Endogenous and exogenously-induced immunomodulation of tumour-host responsiveness

In spite of the availability of multiple effector mechanisms of the immune system to combat tumour growth and metastases, their impairment frequently accompanies the appearance of cancer. Factors contributing to this impairment may be related to properties of the host and/or the tumour itself and may be with respect to their origin -endogenous or exogenour. Based on the unique biological behavior of prostate cancer (PCa), and its apparent escape from immune surveillance in the presence of tumour immuno genicity, continuing investigation of endogenous and exogenous factors thought to be relevant to its pathogenesis have been made. For this purpose further studies of the suggested role of human seminal plasma (SePl) and the synthetic oestrogen, diethylstiboestrol (DES), as representative endogenous and exogenous immunomodulatory factors (IMF) of tumour-host responsiveness, together with evaluation of human prostatic tissue extracts and leuprolide (the luteinizing-hormone-releasing-hormone proposed as an alternate to DES therapy) have been made by evaluating their effect on the lytic activity of natural killer (NK) cells. SePl and prostate extracts significantly suppressed NK cell lysis. Physicochemical studies suggest SePl and prostate IMF to be associated with high and low molecular weight macromolecules; and implicate the participation of transglutaminase and prostaglandins. Comparative study of therapeutic levels of DES vs. leuprolide on NK cell lysis demonstrated significant suppression by DES vs. a negligible effect of leuprolide. Metastases are highly prevalent in PCa, and contribute significantly to its morbidity and mortality. Further knowledge of the range of effects of endogenous and exogenous IMF on effector mechanisms of tumour-host responsiveness, to include suppression of NK cells, and elucidation of their nature, may contribute toward our understanding of the unique biological behavior of tumours of the prostate, in addition to improvement in their clinical management.

Harmonization guidelines for HLA-peptide multimer assays derived from results of a large scale international proficiency panel of the Cancer Vaccine Consortium.

PURPOSE: The Cancer Vaccine Consortium of the Cancer Research Institute (CVC-CRI) conducted a multicenter HLA-peptide multimer proficiency panel (MPP) with a group of 27 laboratories to assess the performance of the assay. EXPERIMENTAL DESIGN: Participants used commercially available HLA-peptide multimers and a well characterized common source of peripheral blood mononuclear cells (PBMC). The frequency of CD8+ T cells specific for two HLA-A2-restricted model antigens was measured by flow cytometry. The panel design allowed for participants to use their preferred staining reagents and locally established protocols for both cell labeling, data acquisition and analysis. RESULTS: We observed significant differences in both the performance characteristics of the assay and the reported frequencies of specific T cells across laboratories. These results emphasize the need to identify the critical variables important for the observed variability to allow for harmonization of the technique across institutions. CONCLUSIONS: Three key recommendations emerged that would likely reduce assay variability and thus move toward harmonizing of this assay. (1) Use of more than two colors for the staining (2) collect at least 100,000 CD8 T cells, and (3) use of a background control sample to appropriately set the analytical gates. We also provide more insight into the limitations of the assay and identified additional protocol steps that potentially impact the quality of data generated and therefore should serve as primary targets for systematic analysis in future panels. Finally, we propose initial guidelines for harmonizing assay performance which include the introduction of standard operating protocols to allow for adequate training of technical staff and auditing of test analysis procedures.

The dermal leishmaniases of Brazil, with special reference to the eco-epidemiology of the disease in Amazonia

Six species of Leishmania are at present known to cause cutaneous and/or mucocutaneous leishamniasis in Brazil, and they are all to be found in the Amazon region of this country. The eco-epidemiology of each is discussed, with the observation that the Amazonian leishmaniases are all zoonoses, with their source in silvatic mammals and phlebotomine sandfly vectors. With man's destruction of the natural forest in southern Brazil, some sandfly species have survived by adapting to a peridomestic or domiciliary habitat in rural areas. Some domestic animals, such as dogs and equines are seemingly now involved in the epidemiology of the disease. No such process has yet been reported in the Amazon region, but may well take place with the continuing devastation of its forest.

Neues aus Diagnostik und Therapie der spinalen Erkrankungen [Novel aspects of diagnostics and therapy of spinal cord diseases].

BACKGROUND: Both non-traumatic and traumatic spinal cord injuries have in common that a relatively minor structural lesion can cause profound sensorimotor and autonomous dysfunction. Besides treating the cause of the spinal cord injury the main goal is to restore lost function as far as possible. AIM: This article provides an overview of current innovative diagnostic (imaging) and therapeutic approaches (neurorehabilitation and neuroregeneration) aiming for recovery of function after non-traumatic and traumatic spinal cord injuries. MATERIAL AND METHODS: An analysis of the current scientific literature regarding imaging, rehabilitation and rehabilitation strategies in spinal cord disease was carried out. RESULTS: Novel magnetic resonance imaging (MRI) based techniques (e.g. diffusion-weighted MRI and functional MRI) allow visualization of structural reorganization and specific neural activity in the spinal cord. Robotics-driven rehabilitative measures provide training of sensorimotor function in a targeted fashion, which can even be continued in the homecare setting. From a preclinical point of view, defined stem cell transplantation approaches allow for the first time robust structural repair of the injured spinal cord. CONCLUSION: Besides well-established neurological and functional scores, MRI techniques offer the unique opportunity to provide robust and reliable "biomarkers" for restorative therapeutic interventions. Function-oriented robotics-based rehabilitative interventions alone or in combination with stem cell based therapies represent promising approaches to achieve substantial functional recovery, which go beyond current rehabilitative treatment efforts.

Study of Schistosoma mansoni isolates from patients with failure of treatment with oxamniquine

After three successive treatments with oxamniquine the continuing elimination of Schistosoma mansoni eggs was observed in patients, who came from various regions of Brazil, with different clinical forms of schistosomiasis. The objective of the present study was to determine the experimental behaviour of five different S. mansoni isolates in Swiss Webster mice that were submitted to treatment with the same drug. The experimental group with failure of treatment showed higher mean number of surviving male worms when it was compared to the group without failure of treatment. These date suggest the possibility of resistance to oxamniquine.

Effective Utilisation of Professional Skills of Nurses and Midwives

The Working Group recommends that the grade of Health Care Assistant/Maternity Health Care Assistant be introduced as a member of the healthcare team to assist and support the nursing and midwifery function. Chapter two of the report explores the complementary roles of health care assistants and nurses and midwives. Chapter three examines issues related to delegation and integration of the health care assistant to the care team. Chapter four makes recommendations related to the education and training of health care assistants. The Working Groupâ?Ts recommendations are underpinned by a comprehensive literature review Download the Report here

Speech by Mr. Micheál Martin TD – Meeting The Challenges Of Cultural Diversity In The Irish Healthcare Sector

It gives me great pleasure to accept the invitation to address this conference on “Meeting the Challenges of Cultural Diversity in the Irish Healthcare Sector” which is being organised by the Irish Health Services Management Institute in partnership with the National Consultative Committee on Racism and Interculturalism. The conference provides an important opportunity to develop our knowledge and understanding of the issues surrounding cultural diversity in the health sector from the twin perspectives of patients and staff. Cultural diversity has over recent years become an increasingly visible aspect of Irish society bringing with it both opportunities and challenges. It holds out great possibilities for the enrichment of all who live in Ireland but it also challenges us to adapt creatively to the changes required to realise this potential and to ensure that the experience is a positive one for all concerned but particularly for those in the minority ethnic groups. In the last number of years in particular, the focus has tended to be on people coming to this country either as refugees, asylum seekers or economic migrants. Government figures estimate that as many as 340,000 immigrants are expected in the next six years. However ethnic and cultural diversity are not new phenomena in Ireland. Travellers have a long history as an indigenous minority group in Ireland with a strong culture and identity of their own. The changing experience and dynamics of their relationship with the wider society and its institutions over time can, I think, provide some valuable lessons for us as we seek to address the more numerous and complex issues of cultural diversity which have arisen for us in the last decade. Turning more specifically to the health sector which is the focus of this conference, culture and identity have particular relevance to health service policy and provision in that The first requirement is that we in the health service acknowledge cultural diversity and the differences in behaviours and in the less obvious areas of values and beliefs that this often implies. Only by acknowledging these differences in a respectful way and informing ourselves of them can we address them. Our equality legislation – The Employment Equality Act, 1998 and the Equal Status Act, 2000 – prohibits discrimination on nine grounds including race and membership of the Traveller community. The Equal Status Act prohibits discrimination on an individual basis in relation to the nine grounds while for groups it provides for the promotion of equality of opportunity. The Act applies to the provision of services including health services. I will speak first about cultural diversity in relation to the patient. In this respect it is worth mentioning that the recognition of cultural diversity and appropriate responses to it were issues which were strongly emphasised in the public consultation process which we held earlier this year in the context of developing National Anti-Poverty targets for the health sector and also our new national health strategy. Awareness and sensitivity training for staff is a key requirement for adapting to a culturally diverse patient population. The focus of this training should be the development of the knowledge and skills to provide services sensitive to cultural diversity. Such training can often be most effectively delivered in partnership with members of the minority groups themselves. I am aware that the Traveller community, for example, is involved in in-service training for health care workers. I am also aware that the National Consultative Committee on Racism and Interculturalism has been involved in training with the Eastern Regional Health Authority. We need to have more such initiatives. A step beyond the sensitivity training for existing staff is the training of members of the minority communities themselves as workers in our health services. Again the Traveller community has set an example in this area with its Primary Health Care Project for Travellers. The Primary Health Care for Travellers Project was established in 1994 as a joint partnership initiative with the Eastern Health Board and Pavee Point, with ongoing technical assistance being provided from the Department of Community Health and General Practice, Trinity College, Dublin. This project was the first of its kind in the country and has facilitated The project included a training course which concentrated on skills development, capacity building and the empowerment of Travellers. This confidence and skill allowed the Community Health Workers to go out and conduct a baseline survey to identify and articulate Travellers’ health needs. This was the first time that Travellers were involved in this process; in the past their needs were assumed. The results of the survey were fed back to the community and they prioritised their needs and suggested changes to the health services which would facilitate their access and utilisation. Ongoing monitoring and data collection demonstrates a big improvement in levels of satisfaction and uptake and ulitisation of health services by Travellers in the pilot area. This Primary Health Care for Travellers initiative is being replicated in three other areas around the country and funding has been approved for a further 9 new projects. This pilot project was the recipient of a WHO 50th anniversary commemorative award in 1998. The project is developing as a model of good practice which could inspire further initiatives of this type for other minority groups. Access to information has been identified in numerous consultative processes as a key factor in enabling people to take a proactive approach to managing their own health and that of their families and in facilitating their access to health services. Honouring our commitment to equity in these areas requires that information is provided in culturally appropriate formats. The National Health Promotion Strategy 2000-2005, for example, recognises that there exists within our society many groups with different requirements which need to be identified and accommodated when planning and implementing health promotion interventions. These groups include Travellers, refugees and asylum seekers, people with intellectual, physical or sensory disability and the gay and lesbian community. The Strategy acknowledges the challenge involved in being sensitive to the potential differences in patterns of poor health among these different groups. The Strategic aim is to promote the physical, mental and social well-being of individuals from these groups. The objective of the Strategy on these issues are: While our long term aim may be to mainstream responses so that our health services is truly multicultural, we must recognise the need at this point in time for very specific focused responses particularly for groups with poor health status such as Travellers and also for refugees and asylum seekers. In the case of refugees and asylum seekers examples of targeted services are screening for communicable diseases – offered on a voluntary basis – and psychological support services for those who have suffered trauma before coming here. The two approaches of targeting and mainstreaming are not mutually exclusive. A combination of both is required at this point in time but the balance between them must be kept under constant review in the light of changing needs. A major requirement if we are to meet the challenge of cultural diversity is an appropriate data and research base. I think it is important that we build up our information and research data base in partnership with the minority groups themselves. We must establish what the health needs of diverse groups are; we must monitor uptake of services and how well we are responding to needs and we must monitor outcomes and health status. We must also examine the impact of the policies in other sectors on the health of minority groups. The National Health Information Strategy, currently being developed, and the recently published National Strategy for Health Research – Making Knowledge Work for Health provide important frameworks within which we can improve our data and research base. A culturally diverse health sector workforce – challenges and opportunities The Irish health service can benefit greatly from successful international recruitment. There has been a strong non-national representation amongst the medical profession for more than 30 years. More recently there have been significant increases in other categories of health service workers from overseas. The Department recognises the enormous value that overseas recruitment brings over a wide range of services and supports the development of effective and appropriate recruitment strategies in partnership with health service employers. These changes have made cultural diversity an important issue for all health service organisations. Diversity in the workplace is primarily about creating a culture that seeks, respects, values and harnesses difference. This includes all the differences that when added together make each person unique. So instead of the focus being on particular groups, diversity is about all of us. Change is not about helping “them” to join “us” but about critically looking at “us” and rooting out all aspects of our culture that inappropriately exclude people and prevent us from being inclusive in the way we relate to employees, potential employees and clients of the health service. International recruitment benefits consumers, Irish employees and the overseas personnel alike. Regardless of whether they are employed by the health service, members of minority groups will be clients of our service and consequently we need to be flexible in order to accommodate different cultural needs. For staff, we recognise that coming from other cultures can be a difficult transition. Consequently health service employers have made strong efforts to assist them during this period. Many organisations provide induction courses, religious facilities (such as prayer rooms) and help in finding suitable accommodation. The Health Service Employers Agency (HSEA) is developing an equal opportunities/diversity strategy and action plans as well as training programmes to support their implementation, to ensure that all health service employment policies and practices promote the equality/diversity agenda to continue the development of a culturally diverse health service. The management of this new environment is extremely important for the health service as it offers an opportunity to go beyond set legal requirements and to strive for an acceptance and nurturing of cultural differences. Workforce cultural diversity affords us the opportunity to learn from the working practices and perspectives of others by allowing personnel to present their ideas and experience through teamwork, partnership structures and other appropriate fora, leading to further improvement in the services we provide. It is important to ensure that both personnel units and line managers communicate directly with their staff and demonstrate by their actions that they intend to create an inclusive work place which doesn´t demand that minority staff fit. Contented, valued employees who feel that there is a place for them in the organisation will deliver a high quality health service. Your conference here today has two laudable aims – to heighten awareness and assist health care staff to work effectively with their colleagues from different cultural backgrounds and to gain a greater understanding of the diverse needs of patients from minority ethnic backgrounds. There is a synergy in these aims and in the tasks to which they give rise in the management of our health service. The creative adaptations required for one have the potential to feed into the other. I would like to commend both organisations which are hosting this conference for their initiative in making this event happen, particularly at this time – Racism in the Workplace Week. I look forward very much to hearing the outcome of your deliberations. Thank you.

Age does not hamper the response to pulmonary rehabilitation of COPD patients

Pulmonary rehabilitation (PR) improves health status and exercise tolerance, but not respiratory function in patients with chronic obstructive pulmonary disease (COPD). The objective of the study was to identify predictors of improvement in the 6-min walked distance (6'WD) in elderly COPD patients after PR. Methods: this was a prospective observational study performed in an ambulatory rehabilitation setting. The authors enrolled 74 patients aged 65-83 years (mean: 74.2, SD: 4.4) with stable COPD in GOLD stage 3-4. About half (45.6%) of them had a basal O2 saturation of 90% or less. After a baseline multi-dimensional assessment, patients underwent a 20-session rehabilitation cycle including training of the upper and lower extremities, and respiratory exercises, along with education sessions.

Impact of a smoking ban in public places: a rapid assessment in the Seychelles.

Background We assessed the impact of a smoking ban in hospitality venues in the Seychelles 9 months after legislation was implemented. Methods Survey officers observed compliance with the smoking ban in 38 most popular hospitality venues and administered a structured questionnaire to two customers, two workers and one manager in each venue. Results Virtually no customers or workers were seen smoking in the indoor premises. Patrons, workers and managers largely supported the ban. The personnel of the hospitality venues reported that most smokers had no difficulty refraining from smoking. However, a third of workers did not systematically request customers to stop smoking and half of them did not report adequate training. Workers reported improved health. No substantial change in the number of customers was noted. Conclusion A ban on public smoking was generally well implemented in hospitality venues but some less than optimal findings suggest the need for adequate training of workers and strengthened enforcement measures. The simple and inexpensive methodology used in this rapid survey may be a useful approach to evaluate the implementation and impact of clean air policy in low and middle-income countries.

The use of biodiversity as source of new chemical entities against defined molecular targets for treatment of malaria, tuberculosis, and T-cell mediated diseases: a review

The modern approach to the development of new chemical entities against complex diseases, especially the neglected endemic diseases such as tuberculosis and malaria, is based on the use of defined molecular targets. Among the advantages, this approach allows (i) the search and identification of lead compounds with defined molecular mechanisms against a defined target (e.g. enzymes from defined pathways), (ii) the analysis of a great number of compounds with a favorable cost/benefit ratio, (iii) the development even in the initial stages of compounds with selective toxicity (the fundamental principle of chemotherapy), (iv) the evaluation of plant extracts as well as of pure substances. The current use of such technology, unfortunately, is concentrated in developed countries, especially in the big pharma. This fact contributes in a significant way to hamper the development of innovative new compounds to treat neglected diseases. The large biodiversity within the territory of Brazil puts the country in a strategic position to develop the rational and sustained exploration of new metabolites of therapeutic value. The extension of the country covers a wide range of climates, soil types, and altitudes, providing a unique set of selective pressures for the adaptation of plant life in these scenarios. Chemical diversity is also driven by these forces, in an attempt to best fit the plant communities to the particular abiotic stresses, fauna, and microbes that co-exist with them. Certain areas of vegetation (Amazonian Forest, Atlantic Forest, Araucaria Forest, Cerrado-Brazilian Savanna, and Caatinga) are rich in species and types of environments to be used to search for natural compounds active against tuberculosis, malaria, and chronic-degenerative diseases. The present review describes some strategies to search for natural compounds, whose choice can be based on ethnobotanical and chemotaxonomical studies, and screen for their ability to bind to immobilized drug targets and to inhibit their activities. Molecular cloning, gene knockout, protein expression and purification, N-terminal sequencing, and mass spectrometry are the methods of choice to provide homogeneous drug targets for immobilization by optimized chemical reactions. Plant extract preparations, fractionation of promising plant extracts, propagation protocols and definition of in planta studies to maximize product yield of plant species producing active compounds have to be performed to provide a continuing supply of bioactive materials. Chemical characterization of natural compounds, determination of mode of action by kinetics and other spectroscopic methods (MS, X-ray, NMR), as well as in vitro and in vivo biological assays, chemical derivatization, and structure-activity relationships have to be carried out to provide a thorough knowledge on which to base the search for natural compounds or their derivatives with biological activity.

Effects of pyrimethamine-sulphadoxine, chloroquine plus chlorpheniramine, and amodiaquine plus pyrimethamine-sulphadoxine on gametocytes during and after treatment of acute, uncomplicated malaria in children

The effects of pyrimethamine-sulphadoxine (PS), chloroquine plus chlorpheniramine, a H1 receptor antagonist that reverses chloroquine resistance in Plasmodium falciparum in vitro and in vivo (CQCP), and amodiaquine plus pyrimethamine-sulphadoxine (AQPS) on gametocyte production were evaluated in 157 children with acute, symptomatic, uncomplicated falciparum malaria who were treated with these drugs. PS was significantly less effective than CQCP or AQPS at clearing asexual parasitaemia or other symptoms of malaria. Gametocyte carriage on days 3, 7, and 14 were significantly higher in those treated with PS. The ratio of the density (per µl blood) of peripheral young gametocyte (PYG), that is, < stage III to peripheral mature gametocyte (PMG), that is, stage IV and V, an index of continuing generation of gametocytes, rose to 1 by day 7 of treatment in those treated with PS, but remained consistently below 1 in the other treatment groups. PYG-PMG density ratio increased significantly from day 0-14 in those treated with PS and CQCP (chi2 = 76, P = 0.000001 and chi2 = 42.2, P = 0.00001, respectively) but decreased significantly in those treated with AQPS (chi2 = 53.2, P = 0.000001). Both PS-sensitive and -resistant infections generated PYG (18 of 29 vs 13 of 20, chi2 = 0.04, P = 0.93) but PYG was present only in those with resistant response to CQCP. Combination of PS with amodiaquine (AQ), that is, (AQPS) resulted in less production of PYG, but in this setting, PYG was not indicative of response to AQPS. These data indicate that PS enhanced production or release of young gametocytes when used alone, but generated less young gametocytes when used in combination with AQ. PYG may be used as an indicator of response to CQCP but not PS or PS-based combination drugs.

Multimedia materials for education, training, and advocacy in international health: experiences with the Schistosomiasis Control Initiative CD-ROM

We describe an innovative use of multimedia materials to support training and advocacy within a schistosomiasis control programme. The Schistosomiasis Control Initiative (SCI) at Imperial College London works with selected sub-Saharan African countries to develop schistosomiasis control programmes. Two elements of the SCI programme were supported by multimedia materials developed at the Wellcome Trust in collaboration with the SCI: (1) training of programme managers, district health officers, and those delivering practical elements of the programme; and (2) advocacy targeted at decision-makers and donors. Evaluation of the materials revealed high reported ratings for both user satisfaction and impact from use of the product. From this experience we draw out several general messages about development of multimedia materials and how these will play a growing future role in promoting training within international health.

Postmortem circulation: a new model for testing endovascular devices and training clinicians in their use.

The development of new medical devices, such as aortic valves, requires numerous preliminary studies on animals and training of personnel on cadavers before the devices can be used in patients. Postmortem circulation, a technique used for postmortem angiography, allows the vascular system to be reperfused in a way similar to that in living persons. This technique is used for postmortem investigations to visualize the human vascular system and to make vascular diagnoses. Specific material for reperfusing a human body was developed recently. Our aim was to investigate whether postmortem circulation that imitates in vivo conditions allows for the testing of medical materials on cadavers. We did this by delivering an aortic valve using minimally invasive methods. Postmortem circulation was established in eight corpses to recreate an environment as close as possible to in vivo conditions. Mobile fluoroscopy and a percutaneous catheterization technique were used to deliver the material to the correct place. Once the valve was implanted, the heart and primary vessels were extracted to confirm its position. Postmortem circulation proved to be essential in several of the cadavers because it helped the clinicians to deliver the material and improve their implantation techniques. Due to the intravascular circulation, sites with substantial arteriosclerotic stenosis could be bypassed, which would have been impossible without perfusion. Although originally developed for postmortem investigations, this reperfusion technique could be useful for testing new medical devices intended for living patients.

Paid employment and the changing system of gender relations: a cross-national comparison

Equality with men in the world of paid work has been a major feminist objective. Given that work in the `public' sphere has historically been shaped on the assumption that the `worker' will be male, then national employment systems which facilitate masculine employment patterns (i.e. full-time work and unbroken employment careers) might be expected to be more likely to generate gender equality. This paper compares women's employment in France (where `masculine' careers for women are common) and Britain (where part-time work and broken employment careers are more likely) at the macro, meso (occupational), and micro (individual) levels. The two occupations studied are finance and pharmacy. The evidence presented suggests that there are considerable similarities between women in the two countries at the occupational and individual level, despite national variations. In the light of this evidence, structural and individual explanations of women's employment behaviour are examined, and the continuing significance of structural constraint on the patterning of gender relations is emphasised.

Surveillance, health promotion and control of Chagas disease in the Amazon Region - Medical attention in the Brazilian Amazon Region: a proposal

We refer to Oswaldo Cruz’s reports dating from 1913 about the necessities of a healthcare system for the Brazilian Amazon Region and about the journey of Carlos Chagas to 27 locations in this region and the measures that would need to be adopted. We discuss the risks of endemicity of Chagas disease in the Amazon Region. We recommend that epidemiological surveillance of Chagas disease in the Brazilian Amazon Region and Pan-Amazon region should be implemented through continuous monitoring of the human population that lives in the area, their housing, the environment and the presence of triatomines. The monitoring should be performed with periodic seroepidemiological surveys, semi-annual visits to homes by health agents and the training of malaria microscopists and healthcare technicians to identify Trypanosoma cruzi from patients’ samples and T. cruzi infection rates among the triatomines caught. We recommend health promotion and control of Chagas disease through public health policies, especially through sanitary education regarding the risk factors for Chagas disease. Finally, we propose a healthcare system through base hospitals, intermediate-level units in the areas of the Brazilian Amazon Region and air transportation, considering the distances to be covered for medical care.