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  • 1.
    Aldrimer, Mattias
    et al.
    Department of Clinical Chemistry, County Hospital of Falun.
    Ridefelt, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Rodoo, Peo
    Department of Pediatrics, County Hospital of Falun.
    Niklasson, Frank
    Department of Clinical Chemistry, County Hospital of Falun.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Population-based pediatric reference intervals for hematology, iron and transferrin2013In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 73, no 3, p. 253-261Article in journal (Refereed)
    Abstract [en]

    Reference intervals are crucial decision-making tools aiding clinicians in differentiating between healthy and diseased populations. However, for children such values often are lacking or incomplete. Blood samples were obtained from 689 healthy children, aged 6 months to 18 years, recruited in day care centers and schools. Hematology and anemia analytes were measured on the Siemens Advia 2120 and Abbott Architect ci8200 platforms (hemoglobin, erythrocyte volume fraction [EVF], erythrocytes, mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC], reticulocytes, leukocytes, lymphocytes, monocytes, neutrophils, eosinophils, basophils, platelets, iron, transferrin, transferrin saturation). Age-and gender-specific pediatric reference intervals were defined by calculating 2.5th and 97.5th percentiles. The data generated is primarily applicable to a Caucasian population, but could be used by any laboratory if verified for the local patient population.

  • 2. Aldrimer, Mattias
    et al.
    Ridefelt, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Rodoo, Peo
    Niklasson, Frank
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Reference intervals on the Abbot Architect for serum thyroid hormones, lipids and prolactin in healthy children in a population-based study2012In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, no 4, p. 326-332Article in journal (Refereed)
    Abstract [en]

    Pediatric reference intervals for thyroid hormones, prolactin and lipids are of high clinical importance as deviations might indicate diseases with serious consequences. In general, previous reference intervals are hampered by the inclusion of only hospital-based populations of children and adolescents. The study included 694 children, evenly distributed from 6 months to 18 years of age. They were recruited as volunteers at child care units and schools. All subjects were apparently healthy and a questionnaire on diseases and medications was filled out by parents and by the older children. TSH, free T4, free T3, total cholesterol, LDL, HDL, triglycerides and prolactin were analyzed on Abbott Architect ci8200. Age- and gender-related 2.5 and 97.5 percentiles were estimated. The thyroid hormone levels were similar to previous data for the Abbott Architect platform, but exhibited differences from studies performed with other methods. Prolactin displayed wide reference ranges, but relatively small age-related changes, and a marginal difference between sexes during adolescence. Reference intervals for lipids in the different age groups are known to vary geographically. Levels of LDL and total cholesterol were higher than those reported for children in Canada, but lower than those reported for children in China. The study gives age-and gender-specific pediatric reference intervals, measured with modern methods for a number of important analytes. The results presented here differ from previously recommended reference intervals. In many earlier studies, retrospective hospital-based reference intervals, which may include various sub-groups have been presented. By non-hospital studies it is possible to avoid some of these biases.

  • 3.
    Andersson, Christoffer R.
    et al.
    Orebro Univ, Dept Neurol, Fac Med & Hlth, Orebro, Sweden..
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Theodorsson, Elvar
    Linkoping Univ, Dept Clin Chem, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Strom, Jakob O.
    Orebro Univ, Dept Neurol, Fac Med & Hlth, Orebro, Sweden.;Linkoping Univ, Dept Clin Chem, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Comparisons between commercial salivary testosterone enzyme-linked immunosorbent assay kits2017In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 77, no 8, p. 582-586Article in journal (Refereed)
    Abstract [en]

    Introduction: Measuring testosterone concentrations is of interest both in clinical situations and for research, the latter expanding rapidly during recent years. An increased demand for convenient methods has prompted a number of companies to develop enzyme-linked immunosorbent assay (ELISA) kits to measure testosterone concentrations in saliva. However, the inter-comparability of kits from different manufacturers have yet to be determined. Aim of study: The aim of this study was to compare commercially available ELISA kits from four different manufacturers (Salimetrics, IBL, DRG and Demeditec). Methods: Saliva was collected from 50 participants (25 men and 25 women). Each sample was analysed by the four ELISA kits. Results: The correlations between the ELISA kits from Demeditec, DRG and Salimetrics were moderate to high with r-values >.77; however, proportional errors between the methods calls for caution. The ELISA kit from IBL malfunctioned and no results from this kit was obtained. Conclusions: Results from studies using the ELISA kits from Demeditec, DRG and Salimetrics are generally comparable; however, translation using the formulae presented in the current study could increase the accuracy of these comparisons.

  • 4.
    Arvidson, Nils Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsen, A.
    Aaseth, J.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Short-term effects of the TNFalpha antagonist infliximab on the acute phase reaction and activities of daily life in patients with rheumatoid arthritis2007In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 67, no 3, p. 337-342Article in journal (Refereed)
    Abstract [en]

    Objective. To investigate the short-term effects of the tumour necrosis factor alpha (TNFα) antagonist infliximab on the acute phase reaction and activities of daily life (ADL) in patients with rheumatoid arthritis (RA). Methods. Fourteen patients with active RA were treated with an intravenous infusion of 200 mg infliximab. The values of the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, granulocyte count, lymphocyte count, platelet count and a patient questionnaire score on ADL, the Health Assessment Questionnaire (HAQ), were obtained at baseline and on days 4 and 14. The significance levels and effect sizes (ESs) of the changes from baseline were calculated. Results. Changes by day 4: The ESs and significance levels were: CRP 1.7, p<0.005; lymphocyte count 1.4, p<0.005; fibrinogen 0.9, p<0.005; ESR 0.7, p<0.005; and HAQ 0.6, p<0.01. Changes by day 14: CRP 1.6, p<0.005; ESR 1.5, p<0.005; fibrinogen 1.3, p<0.005; lymphocyte count 1.0, p<0.005; granulocyte count 0.7, p<0.05; and HAQ 0.6, p<0.05. Conclusion. CRP, fibrinogen and ESR showed the largest ESs and were thus the most sensitive variables showing the early effect of infliximab in this study. The score on ADL (HAQ) showed less ES, but still significant short-term improvements.

  • 5.
    Biglarnia, Alireza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wadström, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Decentralized glomerular filtration rate (GFR) estimates in healthy kidney donors show poor correlation and demonstrate the need for improvement in quality and standardization of GFR measurements in Sweden2007In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 67, no 2, p. 227-235Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Glomerular filtration rate (GFR) is generally accepted as the best overall index of renal function. Thus, all potential live kidney donors are tested to ensure that they have a normal GFR before they are eligible for kidney transplantation. The choice of GFR test is very much dependent on local traditions and may include iohexol, 51Cr-EDTA, inulin, or creatinine clearance based on urine collection, and creatinine clearance calculated from the Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) equation as well as cystatin C. The aim of this study was to compare the results of GFR measurements performed in all actual live kidney donors who have undergone live donor nephrectomy at the University Hospital in Uppsala, Sweden, between the years 2000 and 2004. MATERIAL AND METHODS: The patients were selected from all parts of Sweden and the measurements were performed at their local hospital. RESULTS: We found large discrepancies between repeated iohexol measurements in these presumably healthy individuals. There was also a poor correlation between iohexol clearance and calculated creatinine clearance using the Cockcroft-Gault (R2=0.046) or MDRD formula (R2=0.045). CONCLUSIONS: The study shows that the standardization and quality of GFR measurements in Sweden have to be improved.

  • 6.
    Birgegård, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sandhagen, B.
    Erythropoetin treatment can increase 2,3-diphosphoglycerate levels in red blood cells2001In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 61, no 5, p. 337-340Article in journal (Refereed)
    Abstract [en]

    Some patients experience an improved well-being during treatment with recombinant human erythropoietin even with an unchanged Hb level. We have hypothesized that this may not be only a placebo effect. 2,3-diphosphoglycerate (2,3-DPG) in red blood cells increases in response to anaemia/hypoxia and causes a shift of the oxygen dissociation curve, allowing a more effective oxygen delivery. We have investigated red cell 2,3-DPG concentrations during erythropoietin treatment in healthy volunteers as a mediator of a possible physiological explanation. Thirteen healthy subjects with no iron deficiency were recruited and randomly assigned to a treatment group comprising five males and three females and a control group including three males and two females. The treatment group was treated with erythropoietin (Recormon), 20 IE/kg subcutaneously three times/week for 4 weeks. Blood samples were collected at each injection day and 10 days after the last injection and at corresponding times in the control group. B-Hb, red cell 2,3-DPG and P50 were measured by standard techniques and oxygen-releasing capacity was calculated. RESULTS: due to the sampling (26 ml each time, three times/week) the mean Hb level was lowered from 140.5 +/- 5.9 to 128.6 +/- 10.4 g/L in the control group whereas the erythropoietin treatment group maintained a mean Hb level of about 142 g/L (p<0.002). The 2,3-DPG mean level curve as well as that for oxygen releasing capacity also differed significantly between the two groups (p < 0.002), the treatment group showing higher levels. CONCLUSION: treatment with erythropoietin causes an increase in red cell 2,3-DPG levels.

  • 7.
    Björk, Jonas
    et al.
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Nyman, Ulf
    Department of Translational Medicine, Division of Medical Radiology, Lund University, Malmö, Sweden.
    Delanaye, Pierre
    Department of Nephrology-Dialysis-Transplantation, University of Liège (ULg CHU), CHU Sart Tilman, Liège, Belgium.
    Grubb, Anders
    Department of Clinical Chemistry, Skåne University Hospital, Lund, Lund University, Lund, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Vranken, Laura
    Department of Clinical Chemistry, University of Liège (ULg CHU), CHU Sart Tilman, Liège, Belgium.
    Åkesson, Anna
    Clinical Studies Sweden, Skåne University Hospital, Lund, Sweden.
    Pottel, Hans
    Department of Public Health and Primary Care, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
    A novel method for creatinine adjustment makes the revised Lund-Malmö GFR estimating equation applicable in children2020In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 80, no 6, p. 456-463Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to establish creatinine growth curves separately for males and females that can be used to adjust childhood levels of serum creatinine to corresponding adult levels. Linear regression with fractional polynomials of age as independent variable was used to construct creatinine growth curves for a reference cohort (n = 83,157 samples from Belgium and Sweden, age 2-40 years). Adjusted creatinine obtained from the growth curves was used to improve accuracy of estimated glomerular filtration rate (eGFR) based on the Lund-Malmö revised (LMR) equation in children. The LMR equation based on creatinine values adjusted to age 18 years was validated against measured GFR (mGFR) in a separate cohort of 4005 children from four different European countries. Validation metrics included median bias, precision, and accuracy expressed as percentage of estimates within ±30% (P30) of mGFR. Remarkable improvements in bias and accuracy were observed; P30 increased from 56% to 74% after creatinine adjustments in children with mGFR <75 mL/min/1.73 m2 (n = 932), while P30 was relatively unchanged (89-90%) at mGFR ≥75 mL/min/1.73 m2 (n = 3073). The suggested approach with adjusted creatinine makes LMR applicable in children irrespective of their renal function.

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  • 8.
    Block, T
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nilsson, T K
    Björck, M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Acosta, S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Diagnostic accuracy of plasma biomarkers for intestinal ischaemia2008In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 68, no 3, p. 242-248Article in journal (Refereed)
    Abstract [en]

    Objective . Intestinal ischaemia is a life-threatening condition with high mortality, and the lack of accurate and readily available diagnostic methods often results in delay in diagnosis and treatment. The aim of this study was to investigate the accuracy of different plasma biomarkers in diagnosing intestinal ischaemia. Material and methods . Prospective inclusion of patients older than 50 years with acute abdomen admitted to hospital in Karlskrona, Sweden, between 2001 and 2003. Venous blood was sampled prior to any surgery and within 24 h from onset of pain. D-lactate, alpha glutathione S-transferase, intestinal fatty acid binding protein, creatine kinase B, isoenzymes of lactate dehydrogenase (LD) and alkaline liver phosphatase (ALP) were analysed. D-dimer was analysed using four different commercially available test kits. Results . In-hospital mortalities among patients with (n = 10) and without (n = 61) intestinal ischaemia were 40 % and 3 %, respectively (p = 0.003). D-dimer was associated with intestinal ischaemia (p = 0.001) independently of which assay was used. No patient presenting with a normal D-dimer had intestinal ischaemia. D-dimer >0.9 mg/L had a specificity, sensitivity and accuracy of 82 %, 60 % and 79 %, respectively. Total LD, isoenzymes of LD 1-4 and liver isoenzyme of ALP (ALP liver) were significantly higher in patients with intestinal ischaemia, and accuracies for LD 2 (cut-off 2.3 µkat/L) and ALP liver (cut-off 0.7 µkat/L) were 69 % and 66 %, respectively. Conclusions. D-dimer may be used as an exclusion test for intestinal ischaemia, but lacks specificity. The other plasma biomarkers studied had insufficient accuracy for this group of patients. Further studies are needed.

  • 9. Bolinder, J
    et al.
    Fernlund, P
    Borg, H
    Arnqvist, H J
    Björk, E
    Blohmé, G
    Eriksson, Jan W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Nyström, L
    Ostman, J
    Sundkvist, G
    Hyperproinsulinemia segregates young adult patients with newly diagnosed autoimmune (type 1) and non-autoimmune (type 2) diabetes.2005In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 65, no 7, p. 585-94Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate whether measurements of proinsulin and/or intermediate proinsulin degradation products could be used to differentiate between autoimmune (type 1) and non-autoimmune (type 2) diabetes in young adults.

    MATERIAL AND METHODS: Total proinsulin, intact proinsulin and 32,33 split proinsulin concentrations were measured in 25 patients aged 15-34 years with type 1 diabetes, as defined by the presence of at least two positive islet autoantibodies, and in 23 antibody-negative patients of similar age with type 2 diabetes, at the time of clinical onset of diabetes and at 3-4 months thereafter. Comparisons were made with data from 25 healthy subjects matched for gender and age.

    RESULTS: Plasma levels of total proinsulin, intact proinsulin and 32,33 split proinsulin were significantly increased 2-3-fold in the patients with newly diagnosed type 2 diabetes as compared with the controls, both in absolute terms (p<0.0001) and when related to circulating insulin (p<0.01-0.0002). In contrast, absolute proinsulin and 32,33 split proinsulin concentrations were significantly lower in patients with onset of type 1 diabetes than in controls. When proinsulin and split proinsulin release were related to plasma insulin, however, similar ratios were found in the type 1 diabetes patients and in controls. Using the 90th percentile for total proinsulin in the control group as the cut-off, the sensitivity and specificity for differentiation between autoimmune and non-autoimmune diabetes were 87% and 92%, respectively. At 3-4 months after clinical onset of diabetes, proinsulin secretion was still 2-3 times higher in type 2 than in type 1 diabetes patients (p<0.001).

    CONCLUSIONS: Young adult patients with newly diagnosed type 2 diabetes display disproportionate hyperproinsulinemia, whereas proinsulin secretion appears to be normal in patients with clinical onset of type 1 diabetes. Evaluation of proinsulin and 32,33 split proinsulin concentrations may be useful as a diagnostic tool in differentiating between autoimmune and non-autoimmune diabetes in young adults, particularly in those lacking islet autoantibodies at diagnosis.

  • 10.
    Carlsson, Per-Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Bodin, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Andersson, Arne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Jansson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carbon monoxide and pancreatic islet blood flow in the rat: inhibition of haem oxygenase does not affect islet blood perfusion2006In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 66, no 7, p. 543-548Article in journal (Refereed)
    Abstract [en]

    Objective. To determine whether carbon monoxide, a known gaseous vasorelaxator, affects pancreatic islet blood flow in rats. Material and methods. Sprague-Dawley rats were anaesthetized with thiobutabarbital and injected intravenously with the haem oxygenase inhibitor tin-protoporphyrin IX dichloride ( SnPP; 4, 10 or 20 mg/kg body-weight). After 15 min, blood flow measurements were performed using a microsphere technique. Results. There was a slight increase in mean arterial blood pressure with the highest dose of SnPP. No effects on total pancreatic, islet, duodenal, colonic, renal or adrenal blood flow were seen with any of the applied doses. Conclusions. The findings of this study suggest that the haem oxygenase-carbon monoxide system is likely to be of limited importance in the regulation of blood perfusion to the pancreas, the islets of Langerhans or any of the other studied organs.

  • 11.
    Chaireti, Roza
    et al.
    Department of Molecular Medicine and Surgery , Karolinska Institutet , Stockholm.
    Lindahl, Tomas L
    Department of Clinical and Experimental Medicine , Linköping University , Linköping.
    Byström, Birgitta
    Department of Women's and Children's Health, Division of Obstetrics and Gynecology , Karolinska Institutet , Stockholm.
    Bremme, Katarina
    Department of Women's and Children's Health, Division of Obstetrics and Gynecology , Karolinska Institutet , Stockholm.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Inflammatory and endothelial markers during the menstrual cycle.2016In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 76, no 3, p. 190-194Article in journal (Refereed)
    Abstract [en]

    Background The menstrual cycle exhibits a pattern of repeated inflammatory activity. The present study aims to evaluate inflammatory and endothelial markers during the two phases of a menstrual cycle.

    Methods The study cohort consisted of 102 women with regular menstrual cycles. Inflammatory and endothelial markers (interleukin-6 [IL-6], pentraxin-3 [PTX-3], hs-C reactive protein [hs-CRP], sE-selectin, sP-selectin, intracellular and vascular cell adhesion molecules [ICAM-1 and VCAM-1] and cathepsins L, B and S) were measured during the early follicular and the late luteal phase of a normal menstrual cycle.

    Results Pentraxin-3 (PTX-3) and hs-CRP were significantly higher during the follicular phase compared to the luteal phase (p < 0.001 respectively p = 0.025). The other inflammatory and endothelial markers, with the exception of cathepsin B, were higher, albeit not significantly, during the follicular phase.

    Conclusions Inflammatory activity, expressed mainly by members of the pentraxin family, is higher during the early follicular compared to the luteal phase. This could be associated to menstruation but the exact mechanisms behind this pattern are unclear and might involve the ovarian hormones or an effect on hepatocytes.

  • 12.
    Christersson, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Johnell, Matilda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Evaluation of microparticles in whole blood by multicolour flow cytometry assay2013In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 73, no 3, p. 229-239Article in journal (Refereed)
    Abstract [en]

    Objective

    To develop and evaluate a multicolour flow cytometry method for analysis of microparticles (MPs) in fresh whole blood without any centrifugation steps or freezing/thawing procedure.

    Materials and methods

    Flow cytometry was performed using a FC500 MPL cytometer. The compensation in the protocol was performed based on the platelet population. Polystyrene microspheres 0.50–1.27 μm were used for size position, and the MP gate was set as particles 0.5–1.0 μm. Whole blood was incubated with annexin V and antibodies to tissue factor (TF), platelets (CD41 and CD62P), monocyte (CD14) and endothelial cells (CD144). For comparison, MPs from platelet free supernatant was used. The TF activity was evaluated by Calibrated Automated Thrombogram.

    Results

    Annexin V was used to distinguish true events from background noise. For standardization, each analysis included 10,000 events in the gate of platelets. There were 622(462–1001) MPannV+/10,000 platelets and of these, 66 (49–82)/10,000 platelets expressed TF. After correction for the individual platelet counts, the amount of circulating MPannV+ was 17.1 (12.1–24.9) × 109/L in whole blood, and of these, 10% (6–12%) expressed TF. The majority of the MPs expressed CD41, and 5.6% (2.2–6.9%) of these co-expressed TF. The amount of CD41 + MPannV+ tended to correlate to the TF activity in whole blood. There was no correlation between the MPannV+ in whole blood and MPs derived from platelet free supernatant. Patients with pulmonary arterial hypertension and stable coronary artery disease had increased concentrations of CD41 + MPannV+ in whole blood.

    Conclusion

    This multicolour flow cytometry assay in whole blood mimics the in vivo situation by avoiding several procedure steps interfering with the MP count. By standardized quantification of MPs a reference interval of MPs can be created.

  • 13.
    Christersson, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    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.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The composition and daily variation of microparticles in whole blood in stable coronary artery disease2016In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 76, no 1Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The knowledge of circadian variation of microparticles (MPs) in stable coronary artery disease (SCAD) is limited. The aim of this study was to evaluate the daily variation of platelet-, endothelial- and monocyte-derived MPs in whole blood and their tissue factor expression (TF) in SCAD and whether these MPs were related to other endothelial and coagulation markers.

    MATERIALS AND METHODS: Serial blood samples from patients with SCAD were collected during one day. Flow cytometry was used to evaluate the amount of large MPs 0.5-1.0 μm, positive for annexin, and their expression of CD41, CD62P, CD144, CD14 and TF. The lag time and endogenous thrombin potential (ETP) was calculated by Calibrated Automated Thrombogram and soluble (s)P-selectin, sTF and vWF by ELISA.

    RESULTS: The majority of MPs in whole blood consisted of CD41 + MPs with no significant daily variation. In contrast, the concentration of CD62P + MPs described a daily variation with the lowest concentrations found in the evening (p = 0.031). CD62P + and CD144 + MPs had the highest expression of TF, 52.6% and 42.9%, respectively, and correlated to the endothelial activity evaluated by vWF. There was a circadian rhythm of lag time (p < 0.001) and ETP (p = 0.001). The CD62P+, CD14 + and CD144 + MPs correlated to the lag time.

    CONCLUSION: The different subsets of platelet-, endothelial- and monocyte-derived MPs do not present the same circadian variation and they differ in TF expression in SCAD. The MPs from activated platelets, endothelial cells and monocytes exist in low concentrations in whole blood but are related to the endothelial and coagulation activity found in SCAD.

  • 14.
    Dahlbom, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Nyberg, Britt-Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Berntson, Lillemor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hansson, Tony
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Simultaneous detection of IgA and IgG antibodies against tissue transglutaminase: The preferred pre-biopsy test in childhood celiac disease2016In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 76, no 3, p. 208-216Article in journal (Refereed)
    Abstract [en]

    Objectives: IgA antibodies against tissue transglutaminase (anti-TG2) is a reliable marker of celiac disease (CD). However, IgA-deficient patients are not identified and young children may lack IgA anti-TG2. Combined detection of IgA and IgG (IgA/IgG) against deamidated gliadin peptides (DGP) has shown a high diagnostic performance for untreated CD. Here we examined the utility of IgA/IgG anti-TG2, IgA/IgG anti-DGP and IgA/IgG against a mix of TG2 and DGP (anti-TG2/DGP) in finding CD among children.

    Methods: Serum antibodies against TG2, DGP, and TG2/DGP were determined with ELISA in 242 children referred to a paediatric gastroenterologist. Fifty had untreated CD verified by an intestinal biopsy and 192/242 children had other diseases than CD.

    Results: Forty-eight untreated CD children had increased IgA/IgG anti-TG2, 47/50 had increased IgA/IgG anti-DGP and 46/50 had increased IgA/IgG anti-TG2/DGP. One control subject had increased IgA/IgG anti-TG2 and IgA/IgG anti-TG2/DGP, whereas 7/192 control subjects had increased IgA/IgG anti-DGP. The IgA/IgG anti-TG2 assay had the best performance with a sensitivity of 96%, a specificity of 99.5% and the area under the ROC-curve was 0.996 (95% CI 0.992-1, p < 0.0001).

    Conclusions: Detection of one antibody is not sufficient when screening for untreated CD among children due to cases of IgA deficiency. The inclusion of DGP antigens in the IgA/IgG combination assays seems to affect the sensitivity and specificity negatively, whereas detection of IgA/IgG anti-TG2 has the potential of finding most untreated CD patients, including those with IgA deficiency.

  • 15. Edelstam, Greta
    et al.
    Löwbeer, C.
    Kral, G.
    Gustafsson, S. A.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    New reference values for routine blood samples and human neutrophilic lipocalin during third-trimester pregnancy2001In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 61, no 8, p. 583-592Article in journal (Refereed)
    Abstract [en]

    Reference values are usually based on blood samples from healthy men or non-pregnant women. Blood samples from pregnant women may be compared with these reference values. Correct references for pregnancy can be extremely important for clinical decisions such as ablatio placentae, appendicitis, premature rupture of membranes and preeclampsia. Previous studies of normal variations during third-trimester pregnancy are incomplete. Blood samples during pregnancy weeks 33, 36 and 39 as well as 1-3 h postpartum were collected from pregnant women with dietary iron supplement and at least one previous pregancy without a history of hypertension or preeclampsia. When the sampled values were compared with the present reference values from men and non-pregnant women, the following differences were found during normal pregnancy: Haemoglobin and ferritin were reduced, CRP was slightly elevated, WBC (white blood cell count) and HNL (human neutrophilic lipocalin) were elevated during pregnancy and significantly increased postpartum. Albumin was reduced. ALT and AST were slightly elevated and GGT was unchanged during pregnancy. ALP, D-dimer and fibrinogen were elevated. Uric acid increased during the third trimester and thrombocyte count decreased. Separate reference values for pregnant women are essential for correct diagnostic decisions during third-trimester pregnancy. Elevated levels of D-dimer do not necessarily indicate ablatio placentae. A diagnosis of progressive preeclampsia cannot be based on increasing uric acid levels and reduced platelet count in a stable clinical condition. HNL signals activation of neutrophilic granulocytes and can thereby offer a helpful tool for diagnosing infection during pregnancy and postpartum.

  • 16.
    Eggers, Kai M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kempf, Tibor
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wollert, Kai C
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Relations of growth-differentiation factor-15 to biomarkers reflecting vascular pathologies in a population-based sample of elderly subjects2012In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, no 1, p. 45-51Article in journal (Refereed)
    Abstract [en]

    Background.

    Growth-differentiation factor-15 (GDF-15) has recently emerged as a risk predictor in patients with cardiac diseases. GDF-15 is commonly related to cardiovascular risk factors, inflammatory activity and cardiac abnormalities. However, it is not clear whether it might be an indicator of vascular pathologies as well.

    Methods.

    Circulating levels of GDF-15 were measured in 1004 elderly community dwellers participating in the PIVUS study. The relations of GDF-15 to biomarkers of endothelial activation (E-selectin, P-selectin, ICAM-1, VCAM-1), extracellular matrix degradation (MMP-9, TIMP-1), coagulatory activity (D-dimer, von Willebrand factor, prothrombin fragment 1 + 2, factor VIIa), and fibrinolytic activity (PAI-1 activity, tPA-antigen) were assessed by multiple linear regressions.

    Results.

    The median GDF-15 level was 1135 ng/L. By linear correlation analysis, GDF-15 exhibited a moderate relation to von Willebrand factor (r = 0.30), and weak, albeit significant relations (r = 0.13-0.29) to E-selectin, P-selectin, ICAM-1, VCAM-1, MMP-9, TIMP-1, D-dimer, PAI-1 activity and tPA-antigen. The relations to the assessed biomarkers of endothelial activation, TIMP-1, D-dimer and von Willebrand factor remained significant applying multiple linear regression models adjusted for clinical covariates and echocardiographic data. There were no significant relations between GDF-15 and biomarkers solely reflecting coagulatory activity.

    Conclusions.

    In the elderly, GDF-15 reflects endothelial activation and vascular inflammation and thus, multiple pathways involved in the development and progression of atherosclerosis.

  • 17.
    Eriksson, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Evaluation of intraosseous sampling for measurements of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, creatinine kinase, gamma-glutamyl transferase and lactate dehydrogenase.2016In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 76, no 8, p. 597-600Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Intraosseous (IO) access can be established faster than a venous or arterial access when there is an urgent need for rapid initiation of treatment. The access can also be used to draw marrow samples. The aim of the present study was to evaluate the potential use of IO samples for enzyme determinations using a porcine model.

    MATERIALS AND METHODS: Bilateral tibial intraosseous cannulae and an arterial catheter were used for blood sampling from five healthy anesthetized pigs. Samples were collected at baseline and thereafter hourly for 6 h and analyzed for alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, creatinine kinase, gamma-glutamyl transferase and lactate dehydrogenase.

    RESULTS: Creatinine kinase, lactate dehydrogenase and alkaline phosphatase levels decreased over time. The differences between IO and arterial sampling were limited for all studied markers.

    CONCLUSION: The correlation between marrow and blood analysis for liver function tests and CK is sufficiently accurate in an emergency situation.

  • 18.
    Eriksson, Oskar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Håkansson, Lena Douhan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Karawajczyk, Malgorzata
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Garwicz, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Neutrophil CD64 expression - comparison of two different flow cytometry protocols on EPICs MCL and the Leuko64 (TM) assay on a Celldyn Sapphire haematology analyser2015In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 75, no 5, p. 428-433Article in journal (Refereed)
    Abstract [en]

    Objective. To evaluate the Trillium Diagnostics Leuko64 (TM) assay on Abbott Celldyn Sapphire haematology analyser compared to two flow cytometry protocols on Beckman Coulter EPICS MCL flow cytometer. Materials and methods. CD64 expression on neutrophils was determined by two flow cytometry protocols and by a commercial assay on an automatic haematology analyser. The inclusion of study subjects was based on elevated procalcitonin (PCT) values, identifying patients where a systemic infection was suspected. Healthy blood donors were used as a reference group. Results. Statistically significant correlations between the Trillium Diagnostics Leuko64 (TM) assay and the flow cytometry methods were found when measuring neutrophil CD64 expression. Conclusions. The good correlation between a reference method and an automated haematology analyser method for CD64 expression on neutrophils supports introduction of the latter assay for routine use as an independent biomarker of bacterial infection and inflammation.

  • 19.
    Flodin, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jonsson, A-S.
    Hansson, L-O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Danielsson, L-A.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Evaluation of Gentian cystatin C reagent on Abbott Ci8200 and calculation of glomerular filtration rate expressed in mL/min/1.73 m(2) from the cystatin C values in mg/L2007In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 67, no 5, p. 560-567Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Estimation of the glomerular filtration rate (GFR) is essential when evaluating patients with kidney disease and treating patients with drugs eliminated from the circulation by the kidneys. Cystatin C has been shown in several studies to be superior to creatinine in the estimation of GFR. At our hospitals, there is an increasing demand for cystatin C and at present we perform approximately 1500 cystatin C analyses a month. We thus need the assay available 24 h/day and to have it on our routine chemistry instrument to minimize handling time per test and time to reported test results. MATERIAL AND METHODS: We have evaluated a new cystatin C immunoassay from Gentian (Gentian, Moss, Norway) on Architect ci8200 (Abbott Laboratories, Abbott Park, Ill., USA). A prerequisite at our hospital is that cystatin C results are reported as a calculated GFR in mL/min/1.73 m(2), so we also made a comparison with iohexol clearance. RESULTS: The Gentian cystatin C assay showed good agreement with the corresponding assay from Dade Behring (Deerfield, Ill., USA) and good inter-laboratory concordance. The assay has very low total imprecision, good linearity and strong correlation with iohexol clearance (R (2) = 0.956). The equation for the correlation curve is: y = 79.901x(-1.4389). CONCLUSIONS: There was low inter-laboratory variation between the three laboratories involved in the cystatin C evaluation, and thus all three laboratories can use the same equation for calculating the estimated GFR.

  • 20.
    Gustafsson, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Eriksson, J.
    Marcus, C.
    Glucose metabolism in human adipose tissue studied by 13C-glucose and microdialysis2007In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 67, no 2, p. 155-164Article in journal (Refereed)
    Abstract [en]

    Objective. Microdialysis can be used to monitor carbohydrate metabolism and lipolysis in adipose tissue. This method, however, does not discriminate between local metabolite production and delivery from other tissues. Our aim was to study glucose metabolism by direct delivery of 13C-labelled glucose into adipose tissue by microdialysis. Material and methods. Seven healthy adults were studied after an overnight fast. In three of them the effect of physical activity on glucose metabolism was tested. Microdialysis catheters were introduced into abdominal adipose tissue and 25 mM 13C-labelled glucose was added to the perfusion fluid. An extraction procedure for separating lactic acid from glucose and glycerol in the microdialysate samples was developed. After derivatization, the 13C enrichment of the compounds was analysed by gas chromatography-mass spectrometry. Results. 13C-labelled lactate was detected in the first 15-min eluate fraction following that in which 13C-glucose had reached the microdialysis probe. In the different subjects, 22-35 % of adipose tissue lactate was produced locally. During exercise there was an increase in the lactate concentration and a decrease in 13C enrichment of lactate. Although lactate production in the adipose tissue increased during exercise, most adipose tissue lactate resulted from inflow. The administered 13C-labelled glucose also rapidly converted to 13C-glycerol. The 13C enrichment of glycerol was lower than that of lactate. During exercise the 13C enrichment of glycerol increased, indicating that newly synthesized depot fat was preferentially hydrolysed during physical activity. Conclusions. Metabolism of glucose to lactate and glycerol in subcutaneous adipose tissue is a rapid process that can be monitored in vivo by administration of stable isotope labelled glucose into the microdialysis probe. In adults at rest about one-fourth of adipose tissue lactate is produced locally.

  • 21. Hagberg, A.
    et al.
    Barbany, G.
    Landegren, U.
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Beta-globin mRNA increases rapidly during erythropoietin treatment2003In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 63, no 3, p. 239-245Article in journal (Refereed)
    Abstract [en]

    Recombinant human erythropoietin (r-HuEpo) has an important role in the treatment of anaemic patients. Because of the high cost of r-HuEpo treatment, an early indicator of whether a patient is responding to the therapy would be valuable. Although measurement of gene expression is a promising new tool, it has not yet been established in clinical practice. The response pattern of a possible new marker, beta-globin mRNA, is compared with reticulocyte count, levels of haemoglobin, transferrin receptor and ferritin after r-HuEpo treatment. Eight healthy volunteers were stimulated with erythropoietin three times a week for four weeks and compared with five untreated control subjects. Blood samples were collected before each erythropoietin injection. Quantitative measurement of beta-globin mRNA was performed by poly(A) selection onto a manifold plastic support, coated with oligo(dT). The mRNA was reverse transcribed, followed by quantitative analysis using PCR via the 5' nuclease assay. The individuals treated with rHuEpo showed a more distinct increase in beta-globin mRNA levels than all other laboratory measurements. Beta-globin mRNA levels are therefore promising as a marker for the response to treatment with Epo.

  • 22. Hansson, Lars-Olof
    et al.
    Grubb, Anders
    Lidén, Anders
    Flodin, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berggren, Annacarin
    Delanghe, Joris
    Stove, Veronique
    Luthe, Hilmar
    Rhode, Karl-Heinz
    Beck, Claus
    Domke, Ingrid
    Performance evaluation of a turbidimetric cystatin C assay on different high-throughput platforms2010In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 70, no 5, p. 347-353Article in journal (Refereed)
    Abstract [en]

    Objective. The goal with this study was to evaluate the analytical performance of a new cystatin C immunoassay (Tina-quant (R) a Cystatin C, Roche Diagnostics GmbH). The evaluation was carried out at four centers according to a standardized protocol. Material and methods. The Tina-quant (R) a Cystatin C is a latex particle-enhanced immunoturbidimetric assay. Roche cobas (R) 6000, MODULAR ANALYTICS SWA and COBAS INTEGRA (R) instruments were included in the study. Method comparison studies were carried out against two turbidimetric methods (Dako Cystatin C, Gentian Cystatin C), and one nephelometric method (Siemens N-Latex Cystatin C). Results. Linearity was proven throughout the measuring range from 0.4 to 8 mg/L. Within-run CVs ranged from 0.7-2.8%, and total CVs from 1.4-4.7 % (concentration range 0.6-3.9 mg/L). Comparable results were obtained with paired serum and Li-heparinate plasma samples. Good agreement was achieved in the comparisons between the Tina-quant (R) a Cystatin C assay and the other commercially available cystatin C assays, two different turbidimetric methods (slope range 0.88-1.04, intercept < 0.17 mg/L, r >= 0.993) and one nephelometric assay (slope range 0.90-1.05, intercept < 0.21 mg/L, r >= 0.986). Conclusions. The Tina-quant (R) a Cystatin C assay was shown to be precise and accurate with proven linearity over the measuring range. Good comparability was obtained with other commercially available assays for the determination of cystatin C. The Tina-quant (R) a Cystatin C assay is very well suited for clinical use on routine clinical chemistry analysers to detect renal dysfunction with a 24 h availability.

  • 23.
    Helliksson, Fredrik
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, CLINTEC, Stockholm, Sweden.;Cent Hosp Karlstad, Dept Anesthesiol & Intens Care, SE-65285 Karlstad, Sweden..
    Wernerman, Jan
    Karolinska Inst, Dept Clin Sci Intervent & Technol, CLINTEC, Stockholm, Sweden..
    Wiklund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala Univ, Dept Surg Sci, Uppsala, Sweden..
    Rosell, Jon
    Cent Hosp Karlstad, Dept Anesthesiol & Intens Care, SE-65285 Karlstad, Sweden..
    Karlsson, Mathias
    Karolinska Inst Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.;Cent Hosp Karlstad, Dept Clin Chem, Karlstad, Sweden..
    The combined use of three widely available biochemical markers as predictor of organ failure in critically ill patients2016In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 76, no 6, p. 479-485Article in journal (Refereed)
    Abstract [en]

    Background: We hypothesized that lactate dehydrogenase, LDH/albumin ratio in combination with or without magnesium (Mg2+) could predict organ failure in critically ill adult patients. The aim of this study was to describe a new risk index for organ failure or mortality in critically ill patients based on a combination of these routinely available biochemical plasma biomarkers.Methods: Patients18 years admitted to the intensive care unit (ICU) were screened. Albumin and LDH were analyzed at the time of admission to ICU (n=347). Organ failure assessed with Sequential Organ Failure Assessment' (SOFA) score was used, and 30-day mortality was recorded. The predictive value of the test was calculated using the areas under the receiving operating characteristic (ROC) curve.Results: The LDH/albumin ratio was higher in patients who developed organ failure as compared to those who did not (p<0.001). The areas under the ROC curve were 0.77 both for prediction of multiple organ failure and for 30-day mortality. In a subgroup of patients (n=183) admitted to ICU from the emergency department, the predictive values were 0.86 and 0.80, respectively.Conclusion: The LDH/albumin ratio at ICU admission was associated with the development of multiple organ failure and 30-day mortality in this prospective study. The clinical value of this biomarker as a predictor of organ failure in critically ill patients is yet to be defined.

  • 24.
    Hellman, Urban
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Lang, Kenneth
    Piteå Hosp, Dept Med, Piteå, Sweden.
    Ihse, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Jonasson, Jenni
    Umea Univ, Dept Med Biosci Med & Clin Genet, Lab Med, Clin Genet, Umea, Sweden.
    Olsson, Malin
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden;Umea Univ, Wallenberg Ctr Mol Med, Umea, Sweden.
    Lundgren, Hans-Erik
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Pilebro, Bjorn
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Westermark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.
    Wixner, Jonas
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Anan, Intissar
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden;Umea Univ, Wallenberg Ctr Mol Med, Umea, Sweden.
    Transthyretin Glu54Leu-an unknown mutation within the Swedish population associated with amyloid cardiomyopathy and a unique fibril type2019In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 79, no 6, p. 372-376Article in journal (Refereed)
    Abstract [en]

    For the first time, we report of a Swedish family of five individuals with a TTR Glu54Leu (p. Glu74Leu) mutation in the transthyretin gene. This mutation has been previously described a few times in the literature, but no phenotypic or clinical description has been done before. The most common mutation in the Swedish population is TTRVal30Met and is mostly found in the Northern part of Sweden. Interestingly, the TTRGlu54Leu mutation was found in the same endemic area. The main phenotype of the TTR Glu54Leu patients is severe cardiomyopathy, which resulted in heart transplantation for the index person. As previously seen for ATTR amyloidosis patients with mainly cardiomyopathy, the amyloid fibrils consisted of a mixture of full-length and fragmented TTR species. However, western blot analyses detected a previously unrecognized band, indicating that these patients may have a third, so far unrecognized, fibril composition type that is distinct from the usual type A band pattern.

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  • 25.
    Hurtig-Wennlöf, Anita
    et al.
    Örebro universitet, Institutionen för klinisk medicin.
    Yngve, Agneta
    Nilsson, Torbjörn K.
    Örebro universitet, Institutionen för klinisk medicin.
    Sjöström, Michael
    Serum lipids, glucose and insulin levels in healthy schoolchildren aged 9 and 15 years from Central Sweden: reference values in relation to biological, social and lifestyle factors2005In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 65, no 1, p. 65-76Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    There is a shortage of reference values for cardiovascular risk factors such as serum lipids, glucose and insulin related to biological, social and lifestyle factors for Swedish children and adolescents. Such values are needed for planning and evaluation of public health activities, and for clinical use.

    DESIGN AND METHODS:

    Data for this cross-sectional, school-based study were collected during a school year (September to May). A random sample of 1137 girls and boys aged 9 and 15 years from two locations in central Sweden participated in the study, and blood samples were taken from 969 of them.

    METHODS:

    Fasting serum blood samples were analysed for triglycerides, total cholesterol, high-density lipoprotein cholesterol, glucose and insulin. Physical examination included measurement of height, weight and pubertal status. Questionnaires provided family background data. Total physical activity was measured by accelerometer registration.

    RESULTS:

    Serum levels differed significantly between age and gender groups and were correlated to pubertal status. Neither genetic nor socio-economic background nor smoking status influenced the serum levels. Insulin levels were elevated in subjects with a body mass index in the highest decentile, compared with the levels in the rest of the subjects. The insulin levels were inversely associated with total physical activity, and physical activity varied with season.

    CONCLUSIONS:

    Pubertal status (biological age) should to be considered in the interpretation of serum values in schoolchildren rather than chronological age. The interpretation of insulin values should include both body mass index and physical activity level, and perhaps also season. Previously described regional differences in serum lipid levels in Swedish adults seem to be present also in children.

  • 26.
    Högberg, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Meurling, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Stenbäck, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Intestinal ischemia measured by intraluminal microdialysis2012In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, no 1, p. 59-66Article in journal (Refereed)
    Abstract [en]

    Objective.

    To evaluate the possibility of detecting intestinal ischemia by intraluminal microdialysis and comparing the ileum and colon.

    Methods.

    The studies were performed on male Sprague-Dawley rats. In the fi rst part of the study, microdialysis catheters were placed in the sigmoid part of the colon and in the subcutaneous adipose tissue. In the second part of the study, microdialysis catheters were placed in the lumen of the ileum and the colon. The infrarenal aorta was clamped proximal to the cranial mesenteric artery. Microdialysate levels of glucose, lactate, pyruvate and glycerol were measured. Intestinal specimens were removed at the end of the ischemic period for microscopic evaluation.

    Results.

    Intraluminal microdialysis could detect early signs of ischemic injury in the ileum, as well as in the colon, with a marked increase of lactate, lactate/pyruvate ratio and glycerol. The increased levels of intraluminal glycerol showed a positive correlation to prolonged ischemia and to higher degrees of intestinal damage.

    Conclusion.

    Intraluminal measurement of glycerol is a good marker for intestinal ischemia. Intraluminal microdialysis in the colon is easily accessible through the rectum, and ay prove to be a valuable clinical tool for diagnosing intestinal ischemia.

  • 27. Jonsson, A-S.
    et al.
    Flodin, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hansson, L-O.
    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, Clinical Chemistry.
    Estimated glomerular filtration rate (eGFRCystC) from serum cystatin C shows strong agreement with iohexol clearance in patients with low GFR2007In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 67, no 8, p. 801-809Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Estimation of glomerular filtration rate (eGFR) is essential in the diagnosis and monitoring of patients with kidney disease and for correct dosage of drugs eliminated from the circulation by the kidneys. Cystatin C has been shown in several studies to be superior to creatinine in estimating eGFR. However, there are few studies on the performance of cystatin C estimated eGFR (eGFRCystC) in patients with advanced kidney disease and low GFR. MATERIAL AND METHODS: We measured serum cystatin C, together with serum creatinine, during iohexol clearance in patients with iohexol clearance below 30 mL/min/1.73 m2. The cystatin C values were used to calculate eGFRCystC using the formula eGFR (mL/min/1.73 m2) = 79.901*(cystatin C value in mg/L)-1.4389. RESULTS: There was good correlation between eGFRCystC and iohexol clearance (r = 0.88) in patients with iohexol clearance.

  • 28.
    Jönelid, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research, County of Västmanland.
    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, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Screening of biomarkers for prediction of multisite artery disease in patients with recent myocardial infarction2021In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 81, no 5, p. 353-360Article in journal (Refereed)
    Abstract [en]

    A few studies have examined biomarkers in patients with myocardial infarction (MI) and peripheral artery disease (PAD), i.e. multisite artery disease (MSAD). The aim of the study was firstly, to associate biomarkers with the occurrence of PAD/MSAD and secondly, if those can, in addition to clinical characteristics, identify MI patients with MSAD.In two prospectively observational studies including unselected patients with recent MI, PAD was defined as an abnormal ankle-brachial index (ABI) score (1.4). The proximity extension assay (PEA) technique was used, simultaneously analyzing 92 biomarkers with association to cardiovascular disease. Biomarkers were tested for univariate associations with PAD. Random forest was used to identify biomarkers with a higher association to PAD. The additional discriminatory accuracy of adding biomarkers to clinical characteristics was analyzed by the c-statistics. Nine biomarkers were identified as significantly associated with MSAD/PAD in the primary patient cohort, analyzed early after the MI. In the prediction analysis, six biomarkers were identified associated with PAD. Three of these; Tumor necrosis factor receptor (TNFR-1), Tumor necrosis factor receptor 2 (TNFR-2) and Growth Differentiation Factor 15 (GDF-15) improved c-statistics when added to clinical characteristics from 0.683 (95% CI 0.610-0.756) to 0.715 (95% CI 0.645-0.784) in the primary patient cohort with a similar result, 0.729 (95% CI 0.687-0.770) to 0.752 (95% CI 0.771-0.792) in the secondary patient cohort. Biomarkers associated with inflammatory pathways are associated with MSAD in MI patients. Three biomarkers of 92; TNFR-1, TNFR-2 and GDF-15, in this exploratory added information in the prediction of MSAD and emphasis the importance of further studies.

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  • 29.
    Kafian, Sam
    et al.
    Karolinska Inst, Danderyd Hosp, Div Cardiovasc Med, Dept Clin Sci, Stockholm, Sweden.
    Wallen, Hakan
    Karolinska Inst, Danderyd Hosp, Div Cardiovasc Med, Dept Clin Sci, Stockholm, Sweden.
    Samad, Bassem A.
    Karolinska Inst, Danderyd Hosp, Div Cardiovasc Med, Dept Clin Sci, Stockholm, Sweden.
    Mobarrez, Fariborz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Microvesicles from patients with acute coronary syndrome enhance platelet aggregation2019In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 79, no 7, p. 507-512Article in journal (Refereed)
    Abstract [en]

    Microvesicles (MVs) released from leukocytes, platelets and endothelial cells are elevated in patients with acute coronary syndrome (ACS). In the present study, we assessed the potential pro-aggregatory properties of MVs obtained from ACS patients. Thus, we divided the patients into two groups based on clopidogrel-responsiveness, i.e. high on-treatment platelet reactivity (HPR; n = 16), and low or normal on-treatment platelet reactivity (non-HPR; n = 14), respectively. MVs from patients were obtained by high-speed centrifugation, and the pro-aggregatory effect of MVs added to fresh isolated platelets from healthy subjects were analyzed by 96-well microplate aggregometry. MVs from HPR patients significantly enhanced spontaneous platelet aggregation around two times more than MVs from non-HPR patients. The pro-aggregatory effect of three out of four MV phenotypes correlated to MV-concentrations as determined by flow cytometry. Furthermore, MVs from patients with diabetes mellitus (n = 9) had a stronger pro-aggregatory effect compared to MVs from those without diabetes (n = 21; p = .025 between groups). In conclusion, MVs from ACS patients with clopidogrel non-responsiveness enhance platelet aggregation, as do MVs from ACS patients with diabetes. Thus, MVs from patients with hyperreactive platelets boost platelet aggregation. Blocking MV-formation may reduce platelet hyperreactivity.

  • 30.
    Larsson, Anders
    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 Public Health and Caring Sciences.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Increased serum cyststin C is associated with increased mortality in elderly men2005In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 65, no 4, p. 301-305Article in journal (Refereed)
    Abstract [en]

    Renal dysfunction measured by serum creatinine is associated with increased cardiovascular morbidity and mortality. Plasma cystatin C has been shown in several studies to be superior to plasma creatinine for the estimation of glomerular filtration rate (GFR). The aim of the present study was to investigate the relationship between cystatin C and mortality in elderly men. Serum cystatin C was analyzed by nephelometry in a group of 77-year-old men (n=792) and correlated cystatin C levels with mortality during a follow-up period of 1-4 years. The cystatin C values were significantly correlated with overall mortality (p=0.013). Mortality was three times higher in the highest cystatin C quintile in relation to the lowest quintile.

  • 31.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Department of Medical Sciences, Clinical Chemistry, University Hospital, Uppsala, Sweden.
    Tydén, Jonas
    Department of Surgical and Perioperative Sciences, Anaesthesiology and Critical Care Medicine (Östersund), Umeå University, Umeå, Sweden..
    Johansson, Joakim
    Department of Surgical and Perioperative Sciences, Anaesthesiology and Critical Care Medicine (Östersund), Umeå University, Umeå, Sweden..
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bergquist, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Kultima, Kim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Department of Medical Sciences, Clinical Chemistry, University Hospital, Uppsala, Sweden.
    Mandic-Havelka, Aleksandra
    Department of Molecular Medicineand Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Calprotectin is superior to procalcitonin as a sepsis marker and predictor of 30-day mortality in intensive care patients2020In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 80, no 2, p. 156-161Article in journal (Refereed)
    Abstract [en]

    Sepsis is the most frequent cause of death in the intensive care unit (ICU). A rapid and correct diagnosis and initiation of therapy is crucial for improving patient outcomes. The aim of this study was to compare the performance of calprotectin with the more widely used sepsis biomarker procalcitonin (PCT) in ICU patients. The performance of calprotectin and PCT as sepsis and prognostic markers for 30-d mortality was compared in a prospective, observational study in an eight-bed ICU. We investigated concentrations of the biomarkers in plasma collected at admission from all ICU patients admitted during a year (2012-2013, n = 271) together with simplified acute physiology 3 scores (SAPS3) and sequential organ failure assessment (SOFA) scores. The receiver operating characteristic (ROC) analysis showed a higher area under the curve (AUC) value for calprotectin (0.79) than for PCT (0.49) when used as a sepsis marker. The calprotectin concentrations at admission were higher in non-survivors than in survivors at day 30. In our study, calprotectin was superior to PCT for distinguishing between ICU patients with sepsis and non-sepsis patients. Calprotectin also had higher predictive ability regarding 30-d mortality.

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  • 32.
    Larsson, Sara Marie
    et al.
    Hosp Halland, Dept Clin Chem, SE-43281 Varberg, Sweden;Lund Univ, Dept Clin Sci Lund, Pediat Neonatol, Lund, Sweden.
    Hillarp, Andreas
    Hosp Halland, Dept Clin Chem, SE-43281 Varberg, Sweden.
    Hellström-Westas, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Domellof, Magnus
    Umea Univ, Dept Clin Sci, Pediat, Umea, Sweden.
    Lundahl, Tom
    Hosp Halland, Dept Clin Chem, SE-43281 Varberg, Sweden.
    Andersson, Ola
    Lund Univ, Dept Clin Sci Lund, Pediat Neonatol, Lund, Sweden.
    When age really matters: ferritin reference intervals during infancy revisited2019In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 79, no 8, p. 590-594Article in journal (Refereed)
    Abstract [en]

    Infants are at risk for iron deficiency. Despite research advances, assessing iron stores during infancy remains a challenge to the clinician. Ferritin is the first-choice laboratory marker for measuring iron stores but it is today still unclear how to evaluate reference intervals among infants. We have studied Swedish infants (n = 456), born at term after normal pregnancies. Ferritin was measured at birth (umbilical cord sample), 48-72 h, 4 months and 12 months. Lower and upper reference interval limits were constructed as the 2.5th and 97.5th percentiles. By a large study population, we were able to use more stringent measures to avoid interference from the acute phase response than previous reports on ferritin reference intervals. When we used mathematical transformation we furthermore avoided potential information loss in precision and confirmed earlier reports of sex differences. At the lower reference interval limits there were small differences between sexes. For the higher limits, the differences were more pronounced in the older infant. At 0-3 d of age we observed a difference between the sexes of only 5% at the upper limits. The differences peaked at 12 months, where the boys' upper 97.5th percentile was 56% compared to girls.

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  • 33.
    Larsson, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bondesson, Ulf
    National Veterinary Institute (SVA), Department of Chemistry, Environment and Feed Hygiene, Uppsala, Sweden.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Intraosseous samples can be used for opioid measurements: An experimental study in the anaesthetized pig2013In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 73, no 2, p. 102-106Article in journal (Refereed)
    Abstract [en]

    Aim.

    The intraosseous route provides access to the systemic circulation in an emergency situation when other forms of vascular access are unavailable and there is an urgent need for fluid or drug therapy. The intraosseous access has also been used for collecting samples for laboratory testing. A question that may arise in an unconscious or severely exhausted patient is whether this condition is caused by an unknown drug. We aimed to evaluate whether intraosseous samples could be used to measure opioids and to study the accuracy and precision of such measurements.

    Methods.

    Five healthy, anaesthetized pigs were treated with a continuous morphine infusion as part of the anaesthesia procedure. Samples for morphine testing were collected hourly for 6 h from two tibial intraosseous cannulae and a central venous catheter.

    Results.

    The differences in morphine concentrations between the two tibial intraosseous cannulae were less than 10% in 32/33 times. The values were also relatively stable over time.

    Conclusion.

    Our findings suggest that intraosseous samples can be used for the analysis of opioids if an IV route is not available.

  • 34.
    Laurent, Torvald C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical and Physiological Chemistry.
    Lilja, K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical and Physiological Chemistry.
    Brunnberg, L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical and Physiological Chemistry.
    Engström-Laurent, A.
    Laurent, U. B.
    Lindqvist, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Murata, K.
    Ytterberg, D.
    Urinary excretion of hyaluronan in man1987In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 47, no 8, p. 793-799Article in journal (Refereed)
    Abstract [en]

    A specific assay for hyaluronan (hyaluronic acid) has been applied to the determination of the polysaccharide in urine. The excretion in 22 healthy subjects was 330 micrograms/24 h (SD 77). The excretion was correlated with body weight and was therefore somewhat higher in males than in females. The molecular weight of the main fraction of urinary hyaluronan was in the range of 4000 to 12,000 in accordance with the hypothesis that it originates from blood and arises by glomerular filtration. A small fraction was of higher molecular weight and could have been produced in the urinary tract. Hyaluronan in male and female urine displayed the same molecular weight distributions. Patients with rheumatoid arthritis and primary biliary cirrhosis showed a two-fold and three-fold increase, respectively, of hyaluronan in urine with concurrently high levels of the polysaccharide in serum. A patient with Werner's syndrome displayed a ten-fold increase of the polysaccharide in both serum and urine.

  • 35. Leion, Felicia
    et al.
    Hegbrant, Josefine
    den Bakker, Emil
    Jonsson, Magnus
    Abrahamson, Magnus
    Nyman, Ulf
    Björk, Jonas
    Lindström, Veronica
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Bökenkamp, Arend
    Grubb, Anders
    Estimating glomerular filtration rate (GFR) in children. The average between a cystatin C- and a creatinine-based equation improves estimation of GFR in both children and adults and enables diagnosing Shrunken Pore Syndrome.2017In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 77, no 5, p. 338-344Article in journal (Refereed)
    Abstract [en]

    Estimating glomerular filtration rate (GFR) in adults by using the average of values obtained by a cystatin C- (eGFRcystatin C) and a creatinine-based (eGFRcreatinine) equation shows at least the same diagnostic performance as GFR estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparison of eGFRcystatin C and eGFRcreatinine plays a pivotal role in the diagnosis of Shrunken Pore Syndrome, where low eGFRcystatin C compared to eGFRcreatinine has been associated with higher mortality in adults. The present study was undertaken to elucidate if this concept can also be applied in children. Using iohexol and inulin clearance as gold standard in 702 children, we studied the diagnostic performance of 10 creatinine-based, 5 cystatin C-based and 3 combined cystatin C-creatinine eGFR equations and compared them to the result of the average of 9 pairs of a eGFRcystatin C and a eGFRcreatinine estimate. While creatinine-based GFR estimations are unsuitable in children unless calibrated in a pediatric or mixed pediatric-adult population, cystatin C-based estimations in general performed well in children. The average of a suitable creatinine-based and a cystatin C-based equation generally displayed a better diagnostic performance than estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparing eGFRcystatin and eGFRcreatinine may help identify pediatric patients with Shrunken Pore Syndrome.

  • 36.
    Lindqvist, Ulla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Engström-Laurent, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical and Physiological Chemistry.
    Laurent, U.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical and Physiological Chemistry.
    Nyberg, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Björklund, U.
    Eriksson, H.
    Pettersson, R.
    Tengblad, A.
    The diurnal variation of serum hyaluronan in health and disease1988In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 48, no 8, p. 765-770Article in journal (Refereed)
    Abstract [en]

    The variation of the serum concentration of hyaluronan during the day and between days has been investigated. In a group of healthy volunteers, the mean hyaluronan level was very stable over time except for a moderate but significant elevation after rising from bed in the morning. Patients with rheumatoid arthritis showed markedly increased hyaluronan concentrations 0.5-2 h after leaving bed. Patients with primary biliary cirrhosis exhibited high and rather constant levels during the day. A reference group of hospitalized patients with other diseases did not show any diurnal variation. The best reproducibility in hyaluronan determinations is obtained if specimens are taken before the subjects rise from bed or a few hours later, i.e. after the morning elevation of serum hyaluronan has subsided. In rheumatoid arthritis valuable information can be obtained by repeated sampling during the morning hours.

  • 37.
    Lindqvist, Ulla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Groth, T.
    Lebel, L.
    Evaluation of various models of hyaluronan kinetics for assessment of liver function1997In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 57, no 1, p. 49-58Article in journal (Refereed)
    Abstract [en]

    The purpose of this study of various models of hyaluronan kinetics has been to find the most appropriate model for estimation of parameters which characterize liver endothelial cell function. Five theoretical models for serum hyaluronan distribution and elimination were evaluated by computer analysis of serial measurements of the mass concentration of hyaluronan in serum following an intravenous bolus dose. Three of the models were based on one-compartment distribution of intravenously injected hyaluronan. Model 1A, with assumed first-order elimination, was found to be compatible with measured data and had identifiable parameters. Model 1B, with assumed non-linear Michaelis-Menten kinetics, was also found to be compatible but the Michaelis-Menten constant (K(m)) was not well determined. In model 1C, with non-linear Michaelis-Menten elimination kinetics, K(m) was set to a fixed value of 340 micrograms l-1, and the remaining parameters were well determined and the model was found to be compatible. Two models with an assumed two-compartment distribution of intravenously injected hyaluronan, were not acceptable due to unidentified parameters not discriminating between patients and healthy persons. In conclusion, model 1C, with one-compartment distribution and non-linear Michaelis-Menten kinetics, best fulfilled the criteria of validity and was accepted for further evaluation of clinical materials.

  • 38.
    Lindqvist, Ulla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Laurent, Torvald C.
    Serum hyaluronan and aminoterminal propeptide of type III procollagen: variation with age1992In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 52, no 7, p. 613-621Article in journal (Refereed)
    Abstract [en]

    The serum levels of hyaluronan and the aminoterminal propeptide of Type III procollagen (PIIINP) were compared in 585 healthy individuals as a function of age. Newborn children displayed high hyaluronan (695 +/- 634 micrograms l-1, mean +/- SD) and PIIINP (295 +/- 152 micrograms l-1) values. The values were not correlated to the gestational week in which the children were born or to the birth weight but there was a significant correlation (p < 0.05) between the hyaluronan and PIIINP levels. During the first year the levels dropped and in childhood (1-16 years of age) both hyaluronan and PIIINP levels were fairly constant at 27 +/- 16 and 22 +/- 8.4 micrograms l-1, respectively. The PIIINP level showed a marked drop in adults compared to children. The drop continued to about 50 years of age (6.5 +/- 2.2 micrograms l-1) and then there was a slight increase in elderly people. The hyaluronan showed a continued increase with age from the level at 16 years of 29 +/- 17 micrograms l-1 to a mean value of 177 +/- 133 micrograms l-1 in people over 75 years. There was no increase in serum hyaluronan in women during pregnancy but the PIINP level increased in the later part of the gestational period. There was no correlation between the serum values of hyaluronan and PIIINP when compared throughout the life span which indicates that the blood levels of the two markers are regulated by independent factors.

  • 39. Luttropp, Karin
    et al.
    Nordfors, Louise
    Ekstrom, Tomas J.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Physical activity is associated with decreased global DNA methylation in Swedish older individuals2013In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 73, no 2, p. 184-185Article in journal (Refereed)
  • 40.
    Malmberg, P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    Time Course of Enzyme Escape via Heart Lymph Following Myocardial Infarction in the Dog1972In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 30, no 4, p. 405-409Article in journal (Refereed)
    Abstract [en]

    The activities of the four myocardial enzymes aspartate aminotransferase (also known as GOT), alanine aminotransferase (GPT), lactate dehydrogenase (LDH), and creatine kinase (CPK) were measured in dog heart lymph following myocardial infarction. The activity of all enzymes increased to very high values, and the time course of activity changes was identical for all enzymes. This is interpreted as reflecting a simultaneous escape of these enzymes from damaged myocardial cells.

  • 41.
    Michaëlsson, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    Evaluation of a Method for Determination of Bilirubin in Serum Using Direct Spectrophotometry1972In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 30, no 4, p. 387-390Article in journal (Refereed)
    Abstract [en]

    An evaluation of bilirubin spectrophotometry with the AO bilirubinometer as compared to an accepted diazo coupling method is presented. The bilirubinometer is a simple and accurate method suitable for monitoring total bilirubin in neonatal jaundice. The method may serve as a good complement to diazo coupling procedures in icteric newborns.

  • 42.
    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.
    Long-term effects of an education programme on the optimal use of clinical chemistry testing in primary health care2009In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 69, no 4, p. 481-486Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to investigate whether continuing education on the optimal use of clinical chemistry testing in primary health care has had any long‐term effects on the test‐ordering behaviour of the participating physicians. Methods: The effects were monitored using 12 laboratory test ratios. Twenty‐three general practitioners at 16 primary health‐care centres in the county of Uppsala, Sweden, participated. A sign test was used to evaluate how individual physicians' test‐ordering patterns have changed during the 8 years since implementation of the educational programme. Maintained or improved ratios were interpreted as a sustained effect on the primary health‐care physician's test‐ordering habits. Results: Eleven out of 12 of the investigated ratios were the same or improved since the time of the short‐term follow‐up 6 months after the education. Conclusion: A short continuation course on optimal use of clinical chemistry assays can achieve permanent changes in the test‐ordering patterns of primary health‐care physicians. These findings highlight education as one possible means towards achieving cost‐efficiency and quality in test‐ordering.

  • 43.
    Mindemark, Mirja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Costly regional variations in primary health care test utilization in Sweden2010In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 70, no 3, p. 164-170Article in journal (Refereed)
    Abstract [en]

    Objective: Laboratory tests are used increasingly in primary health care and they are thus associated with rapidly growing costs. Variations in clinical practice, an important determinant of expenditure for laboratory tests, could further increase the financial burden. The study's threefold objective was to determine the presence and extent of regional variations in test ordering between eight counties in Sweden, to investigate the influence on these variations by factors earlier described in the literature as explanatory, and to calculate the achievable savings that could be realized through optimized test ordering. Design: A retrospective study using test request data. Setting: A total of 223 primary health care centers in eight counties in Sweden. Main outcome measures: Thirteen ratios of commonly used laboratory tests, demographic data and the number of ordered tests per 1000 inhabitants served as the basis of comparison. The total savings per 100,000 inhabitants that could be achieved through optimized test ordering was estimated. Results: Large variations were found between all studied counties for all investigated ratios. However, none of the demographic variables investigated seemed to be able to explain the full extent of the variations. The range of achievable yearly savings per 100,000 inhabitants was euro14,000-euro185,000. Conclusion: The inter-county variations in Sweden are large and the savings associated with optimized test utilization are substantial. The investigated factors previously described as explaining the variations in test ordering only seem to explain a small part of the variation, and the variations are likely influenced by regional habits and traditions.

  • 44.
    Nälsén, C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Öhrvall, M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Kamal-Eldin, A
    Vessby, B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Plasma antioxidant capacity among middle-aged men: the contribution of uric acid2006In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 66, no 3, p. 239-248Article in journal (Refereed)
    Abstract [en]

    Objective. Although assays of plasma antioxidant capacity encompass interactions between various antioxidants, uric acid concentration can exert a predominant effect on results. Therefore, individual differences in uric acid concentration may explain a many of the differences in antioxidant capacity. The objective of this study was to measure the antioxidant capacity of plasma samples with and without uric acid in order to provide more information about how the concept of antioxidant capacity could be applied. Material and methods. Antioxidant capacity was measured using an enhanced chemiluminescence assay, and uric acid was removed from the samples using uricase. Results. Antioxidant capacity was positively correlated with uric acid concentration, body mass index, waist circumference, abdominal sagittal diameter and the concentrations of insulin and triglycerides. These correlations were not evident when uric acid was eliminated from the sample, but antioxidant capacity was correlated with lipid concentration; this may partly reflect tocopherols that are transported by lipid molecules. Conclusions. The significance of the contribution of uric acid to the antioxidant capacity could differ according to the type of study. Antioxidant capacity measurements in cross‐sectional studies may be presented both with and without the contribution of uric acid, because the absence of such data complicates interpretation of results when different populations are compared.

  • 45.
    Penno, Hendrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nilsson, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Brändström, Helena
    Winqvist, Ola
    Ljunggren, Osten
    Expression of RANK-ligand in prostate cancer cell lines2009In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 69, no 1, p. 151-155Article in journal (Refereed)
    Abstract [en]

    The molecular mediators of bone remodelling, receptor activator of nuclear factor-kappaB ligand (RANKL), receptor activator of nuclear factor-kappaB (RANK) and osteoprotegerine (OPG), are believed to be involved in the cellular mechanisms by which tumours metastasize to bone. RANKL is a potent stimulator of osteoclastic bone resorption and is expressed in a variety of tumour cells. We have investigated if the membrane bound form of RANKL is expressed in prostate cancer cell lines, and whether this expression might be regulated by the presence of human osteoblasts. Three prostate cancer cell lines were co-cultured with human osteoblast-like cells (hOB) and RANKL expression on cell surface was measured by FACS. We found basal expression of RANKL on the cell surface, and in co-culture with hOBs the number of cells expressing RANKL was increased between 2.5 and 4 times. These data suggest a signalling mechanism between bone cells and prostate cancer cells that might increase bone resorption and thereby promote bone metastases.

  • 46.
    Peterson, Christer G. B.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Hansson, Tony
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Lidén, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Haellgren, Roger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Evaluation of biomarkers for ulcerative colitis comparing two sampling methods: fecal markers reflect colorectal inflammation both macroscopically and on a cellular level2016In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 76, no 5, p. 393-401Article in journal (Refereed)
    Abstract [en]

    Objective: Simple, objective and inexpensive tools for the assessment of mucosal inflammation in ulcerative colitis (UC) are highly desirable. The aim of this study was to evaluate a broad spectrum of activity markers comparing two sampling methods: fecal samples and the mucosal patch technique.

    Methods: Twenty patients with active UC and 14 healthy controls were characterized by means of clinical indices and endoscopy together with histology and immunohistochemistry on colorectal sections. Neutrophil myeloperoxidase (MPO), calprotectin, eosinophil cationic protein (ECP), eosinophil protein X (EPX/EDN) and IL-1 were analyzed in fecal samples and rectal fluid collected by the patch technique. Nitric oxide (NO) was analyzed in rectal gas samples. Expression of activity markers on colorectal neutrophils and eosinophils were analyzed by flow cytometry.

    Results: All fecal and patch markers were increased in UC patients compared with healthy controls. Fecal markers and the level of neutrophil activation correlated to disease activity, whereas patch markers did not. The best markers in terms of discriminative power were fecal MPO and IL-1. Fecal marker levels were related to sigmoidal histology scores and to neutrophil number and activation. Patch markers were related to rectal inflammation only.

    Conclusions: The levels of inflammation markers in feces and patch fluid distinctly reflected active inflammation in UC. The degree of disease activity was however best assessed by fecal markers, particularly MPO and IL-1. Fecal markers reflect colorectal inflammation both macroscopically and on a cellular level, and may be useful for the evaluation of subclinical inflammation. The applicability of patch markers is restricted to rectal inflammation.

  • 47.
    Peterson, Christer G. B.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Sangfelt, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wagner, M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hansson, Tony
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Lettesjö, H.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fecal levels of leukocyte markers reflect disease activity in patients with ulcerative colitis2007In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 67, no 8, p. 810-820Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    A prominent feature of inflammatory bowel disease (IBD) is the presence of inflammatory cells in the gut mucosa, and which contribute to the ongoing inflammatory process. The aim of the study was to evaluate fecal neutrophil, eosinophil, mast cell and macrophage markers in the assessment of disease activity in patients with ulcerative colitis (UC).

    METHODS:

    Twenty-eight patients with active UC; 4 with proctitis, 16 with left-side colitis and 8 with total colitis, were included in the study. Patient history, endoscopy and histopathology were examined and fecal and serum samples were evaluated at inclusion and after 4 and 8 weeks of treatment. Fecal samples were analysed for myeloperoxidase (MPO), eosinophil protein X (EPX), mast cell tryptase, IL-1beta and TNF-alpha using immunoassays. Blood samples were analysed for MPO, EPX, C-reactive protein, orosomucoid and leucocyte counts.

    RESULTS:

    Fecal MPO and IL-1beta levels were elevated in all patients at inclusion despite different disease extensions. Striking reductions in fecal levels of MPO, EPX, tryptase and IL-1beta were observed after 4 weeks of treatment in 20/28 patients with complete remission after 8 weeks. No further reductions were seen in 20/27 patients at 8 weeks. Endoscopic score correlated to IL-1beta at all visits (p<0.01), to MPO at visits 2 and 3 (p<0.05, p<0.001), EPX at visit 2 (p<0.05) and tryptase at visit 3 (p<0.01). Levels of fecal markers also related to histological indices of the disease.

    CONCLUSIONS:

    Measurements of fecal MPO, EPX and IL-1beta could be objective complements to endoscopical and histopathological evaluations in the daily care of patients with UC.

  • 48.
    Peura, Sari
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Swedish Univ Agr Sci, Dept Forest Mycol & Plant Pathol, Sci Life Labs, Almas Alle 5, S-75007 Uppsala, Sweden.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Almqvist, Catarina
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden; Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Unit Paediat Allergy & Pulmonol, Stockholm, Sweden.
    Andolf, Ellika
    Karolinska Inst, Danderyd Hosp, Div Obstet & Gynaecol, Dept Clin Sci, Stockholm, Sweden.
    Hedman, Anna
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Pershagen, Göran
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Helmersson-Karlqvist, Johanna
    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.
    Normal values for calprotectin in stool samples of infants from the population-based longitudinal born into life study2018In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 78, no 1-2, p. 120-124Article in journal (Refereed)
    Abstract [en]

    Faecal calprotectin is a protein used as a diagnostic marker for inflammatory bowel diseases. We determined upper limits for normal calprotectin values for neonatal, 6, 12 and 24 months old children using a turbidimetric immunoassay in a cohort of Swedish children. The advantage of the method is that opposite to previously used enzyme-linked immunosorbent assay (ELISA) method, it enables measuring single samples, and thus, shortens the analysis time significantly. There were 72 samples (41.7% female) collected neonatally, 63 samples (34.9% female) at 6 months, 60 samples (40.0% female) at 12 months and 51 samples (43.1% female) at 24 months. The upper limits for normal values were 233, 615, 136 and 57 µg mg-1 for infants aged 0, 6, 12 and 24 months, respectively.

  • 49. Raittinen, Lassi P.
    et al.
    Berg, Leena
    Nunes, Silvia
    Ahonen, Heikki
    Parviainen, Ilkka
    Laranne, Jussi
    Tenhunen, Jyrki J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sympathetic innervation does not contribute to glycerol release in ischemic flaps2012In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, no 5, p. 420-426Article in journal (Refereed)
    Abstract [en]

    Background. Extracellular glycerol as detected by microdialysis has been used as a surrogate marker for (ischemic) tissue damage and cellular membrane breakdown in the monitoring of free microvascular musculocutaneous flaps. One confounding factor for glycerol as a marker of ischemic cell damage is the effect of lipolysis and associated glycerol release as induced by sympathetic signalling alone. We hypothesized that extracellular glycerol concentrations in a microvascular flap with sympathetic innervation would be confounded by intact innervation per se as compared to denervated flap. Clinical relevance is related to the use of both free and pedicled flaps in reconstructive surgery. We tested the hypothesis in an experimental model of microvascular musculocutaneal flaps.

    Methods. Twelve pigs were anesthetized and mechanically ventilated. Two identical rectus abdominis musculocutaneal flaps were raised for the investigation. In the A-flaps the adventitia of the artery and accompanying innervation was carefully stripped, while in the B-flaps it was left untouched. Flap ischemia was induced by clamping both vessels for 60 minutes. The ischemia was confirmed by measuring tissue oxygen pressure, while extracellular lactate to pyruvate ratio indicated the accompanying anaerobic metabolism locally.

    Results. Intramuscular and sub-cutaneal extracellular glycerol concentrations were measured by microdialysate analyzer. Contrary to our hypothesis, glycerol concentrations were comparable between the two ischemia groups at 60 minutes (p = 0.089, T-test).

    Conclusions. In this experimental model of vascular flap ischemia, intact innervation of the flap did not confound ischemia detection by glycerol. Extrapolation of the results to clinical setting warrants further studies.

  • 50.
    Rautelin, Hilpi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
    Tervahartiala, Taina
    Lauhio, Anneli
    Sorsa, Timo
    Kolho, Kaija-Leena
    Assessment of systemic matrix metalloproteinase and their regulator response in children with Helicobacter pylori gastritis2010In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 70, no 7, p. 492-496Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Helicobacter pylori causes gastritis and is the most important risk factor of peptic ulcer disease and gastric cancer. In chronic adulthood H. pylori infection some matrix metalloproteinases (MMPs), which are proteolytic metalloendopeptidases regulated by tissue inhibitors of metalloproteinases (TIMPs), are upregulated. Our aim was to determine circulating levels of MMPs and their regulators TIMP-1, human neutrophil elastase (HNE) and myeloperoxidase (MPO) in childhood H. pylori infection.

    DESIGN AND METHODS: Twenty-six H. pylori positive and 34 H. pylori negative children whose H. pylori status was verified by histological examination of gastric biopsies were included. Serum samples were analysed by enzyme-linked immunosorbent assay.

    RESULTS: Significantly decreased serum levels of TIMP-1 were detected in H. pylori-infected children (median, 97.50 ng/mL) as compared to H. pylori-negative children (median, 118.5 ng/mL, p = 0.003). However, there were no significant differences in serum levels of MMP-2, -7, -8, -9, and their regulators HNE and MPO between H. pylori-positive and -negative children.

    CONCLUSIONS: Differing from the recent findings in adulthood H. pylori infection, only circulating TIMP-1 levels were significantly different between H. pylori-positive and -negative children. Whether this reflects the first sign of a proteolytic cascade later leading to increased levels of MMPs remains to be shown.

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