54 research outputs found

    Factors influencing a mother's choice of feeding after discharge of her baby from a neonatal unit

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    Objective. To assess feeding methods chosen by mothers of babies who spent time in a neonatal unit.  Factors influencing this decision were investigated.Design. Descriptive study.Methods. Mothers were interviewed on the day they took their babies home. Basic demographic data on mother and baby were collected from the hospital records.Setting. The neonatal unit, Pelonomi Hospital, Bloemfontein from May 1996 to May 1998.Subjects. Eighty-one mothers of babies admitted to the neonatal unit.Outcome measures. At discharge 60% of mothers intended to breast-feed their babies exclusively the  next day. The mother's decision to breasHeed her baby at home was significantly associated with her decision before delivery (P = 0.0050). Otherfactors positively associated with the decision to breast-feed exclusively at home were a significantly higher birth weight of the baby (P < 0.0008) and gestational age of the baby (P < 0.0005). The only hospital practice positively associated with this decision was the frequency with which mothers saw their babies during their stay in the unit (P = 0.0153). Mothers' knowledge of how to increase breast-milk supply was very poor.Conclusions. Infants with a lower weight and gestational age, who stayed in the unit longer, were less  likely to be breast-fed after discharge from the neonatal unit. The mothers' experience in the unit did not seem to alter their choice of feeding method decided upon before delivery. This suggests that efforts to promote breast-feeding in the neonatal unit were either ineffectual or inadequate. In order to remedy this situation it is necessary to keep the motherinfant pair together (lodger mothers) and to promote  breastfeeding before and after delivery. It would also be necessary to train staff in the management of lactation problems

    Reregistration of gynaecologists in South Africa - results of a 1-year trial run

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    Objective. Evaluation of an Australian system of reregistration with recommendations for a possible future South African system.Design. Cohort descriptive study.Setting. Gynaecologists from both private and full-time academic practices.Participants. One hundred and eighty volunteers participated for a period of 1 year.Intervention. Each participant had to obtain a minimum of 25 points and an additional subminimum in at least two of the following practice-related categories: audit, continuing medical education (CME), self-study and research or tuition.Outcome measures. Compliance with the rules of the system and participants' comments.Results. Ten of the 180 volunteers withdrew from the study. Only 42% of the remaining 170 participants retumed their logbooks and a mere 32% their self-studyquestionnaires. The majority were in favour of self-study programmes or CME as future methods of reregistration.Conclusion. A future system of reregistration must be based on self-study programmes and a well-structured and relevant CME curriculum

    Polyamine uptake in the malaria parasite, Plasmodium falciparum, is dependent on the parasite's membrane potential

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    Polyamines are present at high levels in proliferating cells, including cancerous cells and protozoan parasites and the inhibition of their synthesis has been exploited in antiproliferative strategies. Inhibition of the malaria parasite’s polyamine biosynthetic pathway causes cytostatic arrest in the trophozoite stage but does not cure in vivo infections in the murine model of malaria. This is possibly due to exogenous polyamine salvage from the host, which replenishes the intracellular polyamine pool. This implies that disruption of polyamine metabolism as an antimalarial chemotherapy strategy may require targeting both polyamine biosynthesis and transport simultaneously

    Maternal deaths in Bloemfontein, South Africa -1986 - 1992

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    Objective. Determination of the maternal mortality ratio and the main causes of maternal death.Setting. Pelonomi Hospital, a tertiary care and referral hospital in Bloemfontein.Methods. Review of prospectively completed structured questionnaires on all maternal deaths from 1986 to 1992.Results. The maternal mortality ratio at our institution was 171 per 100000 live births. Haemorrhage (25%), infection (24%) and hypertensive disease (18%) were the most important causes of death. Seventy-one per cent were direct obstetric deaths and 23% indirect; in the remaining 6%, the cause was uncertain. Of all deaths, 35% were considered preventable.Conclusions. The maternal mortality ratio has decreased since our previous report for the period 1980 - 1985, and haemorrhage has replaced infection as the leading cause of death

    Expression of M. tuberculosis-induced suppressor of cytokine signaling (SOCS) 1, SOCS3, FoxP3 and secretion of IL-6 associates with differing clinical severity of tuberculosis

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    Background Appropriate immune activation of T cells and macrophages is central for the control of Mycobacterium tuberculosis infections. IFN-γ stimulated responses are lowered in tuberculosis (TB), while expression of Suppressor of Cytokine Signaling (SOCS) molecules – 1 and 3 and CD4+CD25+FoxP3+T regulatory cells is increased. Here we investigated the association of these molecules in regard to clinical severity of TB. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from patients with pulmonary TB (PTB, n = 33), extra-pulmonary TB (ETB, n = 33) and healthy endemic controls (EC, n = 15). Cases were classified as moderately advanced or far advanced PTB, and less severe or severe disseminated ETB. M. tuberculosis -stimulated IFN-γ, SOCS1, SOCS3 and FoxP3 gene expression and secretion of Th1 and Th2 cytokines was measured. Statistical analysis was performed using Mann–Whitney U, Wilcoxon Rank and Kruskal Wallis non-parametric tests. Results In un-stimulated PBMCs, IL-6 (p = 0.018) and IL-10 (p = 0.013) secretion levels were increased in PTB while IL-10 was also increased in ETB (p = 0.003), all in comparison with EC. M. tuberculosis-stimulated IL-6 (p = 0.003) was lowered in ETB as compared with EC. SOCS1 mRNA expression in M. tuberculosis stimulated PBMCs levels in moderately advanced PTB (p = 0.022), far advanced (p = 0.014) PTB, and severe ETB (p = 0.009) were raised as compared with EC. On the other hand, SOCS1 mRNA titers were reduced in less severe ETB, in comparison with severe ETB (p = 0.027) and far advanced PTB (p = 0.016). SOCS3 mRNA accumulation was reduced in far advanced PTB (p = 0.007) and FoxP3 mRNA expression was increased in less severe ETB as compared with EC (p = 0.017). Conclusions The lowered SOCS1 mRNA levels in patients with less severe extra-pulmonary TB as compared to those with more severe ETB and PTB may lead to elevated IFN-γ pathway gene expression in the latter group. As localized ETB has shown to be associated with more effective Th1 immunity and adaptive responses, this suggests a role for SOCS1 in determining disease outcome in extra-pulmonary TB

    Polyamine homoeostasis as a drug target in pathogenic protozoa: peculiarities and possibilities

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    New drugs are urgently needed for the treatment of tropical and subtropical parasitic diseases, such as African sleeping sickness, Chagas' disease, leishmaniasis and malaria. Enzymes in polyamine biosynthesis and thiol metabolism, as well as polyamine transporters, are potential drug targets within these organisms. In the present review, the current knowledge of unique properties of polyamine metabolism in these parasites is outlined. These properties include prozyme regulation of AdoMetDC (S-adenosylmethionine decarboxylase) activity in trypanosomatids, co-expression of ODC (ornithine decarboxylase) and AdoMetDC activities in a single protein in plasmodia, and formation of trypanothione, a unique compound linking polyamine and thiol metabolism in trypanosomatids. Particularly interesting features within polyamine metabolism in these parasites are highlighted for their potential in selective therapeutic strategies

    Potent Plasmodium falciparum gametocytocidal compounds identified by exploring the kinase inhibitor chemical space for dual active antimalarials

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    OBJECTIVES : Novel chemical tools to eliminate malaria should ideally target both the asexual parasites and transmissible gametocytes. Several imidazopyridazines (IMPs) and 2-aminopyridines (2-APs) have been described as potent antimalarial candidates targeting lipid kinases. However, these have not been extensively explored for stage-specific inhibition of gametocytes in Plasmodium falciparum parasites. Here we provide an in-depth evaluation of the gametocytocidal activity of compounds from these chemotypes and identify novel starting points for dual-acting antimalarials. METHODS : We evaluated compounds against P. falciparum gametocytes using several assay platforms for cross-validation and stringently identified hits that were further profiled for stage specificity, speed of action and ex vivo efficacy. Physicochemical feature extraction and chemogenomic fingerprinting were applied to explore the kinase inhibition susceptibility profile. RESULTS : We identified 34 compounds with submicromolar activity against late stage gametocytes, validated across several assay platforms. Of these, 12 were potent at 1000-fold selectivity towards the parasite over mammalian cells. Front-runner compounds targeted mature gametocytes within 48 h and blocked transmission to mosquitoes. The resultant chemogenomic fingerprint of parasites treated with the lead compounds revealed the importance of targeting kinases in asexual parasites and gametocytes. CONCLUSIONS : This study encompasses an in-depth evaluation of the kinase inhibitor space for gametocytocidal activity. Potent lead compounds have enticing dual activities and highlight the importance of targeting the kinase superfamily in malaria elimination strategies.The South African Medical Research Council (SAMRC) Self-initiated Research (to JN) and Strategic Health Initiatives Partnerships (MRC-SHIP) programmes to L.B., T.C., D.M. K.C. further acknowledges the SAMRC for funding of the extramural Drug Discovery and Development Research Unit at UCT. The SAMRC is acknowledged for funding of the UP ISMC (LMB) and WRIM (TLC) as Collaborating Centres for Malaria Research. The Council for Scientific and Industrial Research and the 3R Foundation (project 118–10) to D.M. We thank the Medicines for Malaria Venture and South African Technology Innovation Agency (TIA) for funding to K.C. (Project MMV09/0002). The University of Cape Town, University of Pretoria, and South African Research Chairs Initiative of the Department of Science and Technology, administered through the South African National Research Foundation are gratefully acknowledged for support to K.C. and L.B. (UID84627). JN was supported through an International Society for Infectious Diseases grant.https://academic.oup.com/jac2019-05-01hj2018Biochemistr

    The study of atmospheric ice-nucleating particles via microfluidically generated droplets

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    Ice-nucleating particles (INPs) play a significant role in the climate and hydrological cycle by triggering ice formation in supercooled clouds, thereby causing precipitation and affecting cloud lifetimes and their radiative properties. However, despite their importance, INP often comprise only 1 in 10³–10⁶ ambient particles, making it difficult to ascertain and predict their type, source, and concentration. The typical techniques for quantifying INP concentrations tend to be highly labour-intensive, suffer from poor time resolution, or are limited in sensitivity to low concentrations. Here, we present the application of microfluidic devices to the study of atmospheric INPs via the simple and rapid production of monodisperse droplets and their subsequent freezing on a cold stage. This device offers the potential for the testing of INP concentrations in aqueous samples with high sensitivity and high counting statistics. Various INPs were tested for validation of the platform, including mineral dust and biological species, with results compared to literature values. We also describe a methodology for sampling atmospheric aerosol in a manner that minimises sampling biases and which is compatible with the microfluidic device. We present results for INP concentrations in air sampled during two field campaigns: (1) from a rural location in the UK and (2) during the UK’s annual Bonfire Night festival. These initial results will provide a route for deployment of the microfluidic platform for the study and quantification of INPs in upcoming field campaigns around the globe, while providing a benchmark for future lab-on-a-chip-based INP studies

    Reregistration of gynaecologists in South Africa - the profession's opinion

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    Objective. Testing of the profession's opinions and attitudes with regard to a possible reregistration system.Methods. A questionnaire was sent to all the gynaecologists in South Africa to test their opinions and, attitudes with regard to reregistration.Results. After two mailings, 62,4% of the 603 gynaecologists had responded. Seventy per cent of the respondents were in private practice while 19% were in full-time academic positions. More than two-thirds (68%) of the respondents resided in a city, close to a medical school. Although 74% were in favour of the implementation of a reregistration system, only 56% were enthusiastic about it. Congress attendance and self-study programmes were the categories in which more than 85% of the respondents would be able to earn points. The general feeling was that such a system should be governed by the profession.Conclusions. The profession was in favour of a system of reregistration, but great concern was expressed at the contents of such a programme and the manner in which it would be governed

    Polyamine uptake by the intraerythrocytic malaria parasite, Plasmodium falciparum

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    Polyamines and the enzymes involved in their biosynthesis are present at high levels in rapidly proliferating cells, including cancer cells and protozoan parasites. Inhibition of polyamine biosynthesis in asexual blood-stage malaria parasites causes cytostatic arrest of parasite development under in vitro conditions, but does not cure infections in vivo. This may be due to replenishment of the parasite's intracellular polyamine pool via salvage of exogenous polyamines from the host. However, the mechanism(s) of polyamine uptake by the intraerythrocytic parasite are not well understood. In this study, the uptake of the polyamines, putrescine and spermidine, into Plasmodium falciparum parasites functionally isolated from their host erythrocyte was investigated using radioisotope flux techniques. Both putrescine and spermidine were taken up into isolated parasites via a temperature-dependent process that showed cross-competition between different polyamines. There was also some inhibition of polyamine uptake by basic amino acids. Inhibition of polyamine biosynthesis led to an increase in the total amount of putrescine and spermidine taken up from the extracellular medium. The uptake of putrescine and spermidine by isolated parasites was independent of extracellular Na+ but increased with increasing external pH. Uptake also showed a marked dependence on the parasite's membrane potential, decreasing with membrane depolarization and increasing with membrane hyperpolarization. The data are consistent with polyamines being taken up into the parasite via an electrogenic uptake process, energised by the parasite's inwardly negative membrane potential
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