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Biomedical subjects

S A Simpson

Publications and source records attributed to S A Simpson.

At least 19 recordsLinked to original sources
PubMed2005

A community based investigation of the association between cannabis use, injuries and accidents.

There are well documented acute and chronic effects of cannabis use. However, less is known about any effects on safety within the context of work and everyday life. The aim of the study was to examine any association between cannabis use and injuries and accidents. A postal questionnaire survey was conducted among people selected at random from the electoral registers of Cardiff and Merthyr Tydfil. Cannabis use was associated with both minor injuries and accidents, particularly among those with high levels of other associated risk factors. Cannabis use was associated with a significant detrimental impact on safety. It is possible that this is linked to an amplification of other risk factors associated with accidents and injuries. This has potentially wide reaching implications particularly in the context of other work and lifestyle characteristics.

Accidents↗
PubMed2005

Cannabis use, cognitive performance and mood in a sample of workers.

There are well documented acute and chronic effects of cannabis use on mental functioning. However, less is known about any effects on cognition within the context of work and everyday life. The aim of the study was to examine any association between cannabis use and cognitive performance, mood and human error at work. Cannabis users and controls completed a battery of laboratory based computer tasks measuring mood and cognitive function pre- and post-work at the start and end of a working week. They also completed daily diaries reporting their work performance. Cannabis use was associated with impairment in both cognitive function and mood, though cannabis users reported no more workplace errors than controls. Cannabis use was associated with lower alertness and slower response organization. In addition, users experienced working memory problems at the start, and psychomotor slowing and poorer episodic recall at the end of the working week. This pattern of results suggests two possible effects. First a 'hangover'-type effect which may increase with frequency of use. Second a subtle effect on cognitive function, perhaps more apparent under cognitive load and/or fatigue, which may increase with more prolonged use. The results also highlight the importance of the timing of testing within the context and routine of everyday life.

Adolescent↗
PubMed2005

Induction of heat shock protein 70 in rat olfactory epithelium by toxic chemicals: in vitro and in vivo studies.

We have previously developed a rat nasal explant system for investigating upper respiratory tract toxicity, and the aims of this study were to determine whether heat shock protein (HSP) 70 is induced in this model following exposure to carbon tetrachloride (CCl4), dimethyl adipate (DMA), methyl iodide (CH3I) or paracetamol, and whether HSP70 can also be induced in the nasal cavity in vivo. Intracellular ATP was significantly depleted in ethmoturbinates incubated for 4 h with the toxins (0-100 mM; EC50 concentrations: CCl4 32 mM, DMA 3 mM, CH3I 1.5 mM, paracetamol 70 mM), but there was little induction of HSP70. Turbinates were then incubated for 1 h with CCl4 (5 mM), DMA (1.5 mM), CH3I (0.57 mM) or paracetamol (30 mM) and allowed to recover for up to 24 h. Treatment with CCl4, DMA or paracetamol resulted in 250-300% induction of HSP70. Male rats were administered a single oral dose of CCl4 (1600 mg/kg) and killed 16 h later. Degenerative lesions (epithelial undulation and hydropic vacuolation) were evident in the olfactory epithelium, and immunohistochemical analysis of HSP70 revealed increased staining in, or proximate to, areas of damage. Thus, HSP70 can be induced in the olfactory epithelium both in vitro and in vivo.

Acetaminophen↗
PubMed2005

Psychotropic medication use and accidents, injuries and cognitive failures.

BACKGROUND: Psychotropic medication has the potential to impair psychomotor and cognitive function, and several medications have well documented links to increased accident and injury susceptibility. Those developed more recently have many fewer side effects. However, there is little work examining any association between psychotropic medication use and safety within the context of other demographic, health and lifestyle factors. AIMS: To examine and compare any associations between psychotropic medication use (including benzodiazepines, tricyclics and SSRIs) and accidents, injuries and cognitive failures in a community sample. METHODS: A postal questionnaire survey was conducted among people selected at random from the electoral registers of Cardiff and Merthyr Tydfil. RESULTS: Psychotropic medication use was associated with accidents, injuries and cognitive failures, particularly among those who already had higher levels of other risk factors and/or continuing mental health problems. CONCLUSIONS: The well established associations between accidents and injuries and older psychotropic medications were replicated. SSRIs, however, were relatively safer. The study also highlighted the need to consider any effect of psychotropic medication within the context of both mental health status and other factors.

Accidents↗
PubMed2004

Frontotemporal dementia with Pick-type histology associated with Q336R mutation in the tau gene.

In this report, we describe the clinical and neuropathological features of a case of familial frontotemporal dementia (FTD), with onset at 58 years of age and disease duration of 10 years, associated with a novel mutation, Q336R, in the tau gene (tau). In vitro studies concerning the properties of tau proteins bearing this mutation, with respect to microtubule assembly and tau filament aggregation, are reported. Clinically, the patient showed alterations in memory, language and executive functions and marked behavioural change consistent with FTD, although the extent of memory impairment was more than is characteristic of FTD. At autopsy, there was degeneration of the frontal and temporal lobes associated with the presence of hyperphosphorylated tau proteins in swollen (Pick) cells and intraneuronal inclusions (Pick bodies). By immunohistochemistry, the Pick bodies contained both 3-repeat and 4-repeat tau proteins although, because no fresh tissues were available for analysis, the exact isoform composition of the aggregated tau proteins could not be determined. Neurons within frontal cortex contained neurofibrillary tangle-like structures, comprising both straight and twisted tubules, or Pick bodies in which the filaments were short and randomly orientated. In vitro, and in common with other tau missense mutations, Q336R caused an increase in tau fibrillogenesis. However, in contrast to most other tau missense mutations, Q336R increased, not decreased, the ability of mutant tau to promote microtubule assembly. Nonetheless, this latter functional change may likewise be detrimental to neuronal function by inducing a compensatory phosphorylation that may yield increased intracellular hyperphosphorylated tau species that are also liable to fibrillize. We believe the mutation is indeed pathogenic and disease causing and not simply a coincidental rare and benign polymorphism. Since this mutation is segregating with the FTD clinical and neuropathological phenotype, it has not been found in unaffected individuals and it has novel functional properties in vitro which are likely to be detrimental to neuronal function in vivo.

Aged↗
PubMed2003

Differential deficits in expression recognition in gene-carriers and patients with Huntington's disease.

Previous studies in symptomatic patients and asymptomatic gene-carriers of Huntington's disease (HD) reported a differential deficit in the recognition of facial expressions of disgust. This impairment may point to involvement of the basal ganglia in the recognition of disgust. In this study, we compared the performance of 20 patients with symptoms of HD, 20 gene-carriers of HD and 20 healthy controls on two tests of facial expressions in order to further investigate the role of the basal ganglia in disgust recognition. Recognition of fear, rather than disgust, was most severely impaired in the patients, who were also impaired at recognising expressions of anger, disgust and sadness. Direct testing for a differential deficit in disgust at the group level (and at the level of individual HD cases) revealed that the patients were in fact significantly more impaired on the other negative expressions than on disgust. The gene-carriers were not impaired on any expression, although there was a trend for the gene-carriers to be poorer at recognising fearful faces than the controls. We argue that the expression recognition performance of the patients and gene-carriers simply reflects differences in task difficulty, rather than dysfunction of any mechanisms dedicated to specific emotions. In contrast to previous studies in patients or gene-carriers of HD, our findings provide no evidence for a role of the basal ganglia in the recognition of disgust and cast doubt on whether results from HD patients and gene-carriers can be used in support of a double dissociation between recognition of disgust and fear.

Adult↗
PubMed2003

To tell or not to tell: barriers and facilitators in family communication about genetic risk.

Communication about genetic risk in families is an important issue for genetic counsellors. The objective of this study was to explore the barriers and facilitators in family communication about genetic risk. Semi-structured interviews were undertaken with patients in the Northeast of Scotland who had attended genetic counselling for risk of hereditary breast and ovarian cancer and Huntington's disease, and with some spouses/partners. The interviews confirmed that the issue of disclosure was a problem for some, and that there were generic communication issues common to both groups. Telling family members about genetic risk was generally seen as a family responsibility and family structures, dynamics and 'rules' influenced disclosure decisions. A sense of responsibility towards younger generations was also important. The level of certainty felt by a person in relation to his or her own risk estimate also influenced what he or she could tell other family members. Communication within a family about genetic risk is a complex issue and is influenced by both pre-existing familial and cultural factors and individuals' responses to risk information. If genetic counsellors understood how these factors operate in individual families they might be able to identify effective strategies to promote considered decisions and prevent unnecessary emotional distress.

Adult↗
PubMed2003

The Bristol Stress and Health Study: accidents, minor injuries and cognitive failures at work.

BACKGROUND: Accidents and injuries at work account for several million working days lost each year. Cognitive failures (problems of memory, attention or action) can lead to accidents and injuries in certain contexts. AIM: This work describes the prevalence and associations of workplace accidents, minor injuries and cognitive failures reported by respondents to a follow-up postal questionnaire as part of the community-based Bristol Stress and Health Study. METHODS: Postal questionnaires were sent to 4673 people who participated in the first phase of the study (in which questionnaires were sent to individuals selected at random from the electoral roll). RESULTS: Four per cent of workers reported an accident at work, 8% reported quite or very frequent minor injuries and 13% reported quite or very frequent cognitive failures. Accidents at work were associated with being male, smoking and higher negative job characteristics. Respondents reported workplace accidents at a level similar to the overall UK rate. Accidents and minor injuries, and minor injuries and cognitive failures, shared common associations and all three outcomes were associated with each other. CONCLUSION: Information about cognitive failures is important in the study of accidents and injuries at work. In addition, negative job characteristics represent part of the context in which human error is translated into injury.

Accidents, Occupational↗
PubMed2001

Breast cancer in two sisters with Friedreich's ataxia.

Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder causing progressive ataxia and dysarthria. We report two sisters who had breast cancer aged 39 years and 42 years and who both developed a late onset form of FRDA with onset of neurological symptoms in their thirties. We discuss whether there may be an association between the late onset form of FRDA and malignancy.

Adult↗
PubMed2001

Additional glomangioma families link to chromosome 1p: no evidence for genetic heterogeneity.

Venous malformations are a common abnormality of the vasculature that may occur sporadically or, more rarely, as an autosomal dominant trait. One familial form of venous malformations has previously been linked to chromosome 9p. Mutations in the gene encoding Tie2, an endothelial specific receptor tyrosine kinase, have been identified in four different families. Glomangiomas are a subtype of venous malformations with glomus cell involvement. These cutaneous lesions can be inherited as an autosomal dominant disease with reduced penetrance and variable expressivity. We present evidence of linkage to chromosome 1p21-1p22 using four new glomangioma families, with a combined maximum two-point lod score of 7.32 at marker D1S2804. Markers D1S2129 and D1S2881 define the 24-cM linkage interval determined by recombination within affected individuals. A recent report also showed linkage of the glomangioma locus to chromosome 1p. A total of 9 families now map to this region, suggesting a decreased likelihood of locus heterogenity in familial glomangiomas. Investigation of candidate genes within the interval should provide new insights into lesion formation in inherited venous malformations.

Adolescent↗
PubMed2000

A rat nasal epithelial model for predicting upper respiratory tract toxicity: in vivo-in vitro correlations.

An in vitro model of the rat nasal cavity has been used to compare the responses of nasal tissues in vitro, using loss of intracellular ATP and potassium as indices of toxicity, with the pathological changes occurring following in vivo exposure to four test compounds. Turbinates were incubated in vitro with the test compounds for 4 h, for 24 h or for 4 h followed by 20 h in fresh medium. Titanium dioxide caused little or no loss of ATP in either olfactory epithelium (OE) or respiratory epithelium (RE). Sodium carbonate decreased olfactory, but not respiratory ATP, while acetic acid and 3-methylindole markedly decreased ATP in both tissues. Intracellular potassium concentrations were generally affected to a lesser degree. In vivo, no morphological changes were observed in the nasal cavity following inhalation exposure to either titanium dioxide or sodium carbonate. Inhalation of acetic acid resulted in a very focal lesion in the RE of the dorsal meatus of level 1, while administration of 3-methylindole by intraperitoneal injection caused severe degeneration of OE. In further experiments olfactory turbinates were exposed to a range of concentrations (0-100 mM) of sodium carbonate, acetic acid and 3-methylindole for 4 h and ATP concentrations determined. Concentration-dependent decreases in ATP were observed for sodium carbonate and 3-methylindole, with EC(50) values estimated as 2.57 and 0.91 mM, respectively. Acetic acid only decreased ATP significantly at the 100-mM concentration. In summary, this in vitro model has predicted the nasal toxicity of several compounds, including both direct-acting agents (sodium carbonate, acetic acid) and one requiring metabolic activation (3-methylindole). However, the lack of airflow-dependent dosimetry, results in some lack of discrimination between the different regions of the nasal cavity and may make this model overly sensitive.

Acetic Acid↗
PubMed2000

Managing a sound industrial radiography radiation safety program.

This article was developed to provide new radiation safety officers with the basic information needed for ensuring safety, security, and control of industrial radiography sources and to discuss licensing requirements and other information pertaining to the management of radiation safety programs associated with these sources.

Humans↗
PubMed1999

Bestrophin gene mutations in patients with Best vitelliform macular dystrophy.

Best vitelliform macular dystrophy (VMD2) is an autosomal dominant dystrophy with a juvenile age of onset. Mutations in the Bestrophin gene were shown in patients affected with VMD2. In a mutation study, we made three new and interesting observations. First, we identified possible mutation hotspots within the gene, suggesting that particular regions of the protein have greater functional significance than others. Second, we described a 2-bp deletion in a part of the gene where mutations have not previously been reported; this mutation causes a frameshift and subsequent premature termination of the protein. Finally, we have evidence that some mutations are associated with variable expression of the disease, suggesting the involvement of other factors or genes in the disease phenotype.

Amino Acid Substitution↗
PubMed1999

Allelic and locus heterogeneity in inherited venous malformations.

Venous malformations are low-flow vascular lesions consisting of disorganized thin-walled vascular channels. These can occur sporadically but also as an autosomal dominant condition termed venous malformations, cutaneous and mucosal (VMCM; OMIM 600195). In two large unrelated kindreds mapping to chromosome 9, the identical R849W missense mutation was identified in the first kinase domain of Tie2, an endothelial cell-specific receptor tyrosine kinase. We report here the identification of four new kindreds with inherited venous malformations. Unlike the initial two families described, these four families demonstrate allelic and locus heterogeneity. In one of these families, the R849W mutation co-segregates with the disease phenotype. Three other families with venous malformations lack this mutation. One of these families is linked to markers near TIE2 on chromosome 9. In this family, we identified a novel mutation within the first kinase domain of Tie2 resulting in a Y897S change. Results from COS-1 cell transfections using expression constructs containing either the R849W or the Y897S mutation suggest that the receptors containing either mutation show ligand-independent hyperphosphorylation. These results suggest a gain-of-function mechanism for development of venous malformations in these families. Of the two remaining families, one excludes linkage to the TIE2 locus, establishing the existence of at least one additional locus for dominantly inherited venous malformations.

Amino Acid Sequence↗
PubMed1997

A sequence-ready high-resolution physical map of the best macular dystrophy gene region in 11q12-q13.

Best disease, an autosomal dominant inherited macular degenerative disorder, was previously localized between D11S1765 and UGB (uteroglobin) in 11q13 by genetic linkage analysis. Since this region was found to be refractory to cloning in YAC (yeast artificial chromosome)-based vectors, a P1 artificial chromosome (PAC) contig was assembled. Gridded PAC libraries representing a 16-fold genome equivalent were screened by hybridization using PCR products representing STSs derived from YAC end sequences, markers binned to 11q13, and PAC-derived insert ends. A highly marker dense approximately 1.7-Mb PAC contig that encompassed the disease gene region was constructed, allowing us to order accurately the markers throughout the region and to provide the most precise estimate of its physical size. Using this contig, thus far we have mapped seven anonymous ESTs and five known genes into this region. This high-resolution physical map will facilitate the isolation of polymorphic markers for refinement of the disease gene region, as well as the identification of candidate genes by exon trapping, cDNA selection, and gene prediction from PAC-derived genomic sequence.

Chromosome Mapping↗
PubMed1996

Low dose rate teletherapy: updated tumour response.

This report presents an update of tumour response experience in patients with locally advanced head and neck cancer treated on the low dose rate teletherapy project at the Mater Misericordiae Hospital, Newcastle. Long-term progression-free survival figures are disappointing in all dose rate/total dose groupings and offer little encouragement that an improvement in therapeutic ratio can be achieved for head and neck cancer patients using teletherapy apparatus adjusted to treat at low and intermediate dose rates.

Cesium Radioisotopes↗