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Biomedical subjects

Robert Heard

Publications and source records attributed to Robert Heard.

12 recordsLinked to original sources
PubMed2006

Linkage disequilibrium screening for multiple sclerosis implicates JAG1 and POU2AF1 as susceptibility genes in Europeans.

By combining all the data available from the Genetic Analysis of Multiple sclerosis in EuropeanS (GAMES) project, we have been able to identify 17 microsatellite markers showing consistent evidence for apparent association. As might be expected five of these markers map within the Major Histocompatibility Complex (MHC) and are in LD with HLA-DRB1. Individual genotyping of the 12 non-MHC markers confirmed association for three of them--D11S1986, D19S552 and D20S894. Association mapping across the candidate genes implicated by these markers in 937 UK trio families revealed modestly associated haplotypes in JAG1 (p=0.019) on chromosome 20p12.2 and POU2AF1 (p=0.003) on chromosome 11q23.1.

Calcium-Binding Proteins↗
PubMed2006

An investigation of polymorphisms in the 17q11.2-12 CC chemokine gene cluster for association with multiple sclerosis in Australians.

BACKGROUND: Multiple sclerosis (MS) is a disorder of the central nervous system (CNS) characterised by inflammation and neuronal degeneration. It is believed to result from the complex interaction of a number of genes, each with modest effect. Chemokines are vital to the migration of cells to sites of inflammation, including the CNS, and many are implicated in MS pathogenesis. Most of the CC chemokine genes are encoded in a cluster on chromosome 17q11.2-12, which has been identified in a number of genome wide screens as being potentially associated with MS. METHODS: We conducted a two-stage analysis to investigate the chemokine gene cluster for association with MS. After sequencing the chemokine genes in several DNA pools to identify common polymorphisms, 12 candidate single-nucleotide polymorphisms (SNPs) were genotyped in a cohort of Australian MS trio families. RESULTS: Marginally significant (uncorrected) transmission distortion was identified for four of the SNPs after stratification for several factors. We also identified marginally significant (uncorrected) transmission distortion for haplotypes encompassing the CCL2 and CCL11 genes, using two independent cohorts, which was consistent with recent reports from another group. CONCLUSION: Our results implicate several chemokines as possibly being associated with MS susceptibility, and given that chemokines and their receptors are suitable targets for therapeutic agents, further investigation is warranted in this region.

Australia↗
PubMed2006

A modified postural drainage position produces less cardiovascular stress than a head-down position in patients with severe heart disease: a quasi-experimental study.

QUESTION: Does a modified postural drainage position (horizontal) produce less cardiovascular and respiratory stress than a head-down postural drainage position (30 degrees) in people with severe heart disease? DESIGN: A quasi-experimental study. PARTICIPANTS: Thirty-one patients (mean age 69 years, SD 13) with severe left ventricular systolic dysfunction (mean ejection fraction 23%, SD 7) who were stable, receiving regular medication and free of acute respiratory illness. INTERVENTION: Two manoeuvres were performed--one from long sitting to a modified (horizontal) postural drainage position, and one from long sitting to a head-down (30 degrees) postural drainage position. OUTCOME MEASURES: Cardiovascular responses examined were blood pressure, sphygmocardiographic indices, and cardiac rhythm. Respiratory responses examined were respiratory rate, transcutaneous arterial oxyyhaemoglobin saturation, and dyspnoea. RESULTS: Three participants were intolerant to the postural drainage positions--two during head-down and one during modified positioning. The remaining 28 participants maintained their resting cardiac rhythm and did not complain of chest pain or dyspnoea. The changes in cardiovascular responses during the sitting to head-down postural drainage manoeuvre in the tolerant participants were significantly greater (p < 0.05) than the changes during the sitting to the modified postural drainage manoeuvre for most of the sphygmocardiographic indices. In contrast, there were no significant respiratory responses to either postural drainage manoeuvre. CONCLUSION: Modified positioning is associated with less cardiovascular stress than head-down positioning, yet for most patients with severe heart disease, both positions are generally well tolerated. For a subset of these patients, either position may be inappropriate. This suggests that modified positioning should be attempted first but that a head-down position may be attempted if the modified position proves ineffective.

Aged↗
PubMed2005

Analysis of neutralizing antibodies to therapeutic interferon-beta in multiple sclerosis patients: a comparison of three methods in a large Australasian cohort.

Persistent high-titre neutralizing antibodies (NAB) to therapeutic interferon-beta(IFNbeta)in multiple sclerosis patients reduce therapeutic efficacy. Difficulties in standardization of cell-based bioactivity assays have hindered interlaboratory comparison of NAB titres and the determination of a clinically relevant definition of seropositivity. We determined NAB status in Australasian multiple sclerosis patients receiving IFNbetausing both the antiviral cytopathic effect (CPE) assay (n = 227) and the more specific ELISA for the type I interferon-inducible MxA protein (n = 350). While the log(10) titres determined in the two assays were highly correlated (p < 0.0001; r = 0.967) with similar distributions, the MxA assay was more sensitive, detecting lower concentrations of NAB than the CPE assay. The range of titres determined in the CPE assay was 10 to >7290; and 9 to 53,700 in the MxA assay, with ranked titre distribution highlighting the arbitrary nature of currently accepted definitions of NAB seropositivity. Bioactivity of injected IFNbetawas significantly reduced in NAB-positive patients (p = 0.006; NAB MxA titres = 184 to 5340) compared to NAB-negative patients as assessed ex vivo using real-time RT-PCR analysis of MxA gene induction. The range of MxA mRNA levels in healthy controls was remarkably consistent with previously published results, regardless of the assay standardization method [Gilli, F., Sala, A., Marnetto, F., Lindberg, R.L., Leppert, D. and Bertolotto, A. (2003) Comparison of IFNbeta bioavailability evaluations by MxA mRNA using two independent quantification methods. Abstract, ECTRIMS Meeting, Milan, Italy; Pachner, A., Narayan, K., Price, N., Hurd, M. and Dail, D. (2003a) MxA Gene Expression Analysis as an Interferon-beta Bioactivity Measurement in Patients with Multiple Sclerosis and the Identification of Antibody-Mediated Decreased Bioactivity. Mol. Diagn. 7, 17-25]. Assessment of IFNbetaresponse ex vivo accounts for both circulating factors and the cellular response to IFNbeta, and the data support the development of the MxA gene induction assay for the routine screening of patients receiving IFNbeta.

Antibodies↗
PubMed2005

A high-density screen for linkage in multiple sclerosis.

To provide a definitive linkage map for multiple sclerosis, we have genotyped the Illumina BeadArray linkage mapping panel (version 4) in a data set of 730 multiplex families of Northern European descent. After the application of stringent quality thresholds, data from 4,506 markers in 2,692 individuals were included in the analysis. Multipoint nonparametric linkage analysis revealed highly significant linkage in the major histocompatibility complex (MHC) on chromosome 6p21 (maximum LOD score [MLS] 11.66) and suggestive linkage on chromosomes 17q23 (MLS 2.45) and 5q33 (MLS 2.18). This set of markers achieved a mean information extraction of 79.3% across the genome, with a Mendelian inconsistency rate of only 0.002%. Stratification based on carriage of the multiple sclerosis-associated DRB1*1501 allele failed to identify any other region of linkage with genomewide significance. However, ordered-subset analysis suggested that there may be an additional locus on chromosome 19p13 that acts independent of the main MHC locus. These data illustrate the substantial increase in power that can be achieved with use of the latest tools emerging from the Human Genome Project and indicate that future attempts to systematically identify susceptibility genes for multiple sclerosis will have to involve large sample sizes and an association-based methodology.

Australia↗
PubMed2004

The effectiveness of a community-based program for reducing the incidence of falls in the elderly: a randomized trial.

OBJECTIVES: To test whether Stepping On, a multifaceted community-based program using a small-group learning environment, is effective in reducing falls in at-risk people living at home. DESIGN: A randomized trial with subjects followed for 14 months. SETTING: The interventions were conducted in community venues, with a follow-up home visit. PARTICIPANTS: Three hundred ten community residents aged 70 and older who had had a fall in the previous 12 months or were concerned about falling. INTERVENTION: The Stepping On program aims to improve fall self-efficacy, encourage behavioral change, and reduce falls. Key aspects of the program are improving lower-limb balance and strength, improving home and community environmental and behavioral safety, encouraging regular visual screening, making adaptations to low vision, and encouraging medication review. Two-hour sessions were conducted weekly for 7 weeks, with a follow-up occupational therapy home visit. MEASUREMENTS: The primary outcome measure was falls, ascertained using a monthly calendar mailed by each participant. RESULTS: The intervention group experienced a 31% reduction in falls (relative risk (RR)=0.69, 95% confidence interval (CI)=0.50-0.96; P=.025). This was a clinically meaningful result demonstrating that the Stepping On program was effective for community-residing elderly people. Secondary analysis of subgroups showed that it was particularly effective for men (n=80; RR=0.32, 95% CI=0.17-0.59). CONCLUSION: The results of this study renew attention to the idea that cognitive-behavioral learning in a small-group environment can reduce falls. Stepping On offers a successful fall-prevention option.

Accidental Falls↗
PubMed2003

Randomized phase I trial of recombinant human keratinocyte growth factor plus chemotherapy: potential role as mucosal protectant.

PURPOSE: To evaluate the safety of recombinant human keratinocyte growth factor (KGF) when administered with fluorouracil (FU) in patients with metastatic colorectal cancer. PATIENTS AND METHODS: Patients (N = 81) received KGF by intravenous (IV) bolus on days 1 to 3, followed by FU 425 mg/m2/d IV bolus plus leucovorin 20 mg/m2/d IV on days 4 to 8. KGF dose levels were 1, 10, 20, 40, 60, and 80 microg/kg/d. A randomized, placebo-controlled design was employed (2:1 randomization of KGF to placebo). Oral mucositis was assessed by examination on days 1, 4, 8, 15, and 28. In addition, patients provided daily assessments of oral symptoms using a self-administered questionnaire. RESULTS: Skin and oral events occurred in 13 of 18 patients (eight patients, grade 1; four patients, grade 2; and one patient, grade 3) treated with 60 and 80 microg/kg of KGF and three of 11 patients treated with 40 microg/kg (grade 1). These symptoms were dose limiting in three cases (ie, in two of 10 patients treated with 80 microg/kg and in one of eight patients treated with 60 microg/kg). The frequency of grade 2 to 4 mucositis was 43% in patients treated with KGF, compared with 67% in patients treated with placebo (P =.06). Patient self-assessments of oral pain and clinical assessments of mucositis showed good correlation (Kendall's tau = 0.75). CONCLUSION: KGF is generally well tolerated when administered IV at doses up to 40 microg/kg/d for 3 days before a 5-day course of FU plus leucovorin. A clinically meaningful biologic effect was also suggested in that patients treated with the epithelial growth factor KGF had a lower rate of grade 2 to 4 mucositis than did patients treated with placebo.

Adult↗
PubMed2003

Breast compression in mammography: how much is enough?

The amount of breast compression that is applied during mammography potentially influences image quality and the discomfort experienced. The aim of this study was to determine the relationship between applied compression force, breast thickness, reported discomfort and image quality. Participants were women attending routine breast screening by mammography at BreastScreen New South Wales Central and Eastern Sydney. During the mammographic procedure, an 'extra' craniocaudal (CC) film was taken at a reduced level of compression ranging from 10 to 30 Newtons. Breast thickness measurements were recorded for both the normal and the extra CC film. Details of discomfort experienced, cup size, menstrual status, existing breast pain and breast problems were also recorded. Radiologists were asked to compare the image quality of the normal and manipulated film. The results indicated that 24% of women did not experience a difference in thickness when the compression was reduced. This is an important new finding because the aim of breast compression is to reduce breast thickness. If breast thickness is not reduced when compression force is applied then discomfort is increased with no benefit in image quality. This has implications for mammographic practice when determining how much breast compression is sufficient. Radiologists found a decrease in contrast resolution within the fatty area of the breast between the normal and the extra CC film, confirming a decrease in image quality due to insufficient applied compression force.

Adult↗
PubMed1999

Stroke rehabilitation: Does the therapy area provide a physical challenge?

It has been previously shown that stroke patients undergoing rehabilitation perform most physical activity under the supervision of a therapist when in the therapy area and very little activity when elsewhere. The aim of this paper was to identify conditions surrounding the performance of physical activity in the therapy area, in order to design strategies which would increase physical activity throughout the rehabilitation unit. Sixteen hemiplegic patients were observed in the therapy area. They were most active when with a therapist, whereas when alone, nearly two-thirds of their time was spent inactive. It appears that it is too difficult for patients to bridge the gap between fully-supervised and unsupervised practice. Strategies to provide patients with semi-supervised practice as a way of increasing the amount of overall physical activity, such as group sessions, are explored.

Journal Article↗
PubMedDate not supplied

Physiotherapist attitudes and practices regarding head-down and modified postural drainage in the presence of heart disease.

Modification of chest physiotherapy interventions is recommended for patients with concomitant respiratory and cardiac diseases. What modifications are necessary and for whom, and what strategies physiotherapists adopt when heart disease is present, have not been investigated. Consequently, few guidelines exist. A questionnaire survey was conducted to identify attitudes and practices of senior cardiopulmonary physiotherapists (SCPP) and "other" physiotherapists (OP) regarding modified and head-down postural drainage (HDPD) when heart disease is present. The overall response rate was 44% (178/407); the response rate from SCPP (78%, 50/64) was higher than from OP (37%, 128/343). Major findings included that: postural modification in the presence of heart disease is common and is not reserved for patients with severe disease; the most commonly adopted modified position is the horizontal; and that the rationale for modification is commonly based on the assumptions that the cardiovascular load is less and, thus, adverse outcomes will be avoided. In the main, the response patterns for both groups were similar, but some between-group differences were found. The findings overall suggest physiotherapists adopt a cautious approach to HDPD when heart disease is present. Whether this approach is justified remains to be investigated.

Drainage, Postural↗
PubMedDate not supplied

The development of an assessment to evaluate behavioral factors associated with falling.

The purpose of this study was to report the development of the Falls Behavioral (FaB) Scale for Older People, an assessment designed to evaluate behavioral factors that could potentially protect against falling. Instrument development included content analysis, expert review, and factor analysis. Ten behavioral dimensions were identified including Cognitive Adaptations, Protective Mobility, Avoidance, Awareness, Pace, Practical Strategies, Displacing Activities, Being Observant, Changes in Level, and Getting to the Phone. The final 30-item scale had a Content Validity Index of 0.93. Test-retest reliability was ICC = 0.94 (p < .01). Construct validity was established by showing that, as expected, scale scores were positively associated with increasing age (rs = 0.46, p < .01) and negatively associated with greater physical mobility (rs = -0.68, p < .01). People who had fallen utilized safer behaviors than those who had not reported a fall (p < .05) providing a benchmark for using the scale in future studies. The FaB is an easily completed, reliable, and valid tool for determining the presence or absence of protective behaviors. It has potential to assist in goal setting for falls prevention and to evaluate behavioral outcomes of fall prevention programs.

Accidental Falls↗