Change search
Refine search result
123456 101 - 150 of 295
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 101.
    Helmersson, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Alfthan, Georg
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Serum selenium predicts levels of F2-isoprostanes and prostaglandin F2alpha in a 27 year follow-up study of Swedish men2005In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 39, no 7, p. 763-770Article in journal (Refereed)
    Abstract [en]

    Low concentrations of selenium (Se) predict mortality and cardiovascular diseases in some populations. The effect of Se on in vivo indicators of oxidative stress and inflammation, two important features of atherosclerosis, in human populations is largely unexplored. This study investigated the longitudinal association between serum selenium (s-Se) and a golden standard indicator of oxidative stress in vivo (8-iso-prostaglandin F2, a major F2-isoprostane), an indicator of cyclooxygenase (COX)-mediated inflammation (prostaglandin F2), high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6) and serum amyloid A protein (SAA) in a follow-up study of 27 years. The s-Se was measured in 615 Swedish men at 50 years of age in a health investigation. The status of oxidative stress and inflammation was evaluated in a re-investigation 27 years later by quantification of urinary 8-iso-PGF2 and 15-keto-dihydro- PGF2 (a major metabolite of PGF2) and serum hsCRP, SAA and IL-6. Men in the highest quartile of s-Se at age 50 had decreased levels of 8-iso-PGF2 compared to all lower quartiles   and decreased levels of PGF2 compared to all lower quartiles   at follow-up. These associations were independent of BMI, diabetes, hyperlipidemia, hypertension, smoking, -tocopherol and β-carotene at baseline. The s-Se was not associated with hsCRP, SAA or IL-6 at follow-up. In conclusion, high concentrations of s-Se predict reduced levels of oxidative stress and subclinical COX-mediated (but not cytokine-mediated) inflammation in a male population. The associations between Se, oxidative stress and inflammation, respectively, might be related to the proposed cardiovascular protective property of Se.

  • 102.
    Helmersson-Karlqvist, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Miles, Elizabeth A
    Vlachava, Maria
    Kremmyda, Lefkothea-Stella
    Noakes, Paul S
    Diaper, Norma D
    Godfrey, Keith M
    Calder, Philip C
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Enhanced prostaglandin F(2α) formation in human pregnancy and the effect of increased oily fish intake: Results from the Salmon in Pregnancy Study2012In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 86, no 1-2, p. 35-38Article in journal (Refereed)
    Abstract [en]

    Oily fish intake during pregnancy may reduce the risk of allergic diseases in infancy possibly by shifts in the fatty acid balance and subsequent altered prostaglandin (PG) formation. This intervention is the first study to evaluate if increased oily fish intake affects in vivo PGF(2α) formation during pregnancy. British pregnant women were randomised to two portions of farmed salmon weekly (n=47), or maintenance of their normal diet low in fish (n=41), from pregnancy week 20 until parturition. The concentrations of eicosapentaenoic and docosahexaenoic acids in plasma phosphatidylcholine (PC) were higher and the concentration of arachidonic acid in plasma PC was lower in the salmon group than the control group at weeks 34 and 38 of pregnancy. PGF(2α) formation was evaluated by urinary measurement of 15-keto-dihydro-PGF(2α), a major PGF(2α) metabolite, at 20, 34 and 38 weeks. In both the salmon and control groups urinary 15-keto-dihydro-PGF(2α) concentrations increased significantly during pregnancy, which may be of physiological importance. Oily fish intervention altered fatty acid concentrations but did not affect urinary 15-keto-dihydro-PGF(2α) concentrations in pregnant women.

  • 103.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Granger, Christopher B
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Biomarkers in atrial fibrillation: a clinical review2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 20, p. 1475-1480Article in journal (Refereed)
    Abstract [en]

    Assessment of atrial fibrillation (AF)-associated stroke risk is at present mainly based on clinical risk scores such as CHADS2 and CHA2DS2-VASc, although these scores provide only modest discrimination of risk for individual patients. Biomarkers derived from the blood may help refine risk assessment in AF for stroke outcomes and for mortality. Recent studies of biomarkers in AF have shown that they can substantially improve risk stratification. Cardiac biomarkers, such as troponin and natriuretic peptides, significantly improve risk stratification in addition to current clinical risk stratification models. Similar findings have recently been described for markers of renal function, coagulation, and inflammation in AF populations based on large randomized prospective clinical trials or large community-based cohorts. These new findings may enable development of novel tools to improve clinical risk assessment in AF. Biomarkers in AF may also improve the understanding of the pathophysiology of AF further as well as potentially elucidate novel treatment targets. This review will highlight novel associations of biomarkers and outcomes in AF as well as recent progress in the use of biomarkers for risk stratification.

  • 104.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wallentin, Lars
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ezekowitz, Justin
    Gersh, Bernard J
    Hanna, Michael
    Hohnloser, Stefan
    Horowitz, John
    Huber, Kurt
    Hylek, Elaine M
    Lopes, Renato D
    McMurray, John J V
    Granger, Christopher B
    N-Terminal Pro-B-Type Natriuretic Peptide for Risk Assessment in Patients With Atrial Fibrillation: Insights from the ARISTOTLE trial2013In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 61, no 22, p. 2274-2284Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    This study sought to assess the prognostic value of N-terminal pro–B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF) enrolled in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial, and the treatment effect of apixaban according to NT-proBNP levels.

    BACKGROUND:

    Natriuretic peptides are associated with mortality and cardiovascular events in several cardiac diseases.

    METHODS:

    In the ARISTOTLE trial, 18,201 patients with AF were randomized to apixaban or warfarin. Plasma samples at randomization were available from 14,892 patients. The association between NT-proBNP concentrations and clinical outcomes was evaluated using Cox proportional hazard models, after adjusting for established cardiovascular risk factors.

    RESULTS:

    Quartiles of NT-proBNP were Q1:≤363, Q2:364-713, Q3:714-1250 and Q4:>1250 ng/L. During 1.8 years the annual rates of stroke or systemic embolism ranged from 0.74% in the bottom NT-proBNP quartile to 2.21% in the top quartile, adjusted hazard ratio (HR) 2.35 (95% CI 1.62-3.40, p<0.0001. Annual rates of cardiac death ranged from 0.86% in Q1 to 4.14% in Q4, adjusted HR 2.50 (1.81-3.45), p<0.0001. Adding NT-proBNP levels to the CHA2DS2VASc score improved C-statistics from 0.62 to 0.65 (p=0.0009) for stroke or systemic embolism and from 0.59 to 0.69 for cardiac death (p<0.0001). Apixaban reduced stroke, mortality, and bleeding regardless of the NT-proBNP level.

    CONCLUSIONS:

    NT-proBNP levels are often elevated in AF and independently associated with an increased risk of stroke and mortality. NT-proBNP improves risk stratification beyond the CHA2DS2VASc score and might be a novel tool for improved stroke prediction in AF. The efficacy of apixaban compared with warfarin is independent of the NT-proBNP level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE].

  • 105. Hjortshoj, Sören
    et al.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Ravkilde, Jan
    Clinical performance of a new point-of-care cardiac troponin I assay compared to three laboratory troponin assays2011In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 412, no 3-4, p. 370-375Article in journal (Refereed)
    Abstract [en]

    Background: Studies of cardiac markers in diagnosing acute myocardial infarction (AMI) have mostly been performed using central laboratory platforms. The AQT90 FLEX TnI (troponin I) assay is designed for quantitative point of care testing (POCT). This study evaluated clinical performance in diagnosing AMI of the AQT90 FLEX TnI POCT assay compared with central laboratory troponin assays. Methods: The study included 458 chest pain patients. Blood samples were obtained on admission and after 69 h. Blood was analyzed using the following assays: AQT90 FLEX TnI, Access AccuTnI, Abbott AxSYM ADV. Roche cTnT, Roche CKMBmass. Patients were diagnosed with AMI according to the new universal definition of AMI. Results: The performance of the AQT90 FLEX TnI assay on admission was equivalent to the Abbott AxSYM ADV cTnI but inferior to the AccuTnI. After 6-9 h both laboratory based assays were superior. The AQT90 FLEX TnI had a negative predictive value (NPV) of 90 and 96% (admission: 6-9 h). No statistical differences were seen in receiver operating characteristics analysis. Conclusions: The AQT90 FLEX TnI POCT assay was marginally inferior to the two laboratory based assays of cTnI in diagnosing AMI. A high (NPV) may make this assay suitable as a rule out marker.

  • 106.
    Holdstock, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eden Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öhrvall, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Karlsson, Anders
    CRP reduction following gastric bypass surgery is most pronounced in insulin-sensitive subjects2005In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 29, no 10, p. 1275-1280Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Obesity is frequently associated with insulin resistance, dyslipidemia, hypertension and an increased risk ofcardiovascular disease, reflected in elevated markers of inflammation, in particular C-reactive protein (CRP). To what extent theinsulin resistance or the obesity per se contributes to increased CRP levels is unclear. In morbidly obese patients, gastric bypasssurgery causes marked changes in body weight and improves metabolism, thereby providing informative material for studies onthe regulation of inflammatory markers.DESIGN: Prospective, surgical intervention study of inflammatory markers in morbidly obese subjects.

    SUBJECTS: In total, 66 obese subjects with mean age 39 y and mean body mass index (BMI) 45 kg/m2 were studied prior to and6 and 12 months following Roux-en-Y gastric bypass (RYGBP) surgery.

    MEASUREMENTS: Serum concentrations of high sensitivity CRP, serum amyloid A (SAA) and interleukin-6 (IL-6), as well asmarkers of glucose and lipid metabolism.

    RESULTS: Prior to surgery, CRP levels were elevated compared to the reference range of healthy, normal-weight subjects. CRPcorrelated with insulin sensitivity, as reflected by the homeostatic model assessment (HOMA) index, but not BMI, whencorrected for age and gender. Surgery reduced BMI from 45 to 31 kg/m2 and lowered CRP, SAA and IL-6 levels by 82, 57 and50%, respectively, at 12 months. The reduction in CRP was inversely related to HOMA at baseline independently of the changein body weight (r=-0.36, P=0.005). At 12 months, 140 and 40% reductions in CRP were seen in subjects with HOMA o 4(insulin sensitive) and HOMA49 (insulin resistant) despite similar reductions in BMI. Reductions in SAA and IL-6 tended toparallel the changes in CRP, but were less informative.

    CONCLUSION: In morbidly obese subjects, gastric bypass surgery lowers energy intake, reduces inflammatory markers andimproves insulin sensitivity. Despite a marked reduction in body weight, only a small effect on CRP levels was seen in insulinresistantpatients, indicating that flexibility of circulating CRP levels is primarily dependent upon insulin sensitivity rather thanenergy supply.

  • 107.
    James, Stefan K.
    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.
    Timmer, Jorik R.
    Ottervanger, Jan Paul
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Armstrong, Paul
    Califf, Robert
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Simoons, Maarten L.
    Usefulness of biomarkers for predicting long-term mortality in patients with diabetes mellitus and non-ST-elevation acute coronary syndromes (A GUSTO IV substudy)2006In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 97, no 2, p. 167-172Article in journal (Refereed)
    Abstract [en]

    The present study evaluated whether biomarkers of ischemia, inflammation, myocardial damage, and dysfunction are equally useful in patients who have diabetes mellitus (DM) for prediction of cardiac events in non-ST-elevation acute coronary syndrome (ACS). DM was present in 1,677 of 7,800 patients (21.5%) who had non-ST-elevation ACS and were included in the Fourth Global Utilization of Strategies To Open Occluded Arteries (GUSTO IV) trial. Creatinine, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), troponin T, C-reactive protein, and interleukin-6 were analyzed in serum samples that were obtained at a median of 9.5 hours from symptom onset. One-year mortality rates were 13.5% among patients who had DM (n = 227) and 6.9% among those who did not (n = 418, p < 0.001). The median level of NT-pro-BNP was 2 times as high in patients who had DM, whereas troponin T levels did not differ by DM status. Mortality increased with ascending quartiles of NT-pro-BNP, with 1-year mortality rates of 3.9% (n = 11) in the bottom quartile and 29% (n = 103) in the top quartile. In multivariable analyses, factors that were predictive of 1-year mortality in patients who did not have DM were also significant for those who did. Presence of ST depression > 0.5 mm had the highest odds ratio of 2.3 (95% confidence interval 1.2 to 4.6). NT-pro-BNP levels > 669 ng/L (odds ratio 2.0, 95% confidence interval 1.1 to 3.6) and interleukin-6 levels > 10 ng/L (odds ratio 1.9, 95% confidence interval 1.2 to 3.0) were significant biomarker predictors. In conclusion, DM confers a high long-term mortality in non-ST-elevation ACS. Despite a larger proportion of ST depression and increased levels of NT-pro-BNP and interleukin-6 at admission, these factors provide independent prognostic information that may improve risk stratification and guidance of treatment.

  • 108.
    James, Stefan K
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Siegbahn, Agneta
    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.
    An acute inflammatory reaction induced by myocardial damage is superimposed on a chronic inflammation in unstable coronary artery disease2005In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 149, no 4, p. 619-626Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Inflammation plays an important role in unstable coronary artery disease (CAD). We assessed the kinetics of inflammatory markers from symptom onset in patients with unstable CAD and their relation to myocardial damage.

    METHODS:

    Serial measurements of inflammatory mediators were performed in consecutive patients with unstable CAD enrolled at selected sites in the FRISC II (n = 558) and the GUSTO IV (n = 404) trials. The time from symptom onset was calculated for every serum sample (total 4400 samples).

    RESULTS:

    Median levels of interleukin 6 and C-reactive protein reached their peaks at 36 to 42 hours and at 48 to 54 hours, respectively, from symptom onset and returned to early postsymptom levels within 6 weeks. The early increase occurred almost exclusively in patients with baseline troponin T elevation (>0.01 microg/L). In contrast, median levels of fibrinogen increased continuously up to 120 hours after symptom onset, independently of myocardial damage. At 6 months, fibrinogen levels were still higher than in the early phase after symptom onset. The median levels of interleukin 6, C-reactive protein, and fibrinogen were still higher at 6 months than in healthy controls matched for age and sex to a population with unstable CAD.

    CONCLUSIONS:

    An early acute inflammatory reaction induced by myocardial damage seems to be superimposed on a chronic inflammatory condition, both of which might influence long-term outcome in unstable CAD.

  • 109.
    James, Stefan K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Armstrong, P
    Barnathan, E
    Califf, R
    Lindahl, B
    Simoons, M
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Activation of the inflammation, coagulation, and fibrinolysis systems, without influence of abciximab infusion in patients with non-ST–elevation acute coronary syndromes treated with dalteparin: a GUSTO IV substudy2004In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 147, no 2, p. 267-274Article in journal (Refereed)
    Abstract [en]

    Background

    In acute coronary syndromes, the inflammation and the coagulation systems are activated, implying an impaired outcome. In addition to platelet inhibition, recent evidence suggests that the glycoprotein IIb/IIIa receptor inhibitor abciximab attenuates inflammation and coagulation activity.

    Methods

    The Swedish Global Utilization of Strategies To open Occluded arteries-IV (GUSTO-IV) substudy included 404 patients with non-ST–elevation acute coronary syndromes. In addition to aspirin and dalteparin, all patients were randomized to receive abciximab infusion for 24 hours or 48 hours or corresponding placebo without early coronary revascularization. Plasma samples were obtained at baseline and 24, 48, and 72 hours.

    Results

    The median levels of the coagulation markers thrombin/antithrombin complex and soluble fibrin increased significantly from 3.1 to 3.7 ug/L (baseline to peak; P <.001) and from 20 to 23 nmol/L (P <.001), respectively. The fibrinolysis marker, tissue plasminogen-activator, also increased its median levels, from 11.7 to 17.5 ug/L (P <.001), whereas the median level of plasminogen-activator-inhibitor was unchanged. The inflammatory markers interleukin-6, C-reactive protein, and fibrinogen also increased their median levels (5.4–7.8 ng/L, P <.001; 4.4–8.7 mg/L, P <.001; 3.3–3.9 g/L, P <.001). However, there were no differences in median levels or in changes of median levels of any marker at any point between the placebo group and any of the abciximab groups.

    Conclusions

    In non-ST–elevation acute coronary syndrome, there was a simultaneous activation of the inflammation, coagulation, and fibrinolysis systems, despite aspirin and dalteparin treatment. Prolonged treatment with abciximab had no influence of the activation of these systems.

    Unstable coronary artery disease (CAD) intricately involves inflammatory mediators in the development of an atherosclerotic plaque and in thrombus formation by platelet aggregation.1 Acute phase elevation of inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and fibrinogen are important predictors of the short- and long-term prognosis in unstable CAD.2, 3 and 4 Activation of the coagulation and fibrinolysis systems, as demonstrated with elevated markers of thrombin generation, thrombin activity, and fibrin turnover, also have been found in the acute phase of unstable CAD and are associated with an adverse outcome.5, 6 and 7 Glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors potently inhibit platelet aggregation and reduce the incidence of ischemic events in patients undergoing percutaneuos coronary interventions8, 9 and 10 and in patients with unstable CAD.11 The GP IIb/IIIa inhibitor abciximab, in addition to its antithrombotic effect, also suppresses the rise in levels of inflammatory markers after percutaneous coronary interventions.12 This anti-inflammatory effect might be related to abciximab's cross-reaction with other integrin receptors.13 Furthermore, by inhibiting platelet aggregation, abciximab might also attenuate the coagulation and fibrinolysis activation as shown in vitro and in vivo.14 and 15

    The Global Utilization of Strategies To Open occluded arteries in acute coronary syndromes (GUSTO IV-ACS) trial unexpectedly failed to show any benefit of abciximab treatment in a high risk ACS population not undergoing early coronary revascularization.16 In the GUSTO IV-ACS low-molecular weight heparin substudy,17 dalteparin was used as the anticoagulant. Dalteparin, which is an inhibitor of the coagulation cascade, mainly by inhibition of factor Xa and less of factor IIa, has previously been shown to reduce the generation and activity of thrombin in unstable coronary disease.18 There is evidence that a combination of abciximab and a low-molecular-weight heparin have additive effects on the lag-time to platelet aggregation,19 and there are several theoretical advantages with the combination treatment. There was still no significant reduction in clinical events with abciximab in combination with dalteparin.17 The aim of this Swedish substudy of GUSTO IV-ACS was to evaluate the influence of abciximab infusion on markers on inflammation, coagulation, and fibrinolysis in patients with unstable CAD treated with aspirin and subcutaneous dalteparin.

  • 110.
    James, Stefan
    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.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Armstrong, P
    Barnathan, E
    Califf, R
    Topol, E
    Simoons, Maarten L
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    N-Terminal Pro–Brain Natriuretic Peptide and Other Risk Markers for the Separate Prediction of Mortality and Subsequent Myocardial Infarction in Patients With Unstable Coronary Artery Disease: A Global Utilization of Strategies To Open occluded arteries (GUSTO)-IV Substudy2003In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 108, no 3, p. 275-281Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Biochemical markers are useful for prediction of cardiac events in patients with non-ST-segment-elevation acute coronary syndrome (ACS). The associations between N-terminal pro-brain natriuretic peptide (NT-proBNP) and other biochemical and clinical risk indicators, as well as their prognostic value concerning the individual end points of death and myocardial infarction (MI), were elucidated in a large cohort of ACS patients. METHODS AND RESULTS: NT-proBNP, troponin T, and C-reactive protein (CRP) were analyzed in blood samples obtained at a median of 9.5 hours from symptom onset in 6809 of 7800 ACS patients in the Global Utilization of Strategies To Open occluded arteries-IV (GUSTO-IV) trial. Levels of NT-proBNP were correlated independently with age, female gender, low body weight, diabetes, renal dysfunction, history of MI, heart failure, heart rate, ongoing myocardial damage, and time since onset of ischemia. Increasing quartiles of NT-proBNP were related to short- and long-term mortality that reached 1.8%, 3.9%, 7.7%, and 19.2%, (P<0.001), respectively, at 1 year. Levels of troponin T, CRP, heart rate, and creatinine clearance, in addition to ST-segment depression, were also correlated independently with 1-year mortality, but NT-proBNP was the marker with the strongest relation. In contrast, only troponin T, creatinine clearance, and ST-segment depression were independently related to future MI. The combination of NT-proBNP and creatinine clearance provided the best prediction, with a 1-year mortality of 25.7% with both markers in the top quartile vs 0.3% with both markers in the bottom quartile. CONCLUSIONS: The use of NT-proBNP appears to add critical prognostic insight to the assessment of patients with ACS.

  • 111.
    Janson, Eva Tiensuu
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Chromogranin A is a Sensitive Marker for Detection of Recurrence in Neuroendocrine Tumors2010In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 92, no 1, p. 63-63Article in journal (Other academic)
  • 112.
    Jernberg, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. 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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Natriuretic peptides in unstable coronary artery disease2004In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 25, no 17, p. 1486-1493Article in journal (Other academic)
    Abstract [en]

    Patients with unstable coronary artery disease (CAD), i.e., unstable angina or non-ST-elevation myocardial infarction, vary widely in clinical presentation, prognosis and response to treatment. To select appropriate therapy, early risk stratification has become increasingly important. This review focuses on the emerging role of natriuretic peptides in the early assessment of patients with unstable CAD. We conclude that levels of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are strongly associated to mortality and the risk of future congestive heart failure, and carry important prognostic information independent from previously known risk factors in unstable CAD. There are some data indicating that these markers can also be helpful in the selection of appropriate therapy in these patients but further studies are needed. Before a routine use of BNP or NT-proBNP in unstable CAD can be recommended, the cost-effectiveness of adding these new markers to the currently routine markers and their impact on selection of treatment needs further evaluation.

  • 113. Johanson, Viktor
    et al.
    Ahlman, Håkan
    Bernhardt, Peter
    Jansson, Svante
    Kölby, Lars
    Persson, Fredrik
    Stenman, Göran
    Swärd, Christina
    Wängberg, Bo
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Nilsson, Ola
    A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis2007In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 14, no 2, p. 433-444Article in journal (Refereed)
    Abstract [en]

    Hereditary medullary thyroid carcinoma (MTC) is caused by germline mutations in the RET proto-oncogene, resulting in constitutive activation of the RET tyrosine kinase. A substantial proportion of sporadic MTCs also have RET mutations, making the RET tyrosine kinase a potential therapeutic target in MTC. We have established a transplantable MTC in nude mice from a sporadic human MTC carrying a RET C634R mutation. Transplanted tumors had an exponential growth rate with an approximate doubling time of about 3 weeks, and expressed a neuroendocrine phenotype characteristic of MTC, e.g., expression of calcitonin, chromogranin A (CgA), synaptophysin, synaptic vesicle protein 2 (SV2), vesicular monoamine transporter-1 and -2, carcinoembryonic antigen, cytokeratin 8/18, epithelial cadherin, and neural cell adhesion molecule. Plasma calcitonin and CgA levels were elevated in tumor-bearing mice and correlated with tumor size. Cytogenetic analysis, including spectral karyotyping, confirmed the human origin of the xenografted tumors and demonstrated an abnormal, near triploid karyotype. Treatment of tumor-bearing nude mice with the tyrosine kinase inhibitor ZD6474, which specifically inhibits RET, epidermal growth factor receptor (EGFR), and vascular endothelium growth factor receptor (VEGFR) tyrosine kinases, resulted in a dose-dependent inhibition of tumor growth. Oral ZD6474 given once daily (250 mg/kg, 5 days/week) reduced tumor volume to 11% when compared with controls after 4 weeks. Our results show that this transplantable MTC, designated GOT2, represents a novel and useful model for studies of MTC and RET tyrosine kinase-dependent tumor growth.

  • 114.
    Johansson, Ann-Christin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Gunnarsson, Lars-Gunnar
    Linton, Steven J.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Nilsson, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Cornefjord, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Pain, disability and coping reflected in the diurnal cortisol variability in patients scheduled for lumbar disc surgery2008In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 12, no 5, p. 633-640Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Symptoms of lumbar disc herniation can be induced by both mechanical compression of the nerve roots and by biochemical irritants from the disc tissues. Proinflammatory cytokines, as well as stress are potent stimulators of the hypothalamic-pituitary-adrenal axis, reflected in enhanced release of cortisol from the adrenal cortex. Altered cortisol production is also associated to behaviour and coping patterns. The aim of the present study was to explore the relation between pain, physical function, psychosocial factors and quality of life to the diurnal cortisol variability, in patients with lumbar disc herniation.

    METHOD:

    This study had a cross-sectional design. Forty-two patients with lumbar disc herniation, verified by magnetic resonance imaging and a clinical examination by an orthopaedic surgeon, were included in the study. All patients were scheduled for disc surgery. The diurnal cortisol variability was examined before surgery. The patients were dichotomised into two groups based on low or high diurnal cortisol variability. Pain, disability, work related stress, quality of life, coping and fear avoidance beliefs, were estimated by standardised questionnaires.

    RESULTS:

    The low diurnal cortisol variability group was distinguished by a higher median score regarding leg pain at activity and significantly more disability (p<0.05). The patients with a low diurnal cortisol variability had significantly lower coping self-statement scores, but higher pain coping catastrophising scores (p<0.05).

    CONCLUSION:

    Patients with lumbar disc herniation and a low diurnal cortisol variability had lower physical function, perceived lower possibilities of influencing their pain, and were more prone to catastrophise than patients with lumbar disc herniation and a high diurnal cortisol variability.

  • 115.
    Johansson, M
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolutionary Biology, Physiological Botany.
    Patarroyo, M
    Öberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Nilsson, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Myeloperoxidase mediates cell adhesion via the alpha M beta 2 integrin (Mac-1, CD11b/CD18)1997In: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 110, no 9, p. 1133-1139Article in journal (Refereed)
    Abstract [en]

    Myeloperoxidase is a leukocyte component able to generate potent microbicidal substances. A homologous invertebrate blood cell protein, peroxinectin, is not only a peroxidase but also a cell adhesion ligand. We demonstrate in this study that human myeloperoxidase also mediates cell adhesion. Both the human myeloid cell line HL-60, when differentiated by treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or retinoic acid, and human blood leukocytes, adhered to myeloperoxidase; however, undifferentiated HL-60 cells showed only minimal adhesion. No cells adhered to horseradish peroxidase, and cell adhesion to myeloperoxidase was not decreased by catalase, thus showing that peroxidase activity, per se, was neither sufficient nor necessary for the adhesion activity. Mannan, which has been reported to inhibit the binding of peroxidases to cells, did not affect adhesion to myeloperoxidase. However, adhesion to myeloperoxidase was inhibited by monoclonal antibodies to alpha M (CD11b) or to beta2 (CD18) integrin subunits, but not by antibodies to alpha L (CD11a), alpha M (CD11c), or to other integrins. Native myeloperoxidase mediated dose-dependent cell adhesion down to relatively low concentrations, and denaturation abolished the adhesion activity. It is evident that myeloperoxidase supports cell adhesion, a function which may be of considerable importance for leukocyte migration and infiltration in inflammatory reactions, that alpha M beta2 integrin (Mac-1 or CD11b/CD18) mediates this adhesion, and that the alphaM beta2 integrin-mediated adhesion to myeloperoxidase is distinct from the previously reported ability of this integrin to bind to certain denatured proteins at high concentrations.

  • 116.
    Johnell, Matilda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    The influence of different heparin surface concentrations and antithrombin-binding capacity on inflammation and coagulation2005In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 26, no 14, p. 1731-1739Article in journal (Refereed)
    Abstract [en]

    The corline heparin surface (CHS) used in the extracorporeal circuit during coronary artery bypass grafting is shown to decrease the activation of inflammation and coagulation. Synchrotron radiation studies have shown that a single layer of the CHS may not completely cover the substrate surface. However, a double layer of CHS results in a uniform surface. We investigated the effect of surfaces with different surface concentrations of heparin on cell activation and coagulation compared to an uncoated surface.

    The CHS is prepared by a conditioning layer of polymeric amine onto which a macromolecular heparin conjugate is attached. We used PVC tubing, uncoated or modified with a single or double layer of the CHS, and circulated fresh whole blood from healthy volunteers in a loop model system at 37°C up to 4 h. Blood was drawn from the loops at different times and activation of inflammation and coagulation was studied by real-time PCR, flow cytometry and ELISA. The activation of leukocytes and platelets and formation of leukocyte–platelet aggregates were reduced by use of the single-layered CHS compared to the uncoated surface. Use of double-layered CHS resulted in significantly reduced cell activation and thrombin generation. Development of the CHS obtained by the double layer of the coating has improved the biocompatibility of the surface.

  • 117.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jernberg, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Biochemical indicators of cardiac and renal function in a healthy elderly population2004In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 37, no 3, p. 210-216Article in journal (Refereed)
    Abstract [en]

    Objectives:

    To examine the distributions of NT-proBNP and cystatin C and their relation to age, gender, and other physiological factors in an apparently healthy elderly population.

    Method:

    NT-proBNP and cystatin C were analyzed in 407 and 408 healthy individuals, median age: 65 (range 40–76).

    Results:

    Increasing age, female gender and CRP were independently associated to higher NT-proBNP levels. Age, body mass index, and CRP level were independently associated to the cystatin C level. In women and men, ≤65 years, the 97.5th percentile value for NT-proBNP was 268 ng/l and 184 ng/l, in those older, 391 ng/l and 269 ng/l. For those ≤65 years the 97.5th percentile value for cystatin C was 1.12 mg/l, and for those older 1.21 mg/l.

    Conclusion:

    In a healthy elderly population, NT-proBNP is influenced by age and gender, whereas cystatin C is influenced by age but not by gender. Both markers seem to be associated to the CRP level.

  • 118. 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.

  • 119.
    Jönsson, Ulla-Britt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Byström, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Stålenheim, Gunnemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    A (G -> C) transversion in the 3 ' UTR of the human ECP (eosinophil cationic protein) gene correlates to the cellular content of ECP2006In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 79, no 4, p. 846-851Article in journal (Refereed)
    Abstract [en]

    Eosinophil cationic protein (ECP) is a cytotoxic protein produced by and secreted from human eosinophil granulocytes. ECP may be involved in the injury of epithelial cells in allergic diseases such as asthma. The objectives were to determine the prevalence of the ECP gene polymorphism 562(G > C) in apparently healthy subjects and subjects with allergy and relate the prevalence to clinical disease and to serum and cellular levels of ECP. The 562(G > C) ECP gene polymorphism was determined by gene sequencing of the ECP gene from DNA prepared from 163 apparently healthy subjects and 151 subjects with allergic and nonallergie asthma or other diseases. ECP was measured by a sensitive radioimmunoassay. A polymorphism was detected at position 562, which mapped to the 3' untranslated region (UTR) of the gene encoding the ECP (RNase 3). Sixty-nine percent of the population had the 562GG genotype and 4%, the 562CC genotype. The cellular content of ECP in peripheral blood cosinophid granulocytes was significantly lower in cells from subjects with the 562GC (4.6 +/- 1.5 mu g/10(6) eosinophils) and 562CC (3.2 +/- 0.7 mu g/10(6) eosinophils) genotypes as compared with those with the 562GG genotype (6. 0 +/- 1.9 mu g/10(6) eosinophils; P < 0.001). A close link was found to the 434(G > C) ECP gene polymorphism. Associations between the 562(G > C) polymorphism or haplotypes of the two polymorphisms to allergy were not found. The 562(G > C) polymorphism in the 3'-end of the UTR of the ECP gene may determine the ECP content in human eosinophils, but unlike the 434(G > C) polymorphism, the 562(G > C) polymorphism is not related to allergy.

  • 120. Kenan, Naama
    et al.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Helander, Anders
    Changes in transferrin glycosylation during pregnancy may lead to false-positive carbohydrate-deficient transferrin (CDT) results in testing for riskful alcohol consumption2011In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 412, no 1-2, p. 129-133Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: An alcohol-induced change in serum transferrin glycosylation, termed carbohydrate-deficient transferrin (CDT), is widely used as a biomarker of heavy long-term drinking. This study examined the transferrin glycosylation profile and the risk for false-positive CDT results during pregnancy. METHODS: Serum samples were collected from 24 healthy pregnant women starting in gestation week 9-21, throughout pregnancy, and 8 or more weeks after delivery. Altogether 171 sera (5-9 samples/person) were analysed. Transferrin glycoforms were quantified as a percentage of total transferrin, using an HPLC candidate reference method for CDT. RESULTS: During pregnancy, the relative disialo-, pentasialo- and hexasialotransferrin levels increased gradually, whereas trisialo- and tetrasialotransferrin were reduced. This effect was most pronounced in the third trimester. For disialotransferrin, the main target in CDT testing, initial values of 1.07±0.17% (mean±SD) increased to 1.61±0.23% before delivery (~50% increase). Nine (38%) pregnant women reached %disialotransferrin values ≥1.7% (97.5th percentile for controls) but all results were <2.0%. In the postpartum samples, all glycoform levels had returned towards the starting values. CONCLUSIONS: These results suggest that the cutoff for %disialotransferrin and %CDT employed to indicate heavy long-term drinking need to be raised slightly in pregnant women, to minimize the risk for false-positive results on CDT testing.

  • 121.
    Kloster Smerud, Hilde
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hällgren, Roger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Osagie, Sonia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Kristjansson, Gudjon A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gastrointestinal sensitivity to soy and milk proteins in patients with IgA nephropathy2010In: Clinical Nephrology, ISSN 0301-0430, Vol. 74, no 5, p. 364-371Article in journal (Refereed)
    Abstract [en]

    Background Sensitivity to food antigens has been postulated as a contributing factor to the pathogenesis of IgA nephropathy (IgAN) Methods In this study we used a recently developed mucosal patch technique to evaluate rectal mucosal sensitivity to soy and cow's milk (CM) proteins in IgAN patients (n = 28) compared to healthy subjects (n = 18) The rectal mucosal production of nitric oxide (NO) and release of myeloperoxidase (M PO) and eosinophil cationic protein (ECP) were measured Serum samples were analyzed for IgA and IgG antibodies to a-lactalbumin, P-lactoglobulin, casein and soy Results 14 of 28 (14/28) patients experienced a rectal mucosal reaction, measured by increased NO and/or MPO levels, upon rectal challenge with soy and/or cow's milk proteins The levels of IgG antibodies to a-lactalbumin, beta-lactoglobulin and casein were significantly higher in CM sensitive as compared with non-sensitive IgAN patients, whereas the mean serum levels of IgA antibodies were similar No differences were seen in serum levels of IgA or IgG antibodies to soy Conclusion It is concluded that approximately half of our IgAN patients have a rectal mucosal sensitivity to soy or CM, and that an immune reactivity against antigens may be involved in the pathogenesis of IgAN in this subgroup of patients

  • 122.
    Kårehed, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Olsson, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Fibrinogen and histidine-rich glycoprotein in early-onset preeclampsia2010In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 89, no 1, p. 131-139Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To determine whether plasma levels of fibrinogen and the placental tissue distributions of fibrinogen and histidine-rich glycoprotein (HRG) differ between early- and late-onset preeclampsia. DESIGN: The study comprised 18 women with early-onset (gestational weeks 24-32) and 19 women with late-onset (gestational weeks 35-42) preeclampsia. As controls concerning the plasma levels of fibrinogen, we used samples from non-pregnant fertile women, healthy pregnant women at gestational weeks 24-32 and healthy pregnant women at gestational weeks 35-42. Placental samples from women with healthy pregnancies at gestational weeks 35-42 served as controls in the immunohistochemical staining. SETTING: Uppsala University Hospital, Uppsala. METHODS: Plasma fibrinogen levels were analyzed and the placental tissue expression of fibrinogen and HRG determined by immunohistochemistry. RESULTS: Plasma level of fibrinogen was increased in early-onset, but not late-onset, preeclampsia. Levels of fibrinogen were significantly lower, and that of HRG significantly higher, in placentas from women with early-onset preeclampsia as compared with control placentas (p = 0.01 and 0.001). CONCLUSIONS: HRG and fibrinogen might be involved in the hypercoagulability and the angiogenic imbalance seen in early-onset preeclampsia.

  • 123.
    Lahtinen, Mika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Blomberg, Pontus
    Baliulis, Giedrius
    Carlsson, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Khamis, Harry
    Zerngulis, Vitas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    In vivo h-VEGF(165) gene transfer improves early endothelialisation and patency in synthetic vascular grafts2007In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 31, no 3, p. 383-390Article in journal (Refereed)
    Abstract [en]

    Objectives: Small-diameter synthetic vascular graft performance is inferior to autologous vein grafts. This study tested the hypotheses that local in vivo administration of plasmids encoding for human vascular endothelial. growth factor (VEGF), or co-administration of plasmids encoding for human vascular endothelial growth factor/plasmids encoding for fibroblast growth factor-2 in the tissues surrounding a porous synthetic vascular graft would enhance graft endothelialisation and, consecutively, graft patency. Methods: First, optimal gene for small-diameter synthetic graft endothelialisation was studied in rat abdominal aorta model (n = 132): plasmids encoding for human vascular endothelial growth factor; co-administration of plasmids encoding for human vascular endothelial growth factor/plasmids encoding for fibroblast growth factor-2; or control plasmids were injected around 60 mu m ePTFE graft. Second, optimal small-diameter synthetic graft design for endothelialisation was explored in rabbit abdominal aorta model (n = 90). Various ePTFE grafts or pre-clotted polyester grafts were used with/without plasmids encoding for human vascular endothelial growth factor. Third, clinically used medium-size synthetic grafts were investigated with/without plasmids encoding for human vascular endothelial growth factor in dog carotid (n = 20) and femoral. arteries (n = 15). Endothelialisation was assessed in midgraft area with scanning electron microscopy. Results: In rats, plasmids encoding for human vascular endothelial growth factor enhanced endothelialisation; whereas co-administration of plasmids encoding for human vascular endothelial growth factor/plasmids encoding for fibroblast growth factor-2 had worst outcome at 1 week (NS), 2 weeks (P = 0.01) and 4 weeks (P = 0.02). In rabbits, pre-clotted polyester grafts had a trend for faster endothelialisation than ePTFE grafts (P = 0.08); whereas plasmids encoding for human vascular endothelial growth factor enhanced endothelialisation compared to controls at 2 weeks (P = 0.06), however, the effect reversed at 4 weeks (P = 0.03). In dogs, synthetic graft patency was improved by plasmids encoding for human vascular endothelial growth factor in femoral position (P = 0.103); whereas all carotid grafts were patent at 6 weeks. Conclusions: Thus, these data suggested that endothelialisation was fastest in pre-clotted polyester grafts; and that local application of plasmids encoding for human vascular endothelial growth factor had a potential to improve early endothelialisation and patency in synthetic vascular grafts.

  • 124.
    Lannergård, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Friman, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lind, Lars
    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, Biochemial structure and function. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Serum amyloid A (SAA) protein and high-sensitivity C-reactive protein (hsCRP) in healthy newborn infants and healthy young through elderly adults2005In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 94, no 9, p. 1198-1202Article in journal (Refereed)
    Abstract [en]

    AIM:

    To determine the levels of serum amyloid A (SAA) protein and high-sensitivity C-reactive protein (hsCRP) in different age groups.

    METHODS:

    Serum samples from 70 healthy newborn infants, 80 blood donors and 81 healthy elderly individuals were analysed using a nephelometric method. The 231 samples were grouped as follows: 35 umbilical cords, 35 newborns, 48 young adults, 28 middle-aged adults, and 85 elderly adults.

    RESULTS:

    Serum levels of both SAA and hsCRP were lower in umbilical cords than in the newborns and young, middle-aged and elderly adults (p<0.0001). The SAA and hsCRP levels were comparable in newborns, and young and middle-age adults, but higher in elderly adults (p<0.0001-0.03). SAA (r2=0.159, p<0.0001) and hsCRP (r2=0.059, p<0.0001) were positively correlated with age and to each other (r2=0.385, p<0.0001).

    CONCLUSION:

    Serum levels of SAA and hsCRP in umbilical cord blood are close to the detection limit and lower than in the other age groups investigated. The elderly have generally higher levels than the younger age groups, which require higher decision levels in inflammatory diseases, including infections. In newborns and young and middle-aged adults, the lower decision levels of 10 mg/l for SAA and 5 mg/l for CRP are suggested.

  • 125.
    Lannergård, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Friman, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Human serum amyloid A (SAA) and high sensitive C-reactive protein (hsCRP) in preterm newborn infants with nosocomial infections2008In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 97, no 8, p. 1061-1065Article in journal (Refereed)
    Abstract [en]

    Human serum amyloid A (SAA) and high sensitive C-reactive protein (hsCRP) and their relation to suggestive nosocomial infections (NIs) were investigated in very preterm (VPT) newborn infants. In a retrospective analysis, information of suggestive NI was matched to levels of SAA and hsCRP in 224 serum samples from 72 VPT newborn infants. As a control group, 35 healthy-term newborn infants were chosen. Of the 224 serum samples, 145 samples were not associated with nosocomial infections. However, 79 were associated with NI: of these 79, 42 were found to be culture-proven NI. Trimmed mean (alpha= 0.05) levels for SAA and hsCRP in VPT newborn infants were higher than in control term newborn infants (1.74, 2.67 mg/L vs. 0.78, 0.16 mg/L; p = 0.01 and <0.0001, respectively), and higher in the NI group than in the non-NI group (5.14, 5.74 mg/L vs. 1.03, 1.18; p < 0.01 and <0.0001; respectively). The areas under the curve (AUC) for hsCRP, calculated from the receiver-operator characteristic (ROC) curves, was greater (0.816; 95% CI 0.759-0.864) than for SAA (0.610; 95% CI 0.543-0.675). CONCLUSION: Identifying and monitoring of bacterial and fungal infections in VPT might be further improved by the use of SAA and hsCRP.

  • 126.
    Lannergård, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Viberg, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Cars, Otto
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Karlsson, Mats O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Sandström, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    The time course of body temperature, serum amyloid A protein, C-reactive protein and interleukin-6 in patients with bacterial infection during the initial 3 days of antibiotic therapy2009In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 41, no 9, p. 663-671Article in journal (Refereed)
    Abstract [en]

    The accuracy of using body temperature, serum amyloid A (SAA), C-reactive protein (CRP) and interleukin-6 (IL-6) in the work-up for early or late step-down therapy after an initial course of intravenous cefuroxime was investigated. Eighty-one hospitalized patients with an initial course of cefuroxime were retrospectively classified with one of the following diagnoses: bacterial infection without known focus, pneumonia, bronchitis, pyelonephritis, skin and soft-tissue infections or fever of other origin. The majority of the patients had sepsis (91% or 74/81) of whom 6 patients had severe sepsis. The inter-individual variability of body temperature, SAA, CRP and IL-6 was considerable. The time course of SAA and CRP during the first 24 h in patients with sepsis with a short duration of illness but without septic shock showed increasing levels during the initial course of intravenous therapy. In contrast, body temperature and IL-6 decreased, regardless of illness duration. Beyond 24 h, all 4 biomarkers declined, again regardless of the duration of illness. After the initial course of cefuroxime, biomarkers were non-distinguishing in terms of guidance in the judgement of early or late step-down therapy. Further studies are proposed for biomarker guidance antibiotic therapy in sepsis patients without septic shock.

  • 127.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Author response to: Reference values for clinical chemistry tests during normal pregnancy2008In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 115, no 13, p. 1716-1717Article in journal (Refereed)
  • 128.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Reference values for clinical chemistry tests during normal pregnancy. Author reply.2008In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 115, no 13, p. 1716-1717Article in journal (Refereed)
  • 129.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Reference values for clinical chemistry tests during normal pregnancy: Author's reply2008In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 115, no 12, p. 1580-1581Article in journal (Refereed)
  • 130.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    What can we learn from studies on regional differences in the utilization of laboratory tests?2011In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 116, no 4, p. 225-226Article in journal (Refereed)
  • 131.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Flodin, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Carlsson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Patient selection has a strong impact on cystatin C and Modification of Diet in Renal Disease (MDRD) estimated glomerular filtration rate2008In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 41, no 16-17, p. 1355-1361Article in journal (Refereed)
    Abstract [en]

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

  • 132.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Flodin, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Katz, Ronit
    Shlipak, Michael G.
    Calibration of the Siemens Cystatin C Immunoassay Has Changed over Time2011In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 57, no 5, p. 777-778Article in journal (Refereed)
  • 133.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hassan, Moustapha
    2Experimental Cancer Medicine, KFC Novum, Karolinska University Hospital Huddinge,.
    Ridefelt, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Axelsson, John
    Section of Psychology, Department of Clinical Neurosciences, Karolinska Institutet,.
    Circadian variability of bilirubin in healthy men during normal sleep and after an acute shift of sleep2009In: Chronobiology International, ISSN 0742-0528, E-ISSN 1525-6073, Vol. 26, no 8, p. 1613-1621Article in journal (Refereed)
    Abstract [en]

    Bilirubin is a laboratory test widely used for patient care, especially neonatal patients and patients with anemia or suspected liver disorders. Bilirubin has also been shown to be associated with sleep pattern and oxidative stress. The aim of this study was to investigate the variation of bilirubin in a group of healthy individuals with normal night sleep as well as during acutely displaced sleep, as sleep timing varies immensely between individuals while clinical samples are still mainly taken in the morning. We studied the diurnal variation of bilirubin during night-sleep and day-sleep conditions in seven healthy volunteers. Serum samples were collected every hour (50 samples/individual) to evaluate the effect of different sampling times and sleep displacement on the test results. The mean acrophases (peak time) occurred at 10.6 h during the night-sleep condition and at 18.4 h during the day-sleep condition. The diurnal intraindividual variation was high during both the night-sleep and day-sleep conditions, with coefficients of variation (CV) in the range of 12.8 to 42.5%. The diurnal variation was higher during the day compared to night-sleep condition. Thus, bilirubin sampling should be restricted to the morning, preferably after a normal night sleep, to minimize intraindividual variation.

  • 134.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    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, Clinical Chemistry.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Serum cystatin C is associated with other cardiovascular risk markers and cardiovascular disease in elderly men2008In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 125, no 2, p. 263-264Article in journal (Refereed)
    Abstract [en]

    Renal dysfunction is associated with increased cardiovascular morbidity and mortality. The aim of this cross-sectional study was to investigate the relationship between the glomerular filtration marker cystatin C and other cardiovascular risk markers and morbidity in elderly males. Cystatin C was measured in a group of 77-year-old males (n=792) and compared cystatin C with other known risk markers for cardiovascular disease. Cystatin C values were significantly increased in individuals with diabetes (p=0.05) and cardiovascular diseases (p<0.0001). There were significant correlations between cystatin C values and body mass index, HbA1c, insulin, triglycerides and hsCRP.

  • 135.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lindqvist, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Pseudoparaproteinemia Detected by CE due to Omnipaque™ Infusion: A Case Report2007In: Chromatographia, ISSN 0009-5893, E-ISSN 1612-1112, Vol. 65, no 11-12, p. 775-777Article in journal (Refereed)
    Abstract [en]

    Serum or plasma protein electrophoresis is often performed in clinical laboratories to detect and monitor M-components. During the last decade, capillary electrophoresis (CE) has emerged as an interesting alternative to traditional analysis of serum, plasma and urine proteins by agarose gel electrophoresis. We here report a case of pseudoparaproteinemia detected by capillary electrophoresis after Omnipaque™ (iohexol) infusion in a patient with normal kidney function. It is important for the laboratories to be aware of this source of erroneous results and not misclassify it as monoclonal gammopathies.

  • 136.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Palm, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Insulin-like growth factor binding protein-1 (IGFBP-1) during normal pregnancy2013In: Gynecological Endocrinology, ISSN 0951-3590, E-ISSN 1473-0766, Vol. 29, no 2, p. 129-132Article in journal (Refereed)
    Abstract [en]

    Background:

    Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is the main binder of IGFs in secretory endometrium and decidualized stromal endometrial cells and IGFBP-1 has been shown to modulate IGF bioactivities and influence fetal growth. To be able to evaluate IGFBP-1 values during pregnancy it is important to establish normal values in pregnant women.

    Materials & Methods:

    We have studied IGFBP-1 concentrations in maternal plasma from 52 healthy women with normal singleton pregnancies. Several plasma samples were collected from each woman and the samples were grouped according to gestational age into the following periods: week 7-17; week 17-24; week 24-28; week 28-31; week 31-34; week 34-38; -2 to 0 weeks prior to delivery and postpartum (>6 weeks after delivery).

    Results:

    The 2.5 and 97.5 percentiles for IGFBP-1 were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values.

    Conclusions:

    IGFBP-1 is increased during pregnancy compared to postpartum. Two peaks, at week 17-24 and just before delivery, were observed.

  • 137.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Palm, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Cystatin C and modification of diet in renal disease (MDRD) estimated glomerular filtration rate differ during normal pregnancy2010In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 89, no 7, p. 939-944Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To calculate normal values for estimation of the glomerular filtration rate (eGFR) for pregnant females. eGFR is used to monitor patients with suspected kidney disease and to optimize the dosage of drugs that are eliminated by the kidneys. Plasma creatinine and cystatin C are the two most widely used GFR markers. Both markers are recommended to be automatically reported as estimated GFR.

    DESIGN: Retrospective study.

    SETTING: Tertiary university hospital.

    POPULATION: We have studied creatinine (eGFR(MDRD)) (MDRD, modified diet in renal disease) and cystatin C (eGFR(cystc)) estimated GFR during 52 normal pregnancies from pregnancy week 10 to delivery and postpartum.

    METHODS: Each woman was sampled repeatedly and the samples were grouped according to gestational age into the following periods: week 7-16; week 18-24; week 24-28; week 28-31; week 31-34; week 34-38; -2-0 weeks prior to delivery and postpartum (> 6 weeks after delivery).

    MAIN OUTCOME MEASURES: The 2.5 and 97.5 percentiles for these markers were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values.

    RESULTS: In healthy pregnant females eGFR(cystc) was higher in the first two trimesters and lower prior to delivery in comparison with eGFR(MDRD). eGFR(cystc) and eGFR(MDRD) give different results. No significant correlations between the two estimates were found in any of the time groups.

    CONCLUSIONS: It is important to distinguish between the two GFR estimates and use separate reference intervals for pregnant females.

  • 138.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Palm, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hansson, Lars-Olof
    Dept of Physical and Analytical Chemistry, Uppsala University, Sweden.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Reference values for alpha1-acid glycoprotein, alpha1-antitrypsin, albumin, haptoglobin, C-reactive protein, IgA, IgG and IgM during pregnancy2008In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 87, no 10, p. 1084-8Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to establish reference intervals and decision limits for the interpretation of the acute phase proteins alpha(1)-acid glycoprotein (orosomucoid), alpha(1)-antitrypsin, C-reactive protein (CRP), haptoglobin and albumin, IgA, IgG and IgM during pregnancy by longitudinal sampling from 52 healthy women with normal pregnancies. Each woman was sampled in weeks 7-17; weeks 17-24; weeks 24-28; weeks 28-31; weeks 31-34; weeks 34-38 and predelivery (-14-0 days prior to delivery) and postpartum (>6 weeks after delivery). The 2.5th and 97.5th percentiles were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values. Reference values for alpha(1)-acid glycoprotein, alpha(1)-antitrypsin, albumin, haptoglobin, CRP, IgA, IgG and IgM are reported. Most of these proteins changed during normal pregnancy, as a reflection of the major physiological and biochemical changes that occur in pregnancy. A laboratory test result from a pregnant woman should be compared with pregnancy-specific reference intervals.

  • 139.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Palm, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Pentraxin 3 Values During Normal Pregnancy2011In: Inflammation, ISSN 0360-3997, E-ISSN 1573-2576, Vol. 34, no 5, p. 448-451Article in journal (Refereed)
    Abstract [en]

    Pentraxin 3 (PTX3) is an inflammatory molecule that has been reported to be a promising early biomarker for subsequent preeclampsia. The levels of PTX3 vary during pregnancy and it is thus a need to establish reference intervals during normal pregnancy. Repeated blood samples were collected from 52 healthy pregnant females. The samples were divided according to collection time into the following groups: week 7-17, week 17-24, week 24-28, week 28-31, week 31-34, week 34-38, before delivery and after delivery. The samples were analyzed for PTX3 with a sandwich ELISA and the 2.5 and 97.5 percentiles for each sample period was calculated. There was a continuous increase of serum PTX3 as pregnancy progressed. The increase was most evident after week 31 with the highest levels just before delivery.

  • 140.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Ronquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wülfing, Christian
    Eltze, Elke
    Bettendorf, Olaf
    Carlsson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Nilsson, B. Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Semjonow, Axel
    Antiprostasome antibodies: possible serum markers for prostate cancer metastasizing liability2006In: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 24, no 3, p. 195-200Article in journal (Refereed)
    Abstract [en]

    Prostasomes are secretory granules synthesized, stored, and secreted by normal and neoplastic human prostate epithelial cells. In prostate cancer, they are anticipated to be released into the blood circulation where they may be immunogenic. The aim of our study was to examine whether prostasome antibody presence in serum bears any prognostic significance for men with prostate cancer. We developed a sensitive and specific immunoassay (enzyme-linked immunosorbent assay) to establish the presence of antiprostasome antibodies in serum. The antiprostasome antibody titer in serum, sampled before any kind of therapy for prostate cancer, was examined together with clinicopathologic variables and outcome over a median follow-up of 350 days in 218 patients with verified prostate cancer. We detected these antibodies in 191 (88%) of these patients. This antibody titer did not correlate to serum values of prostate-specific antigen. Significant, inverse relationships were registered for antiprostasome antibody titer, and metastases to bone and/or lymph nodes (P = 0.035) and pT (P = 0.025). These results indicate that the antiprostasome antibody titer in serum may be a novel marker for prostate cancer liability to metastasize.

  • 141.
    Lidén, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kristjánsson, G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Valtysdottir, S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hällgren, R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cow's milk protein sensitivity assessed by the mucosal patch technique is related to irritable bowel syndrome in patients with primary Sjögren's syndrome2008In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 38, no 6, p. 929-935Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Patients with primary Sjögren's syndrome (pSS) are reported to have a variety of gastrointestinal symptoms partly attributed to an overrepresentation of celiac disease. We have observed that irritable bowel syndrome (IBS)-like symptoms are frequent complaints in this patient group. Allergic manifestations to various drugs are also common in pSS. A role of food allergy in IBS has been proposed. OBJECTIVE: This study is aimed at evaluating the mucosal response to rectal challenge with cow's milk protein (CM) in patients with pSS and relates possible CM reactivity to their intestinal symptoms. Methods: A rectal challenge with CM was performed in 21 patients with pSS and 18 healthy controls. Fifteen hours after challenge the mucosal production of nitric oxide (NO) and the release of myeloperoxidase (MPO) as signs of mucosal inflammatory reaction were measured using the mucosal patch technique. RESULTS: Eight out of 21 patients with pSS had a definite increase of mucosal NO synthesis and the luminal release of MPO after rectal CM challenge. This sign of milk sensitivity was not linked to IgG/IgA antibodies to milk proteins. The symptoms for IBS according to Rome III criteria were fulfilled in 13 patients. All patients who were CM sensitive suffered from IBS. In a small open study, patients reactive to CM reported an improvement of intestinal symptoms on a CM-free diet. CONCLUSION: A rectal mucosal inflammatory response after CM challenge is seen in 38% of patients with pSS as a sign of CM sensitivity. IBS-like symptoms were common in pSS, linked to CM sensitivity.

  • 142.
    Lidén, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Kristjánsson, Gudjón
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Valtysdóttir, Sigridur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hällgren, Roger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Self-reported food intolerance and mucosal reactivity after rectal food protein challenge in patients with rheumatoid arthritis2010In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 39, no 4, p. 292-298Article in journal (Refereed)
    Abstract [en]

    Objectives: A dietary link to rheumatoid arthritis (RA) has been suspected and an influence on arthritic symptoms by different diets has been reported. Our primary aim was to record the self-experienced adverse food reactions in patients with RA. A secondary aim was to relate self-experienced adverse reactions to dairy produce and wheat to the local mucosal reactivity observed after rectal challenge with cow's milk protein (CM) and wheat gluten. Methods: A questionnaire about self-experienced adverse reaction to food was sent to 347 RA patients. Rectal challenge with CM and gluten was performed in 27 of these patients and in healthy controls (n = 18). After a 15-h challenge the mucosal production of nitric oxide (NO) and the mucosal release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured by using the mucosal patch technique. Results: Twenty-seven per cent of the RA patients reported food intolerance (FI) to various foods, and in particular to CM, meat, and wheat gluten. Strong mucosal reactivity to CM was observed in 11% of the patients. Moderately increased mucosal reactivity to CM and gluten was found in 22% and 33%, respectively, of the patients. No relationship was found between self-experienced adverse reactions to CM or gluten and mucosal reactivity to these proteins. Conclusions: Perceived FI is reported frequently by RA patients, with a prevalence similar to that reported previously in the general population. Mucosal reactivity to CM and gluten is seen in a minor fraction of RA patients and is not related to the frequently perceived intolerance to these proteins.

  • 143.
    Lidén, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Kristjánsson, Gudjón
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Valtýsdóttir, Sigrídur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Olofsson-Sahlqvist, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hällgren, Roger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Cow's milk protein and gluten-enviromental factors to be considered in the pathogenesis of spondyloarthropathiesManuscript (preprint) (Other academic)
  • 144.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Andersson, Jessika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Sandhagen, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Shear stress in the common carotid artery is related to both intima-media thickness and echogenecity: the prospective investigation of the vasculature in Uppsala seniors study2009In: Clinical hemorheology and microcirculation, ISSN 1386-0291, E-ISSN 1875-8622, Vol. 43, no 4, p. 299-308Article in journal (Refereed)
    Abstract [en]

    It has previously been shown that the degree of shear stress (SS) in the carotid artery is related to both plaque occurrence and intima-media thickness (IMT). Since the echogenecity also is an important feature of plaques, we investigated if a reduced shear stress also is related to the echolucency of plaque and the intima-media complex. In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, a population-based study of 1016 subjects aged 70, left common carotid artery diameter, IMT, the grey scale median (GSM) of the intima-media complex (IM-GSM) and the blood flow velocity were measured by ultrasound. Occurrence of plaque was noted, and the echogenecity of the plaques was visually estimated by the Gray-Weale classification. Shear stress was inversely related to both IMT and IM-GSM (p=0.0084 and p=0.003, respectively), independently of gender and coronary risk, estimated by the Framingham risk score. Shear stress was lower in subjects with carotid plaque (44% of the sample) than in those without (p=0.0013), and was inversely related to the echogenecity in the subjects with plaque (p=0.0092), independently of gender and coronary risk. A low shear stress in the common carotid artery was associated with both a thick IMT and an echolucent intima-media complex. A similar picture was seen when overt plaques were evaluated, suggesting that shear stress is of importance for both the extent and composition of atherosclerosis.

  • 145.
    Lind, Lars
    et al.
    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.
    Teerlink, Tom
    Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
    L-Arginine is related to endothelium-dependent vasodilation in resistance and conduit arteries in divergent ways-The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study2009In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Atherosclerosis, Vol. 203, no 2, p. 544-549Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of the conversion of l-arginine to the endothelium-derived vasodilator nitric oxide. We evaluated if circulating levels of l-arginine and ADMA, and the ratio thereof, were related to endothelium-dependent vasodilation in both resistance and conductance arteries in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study. METHODS AND RESULTS: In this population-based study, vascular function of 1016 subjects aged 70 was evaluated by the invasive forearm technique with intra-brachial infusion of acetylcholine (EDV), by measurement of flow-mediated dilation (FMD) of the brachial artery, and by change in reflectance index (RI) by pulse wave analysis. After adjustment for resting forearm blood flow, gender, Framingham risk score, and glomerular filtration rate, the l-arginine/ADMA ratio was positively related to EDV (P=0.005). This association was mainly driven by l-arginine, because if both l-arginine and ADMA were entered as predictor variables in a single regression model, l-arginine was positively associated with EDV (P=0.001), whereas the negative association between ADMA and EDV was not significant. In contrast, after adjustment for baseline brachial diameter, gender, Framingham risk score, and glomerular filtration rate, the l-arginine/ADMA ratio was negatively related to FMD (P=0.004). Again, this association was mainly driven by l-arginine (P=0.002), whereas ADMA was not significantly related to FMD. The change in RI was not related to l-arginine, ADMA or their ratio. CONCLUSIONS: In elderly subjects the l-arginine/ADMA ratio and l-arginine, but not ADMA, are positively related to endothelium-dependent vasodilation in resistance arteries, but negatively in a conduit artery.

  • 146.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hulthe, Johannes
    Elmgren, Anders
    C-reactive protein and e-selectin levels are related to vasodilation in resistance, but not conductance arteries in the elderly: the prospective investigation of the Vasculature in Uppsala Seniors (PIVUS) study2008In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 199, no 1, p. 129-137Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Divergent results have emerged in the past when relating single markers of inflammation to measures of vascular reactivity. The aim of the present study is to relate a wide range of inflammatory markers to vasoreactivity in both resistance and conductance arteries. METHODS: In the Prospective Investigation of the Vasculature in Uppsala Seniors (the PIVUS study), endothelium-dependent vasodilation was evaluated by the invasive forearm technique with acetylcholine given in the brachial artery (EDV), the brachial artery ultrasound technique with measurement of flow-mediated dilatation (FMD) and the pulse wave analysis method with beta-2 receptor agonist (terbutaline) provocation in 1016 subjects aged 70. A panel of 14 inflammatory markers, including cytokines, chemokines, adhesion molecules, CRP, sCD40 ligand and leukocyte count, was measured. RESULTS: After adjustment for gender and coronary risk factors, EDV was independently related to CRP levels and e-selectin in an inverse way (p<0.006 for both). FMD was not significantly related to any marker of inflammation after adjustment. Endothelium-independent vasodilation evaluated by the invasive forearm technique with sodium nitroprusside was also found to be related to both CRP and e-selectin in an inverse way (p=0.005 and p=0.045, respectively). CONCLUSION: Acetylcholine-induced vasodilation in the forearm, but not FMD, was inversely related to CRP and e-selectin levels independently of traditional risk factors in elderly subjects. As also endothelium-independent vasodilation was related to CRP and e-selectin, general vasoreactivity in resistance arteries seems to be effected by low-grade inflammation in elderly subjects.

  • 147.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kempf, Tibor
    Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany .
    Tapken, Heike
    Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany .
    Quint, Anja
    Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany .
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Olofsson, Sylvia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    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.
    Hulthe, Johannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Elmgren, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wollert, Kai C
    Growth-differentiation factor-15 is an independent marker of cardiovascular dysfunction and disease in the elderly: results from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) Study2009In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 30, no 19, p. 2346-2353Article in journal (Refereed)
    Abstract [en]

    AIMS: Growth-differentiation factor-15 (GDF-15) is emerging as an independent prognostic biomarker in patients with cardiovascular (CV) disease. Little is known about the pathophysiological basis for the close association of GDF-15 to future CV events. We hypothesized that GDF-15 is related to underlying CV pathologies. METHODS AND RESULTS: To relate the levels of GDF-15 to indices of CV dysfunction and disease in elderly individuals, serum levels of GDF-15 were measured in 1004 subjects aged 70 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Carotid intima-media thickness and plaque burden, and left ventricular (LV) geometry and function were assessed by ultrasound. Endothelial function was evaluated in forearm resistance vessels and in the brachial artery by venous occlusion plethysmography and ultrasound imaging, respectively. Elevated levels of GDF-15 were related to several CV risk factors (male gender, current smoking, body mass index, waist circumference, diabetes, fasting glucose, triglycerides, and low HDL cholesterol). After adjustment for CV risk factors, increased levels of GDF-15 were associated with reduced endothelium-dependent vasodilation in resistance vessels, plaque burden, LV mass and concentric LV hypertrophy, reduced LV ejection fraction, and clinical manifestations of coronary artery disease and heart failure. CONCLUSION: GDF-15 carries information on CV dysfunction and disease that is not captured by traditional CV risk factors in elderly individuals.

  • 148.
    Lindahl, Bertil
    et al.
    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.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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.
    Serial analyses of N-terminal pro-B-type natriuretic peptide in patients with non-ST-segment elevation acute coronary syndromes: a Fragmin and fast Revascularisation during In Stability in Coronary artery disease (FRISC)-II substudy2005In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 45, no 4, p. 533-541Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    The aim of this research was to describe N-terminal part of the pro-B-type natriuretic peptide (NT-proBNP) levels over time in non-ST-segment elevation acute coronary syndromes (NSTEACS), to elucidate factors associated with changes of NT-proBNP levels, and to examine association with long-term mortality.

    BACKGROUND:

    The NT-proBNP levels are associated with mortality. Long-term temporal changes of NT-proBNP levels and their relation to other factors have not been examined.

    METHODS:

    The NT-proBNP was analyzed at randomization and at 48 h, after 6 weeks, 3 and 6 months in NSTEACS patients enrolled in the Fragmin and fast Revascularisation during InStability in Coronary artery disease (FRISC)-II trial. The NT-proB-type natriuretic peptide was analyzed at least three time points in 1,216 patients.

    RESULTS:

    The median NT-proBNP level, which at randomization was 529 ng/l, decreased throughout the whole sampling period to 238 ng/l at six months. Elevated troponin T, C-reactive protein, and female gender were associated with higher reduction rates, and high age, diabetes, previous myocardial infarction, treatment with diuretics, and nitrates on admission with lower reduction rates. At each time point, the NT-proBNP level was predictive of the two-year mortality. However, the adjusted odds ratio increased for each time point.

    CONCLUSIONS:

    The initial rise of NT-proBNP in NSTEACS is mainly reversible. Factors associated with less reversibility are related to chronically impaired left ventricular function, and factors associated with greater reversibility are related to the acute myocardial damage. The NT-proBNP level measured during a chronic, relatively stable phase is a better predictor of mortality than during an acute unstable phase. The clinical setting and timing of measurement will be important to consider when using NT-proBNP for risk assessment.

  • 149.
    Lindahl, Bertil
    et al.
    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.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    James, Stefan
    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.
    The new high-sensitivity cardiac troponin T assay improves risk assessment in acute coronary syndromes2010In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 160, no 2, p. 224-229Article in journal (Refereed)
    Abstract [en]

    Background Cardiac troponins are currently the markers of choice for diagnosis of acute myocardial infarction and risk assessment in acute coronary syndrome (ACS). With the introduction of the new high-sensitivity cardiac troponin T (hs-cTnT) assay, it has become possible to measure cTnT even in healthy subjects. However, how the hs-cTnT assay compares with the old cTnT assay for risk assessment in ACS is still unknown. Methods Cardiac troponin T levels were measured with the new hs-cTnT assay and the old third-generation cTnT assay in serum samples collected 48 hours after randomization in 1,452 randomly selected ACS patients enrolled in the GUSTO-IV trial. During 30 days of follow-up, deaths and myocardial infarctions were recorded. At 12 months, only all-cause mortality was collected. Results The 16% of the patients that had levels higher than the 99th percentile cutoff for hs-cTnT but less than for cTnT had a similar 1-year mortality as the 60% that were positive for both assays (9.2% vs 10.7%, P = .52) and a higher 1-year mortality compared with the 24% that were negative for both assays (9.2% vs 2.6%, P = .001). For death or acute myocardial infarction at 30 days, the group that was positive only for hs-cTnT had an intermediate risk compared with the groups negative or positive for both assays (2.4%, 5.2%, and 8.7%; P < .001). Conclusion The new hs-cTnT assay, compared with the old cTnT assay, identified more patients with myocardial damage and who were at an increased risk for new cardiac events.

  • 150.
    Lindholm, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bixo, Marie
    Björn, Inger
    Wölner-Hanssen, Pål
    Eliasson, Mats
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Johnson, Owe
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Effect of sibutramine on weight reduction in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial2008In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 89, no 5, p. 1221-1228Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine the efficacy of sibutramine together with brief lifestyle modification for weight reduction in obese women with polycystic ovary syndrome (PCOS). DESIGN: Investigator-initiated, multicenter, double-blind, randomized, parallel-group clinical trial. SETTING: Departments of Obstetrics and Gynecology in primary care, referral centers, and private practice. PATIENT(S): Forty-two patients with confirmed PCOS were included in the study, and 34 patients completed the study. INTERVENTION: Sibutramine 15 mg once daily together with brief lifestyle modification was compare with placebo together with brief lifestyle modification. MAIN OUTCOME MEASURE(S): The primary endpoint was to assess weight loss. Secondary endpoints included the efficacy of sibutramine for treatment of menstrual pattern and cardiovascular risk factors. RESULT(S): After 6 months the sibutramine group had lost 7.8 +/- 5.1 kg compared with a weight loss of 2.8 +/- 6.2 kg in the placebo group. Sibutramine treatment resulted in significant decreases in apolipoprotein B, apolipoprotein B/apolipoprotein A ratio, triglycerides, and cystatin C levels. CONCLUSION(S): Sibutramine in combination with lifestyle intervention results in significant weight reduction in obese patients with PCOS. In addition to the weight loss, sibutramine seems to have beneficial effects on metabolic and cardiovascular risk factors.

123456 101 - 150 of 295
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf