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Biomedical subjects

G Davey

Publications and source records attributed to G Davey.

At least 19 recordsLinked to original sources
PubMed2006

Use and misuse of aspirin in rural Ethiopia.

OBJECTIVES: To investigate ability to distinguish simple analgesics, to document misconceptions about aspirin use, and to identify strategies to diminish potentially harmful aspirin use in Ethiopia. DESIGN: Qualitative study (eight focus group discussions) used to inform cross-sectional survey. SETTING: Butajira, a small town in southern Ethiopia, and surrounding rural areas. PARTICIPANTS: Purposively selected informants for focus groups; random sample of urban and rural residents for cross-sectional survey. MAIN OUTCOME MEASURES: Ability to distinguish aspirin from paracetamol; proportion using aspirin; proportion aware of common risks of aspirin. RESULTS: Questionnaires were completed by 204 of the 250 residents sampled (82% response). Three-quarters of survey participants knew the difference between aspirin and paracetamol. Aspirin was used by 7.3% of respondents, and was mainly taken for headache and fever. In focus group discussions there was a suggestion that aspirin was considered particularly useful for children. There was very low awareness of the risks of using aspirin in children (2.5% unprompted, 18.6% prompted) or in people with asthma (1% unprompted, 5.9% prompted). Aspirin is cheap and widely available in urban and rural areas. CONCLUSION: Awareness of the risks of aspirin use by children and in asthma is extremely low in this rural Ethiopian setting. Medications are purchased with minimal packaging by a population with low literacy. Drug dispensers and vendors must be trained to convey simple verbal warnings about aspirin use.

Acetaminophen↗
PubMed2005

Wheeze, allergic sensitization and geohelminth infection in Butajira, Ethiopia.

BACKGROUND: The effect of geohelminth infection on wheeze and allergen sensitization is inconsistent across different epidemiological studies. OBJECTIVE: To investigate the association between self-reported wheeze, self-reported asthma, allergic sensitization and geohelminth infection in urban and rural areas of Butajira, southern Ethiopia. METHODS: Questionnaire data on wheeze, asthma and a range of confounding variables was gathered in a cross-sectional study of 7649 people aged 5 years or more from the Butajira Rural Health Project database. Allergic skin sensitization to Dermatophagoides pteronyssinus and cockroach was measured, and a stool sample collected for qualitative and quantitative geohelminth analysis. RESULTS: Wheeze was weakly associated with allergic sensitization to D. pteronyssinus and cockroach (odds ratios (OR) 1.21, 95% confidence interval (CI) 0.98-1.51, and 1.27, 95% CI 1.00-1.62, respectively). Self-reported asthma was related to sensitization to D. pteronyssinus only (OR 4.09, 95% CI 2.86-5.84). Geohelminths were present in 33.8% of participants, and the median egg load in infested individuals was 6 eggs/g. Overall, presence of any geohelminths was associated with a diminished risk of cockroach sensitization (adjusted OR 0.82, 95% CI 0.68-0.99) but there were no significant protective effects of any geohelminth infection against wheeze or asthma. CONCLUSION: In a developing country community with relatively low geohelminth prevalence and intensity, we found weak association between allergic sensitization and wheeze, but no evidence of a protective effect of geohelminths against wheeze or asthma.

Adolescent↗
PubMed2002

Cooking of meat and fish in Europe--results from the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVES: There is epidemiologic evidence that the consumption of fried, grilled or barbecued meat and fish that are well-done or browned may be associated with an increased cancer risk. These high-temperature cooking methods are thought to be surrogates for mutagens and carcinogens produced in meat and fish, eg heterocyclic amines or polycyclic hydrocarbons. Since data on food cooking methods are scarce, the aim of this study was to describe the variation in meat and fish cooking methods in different parts of Europe. DESIGN: Using a standardized 24 h recall from a sub-sample of the EPIC cohort (35 644 persons, 35-75 y old), mean daily intake of meat and fish prepared by different cooking methods and the relative contribution of the cooking methods to the overall cooking of meat and fish was calculated. RESULTS: Whereas frying was more often noted in northern Europe, roasting and stir frying were more often used in the south. Concerning high-temperature cooking methods, their frequency of application varies between 15% in the EPIC cohort of North-Italy and 49% in the cohort of The Netherlands. Average consumption of fried, grilled and barbecued meat and fish ranges from a low of 12 g/day in the centres in southern Spain to a high of 91 g/day in northern Spain. CONCLUSION: High variation in both the kind of meat/fish consumed as well as its cooking methods is observed within EPIC. In order to use this variation for the evaluation of the impact of cooking methods on cancer risk, a questionnaire on meat and fish cooking methods is being developed and could be applied in the whole EPIC cohort.

Adult↗
PubMed2002

European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study: rationale, design and population characteristics.

The European Prospective Investigation into Cancer and Nutrition (EPIC), which covers a large cohort of half a million men and women from 23 European centres in 10 Western European countries, was designed to study the relationship between diet and the risk of chronic diseases, particularly cancer. Information on usual individual dietary intake was assessed using different validated dietary assessment methods across participating countries. In order to adjust for possible systematic over- or underestimation in dietary intake measurements and correct for attenuation bias in relative risk estimates, a calibration approach was developed. This approach involved an additional dietary assessment common across study populations to re-express individual dietary intakes according to the same reference scale. A single 24-hour diet recall was therefore collected, as the EPIC reference calibration method, from a stratified random sample of 36 900 subjects from the entire EPIC cohort, using a software program (EPIC-SOFT) specifically designed to standardise the dietary measurements across study populations. This paper describes the design and populations of the calibration sub-studies set up in the EPIC centres. In addition, to assess whether the calibration sub-samples were representative of the entire group of EPIC cohorts, a series of subjects' characteristics known possibly to influence dietary intakes was compared in both population groups. This was the first time that calibration sub-studies had been set up in a large multi-centre European study. These studies showed that, despite certain inherent methodological and logistic constraints, a study design such as this one works relatively well in practice. The average response in the calibration study was 78.3% and ranged from 46.5% to 92.5%. The calibration population differed slightly from the overall cohort but the differences were small for most characteristics and centres. The overall results suggest that, after adjustment for age, dietary intakes estimated from calibration samples can reasonably be interpreted as representative of the main cohorts in most of the EPIC centres.

Adult↗
PubMed2002

Evaluation of under- and overreporting of energy intake in the 24-hour diet recalls in the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVE: To evaluate under- and overreporting and their determinants in the EPIC 24-hour diet recall (24-HDR) measurements collected in the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: Cross-sectional analysis. 24-HDR measurements were obtained by means of a standardised computerised interview program (EPIC-SOFT). The ratio of reported energy intake (EI) to estimated basal metabolic rate (BMR) was used to ascertain the magnitude, impact and determinants of misreporting. Goldberg's cut-off points were used to identify participants with physiologically extreme low or high energy intake. At the aggregate level the value of 1.55 for physical activity level (PAL) was chosen as reference. At the individual level we used multivariate statistical techniques to identify factors that could explain EI/BMR variability. Analyses were performed by adjusting for weight, height, age at recall, special diet, smoking status, day of recall (weekday vs. weekend day) and physical activity. SETTING: Twenty-seven redefined centres in the 10 countries participating in the EPIC project. SUBJECTS: In total, 35 955 men and women, aged 35-74 years, participating in the nested EPIC calibration sub-studies. RESULTS: While overreporting has only a minor impact, the percentage of subjects identified as extreme underreporters was 13.8% and 10.3% in women and men, respectively. Mean EI/BMR values in men and women were 1.44 and 1.36 including all subjects, and 1.50 and 1.44 after exclusion of misreporters. After exclusion of misreporters, adjusted EI/BMR means were consistently less than 10% different from the expected value of 1.55 for PAL (except for women in Greece and in the UK), with overall differences equal to 4.0% and 7.4% for men and women, respectively. We modelled the probability of being an underreporter in association with several individual characteristics. After adjustment for age, height, special diet, smoking status, day of recall and physical activity at work, logistic regression analyses resulted in an odds ratio (OR) of being an underreporter for the highest vs. the lowest quartile of body mass index (BMI) of 3.52 (95% confidence interval (CI) 2.91-4.26) in men and 4.80 (95% CI 4.11-5.61) in women, indicating that overweight subjects are significantly more likely to underestimate energy intake than subjects in the bottom BMI category. Older people were less likely to underestimate energy intake: ORs were 0.58 (95% CI 0.45-0.77) and 0.74 (95% CI 0.63-0.88) for age (> or =65 years vs. <50 years). Special diet and day of the week showed strong effects. CONCLUSION: EI tends to be underestimated in the vast majority of the EPIC centres, although to varying degrees; at the aggregate level most centres were below the expected reference value of 1.55. Underreporting seems to be more prevalent among women than men in the EPIC calibration sample. The hypothesis that BMI (or weight) and age are causally related to underreporting seems to be confirmed in the present work. This introduces further complexity in the within-group (centre or country) and between-group calibration of dietary questionnaire measurements to deattenuate the diet-disease relationship.

Adult↗
PubMed2001

Soya intake and plasma concentrations of daidzein and genistein: validity of dietary assessment among eighty British women (Oxford arm of the European Prospective Investigation into Cancer and Nutrition).

Soya products contain high levels of the isoflavones genistein and daidzein, and their glucosides, and may lower the risk of cardiovascular disease, osteoporosis and cancer. The present cross-sectional study investigated plasma concentrations of daidzein and genistein and their correlations with dietary soya consumption in four groups of twenty premenopausal British women. The women were selected from the Oxford arm of the European Prospective Investigation into Cancer and Nutrition using data from food-frequency questionnaires (FFQ) to guarantee a wide variation in soya consumption, and to investigate the utility of the question related to soya milk consumption compared with the utility of the question related to other soya foods. Dietary intakes of isoflavones were additionally assessed by 7 d food diaries. Plasma concentrations of daidzein and genistein were measured by time-resolved fluoroimmunoassay. Geometric mean plasma concentrations (nmol/l) were for the four groups, which were based on increasing soya intake, 4.9, 8.4, 39.2 and 132 for daidzein and 14.3, 16.5, 119 and 378 for genistein. The Spearman correlation coefficients for plasma isoflavone concentrations with estimated dietary intakes were between 0.66 and 0.80 for the diary-based estimates and between 0.24 and 0.74 for the FFQ-based estimates. The correlations for soya milk intakes were clearly higher than the correlations for intakes of other soya foods. We conclude that both the food diary and the FFQ estimate dietary soya isoflavone intakes sufficiently well to use them in epidemiological studies, and that plasma concentrations of daidzein and genistein in Western women who consumed soya products as a part of their regular diet were close to those in Asian populations.

Adult↗
PubMed2000

The mitochondrial permeability transition and taurine.

Perturbed cellular calcium homeostasis has been implicated in both apoptosis and necrosis, but the role of altered mitochondrial calcium handling in the cell death process is unclear. Recently we found that taurine, a naturally occurring amino acid potentiates Ca2+ sequestration by rat liver mitochondria. These data, which accounted for the taurine antagonism on Ca2+ release induced by the neurotoxins 1-methyl-4-phenylpyridinium plus 6-hydroxy dopamine previously reported, prompted us to investigate the effects of taurine on the permeability transition (PT) induced experimentally by high Ca2+ plus phosphate concentrations. The parameters used to measure the PT were, mitochondrial swelling, cytochrome c release and membrane potential changes. The results showed that, whereas taurine failed to reverse changes of these parameters, cyclosporin A completely reversed them. Even though these results exclude a role in PT regulation under such gross insult conditions, they cannot exclude an important role for taurine in controlling pore-opening under milder more physiological PT-inducing conditions.

Animals↗
PubMed2000

Familial aggregation of central obesity in Southern Indians.

BACKGROUND: High prevalence of diabetes in South Asians is associated with a pronounced tendency to abdominal obesity. This intermediate quantitative trait may be more amenable than type 2 diabetes to genetic linkage studies. OBJECTIVES: To derive a measure of central obesity independent of total adiposity and adjusted for factors under environmental influence, and to estimate the genetic contribution to familial aggregation of this trait. SUBJECTS AND METHODS: A total of 1,295 individuals from 300 families were studied in a community-based cross-sectional study in Chennai, India. Central fat was measured using sagittal abdominal diameter, and adjusted for age, BMI and body fat percentage measured by impedance. Intra-sibship correlations were calculated for adjusted sagittal abdominal diameter and a comparison variable, adjusted body fat percentage. RESULTS: Among individuals free of diabetes, intra-sibship correlations were 0.48 for adjusted sagittal abdominal diameter and 0.14 for adjusted body fat percentage. CONCLUSIONS: Even after adjustment for possible assortative mating, these results are consistent with a heritability exceeding 90% for a trait defined as abdominal fat accumulation adjusted for total adiposity, sex and age. Linkage studies of abdominal obesity that map one or more of the genes underlying this high heritability are therefore a possible route to identifying genes for type 2 diabetes in South Asians.

Abdomen↗
PubMed1999

CD8 T cell ignorance or tolerance to islet antigens depends on antigen dose.

There are two major mechanisms reported to prevent the autoreactivity of islet-specific CD8(+) T cells: ignorance and tolerance. When ignorance is operative, naïve autoreactive CD8(+) T cells ignore islet antigens and recirculate without causing damage, unless activated by an external stimulus. In the case of tolerance, CD8(+) T cells are deleted. Which factor(s) contributes to each particular outcome was previously unknown. Here, we demonstrate that the concentration of self antigen determines which mechanism operates. When ovalbumin (OVA) was expressed at a relatively low concentration in the pancreatic islets of transgenic mice, there was no detectable cross-presentation, and the CD8(+) T cell compartment remained ignorant of OVA. In mice expressing higher doses of OVA, cross-presentation was detectable and led to peripheral deletion of OVA-specific CD8(+) T cells. When cross-presentation was prevented by reconstituting the bone marrow compartment with cells incapable of presenting OVA, deletional tolerance was converted to ignorance. Thus, the immune system uses two strategies to avoid CD8(+) T cell-mediated autoimmunity: for high dose antigens, it deletes autoreactive T cells, whereas for lower dose antigens, it relies on ignorance.

Adoptive Transfer↗
PubMed1999

Transforming growth factor-beta overrides the adhesion requirement for surface expression of alpha(5)beta(1) integrin in normal rat kidney fibroblasts. A necessary effect for induction of anchorage-independent growth.

We have previously shown that the expression of alpha(5)beta(1) integrin on the cell surface is dependent upon cell adhesion to the extracellular matrix, and we report here that transforming growth factor-beta (TGF-beta) overcomes this requirement in normal rat kidney (NRK) fibroblasts. Thus, suspended NRK cells treated with TGF-beta show levels of surface alpha(5)beta(1) integrin that are equivalent to those seen in adherent cells. Moreover, several experiments showed that this effect is necessary for the induction of anchorage-independent growth by TGF-beta. First, a kinetic analysis showed that surface expression of alpha(5)beta(1) integrin was restored in TGF-beta-treated NRK cells prior to the induction of anchorage-independent growth. Second, NRK cell mutants that have lost their TGF-beta requirement for surface expression of alpha(5)beta(1) integrin were anchorage-independent in the absence of TGF-beta. Third, an antisense oligonucleotide to the beta(1) integrin subunit or, fourth, stable expression of an alpha(5)-antisense cDNA blocked the ability of TGF-beta to stimulate anchorage-independent growth. Thus, TGF-beta overrides the adhesion requirement for surface expression of alpha(5)beta(1) integrin in NRK cells, and this effect is necessary for the induction of anchorage-independent growth.

Animals↗
PubMed1999

Risk factors for testicular germ cell tumours by histological tumour type. United Kingdom Testicular Cancer Study Group.

There are two main histological groups of testicular germ cell tumours, which may have different risk factors. Some authors have analysed potential risk factors by histological group but few consistent differences have been identified. In this paper we examine risk factors for pure seminoma and other tumours using data from the United Kingdom case control study of testicular cancer. Seven hundred and ninety-four cases were included in the study, each with a matched control; 400 cases had pure seminoma tumours, and 394 had other testicular tumours. The risk of seminoma associated with undescended testis was slightly higher than that for other tumours (odds ratio of 5.3 compared with 3.0). When split at the median age at diagnosis, this difference was greater in men aged 32 and over (odds ratio of 11.9 compared with 5.1) than in the younger men (3.0 compared with 2.5). Risks associated with testicular or groin injuries were higher in the non-seminoma group, as was the risk for a history of sexually transmitted disease. The protective effect of a late puberty was more marked for tumours of other histologies. Some differences were also detected for participation in sports. Whilst some of the differences detected may have arisen by chance, the stronger association between undescended testis and pure seminoma has been identified by a number of other studies and may reflect a genuine difference in aetiology.

Adult↗
PubMed1999

Alpha5beta1 integrin controls cyclin D1 expression by sustaining mitogen-activated protein kinase activity in growth factor-treated cells.

Cyclin D1 expression is jointly regulated by growth factors and cell adhesion to the extracellular matrix in many cell types. Growth factors are thought to regulate cyclin D1 expression because they stimulate sustained extracellular signal-regulated kinase (ERK) activity. However, we show here that growth factors induce transient ERK activity when added to suspended fibroblasts and sustained ERK activity only when added to adherent fibroblasts. Cell attachment to fibronectin or anti-alpha5beta1 integrin is sufficient to sustain the ERK signal and to induce cyclin D1 in growth factor-treated cells. Moreover, when we force the sustained activation of ERK, by conditional expression of a constitutively active MAP kinase/ERK kinase, we overcome the adhesion requirement for expression of cyclin D1. Thus, at least in part, fibroblasts are mitogen and anchorage dependent, because integrin action allows for a sustained ERK signal and the expression of cyclin D1 in growth factor-treated cells.

3T3 Cells↗