E-Cadherin distribution in normal and dysplastic conjunctival epithelium.
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Cadherins↗
Biomedical subjects
R Haynes
Publications and source records attributed to R Haynes.
Cataract surgery in a community hospital outreach clinic: patients' costs and satisfaction.
A cataract day surgery service for the population of central Norfolk, UK, was provided by the main ophthalmic department in a district general hospital and in an outreach clinic in a community hospital 40 km distant. The outreach clinic aimed to extend the accessibility of this particular service in a rural area where many patients faced long journeys to the main hospital. Samples of 201 patients attending the main hospital for day cataract surgery and 198 patients attending the outreach clinic for the same procedure were identified. Patients were interviewed and given questionnaire forms to establish their general health before the operation, their arrangements to get to hospital and their satisfaction with the clinic and the care they had received. The sample of patients attending the outreach clinic was slightly older, less affluent and in slightly poorer general health than the patients attending the main hospital. The two samples were similar in terms of visual acuity after the operation, complication rates, satisfaction with the outcome of the operation and subsequent use of health services. The journey to hospital was quicker, more convenient and less costly for the outreach clinic patients than the main hospital patients. The net benefit to patients of the outreach clinic was estimated as pounds sterling 39,000 per annum. Satisfaction with administrative matters, facilities at the two clinics and the care received was high in both samples, but patients were significantly more satisfied with arrangements at the smaller outreach clinic. This evidence suggests that an outreach clinic in a small community hospital can provide cataract day surgery under local anaesthesia as effectively as a district centre, at a reduced social cost and with positive social benefits. Further study of heath service costs is vital, but political pressure to acknowledge patient preferences for more local services is growing.
Aged↗
p53-independent apoptosis mediated by tachpyridine, an anti-cancer iron chelator.
Iron is involved in essential biochemical reactions ranging from respiration to DNA synthesis. Consequently, iron deprivation has been proposed as a strategy for inhibition of tumor cell growth. We recently described a novel iron chelator, tachypyridine [N,N',N"-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane], and demonstrated that it not only inhibited growth of cultured tumor cells, but was actively cytotoxic. Here we explore the mechanisms underlying tachpyridine cytotoxicity. Using several criteria, including time-lapse video microscopy, DNA staining and TUNEL assays, tachpyridine was shown to specifically induce apoptotic cell death. Further, unlike numerous cytotoxic chemotherapeutic drugs which induce apoptosis by activating p53-dependent pathways, tachpyridine-mediated cell death did not require p53 activation. Although immunoblotting revealed rapid accumulation of p53 following treatment with tachpyridine, p21(WAF1) was not induced. Further, neither cytotoxicity nor apoptosis required p53. p53 null human lung cancer H1299 cells transfected with an ecdysone-inducible p53 exhibited equivalent sensitivity to tachpyridine in the presence and absence of p53, demonstrating the lack of requirement for p53 in an isogenic cell system. Further, time-lapse video microscopy and TUNEL assays demonstrated that both p53 null and p53 wild-type cells underwent apoptotic cell death in response to tachpyridine. In addition, in 55 human cancer cell lines the mean GI(50) of tachpyridine in cells with mutant p53 was virtually identical to the GI(50) in cells with wild-type p53. These results demonstrate that tachpyridine initiates an apoptotic mode of cell death that does not require functional p53. Since over 50% of human tumors contain a functionally defective p53 that reduces sensitivity to commonly used chemotherapeutic agents, such as etoposide and cisplatin, the ability of tachpyridine to induce apoptosis independently of p53 may offer an advantage in anti-tumor therapy.
Anticarcinogenic Agents↗
A comparison of cardiovascular risk factors among Indo-Asian and caucasian patients admitted with acute myocardial infarction in Kuala Lumpur, Malaysia and Birmingham, England.
Indo-Asians in the UK are at an increased risk of coronary artery disease (CAD); this may be a reflection of their cardiovascular risk factor profile as well as of a more sedentary lifestyle. We hypothesised that Indo-Asians in Malaysia and the UK may exhibit a similar cardiovascular risk factor and physical activity profile, which would be more adverse compared with caucasians. We studied 70 consecutive Indo-Asian patients admitted to hospitals in Kuala Lumpur, Malaysia (n=42; 35 males; mean age 60.6 years, SD 11.8); and Birmingham, England (n=28; 20 males; mean age 60.8 years, SD 12.9). Both groups of Indo-Asian patients were compared with 20 caucasian patients (13 males; mean age 62.7 years, SD 9.4) admitted with myocardial infarction from Birmingham. There was a higher prevalence of diabetes among Indo-Asians in both countries than among caucasians (p=0.0225). By contrast, caucasians had a higher prevalence of hypercholesterolaemia (p=0.0113), peripheral vascular disease (p=0.0008), regular alcohol consumption (p<0.0001) and family history of CAD (p=0.0041). There were no significant differences in mean age, body mass index or blood pressures. There was a significantly lower leisure activity score (p=0.001) and total physical activity score (p=0.003) among Indo-Asians in both countries than among caucasians. This survey has demonstrated differences in cardiovascular risk factors among Indo-Asian and caucasian patients. The high prevalence of diabetes, as well as the lower physical activity and sedentary lifestyles among Indo-Asians, in both Malaysia and the UK, may in part contribute to the high incidence of CAD in this ethnic group.
Aged↗
Deprivation and poor health in rural areas: inequalities hidden by averages.
Poor health and social deprivation scores in 570 wards in East Anglia, UK, were much less associated in rural than in urban areas. The deprivation measure most closely related to poor health in the least accessible rural wards was male unemployment, but use of this measure did not remove the urban-rural gradient of association strength. Neither did replacing wards by smaller enumeration districts as the units of analysis. The differences between urban and rural correlations were removed by restricting the comparison to wards with the same unemployment range and combining pairs of rural wards with similar deprivation values. Apparent differences between rural and urban associations are therefore not due to the choice of deprivation indices or census areas but are artifacts of the greater internal variability, smaller average deprivation range and smaller population size of rural small areas. Deprived people with poor health in rural areas are hidden by favourable averages of health and deprivation measures and do not benefit from resource allocations based on area values.
Cultural Deprivation↗
Accidents to preschool children: comparing family and neighbourhood risk factors.
Accidental injury in young children is more common among poorer families and in deprived areas but little is known about how these factors interact. This paper describes a study to measure the contribution of individual family factors and area characteristics in determining risk of accidental injury among preschool children. We conducted a population based study of preschool accident and emergency attendances over two years in and around the city of Norwich, UK. Information on individual families was extracted from the district child health information system while "social areas" were constructed from adjacent census enumeration districts with homogeneous social and demographic characteristics. Statistical analysis was by multilevel modelling. Accidental injury rates were much higher in deprived urban neighbourhoods than in affluent areas but the multilevel analysis showed that, for all accidents, much of the variation in rates was accounted for by factors at the individual level i.e. male sex, young maternal age, number of elder siblings and distance from hospital, with a smaller, but independent, influence of living in a deprived neighbourhood. The model for more severe injuries was similar except single parenthood was now significant at the level of individuals and the effect of area deprivation was stronger. We conclude that preschool accidental injuries are influenced by factors operating at both the level of individual families and between areas. This evidence suggests that both social policy changes to improve child care among unsupported young families and targeting accident prevention measures at a local level towards deprived neighbourhoods would reduce accidents.
Accidents↗
Effects of distances to hospital and GP surgery on hospital inpatient episodes, controlling for needs and provision.
Age and sex adjusted inpatient episode ratios were calculated from hospital records over a two year period for 555 census wards in Cambridgeshire, Norfolk and Suffolk, UK. Hospital episodes were divided into acute, psychiatric and geriatric specialties, and elective and emergency acute admissions were distinguished. Variations in inpatient episode ratios between wards were compared with census indicators of the 'needs' of local populations for inpatient services, measures of the local provision of hospital and other related services, and measures of the distance to the nearest general practitioner surgery and the distance to the nearest hospital. Hospital episodes were found to be strongly related to both distance measures, but the associations were partially explained by a tendency for the health status of local populations (measured by the needs indicators) to be worst in urban areas close to health services. Including needs and provision variables together with the distance variables explained most of the variations in age and sex adjusted inpatient ratios for small areas. Needs were the most important determinants of emergency acute and psychiatric inpatient rates, but service provision was more important for elective acute and geriatric inpatients. Controlling for needs and provision, distance to hospital produced 17% reduction in acute episodes, 37% reduction in psychiatric episodes and 23% reduction in geriatric episodes over the range of distances observed. Distance to nearest GP surgery reduced elective acute episodes by up to 15% after controlling for confounders. These results demonstrate that the NHS is falling short of its aim to provide fair access to services irrespective of geography, and new policies will be required if geographical inequities are to be reduced.
England↗
Mortality, long-term illness and deprivation in rural and metropolitan wards of England and Wales.
The relationships between mortality, limiting long-term illness and indicators of social deprivation were investigated using regression analysis on data for rural wards, metropolitan wards and the remaining wards in England and Wales. Regional differences were controlled. In rural wards, people had better health than average and slightly better health than would be expected from their deprivation scores. Average levels of health in rural areas were only weakly related to deprivation, which was partly but not fully due to the restricted range of average deprivation values in rural wards. In metropolitan areas, relatively poor levels of health were largely explained by social deprivation, but people in Inner London were healthier than might be expected from measures of deprivation. The relationship between health and social deprivation is therefore not uniform over England and Wales, but varies between geographical types of area. One consequence is that resource allocation on the basis of social deprivation would put the populations of rural areas and Inner London at an advantage.
Adolescent↗
Urban-rural variations in suicides and undetermined deaths in England and Wales.
BACKGROUND: Given that a high proportion of undetermined deaths are thought to be suicides, the objective of the study was to compare the geography of the two verdicts, with emphasis on urban-rural differences, to determine whether the likelihood of a death being classified as suicide varies according to location. METHODS: Standardized mortality ratios (SMRs) were mapped for the local authority districts of England and Wales, using data aggregated over the period 1989-1992. Districts were classified according to population density, and SMRs calculated for each quartile. Finally, regression equations were obtained to model the relationship of suicide and undetermined death with a series of risk factors. RESULTS: Both male and female undetermined deaths showed a significant deficit in the most sparsely populated districts and a significant excess in the most densely populated districts. Female suicides were also significantly high in densely populated districts, but male suicides were highest in the most rural areas (SMR 110, 95 per cent confidence intervals 105-115). District variations in both verdicts were associated with the proportion of single-person households for both sexes, but male suicides and male undetermined deaths were associated with additional predictors, consistent with their distinct geographical distributions. CONCLUSIONS: Differences in suicide methods, the likelihood of communicating suicidal intent and, perhaps, variations in access to psychiatric services might be contributory factors to the observed differences between the verdicts. The results suggest that recorded suicides are a biased subset of actual suicides, particularly for males, and that the study of suicide verdicts alone is potentially misleading.
England↗
Effect of labour market conditions on reporting of limiting long-term illness and permanent sickness in England and Wales.
STUDY OBJECTIVE: To identify any bias in the reporting of limiting long term illness and permanent sickness due to labour market conditions, and show the absence of the effect in mortality rates. DESIGN: A geographically based study using data from the 1991 census. Standardised ratios for mortality and long term illness in people aged 0-64 years and permanent sickness in people of working age were compared with Carstairs deprivation scores in multilevel models which separated the effects operating at three geographical scales: census wards, travel to work areas, and standard regions. Holding ward and regional effects constant, variations between travel to work areas were compared with long term unemployment rates. SETTING: Altogether 8690 wards and 262 travel to work areas in England and Wales. MAIN RESULTS: Variations in mortality, limiting long term illness, and permanent sickness were related to Carstairs deprivation scores and standard region. With these relationships controlled, limiting long term illness and permanent sickness were significantly related to long term unemployment levels in travel to work areas, but mortality was not affected. Self reported morbidity was more sensitive to variations in long term unemployment rates in conditions of high social deprivation than in affluent populations. CONCLUSIONS: Limiting long term illness and permanent sickness measures may reflect a tendency for higher positive response in difficult labour market conditions. For average social deprivation conditions, standardised limiting long term illness for people aged 0-64 years was 20% higher in travel to work areas where employment prospects were relatively poor compared with areas with relatively good employment prospects. This casts doubt on the use of limiting long term illness as an indicator of objective health care needs for resource allocation purposes at national level.
Adolescent↗
Activation of MAP kinases in airway smooth muscle.
To test the hypothesis that mitogen-activated protein (MAP) kinases are activated by contractile agonists in intact nonproliferating airway smooth muscle, kinase activities were compared in resting and stimulated canine tracheal smooth muscle. Kinase activities in sodium dodecyl sulfate extracts were assayed by a gel renaturation method. Myelin basic protein kinase activities corresponding to ERK1 and ERK2 immunoreactive proteins were activated twofold above the basal level within 5 min by 1 microM carbachol. MAP kinase activity assayed in crude homogenates using a synthetic peptide substrate (APRTPGGRR) also increased twofold above basal in muscles stimulated with 1 microM carbachol. Two protein kinases separated by Mono-Q chromatography were identified on Western blots as ERK1 and ERK2 MAP kinases. Carbachol stimulation increased caldesmon phosphorylation in intact muscle, and purified caldesmon was a substrate for activated murine ERK2 MAP kinase. Activated ERK2 MAP kinase added to Triton X-100-permeabilized fibers potentiated Ca2+-induced contraction. The results show that ERK MAP kinases are activated after stimulation of muscarinic receptors in airway smooth muscle, which is consistent with coupling of MAP kinases to phosphorylation of caldesmon in vivo.
Animals↗
Activation of MAP kinases and phosphorylation of caldesmon in canine colonic smooth muscle.
1. Phosphorylation of caldesmon was assayed in canine colonic circular smooth muscle strips labelled with 32P and stimulated with 10 microM acetylcholine. Caldesmon was isolated by two-dimensional non-equilibrium pH gel electrophoresis. Stimulation with acetylcholine increased caldesmon phosphorylation significantly from a basal level of 0.6 +/- 0.07 to 1.1 +/- 0.15 mol P1 (mol caldesmon)-1 after 2 min. 2. MAP kinase activities were measured in SDS extracts of muscle by a gel reconstitution method using myelin basic protein. Myelin basic protein kinase activities were observed at 38, 44, 50 and 57 kDa by the gel reconstitution method. Endogenous caldesmon kinase activities were also identified by the gel reconstitution method at 38, 44 and 50 kDa. The 38 and 44 kDa kinases comigrated with proteins labelled by anti-ERK1 MAP kinase antibodies on Western blots. Both 38 and 44 kDa MBP kinase activities increased significantly during contractions induced by 10 microM acetylcholine, 0.1 microM neurokinin A and 70 mM potassium. 3. Phorbol dibutyrate (0.1 microM) potentiated activation of MAP kinases and contraction of depolarized muscles while producing a decrease in fura-2 fluorescence ratio. This suggests that protein kinase C activation is coupled to MAP kinase activity in colonic smooth muscle. 4. MAP kinases isolated form muscle homogenates by Mono Q chromatography were assayed using the specific MAP kinase substrate peptide APRTPGGRR. Stimulation of muscles for 2 min with 10 microM acetylcholine activated both ERK1 and ERK2 MAP kinase activities 2-fold. 5. To determine the effects of caldesmon phosphorylation by MAP kinase on the cross-bridge cycle, actin sliding velocity was measured with an in vitro motility assay. Unphosphorylated turkey gizzard caldesmon (3 microM) significantly reduced mean sliding velocity. Phosphorylation of caldesmon with sea star ERK1 MAP kinase reversed the inhibitory effect of caldesmon on sliding velocity. The results are consistent with a protein kinase cascade being activated by contractile agonists in gastrointestinal smooth muscle which activates ERK MAP kinases leading to phosphorylation of caldesmon. Phosphorylation of caldesmon in vivo may reverse inhibitory influences of caldesmon on cross-bridge cycling.
Acetylcholine↗
Acrylic bone-cement. Influence of mixer design and unmixed powder.
The effects of hand mixing with two different mechanical mixing systems (fixed versus rotating central axis) on unmixed powder content, macroporosity, density, and bending strength of acrylic bone-cement are compared. The effects of voids and unmixed powder on cement bending strength are also evaluated. In acrylic cement, both unmixed powder monomer and voids 1 mm and larger can be easily visualized and analyzed on radiographs of 3-mm-thick samples. Image analysis allowed demonstration of a significant increase in unmixed powder content (P < .0001), in cement prepared using a vacuum mixing system with a fixed central axis compared with both the rotating axis system and hand mixing. The rotating-axis system produced cement of higher density compared with hand mixing only (P = .004). There was a significant correlation between the number of voids measured per square centimeter and cement bending strength (P < .0001), as well as an independent and significant correlation between unmixed powder content and cement bending strength (P < .0001). Mechanical mixing using a fixed central axis produced significantly weaker cement compared with both hand mixing (P < .015) and the rotating-central-axis system (P < .0001). A 15% drop in strength between the two mechanical mixing systems was observed. It is therefore concluded that the use of different rotating systems in mechanical mixers can influence void and unmixed powder content and, consequently, the mechanical properties of acrylic cement, and that unmixed powder is an independent factor affecting the bending strength of the cement.
Acrylates↗
Unemployment rate as an updatable health needs indicator for small areas.
BACKGROUND: The objective of the study was to compare updatable unemployment rates with the unemployment rate and composite deprivation indices from the 1991 Census as health needs indicators for small areas. METHODS: Townsend, Carstairs and Jarman indices and male unemployment rates were calculated from the 1991 Census, for 275 wards of the former East Anglian health region with unchanged boundaries between 1981 and 1991. Male unemployment rates were also derived from April 1991 unemployment benefit claimant figures, using both Office of Population Censuses and Surveys mid-year estimates of population and estimates derived from Family Health Services Authority patient registers as the denominator. Ward values were compared using Pearson product moment correlation. RESULTS: All three unemployment measures were closely related to each other and all were broadly as effective in predicting ward variations in mortality and long-term illness in 1991 as the compound deprivation indices of Jarman. Townsend and Carstairs. CONCLUSION: Updatable unemployment rates were as suitable as the composite indices as an indicator of relative health needs for small areas in the year of the Census and might be expected to be superior in inter-censal years.
Adolescent↗
Factors affecting non-response to cervical cytology screening in Norfolk, England.
A geographic information system was used to integrate information on the uptake of cervical cytology screening for general medical practices in Norfolk with other data on the characteristics of the practices and the population they served. Regression analysis was employed to explore the extent to which variations in non-response were associated with explanatory factors. Non-response to the earlier system of opportunistic screening was found to be associated with the size of practice, the presence of a female doctor, the District Health Authority in which the practice was located, the age structure of the practice population, its degree of socio-economic deprivation and levels of rural remoteness. Compared with the earlier system, the new population-based call and recall system was found to be reaching a larger proportion of the population at risk. The former relationships were weaker under the new system, but non-response was still significantly associated with both social and organisational factors.
Adult↗
Stage- and ribosome-specific alterations in nascent chain-Sec61p interactions accompany translocation across the ER membrane.
Near-neighbor interactions between translocating nascent chains and Sec61p were investigated by chemical cross-linking. At stages of translocation before signal sequence cleavage, nascent chains could be cross-linked to Sec61p at high (60-80%) efficiencies. Cross-linking occurred through the signal sequence and the mature portion of wild-type and signal cleavage mutant nascent chains. At later stages of translocation, as represented through truncated translocation intermediates, cross-linking to Sec61p was markedly reduced. Dissociation of the ribosome into its large and small subunits after assembly of the precursor into the translocon, but before cross-linking, resulted in a dramatic reduction in subsequent cross-linking yield, indicating that at early stages of translocation, nascent chain-Sec61p interactions are in part mediated through interactions of the ribosome with components of the ER membrane, such as Sec61p. Dissociation of the ribosome was, however, without effect on subsequent translocation. These results are discussed with respect to a model in which Sec61p performs a function essential for the initiation of protein translocation.
Base Sequence↗
Monoclonal antibody therapy of chronic intraocular inflammation using Campath-1H.
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Adult↗
Limiting long-term illness and its associations with mortality and indicators of social deprivation.
STUDY OBJECTIVE: To examine geographical variation in limiting long-term illness in England and Wales and assesses the extent of its similarity with the distribution of mortality rates and of deprivation. DESIGN: A geographically based study using data from the 1991 census on limiting long term illness. Maps and regression analysis are used to compare the distribution of standardised illness ratios with standardised mortality ratios and indicators of social deprivation. SETTING: A total of 401 local authority districts in England and Wales. PARTICIPANTS: The population of England and Wales enumerated in the 1991 census. MAIN RESULTS: The geographical pattern of limiting long term illness shows many similarities with that of mortality but there are also some differences. Both are positively associated with indicators of social deprivation, with limiting long term illness tending to show stronger correlations, particularly in the elderly. Most of Wales and many industrial areas of northern England have higher rates of long term illness than would be expected from their mortality rates, while much of south eastern England has lower than expected rates. CONCLUSIONS: Moves towards using data on limiting long term illness instead of standardised mortality rates would have important implications for NHS resource allocations. Further assessment of the reliability of these data on self reported morbidity is required. in particular, there is a need to assess how much they reflect real differences in ill health rather than the influence of socioeconomic or cultural factors affecting the likelihood of a positive answer to the census question on limiting long term illness.
Adolescent↗