Clinical Biochemist Reviews最新文献

Adverse drug reactions are a common cause of patient morbidity and mortality. Type B drug reactions comprise only 20% of all drug reactions but they tend to be primarily immunologically mediated and less dependent on the drug's pharmacological action and dose. Common Type B reactions seen in clinical practice are those of the immediate, IgE, Gell-Coombs Type I reactions, and the delayed, T-cell mediated, Type IV reactions. Management of these types of reactions, once they have occurred, requires careful consideration and recognition of the utility of routine diagnostic tests followed by ancillary specialised diagnostic testing. For Type I, IgE mediated reactions this includes prick/intradermal skin testing and oral provocation. For Type IV, T-cell mediated reactions this includes a variety of in vivo (patch testing) and ex vivo tests, many of which are currently mainly used in highly specialised research laboratories. The recent association of many serious delayed (Type IV) hypersensitivity reactions to specific drugs with HLA class I and II alleles has created the opportunity for HLA screening to exclude high risk populations from exposure to the implicated drug and hence prevent clinical reactions. For example, the 100% negative predictive value of HLA-B*5701 for true immunologically mediated abacavir hypersensitivity and the development of feasible, inexpensive DNA-based molecular tests has led to incorporation of HLA-B*5701 screening in routine HIV clinical practice. The mechanism by which drugs specifically interact with HLA has been recently characterised and promises to lead to strategies for pre-clinical screening to inform drug development and design.

Reduced immunity following exposure of skin to UV radiation (UVR) may explain the positive latitude gradient measured for a number of autoimmune diseases (greater incidence of disease with residence at higher latitudes), including multiple sclerosis, allergic asthma and diabetes. Humans obtain >80% of their vitamin D3 by exposure of skin to UVR in sunlight. In experimental models, both vitamin D3-dependent and vitamin D3-independent pathways have been implicated in the mechanisms of UVR-induced systemic suppression of immunity. However, where does the balance of control lie? How important is vitamin D3 other than providing a biomarker of sun exposure? Are other molecules/pathways activated by UVR more important? Murine and human studies suggest many molecules may play a role and their participation may vary with different diseases and the time of UVR exposure or vitamin D3 sufficiency/deficiency. Although low vitamin D3 levels have been associated with increased prevalence and progression of human autoimmune diseases, the benefits of supplementation with vitamin D3 have not been definitive. Vitamin D3 levels are a measure of past sun exposure but vitamin D3-dependent and vitamin D3-independent immunosuppressive effects of UVR may play a role in control of autoimmune diseases.

The Stockholm Hierarchy is a professional consensus created to define the preferred approaches to defining analytical quality. The quality of a laboratory measurement can also be classified by the quality of the limits that the value is compared with, namely reference interval limits and clinical decision limits. At the highest level in the hierarchy would be placed clinical decision limits based on clinical outcome studies. The second level would include both formal reference interval studies (studies of intra and inter-individual variations) and clinical decision limits based on clinician survey. While these approaches are commonly used, they require a lot of resources to define accurately. Placing laboratory experts on the third level would suggest that although they can also define reference intervals by consensus, theirs aren't as well regarded as clinician defined limits which drive clinical behaviour. Ideally both analytical and clinical considerations should be made, with clinicians and laboratorians both having important information to consider. The fourth level of reference intervals would be for those defined by survey or by regulatory authorities because of the focus on what is commonly achieved rather than what is necessarily correct. Finally, laboratorians know that adopting reference limits from kit inserts or textbook publications is problematic because both methodological issues and reference populations are often not the same as their own. This approach would rank fifth and last. When considering which so called 'common' or 'harmonised reference intervals' to adopt, both these characteristics and the quality of individual studies need to be assessed. Finally, we should also be aware that reference intervals describe health and physiology while clinical decision limits focus on disease and pathology, and unless we understand and consider the two corresponding issues of test specificity and test sensitivity, we cannot assure the quality of the limits that we report.

Radioactive, chromogenic, fluorescent and other labels have long provided the basis of detection systems for biomolecular interactions including immunoassays and receptor binding studies. However there has been unprecedented growth in a number of powerful label free biosensor technologies over the last decade. While largely at the proof-of-concept stage in terms of clinical applications, the development of more accessible platforms may see surface plasmon resonance (SPR) emerge as one of the most powerful optical detection platforms for the real-time monitoring of biomolecular interactions in a label-free environment.In this review, we provide an overview of SPR principles and current and future capabilities in a diagnostic context, including its application for monitoring a wide range of molecular markers of disease. The advantages and pitfalls of using SPR to study biomolecular interactions are discussed, with particular emphasis on its potential to differentiate subspecies of analytes and the inherent ability for quantitation through calibration-free concentration analysis (CFCA). In addition, recent advances in multiplex applications, high throughput arrays, miniaturisation, and enhancements using noble metal nanoparticles that promise unprecedented sensitivity to the level of single molecule detection, are discussed.In summary, while SPR is not a new technique, technological advances may see SPR quickly emerge as a highly powerful technology, enabling rapid and routine analysis of molecular interactions for a diverse range of targets, including those with clinical applicability. As the technology produces data quickly, in real-time and in a label-free environment, it may well have a significant presence in future developments in lab-on-a-chip technologies including point-of-care devices and personalised medicine.

Timely release and communication of critical test results may have significant impact on medical decisions and subsequent patient outcomes. Laboratories therefore have an important responsibility and contribution to patient safety. Certification, accreditation and regulatory bodies also require that laboratories follow procedures to ensure patient safety, but there is limited guidance on best practices. In Australasia, no specific requirements exist in this area and critical result reporting practices have been demonstrated to be heterogeneous worldwide.Recognising the need for agreed standards and critical limits, the AACB started a quality initiative to harmonise critical result management throughout Australasia. The first step toward harmonisation is to understand current laboratory practices. Fifty eight Australasian laboratories responded to a survey and 36 laboratories shared their critical limits. Findings from this survey are compared to international practices reviewed in various surveys conducted elsewhere. For the successful operation of a critical result management system, critical tests and critical limits must be defined in collaboration with clinicians. Reporting procedures must include how critical results are identified; who can report and who can receive critical results; what is an acceptable timeframe within which results must be delivered or, if reporting fails, what escalation procedures should follow; what communication channels or systems should be used; what should be recorded and how; and how critical result procedures should be maintained and evaluated to assess impact on outcomes.In this paper we review the literature of current standards and recommendations for critical result management. Key elements of critical result reporting are discussed in view of the findings of various national surveys on existing laboratory practices, including data from our own survey in Australasia. Best practice recommendations are made that laboratories are expected to follow in order to provide high quality and safe service to patients.

Globally, harmonisation in laboratory medicine is a significant project. The relatively new implementation of liquid chromatography coupled with tandem mass spectrometry (LC-MSMS) techniques as routine assays in diagnostic laboratories provides the unique opportunity to harmonise, and in many cases standardise, methods from an early stage. This guide aims to provide a practical overview of the steps required to achieve agreement between LC-MSMS analytical procedures for routine clinical biochemistry diagnostic assays, with particular focus on the harmonisation and standardisation of methods currently implemented.To achieve harmonisation, and where practical standardisation, the approach is more efficient if divided into sequential stages. The suggested division entails: (i) planning and preliminary work; (ii) initial assessment of performance; (iii) standardisation and harmonisation initiative; (iv) establishing common reference intervals and critical limits; (v) developing best practice guidelines; and (vi) performing an ongoing review.The profession has a unique and significant opportunity to bring clinical mass spectrometry-based assays into agreement. Harmonisation of assays should ultimately provide the same result and interpretation for a given patient's sample, irrespective of the laboratory that produced the result. To achieve this goal, we need to agree on the best practice LC-MSMS methods for use in routine clinical measurement.