We read with interest the paper by Schini et al 1 regarding the derivation of adjusted calcium re... more We read with interest the paper by Schini et al 1 regarding the derivation of adjusted calcium reference interval. In particular, their implied suggestion that they can replace the Pathology Harmony reference interval. They propose a slightly lower interval (2.19-2.56 mmol/L) than the Pathology Harmony reference interval (2.2-2.6). We would argue that this reference interval is not valid for universal applications due to variations between analytical methods.
Background Aldosterone and renin are pivotal hormones in the regulation of salt and water homeost... more Background Aldosterone and renin are pivotal hormones in the regulation of salt and water homeostasis and blood pressure. Measurement of renin and aldosterone in serum/plasma is essential for the investigation of primary hyperaldosteronism (PA) and monitoring of glucocorticoid replacement therapy. Methods We report 2 LC-MS/MS methods developed to measure aldosterone and plasma renin activity (PRA). PRA was determined by endogenous enzymatic generation of angiotensin I using 150 µL of sample. Generated angiotensin I was purified by solid phase extraction prior to chromatographic separation and mass spectrometry. Aldosterone measurement required 300 μL of sample extracted with MTBE prior to LC-MS/MS analysis. Results The PRA method was linear (1.2–193 nmol/L), sensitive (LLOQ = 1.2 nmol/L), precise (CV = 4.1%), and specific (no cross reactivity for a number of structurally similar steroids). Dilutional linearity and recovery (84%) were acceptable. Accuracy was confirmed by comparison ...
Clinical chemistry and laboratory medicine, Jan 22, 2016
Optimum patient care in relation to laboratory medicine is achieved when results of laboratory te... more Optimum patient care in relation to laboratory medicine is achieved when results of laboratory tests are equivalent, irrespective of the analytical platform used or the country where the laboratory is located. Standardization and harmonization minimize differences and the success of efforts to achieve this can be monitored with international category 1 external quality assessment (EQA) programs. An EQA project with commutable samples, targeted with reference measurement procedures (RMPs) was organized by EQA institutes in Italy, the Netherlands, Portugal, UK, and Spain. Results of 17 general chemistry analytes were evaluated across countries and across manufacturers according to performance specifications derived from biological variation (BV). For K, uric acid, glucose, cholesterol and high-density density (HDL) cholesterol, the minimum performance specification was met in all countries and by all manufacturers. For Na, Cl, and Ca, the minimum performance specifications were met by...
The aim of this study was to investigate changes in cardiometabolic clustering characteristics in... more The aim of this study was to investigate changes in cardiometabolic clustering characteristics in response to highly significant weight loss. Pre-post analysis of a lifestyle intervention for the treatment of obesity and the assessment of interrelated metabolic changes were analyzed using principal component analysis (PCA). A total of n=75 clinically obese boys and girls [standardized body mass index (sBMI) 3.07±0.59] aged 8-18 years were assessed after lifestyle intervention (30±12 days). There were favorable improvements in BMI waist circumference, fasting insulin, triglycerides (TGs), systolic blood pressure (SBP) and diastolic blood pressure (DBP) (all P<0.001). PCA was performed using a simple conceptual model of changes in six metabolic variables: Overall and central obesity (BMI and waist circumference), dyslipidemia [TG and high-density lipoprotein cholesterol (HDL-C)], insulin resistance [fasting insulin or homeostasis model assessment of insulin resistance (HOMA-IR)], a...
Endocrinology, Diabetes & Metabolism Case Reports, 2014
Summary A lean 15-year-old girl was diagnosed with type 1 diabetes based on symptomatic hyperglyc... more Summary A lean 15-year-old girl was diagnosed with type 1 diabetes based on symptomatic hyperglycaemia and positive anti-islet cell antibodies. Glycaemia was initially stabilised on twice-daily mixed insulin. After 11 months from the time of diagnosis, she complained of hyperglycaemia and ketosis alternating with hypoglycaemia. This progressively worsened until prolonged hospital admission was required for treatment of refractory hypoglycaemia. A high titre of anti-insulin antibodies was detected associated with a very low recovery of immunoreactive (free) insulin from plasma after precipitation with polyethylene glycol, suggesting the presence of insulin in bound complexes. Insulin autoimmune syndrome was diagnosed and metabolic fluctuations were initially managed supportively. However, due to poor glucose control, immunosuppressive therapy was initiated first with steroids and plasmapheresis and later with anti-CD20 antibody therapy (Rituximab). This treatment was associated with ...
Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, 2013
Background Considerable intermethod bias has been observed between cortisol immunoassays, with so... more Background Considerable intermethod bias has been observed between cortisol immunoassays, with some also displaying a gender difference. Cortisol immunoassay performance is affected by serum matrix effects such as changes in steroid binding proteins and presence of interfering steroids which can be altered in various clinical settings. This study investigates cortisol immunoassay bias in pregnancy, renal failure and intensive care patients. Methods Serum remaining after routine analysis from pregnant patients, patients on the intensive care unit and patients with renal failure were obtained prior to disposal and used to create 20 anonymous samples per group. A male and female serum pool was prepared and spiked with cortisol. Samples were aliquoted and distributed to four hospitals for cortisol analysis by immunoassays from four different manufacturers. Cortisol was also measured by an isotope dilution-gas chromatography–mass spectrometry method for comparison of assay bias. Results ...
The metabolic triad [fasting insulin, apolipoprotein B, and low-density lipoporotein (LDL) peak p... more The metabolic triad [fasting insulin, apolipoprotein B, and low-density lipoporotein (LDL) peak particle density] is characteristic of increased intra-abdominal adipose tissue and insulin resistance and can be predicted by the simple and adoptable screening tool, the hypertriglyceridemic waist. The associations between hypertriglyceridemic waist components [fasting triglycerides (TG) and waist circumference cut-points derived from a child-specific metabolic syndrome definition] with the metabolic triad were examined in obese youth before and after weight loss. A continuous metabolic triad score (MTS) was calculated as a cumulative and standardized residual score of fasting insulin, apolipoprotein B, and LDL peak particle density (z-scores of the metabolic triad variables regressed onto age and sex). The predictive ability of TG and waist in assessing metabolic triad change was undertaken in 75 clinically obese boys and girls, aged 8-18, body mass index (BMI) 34.2±6.4 kg/m(2) before ...
Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, 2000
The biochemical investigation of carcinoid disease has relied on measurement of the daily excreti... more The biochemical investigation of carcinoid disease has relied on measurement of the daily excretion of 5-hydroxyindoleacetic acid (5HIAA) in urine. 1 Collection of 24-h urine has considerable disadvantages for the patient. Inconvenience, embarrassment, strict dietary requirements and the need for hazardous preservatives make this test unpopular, and signi® cant errors in collection may be made. The measurement of 5-HIAA in plasma would offer a more convenient alternative. However, the value of plasma 5-HIAA measurements in carcinoid disease has not been evaluated. Highperformance liquid chromatographic (HPLC) methods for measuring plasma 5-HIAA have been described previously, but applied to the investigation of patients with psychiatric and neurological disorders. 2 We describe a simple, isocratic HPLC method
Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, 2002
Background Carcinoid disease is an uncommon disorder resulting from tumours of the enterochromaff... more Background Carcinoid disease is an uncommon disorder resulting from tumours of the enterochromaffin cells. Current biochemical investigation usually involves the measurement of 5-hydroxyindole-3-acetic acid (5-HIAA) in 24-h urine collections. Because of the problems associated with urine collections (i.e. inconvenience, accuracy of collection and requirement for preservatives) two alternative markers, fasting plasma 5-HIAA and whole blood serotonin (5-hydroxytryptamine), have been studied. Methods and results Whole blood serotonin concentration and plasma and urine 5-HIAA concentrations were measured by high-performance liquid chromatography in 31 patients suspected of having carcinoid and 26 known carcinoid patients. Receiver operator characteristic curve analysis of the data showed no statistical difference between the three markers ( P>0·01) with regard to their discriminating function. However, fasting plasma 5-HIAA assay showed greater stability than whole blood serotonin as...
Small, dense low-density lipoprotein (LDL) particles are highly atherogenic and strongly associat... more Small, dense low-density lipoprotein (LDL) particles are highly atherogenic and strongly associated with obesity-related dyslipidemia. The metabolic inter-relationships between weight loss induced changes in waist circumference, triglycerides, insulin sensitivity and small-dense LDL particles in clinically obese children and adolescents have not been studied. Seventy-five clinically obese boys and girls (standardized body mass index 3.07 ± 0.59, aged 8-18 years) were recruited. Anthropometric, body composition and cardiometabolic risk factors were measured pre- and post-weight loss. There were highly significant reductions in anthropometric, body composition and cardiometabolic risk factors. Triglyceride change was positively correlated with LDL peak particle density and percentage LDL pattern B changes (relative abundance of small, dense LDL particles). Multiple regression analyses showed that changes in triglyceride concentration accounted for between 24 and 18% of the variance in...
SummaryBariatric surgery is recognized as the most clinically and cost‐effective treatment for pe... more SummaryBariatric surgery is recognized as the most clinically and cost‐effective treatment for people with severe and complex obesity. Many people presenting for surgery have pre‐existing low vitamin and mineral concentrations. The incidence of these may increase after bariatric surgery as all procedures potentially cause clinically significant micronutrient deficiencies. Therefore, preparation for surgery and long‐term nutritional monitoring and follow‐up are essential components of bariatric surgical care. These guidelines update the 2014 British Obesity and Metabolic Surgery Society nutritional guidelines. Since the 2014 guidelines, the working group has been expanded to include healthcare professionals working in specialist and non‐specialist care as well as patient representatives. In addition, in these updated guidelines, the current evidence has been systematically reviewed for adults and adolescents undergoing the following procedures: adjustable gastric band, sleeve gastrec...
We read with interest the paper by Schini et al 1 regarding the derivation of adjusted calcium re... more We read with interest the paper by Schini et al 1 regarding the derivation of adjusted calcium reference interval. In particular, their implied suggestion that they can replace the Pathology Harmony reference interval. They propose a slightly lower interval (2.19-2.56 mmol/L) than the Pathology Harmony reference interval (2.2-2.6). We would argue that this reference interval is not valid for universal applications due to variations between analytical methods.
Background Aldosterone and renin are pivotal hormones in the regulation of salt and water homeost... more Background Aldosterone and renin are pivotal hormones in the regulation of salt and water homeostasis and blood pressure. Measurement of renin and aldosterone in serum/plasma is essential for the investigation of primary hyperaldosteronism (PA) and monitoring of glucocorticoid replacement therapy. Methods We report 2 LC-MS/MS methods developed to measure aldosterone and plasma renin activity (PRA). PRA was determined by endogenous enzymatic generation of angiotensin I using 150 µL of sample. Generated angiotensin I was purified by solid phase extraction prior to chromatographic separation and mass spectrometry. Aldosterone measurement required 300 μL of sample extracted with MTBE prior to LC-MS/MS analysis. Results The PRA method was linear (1.2–193 nmol/L), sensitive (LLOQ = 1.2 nmol/L), precise (CV = 4.1%), and specific (no cross reactivity for a number of structurally similar steroids). Dilutional linearity and recovery (84%) were acceptable. Accuracy was confirmed by comparison ...
Clinical chemistry and laboratory medicine, Jan 22, 2016
Optimum patient care in relation to laboratory medicine is achieved when results of laboratory te... more Optimum patient care in relation to laboratory medicine is achieved when results of laboratory tests are equivalent, irrespective of the analytical platform used or the country where the laboratory is located. Standardization and harmonization minimize differences and the success of efforts to achieve this can be monitored with international category 1 external quality assessment (EQA) programs. An EQA project with commutable samples, targeted with reference measurement procedures (RMPs) was organized by EQA institutes in Italy, the Netherlands, Portugal, UK, and Spain. Results of 17 general chemistry analytes were evaluated across countries and across manufacturers according to performance specifications derived from biological variation (BV). For K, uric acid, glucose, cholesterol and high-density density (HDL) cholesterol, the minimum performance specification was met in all countries and by all manufacturers. For Na, Cl, and Ca, the minimum performance specifications were met by...
The aim of this study was to investigate changes in cardiometabolic clustering characteristics in... more The aim of this study was to investigate changes in cardiometabolic clustering characteristics in response to highly significant weight loss. Pre-post analysis of a lifestyle intervention for the treatment of obesity and the assessment of interrelated metabolic changes were analyzed using principal component analysis (PCA). A total of n=75 clinically obese boys and girls [standardized body mass index (sBMI) 3.07±0.59] aged 8-18 years were assessed after lifestyle intervention (30±12 days). There were favorable improvements in BMI waist circumference, fasting insulin, triglycerides (TGs), systolic blood pressure (SBP) and diastolic blood pressure (DBP) (all P<0.001). PCA was performed using a simple conceptual model of changes in six metabolic variables: Overall and central obesity (BMI and waist circumference), dyslipidemia [TG and high-density lipoprotein cholesterol (HDL-C)], insulin resistance [fasting insulin or homeostasis model assessment of insulin resistance (HOMA-IR)], a...
Endocrinology, Diabetes & Metabolism Case Reports, 2014
Summary A lean 15-year-old girl was diagnosed with type 1 diabetes based on symptomatic hyperglyc... more Summary A lean 15-year-old girl was diagnosed with type 1 diabetes based on symptomatic hyperglycaemia and positive anti-islet cell antibodies. Glycaemia was initially stabilised on twice-daily mixed insulin. After 11 months from the time of diagnosis, she complained of hyperglycaemia and ketosis alternating with hypoglycaemia. This progressively worsened until prolonged hospital admission was required for treatment of refractory hypoglycaemia. A high titre of anti-insulin antibodies was detected associated with a very low recovery of immunoreactive (free) insulin from plasma after precipitation with polyethylene glycol, suggesting the presence of insulin in bound complexes. Insulin autoimmune syndrome was diagnosed and metabolic fluctuations were initially managed supportively. However, due to poor glucose control, immunosuppressive therapy was initiated first with steroids and plasmapheresis and later with anti-CD20 antibody therapy (Rituximab). This treatment was associated with ...
Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, 2013
Background Considerable intermethod bias has been observed between cortisol immunoassays, with so... more Background Considerable intermethod bias has been observed between cortisol immunoassays, with some also displaying a gender difference. Cortisol immunoassay performance is affected by serum matrix effects such as changes in steroid binding proteins and presence of interfering steroids which can be altered in various clinical settings. This study investigates cortisol immunoassay bias in pregnancy, renal failure and intensive care patients. Methods Serum remaining after routine analysis from pregnant patients, patients on the intensive care unit and patients with renal failure were obtained prior to disposal and used to create 20 anonymous samples per group. A male and female serum pool was prepared and spiked with cortisol. Samples were aliquoted and distributed to four hospitals for cortisol analysis by immunoassays from four different manufacturers. Cortisol was also measured by an isotope dilution-gas chromatography–mass spectrometry method for comparison of assay bias. Results ...
The metabolic triad [fasting insulin, apolipoprotein B, and low-density lipoporotein (LDL) peak p... more The metabolic triad [fasting insulin, apolipoprotein B, and low-density lipoporotein (LDL) peak particle density] is characteristic of increased intra-abdominal adipose tissue and insulin resistance and can be predicted by the simple and adoptable screening tool, the hypertriglyceridemic waist. The associations between hypertriglyceridemic waist components [fasting triglycerides (TG) and waist circumference cut-points derived from a child-specific metabolic syndrome definition] with the metabolic triad were examined in obese youth before and after weight loss. A continuous metabolic triad score (MTS) was calculated as a cumulative and standardized residual score of fasting insulin, apolipoprotein B, and LDL peak particle density (z-scores of the metabolic triad variables regressed onto age and sex). The predictive ability of TG and waist in assessing metabolic triad change was undertaken in 75 clinically obese boys and girls, aged 8-18, body mass index (BMI) 34.2±6.4 kg/m(2) before ...
Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, 2000
The biochemical investigation of carcinoid disease has relied on measurement of the daily excreti... more The biochemical investigation of carcinoid disease has relied on measurement of the daily excretion of 5-hydroxyindoleacetic acid (5HIAA) in urine. 1 Collection of 24-h urine has considerable disadvantages for the patient. Inconvenience, embarrassment, strict dietary requirements and the need for hazardous preservatives make this test unpopular, and signi® cant errors in collection may be made. The measurement of 5-HIAA in plasma would offer a more convenient alternative. However, the value of plasma 5-HIAA measurements in carcinoid disease has not been evaluated. Highperformance liquid chromatographic (HPLC) methods for measuring plasma 5-HIAA have been described previously, but applied to the investigation of patients with psychiatric and neurological disorders. 2 We describe a simple, isocratic HPLC method
Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, 2002
Background Carcinoid disease is an uncommon disorder resulting from tumours of the enterochromaff... more Background Carcinoid disease is an uncommon disorder resulting from tumours of the enterochromaffin cells. Current biochemical investigation usually involves the measurement of 5-hydroxyindole-3-acetic acid (5-HIAA) in 24-h urine collections. Because of the problems associated with urine collections (i.e. inconvenience, accuracy of collection and requirement for preservatives) two alternative markers, fasting plasma 5-HIAA and whole blood serotonin (5-hydroxytryptamine), have been studied. Methods and results Whole blood serotonin concentration and plasma and urine 5-HIAA concentrations were measured by high-performance liquid chromatography in 31 patients suspected of having carcinoid and 26 known carcinoid patients. Receiver operator characteristic curve analysis of the data showed no statistical difference between the three markers ( P>0·01) with regard to their discriminating function. However, fasting plasma 5-HIAA assay showed greater stability than whole blood serotonin as...
Small, dense low-density lipoprotein (LDL) particles are highly atherogenic and strongly associat... more Small, dense low-density lipoprotein (LDL) particles are highly atherogenic and strongly associated with obesity-related dyslipidemia. The metabolic inter-relationships between weight loss induced changes in waist circumference, triglycerides, insulin sensitivity and small-dense LDL particles in clinically obese children and adolescents have not been studied. Seventy-five clinically obese boys and girls (standardized body mass index 3.07 ± 0.59, aged 8-18 years) were recruited. Anthropometric, body composition and cardiometabolic risk factors were measured pre- and post-weight loss. There were highly significant reductions in anthropometric, body composition and cardiometabolic risk factors. Triglyceride change was positively correlated with LDL peak particle density and percentage LDL pattern B changes (relative abundance of small, dense LDL particles). Multiple regression analyses showed that changes in triglyceride concentration accounted for between 24 and 18% of the variance in...
SummaryBariatric surgery is recognized as the most clinically and cost‐effective treatment for pe... more SummaryBariatric surgery is recognized as the most clinically and cost‐effective treatment for people with severe and complex obesity. Many people presenting for surgery have pre‐existing low vitamin and mineral concentrations. The incidence of these may increase after bariatric surgery as all procedures potentially cause clinically significant micronutrient deficiencies. Therefore, preparation for surgery and long‐term nutritional monitoring and follow‐up are essential components of bariatric surgical care. These guidelines update the 2014 British Obesity and Metabolic Surgery Society nutritional guidelines. Since the 2014 guidelines, the working group has been expanded to include healthcare professionals working in specialist and non‐specialist care as well as patient representatives. In addition, in these updated guidelines, the current evidence has been systematically reviewed for adults and adolescents undergoing the following procedures: adjustable gastric band, sleeve gastrec...
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