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B-cell chronic lymphocytic leukemia (B-CLL) is characterised by the proliferation and accumulation of sIgM[sup +]/CD5[sup +] B-cells that fail to progress to the final stages of B-cell development. Despite their developmental arrest, leukemic CD5[sup +] B-cells can undergo proliferation in vitro in the presence of different activators including phorbol esters, antibodies to cell surface antigens and human cytokines. Interleukin-10 (IL-10) has recently been found to inhibit CLL B-cell function in vitro by inducing apoptosis and down-regulating expression of bcl-2. Here, we examined the effect of IL-10 on proliferation, RNA synthesis, immunoglobulin (IgM) secretion and viability of leukemic CD5[sup +] B-cells induced by activation with the phorbol ester PMA, alone or in combination with anti-Ig. IL-10 reduced PMA and PMA/anti-Ig induced proliferation and RNA synthesis by 50-80% and 15-40% respectively. Although proliferation and RNA synthesis induced by PMA/anti-Ig could be enhanced by the addition of IL-2, IL-4, IL- 13, IFN-γ or TNF-α, the presence of these cytokines failed to abrogate the IL- 10-mediated inhibition of leukemic CD5[sup +] B-cell activation. In contrast to the effects on proliferation and RNA synthesis, IL-10 did not inhibit IgM secretion, and had only a minimal effect on the viability of activated cells. Our results indicate that IL-10 inhibits proliferation of leukemic CD5[sup +] B-cells by a mechanism distinct from induction of apoptosis and support the proposal for the utilisation of IL-10 in the therapy of B-CLL. [ABSTRACT FROM AUTHOR]

Studies the in vivo binding of immunoglobulin genes via polyreactive surface immunoglobulin M abrogates progressive lymphocytosis in prolymphocytic leukemia. Effects of the infusion of K121, a mouse monoclonal antibody into a B-cell prolymphocytic patient; Phenotypic characterization of leukemic cells.

Purified leukaemic CD5+ B cells obtained from patients with B cell chronic lymphocytic leukaemia (B-CLL) undergo activation and differentiation following in vitro stimulation with optimal concentrations of the phorbol ester PMA. This paper examines the ability of exogenous cytokines, anti-Ig antibodies, or combinations of these, to enhance or replace the activation signal provided by PMA to different populations of leukaemic B cells. Proliferation induced by PMA was enhanced 2-20-fold when the cells were co-cultured with either anti-Ig, IL-2, IL-4. IL-I3. IFN-γ or TNF-α. Moreover, the combination of anti-Ig. PMA and any one of the above cytokines further enhanced proliferation. Anti-Ig and exogenous cytokines were also capable of inducing proliferation in leukaemic B cells cultured with a non-mitogenic concentration of PMA. When taken together with the finding that IL-2, IL-4, IL-13, IFN-γ and TNF-α prevent in vitro apoptosis of leukaemic CD5+ B cells, the results presented here suggest that these cytokines, in conjunction with signals delivered via sIg, may play a role in the proliferation of leukaemic B cells in vivo and, consequently, the pathogenesis of B-CLL. [ABSTRACT FROM AUTHOR]

B cell chronic lymphocytic leukaemia (B-CLL) is characterized by the proliferation and accumulation of slgM + CD5 + lymphocytes that fail to progress to the final stages of B cell development. Stimulation of unfractionated PBL from three patients with B-CLL with the phorbol ester PMA and the mitogens PHA and PWM resulted in significant increases in cell proliferation, RNA synthesis and IgM secretion when compared to unstimulated cell populations. PMA was the most potent inducer of IgM secretion and this occurred irrespective of the presence of residual T cells. PMA-induced proliferation and RNA synthesis was also independent of T cells. However, in the presence of T cells, these parameters of cellular activation were enhanced during in vitro culture. Thus, the inductive ability of PMA on CD5 + CLL B cells was independent of T cells. In contrast, activation and differentiation of the malignant CD5 + B cells into IgM-secreting cells following culture with mitogens did not occur in the absence of T cells. [ABSTRACT FROM AUTHOR]

A humoral recognition molecule that is homologous to the mammalian complement components C3, C4 and C5 has recently been identified in the Pacific hagfish, Eptatretus stouti. One function of this complement-like protein (CLP) is to opsonize foreign material for phagocytosis by hagfish leucocytes. Here, we demonstrate that CLP's opsonic activity can be abrogated by pre-incubating phagocytes with an anti-hagfish leucocyte mAb (1B1). Moreover, antigen-activated CLP can block the binding of the 1B 1 antibody to hagfish leucocytes. Flow cytometry and immunoprecipitation indicate that 1B1 recognizes a 105 kDa cell-surface, monomeric protein that is expressed exclusively on phagocytic hagfish leucocytes. It is concluded that this 105 kDa protein represents the cell surface receptor by which CLP mediates the phagocytosis of opsonized targets. [ABSTRACT FROM AUTHOR]

The value of history is, indeed, not scientific but moral … it prepares us to live more humanely in the present, and to meet rather than to foretell, the future - Carl Becker. Becker's quote reminds us of the importance of revealing and understanding historical practices in order to influence actions in the future. There are compelling reasons for uncovering this history, in particular to better inform government policy makers and health advocates, and to address the impacts of growing community expectations to 'make the punishment fit the crime'., (Copyright © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Objective: To investigate consumers' knowledge about commonly purchased over-the-counter (OTC) products containing ibuprofen., Methods: Customers buying two popular OTC ibuprofen-containing products (Nurofen ™ or Nurofen Plus ™ ) were asked to complete a short survey assessing their knowledge about the products., Results: The survey was completed by 262 respondents, most of whom were older than 50 years of age; female; well-educated; with adequate functional health literacy. The majority correctly identified ibuprofen as an active ingredient and knew the correct intervals between doses. However, almost a third couldn't correctly identify the maximum daily dose and were unaware of some contraindications. Furthermore, fewer than half recognised potential side effects. Those who hadn't completed high school were significantly less likely to seek medical advice (when required) and significantly less likely to know when it was safe to take these products., Conclusions: The gaps in consumer knowledge, especially about the maximum daily dose, contraindications and potential side effects may be placing consumers at risk of experiencing ibuprofen-related adverse events. Implications for public health: Improving consumer knowledge to address these gaps in their understanding about the safe use of popular OTC ibuprofen-containing products is an important public health concern., (© 2016 Public Health Association of Australia.)

Introduction: Two small rural towns in Australia, where medical practitioners provide primary care to the population, including emergency, anaesthetic and obstetric services, were early adopters of an innovative year-long integrated clerkship (clinical placement) designed to foster medical student skill attainment and a commitment to underserved rural communities. Primary care vocational trainees had previously trained in the region. Engaging with the university to participate in the clerkship initiative for undergraduate medical education offered the local healthcare service an opportunity to really integrate education with service. This study sought perspectives from a multidisciplinary group of stakeholders on the impact of the longitudinal integrated clerkship (LIC) on the healthcare community., Method: Three analysts independently analysed the transcripts arising from semi-structured interviews with a range of health care clinicians and managers ( N =23). Themes were identified using inductive content analysis methodology., Results: Four major themes emerged from the perspectives of a multi-professional group of participants from both towns: transforming a community of practice, realising the potential of the health service, investment in rural return, and sustainability., Conclusions: There was significant clinical exposure, skill and teaching capacity in these previously unrecognised rural placements but realising the potential of the health service needs careful management to sustain this resource. Early engagement and initial enthusiasm have produced many positive outcomes for the healthcare community, but this alone is not sufficient to sustain an increasing role for rural primary care in medical education. The study identified issues that need addressing for sustainability, namely validation, time and costs. Strategies to address these are key to continuation of LICs in small rural communities.

Objective: All senior medical students at the University of Wollongong undertake a longitudinal integrated community-based clerkship, supervised by experienced general practitioners in a regional or rural community. This study investigates the influence of the longitudinal integrated clerkship model of medical education on scholarship among preceptors in these practice communities., Design: General practitioner preceptors were interviewed after the first student cohort had completed their 38-week placements. Analysis of transcripts identified themes supporting clinical scholarship among preceptors. The entire transcript for each preceptor was analysed, permitting a quantitative determination of each theme. Quotations supporting the themes were selected., Setting: The setting was the primary health care practices supervising the longitudinal integrated clerkship medical students., Participants: Twenty-six preceptors who supervised longitudinal integrated clerkship medical students in rural and regional New South Wales participated. None had previously been involved in this model of medical education., Main Outcome Measure: The study looked for evidence of clinical scholarship among preceptors supervising students in the longitudinal medical student clerkship., Results: Thematic analysis of interview transcripts revealed evidence of clinical scholarship in regional/rural clinical medicine. The 'practice' was validated as a place where scholarship occurs, an 'academy of learning' and part of the university. About half of the preceptors believed the longitudinal integrated clerkship gave students a deeper link with the community. Two thirds of participants perceived an improved quality of care in their practice., Conclusion: Longitudinal integrated clerkships in teaching communities of practice provide the opportunity for emergence of clinical scholarship among preceptors supporting the learning needs of medical students., (© 2014 National Rural Health Alliance Inc.)

During February and March 2011, an outbreak of 26 confirmed cases of measles was reported to the Parramatta Public Health Unit (PHU) in western Sydney. This paper describes the impact of the outbreak on PHU resources. A retrospective review of information obtained from case notification forms and associated contact tracing records was carried out for each of the confirmed cases. Seven cases (27%) required hospital admission for more than 1 day and 10 (38%) cases required management within a hospital emergency department. There were no cases of encephalitis or death. The number of contacts was determined for each case as well as the number who required post-exposure prophylaxis. In total, 1,395 contacts were identified in this outbreak. Of these, 79 (5.7%) required normal human immunoglobulin and 90 (6.5%) were recommended to receive the measles-mumps-rubella vaccine. A case study detailing the PHU costs associated with the contact management of a hospitalised measles case with 75 identified contacts is also included and the estimated total cost to the PHU of containing this particular case of measles was A$2,433, with staff time comprising the major cost component. Considerable effort and resources are required to manage measles outbreaks. The total cost of this outbreak to the PHU alone is likely to have exceeded A$48,000., (This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any process without prior written permission from the Commonwealth. Requests and inquiries concerning reproduction and rights should be addressed to the Commonwealth Copyright Administration, Attorney General's Department, Robert Garran Offices, National Circuit, Barton ACT 2600 or posted at http://www.ag.gov.au/cca.)

Background: Medical students at the University of Wollongong experience continuity of patient care and clinical supervision during an innovative year-long integrated (community and hospital) clinical clerkship. In this model of clinical education, students are based in a general practice 'teaching microsystem' and participate in patient care as part of this community of practice (CoP). This study evaluates patients' perceptions of the clerkship initiative, and their perspectives on this approach to training 'much-needed' doctors in their community., Methods: Semi-structured, face-to-face, interviews with patients provided data on the clerkship model in three contexts: regional, rural and remote health care settings in Australia. Two researchers independently thematically analysed transcribed data and organised emergent categories into themes., Results: The twelve categories that emerged from the analysis of transcribed data were clustered into four themes: learning as doing; learning as shared experience; learning as belonging to a community; and learning as 'becoming'. Patients viewed the clerkship learning environment as patient- and student-centred, emphasising that the patient-student-doctor relationship triad was important in facilitating active participation by patients as well as students. Patients believed that students became central, rather than peripheral, members of the CoP during an extended placement, value-adding and improving access to patient care., Conclusions: Regional, rural and remote patients valued the long-term engagement of senior medical students in their health care team(s). A supportive CoP such as the general practice 'teaching microsystem' allowed student and patient to experience increasing participation and identity transformation over time. The extended student-patient-doctor relationship was seen as influential in this progression. Patients revealed unique insights into the longitudinal clerkship model, and believed they have an important contribution to make to medical education and new strategies addressing mal-distribution in the medical workforce.

Objective: The sustainability of community-based medical education relies on maintaining consultation quality as perceived by patients. This study aims to investigate the effect of an alternative model (parallel consultation) of teaching on patients' views of consultation quality as compared to the conventional consultation model in a general practice setting., Design: A cross-sectional questionnaire study., Setting and Participants: Patients attending a regional general practice in the Southern Highlands of New South Wales between February and May 2010, who consented to student involvement in their consultation., Main Outcome Measures: Instruments to measure 'empathy' (CARE score) and 'enablement' (PEI score) as markers for consultation quality were administered after patient consultations., Results: There was no difference in consultation length between the two groups. There was a small increase in the level of empathy experienced by patients attending parallel consultations compared to conventional consultations (P<0.05). The level of enablement did not differ between the groups. Although generally encouraging towards student involvement, patients' attitudes were significantly more positive towards students involved in the parallel consultation group (P<0.01)., Conclusions: There is no loss in consultation quality, as experienced by the patient, when using the parallel consulting model. Parallel consulting does not change the length of time a patient spends with their doctor, and patients have a positive perception of the students involved in this model of clinical teaching.

Introduction: Medical student education is perceived as utilising significant amounts of preceptors' time, negatively impacting on clinical productivity. Most studies have examined short-term student rotations in urban settings, limiting their generalisability to other settings and educational models. To test Worley and Kitto's hypothetical model which proposed a 'turning point' when students become financially beneficial, this study triangulated practice financial data with the perspectives of clinical supervisors before and after regional/rural longitudinal integrated community-based placements., Methods: Gross practice financial data were compared before and during the year-long placement. Interview data pre- and post-placement were analysed by two researchers who concurred on emergent themes and categories., Methods: This study suggested a financial 'turning point' of 1-2 months when the student became beneficial to the practice. Most preceptors (66%) perceived the longitudinal placement as financially neutral or favourable. Nineteen per cent of supervisors reported a negative financial impact, some attributing this to reduced patient throughput, inadequacy of the government teaching subsidy and/or time spent on assessment preparation. Other supervisors were unconcerned about costs, perceiving that minor financial loss was outweighed by personal satisfaction. CONCLUISONS: Senior students learning in long-term clerkships are legitimate members of regional/rural communities of practice. These students can be cost-neutral or have a small positive financial impact on the practice within a few months. Further financial impact research should include consideration of different models of supervisor teaching subsidies. The ultimate financial benefit of a model may lie in the recruitment and retention of much-needed regional and rural practitioners.

Background: Residents of nursing homes and long-term care facilities are at a higher risk of outbreaks of influenza and of serious complications of influenza than those in the community. In late July 2005, a 90-bed chronic care psycho-geriatric hospital in Sydney, Australia, reported cases of influenza-like illness (ILI) occurring amongst its residents., Methods: An investigation to confirm the outbreak, and its cause, was undertaken. Influenza vaccination levels amongst residents, and the effects of antiviral drugs used for prevention and treatment, were assessed. Oseltamivir was only given to the residents, in the form of both treatment and prophylaxis., Results: A total of 22 out of 89 residents met the clinical case definition of ILI with onset on or after 27 July 2005. This represents an attack rate of 25%. Oseltamivir was commenced on day 9 of the outbreak. Influenza B was identified in six residents as the causative agent of the outbreak. No deaths or acute hospitalization were recorded for this outbreak and there were no further reported cases after the introduction of oseltamivir. Vaccine effectiveness was 75% and the strain of influenza B isolated was well matched to that year's vaccine., Conclusions: There are few data on the use of oseltamivir in influenza B outbreaks. Early antiviral intervention appeared to curtail this outbreak of influenza B in a chronic care facility. We found high vaccine effectiveness in this frail, institutionalized population, highlighting the importance of influenza vaccination for residents of chronic care facilities.

Measles is uncommon in Australia due to effective national vaccination strategies. In mid-2003, a cluster of nine cases of measles occurred in western Sydney. The index case was a 29-year-old traveller recently returned from Nepal. The case presented to hospital and transmitted the disease to two others in the Emergency Department. Further cases resulted from both community and nosocomial transmission. The median age of cases was 24 years, with three cases in children aged under four years. Only one person had a documented history of measles vaccination, a child who had received one dose of vaccine overseas. One case was a 2-month-old infant whose mother was immune and two cases were hospital staff members. Molecular analysis of measles virus isolates from four cases revealed the same D8 genotype, a strain previously identified in Nepal. Staff vaccination strategies implemented as a result of the outbreak were poorly patronised despite nosocomial transmission. As diseases such as measles become rare it is important to thoroughly investigate any outbreaks, and to maintain a high index of suspicion of measles, particularly in travellers presenting with a rash having returned from measles-endemic areas. Genetic analysis is important in tracing the origins of an outbreak, and to confirm relatedness between cases. The highly infectious nature of measles virus also underscores the need for appropriate infection control in minimising risk of nosocomial transmission. Such policies are of increasing importance with the emergence of novel viruses or the threat of pandemic influenza.