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Biomedical subjects

P Burton

Publications and source records attributed to P Burton.

At least 19 recordsLinked to original sources
PubMed2003

Why are parasite contingency genes often associated with telomeres?

Contingency genes are common in pathogenic microbes and enable, through pre-emptive mutational events, rapid, clonal switches in phenotype that are conducive to survival and proliferation in hosts. Antigenic variation, which is a highly successful survival strategy employed by eubacterial and eukaryotic pathogens, involves large repertoires of distinct contingency genes that are expressed differentially, enabling evasion of host acquired immunity. Most, but not all, antigenic variation systems make extensive use of subtelomeres. Study of model systems has shown that subtelomeres have unusual properties, including reversible silencing of genes mediated by proteins binding to the telomere, and engagement in ectopic recombination with other subtelomeres. There is a general theory that subtelomeric location confers a capacity for gene diversification through such recombination, although experimental evidence is that there is no increased mitotic recombination at such loci and that sequence homogenisation occurs. Possible benefits of subtelomeric location for pathogen contingency systems are reversible gene silencing, which could contribute to systems for gene switching and mutually exclusive expression, and ectopic recombination, leading to gene family diversification. We examine, in several antigenic variation systems, what possible benefits apply.

Animals↗
PubMed2001

Wavelets for QRS detection.

This paper examines the use of different wavelet functions for QRS complex detection in ECG. Wavelets provide time and frequency analysis simultaneously and offer flexibility with a number of wavelet functions with different properties available. This research has examined wavelet functions with different properties to determine the effects of orthogonality and time/frequency compactness of the wavelet on the ability to correctly detect the QRS. The error in detection (false negatives and positives) is the criterion for determining the efficacy of the wavelet function. The paper reports a significant reduction in error in detection of QRS complexes with mean error reduced to 0.75%. It also reports that wavelet functions that support symmetry and compactness provide better results.

Electrocardiography↗
PubMed2001

[An unusual intratarsal dislocation: cuneonavicular and calcaneocuboid dislocation].

We report a case of tarsal dislocation with cuneonavicular dislocation associated with calcaneocuboidal dislocation. This dislocation is rare and severe because it causes disruption of both the medial and lateral columns of the foot. Early and prompt reduction of this rare injury was successful in this case and appears important.

Accidental Falls↗
PubMed2000

Mental health disorders in children and young people: scope, cause and prevention.

OBJECTIVE: To review the scope and characteristics of mental health disorders in children and young people in Australia; detail some emerging concepts of the causal pathways of mental health disorders in children and young people; and discuss aspects of the prevention of mental health disorders and the promotion of mental health in children and young people. METHOD: An integrated review of selected literature. RESULTS: (i) While as many as one in five Australian children aged from four to 17 have significant mental health problems there remains a need for prevalence estimates in subsections of the population, notably children and young people of Aboriginal and Torres Strait Islander descent; (ii) appropriate studies of gene-environment interaction will require better measurement and developmental exposition of those risk exposures that are known to be on the causal pathway to mental health disorder; and (iii) universal, selective and indicated prevention trials and evaluations directed at anxiety, depression and conduct disorder are needed. CONCLUSION: Preventive intervention and promotion in mental health must entail effective collaboration at national, state and local levels between health, welfare and education sectors. These sectors must be informed by high quality epidemiology and a knowledge of the causal pathways of mental health disorders. Such intervention must also improve the movement of scientific knowledge to political policy on one hand and to praxis on the other. This will require a clear and persistent vision of the urgency, costs and consequences of mental health disorders in children and young people coupled with effective leadership and political resolve.

Adolescent↗
PubMed1999

Mycophenolic acid increases apoptosis, lysosomes and lipid droplets in human lymphoid and monocytic cell lines.

BACKGROUND: Mycophenolic acid (MPA), a selective inhibitor of inosine monophosphate dehydrogenase, is the active agent of the immunosuppressive drug, mycophenolate mofetil (MMF). Previous studies have shown that MPA inhibits DNA synthesis in T and B lymphocytes by blocking de novo guanosine synthesis, and that MPA induces monocyte differentiation. MMF is being used for prevention of organ graft rejection and has also shown efficacy in rheumatoid arthritis trials. This study was designed to determine if apoptosis also plays a role in the immunosuppressive and anti-inflammatory effects of MMF. METHODS: Cultured human T lymphocytic (MOLT-4) and monocytic (THP-1 and U937) cell lines were treated with MPA. Apoptosis, cell viability, DNA content, lipid content, cell volume, and lysosomes were measured by a variety of microscopic, flow cytometric, and biochemical techniques. RESULTS: MPA inhibits proliferation, arrests cell cycle in S phase, and increases apoptosis in all three cell lines. Exogenous guanosine added within 24 hr of MPA treatment, but not later, partially reversed MPA-induced apoptosis in MOLT-4 cells. MPA increased lipid droplets in all three cell lines and increased both cell volumes and numbers of lysosomes in the monocytic cell lines. In both monocytic cell lines, MPA also reduced the number of nuclei containing nucleoli and greatly increased neutral lipids, primarily triacylglycerols, suggesting that these cells were differentiating. CONCLUSIONS: Increased apoptosis and terminal differentiation of both lymphocytes and monocytes may promote the antiproliferative, immunosuppressive, and anti-inflammatory effects of MMF seen clinically in transplantation and rheumatoid arthritis.

Apoptosis↗
PubMed1999

Regulation of T-helper cell responses to inhalant allergen during early childhood.

BACKGROUND: Recent evidence suggests that preschool children manifest patterns of allergen-specific skin prick test (SPT) reactivity and in vitro T-cell cytokine production which are similar to that of either atopic or nonatopic adults. However, published studies on this age group involve small sample sizes and a restricted number of cytokines, usually in response to polyclonal stimuli. OBJECTIVE: To elucidate the relationship between in vivo and in vitro immune responses to a major inhalant allergen house dust mite (HDM) in preschoolers. METHODS: Peripheral blood mononuclear cells (PBMCs) from matched groups of HDM-SPT+ and SPT- 6-year-olds (n = 30 and 29, respectively) tested for PBMC responses to HDM, and cytokine production measured at both the protein and mRNA levels. Immunoglobulin (Ig) E and IgG subclass antibody titres were determined in serum. Interrelationships between in vitro and in vivo HDM responses were examined via multivariate analyses. RESULTS: SPT reactivity to HDM was associated with in vitro production by putative T cells of interleukin (IL) -4, IL-5, IL-9, IL-10, IL-13 and low level IFNgamma, and with production in vivo of IgE and (all) IgG subclass antibodies; HDM responses in the SPT- group were restricted mainly to IL-10 and IFNgamma and very low levels of IL-4; IL-6 production from non-T-cell sources was common. The cytokine most associated with positive SPT responses was IL-9; SPT weal diameter correlated positively with IL-4, IL-5 and IL-13 and negatively with IL-10. CONCLUSION: Detailed analysis of cytokine responses in this very young age group have the potential to uncover subtle relationships between in vivo and in vitro allergen reactivity which may be less clear in adults, in whom T-cell response patterns are modified via chronic stimulation. The present findings which suggest potentially important roles for IL-9 and IL-10 in the early phase of allergic disease, may be one such example.

Administration, Inhalation↗
PubMed1998

Extending the simple linear regression model to account for correlated responses: an introduction to generalized estimating equations and multi-level mixed modelling.

Much of the research in epidemiology and clinical science is based upon longitudinal designs which involve repeated measurements of a variable of interest in each of a series of individuals. Such designs can be very powerful, both statistically and scientifically, because they enable one to study changes within individual subjects over time or under varied conditions. However, this power arises because the repeated measurements tend to be correlated with one another, and this must be taken into proper account at the time of analysis or misleading conclusions may result. Recent advances in statistical theory and in software development mean that studies based upon such designs can now be analysed more easily, in a valid yet flexible manner, using a variety of approaches which include the use of generalized estimating equations, and mixed models which incorporate random effects. This paper provides a particularly simple illustration of the use of these two approaches, taking as a practical example the analysis of a study which examined the response of portable peak expiratory flow meters to changes in true peak expiratory flow in 12 children with asthma. The paper takes the reader through the relevant practicalities of model fitting, interpretation and criticism and demonstrates that, in a simple case such as this, analyses based upon these model-based approaches produce reassuringly similar inferences to standard analyses based upon more conventional methods.

Adolescent↗
PubMed1998

Measuring the impact of conjugate vaccines on invasive Haemophilus influenzae type b infection in Western Australia.

Haemophilus influenzae type b (Hib) causes serious infections in 26-59 per 100,000 non-Aboriginal Australian children under five years of age. Aboriginal children suffer much higher rates of infection (> or = 150 per 100,000), and at an earlier age, and have a greater risk of death and disability due to Hib infection. In 1992 and 1993, four conjugate Hib vaccines were introduced in Australia, and a nationally funded program of infant vaccination was begun in July 1993. This study aimed at evaluating the effectiveness of Hib vaccination in Aboriginal and non-Aboriginal children in Western Australia using a population-based active surveillance system for non-Aboriginal children and a case control study for Aboriginal children. The incidence of invasive Hib disease in non-Aboriginal children fell from 30.9 per 100,000 before vaccination was available to 6.3 per 100,000 in the second year after its introduction. The vaccine efficacy was estimated to be 80 per cent for Aboriginal children (odds ratio 0.20, 95 per cent CI 0.01-2.76) and, after adjustment for confounders, 75 per cent (odds ratio 0.25, CI 0.02-3.66). Based on the adjusted value (75 per cent), and using a Bayesian approach, we estimate that the posterior probability was 0.55 that the true vaccine efficacy is greater than 70 per cent, and 0.69 that the efficacy is greater than 50 per cent. We conclude that Hib vaccination is effective in preventing invasive Hib disease in Aboriginal and non-Aboriginal children in Australia.

Bacteremia↗
PubMed1997

Influenza epidemics and incidence of schizophrenia, affective disorders and mental retardation in Western Australia: no evidence of a major effect.

In-utero exposure to influenza has been implicated as a risk factor for developmental CNS damage. This study tests the hypothesis that in-utero exposure to influenza: (1) in the second gestational trimester is associated with an increased risk of schizophrenia and affective psychoses; and (2) in the first gestational trimester is associated with an increased risk of mental retardation. Analysis was confined to 1852 cases on the Western Australian psychiatric case register with ICD-9 diagnoses of schizophrenia, affective psychoses, or neurotic depression (comparison group), and 804 cases on the Intellectual Handicap Register with mental retardation that were related to 82,963 'exposed' and 32,462 'non-exposed' births between 1950 and 1960 in the total population of Western Australia. The data were examined for effects associated with six influenza epidemics in the period 1950-1960. Using relative risk ratios for individual epidemics as well as Poisson regression and a proportional hazards model to examine systematic effects for the whole period, no major effect could be identified for maternal influenza on the incidence of schizophrenia, affective psychoses and neurotic depression, despite sufficient statistical power to detect an effect. However, a possible effect was found for mental retardation in males exposed in the first and second gestational trimester.

Adolescent↗
PubMed1997

The intrapartum CTG prior to neonatal encephalopathy at term: a case-control study.

OBJECTIVE: To compare cardiotocograph (CTG) records during labour in cases of neonatal encephalopathy and matched controls. DESIGN: Case-control study. SETTING: Metropolitan area of Perth, Western Australia. SUBJECTS: Term deliveries complicated by neonatal encephalopathy and controls matched for sex, hospital, time of birth, day of week of birth and maternal health insurance. MAIN OUTCOME MEASURES: Low fetal heart rate (FHR) variability, FHR accelerations, late decelerations, total Kreb's score and FIGO classification of CTG records. RESULTS: The neonatal encephalopathy group had significantly more abnormal CTG records (89%) classified according to FIGO, although 52% of control CTG records were also abnormal. CTG records from cases developed significant differences in terms of absence of FHR accelerations and low FHR variability, but not late decelerations, prior to delivery. CONCLUSION: Given the low incidence of neonatal encephalopathy in this study (7 per 1000) the predictive value of an abnormal CTG record is clinically unhelpful. However, the changes in the FHR in such cases suggest a greater disturbance of fetal (rest-activity) behaviour during labour.

Brain Diseases↗
PubMed1997

[A unicompartment knee prosthesis: the effect of the positioning of the tibial plate on the functional results].

The authors analyse the results of 51 unicompartmental knee prostheses with 1 to 12 years follow-up (mean follow-up: 5 years). The results were evaluated using the scoring system of the "Knee Group" of the SO.B.C.O.T. (Société Belge de Chirurgie Orthopédique et de Traumatologie). This analysis demonstrates that the quality of the results depends on implant positioning. The authors suggest positioning the tibial implant parallel with the healthy plateau and slightly distal, i.e. to position the tibial implant perpendicular to the epiphyseal axis and not to the mechanical axis, as is systematically done with the usual tibial cutting guides. When this ideal positioning was respected, 77.5% of the patients had a score above 90 points (out of a possible maximum of 100 points) and 12.5% had a score between 75 and 89 points. When this condition was not respected, none of the knees obtained more than 75 points. The difference was statistically significant (p = 0.0001).

Adult↗
PubMed1996

Differing patterns of mechanical response to direct fetal hormone treatment.

A single combined intramuscular dose of betamethasone and l-thyroxine (T4) or placebo was injected into the shoulder of fetal lambs 48 hours prior to delivery at days 121 (n = 14), 128 (n = 25) or 135 (n = 20) of gestation. Respiratory mechanics were calculated using multiple linear regression analysis. Both respiratory system resistance (RRS) and elastance (ERS) decreased approximately 4 fold between gestational days 121 (D121) and 135 (D135). Both variables were also reduced by hormone treatment. Reduction in ERS was due to a reduction in both lung (EL) and chest wall (EW) components. In absolute terms EW decreased with gestational age; however, EW as a proportion of total elastance (% EW) increased. Inclusion of a volume-dependent elastance term in the multiple linear regression model enabled us to separate total elastance into volume-independent (E1) and volume-dependent (E2V) components. E1 decreased almost 8-fold compared with only a 2.5-fold fall in E2V between D121 and D135. %E2, the proportion of ERS which is volume-dependent and which provides an index of overventilation, doubled over this time period. Hormone treatment affected E1 and E2V components equally hence %E2 was not altered. Both excised lung volume and end expiratory alveolar volume increased with gestational age and with treatment. The response to treatment was qualitatively similar at each of the gestational ages examined, however, for all mechanics variables, except resistance and E1, the magnitude of response to treatment was significantly smaller in D135 animals compared with other age groups.

Airway Resistance↗
PubMed1996

A case-control study of childhood pedestrian injuries in Perth, Western Australia.

STUDY OBJECTIVES: To identify the determinants of childhood pedestrian injuries, taking the child's exposure to the road environment into account. DESIGN: This was a case-control study. SETTING AND PARTICIPANTS: The study was conducted in Perth, Western Australia between 1991 and 1993. Altogether 100 injured and 400 uninjured child pedestrians aged 1 to 14 years were studied. Aspects of the child's social and physical environments, measures of his or her behaviour, cognitive skills, and "habitual" exposure to the road environment, as well as his or her knowledge of road safety, were recorded. MAIN RESULTS: The likelihood of injury increased by 12% with each 10,000 vehicles per day increase in the volume of traffic (odds ratio (OR) 1.12, 95% confidence interval (CI) = 1.05, 1.19) on roads most frequently crossed. In addition, the presence of visual obstacles on the verge of the child's street of residence increased the likelihood of injury by more than 2.6 times (OR 2.68, 95% CI = 1.42, 5.02). In contrast, the absence of footpaths was associated with a 52% reduction in the likelihood of injury compared with the presence of footpaths on the child's street of residence (OR 0.48, 95% CI = 0.27, 0.87). CONCLUSION: The amount of exposure to the road environment and the nature of the road environment to which the child pedestrian was exposed partly influenced the likelihood of injury in children from low socioeconomic areas, male children, and children aged 13 to 14 years. Until now, the excess incidence of childhood pedestrian injuries in these subgroups of the population had not been explained because the child's exposure per se had not been examined.

Accidents, Traffic↗