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Biomedical subjects

G R Webb

Publications and source records attributed to G R Webb.

At least 19 recordsLinked to original sources
PubMed1998

An immunodominant epitope from mycobacterial 65-kDa heat shock protein protects against pristane-induced arthritis.

Previous studies showed that mice with pristane-induced arthritis (PIA) and those protected from the disease by preimmunization with mycobacterial 65-kDa heat shock protein (hsp65) possess raised immune responses to hsp65. Additionally, T cells from hsp65-protected mice, but not from pristane-injected or normal mice, produced the Th2-associated cytokines IL-4, IL-5, and IL-10 in response to stimulation with hsp65. Here we demonstrate that the specificity of the immune response to hsp65 and related heat shock protein (hsps) differs between protected and PIA mice. T cells from hsp65-protected mice respond to the bacterial hsps tested but not to the mammalian homologue, hsp58. Similarly, they exhibit high serum titers of anti-hsp65 Abs, yet they have virtually undetectable levels of anti-hsp58 IgG. By contrast, both cellular and humoral immune responses are detectable to bacterial and mammalian hsps in mice with PIA. An immunodominant T cell epitope has been identified in hsp65-protected mice corresponding to amino acids 261-271 from hsp65. Immunization of mice, either before or after the induction of arthritis, with this bacterial peptide, but not its mammalian homologue, protects mice from the development of PIA, and protection is associated with the production of Th2-type cytokines. Other experiments revealed that T cells primed with bacterial 261-271 or the mammalian homologue do not cross-react at the proliferative or cytokine level. These results demonstrate that an hsp65 peptide-specific Th2 response confers protection from PIA but do not support the idea that protection is mediated by a cross-reaction with self hsp58 in the joints.

Animals↗
PubMed1998

Osteoarthritic synovial fluid and synovium supernatants up-regulate tumor necrosis factor receptors on human articular chondrocytes.

OBJECTIVE: To determine whether the up-regulation of chondrocyte tumor necrosis factor receptor (TNF-R) expression in osteoarthritis (OA) is due to molecules released within the OA knee joint. DESIGN: Non-arthritic (NA) human articular chondrocytes were incubated with normal serum, OA synovial fluid, or supernatants from either cultured NA or OA synovium, and TNF-R expression measured by flow cytometry. RESULTS: OA synovial fluid, but not normal serum, significantly up-regulated the proportion of chondrocytes expressing p55 TNF-R as well as the number of p55 TNF-R/chondrocyte. Similarly, supernatants from OA, but not NA, synovia significantly up-regulated chondrocyte p55 TNF-R expression. Chondrocyte p75 TNF-R expression was also significantly increased by some of the OA supernatants but not others, and overall no significant increase was seen. OA synovium supernatants contained higher concentrations of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) than NA synovium supernatants and neutralizing antibodies to these cytokines either partially or totally abrogated the ability of the OA supernatants to increase chondrocyte p55 TNF-R expression. Finally, various concentrations of recombinant human (rh)IL-1 beta and rhIL-6 up-regulated chondrocyte p55 TNF-R expression. CONCLUSION: These results suggest that IL-1 and IL-6 produced by OA synovium contribute to the progression of the disease by rendering chondrocytes more susceptible to stimulation by catabolic cytokines.

Aged↗
PubMed1997

Alteration of cartilage metabolism by cells from osteoarthritic bone.

OBJECTIVE: To determine whether bone cells alter cartilage metabolism. METHODS: Bone cell cultures were established using explants obtained from the hip and knee joints of 9 patients with osteoarthritis (OA) and 6 subjects without arthritis (nonarthritic [NA]). NA human cartilage biopsy samples were incubated in the presence or absence of bone-derived cells, and the effects on glycosaminoglycan (GAG) release from cartilage were measured. RESULTS: Bone cell cultures secreted osteocalcin (OC) and did not contain cells expressing leukocyte common antigen. None of the 8 cultures established from NA bone, compared with 17 of 32 from OA bone, significantly altered GAG release from cartilage (P = 0.006). In knees with medial joint damage, 38% of the cultures derived from the medial side of the joint increased GAG release from cartilage. In contrast, 77% of the cultures derived from the lateral side of the joint had an effect on GAG, with 38% increasing and 38% decreasing GAG release. Seven cytokines were measured in OA bone cell supernatants. No significant difference was apparent in the concentration of any one cytokine when supernatants were compared according to their effects on GAG release. CONCLUSION: Bone cells from OA patients can influence cartilage metabolism. This might explain why increased subchondral bone activity can predict cartilage loss.

Aged↗
PubMed1997

Chondrocyte tumor necrosis factor receptors and focal loss of cartilage in osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is characterized by focal loss of cartilage. Here we show for the first time that tumor necrosis factor (TNF) alpha can act on cartilage but only at specific sites where chondrocyte TNF alpha-receptor (R) expression is high. DESIGN: Cartilage explants from specified sites in the knee joints of both OA patients and non-arthritic (NA) subjects were cultured with and without TNF alpha for 14 days and cumulative glycosaminoglycan (GAG) release into the supernatant measured. p55 and p75 TNF-R expression was measured by flow cytometry on chondrocytes isolated from the same sites. RESULTS: Cartilage explants from different sites in knee joints from both OA patients and NA subjects varied in their susceptibility to TNF alpha. Overall, the proportion of samples that responded to TNF alpha was higher in cartilage taken from OA joints than cartilage from NA subjects. Variations in p55 and p75 TNF-R expression were found between chondrocytes from different sites. p55, but not p75 TNF-R, expression on chondrocytes was closely related to the susceptibility of explants from the same site to TNF alpha-induced GAG loss. CONCLUSION: It is considered that focal loss of cartilage will occur at sites where chondrocyte p55 TNF-R expression is high, if sufficient TNF alpha is present, and that these results identify a mechanism by which cytokine-mediated focal loss of cartilage may occur.

Adult↗
PubMed1995

A filter model to describe bias in official statistics on alcohol-related injuries.

The paper describes a filter model that can be used to explore the possible biases that occur in reporting of alcohol-related injuries. These biases occur because of loss of data at various stages of injury reporting systems. The filter model consists of four levels or incidences, with a filter between each level. Level 1 is the total incidence of alcohol-related injuries. Level 2 is the incidence of reported alcohol-related injuries. Level 3 is the incidence of reported alcohol-related injuries where the contribution of alcohol has been correctly identified. Level 4 consists of official statistics on alcohol-related injuries. Between each of these levels is a filtering mechanism that allows some but not all data to pass through to the next level. The paper describes the nature of data at each level and the mechanisms operating at each filter to result in progressive loss of data. Estimates are provided regarding the extent of loss of data at each filter. Suggestions are provided for improving the quality of official statistics on alcohol-related injuries.

Accidents, Traffic↗
PubMed1994

The relationships between high-risk and problem drinking and the occurrence of work injuries and related absences.

A review of studies on the relationship between alcohol and work injuries revealed that the evidence is contradictory and that many of the studies contain methodological flaws. The present study aimed to determine whether there are relationships between problem drinking and high alcohol consumption and outcomes such as work injuries and related absences. The sample consisted of 833 employees at an industrial worksite. Problem drinking was measured by the Mortimer-Filkins test, while alcohol consumption was measured by a 7-day retrospective diary. Work injury data were obtained from medical reports completed at the worksite medical center, while absences data were obtained from company records. Chi-square analyses revealed significant relationships between problem drinking and work injuries and injury-related absences, but not between high alcohol consumption and work injuries and related absences. Logistic regression analysis revealed that no variables were significant predictors of work injuries. However, when uninjured subjects were excluded, a second analysis revealed that Mortimer-Filkins test scores, recent stressful life events, age and job satisfaction were significant predictors of two or more injuries. Injured subjects were almost twice as likely to have two or more injuries if they had high numbers of recent stressful life events and low levels of job satisfaction. Logistic regression analysis revealed that age, Mortimer-Filkins test categories and job satisfaction significantly predicted injury-related absences. Problem drinkers were 2.7 times more likely to have injury-related absences than non-problem drinkers, and subjects with low levels of job satisfaction were 2.2 times more likely than others to have injury-related absences. The implications of the results for workplace alcohol policies and programs are discussed.

Absenteeism↗
PubMed1992

The reliability and stability of the Mortimer-Filkins test.

The Mortimer-Filkins test has been used widely as an instrument for detecting problem drinkers among drink-driving offenders. While extensive psychometric testing has been undertaken by the developers of the test, few independent validation studies have been conducted, and few studies have used the Mortimer-Filkins test with general populations. The present study investigated the test-retest and internal-consistency reliability of the instrument, and the stability of problem drinking, as measured by the instrument. The test was administered to moderate and heavy drinkers at an industrial workplace on three occasions. The results indicated that the Mortimer-Filkins test has high test-retest and internal-consistency reliability, and problem drinking, as measured by the test, appears to be a stable characteristic across time.

Accidents, Occupational↗
PubMed1992

Differential effects of immunisation with mycobacterial 65 kD heat shock protein on two models of autoimmunity.

The effects of preimmunisation with the 65 kD mycobacterial heat shock protein (hsp65) on 2 murine models of autoimmunity were compared. Experimental autoimmune haemolytic anaemia (AIHA) can be provoked in mice by repeated injection with rat red blood cells (RBC). In this model, preimmunisation with hsp65 10 days before induction of disease resulted in a partial, but significant, reduction in RBC-bound autoantibody levels measured by Coombs' test. However, preimmunisation with human IgG (hIgG) was associated with a similar suppressive effect. Administration of neither hsp65 nor hIgG affected the direct or indirect anti-rat agglutinin titres of mice subsequently injected with rat RBC. Injection of hsp65 or hIgG prior to induction of AIHA elicited the production of IgG antibodies against the respective immunogen, as judged by enzyme-linked immunosorbent assays. In contrast to the results in experimental AIHA, pristane-induced arthritis (PIA) was effectively prevented by preimmunisation with hsp65, but not with hIgG. It is considered that, whilst hsp65 injection may slightly reduce subsequent anti-RBC autoantibody production in AIHA by antigenic competition, such a mechanism cannot account for the substantial protection against PIA afforded by hsp65 preimmunisation. We suggest that the high, sustained production of anti-hsp65 antibodies observed in mice given hsp65 and pristane may play a role in specifically suppressing arthritogenic immune responses in PIA.

Anemia, Hemolytic, Autoimmune↗
PubMed1991

The effects of gender on diagnosis of psychological disturbance.

This research examines the effect of patient gender on the detection of psychological disturbance. In Study 1, primary-care patients were requested to complete the General Health Questionnaire (GHQ), a measure of nonpsychiatric psychological disturbance, prior to their consultation. The patient's GHQ score was compared with physician judgments about the level of disturbance in that patient (N = 1913). Although there were a similar number of GHQ high scorers among males and females, the physicians classified significantly more females than males as disturbed. The doctors classified as disturbed a larger proportion of nondisturbed women than nondisturbed men. In order to explore the behavior of recent medical graduates, Study 2 examined the detection behavior of interns in an outpatient department with 384 of their patients. The interns behaved in a similar manner to the primary-care physicians.

Adolescent↗
PubMed1991

The reliability and stability of a quantity-frequency method and a diary method of measuring alcohol consumption.

The study aimed to assess the test-retest reliability of two commonly used measures of alcohol consumption, the quantity-frequency (QF) method and the diary method, as well as the stability of scores on the two measures over time. Two methods of assessing reliability and stability were employed. The first was a traditional method based on calculation of correlation coefficients for agreement between scores on repeated measures over a short retest interval to yield test-retest reliability coefficients, and over a long retest interval to yield stability coefficients. The second method was that devised by Wiley and Wiley (1970) to differentiate the effects of reliability and stability on repeated measures over time. The two methods were applied to a sample of heavy drinkers and to a sample of light drinkers. The results indicated that both the QF and diary measures are reliable in measuring alcohol consumption of light drinkers. Both measures are less reliable for heavy drinkers. The results indicate, in addition, that drinking consumption levels of light drinkers demonstrate a high degree of stability. However, the consumption levels of heavy drinkers demonstrate less stability, especially over a long time period. Heavy drinkers significantly reduced reported levels of alcohol consumption on both measures after the first test, suggesting a regression to the mean effect or the possibility of unintended intervention effects due to repeated measurement of drinking behaviour.

Adult↗
PubMed1990

The Mortimer-Filkins test of problem drinking: a review of psychometric properties.

This paper contains a literature review of the psychometric properties of the Mortimer-Filkins test of problem drinking. The test was devised initially to identify problem drinkers from among drink-driving offenders. It was initially validated against a general population, and has since been used with worksite populations. The test demonstrates high degrees of internal-consistency reliability, test-retest reliability and concurrent validity. It has been shown to be predictive of drink-driver racidivism and the occurrence of work injuries and injury-related absences.

Alcohol Drinking↗
PubMed1990

The prevalence and sociodemographic correlates of high-risk and problem drinking at an industrial worksite.

The study of 833 employees aimed to determine the prevalence and sociodemographic correlates of high-risk and problem drinking in an industrial population. Variables measured included stressful life events, neuroticism, job satisfaction, years of service, job classification and type of shift. As measured by a 7-day retrospective diary, 12.5% of the sample were abstainers, 78.7% were light drinkers and 8.8% were high-risk drinkers. As measured by the Mortimer-Filkins test of problem drinking, 79.2% were non-problem drinkers, 15.2% were presumptive problem drinkers and 5.7% were problem drinkers. Variables that best predicted high-risk drinking were marital status, type of shift and education. Variables that best predicted problem drinking were stressful life events, marital status, education and neuroticism. The results indicate the need for a work-based intervention and provide information to identify at-risk employees and assist in the design of appropriate treatment programmes, including assistance with social and other problems.

Absenteeism↗
PubMed1990

Drug research: a comparison of ongoing research and perceived research priorities.

Since drug abuse results in high costs to the community, it is vital that research funding be allocated in a way which ensures a maximum improvement in health for the money spent. This study explores the extent to which current research into drug and alcohol abuse in Australia reflects perceived research priorities. Two hundred and seventy-four ongoing research projects into drug and alcohol misuse were identified. Researchers currently working in this area were surveyed to ascertain perceived research priorities in terms of the drug studied, the type of data collected and the setting in which the study occurred. A comparison of ongoing projects with perceived research priorities indicated considerable discrepancies. Fewer intervention projects and more studies in laboratory and clinical settings were being undertaken than was perceived as desirable by the researchers. The findings are discussed in terms of their implications for strategies for distributing research funds.

Australia↗
PubMed1990

Comparison of a quantity-frequency method and a diary method of measuring alcohol consumption.

This study compared the results obtained with two measures of alcohol consumption, a quantity-frequency (QF) method and a retrospective diary method, using a worksite sample. In order to control for the possibility of order effects, a subsample was chosen for readministration of the alcohol measures, when the order of presentation of the two measures was reversed for half of the subsample. Varying the order of presentation of the alcohol consumption items did not significantly affect the results obtained, except for an interaction effect between drinking group and order of presentation. Although subjects reported greater alcohol use on the diary than on the QF method at lower levels of consumption, the findings were reversed for higher levels of consumption. The relationship between the two measures is linear, with slope less than 1. Overall, subjects reported statistically significantly more alcohol consumption on the diary (mean [+/- SD] = 18.3 +/- 19.1 drinks) than on the QF method (mean = 16.9 +/- 19.5 drinks). The diary measure identified 20.9% of drinkers reporting consumption of more than 28 drinks per week, compared with 17.8% for the QF. However, the diary measure identified only 10.6% of drinkers reporting more than 42 drinks per week, compared with 10.2% for the QF. Consequently, the usefulness of the diary in detecting heavy drinkers appears to decrease with increasing consumption. These findings suggest the need for careful selection of alcohol consumption measures for research purposes and the need for caution in comparing the results of studies using different measures of alcohol consumption.

Accidents, Occupational↗
PubMed1989

Filtering effects in reporting work injuries.

Research efforts in the field of occupational injuries have been hampered by difficulties in ascertaining true prevalence rates. Lack of accuracy in reporting and documentation of work injuries leads to loss of information and lack of comparability of work injury statistics. The paper explores some of the factors related to loss of information about work injuries and proposes a descriptive model of the information processing system. The Filter Model describes the way in which information about a given injury proceeds through a series of levels, from true prevalence of injuries in the workplace, to prevalence as indicated by national aggregate statistics. Between each level is a "filter" or barrier that is selectively permeable, ensuring that information about some, but not all, injuries will pass through to the next level. Consequently, the type of work injury data collected at each level will differ. The Filter Model can aid in choice of appropriate level of data for research purposes, and provides a framework for investigation into the nature and extent of filtering processes within work injury reporting systems.

Accidents, Occupational↗
PubMed1988

Psychosocial factors related to parental restraint of pre-school children in motor vehicles.

While the use of safety restraints effectively reduces the risk of death or injury in accidents, many children still travel unrestrained in motor vehicles. Compulsory seat belt legislation in Australia increased rates of adult use dramatically, but did not have the same impact with children. In order to understand why levels of children's restraint use remain low, it is necessary to investigate parental factors related to use and non-use of restraints. This study assessed the rates of safety restraint use of parents and their pre-school children, and the sociodemographic, attitudinal and belief characteristics of parents which relate to children's restraint use, using the Health Belief Model as a basis for investigation. Restraint use for adults was substantially higher than for pre-school children. Children were more likely to be restrained if their parents were wearing seat belts, were married, were of high socioeconomic status, did not smoke, engaged in certain other preventive health behaviors on their children's behalf, traveled longer distances to pre-school and provided child seats for their children. In terms of the Health Belief Model, parents of restrained and unrestrained children differed in their evaluation of the "costs" and "benefits" of using restraints for their children, and in health locus of control. Parents of unrestrained children perceived the "costs" of restraint use, in terms of nuisance value, installation difficulty and financial cost, to be high. They were also less likely to believe that they could play a significant role in preventing injury to their children. Implications of these findings for safety restraint campaigns are discussed.

Adolescent↗
PubMed1988

Studies of child safety restraint use in motor vehicles--some methodological considerations.

Despite the effectiveness of safety restraints in reducing the risk of death or injury in motor vehicle accidents, many children still travel unrestrained. Two methodological issues related to child restraint studies which had not been adequately addressed were identified: firstly, the accuracy of parental self-reports of restraint use with their children; and secondly, the consistency of observational data over time. These issues were investigated in the present research. The data indicate that parents' report is inaccurate, suggesting that if self-report measures are used, there is a need to compare them with direct observational measures to obtain information on reporting bias. A single observation of a child's restraint use appears to provide an accurate reflection of restraint use on other occasions in the same setting.

Adolescent↗