Search PubMed⌕ Search

Biomedical subjects

C Campbell

Publications and source records attributed to C Campbell.

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

Is social capital a useful conceptual tool for exploring community level influences on HIV infection? An exploratory case study from South Africa.

This paper reports on an exploratory study investigating links between sexual health and social capital in a South African mining community. In this study, social capital is defined in terms of people's membership of voluntary community organizations (e.g. church, residents' associations, youth groups). Using biomedical and social survey data from a stratified random sample of 1,211 Carletonville residents, we tested the hypothesis that organizational members were less likely to have HIV. Multivariate analysis of variance sought to identify significant associations between nine organizational memberships and HIV infection, as well as three risk factors for infection (casual partners, condom use with casual partners and alcohol consumption). Analysis yielded a range of significant results, but findings varied across age and gender, and were not all in the hypothesized direction. For example, young men and young women who belonged to sports clubs were less likely to be HIV-positive, and young women who belonged to sports clubs were more likely to use condoms with casual partners than non-members. Amongst members of stokvels (voluntary savings clubs accompanied by social festivities), however, young men were more likely to be HIV-positive, women of all ages were more likely to have a casual partner, and both young men and young women were more likely to drink alcohol than non-members. While our exploratory study has produced sufficient evidence to justify the need for further research in this area, it also highlights that the interface between HIV infection and social capital is a complex area that defies easy generalization.

Adolescent↗
PubMed2002

The potential cardiotoxicity of antipsychotic drugs as assessed by heart rate variability.

Most antipsychotic drugs have cardiac effects as a consequence of their pharmacological actions. Recently, thioridazine has been subjected to a restricted indications notice and sertindole had its license withdrawn because of concerns about their potential cardiotoxicity. In the development of new atypical agents, heart-rate corrected QT effects are evaluated but it is unclear how predictive these are of clinically significant cardiotoxicity or sudden death. Heart rate variability (HRV) is a potential index of cardiotoxicity which has been found to be decreased following antidepressants and clozapine. We studied acute HRV changes following antipsychotic agents. Sixteen healthy male volunteers received risperidone (4 mg), olanzapine (10 mg), thioridazine (50 mg) or placebo in a randomized cross-over design. Subjective effects and psychomotor function were assayed at 2 h and both linear (summary statistics) and non-linear (scatterplot) measures of HRV were evaluated by continuous electrocardiogram recording over 10 h. Differential effects of single doses of the three antipsychotic drugs on HRV were found, and these were independent of their sedative effects. Olanzapine increased, and thioridazine decreased HRV, while risperidone had no effect. HRV is sensitive to the acute effects of antipsychotics. It may prove to be a reliable index of their potential for cardiotoxicity. Further studies in both healthy volunteers and patients on antipsychotic medication will be valuable.

Adult↗
PubMed2002

Relative risk of HIV infection among young men and women in a South African township.

The prevalence of HIV infection in Africa is substantially higher among young women than it is among young men. Biological explanations of this difference have been presented but there has been little exploration of social factors. In this paper we use data from Carletonville, South Africa to explore various social explanations for greater female infection rates. This paper reports on data from a random sample of 507 people between 13 and 24 years old. Subjects were tested for HIV, as well as other sexually transmitted infections (STIs), and answered a behavioural questionnaire. The age-prevalence of HIV infection differs between men and women with considerably higher rates of increase with age among young women. The age of sexual debut did not differ significantly between men and women (15.9 and 16.3 years, respectively) and below the age of 20 years there was no difference in the number or distribution of the number of sexual partners reported by men or women. The risk of infection per partnership was substantially higher among women than among men. Women have sexual partners who are, on average, about five years older than they are with some variation with age. Scaling the age-prevalence curve for men by the age of their sexual partners gives a curve whose shape is indistinguishable from that for women but is about 30% lower for men than for women. In terms of social explanations for HIV rates among women, the data indicates that this difference can be explained by the relative age of sexual partners, but not by other factors explored. In addressing the epidemic among young women it will be essential to deal with the social factors that lead young women to select their partners from older-age cohorts and that shape their sexual networking patterns.

Age Factors↗
PubMed2001

A role for IL-18 in neutrophil activation.

IL-18 expression and functional activity has been identified in several autoimmune and infectious diseases. To clarify the potential role of IL-18 during early innate immune responses, we have explored the capacity of IL-18 to activate neutrophils. Human peripheral blood-derived neutrophils constitutively expressed IL-18R (alpha and beta) commensurate with the capacity to rapidly respond to IL-18. IL-18 induced cytokine and chemokine release from neutrophils that was protein synthesis dependent, up-regulated CD11b expression, induced granule release, and enhanced the respiratory burst following exposure to fMLP, but had no effect upon the rate of neutrophil apoptosis. The capacity to release cytokine and chemokine was significantly enhanced in neutrophils derived from rheumatoid arthritis synovial fluid, indicating differential responsiveness to IL-18 dependent upon prior neutrophil activation in vivo. Finally, IL-18 administration promoted neutrophil accumulation in vivo, whereas IL-18 neutralization suppressed the severity of footpad inflammation following carrageenan injection. The latter was accompanied by reduction in tissue myeloperoxidase expression and suppressed local TNF-alpha production. Together, these data define a novel role for IL-18 in activating neutrophils and thereby promoting early innate immune responses.

Animals↗
PubMed2001

HIV infection among youth in a South African mining town is associated with herpes simplex virus-2 seropositivity and sexual behaviour.

OBJECTIVES: To determine the seroprevalence of HIV and herpes simplex virus-2 (HSV-2) by age and gender among young people aged 14--24 years in a South African town and to identify risk factors for HIV infection. DESIGN: A community-based, cross-sectional study was conducted on a random sample of men (n = 723) and women (n = 784) living in a township in the Carletonville district of South Africa. METHODS: Potential demographic and behavioural risk factors associated with HIV were recorded by questionnaire and biological tests were performed on serum and urine. Data analysis was performed using multivariate logistic regression. RESULTS: Among men and women the prevalence of HIV infection was 9.4 and 34.4%, respectively, and of positive HSV-2 serology was 17.0 and 53.3%, respectively. Among 24-year-old women the prevalence of HIV was 66.7% [95% confidence interval (CI), 54.6--77.3%]. HSV-2 seropositivity was a strong independent risk factor for HIV infection with odds ratios of 5.3 (95% CI, 2.7--10.3) for men and 8.4 (95% CI, 4.9--14.2) for women. There was no independent effect of age at first sex or serological markers of other sexually transmitted infections on HIV infection. CONCLUSIONS: HIV infection among young women increases rapidly after the onset of sexual activity and reaches extremely high levels by 24 years of age. These findings suggest that rates of HIV transmission from men to women are high and that HSV-2 plays a major role in the spread of HIV in this population.

Adolescent↗
PubMed2001

Mitochondrial DNA ligase function in Saccharomyces cerevisiae.

The Saccharomyces cerevisiae CDC9 gene encodes a DNA ligase protein that is targeted to both the nucleus and the mitochondria. While nuclear Cdc9p is known to play an essential role in nuclear DNA replication and repair, its role in mitochondrial DNA dynamics has not been defined. It is also unclear whether additional DNA ligase proteins are present in yeast mitochondria. To address these issues, mitochondrial DNA ligase function in S.cerevisiae was analyzed. Biochemical analysis of mitochondrial protein extracts supported the conclusion that Cdc9p was the sole DNA ligase protein present in this organelle. Inactivation of mitochondrial Cdc9p function led to a rapid decline in cellular mitochondrial DNA content in both dividing and stationary yeast cultures. In contrast, there was no apparent defect in mitochondrial DNA dynamics in a yeast strain deficient in Dnl4p (Deltadnl4). The Escherichia coli ECO:RI endonuclease was targeted to yeast mitochondria. Transient expression of this recombinant ECO:RI endonuclease led to the formation of mitochondrial DNA double-strand breaks. While wild-type and Deltadnl4 yeast were able to rapidly recover from this mitochondrial DNA damage, clones deficient in mitochondrial Cdc9p were not. These results support the conclusion that yeast rely upon a single DNA ligase, Cdc9p, to carry out mitochondrial DNA replication and recovery from both spontaneous and induced mitochondrial DNA damage.

Cell Division↗
PubMed2001

Antisense-mediated decrease in DNA ligase III expression results in reduced mitochondrial DNA integrity.

The human DNA ligase III gene encodes both nuclear and mitochondrial proteins. Abundant evidence supports the conclusion that the nuclear DNA ligase III protein plays an essential role in both base excision repair and homologous recombination. However, the role of DNA ligase III protein in mitochondrial genome dynamics has been obscure. Human tumor-derived HT1080 cells were transfected with an antisense DNA ligase III expression vector and clones with diminished levels of DNA ligase III activity identified. Mitochondrial protein extracts prepared from these clones had decreased levels of DNA ligase III relative to extracts from cells transfected with a control vector. Analysis of these clones revealed that the DNA ligase III antisense mRNA-expressing cells had reduced mtDNA content compared to control cells. In addition, the residual mtDNA present in these cells had numerous single-strand nicks that were not detected in mtDNA from control cells. Cells expressing antisense ligase III also had diminished capacity to restore their mtDNA to pre-irradiation levels following exposure to gamma-irradiation. An antisense-mediated reduction in cellular DNA ligase IV had no effect on the copy number or integrity of mtDNA. This observation, coupled with other evidence, suggests that DNA ligase IV is not present in the mitochondria and does not play a role in maintaining mtDNA integrity. We conclude that DNA ligase III is essential for the proper maintenance of mtDNA in cultured mammalian somatic cells.

DNA Damage↗
PubMed2001

Pendred syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel mutations and possible genotype-phenotype correlations.

Mutations in PDS (SLC26A4) cause both Pendred syndrome and DFNB4, two autosomal recessive disorders that share hearing loss as a common feature. The hearing loss is associated with temporal bone abnormalities, ranging from isolated enlargement of the vestibular aqueduct (dilated vestibular aqueduct, DVA) to Mondini dysplasia, a complex malformation in which the normal cochlear spiral of 2(1/2) turns is replaced by a hypoplastic coil of 1(1/2) turns. In Pendred syndrome, thyromegaly also develops, although affected persons usually remain euthyroid. We identified PDS mutations in the proband of 14 of 47 simplex families (30%) and nine of 11 multiplex families (82%) (P=0.0023). In all cases, mutations segregated with the disease state in multiplex families. Included in the 15 different PDS allele variants we found were eight novel mutations. The two most common mutations, T416P and IVS8+1G>A, were present in 22% and 30% of families, respectively. The finding of PDS mutations in five of six multiplex families with DVA (83%) and four of five multiplex families with Mondini dysplasia (80%) implies that mutations in this gene are the major genetic cause of these temporal anomalies. Comparative analysis of phenotypic and genotypic data supports the hypothesis that the type of temporal bone anomaly may depend on the specific PDS allele variant present.

Abnormalities, Multiple↗
PubMed2001

Probabilistic exposure assessment of operator and residential exposure; a Canadian regulatory perspective.

An overview of the considerations central to selection of probabilistic versus deterministic approaches to assessment of operator and residential exposure are provided. From a regulatory perspective, the decision to use probabilistic over deterministic assessments should include consideration of factors such as the nature of the populations being assessed, including the expected duration and frequency of their exposures, as well as an understanding of the toxicity endpoints that the exposure assessment will be linked to during risk assessment. In situations where there is an identifiable need to characterize variability and uncertainty and/or quantify the exposure that will represent most of the exposed population, and where there are adequate data to characterize input parameters, probabilistic assessments may be appropriate. Issues with respect to probabilistic assessments for which detailed, harmonized guidance are required are outlined. These issues are discussed within the context of a tiered approach to exposure and risk assessment.

Canada↗
PubMed2001

'I think condoms are good but, aai, I hate those things': condom use among adolescents and young people in a Southern African township.

Levels of heterosexually transmitted HIV infection are high amongst South African youth, with one recent survey reporting levels of 18.9% amongst 17-20 year olds and 43.1% amongst 21-25 year olds. In these groups levels of knowledge about HIV are high, but perceived vulnerability and reported condom use are low. Much existing research into youth HIV in developing countries relies on survey measures which use individual knowledge, attitudes and reported behaviour as variables in seeking to explain HIV transmission amongst this group. This paper reports on a focus group study that seeks to complement existing individual-level quantitative findings with qualitative findings highlighting community and social factors that hinder condom use amongst youth in the township of Khutsong, near Carletonville. Study informants comprised 44 young women and men in the 13-25 year age group. Data analysis highlighted six factors hindering condom use: lack of perceived risk; peer norms; condom availability; adult attitudes to condoms and sex; gendered power relations and the economic context of adolescent sexuality. Informants did not constitute a homogenous group in terms of their understandings of sexuality. While there was clear evidence for the existence of dominant social norms which place young peoples' sexual health at risk, there was also evidence that many young people are self-consciously critical of the norms that govern their sexual behaviour, despite going along with them, and that they are aware of the way in which peer and gender pressures place their health at risk. There was also evidence that a minority of youth actively challenge dominant norms and behave in counter-normative and health-enhancing ways. The actively contested nature of dominant sexual norms provides a fertile starting point for peer education programmes that seek to provide the context for the collective negotiation of alternative sexual norms that do not endanger young peoples' sexual health.

Adolescent↗
PubMed2001

Invasive procedures carried out in conscious children: contrast between North American and European paediatric oncology centres.

AIM: To define practice in managing repeated invasive procedures in selected paediatric oncology centres in North America and Europe, especially the United Kingdom; to define and contrast concerns that shape policy making, and to contrast practice, particularly regarding procedures performed on conscious patients. METHODS: Postal survey: 118 centres of the Pediatric Oncology Group and the United Kingdom Children's Cancer Study Group received questionnaires. RESULTS: 68 questionnaires (58%) were returned (52 from North America, 12 from Europe). For all procedures, North American centres tended to use less effective techniques than European, especially for bone marrow procedures. Many North American centres reported performing these on conscious patients on at least three quarters (25%) or half (30%) the occasions. In contrast, corresponding figures for the European centres were 6% and 0%. CONCLUSIONS: Many bone marrow procedures are still carried out in the conscious patient despite the safety and effectiveness of modern anaesthetic and deep sedation techniques. There appears to be a greater reluctance to offer these to patients in North American centres than in European ones. This may reflect a misperception that the risks of adverse effects are high. Several non-pharmacological techniques are used, but they remain uncommon.

Anesthesia, General↗
PubMed2001

Born again bone: tissue engineering for bone repair.

Destruction of bone tissue due to disease and inefficient bone healing after traumatic injury may be addressed by tissue engineering techniques. Growth factor, cytokine protein, and gene therapies will be developed, which, in conjunction with suitable carriers, will regenerate missing bone or help in cases of defective healing.

Animals↗
PubMed2001

The differential effects of chlorpromazine and haloperidol on latent inhibition in healthy volunteers.

Latent inhibition (LI) is a measure of reduced learning about a stimulus to which there has been prior exposure without any consequence. It therefore requires a comparison between a pre-exposed (PE) and a non-pre-exposed (NPE) condition. Since, in animals, LI is disrupted by amphetamines and enhanced by antipsychotics, LI disruption has been proposed as a measure of the characteristic attentional deficit in schizophrenia: the inability to ignore irrelevant stimuli. The findings in humans are, however, inconsistent. In particular, a recent investigation suggested that since haloperidol disrupted LI in healthy volunteers, and LI was normal in non-medicated patients with schizophrenia, the previous findings in schizophrenic patients were entirely due to the negative effects of their medication on LI (Williams et al., 1998). We conducted two studies of antipsychotic drug effects on auditory LI using a within-subject, parallel group design in healthy volunteers. In the first of these, single doses of haloperidol (1 mg. i.v.) were compared with paroxetine (20 mg p.o.) and placebo, and in the second, chlorpromazine (100 mg p.o.) was compared with lorazepam (2 mg. p.o.) and placebo. Eye movements, neuropsychological test performance (spatial working memory (SWM), Tower of London and intra/extra dimensional shift, from the CANTAB test battery) and visual analogue rating scales, were also included as other measures of attention and frontal lobe function. Haloperidol was associated with a non-significant reduction in LI scores, and dysphoria/akathisia (Barnes Akathisia Rating Scale) in three-quarters of the subjects. The LI finding may be explained by increased distractibility which was indicated by an increase in antisaccade directional errors in this group. In contrast, LI was significantly increased by chlorpromazine but not by an equally sedative dose of lorazepam (both drugs causing marked decreases in peak saccadic velocity). Paroxetine had no effect on LI, eye movements or CANTAB neuropsychological test performance. Haloperidol was associated with impaired SWM, which correlated with the degree of dysphoria/akathisia, but no other drug effects on CANTAB measures were detected. We conclude that the effect of antipsychotics on LI is both modality and pharmacologically dependent and that further research using a wider range of antipsychotic compounds is necessary to clarify the cognitive effects of these drugs, and to determine whether there are important differences between them.

Acoustic Stimulation↗