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  • 1. Apple, FS
    et al.
    Jaffe, AS
    Collinson, P
    Mockel, M
    Ordonez-Llanos, J
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hollander, J
    Plebani, M
    Than, M
    Chan, MH
    IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac troponin assays2015In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 48, no 4-5, p. 201-203Article in journal (Refereed)
    Abstract [en]

    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.

  • 2. Bjurman, Christian
    et al.
    Petzold, Max
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Farbemo, Julia
    Fu, Michael L. X.
    Hammarsten, Ola
    High-sensitive cardiac troponin, NT-proBNP, hFABP and copeptin levels in relation to glomerular filtration rates and a medical record of cardiovascular disease2015In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 48, no 4-5, p. 302-307Article in journal (Refereed)
    Abstract [en]

    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/).

  • 3. Dzialanski, Zbigniew
    et al.
    Barany, Michael
    Engfeldt, Peter
    Magnuson, Anders
    Olsson, Lovisa A.
    Nilsson, Torbjörn K.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Lactase persistence versus lactose intolerance: Is there an intermediate phenotype?2016In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 49, no 3, p. 248-252Article in journal (Refereed)
    Abstract [en]

    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 120 min 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. 

  • 4.
    Dzialanski, Zbigniew
    et al.
    University Health Care Research Center, Region Örebro County, Örebro, Sweden; School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Barany, Michael
    Department of Clinical Physiology, Örebro University Hospital, Örebro, Sweden; School of Health and Medicine Sciences, Örebro University, Örebro, Sweden.
    Engfeldt, Peter
    Örebro University, School of Medical Sciences. University Health Care Research Center, Region Örebro County, Örebro, Sweden; School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Magnuson, Anders
    School of Health and Medicine Sciences, Örebro University, Örebro, Sweden.
    Olsson, Lovisa A.
    Department of Clinical Chemistry, Örebro University Hospital, Örebro, Sweden; School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Nilsson, Torbjörn K.
    Department of Medical Biosciences/Clinical Chemistry, Faculty of Medicine and Health, Umeå University, Umeå, Sweden.
    Lactase persistence versus lactose intolerance: Is there an intermediate phenotype?2016In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 49, no 3, p. 248-252Article in journal (Refereed)
    Abstract [en]

    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.

  • 5. Edlund, Bror
    et al.
    Nilsson, Torbjörn K.
    Örebro University, School of Health and Medical Sciences.
    A proposed stoichiometrical calibration procedure to achieve transferability of D-dimer measurements and to characterize the performance of different methods2006In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 39, no 2, p. 137-142Article in journal (Refereed)
    Abstract [en]

    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.

  • 6.
    Eggers, Kai
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Apple, Fred S.
    Hennepin Cty Med Ctr, Dept Lab Med & Pathol, Minneapolis, MN 55415 USA;Abbott NW Hosp, Minneapolis Heart Inst, Minneapolis, MN USA .
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    The applied statistical approach highly influences the 99th percentile of cardiac troponin I2016In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 49, no 15, p. 1109-1112Article in journal (Refereed)
    Abstract [en]

    Background

    Cardiac 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.

    Methods

    cTnI (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.

    Results

    The 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.

    Conclusions

    Our 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.

  • 7.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Armstrong, Paul W.
    Califf, Robert M.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Simoons, Maarten L.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Clinical and prognostic implications of circulating pentraxin 3 levels in non ST-elevation acute coronary syndrome2013In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 46, no 16-17, p. 1655-1659Article in journal (Refereed)
    Abstract [en]

    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.

  • 8.
    Eggers, Kai M
    et al.
    Department of Medical Sciences, Cardiology, Uppsala University Hospital and Uppsala Clinical Research Center, Uppsala, Sweden.
    Dellborg, Mikael
    Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Johnston, Nina
    Department of Medical Sciences, Cardiology, Uppsala University Hospital and Uppsala Clinical Research Center, Uppsala, Sweden.
    Oldegren, Jonas
    Department of Medical Sciences, Cardiology, Uppsala University Hospital and Uppsala Clinical Research Center, Uppsala, Sweden.
    Swahn, Eva
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Venge, Per
    Department of Medical Sciences, Clinical Chemistry, Uppsala University Hospital, Uppsala, Sweden.
    Lindahl, Bertil
    Department of Medical Sciences, Cardiology, Uppsala University Hospital and Uppsala Clinical Research Center, Uppsala, Sweden.
    Myeloperoxidase is not useful for the early assessment of patients with chest pain.2010In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 43, no 3, p. 240-245Article in journal (Refereed)
    Abstract [en]

    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.

  • 9.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Dellborg, Mikael
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Swahn, Eva
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Myeloperoxidase is not useful for the early assessment of patients with chest pain2010In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 43, no 3, p. 240-245Article in journal (Refereed)
    Abstract [en]

    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.

  • 10.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Cardiac troponin I levels in an elderly population from the community - The implications of sex2015In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 48, no 12, p. 751-756Article in journal (Refereed)
    Abstract [en]

    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.

  • 11.
    Flodin, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Performance evaluation of a particle-enhanced turbidimetric cystatin C assay on the Abbott ci8200 analyzer2009In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 42, no 9, p. 873-876Article in journal (Refereed)
    Abstract [en]

    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.

  • 12.
    Garwicz, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karlman, Mattias
    Early recognition of reverse pseudohyperkalemia in heparin plasma samples during leukemic hyperleukocytosis can prevent iatrogenic hypokalemia2012In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 45, no 18, p. 1700-1702Article in journal (Refereed)
    Abstract [en]

    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.

  • 13. Greiser, Anne
    et al.
    Winter, Theresa
    Mahfoud, Hala
    Kallner, Anders
    Ittermann, Till
    Masuch, Annette
    Lubenow, Norbert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Kohlmann, Thomas
    Greinacher, Andreas
    Nauck, Matthias
    Petersmann, Astrid
    The 99th percentile and imprecision of point-of-care cardiac troponin I in comparison to central laboratory tests in a large reference population2017In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 50, no 18, p. 1198-1202Article in journal (Refereed)
    Abstract [en]

    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.

  • 14.
    Hammarsten, Ola
    et al.
    University of Gothenburg, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Bjurman, Christian
    University of Gothenburg, Sweden.
    Petzold, Max
    University of Gothenburg, Sweden.
    Risk of myocardial infarction at specific troponin T levels using the parameter predictive value among lookalikes (PAL)2017In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 50, no 1-2Article in journal (Refereed)
    Abstract [en]

    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.

  • 15.
    Helmersson-Karlqvist, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Flodin, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    The age related association is more pronounced for cystatin C estimated GFR than for creatinine estimated GFR in primary care patients2013In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 46, no 16-17, p. 1761-1763Article in journal (Refereed)
    Abstract [en]

    Objectives

    There 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 methods

    1552 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.

    Results

    The 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.

    Conclusions

    The 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.

  • 16.
    Helmersson-Karlqvist, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Carlsson, Axel C.
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden; Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Family Med, Huddinge, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Urinary KIM-1, but not urinary cystatin C, should be corrected for urinary creatinine2016In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 49, no 15, p. 1164-1166Article in journal (Refereed)
    Abstract [en]

    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.

  • 17. Helmersson-Karlqvist, Johanna
    et al.
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Carlsson, Axel C
    Lind, Lars
    Larsson, Anders
    Urinary KIM-1, but not urinary cystatin C, should be corrected for urinary creatinine2016In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 49, no 15, p. 1164-1166Article in journal (Refereed)
    Abstract [en]

    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.

  • 18. Helmersson-Karlqvist, Johanna
    et al.
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science.
    Larsson, Anders
    Day-to-day variation of urinary NGAL and rational for creatinine correction2013In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 46, no 1-2, p. 70-72Article in journal (Refereed)
    Abstract [en]

    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.

  • 19.
    Helmersson-Karlqvist, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Day-to-day variation of urinary NGAL and rational for creatinine correction2013In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 46, no 1-2, p. 70-72Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    Clinical studies evaluating the new tubular biomarker urinary neutrophil gelatinase-associated lipocalin (U-NGAL) in urine increase and 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 one day 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 provide 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.

  • 20.
    Isaksson, Helena S.
    et al.
    Örebro University, Department of Clinical Medicine.
    Nilsson, Torbjörn K.
    Örebro University, Department of Clinical Medicine.
    Preanalytical aspects of quantitative TaqMan real-time RT-PCR: applications for TF and VEGF mRNA quantification2006In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 39, no 4, p. 373-377Article in journal (Refereed)
    Abstract [en]

    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.

  • 21.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jernberg, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Biochemical indicators of cardiac and renal function in a healthy elderly population2004In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 37, no 3, p. 210-216Article in journal (Refereed)
    Abstract [en]

    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.

  • 22.
    Jurek, Aleksandra
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
    Turyna, Bohdan
    Kubit, Piotr
    Klein, Andrzej
    The ability of HDL to inhibit VCAM-1 expression and oxidized LDL uptake is impaired in renal patients2008In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 41, no 12, p. 1015-1018Article in journal (Refereed)
    Abstract [en]

    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.

  • 23.
    Kushnir, Mark M.
    et al.
    ARUP Institute for Clinical and Experimental Pathology and Department of Pathology, University of Utah, Salt Lake City, UT, USA.
    Rockwood, Alan L.
    ARUP Institute for Clinical and Experimental Pathology and Department of Pathology, University of Utah, Salt Lake City, UT, USA.
    Roberts, William L.
    ARUP Institute for Clinical and Experimental Pathology and Department of Pathology, University of Utah, Salt Lake City, UT, USA.
    Yue, Bingfang
    ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Meikle, A. Wayne
    ARUP Institute for Clinical and Experimental Pathology. Department of Pathology and Department of Medicine, University of Utah, Salt Lake City, UT, USA.
    Liquid chromatography tandem mass spectrometry for analysis of steroids in clinical laboratories2011In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 44, no 1, p. 77-88Article, review/survey (Refereed)
    Abstract [en]

    Liquid chromatography tandem mass spectrometry is one of the most specific techniques available in clinical laboratories. In the past, immunoassays were the primary methodology for analysis of steroids in biological samples because they are rapid and easy to perform. However, these methods were shown to suffer from the lack of specificity for measuring many of the diagnostically important steroids. LC-MS/MS overcomes many of the limitations of immunoassays, enhances diagnostic utility of the testing, and expands diagnostic capabilities in endocrinology. In addition to the superior quality of the measurements, LC-MS/MS allows high throughput testing using small sample volume with minimal sample preparation, and frees the laboratory from dependence on suppliers of assay specific reagents. LC-MS/MS is being widely employed for routine measurement of steroids, and the methodology plays an important role in the standardization and harmonization of measurements among clinical laboratories.

  • 24.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Carlsson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Axelsson, John
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Low diurnal variability of apolipoprotein A1, apolipoprotein B and apolipoprotein B/apolipoprotein A1 ratio during normal sleep and after an acute shift of sleep2008In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 41, no 10-11, p. 859-862Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study was to study the diurnal variation of the cardiovascular risk markers apolipoprotein A1 and B and apo B/apo A1 ratio. DESIGN AND METHODS: We have studied the diurnal variation of apolipoprotein A1, apolipoprotein B and apo B/apo A1 ratio during night sleep and the day sleep conditions in seven healthy volunteers (age 22-32 yr). Samples were collected every hour to evaluate the effect of different sampling times on the test results. RESULTS: The lowest diurnal coefficient of variation (CV) was observed for the apo B/apo A1 ratio, which usually was below 2% but also apolipoprotein A1, apolipoprotein B showed low CV. There were no significant differences between nightsleep and daysleep for any of the studied markers. CONCLUSION: Even if there was a diurnal variation for these markers, the variation was very low. Thus, sampling does not have to be restricted to certain times of the day.

  • 25.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Flodin, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Carlsson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Patient selection has a strong impact on cystatin C and Modification of Diet in Renal Disease (MDRD) estimated glomerular filtration rate2008In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 41, no 16-17, p. 1355-1361Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Estimation of the glomerular filtration rate (GFR) is essential for the evaluation of patients with kidney disease, and for correct dosage of drugs that are eliminated from the circulation by the kidneys. In most cases GFR is estimated based on serum creatinine and the Modification of Diet in Renal Disease (MDRD) formula. As both cystatin C and creatinine are used for the determination of GFR it is important to investigate if estimated GFR by the two methods differ in various patient groups. DESIGN AND METHODS: We have compared cystatin C and MDRD estimated GFR calculated from the same request from primary care units (n=488), a cardiology ward (n=826), the cardiointensive care unit (n=1026), two oncology wards (n=919 and 1021), and the neurosurgical intensive care unit (n=1515) in an observational cross-sectional study. RESULTS: We found better agreement between the two GFR estimates in samples from primary care patients and patients in the cardiology wards, than in samples from oncology wards or the neurosurgical intensive care unit. In the latter settings there was a pronounced difference between the two GFR estimates. CONCLUSION: The comparisons show that differences in patient selections have a strong impact on the agreement between cystatin C and MDRD estimated glomerular filtration rate.

  • 26.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Reference values for fasting insulin in 75 year old females and males2013In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 46, no 12, p. 1125-1127Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    Reference intervals for insulin are often based on fairly small study groups with unknown body mass index (BMI). They are also much younger than most patients seeking care. These values are not optimal for elderly patients, as many biological markers change over time and adequate reference intervals are important for correct clinical decisions.

    DESIGN AND METHODS:

    We studied fasting insulin (f-insulin) values in a cohort of 698 75-year old non-diabetic males and females. The 2.5th and 97.5th percentiles for all individuals, males and females were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference intervals.

    RESULTS:

    There was a strong positive correlation between BMI and f-insulin, which led to the calculation of separate reference intervals for individuals with BMI ≤30.

    CONCLUSIONS:

    The reference interval for f-insulin for all study subjects was 1.74-18.27mIU/L and for individuals with BMI ≤30 (n=574) the reference interval was 1.66-15.05mIU/L.

  • 27.
    Lind, Marcus
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Torbjörn
    Slunga-Järvholm, Lisbeth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    D-dimer predicts major bleeding, cardiovascular events and all-cause mortality during warfarin treatment2014In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 47, no 7-8, p. 570-573Article in journal (Refereed)
    Abstract [en]

    Objectives: Previous studies have shown that biomarkers in blood plasma can predict bleeding complications during anticoagulant treatment as well as thromboembolic events and may improve existing risk stratification schemes in patients on or considered for oral anticoagulant treatment. The aim of this study was to investigate if levels of D-dimer, tissue plasminogen activator (tPA) and its complex with plasminogen inhibitor type 1 (tPA/PAI-1 complex) can predict major bleedings, cardiovascular events and all-cause mortality in patients with warfarin treatment.

    Design and methods: In a longitudinal cohort study, 719 patients on oral anticoagulant treatment were followed for a total of 3001 treatment years. Major bleeding, stroke, arterial emboli, myocardial infarction and death were recorded and classified. Blood samples collected at baseline were analyzed for D-dimer, tPA, and tPA/PAI-1 complex.

    Results: In multivariate Cox regression analysis, high levels of D-dimer were associated with major bleeding (HR 1.27 per SD; 95% CI: 1.01-1.60), cardiovascular events (HR 1.23 per SD; 95% CI: 1.05-1.45) and all-cause mortality (HR 1.25 per SD; 95% CI: 1.06-1.47). Neither tPA nor the tPA/PAI-1 complex was associated with major bleeding, cardiovascular events or all-cause mortality.

    Conclusion: We conclude that high levels of D-dimer predict major bleeding, cardiovascular events and all-cause mortality during warfarin treatment. (C) 2014 The Canadian Society of Clinical Chemists. 

  • 28.
    Milovanovic, Micha
    et al.
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Eriksson, Kristoffer
    Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Winblad, Bengt
    Karolinska Institute, Sweden.
    Nilsson, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Primary Health Care in Norrköping.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Post, Claes
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Järemo, Petter
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Alzheimer and platelets: Low-density platelet populations reveal increased serotonin content in Alzheimer type dementia2014In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 47, no 15, p. 51-53Article in journal (Refereed)
    Abstract [en]

    Introduction: Alzheimers disease (AD) is a progressive form of dementia characterized by an increase in the toxic substance beta-amyloid in the brain. Platelets display a substantial heterogeneity with respect to density. They further contain a substantial amount of beta-amyloid precursor protein. Platelets take up and store serotonin (5-HT) that plays an important role in the pathogenesis of severe depression. The current study aims to investigate platelet serotonin content in different platelet density populations. Material and methods: The study involved 8 patients (age 70 +/- 8 (SD) years) (3 females/5 males) with moderate AD. 6 healthy elderly subjects (age 66 +/- 9 (SD) years) (3 females/3 males) served as controls. The platelet population was divided into 17 subpopulations according to density, using a linear Percoll (TM) gradient. Platelets were counted in all fractions. After cell lysis an ELISA technique was employed to determine the 5-HT content in each platelet subfraction. Results: The two study groups did not differ significantly regarding platelet distribution in the gradients, but AD sufferers have a significantly higher 5-HT content (p less than 0.05) in the lighter platelet populations. Discussion: AD-type dementia proved to be associated with lighter platelets containing more 5-HT. It is possible that platelets from AD patients release less 5-HT. It is speculated that AD synapses are affected in a manner comparable to platelets, which could explain why 5-HT reuptake inhibitors are less effective in AD dementia.

  • 29.
    Mindemark, Mirja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Ruling out IBD: Estimation of the possible economic effects of pre-endoscopic screening with F-calprotectin2012In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 45, no 7-8, p. 552-555Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To estimate the possible economic effects of a sequential testing strategy with F-calprotectin to minimize colonoscopies.

    DESIGN AND METHODS: Retrospective study in a third party payer perspective. The costs were calculated from initial F-calprotectin test results of 3639 patients. Two cut-off levels were used: 50μg/g feces and 100μg/g feces, respectively. The cost-effectiveness of the testing strategy was estimated through the short-term cost avoidance and reduction in demand for colonoscopies.

    RESULTS: The estimated demand for colonoscopies was reduced by 50% with the 50μg/g cut-off and 67% with the 100μg/g cut-off. This corresponded to a cost avoidance of approximately €1.57million and €2.13million, respectively.

    CONCLUSIONS: The use of F-calprotectin as a screening test substantially could reduce the number of invasive measurements necessary in the diagnostic work-up of patients with suspected IBD, as well as the associated costs.

  • 30.
    Nilsen, Tom
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Serum calprotectin levels in elderly males and females without bacterial or viral infections2014In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 47, no 12, p. 1065-1068Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Calprotectin is released from activated leukocytes and calprotectin can thus be used as a marker for leukocyte activation. Faeces calprotectin is not only used as a marker for inflammatory bowel disease but can also be used to detect leukocyte activation in other body fluids. The aim of the present study was to study serum calprotectin levels in non-infected elderly individuals to establish reference intervals for the marker.

    METHODS: Serum calprotectin was analyzed by immunoturbidimetry in 75year old females and males without known infections. Individuals with CRP>20mg/L were excluded as this could indicate a subclinical infection. The calprotectin levels in the remaining 713 individuals were used to calculate reference values for this population. The Spearman rank correlations between calprotectin and 27 other laboratory biomarkers were also investigated.

    RESULTS: There was a strong positive Spearman rank correlation between calprotectin and CRP (p<0.000001) and alkaline phosphatase (p<0.000001). There were also significant negative correlations between calprotectin and ApoA1 and direct HDL-cholesterol.

    CONCLUSIONS: The reference interval for serum-calprotectin for all study subjects was 0.3-2.6mg/L. Leukocyte alkaline phosphatase contributes to serum alkaline phosphatase levels.

  • 31.
    Ognissanti, Damiano
    et al.
    Chalmers Univ Technol, Sweden; Univ Gothenburg, Sweden.
    Bjurman, Christian
    Univ Gothenburg, Sweden.
    Holzmann, Martin J.
    Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Petzold, Max
    Univ Gothenburg, Sweden.
    Cvijovic, Marija
    Chalmers Univ Technol, Sweden; Univ Gothenburg, Sweden.
    Hammarsten, Ola
    Univ Gothenburg, Sweden.
    Cardiac troponin T concentrations and patient-specific risk of myocardial infarction using the novel PALfx parameter2019In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 66, p. 21-28Article in journal (Refereed)
    Abstract [en]

    Background: Myocardial infarction (MI) is more likely if the heart damage biomarker cardiac troponin T (cTnT) is elevated in a blood sample from a patient with chest pain. There is no conventional method to estimate the risk of MI at a specific cTnT concentration. The purpose of this study was to evaluate the performance of a novel method that converts cTnT concentrations to patient-specific risks of MI. Methods: Admission cTnT measurements in 15,425 ED patients from three hospitals with a primary complaint of chest pain, with or without a clinical diagnosis of MI, were Box-Cox-transformed to normality density functions to calculate the percentage with MI among patients with a given cTnT concentration, the parametric predictive value among lookalikes (PALfx). The ability of the PALfx to generate stable risk estimates of MI was examined by bootstrapping and expressed as the coefficient of variation (CV). Results: Four age and sex-specific subgroups above or below 60 years of age with distinct cTnT distributions were identified among patients without MI. The cTnT distributions across subgroups with MI were similar, allowing us to use all admissions with MI to calculate the PALfx in the four subgroups. For instance, at a baseline cTnT concentration of 7 ng/L, a female patient amp;lt;60 years would have a 0.5% risk of MI whereas a male patient amp;gt;60 years would have a 1.9% risk of MI. To assess the stability of the PALfx method we bootstrapped smaller and smaller subsets of the 15,422 ED visits. We found that 1950 patients without MI and 50 patients with MI were sufficient to limit the variation of the PALfx with a CV of 0.8-5.4%, close to the CV using the entire dataset. The MI risk estimates were similar when data from the three hospitals were used separately to derive the PALfx equations. Conclusions: The PALfx can be used to estimate the risk of MI at patient-specific cTnT concentrations with acceptable margins of error. The patient-specific risk of disease using the PALfx could complement decision limits.

  • 32.
    Piirainen, Robert
    et al.
    Sundsvall Cty Hosp, Dept Lab Med, Sundsvall.
    Englund, Erling
    Sundsvall Cty Hosp, Dept Res & Dev, Sundsvall.
    Henriksson, Anders E.
    Mid Sweden University, Faculty of Science, Technology and Media, Department of Natural Sciences. Sundsvall Cty Hosp, Dept Lab Med, Sundsvall.
    The impact of seasonal variation of 25-hydroxyvitamin D and parathyroid hormone on calcium levels2016In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 49, no 12, p. 850-853Article in journal (Refereed)
    Abstract [en]

    Background: Primary hyperparathyroidism is often diagnosed by high calcium levels in blood. It is well known that calcium levels are dependent on vitamin D and Parathyroid hormone (PTH). Since vitamin D has a seasonal variation the calcium levels might also be influenced by seasonal variation. If a seasonal variation in calcium levels exists, this must be considered in the investigation of suspected hyperparathyroidism. The aim of the present study was to investigate the possible influence and magnitude of the seasonal variation of vitamin D and PTH on calcium levels. Method: In the present study the individual seasonal variation of 25-hydroxyvitamin D [25(OH) D], PTH and calcium in 69 healthy volunteers living at latitudes with extremely variable seasonal exposure to sunlight have been investigated. Results: As expected the 25(OH) D levels were significantly higher (42%) in summer compared to winter. PTH levels were significantly lower (7%) in summer than in winter. The mean serum concentration of calcium was 1% higher in August than in February, however not statistically significant. A good agreement between summer and winter calcium values was confirmed by Bland-Altman analysis. Conclusion: This study did not show any clinically important influence of seasonal variation of 25(OH) D and PTH on calcium that may influence a clinician's decision to investigate suspected hyperparathyroidism.

  • 33.
    Ridefelt, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Pediatric reference intervals - The Swedish experience2014In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 47, no 9, p. 740-741Article in journal (Refereed)
  • 34.
    Ridefelt, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Rehman, Javaid-ur
    Karolinska Institutet.
    Axelsson, John
    Karolinska Institutet.
    Influences of sleep and the circadian rhythm on iron-status indices2010In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 43, no 16-17, p. 1323-1328Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The aim was to study the influence of sampling time, food intake and sleep on tests used to screen for and monitor conditions of iron deficiency and overload. DESIGN AND METHODS: The 24 h variations of iron, transferrin, transferrin saturation (TS) and ferritin were studied in seven healthy individuals during standardised food intake, and during night or day sleep. RESULTS: Iron and TS showed clear diurnal variations, with peaks at 12.6 h and 12.8 h respectively, during night sleep, and at 19.7 h and 19.3 h, respectively, during day sleep. Ferritin did not demonstrate any circadian variation. Transferrin and ferritin were unaffected by sleep-condition. Meals did not have any effect except a slight decline of transferrin. CONCLUSIONS: Time of day and sleeping patterns had great influence on iron and TS, whereas no or only minor effects are seen on the concentration of ferritin and transferrin. Meals have limited effects.

  • 35. Ridefelt, Peter
    et al.
    Larsson, Anders
    Rehman, Javaid-ur
    SUBAxelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Influences of sleep and the circadian rhythm on iron-status indices2010In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 43, no 16-17, p. 1323-1328Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim was to study the influence of sampling time, food intake and sleep on tests used to screen for and monitor conditions of iron deficiency and overload. Design and methods: The 24 h variations of iron, transferrin, transferrin saturation (TS) and ferritin were studied in seven healthy individuals during standardised food intake, and during night or day sleep. Results: Iron and TS showed clear diurnal variations, with peaks at 12.6 h and 12.8 h respectively, during night sleep, and at 19.7 h and 19.3 h, respectively, during day sleep. Ferritin did not demonstrate any circadian variation. Transferrin and ferritin were unaffected by sleep-condition. Meals did not have any effect except a slight decline of transferrin. Conclusions: Time of day and sleeping patterns had great influence on iron and TS, whereas no or only minor effects are seen on the concentration of ferritin and transferrin. Meals have limited effects. (C) 2010 The Canadian Society of Clinical Chemists.

  • 36.
    Ridefelt, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Åkerfeldt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Increased plasma glucose levels after change of recommendation from NaF to citrate blood collection tubes2014In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 47, no 7-8, p. 625-628Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate changes in plasma glucose measurements in an unselected patient population after a change of recommendation from NaF to citrate blood collection vacuum tubes. Design and methods: Glucose (n = 460 751) and HbA1c (n = 55 190) determinations during a period of approximately three years before and after the tube change were extracted from a laboratory information system. Results: Median values for plasma glucose determinations increased from 6.03 before to 6.28 mmol/L after the tube change. The proportion of glucose determinations above the WHO limit for impaired fasting glucose (6.1 mmol/L) and the medical decision limit for diabetes (7.0 mmol/L) increased from 48.1 to 55.4% after the change. Conclusions: The change from NaF to citrate tubes caused higher glucose values, and consequently more glucose determinations above the decision limit for diabetes.

  • 37.
    Risberg, Anitha
    et al.
    Department of Health Sciences, Section of Health and Rehab, Luleå University of Technology, Luleå, Sweden..
    Sjöquist, Mats
    Swedish Centre for Animal Welfare, Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Wedenberg, Kai
    Västerås Sjukus.
    Olsson, Ulf
    Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Water balance during parturition and early puerperium: A prospective open trial2015In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 48, no 13-14, p. 837-842Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate how water balance is regulated during labor and 27h postpartum.

    DESIGN AND METHODS: A prospective open trial with 49 women giving birth vaginally. Ringer-acetate was infused intravenously and combined with epidural analgesia in seven women (fluid group). Intravenous infusions of oxytocin in 5% glucose were given to 12 women (oxytocin group). Thirty women delivered their babies without infusion (nofluid group). Blood and urine samples were collected at arrival, at early stage 1, at early stage 2, and at aftercare, and 9, 15, and 27h postpartum. Plasma osmolality, sodium, cystatin C, vasopressin, oxytocin, urine flow, urine osmolality, and urine sodium were measued.

    RESULTS: The oxytocin group had significantly lower plasma osmolality than the nofluid group before parturition, and they had lower plasma sodium concentration at early stage 1 and 2. Plasma vasopressin concentration was low and did not differ between groups or before and after parturition. Water diuresis developed postpartum in all groups. The cystatin C concentration decreased significantly after parturition in the oxytocin and nofluid groups.

    CONCLUSIONS: The vasopressin levels were suppressed during parturition irrespective of the P-osmolality and the nongravid regulation of water balance had not returned within 27h postpartum.

  • 38.
    Risberg, Anitha
    et al.
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Sjöquist, Mats
    Sveriges Lantbruksuniversitet, Swedish Centre for Animal Welfare, Swedish University of Agricultural Sciences, Uppsala.
    Wedenberg, Kaj
    Västerås Hospital.
    Olsson, Ulf
    Department of Economics, Unit of Applied Statistics and Mathematics, Swedish University of Agricultural Sciences, Uppsala.
    Larsson, Anders
    Department of Medical Sciences, Clinical Chemistry, Uppsala University.
    Water balance during parturition and early puerperium: a prospective open trial2015In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 48, no 13-14, p. 837-842Article in journal (Refereed)
    Abstract [en]

    ObjectivesTo investigate how water balance is regulated during labour and 27 h postpartum. Design and methods A prospective open trial with 49 women giving birth vaginally. Ringer-acetate was infused intravenously and combined with epidural analgesia in seven women (fluid group). Intravenous infusions of oxytocin in 5% glucose were given to 12 women (oxytocin group). Thirty women delivered their babies without infusion (nofluid group). Blood and urine samples were collected at arrival, at early stage 1, at early stage 2, and at aftercare, and 9-, 15-, and 27-h postpartum. Plasma osmolality, sodium, cystatin C, vasopressin, oxytocin, urine flow, urine osmolality and urine sodium were measued.ResultsThe oxytocin group had significantly lower plasma osmolality than the nofluid group before parturition, and they had lower plasma sodium concentration at early stage one and two. Plasma vasopressin concentration was low and did not differ between groups or before and after parturition. Water diuresis developed postpartum in all groups. The cystatin C concentration decreased significantly after parturition in the oxytocin and nofluid groups.ConclusionsThe vasopressin levels were suppressed during parturition irrespective of the P-osmolality and the nongravid regulation of water balance had not returned within 27 h postpartum.

  • 39. Savukoski, Tanja
    et al.
    Mehtala, Laura
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Pettersson, Kim
    Elevation of cardiac troponins measured after recreational resistance training2015In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 48, no 12, p. 803-806Article in journal (Refereed)
    Abstract [en]

    Background: Whereas elevated cardiac troponin (cTn) concentrations i.e. above the 99th percentile of healthy reference population (recommended cutoff for the diagnosis of myocardial infarction) are well-documented in healthy individuals after prolonged and/or intensive exercises such as marathons, data on less-strenuous sports are scarce. Therefore, our aim was to investigate cTnI and cTnT release in response to recreational resistance training, here a single-bout of 1-h kettlebell workout. Methods: Serum samples were collected from 11 apparently healthy volunteers the previous day (pre-exercise), three hours after the kettlebell class (post-exercise), the next day and three days later. The aliquoted samples were analyzed with Abbott Laboratories' Architect high-sensitivity (hs)-cTnI assay (limit of detection, LoD = 2 ng/L), our 3 + 1-type cTnI assay free from cTn-specific autoantibody interference (LoD = 3 ng/L) and Roche Diagnostics' hs-cTnT assay CLOD = 5 ng/L). Results: The post-exercise cTn concentrations were significantly higher than the pre-exercise values (median 5.5-9.6 ng/L vs. <LoD, P < 0.05 for all) and they correlated strongly between the three assays (Spearman r = 0.881-0.960, P < 0.001 for all). Furthermore, a few post-exercise concentrations even exceeded the 99th percentile of Architect hs-cTnI (>26 ng/L, n = 2) and/or hs-cTnT (>14 ng/L, n = 4). The cTn concentrations returned to baseline during the three days of follow-up. Conclusions: Our study demonstrates abnormally elevated cTns with well-validated sensitive cTn assays after resistance training. This confirms that different kinds of recreational physical activity are yet another confounder that may affect the determination and use of 99th percentile reference values. Therefore, exercise-associated changes should be carefully addressed as part of the evaluation what is "normal cTn".

  • 40.
    Sohrabian, Azita
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Noraddin, Feria Hikmet
    Flodin, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Fredricsson, Annika
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Particle enhanced turbidimetric immunoassay for the determination of urine cystatin C on Cobas c5012012In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 45, no 4-5, p. 339-344Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Urinary cystatin C has been reported to be a good marker for tubular damage and acute kidney injury. The aim of this study was to develop a high throughput assay for the quantification of urine cystatin C.

    METHODS:

    Antigen-excess, imprecision, interference, linearity, recovery, sample stability and reference values were evaluated on Cobas c501.

    RESULTS:

    The assay was linear over the dynamic range of the study (R(2)=0.9994). The total assay imprecision was below 5%. The assay recovery was estimated at 87-100%. No tendency to antigen-excess (up to 35mg/L), nor interference with haemoglobin (1.25-10g/L) was observed. Cystatin C was stable for 1day at ambient temperature (19-23°C) but for 2days at +4°C. The reference interval for cystatin C in urine was <0.414mg/L.

    CONCLUSIONS:

    The urinary cystatin C assay verified to be a reliable assay with convenient performance characteristics, enabling routine testing on clinical chemistry platforms.

  • 41.
    Uggla, Bertil
    et al.
    Örebro University, School of Medicine, Örebro University, Sweden.
    Nilsson, Torbjörn
    Department of Medical Biosciences/Clinical Chemistry, Umeå University, Umeå, Sweden.
    Whole blood viscosity in plasma cell dyscrasias2015In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 48, no 3, p. 122-124Article in journal (Refereed)
    Abstract [en]

    Objectives: Plasma or serum hyperviscosity in plasma cell dyscrasias (PCD) has been described as a risk factor for circulatory disturbances. Whole blood viscosity (WBV) would theoretically be a better biomarker but has not been studied in PCD.

    Design and methods: Plasma viscosity (PV) and WBV were measured in 89 subjects with PCD and in 60 healthy blood donors by free oscillation rheometry. A complete blood count was obtained using an automated hematology analyzer. Plasma proteins were quantitated by immunoturbidimetry.

    Results: The reference intervals for men & women were 1.16-1.36 & 1.16-1.38. mPa for PV, and 4.9-6.3 & 4.4-6.2. mPa for WBV, respectively. Of the PCD patients, 71% had PV above the reference limit and 40% were above the WBV limit. Multivariate analysis showed that WBV was independently related to hematocrit, PV, concentration of the monoclonal protein (M-protein), plasma fibrinogen concentration and albumin concentration. This model accounted for 76% of the variance in WBV. When the same model was applied to PV, only the concentration of the M-protein was significantly related and the model accounted only for 20% of the variance in PV.

    Conclusion: PV cannot be used as a surrogate marker for WBV in PCD patients. Whole blood viscosity should replace plasma viscosity in patients with PCD.

  • 42. Uggla, Bertil
    et al.
    Nilsson, Torbjörn K.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Whole blood viscosity in plasma cell dyscrasias2015In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 48, no 3, p. 122-124Article in journal (Refereed)
    Abstract [en]

    Objectives: Plasmaor serum hyperviscosity in plasma cell dyscrasias (PCD) has been described as a risk factor for circulatory disturbances. Whole blood viscosity (WBV) would theoretically be a better biomarker but has not been studied in PCD. Design and methods: Plasma viscosity (PV) and WBV were measured in 89 subjects with PCD and in 60 healthy blood donors by free oscillation rheometry. A complete blood count was obtained using an automated hematology analyzer. Plasma proteins were quantitated by immunoturbidimetry. Results: The reference intervals for men & women were 1.16-1.36 & 1.16-1.38 mPa for PV, and 4.9-6.3 & 4.4-6.2 mPa for WBV, respectively. Of the PCD patients, 71% had PV above the reference limit and 40% were above the WBV limit. Multivariate analysis showed that WBV was independently related to hematocrit, PV, concentration of the monoclonal protein (M-protein), plasma fibrinogen concentration and albumin concentration. This model accounted for 76% of the variance in WBV. When the same model was applied to PV, only the concentration of the M-protein was significantly related and the model accounted only for 20% of the variance in PV. Conclusion: PV cannot be used as a surrogate marker for WBV in PCD patients. Whole blood viscosity should replace plasma viscosity in patients with PCD.

  • 43.
    Åkerfeldt, Torbjörn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Postsurgical inflammatory response is not associated with increased serum cystatin C values2010In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 43, no 13-14, p. 1138-1140Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Cystatin C is used both as a glomerular filtration (GFR) marker and a cardiovascular risk marker. There are several studies showing an association between cystatin C and inflammatory markers and it has been suggested that the inflammatory response in itself could result in elevated cystatin C levels. The aim of this study was to evaluate if an induced inflammatory response has an effect on cystatin C levels in humans. MATERIALS AND METHODS: CRP and cystatin C were analyzed in serum samples from orthopedic surgery patients (n=29). The patients were sampled prior to surgery and four and thirty days after surgery. RESULTS: The surgery induced a pronounced CRP elevation on day four, median 137.3 (interquartile range 104.1-178.2) mg/L compared to 1.94 (1.20-8.70) mg/L before surgery, P<0.001, but no significant difference in cystatin C levels before and four and thirty days after surgery could be seen. CONCLUSIONS: The orthopedic surgery-induced inflammatory response does not cause changes in cystatin C levels.

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