantly elevated PMR were found for deaths from all cancers, including cancer of the lung and stomach, and for accidental deaths. Associations were demonstrated between several job categories and an increased risk of cancer mortality. Occupational exposures to hazardous substances may have contributed to the elevated cancer mortality, although the study findings should be interpreted with caution. Inadequate supervision of safety procedures, together with a high proportion of young and inexperienced workers, may be associated with the high number of accidental deaths. CONCLUSIONS: The results support the hypothesis that working in the construction industry is associated with a high risk for accidental death and probably also for malignant diseases including lung, mesothelium and stomach cancers. Further epidemiological studies among construction workers are needed to support policies aimed at improving occupational health, including the prevention of accidents.

Accidents, Occupational↗