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Biomedical subjects

M Evans

Publications and source records attributed to M Evans.

At least 91 records · Page 5Linked to original sources
PubMed2000

Hepatic stellate cells express the low affinity nerve growth factor receptor p75 and undergo apoptosis in response to nerve growth factor stimulation.

We have examined the expression of p75, a member of the TNF receptor superfamily in hepatic stellate cells (HSC) and pancreatic stellate cells (PSC). Activated HSC and PSC were demonstrated by Western blot analysis to express p75. p75 was immunolocalized to cells with a myofibroblast-like morphology in the fibrotic bands of six fibrotic and cirrhotic liver biopsies and three biopsies of fibrotic human pancreas. Immunostaining of parallel sections indicated that these cells were alpha-smooth muscle actin-positive, identifying them as activated HSC and PSC, respectively. HSC apoptosis in tissue culture in the presence of serum was quantified after addition of 0.1 to 100 ng/ml of nerve growth factor (NGF) a ligand for p75, by in situ counting of apoptotic bodies after addition of acridine orange. HSC demonstrated a significant increase in apoptosis in response to 100 ng/ml NGF (0.05 > P by Wilcoxon's rank; n = 7) after 24 hours. NGF 100 ng/ml had no effect on HSC proliferation, but reduced total HSC DNA by 19% relative to control after 24 hours (n = 3). These data demonstrate that activated HSC express p75 and respond to NGF stimulation by undergoing apoptosis. We therefore report p75 as a novel marker of activated HSC and suggest that signaling via ligand binding to p75 may provide a mechanism for selective apoptosis of HSC.

Animals↗
PubMed2000

Stiffness, strength and healing assessment in different bone fractures--a simple mathematical model.

External fixators can only be removed safely when fractures have healed sufficiently to restore mechanical integrity to the bone. A bending stiffness of 15 N m/ degrees has been suggested as a means of estimating mechanical integrity. To examine whether this end point stiffness value can be applied to all fractures, the present study examined the degree of variability in predicted stiffness and strength that arises from variations in bone dimensions. Results imply that there is no common value for the end-point of bending stiffness in different bones. At an end point value of 15 N m/degrees, the maturity of the fracture repair tissue (represented by its elastic modulus) can vary 500-fold between an adult femur with a 0.5-mm gap to a child's mid diaphyseal tibia with a 1.0-mm gap. Fortunately, the strength does not vary by as large an extent as the modulus. However, even though two fractures each have reached a stiffness of 15 N m/degrees, a fracture in a bone of 50 mm diameter may exhibit only 60% of the strength of repair in a bone of 30 mm diameter. Therefore, caution should be exercised when using the bending stiffness as an end point indicator for different bones.

Adult↗
PubMed2000

Designing attenuators for total-body irradiation using virtual simulation.

In total-body photon irradiation, the lungs are the most commonly shielded organ. Lung compensators are often designed by using high-energy portal films. Other organs, such as the kidneys and liver, are poorly visualized in portal films due to their unit-density composition. A computed tomography-based technique to design kidney and liver attenuators involves outlining these organs in a virtual simulation. The position and the shape of the attenuator are then determined from a digitally-reconstructed radiograph. Appropriate attenuator thickness is determined from measured transmission curves. This article provides a summary of this technique for total-body photon irradiation in a 4-MV photon beam.

Computer Simulation↗
PubMed2000

Are recent increases in deliberate self-harm associated with changes in socio-economic conditions? An ecological analysis of patterns of deliberate self-harm in bristol 1972-3 and 1995-6.

BACKGROUND: The incidence of deliberate self-harm (DSH) in Britain has increased markedly over the last 30 years. Reasons for this rise are not clear. We have investigated whether changes in the social and economic environment underlie any of the recent increase in DSH incidence. METHODS: An ecological analysis was used to assess associations between changes in census-based measures of the social and economic environment--the Townsend Deprivation Index and a three-factor social fragmentation index--and changes in age- and sex-specific hospital attendance rates for DSH for the 28 wards of the city of Bristol between 1972-3 and 1995-6. RESULTS: There were significant cross-sectional associations between the Townsend Index and rates of DSH in both males and females in both time periods. Increases in Townsend Index were also associated with increases in DSH. This association was statistically significant at the 5% level in 25-34 year-old females. Associations with the social fragmentation index were weak, although our index was based on rather limited data. CONCLUSIONS: This analysis suggests that changes in levels of socio-economic deprivation may influence area-specific patterns of DSH and such changes may have contributed to recent rises in DSH.

Adolescent↗
PubMed2000

The role of outbreaks in developing food safety policy: population based surveillance of salmonella outbreaks in Wales 1986-98.

In developing public policy on food safety, systematic identification and thorough investigation of all general outbreaks is necessary in order to avoid bias towards highly publicised outbreaks. In Wales, from 1986 to 1998, 87 general foodborne outbreaks of salmonellosis were identified. Most outbreaks occurred at functions or were associated with small catering outlets such as bakeries and sandwich bars. In 50 outbreaks, a vehicle of infection was confirmed microbiologically and/or epidemiologically. The most common food vehicles were those containing shell eggs. Salmonella enteritidis outbreaks were significantly more likely than outbreaks of other serotypes to be associated with vehicles containing shell eggs, suggesting that eggs were also the source of infection in many outbreaks. The routine use of analytical epidemiological studies to identify vehicles in outbreaks is recommended.

Disease Outbreaks↗
PubMed2000

Dual analyte flow injection fluorescence immunoassays using thiophilic gel reactors and synchronous scanning detection.

Heterogeneous fluorescence immunoassays have been automated using flow injection manifolds incorporating thiophilic gel solid phase reactors to separate antibody-bound and unbound analyte molecules. Antibody elution is achieved by changes in ionic strength, thus allowing the use of pH sensitive fluorescent labels. This facilitates the development of dual analyte systems, in which two competitive immunoassays with separate labels are monitored in parallel. Detection of the fluorophores by high speed synchronous fluorescence scanning while the flow is briefly stopped utilises either one synchronous interval which detects both fluorophores, or two separate scans at different wavelength intervals, one for each fluorophore. Simultaneous analyses of serum albumin and transferrin exemplify these novel approaches. Spectroscopic interferences are very small, analyte recoveries are close to 100%, with a relative standard deviation of 5-6% and a sampling rate of 20 h-1.

Animals↗
PubMed2000

Emotional and behavioural problems and family functioning in children with haemophilia: a cross-sectional survey.

A comparative study is presented about emotional and behavioural problems in haemophilia and family functioning. This cross-sectional survey looked at boys, aged between 4 and 15 years, with haemophilia and compared them with a group of their healthy school peers. A basic demographic questionnaire was used for both groups along with the Child Behaviour Checklist (CBCL) and the Family Assessment Measure (FAM). Seventeen of 24 families of boys with haemophilia participated (70.8% response). The comparison group consisted of 12 boys, i.e. 70.6% of the haemophilia sample. The groups did not differ in terms of the children's ages and family sizes but significantly fewer of the mothers of the boys with haemophilia worked outside the home. The two groups were compared for scores on the CBCL and FAM. More problems were identified in the haemophilia group on both measures, i.e. there were more emotional, behavioural and family difficulties compared with the healthy group; however, because of the small sample sizes, the differences between the groups did not reach statistical significance. A larger study would be indicated in order to explore these differences further.

Adolescent↗
PubMed2000

Psychotic disorders in urban areas: an overview of the Study on Low Prevalence Disorders.

OBJECTIVE: This paper reports on a study designed within the framework of the National Survey of Mental Health and Wellbeing to: estimate the prevalence of psychoses in urban areas of Australia; identify profiles of symptomatology, impairments and disabilities; collect information on services received and needed; and explore quality of life issues in a broadly representative sample of people with psychotic illnesses. METHOD: The study was conducted over four areas in the Australian Capital Territory, Queensland, Victoria and Western Australia, as a two-phase survey: (i) a census and screening for psychosis of all individuals who made contacts with mental health services during a period of 1 month in 1997; and (ii) interviews with a stratified random sample (n=980) of the screen-positive individuals (n=3800) using a standardised instrument. RESULTS: The point prevalence (1 month) of psychotic disorders in the urban population aged 18-64 is in the range of 4-7 per 1000 with a weighted mean of 4.7 per 1000. People with psychotic disorders experience high rates of functional impairments and disability, decreased quality of life, persistent symptoms, substance-use comorbidity and frequent side effects of medication. Although the utilisation of hospital-based and community mental health services, as well as of public and non-governmental helping agencies, is high, the majority live in extreme social isolation and adverse socioeconomic circumstances. Among the many unmet needs, the limited availability of community-based rehabilitation, supported accommodation and employment opportunities is particularly prominent. CONCLUSIONS: The so-called 'low-prevalence' psychotic disorders represent a major and complex public health problem, associated with heavy personal and social costs. There is a need for a broad programmatic approach, involving various sectors of the community, to tackle the multiple dimensions of clinical disorder, personal functioning and socioeconomic environment that influence the course and outcome of psychosis and ultimately determine the effectiveness of service-based intervention.

Activities of Daily Living↗
PubMed2000

Characterising psychosis in the Australian National Survey of Mental Health and Wellbeing Study on Low Prevalence (psychotic) Disorders.

OBJECTIVE: This study examines the factorial structure of symptoms and signs in psychosis in data from the Study on Low Prevalence (psychotic) Disorders which is part of the National Survey of Mental Health and Wellbeing, Australia 1997-1998. METHOD: The present study examined a wide variety of symptoms taken from the Schedules for Clinical Assessment in Neuropsychiatry items and the substance use items in the Diagnostic Interview for Psychosis, an instrument specially constructed for the national study. The instrument was applied to 980 community and hospital subjects with a wide range of psychotic illness diagnoses. The data were factor analysed and scales of 'domains of psychopathology' derived. RESULTS: The data were best fitted by five principal factors ('domains') which can be approximately labelled dysphoria, positive symptoms, substance use, mania and negative symptoms/incoherence. These factors together explained 55.4% of variance in symptoms. Solutions with more numerous factors did not improve the representation. CONCLUSION: The five domains successfully characterise a large part of the variance in psychopathology found in the present study of low prevalence (psychotic) disorders. The approach allows sufferer's symptom range and severity to be well expressed without multiple comorbid diagnoses or the limits imposed by categorical diagnosis. Knowledge of alternative dimensional representations of psychopathology may usefully complement our use of categories, enhance awareness of symptoms and ensure that important psychopathology is heeded in practice and research.

Adult↗
PubMed2000

Epitope analysis of the human thyrotropin (TSH) receptor using monoclonal antibodies.

A panel of thyrotropin (TSH) receptor (TSHR) monoclonal antibodies (mAbs), produced using highly purified Chinese hamster ovary (CHO) cell-produced TSHR, has been used to study TSHR structure. All 41 mAbs recognized full-length TSHR containing complex carbohydrate (120 kDa), and 40 mAbs recognized full-length precursor-containing high mannose sugars (100 kDa). The mAbs also recognized TSHR cleavage products with three types of reactivity: type 1 mAbs reacting with bands at 70 kDa and 58 kDa, type 2 with bands at 70 kDa and 52 kDa, and type 3 with bands at 52 kDa and 40 kDa. Deglycosylation studies showed that the 70-kDa and 58-kDa bands contained complex carbohydrate, whereas the 52-kDa and 40-kDa bands were unglycosylated. These results are consistent with TSHR cleavage occurring at two sites. Cleavage at both sites gives rise to glycosylated A subunit (58 kDa) corresponding to the extracellular domain of the receptor and nonglycosylated B subunit (40 kDa) corresponding to the C-terminal transmembrane domain. Cleavage only at site 1 gives rise to the 58-kDa A subunit and a large B subunit (52 kDa). Cleavage only at site 2 gives rise to a large A subunit (70 kDa) and the B subunit (40 kDa). Four of the mAbs inhibited 125I-labeled TSH binding to solubilized full-length TSHR. TSH binding was inhibited by (a) two type 3 mAbs reactive with the N-terminal region of the B subunit (epitopes between amino acids 381 and 385 and between 380 and 418, respectively) and (b) two type 2 mAbs reactive with epitopes on the A subunit (between amino acids 246 and 260). These results together with previous studies on the direct binding of TSH to the TSHR A subunit suggest that at least two distinct regions of the TSHR sequence, including one region on the A subunit and one region on the B subunit, fold together to form part of a complex TSH binding site.

Amino Acid Sequence↗
PubMed2000

Overexpression of beta-catenin induces apoptosis independent of its transactivation function with LEF-1 or the involvement of major G1 cell cycle regulators.

beta-Catenin promotes epithelial architecture by forming cell surface complexes with E-cadherin and also interacts with TCF/LEF-1 in the nucleus to control gene expression. By DNA transfection, we overexpressed beta-catenin and/or LEF-1 in NIH 3T3 fibroblasts, corneal fibroblasts, corneal epithelia, uveal melanoma cells, and several carcinoma cell lines. In all cases (with or without LEF-1), the abundant exogenous beta-catenin localizes to the nucleus and forms distinct nuclear aggregates that are not associated with DNA. Surprisingly, we found that with time (5-8 d after transfection) cells overexpressing beta-catenin all undergo apoptosis. LEF-1 does not need to be present. Moreover, LEF-1 overexpression in the absence of exogenous beta-catenin does not induce apoptosis, even though some endogenous beta-catenin moves with the exogenous LEF-1 into the nucleus. TOPFLASH/FOPFLASH reporter assays showed that full-length beta-catenin is able to induce LEF-1-dependent transactivation, whereas Arm beta-catenin totally abolishes the transactivating function. However, Arm beta-catenin, containing deletions of known LEF-1-transactivating domains, has the same apoptotic effects as full-length beta-catenin. Overexpressed beta-catenin also induces apoptosis in cells transfected with nuclear localization signal-deleted LEF-1 that localizes only in the cytoplasm. Thus, the apoptotic effects of overexpressed exogenous beta-catenin do not rely on its transactivating function with nuclear LEF-1. Overexpressed delta-catenin, containing 10 Arm repeats, induces only minor apoptosis, suggesting that the major apoptotic effect may be due to domains specific to beta-catenin as well as to Arm repeats. The absence of p53, Rb, cyclin D1, or E2F1 does not affect the apoptotic effect of overexpressed beta-catenin, but Bcl-x(L) reduces it. We hypothesize that in vivo apoptosis of cells overexpressing beta-catenin might be a physiological mechanism to eliminate them from the population.

3T3 Cells↗
PubMed2000

Justified deception? The single blind placebo in drug research.

"Run-in" and "washout" periods involving the withholding of medication are widely used in drug research trials in pursuit of both patient safety and scientific reliability. Such no-medication periods can be justified ethically provided that they are apparent to patients, who can thereby properly consent to undergoing them. Less widespread, but still common, is the practice of "single blinding" no-medication periods, concealing them from patients by means of placebo. Whilst all placebos involve a measure of concealment, their use is typically justified in drug research trials (i) by their preserving the uncertainty generated by the random allocation of different treatments within a drug trial; and (ii) by the researchers openly declaring both the randomisation process and the chances of receiving placebo. In the single blind placebo "run-in" or "washout", neither of these conditions is met. This paper considers three possible defences of the practice of using single blind placebo "run-ins" or "washouts" and finds them all to fail; the practice appears ethically unjustified.

Clinical Trials as Topic↗
PubMed2000

Prevalence of mental illness in a rehabilitation unit for older adults.

The prevalence of psychiatric disorders was studied in 78 elderly people in a rehabilitation unit for older adults. The patients were assessed using the Evans Liverpool depression rating scale, Hospital Anxiety and Depression scale and Mini-Mental State Examination. Twenty-eight (35.9%) patients were found to be depressed, 15 of these also had raised anxiety. Thirty-one (41.0%) patients had significant cognitive impairment and 14 of these had associated depression. Only 33 (42%) had no evidence of either cognitive impairment or mood disorder. On discharge, 20 (25.6%) patients were on antidepressant treatment but only 50% of those had this diagnosis recorded on the discharge summary. Our results showed higher prevalence of depression in this situation compared with the reported prevalence of 20-30% in the acute hospital setting. We recommend that all patients undergoing rehabilitation should be routinely screened for depression as it is common and treatment will improve the overall outcome.

Aged↗
PubMed2000

Oxygen consumption, carbon dioxide production and lactic acid during normothermic cardiopulmonary bypass.

The objective of this study was to measure oxygen consumption, carbon dioxide production and lactic acid levels during normothermic cardiopulmonary bypass. A prospective study was undertaken in a tertiary care community hospital, involving 20 adults undergoing cardiopulmonary bypass with prolonged (>65 min) crossclamping of the aorta. O2 consumption, CO2 production, hemoglobin and lactic acid levels were measured 5, 35 and 65 min after crossclamping of the aorta. O2 consumption was 79.7 +/- 14.5, 78.8 +/- 15.4 and 81.5 +/- 14.1 ml/min/m2 at 5, 35 and 65 min after crossclamping the aorta. CO2 production was 61.8 +/- 42.9, 60.6 +/- 26.3 and 62.2 +/- 35.9 ml/min/m2 at the same times. Lactic acid levels were 1.6 +/- 0.5 mM/dl at all three times and did not correlate with O2 consumption or CO2 production. In conclusion, although oxygen consumption was low, there was no evidence of abnormal lactate or anaerobic metabolism to suggest tissue ischemia.

Acidosis, Lactic↗