Showing papers in "Annals of Clinical Biochemistry in 2006"
TL;DR: The aim of this review is to survey differences in human exposure and in the toxicology of different forms of mercury to study subclinical effects in population studies.
Abstract: Mercury is ubiquitous in the environment and therefore every human being, irrespective of age and location, is exposed to one form of mercury or another. The major source of environmental mercury is natural degassing of the earth's crust, but industrial activities can raise exposure to toxic levels directly or through the use or misuse of the liquid metals or synthesized mercurial compounds. The aim of this review is to survey differences in human exposure and in the toxicology of different forms of mercury. It covers not only symptoms and signs observed in poisoned individuals by a clinician but also subclinical effects in population studies, the final evaluation of which is the domain of statisticians.
221 citations
TL;DR: The aim of this review is not to replicate information that has been reported in a number of reviews of the human circadian timing system and the role of melatonin and light, but rather to extract findings relevant to the field of clinical biochemistry.
Abstract: Ocular light plays a key role in human physiology by transmitting time of day information. The production of the pineal gland hormone melatonin is under the control of the light-dark cycle. Its profile of secretion defines biological night and it has been called the 'darkness hormone'. Light mediates a number of non-visual responses, such as phase shifting the internal circadian clock, increasing alertness, heart rate and pupil constriction. Both exogenous melatonin and light, if appropriately timed, can phase shift the human circadian system. These 'chronobiotic' effects of light and melatonin have been used successfully to alleviate and correct circadian rhythm disorders, such as those experienced following travel across time zones, in night shift work and in circadian sleep disorders. The effectiveness of melatonin and light are currently being optimized in terms of time of administration, light intensity, duration and wavelength, and melatonin dose and formulation. The aim of this review is not to replicate information that has been reported in a number of reviews of the human circadian timing system and the role of melatonin and light, but rather to extract findings relevant to the field of clinical biochemistry.
168 citations
TL;DR: The results demonstrate the need for assay-specific decision limits for 25(OH)D3 in order to define appropriate thresholds for treatment institution and suggest treatment with vitamin D2 may not be accurately monitored with any of the three commercial assays studied.
Abstract: Background: Clinical demand for quick, cheap, precise and accurate 25-hydroxyvitamin D (25(OH)D) results has led to the development of a variety of assay methods. Lack of standardization of these m...
123 citations
TL;DR: The aetiology and mechanics of the autoimmune cellular and antibody responses involves a combination of human leucocyte antigen (HLA) linkage, genetics and environmental factors to determine the initial and subsequent stages of the development of autoimmune thyroid disease.
Abstract: This review describes the aetiology of the major thyroid antigens. Iodination of thyroglobulin produces multiple antigen configurations which are functionally active but immunologically distinct. The thyroid stimulating hormone (TSH) receptor is a two-subunit glycoprotein; the extracellular A subunit is recognized by thyroid stimulating antibodies, while those antibodies recognizing the B subunit, located much nearer the cell surface, appear to function as blocking antibodies. Thyroid peroxidase (TPO), originally described as thyroid microsomal antigen, is present on the apical surface of thyroid follicular cells and is the antigen involved in cell-mediated cytotoxicity. Multiple B-cell-reactive epitopes exist, each giving rise to different antibodies. The aetiology and mechanics of the autoimmune cellular and antibody responses involves a combination of human leucocyte antigen (HLA) linkage, genetics and environmental factors to determine the initial and subsequent stages of the development of autoimmune thyroid disease. Depending on the antibody, a combination of enzyme-linked immunosorbent assay for TPO and thyroglobulin and bioassays and/or radioimmunoassay for TSH receptor antibodies are used to estimate their concentrations. The other conditions with which autoimmune thyroid diseases are associated include, for example, pernicious anaemia, connective tissue disorders, diabetes, coeliac disease, mood disorders like depression and fertility-related problems such as miscarriage, infertility, in vitro fertilization failure, pre-term delivery and postpartum thyroiditis. Often, there is no cause-and-effect relationship between them and it is debatable in some cases whether it is worthwhile monitoring patients with autoimmune thyroid disease for other conditions or vice versa. The review also itemizes the circumstances in which it might be useful to measure each antibody (i.e. the use of TPO antibodies in investigation of goitre, diagnosis of Graves' and Hashimoto's disease and the prediction of risk of developing hypothyroidism during subclinical thyroid disease; TSH receptor antibodies in maternal and neonatal hyperthyroidism and thyroglobulin antibodies in the monitoring and treatment of thyroid carcinoma). Finally, taking the current literature into account, an algorithm is recommended for the most effective use of these antibodies in the investigation of autoimmune thyroid disease.
97 citations
TL;DR: A high prevalence of vitamin D deficiency in Afro-Caribbean and Asians, and, in particular, women, is found, and it is clear that more routine screening ofitamin D is needed.
Abstract: Background: Vitamin D deficiency is still thought to be widespread in the UK and in recent years the number of cases of rickets reported in children has increased. In this study, the distribution of vitamin D and the prevalence of vitamin D deficiency have been determined for a multi-ethnic population from the inner-city area of Birmingham, UK, where a vitamin D testing service has been readily available for over 10 years.Methods: Serum 25-hydroxyvitamin D concentration was determined using an automated platform (Nichol's Advantage Speciality System) for 830 outpatient samples collected randomly at the end of summer (September).Results: In our total study population, prevalence of vitamin D deficiency, defined as a 25-hydroxyvitamin D concentration < 10 μg/L, was high (24%): one in eight Caucasians, one in four Black Afro-Caribbeans and one in three Asians were found to be deficient. Levels of deficiency were much higher in Asian women, with almost one in two individuals (43%) found to have a vitamin D le...
87 citations
TL;DR: The differential diagnosis for RTH includes a TSH-secreting pituitary adenoma and the presence of endogenous antibodies directed against thyroxine (T4) and triiodothyronine ( T3).
Abstract: Resistance to thyroid hormone (RTH) is a rare autosomal dominant inherited syndrome of reduced end-organ responsiveness to thyroid hormone. Patients with RTH have elevated serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations and normal or slightly elevated serum thyroid stimulating hormone (TSH) level. Despite a variable clinical presentation, the common characteristic clinical features are goitre but an absence of the usual symptoms and metabolic consequences of thyroid hormone excess. Patients with RTH can be classified on clinical grounds alone into either generalized resistance (GRTH), pituitary resistance (PRTH) or combined. Mutations in the thyroid hormone receptor (TR) β gene are responsible for RTH and 122 different mutations have now been identified belonging to 300 families. With the exception of one family found to have complete deletion of the TRβ gene, all others have been demonstrated to have minor alterations at the DNA level. The differential diagnosis includes a TSH-s...
81 citations
TL;DR: It is suggested that CFT be incorporated into the investigation regimen for suspected hypogonadism when total testosterone results are equivocal and various equations to derive reference ranges for CFT in healthy men aged 20-45 years are used.
Abstract: Background: Serum testosterone remains the most important investigation in the diagnosis of androgen deficiency in men. Most of the circulating testosterone is bound to albumin and sex hormone-binding globulin (SHBG), whereas free testosterone accounts for approximately 2% of total testosterone. Because direct measurement of free testosterone is impractical in routine practice, several equations are used to provide clinically useful estimates of free testosterone concentration. This study aimed to (1) obtain locally derived reference limits for total testosterone and calculated free testosterone (CFT) concentrations, and (2) critically evaluate the equations commonly used to estimate free testosterone.Methods: Serum total testosterone, SHBG and albumin were assayed in morning blood samples obtained from 126 healthy men (aged 20-45 years) known to have normal semen analysis. CFT concentrations calculated using four published methods (i.e. the Sodergard, Nanjee-Wheeler, Vermeulen and Ly-Handelsman equations...
69 citations
TL;DR: Routine biochemical assessment of gonadal function in men should include measurement of early morning luteininzing hormone, follicle stimulating hormone, prolactin and SHBG together with total testosterone, and if necessary some estimate of bioactive testosterone.
Abstract: Most hospital laboratories estimate the concentration of total circulating testosterone using a non-extraction method on an automated multi-channel immunoassay analyser supplied by a small number of multi-national diagnostic companies. Although these platforms offer advantages of quick turnaround times, small volume sampling and random access analysis, proficiency testing schemes suggest the quality of results produced remains similar to that of the early manual radioimmunoassay. An estimate of the bioavailable, non-sex hormone binding globulin (SHBG) bound fraction of circulating testosterone, be that the free or the free plus albumin-bound, may be a better index of gonadal status than total testosterone alone, especially when a borderline hypogonadal level of total testosterone is found, and may avoid misclassification of hypogonadal or eugonadal men. Free or bioavailable testosterone may be calculated or measured. The free androgen index may not give a true reflection of androgen status in men. In the interpretation of serum testosterone concentrations with results >40 nmol/L, the possibility of exogenous administration or abuse needs to be considered. The marked diurnal rhythm in total testosterone should also be taken into account. There may be a diminution of testosterone secretion with advancing age, but the great majority of older men have a circulating total testosterone concentration well within the accepted reference intervals established for younger men. As testosterone concentration may fluctuate markedly both seasonally and from day to day, it may be judicious to measure levels on more than one occasion. Provided that estimates of serum testosterone are unequivocally eugonadal (12.5-40 nmol/L) or hypogonadal (<7.0 nmol/L), results produced by routine automated immunoassays will in all probability give a satisfactory assessment of androgen status in men.Routine biochemical assessment of gonadal function in men should include measurement of early morning luteinizing hormone, follicle stimulating hormone, prolactin and SHBG together with total testosterone, and if necessary some estimate of bioactive testosterone.
63 citations
TL;DR: Clinical Guideline CG3 from the National Institute for Health and Clinical Excellence (NICE) makes recommendations on appropriate clinical practice in preoperative testing for elective surgery on the basis of professional opinion, but is extremely complex and inadequately rigorous for routine use.
Abstract: Clinical Guideline CG3 from the National Institute for Health and Clinical Excellence (NICE) makes recommendations on appropriate clinical practice in preoperative testing for elective surgery. Unfortunately, there is minimal evidence on which the guidelines could be based and therefore they were constructed on the basis of professional opinion. This resulted in the construction of a decision matrix of Byzantine complexity built on foundations of sand: surgical risk is estimated using an unvalidated ad hoc risk estimation method; anaesthetic risk is estimated using the American Society of Anesthesiologists (ASA) risk method that has been demonstrated to be incapable of generating consistent risk assessments. The resultant matrix may be suitable for use as a template for future research, but is extremely complex and inadequately rigorous for routine use.
58 citations
TL;DR: This study confirms that measurement of the LH/FSH ratio is of limited use in the diagnosis of PCOS and compares it with that of normal menstruating women over a full cycle.
Abstract: Background: The luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio is often requested to help diagnose polycystic ovarian syndrome (PCOS) despite a recent consensus recommending agains...
57 citations
TL;DR: Post-2000 trends in the development of two-dimensional protein microarrays and nanoarrays are reviewed, with an emphasis on issues surrounding the implementation of arrays in clinical diagnostics.
Abstract: This article reviews post-2000 trends in the development of two-dimensional protein microarrays and nanoarrays. Progress in array manufacture, assay design and applications are considered, with an emphasis on issues surrounding the implementation of arrays in clinical diagnostics. These include the effect of factors in the pre-analytical phase (quality of the reagents, sample integrity, etc.), and those in the analytical phase that contribute to inaccuracy and imprecision of an array-based assay. Important requirements for the quality control and quality assurance of protein microarray assays as they move from the research environment into routine clinical application are also discussed.
TL;DR: This review examines the evidence for adopting IgA anti-tissue TGA as the first-line diagnostic test for CD and recommends a laboratory algorithm for the use and interpretation of TGA to enable the clinical laboratory to play a full part in detecting and monitoring a disorder that is eminently treatable once the diagnosis has been considered and confirmed.
Abstract: Coeliac disease (CD), caused by an inappropriate T-cell-mediated immune response to the ingestion of cereal proteins in genetically susceptible individuals, is a common disorder with a prevalence of about 1% in Caucasian populations. It has a strong association with other autoimmune disorders, particularly type 1 diabetes and autoimmune thyroid disease. Although primarily affecting the small bowel, CD is a multisystem disorder and the adult or child patient may initially present to a wide range of clinical specialties. The concept of the 'coeliac iceberg' has been used to emphasize that many cases currently remain undiagnosed. The identification of tissue transglutaminase (TGA)-2 as the antigen against which the autoantibodies are directed has led to a greater understanding of the pathogenesis of CD and to the development of improved serological tests. Enzyme-linked immunoassays using human tissue TGA as antigen have high diagnostic sensitivity and specificity for the detection of CD. This review examines the evidence for adopting IgA anti-tissue TGA as the first-line diagnostic test for CD. It recommends a laboratory algorithm for the use and interpretation of TGA to enable the clinical laboratory to play a full part in detecting and monitoring a disorder that is eminently treatable once the diagnosis has been considered and confirmed.
TL;DR: The C677T polymorphism of the MTHFR gene is associated with hyperhomocysteinaemia, lipid dysregulation and the presence of CAD in this Tunisian Arab population.
Abstract: BACKGROUND Hyperhomocysteinaemia is an independent, graded risk factor for coronary artery disease (CAD). The methylenetetrahydrofolate reductase (MTHFR) polymorphism is associated with hyperhomcysteinaemia and may therefore influence individual susceptibility to CAD. We have investigated this risk factor in a Tunisian Arab population. METHODS Polymerase chain reaction-restriction fragment length polymorphism analysis was used to detect the C677T and A1298C variants of the MTHFR gene in 100 patients with CAD and 120 healthy controls. The severity of CAD was expressed as the number of affected vessels. Plasma total homocysteine (tHcy) concentration was determined using a direct chemiluminescence assay. RESULTS MTHFR CC, CT and TT genotype frequencies in the CAD group were significantly different from those observed in the control group (49%, 35% and 16% versus 48.3%, 45.8% and 5.8%, respectively; P = 0.031). However, MTHFR AA, AC and CC genotypes frequencies in the CAD group were not significantly different from the control group ( P = 0.568). Patients with CAD showed higher plasma tHcy concentrations than patients without CAD (15.86 +/- 8.63 micromol/L versus 11.90 +/- 3.25 micromol/L, P < 0.001). There was no association between the MTHFR polymorphisms and the number of stenosed vessels. Patients with the MTHFR TT genotype had higher plasma tHcy, serum creatinine, cholesterol and triglyceride concentrations than patients with the MTHFR CC genotype. CONCLUSIONS The C677T polymorphism of the MTHFR gene is associated with hyperhomocysteinaemia, lipid dysregulation and the presence of CAD in this Tunisian Arab population.
TL;DR: The most important issue in quantitative method comparison studies is to determine limits of agreement that are valid across the whole range of values in the study so that correct data interpretation and conclusions occur as mentioned in this paper.
Abstract: Quantitative method comparison studies are fundamental to clinical biochemistry. The interpretation of quantitative method comparison studies relied heavily on correlation and regression methods until Bland and Altman first described the concept of absolute difference plots. Since then, many clinical biochemistry journals advocate the use of difference plots; however, there is a lot of ignorance about the validity as well as the pros and cons of the various difference plots. The most important issue in quantitative method comparisons studies is to determine limits of agreement that are valid across the whole range of values in the study so that correct data interpretation and conclusions occur. This article discusses validity as well as the pros and cons of difference plots and provides means to determine limits of agreement that are valid across the whole range of values in method comparison studies. Accordingly, correct data interpretation will be more likely and better conclusions should be arrived as a result.
TL;DR: Methods for PSA should be equimolar and calibrated to the international standard to minimize the likelihood of clinical errors, but some methods have estimated biases over 10% which can result in unacceptable clinical performance characteristics.
Abstract: Background: The UK Prostate Cancer Risk Management Programme has recommended that all assays for prostate-specific antigen (PSA) should be both equimolar in their response to free and complexed PSA and calibrated to the World Health Organization (WHO) First International Standard for PSA (90:10). To determine which assays currently being used by diagnostic laboratories in England fulfil these criteria, a PSA recovery experiment was performed.Methods: In all, 15 samples containing varying mixtures and concentrations of the WHO International Standards for PSA and free PSA were sent to 223 laboratories in England who participate in the UK National External Quality Assessment Service (UK NEQAS) scheme for analysis. Analytical platforms were assigned to one of 11 methods, and the results were converted into recovery percentages and analysed by means of a linear random intercept model.Results: No method was both unbiased and equimolar; estimates of bias ranged from -5% to 22% and estimates of non-equimolarity (...
TL;DR: Clinicians should be aware of this significant limitation in the ability to detect non-compliance or overdose with recombinant insulin treatment, which could lead to misdiagnosis.
Abstract: Insulin assays are utilized in various clinical scenarios, including the assessment of insulin therapy compliance or of suspected insulin overdose. In an interpretative exercise carried out by UK National External Quality Assessment Service (NEQAS), serum sent to the participating laboratories was spiked with 30 pmol/L of the short-acting insulin analogue Human Actrapid. Only two out of 24 participant laboratories had sufficient assay cross-reactivity with Actrapid to interpret the results as suggestive of insulin administration. The development of specific insulin assays has led to deterioration in the ability to detect non-compliance or overdose with recombinant insulin treatment. Clinicians should be aware of this significant limitation, which could lead to misdiagnosis.
TL;DR: Gilbert's syndrome (GS) is a benign and inherited state characterized by mild, lifelong, unconjugated hyperbilirubinaemia in the absence of haemolysis or evidence of liver disease.
Abstract: Gilbert's syndrome (GS) is a benign and inherited state characterized by mild, lifelong, unconjugated hyperbilirubinaemia in the absence of haemolysis or evidence of liver disease. Its molecular basis, mutations in the TATA box upstream of the uridine diphosphoglucose glucuronyltransferase gene, leads to impaired bilirubin glucuronidation. This synopsis outlines the pathophysiology and investigation appropriate for this innocent anomaly.
TL;DR: The determination of vitamin E:cholesterol ratios can be used to better define the vitamin E status of patients with disease states or disorders likely to raise LDL cholesterol, for example cholestasis.
Abstract: Background: If the lipid concentration is not taken into account, then in certain situations the vitamin E status of a patient may be wrongly assigned based on serum measurement alone. In this study, the utility of using the calculated vitamin E:cholesterol ratio to determine vitamin E status was compared to the measurement of vitamin E alone.Methods: The vitamin E:cholesterol ratio was measured in 457 patient samples received for routine vitamin E analysis. Serum vitamin E concentration was determined by high-performance liquid chromatography (HPLC) with UV detection and cholesterol concentration, using a Roche analyser and reagents.Results: The mean vitamin E concentration and vitamin E:cholesterol ratio for the total study population was 22.0 μmol/L and 5.9 μmol/mmol, respectively. Of the 457 patient samples analysed, 57 (12.5%) were found to have a low vitamin E concentration, but only 25 (47%) of these patients had a low vitamin E:cholesterol ratio as well. Two patients both with cholestasis had a no...
TL;DR: A novel, simple, sensitive LC-MS/MS assay for the analysis of creatinine in serum, developed for use in comparative studies or when the results of either Jaffe or enzymatic assays are in question.
Abstract: Background Glomerular filtration rate (GFR) can be estimated using creatinine clearance or calculated formulae, methods which rely on creatinine quantification in serum. Creatinine is most frequently measured using the Jaffe method, but this is prone to interference by, for example, bilirubin, protein and ketones. Recent amendments to this assay have been made by manufacturers in an attempt to compensate for the protein interference. Methods We developed a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the analysis of creatinine in serum, using a strong cation exchange column to give a short run time of 1.5 min and minimal ion suppression. The method had a lower limit of quantification of 5 micromol/L and the intra- and inter-assay imprecision was Results The compensated Jaffe and enzymatic methods gave similar results to the LC-MS/MS method at concentrations below 150 micromol/L. At concentrations above this value, creatinine was underestimated by both the compensated Jaffe and enzymatic methods compared with the LC-MS/MS method. Conclusions We have developed a novel, simple, sensitive LC-MS/MS assay for use in comparative studies or when the results of either Jaffe or enzymatic assays are in question.
TL;DR: In this paper, a case of hepatoblastoma in a baby was delayed as a result of unrecognized "hooking" of a very high AFP concentration in the automated immunoassay method used.
Abstract: The hook effect is a well-recognized problem that can occur in assays of most tumour markers, including alpha feto-protein (AFP). We present a case of hepatoblastoma in a baby. The diagnosis was delayed as a result of unrecognized 'hooking' of a very high AFP concentration in the automated immunoassay method used. The falsely low result obtained was considered normal for the patient's age and supported the diagnosis of benign haemangioendothelioma. Liaison between clinical and laboratory staff was critical in obtaining an accurate AFP result, proceeding to liver biopsy and establishing the definitive diagnosis of hepatoblastoma. While the reasons and solutions for hook effect have been well researched and published, we believe the presence of extremely high serum AFP concentration in some hepatoblastoma patients means that the hook effect remains a problem and can generate erroneously low AFP results despite assay reformulation by manufacturers. Therefore constant vigilance by laboratory staff is still needed.
TL;DR: It is demonstrated that the new whole-blood TPMT phenotyping method performs as well as the conventional RBC lysate assay, and is better suited to a regional or national T PMT phenotypesing service.
Abstract: Background: We have developed a new thiopurine S-methyltransferase (TPMT) phenotyping method that measures TPMT activity in whole blood. To evaluate this assay, we compared it with conventional TPMT phenotyping, which uses a red blood cell (RBC) lysate and genotyping for analysis of common TPMT mutations.Methods: Whole-blood and RBC lysates were prepared from 402 patients' samples received for routine analysis. The TPMT activity of lysates was determined using 6-thioguanine as substrate with high-performance liquid chromatographic (HPLC) analysis and fluorimetric detection. DNA was extracted from buffy coats using phenol-chloroform extraction. A multiplex amplification refractory mutation system (ARMS) strategy was used to screen for the common TPMT mutations TPMT*2 and TPMT*3 (TPMT*3A, TPMT*3C and TPMT*3D).Results: TPMT activities were higher in the whole-blood (mean TPMT activity 51 nmol 6-MTG/gHb/h) compared with the RBC lysate (37 nmol 6-MTG/gHb/h). Overall, concordance with TPMT genotypic analysis wa...
TL;DR: In this article, the authors presented a very early diagnosis of acute myocardial infarction (AMI) in patients presenting to the Emergency Department (ED) for rule out of AMI.
Abstract: Objective Creatine kinase MB isoenzyme (CK-MB) mass and rate of change of CK-MB have been proposed as superior to cardiac troponin measurement for very early exclusion of acute myocardial infarction (AMI). All three markers were examined prospectively in patients presenting to the Emergency Department (ED) for rule out of AMI. Methods Consecutive admissions to the ED with undifferentiated chest pain were initially assessed clinically and by electrocardiography. A total of 786 patients (490 male, median age 52.5 years) considered at low risk of AMI had blood drawn on admission. If the first sample was less than 12 h from onset of chest pain, a second sample was then drawn at least 2 h later and at least 6 h from onset of chest pain. CK-MB mass was measured on the first sample and CK-MB mass and cardiac troponin T (cTnT) were measured on the second sample. Measurement of cTnT was using an Elecsys 2010 with the third generation assay (Roche Diagnostics, Lewes, UK). Assay coefficient of variation (CV) was 5.8% and 5.7% at 0.47 and 11.5 microg/L, respectively, with measuring range 0.01-25.0 microg/L; analytical sensitivity of 0.01 microg/L and functional sensitivity of 0.03 microg/L. CK-MB (mass) was measured by electrochemiluminesence using an Elecsys 2010 (Roche Diagnostics). The assay CV was 4.0% at 5.89 microg/L and 4.1% at 60.5 microg/L, with a detection limit of 0.1 microg/L and an upper measuring limit of 500 microg/L. Myocardial infarction was diagnosed if either sample had a CK-MB of more than 5 microg/L, if there was a change in CK-MB (DeltaCK-MB) of more than 1.5 microg/L or if the cTnT was more than 0.05 microg/L. When AMI was excluded, patients proceeded to stress electrocardiography and reattended 72 h from presentation for follow up phlebotomy for cTnT measurement. A final diagnosis of AMI was made according to American College of Cardiology/ European Society of Cardiology criteria using a cut-off of 0.05 microg/L cTnT in any of the samples. Diagnostic efficiency was compared by receiver operator characteristic (ROC) curve analysis with comparison of area under the curve (AUC) for four strategies: admission CK-MB measurement; 6-h post-pain CK-MB measurement; DeltaCK-MB; and 6-h post-pain cTnT measurement. Results On admission the AUC for CK-MB was 0.830 (95% confidence interval [CI] 0.757-0.904). At 6 h post pain the respective values were: CK-MB 0.939 (95% CI 0.889-0.988); DeltaCK-MB 0.948 (95% CI 0.906-0.990); and cTnT 0.989 (95% CI 0.966-1.0). Conclusion cTnT at 6 h has high diagnostic sensitivity for AMI and is superior to CK-MB mass and DeltaCK-MB even using a low cut-off value.
TL;DR: This is the first study to show that tissue non-specific AP inhibitors can block adipogenesis in human preadipocytes, and fluorescent microscopy showed AP activity was localized to the triglyceride-containing droplets of the cell.
Abstract: BACKGROUND: A previous study has demonstrated that alkaline phosphatase (AP) may play a role in the control of intracellular lipid accumulation in the rodent preadipocyte cell line, 3T3-L1. The present study investigated whether AP may have a similar function in preadipocytes isolated from human mammary gland tissue. METHODS: Preadipocyte maturation was induced in the presence or absence of the tissue non-specific AP inhibitors levamisole and histidine, and the tissue-specific AP inhibitor PheGlyGly. Cellular AP activity and adipogenesis were both assessed at 0 and 12 days post-induction of differentiation. RESULTS: After differentiation, AP activity increased 5.1 +/- 1.3-fold in the absence and 8.9 +/- 2.8-fold (P < 0.05) in the presence of levamisole. However, adipogenesis increased 1.95 +/- 0.11-fold in the absence but only 1.36 +/- 0.06-fold (P < 0.001) in the presence of levamisole. There was a 4.2 +/- 2.2-fold increase in AP activity in the absence and a 0.51 +/- 0.46-fold (P < 0.05) decrease in the presence of histidine. Adipogenesis increased 2.09 +/- 0.35-fold in the absence of histidine but only 1.22 +/- 0.30-fold (P < 0.05) in the presence of histidine. PheGlyGly had no effects. Fluorescent microscopy showed AP activity was localized to the triglyceride-containing droplets of the cell. CONCLUSION: This is the first study to show that tissue non-specific AP inhibitors can block adipogenesis in human preadipocytes.
TL;DR: Using data from 14 published studies, suitable spot urine Ca/Cr cut-offs from birth to 18 years of age were determined.
Abstract: Background: The purpose of this study was to determine a cut-off above which a result is considered abnormal for 'spot' calcium-to-creatinine ratio (Ca/Cr) in urine in the paediatric age group. Whi...
TL;DR: DHEA-S cross-reacts in the Abbott Architect direct immunoassay for testosterone to a clinically significant effect and is likely to be responsible for much of the interference observed when measuring testosterone in women by this method.
Abstract: Background: There are known difficulties in measuring testosterone in women using 'direct' (non-extraction) immunoassays. The positive bias encountered in many of these assays has been attributed t...
TL;DR: Both haemolysis, haemoglobin per se and possibly proteolysis play a role in the negative interference in cTnT assays, and measures to reduce this interference must be implemented.
Abstract: Background: The cardiac troponins have been shown to be sensitive and specific biochemical markers of myocardial infarction and highly prognostic for future adverse events in patients with acute co
TL;DR: Clinicians need to be made more aware of the clinical features of FH and how to diagnose it in order to increase the index of suspicion and instigate appropriate treatment early, with the aim of preventing premature coronary heart disease.
Abstract: Familial hypercholesterolaemia (FH) is a genetic disorder in which the concentration of serum cholesterol is elevated from birth and leads to premature coronary heart disease. FH is commonly caused by a mutation in the LDL receptor, but mutations in other genes can lead to a phenotype similar to FH. FH exhibits marked phenotypic variability due to genetic, metabolic and environmental factors. The presence of tendon xanthomata is the characteristic clinical sign seen in many patients with FH, but they may also have other non-specific signs of lipid disorders such as corneal arcus and xanthelasmata. Premature vascular disease is apparent in many patients. The wide variety of mutations and phenotypic variability have made it difficult to establish definite diagnostic criteria, but three sets of clinical criteria commonly used are the Simon Broome criteria, the Dutch Lipid Clinic criteria and the American criteria. FH screening fits the Wilson and Jungner recommendations for validity of a screening programme. Screening could be carried out on a population basis, in a clinical setting or by application to relatives of probands. This latter approach, termed cascade testing, appears to be the more cost-effective compared with population screening and can be carried out using clinical criteria or genetic testing, or by a combination of both methods. Clinicians need to be made more aware of the clinical features of FH and how to diagnose it in order to increase the index of suspicion and instigate appropriate treatment early, with the aim of preventing premature coronary heart disease.
TL;DR: The method is certi¢ed and traceable to the Diabetes Control and Complications Trial (DCCT) reference method and according to External Quality Assessment data (WEQAS), the results show no sign of bias when compared to the same group or indeed the overall mean.
Abstract: more false positive than true positive patients, it is generally well-recognized that with screening tests, as opposed to diagnostic tests, the proportion of a¡ected persons is likely to be small and that many positive results are likely to be false positive. 2 This ¢nding is not necessarily serious if the screening test is followed up by a con¢rmatory test such as OGTT. We believe that our approach meets the criteria set out for screening of high-risk individuals. Based on our data, there were 22 patients with FPG o6.0mmol/l and HbA1c concentration o5.0% and all of them had normal OGTT, hence our comment that in patients with FPG o6.0mmol/l and HbA1c o5.0%, abnormal glucose tolerance can be ruled out with 100% certainty. There was one patient with HbA1c of 5.0% who had an abnormal OGTTand, therefore, the sensitivity at HbA1c of 5.0% in ruling out an abnormal OGTT is 98% (which may not be clear from Figure1). We note their comment about the traceability of our method and that in their low-risk population for diabetes, using the same analytical method, the geometric mean for HbA1c was 5.6%, suggesting that our method may have a negative analytical bias. Our method is certi¢ed and traceable to the Diabetes Control and Complications Trial (DCCT) reference method (University of Missouri, USA) and according to External Quality Assessment data (WEQAS), our results show no signi¢cant bias when compared to the same group or indeed the overall mean. However, we agree with their comment that our results or cut-o¡ levels for HbA1c may not be transferable to other laboratories and that each laboratory must establish its own cut-o¡ levels. We acknowledge that our datawere expressed as mean + SD and not as mean + SEM as stated and we thank them for pointing this out to us.
TL;DR: It is possible that even with a low cross reactivity, DHEA-S or one of its metabolites significantly interferes in the testosterone assay when at higher concentrations.
Abstract: BACKGROUND Direct (non-extracted) testosterone immunoassays may give spuriously high results in women. The presumed interferents may be removed if testosterone is extracted into an organic phase before being measured. We aimed to clarify possible causes and effects of interference in testosterone measurement in women. METHODS Women who had a blood sample referred to Hope Hospital Clinical Biochemistry laboratory for measurement of serum testosterone concentration over a six-month period were studied. Clinical and treatment data were recorded. A difference (direct-minus-extracted testosterone) of less than 1.0 nmol/L was used to define a group with low interference. A difference of 2.5 nmol/L or more was used to define a group with significant interference. RESULTS The distribution of interference in 1271 serum samples from female patients was unimodal. There were no group differences in clinical presentation or treatment. The median degree of interference was 1.4 nmol/L. In 42 female patients with varying degrees of interference, identified on routine assay, regression analysis showed strong association between dehydroepiandrosterone sulphate (DHEA-S) and interference (direct-minus-extracted testosterone) (r = 0.77, P < 0.001). CONCLUSIONS Given that DHEA-S is present in very variable amounts in blood, it is possible that even with a low cross reactivity, DHEA-S or one of its metabolites significantly interferes in the testosterone assay when at higher concentrations.