Clinical Biochemist Reviews最新文献

Plumbism refers to the clinical features of lead toxicity, a condition which has been identified and then forgotten in a depressingly cyclical fashion since ancient times. For the past 6000 years antiquarians have described the human use of lead despite the well documented and severe adverse effects of exposure. As the analytical methods of lead measurement bring improved detection capability, it is clear that there is no safe amount of lead in the body. Sadly, we continue to identify affected patients in contemporary Australia, including young children. While there is little evidence that chelation therapy improves outcomes in affected individuals, it is recommended for use in patients with acute encephalopathy or in those with particularly elevated levels. The paucity of evidence supporting active treatment of plumbism highlights the importance of primary prevention, particularly in our most vulnerable.

Calprotectin is a calcium- and zinc-binding protein of the S-100 protein family which is mainly found within neutrophils and throughout the human body. The presence of calprotectin in faeces is a consequence of neutrophil migration into the gastrointestinal tissue due to an inflammatory process. Faecal calprotectin concentrations demonstrate good correlation with intestinal inflammation and faecal calprotectin is used as a biomarker in gastrointestinal disorders. Faecal calprotectin is a very sensitive marker for inflammation in the gastrointestinal tract, and useful for the differentiation of inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS). Faecal calprotectin is used for the diagnosis, monitoring disease activity, treatment guidance and prediction of disease relapse and post-operative recurrence in IBD. There may also potentially be a role for faecal calprotectin in the management of infectious gastroenteritis, acute appendicitis, peptic ulcer disease, cystic fibrosis, coeliac disease, transplant rejection and graft versus host disease. Further studies are needed to confirm its utility in these conditions. Analysis of faecal calprotectin consists of an extraction step followed by quantification by immunoassay. Over the past few decades, several assays and extraction devices including point-of-care methods have been introduced by manufacturers. The manufacturer-quoted cut-off values for different faecal calprotectin assays are generally similar. However, the sensitivities and specificities at a given cut-off, and therefore the optimum cut-off values, are different between assays. A reference standard for calprotectin is lacking. Therefore, assay standardisation is required for more accurate and traceable test results for faecal calprotectin.

Atherosclerosis often begins in childhood or adolescence. Post-mortem studies in children have shown the presence of coronary atheroma, and there are hereditary conditions associated with hyperlipidaemia in childhood which lead to premature cardiovascular disease. Detection of hyperlipidaemia early in life can be crucial in the prevention of premature death from atherosclerosis. The circulating lipoproteins are in a constant state of flux, with passage of apolipoproteins and lipids between the various particles. Genetic variants of apolipoproteins can cause both hypercholesterolaemia and hypertriglyceridaemia. Elevated concentrations of lipoprotein(a) predispose to coronary artery disease. Another important molecule in lipid metabolism, proprotein convertase subtilisin/kexin type 9 (PCSK9), plays a crucial role in the removal of low-density lipoprotein (LDL) receptors. Reference intervals for the various lipid subfractions are now available for children, and there are guidelines regarding when to take action regarding paediatric hyperlipidaemia. The most important genetic condition in children which may lead to premature death from coronary heart disease is familial hypercholesterolaemia (FH). FH is best diagnosed and treated early in life. Most cases are due to defects in the LDL receptor. Pharmacotherapy for FH usually involves the statin group of drugs, although newer medications are now available, especially for the treatment of homozygous FH. Statin therapy has been demonstrated to be successful in preventing cardiac events in FH. Secondary dyslipidaemia in childhood can be associated with numerous diseases including diabetes, lifestyle disorders such as obesity, and drugs. Treatment of the underlying condition usually resolves the hyperlipidaemia.

Biochemical testing of peritoneal and pleural fluids is carried out widely, although the range of tests likely to be useful is limited in comparison to the repertoire of tests available in a modern biochemistry laboratory. Fluids accumulate when pathological processes cause an imbalance between hydrostatic pressure gradients, capillary membrane permeability and lymphatic capacity, resulting in protein-poor transudates or inflammatory exudates. In peritoneal fluid, albumin is the most useful test, for the calculation of the serum-ascites albumin gradient; protein and LDH have a role regarding risk and diagnosis of spontaneous bacterial peritonitis and amylase may be useful in diagnosing fluid accumulation due to pancreatitis. Peritoneal fluid pH and glucose are not indicated analyses. For pleural fluid, protein and LDH are important in distinguishing between transudate and exudate using Light's criteria; albumin and the serum-effusion albumin gradient may have a complementary role in patients already on diuretics. Pleural fluid pH is the most useful marker of infection although LDH and glucose are also used. Pleural fluid amylase is often measured but, if raised, is more likely to reflect a malignant process than pancreatic disease as the former is much more prevalent. Tumour markers in both peritoneal and pleural fluids generally have limited diagnostic accuracy for detecting local malignancy. Limited studies validating standard serum test methods for use with pleural and peritoneal fluids have been published but work is progressing in this area both in Australasia and overseas and opportunities exist for contributing to this effort.

Lot-to-lot variation affecting calibrators and reagents is a frequent challenge that limits the laboratory's ability to produce consistent results over time. This variation is not without clinical consequence and there are several well-documented examples of adverse clinical outcomes. It is important that laboratories have procedures in place for quantification of this inaccuracy, and for determining whether the amount of variation is acceptable for the release of patient results. Various approaches have been taken to the assessment of new lots, including the evaluation protocol published by the Clinical and Laboratory Standards Institute (CLSI). Internal quality control and external quality assurance material is often not commutable, and so the use of native patient samples is preferred. Published evaluation protocols differ significantly in ease of use and statistical rigour, and some may be underpowered to detect a clinically meaningful change between lots. Furthermore, current protocols (including the CLSI protocol) will not detect cumulative shifts between reagent lots. This shortcoming may at least partly be addressed by laboratories adopting moving patient averages or similar quality procedures. Collaboration and data-sharing between laboratories and manufacturers also has an important role to play in the detection of lot-to-lot variation. While the laboratory may take steps to evaluate and detect variation, the ideal is to reduce variation between lots at the point of manufacture. Using appropriate acceptance criteria based on medical need or biological variation requirements instead of some arbitrary percentage may go some steps toward achieving this.

The Australian Commonwealth Government has funded a project to investigate options for a sustainable certification scheme for medical laboratory scientists (MLSs). This has been a sought-after goal for the profession in Australia for many years. Certification is not registration as certification may not be mandatory and does not have the legal teeth of the more formal process. Models of overseas registration schemes are discussed and the key features exposed. The definition of an MLS is needed as certification will provide protection of the title. What are the basic requirements for certification and recertification, what could the process be, the likely cost and period of validity? An essential component of the certification process would be some form of continuing professional development, but it is suggested that there should be a broader requirement for competence assessment for recertification. How this process could occur and be linked to the competency-based standards endorsed by the Pathology Associations Council is canvassed. The connection between certification and course accreditation should also be considered if courses are to provide work-ready MLSs in sufficient numbers to ensure the workforce can provide the necessary skills for the protection of the public.

Prolactin is a 23 kDa single chain protein of 199 amino acids synthesised and released principally by lactotrophs in the anterior pituitary gland. The secretion is mainly under inhibitory control by hypothalamic dopamine and regulated in a negative feedback manner, with prolactin itself providing the afferent signal: short-loop feedback. The main function of prolactin is during pregnancy and lactation in the development of mammary glands, milk synthesis and maintenance of milk secretion. Serum prolactin levels rise rapidly during pregnancy with increase in the size and number of lactotrophs. During lactation suckling induces rapid secretion of prolactin via a neuroendocrine reflex pathway. In the absence of pregnancy, hyperprolactinaemia may present with symptoms of hypogonadotropic hypogonadism including menstrual disturbance and infertility or visual symptoms from a pituitary mass effect by a prolactinoma, the most common pituitary tumour. Hyperprolactinaemia is diagnosed by laboratory measurement of serum prolactin. There is considerable variability in routinely available prolactin immunoassays as a result of differing reactivity towards monomeric prolactin and macroprolactin and lack of commutability of the WHO 3^rd International Standard between routine methods. Macroprolactinaemia is a relatively common cause of interference in the prolactin assay that may lead to incorrect diagnosis and unnecessary investigations. Measurement of prolactin post polyethylene glycol precipitation (PEG) when prolactin levels are above the reference interval is routinely used to identify macroprolactin, however harmonisation of PEG precipitation process and reporting may improve clinical care.

The recent genomic revolution, characterised by surges in the number of available genetic tests and known genetic associations, calls for improved genetic literacy amongst medical scientists and clinicians. This has been driven by next generation sequencing, a technology allowing multiple genes to be sequenced in parallel, thereby reducing the time and financial costs associated with genetic testing in both research and clinical settings. Endocrinology is an intuitive setting in which to consider the principles of genetic testing because endocrine disorders are due to defects in circumscribed pathways, providing clues to candidate genes. This article discusses genetic testing in contemporary endocrine practice with reference to examples of endocrine genetic disorders or multisystem genetic disorders with endocrine manifestations. Monogenic disorders are prioritised as these form the bulk of endocrine genetic disorders and the associated genetic testing is readily understandable, clinically available and practice-changing. Although it remains true that genetic testing should be embarked upon only if the result will alter management, the clinical utility of genetic testing is often underestimated and there are expanding indications for genetic testing across all areas of endocrinology.

The value of medical laboratory testing is often directed to the cost of testing however the clinical benefits of these tests are at least as important. Laboratory testing has an acknowledged widespread role in clinical decision making, and therefore a role in determining clinical outcome. Consequently, the value of laboratory testing should be considered in its role in affecting beneficial actions and outcomes. This includes both the requesting phase of choosing tests which will influence clinical decision making as well as the reporting phase in a way that guides clinical decisions and actions. Clinical decision support systems and software can enhance the value of medical laboratory testing if they are directed toward facilitating those clinical decisions where there is either evidence, or agreed consensus, addressing patient outcomes.