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Biomedical subjects

J Harrison

Publications and source records attributed to J Harrison.

At least 19 recordsLinked to original sources

Metabolism and blood-brain clearance of L-3,4-dihydroxy-[3H]phenylalanine ([3H]DOPA) and 6-[18F]fluoro-L-DOPA in the rat.

6-[18F]fluoro-L-DOPA (FDOPA) has been used as a tracer for the cerebral activity of L-3,4-dihydroxyphenylalanine (DOPA)-decarboxylase in studies of positron emission tomography (PET). However, the substitution of fluorine on the aromatic ring may alter the disposition and metabolism of FDOPA from that of endogenous DOPA. In the present study, the kinetics of the peripheral metabolism and the facilitated unidirectional blood-brain clearance of [3H]DOPA and FDOPA were compared in Wistar rats pretreated with carbidopa. In arterial plasma, FDOPA was O-methylated with an apparent rate constant (0.031 min-1) 3-fold that of [3H]DOPA in the same rats. The O-methylated metabolite of FDOPA (OMe-FDOPA) was eliminated from plasma at a rate constant (0.018 min-1) 3-fold that of OMe-[3H]DOPA. The mean unidirectional blood-brain clearance of FDOPA (4.5 mL.hg-1.min-1) in six brain regions was 60% higher than that of [3H]DOPA.

Animals

The internal control of action and Parkinson's disease: a kinematic analysis of visually-guided and memory-guided prehension movements.

This paper reports two experiments which examined the effects of Parkinson's disease (PD) upon the sensorimotor mechanisms used to control prehension movements. Transport and grasp kinematics for visually-guided and memory-guided prehension movements were examined in healthy control subjects and compared against those of patients with idiopathic PD. Two research questions were addressed: (1) Are patients with PD particularly susceptible to distraction by non-relevant objects? (2) Are patients with PD especially reliant on external feedback when executing goal-directed actions? The results indicated that the patient group were no more susceptible to distraction by non-relevant objects than the control group. In contrast, the patients with PD were shown to be significantly impaired when executing memory-guided reaches. Furthermore, the deficits exhibited by the PD group on memory-guided reaches were confined solely to those markers associated with the transport component of the prehension movement. That is, while both controls and patients with PD widened their grip aperture on memory-guided trials, the magnitude of this adjustment was comparable across the two groups. The implications of these findings for theories of visuomotor processing in sufferers of PD and the control of prehension movements more generally are discussed.

Aged

Serial reaction time learning and Parkinson's disease: evidence for a procedural learning deficit.

This paper presents evidence in support of a serial reaction time (SRT) deficit associated with Parkinson's disease, and related to the acquisition or execution of serial-order information. Eleven patients with idiopathic Parkinson's disease, and 10 age-matched but otherwise healthy control subjects, were compared on a variant of the SRT task introduced by Nissen and Bullemer (Cognit. Psychol. 19, 1-32, 1987). The results of this study clearly demonstrate that PD patients produce a quite different pattern of RT performance to that of control subjects. Such a pattern of results may reflect either: (1) a deficit in the patients' ability to learn the temporal order information provided by a repeating sequence of target locations in the SRT task; or (2) a deficit in the patients' ability to express temporal order information provided by the repeating sequence of target locations in the SRT task.

Aged

Ambient, biological, and biological effect monitoring of exposure to polycyclic aromatic hydrocarbons (PAHs).

A novel strategy was utilised to assess the risk to health from exposure to polycyclic aromatic hydrocarbons (PAHs). Ambient monitoring was carried out by personal sampling. Urinary thioethers (UTh) and urinary 1-hydroxypyrene (1-HP) were utilised for biological monitoring. Urinary d-glucaric acid (UDGA) and sister chromatid exchange (SCE) in peripheral blood lymphocytes were used as biological effect markers. The population was categorised into exposed and control groups according to the external dose of PAHs. The excretion of 1-HP in the controls over the 3-day period showed a relatively stable baseline, while the exposed showed a significant increase over the same period of time. SCE frequency in the exposed population was significantly different from controls.

Adult

A multidisciplinary audit of manual hyperinflation technique (sigh breath) in a neurosurgical intensive care unit.

Manual hyperinflation of the lungs (sigh breath) is a technique which is used to deliver a large volume of gas to the lungs. The purpose of this technique is to either maintain or improve the respiratory status of the patient. However, the volume of gas delivered is rarely measured, and therefore there is little evidence that hyperinflation occurs. Through the process of audit staff were able to examine the technique critically and improve it. With the addition of measurement tools a defined standard was developed against which performance was measured. To explore the effects of a particular technique it is essential that the delivery of that technique is standardised. This audit has enabled staff to achieve a standard technique and create a position from which research into its effects can now take place.

Clinical Protocols

CpNpG methylation in mammalian cells.

In vertebrate DNA, 3% to 5% of cytosine residues are present as 5-methylcytosine, and it is generally accepted that essentially all of this methylation occurs at cytosines which are contained in the symmetrical dinucleotide CpG. In this report we demonstrate, using bisulphite genomic sequencing, that the methylation machinery of mammalian cells is capable of both maintenance and de novo methylation at CpNpG sites. The existence of inherited CpNpG methylation in mammalian cells has important implications in gene regulation and in the aetiology of disease.

3T3 Cells

The physiology of coloured hearing. A PET activation study of colour-word synaesthesia.

In a small proportion of the normal population, stimulation in one modality can lead to perceptual experience in another, a phenomenon known as synaesthesia. In the most common form of synaesthesia, hearing a word can result in the experience of colour. We have used the technique of PET, which detects brain activity as changes of regional cerebral blood flow (rCBF), to study the physiology of colour-word synaesthesia in a group of six synaesthete women. During rCBF measurements synaesthetes and six controls were blindfolded and were presented with spoken words or pure tones. Auditory word, but not tone, stimulation triggered synaesthesia in synaesthetes. In both groups word stimulation compared with tone stimulation activated the classical language areas of the perisylvian regions. In synaesthetes, a number of additional visual associative areas, including the posterior inferior temporal cortex and the parieto-occipital junctions, were activated. The former has been implicated in the integration of colour with shape and in verbal tasks which require attention to visual features of objects to which words refer. Synaesthetes also showed activations in the right prefrontal cortex, insula and superior temporal gyrus. By contrast, no significant activity was detected in relatively lower visual areas, including areas V1, V2 and V4. These results suggest that colour-word synaesthesia may result from the activity of brain areas concerned with language and visual feature integration. In the case of colour-word synaesthesia, conscious visual experience appears to occur without activation of the primary visual cortex.

Adult

Human parvovirus B19 infection in healthcare workers.

This paper reports the occurrence of human parvovirus B19 infection in seven healthcare workers in an acute hospital. The clinical presentation mimicked that of rubella and the diagnosis was made by the detection of human parvovirus B19 IgM antibody in blood samples taken from the affected members of staff. The paper discusses the importance of accurate diagnosis of B19 infection because this virus has been implicated in causing or exacerbating a variety of medical conditions. B19 infection may be serious for people with chronic haemolytic anaemias, those who are immunocompromised or those who are pregnant. B19 infection in pregnancy may be a cause of hydrops fetalis, particularly if the infection occurs during the second trimester. This is in contrast to the risk of intra-uterine rubella infection which is maximal in the first few weeks of pregnancy and which affects fetal development. The paper highlights the need for guidelines for occupational health practitioners on the management of parvovirus B19 infection and the need to make healthcare workers aware of the importance of this infection.

Adult

Work-related deaths of children and adolescents in Australia, 1982 to 1984.

Work-related deaths of children and adolescents up to the age of 19 years were studied as part of a larger investigation into all work-related fatalities in Australia in the three-year period, 1982 to 1984. This study aimed to characterise the circumstances which led to the deaths of these children. Of 1738 work-related fatalities identified over the three years in the larger investigation, 67 (4 per cent) were aged under 15 years, and 117 (7 per cent) were aged 15 to 19 years. The fatalities were characterised by a number of variables, the most important being age, sex, bystander status, location (farm or other) and vehicle involvement (especially tractors). The causes of death differed between subgroups. Although existing controls may be reasonably effective in minimising child deaths in most work places, farms are an exception. On farms, home and work activities overlap, and informal participation in work by the young is quite common. Preventive efforts should give special attention to farms and tractors, to toddlers and male children, and to measures (such as safety devices and other external control measures) which do not rely on behavioural change in the young people at risk. Adults responsible for young children should be educated to anticipate dangerous situations and thus ensure children are protected from injury hazards.

Accidents, Occupational

Analysis of violent incidents in a regional secure unit.

This study examined violent incidents occurring over a four-year period in a Regional Secure Unit. Data were collected from incident reports and case notes. Patients referred from district general psychiatric hospitals because of unmanageable behaviour were over-represented among the small number of patients who were responsible for the majority of incidents. Most patients exhibited little or no aggression. Seclusion was found unnecessary in the management of such patients. Suggestions for further research in this area are made.

Adult

The effect of regular sunscreen use on vitamin D levels in an Australian population. Results of a randomized controlled trial.

BACKGROUND AND DESIGN: Studies published have suggested a possibility that regular use of sunscreen to prevent skin cancer may put the population, particularly elderly people, at risk of vitamin D deficiency. We aimed to determine whether regular use of sunscreens in the normal adult population, as recommended by public health authorities for the prevention of skin cancer, may put individuals at risk of vitamin D deficiency. A randomized double-blind control trial of the daily use of a broad-spectrum sunscreen (sun protection factor [SPF] 17) vs placebo cream over a summer period in Australia was conducted in 113 people aged 40 years and over, with sampling stratified by age. All participants had at least one solar keratosis. Serum samples taken at the beginning and at the end of the study were analyzed for 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3. RESULTS: Mean levels of 25-hydroxyvitamin D3 rose significantly by the same amount in both groups over the period of the study (placebo, +12.8 mmol/L; sunscreen, +11.8 mmol/L). Mean levels of 1,25-dihydroxyvitamin D3 increased significantly in the placebo group only (placebo, +10.8 pmol/L; sunscreen, +1.3 pmol/L), but for no subject in either group was the level of 1,25-dihydroxyvitamin D3 outside the reference range either at the start or at the end of the study. There were no significant differences by age, sex, and skin type in the change in 25-hydroxyvitamin D3 or 1,25-dihydroxyvitamin D3 over the study period. CONCLUSIONS: No person, including those aged 70 years and over, developed any vitamin D levels outside the normal reference range during the period of the study. The data suggest that over an Australian summer sufficient sunlight is received, probably through both the sunscreen itself and the lack of total skin cover at all times, to allow adequate vitamin D production in people who are recommended to use sunscreens regularly. More work is required to elucidate the relationship between 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3, particularly during the different seasons of the year.

Adult

Splicing variability in HIV type 1 revealed by quantitative RNA polymerase chain reaction.

A quantitative RNA-polymerase chain reaction (PCR) method able to detect the majority of mRNAs produced by human immunodeficiency virus type 1 (HIV-1) was developed and used to study expression of different HIV-1 clones in human cells. Amplified mRNAs were compared to known cDNA standards. This comparison permitted the optimization of PCR conditions and eliminated the generation of artifactual PCR bands. The use of RNA and cDNA standards demonstrated that the RNA amplification is linear within the tested range and suggested that it can be used to quantitate individual mRNAs. The results demonstrate the overall conservation of splicing in different HIV-1 clones. Although, in general, splicing was conserved, extensive qualitative and quantitative variability was observed in different HIV-1 clones. This variability is likely one determinant of the biological characteristics of the different HIV-1 clones, and demonstrates a great plasticity of the HIV-1 genome. The described RNA-PCR methodology was used for the study of HIV-1 expression in unstimulated peripheral blood mononuclear cells (PBMCs) of infected individuals. In general, the same mRNAs were identified in HIV-infected cultured cell lines and in unstimulated PBMCs. Analysis of a variant band found after amplification of PBMC RNA from an HIV-infected individual revealed a new splice site for the generation of Rev/Nef-encoding mRNAs. The availability of a sensitive, rapid, and essentially quantitative method to examine the major HIV-1 mRNAs will facilitate the detailed analysis of HIV-1 expression in human cells.

Base Sequence

Predictors of psychiatric morbidity in cancer patients.

BACKGROUND: A significant proportion of cancer patients experience psychiatric morbidity in association with diagnosis and treatment. If this morbidity is to be reduced, a better understanding is needed of the factors which influence adjustment to cancer. METHOD: A review of the literature was carried out to explore those factors associated with poor psychological adjustment to cancer. These are described under four heading: characteristics of the patient; disease and treatment variables; the interaction between patient and illness; and environmental factors. RESULTS: A number of risk factors for psychiatric morbidity can be identified from each of the four areas. Methodological limitations are highlighted, in particular the preponderance of cross-sectional study designs. CONCLUSIONS: Increased awareness of the risk factors for psychiatric morbidity should lead to earlier detection and more appropriate treatment. Future research should focus on those risk factors which are potentially modifiable.

Adaptation, Psychological