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Biomedical subjects

L Murray

Publications and source records attributed to L Murray.

At least 37 records · Page 2Linked to original sources
PubMed2002

Repeatability of long and short echo-time in vivo proton chemical-shift imaging.

We carried out long (145 ms) and short (25 ms) echo time spectroscopic imaging of the brain (chemical-shift imaging, CSI) on two occasions 1 week apart on 15 healthy individuals. We found coefficients of variation (CVs) generally in the range 10-25% for long and 15-30% for short echo-time measurements. The CVs of metabolite ratios were higher by about 5-10%. Limits of agreement (defined as mean+/-2 SD of the week 1-week 2 differences) were wider at the shorter echo time. The modest repeatability may be due in part to the difficulty of repositioning spectroscopic voxels at a scale of 1 mm. The generally higher CVs and wider limits of agreement at TE25 ms suggest that the increased spectral complexity more than offsets the theoretical advantage of increased signal at short echo-times. Analysis of variance general linear modelling of metabolites and metabolite ratios showed that, in general, the subject, region of the brain and hemisphere were more important than the occasion in explaining the variability of results. Unless information on short-T2 metabolites is specifically required, better results can probably be achieved with longer echo-times. The magnitude of the CVs needs to be taken into account in the calculation of sample size for cross-sectional or linear studies.

Adult↗
PubMed2002

Association of early life factors and acute lymphoblastic leukaemia in childhood: historical cohort study.

In a historical cohort study of all singleton live births in Northern Ireland from 1971-86 (n=434,933) associations between early life factors and childhood acute lymphoblastic leukaemia were investigated. Multivariable analyses showed a positive association between high paternal age (> or =35 years) and acute lymphoblastic leukaemia (relative risk=1.49; 95% confidence interval (CI)=0.96--2.31) but no association with maternal age. High birth weight (> or =3500 g) was positively associated with acute lymphoblastic leukaemia (relative risk=1.66; 95% CI=1.18--2.33). Children of mothers with a previous miscarriage or increased gestation (> or =40 weeks) had reduced risks of ALL (respective relative risks=0.49; 95% CI=0.29--0.80, and 0.67; 95% CI=0.48--0.94). Children born into more crowded households (> or =1 person per room) had substantially lower risks than children born into less crowded homes with also some evidence of a lower risk for children born into homes with three adults (relative risks=0.56; 95% CI=0.35-0.91 and 0.58; 95% CI=0.21-1.61 respectively). These findings indicate that several early life factors, including living conditions in childhood and maternal miscarriage history, influence risk of acute lymphoblastic leukaemia in childhood.

Abortion, Spontaneous↗
PubMed2002

Associations between physical fitness and activity patterns during adolescence and cardiovascular risk factors in young adulthood: the Northern Ireland Young Hearts Project.

The aim of the present study was to examine relationships between cardiovascular disease (CVD) risk factor status in young adulthood (mean age = 22.5 yrs) and antecedent physical fitness and physical activity at ages 12 and 15 years. The data were obtained from the Young Hearts Project, a longitudinal observational study of CVD risk factors in a representative sample of young people from Northern Ireland. Physical fitness was measured by the 20-metre endurance shuttle run, and physical activity and sports participation by a self-report recall questionnaire. CVD risk factors examined included serum total cholesterol (TC) and HDL cholesterol concentrations, the TC:HDL ratio, systolic and diastolic blood pressure and body fatness (sum of four skinfolds). Linear regression analyses showed modest relationships between physical fitness in adolescence and both TC:HDL ratio and body fatness in young adulthood. No such relationships were apparent for adolescent physical activity. The promotion of physical fitness during adolescence may reduce exposure to other risk factors lasting into early adulthood.

Adolescent↗
PubMed2001

Treatment of attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is a common disorder among children and adolescents with reported prevalence rates of between 3 and 10%. Recent reports suggest that a multimodal treatment approach is preferable to address many symptoms of ADHD and its associated problems for the children, the family, and the school. Stimulant medications remain the mainstay of treatment and are highly effective in more than 75% of patients. Improvement in the core symptoms of inattention, impulsivity, and hyperactivity are most noticeable. Recently approved extended release preparation of methylphenidate will allow once a day dosing. Reports of effectiveness of some non-stimulant medications such as bupropion, especially for adolescents, appear promising. A number of behavioral and psychosocial interventions can be used effectively as part of multimodal approach to address many ADHD-related problems. This article provides an update on practical information on the treatment of children and adolescents with ADHD who do not have other associated psychiatric disorders.

Antidepressive Agents↗
PubMed2001

A selective impairment in the processing of sad and fearful expressions in children with psychopathic tendencies.

The processing of emotional expressions is fundamental for normal socialisation and interaction. Reduced responsiveness to the expressions of sadness and fear has been implicated in the development of psychopathy (R. J. R. Blair, 1995). The current study investigates the sensitivity of children with psychopathic tendencies to facial expressions. Children with psychopathic tendencies and a comparison group, as defined by the Psychopathy Screening Device (PSD; P. J. Frick & R. D. Hare, in press), were presented with a cinematic display of a standardised set of facial expressions that depicted sadness, happiness, anger, disgust, fear, and surprise. Participants observed as these facial expressions slowly evolved through 20 successive frames of increasing intensity. The children with psychopathic tendencies presented with selective impairments; they needed significantly more stages before they could successfully recognise the sad expressions and even when the fearful expressions were at full intensity were significantly more likely to mistake them for another expression. These results are interpreted with reference to an amygdala and empathy impairment explanation of psychopathy.

Adolescent↗
PubMed2001

The incidence and aetiology of stroke in the Caerphilly and Speedwell Collaborative Studies I: methods and incidence of events.

Stroke mortality and morbidity remain high despite downward trends in incidence and case fatality. Population-based longitudinal studies which include collection of risk factor data are required for a better understanding of stroke aetiology. From a representative cohort of men from South Wales and South-west England, followed up for a median of 17 y, details of possible cerebrovascular events were collected from questionnaires, hospital admission data, general practitioner records, death certificates, radiology records and post-mortem reports. Radiology records, and strokes and transient ischaemic attacks were independently validated. There were 433 strokes and 163 transient ischaemic attacks identified during follow-up. Of these, 333 were the first ever in a lifetime strokes of which 139 were definite ischaemic, 20 were haemorrhagic and 168 were probable ischaemic strokes. The crude incidence rate for stroke was 445 (95% confidence interval 398-493) per 100 000 person years. The age-standardised rates for 10 y age-bands were: 45-54 y 91 (10-172); 55-64 y 351 (269-432) and 65-74 y 855 (669-1040). The 30 d case-fatality rate was 21.0% (70/333) for all strokes and 19.2% (60/312) for ischaemic strokes. For transient ischaemic attacks the age-standardised incidence rates for the same 10 y age bands were 92 (4-179), 111 (64-157), and 273 (167-80), respectively. These rates for stroke transient ischaemic attack are likely to be accurate given the high ascertainment of events in this representative population of middle-aged men. Such studies, reporting reliable measures of cerebrovascular events, are important for measuring burden of disease, and for analysis of risk factor associations to help improve understanding of stroke aetiology and inform preventive efforts.

Cohort Studies↗
PubMed2001

The incidence and aetiology of stroke in the Caerphilly and Speedwell Collaborative Studies II: risk factors for ischaemic stroke.

Reduction of stroke burden requires preventive interventions targeted at important risk factors. This report presents the analysis of risk factors for ischaemic stroke from a representative cohort of middle aged men from South Wales and south-west England. Data on risk factors were collected through validated questionnaires and physical and clinical measurements. Details of possible cerebrovascular events were retrieved, classified into ischaemic, haemorrhagic and uncertain subtypes, and validated. The ratio of definite ischaemic to definite haemorrhagic strokes was calculated. This showed that the vast majority of strokes of unknown subtype were likely to ischaemic. After exclusion of known haemorrhagic strokes and subarrachnoid haemorrhages the remaining strokes were labelled ischaemic. Hazard ratios for possible risk factors were calculated for all ischaemic, and for fatal and non-fatal strokes. There were 293 ischaemic strokes. Statistically significant age-adjusted hazard ratios were: 1.50 (95% confidence interval 1.16-1.95) for being in a manual social class, 1.82 (1.24-2.67) if smoking >15 cigarettes/d at enrollment, 1.19 (1.13-1.24) and 1.23 (1.14-1.34) per 10 mmHg increase in systolic and diastolic blood pressure, respectively, 0.67 (0.46-0.96) for the top quintile high density lipoprotein-cholesterol:cholesterol ratio compared to the bottom quintile, 2.04 (1.40-2.99) for presence of angina, 3.90 (2.01-7.58) for presence of atrial fibrillation, and 3.35 (1.90-5.80) for presence of diabetes. Risk factors were more strongly associated with fatal than non-fatal strokes. Multivariate analyses revealed that, while there was some attenuation of the effect of social class, angina and elevated BP, the risks from atrial fibrillation and diabetes were increased.

Brain Ischemia↗
PubMed2001

Birthweight and aerobic fitness in adolescents: the Northern Ireland Young Hearts Project.

The purpose of this study was to examine relationships between aerobic fitness and birthweight in adolescents. A representative cohort of 1015 males and females aged 12 and 15 y was studied, at baseline, with 89% of the 12-y-olds being re-examined 3 y later. The main outcome measures were an index of aerobic fitness, measured in laps completed at voluntary exhaustion by a twenty-metre shuttle run test, and recorded birthweight. Multiple linear regression, with and without adjustment for known and potential confounding variables, was performed to examine associations between fitness and birthweight. Birthweight and aerobic fitness were positively related so that for each kg decrease in birthweight, there was a mean (95% confidence interval) decrease in fitness score of 4.84 (0.35 to 9.33) laps and 3.21 (0.32 to 6.10) laps, in 12-y-old boys and girls respectively. This relationship is of a similar order to the strength of association between birthweight and adult blood pressure previously reported. Associations between birthweight and physical fitness at the age of 15 were weaker and were not significant. Our findings suggest that aerobic fitness may be involved in mediating the association between birthweight and cardiovascular disease risk later in life. The weakening of the association between birthweight and fitness between the ages of 12 and 15 y is similar to the weaker associations between birthweight and blood pressure seen among adolescents compared to younger children. We are currently re-examining this cohort to see if, as with blood pressure, the association with fitness re-emerges at an older age.

Adolescent↗
PubMed2001

Implementation and evaluation of an undergraduate emergency medicine curriculum.

OBJECTIVE: To describe the implementation and evaluation of an undergraduate course in the first Australian academic emergency medicine unit. METHODS: A descriptive study of a course involving fifth year medical students at the University of Western Australia was undertaken. Teaching included self-directed case problem solving, small group tutorials, practical-skills teaching, clinical attachments and information handouts. Evaluation involved questionnaire scores and written feedback regarding life-support skills, tutorial teaching, course materials, clinical attachments and the course in general. Some groups of students underwent pre-course and post-course examinations. RESULTS: Subjective and objective testing showed that student knowledge significantly improved. Feedback was especially positive toward clinical attachments in emergency departments, practical skills tutorials and the case-based learning method. Students requested longer attachments to emergency departments, and more practical, case-based, interactive and bedside teaching. Problems encountered included inadequate time for teaching, vagueness about student roles and objectives, and dealing with death for the first time without adequate preparation. CONCLUSION: Undergraduate emergency medicine education should become an essential part of Australian and international undergraduate medical education. Emergency medicine is enjoyable and eminently suitable for problem-based, interactive and integrated teaching and improves confidence, clinical experience in emergencies, practical skills and teamwork. Improvements include more problem-based teaching, more practical skills sessions and better definition of student roles. These are general principles that can be applied to other undergraduate courses and to designers of other emergency medicine courses, both undergraduate and postgraduate.

Analysis of Variance↗
PubMed2001

Investigation into an engraftment defect induced by culturing primitive hematopoietic cells with cytokines.

BACKGROUND: Strategies for transplanting primitive hematopoietic progenitor (PHP) cells are under development that require in vitro manipulation of cells for several hours to several days prior to transplantation. This applies to gene-therapy protocols involving transduction with adenoviral or lentiviral vectors (typically 1 day of ex vivo culture) or retroviral vectors (up to 3 days of culture). METHODS: Human mobilized peripheral blood (MPB) CD34(+) cells were cultured with the cytokines thrombopoietin mimetic peptide (mTPO), flt3 ligand (FL), and c-kit ligand (KL). Equal numbers of CD34(+) cells, either uncultured or cultured for various time periods up to 5 days, were tested for engraftment in sublethally irradiated 8-10 week-old NOD/SCID mice. Cells were also compared for expression and function of several key surface molecules. RESULTS: At a limiting dose of 1 million cells, mice receiving uncultured cells had a mean of 20% CD45(+) (human) cells in their BM 6 weeks post-transplantation, versus 3% for mice receiving 3-5 day cultured cells. Analysis of 10 surface molecules, CD11a, CD18, CD29, CD49d, CD49e, CXCR-4, CD62L, CD31, CD43, and CD44 over a 5-day culture period showed that their expression levels were either maintained or up-regulated on CD34(+) cells and the primitive Thy-1(+) subset. Similar percentages of uncultured and 3-day cultured MPB CD34(+) cells bound to plates coated with vascular cell adhesion molecule-1 (VCAM-1) under both static and physiological flow conditions, and chemotaxis of cultured cells towards stromal-derived factor-1 (SDF-1) was not impaired, suggesting that VLA-4 and CXCR-4 were functional on cultured cells. CD34(+) Thy-1(+) MPB cells cultured with cytokines expressed increasing levels of Fas receptor beginning at 20 h in culture, with peak expression levels after 3 days (mean Day 0 expression, 39%; mean Day 3 expression, 86%), without increased apoptosis. Including inhibitors of caspases in the media of cells cultured for 24-48 h significantly improved their engraftment in a SCID-hu bone-engraftment model. DISCUSSION: Increased susceptibility to apoptosis upon in vivo injection may contribute to impaired engraftment of in vitro manipulated cells. Inhibitors of apoptosis may increase their engrafting capacity in clinical settings.

Animals↗
PubMed2001

Fitness, fatness, and coronary heart disease risk in adolescents: the Northern Ireland Young Hearts Project.

PURPOSE: The purpose of this study was to examine the independence and relative strengths of association between coronary heart disease (CHD) risk status and both body fatness and cardiorespiratory (C-R) fitness in 12- and 15-yr-old adolescents. METHODS: The study cohort consisted of 1015 schoolchildren aged 12 and 15 yr (251 12-yr-old boys, 258 12-yr-old girls, 252 15-yr-old boys, and 254 15-yr-old girls), representing a 2% random sample of each population group. For each child, height, weight, sexual maturity (pubertal status), skin-fold thicknesses (4 sites), blood pressure (random zero sphygmomanometer), nonfasting serum total, and high density lipoprotein (HDL)-cholesterol and C-R fitness (20-m shuttle run; 20-MST) were determined under standardized conditions. Socioeconomic status and habitual physical activity were also determined from questionnaire information. Multiple regression analyses were carried out to examine relationships between five CHD risk factors, and fitness and fatness and to examine the relative strengths of fitness and fatness on CHD risk status, correcting for potential confounding variables. RESULTS: Our main findings were: 1) Relationships between fatness and CHD risk factors are invariably stronger than between fitness and the same risk factors. For example, partially adjusted standardized regression coefficients for 12-yr-old boys revealed significant relationships between all five CHD risk factors and fatness, compared with three of five for fitness. The corresponding figures for 12-yr-old girls were three of five (fatness) and one of five (fitness). Broadly similar results were apparent for 15-yr-olds. 2) Although relationships between fitness and CHD risk factors do not survive further adjustment for fatness, the relationships between fatness and CHD risk are more robust and are unaffected by further adjustment for fitness. CONCLUSION: Our results indicate that the observed relationships between C-R fitness and CHD risk status in adolescents are mediated by fatness, whereas the observed relationships with fatness are independent of fitness. Primary prevention of CHD during childhood should therefore concentrate upon preventing or reversing undue weight gain.

Adipose Tissue↗
PubMed2001

Cognitive vulnerability to depression in 5-year-old children of depressed mothers.

Studies of cognitive vulnerability to depression in young children have, in the main, relied on self-report questionnaires (e.g. of self-esteem, attributional style). They have failed to produce convincing evidence of a cognitive vulnerability to depression in children under 8 years. In the current study latent depressive cognitions were investigated in the 5-year-old children (N = 94) of depressed and well mothers in a situation of mild stress, that is, the threat of losing a card deal in a modified version of the competitive children's card game "Snap"'. In the context of "losing", but not "winning", deals, children who had been exposed to maternal depression, either in the previous 12 months or at any other time during their lifetime, were more likely than nonexposed children to express depressive cognitions (hopelessness, pessimism, and low self-worth). The association between depressive cognitions and recent exposure to maternal depression was in part accounted for by current maternal hostility to the child. The results of this study stand in contrast to those of studies which have used questionnaire methods to assess vulnerability to depressive cognitions in this age group. They suggest that it might be important to employ ecologically realistic situations to access latent self-cognitions in young children; and they underscore the importance. increasingly evident in research with adults and older children, of employing methods that involve the induction of low mood in order to elicit cognitions relevant to depression.

Adaptation, Psychological↗
PubMed2001

Influence of psychiatric disorder on the controlling behaviour of mothers with 1-year-old infants. A study of women with maternal eating disorder, postnatal depression and a healthy comparison group.

BACKGROUND: Certain styles of parental controlling behaviour influence child development. Work with mothers with eating disorders suggests that they may be particularly controlling of their infants. AIMS: To examine the nature and specificity of maternal controlling behaviour in mothers with eating disorders compared with mothers who had experienced postnatal depression and a healthy comparison group. METHOD: Mothers with eating disorders (n=34), postnatal depression (n=39) and a healthy comparison group (n=61) and their 12-month-old infants were observed during play and mealtimes, and blind ratings made of verbal and non-verbal control exerted by the mother. RESULTS: Mothers in the eating disorder group used more verbal control, especially strong control. There were no differences between the groups on gentle verbal control and physical contact. Maternal dietary restraint was the one feature of eating disorder psychopathology associated with the use of verbal control. Marital criticism was also associated with the extent of verbal controlling behaviour. CONCLUSIONS: Aspects of maternal control of infants were found to be specific to maternal eating disorder psychopathology.

Analysis of Variance↗