| 1. |
- Lohmander, L. Stefan, et al.
(författare)
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Cartilage matrix metabolism in osteoarthritis : markers in synovial fluid, serum, and urine
- 1992
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Ingår i: Clinical Biochemistry. - 0009-9120. ; 25:3, s. 167-174
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis is a major cause of disability and early retirement. Yet we lack the means to diagnose the disease in its early stages or to monitor the effects of treatment on the target tissue, the joint cartilage. Neither can we identify the disease mechanisms at the tissue or cell level. Current research focuses on the use of markers of cartilage matrix metabolism in body fluids as a means to diagnose and monitor osteoarthritis. Cartilage proteoglycan, collagen and glycoprotein fragments, as well as proteinases and their inhibitors, are being suggested for this purpose. Structural information on matrix molecule fragments released into body fluids may also help to identify the enzymes active in the destruction of the cartilage, a central issue in osteoarthritis.
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| 2. |
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| 7. |
- Ahnström, Josefin, et al.
(författare)
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Plasma concentrations of apolipoproteins A-I, B, and M in patients with abdominal aortic aneurysms.
- 2010
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 1873-2933 .- 0009-9120. ; 43:4-5, s. 407-410
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Apolipoproteins play important roles in the development of atherosclerosis but their involvement in the pathogenesis of abdominal aortic aneurysm (AAA) is poorly understood. The aim was to investigate whether apoA-I, apoB and apoM are independently associated with AAA. Design and methods: Plasma apoA-I, apoB and apoM were measured in 343 patients with AAA and in 214 elderly apparently healthy control individuals from the background population. Results: AAA patients had lower apolipoprotein levels, as compared to healthy individuals; apoA-I, 1.62 vs. 2.08 g/l; apoB, 0.91 vs. 1.04 g/l; apoM, 0.72 vs. 0.91 mumol/l (p<0.0001 for all three). In multivariate analyses, apoA-I and apoB were associated with AAA, odds ratios (95% confidence intervals) being 0.53 (0.43-0.64) and 0.86 (0.75-0.998), respectively. Conclusions: ApoA-I, apoB and apoM levels were significantly lower in patients with AAA than in the control individuals, but only apoA-I and apoB were independently associated to AAA.
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| 8. |
- Ahnström, Josefin, et al.
(författare)
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Plasma concentrations of apolipoproteins A-I, B, and M in patients with critical limb ischemia.
- 2010
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 1873-2933 .- 0009-9120. ; 43, s. 599-603
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Apolipoproteins affect development of atherosclerosis, but their involvement in the pathogenesis of critical limb ischemia (CLI), a severe form of atherosclerosis, has not previously been examined. DESIGN AND METHODS: ApoA-I, apoB, and apoM were measured in plasma from 196 CLI subjects and 214 control individuals from the background population. RESULTS: Cases had lower levels of the apolipoproteins, as compared to controls; apoA-I, 1.23 vs. 2.08 g/L; apoB, 0.93 vs. 1.04 g/L; apoM, 0.75 vs. 0.91 mumol/L (p<0.0001 for all three). ApoA-I and apoM correlated negatively with inflammatory markers and positively to 1- and 3-year survival rates, whereas apoB did not. In multivariate analyses, apoA-I, but not apoB and apoM, was independently associated with CLI, the odds ratio being 0.015. CONCLUSIONS: In subjects with CLI, plasma concentrations of apoA-I, apoB and apoM were significantly lower than in control individuals, but only apoA-I was independently associated to CLI.
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| 9. |
- Apple, FS, et al.
(författare)
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IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac troponin assays
- 2015
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 48:4-5, s. 201-203
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Tidskriftsartikel (refereegranskat)abstract
- In 2011, the IFCC Task Force on Clinical Applications of Cardiac Bio-Markers (TF-CB) was formed, with the purpose of providing evidence based educational materials to assist all biomarker users, i.e. laboratorians, clinicians, researchers, in-vitro diagnostics and regulatory agencies, in better understanding important analytical and clinical aspects of established and novel cardiac biomarkers for use in clinical practice and research. The goal of the task force was to promulgate the same information conjointly through the in vitro diagnostic industry to the laboratory, emergency department and cardiologists. The initial undertaking of the TF-CB, which is comprised of laboratory medicine scientists, emergency medicine physicians and cardiologists, was to address two key issues pertaining to implementing high-sensitivity cardiac troponin (hs-cTn) assays in clinical practice: the 99th percentile upper reference limit (URL) and calculating serial change values in accord with the Universal Definition of AMI. The highlights of both concepts from IFCC statements are described.
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| 10. |
- Arkblad, Eva L, et al.
(författare)
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Two cases of 5-fluorouracil toxicity linked with gene variants in the DPYD gene.
- 2010
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Ingår i: Clinical biochemistry. - : Elsevier BV. - 1873-2933 .- 0009-9120. ; 43:3, s. 331-4
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Dihydropyrimidine dehydrogenase (DPD) is the initial rate-limiting enzyme in endogenous pyrimidine catabolism and is responsible for the reduction of the pyrimidine analog 5-fluorouracil (5-FU). DPD deficiency is known to cause potentially lethal toxicity in patients receiving 5-FU. We here report a frequency analysis of one of the major splice-site mutations in the DPDY gene, and further two new DPYD gene variants. DESIGN AND METHODS: Restriction fragment length polymorphism (RFLP) and DNA sequence analysis were performed on genomic DNA and mRNA. RESULTS: In 400 patients that were diagnosed with cancer and were eligible for 5-FU treatment, 14 patients were found to be heterozygous for the splice-site mutation DPYD IVS14+1G>A, which corresponds to a population frequency of 3.5%. Two novel variants in the DPYD gene were identified. The first case was heterozygous for DPYD c.1796T>C (p.M599T). In the second case, we observed heterozygosity for the splice-site mutation DPYD IVS14+17A>G. CONCLUSIONS: We report two new DPYD gene variants, of which DPYD c.1796T>C is potentially pathogenic, whereas DPYD IVS14+17A>G is suggested as a variant without clinical significance.
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| 11. |
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| 12. |
- Bjurman, Christian, 1983, et al.
(författare)
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High-sensitive cardiac troponin, NT-proBNP, hFABP and copeptin levels in relation to glomerular filtration rates and a medical record of cardiovascular disease
- 2015
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 48:4-5, s. 302-307
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Tidskriftsartikel (refereegranskat)abstract
- Background: Elevation of cardiac markers in patients with renal dysfunction has not been fully assessed reducing the diagnostic usefulness of these biomarkers. Objective: To examine the effects of renal function and a medical record of cardiovascular disease on levels of cardiac biomarkers. Methods: Serum samples were collected from 489 patients referred for GFR measurement using Cr51-EDTA or iohexol plasma clearance (measured GFR). The cardiac biomaiters Troponin T (hs-cTnT), Troponin I (hsTnI), N-Terminal pro Brain Natriuretic Peptide (NTproBNP), Copeptin, Human Fatty Acid Binding Protein (hFABP), as well as the kidney function biomarkers creatinine and cystatin C, were measured. Regression was used to analyse the relationship between biomarker levels and the glomerular filtration rate (GFR) between 15 and 90 mL/min/1.73 m(2). Results: Compared with normal kidney function, the estimated increases in the studied cardiac biomarkers at a CUR of 15 mL/mM/1.73 m(2) varied from 2-fold to 15 fold but were not very different between patients with or without a medical record of cardiovascular disease and were most prominent for cardiac biomarkers with low molecular weight. hs-cTnT levels correlated more strongly to measured CUR and increased more at low CUR compared to hs-cTnI. For hFABP and NT-proBNP increases at low kidney function were more correctly predicted by a local Cystatin C-based eGFR formula compared with creatinine-based eGFR (using the MDRD or CKD-EPI equations) Conclusion: The extent of the elevation of cardiac markers at low renal function is highly variable. For hFABP and NTproBNP Cystatin C-based eGFR provides better predictions of the extent of elevation compared to the MDRD or CKD-EPI equations. (C) 2015 The Authors. The Canadian Society of Clinical Chemists. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd,40/).
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| 13. |
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| 14. |
- Brynildsen, Jon, et al.
(författare)
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Circulating secretoneurin concentrations in patients with moderate to severe aortic stenosis
- 2019
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Ingår i: Clinical Biochemistry. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0009-9120 .- 1873-2933. ; 71, s. 17-23
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Tidskriftsartikel (refereegranskat)abstract
- Background: Secretoneurin (SN) concentrations provide important prognostic information in patients with myocardial dysfunction. Whether preoperative SN concentrations improve risk assessment in patients with moderate to severe aortic stenosis (AS) is unknown. Methods: We included 57 patients with moderate to severe AS referred for presurgical evaluation. All patients were examined with comprehensive echocardiography, electrocardiogram (ECG), and biochemical measurements and compared to 10 age- and sex-matched healthy subjects. Results: Median (quartile 1-3) SN concentrations were 141 (121-163) pmol/L in AS patients and 132 (106-148) pmol/L in control subjects (p = .17). Lower estimated creatinine clearance and use of diuretics, but not standard ECG or echocardiographic indices and cardiac biomarkers, were associated with increasing SN concentrations. Fifteen patients (26%) died during 3.5 years median follow-up. SN concentrations were higher in non-survivors than survivors: 156 (133-209) vs. 140 (116-155) pmol/L, p = .007. Higher SN concentrations were associated with increased risk of mortality also after adjustment for established risk indices, biomarkers, and status regarding valvular surgery: hazard ratio per lnSN 15.13 (95% CI 1.05-219.00); p = .046. Receiver operating characteristics area under the curve for SN to predict mortality was 0.74 (95% CI 0.60-0.88) compared to 0.73 (0.59-0.87) for high-sensitivity cardiac troponin T and 0.67 (0.51-0.82) for N-terminal pro-B-type natriuretic peptide. The previously identified cut-off of SN > 204 pmol/L in cardiac surgical patients predicted mortality also in this cohort. Conclusions: SN concentrations improve risk assessment in patients with moderate to severe AS by providing additional prognostic information to established risk indices such as echocardiography, ECG, and established cardiac biomarkers.
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| 15. |
- Cao, Yang, Associate Professor, 1972-, et al.
(författare)
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Determination of clinically acceptable cut-offs for hemolysis index : an application of bootstrap method using real-world data
- 2021
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Ingår i: Clinical Biochemistry. - : Elsevier. - 0009-9120 .- 1873-2933. ; 94, s. 74-79
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To assess the impact of hemolysis on laboratory results under local conditions and to verify the hemolysis index cut-off for potassium using real-world data.Methods: The statistical bootstrapping method was performed on 54,125 samples collected at the University Hospital of Örebro (USÖ) and the results were compared to a method based on stratification of samples according to hemolysis level, and on paired difference testing.Results: Setting the acceptable allowable limit of error to 10 %, the three assessed strategies yielded comparable results with respect to the impact of haemolytic interference on test results for potassium. The suggested cut-offs were 111 mg Hb/dL for the bootstrapping method, between 100-125 mg Hb/dL for the method based on stratification, and around 150 mg/dL for the paired difference testing strategy. The impact of hemolysis on potassium measurement is likely different between primary care patients and inpatients.Conclusions: Using the effect of hemolysis on potassium measurement as a model, a novel approach towards finding clinically acceptable limits for analytical interference is presented, that relies on the bootstrapping method and on actual patient data from routine laboratory operation, hence incorporating local population characteristics, equipment and instrumental settings.
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| 16. |
- Carlsson, Axel C, et al.
(författare)
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Endostatin predicts mortality in patients with acute dyspnea - a cohort study of patients seeking care in emergency departments.
- 2019
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 75
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Increased levels of circulating endostatin predicts cardiovascular morbidity and impaired kidney function in the general population. The utility of endostatin as a risk marker for mortality in the emergency department (ED) has not been reported.AIM: Our main aim was to study the association between plasma endostatin and 90-day mortality in an unselected cohort of patients admitted to the ED for acute dyspnea. Design Circulating endostatin was analyzed in plasma from 1710 adults and related to 90-day mortality in Cox proportional hazard models adjusted for age, sex, body mass index, oxygen saturation, respiratory rate, body temperature, C-reactive protein, lactate, creatinine and medical priority according to the Medical Emergency Triage and Treatment System-Adult score (METTS-A). The predictive value of endostatin for mortality was evaluated with receiver operating characteristic (ROC) analysis and compared with the clinical triage scoring system and age.RESULTS: Each one standard deviation increment of endostatin was associated with a HR of 2.12 (95 % CI 1.31-3.44 p< 0.01) for 90-day mortality after full adjustment. Levels of endostatin were significantly increased in the group of patients with highest METTS-A (p<0.001). When tested for the outcome 90-day mortality, the area under the ROC curve (AUC) was 0.616 for METTS-A, 0.701 for endostatin, 0.708 for METTS -A and age and 0.738 for METTS-A, age and levels of endostatin.CONCLUSIONS: In an unselected cohort of patients admitted to the ED with acute dyspnea, endostatin had a string association to 90-day mortality and improved prediction of 90-day mortality in the ED beyond the clinical triage scoring system and age with 3 %.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
- Dzialanski, Zbigniew, et al.
(författare)
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Lactase persistence versus lactose intolerance : Is there an intermediate phenotype?
- 2016
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Ingår i: Clinical Biochemistry. - : Elsevier. - 0009-9120 .- 1873-2933. ; 49:3, s. 248-252
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Tidskriftsartikel (refereegranskat)abstract
- Background: According to the prevailing theory about the genetic background to lactose intolerance, there are three genotypes but only two adult physiological phenotypes: lactase persistence in individuals with the CT and TT genotypes and lactase non-persistence in individuals with the CC genotype. However, analysis of lactase activity from intestinal biopsies has revealed three distinct levels of activity, suggesting that an intermediate physiological phenotype may exist.Aim: To assess possible disparities between different genotypes with regard to biomarkers of lactase activity and physical symptoms during an oral lactose load test.Methods: A retrospective study using an oral lactose load test (n=487). Concentrations of hydrogen in exhaled air and blood glucose were measured. Afterwards, subjects were asked to provide oral mucosa samples for genotyping and answer a questionnaire (participation rate 56%, n=274).Results: Mean hydrogen levels in exhaled air at 120min were significantly higher in the CT genotype than in the TT genotype. There was no significant difference in blood glucose levels between the two groups. Reported symptoms, with the possible exception of abdominal pain, were equally prevalent in both groups.Conclusions: Subjects with the CT and TT genotypes, hitherto classified as lactase-persistent, differ in their physiological response to lactose intake, indicating differences in phenotype which could have clinical significance.
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| 21. |
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| 22. |
- Edlund, Bror, et al.
(författare)
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A proposed stoichiometrical calibration procedure to achieve transferability of D-dimer measurements and to characterize the performance of different methods
- 2006
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 39:2, s. 137-142
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is little transferability between D-dimer levels obtained by different reagents today. This makes it difficult to compare results from different clinical studies. OBJECTIVES: We give a comprehensive proposal for calibration of D-dimer assays. All crucial steps and underlying assumptions are made explicit. METHODS: The new approach is based on using a set of fibrinolysates of patient samples clotted and treated with tPA to obtain maximal conversion to D-dimers. Their expected maximal D-dimer concentrations are calculated stoichiometrically from their different fibrinogen values and the published molecular masses of fibrinogen and average D-dimer. The characteristics of five latex enhanced D-dimer immunoassays were also tested against early and late fibrin fragments using this procedure. These were produced by prolonged fibrinolysis of a set of patient samples of varying fibrinogen concentrations. RESULTS: These varied typically between methods and lysis times. One of the methods showing the highest yield irrespective of lysis time was used for calibration. A linear standard curve with zero intercept and R2 = 0.95 was obtained. CONCLUSION: Following this procedure will allow better transferability of D-dimer in future clinical trails.
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| 23. |
- Eggers, Kai M., et al.
(författare)
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Cardiac troponin I levels in an elderly population from the community - The implications of sex
- 2015
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 48:12, s. 751-756
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The importance of sex on cardiac troponin levels is increasingly recognized. We investigated whether the entities associated with troponin leakage and the prognostic consequences thereof would differ between elderly men and women from the community. Design and methods: Cardiac troponin I (cTnI) levels were measured using a high-sensitivity assay (Abbott Laboratories) in 70-year old men (n = 502) and women (n = 502) from the PIVUS study. All study participants were followed up for 10 years regarding all-cause mortality and incident cardiovascular (CV) disease. Results: Median cTnI levels were 4.1 and 3.0 ng/L in men and women, respectively (p < 0.001). By multiple linear regression, the relative contribution of lower left-ventricular ejection fraction and ischemic ECG changes to cTnI levels was greater in men compared to women. For other clinical and echocardiographic variables, similar associations were found. cTnI independently predicted all-cause mortality in men (n = 93 [18.5%]; hazard ratio [HR] 1.38 [1.12-1.70]) and women (n = 62 [12.4%]; HR 1.59 [1.11-2.28]) but not incident CV disease in subjects being CV healthy at baseline (n = 163/857). The interaction terms of sex on the associations of cTnI with both outcomes were non-significant. Sex-specific cut-offs did not improve prognostication. Variations in the pattern of entities associated with cTnI leakage had no impact on event rates. Conclusions: We found some differences in the entities associated with higher cTnI levels in elderly community-dwelling men and women. However, this did not translate into differences in the associations of cTnI with adverse outcome.
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| 24. |
- Eggers, Kai M., et al.
(författare)
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Clinical and prognostic implications of circulating pentraxin 3 levels in non ST-elevation acute coronary syndrome
- 2013
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 46:16-17, s. 1655-1659
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Pentraxin 3 (PTX3) is the prototype of the long pentraxin family. PTX3 is involved in inflammatory processes affecting the cardiovascular system, and PTX3 levels have been shown to be elevated and independently prognostic in ST-elevation myocardial infarction. Data on PTX3 levels in non-ST-elevation acute coronary syndrome (NSTE-ACS), in contrast, are limited. The aim of the present analysis was to investigate the implications of PTX3 levels in a fairly large sample of NSTE-ACS patients and in comparison to levels of C-reactive protein (CRP). Design and methods: We measured levels of PTX3 and CRP in both 82 healthy controls and 401 NSTE-ACS patients from the GUSTO IV study, and studied the associations of these biomarkers to clinical data and 1-year mortality. Results: NSTE-ACS patients had significantly higher median PTX3 levels compared to healthy controls (3.8 vs. 1.9 mu g/L; p < 0.001). PTX3 levels in patients with NSTE-ACS were independently related to female sex and cardiac troponin T levels, but not to age or cardiovascular risk factors. PTX3 levels were higher in patients who died within 1 year but did not emerge as an independent predictor of 1-year mortality (adjusted OR 1,2 [95% Cl 0.6-2.31). This was in contrast to CRP (adjusted OR 1.5 [95% Cl 1.1-2.3]). Neither PTX3 nor CRP yielded significant discriminative value regarding mortality prediction. Conclusions: PTX3 levels are elevated in NSTE-ACS. However, the prognostic information provided by PTX3 levels is limited and inferior compared to CRP. Our data, thus, do not support the measurement of PTX3 in patients with NSTE-ACS.
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| 25. |
- Eggers, Kai M., 1962-, et al.
(författare)
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Myeloperoxidase is not useful for the early assessment of patients with chest pain
- 2010
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 43:3, s. 240-245
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Myeloperoxidase (MPO) has been listed as a potentially useful risk marker in acute coronary syndrome. However, its clinical utility in patients with acute chest pain is not yet defined. DESIGN AND METHODS: MPO (Architect, Abbott Diagnostics) was measured in 120 healthy controls and 303 chest pain patients who had been admitted to the coronary care units of three Swedish hospitals. RESULTS: Chest pain patents had significantly higher median MPO levels compared to healthy controls (120.6 vs. 78. 9 pmol/L; p<0.001). However, MPO was not useful for the diagnosis of myocardial infarction (c-statistics 0.61 [95% CI 0.54-0.67]), and Cox regression analysis revealed no independent association between MPO and mortality (adjusted hazard ratio 1.3 [95% CI 0.8-2.0]) or the composite endpoint (adjusted hazard ratio 1.1 [95% CI 0.8-1.5]) after a median follow-up of 4.9 years. CONCLUSIONS: MPO provided no clinically relevant information in the present population of chest pain patients.
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| 26. |
- Eggers, Kai, 1962-, et al.
(författare)
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The applied statistical approach highly influences the 99th percentile of cardiac troponin I
- 2016
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 49:15, s. 1109-1112
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCardiac troponin (cTn) is the biomarker of choice for assessment of patients with acute coronary syndromes. Guidelines recommend the cTn 99th percentile derived from a cardiovascular healthy reference population as decision threshold. The importance of standardized criteria for the composition of such a reference population is well acknowledged. In this analysis, we investigated to which extent different statistical methods might have bearing on the calculated cTnI 99th percentile.MethodscTnI (Abbott) 99th percentiles were determined in 521 cardiovascular healthy community-dwelling subjects using the nonparametric method, the Harrell-Davis bootstrap method and the robust method together with different tests to identify potential outliers (Dixon, Tukey, Reed) and different statistical softwares.ResultsThe cTnI 99th percentiles (nonparametric method) were 37 ng/L (total population), 42 ng/L (men) and 25 ng/L (women). These estimates differed by − 7.4% to + 5.7% using the Harrell-Davis bootstrap method and were up to 64.1% lower using the robust method. For the robust method, cTnI 99th percentiles varied by 44.2% depending on the applied software. The method of Tukey classified nine subjects as outliers while no outlier was detected using the other methods. Excluding these nine subjects resulted in up to 60.2% lower cTnI 99th percentiles.ConclusionsOur results emphasize the need of a standardized statistical approach to calculate cTnI 99th percentiles. Our findings support the use of the nonparametric method and a conservative approach to detect outliers. This requires that the assessed population is sufficiently large and well selected on the basis of stringently applied clinical criteria.
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| 27. |
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| 28. |
- Ekman, Carl, et al.
(författare)
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Plasma concentrations of Gas6 and soluble Axl correlate with disease and predict mortality in patients with critical limb ischemia.
- 2010
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 1873-2933 .- 0009-9120. ; May 4, s. 873-876
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Critical limb ischemia (CLI) is a severe peripheral arterial disease, characterized by rest pain, ulcers and gangrene in the legs. Gas6 is a vitamin K-dependent protein, which binds and activates the tyrosine kinase receptor Axl. Gas6-mediated Axl-signaling influences endothelial activation, neointima formation and immune regulation. Axl can be cleaved and soluble Axl (sAxl) is detectable in circulation. DESIGN AND METHODS: We quantified plasma concentrations of Gas6 and sAxl in 189 CLI patients and 204 controls. RESULTS: Gas6 and sAxl concentrations were increased in the CLI patients (p<0.0001) and correlated to C-reactive protein, interleukin-6, tumor necrosis factor alpha and neopterin. Patients who died within three years of sampling (n=84) had increased concentrations of Gas6 and sAxl as compared to survivors (p=0.0009 and p=0.0011). CONCLUSIONS: Plasma concentrations of Gas6 and sAxl correlate to inflammation and predict survival. This indicates that Gas6 and sAxl have a role in CLI, presumably connected to the inflammatory process.
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| 29. |
- Ekman, Carl, et al.
(författare)
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Plasma concentrations of growth arrest specific protein 6 and the soluble form of its tyrosine kinase receptor Axl as markers of large abdominal aortic aneurysms.
- 2010
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 1873-2933 .- 0009-9120. ; 43, s. 110-114
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The tyrosine kinase receptor Axl is expressed in the vasculature and Gas6 is the ligand. The extracellular part of Axl (sAxl) can be found in circulation. The aim of this study was to determine plasma concentrations of Gas6 and sAxl in patients with abdominal aortic aneurysms (AAA) and to evaluate if Gas6 and sAxl can be used as biomarkers. DESIGN AND METHODS: Immunoassays for sAxl and Gas6 were used to investigate plasma from AAA patients. Patients with large (n=123) or small AAA (n=122) were compared with healthy controls (n=141). RESULTS: Gas6 correlated positively and sAxl correlated negatively with AAA size. As a consequence, the calculated Gas6/sAxl ratios correlated even better to AAA size. Forty percent of all patients with a large AAA had higher Gas6/sAxl ratio than any in the control group. DISCUSSION: The Gas6/Axl system might be involved in AAA pathogenesis, and the Gas6/sAxl ratio may be useful as a biomarker.
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| 30. |
- Filler, G, et al.
(författare)
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Cystatin C as a marker of GFR - history, indications, and future research
- 2005
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 1873-2933 .- 0009-9120. ; 38:1, s. 1-8
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Forskningsöversikt (refereegranskat)abstract
- Objective: To summarize recent knowledge on the small molecular weight protein cystatin C (cys-C) and its use as a marker of the glomerular filtration rate (GFR). Methods: A multinational expert meeting was held in April 2002 in Marburg, Germany. Contributors summarized their main findings. Conclusions: Cys-C is at least equal if not superior to serum creatinine as a marker of GFR. The independence from height, gender, age. and muscle mass is advantageous. Select patient groups such as children, the elderly, and patients with reduced muscle mass benefit in particular.
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| 31. |
- Flodin, Mats, et al.
(författare)
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Performance evaluation of a particle-enhanced turbidimetric cystatin C assay on the Abbott ci8200 analyzer
- 2009
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 42:9, s. 873-876
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Glomerular filtration rate (GFR) is widely accepted as the best overall measure of kidney function. Cystatin C is a novel endogenous GFR marker that has been shown to be superior to creatinine for estimation of GFR in several studies. There is a need for cystatin C assays adapted to routine chemistry instrument to minimize turnaround times and allowing 24 h/day availability. MATERIALS AND METHODS: We have evaluated a new cystatin C assay developed for Architect cSystem (Abbott Laboratories, Abbott Park, IL, USA). RESULTS: The cystatin C assay showed good agreement with the corresponding assay from Dade Behring (Deerfield, IL, USA). The assay has a very low total imprecision and a good linearity. CONCLUSIONS: The new cystatin C assay is an interesting alternative to current cystatin C assays. On an Architect cSystem the assay can be performed with the same turnaround times and availability as creatinine.
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| 32. |
- Fridén, Vincent, 1975, et al.
(författare)
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Clearance of cardiac troponin T with and without kidney function
- 2017
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120. ; 50:9, s. 468-474
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The extent of kidney-dependent clearance of the cardiac damage biomarker cardiac troponin T (cTnT) is not known. Methods and results: We examined clearance of cTnT after injection of heart extracts in rats with or without clamped kidney vessels. The extent of degradation of cTnT to fragments able to pass the glomerular membrane and the kidney extraction index of cTnT was examined in human subjects. After a bolus injection of rat cardiac extract, simulating a large myocardial infarction, there was no significant difference in clearance of cTnT with or without kidney function. However, a slower clearance was observed late in the clearance process, when cTnT levels were low. When low levels of rat cardiac extract were infused at a constant rate to steady state, clamping of the renal vessels resulted in significant 2-fold reduction in clearance of cTnT. Over 60% of the measured cTnT in human subjects had a molecular weight below 17 kDa, expected to have a relatively free passage over the glomerular membrane. The extraction index of cTnT in three heart failure patients undergoing renal vein catheterization was 8-19%. Kidney function adjusted cTnT levels increased the area under the ROC curve for diagnosis of myocardial infarction of the cTnT analysis in an emergency room cohort. Conclusions: At high concentrations, often found after a large myocardial infarction, extrarenal clearance of cTnT dominates. At low levels of cTnT, often found in patients with stable cTnT elevations, renal clearance also contribute to the clearance of cTnT. This potentially explains why stable cTnT levels tend to be higher in patients with low kidney function. (C) 2017 Published by Elsevier Inc. on behalf of The Canadian Society of Clinical Chemists.
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| 33. |
- Garwicz, Daniel, et al.
(författare)
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Early recognition of reverse pseudohyperkalemia in heparin plasma samples during leukemic hyperleukocytosis can prevent iatrogenic hypokalemia
- 2012
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 45:18, s. 1700-1702
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the cause of apparent hyperkalemia in leukemic heparin plasma. Design and methods: Lithium heparin plasma and serum samples from a patient with chronic lymphocytic leukemia (CLL) with hyperleukocytosis were transported by either a pneumatic tube system or manual transport and analyzed either immediately or after 4 h. Results: Pneumatic tube transported samples resulted in higher plasma potassium levels than manually transported samples. Serum potassium was lower than plasma potassium, confirming the suspicion of "reverse" pseudohyperkalemia. Letting the pneumatic tube transported samples stand on the bench for 4 h before centrifugation surprisingly resulted in decreased or unchanged plasma potassium. Conclusions: The reverse pseudohyperkalemia in heparin plasma samples from a CLL patient was caused by pneumatic tube transport. Our results suggest extracellular leakage of potassium, followed by active transport of potassium into intact leukemic cells. This is the first Swedish case of reverse pseudohyperkalemia in a CLL patient, where clinical suspicion of false hyperkalemia and awareness of the phenomenon lead to a rapid laboratory diagnosis. The demonstration of reverse pseudohyperkalemia prevented potentially dangerous medical interventions, such as potassium lowering treatment.
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| 34. |
- Grahn, Ammi, 1961, et al.
(författare)
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A novel mutation on the transferrin gene abolishes one N-glycosylation site and alters the pattern of transferrin isoforms, mimicking that observed after excessive alcohol consumption
- 2016
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Ingår i: Clinical Biochemistry. - 0009-9120. ; 49:6, s. 511-513
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: In the process of obtaining a driver's license, a healthy 28year old man presented increased levels of disialo-transferrin (TF) (approx. 20%, ref. value<2) by HPLC analysis of TF isoforms (%,CDT), while other markers of excessive alcohol consumption (PEth, MCV and gamma-GT) were in the normal range. The objective of this study was to determine the cause of the increased %,CDT levels. DESIGN AND METHODS:Serum TF isoforms were re-analyzed by LC-MS. All coding exons of the TF gene were Sanger sequenced. RESULTS:Analysis of TF isoforms by LC-MS confirmed the presence of increased disialo-TF and revealed a discrepancy in the mass difference between disialo-TF and tetrasialo-TF which suggested the presence of a genetic TF isoform with one abolished N-glycosylation site. Sanger sequencing of the TF gene revealed the presence of two missense mutations in heterozygous form: c.1295A>G (p.N432S) and c.1765C>T (p.P589S). p.N432S is a novel mutation that abolishes one N-glycosylation site of TF, while p.P589S is the polymorphism that defines the C2 isoform of TF. The sum of mass shifts caused by both amino acid substitutions agrees with the mass shift observed by LC-MS, which indicates that both variants are located in cis. CONCLUSIONS:An individual initially suspected of alcohol abuse based on elevated %CDT was shown to be carrier of a novel mutation in the TF gene that abolishes the N-glycosylation site at position p.N432. The presence of this genetic variant has to be kept in mind when interpreting TF isoform patterns.
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| 35. |
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| 36. |
- Greiser, Anne, et al.
(författare)
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The 99th percentile and imprecision of point-of-care cardiac troponin I in comparison to central laboratory tests in a large reference population
- 2017
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 50:18, s. 1198-1202
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Determination of cardiac troponin (cTn) is central in the emergency department (ED) for the diagnosis of myocardial infarction. In view of adverse effects of long waiting time on patient outcome, implementation of point-of-care-testing (POCT) is suggested if the turn-around-time is longer than 60min. The present study aimed to determine the 99th percentile and imprecision of two POCT in a healthy population measuring cTnI and cTnT and compare these analytical characteristics against three central laboratory test (CLT) for cTnI.DESIGN & METHODS: CTnI and cTnT were determined in parallel by means of the AQT90 FLEX analyzer in about 2250 plasma samples from individuals with known health status. Results were compared to previously determined performance data of three CLT.RESULTS: The 99th percentile of cTnI in the POCT was determined at 19ng/L, the lowest concentration with an imprecision of 10% was reached at 22ng/L while an imprecision of 20% was reached at 13ng/L. Age, sex, or physical activity did not affect the 99th percentile of cTnI. Compared to CLT the AQT90 cTnI POCT the analytical performance was equivalent. The cTnT POCT could not be assessed due a considerable number of high values and an inadequate imprecision profile.CONCLUSION: While the cTnI POCT showed analytical performance comparable to CLT, the results of the cTnT assay on the same device did not suffice to determine a reliable 99th percentile. The present evaluation supports the usage of the cTnI POCT, but application of the cTnT POCT needs further evaluation.
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| 37. |
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| 38. |
- Grubb, Anders
(författare)
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Shrunken pore syndrome - a common kidney disorder with high mortality. Diagnosis, prevalence, pathophysiology and treatment options
- 2020
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 1873-2933 .- 0009-9120. ; 83, s. 12-20
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Forskningsöversikt (refereegranskat)abstract
- Invasive studies show that the glomerular sieving coefficients for 5–30 kDa plasma proteins in the human kidney may be selectively reduced compared to those for small molecules < 0.9 kDa, commonly used to measure glomerular filtration rate (GFR). Identification of this pathophysiological state, called shrunken pore syndrome (SPS), can easily and non-invasively be done by comparing estimations of GFR using cystatin C (13.3 kDa) and creatinine (0.113 kDa). SPS is present if the estimate of GFR using cystatin C is lower than 60 or 70% of the estimate using creatinine in the absence of non-renal influences on cystatin C or creatinine. All studies of SPS show that the 3- or 5-year mortality is strongly increased and high hazard ratios for mortality associated with SPS have been observed for many different patient cohorts, including cohorts with normal measured GFR, no albuminuria and no diagnosis. The prevalence of SPS in the cohorts so far investigated is between 0.2 and 36%. Proteome studies of SPS demonstrate that the high mortality associated with the syndrome might be caused by the accumulation of 10–30 kDa signalling proteins promoting development of atherosclerosis and thus suggesting use of monoclonal antibodies to reduce the levels of the most detrimental signalling proteins as a treatment option. The KDIGO recommendations for classification of chronic kidney disease (CKD) comprise determination, or estimation, of GFR and analysis of albuminuria and therefore cannot identify a large fraction of the patients with SPS. The high prevalence and mortality of SPS and the possible treatment options strongly suggest that the KDIGO recommendations should be expanded to include determination of cystatin C to be able to identify all patients with SPS.
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| 39. |
- Hammarsten, Ola, et al.
(författare)
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Long-time quality assessment of the Elecsys Troponin T hs assay
- 2013
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120. ; 46:12, s. 1055-1057
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Tidskriftsartikel (refereegranskat)abstract
- Recently, Roche announced a problem with the calibrators for their high sensitive cardiac troponin T (hscTnT) assay. We have monitored the performance of the assay since its introduction into clinical use in December 2009 and we're in a unique position to provide quantitative information concerning the effects of this problem. Our data document that the measured cTnT concentration in the hscTnT assay dropped by 5.8 ng/L around the 99th percentile before its recalibration in May 2012. Thus, the hscTnT levels in our hospital have been underestimated around this cut-off value since its introduction. The approach we used may be one that other laboratories should consider.
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| 40. |
- Hammarsten, Ola, et al.
(författare)
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Methods for analyzing positive cardiac troponin assay interference
- 2023
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120. ; 116, s. 24-30
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The cardiac damage biomarkers cardiac troponin T (cTnT) and troponin I (cTnI) are used to identify patients with myocardial infarction (MI). To make the correct clinical decisions it is important to identify false positive results due to troponin assay interference. Often interferences are caused by high-molecular weight immunocomplexes called macrotroponin that may result in false troponin elevations because of delayed troponin clearance, or heterophilic antibodies that crosslink troponin assay antibodies and generate troponin-independent signals.Design & Methods: We describe and compare four methods for cTnI assay interference analysis using a protein G spin column method, gel filtration chromatography and two versions of a sucrose gradient ultracentrifugation for cTnI assay interference analysis on five patients with confirmed cTnI interference and one MI patient without cTnI interference from our troponin interference referral center. Results: The protein G spin column method had a high between run variability but was still able to identify all five patients with cTnI interference. The sucrose gradient ultracentrifugation methods and the gel filtration method had simlar performancec and correctly identified the immunocomplexes that caused the cTnI interference. Conclusions: Our experience is that these methods are sufficient to safely confirm or exclude positive cTnI assay interference.
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| 41. |
- Hammarsten, Ola, et al.
(författare)
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Risk of myocardial infarction at specific troponin T levels using the parameter predictive value among lookalikes (PAL)
- 2017
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Ingår i: Clinical Biochemistry. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0009-9120 .- 1873-2933. ; 50:1-2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Myocardial infarction is more likely if the heart damage biomarker cardiac troponin T (cTnT) is elevated in a blood sample, indicating that cardiac damage has occurred. No method allows the clinician to estimate the risk of myocardial infarction at a specific cTnT level in a given patient. Methods: Predictive value among lookalikes (PAL) uses pre-test prevalence, sensitivity and specificity at adjacent cTnT limits based on percentiles. PAL is the pre-test prevalence-adjusted probability of disease between two adjacent cTnT limits. If a chest pain patients cTnT level is between these limits, the risk of myocardial infarction can be estimated. Results: The PAL based on percentiles had an acceptable sampling error when using 100 bootstrapped data of 18 different biomarkers from 38,945 authentic lab measurements. A PAL analysis of an emergency room cohort (n = 11,020) revealed that the diagnostic precision of a high-sensitive cTnT assay was similar among chest pain patients at different ages. The higher incidence of false positive results due to non-specific increases in cTnT in the high-age group was counterbalanced by a higher pre-test prevalence of myocardial infarction among older patients, a finding that was missed when using a conventional ROC plot analysis. Conclusions: The PAL was able to calculate the risk of myocardial infarction at specific cTnT levels and could complement decision limits. 2016 The Authors. The Canadian Society of Clinical Chemists. Published by Elsevier Inc.
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| 42. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
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Day-to-day variation of urinary NGAL and rational for creatinine correction
- 2013
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Ingår i: Clinical Biochemistry. - : Elsevier. - 0009-9120 .- 1873-2933. ; 46:1-2, s. 70-72
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The number of clinical studies evaluating the new tubular biomarker urinary neutrophil gelatinase-associated lipocalin (U-NGAL) in urine are increasing. There is no consensus whether absolute U-NGAL concentrations or urinary NGAL/creatinine (U-NGAL/Cr) ratios should be used when chronic tubular dysfunction is studied. The aim was to study the biological variation of U-NGAL in healthy subjects and the rational for urinary creatinine (U-Cr) correction in two different study samples.DESIGN AND METHODS: To study biological variation of U-NGAL and U-NGAL/Cr ratio and the association between U-NGAL and U-Cr in healthy subjects 13 young males and females (median age 29years) collected morning urine in 10 consecutive days. Additionally, a random subsample of 400 males from a population-based cohort (aged 78years) collecting 24-hour urine during 1day was studied.RESULTS: The calculated biological variation for absolute U-NGAL was 27% and for U-NGAL/Cr ratio, 101%. Absolute U-NGAL increased linearly with U-Cr concentration (the theoretical basis for creatinine adjustment) in the older males (R=0.19, P<0.001) and with borderline significance in the young adults (R=0.16, P=0.08). The U-NGAL/Cr ratio was, however, negatively associated with creatinine in the older males (R=-0.14, P<0.01) and in the young adults (R=-0.16, P=0.07) indicating a slight "overadjustment."CONCLUSIONS: The study provides some support for the use of U-NGAL/Cr ratio but the rather large biological variation and risk of possible overadjustment need to be considered. Both absolute U-NGAL and U-NGAL/Cr ratios should be reported for the estimation of chronic tubular dysfunction.
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| 43. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
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The age related association is more pronounced for cystatin C estimated GFR than for creatinine estimated GFR in primary care patients
- 2013
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 46:16-17, s. 1761-1763
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesThere is an age associated change in GFR but this association may be influenced by the method used. The aims of the present study were to assess the association between age and cystatin C and creatinine based glomerular filtration rate estimates in primary care patients, and to determine the proportion of patients with clinically important renal impairment.Materials and methods1552 samples with simultaneous requests for creatinine and cystatin C from 1552 primary care patients in the county of Uppsala, Sweden were analysed. MDRD, CKD-EPI and cystatin C equations were used to calculate glomerular filtration rate (GFR) and the associations between GFR and age were explored.ResultsThe yearly change in cystatin C estimated GFR was 1.24 mL/min/1.73 m2 while the corresponding decline for creatinine estimated GFR was 0.76 mL/min/1.73 m2 for MDRD and 0.99 mL/min/1.73 m2 for CKD-EPI.ConclusionsThe age related association with GFR estimates is smaller for creatinine estimates than for cystatin C estimates. This leads to differences in the number of patients with reduced eGFR detected with the three estimates and the patient treatment will depend on the estimate used. This is not coherent with a good patient care and we thus need to develop new eGFR equations with better agreement between the estimates.
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| 44. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
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Urinary KIM-1, but not urinary cystatin C, should be corrected for urinary creatinine
- 2016
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 49:15, s. 1164-1166
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The interest for tubular damage markers such as urinary cystatin C (U-CystC) and kidney injury molecule-1 (U-KIM-1) grows, especially for the diagnosis of acute kidney injury. The trend to measure proteins in spot urine samples instead of 24-h urine collections calls for adjustment of urine dilution with urinary creatinine (UCr). However, it is not known whether UCr adjustment provides a more true value of basal U-CystC and U-KIM-1 levels than absolute values.DESIGN & METHODS: This study examines the rationale for UCr correction for U-CystC and U-KIM-1 by exploring the linear relations between U-CystC and U-KIM-1 and UCr, respectively, and the biological day to day variation of absolute concentrations and UCr adjusted values of the two biomarkers.RESULTS: Both U-CystC and U-KIM-1 concentrations correlated positively with UCr (R=0.37, P<0.001 and R=0.62, P<0.001, respectively) in 378 participants in a community cohort, which indicated a rationale for adjustment with UCr. However, U-CystC/Cr ratio associated negatively with UCr (R=- 0.31, P<0.001), which could indicate a certain amount of 'over-adjustment'. Morning urine collected for 10 consecutive days from 13 healthy volunteers showed a biological day to day variation of 82% for U-CystC, 75% for U-cystC/Cr ratio, 70% for U-KIM-1 and 46% for U-KIM-1/Cr ratio.CONCLUSIONS: This study supports the use of U-KIM-1/Cr ratio in clinical population studies. Data supporting the use of U-CysC/U-Cr ratio were less convincing and the possible confounding of UCr has to be acknowledged in clinical settings.
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| 45. |
- Hjort, Marcus, et al.
(författare)
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Differences in biomarker concentrations and predictions of long-term outcome in patients with ST-elevation and non-ST-elevation myocardial infarction
- 2021
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 42, s. 1268-1268
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Tidskriftsartikel (refereegranskat)abstract
- Background: Differences in biomarkers reflective of pathobiology and prognosis between ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) are incompletely understood and may offer insights for tailoring of treatment. Methods: This registry-based study included 538 STEMI and 544 NSTEMI patients admitted 2008–2014. Blood samples were collected day 1–3 after admission and 175 biomarkers were analyzed using Proximity Extension Assay and Multiple Reaction Monitoring mass spectrometry. Adjusted Lasso analysis (penalized logistic regression model) was used to select biomarkers that discriminated STEMI from NSTEMI patients. Biomarkers identified by the Lasso analysis were then evaluated in adjusted Cox regressions for associations with death or major adverse cardiovascular events. Results: Biomarkers strongly discriminated STEMI and NSTEMI when considered simultaneously in adjusted Lasso analysis (c-statistic 0.764). Eleven biomarkers independently discriminated STEMI and NSTEMI; seven showing higher concentrations in STEMI: myoglobin, N-terminal pro-B-type natriuretic peptide, serum amyloid A-1 and A-2 protein, ST2 protein, interleukin-6 and chitinase-3-like protein 1; and four showing higher concentrations in NSTEMI: fibroblast growth factor 23, membrane-bound aminopeptidase P, tumor necrosis factor-related activation-induced cytokine and apolipoprotein C-I. During up to 6.6 years of prognostic follow-up, none of these biomarkers exhibited different associations with adverse outcome between STEMI and NSTEMI. Conclusions: In the acute setting, biomarkers indicated greater myocardial dysfunction and inflammation in STEMI, whereas they displayed a more diverse pathophysiologic pattern in NSTEMI patients. These biomarkers were similarly prognostic in STEMI and NSTEMI patients. The results do not support treating STEMI and NSTEMI patients differently based on the concentrations of these biomarkers.
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| 46. |
- Hultberg, Malin, et al.
(författare)
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The polyphenol quercetin strongly increases homocysteine production in a human hepatoma (Hep G2) cell line.
- 2006
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 1873-2933 .- 0009-9120. ; 39:2, s. 160-163
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The metabolism of homocysteine is influenced by several dietary factors, including folate, cobalamin and possibly also the intake of polyhydroxylated phenolic compounds (polyphenols), which were shown to increase plasma homocysteine (tHcy) concentration. In order to reveal the cause of the increased plasma tHcy, we have therefore investigated the effects of a polyphenol in cell cultures from human cell lines. Design and methods: We have studied the influence of the polyphenol quercetin (Quer) on intra- and extracellular homocysteine concentrations in HeLa and hepatoma cell cultures. Results: The main finding is an increased concentration of extracellular homocysteine in the presence of Quer in hepatoma cell cultures, whereas there were no significant changes of homocysteine concentration in HeLa cell cultures. There was no effect on cellular growth, as judged by cell protein. The presence of adenosyl-dialdehyde, an inhibitor of adenosyl-homocysteine hydrolase, abolished the increased extracellular concentration of homocysteine observed in hepatoma cell cultures in the presence of Quer. Conclusion: The antioxidative agent Quer strongly increased the extracellular concentration of homocysteine in hepatoma cell cultures probably due to increased cellular methylation. In the human body, the same phenomenon might lead to increased plasma tHcy. Since elevated plasma tHcy is associated with premature vascular disease, high long-lasting dietary intake of polyphenols might be harmful. The interaction between Quer and homocysteine turnover may therefore warrant a re-evaluation of polyphenols as relatively harmless antioxidative food supplements or therapeutic antioxidative agents. (c) 2005 The Canadian Society of Clinical Chemists. All rights reserved.
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| 47. |
- Isaksson, Helena S., et al.
(författare)
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Preanalytical aspects of quantitative TaqMan real-time RT-PCR : applications for TF and VEGF mRNA quantification
- 2006
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Ingår i: Clinical Biochemistry. - Ottawa : Canadian soc. of clinical chemists. - 0009-9120 .- 1873-2933. ; 39:4, s. 373-377
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The present paper focuses on preanalytical aspects of tissue factor (TF) and vascular endothelial growth factor (VEGF) mRNA quantification: the choice of blood collection tubes and defining the time frame allowed before processing the sample. DESIGN AND METHODS: Blood was collected from healthy volunteers in K(3) EDTA tubes, CPT, endotoxin-free EndoTube tubes and in PAXgene tubes. Total RNA concentration was determined by absorbance readings at 260 nm with a GeneQuantII UV spectrophotometer. RNA quantity and quality were also determined by the Lab on a Chip technique (Agilent 2100 Bioanalyzer). Real-time RT-PCR assays were performed by the TaqMan technology. RESULTS: The more expensive PAXgene and CPT tubes and the Endo tubes did not give superior results from those obtained in inexpensive routine K(3) EDTA tubes. The PAXgene tubes preserved high molecular mass rRNA better than the other tubes. CONCLUSION: Both the PAXgene system and routine EDTA tubes are suitable for clinical purposes aimed at quantitation of mRNA for TF and VEGF. PAXgene yielded rRNA that was less degraded but had lower mRNA per microg extracted RNA. A time frame up to 24 h until sample processing is acceptable for TF and VEGF mRNA.
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| 48. |
- Johnston, Nina, et al.
(författare)
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Biochemical indicators of cardiac and renal function in a healthy elderly population
- 2004
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 37:3, s. 210-216
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Tidskriftsartikel (refereegranskat)abstract
- Objectives:To examine the distributions of NT-proBNP and cystatin C and their relation to age, gender, and other physiological factors in an apparently healthy elderly population.Method:NT-proBNP and cystatin C were analyzed in 407 and 408 healthy individuals, median age: 65 (range 40–76).Results:Increasing age, female gender and CRP were independently associated to higher NT-proBNP levels. Age, body mass index, and CRP level were independently associated to the cystatin C level. In women and men, ≤65 years, the 97.5th percentile value for NT-proBNP was 268 ng/l and 184 ng/l, in those older, 391 ng/l and 269 ng/l. For those ≤65 years the 97.5th percentile value for cystatin C was 1.12 mg/l, and for those older 1.21 mg/l.Conclusion:In a healthy elderly population, NT-proBNP is influenced by age and gender, whereas cystatin C is influenced by age but not by gender. Both markers seem to be associated to the CRP level.
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| 49. |
- Jurek, Aleksandra, et al.
(författare)
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The ability of HDL to inhibit VCAM-1 expression and oxidized LDL uptake is impaired in renal patients
- 2008
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 41:12, s. 1015-1018
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study examines the ability of HDL from hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients to suppress the expression of adhesion molecules in endothelial cells (ICAM-1, VCAM-1) and in monocytes (LFA-1, VLA-4) and to inhibit the uptake of oxidized LDL by macrophages. Design and methods: Gene expression and the uptake of oxidized LDL were determined in 12 HD patients, 12 CAPD patients and 14 healthy volunteers. Results: HDL from renal patients were less effective than control lipoproteins in reducing VCAM-1 expression. HDL from CAPD patients inhibited LFA-1 expression to the highest extent. The ability of HDL from renal patients to reduce oxidized LDL uptake was lower compared to control group. Conclusions: Decreased ability of HDL to suppress expression of VCAM-1 in endothelial cells and the uptake of oxidized LDL by macrophages can be one of the risk factors for atherosclerosis development in patients with renal failure.
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| 50. |
- Karlsson, Leif, et al.
(författare)
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Novel non-classic CYP21A2 variants, including combined alleles, identified in patients with congenital adrenal hyperplasia
- 2019
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 73, s. 50-56
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Congenital adrenal hyperplasia (CAH) is an inborn error of metabolism and a common disorder of sex development where >90% of all cases are due to 21-hydroxylase deficiency. Novel and rare pathogenic variants account for 5% of all clinical cases. Here, we sought to investigate the functional and structural effects of four novel (p.Val358Ile, p.Arg369Gln, p.Asp377Tyr, and p.Leu461Pro) and three combinations of CYP21A2 variants (i.e. one allele containing two variants p.[Ile172Asn;Val358Ile], p.[Val281Leu;Arg369Gln], or p.[Asp377Tyr;Leu461Pro]) identified in patients with CAH.Methods: All variants were reconstructed by in vitro site-directed mutagenesis, the proteins were transiently expressed in COS-1 cells and enzyme activities directed toward the two natural substrates (17-hydroxyprogesterone and progesterone) were determined. In parallel, in silico prediction of the pathogenicity of the variants based on the human CYP21 X-ray structure was performed.Results: The novel variants, p.Val358Ile, p.Arg369Gln, p.Asp377Tyr, and p.Leu461Pro exhibited residual enzymatic activities within the range of non-classic (NC) CAH variants (40–82%). An additive effect on the reduction of enzymatic activity (1–17%) was observed when two variants were expressed together, as identified in several patients, resulting in either NC or more severe phenotypes. In silico predictions were in line with the in vitro data except for p.Leu461Pro.Conclusions: Altogether, the combination of clinical data, in silico prediction, and data from in vitro studies are important for establishing a correct genotype and phenotype correlation in patients with CAH.
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