Increased potential of a cationic liposome-based delivery system:enhancing stability and sustained immunological activity in pre-clinical development

The combination of dimethyl dioctadecyl ammonium bromide (DDA) and the synthetic cord factor trehalose dibehenate (TDB) with Ag85B-ESAT-6 (H1 fusion protein) has been found to promote strong protective immune responses against Mycobacterium tuberculosis. The development of a vaccine formulation that is able to facilitate the requirements of sterility, stability and generation of a vaccine product with acceptable composition, shelf-life and safety profile may necessitate selected alterations in vaccine formulation. This study describes the implementation of a sterilisation protocol and the use of selected lyoprotective agents in order to fulfil these requirements. Concomitantly, close analysis of any alteration in physico-chemical characteristics and parameters of immunogenicity have been examined for this promising DDA liposome-based tuberculosis vaccine. The study addresses the extensive guidelines on parameters for non-clinical assessment, suitable for liposomal vaccines and other vaccine delivery systems issued by the World Health Organisation (WHO) and the European Medicines Agency (EMEA). Physical and chemical stability was observed following alteration in formulations to include novel cryoprotectants and radiation sterilisation. Immunogenicity was maintained following these alterations and even improved by modification with lysine as the cryoprotective agent for sterilised formulations. Taken together, these results outline the successful alteration to a liposomal vaccine, representing improved formulations by rational modification, whilst maintaining biological activity.

Novel b-lactams, their antibacterial and pharmacokinetic properties and pre-clinical evaluation

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Medical error:a discussion of the medical construction of error and suggestions for reforms of medical education to decrease error

Introduction: There is a growing public perception that serious medical error is commonplace and largely tolerated by the medical profession. The Government and medical establishment's response to this perceived epidemic of error has included tighter controls over practising doctors and individual stick-and-carrot reforms of medical practice. Discussion: This paper critically reviews the literature on medical error, professional socialization and medical student education, and suggests that common themes such as uncertainty, necessary fallibility, exclusivity of professional judgement and extensive use of medical networks find their genesis, in part, in aspects of medical education and socialization into medicine. The nature and comparative failure of recent reforms of medical practice and the tension between the individualistic nature of the reforms and the collegiate nature of the medical profession are discussed. Conclusion: A more theoretically informed and longitudinal approach to decreasing medical error might be to address the genesis of medical thinking about error through reforms to the aspects of medical education and professional socialization that help to create and perpetuate the existence of avoidable error, and reinforce medical collusion concerning error. Further changes in the curriculum to emphasize team working, communication skills, evidence-based practice and strategies for managing uncertainty are therefore potentially key components in helping tomorrow's doctors to discuss, cope with and commit fewer medical errors.