Clinical Biochemist Reviews最新文献

Angiogenesis is a normal biological process wherein new blood vessels form from the growth of pre-existing blood vessels. Preventing angiogenesis in solid tumours by targeting pro-angiogenic factors including vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), basic fibroblast growth factor (bFGF), hepatocyte growth factor, and platelet-derived growth factor (PDGF) is currently under investigation for cancer treatment. Concurrently targeting the cell signalling pathways involved in the transcriptional and post-translational regulation of these factors may provide positive therapeutic results. One such pathway is the Wnt signalling pathway. Wnt was first discovered in mice infected with mouse mammary tumour virus, and has been crucial in improving our understanding of oncogenesis and development. In this review, we summarise molecular and cellular aspects of the importance of Wnt signalling to angiogenesis, including β-catenin-dependent mechanisms of angiogenic promotion, as well as the study of Wnt antagonists, such as the secreted frizzled-related protein family (SFRPs) which have been shown to inhibit angiogenesis. The growing understanding of the underlying complexity of the biochemical pathways mediating angiogenesis is critical to the identification of new molecular targets for therapeutic applications.

Procalcitonin (PCT), regarded as a biomarker specific for bacterial infections, is used in a variety of clinical settings including primary care, emergency department and intensive care. PCT measurement aids in the diagnosis of sepsis and to guide and monitor antibiotic therapy. This article gives a brief overview of PCT and its use in guiding antibiotic therapy in various clinical settings, as well as its limitations. PCT performance in comparison with other biomarkers of infection in particular CRP is also reviewed. Owing to its greater availability, CRP has been widely used as a biomarker of infection and sepsis. PCT is often reported to be more superior to CRP, being more specific for sepsis and bacterial infection. PCT starts to rise earlier and returns to normal concentration more rapidly than CRP, allowing for an earlier diagnosis and better monitoring of disease progression.

Clinical laboratories may systematically apply factors to assay results after analysis, but before reporting, in order to facilitate comparison of data from different methods. This may be done to align with other patient results, reference intervals or clinical decision points. These factors, which we term Post Analytical Correction Factors (PACF), may be applied to all types of results derived from the method, i.e. quality control (QC) and external quality assurance (EQA), as well as the patient results. As the principal use of PACF is comparing patient results, it is important that the laboratory use commutable materials (i.e. patient samples) and a formal process to establish, apply and manage PACF. We report on preliminary guidelines for PACF from a recent workshop.

The tremendous advances over the past two decades in both clinical genetics and biochemical testing of chromaffin cell tumours have led to new considerations about how these aspects of laboratory medicine can be integrated to improve diagnosis and management of affected patients. With germline mutations in 15 genes now identified to be responsible for over a third of all cases of phaeochromocytomas and paragangliomas, these tumours are recognised to have one of the richest hereditary backgrounds among all neoplasms. Depending on the mutation, tumours show distinct differences in metabolic pathways that relate to or even directly impact clinical presentation. At the same time, there has been improved understanding about how catecholamines are synthesised, stored, secreted and metabolised by chromaffin cell tumours. Although the tumours may not always secrete catecholamines it has become clear that almost all continuously produce and metabolise catecholamines. This has not only fuelled changes in laboratory medicine, but has also assisted in recognition of genotype-biochemical phenotype relationships important for diagnostics and clinical care. In particular, differences in catecholamine and energy pathway metabolomes can guide genetic testing, assist with test interpretation and provide predictions about the nature, behaviour and imaging characteristics of the tumours. Conversely, results of genetic testing are important for guiding how routine biochemical testing should be employed and interpreted in surveillance programmes for at-risk patients. In these ways there are emerging needs for modern laboratory medicine to seamlessly integrate biochemical and genetic testing into the diagnosis and management of patients with chromaffin cell tumours.

Healthcare is a significant contributor to environmental impact but this has received little attention. The typical laboratory uses far more energy and water per unit area than the typical office building. There is a need to sensitise laboratories to the importance of adopting good environmental practices. Since this comes at an initial cost, it is vital to obtain senior management support. Convincing management of the various tangible and intangible benefits that can accrue in the long run should help achieve this support. Many good environmental practices do not have a cost but will require a change in the culture and mind-set of the organisation. Continuing education and training are important keys to successful implementation of good practices. There is a need to undertake a rigorous cost-benefit analysis of every change that is introduced in going green. The adoption of good practices can eventually lead to ISO certification if this is desired. This paper provides suggestions that will allow a laboratory to start going green. It will allow the industry to enhance its corporate citizenship whilst improving its competitive advantage for long-term.

Chronic wounds, in particular venous leg ulcers (VLU), represent a substantial burden for economies, healthcare systems and societies worldwide. This burden is exacerbated by the recalcitrant nature of these wounds, despite best practice, evidence-based care, which substantially reduces the quality of life of patients. Furthermore, co-morbidities such as diabetes and cardiovascular disease within ageing populations further contribute to the increasing prevalence in developed countries. This review provides an overview of the literature concerning the cellular and molecular mechanisms of wound healing and aspects where this process fails, resulting in a chronic wound. VLU may arise from chronic venous disease, which presents with many clinical manifestations and can lead to a highly complex disease state. Efforts to comprehend this state using various omics based approaches have delivered some insight into the underlying biology of chronic wounds and revealed markers of differentiation at the genomic, transcriptomic, proteomic and metabolomic levels. Furthermore, this review outlines the array of analytical tools and approaches that have been utilised for capturing multivariate data at each of these molecular levels. Future developments in spatiotemporal analysis of wounds along with the integration of multiple omics datasets may provide much needed information on the key molecules that drive wound chronicity. Such biomarkers have the potential to be developed into clinically relevant diagnostic tools to aid in personalised wound management.

Introduction: Human sweat is a complex biofluid of interest to diverse scientific fields. Metabolomics analysis of sweat promises to improve screening, diagnosis and self-monitoring of numerous conditions through new applications and greater personalisation of medical interventions. Before these applications can be fully developed, existing methods for the collection, handling, processing and storage of human sweat need to be revised. This review presents a cross-disciplinary overview of the origins, composition, physical characteristics and functional roles of human sweat, and explores the factors involved in standardising sweat collection for metabolomics analysis.

Methods: A literature review of human sweat analysis over the past 10 years (2006-2016) was performed to identify studies with metabolomics or similarly applicable 'omics' analysis. These studies were reviewed with attention to sweat induction and sampling techniques, timing of sweat collection, sweat storage conditions, laboratory derivation, processing and analytical platforms.

Results: Comparative analysis of 20 studies revealed numerous factors that can significantly impact the validity, reliability and reproducibility of sweat analysis including: anatomical site of sweat sampling, skin integrity and preparation; temperature and humidity at the sweat collection sites; timing and nature of sweat collection; metabolic quenching; transport and storage; qualitative and quantitative measurements of the skin microbiota at sweat collection sites; and individual variables such as diet, emotional state, metabolic conditions, pharmaceutical, recreational drug and supplement use.

Conclusion: Further development of standard operating protocols for human sweat collection can open the way for sweat metabolomics to significantly add to our understanding of human physiology in health and disease.

Acute kidney injury (AKI) is a significant independent risk factor for morbidity and mortality. In the last ten years a large number of publications have highlighted the limitations of traditional approaches and the inadequacies of conventional biomarkers to diagnose and monitor renal insufficiency in the acute setting. A great effort was directed not only to the discovery and validation of new biomarkers aimed to detect AKI more accurately but also to standardise the definition of AKI. Despite the advances in both areas, biomarkers have not yet entered into routine clinical practice and the definition of this syndrome has many areas of uncertainty. This review will discuss the controversies in diagnosis and the potential of novel biomarkers to improve the definition of the syndrome.

In clinical chemistry, harmonisation of the testing process is a global initiative with the purpose of improving patient safety, allowing better integration of research data and enabling the use of national electronic heath records. In Australia, as in other countries, the initial focus has been on the harmonisation of the more commonly measured analytes. There are also a number of calculated parameters, derived from these measured analytes, which could also be considered for harmonisation. Calculated parameters that are reported by laboratories and used for clinical decision-making should undergo the same robust process of harmonisation as is the case for the measured analytes. Aspects that should be considered for harmonisation are: terminology, the formulae used and where possible the use of common reference intervals. To investigate pathways towards the harmonisation of calculated parameters, three commonly reported parameters are considered. Calculated osmolality, the anion gap and albumin-adjusted calcium are all derived from common analytes which have individually been considered for harmonisation. They present different methodological, measurement uncertainty and terminological hurdles to harmonisation and are likely to require different pathways and solutions.

For more than a decade there has been a global effort to harmonise all phases of the testing process, with particular emphasis on the most frequently utilised measurands. In addition, it is recognised that calculated parameters derived from these measurands should also be a target for harmonisation. Using data from the Aussie Normals study we report reference intervals for three calculated parameters: serum osmolality, serum anion gap and albumin-adjusted serum calcium. The Aussie Normals study was an a priori study that analysed samples from 1856 healthy volunteers. The nine analytes used for the calculations in this study were measured on Abbott Architect analysers. The data demonstrated normal (Gaussian) distributions for the albumin-adjusted serum calcium, the anion gap (using potassium in the calculation) and the calculated serum osmolality (using both the Bhagat et al. and Smithline and Gardner formulae). To assess the suitability of these reference intervals for use as harmonised reference intervals, we reviewed data from the Royal College of Pathologists of Australasia/Australasian Association of Clinical Biochemists (RCPA/AACB) bias survey. We conclude that the reference intervals for the calculated serum osmolality (using the Smithline and Gardner formulae) may be suitable for use as a common reference interval. Although a common reference interval for albumin-adjusted serum calcium may be possible, further investigations (including a greater range of albumin concentrations) are needed. This is due to the bias between the Bromocresol Green (BCG) and Bromocresol Purple (BCP) methods at lower serum albumin concentrations. Problems with the measurement of Total CO₂ in the bias survey meant that we could not use the data for assessing the suitability of a common reference interval for the anion gap. Further study is required.