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Biomedical subjects

D Bradshaw

Publications and source records attributed to D Bradshaw.

At least 19 recordsLinked to original sources
PubMed1997

Seasonal variation of suicide in South Africa.

Seasonal trends in South African suicide incidence were investigated with a view to ascertaining whether they are consistent with those in the northern hemisphere regarding: (1) the existence of the expected pattern; (2) this pattern being more pronounced for less urbanized groups; and (3) the presence of a secondary fall peak for youth and females. Log-linear modelling was performed to investigate the effect of month and relevant demographic variables on the suicide counts. The 16,389 nationally registered suicide deaths during 1980-1989 were analysed. The expected pattern, with a peak in the spring (that is, in September/October) or summer and a trough in winter, was present. This pattern was more pronounced for a sub-group that is less urbanized and for another sub-group with a relatively low standard of living. The secondary peak in autumn was not present for youth or females. In the northern hemisphere, this secondary peak has been ascribed to sociodemographic factors associated with the commencement of the academic year and (for females) bioclimatic factors associated with gender-specific biological circannual rhythms. The fact that the academic year commences in summer in South Africa indicates that the present findings are consistent with the former explanation.

Adolescent↗
PubMed1996

Trends in cervical cancer mortality in South Africa.

BACKGROUND: Cervical cancer is an important cause of death throughout the world, especially in less developed countries. Reports of trends in cervical cancer mortality from less developed countries have been limited by poor data quality and inaccurate population estimates. This paper examines trends in cervical cancer mortality in South Africa from 1949 to 1990 and discusses the impact of cytology screening on these trends. METHODS: Analysis of national mortality statistics and reconstructed population data. RESULTS: The age-standardized mortality rates for Whites declined after the mid 1960s, while that for Coloureds rose, particularly before the 1970s. These trends were affected predominantly by trends among women in the 35-64 age range. CONCLUSIONS: The pattern of mortality in successive birth cohorts for Whites is consistent with a reduction in age-specific mortality following the advent of cytological screening. The same pattern is not evident in trends for Coloureds, among whom screening has apparently had a minor impact if any at all. The apparent lack of impact of screening in those groups of women most at risk of cervical cancer lends weight to demands for the implementation of equitable and rational screening programmes for cervical cancer in South Africa and internationally.

Adult↗
PubMed1996

Activin inhibition of prostate cancer cell growth: selective actions on androgen-responsive LNCaP cells.

Prostate epithelial cell growth is under the control of both steroid and peptide factors. Human prostate cancer cell lines have been used to investigate similar agents in malignancy. Activins are dimeric peptides structurally related to transforming growth factor-beta and produced in the gonads and a wide array of extragonadal tissues. The activins act at the pituitary to regulate the synthesis and secretion of FSH. At other sites, such as bone marrow, liver, and gonads, activin may play an important role in the regulation of cell growth and differentiation. It was the purpose of the current study to determine whether activin had similar actions on prostate cancer cells, specifically the androgen-responsive LNCaP and the androgen-resistant PC-3 cell lines. Using reverse transcription-PCR, messenger RNAs for type I and type II activin receptor subunits as well as the activin-binding protein follistatin were detected in both cell lines. Activin treatment rapidly (<24 h) inhibited LNCaP, but not PC-3, cell growth. The effects of activin were evident at low levels, with a concentration of 5 ng/ml being effective at 24 h, and a concentration of 0.5 ng/ml being effective at 48 h. These results contrasted with the actions of transforming growth factor-beta, which inhibited only PC-3 cells and required a greater treatment duration (96 h) to be effective. To determine whether these prostate cancer cell lines were also producing activin, LNCaP and PC-3 cells were treated with follistatin. Again, only the LNCaP cells responded, with growth acceleration noted by 24 h. As PC-3 cell responses to activin could be independent of cell proliferation, we transfected LNCaP and PC-3 cells with a known activin-responsive promoter/reporter gene construct (p3TP-Lux) and treated cells with activin. Only LNCaP cells produced a measurable response in luciferase activity. Finally, we attempted to determine whether the PC-3 cell resistance to activin was mediated via a transferable factor. PC-3 conditioned medium was added to LNCaP cells in the absence or presence of exogenous activin and had a small, but statistically nonsignificant (P < 0.09), action to blunt the actions of activin. We conclude that activin is a potent growth inhibitor of LNCaP cell growth. Moreover, these cells also produce activin, suggesting that locally derived activin may play a role in regulating cell proliferation. Despite expressing messenger RNAs for activin receptors, PC-3 cells are resistant to activin, perhaps the result of the production of an activin-blocking factor or a defective activin response system. These cell lines will thus serve as useful models in which to further study the cellular basis of activin action.

Activin Receptors↗
PubMed1994

A national sentinel surveillance network for the measurement of ill-health in South Africa. A prerequisite for epidemiological research and health planning.

Data on births, on deaths by cause and on morbidity are essential in planning appropriate health interventions, but the scarcity of these data in South Africa is striking. Some of the limitations of national mortality and morbidity data collection systems are reviewed. In order to improve the usefulness of vital statistical information, it is proposed that active disease monitoring be introduced in a number of surveillance sites where the population has been properly enumerated. A network of these sites would routinely gather information on births and deaths by cause and on a list of conditions that are: (i) easy to identify clinically; (ii) would bring most people to the attention of health personnel; and (iii) would indicate failure of health service provision, environmental control or resource allocation. The measurement of the geographical variation of a number of conditions, coupled with geographical information on health care indicators and risk and health promotive factors in each site, would facilitate the planning of interventions in a rational manner.

Female↗
PubMed1994

Ro 32-0432, a selective and orally active inhibitor of protein kinase C prevents T-cell activation.

Several lines of circumstantial evidence support the assumption that protein kinase C (PKC) activation together with elevated levels of cytosolic Ca++ are necessary for T-cell activation and proliferation in response to a physiological stimulus, i.e., MHC class II restricted antigen presentation. By using a potent, cell-permeable and selective inhibitor of PKC, Ro 32-0432, we have tested this hypothesis. Ro 32-0432 inhibits interleukin-2 (IL-2) secretion, IL-2 receptor expression in, and proliferation of, peripheral human T-cells stimulated with phorbol ester together with phytohemagglutin or anti-CD3, but does not inhibit IL-2 induced proliferation in cells already stimulated to express IL-2 receptors. Proliferation of the influenza peptide antigen HA 307-319-specific human T-cell clone (HA27) after exposure to antigen-pulsed autologous presenting cells was also inhibited by Ro 32-0432. Oral administration of Ro 32-0432 inhibited subsequent phorbol ester-induced edema in rats demonstrating the systemic efficacy of the compound to inhibit PKC-driven responses. Induction of more physiologically T-cell driven responses such as host vs. graft responses and the secondary paw swelling in adjuvant-induced arthritis were also inhibited by Ro 32-0432. These data demonstrate the crucial role for PKC in T-cell activation and that selective p.o. bioavailable PKC inhibitors are efficacious in preventing T-cell driven chronic inflammatory responses in vivo. Inhibition of PKC represents an important mechanistic approach to prevent T-cell activation and compounds of this class may have important therapeutic applicability to chronic inflammatory and autoimmune diseases.

Administration, Oral↗
PubMed1994

Cervicography.

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Cervix Uteri↗
PubMed1993

Therapeutic potential of protein kinase C inhibitors.

The serine/threonine protein kinase, protein kinase C (PKC) is a family of closely related isoforms which are physiologically activated by diacylglycerol generated by the binding of a variety of agonists to their cellular receptors. Free fatty acids may also play a role in activating PKC. The enzyme apparently mediates a wide range of signal transduction processes in cells and, therefore, inhibitors directed selectively against PKC may have wide-ranging therapeutic potential. This review highlights the evidence that inappropriate activation of PKC occurs in a number of disease states. Such evidence, however, is often seriously flawed because it relies on the use of phorbol esters, which are potent and direct PKC activators but may not mimic the physiological triggering of the enzyme in cells, or on the use of non-selective protein kinase inhibitors such as H7 and staurosporine. A new generation of bis-indolylmaleimides, derived from the lead provided by staurosporine, shows a high degree of selectivity for PKC over closely related protein kinases and such agents may provide more appropriate tools to investigate the role of PKC in cellular processes.

Alzheimer Disease↗
PubMed1993

Isokinetic trunk strength and lifting strength measures. Differences and similarities between low-back-injured and noninjured workers.

Fifty-eight back pain patients and 21 entry-level Postal Service workers without low-back pain were evaluated using a variety of lumbar function measures. Isolated trunk strength and full lifting strength were gauged with isokinetic and isometric methods. Lumbar range-of-motion was computed using toe-touch and goniometers. Conventional clinical techniques such as toe touch and straight leg raise were effective in distinguishing back-injured from normal subjects. Isometric and isokinetic peak force and torque tests failed to show significant differences between low-back pain and job applicant groups. When compared with published norms, our job applicant group was significantly deconditioned. Our data suggest that asymptomatic, deconditioned subjects could be mistaken for back-impaired patients or symptom magnifiers.

Adult↗
PubMed1993

The prevalence and identification of risk factors for NIDDM in urban Africans in Cape Town, South Africa.

OBJECTIVE: To determine the prevalence of NIDDM and associated risk factors in urban Africans in Cape Town, South Africa. RESEARCH DESIGN AND METHODS: With a three-stage, proportional, stratified, random cluster method, we sampled 1000 Africans, > 30 yr of age, living in African residential areas in Cape Town. We assessed glucose tolerance with a 75-g oral glucose tolerance test, according to World Health Organization criteria, and obtained anthropometric and demographic data. RESULTS: The response rate was 79%. The prevalence of NIDDM was 8.0% (confidence interval 5.8-10.3%), age-adjusted to world population figures and that of impaired glucose tolerance, 7.0% (confidence interval 4.9-9.1%). Multivariate analysis indicated that increased age (odds ratio 4.18), upper-segment fat distribution (odds ratio 2.94), proportion of life spent in an urban area (odds ratio 2.32), and obesity (odds ratio 2.31) were significant independent risk factors for NIDDM. In contrast, sex, family history, alcohol intake, and physical activity were not independent risk factors. Only increased age (odds ratio 4.06) was a significant risk factor for impaired glucose tolerance. CONCLUSIONS: The prevalence of NIDDM in urban Africans in Cape Town, South Africa, is moderately high, and considerably higher than previous reports from Africa. The association of NIDDM with urbanization has important implications in view of the large-scale urbanization occurring in southern Africa.

Adult↗
PubMed1993

Pet therapy.

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Aged↗
PubMed1992

Oral, anti-inflammatory activity of a potent, selective, protein kinase C inhibitor.

The protein kinase C family of enzymes is thought to be important in mediating signal transduction. Ro 31-8830 is a novel, potent inhibitor of protein kinase C, derived from the non-selective protein kinase inhibitor staurosporine. In this paper we demonstrate the selectivity of Ro 31-8830 for protein kinase C over other protein kinases and its ability to inhibit protein kinase-C-mediated events in platelets and lymphocytes. In addition, we describe a novel system for the in vivo evaluation of inhibitors of protein kinase C, and we demonstrate the oral anti-inflammatory activity of Ro 31-8830. This finding has implications for the treatment of inflammatory disorders in the clinic.

Administration, Oral↗
PubMed1992

The impact of chronic diseases of lifestyle and their major risk factors on mortality in South Africa.

The purpose of this study was to determine the impact of chronic diseases of lifestyle on the mortality pattern of South Africans and to estimate the number of South Africans affected by major risk factors for these diseases. The proportion of deaths due to chronic diseases of lifestyle was calculated from the deaths reported to the Central Statistical Services. This group of diseases was responsible for 24.5% of deaths of all South Africans and 28.5% of those aged 35-64 years whose deaths were reported in 1988. The major causes of death contributing to these figures were cerebrovascular diseases (7.2% of all deaths and 7.9% of deaths of persons aged 35-64 years) and ischaemic heart disease (8.7% of all deaths and 9.6% of deaths of persons aged 35-64 years). The age-standardised prevalence rates for the major risk factors reported in five cross-sectional studies in different areas and groups are compared. Estimates from the reported prevalence rates, based on the size of the South African population recorded in the 1985 census figures, were calculated for the major risk factors. Overall 4.88 million South Africans smoked, the largest group of smokers being black males (2.6 million). for hypertension 5.5 million South Africans had blood pressures above 140/90 mmHg; again the largest groups were blacks (3.0 million). For hypercholesterolaemia and raised low-density lipoprotein cholesterol levels, 4.8 million and 3.1 million South Africans respectively had an increased risk for ischaemic heart disease, blacks having the lowest levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The level of mortality in South Africa in 1985--what does it tell us about health?

South African mortality data are inadequate for health planning. Estimates of mortality levels in blacks for 1985, derived using indirect demographic techniques, have provided an opportunity to analyse South African mortality in a health context. The infant mortality rate (IMR) for the population as a whole was 64/1,000 live births in 1985, which is high when compared with those of other countries. The IMR varied between population groups and was highest in blacks (males 73, females 68) and lowest in whites (males 11, females 7). Adult mortality rates, measured in terms of the chance of a 15-year-old dying before reaching the age of 60, ranged from 42.8% for black males and 29.4% for black females, to 21.8% and 11.5% for white males and females respectively. Life expectancy at birth of black males and females was 55 and 61 years respectively, while for white males and females it was 68 and 76 years respectively. Infectious diseases are a leading cause of death in blacks under 5 years of age, while trauma, poverty-related diseases and chronic diseases related to lifestyle all contribute to the high levels of adult mortality in this group. Prevention and health promotion strategies focusing on these as well as HIV/AIDS must be incorporated in a primary health care strategy to reduce premature mortality. Most importantly, it is crucial to improve the registration system that is vital to facilitate ongoing evaluation.

Adolescent↗
PubMed1991

Women doctors in South Africa. A survey of their experience and opinions.

The proportion of women entering medical school has increased at some faculties but remains at around 20% at others. A postal survey of 2,626 women on the Medical Register of the South African Medical and Dental Council was conducted to investigate aspects related to their work. Fifty-five per cent responded, with a possible bias towards older doctors and graduates from Afrikaans-language faculties. Although a significant majority (86.5%) are in practice, about one-third (33.4%) are employed part-time and nearly one-third (29.4%) reported that they had experienced an interruption of their careers for periods of more than 5 years. Major factors relating to this wastage of medical resources identified by this study were the women's dual responsibility at home and at work, the one-time joint taxation system and discrimination in the workplace, in particular with regard to housing loans. Few women find their way into specialist practice (10.8%) [corrected], although 68.2% indicated that they would have liked to specialise. Home responsibilities (48.2%) and the structure of the curriculum (31.5%) were the commonly reported difficulties experienced with further study. In addition, the lack of part-time training and the geographical location of such facilities also played a role.

Adult↗
PubMed1991

Preschool development of coloured children in Cape Town.

Developmental screening was applied during infancy to a birth cohort of 1,000 coloured infants born consecutively in Cape Town. The developmental progress of a sample of 187 children randomly selected from the cohort was followed over a period of 5 years. The value of the use of developmental screening is questioned, since 4 of the children in the cohort with major handicap had been diagnosed before the first screening was carried out and a 5th child with deafness was not detected by the screening process. Developmental milestones were similar to those studies reported in the literature. At 12 months the development correlated best with family stability. Language development at 30 months was associated with mother's education and family stability and reflected a general lag in verbal skills. By 5 years there was a good correlation between development and social indicators, particularly income and mother's education.

Black or African American↗
PubMed1991

Growth of preschool coloured children in Cape Town.

The growth of a random sample of coloured children in Cape Town was studied from birth until 5 years. At birth they were relatively light and short for gestational age. Size at birth correlated with social class. A rapid postnatal weight gain rendered them relatively overweight between 3 and 6 months. Thereafter they became lighter and shorter than the NCHS reference values and this persisted throughout the preschool period. Genetic factors, reflected by parental growth, were found to predict growth during childhood, but they were more predictive of weight and head circumference than of length. From 12 months onwards, socio-economic factors played a significant role in determining growth even after the effects of the genetic factors had been taken into account.

Black People↗
PubMed1991

Factors associated with elevated blood lead levels in inner city Cape Town children.

A cross-sectional analytical study was carried out to determine risk factors for childhood lead exposure. Blood lead levels of inner-city Sub A coloured children living in Woodstock were examined in relation to information obtained by questionnaire on environmental and social factors. The mean blood lead concentration of the population was 18 micrograms/dl. Thirteen per cent of children had blood lead levels greater than or equal to 25 micrograms/dl, the present USA 'action' level. Dusty homes and homes in a poor state of repair, over-crowding, low parental education and income, and other aspects related to family structure and socio-economic status, were associated with raised blood lead levels. It is suggested that social factors assume importance in predisposing children to lead in the environment. In particular, the over-crowded nature of the homes could have a direct bearing on the quality of the care-giving environment, providing opportunity for children's activities to go unsupervised. This could lead young children to be more exposed to accessible sources of lead associated with poor housing conditions. More attention needs to be given to examining the interaction of social and environmental factors in studies of childhood lead exposure.

Child↗