PubMed Health⌕ Search

Biomedical subjects

A Stevens

Publications and source records attributed to A Stevens.

At least 19 recordsLinked to original sources

Hypoxia-regulated carbonic anhydrase IX expression is associated with poor survival in patients with invasive breast cancer.

Tumour hypoxia is a microenvironmental factor related to poor response to radiation, chemotherapy, genetic instability, selection for resistance to apoptosis, and increased risk of invasion and metastasis. Hypoxia-regulated carbonic anhydrase IX (CA IX) has been studied in various tumour sites and its expression has been correlated with the clinical outcome. The purpose of this study was to investigate the correlation of CA IX expression with outcome in patients with invasive breast cancer. We conducted a retrospective study examining the effects of carbonic anhydrase IX (CA IX) on survival in patients with breast cancer. To facilitate the screening of multiple tissue blocks from each patient, tissue microarrays were prepared containing between two and five representative samples of tumour per patient. Immunohistochemistry was used to examine expression of CA IX in patients with breast cancer. The study includes a cohort of 144 unselected patients with early invasive breast cancer who underwent surgery, and had CA IX expression and follow-up data available for analysis. At the time of analysis, there were 28 deaths and median follow-up of 48 months with 96% of patients having at least 2 years of follow-up. CA IX was negative for 107 patients (17 deaths) and positive for 37 patients (11 deaths). Kaplan-Meier survival curves show that survival was superior in the CA IX-negative group with a 2-year survival of 97% for negatives and 83% for positives (log-rank test P=0.01). Allowing for potential prognostic variables in a Cox regression analysis, CA IX remained a significant independent predictor of survival (P=0.035). This study showed in both univariate and multivariate analysis that survival is significantly inferior in patients with tumour expressing CA IX. Prospective studies are underway to investigate this correlation in clinical trial setting.

Adult↗

[Negative response bias and the validity of personality profiles in neuropsychiatric assessment].

Although symptom validity tests have become available to German test users during the last few years, there is very little research into measures of negative response bias in personality assessment. The present study investigates the effects of negative response bias as measured by the Word Memory Test (WMT) and the Structured Inventory of Malingered Symptomatology (SIMS) on self-report personality scales. A retrospective analysis was performed on data from 93 patients who had undergone neuropsychiatric assessment in the context of independent medical examination. Complete data sets were available for the WMT, the SIMS, and the Freiburg Personality Inventory-Revised (FPI-R). Significant differences were found for a number of personality scales, depending on WMT and SIMS classification. The FPI-R validity scale (Openness) was linked to neither WMT nor SIMS, whereas the results in the latter two instruments showed a significant overlap of classification results (phi=0.44). A principal axis analysis yielded corresponding results. It is concluded that self-report personality measures may be considerably distorted by negative response bias. FPI-R Openness scale scores do not allow any interpretation in terms of negative response bias. More effort should be directed in German-speaking countries towards the development and validation of appropriate validity scales.

Adult↗

Atypical anxiolytic-like response to naloxone in benzodiazepine-resistant 129S2/SvHsd mice: role of opioid receptor subtypes.

RATIONALE: Mice of many 129 substrains respond to environmental novelty with behavioural suppression and high levels of anxiety-like behaviour. Although resistant to conventional anxiolytics, this behavioural phenotype may involve stress-induced release of endogenous opioids. OBJECTIVES: To assess the effects of opioid receptor blockade on behavioural reactions to novelty stress in a chlordiazepoxide-resistant 129 substrain. MATERIALS AND METHODS: Experiment 1 contrasted the effects of the broad-spectrum opioid receptor antagonist naloxone (1.0-10.0 mg/kg) in C57BL/6JOlaHsd and 129S2/SvHsd mice exposed to the elevated plus-maze. Experiments 2-4 examined the responses of 129S2/SvHsd mice to the mu-selective opioid receptor antagonist beta-funaltrexamine (2.5-10.0 mg/kg), the delta-selective antagonist naltrindole (2.5-10.0 mg/kg) and the kappa-selective antagonist nor-binaltorphimine (2.5-5.0 mg/kg). RESULTS: 129 mice displayed higher levels of anxiety-like behaviour and lower levels of general exploration relative to their C57 counterparts. Although naloxone failed to alter the behaviour of C57 mice, both doses of this antagonist produced behaviourally selective reductions in open-arm avoidance in 129 mice. Surprisingly, none of the more selective opioid receptor antagonists replicated this effect of naloxone: beta-funaltrexamine was devoid of behavioural activity, naltrindole suppressed rearing (all doses) and increased immobility (10 mg/kg), while nor-binaltorphimine (5 mg/kg) nonspecifically increased percent open arm entries. CONCLUSIONS: Recent evidence suggests differential involvement of opioid receptor subtypes in the anxiolytic efficacy of diverse compounds including conventional benzodiazepines. The insensitivity of 129 mice to the anxiolytic action of chlordiazepoxide, coupled with their atypical anxiolytic response to naloxone (but not more selective opioid receptor antagonists), suggests an abnormality in anxiety-related neurocircuitry involving opioid-GABA interactions.

Animals↗

[Insufficient cooperativeness in forensic neuropsychiatric assessment: prevalence estimates of negative response bias].

In the context of independent medical examinations, negative response bias in patients is a problem of primary importance, especially in cases where self-reported symptoms cannot be directly verified by the examiner. Estimates of the prevalence of uncooperativeness in neuropsychological evaluations demonstrated that invalid test profiles are to be expected in a sizable minority of examinees. However, no estimates have ever been published in German-speaking countries. Symptom validity was checked in 235 patients who reported cognitive symptoms after suffering an accident and who underwent forensic neuropsychiatric assessment. Patient classification was based on the results obtained with the Word Memory Test (WMT) or the Medical Symptom Validity Test (MSVT). When applying the recommended cutoffs for these tests, 44.3 percent of the sample was found to be classified as suspect for insufficient effort. In a subsample of 47 patients with claims of posttraumatic stress disorder 51.1 percent were found to score below the cutoffs. These findings underline the importance of modern methods for assessment of symptom validity in forensic contexts. Cooperativeness of compensation claimants cannot be assumed solely on the basis of clinical impression.

Brain Injury, Chronic↗

Transforming growth factor beta regulates cyclooxygenase-2 in glomerular mesangial cells.

This study examines the hypothesis that transforming growth factor beta (TGFbeta) regulates cyclooxygenase-2 (COX-2) and induces prostaglandin E synthase (mPGES-1) in rat mesangial cells. COX-2 expression was determined by Northern blot analysis after treatment with either TGFbeta1 or the selective COX-2 inhibitor, NS398. mPGES-1 expression was determined by real-time polymerase chain reaction. The effect of TGFbeta1 on COX-2 gene transcription was assessed using a luciferase reporter assay, and mRNA stability was also determined. To determine whether TGFbeta1 activates elements of the COX-2 promoter, we performed gel shift analyses to examine activation of activator protein-1 (AP-1) and nuclear factor kappaB (NF-kappaB). Prostaglandin E(2) (PGE(2)) and thromboxane B2 (TxB2) production was assayed by enzyme immunoassay. Finally, the pathophysiological relevance of COX-2 inhibition on the downstream effects of TGFbeta was assessed by examining collagen type I mRNA and net collagen production. COX-2 mRNA and mPGES-1 were induced after treatment with TGFbeta1 for 4 h, and this rise was accompanied by a three-fold increase in PGE(2) production that could be antagonized by selective inhibition of COX-2 with NS398. TGFbeta1 increased transcription by approximately 50% and activated both AP-1 and NF-kappaB. These effects were antagonized by co-treatment with NS398. Treatment with TGFbeta1 also doubled the half-life of COX-2 mRNA. Neither collagen type I mRNA nor net collagen production were altered by co-treatment with NS398. In conclusion, these results indicate that TGFbeta stimulates COX-2 and mPGES-1, with additional effects on transcription and stability of COX-2 mRNA.

Animals↗

Complete genome sequence of Vibrio fischeri: a symbiotic bacterium with pathogenic congeners.

Vibrio fischeri belongs to the Vibrionaceae, a large family of marine gamma-proteobacteria that includes several dozen species known to engage in a diversity of beneficial or pathogenic interactions with animal tissue. Among the small number of pathogenic Vibrio species that cause human diseases are Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus, the only members of the Vibrionaceae that have had their genome sequences reported. Nonpathogenic members of the genus Vibrio, including a number of beneficial symbionts, make up the majority of the Vibrionaceae, but none of these species has been similarly examined. Here we report the genome sequence of V. fischeri ES114, which enters into a mutualistic symbiosis in the light organ of the bobtail squid, Euprymna scolopes. Analysis of this sequence has revealed surprising parallels with V. cholerae and other pathogens.

Aliivibrio fischeri↗

Assessing investment in manual handling risk controls: a scoring system for use in observational studies.

Most UK hospitals now have manual handling policies, but few studies have assessed their impact. To facilitate such research, a system for ranking the investment in manual handling risk controls was devised and applied to 109 acute hospitals in the UK. High scoring hospitals performed well on all aspects of manual handling risk management. Low scoring hospitals had a manual handling policy and recorded accidents and sickness absence, but had limited resource for expert manpower and equipment.

Ergonomics↗

Glucocorticoids suppress macrophage migration inhibitory factor (MIF) expression in a cell-type-specific manner.

MIF is a potent proinflammatory cytokine involved in inflammatory arthritis. Glucocorticoids (GC) have been reported to induce secretion of MIF in rodent cells, and as MIF counteracts the anti-inflammatory effects of GC, this has implications for human inflammatory disease. Transient transfection studies showed that the MIF promoter was repressed by dexamethasone (Dex) (10 nM) in CEM C7A cells, with up to 50% suppression by 100 nM. However, there was no regulation of the promoter by GC in A549 cells. We also found that subnanomolar concentrations of Dex suppressed MIF secretion, measured by ELISA, by 80% in both human T lymphoblasts (CEM C7A) and human lung epithelial cells (A549). Endogenous MIF mRNA was also repressed by GC in CEM C7A cells, measured both by Northern blot and quantitative RT-PCR assays, but there was no such regulation in A549 cells. This suggests that GC affects translation rather than transcription of MIF in A549 cells. These results contradict earlier results with the rat cell line RAW 264.7. Therefore, we analysed MIF secretion from RAW 264.7 cells but found no GC effect on secretion. Understanding how GC regulates MIF in a cell-type-dependent manner may give insights into GC-refractory human inflammatory diseases.

Animals↗

Potential use of routine databases in health technology assessment.

OBJECTIVES: To develop criteria for classifying databases in relation to their potential use in health technology (HT) assessment and to apply them to a list of databases of relevance in the UK. To explore the extent to which prioritized databases could pick up those HTs being assessed by the National Coordinating Centre for Health Technology Assessment (NCCHTA) and the extent to which these databases have been used in HT assessment. To explore the validation of the databases and their cost. DATA SOURCES: Electronic databases. Key literature sources. Experienced users of routine databases. REVIEW METHODS: A 'first principles' examination of the data necessary for each type of HT assessment was carried out, supplemented by literature searches and a historical review. The principal investigators applied the criteria to the databases. Comments of the 'keepers' of the prioritized databases were incorporated. Details of 161 topics funded by the NHS R&D Health Technology Assessment (HTA) programme were reviewed iteratively by the principal investigators. Uses of databases in HTAs were identified by literature searches, which included the title of each prioritized database as a keyword. Annual reports of databases were examined and 'keepers' queried. The validity of each database was assessed using criteria based on a literature search and involvement by the authors in a national academic network. The costs of databases were established from annual reports, enquiries to 'keepers' of databases and 'guesstimates' based on cost per record. For assessing effectiveness, equity and diffusion, routine databases were classified into three broad groups: (1) group I databases, identifying both HTs and health states, (2) group II databases, identifying the HTs, but not a health state, and (3) group III databases, identifying health states, but not an HT. Group I datasets were disaggregated into clinical registries, clinical administrative databases and population-oriented databases. Group III were disaggregated into adverse event reporting, confidential enquiries, disease-only registers and health surveys. RESULTS: Databases in group I can be used not only to assess effectiveness but also to assess diffusion and equity. Databases in group II can only assess diffusion. Group III has restricted scope for assessing HTs, except for analysis of adverse events. For use in costing, databases need to include unit costs or prices. Some databases included unit cost as well as a specific HT. A list of around 270 databases was identified at the level of UK, England and Wales or England (over 1000 including Scotland, Wales and Northern Ireland). Allocation of these to the above groups identified around 60 databases with some potential for HT assessment, roughly half to group I. Eighteen clinical registers were identified as having the greatest potential although the clinical administrative datasets had potential mainly owing to their inclusion of a wide range of technologies. Only two databases were identified that could directly be used in costing. The review of the potential capture of HTs prioritized by the UK's NHS R&D HTA programme showed that only 10% would be captured in these databases, mainly drugs prescribed in primary care. The review of the use of routine databases in any form of HT assessment indicated that clinical registers were mainly used for national comparative audit. Some databases have only been used in annual reports, usually time trend analysis. A few peer-reviewed papers used a clinical register to assess the effectiveness of a technology. Accessibility is suggested as a barrier to using most databases. Clinical administrative databases (group Ib) have mainly been used to build population needs indices and performance indicators. A review of the validity of used databases showed that although internal consistency checks were common, relatively few had any form of external audit. Some comparative audit databases have data scrutinised by participating units. Issues around coverage and coding have, in general, received little attention. NHS funding of databases has been mainly for 'Central Returns' for management purposes, which excludes those databases with the greatest potential for HT assessment. Funding for databases was various, but some are unfunded, relying on goodwill. The estimated total cost of databases in group I plus selected databases from groups II and III has been estimated at pound 50 million or around 0.1% of annual NHS spend. A few databases with limited potential for HT assessment account for the bulk of spending. CONCLUSIONS: Suggestions for policy include clarification of responsibility for the strategic development of databases, improved resourcing, and issues around coding, confidentiality, ownership and access, maintenance of clinical support, optimal use of information technology, filling gaps and remedying deficiencies. Recommendations for researchers include closer policy links between routine data and R&D, and selective investment in the more promising databases. Recommended research topics include optimal capture and coding of the range of HTs, international comparisons of the role, funding and use of routine data in healthcare systems and use of routine database in trials and in modelling. Independent evaluations are recommended for information strategies (such as those around the National Service Frameworks and various collaborations) and for electronic patient and health records.

Biomedical Technology↗

Deep brain stimulation for Parkinson's disease: association between stimulation parameters and cognitive performance.

Chronic subthalamic nucleus stimulation produces inconsistent patterns of cognitive change in Parkinson's disease patients. Individually tailored stimulation parameters may contribute to this variable pattern of change. Systematic variation of amplitude, pulse width, and rate of stimulation has been reported to produce unique changes in motor and limbic response. To evaluate the association between stimulation parameters and cognitive/behavioral response, neuropsychological performance and stimulation parameter data of 8 Parkinson's disease patients were submitted to Pearson r correlation analysis. Results indicate that each stimulation parameter was significantly associated with a subset of measures. The current findings raise the possibility that adverse cognitive/behavioral responses may be treated through parameter modification while maintaining motor symptom efficacy.

Aged↗

Work practices and histopathological changes in the tenosynovium in carpal tunnel syndrome in men.

The aim of this prospective study was to assess whether the fibrous thickening of the carpal tunnel tenosynovium is influenced by working practices. We did this by investigating 50 men (58 hands) with idiopathic carpal tunnel syndrome, who were undergoing carpal tunnel decompression. Occupational history, including vibration tool exposure, and presence of callosities and/or ingrained dirt on hands was recorded at the time of surgery. The flexor tenosynovium was biopsied, and assessed histologically by an observer blinded to occupational history. Occupational group, age, weight and smoking showed no significant association with fibrous tenosynovial thickening. There was also no significant association between fibrous tenosynovial thickening and the presence of hand callosities/in-grained dirt or regular use of vibration tools. Thus no association was found between heavy occupational hand usage and the development of fibrous tenosynovial thickening around tendons within the carpal tunnel.

Adult↗

Randomisation in trials: do potential trial participants understand it and find it acceptable?

OBJECTIVE: To examine lay persons' ability to identify methods of random allocation and their acceptability of using methods of random allocation in a clinical trial context. DESIGN: Leaflets containing hypothetical medical, non-medical, and clinical trial scenarios involving random allocation, using material from guidelines for trial information leaflets. SETTING AND PARTICIPANTS: Adults attending further education colleges (n = 130), covering a wide range of ages, occupations, and levels of education. MAIN MEASURES: Judgements of whether each of five methods of allocation to two groups was random in a medical or non-medical scenario. Judgements of whether these allocation methods were acceptable in a randomised clinical trial scenario, with or without a scientific justification for randomisation. RESULTS: The majority of our group of participants judged correctly that allowing people their preference was not random, and that the following were random: using a computer with no information about the individual (recommended wording for MREC trial leaflets), tossing a coin, drawing a name out of a hat. Judgements were split over allocating people in turn (not a random allocation method but shares features with randomisation). Judgements were no different in medical and non-medical scenarios. Few of the correctly identified random methods were judged to be acceptable in a clinical trial scenario. Inclusion of a scientific justification for randomising significantly increased the acceptability of only one random method: allocation by computer. CONCLUSIONS: Current UK guidelines' recommended description of random allocation by computer seems warranted. However, while potential trial participants may understand what random allocation means, they may find it unacceptable unless offered an acceptable justification for its use.

Adolescent↗

Manual handling risk controls in hospitals (MARCH): a cross-sectional survey of UK hospitals.

Injury and ill health among healthcare staff associated with handling patients is an important area of risk for UK National Health Service (NHS) employers. Since the introduction of a specific legal duty to control this risk in 1992, many Trusts have developed manual handling risk management strategies. Anecdotally, however, practice varies between Trusts and there is no published description of common practice among NHS employers. The latter would be useful as a benchmark for risk managers. Therefore, we undertook a cross-sectional survey of 158 UK trusts (81% of those invited) using a structured interviewer-administered questionnaire to collect information about manual handling risk controls. Most Trusts had basic systems for risk management, including defined management accountability, written policies, provision of handling equipment, training, expert advice about manual handling and access to occupational health services and physiotherapy for injured employees. However, there was wide variation in important aspects, including the extent of expert manpower and criteria for referral to occupational health. Arrangements for monitoring risk controls were generally poor, and the variation in practice was a cause for concern. These data will help NHS employers by providing a benchmark against which to measure and develop risk management systems for manual handling. Future research should aim to develop standards through consensus opinion and ultimately evidence of effectiveness of risk controls.

Accidents, Occupational↗

Analysis of co-factor function in a glucocorticoid-resistant small cell carcinoma cell line.

Human small cell lung carcinoma (SCLC) tumours exhibit neuroendocrine differentiation, secreting hormones such as ACTH and related peptides. While glucocorticoids inhibit ACTH secretion from the pituitary, this does not occur in SCLC tumours and SCLC cell lines. Failure of glucocorticoids to suppress ACTH peptides is accompanied by a global lack of glucocorticoid action in a number of SCLC cell lines. In the human SCLC cell line, COR L103, activation of a human tyrosine aminotransferase (TAT3)-luciferase reporter gene is resistant to glucocorticoids despite similar glucocorticoid receptor (GR) expression to the glucocorticoid-sensitive A549 human lung cancer cell line; moreover, the GR is free of deleterious mutations. Over-expression of a wild-type GR restores glucocorticoid regulation of TAT3-luciferase, and this is enhanced when the activation function (AF)-2 domain is deleted but much reduced when the AF-1 domain is deleted. This suggests aberrant AF-2 activation domain function. We identified defective steroid receptor co-activator 1 (SRC1) recruitment to the GR AF-2 in COR L103 cells, although SRC1 was successfully recruited to the steroid X receptor with rifampicin, suggesting a defect in the GR. Analysis of other GR C-terminal co-factors identified increased expression of nuclear co-repressor (NCoR) in COR L103 cells. To determine the impact of this, NCoR was over-expressed in A549 cells, where it reduced GR transactivation by 55%. In summary, glucocorticoid resistance is associated with altered SRC protein recruitment and increased expression of NCoR in these SCLC cells, suggesting that glucocorticoid sensitivity may be modified by subtle changes in co-factor recruitment.

Adrenocorticotropic Hormone↗

Disaggregation of collective dose--a worked example based on future discharges from the Sellafield nuclear fuel reprocessing site, UK.

Collective dose has long been advocated as an important measure of the detriment associated with practices that involve the use of radioactivity. Application of collective dose in the context of worker protection is relatively straightforward, whereas its application in the context of discharges to the environment can yield radically different conclusions depending upon the population groups and integration times that are considered. The computer program PC-CREAM98 has been used to provide an indicative disaggregation into individual dose bands of the collective dose due to potential future radioactive discharges from the nuclear fuel reprocessing site at Sellafield in the UK. Two alternative discharge scenarios are considered, which represent a 'stop reprocessing early, minimum discharge' scenario and a 'reprocessing beyond current contracts' scenario. For aerial discharges, collective dose at individual effective dose rates exceeding 0.015 microSv y(-1) is only incurred within the UK, and at effective dose rates exceeding 1.5 microSv y(-1) is only incurred within about 20 km of Sellafield. The geographical distribution of collective dose from liquid discharges is harder to assess, but it appears that collective dose incurred outside the UK is at levels of individual effective dose rate below 1.5 microSv y(-1), with the majority being incurred at rates of 0.002 microSv y(-1) or less. In multi-attribute utility analyses, the view taken on the radiological detriment to be attributed to the two discharge scenarios will depend critically on the weight or monetary value ascribed to collective doses incurred within the differing bands of individual dose rate.

England↗

The role of the mother-child interaction as a factor in nursing caries (ECC): a preliminary communication.

AIM: This was to investigate the role of the mother-child interaction as a factor in nursing caries. METHODS: A convenience sample of 34 parents whose children had been diagnosed with nursing caries (Early Childhood Caries, ECC) was gathered. A series of non-structured interviews with parents were conducted. The interviews were transcribed and analysed using Grounded Theory. RESULTS: The overarching category which explained the basic social process associated with nursing caries was 'nursing caries mothering'. The three categories which emerged characterised the basic social process of 'nursing caries mothering' were regressive mothering, culpable mothering and convenience mothering. CONCLUSION: ECC is characterised by regressive mothering, culpable mothering and convenience mothering. In each of these typologies the bottle once used to nourish the baby has become imbued with other behaviours and meanings. An awareness of these meanings of what the breast/bottle have come to represent should be incorporated and form a central strand of a joined-up health promotion approach.

Adult↗