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Biomedical subjects

R Newton

Publications and source records attributed to R Newton.

At least 55 records · Page 3Linked to original sources
PubMed2001

From long-stay psychiatric hospital to Community Care Unit: evaluation at 1 year.

BACKGROUND: In the context of deinstitutionalization of psychiatric services, Community Care Units (CCUs) were developed to provide accommodation, clinical care and rehabilitation for patients discharged from the long-stay open wards of a large psychiatric hospital that was in the process of closing. CCUs are 20-bed units built in suburban locations and staffed on a 24-h basis by multidisciplinary clinical teams. METHOD: An initial group of 125 hospital patients was assessed at 1 month pre-move, 1 month post-move, and again at 1 year, on range of measures covering clinical status, personal functioning, quality of life, residential preferences, aggressive behaviour, and social networks. Staff attitudes, relative and carer perceptions and preferences, and residential environments were also assessed. RESULTS: Most of the transferred patients were still resident in their CCU at 1 year. The clearest result was that patients showed improved quality of life in relation to their living environment. Comparison of the hospital and CCU environments showed that the latter were significantly less restrictive and regimented. Most relatives and carers also preferred the CCU. On average, symptom and disability levels were little changed at 1 year. CONCLUSIONS: Our results suggest that the CCU is an appropriate form of service delivery for most long-stay hospital inpatients, but that both more and less supervised settings are also required. While symptoms and disability were little changed at 1 year, it is possible that further follow-up may detect delayed or slow changes. Given the widespread replacement of psychiatric hospitals with community-based services, the future role of the CCU needs to be reviewed.

Adult↗
PubMed2001

Development of a lipid-rich, soft plaque in rabbits, monitored by histology and intravascular ultrasound.

Lipid rich, soft plaques in the clinic are a common forerunner to occlusive thrombus formation, even with modest arterial stenosis. Animal models of atherosclerosis, obtained by various methods, do not generally allow direct in vivo evaluation of the lesion and, furthermore, cannot be examined more than once. The aim of the study was the generation of a rabbit model of atherosclerosis, with morphological characteristics similar to human lipid-rich, soft atheromatous plaques, and the evaluation of the reliability of intravascular ultrasound (IVUS) technology in the study of the development of atherosclerotic lesions in this model. Briefly, New Zealand white rabbits undergo perivascular electrical injury at both common carotid arteries, together with a 1.5% cholesterol diet for up to 90 days. The lesioned arterial segments show progressive changes, from diffuse cellular mortality, to macrophage infiltration in the media, up to the final migration of macrophages to the neointima, resulting in bulky, eccentric, macrophage and lipid-rich lesions. At IVUS, the produced lesions clearly resemble those described as 'soft plaques' in the clinical setting, with minimal calcification and reduced echo-reflectivity versus the adventitial layer. Quantitative and morphometric analysis of plaques shows a significant correlation between histological and IVUS measurements at each time point. In conclusion, vascular injury in the common carotids of rabbits generates atherosclerotic lipid-rich, soft plaques, that can be properly assessed by the IVUS methodology. The easy accessibility of the arterial lesion allows serial IVUS investigations and the direct evaluation of a number of locally or generally delivered therapeutic agents.

Analysis of Variance↗
PubMed2001

A framework for developing excellence as a clinical educator.

The current emphasis on providing quality undergraduate and postgraduate medical education has focused attention on the educational responsibilities of all doctors. There is a greater awareness of the need to train doctors as educators and courses have been set up to satisfy this need. Some courses, such as those on how to conduct appraisal, are specific to one task facing a medical educator. Other courses take a broader view and relate educational theory to practice. In this paper we describe an outcome-based approach in which competence in teaching is defined in terms of 12 learning outcomes. The framework provides a holistic approach to the roles of the teacher and supports the professionalism of teaching. Such a framework provides the basis for the development of a curriculum for teaching excellence. It helps to define important competences for different categories of teachers, communicate the areas to be addressed in a course, identify gaps in course provision, evaluate courses, assist in staff planning and allow individuals to assess their personal learning needs. The framework is presented to encourage wider debate.

Curriculum↗
PubMed2001

Human labour is associated with nuclear factor-kappaB activity which mediates cyclo-oxygenase-2 expression and is involved with the 'functional progesterone withdrawal'.

Human labour is associated with the up-regulation of prostaglandins within the uterus, synthesized via the type-2 cyclo-oxygenase enzyme (COX-2). These lead to remodelling of the fetal membranes and cervix and to stimulation of myometrial contractions. In the human, the principal source of prostaglandins is the amnion. Progesterone acts to promote myometrial quiescence, and in many species the onset of labour is preceded by withdrawal of progesterone. Humans show no systemic progesterone withdrawal, although biochemical changes within the uterus are similar to those in other species. A mutual negative interaction between the transcription factor nuclear factor (NF)-kappaB and the progesterone receptor (PR) has been reported. Using transient transfections and assays for transcriptional activation and promoter binding, we have shown that there is constitutive activity of NF-kappaB in amnion cells at the time of labour, and that COX-2 expression depends upon NF-kappaB. In cells obtained before labour, in which NF-kappaB activity is low, increasing the concentration of PR represses NF-kappaB dependent transcription, while stimulation with IL-1beta both increases NF-kappaB activity and represses PR activity. Our data suggest that human labour is associated with constitutive NF-kappaB activity within the amnion, which functions to increase the expression of COX-2 and appears to contribute to the 'functional progesterone withdrawal'.

Cells, Cultured↗
PubMed2001

Kaposi's sarcoma in South Africa.

Kaposi's sarcoma was endemic in South Africa even before the advent of the human immunodeficiency virus (HIV). Between 1988 and 1996, the incidence of Kaposi's sarcoma in South Africa has risen at least threefold and continues to increase as the HIV epidemic grows. Research from South Africa has shown that infection with human herpesvirus 8 (HHV8) is associated with Kaposi's sarcoma but not with any other major cancer site or type. In addition, the risk of Kaposi's sarcoma increases with increasing antibody titer to HHV8, but, for a given titer, the risk is greater in HIV-seropositive compared with HIV-seronegative individuals. The age- and sex-standardized seroprevalence of HHV8 in black South African hospital patients was found to be slightly more than 30%; the seroprevalence of HHV8 increased with age and was similar in men and in women. The modes of transmission of HHV8 are yet to be fully elucidated. Limited evidence exists for sexual transmission in black South African adults, but mother-to-child and person-to-person transmission in childhood is also likely. Furthermore, the seroprevalence of HHV8 decreases with increasing levels of education and is lower in whites than in blacks, suggesting that factors associated with poverty may be important determinants of transmission. Future research should focus on risk factors for Kaposi's sarcoma in HHV8-infected individuals, on determinants and mode of transmission of HHV8, and on the elucidation of the effect of primary HHV8 infection in adults and in children.

Adult↗
PubMed2001

Physical fitness qualities of professional rugby league football players: determination of positional differences.

A total of 146 professional rugby league football players, contracted to 2 teams competing in England (n = 45) and Australia (n = 101), participated in this study. All players completed the following series of physical fitness performance tests: 1 repetition maximum squat and bench press, 15- and 40-m sprint, agility run, 5-minute run for distance, 60-second sit-up, 30-second plyometric push-up, and measurement of body weight and subcutaneous skinfold (4 sites). Analysis of variance with a criterion alpha level of p < 0.05, was used to determine if any significant difference could be found when grouping players into 3 different positional categories typically identified in the sport. There were a number of significant differences with respect to test results between categories, and this was apparent for all 3 systems of categorization. On the basis of these findings, we recommend that to more efficiently structure the physical fitness training of players, the players should be grouped either according to the 2 broad positional categories of forwards or backs or according to the 4 categories of forwards, distributors, adjustables, and outside backs. Grouping players according to the 9 specific positions played on the team is not warranted.

Analysis of Variance↗
PubMed2000

Ceramide induction of COX-2 and PGE(2) in pulmonary A549 cells does not involve activation of NF-kappaB.

Ceramide is generated by the hydrolysis of membrane sphingomyelin by sphingomyelinase (SMase) and is implicated in multiple signaling pathways, including activation of NF-kappaB. As NF-kappaB is pivotal in the expression of numerous genes associated with airway inflammation and asthma, the effects of ceramide and SMase were examined in human pulmonary A549 cells. Ceramide and SMase both induced cyclooxygenase (COX)-2 protein expression and stimulated PGE(2) release. However, neither ceramide nor SMase induced NF-kappaB DNA-binding, loss of IkappaBalpha, or NF-kappaB-dependent transcription. Both ceramide and SMase were efficient inducers of the extracellular regulated kinase (ERK), but not Jun N-terminal kinase (JNK) or p38 mitogen-activated protein kinase. Since ERK is implicated in arachidonic acid availability, these data partly explain the ability of ceramide to induce PGE(2) release. However, as ERK is not required for IL-1beta-dependent induction of COX-2, the mechanism of ceramide and SMase induction of COX-2 remains unclear.

Bridged-Ring Compounds↗
PubMed2000

The spectrum of HIV-1 related cancers in South Africa.

Despite the high prevalence of infection by the Human Immunodeficiency Virus (HIV) in South Africa, information on its association with cancer is sparse. Our study was carried out to examine the relationship between HIV and a number of cancer types or sites that are common in South Africa. A total of 4,883 subjects, presenting with a cancer or cardiovascular disease at the 3 tertiary referral hospitals in Johannesburg, were interviewed and had blood tested for HIV. Odds ratios associated with HIV infection were calculated by using unconditional logistic regression models for 16 major cancer types where data was available for 50 or more patients. In the comparison group, the prevalence of HIV infection was 8.3% in males and 9.1% in females. Significant excess risks associated with HIV infection were found for Kaposi's sarcoma (OR=21.9, 95% CI=12.5-38.6), non-Hodgkin lymphoma (OR=5.0, 95%CI=2.7-9.5), vulval cancer (OR=4.8, 95%CI= 1.9-12.2) and cervical cancer (OR= 1.6, 95%CI= 1.1-2.3) but not for any of the other major cancer types examined, including Hodgkin disease, multiple myeloma and lung cancer. In Johannesburg, South Africa, HIV infection was associated with significantly increased risks of Kaposi's sarcoma, non-Hodgkin lymphoma and cancers of the cervix and the vulva. The relative risks for Kaposi's sarcoma and non-Hodgkin lymphoma associated with HIV infection were substantially lower than those found in the West.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Stimulus-specific inhibition of IL-5 by cAMP-elevating agents and IL-10 reveals differential mechanisms of action.

Interleukin-5 (IL-5) is a Th2 cytokine, which is implicated in the pathogenesis of eosinophilic diseases such as asthma. Peripheral blood mononuclear cells (PBMC), costimulated with phorbol 12-myristate 13-acetate (PMA) plus phytohemagglutinin (PHA) or activating antibodies to the CD3 and CD28 T-lymphocyte surface markers, produced similar patterns of IL-5 expression. However, in PMA + PHA-treated cells, 8-bromo-cAMP and PGE(2) did not affect IL-5 expression, whereas in CD3 + CD28-stimulated cells, almost total repression was observed. IL-10 failed to inhibit IL-5 mRNA from PMA + PHA-treated cells, yet reduced release by 40%. By contrast, IL-10 totally inhibited CD3 + CD28-induced IL-5 release and inhibited mRNA by 50-60%. These results highlight important biological differences in the induction of IL-5 by the nonspecific stimulus PMA + PHA and the more physiological CD3 + CD28 costimulation. Finally, the potential for downregulating Th2 responses by cAMP-elevating agents or IL-10 is demonstrated and a significant role for posttranscriptional mechanisms in the inhibition by IL-10 is suggested.

CD28 Antigens↗
PubMed2000

The MAP kinase inhibitors, PD098059, UO126 and SB203580, inhibit IL-1beta-dependent PGE(2) release via mechanistically distinct processes.

1. In common with human bronchial epithelial cells, pulmonary A549 cells release prostaglandin (PG) E(2) in response to pro-inflammatory cytokines. We have therefore used these cells to examine the effect of the selective mitogen activated protein (MAP) kinase inhibitors; PD098059, a mitogen activated and extracellular regulated kinase kinase (MEK) 1 inhibitor, UO126, a dual MEK1 & MEK2 inhibitor, and SB203580, a p38 MAP kinase inhibitor in the IL-1beta-dependent release of PGE(2). 2. Following IL-1beta treatment the extracellular regulated kinases (ERKs) and the p38 MAP kinases were rapidly phosphorylated. 3. PD09059, UO126 and SB203580 prevented IL-1beta-induced PGE(2) release at doses that correlated closely with published IC(50) values. Small or partial effects at the relevant doses were observed on induction of cyclo-oxygenase (COX) activity or COX-2 protein suggesting that the primary effects were at the level of arachidonate availability. 4. Neither PD098059 nor SB203580 showed any effect on IL-1beta-induced arachidonate release. We therefore speculate that the MEK1/ERK and p38 kinase cascades play a role in the functional coupling of arachidonate release to COX-2. 5. In contrast, UO126 was highly effective at inhibiting IL-1beta-dependent arachidonate release, implicating MEK2 in the activation of the PLA(2) that is involved in IL-1beta-dependent PGE(2) release. 6. We conclude that the MEK1, MEK2 and p38 MAP kinase inhibitors, PD098059, UO126 and SB203580, are highly potent in respect of inflammatory PG release. Finally, we conclude that these inhibitors act via mechanistically distinct processes, which may have anti-inflammatory benefits.

Arachidonic Acid↗
PubMed2000

The information needs and understanding of 5-10-year old children with epilepsy, asthma or diabetes.

This exploratory study compared the information needs and understanding of 25 5-10-year olds with epilepsy with those of 10 children with asthma and 10 with diabetes (of the same age range). The children were interviewed whilst attending specialist clinics by the first author and were unaware of her professional status. All the children had access to specialist nurses and their families had received literature about their condition. The interview covered five main areas: knowledge of their condition, psychological effects, medication, restrictions on lifestyle, where they obtained their information and if they had unanswered questions. The children with epilepsy had far more unanswered questions and felt excluded from discussions with doctors. They also appeared reluctant to tell their friends their diagnosis and, at such a young age, felt stigmatized by their condition. The results highlight a contrast in the understanding of children with epilepsy when compared with those with asthma or diabetes. It is proposed that if a simple biological model were used to explain epilepsy this could aid children's understanding and reduce their reluctance to disclose their diagnosis.

Asthma↗
PubMed2000

N-acetyltransferase 2 and bladder cancer: an overview and consideration of the evidence for gene-environment interaction.

Genetic polymorphism of the carcinogen metabolizing enzyme N-acetyl transferase 2 (NAT2) may influence susceptibility to bladder cancers related to smoking or to occupational exposure to arylamine carcinogens. This article reviews the results of 21 published case-control studies of NAT2 polymorphism and bladder-cancer risk, with a total of 2700 cases and 3426 controls. The published evidence suggests that NAT2 slow acetylator phenotype or genotype may be associated with a small increase in bladder cancer risk. However, given the possibility of selective publication of results from studies that found an excess risk, the current evidence is not sufficient to conclude that there is a real increase in risk. Only five of the 21 studies reported results separately for the effect of NAT2 on bladder cancer risk in smokers and non-smokers. Although the results suggest that the effect may be greater in smokers than in non-smokers, the possibility of publication bias makes these results difficult to interpret. There was insufficient evidence to assess the joint effect of NAT2 and occupational exposure to arylamines on bladder cancer risk. Even if estimates of the effect of NAT2 from published data are correct, studies with around 3000-5000 cases will be needed to confirm them.

Arylamine N-Acetyltransferase↗
PubMed2000

NF-kappaB and AP-1 are required for cyclo-oxygenase 2 gene expression in amnion epithelial cell line (WISH).

Prostaglandins are known to play an important role in human labour and are used clinically to induce labour onset. Cytokines, e.g. interleukin 1 beta (IL-1beta), are up-regulated in the amniotic fluid late in gestation and can increase prostaglandin production through the expression of cyclo-oxygenase 2 (COX-2), the prostaglandin synthetic isoform involved in human labour. We demonstrate in immortalized amnion epithelial (WISH) cells, that IL-1beta causes increased transcription of the COX-2 gene. Luciferase reporter constructs with site-directed mutagenesis of the two NF-kappaB sites and an AP-1 site in the COX-2 promoter showed reduced expression of luciferase in transient transfection studies. This suggests that the binding of transcription factors to these sites is essential for the regulation of COX-2 transcription in IL-1beta-treated WISH cells.

Amnion↗