Search PubMed⌕ Search

Biomedical subjects

M Stafford

Publications and source records attributed to M Stafford.

At least 19 recordsLinked to original sources
PubMed2006

Building health: an epidemiological study of "sick building syndrome" in the Whitehall II study.

OBJECTIVES: Sick building syndrome (SBS) is described as a group of symptoms attributed to the physical environment of specific buildings. Isolating particular environmental features responsible for the symptoms has proved difficult. This study explores the role and significance of the physical and psychosocial work environment in explaining SBS. METHODS: Cross sectional data on the physical environment of a selection of buildings were added to individual data from the Whitehall II study--an ongoing health survey of office based civil servants. A self-report questionnaire was used to capture 10 symptoms of the SBS and psychosocial work stress. In total, 4052 participants aged 42-62 years working in 44 buildings were included in this study. RESULTS: No significant relation was found between most aspects of the physical work environment and symptom prevalence, adjusted for age, sex, and employment grade. Positive (non-significant) relations were found only with airborne bacteria, inhalable dust, dry bulb temperature, relative humidity, and having some control over the local physical environment. Greater effects were found with features of the psychosocial work environment including high job demands and low support. Only psychosocial work characteristics and control over the physical environment were independently associated with symptoms in the multivariate analysis. CONCLUSIONS: The physical environment of office buildings appears to be less important than features of the psychosocial work environment in explaining differences in the prevalence of symptoms.

Adult↗
PubMed2005

Gender differences in the associations between health and neighbourhood environment.

Multiple deprivation indicators are frequently used to capture the characteristics of an area. This is a useful approach for identifying the most deprived areas, and summary indices are good predictors of mortality and morbidity, but it remains unclear which aspects of the residential environment are most salient for health. A further question is whether the most important aspects vary for different types of residents. This paper focuses on whether associations with neighbourhood characteristics are different for men and women. The sociopolitical and physical environment, amenities, and indicators of economic deprivation and affluence were measured in neighbourhoods in the UK, and their relationship with self-rated health was investigated using multilevel regression models. Each of these contextual domains was associated with self-rated health over and above individual socioeconomic characteristics. The magnitude of the association was larger for women in each case. Statistically significant interactions between gender and residential environment were found for trust, integration into wider society, left-wing political climate, physical quality of the residential environment, and unemployment rate. These findings add to the literature indicating greater effects of non-work-based stressors for women and highlight the influence of the residential environment on women's health.

Adult↗
PubMed2005

Neighbourhood unemployment and all cause mortality: a comparison of six countries.

STUDY OBJECTIVE: Studies have shown that living in more deprived neighbourhoods is related to higher mortality rates, independent of individual socioeconomic characteristics. One approach that contributes to understanding the processes underlying this association is to examine whether the relation is modified by the country context. In this study, the size of the association between neighbourhood unemployment rates and all cause mortality was compared across samples from six countries (United States, Netherlands, England, Finland, Italy, and Spain). DESIGN: Data from three prospective cohort studies (ARIC (US), GLOBE (Netherlands), and Whitehall II (England)) and three population based register studies (Helsinki, Turin, Madrid) were analysed. In each study, neighbourhood unemployment rates were derived from census, register based data. Cox proportional hazard models, taking into account the possible correlation of outcomes among people of the same neighbourhood, were used to assess the associations between neighbourhood unemployment and all cause mortality, adjusted for education and occupation at the individual level. RESULTS: In men, after adjustment for age, education, and occupation, living in the quartile of neighbourhoods with the highest compared with the lowest unemployment rates was associated with increased hazards of mortality (14%-46%), although for the Whitehall II study associations were not statistically significant. Similar patterns were found in women, but associations were not statistically significant in two of the five studies that included women. CONCLUSIONS: Living in more deprived neighbourhoods is associated with increased all cause mortality in the US and five European countries, independent of individual socioeconomic characteristics. There is no evidence that country substantially modified this association.

Adolescent↗
PubMed2001

The clinical relevance of molecular staging for melanoma.

The presence of metastatic disease in the regional nodal basin is the most important prognostic indicator for patients with malignant melanoma. The metastatic status of the sentinel lymph node (SLN), defined as the first node in the basin to drain a primary tumor, has been shown to represent that of the entire basin. Since routine histologic examination of lymph nodes often underestimates the presence of micrometastatic disease, a more sensitive assay for detecting tumor cells is needed. We have previously shown that a molecular assay based on the reverse transcriptase polymerase chain reaction (RT-PCR) was able to define a population of patients at higher risk for both recurrence and death, compared with routine H&E histology. Recently, we have compared "molecular staging" of patients by RT-PCR with conventional S-100 immunohistochemistry (IHC) staining of the SLNs. In these studies, SLN specimens were bivaled, and half of each specimen was examined by routine histology, including both H&E and S-100 IHC. The other half of each specimen was analyzed by a nested RT-PCR assay. H&E histology alone detected metastatic disease in 36 of 233 (16%) patients tested. Serial sectioning and IHC detected micrometastatic disease in another 16 patients, thus increasing the proportion of patients with nodal disease to 22%. RT-PCR detected micrometastatic disease in 114 of 181 patients who were negative by conventional methods, further increasing the proportion of patients with evidence of nodal disease to 70% overall. The clinical significance of these findings is still uncertain. The value of additional therapy (including elective lymph node dissection and interferon therapy) for patients who are positive only by the molecular method is currently being investigated by the national multi-center Sunbelt Melanoma Trial.

Biomarkers, Tumor↗
PubMed2001

Characteristics of individuals and characteristics of areas: investigating their influence on health in the Whitehall II study.

There is evidence that health is determined by macro-level factors as well as by individual risk factors. Using data from the Whitehall II study we consider area-level determinants of health and ask two related questions. Firstly, are health differences between areas explained by the individual risk profiles of residents in those areas? Secondly, since poorer people tend to live in poorer places, are individual socio-economic effects on health explained by where people live? The demographic characteristics of residents, level of deprivation in the area, housing and neighbourhood quality and social integration were independently associated with health but did not fully explain differences between areas. Although there was considerable residential polarisation, area deprivation did not explain why lower status participants had poorer health.

Adult↗
PubMed2001

The role of ITAM- and ITIM-coupled receptors in platelet activation by collagen.

The major activation-inducing collagen receptor glycoprotein VI (GPVI) has been cloned within the last two years. It is a member of the Ig superfamily of proteins and is constitutively associated with the ITAM-bearing Fc receptor gamma-chain (FcR gamma-chain). GPVI signals through a pathway that involves several of the proteins used by Fc, B- and T-lymphocyte receptors and which takes place in glycolipid-enriched membrane domains in the plasma membrane known as GEMs. Responses to GPVI are regulated by PECAM-1 (CD31) and possibly other ITIM-bearing receptors. Despite a pivotal role for GPVI, there are important differences between signalling events to collagen and GPVI-specific ligands. This may reflect a role for co-receptors in the response to collagen.

Amino Acid Motifs↗
PubMed2000

P2Y purinoceptor activation mobilizes intracellular Ca2+ and induces a membrane current in rat intracardiac neurones.

1. The mobilization of Ca2+ by purinoceptor activation and the relative contributions of intra- and extracellular sources of Ca2+ were investigated using microfluorimetric measurements of fura-2 loaded in cultured neurones from rat intracardiac ganglia. 2. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed expression of mRNA for the G protein-coupled P2Y2 and P2Y4 receptors. 3. Brief application of either 300 microM ATP or 300 microM UTP caused transient increases in [Ca2+]i of 277 +/- 22 nM and 267 +/- 39 nM, respectively. Removal of external Ca2+ did not significantly reduce these [Ca2+]i responses. 4. The order of purinoceptor agonist potency for [Ca2+]i increases was ATP = UTP > 2-MeSATP > ADP >> adenosine, consistent with the profile for P2Y2 purinoceptors. ATP- and UTP-induced rises in [Ca2+]i were completely and reversibly blocked by 10 microM PPADS (a P2 purinoceptor antagonist) and partially inhibited by 100 microM suramin (a relatively non-specific purinoceptor antagonist). 5. In the presence of the endoplasmic reticulum Ca2+-ATPase inhibitor cyclopiazonic acid (10 microM) in Ca2+-free media, the [Ca2+]i responses evoked by ATP were progressively decreased and abolished. 6. ATP- and UTP-induced [Ca2+]i rises were insensitive to pertussis toxin, caffeine (5 mM) and ryanodine (10 microM) but were significantly reduced by U-73122, a phospholipase C (PLC) inhibitor. 7. In fura-2-loaded cells, perforated patch whole-cell recordings show that ATP and UTP evoked slow outward currents at -60 mV, concomitant with the rise in [Ca2+]i, in approximately 30 % of rat intracardiac neurones. 8. In conclusion, these results suggest that in r intracardiac neurones, ATP binds to P2Y2 purinoceptors to transiently raise [Ca2+]i and activate an outward current. The signalling pathway appears to involve a PTX-insensitive G protein coupled to PLC generation of IP3 which triggers the release of Ca2+ from a ryanodine-insensitive Ca2+ store(s).

Adenosine Triphosphate↗
PubMed2000

Effects of size at birth, gestational age and early growth in preterm infants on glucose and insulin concentrations at 9-12 years.

AIMS/HYPOTHESIS: To test the hypothesis that small size for gestation and poor postnatal growth in preterm infants is associated with higher fasting and post-load plasma glucose and insulin concentrations at 9-12 years of age. METHODS: Prospective follow-up at 9-12 years of 385 preterm children with birth weight less than 1850 g, who had anthropometry recorded at birth, 18 months and 7 years. Fasting plasma glucose, insulin, proinsulin and 32.33 split proinsulin concentrations and glucose and insulin concentrations 30 min after a standard glucose load were measured. RESULTS: Post-load glucose concentrations were negatively related to birth weight, independently of gestation or subsequent growth. Fasting split proinsulin and 30-min insulin concentrations were highest in children who showed the greatest increase in weight centile between birth and current follow-up, regardless of gestation. When weight during childhood was included, birthweight centile was, however, no longer statistically significant: concentrations of fasting, split, proinsulin and 30-min insulin were highest in those children who had shown the greatest increase in weight centile between 18 months of age and current follow-up, with no evidence of a greater effect in those who were smallest at 18 months. CONCLUSION/INTERPRETATION: Our findings suggest that fetal growth influences plasma glucose 30 min after a glucose load in preterm children at 9-12 years. In contrast, childhood weight gain is the most important factor influencing insulin concentrations and this effect is the same regardless of early size.

Blood Glucose↗
PubMed1999

Efficacy and safety of long-chain polyunsaturated fatty acid supplementation of infant-formula milk: a randomised trial.

BACKGROUND: We tested whether addition of n-3 and n-6 long-chain polyunsaturated fatty acids (LCPUFA) to infant-formula milk during the first 6 months promotes long-term cognitive and motor development, without adverse consequences. METHODS: We did a double-blind, randomised, controlled, efficacy and safety trial of formula with and without LCPUFAs, with an additional breastfed reference group, in four hospitals in two cities in the UK. The participants were 447 healthy full-term babies. 309 were fed formula (155 without LCPUFAs) and 138 were breastfed for at least 6 weeks. The main outcome measures were: Bayley Mental and Psychomotor Development Indices (MDI, PDI) at 18 months (primary efficacy outcome) and Knobloch, Passamanick, and Sherrards test at 9 months (secondary outcome). Principal safety outcomes were: infection, atopy, growth, and gastrointestinal tolerance. FINDINGS: Babies fed formula with and without LCPUFA did not differ in cognitive or motor development, growth, infection, atopy or tolerance. The mean (95% CI) MDI was 0.5 (-2.7 to 3.8) units and the PDI 0.6 (-1.8 to 3.0) units higher in the supplementation group. Formula-fed infants had similar developmental scores to the breastfed reference group after adjustment for higher social class and maternal education in the latter. INTERPRETATION: There was no evidence of a beneficial or adverse effect on cognitive and motor development or growth up to 18 months. Although no significant differences in safety outcomes were observed, we suggest such data should be collected in future LCPUFA trials. Our trial does not provide support for addition of LCPUFA to standard infant formula but we are now doing further follow-up of this cohort.

Animals↗
PubMed1999

The effects of dexmedetomidine on neuromuscular blockade in human volunteers.

UNLABELLED: The neuromuscular effects of dexmedetomidine in humans are unknown. We evaluated the effect of dexmedetomidine on neuromuscular block and hemodynamics during propofol/alfentanil anesthesia. During propofol/alfentanil anesthesia, the rocuronium infusion rate was adjusted in 10 volunteers to maintain a stable first response (T1) in the train-of-four sequence at 50% +/- 3% of the pre-rocuronium value. Dexmedetomidine was then administered by computer-controlled infusion, targeting a plasma dexmedetomidine concentration of 0.6 ng/mL for 45 min. The evoked mechanical responses of the adductor pollicis responses (T1 response and T4/T1 ratio), systolic blood pressure (SBP), heart rate (HR), and transmitted light through a fingertip were measured during the dexmedetomidine infusion and compared with predexmedetomidine values using repeated-measures analysis of variance and Dunnett's test. Plasma dexmedetomidine levels ranged from 0.68 to 1.24 ng/mL. T1 values decreased during the infusion, from 51% +/- 2% to 44% +/- 9% (P < 0.0001). T4/T1 values did not change during the infusion. Plasma rocuronium concentrations increased during the infusion (P = 0.02). Dexmedetomidine increased SBP (P < 0.001) and decreased HR (P < 0.001) (5-min median values) during the infusion compared with values before the infusion. Dexmedetomidine increased the transmitted light through the fingertip by up to 41% +/- 8% during the dexmedetomidine infusion (P < 0.001).We demonstrated that dexmedetomidine (0.98 +/- 0.01 microg/kg) increased the plasma rocuronium concentration, decreased T1, increased SBP, and decreased finger blood flow during propofol/alfentanil anesthesia. We conclude that dexmedetomidine-induced vasoconstriction may alter the pharmacokinetics of rocuronium. IMPLICATIONS: We studied the effect of an alpha2-agonist (dexmedetomidine) on rocuronium-induced neuromuscular block during propofol/alfentanil anesthesia. We found that the rocuronium concentration increased and the T1 response decreased during the dexmedetomidine administration. Although these effects were statistically significant, it is unlikely that they are of clinical significance.

Adrenergic alpha-Agonists↗
PubMed1999

Prognostic markers in clinically localised prostate cancer.

The prognostic value of immunohistochemical staining of P53, BCL-2, p27kip1, PSA, AR and MIB-1 was compared with that of established prognostic variables (Gleason score, surgical margins, tumour volume) following radical prostatectomy. Five groups were selected: negative margins with stable serum PSA (n=11), negative margins with rising serum PSA (n=7), positive margins with stable serum PSA (n=7), positive margins with rising serum PSA (6) and patients with micrometastatic disease diagnosed in lymph nodes removed during radical prostatectomy (n=8). Gleason score and tumour volume were of prognostic significance and immunohistochemical staining for MIB-1 and BCL-2 showed added independent prognostic significance in multivariate analysis.

Antigens, Nuclear↗
PubMed1998

Current obesity, steady weight change and weight fluctuation as predictors of physical functioning in middle aged office workers: the Whitehall II Study.

OBJECTIVES: (i) To investigate the effects of current obesity, steady weight change and weight fluctuation on physical functioning and (ii) to determine whether associations are independent of coronary heart disease. DESIGN: Prospective cohort study with body mass index (BMI) measurements at four time points between the ages of 25 and 63 y. SETTING: British civil servants based in London offices at baseline. PARTICIPANTS: 6895 men and 3413 women aged 35-55 y at baseline. MAIN OUTCOME MEASURE: Physical functioning was assessed using the 10-item scale from the Short Form 36 Health Survey, with a score in the lowest quartile indicating poor physical functioning. RESULTS: After adjustment for age and confounders (employment grade, smoking, alcohol, exercise and menopausal status), current BMI was monotonically associated with poor physical functioning in women whereas a threshold effect at a BMI of 27 kg/m2 was seen in men. The odds ratio of poor physical functioning was 1.55 (95% confidence interval (CI) 1.02-2.35) amongst women and 1.04 (95% CI 0.77-1.41) amongst men with BMI 23-24.9 kg/m2 compared to those with BMI < 21 kg/m2. Women in the upper, compared to the lower, tertile of steady weight change, had an odds ratio of poor physical functioning of 1.79 (1.24-2.60) after adjustment for age, confounders, current BMI and weight fluctuation. Women in the upper, compared to the lower, tertile of weight fluctuation had an odds ratio of poor physical functioning of 1.70 (1.23-2.34) adjusting for age, confounders, current BMI and steady weight change. Adjustment for the presence of coronary heart disease did not substantially alter any of these associations. Steady weight change and weight fluctuation had no independent effects in men. CONCLUSION: Among women, current obesity, steady weight change and weight fluctuation are independently and monotonically associated with poor physical functioning. Development of overt coronary heart disease is unlikely to be the mechanism for these associations.

Adult↗
PubMed1998

Behavioural and biological correlates of physical functioning in middle aged office workers: the UK whitehall II study.

STUDY OBJECTIVES: (1) To identify behavioural and biological correlates of poor physical functioning and (2) to determine whether such associations are independent of disease. DESIGN: Potential correlates were obtained from questionnaires and screening visits at baseline and five year follow up. Physical functioning was measured at follow up using the 10 item scale from the short-form 36 health survey. SETTING: London offices at baseline. PARTICIPANTS: 10,308 civil servants (6895 men and 3413 women), with a median age (range) of 49 years (39-63) at follow up. MAIN RESULTS: Multiple logistic regression showed that cigarette smoking, physical activity, body mass index (BMI), triglycerides, fibrinogen, and insulin were independently associated with poor physical functioning for men. For women, physical activity, eating habits, body mass index, fibrinogen, and insulin were independently associated with poor physical functioning. For example, among men, current smokers who had smoked more than 20 pack years were 1.89 (95% CI 1.35 to 2.67) times as likely to have poor physical functioning as never smokers. Men with BMI of 30 kg/m2 or more were 1.71 (95% CI 1.13 to 2.59) times as likely to have poor physical functioning as those with BMI < 20 kg/m2. The corresponding odds ratio for women was 2.66 (95% CI 1.80 to 3.93). With the exceptions of fibrinogen and insulin, associations remained on exclusion of subjects with physical disease. CONCLUSIONS: Risk factors established for physical diseases are associated with poor physical functioning in a population of working age. These associations may be independent of current disease.

Adult↗
PubMed1997

Is the SF-36 a valid measure of change in population health? Results from the Whitehall II Study.

OBJECTIVE: To measure within-person change in scores on the short form general health survey (SF-36) by age, sex, employment grade, and disease status. DESIGN: Longitudinal study with a mean of 36 months (range 23-59 months) follow up, with screening examination and questionnaire to detect physical and psychiatric morbidity. SETTING: 20 civil service departments originally located in London. PARTICIPANTS: 5070 male and 2197 female office based civil servants aged 39-63 years. MAIN OUTCOME MEASURES: Change in the eight scales of the SF-36 (adjusted for baseline score and length of follow up) and effect sizes (adjusted change standard deviation of differences). RESULTS: Within-person declines (worsening health) with age were greater than estimated by cross sectional data alone. General mental health showed greater declines among younger participants (P for linear trend < 0.001). Employment grade was inversely related to change; lower grades had greater deteriorations than higher grades (P < 0.001 for each scale in men; P < 0.05 for each scale in women except general health perceptions and role limitations due to physical problems). The greatest declines were seen among participants with disease at baseline, with the effects of physical and psychiatric morbidity being additive. Effect sizes ranged from 0.20 to 0.65 in participants with both physical and psychiatric morbidity. CONCLUSIONS: Health functioning, as measured by the SF-36, changed in hypothesised directions with age, employment grade, and disease status. These changes occurred within a short follow up period, in an occupational, high functioning cohort which has not been the subject of intervention, suggesting that the SF-36 is sensitive to changes in health in general populations.

Adolescent↗