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Biomedical subjects

Andrew P Smith

Publications and source records attributed to Andrew P Smith.

At least 19 recordsLinked to original sources

Patterns of fatigue among seafarers during a tour of duty.

BACKGROUND: Work-related fatigue is associated with sickness absence and mental and physical health problems, and may increase the risk of accidents and injuries at work. Relatively little is known about fatigue among seafarers, particularly during a tour of duty. The aim of this study was to describe the pattern of day to day fatigue among seafarers during a tour at sea. METHODS: Participants from the offshore support, short sea and coastal, and deep sea sectors of the UK shipping industry completed daily diaries. Information about sleep and fatigue was collected each day on waking and retiring. RESULTS: Fatigue on waking was a more sensitive measure of cumulative occupational fatigue than fatigue on retiring. Fatigue on waking increased between the start and end of tour. This increase took place in particular during the first week at sea, and was most apparent among those on shorter tours of duty. CONCLUSIONS: Day to day changes in fatigue are measurable, and may vary among particular sub-groups of seafarers. Used among larger groups, such a diary method could help identify times and activities associated with the greatest risk.

Absenteeism↗

An investigation of the long-term benefits of antidepressant medication in the recovery of patients with chronic fatigue syndrome.

Two hundred and seventy-five patients fulfilling the Centre for Disease Control (CDC) criteria for Chronic Fatigue Syndrome (CFS) completed measures assessing illness history, global ratings of well being, sleep, activity and psychopathology at baseline, 6 months, 18 months and 3 year follow-up. Forty-nine of these patients had been prescribed antidepressant medication, namely Tricyclic drugs or Selective Serotonin Re-uptake Inhibitors (SSRI). Data from the current study suggests that patients in the antidepressant medication group recover at a faster rate over time when compared to the untreated patient sample. In addition, the positive effects of antidepressant therapy are maintained at the 3-year follow-up point. It appears from these data that the SSRI in particular are responsible for improvements in the condition. Most importantly, these improvements include a reduction in the levels of fatigue recorded by patients. These findings have not been demonstrated in previous studies of the effect of antidepressant therapy for patients with this illness and this may reflect the short time periods studied in the earlier research.

Adult↗

Primary healthcare provision and Chronic Fatigue Syndrome: a survey of patients' and General Practitioners' beliefs.

BACKGROUND: The current study was conducted as part of a research project into the evaluation and assessment of healthcare provision and education in Chronic Fatigue Syndrome (CFS). One aim of the study was the development of informative and educational literature for both General Practitioners (GP) and sufferers. Issues such as diagnosis, management and treatment of the syndrome should be included in information booklets written by healthcare professionals. It was important to begin the process by assessing the level of specialist knowledge that existed in typical GP surgeries. This data would then be compared to data from CFS patients. METHOD: 197 survey booklets were sent to CFS sufferers from an existing research panel. The patients approached for the purpose of the study had been recruited onto the panel following diagnosis of their illness at a specialised CFS outpatient clinic in South Wales. A further 120 booklets were sent to GP surgeries in the Gwent Health Authority region in Wales. RESULTS: Results from the study indicate that the level of specialist knowledge of CFS in primary care remains low. Only half the GP respondents believed that the condition actually exists. CONCLUSION: Steps are recommended to increase the knowledge base by compiling helpful and informative material for GPs and patient groups.

Attitude of Health Personnel↗

Caffeine at work.

RATIONALE: There is a large literature on the effects of caffeine on performance. Most of the studies have been conducted in the laboratory and further information is required on the effects of caffeine consumption on performance and safety at work. OBJECTIVES: The present studies aimed to determine whether the level of caffeine consumption influenced changes in alertness and performance over the working day. Secondary analyses of a large epidemiological database were also conducted to examine associations between caffeine consumption and cognitive failures and accidents at work. METHODS: In the first study 110 volunteers, all of whom were regular caffeine consumers, rated their alertness and carried out a simple reaction time task before and after work on a Monday and Friday. Caffeine consumption during the day was recorded and volunteers were sub-divided into low and high consumers on the basis of a median split (220 mg/day). The second study involved secondary analyses of a database formed by combining the Bristol Stress and Health at Work and Cardiff Health and Safety at Work studies. In the first analyses associations between caffeine consumption and frequency of cognitive failures were examined in a sample of 1253 white-collar workers. The second set of analyses examined associations between caffeine consumption and accidents at work in a sample of 1555 workers who were especially at risk of having an accident. RESULTS: The results from the first study showed that those who consumed higher levels of caffeine reported significantly greater increases in alertness over the working day and a significantly smaller slowing of reaction time. The results from the second study demonstrated significant associations between caffeine consumption and fewer cognitive failures and accidents at work. After controlling for possible confounding factors it was found that higher caffeine consumption was associated with about half the risk of frequent/very frequent cognitive failures and a similar reduction in risk for accidents at work. CONCLUSIONS: Overall, the results from the three analyses show that caffeine consumption may have benefits for performance and safety at work.

Accidents↗

SSRIs and cognitive performance in a working sample.

BACKGROUND: Studies of the impact of antidepressant use on cognitive performance have frequently been carried out among the elderly or on healthy volunteers. Comparatively little research has considered their impact on a relatively young, working population, particularly within the context of everyday life. AIMS: To examine any association between SSRI use and cognitive performance, mood and human error at work. METHODS: SSRI 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. RESULTS: SSRI use was associated with memory impairment: specifically poorer episodic, though not working or semantic memory. Effects of SSRI use on recognition memory seemed to vary according to the underlying psychopathology, while effects on delayed recall were most pronounced among those whose symptoms had not (yet) resolved. There were no detrimental effects on psychomotor speed, attention, mood or perceived human error at work. CONCLUSIONS: The findings lend support to the SSRIs comparative safety, even among workers, particularly as the symptoms of the underlying psychopathology are successfully addressed. Possible memory impairments may, however, be found in those taking SSRIs.

Adult↗

Altered gene expression in normal colonic mucosa of individuals with polyps of the colon.

PURPOSE: Expression levels of many genes are altered in colon cancer, relative to normal colonic mucosa. We recently reported that such differences also exist between grossly normal colonic mucosa of individuals with and without colon cancer, and between individuals with and without a family history of colon cancer. Here we report a study of individuals with no cancer but with polyps in the transverse, ascending/descending, or rectosigmoid colon. METHODS: Biopsies of grossly normal-appearing colonic mucosa from the rectosigmoid colon were taken from individuals with polyps, with or without personal/family history of colon cancer, and gene expression profiles compared with those from biopsies of control patients, with no polyps or known personal/family history. A global expression analysis was conducted of the same 15 genes used in our previous studies. RESULTS: We found significant differences in gene expression in normal-appearing rectosigmoid colonic mucosa between individuals with polyps and controls, regardless of whether personal or family history of cancer was present. CONCLUSIONS: Alterations in gene expression patterns in morphologically normal-appearing colonic mucosa are associated with the presence of adenomatous polyps. Prospective studies will be required to determine whether these alterations in gene expression can be used to predict risk of developing colon cancer.

Adult↗

The concept of well-being: relevance to nutrition research.

The aim of this paper is to discuss issues that fall within the general concept of well-being, with special emphasis on approaches that have been used in studies of nutrition and behaviour. Following this, two specific studies are described in detail, the first examining high-fibre breakfast cereals and the second investigating effects of inulin. Studies of nutrition and well-being can be categorised in a number of ways. One method involves examining acute effects of nutrition on mood and cognitive functioning. Another method has been to examine cross-sectional associations between dietary habits and questionnaire measures of reported health. Examples are given showing that regular consumption of a high-fibre diet is associated with better-reported physical and mental health. The problem with such correlational studies is that it is impossible to infer causality. Intervention studies are necessary to achieve this and some examples of this approach are given. In the first study reported here, we examined whether consumption of high-fibre breakfast cereal led to an increase in energy. Such an effect was observed and plausible biological mechanisms underlying such results are described. A similar methodology has recently been used to examine the effects of inulin. In this case the results showed no negative side-effects of taking inulin but there were no beneficial effects of inulin on measures of well-being (both subjective reports and objective measures). Possible reasons for these effects are discussed.

Dietary Fiber↗

Minor injuries, cognitive failures and accidents at work: incidence and associated features.

BACKGROUND: There is a dearth of information examining minor injuries and cognitive failures in the workplace. AIMS: This study aims to describe the incidence of, and characteristics associated with, minor injuries, cognitive failures and accidents in the workplace. METHODS: The study was a community based postal questionnaire survey of people selected at random from the Electoral Registers of Cardiff and Merthyr Tydfil; 7980 questionnaires were returned. RESULTS: Frequent/very frequent minor injuries were reported by 9.8% of the workers and frequent/very frequent cognitive failures (e.g. problems of memory, attention or action) by 10.5%. Work accidents requiring treatment were reported by 5.6% of the workers. Minor injuries, cognitive failures and accidents were associated with a number of demographic and health factors. In addition, minor injuries, cognitive failures and accidents were found to be related to each other. CONCLUSIONS: A large number of workers experience accidents and minor injuries at work. Minor injuries are not recorded by official sources but could have implications in productivity and worker health. Factors identified in this study, as associated with injuries or accidents, could be addressed by specific workplace policies or by raising individual awareness of the risks.

Accidents, Occupational↗

Effect of neuroprotective drugs on gene expression in G93A/SOD1 mice.

Gene expression analysis is a powerful tool that has been used to define the pathological processes underlying many diseases. Several laboratories, including our own, have used this approach to identify molecular abnormalities in the G93A/SOD1 mouse, an animal model of amyotrophic lateral sclerosis (ALS). Here, we report the results of analysis of an expanded panel of genes throughout the entire lifetime in the spinal cord of these animals. In addition to upregulation of microglia/neuroinflammatory genes identified previously, we observed upregulation of metallothionein-I and -II (MT-I, MT-II). MT-I and MT-II play an important role in disposition of zinc ion, and other studies have also indicated their levels are altered in development of motor neuron disease in these animals. We also analyzed the effect on these expression profiles of several candidate drugs that have been shown to have neuroprotective effects in vivo or in vitro. That is, we asked whether administration to the G93A/SOD1 mice of any of these drugs could reverse the alterations in gene expression patterns that occur as the animals develop. The mice were given daily doses of these drugs when they were 9-11 weeks old, at a stage early in development of motor neuron disease, continuing for 5 weeks, at which time they were sacrificed. Treatment of the mice with l-carnosine, a dipeptide that scavenges free radicals and chelates zinc, did not affect expression of any of the genes altered in these animals. However, it did upregulate 3 genes unaffected by the presence of the G93A/SOD1 mutation: glial fibrillary acidic protein (GFAP), stroma-derived factor-1 (SDF-1), and excitatory amino acid transporter-2 (EAAT2). In contrast, metallothionein-III (MT-III) was downregulated. Treatment of the animals with baicalein, an herbal extract with anti-inflammatory and numerous other effects, downregulated the microglia markers CD68, CD80, and CD86, all of which were upregulated in untreated mutant animals. Baicalein treatment also downregulated tumor necrosis factor receptor (TNFRp55) and upregulated noninducible nitric oxide synthase (nNOS) and glutamine synthase (GS). These 3 genes were unaffected by the presence of the G93A mutation. We discuss the implication of these results for testing the effects of these and other candidate drugs in mutant SOD1 mice.

Amyotrophic Lateral Sclerosis↗

Tolerance develops in spinal cord, but not in brain with chronic [Dmt1]DALDA treatment.

Previously, we reported that H-2',6'-dimethyltyrosine [Dmt(1)]-d-Arg-Phe-Lys-NH(2) (DALDA), an analogue of the naturally occurring opioid peptide dermorphin, is a highly potent and selective mu receptor agonist with low cross-tolerance to morphine. In the present study, we investigated the effect of treating mice chronically with [Dmt(1)]DALDA. The AD(50) of [Dmt(1)]DALDA (s.c.) increased eight-fold in animals given this drug chronically; in contrast, the AD(50) increased two-fold in mice chronically treated with morphine. The AD(50) of morphine (s.c.) in these [Dmt(1)]DALDA-treated animals was increased more than 120 times, while that of the more selective mu agonist [d-Ala(2)-MePhe(4)-Gly-ol(5)]enkephalin (DAMGO) given intrathecally was increased more than 240 times. However, the AD(50) of DAMGO given intracerebroventricularly was essentially the same in animals treated chronically with [Dmt(1)]DALDA as in naive animals. The dose of naloxone required to precipitate withdrawal in [Dmt(1)]DALDA-treated animals was 20 times lower than that in morphine-tolerant animals. Using real-time quantitative PCR, we found that expression of the mu opioid receptor, delta opioid receptor, preproenkephalin and preprodynorphin genes was upregulated in the brain by [Dmt(1)]DALDA treatment. No significant changes in expression of opioid receptor or opioid peptide genes were detected in the spinal cord of [Dmt(1)]DALDA-treated mice, nor in the brain or spinal cord of morphine-treated mice. We conclude that a high degree of tolerance to [Dmt(1)]DALDA develops in the spinal cord but not brain, and cannot be accounted for by changes in expression of opioid receptors or opioid peptides in these tissues.

Animals↗

Alteration of gene expression in normal-appearing colon mucosa of APC(min) mice and human cancer patients.

The expression of many genes is altered in colon cancer, but the roles of these genes in carcinogenesis are unclear. Using real-time quantitative PCR, we demonstrated that several genes previously implicated in human colon cancer undergo altered expression in the APC(min) mouse adenomatous polyp, a precursor of cancer, as well as in normal-appearing surrounding mucosa. The five genes that were most highly up-regulated in mouse polyp were also significantly up-regulated in polyp-free colon mucosa. Similar changes occurred in morphologically normal mucosa of surgical sections taken from human cancer patients, frequently extending to the margins. Thus, morphologically normal colon mucosa in APC(min) mice and in human cancer patients is not metabolically normal. Altered gene expression in this tissue does not appear to result from a field effect because there was no correlation between extent of altered regulation and distance from polyp or tumor. Our data suggest that alterations of expression levels of these genes may be an early event in carcinogenesis and a marker of risk for the development of colon cancer.

Adenomatous Polyposis Coli↗

Recreational drug use: patterns from a South Wales self-report survey.

This study aimed to examine patterns of illicit recreational drug use, alcohol consumption, and smoking in a community-based population sample. A postal questionnaire survey was conducted of people who were selected at random from the Electoral registers of Cardiff and Merthyr Tydfil. Twelve percent of respondents reported illicit recreational drug use in the last year, and 7% in the last month. Among respondents aged under 25 years, 34% (39% of males and 31% of females) had used illicit drugs in the last year, and 19% (23% of males and 17% of females) in the last month. Twenty-one percent of respondents smoked (20% of males and 22% of females). Twenty-seven percent of respondents reported drinking more alcohol than currently recommended sensible limits (36% of males and 21% of females). Among respondents aged under 25 years, 53% of men and 38% of women drank over these limits. Illicit drug use was associated with heavy alcohol consumption and, in particular, with smoking. Smoking and heavy alcohol consumption combined was most strongly associated with illicit drug use. Rates of illicit recreational drug use were higher than have previously been reported for Wales. Illicit drug use and smoking varied with age, sex, work status and geographical location, whereas heavy alcohol consumption varied with age, sex and work status, but not geographical location. Both smoking and alcohol consumption were associated with illicit drug use, with smokers who were also heavy drinkers being those most likely to report illicit drug use.

Adult↗

Factors associated with recreational drug use.

This study aimed to examine demographic, lifestyle, mental health and personality factors associated with illicit recreational drug use, heavy alcohol consumption and smoking in a community-based population sample. A postal questionnaire survey was conducted of people who were selected at random from the Electoral registers of Cardiff and Merthyr Tydfil. Illicit drug use was associated with risk taking, neuroticism, being male, having a higher education qualification, not being married, being unemployed, being aged under 25 years, smoking, heavy alcohol consumption and living in Cardiff. Smoking was associated with anxiety, depression, being female, lower income and educational qualifications, looking after the family or home, being aged over 25 years, illicit drug use and heavy alcohol use. Heavy alcohol consumption was associated with not being depressed, experiencing sleeping problems, risk taking, being male, higher income, no higher educational qualification, not being married, being a student, being aged under 25 years, smoking and illicit drug use. Illicit drug use, smoking and heavy alcohol use were strongly associated with each other. Illicit drug use was associated with alcohol use and, to an even greater extent, with smoking. Illicit drug and alcohol use were associated with similar characteristics, but smoking was associated with a rather different demographic combination.

Adult↗

Opioid receptor interactions: local and nonlocal, symmetric and asymmetric, physical and functional.

The pharmacological effects of opioid drugs and endogenous opioid peptides are mediated by several kinds of receptors, the major ones being mu, delta and kappa. Though classically it has been thought that a particular effect mediated by a drug or other ligand results from its interaction with a single type of receptor, accumulating evidence demonstrates that interactions between receptors play a major role in opioid actions. These interactions may be either local, involving receptors within the same tissue, or nonlocal, between receptors located in different tissues. Nonlocal interactions always involve intercellular mechanisms, whereas local interactions may involve either intercellular or intracellular interactions, the latter including physical association of receptors. Both local and nonlocal interactions, moreover, may be either symmetric, with ligand interaction at one receptor affecting interaction at the other, or asymmetric; and either potentiating or inhibitory. In this article we discuss major examples of these kinds of interactions, and their role in the acute and chronic effects of opioids. Knowledge of these interactions may have important implications for the design of opioids with more specific actions, and for eliminating the addictive liability of these drugs.

Animals↗

Id proteins in epithelial cells.

Id helix-loop-helix (Id HLH) proteins are negative regulators of basic HLH transcription factors. They are expressed during embryonic development and are important for the regulation of cell phenotypes in adults. They participate in the molecular networks controlling cell growth, differentiation, and carcinogenesis, through specific basic HLH and non-basic HLH protein interactions. Recent in vitro and in vivo data implicate Id HLH as important orchestrating proteins of homeostasis in glandular and protective epithelia. In particular, Id proteins have been reported to be involved in cell behavior in epidermis, respiratory system, digestive tract, pancreas, liver, thyroid, urinary system, prostate, testis, endometrium, cervix, ovary, and mammary gland. The purpose of this review is to summarize the evidence implicating Id proteins in the regulation of mammalian epithelial cell phenotypes.

Animals↗

Preliminary investigation of the association between psychotropic medication use and accidents, minor injuries and cognitive failures.

RATIONALE: Psychotropic medication may impair psychomotor and cognitive function, and so increase accident susceptibility. However, few studies examine any association in the framework of other demographic, health and occupational factors. OBJECTIVES: To examine the relationship between sleeping tablets and antidepressants, and accidents, minor injuries and cognitive failures. METHODS: Postal questionnaire study of 3111 individuals who participated in an earlier phase of the Bristol Stress and Health Study. RESULTS: Sleeping tablet use was associated with accidents, minor injuries and cognitive failures both at work and outside work. Antidepressant use was associated with accidents and cognitive failures both at work and outside work. Adjusting for health, demographic and occupational factors explained many of these associations, but sleeping tablet use was independently associated with accidents (both at work and outside work), and antidepressant use with cognitive failures (outside work). CONCLUSIONS: Antidepressant and sleeping tablet use were apparently associated with accidents, minor injuries and cognitive failures. Although most of the associations could be accounted for by other factors the results suggested links between sleeping tablet use and accidents, and between antidepressant use and cognitive failures.

Accidents↗