umu.sePublications
Change search
Refine search result
456789 301 - 350 of 411
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.
  • 301.
    Schneede, Jörn
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences, Clinical chemistry.
    Ueland, Per Magne
    Novel and established markers of cobalamin deficiency: complementary or exclusive diagnostic strategies.2005In: Semin Vasc Med, ISSN 1528-9648, Vol. 5, no 2, p. 140-55Article, review/survey (Other (popular science, discussion, etc.))
  • 302.
    Schock, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. German Cancer Research Center, Heidelberg.
    Fortner, Renée T
    German Cancer Research Center, Heidelberg.
    Surcel, Heljä-Marja
    National Institute for Health and Welfare, Oulu, Finland.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Pukkala, Eero
    School of Public Health, University of Tampere, Finland.
    Lehtinen, Matti
    School of Public Health, University of Tampere, Finland.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Early pregnancy IGF-I and placental GH and risk of epithelial ovarian cancer: A nested case-control study2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 137, no 2, p. 439-447Article in journal (Refereed)
    Abstract [en]

    Insulin-like growth factor-I (IGF-I) signaling may promote ovarian tumor development by exerting mitotic, antiapoptotic and proangiogenic effects. During pregnancy, maternal production of IGF-I is regulated by placental growth hormone (GH). Parity is an established protective factor for ovarian cancer, however, no prior study has evaluated placental GH and IGF-I in pregnancy and epithelial ovarian cancer (EOC). Prior prospective studies on the association between IGF-I and EOC in nonpregnant populations were inconclusive and did not address associations in subtypes of EOC. Among members of the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort, we identified 1,045 EOC cases, diagnosed after recruitment (1975-2008) and before March 2011 and 2,658 individually matched controls. Placental GH and IGF-I were measured in serum from the last pregnancy before EOC diagnosis or selection as control. We used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles and a doubling of hormone concentrations. Higher IGF-I was associated with a nonsignificant decrease in risk for invasive [ORT3 vs. T1 : 0.79 (0.62-1.02); ptrend  = 0.07] and endometrioid tumors [ORT3 vs. T1 : 0.55 (0.28-1.07); ptrend  = 0.07]. The protective association between higher IGF-I levels and risk of invasive EOC was stronger in analyses limited to women aged <55 years at diagnosis [ORT3 vs. T1 : 0.74 (0.57-0.96); ptrend  = 0.03]. Our study provides the first data on placental GH and IGF-I in pregnancy and EOC risk overall and by subtype. Our data suggest higher IGF-I levels in pregnancy may be associated with lower risk of invasive and endometrioid EOC.

  • 303.
    Schock, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Vääräsmäki, M.
    Oulu, Finland.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Fry, A.
    London, UK.
    Dorgan, J. F.
    Baltimore, MD, USA.
    Pukkala, E.
    Helsinki, Finland; Tampere, Finland.
    Lehtinen, M.
    Tampere, Finland.
    Surcel, H. M.
    Oulu, Finland.
    Lukanova, Annekatrin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer.
    Anti-Mullerian hormone and risk of invasive serous ovarian cancer2014In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 25, no 5, p. 583-589Article in journal (Refereed)
    Abstract [en]

    Epithelial ovarian cancers either arise directly from Mullerian-type epithelium or acquire Mullerian characteristics in the course of neoplastic transformation. The anti-Mullerian hormone (AMH) causes regression of Mullerian structures during fetal development in males and has been shown to inhibit the growth of epithelial ovarian cancer. Therefore, we hypothesized that pre-diagnostic serum concentrations of AMH are inversely associated with risk of invasive serous ovarian cancer. A case-control study (107 cases, 208 controls) was nested within the population-based Finnish Maternity Cohort (1986-2007). The sample donated during the first trimester of the last pregnancy preceding cancer diagnosis of the case subjects was selected for the study. For each case, two controls, matched on age and date at sampling, as well as parity at sampling and at cancer diagnosis were selected. AMH was measured by a second-generation AMH ELISA. Conditional logistic regression was used to compute odds ratios (OR) and 95 % confidence intervals (CI) for invasive serous ovarian cancer associated with AMH concentrations. Overall AMH concentrations were not associated with risk of invasive serous ovarian cancer (OR 0.93; 95 % CI 0.49-1.77 for top vs. bottom tertile, P (trend) = 0.83). In women older than the median age at sampling (32.7 years), a doubling of AMH was associated with decreased risk (OR 0.69; 95 % CI 0.49-0.96), whereas an increased risk (OR 1.64; 95 % CI 1.06-2.54) was observed in younger women, P (homogeneity) = 0.002. In this first prospective investigation, risk of invasive serous ovarian cancer was not associated with pre-diagnostic AMH concentrations overall; however, the association may depend on age at AMH measurement.

  • 304.
    Schock, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
    Surcel, Helja-Marja
    Oulu, Finland.
    Zeleniuch-Jacquotte, Anne
    Umeå University, Faculty of Medicine, Department of Biobank Research. New York, USA.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Lakso, Hans-Åke
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Fortner, Renee Turzanski
    Heidelberg, Germany.
    Kaaks, Rudolf
    Heidelberg, Germany.
    Pukkala, Eero
    Helsinki, Finland; Tampere, Finland.
    Lehtinen, Matti
    Tampere, Finland.
    Toniolo, Paolo
    New York, USA; Lausanne, Switzerland.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Early pregnancy sex steroids and maternal risk of epithelial ovarian cancer2014In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 21, no 6, p. 831-844Article in journal (Refereed)
    Abstract [en]

    Well-established associations between reproductive characteristics and epithelial ovarian cancer (EOC) support an involvement of sex steroid hormones in the etiology of EOC. Limited previous studies have evaluated circulating androgens and the risk of EOC, and estrogens and progesterone have been investigated in only one of the previous studies. Furthermore, there is little data on potential heterogeneity in the association between circulating hormones and EOC by histological subgroup. Therefore, we conducted a nested case-control study within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort to investigate the associations between circulating pre-diagnostic sex steroid concentrations and the histological subtypes of EOC. We identified 1052 EOC cases among cohort members diagnosed after recruitment (1975-2008) and before March 2011. Up to three controls were individually matched to each case (n=2694). Testosterone, androstenedione, 17-hydroxyprogesterone (17-OHP), progesterone, estradiol (E-2), and sex hormone-binding globulin levels were measured in serum samples collected during the last pregnancy before EOC diagnosis. We used conditional logistic regression to estimate odds ratios (ORs) and 95% CIs. Associations between hormones and EOC differed with respect to tumor histology and invasiveness. Sex steroid concentrations were not associated with invasive serous tumors; however, doubling of testosterone and 17-OHP concentration was associated with approximately 40% increased risk of borderline serous tumors. A doubling of androgen concentrations was associated with a 50% increased risk of mucinous tumors. The risk of endometrioid tumors increased with higher E-2 concentrations (OR: 1.89 (1.20-2.98)). This large prospective study in pregnant women supports a role of sex steroid hormones in the etiology of EOC arising in the ovaries.

  • 305.
    Schock, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
    Zeleniuch-Jacquotte, Anne
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Lakso, Hans-Åke
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Lehtinen, Matti
    Surcel, Heljä-Marja
    Fortner, Renee T.
    Hormone concentrations throughout uncomplicated pregnancies: a longitudinal study2016In: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 16, article id 146Article in journal (Refereed)
    Abstract [en]

    Background: Evidence suggests that the hormonal milieu of pregnancy is an important determinant of subsequent cancer and other chronic diseases in both the mother and the offspring. Many of the existing maternity and birth cohorts include specimens drawn only once during pregnancy. How well a single blood specimen collected during a pregnancy characterizes exposure to these hormones throughout gestation, and also in subsequent pregnancies, is not well understood.

    Methods: We used serial serum samples from 71 pregnant women (25 primiparous, 25 multiparous, and 21 with two consecutive pregnancies) with natural, complication-free pregnancies and a healthy offspring at term who participated in a population-based screening trial for congenital infections in Finland between January 1st, 1988 and June 30, 1989 and provided a blood sample in each trimester.

    Results: Hormone levels were more strongly correlated between consecutive trimesters of a pregnancy than between the 1st and 3rd trimester (e.g., estradiol, r(T1 vs. T2) = 0.51 and r(T2 vs. T3) = 0.60, p < 0.01; r(T1 vs. T3) = 0.32, p < 0.05). Concentrations of sRANKL remained stable throughout gestation, whereas estradiol, estrone, progesterone, testosterone, prolactin, and osteoprotegerin increased throughout pregnancy. First trimester hormone concentrations explained less of the variation in the third trimester on their own than second trimester hormone levels (e.g. estradiol R-T1(2) = 16 % and R-T2(2) = 42 %). Addition of maternal (e.g., smoking) and/or child characteristics (e.g., sex) improved the accuracy of the 3rd trimester estimates for some of the hormones.

    Conclusions: One hormone measurement in early pregnancy, in conjunction with maternal and fetal characteristics, permits estimation of 3rd trimester hormone concentrations. Therefore, single hormone measurements available from maternity cohorts are suitable to quantify hormone exposure during pregnancy. To our knowledge, we provide the first data on correlations between hormone concentrations both across trimesters of a single pregnancy, as well as between two subsequent pregnancies.

  • 306.
    Sentman, Marie-Louise
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences, Clinical chemistry.
    Granström, Micael
    Umeå University, Faculty of Medicine, Medical Biosciences.
    Jakobson, Håkan
    Umeå University, Faculty of Medicine, Medical Biosciences, Clinical chemistry.
    Reaume, Andrew
    Basu, Samar
    Marklund, Stefan
    Umeå University, Faculty of Medicine, Medical Biosciences, Clinical chemistry.
    Phenotypes of mice lacking extracellular superoxide dismutase and copper- and zinc-containing superoxide dismutase.2006In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 281, no 11, p. 6904-6909Article in journal (Refereed)
  • 307. Simundic, AM
    et al.
    Cornes, M
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Lippi, G
    Nybo, M
    Standardization of collection requirements for fasting samples for the working group on preanalytical phase (WG-PA) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)2014In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 432, p. 33-37Article in journal (Refereed)
    Abstract [en]

    Standardized protocols for patient preparation for laboratory testing are currently lacking. Moreover, a great heterogeneity exists in the definitions of "fasting" currently being used among healthcare workers and in the literature. Marked metabolic and hormonal changes occur after food ingestion, mainly due to the absorption of fluids, lipids, proteins, carbohydrates and other food constituents. This postprandial response varies markedly in response to numerous factors, such as eating behavior, food composition, fasting duration, time of the day, chronic and acute smoking, coffee and alcohol consumption. It is therefore crucial to minimize the total variability by controlling as many of these modifying factors as possible. Control of the abovementioned effects on postprandial response can only be achieved by standardizing the way patients are prepared for laboratory testing, i.e. by defining the fasting duration, as well as what is and what is not allowed (e.g., coffee, tea, smoking, water) during the period of fasting prior to sample collection. The aim of this article is to describe the range of effects of different approaches to fasting on laboratory tests, and to provide a framework for the harmonization of definitions for fasting requirements for laboratory tests.

    (C) 2013 Elsevier B.V. All rights reserved.

  • 308. Simundic, Ana-Maria
    et al.
    Bölenius, Karin
    Umeå University, Faculty of Medicine, Department of Nursing.
    Cadamuro, Janne
    Church, Stephen
    Cornes, Michael P.
    van Dongen-Lases, Edmée C.
    Eker, Pinar
    Erdeljanovic, Tanja
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Guimaraes, Joao Tiago
    Hoke, Roger
    Ibarz, Mercedes
    Ivanov, Helene
    Kovalevskaya, Svetlana
    Kristensen, Gunn B. B.
    Lima-Oliveira, Gabriel
    Lippi, Giuseppe
    von Meyer, Alexander
    Nybo, Mads
    De la Salle, Barbara
    Seipelt, Christa
    Sumarac, Zorica
    Vermeersch, Pieter
    Joint EFLM-COLABIOCLI recommendation for venous blood sampling2018In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 56, no 12, p. 2015-2038Article in journal (Refereed)
    Abstract [en]

    This document provides a joint recommendation for venous blood sampling of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for Preanalytical Phase (WG-PRE) and Latin American Working Group for Preanalytical Phase (WG-PRE-LATAM) of the Latin America Confederation of Clinical Biochemistry (COLABIOCLI). It offers guidance on the requirements for ensuring that blood collection is a safe and patient-centered procedure and provides practical guidance on how to successfully overcome potential barriers and obstacles to its widespread implementation. The target audience for this recommendation are healthcare staff members directly involved in blood collection. This recommendation applies to the use of a closed blood collection system and does not provide guidance for the blood collection with an open needle and syringe and catheter collections. Moreover, this document neither addresses patient consent, test ordering, sample handling and transport nor collection from children and unconscious patients. The recommended procedure is based on the best available evidence. Each step was graded using a system that scores the quality of the evidence and the strength of the recommendation. The process of grading was done at several face-to-face meetings involving the same mixture of stakeholders stated previously. The main parts of this recommendation are: 1) Pre-sampling procedures, 2) Sampling procedure, 3) Post-sampling procedures and 4) Implementation. A first draft of the recommendation was circulated to EFLM members for public consultation. WG-PRE-LATAM was also invited to comment the document. A revised version has been sent for voting on to all EFLM and COLABIOCLI members and has been officially endorsed by 33/40 EFLM and 21/21 COLABIOCLI members. We encourage professionals throughout Europe and Latin America to adopt and implement this recommendation to improve the quality of blood collection practices and increase patient and workers safety.

  • 309. Simundic, Ana-Maria
    et al.
    Church, Stephen
    Cornes, Michael P
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry. European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for Preanalytical Phase (WG-PRE).
    Lippi, Giuseppe
    Nybo, Mads
    Nikolac, Nora
    van Dongen-Lases, Edmee
    Eker, Pinar
    Kovalevskaya, Svjetlana
    Kristensen, Gunn B B
    Sprongl, Ludek
    Sumarac, Zorica
    Compliance of blood sampling procedures with the CLSI H3-A6 guidelines: an observational study by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) working group for the preanalytical phase (WG-PRE)2015In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 53, no 9, p. 1321-1331Article in journal (Refereed)
    Abstract [en]

    Background: An observational study was conducted in 12 European countries by the European Federation of Clinical Chemistry and Laboratory Medicine Working Group for the Preanalytical Phase (EFLM WG-PRE) to assess the level of compliance with the CLSI H3-A6 guidelines. Methods: A structured checklist including 29 items was created to assess the compliance of European phlebotomy procedures with the CLSI H3-A6 guideline. A risk occurrence chart of individual phlebotomy steps was created from the observed error frequency and severity of harm of each guideline key issue. The severity of errors occurring during phlebotomy was graded using the risk occurrence chart. Results: Twelve European countries participated with a median of 33 (18-36) audits per country, and a total of 336 audits. The median error rate for the total phlebotomy procedure was 26.9 % (10.6-43.8), indicating a low overall compliance with the recommended CLSI guideline. Patient identification and test tube labelling were identified as the key guideline issues with the highest combination of probability and potential risk of harm. Administrative staff did not adhere to patient identification procedures during phlebotomy, whereas physicians did not adhere to test tube labelling policy. Conclusions: The level of compliance of phlebotomy procedures with the CLSI H3-A6 guidelines in 12 European countries was found to be unacceptably low. The most critical steps in need of immediate attention in the investigated countries are patient identification and tube labelling.

  • 310. Simundic, Ana-Maria
    et al.
    Cornes, Michael
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Lippi, Giuseppe
    Nybo, Mads
    Kovalevskaya, Svjetlana
    Sprongl, Ludek
    Sumarac, Zorica
    Church, Stephen
    Survey of national guidelines, education and training on phlebotomy in 28 European countries: an original report by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) working group for the preanalytical phase (WG-PA)2013In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 51, no 8, p. 1585-1593Article in journal (Refereed)
  • 311.
    Sitaram, Raviprakash T
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Andersson, Emma
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Oji, Y
    Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
    Sugiyama, H
    Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Li, Ai-Hong
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Wilms' tumour 1 can suppress hTERT gene expression and telomerase activity in clear cell renal cell carcinoma via multiple pathways2010In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 103, no 8, p. 1255-1262Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Wilms' tumour 1 (WT1) gene was discovered as a tumour suppressor gene. Later findings have suggested that WT1 also can be oncogenic. This complexity is partly explained by the fact that WT1 has a number of target genes.

    METHOD: WT1 and its target gene human telomerase reverse transcriptase (hTERT) were analysed in clear cell renal cell carcinoma (ccRCC). In vitro experiments were performed to examine the functional link between WT1 and hTERT by overexpression of WT1 isoforms in the ccRCC cell line, TK-10.

    RESULTS: WT1 demonstrated lower RNA expression in ccRCC compared with renal cortical tissue, whereas hTERT was increased, showing a negative correlation between WT1 and hTERT (P=0.005). These findings were experimentally confirmed in vitro. The WT1 generated effect on hTERT promoter activity seemed complex, as several negative regulators of hTERT transcription, such as SMAD3, JUN (AP-1) and ETS1, were activated by WT1 overexpression. Downregulation of potential positive hTERT regulators, such as cMyc, AP-2α, AP-2γ, IRF1, NFX1 and GM-CSF, were also observed. Chromatin immunoprecipitation analysis verified WT1 binding to the hTERT, cMyc and SMAD3 promoters.

    CONCLUSION: The collected data strongly indicate multiple pathways for hTERT regulation by WT1 in ccRCC.

  • 312.
    Slunga, Lisbeth
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Serum lipoprotein(a) in relation to ischemic heart disease and associated risk factors1993Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Lipoprotein(a) (Lp(a)) consists of an LDL-like particle and the specific protein apo(a), which is very similar to plasminogen. Apo(a) contains repeated kringle structures and a serine protease domain, which cannot be activated by t-PA. Lp(a) is considered to be a predictor for atherosclerotic disease. It has been found incorporated in atherosclerotic plaques and inhibits in vitro fibrinolysis.

    Lp(a) was determined in 1527 randomly selected individuals participating in the Northern Sweden WHO-MONICA project. A weak but significant relation between Lp(a) and increasing age was found. Menopausal status was the strongest independent predictor of Lp(a) level in women. Fibrinogen was independently related to Lp(a) in both sexes. Only a minor fraction of Lp(a) variance could be explained for in a multiple regression model, which is in agreement with the contention that Lp(a) is highly genetically determined.

    Lp(a) was determined in 1571 patients investigated with coronary angiography because of suspected severe coronary artery disease (CAD). Patients with proven CAD at elective angiography had significantly higher Lp(a) than patients without significant CAD or healthy controls. Lp(a) was found to be an independent discriminator of CAD in both sexes.

    HLA-DR genotype 13 or 17 was found more frequently in 30 male patients with angiographic CAD at young age (< 50 years) than in 30 age matched controls. These genotypes were common in patients with high Lp(a) levels, which indicates that Lp(a) may be related to immunological processes.

    The reaction of Lp(a) was investigated in 32 patients with acute myocardial infarction (AMI). Lp(a) increased during the first week, but the response was comparatively weak. Individual Lp(a) responses were heterogeneous and no correlations to infarct size or changes in the acute phase proteins were found.

    In a randomized cross-over study on 36 hypercholesterolaemic patients treated with simvastatin/placebo during 12+12 weeks Lp(a) did not change significantly, but patients with high Lp(a) levels at baseline tended to develop further increased Lp(a).

    To conclude, Lp(a) was found to be an independent predictor of angiographic CAD in both men and women. Lp(a) levels are primarily genetically determined and only a small fraction of Lp(a) variance could be explained by other factors in this study. Lp(a) may be related to HLA DR types and immunological processes involved in atherosclerotic disease. Lp(a) increased slightly during the first week of AMI, but was not related to changes in the acute-phase proteins. The effective LDL-lowering agent simvastatin did not influence Lp(a) significantly.

  • 313.
    Späth, Florentin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Dahlin, Anna M.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Computational Life Science Cluster (CLiC), Umeå University, 901 87 Umeå, Sweden.
    Langseth, Hilde
    Hovig, Eivind
    Johannesen, Tom Borge
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Björkblom, Benny
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Computational Life Science Cluster (CLiC), Umeå University, 901 87 Umeå, Sweden.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Pre-diagnostic serum levels of EGFR and ErbB2 and genetic glioma risk variants: a nested case-control study2016In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 37, no 8, p. 11065-11072Article in journal (Refereed)
    Abstract [en]

    Genetic variants have been associated with the risk of developing glioma, but functional mechanisms on disease phenotypic traits remain to be investigated. One phenotypic trait of glioblastoma is the mutation and amplification of the epidermal growth factor receptor (EGFR) gene. We investigated associations between pre-diagnostic serum protein concentrations of EGFR and ErbB2, both members of the EGFR family, and future risk of glioma. Further, we studied if EGFR glioma risk variants were associated with EGFR and ErbB2 serum levels. We assessed the associations between genetic glioma risk variants and serum concentrations of EGFR and ErbB2, as measured in pre-diagnostic cohort serum samples of 593 glioma patients and 590 matched cancer-free controls. High serum EGFR and ErbB2 levels were associated with risk of developing glioblastoma (P = 0.008; OR = 1.58, 95 % CI = 1.13-2.22 and P = 0.017, OR = 1.63, 95 % CI = 1.09-2.44, respectively). High serum ErbB2 concentration was also associated with glioma risk overall (P = 0.049; OR = 1.39, 95 % CI = 1.00-1.93). Glioma risk variants were not associated with high serum protein abundance. In contrast, the EGFR risk variant rs4947986 (T) was correlated with decreased EGFR serum levels (study cohort P = 0.024 and controls P = 0.009). To our knowledge, this is the first study showing an association of EGFR and ErbB2 serum levels with glioma more than a decade before diagnosis, indicating that EGFR and ErbB2 serum proteins are important in early gliomagenesis. However, we did not find evidence that glioma risk variants were associated with high pre-diagnostic serum concentrations of EGFR and ErbB2.

  • 314.
    Späth, Florentin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Krop, Esmeralda
    Utrecht University.
    Izarra Santamaria, Antonio
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Ann Sofie
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Vermeulen, Roel
    Utrecht University.
    Melin, Beatrice S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Immune marker changes and risk of multiple myeloma: a nested case-control study using repeated prediagnostic blood samples2019In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 104, no 12, p. 2456-2464Article in journal (Refereed)
    Abstract [en]

    Biomarkers reliably predicting progression to multiple myeloma (MM) are lacking. Myeloma risk has been associated with low blood levels of monocyte chemotactic protein-3 (MCP-3), macrophage inflammatory protein-1 alpha (MIP-1 alpha), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), fractalkine, and transforming growth factor-alpha (TGF-alpha). In this study, we aimed to replicate these findings and study the individual dynamics of each marker in a prospective longitudinal cohort, thereby examining their potential as markers of myeloma progression. For this purpose, we identified 65 myeloma cases and 65 matched cancer-free controls each with two donated blood samples within the Northern Sweden Health and Disease Study. The first and repeated samples from myeloma cases were donated at a median 13 and 4 years, respectively, before the myeloma was diagnosed. Known risk factors for progression were determined by protein-, and immunofixation electrophoresis, and free light chain assays. We observed lower levels of MCP-3, VEGF, FGF-2, and TGF-alpha in myeloma patients than in controls, consistent with previous data. We also observed that these markers decreased among future myeloma patients while remaining stable in controls. Decreasing trajectories were noted for TGF-alpha (P=2.5 x 10(-4)) indicating progression to MM. Investigating this, we found that low levels of TGF-alpha assessed at the time of the repeated sample were independently associated with risk of progression in a multivariable model (hazard ratio = 3.5; P=0.003). TGF-alpha can potentially improve early detection of MM.

  • 315.
    Stegmayr, Bernd
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Forsberg, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jonson, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Christofer
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Microbubbles of air may occur in the organs of hemodialysis patients2012In: ASAIO journal (1992), ISSN 1058-2916, E-ISSN 1538-943X, Vol. 58, no 2, p. 177-179Article in journal (Refereed)
    Abstract [en]

    During hemodialysis (HD), blood that passes the dialysis device gets loaded with microbubbles (MB) of air that are returned to the patient without inducing an alarm. The aim with this study was to clarify if these signals are due to microembolies of air, clots, or artifacts, by histopathology of autopsy material of HD patients. These first results are from a patient on chronic HD. Due to pulmonary edema he was ultrafiltered. Within 30 minutes after the start, he suffered from a cardiac arrest and died. Autopsy verified the clinical findings. Microscopic investigation verified microembolies of air that were surrounded by fibrin in the lungs, brain, and heart. The study verified that MBs can enter the blood during HD and are trapped in the lungs. In addition, MBs pass the pulmonary capillaries and enter the arterial part of the body and are dispersed throughout the body. This can contribute to organ damage and be part of the poor prognoses seen in HD patients. Data support the importance to reduce MBs in the dialysis circuit.

  • 316. Stenson, Martin
    et al.
    Pedersen, Anders
    Hasselblom, Sverker
    Nilsson-Ehle, Herman
    Karlsson, Bengt Göran
    Pinto, Rui
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry. Bioinformatics for Life Sciences (BILS), Gothenburg, Sweden.
    Andersson, Per-Ola
    Serum nuclear magnetic resonance-based metabolomics and outcome in diffuse large B-cell lymphoma patients - a pilot study2016In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 57, no 8, p. 1814-1822Article in journal (Refereed)
    Abstract [en]

    The prognosis for diffuse large B-cell lymphoma (DLBCL) patients with early relapse or refractory disease is dismal. To determine if clinical outcome correlated to diverse serum metabolomic profiles, we used H-1 nuclear magnetic resonance (NMR) spectroscopy and compared two groups of DLBCL patients treated with immunochemotherapy: i) refractory/early relapse (REF/REL; n=27) and ii) long-term progression-free (CURED; n=60). A supervised multivariate analysis showed a separation between the groups. Among discriminating metabolites higher in the REF/REL group were the amino acids lysine and arginine, the degradation product cadaverine and a compound in oxidative stress (2-hydroxybutyrate). In contrast, the amino acids aspartate, valine and ornithine, and a metabolite in the glutathione cycle, pyroglutamate, were higher in CURED patients. Together, our data indicate that NMR-based serum metabolomics can identify a signature for DLBCL patients with high-risk of failing immunochemotherapy, prompting for larger validating studies which could lead to more individualized treatment of this disease.

  • 317.
    Stewart, H G
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Mackenzie, I R
    Eisen, A
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Marklund, Stefan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Andersen, P M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Clinicopathological phenotype of ALS with a novel G72C SOD1 gene mutation mimicking a myopathy.2006In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 33, no 5, p. 701-706Article in journal (Refereed)
    Abstract [en]

    A 71-year-old woman with a family history of amyotrophic lateral sclerosis (ALS) was investigated for symmetrical, proximal limb and abdominal muscle weakness. Initial examination showed mild proximal muscle weakness in the arms and legs, slightly elevated serum creatine kinase (CK) level, and normal electromyographic (EMG) findings. A myopathy was the presumed diagnosis. Over the next year, weakness became severe and tendon reflexes became unelicitable; no upper motor signs were present. EMG then showed acute and chronic denervation and a muscle biopsy showed target fibers and grouped atrophy. DNA analysis revealed a G72C CuZn-superoxide dismutase (SOD1) mutation. Fasciculations were absent throughout the disease. The patient died 53 months after symptom onset and autopsy revealed loss of lower motor neurons (LMN) and SOD1-positive inclusions. This case expands the phenotypic spectrum of ALS associated with SOD1 mutations to include presenting features that mimic a myopathy.

  • 318.
    Strand, Isabel
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Temozolomid kan öka strålningskänsligheten hos gliomceller: Uttryck av resistensproteiner hos U-343 MG och U-87 MG2010Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 319. Strand, Tor A
    et al.
    Taneja, Sunita
    Bhandari, Nita
    Refsum, Helga
    Ueland, Per M
    Gjessing, Håkon K
    Bahl, Rajiv
    Schneede, Joern
    Umeå University, Faculty of Medicine, Medical Biosciences, Clinical chemistry.
    Bhan, Maharaj K
    Sommerfelt, Halvor
    Folate, but not vitamin B-12 status, predicts respiratory morbidity in north Indian children.2007In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 86, no 1, p. 139-144Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Vitamin deficiencies are often part of malnutrition, which predisposes to acute lower respiratory tract infections. OBJECTIVE: The objective was to measure the association between cobalamin and folate status and subsequent respiratory morbidity. DESIGN: A prospective cohort study was conducted in 2482 children aged 6-30 mo nested in a zinc supplementation trial. We measured plasma concentrations of folate, cobalamin, methylmalonic acid, and total homocysteine (tHcy) and followed the children for 4 mo. RESULTS: We observed 1176 episodes of acute lower respiratory tract infections. Children with folate concentrations in the lowest quartile (interquartile range: 6.4-20.0 nmol/L) had a 44% higher incidence [adjusted incidence rate ratio (IRR): 1.44; 95% CI: 1.23, 1.70] of acute lower respiratory tract infections than did children in the other 3 quartiles. For tHcy, the IRR was 1.24 (1.07, 1.40) in a comparison of those in the highest quartile with those in the other quartiles. Breastfeeding was associated with high folate concentrations and protection against subsequent respiratory tract infections. This protection was significantly and substantially reduced after adjustment for plasma folate concentrations at baseline. Compared with the children in the other 3 quartiles, the IRR for being in the lowest quartile of cobalamin was 1.13 (0.76, 1.03) and for being in the highest quartile of methylmalonic acid was 1.12 (0.96, 1.31). CONCLUSIONS: Poor folate status appears to be an independent risk factor for lower respiratory tract infections in young children. This study also suggests that the protective effect of breastfeeding is partly mediated by folate provided through breast milk.

  • 320.
    Ström, Mattias
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Preanalytisk inverkan vid klinisk analys av joniserat kalcium, glukos, laktat samt zink i blodprover2014Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 321.
    Stålnacke, Britt-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Björnstig, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Karlsson, Kurt
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Sojka, Peter
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Rehabilitation Medicine.
    One-year follow-up of patients with mild traumatic brain injury: post-concussion symptoms, disabilities and life satisfaction at follow-up in relation to serum levels of S-100B and neuron-specific enolase in acute phase2005In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 37, no 5, p. 300-305Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate, in patients with mild traumatic brain injury, serum concentrations of S-100B and neurone-specific enolase in acute phase and post-concussion symptoms, disabilities and life satisfaction 1 year after the trauma.

    DESIGN: Prospective study.

    PATIENTS: Eighty-eight patients (age range 18-87 years).

    METHODS: Blood samples were taken on admission and about 7 hours later. At follow-up 15 +/- 4 months later, the patients filled in questionnaires about symptoms (Rivermead Post Concussion Symptoms), disability (Rivermead Head Injury Follow-up) and life satisfaction (LiSat-11).

    RESULTS: Concentrations of S-100B and neurone-specific enolase were regularly increased in the first blood sample. Of the 69 patients participating in the follow-up, 45% reported post-concussion symptom, 48% exhibited disability and 55% were satisfied with "life as a whole". In comparison with the "sick-leave" situation on admission to hospital, 3 patients were on sick-leave at the time of follow-up because of the head trauma. Stepwise forward logistic regression analysis revealed a statistically significant association (p<0.05) between disability and S-100B and dizziness.

    CONCLUSION: In spite of frequent persistent symptoms, disabilities and low levels of life satisfaction, the sick-leave frequency was low at follow-up. The association between S-100B and disability supports the notion that long-term consequences of a mild brain injury may partly be a result of brain tissue injury.

  • 322. Sukjumlong, S.
    et al.
    Persson, E.
    Dalin, A-M
    Janson, Veronica
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Sahlin, L
    Messenger RNA levels of estrogen receptors alpha and beta and progesterone receptors in the cyclic and inseminated/early pregnant sow uterus2009In: Animal Reproduction Science, ISSN 0378-4320, E-ISSN 1873-2232, Vol. 112, no 3-4, p. 215-228Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to investigate differences in the expression of mRNAs for ERalpha, ERbeta and PR in the sow uterus at different stages of the estrous cycle as well as in inseminated sows at estrus and during early pregnancy by use of solution hybridization and in relation to plasma levels of estradiol and progesterone. Uterine samples were collected at different stages of the estrous cycle and after insemination/early pregnancy. In the endometrium, the expression of ERalpha mRNA and PR mRNA was similar for cyclic and early pregnant groups. Both were highest at early diestrus/70 h after ovulation and ERalpha mRNA was lowest at late diestrus/d 19 while PR mRNA was lowest at diestrus and late diestrus/d 11 and d 19. The expression of endometrial ERbeta was constantly low during the estrous cycle but higher expression was found in inseminated/early pregnant sows at estrus and 70 h after ovulation. In the myometrium, high expression of ERalpha mRNA and PR mRNA was observed at proestrus and estrus in cyclic sows and at estrus in newly inseminated sows. Higher expression of myometrial ERbeta mRNA was found in inseminated/early pregnant sows compared with cyclic sows, although significant only at estrus. In conclusion, the expression of mRNAs for ERalpha, ERbeta and PR in the sow uterus differed between endometrium and myometrium as well as with stages of the estrous cycle and early pregnancy. In addition to plasma steroid levels, the differences between cyclic and inseminated/early pregnant sows suggest that other factors, e.g. insemination and/or the presence of embryos, influence the expression of these steroid receptor mRNAs in the sow uterus.

  • 323.
    Sundberg, Maria
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Exosomers betydelse för utveckling av resistens mot lungcancerbehandling2017Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 324.
    Sundell, Birgitta
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nilsson, Torbjörn K.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Nygren, Charlotte
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Plasma glucose and insulin, urinary catecholamine and cortisol responses to test breakfasts with high or low fibre content: the importance of the previous diet1989In: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 33, no 6, p. 333-340Article in journal (Refereed)
    Abstract [en]

    A 60-hour high-carbohydrate (high-CHO) diet or a 36-hour low-carbohydrate (low-CHO) diet was followed by 24 healthy women in a cross-over design to modify liver glycogen content. Thereafter each subject was given a high-sucrose breakfast, a high-protein, high-fibre breakfast or no breakfast. The two different breakfasts evoked larger plasma glucose responses following the low-CHO diet than when following the high-CHO diet. When the two breakfasts followed the same pre-period diet, no significant differences were observed. We conclude that the composition of the previous diet influences the postprandial response to meals and that a standardised diet shortly before test meal studies is of importance for the results in this type of studies.

  • 325.
    Sundell, Birgitta
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nilsson, Torbjörn K
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Nygren, Charlotte
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    The effect of body build, diet and endocrine factors on the extrinsic fibrinolytic system in healthy young women1988In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 48, no 6, p. 557-64Article in journal (Refereed)
    Abstract [en]

    In this study, the importance of anthropometric, nutritional and endocrine variables on the plasma concentrations of tissue plasminogen activator antigen (tPA) and plasminogen activator inhibitor (PAI-I) were investigated. Tissue plasminogen activator concentration and PAI-I activity in plasma were studied in 24 healthy young women after diet periods which caused depletion or filling of hepatic glycogen stores. Plasminogen activator inhibitor levels in the glycogendepleted state and the glycogen-repleted state were positively correlated, as were also tPA levels. In fasting subjects with repleted glycogen stores, tPA values correlated with fasting insulin concentration and blood pressures. In fasting subjects depleted of glycogen stores, PA1-I correlated with tPA, plasma insulin, triglycerides, and waist-to-hip girth ratio; triglycerides and waist-to-hip girth ratio also correlated with tPA. Over a 4-h period following intake of a test-meal, the glucose and insulin responses were not correlated with the fibrinolytic variables. Multivariate regression analysis suggested that waist-to-hip girth ratio and diastolic blood pressure were independently associated with tPA concentrations both in subjects with depleted and repleted glycogen stores. Thus, both constitutional factors such as anthropometric variables and blood pressure, and nutritional status of the subjects may be related to tPA and PAI- levels in plasma. This should be taken into account in clinical studies on fibrinolysis.

  • 326.
    Sundell-Rånby, Birgitta
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Food intake, fibrinolysis and risk factors for cardiovascular disease: studies with special focus on plasminogen activator inhibitor type 1 (PAI-1)1993Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Elevated plasminogen activator inhibitor (PAI-1) activity levels, hyperlipemia, hypertension, impaired glucose tolerance and obesity, in particular central obesity, are all related to increased risk for the development of cardiovascular disease.Some risk factors are known to be and shown to be influenced by dietary habits. One aim of this study was to determine the distribution of PAI-1 activity and its linkage to serum lipids, body build, glucose and insulin (including glucose tolerance) among healthy men and women. Another aim was to elucidate the effects of different diet programes on the relationship between PAI-1 activity, serum lipid, glucose and insulin levels.

    Two cross-sectional studies, involving 260 individuals, the Norsjö study 1986, the mean PAI-1 activity among 30-60 year-old men was

    7.9 U/mL and among women 7.8 U/mL. Both men and women with a body mass index over 27 kg/m2 had higher PAI-1 activity, tPA antigen, fasting insulin and insulin responses following an oral glucose tolerance test than persons with body mass index <27. They also had lower HDL-cholesterol. Women with a high waist/hip circumference ratio had a higher mean PAI-1 activity, tPA antigen, triglyceride, blood pressure and insulin response to an oral glucose tolerance test than women with low or normal waist/hip ratio. Men with high waist/hip ratio had higher tPA antigen, glucose and insulin responses to an oral glucose tolerance test than men with low or normal waist/hip ratio.

    In two dietary studies different low-energy diets (a juice fast or a weight reduction program) were followed. PAI-1 activity was decreased in both cases. In a third dietary study, transition from a high-fat/low-carbohydrate diet to a low-fat/high-carbohydrate diet decreased PAI-1 activity provided that it did not also cause a substantial increase in triglycerides or glucose. In a fourth dietary study the regular diet was supplemented with oat-husk. PAI-1 activity was reduced; a small increase in glucose but not in triglyceride levels was observed.

    On the basis of these results it is concluded that PAI-1 activity levels are associated with constitutional factors such as body mass index and waist/hip ratio. PAI-1 is elevated in obesity. Nutritional factors are also of importance for the PAI-1 activity levels. PAI-1 activity levels can be reduced by dietary regiments such as low-energy diets or high-fiber diets.

  • 327. Synofzik, Matthis
    et al.
    Ronchi, Dario
    Keskin, Isil
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Basak, Ayse N.
    Wilhelm, Christian
    Gobbi, Claudio
    Birve, Anna
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Biskup, Saskia
    Zecca, Chiara
    Fernandez-Santiago, Ruben
    Kaugesaar, Toomas
    Schoels, Ludger
    Marklund, Stefan L.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Mutant superoxide dismutase-1 indistinguishable from wild-type causes ALS2012In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 21, no 16, p. 3568-3574Article in journal (Refereed)
    Abstract [en]

    A reason for screening amyotrophic lateral sclerosis (ALS) patients for mutations in the superoxide dismutase-1 (SOD1) gene is the opportunity to find novel mutations with properties that can give information on pathogenesis. A novel c.352CG (L117V) SOD1 mutation was found in two Syrian ALS families living in Europe. The disease showed unusually low penetrance and slow progression. In erythrocytes, the total SOD1 activity, as well as specific activity of the mutant protein, was equal in carriers of the mutation and family controls lacking SOD1 mutations. The structural stabilities of the L117V mutant and wild-type SOD1 under denaturing conditions were likewise equal, but considerably lower than that of murine SOD1. As analyzed with an ELISA specific for misfolded SOD1 species, no differences were found in the content of misfolded SOD1 protein between extracts of fibroblasts from wild-type controls and from an L117V patient. In contrast, elevated levels of misfolded SOD1 protein were found in fibroblasts from ALS patients carrying seven other mutations in the SOD1 gene. We conclude that mutations in SOD1 that result in a fully stable protein are associated with low disease penetrance for ALS and may be found in cases of apparently sporadic ALS. Wild-type human SOD1 is moderately stable, and was found here to be within the stability range of ALS-causing SOD1 variants, lending support to the hypothesis that wild-type SOD1 could be more generally involved in ALS pathogenesis.

  • 328.
    Söderberg, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Sources of preanalytical error in primary health care: implications for patient safety2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background Venous blood tests constitute an important part in the diagnosis and treatment of patients. However, test results are often viewed as objective values rather than the end result of a complex process. This has clinical importance since most errors arise before the sample reaches the laboratory. Such preanalytical errors affect patient safety and are often due to human mistakes in the collection and handling of the sample. The preanalytical performance of venous blood testing in primary health care, where the majority of the patients contact with care occurs, has not previously been reported.

    Aims To investigate venous blood sampling practices and the prevalence of haemolysed blood samples in primary health care.

    Methods A questionnaire investigated the collection and handling of venous blood samples in primary health care centres in two county councils and in two hospital clinical laboratories. Haemolysis index was used to evaluate the prevalence of haemolysed blood samples sent from primary health care centres, nursing homes and a hospital emergency department.

    Results and discussion The results indicate that recommended preanalytical procedures were not always followed in the surveyed primary health care centres. For example, only 54% reported to always use name and Swedish identification number, and 5% to use photo-ID, the two recommended means for patient identification. Only 12% reported to always label the test tubes prior to blood collection. This increases the possibility of sample mix-up. As few as 6% reported to always allow the patient to rest at least 15 minutes before blood collection, desirable for a correct test result. Only 31% reported to have filed an incident report regarding venous blood sampling, indicating underreporting of incidents in the preanalytical phase.

    Major differences in the prevalence of haemolysed blood samples were found. For example, samples collected in the primary health care centre with the highest prevalence of haemolysed samples were six times (95% CI 4.0 to 9.2) more often haemolysed compared to the centre with the lowest prevalence. The significant variation in haemolysed samples is likely to reflect varying preanalytical conditions.

    Conclusions This thesis indicates that the preanalytical procedure in primary health care is associated with an increased risk of errors with consequences for patient safety and care. Monitoring of haemolysis index could be a valuable tool for estimating preanalytical sample quality. Further studies and interventions aimed at the preanalytical phase in primary health care are clearly needed.

  • 329.
    Söderberg, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Wallin, Olof
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Preanalytical errors in primary healthcare: a questionnaire study of information search procedures, test request management and test tube labelling2009In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 47, no 2, p. 195-201Article in journal (Refereed)
    Abstract [en]

    Background: Most errors in laboratory medicine occur in the preanalytical phase and are the result of human mistakes. This study investigated information search procedures, test request management and test tube labelling in primary healthcare compared to the same procedures amongst clinical laboratory staff.

    Methods: A questionnaire was completed by 317 venous blood sampling staff in 70 primary healthcare centres and in two clinical laboratories (response rate = 94%).

    Results: Correct procedures were not always followed. Only 60% of the primary healthcare staff reported that they always sought information in the updated, online laboratory manual. Only 12% reported that they always labelled the test tubes prior to drawing blood samples. No major differences between primary healthcare centres and clinical laboratories were found, except for test tube labelling, whereby the laboratory staff reported better practices. Re-education and access to documented routines were not clearly associated with better practices.

    Conclusions: The preanalytical procedure in the surveyed primary healthcare centres was associated with a risk of errors which could affect patient safety. To improve patient safety in laboratory testing, all healthcare providers should survey their preanalytical procedures and improve the total testing process with a systems perspective.

  • 330.
    Söderberg, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Wallin, Olof
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Incident reporting practices in the preanalytical phase: low reported frequencies in the primary health care setting2009In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 69, no 7, p. 731-735Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Incident reporting is commonly used to improve patient safety. The preanalytical phase of laboratory testing contains several manual error-prone tasks where mistakes can affect patient outcomes. However, the practical use of incident reports in this area has not been previously investigated in the primary health care setting, where the majority of the patients come in contact with health care.

    MATERIAL AND METHODS: All staff responsible for venous blood sampling in 70 primary health care centres and in two hospital clinical laboratories (317 respondents, response rate 94%) completed a questionnaire.

    RESULTS: Of the primary health care staff, 69% reported that they had never filed an incident report regarding venous blood sampling. Barriers for not filing incident reports often/always included lack of time (44%) and a complicated reporting procedure (27%). A higher proportion of staff with re-education (43%) had filed at least one incident report as compared to those without re-education (20%, p < 0.001). No differences in incident reporting practices were found between primary health care and hospital clinical laboratory staff.

    CONCLUSIONS: The investigated incident reporting system is likely to underreport incidents in the preanalytical phase. Therefore, the ability to discover preventable system vulnerabilities needs refinement.

  • 331.
    Söderberg, Johan
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences, Clinical chemistry.
    Jonsson, PA
    Wallin, Olof
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Medical Biosciences, Clinical chemistry.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Medical Biosciences, Clinical chemistry.
    Haemolysis index: an estimate of preanalytical quality in primary health care!2009In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 47, no 8, p. 940-944Article in journal (Refereed)
    Abstract [en]

    Background: Haemolysis is usually caused by inadequate specimen collection or preanalytical handling, and is suggested to be a suitable indicator of preanalytical quality. We investigated the prevalence of detectable haemolysis in all routine venous blood samples to identify differences in preanalytical quality. Methods: Haemolysis index (HI) values were obtained from a Vitros 5,1 in the routine clinical chemistry laboratory for samples collected in primary health care centres (PHCs), nursing homes, and a hospital emergency department (ED). Haemolysis was defined as a HI ≥ 15 (detection limit). Results: Samples from the PHC with the highest prevalence of haemolysis were 6.1 times (95% confidence interval (CI) 4.0-9.2) more often haemolysed compared to the centre with the lowest prevalence. Of the samples collected in primary health care, 10.4% were haemolysed compared to 31.1% in the ED (p< 0.001). A notable difference in haemolysed samples was found between the ED section staffed by emergency medicine physicians and the section staffed by primary health care physicians (34.8% vs. 11.3%, p<0.001). Conclusions: The significant variation in haemolysis indices among the investigated units is likely to reflect varying preanalytical conditions. The HI is a valuable tool for estimation and follow-up of preanalytical quality in primary health care.

  • 332.
    Söderberg, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Wallin, Olof
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Is the test result correct? A questionnaire study of blood collection practices in primary health care2010In: Journal of Evaluation In Clinical Practice, ISSN 1356-1294, E-ISSN 1365-2753, Vol. 16, no 4, p. 707-711Article in journal (Refereed)
    Abstract [en]

    Rationale, aims and objectives  Venous blood tests are important for clinical decision making. Most errors in blood testing are due to human errors before the blood samples reach the laboratory. The present study was designed to investigate venous blood sampling (VBS) practices in primary health care centres (PHCs) compared with clinical laboratory staff.

    Method  A cross-sectional survey of 70 PHCs and two clinical laboratories is conducted. All staff responsible for VBS (317 respondents, response rate 94%) completed a questionnaire on VBS practices.

    Results  Instructions for VBS were not followed in the surveyed PHCs. For example, only 54% reported that they always identified the patient by using name/Swedish identification number and only 5% reported that they always used photo-ID, the two preferred means for patient identification. Only 12% reported that they always released venous stasis as soon as possible. Fewer PHC staff than clinical laboratory staff reported correct VBS practices. For example, 54% of the PHC staff reported that they always identified the patient by name and Swedish identification number, as compared with 95% of the clinical laboratory staff (P < 0.001). Documented VBS routines and re-education in VBS were not clearly associated with reported correct VBS practices.

    Conclusions  In the surveyed PHCs, there are clinically important risks for misidentification of patients and erroneous test results, with consequences for the diagnosis and treatment of patients. Quality interventions, aimed at improving VBS practices, are needed to ensure patient safety.

  • 333.
    Söderberg, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Wallin, Olof
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Jonsson, P. Andreas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Comment on the letter to the editor ‘The importance of incident reporting in laboratory diagnosics’ by Lippi and Plebani2009Other (Other academic)
  • 334.
    Söderström, Elisabet
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johnson, Owe
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Plasma folate, but not homocysteine, is associated with Apolipoprotein A1 levels in a non-fortified population2013In: Lipids in Health and Disease, ISSN 1476-511X, E-ISSN 1476-511X, Vol. 12, p. 74-Article in journal (Refereed)
    Abstract [en]

    Background: Elevated total plasma homocysteine (tHcy) in humans is associated with cardiovascular disease but prevention trials have failed to confirm causality. Reported reasons for this association have been that homocysteine and its major genetic determinant methylenetetrahydrofolate reductase (MTHFR) may have an effect on HDL and Apolipoprotein (Apo) A1 levels. We wanted to study if tHcy and its major determinants were correlated with Apo A1 levels in a large population without folate fortification. Methods: This study was a prospective incident nested case-referent study within the Northern Sweden Health and Disease Study Cohort (NSHDSC), including 545 cases with first myocardial infarction and 1054 matched referents, median age at inclusion was 59 years. Univariate and multiple regression analyzes was used to study the associations between apolipoproteins Apo A1 and B, tHcy, folate and vitamin B12 in plasma as well as MTHFR polymorphisms 677C>T and 1298A>C. Results: Apo A1 and Apo B were strongly associated with the risk of a first myocardial infarction. tHcy was not associated with Apo A1 levels. Instead, folate had an independent positive association with Apo A1 levels in univariate and multiple regression models. The associations were seen in all men and women, among referents but not among cases. MTHFR polymorphisms had no clear effect on Apo A1 levels. Conclusions: Analyzing over 1500 subjects we found an independent positive association between plasma folate (major dietary determinant of tHcy) and Apo A1 levels among those who later did not develop a first myocardial infarction. No association was seen between tHcy and Apo A1.

  • 335.
    Söderström, Elisabet
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Schneede, Jörn
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Homocysteine and cotinine levels in smokers and snus users2015In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 241, no 1, p. E129-E129Article in journal (Other academic)
  • 336. Taneja, Sunita
    et al.
    Bhandari, Nita
    Strand, Tor A
    Sommerfelt, Halvor
    Refsum, Helga
    Ueland, Per M
    Schneede, Jörn
    Umeå University, Faculty of Medicine, Medical Biosciences, Clinical chemistry.
    Bahl, Rajiv
    Bhan, Maharaj Kishan
    Cobalamin and folate status in infants and young children in a low-to-middle income community in India.2007In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 86, no 5, p. 1302-1309Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Population-based data on the prevalence of cobalamin and folate deficiency in India are lacking. OBJECTIVE: The objective was to measure the prevalence of cobalamin and folate deficiency among children aged 6-30 mo residing in a low-to-middle income community in North India. DESIGN: Children aged 6-30 mo (n = 2482) were identified through a community survey in a low-to-middle socioeconomic area in New Delhi, India. Non-fasting venous blood samples were collected before enrollment in another trial. RESULTS: The median (interquartile range; IQR) cobalamin concentration in 6-11-mo-old children was substantially lower in breastfed (183; 120-263 pmol/L) than in nonbreastfed (334; 235-463 pmol/L) children. Cobalamin concentrations decreased progressively with increasing age in the nonbreastfed children. Median (IQR) plasma folate concentrations in the 6-11-mo-old group were higher in breastfed (20.3; 11.7-34.4 nmol/L) than in nonbreastfed (5.3; 3.4-7.7 nmol/L) children (P < 0.001). Folate concentrations decreased with increasing age in the breastfed children. In the nonbreastfed children, folate concentrations increased with increasing age. Low concentrations of plasma cobalamin (<150 pmol/L) were detected in 36% of breastfed and 9% of nonbreastfed children (P < 0.001). The proportions of children with plasma folate concentrations <5 nmol/L in these 2 subgroups were 6% and 33%, respectively (P < 0.001). CONCLUSIONS: In north Indian preschool children, cobalamin and folate concentrations were commonly low and were associated with elevated total homocysteine and methylmalonic acid concentrations. Because low cobalamin and folate concentrations have functional consequences, population-based measures for improving cobalamin and folate concentrations need to be seriously considered.

  • 337.
    Theodorsson, Elvar
    et al.
    Linköpings universitet.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Landin, Britta
    Karolinska universitetslaboratoriet, Stockholm.
    Anemier2012In: Laurells klinisk kemi i praktisk medicin / [ed] Nilsson Ehle P, Berggren Söderlund M, Theodorsson E, Lund: Studentlitteratur, 2012, 9, p. 211-280Chapter in book (Refereed)
  • 338.
    Theodorsson, Elvar
    et al.
    Linköpings universitet.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Nilsson Ehle, Peter
    Institutionen för laboratoriemedicin, Lund.
    Laboratoriernas verksamhet2012In: Laurells klinisk kemi i praktisk medicin / [ed] Nilsson Ehle P, Berggren Söderlund M, Theodorsson E, Lund: Studentlitteratur, 2012, 9, p. 9-22Chapter in book (Refereed)
  • 339.
    Theodorsson, Elvar
    et al.
    Linköpings universitet.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Nilsson Ehle, Peter
    Institutionen för laboratoriemedicin, Lund.
    Tolkning av analysresultat2012In: Laurells klinisk kemi i praktisk medicin / [ed] Nilsson Ehle P, Berggren Söderlund M, Theodorsson E, Lund: Studentlitteratur, 2012, 9, p. 23-51Chapter in book (Refereed)
  • 340. Theofylaktopoulou, Despoina
    et al.
    Midttun, Oivind
    Ueland, Per M.
    Meyer, Klaus
    Fanidi, Anouar
    Zheng, Wei
    Shu, Xiao-Ou
    Xiang, Yong-Bing
    Prentice, Ross
    Pettinger, Mary
    Thomson, Cynthia A.
    Giles, Graham G.
    Hodge, Allison
    Cai, Qiuyin
    Blot, William J.
    Wu, Jie
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Stevens, Victoria L.
    McCullough, Marjorie M.
    Weinstein, Stephanie J.
    Albanes, Demetrius
    Ziegler, Regina
    Freedman, Neal D.
    Langhammer, Arnulf
    Hveem, Kristian
    Naess, Marit
    Sesso, Howard D.
    Gaziano, J. Michael
    Buring, Julie E.
    Lee, I-Min
    Severi, Gianluca
    Zhang, Xuehong
    Stampfer, Meir J.
    Han, Jiali
    Smith-Warner, Stephanie A.
    Zeleniuch-Jacquotte, Anne
    Le Marchand, Loic
    Yuan, Jian-Min
    Wang, Renwei
    Butler, Lesley M.
    Koh, Woon-Puay
    Gao, Yu-Tang
    Rothman, Nathaniel
    Ericson, Ulrika
    Sonestedt, Emily
    Visvanathan, Kala
    Jones, Miranda R.
    Relton, Caroline
    Brennan, Paul
    Johansson, Mattias
    Ulvik, Arve
    Impaired functional vitamin B6 status is associated with increased risk of lung cancer2018In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, no 12, p. 2425-2434Article in journal (Refereed)
    Abstract [en]

    Circulating vitamin B6 levels have been found to be inversely associated with lung cancer. Most studies have focused on the B6 form pyridoxal 5'-phosphate (PLP), a direct biomarker influenced by inflammation and other factors. Using a functional B6 marker allows further investigation of the potential role of vitamin B6 status in the pathogenesis of lung cancer. We prospectively evaluated the association of the functional marker of vitamin B6 status, the 3-hydroxykynurenine:xanthurenic acid (HK:XA) ratio, with risk of lung cancer in a nested case-control study consisting of 5,364 matched case-control pairs from the Lung Cancer Cohort Consortium (LC3). We used conditional logistic regression to evaluate the association between HK:XA and lung cancer, and random effect models to combine results from different cohorts and regions. High levels of HK:XA, indicating impaired functional B6 status, were associated with an increased risk of lung cancer, the odds ratio comparing the fourth and the first quartiles (OR4th vs. 1st) was 1.25 (95% confidence interval, 1.10-1.41). Stratified analyses indicated that this association was primarily driven by cases diagnosed with squamous cell carcinoma. Notably, the risk associated with HK:XA was approximately 50% higher in groups with a high relative frequency of squamous cell carcinoma, i.e., men, former and current smokers. This risk of squamous cell carcinoma was present in both men and women regardless of smoking status.

  • 341.
    Thormark Fröst, Finn
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Investigation of economic factors in laboratory test ordering at a primary health care level in northern Sweden.2012Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 342. Thörn, Ingrid
    et al.
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Botling, Johan
    Thuresson, Britt
    Wasslavik, Carina
    Björklund, Elisabet
    Li, Aihong
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Lindström-Eriksson, Eleonor
    Malec, Maria
    Grönlund, Elisabeth
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Torikka, Kerstin
    Heldrup, Jesper
    Abrahamsson, Jonas
    Behrendtz, Mikael
    Söderhäll, Stefan
    Jacobsson, Stefan
    Olofsson, Tor
    Porwit, Anna
    Lönnerholm, Gudmar
    Rosenquist, Richard
    Sundström, Christer
    Minimal residual disease assessment in childhood acute lymphoblastic leukaemia: a Swedish multi-centre study comparing real-time polymerase chain reaction and multicolour flow cytometry2011In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 152, no 6, p. 743-53Article in journal (Refereed)
    Abstract [en]

    Minimal residual disease (MRD) assessment is a powerful prognostic factor for determining the risk of relapse in childhood acute lymphoblastic leukaemia (ALL). In this Swedish multi-centre study of childhood ALL diagnosed between 2002 and 2006, the MRD levels were analysed in 726 follow-up samples in 228 children using real-time quantitative polymerase chain reaction (RQ-PCR) of rearranged immunoglobulin/T-cell receptor genes and multicolour flow cytometry (FCM). Using an MRD threshold of 0·1%, which was the sensitivity level reached in all analyses, the concordance between RQ-PCR and FCM MRD values at day 29 was 84%. In B-cell precursor ALL, an MRD level of ≥0·1% at day 29 predicted a higher risk of bone marrow relapse (BMR) with both methods, although FCM was a better discriminator. However, considering the higher median MRD values achieved with RQ-PCR, a higher MRD cut-off (≥0·2%) improved the predictive capacity of RQ-PCR. In T-ALL, RQ-PCR was notably superior to FCM in predicting risk of BMR. That notwithstanding, MRD levels of ≥0·1%, detected by either method at day 29, could not predict isolated extramedullary relapse. In conclusion, the concordance between RQ-PCR and FCM was high and hence both methods are valuable clinical tools for identifying childhood ALL cases with increased risk of BMR.

  • 343. Thörn, Ingrid
    et al.
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Thuresson, Britt
    Wasslavik, Carina
    Malec, Maria
    Li, Aihong
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Lindström-Eriksson, Elenor
    Botling, Johan
    Barbany, Gisela
    Jacobsson, Stefan
    Olofsson, Tor
    Porwit, Anna
    Sundström, Christer
    Rosenquist, Richard
    Applicability of IG/TCR gene rearrangements as targets for minimal residual disease assessment in a population-based cohort of Swedish childhood acute lymphoblastic leukaemia diagnosed 2002-20062010In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 84, no 2, p. 117-127Article in journal (Refereed)
    Abstract [en]

    Minimal residual disease (MRD) detection during the early treatment phase has become an important stratification parameter in many childhood acute lymphoblastic leukaemia (ALL) treatment protocols. Here, we aimed to address the applicability of rearranged antigen-receptor genes as potential MRD markers using real-time quantitative polymerase chain reaction (RQ-PCR) in a Swedish population-based cohort. From 334 childhood ALL cases diagnosed during 2002-2006, we analysed 279 diagnostic samples (84%) by screening for rearranged immunoglobulin (IG) and T-cell receptor (TCR) genes. Allele-specific oligonucleotides were designed, and the sensitivity and quantitative level was determined for each target. Overall, clonal IG/TCR rearrangements were detected in 97% (236/244) of B-cell precursor ALL (BCP ALL) and 94% (33/35) of T-ALL. A sensitive RQ-PCR analysis (< or = 10(-4)) was obtained in 89% (216/244) of BCP ALL and in 74% (26/35) of T-ALL, whereas two sensitive targets were only available in 47% (115/244) of BCP ALL and 29% (10/35) of T-ALL cases. With the stratification threshold of > or = 10(-3), which is applied in the current Nordic treatment protocol (NOPHO-ALL 2008) for the identification of high-risk patients, 93% of BCP ALL and 86% of T-ALL reached this quantitative range by at least one target gene. Taken together, this national retrospective study demonstrates that an IG/TCR target for MRD monitoring can be identified in the majority of childhood ALL cases, whereas identification of a second sensitive target gene needs to be improved.

  • 344.
    Thøgersen, Anna M
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Dahlén, Gösta
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Torbjörn K
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Lundberg, Vivan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johnsson, Ove
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ahrén, Bo
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Interactions between fibrinolysis, lipoproteins and leptin related to a first myocardial infarction.2004In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 11, no 1, p. 33-40Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The summarized importance of haemostatic and metabolic variables (insulin, lipids including lipoprotein (a) [Lp(a)] and leptin) in predicting first myocardial infarction, as well as possible interactions among these variables, have not been reported. DESIGN: A prospective case-control study nested within the Northern Sweden Health and Disease Cohort. METHODS: Sixty-two men diagnosed with a first myocardial infarction were sex- and age-matched with 124 controls. Conditional logistic regression was conducted including established risk factors, plasma levels of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) mass concentration, von Willebrand factor, insulin, proinsulin, specific insulin, apolipoprotein A-I (apo A-I), Lp(a), and leptin. Interaction analysis was also performed for tPA, apo A-I, Lp(a), leptin and proinsulin. RESULTS: Smoking, low plasma levels of apo A-I and high plasma levels of cholesterol, Lp(a), tPA, PAI-1, proinsulin and leptin were associated with myocardial infarction in univariate conditional logistic regression analysis. High tPA [odds ratio (OR), 21.3; 95% confidence interval (CI), 2.04-222] and Lp(a) (OR, 7.21; 95% CI, 1.31-39.8) and low apo A-I (OR, 0.15; 95% CI, 0.02-0.93) remained significant risk determinants in multivariate analysis with smoking habits, body mass index, hypertension, cholesterol, and diabetes included as covariates. There were non-significant synergic interactions between high Lp(a) and leptin and tPA, respectively, and between high Lp(a) and low apo A-I. CONCLUSION: Plasma levels of tPA, Lp(a), and apo A-I are independently associated with subsequent development of a first myocardial infarction in men.

  • 345.
    Tokuda, Eiichi
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Marklund, Stefan L.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Low autophagy capacity implicated in motor system vulnerability to mutant superoxide dismutase2016In: Acta neuropathologica communications, E-ISSN 2051-5960, Vol. 4, article id 6Article in journal (Refereed)
    Abstract [en]

    Introduction: The motor system is selectively vulnerable to mutations in the ubiquitously expressed aggregation-prone enzyme superoxide dismutase-1 (SOD1).

    Results: Autophagy clears aggregates, and factors involved in the process were analyzed in multiple areas of the CNS from human control subjects (n = 10) and amyotrophic lateral sclerosis (ALS) patients (n = 18) with or without SOD1 mutations. In control subjects, the key regulatory protein Beclin 1 and downstream factors were remarkably scarce in spinal motor areas. In ALS patients, there was evidence of moderate autophagy activation and also dysregulation. These changes were largest in SOD1 mutation carriers. To explore consequences of low autophagy capacity, effects of a heterozygous deletion of Beclin 1 were examined in ALS mouse models expressing mutant SOD1s. This caused earlier SOD1 aggregation, onset of symptoms, motor neuron loss, and a markedly shortened survival. In contrast, the levels of soluble misfolded SOD1 species were reduced.

    Conclusions: The findings suggest that an inherent low autophagy capacity might cause the vulnerability of the motor system, and that SOD1 aggregation plays a crucial role in the pathogenesis.

  • 346.
    Tokuda, Eiichi
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Okawa, Eriko
    Watanabe, Shunsuke
    Ono, Shin-ichi
    Marklund, Stefan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Dysregulation of intracellular copper homeostasis is common to transgenic mice expressing human mutant superoxide dismutase-1s regardless of their copper-binding abilities2013In: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 54, p. 308-319Article in journal (Refereed)
    Abstract [en]

    Over 170 mutations in superoxide dismutase-1 (SOD1) have been linked to amyotrophic lateral sclerosis (ALS). The properties of SOD1 mutants differ considerably including copper-binding abilities. Nevertheless, they cause the same disease phenotype, suggesting a common neurotoxic pathway. We have previously reported that copper homeostasis is disturbed in spinal cords of SOD1(G93A) mice. However, it is unknown whether copper dyshomeostasis is induced by other SOD1 mutants. Using the additional mouse strains SOD1(G127insTGGG), SOD1(G85R), and SOD1(D90A), which express SOD1 mutants with different copper-binding abilities, we show that copper dyshomeostasis is common to SOD1 mutants. The SOD1 mutants shifted the copper trafficking systems toward copper accumulation in spinal cords of the mice. Copper contents bound to the SOD1 active site varied considerably between SOD1 mutants. Still, copper bound to other ligands in the spinal cord were markedly increased in all. Zinc was also increased, whereas there were no changes in magnesium, calcium, aluminum, manganese and iron. Further support for a role of copper dyshomeostasis in ALS was gained from results of pharmacological intervention. Ammonium tetrathiomolybdate (TTM), a copper chelating agent, prolonged survival and slowed the disease progression of SOD1(G93A) mice, even when the treatment was started after the disease onset. TTM markedly attenuated pathology, including the loss of motor neurons and axons, and atrophy of skeletal muscles. Additionally, TTM decreased amounts of SOD1 aggregates. We propose that pharmacological agents that are capable of modulating copper dyshomeostasis, such as TTM, might be beneficial for the treatment of ALS caused by SOD1 mutations.

  • 347.
    Tokuda, Eiichi
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Watanabe, Shunsuke
    Okawa, Eriko
    Ono, Shin-ichi
    Regulation of Intracellular Copper by Induction of Endogenous Metallothioneins Improves the Disease Course in a Mouse Model of Amyotrophic Lateral Sclerosis2015In: Neurotherapeutics, ISSN 1933-7213, Vol. 12, no 2, p. 461-476Article in journal (Refereed)
    Abstract [en]

    Mutations in SOD1 cause amyotrophic lateral sclerosis (ALS), an incurable motor neuron disease. The pathogenesis of the disease is poorly understood, but intracellular copper dyshomeostasis has been implicated as a key process in the disease. We recently observed that metallothioneins (MTs) are an excellent target for the modification of copper dyshomeostasis in a mouse model of ALS (SOD1(G93A)). Here, we offer a therapeutic strategy designed to increase the level of endogenous MTs. The upregulation of endogenous MTs by dexamethasone, a synthetic glucocorticoid, significantly improved the disease course and rescued motor neurons in SOD1(G93A) mice, even if the induction was initiated when peak body weight had decreased by 10 %. Neuroprotection was associated with the normalization of copper dyshomeostasis, as well as with decreased levels of SOD1(G93A) aggregates. Importantly, these benefits were clearly mediated in a MT-dependent manner, as dexamethasone did not provide any protection when endogenous MTs were abolished from SOD1(G93A) mice. In conclusion, the upregulation of endogenous MTs represents a promising strategy for the treatment of ALS linked to mutant SOD1.

  • 348. Toniolo, Paolo
    et al.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Wulff, Marianne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Chen, Tianhui
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Schock, Helena
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lehtinen, Matti
    Kaaks, Rudolf
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Zeleniuch-Jacquotte, Anne
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lukanova, Annekatrin
    Human chorionic gonadotropin in pregnancy and maternal risk of breast cancer2010In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 70, no 17, p. 6779-6786Article in journal (Refereed)
    Abstract [en]

    Full-term pregnancies are associated with long-term reductions in maternal risk of breast cancer, but the biological determinants of the protection are unknown. Experimental observations suggest that human chorionic gonadotropin (hCG), a major hormone of pregnancy, could play a role in this association. A case-control study (242 cases and 450 controls) nested within the Northern Sweden Maternity Cohort included women who had donated a blood sample during the first trimester of a first full-term pregnancy. Total hCG was determined on Immulite 2000 analyzer. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through conditional logistic regression. Maternal breast cancer risk decreased with increasing hCG (upper tertile OR, 0.67; CI, 0.46-0.99), especially for pregnancies before age 25 (upper tertile OR, 0.41; CI, 0.21-0.80). The association diverged according to age at diagnosis: risk was reduced after age 40 (upper tertile OR, 0.60; CI, 0.39-0.91) and seemed to increase before age 40 (upper tertile OR, 1.78; CI, 0.72-4.38). Risk was reduced among those diagnosed 10 years or longer after blood draw (upper tertile OR, 0.60; CI, 0.40-0.90), but not so among those diagnosed within 10 years (upper tertile OR, 4.33; CI, 0.86-21.7). These observations suggest that the association between pregnancy hCG and subsequent maternal risk of breast cancer is modified by age at diagnosis. Although the hormone seems to be a determinant of the reduced risk around or after age 50, it might not confer protection against, or it could even increase the risk of, cancers diagnosed in the years immediately following pregnancy.

  • 349. Toriola, A T
    et al.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Agborsangaya, C B
    Lukanova, A
    Lehtinen, M
    Surcel, H M
    Changes in pre-diagnostic serum C-reactive protein concentrations and ovarian cancer risk: a longitudinal study2011In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 22, no 8, p. 1916-1921Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Evidence suggests that inflammation may be associated with increased risk of ovarian cancer but there is paucity of studies investigating this association, especially using over-time changes in inflammatory biomarkers.

    MATERIALS AND METHODS: We conducted a prospective population-based case-control study nested within the Finnish Maternity Cohort (FMC). Within the FMC, 170 women with ovarian cancer who had donated serum samples to the cohort twice, ≥1 year apart, before cancer diagnoses were identified. One control per case was matched for age, parity and sampling date.

    RESULTS: Comparing the highest with lowest tertiles, the odds ratio (OR) of ovarian cancer using the first set of serum samples (mean lag time to cancer diagnosis 9.0 years) was 1.62 [95% confidence interval (CI) 0.93-2.83]. However, analysis conducted using the second set of serum samples donated closer to cancer diagnosis (mean lag time 6.4 years) revealed a significantly increased risk of ovarian cancer comparing extreme tertiles of C-reactive protein (CRP) concentrations; OR 1.96 (95% CI 1.11-3.4). Over time, increases in individuals' CRP concentrations were also associated with increased risk; OR 1.90 (95% CI 1.12-3.23).

    CONCLUSION: The results suggest that inflammation may precede ovarian cancer since increasing CRP concentrations, both across tertiles and longitudinally at the individual level, were associated with increased risk.

  • 350. Toriola, Adetunji T
    et al.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Schock, Helena
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Pukkala, Eero
    Chen, Tianhui
    Zeleniuch-Jacquotte, Anne
    Toniolo, Paolo
    Lehtinen, Matti
    Surcel, Helja-Marja
    Lukanova, Annekatrin
    Circulating insulin-like growth factor-I in pregnancy and maternal risk of breast cancer2011In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, no 8, p. 1798-1801Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Elevated serum concentrations of insulin-like growth factor (IGF)-I have been associated with increased risk of developing breast cancer. Previously, we reported a similar association in samples obtained during pregnancy. This study was conducted to further characterize the association of IGF-I during pregnancy with maternal breast cancer risk.

    METHODS: A case-control study was nested within the Finnish Maternity Cohort. The study was limited to primiparous women younger than 40 years, who donated blood samples during early (median, 12 weeks) pregnancy and delivered a single child at term. Seven hundred nineteen women with invasive breast cancer were eligible. Two controls (n = 1,434) were matched with each case on age and date at blood donation. Serum IGF-I concentration was measured using an Immulite 2000 analyzer. Conditional logistic regression was used to estimate ORs and 95% CIs.

    RESULTS: No significant associations were observed between serum IGF-I concentrations and breast cancer risk in both the overall analysis (OR, 1.08; 95% CI, 0.80-1.47) and in analyses stratified by histologic subtype, lag time to cancer diagnosis, age at pregnancy, or age at diagnosis.

    CONCLUSION: There was no association between IGF-I and maternal breast cancer risk during early pregnancy in this large nested case-control study.

    IMPACT: Serum IGF-I concentrations during early pregnancy may not be related to maternal risk of developing breast cancer.

456789 301 - 350 of 411
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