The prevalence of burnout among registrars in the School of Clinical Medicine at the University of the Witwatersrand, Johannesburg, South Africa

Background. Burnout is a response to prolonged stress and consists of three elements: emotional exhaustion (EE), depersonalisation (DP), and feelings of personal accomplishment (PA). The existence of burnout in doctors is often not acknowledged but has major consequences for personal and professional life. Only limited research has been done on the prevalence of burnout among registrars in South Africa (SA).Objectives. To describe the prevalence of burnout in a cohort of SA registrars, and assess relationships between burnout and sociodemographic factors.Methods. A cross-sectional descriptive internet survey was conducted. Respondents were registrars in departments of the School of Clinical Medicine at the University of the Witwatersrand, Johannesburg, SA. The Maslach Burnout Inventory (MBI) was used to measure burnout. Relationships were assessed by the independent-samples t-test and analysis of variance.Results. A total of 585 emails were delivered to registrars, of whom 201 started the survey (response rate 34%); 170 questionnaires were analysed. The mean age of the respondents was 33 years, and the male/female ratio was 1:1.8. The mean (standard deviation) score for EE was 3.5 (1.2), for DP 2.7 (1.1) and for PA 4.1 (1.1). The overall level of burnout was 84%. None of the respondents scored low over all categories. No significant association between sociodemographics (age, sex, discipline, year in the programme and experience) and MBI dimensions was found.Conclusions. The prevalence of burnout in this study was higher than that reported in the national and international literature. Levels of DP were extremely high and are worrying, as DP affects professionalism and engagement of doctors. In keeping with the literature, no associations were found between sociodemographic factors and burnout, suggesting that the cause of burnout should be sought in the work environment. Efforts to improve autonomy in the workplace, development opportunities and promoting peer collaboration are needed to prevent burnout

Analysis of the role of leukocyte function-associated antigen-1 in activation of human influenza virus-specific T cell clones

The role of leukocyte function-associated Ag-1 (LFA-1) in intercellular adhesion is well documented. Previously, we demonstrated that the LFA-1 molecule (CD11a/CD18) can also regulate the induction of proliferation of peripheral blood T cells. In these studies, we observed opposite effects of antibodies against CD11a (LFA-1-alpha-chain) or CD18 (LFA-1-beta-chain). Here, we determined the effects of anti-CD11a and anti-CD18 mAb on proliferation of cloned influenza virus-specific T cells. Anti-CD18 mAb had similar inhibiting effects on the proliferative response of T cell clones induced by immobilized anti-CD3 mAb as it had on the response of peripheral blood T cells. In contrast to its costimulatory effect on resting peripheral blood T cells, anti-CD11a mAb did not increase the proliferation of cloned T cells. Similar differences in effects of anti-CD11a and anti-CD18 mAb were observed when proliferation of the T cell clones was induced by immobilized anti-TCR mAb. When proliferation was induced by influenza virus presented by monocytes as APC, both anti-CD11a and anti-CD18 mAb inhibited T cell proliferation. However, when EBV-transformed B cells were used as APC, neither anti-CD11a nor anti-CD18 mAb inhibited proliferation. These results demonstrate that the effects of antibodies against CD11a (LFA-1-alpha) or CD18 (LFA-1-beta) on T cell proliferation depend on 1) the stage of activation of the T cells, 2) the activation stimulus and its requirement for intercellular adhesion involving LFA-1, and 3) the type of cell used to present A

CD34(+)CD38(-) leukemic stem cell frequency to predict outcome in acute myeloid leukemia

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Tissue distribution and biochemical and functional properties of Tp55 (CD27), a novel T cell differentiation antigen

Two monoclonal antibodies (CLB-CD 27/1 and CLB-CD 27/2) were raised against a novel determinant on human T lymphocytes. One of these antibodies, CLB-CD 27/1 (clone 9F4), was grouped by the Third International Workshop and Conference on Human Leucocyte Differentiation Antigens together with three other monoclonal antibodies (VIT 14, OKT 18A, and S152) in the new cluster CD27. In this paper we show that antibodies belonging to this cluster recognize an antigen present on a large subset of peripheral T lymphocytes and most medullary thymocytes. At least two different nonoverlapping epitopes were identified with directly labeled monoclonal antibodies. Immunoprecipitation studies indicate that the target antigen of CD27 antibodies is a polypeptide of 55 kDa, which appears in the form of a disulfide-linked homodimer on the T lymphocyte membrane (Tp55). Stimulation of T cells via the T3/T cell antigen-receptor complex, with either phytohemagglutinin or CD3 monoclonal antibodies, resulted in a fivefold increase in the membrane expression of Tp55, whereas activation by phorbol myristate acetate caused a marked down-regulation. Moreover, an additional molecule of 32 kDa was precipitated from the membrane of activated but not of resting T cells. Addition of CD27 antibodies to cultures stimulated with either phytohemagglutinin or CD3 monoclonal antibody led to enhanced proliferation, whereas no effect was observed in phorbol myristate acetate or interleukin 2-stimulated cultures. The possible role of the Tp55 antigen in T cell activation is discusse

Characterization of a human plasmacytoma line

The TH line was established by bringing tumour cells from a multiple myeloma patient into suspension culture and subsequently cloning them by limiting dilution. The cultured cells show marked heterogeneity; there are ultrastructural differences between small and large TH cells, particularly with respect to the rough endoplasmatic reticulum (RER). Karyotyping revealed chromosome numbers in the triploid range, with many structural abnormalities, at the 14q32 region among others. A t(14;18) could not be demonstrated. TH was shown to have germline and a rearranged allele for kappa light chain, and only a single rearranged gene for heavy chain immunoglobulin. TH expressed PCA-1, CD9, CD28 and CD38 antigens, HLA class II, RER and kappa light chain, but few or no other antigens associated with the B-cell lineage. Light chain kappa and trace amounts of IgG3 were found intracellularly as well as in culture supernatant. The addition of IL-6 to cultures of TH increased proliferation, as well as the secretion of kappa light chain and the membrane expression of CD28 and CD38 antigens. Because TH has relatively few B cell markers on its membrane, it may be useful for the induction of monoclonal antibodies specific for human plasma cells. It also provides a model for the demonstration that IL-6 can act as a paracrine growth and differentiation factor for cells of myelomal origi

CD34CD38 leukemic stem cell frequency to predict outcome in acute myeloid leukemia.

Current risk algorithms are primarily based on pre-treatment factors and imperfectly predict outcome in acute myeloid leukemia (AML). We introduce and validate a post-treatment approach of leukemic stem cell (LSC) assessment for prediction of outcome. LSC containing CD34+CD38- fractions were measured using flow cytometry in an add-on study of the HOVON102/SAKK trial. Predefined cut-off levels were prospectively evaluated to assess CD34+CD38-LSC levels at diagnosis (n = 594), and, to identify LSC/LSC (n = 302) and MRD/MRD patients (n = 305) in bone marrow in morphological complete remission (CR). In 242 CR patients combined MRD and LSC results were available. At diagnosis the CD34CD38 LSC frequency independently predicts overall survival (OS). After achieving CR, combining LSC and MRD showed reduced survival in MRD/LSC patients (hazard ratio [HR] 3.62 for OS and 5.89 for cumulative incidence of relapse [CIR]) compared to MRD/LSC, MRD/LSC, and especially MRD/LSC patients. Moreover, in the NPM1mutant positive sub-group, prognostic value of golden standard NPM1-MRD by qPCR can be improved by addition of flow cytometric approaches. This is the first prospective study demonstrating that LSC strongly improves prognostic impact of MRD detection, identifying a patient subgroup with an almost 100% treatment failure probability, warranting consideration of LSC measurement incorporation in future AML risk schemes