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  • 1.
    Andersson, Christer
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Floderus, Y
    Wikberg, Agneta
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lithner, Folke
    The W198X and R173W mutations in the porphobilinogen deaminase gene in acute intermittent porphyria have higher clinical penetrance than R167: a populations-based study2000In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 60, no 7, p. 643-648Article in journal (Refereed)
    Abstract [en]

    The biosynthesis of porphyrins is one of the most conserved parthways known, about the same sequence of reactions taking place in all species. By associating different metals, porphyrins give rise to the “pigments of life”: chlorophyll, haem and cobalamin. The unique tetrapyrrolic structure enables it to function in an array of reactions as a single electron carrier and as a catalyst for redox reactions. In this capacity, it constitutes the prosthetic group of enzymes participating in cellular respiration, in conversion reactions involving steroids and lipophilic xenobiotics, in protective mechanisms directed against oxidative stress and in pathways providing central messenger molecules. The formation of haem is accomplished by a sequence of eight dedicated enzymes encoded by different genes, some being active in ubiquitous as well as in erythroid isoforms. Large differences between the participating enzymes with regard to catalytic power, with low capacity steps positioned early in the catalytic chain, constitute a bar against substrate overloading of enzymes processing porphyrins, thus preventing accumulation in the body of these phototoxic compounds under physiological conditions. Most of the haem in the body is produced by the liver and bone marrow, but the mechanisms applied for the control of the synthesis differ between the two organs. The extremely potent hemeprotein enzymes formed in the liver are rapidly turned over in response to current metabolic needs. They have half-lives in the order of minutes or hours and are restored by fast-acting mechanisms for the de novo synthesis, when needed. Uninterrupted and instant availability of the compound is secured by acute deinhibition of the initial enzyme of the synthetic chain, ubiquitous 5-aminolevulinate synthase (ALAS-1), in response to drain of the free cellular haem pool caused by prevailing demands for hemeproteins or by increased catabolism of the compound. In contrast, in the erythroid progenitor cell the haem synthetic machinery is designed for uninterrupted production of huge amounts of haem for combination with globin chains to form hemoglobin at a steady rate. In the erythron the synthesis of the enzymes participating in the formation of haem is under control of erythropoietin, formed under hypoxic conditions. In the absence of iron, to be incorporated in the porphyrin formed in the last step of the synthesis, the mRNA of erythroid 5-aminolevulinate synthase (ALAS-2) is blocked by attachment of an iron-responsive element (IRE) binding cytosolic protein, and transcription of this key enzyme is inhibited. In humans, the genes for each of the haem synthetic enzymes may become the target of mutations that give rise to impaired cellular enzyme activity. Seven of the enzyme deficiencies are associated with accumulation of toxic intermediaries and with disease entities termed porphyrias. The acute porphyrias are characterized by attacks of neuropsychiatric symptoms, which may be due to a toxic surplus of the porphyrin presursor 5-aminolevulinic acid, or a consequence of a deficit of vital hemeproteins resulting from impaired synthesis of haem. In the cutaneous porphyrias, impairment of enzymatic steps where porphyrins are processed gives rise to solar hypersensitivity due to accumulation of phototoxic porphyrins in the skin. Early diagnosis, information to the patient regarding the nature of the illness and counselling aimed at avoidance of triggering factors are cornerstones in the handling of the porphyric diseases. Gene analysis is of incomparable diagnostic reliability in carrier detection, but biochemical methods must be applied in the important task of monitoring porphyric disease activity. In most forms of porphyria the gene carriers run the risk of development of associated diseases in liver or kidneys, a circumstance that prompts application of well-structured surveillance programs.

  • 2. Breimer, Lars H
    et al.
    Nilsson, Torbjörn K
    Departments of Laboratory Medicine, Örebro University Hospital; Departments of Clinical Medicine & Biomedicine, School of Health and Medical Sciences, Örebro University.
    Has folate a role in the developing nervous system after birth and not just during embryogenesis and gestation?2012In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, no 3, p. 185-191Article in journal (Refereed)
    Abstract [en]

    It is now 30 years since the first publications stating that supplementation with folate could prevent neural tube defects appeared and 20 years since the definitive data, including prevention of other birth defects. Since then epidemiological studies and animal experiments have identified folate as a molecule at the crossroads of neural development. Fortification of food has greatly reduced the incidence of spina bifida. Much interest has focussed on long-term sequelae in children born to mothers severely deprived of folate (and other nutrients) such as during the Dutch Hunger Winter of 1944 and in poor parts of the world. In addition, deficiency in folate and B12 are increasingly discussed as a possible contributing factor in dementia and congenital orofacial and heart malformations. The year 2011 saw the publication of a study that implicated low folate intake in poorer school performance of adolescents as judged by school marks. This has enormous social implications but needs confirmation from other settings. This review assesses the current state of evidence and sets the data in context of whether folate has a role in the development and plasticity of the nervous system even after birth, with particular emphasis on childhood and adolescence.

  • 3. Breimer, Lars H
    et al.
    Nilsson, Torbjörn K
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Shedded cell membrane proteins in plasma: pure waste, or informative biomarkers of pathophysiological processes?2015In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 75, no 6, p. 441-443Article in journal (Other academic)
  • 4.
    Byhamre, Marja Lisa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Oskarsson, Viktor
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Association between snus use and lipid status in Swedish men2023In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 83, no 4, p. 241-250Article in journal (Refereed)
    Abstract [en]

    Snus is a common tobacco product in Sweden, but the cardiovascular risk profile for snus users is less known than for cigarette smokers. We examined the association of snus use with lipid status, particularly in comparison to non-tobacco use and cigarette smoking, using data from 5930 men in the Northern Sweden MONICA study. Tobacco use was self-reported in 1986 to 2014 (24.4% used snus) and blood samples were collected at the same time. Harmonized analyses on non-high-density lipoprotein (non-HDL) cholesterol, HDL cholesterol, and triglycerides were conducted in 2016 to 2018. Three hundred eighty-one snus users had also been examined more than once, allowing us to study the effect of discontinued use (achieved by 21.0%). In multivariable linear regression models, snus use was associated with higher HDL cholesterol and triglyceride concentrations compared to non-tobacco use (p values ≤ 0.04), and it was associated with higher HDL cholesterol concentrations and lower triglyceride concentrations compared to cigarette smoking (p values ≤ 0.02). Snus use was not associated with non-HDL cholesterol concentrations, irrespective of the comparison group (p values ≥ 0.07). There was no indication that higher intensity of snus use led to a worse lipid profile, given that high-consumers had higher HDL cholesterol concentrations than low-consumers (p value = 0.02), or that discontinuation of snus use led to a better lipid profile, given that continued users had lower triglyceride concentrations than discontinued users (p value = 0.03). Further studies are needed to confirm or refute our findings.

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  • 5.
    Bylesjö, Ingemar
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Wikberg, Agneta
    Umeå University, Faculty of Medicine, Department of Nursing.
    Andersson, Christer
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Clinical aspects of acute intermittent porphyria in northern Sweden: A population-based study.2009In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 69, no 5, p. 612-618Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to update the clinical issues of acute intermittent porphyria (AIP), as they have not been in focus for years, and to be aware of potentially associated disorders and social consequences. A total of 356 gene carriers of AIP from northern Sweden participated in this retrospective population-based study. Eight mutations were found with a predominance of W198X (89%). Clinical manifestations of AIP (manifest AIP) were identified in 42%, 65% were women. Women were more severely stricken by AIP attacks concerning number and duration, hospital admission and early onset. Men reporting most attacks were > 40 years of age. In addition to traditional symptoms during attacks, fatigue was commonly described. Chronic AIP symptoms and disability pension due to AIP were reported in about 20% of subjects. Precipitating factors were reported with evident sex differences. Half of the gene carriers who were on medications used drugs considered not safe (in 1999), mainly antihypertensive drugs. Smoking was associated with high AIP attack frequency. Elevated levels of ALT, bile acids, creatinine, U-ALA and U-PBG and decreased levels of creatinine clearance were associated with manifest AIP. The same was true for hypertension and myalgia in the legs. Hepatoma was strikingly overrepresented. The high prevalence of manifest AIP in this study could be explained by a mutation-dependent penetrance. Our results emphasize the importance of early diagnosis, counselling and treatment of attacks, screening and treatment of associated disorders.

  • 6.
    Ekblom, Kim
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry. Department of Clinical Chemistry and Transfusion Medicine, Växjö Central Hospital, Växjö.
    Petersson, Annika
    Evaluation of urine dipsticks for quality control of residual erythrocytes and leukocytes in leukocyte-depleted donor plasma2020In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 80, no 1, p. 39-45Article in journal (Refereed)
    Abstract [en]

    Currently used methodologies for quality control of residual leukocytes and erythrocytes in leukocyte-depleted plasma are either expensive or time-consuming. It has been proposed that urine dipsticks could be used as a screening method for residual erythrocytes. The aim was, therefore, to evaluate if urine dipsticks could be used to detect residual erythrocytes and also residual leukocytes in leukocyte-depleted plasma. Dilution series ranging over the decision limits for residual erythrocytes and leukocytes were prepared. Positive, negative and overall agreements, as well as the precision and joint frequency distributions, were calculated for five dipstick analyzers and their corresponding dipsticks. Twenty-four consecutive leukocyte-depleted donor plasma samples were also tested. None of the dipstick analyzers had both a high positive and a high negative agreement. Accordingly, none of the analyzers were able to discriminate between cell concentrations close to the decision limits. The inconsistency count revealed differences in precision between the dipstick analyzers. In the 24 consecutive donor samples, no significant correlation between the dipstick analyzers and the reference methods were found. In conclusion, urine dipsticks are not suitable for quality control of residual leukocytes and erythrocytes in leukocyte-depleted donor plasma.

  • 7.
    Eklund, Patrik
    Department of Computer Science, Åbo Akademi, Åbo, Finland.
    DiagaiD: A Neuro-Fuzzy System for Developing Medical Decision Support1994In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 54, no s218, p. 9-10Article in journal (Refereed)
  • 8.
    Eklund, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Department of Computing Science.
    Bohlin, J.
    Umeå University, Faculty of Science and Technology, Department of Computing Science.
    Probabilistic networks in laboratory medicine1998In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 58, no s228, p. 32-32Article in journal (Refereed)
  • 9.
    Eklund, Patrik
    et al.
    Umeå University, Faculty of Science and Technology, Department of Computing Science.
    Forsström, J. J.
    Department of Medicine, Turku University Central Hospital, Turku, Finland.
    Computational intelligence for laboratory information systems1995In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 55, no s222, p. 21-30Article in journal (Refereed)
    Abstract [en]

    Non-linear models, such as given by neural networks and fuzzy logic, have established a good reputation for medical data analysis as computational and logical counterparts to statistical methods. Whereas multilayer perceptrons perform well with large data sets, a combination of neural learning together with fuzzy logical network interpretations provides a network reduction well suited for smaller data sets. The aim of this paper is to present an approach to neural fuzzy systems data analysis and knowledge acquisition in laboratory information systems. We also describe a software system, DiagaiD, which provides an analysis and development workbench involving laboratory data.

  • 10.
    Eklöf, Vincy
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    The reduced folate carrier (RFC1) 80G>A and folate hydrolase 1 (FOLH1) 1561C>T polymorphisms and the risk of colorectal cancer: a nested case-referent study2008In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 68, no 5, p. 393-401Article in journal (Refereed)
    Abstract [en]

    Objective. Polymorphisms in genes involved in folate uptake and metabolism may affect folate status and, thereby, the risk of cancer. In this nested case‐referent study, we related two such polymorphisms, reduced folate carrier (RFC1) 80G>A and folate hydrolase 1 (FOLH1) 1561C>T, to the risk of colorectal cancer, taking into account pre‐diagnostic plasma folate and total homocysteine concentrations and the MTHFR 677C>T polymorphism, which were analysed in a previous study.

    Material and methods. Subjects were 220 cases and 414 matched referents from the population‐based Northern Sweden Health and Disease Study.

    Results. The RFC1 80A‐allele was associated with reduced plasma folate and elevated plasma total homocysteine concentrations, but the result was statistically significant only for folate. In contrast, the FOLH1 1561T‐allele was associated with higher plasma folate and reduced plasma total homocysteine concentrations, and the result was statistically significant only for homocysteine. Neither polymorphism was related to the risk of colorectal cancer, either in univariate analysis or after adjusting for body mass index, current smoking, recreational and occupational physical activity and alcohol intake. Further adjustment for folate or homocysteine status or the MTHFR 677C>T polymorphism did not affect risk estimates. Subjects with the RFC1 80AA genotype in combination with low plasma folate concentrations or the MTHFR 677TT genotype had a reduced risk of colorectal cancer of borderline statistical significance.

    Conclusions. These findings suggest that although the RFC1 80G>A and FOLH1 1561C>T polymorphisms may influence folate status, they are not likely to have a major independent role in the development of colorectal cancer.

    Read More: http://informahealthcare.com/doi/abs/10.1080/00365510701805431

  • 11.
    Eriksson, Maria A.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Nilsson, Torbjörn K.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Leptin levels are not affected by enalapril treatment after an uncomplicated myocardial infarction, but associate strongly with changes in fibrinolytic variables in men2020In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 80, no 4, p. 303-308Article in journal (Refereed)
    Abstract [en]

    Leptin, an adipocyte-derived hormone, is involved in the regulation of body weight and is associated with obesity-related complications, notably cardiovascular disease (CVD). A putative link between obesity and CVD could be induction of plasminogen activator inhibitor-1 (PAI-1) synthesis by leptin. In this study, we hypothesized that the beneficial effect of the angiotensin-converting enzyme inhibitor (ACE(i)) enalapril on PAI-1 levels is mediated by effects on leptin levels. The association between leptin and components of the fibrinolytic system was evaluated in a non-prespecified post hoc analysis of a placebo-controlled randomized, double-blind trial where the effect of the ACE(i) enalapril on fibrinolysis was tested. A total of 46 men and 37 women were randomized to treatment with enalapril or placebo after (median 12 months) an uncomplicated myocardial infarction. At baseline, the participants were stable and had no signs of congestive heart failure. Leptin and fibrinolytic variables (mass concentrations of PAI-1, tissue plasminogen activator (tPA) and tPA-PAI complex) were measured at baseline, and after 10 days, 6 months and 12 months. Enalapril treatment did not change leptin levels, which increased significantly during 1 year of follow-up (p = .007). Changes in leptin levels were strongly associated with changes of tPA mass (p = .001), tPA-PAI complex (p = .003) and of PAI-1 (p = .006) in men, but not in women. Leptin levels are not influenced by treatment with an ACE(i). In contrast, leptin associates strongly with changes in fibrinolytic variables notably with a sex difference, which could be of importance for obesity-related CVD.

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  • 12.
    Forsström, J. J.
    et al.
    Department of Medicine, University of Turku, Turku, Finland.
    Irjala, K.
    Central Laboratory, Turku University Central Hospital, Turku, Finland.
    Selén, Gustaf
    Åbo Akademi University, Department of Computer Science, Åbo, Finland.
    Nyström, Mats
    Åbo Akademi University, Department of Computer Science, Åbo, Finland.
    Eklund, Patrik
    Åbo Akademi University, Department of Computer Science, Åbo, Finland.
    Using data preprocessing and single layer perceptron to analyze laboratory data1995In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 55, no s222, p. 75-81Article in journal (Refereed)
    Abstract [en]

    During daily work in hospitals a large amount of clinical data is produced each day. Totally computerized patient records are not yet widely used but a large part of essential information is already stored on computer files. These include laboratory test results, diagnoses, codes for operations, codes of histopathological diagnoses and maybe even the patient's medication. Accordingly, these databases include much clinical knowledge that would be useful for clinicians.

    Laboratories try to support clinicians by producing reference values for laboratory tests. It is, of course, necessary information but, however, it does not give very much information about the weight of evidence that an abnormal laboratory test will give in special clinical settings.

    We have developed a software package - DiagaiD - in order to build a smart link between patient databases and clinicians. It utilizes neural network-based machine learning techniques and can produce decision support which meets the special needs of clinicians. From example cases it can learn clinically relevant transformations from original numeric values to logical values. By using data transformation together with a single layer perceptron it is possible to build nonlinear models from a set of preclassified example cases.

    In this paper, we use two small datasets to show how this scheme works in the diagnosis of acute appendicitis and in the diagnosis of myocardial infarction. Results are compared with those obtained using logistic regression or backpropagation neural networks. The performance of our neuro-fuzzy tool seemed to be slightly better in these two materials but the differences did not reach statistical significance.

  • 13.
    Grankvist, Kjell
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Sigthorsson, Gudmundur
    Kristensen, Gunn B.
    Pelanti, Jonna
    Nybo, Mads
    Status on fasting definition for blood sampling in the Nordic countries - time for a harmonized definition2018In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 78, no 7-8, p. 591-594Article in journal (Refereed)
    Abstract [en]

    The preanalytical phase contains a vast number of practices whose variation may influence the results of laboratory testing and should, therefore, be standardized. The Working Group on Preanalytical Phase of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM WG-PA) has suggested a standardization of venous blood specimen collection (VBSC) requirements for fasting samples including 12 h fasting time and water ad lib in the morning prior to specimen collection. The Nordic Scientific Preanalytical Working Group investigated the fasting definitions used in the Nordic countries. The Internet was assessed for stated fasting definitions of official organizations, larger laboratories, or laboratory groups. Fasting instructions for VBSC generally demanded patients to abstain from alcohol a day prior to, and to abstain from coffee, tea, smoking, and snuff intake in the morning of VBSC. Norway had a national fasting definition. Required fasting times varied from 8 to 14 h. The amount of water allowed in the morning of VBSC varied from ad lib to half a glass of water. The list of analytes, where fasting was required, held 9-15 analytes except for Finland with 65 analytes. Implementation of the EFLM WG-PRE standardization of VBSC requirements for fasting samples would decrease preanalytical variability and be beneficial for medical decisions and patient data comparison. We suggest the laboratories in the Nordic countries to implement the suggested fasting requirements, which are in line with those used when fasting reference intervals were established in the Nordic reference interval project.

  • 14. Gustafsson, Dan
    et al.
    Breimer, Lars H
    Isaksson, Helena S
    Nilsson, Torbjörn K
    Department of Laboratory Medicine, and Department of Clinical Medicine & Biomedicine, Örebro University, Örebro, Sweden.
    Tissue zinc levels in a child with hypercalprotectinaemia and hyperzincaemia: a case report and a review of the literature2012In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, no 1, p. 34-38Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A girl suffering from a rare syndrome of unknown aetiology, termed hypercalprotectinaemia, was evaluated for tissue zinc status, because calprotectin is a protein which chelates Zn at multiple binding-sites, which might have affected the distribution of Zn in her body.

    METHODS: Measurement of serum, urine, hair and nail zinc (Zn) concentration, complemented with measurement of total Zn in ultrafiltrates of plasma.

    RESULTS: Her serum Zn concentration was 105-133 μmol/L. Zn levels in her hair (102 μg/g), nail (90 μg/g) and urine (3-12 μmol/L; 20-80 μg/dL) were all at the lower end of the reference intervals described in the sparse literature. Zn concentrations in ultrafiltrates of plasma were below the detection limit (<100 nmol/L). Thus, the elevated serum Zn did not translate into a similarly increased level of Zn in any of the tissues tested, nor in free Zn concentrations. Instead it appeared to be a result of Zn being chelated to binder proteins, most probably calprotectin.

    CONCLUSION: Her grossly elevated serum calprotectin concentration is probably able to raise circulating total Zn concentrations without raising ionized concentrations, but this Zn remains confined to the circulating blood as well as to excreted body fluids, particularly faeces.

  • 15.
    Hellman, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lång, Kenneth
    Department of Medicine, Piteå Hospital , Piteå , Sweden..
    Ihse, Elisabet
    Jonasson, Jenni
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Olsson, Malin
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lundgren, Hans-Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Pilebro, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Westermark, Per
    Wixner, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Transthyretin Glu54Leu - an unknown mutation within the Swedish population associated with amyloid cardiomyopathy and a unique fibril type2019In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 79, no 6, p. 372-376Article in journal (Refereed)
    Abstract [en]

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

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  • 16.
    Karling, Pontus
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lundgren, David
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Eklöf, Vincy
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Improved monitoring of inflammatory activity in patients with ulcerative colitis by combination of faecal tests for haemoglobin and calprotectin2019In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 79, no 5, p. 341-346Article in journal (Refereed)
    Abstract [en]

    Faecal calprotectin (FC) tests and faecal immunological tests (FIT) for haemoglobin have been used to monitor disease activity in patients with ulcerative colitis (UC) but used alone they have some limitation concerning the predictive ability. We aimed to test if an FC test used in combination with FIT could improve the predictive ability. Consecutive out-patients with UC (n = 93) who were admitted for colonoscopy completed a single faecal sample before the start of bowel preparation. A quantitative CALPRO (R) calprotectin ELISA test and a qualitative FIT (cut-off < 40 ng/mL) were analyzed. An estimated Mayo score and a score of histological inflammation was performed blinded to the result of the faecal tests. The sensitivity, specificity, negative predictive value and positive predictive value for endoscopic inflammation (Mayo score > 1) was for FIT 85%, 83%, 96%, 57% and for FC > 186 mu g/g 73%, 87%, 87%, 54%. Corresponding results for FIT*FC > 186 mu g/g (at least one test positive) were 92%, 69%, 97%, 43%. For detecting moderate/severe histological inflammation the results were for FIT 69%, 79%, 92%, 43%, for FC > 75 mu g/g 95%, 62%, 98%, 41%, and for FIT*FC > 75 mu g/g 100%, 60%, 100%, 36%. None of the markers alone or in combination were useful to predict deep remission (Mayo score = 0 and no histological inflammation). We conclude that using the combination of an FC test and FIT shows minor improvement in predictive ability for inflammatory activity and remission in patients with UC.

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  • 17.
    Kralova, Ivana
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Non-traumatic subarachnoid hemorrhage is associated with subnormal blood creatinine levels2010In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 70, no 6, p. 438-446Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study was to examine the hypothesis that patients with non-traumatic subarachnoid hemorrhage (SAH) have statistically significant subnormal creatinine levels and that the creatinine levels are associated with severity of disease.

    MATERIALS AND METHODS: This was a retrospective observational study over 2 years (2005-2006) in which the SAH patients were divided into patients with severe symptoms and patients with mild/moderate symptoms, and were compared to patients with; traumatic brain injury, trauma without brain injury and patients undergoing elective knee surgery. Blood creatinine levels (day 1-3, and day 7) were recorded.

    RESULTS: Compared to a normal distribution, SAH patients had statistically significant subnormal creatinine levels day one through seven. SAH patients with severe symptoms had statistically significant subnormal creatinine levels already on day one, in contrast to patients with mild/moderate symptoms. Women with severe symptoms had statistically significant subnormal creatinine levels throughout the study period in contrast to men with severe symptoms who had a normal distribution of creatinine at admission. Women with mild/moderate symptoms had a normal distribution of creatinine only at admission in contrast to men who had a normal distribution of creatinine throughout the study period. Male patients with traumatic brain injury, all trauma patients without brain injury and all patients undergoing elective knee surgery had a normal distribution of creatinine on all studied days.

    CONCLUSIONS: SAH is associated with subnormal serum creatinine levels. This finding is more pronounced in patients with severe symptoms and in women.

  • 18.
    Larsson, Anders
    et al.
    Dept of Medical Scienses, Clinical Chemistry, Uppsala University.
    Tydén, Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Lipcsey, Miklos
    Dept of Surgical Scienses, Anaesthesiology and Intensive Care, Uppsala University.
    Bergquist, Maria
    Dept of Surgical Scienses, Anaesthesiology and Intensive Care, Uppsala University.
    Kultima, Kim
    Dept of Medical Scienses, Clinical Chemistry, Uppsala University.
    Mandic-Havelka, Aleksandra
    Dept of Molecular Medicine and Surgery, Karolinska University Hospital.
    Calprotectin is superior to procalcitonin as a sepsis marker and predictor of 30-day mortality in intensive care patients2020In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 80, no 2, p. 156-161Article in journal (Refereed)
    Abstract [en]

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

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  • 19. Larsson, Sara Marie
    et al.
    Hillarp, Andreas
    Hellstrom-Westas, Lena
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lundahl, Tom
    Andersson, Ola
    When age really matters: ferritin reference intervals during infancy revisited2019In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 79, no 8, p. 590-594Article in journal (Refereed)
    Abstract [en]

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

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  • 20.
    Li, Aihong
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Grönlund, Elisabeth
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Brattsand, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Automated white blood cell counts in cerebrospinal fluid using the body fluid mode on the platform Sysmex XE-50002014In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 74, no 8, p. 673-680Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Sysmex XE-5000 offers automated quantification of red blood cells and white blood cells (WBCs) in body fluids, with differentiation of polymorphonuclear cells (PMNs) and mononuclear cells (MNCs). METHODS: We evaluated automated WBC counting in cerebrospinal fluid (CSF) using the body fluid mode on the Sysmex XE-5000, comparing it with flow cytometry as the reference method, and also with manual counting by microscopy. Experimental analysis for linearity and limit of detection was performed by diluting isolated WBCs in cell-free CSF. To study the ability to discriminate between PMNs and MNCs, samples were spiked using MNCs separated from peripheral blood. Comparison of WBC counts between a counting chamber and the XE-5000 was performed for 198 CSF samples. RESULTS: In the experimental set-up, within-run (CV 19%) and between-day imprecision (CV 15.3%) in quantitating total number of WBC on XE-5000 was acceptable for WBC counts >= 25x10(6)/L. Compared with expected cell counts, mean bias was +/- 2.6% for flow cytometry, +/- 5.5% for XE-5000 and -73.2% for manual counting. Differentiation between PMNs and MNCs was in concordance with flow cytometry. In comparisons of clinical CSF samples, overall agreement between the XE-5000 and manual counting was observed in 81% of the samples, but mean difference in WBC differentiation was higher for PMN (51.1x10(6)/L) than for MNC (7.95x10(6)/L). CONCLUSION: Despite limited precision at low WBC counts, XE-5000 could be a favourable alternative to the labour-intensive, time-consuming and less reliable manual counting and cuts turnaround times in routine CSF-based diagnosis.

  • 21.
    Ljungberg, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mild impairment of renal function (shrunken pore syndrome) is associated with increased risk for future surgery for aortic stenosis2019In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 79, no 7, p. 524-530Article in journal (Refereed)
    Abstract [en]

    Recently, a new approach was proposed to detect mild impairment in renal function: a reduced ratio between estimated glomerular filtration rate (eGFR) calculated by cystatin C and eGFR calculated by creatinine. We aimed to evaluate if this ratio is associated with aortic stenosis (AS) requiring surgery. We identified 336 patients that first participated in population surveys and later underwent surgery for AS (median age [interquartile range] 59.8 [10.3] years at survey and 68.3 [12.7] at surgery, 48% females). For each patient, two matched referents were allocated. Cystatin C and creatinine were determined in stored plasma. eGFR(cystatin C) and eGFR(creatinine) and their ratio were estimated. Conditional logistic regression analyses were used to estimate the risk (odds ratio (OR) with [95% confidence interval (CI)]) related to one (ln) standard deviation increase in the ratio between eGFR(cystatin C) and eGFR(creatinine). A high ratio was associated with lower risk for AS requiring surgery (OR [95% CI]) (OR 0.84 [0.73-0.97]), especially in women (0.74 [0.60-0.92] vs. 0.93 [0.76-1.13] in men). After further stratification for coronary artery disease (CAD), the association remained in women with CAD but not in women without CAD (0.60 [0.44-0.83] and 0.89 [0.65-1.23], respectively). In conclusion, a high ratio between eGFR(cystatin C) and eGFR(creatinine) was associated with lower risk for surgery for AS, especially in women. Mild impairment of renal function is thus associated with future risk for AS requiring surgery.

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  • 22.
    Mahmood, Dana
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Solveig
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lipoprotein lipase activity is favoured by peritoneal dialysis compared to hemodialysis2014In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 74, no 4, p. 296-300Article in journal (Refereed)
    Abstract [en]

    Background. The lipoprotein lipase (LPL) pool is reduced by 50% in patients on hemodialysis (HD). LPL release by tinzaparin has not been investigated for peritoneal dialysis (PD). Therefore, the aim of this study was to investigate if tinzaparin differently alters the pool of LPL and triglyceride levels of patients on HD versus PD. Materials and methods. Thirty-two patients on chronic PD or HD were matched to nearest age and gender. In order to release and thereby estimate the endothelial pool of LPL, all patients received a bolus of tinzaparin (75 units/kg). Blood samples were drawn for analysis of LPL activity and triglycerides (TG) between the groups. Results. The peak level of LPL released at 40 min after tinzaparin was similar in PD and HD patients. At 180 min, a slightly higher median level of LPL activity was noted in the PD patients (6.1 mU/mL (n = 6) versus 3.4 mU/mL (n = 16), p = 0.005). The TG concentration in plasma at 40 min was reduced relatively more in the PD patients than in the HD patients (p < 0.05). At 180 min, TG had returned to start levels in HD patients while they were still lowered in PD patients. Conclusions. The negative effect of uraemia on the LPL pool in HD patients, known from other studies, here is shown to be similar in PD patients. Tinzaparin administration releases the LPL pool during each HD but does not cause an exhaustion of the LPL system over time. In contrast to HD, the LPL pool is not altered during PD.

  • 23.
    Matsunaga, N
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Anan, Intissar
    Rosenberg, P
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nagai, R
    Lundström, O
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Horiuchi, S
    Ando, Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B
    Advanced glycation end product is implicated in amyloid-related kidney complications2005In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 65, no 4, p. 263-272Article in journal (Refereed)
    Abstract [en]

    Background. Kidney failure is a common complication in familial amyloidotic polyneuropathy (FAP). It has been suggested that advanced glycation end products (AGEs) play an important role in the development and pathogenesis of FAP.

    Material and methods. To evaluate the impact of AGEs on FAP patients' kidney dysfunction, we measured AGE in serum and urine of 28 FAP patients and 18 healthy controls by AGE-specific enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry utilizing antibodies to AGE and the receptor for AGE (RAGE) were used on kidney tissue from 3 FAP patients and 3 diabetic patients to disclose a correlation between amyloid deposits and AGE -RAGE.

    Results. The glomeruli of FAP patients were heavily deposited with amyloid and the glomerular size was enlarged. The space between Bowman's capsule and glomerulus was totally covered by the enlarged glomerulus. AGE and RAGE were deposited in glomeruli and tubuli and correlated with amyloid deposits. Decreased AGE levels in the liver-transplanted FAP patients' serum compared with that of non-transplanted patients were noted, and AGE concentration in serum tended to be higher in non-transplanted FAP patients compared with normal control subjects. There were no differences in the AGE urine levels in FAP patients compared with controls. No correlation could be found between AGE in urine and serum compared with serum albumin, serum creatinine and creatinine clearance.

    Conclusions. The accumulation of AGE, RAGE and amyloid in the kidney of FAP patients suggests that these molecules play an important role in the origin and pathogenesis of renal failure in FAP patients.

  • 24.
    Mickelsson, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Söderström, Elisabet
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry. Norrbotten County Council, Sunderby Hospital, Sweden.
    Stefansson, Kristina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Andersson, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Smoking tobacco is associated with renal hyperfiltration2021In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 81, no 8, p. 622-628Article in journal (Refereed)
    Abstract [en]

    Tobacco consumption is a renal risk factor, but the effects on the estimated glomerular filtration rate (eGFR) remain unclear. We aimed to evaluate the possible impact of using tobacco products (smoking and snus) on eGFR based on creatinine or cystatin C. We used a first cohort with 949 participants and a second cohort with 995 participants; none had pre-existing renal disease. All subjects donated a blood sample and completed a questionnaire, including questions about tobacco use. To assess the effect on eGFR, hierarchical multiple linear regression models were used. Active smoking associated independently with a higher eGFRcreatinine in all subjects (p < 0.001; β = 0.11). Further analyses stratified for sex, showed similar findings for men (p < 0.001; β = 0.14) and for women (p = 0.026; β = 0.10). eGFRcystatin C was significantly associated with active smoking in all subjects (p = 0.040; β = −0.05), but no association was seen after stratification for sex. Snus did not associate with eGFR. In conclusion, smoking associated significantly with a higher eGFRcreatinine. The mechanism may be renal hyperfiltration of smaller molecules such as creatinine. This is probably caused by substances from smoked tobacco other than nicotine, as no effect was seen for snus.

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  • 25.
    Näsström, Birgit
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Olivecrona, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Stegmayr, Bernd G
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Lipoprotein lipase during heparin infusion: lower activity in hemodialysis patients2003In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 63, no 1, p. 45-53Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: [corrected] Patients on hemodialysis often have a moderate hypertriglyceridemia in combination with low HDL cholesterol. A contributing factor may be a derangement of the lipoprotein lipase (LPL) system. During dialysis, with heparin as anticoagulant, the enzyme is released into the circulating blood. METHODS: We have followed LPL activity and triglycerides during ordinary heparin administration in nine hemodialysis patients and controls matched for age and gender. Blood samples were drawn before heparin administration and at 15, 30, 60, 120, 180 and 240 min. RESULTS: LPL activity peaked at 15 or 30 min and then decreased to a plateau that was only 20%, of the peak. The activity was reduced in the patients by about 50% during the peak, and about 20% during the following plateau. During the peak of lipase activity the triglycerides decreased in both groups, but the change was less pronounced in patients, as was expected from the lower circulating lipase activity. During the plateau phase with low lipase activity, the triglycerides increased towards baseline values. CONCLUSIONS: During hemodialysis with heparin, there is a peak in LPL activity as well as a reduction in triglycerides during the first hour. Thereafter LPL activity decreases towards a plateau, while triglycerides increase towards baseline. The peak activity of LPL in the patients was only half that in controls, while the plateau was comparable. The data indicate that during and following each dialysis there is a period when LPL activity becomes depleted to a level that is limiting for normal lipoprotein metabolism.

  • 26.
    Pettersson-Pablo, Paul
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Nilsson, Torbjörn K.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Breimer, Lars H.
    Hurtig-Wennlof, Anita
    Body fat percentage is more strongly associated with biomarkers of low-grade inflammation than traditional cardiometabolic risk factors in healthy young adults: the Lifestyle, Biomarkers, and Atherosclerosis study2019In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 79, no 3, p. 182-187Article in journal (Refereed)
    Abstract [en]

    The primary aim was to appraise the relationship between body fat percentage and the inflammatory markers C-reactive protein (CRP) and orosomucoid in a population of young, non-smoking, healthy, Swedish adults, without any chronic diseases. A secondary aim was to compare whether these associations differed between the women using estrogen contraceptives and those who did not. We assessed the association in linear regression models between body fat percentage based on a bio-impedance measurement and plasma concentrations of CRP and orosomucoid in men and women aged 18-26 years, n = 834. Statistically significant associations were found between body fat percentage and both biomarkers of inflammation, with beta coefficients of 0.30 (95% CI 0.24-0.37) and 0.28 (0.22-0.35) for CRP and orosomucoid, respectively (p < .001). Adjustment for established risk factors marginally lowered the effects sizes (partial betas, 0.28 and 0.20, respectively), while the strong statistically significant associations remained. In the female cohort, estrogen and non-estrogen using subpopulations did not significantly differ in the correlations between body fat percentage and the inflammatory biomarkers, even adjusted for established cardiometabolic risk factors. In conclusion, in healthy young adults, higher levels of body fat percentage are associated with elevations in plasma biomarkers of inflammation, suggesting that a systemic inflammatory process, promoting atherosclerosis, may commence already at this early stage in life. CRP and orosomucoid plasma concentrations differed between users and non-users of estrogen contraceptives, but both subgroups showed similar correlations between increasing body fat percentage and increasing plasma concentrations of the biomarkers of inflammation.

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  • 27.
    Rodling Wahlström, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Subarachnoid haemorrhage induces an inflammatory response followed by a delayed persisting increase in asymmetric dimethylarginine2012In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, no 6, p. 484-489Article in journal (Refereed)
    Abstract [en]

    Object: Subarachnoid haemorrhage (SAH) is associated with an inflammatory systemic response and cardiovascular complications. Asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthase, mediates vasoconstriction and might contribute to cerebral vasoconstriction and cardiovascular complications after SAH. ADMA is also involved in inflammation and induces endo­thelial dysfunction.

    The aim of this study was to evaluate whether and how CRP (marker for systemic inflammation) and ADMA increased in patients during the acute phase (first week) after SAH. The ADMA level was also assessed in the patients in a non-acute phase (three months), and in healthy controls.

    Methods: Prospective study of 20 patients with aneurysmal SAH. ADMA and CRP were followed daily during the first week after SAH and a follow up sample for ADMA was obtained three months later. A single blood sample for ADMA was collected from age and sex matched healthy controls (n=40, 2 for each case).

    Results: CRP increased significantly from day 2; 16  (Confidence interval (CI) 10-23) mg/L to day 4; 84 (CI 47-120) mg/L, (p<0.01). ADMA increased significantly from day 2; 0.22 (CI 0.17-0.27) µmol/L, to day 7; 0.37 (CI 0.21-0.54) µmol/L, p<0.01. ADMA remained elevated at a three-month follow-up 0.36 (CI 0.31-0.42) µmol/L.

    ADMA in the first sample from the patients (day 1-3); 0.25 (CI 0.19-0.30) µmol/L, was not different from ADMA in matched healthy controls; 0.25 (CI 0.20-0.31), p>0.05.

    Conclusion: After SAH, CRP and ADMA in serum increased significantly during the first week and ADMA remained elevated three months later.

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  • 28.
    Spigset, Olav
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Kristoffersson, Anders
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Mjörndal, Tom
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Platelet serotonin 5-HT2A receptor binding in patients with carcinoid tumor2004In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 64, no 1, p. 3-8Article in journal (Refereed)
    Abstract [en]

    Background: As carcinoid tumors produce and secrete serotonin, various serotonin markers in blood, plasma and urine have been used as diagnostic tools, and quantification of the urinary excretion of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) is the method most frequently used.

    Methods: [ 3 H]lysergic acid diethylamide ([ 3 H]LSD) binding to the platelet serotonin 5-HT 2A receptor was investigated in nine patients with carcinoid tumors. The possible effect of serotonin-rich food on the receptor binding was also investigated.

    Results: B max for [ 3 H]LSD binding was significantly lower in the carcinoid group than in the control group (mean±SD: 17.6±1.3 vs. 23.9±5.2 fmol/mg protein; p=0.007). K d for [ 3 H]LSD binding was significantly higher in the carcinoid group than in the control group (median: 1.14 vs. 0.71 nmol/L; p=0.03). B max was inversely related to the urinary 5-HIAA excretion, but the correlation did not reach statistical significance (r s =-0.57; p=0.14). Intake of five bananas per day for one week had no effect on B max or K d in healthy volunteers.

    Conclusions: The results are consistent with a down-regulation of the 5-HT 2A receptor as a response to the high serotonin levels found in patients with carcinoid tumors. Intake of serotonin-rich food does not affect the receptor characteristics. Further studies are needed to determine whether the platelet 5-HT 2A receptor status can be used as a supplement to urinary 5-HIAA and other biochemical variables in carcinoid tumors.

  • 29.
    Suhr, Ole B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lång, K
    Wikström, L
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ando, Y
    El-Salhy, M
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Holmgren, G
    Tashima, K
    Scavenger treatment of free radical injury in familial amyloidotic polyneuropathy: a study on Swedish transplanted and non-transplanted patients.2001In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 61, no 1, p. 11-8Article in journal (Refereed)
    Abstract [en]

    Since oxidative stress has been implicated in amyloid diseases, a study of scavenger treatment of hereditary transthyretin amyloidosis was undertaken on 23 familial amyloidotic polyneuropathy (FAP) patients. Nine patients had undergone a liver transplantation for the disease. Twenty patients completed the 6-month study period of scavenger treatment (vitamin C, 1 g, three times daily, vitamin E, 0.1 g, three times daily and acetylcysteine, 0.2 g three times daily). They were evaluated clinically and by immunohistochemical measurement of hydroxynonenal (HNE), a product of lipid peroxidation, in biopsy specimens. For non-transplanted patients, no improvement was found for HNE in relation to the amyloid content in biopsy specimens, whereas a tendency to a decreased amount was noted for transplanted patients. Clinically, no differences were found for non-transplanted patients, but an increased nutritional status, measured by a modified body mass index (mBMI) was noted for transplanted patients. In summary, scavenger treatment with the drugs and doses used in the present study appears to be unable to decrease lipid peroxidation in amyloid-rich tissue in non-transplanted FAP patients. For transplanted patients, lipid peroxidation tended to decrease, and the nutritional status measured by mBMI improved, even though the findings may be explained by liver transplantation alone, scavenger treatment may facilitate recovery after transplantation.

  • 30.
    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.

  • 31.
    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.

  • 32.
    Söderström, Elisabet
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Blind, Ravna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Andersson, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Nilsson, Torbjörn K.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Mild impairment of renal function (shrunken pore syndrome) is associated with increased risk of a future first-ever myocardial infarction in women2021In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 81, no 6, p. 438-445Article in journal (Refereed)
    Abstract [en]

    Impaired renal function is associated both with the development of cardiovascular disease and its prognosis. A new syndrome called ' Shrunken Pore Syndrome ' has been suggested, as the estimated glomerular filtration rate for cystatin C (eGFR(cystatin C)) is affected earlier due to differences in molecular size compared to eGFR(creatinine). The aim was to investigate if a lower eGFR(cystatin C)/eGFR(creatinine) ratio in a prospective setting increases the risk of later developing a first-ever myocardial infarction (MI) independently of other cardiovascular risk factors. We used a nested case-referent study design within the Northern Sweden Health and Disease Study, and 545 subjects (29.0% women) were identified who prospectively developed a first-ever MI, and their 1054 matched referents. For women, but not for men, one standard deviation (SD) increase of ln z-scores of eGFR(cystatin C)/eGFR(creatinine) ratio was associated with a lower risk of a future MI: odds ratio [95% confidence interval] 0.58 [0.34-0.99], adjusted for apolipoprotein B/A1 ratio, CRP, homocysteine, systolic blood pressure, body mass index, and diabetes. Furthermore, a high eGFR(creatinine) associated independently with an increased risk of future MI in men only: OR 1.25 [1.05-1.48]. Thus, for women, a lower eGFR(cystatin C)/eGFR(creatinine) ratio is associated with a higher risk of having a future first-ever MI, and it may be a valuable, easily implemented biomarker for risk of cardiovascular disease.

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  • 33. Valencia, Liliana
    et al.
    Randazzo, Andres
    Engfeldt, Peter
    Olsson, Lovisa A.
    Chavez, Adolfo
    Buckland, Robert J.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Nilsson, Torbjörn K.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Almon, Ricardo
    Identification of novel genetic variants in the mutational hotspot region 14kb upstream of the LCT gene in a Mexican population2017In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 77, no 5, p. 311-314Article in journal (Refereed)
    Abstract [en]

    Several polymorphic loci linked to lactase persistence (LP) have been described, all located in a small mutational hotspot region far upstream (approximate to 14kb) of the lactase (LCT) gene. One is typically found in Europeans, LCT -13910C>T, several others are found in East Africans and Arabs, e.g. LCT -13907C>G and LCT -13915T>G. The possibility of similar loci, specific to populations in South and Central America, has not received much attention so far. To identify possible novel polymorphisms in the mutational hotspot region, we sampled 158 subjects from a rural area in South-Central Mexico. DNA was isolated from serum, and Sanger sequencing of a 501bp region spanning the LCT -13910C>T hotspot was successfully performed in 150 samples. The frequency of the European-type LCT -13910T-allele was q=0.202, and 35% of the population was thus lactase-persistent (CT or TT). Sixteen novel genetic variants were found amongst 11 of the subjects, all were heterozygotes: seven of the subjects were also carriers of at least one LCT -13910T-allele. Thus, the mutational hotspot region is also a hotspot in the rural Mexican population: 11/150 subjects carried a total of 16 previously unknown private mutations but no novel polymorphism was found. The relationship between such novel genetic variants in Mexicans and lactase persistence is worthy of more investigation.

  • 34.
    Wallin, Olof
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Söderberg, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Patient-centred care - preanalytical factors demand attention: a questionnaire study of venous blood sampling and specimen handling2007In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 67, no 8, p. 836-847Article in journal (Refereed)
    Abstract [en]

    Objective. Most mistakes in laboratory medicine are the result of human error occurring before the blood sample reaches the laboratory. This survey of preanalytical procedures was designed to identify sources of error and potential targets for quality improvement strategies.

    Material and methods. The staff in a highly specialized surgical ward at a university hospital completed a questionnaire addressing the collection and handling of venous blood samples in plastic vacuum test‐tubes for general clinical chemistry testing.

    Results. The results suggest that venous blood sampling instructions are not always followed. When uncertain about how a sample should be collected, the majority of respondents rely on potentially poor sources of information, such as out‐of‐date printed instructions or the advice of a colleague, rather than consult up‐to‐date electronic instructions. Furthermore, they do not always report errors and the referrals are not always handled according to sampling instructions. The respondents were highly motivated, however, and had a strong interest in receiving further education in, and assuming increased responsibility for, venous blood sampling procedures in the ward.

    Conclusions. We believe that the introduction of standardized routines and regular staff training, combined with an exchange of the existing paper‐based referral management system with an electronic system for managing referrals, could increase safety in the preanalytical process, with positive effects on patient safety. Given the importance of venous blood samples in patient care, a more extensive study covering other hospital wards and primary health‐care centres is needed.

    Read More: http://informahealthcare.com/doi/abs/10.1080/00365510701370675

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