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  • 51.
    Lesage, S
    et al.
    Fdn Jean Dausset, Paris, France Epimad, Lille, France Getaid, Liege, Belgium Ewggp Ibd, Paris, France Irebro Hosp, Irebro, Sweden Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hosp Germans Trias & Pujol, Badalona, Spain Herlev Hosp, DK-2730 Herlev, Denmark.
    Chamaillard, M
    Fdn Jean Dausset, Paris, France Epimad, Lille, France Getaid, Liege, Belgium Ewggp Ibd, Paris, France Irebro Hosp, Irebro, Sweden Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hosp Germans Trias & Pujol, Badalona, Spain Herlev Hosp, DK-2730 Herlev, Denmark.
    Colombel, JF
    Fdn Jean Dausset, Paris, France Epimad, Lille, France Getaid, Liege, Belgium Ewggp Ibd, Paris, France Irebro Hosp, Irebro, Sweden Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hosp Germans Trias & Pujol, Badalona, Spain Herlev Hosp, DK-2730 Herlev, Denmark.
    Belaiche, J
    Fdn Jean Dausset, Paris, France Epimad, Lille, France Getaid, Liege, Belgium Ewggp Ibd, Paris, France Irebro Hosp, Irebro, Sweden Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hosp Germans Trias & Pujol, Badalona, Spain Herlev Hosp, DK-2730 Herlev, Denmark.
    Cizard, JP
    Fdn Jean Dausset, Paris, France Epimad, Lille, France Getaid, Liege, Belgium Ewggp Ibd, Paris, France Irebro Hosp, Irebro, Sweden Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hosp Germans Trias & Pujol, Badalona, Spain Herlev Hosp, DK-2730 Herlev, Denmark.
    Tysk, C
    Fdn Jean Dausset, Paris, France Epimad, Lille, France Getaid, Liege, Belgium Ewggp Ibd, Paris, France Irebro Hosp, Irebro, Sweden Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hosp Germans Trias & Pujol, Badalona, Spain Herlev Hosp, DK-2730 Herlev, Denmark.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Gassull, MA
    Fdn Jean Dausset, Paris, France Epimad, Lille, France Getaid, Liege, Belgium Ewggp Ibd, Paris, France Irebro Hosp, Irebro, Sweden Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hosp Germans Trias & Pujol, Badalona, Spain Herlev Hosp, DK-2730 Herlev, Denmark.
    Binder, V
    Fdn Jean Dausset, Paris, France Epimad, Lille, France Getaid, Liege, Belgium Ewggp Ibd, Paris, France Irebro Hosp, Irebro, Sweden Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hosp Germans Trias & Pujol, Badalona, Spain Herlev Hosp, DK-2730 Herlev, Denmark.
    Zouali, H
    Fdn Jean Dausset, Paris, France Epimad, Lille, France Getaid, Liege, Belgium Ewggp Ibd, Paris, France Irebro Hosp, Irebro, Sweden Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hosp Germans Trias & Pujol, Badalona, Spain Herlev Hosp, DK-2730 Herlev, Denmark.
    Thomas, G
    Fdn Jean Dausset, Paris, France Epimad, Lille, France Getaid, Liege, Belgium Ewggp Ibd, Paris, France Irebro Hosp, Irebro, Sweden Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hosp Germans Trias & Pujol, Badalona, Spain Herlev Hosp, DK-2730 Herlev, Denmark.
    Hugot, JP
    Fdn Jean Dausset, Paris, France Epimad, Lille, France Getaid, Liege, Belgium Ewggp Ibd, Paris, France Irebro Hosp, Irebro, Sweden Linkoping Univ Hosp, S-58185 Linkoping, Sweden Hosp Germans Trias & Pujol, Badalona, Spain Herlev Hosp, DK-2730 Herlev, Denmark.
    Protective effect of CYP2D6*4 allele in ulcerative colitis disease.2000In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 118, no 4, p. 1805-Conference paper (Other academic)
  • 52. Lesage, S
    et al.
    Zouali, H
    Cézard, J-P
    Colombel, J-F
    Belaiche, J
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, EMK-magtarm.
    Tysk, C
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology.
    O'Morain, C
    Gassull, M
    Binder, V
    Finkel, Y
    Modigliani, R
    Gower-Rousseau, C
    Macry, J
    Merllin, F
    Chamaillard, M
    Jannot, A-S
    Thomas, G
    hugot, J-P
    CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease.2002In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 70, p. 845-857Article in journal (Refereed)
  • 53. Levenstein, S
    et al.
    Li, Z
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, GE: gastromed.
    Marquis, P
    Moser, G
    Sperber, A
    Toner, B
    Drossman, DA
    Cross-cultural variation in disease-related concerns among patients with inflammatory bowel disease.2001In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 96, p. 1822-1830Article in journal (Refereed)
  • 54.
    Lindgren, Stefan
    et al.
    University Hospital MAS.
    Glaumann, Hans
    Karolinska University Hospital.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Bergquist, Annika
    Karolinska University Hospital.
    Bjornsson, Einar
    Sahlgrenska University Hospital.
    Broome, Ulrika
    Karolinska University Hospital.
    Danielsson, Ake
    Umea University Hospital.
    Lebrun, Barbro
    Karolinska University Hospital.
    Prytz, Hanne
    Lund University Hospital.
    Olsson, Rolf
    Sahlgrenska University Hospital.
    Transitions between variant forms of primary biliary cirrhosis during long-term follow-up2009In: EUROPEAN JOURNAL OF INTERNAL MEDICINE, ISSN 0953-6205, Vol. 20, no 4, p. 398-402Article in journal (Refereed)
    Abstract [en]

    Background: Conditions exhibiting features of two different autoimmune liver diseases are designated overlap syndromes. Variant forms display some, but not all, characteristics of a distinct autoimmune liver disease. We describe transitions over time between variant forms of PBC, i.e. AMA-negative PBC, autoimmune hepatitis (AIH)-PBC overlap and autoimmune cholangitis (AIC) in a large cohort of PBC patients in Sweden. Methods: We retrieved all patients with variant forms of PBC in six university hospitals in Sweden, covering 60% of the Swedish population. The diagnosis of PBC and its variants was based on laboratory findings and compatible histological features. The revised autoimmune hepatitis scoring system proposed by the International Autoimmune Hepatitis Group was used to establish the diagnosis of AIH. Results: In a population of 800 patients with PBC, we identified 35 (5%) variant forms; 25 patients with AIH-PBC overlap, 8 with AIC and 2 with AMA-negative PBC at the time of our study. The initial diagnoses were PBC (3 patients), AIH (3), AIH-PBC overlap (16), AIC (8) and AMA-negative PBC with (1) or without (4) concomitant AIH. The median follow-up was 125 (41-360) months. Immunosuppression and ursodeoxycholic acid induced a complete or good regression of increased aminotransferases in about half of the patients who were given one or both of these treatments. Conclusions: Variant forms of PBC are seen in approximately 5% of PBC patients in Sweden. Transition between different forms may occur, emphasizing the value of repeat biopsies, but established overlapping AIH-PBC seems to be stable over time.

  • 55.
    Lindqvist Appell, Malin
    et al.
    Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MC - Medicincentrum, EMT-magtarm.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Söderkvist, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Real-time RT-PCR methodology for quantification of thiopurine methyltransferase gene expression2003In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 59, no 3, p. 207-211Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of the present study was to develop a real-time reverse-transcription polymerase chain reaction (RT-PCR) methodology for the quantification of thiopurine methyltransferase (TPMT) gene expression in whole blood and compare it with the TPMT enzyme activity measured in red blood cells. Methods: TPMT gene expression was quantified relative to the housekeeping gene cyclophilin (huCYC) and expressed as a TPMT/huCYC ratio. TPMT activity in red blood cells was determined by measuring the formation rate of 6- 14C-methylmercaptopurine from 6-MP using S-adenosyl-L-( 14C-methyl)-methlonine as methyl donor. Thirty-nine individuals were included in the study. A cut-off value of 9 U/ml pRBC was used to distinguish intermediate TPMT enzyme activity from high TPMT enzyme activity. Results: Sequencing of the real-time RT-PCR amplicon proved that the method was specific for the TPMT cDNA, without co-amplification of the highly similar TPMT processed pseudogene. The intra-assay coefficients of variation (CVs), as determined by the threshold cycle, were 0.7% for TPMT and 0.5% for huCYC. The interassay CVs were 1.5% for TPMT and 4.0% for huCYC. The intra- and interassay CVs, as determined by the TPMT/huCYC ratio, were 8.6% and 25%, respectively. There was a statistically significant correlation between TPMT enzyme activity and mRNA level in blood cells from individuals with an enzyme activity above 9 U/ml pRBC (rs = 0.66, P = 0.0001). However, we did not find any statistically significant correlation in individuals with lower enzyme activity or when analysing the whole population. Conclusion: We present a specific and robust real-time RT-PCR method for quantifying TPMT gene expression. The method may be used for studies on TPMT gene regulation.

  • 56.
    Lindqvist Appell, Malin
    et al.
    Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Haglund, Sofie
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Taipalensuu, Jan
    Division of Research and Development in Laboratory Medicine, Ryhov County Hospital, Jönköping.
    Hertervig, Erik
    dDepartment of Medicine, Lund University Hospital, Lund.
    Lyrenäs, Ebbe
    Department of Medicine, Blekinge County Hospital, Karlskrona.
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Identification of two novel sequence variants affecting thiopurine methyltransferase enzyme activity2004In: Pharmacogenetics, ISSN 0960-314X, E-ISSN 1473-561X, Vol. 14, no 4, p. 261-265Article in journal (Refereed)
    Abstract [en]

    The polymorphic enzyme thiopurine methyltransferase (TPMT) is involved in the methylation of thiopurines. On comparing the phenotype with the genotype in Swedish patients with inflammatory bowel disease and healthy individuals, we found two discordant cases with low TPMT enzyme activity (0.3 and 0.4 U/ml packed red blood cells (pRBC). Genotyping by pyrosequencing revealed that they carried the nucleotide substitutions 460G>A and 719A>G, giving two possible genotypes (TPMT*1/*3A or TPMT*3B/ *3C). DNA sequencing of exon III to X was performed in the patients and their parents. We identified an A>G transition in the start codon (exon III, 1A>G, Met>Val, TPMT*14) in one of the patients and her father (6.3 U/ml pRBC). The mother in this family carried the 460G>A and 719A>G nucleotide substitutions (TPMT*3A, 5.0 U/ml pRBC). In the second family, sequencing revealed a G>A transition in the acceptor splice site in intron VII/exon VIII (IVS7 - 1G>A, TPMT*15) in the patient and his mother (6.9 U/ml pRBC). His father was genotyped as TPMT*1/*3A (6.0 U/ml pRBC). Hence, we report the identification of two novel sequence variants, present in highly conserved nucleotide positions of the human TPMT gene, resulting in a loss of enzyme activity.

  • 57.
    Lindqvist Appell, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Hindorf, U
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Ström, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    No induction of thiopurine methyltransferase during thiopurine treatment in inflammatory bowel disease2006In: Nucleosides, Nucleotides & Nucleic Acids, ISSN 1525-7770, E-ISSN 1532-2335, Vol. 25, no 9-11, p. 1033-1037Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to follow, during standardized initiation of thiopurine treatment, thiopurine methyltransferase (TPMT) gene expression and enzyme activity and thiopurine metabolite concentrations, and to study the role of TPMT and ITPA 94C > A polymorphisms for the development of adverse drug reactions. Sixty patients with ulcerative colitis or Crohn's disease were included in this open and prospective multi-center study. Thiopurine naïve patients were prescribed azathioprine (AZA), patients previously intolerant to AZA received 6-mercaptopurine (6-MP). The patients followed a predetermined dose escalation schedule, reaching target dose at Week 3, 2.5 and 1.25 mg/kg body weight for AZA and 6-MP, respectively. The patients were followed every week during Weeks 1-8 from baseline and then every 4 weeks until 20 weeks. TPMT activity and thiopurine metabolites were determined in erythrocytes, TPMT and ITPA genotypes, and TPMT gene expression were determined in whole blood. One homozygous TPMT-deficient patient was excluded. Five non compliant patients were withdrawn during the first weeks. Twenty-seven patients completed the study per protocol, 27 patients were withdrawn because of adverse events. Sixty-seven percent of the withdrawn patients tolerated thiopurines at a lower dose at Week 20. There was no difference in baseline TPMT enzyme activity between individuals completing the study and those withdrawn for adverse events (p = 0.45). A significant decrease in TPMT gene expression (TPMT/huCYC ratio, p = 0.02) was found, however TPMT enzyme activity did not change. TPMT heterozygous individuals had a lower probability of remaining in the study on the predetermined dose (p = 0.039). The ITPA 94C > A polymorphism was not predictive of adverse events (p = 0.35). Copyright © Taylor & Francis Group, LLC.

  • 58.
    Lindqvist Appell, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Hindorf, Ulf
    Lund.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Thiopurines in inflammatory bowel disease - The role of pharmacogenetics and therapeutic drug monitoring2006In: Current Pharmacogenomics, ISSN 1570-1603, Vol. 4, no 4, p. 285-300Article in journal (Refereed)
    Abstract [en]

    Pharmacogenetics represents the study of variability in drug response due to genetic variations. Inflammatory bowel disease (IBD, i.e. primarily Crohn's disease and ulcerative colitis) is characterized by a chronic or relapsing inflammation of the digestive tract. The thiopurines 6-mercaptopurine (6-MP) and azathioprine (AZA), an imidazol derivative and pro-drug of 6-MP, are widely used in IBD, particularly in Crohn's disease. The metabolism of thiopurines is complex and individually variable. Thiopurine methyltransferase (TPMT) is a key enzyme in this metabolism and exhibits a genetic variability due to a number of variant alleles coding for a defective enzyme. The formation of biologically active thioguanine nucleotides (TGN) and methylated metabolites may vary considerably due to the TPMT activity. Patients with decreased TPMT activity are at increased risk of developing severe side effects if treated with conventional thiopurine doses, due to the accumulation of toxic metabolites. Determination of the TPMT phenotype or genotype is often used to identify individuals with increased risk for adverse events. Twenty-one variant TPMT alleles have been described, of which three are more common than the others. An association between inosine triphosphate pyrophosphatase polymorphisms and adverse events during thiopurine treatment has also been proposed. In this review, the clinical value of TPMT status determination and pharmacological monitoring of thiopurine metabolites are discussed as well as the increased interest in the use of 6-thioguanine, a thiopurine with a less complex metabolism, as an alternative for patients who do not tolerate AZA or 6-MP. It can be concluded that TPMT determination before start of thiopurine therapy is of value to identify individuals with increased risk for adverse reactions due to genetic enzyme deficiency. However, large prospective studies are still needed to evaluate the true benefit of monitoring thiopurine metabolites during thiopurine treatment. © 2006 Bentham Science Publishers Ltd.

  • 59.
    Lindqvist Appell, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Hindorf, Ulf
    Lund.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Ström, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Department of Molecular and Clinical Medicine.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    No induction of thiopurine methyltransferase (TPMT) during thiopurine treatment in IBD2005In: 10th Symposium European Society for the Study of Purine and Pyrimidine Metabolism in Man,2005, 2005Conference paper (Refereed)
  • 60.
    Lindqvist Appell, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Hindorf, Ulf
    Lund.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Ström, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Department of Molecular and Clinical Medicine.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    No induction of thiopurine methyltransferase (TPMT) during thiopurine treatment in IBD2005In: 13th United European Gastroenterology week,2005, Stuttgart: Georg Thieme Verlag KG , 2005, p. A173-Conference paper (Refereed)
  • 61.
    Lindqvist Appell, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Pettersson, Birgitta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, GE: gastromed.
    Albertioni, Freidoun
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Söderhäll, Stefan
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    The role of TPMT polymorphism for thiopurine metabolism and clinical effects.2001In: European society for the study of purine and pyrimidine metabolism in Man.,2001, 2001Conference paper (Refereed)
  • 62.
    Lindqvist Appell, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Skoglund, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Karlgren, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Kidhall, Irene
    Danderyds sjukhus.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Explaining TPMT genotype/phenotype discrepancy by haplotyping of TPMT*3A and identification of a novel sequence variant, TPMT*232007In: Pharmacogenetics and Genomics, ISSN 1744-6872, Vol. 17, no 10, p. 891-895Article in journal (Refereed)
    Abstract [en]

    Thiopurine methyltransferase (TPMT) is a polymorphic enzyme involved in the metabolism of thiopurine drugs. Owing to polymorphisms in the TPMT gene (TPMT*2-*22), the enzyme activity varies interindividually. Patients with reduced TPMT activity may develop adverse reactions when treated with standard doses of thiopurines. This work focuses on a TPMT genotype/phenotype discrepancy found in a patient during routine testing. The patient displayed very low TPMT enzyme activity and she was genotyped by pyrosequencing as being heterozygous for the 460G>A and 719A>G polymorphisms (TPMT*3A). Complete sequencing in combination with haplotyping of the TPMT gene revealed a novel sequence variant, 500C>G, on one allele and TPMT*3A on the other allele, giving rise to the novel genotype TPMT*3A/*23. When investigating the patient's relatives, they too had the TPMT*3A/*23 genotype in combination with low enzyme activity. We conclude that this novel variant allele affects enzyme activity, as the individuals carrying it had almost undetectable TPMT activity. © 2007 Lippincott Williams & Wilkins, Inc.

  • 63.
    Lönn, Johanna
    et al.
    PEAS Institut, Linköping, Sweden.
    Sravya, Nakka
    PEAS Institut, Linköping, Sweden.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Bengtsson, Torbjörn
    Örebro University, Sweden.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology. Karolinska Institutet, Stockholm, Sweden.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases. PEAS Institut, Linköping.
    Differences in the expression of hepatocyte growth factor in acute and chronic bowel inflammation - Implications for diagnosis?2013In: Advances in Bioscience and Biotechnology, ISSN 2156-8456, E-ISSN 2156-8502, Vol. 4, no 8A2, p. 33-42Article in journal (Refereed)
    Abstract [en]

    Background: Hepatocyte growth factor (HGF) acts as an acute phase protein with regenerative properties. HGF is produced systemically and locally during inflammation but exhibits decreased binding affinity to heparan sulphate proteoglycan (HSPG)/glycosaminoglycan during chronic inflammation. We previously observed a high faecal concentration and binding affinity of HGF to HSPG during acute gastroenteritis. High faecal concentrations of calprotectin and HGF have been reported in chronic inflammatory bowel disease (IBD).

    Methods: Stool samples from patients with ulcerative colitis in remission (n = 11) or exacerbation (n = 5), microscopic colitis (n = 11), colon cancer (n = 6), or acute gastroenteritis caused by Clostridium difficile (n = 20), as well as healthy controls (n = 7), were analysed for the presence of HGF by ELISA, surface plasmon resonance, SDS-PAGE, and Western blot. Then in two patients with ulcerative colitis exacerbation and C. difficile infection, the expression of HGF and calprotectin was studied in colonic biopsies.

    Results: The faecal concentration of HGF was significantly higher in patients with ulcerative colitis compared to the other groups. The binding affinity to dextran was lower in all groups compared to acute inflammation. HGF receptor binding was similar across groups. In a patient with concomitant C. difficile infection and distal ulcerative colitis, HGF was highly expressed in the part of the bowel unaffected by ulcerative colitis, but no expression was found at the site of chronic inflammation. In the patient with total colitis the biopsies showed low expression of HGF. The areas with chronic inflammation exhibited infiltrating calprotectin-stained neutrophils.

    Conclusion: HGF is produced locally during inflammation of the bowel. The HGF produced during acute inflammation or exacerbations of chronic inflammation by the unaffected area shows binding affinity to glucosaminoglycans. Measuring HGF binding in faeces and biopsies may be a tool for differentiating between acute and chronic bowel inflammation, which should be assessed thoroughly in future studies.

  • 64.
    Mesterton, Johan
    et al.
    i3 Innovus, Stockholm, Sweden.
    Jonsson, Linus
    i3 Innovus, Stockholm, Sweden.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Befrits, Ragnar
    Karolinska Univ Hosp, Div Gastroenterol, Stockholm, Sweden.
    Friis-Liby, Ingalill
    Sahlgrens Univ Hosp, Div Gastroenterol Hepatol, Gothenburg, Sweden.
    Lindgren, Stefan
    Univ Hosp MAS, Dept Clin Sci, Div Gastroenterol Hepatol, S-20502 Malmo, Sweden.
    Resource Use and Societal Costs for Crohns Disease in Sweden2009In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 15, no 12, p. 1882-1890Article in journal (Refereed)
    Abstract [en]

    Background: The usual onset of Crohns disease (CD) is between 15 and 30 years of age, thus affecting people during their most economically productive period in life. Methods: This study intended to estimate societal costs and health-related quality of life (HRQoL) in Swedish patients in different stages of CD. Cross-sectional data on disease activity (measured with the Harvey-Bradshaw Index [HBI]), direct medical resource use, work productivity, and HRQoL (assessed using the 15D instrument) were collected for 420 patients by questionnaires to patients, to the treating physician, and from medical records. Based on HBI, current treatment, and response to treatment, patients were classified into the following disease states: Remission, Response, Active, Refractory, and Surgery. Results: The average 4-week cost per patient in 2007 was estimated at (sic)721 (USD 988), of which 64% was due to lost productivity. The total 4-week cost of care was (sic)255 (USD 349) in Remission, (sic)831 (USD 1138) in Response, (sic)891 (USD 1220) in Active, (sic)1360 (USD 1864) in Refractory, and (sic)16984 (USD 23269) in Surgery. HBI was the most important predictor of costs of care-a 1-point increase in HBI increased total costs by 25% (P less than 0.001). HRQoL differed between the disease states: 0.92 in Remission, 0.90 in Response, 0.82 in Active, 0.81 in Refractory, and 0.77 in Surgery. Conclusions: Patients in remission have the lowest costs and the highest HRQoL. Patients responding to treatment have lower costs of care than patients with high disease activity who are not treated or do not respond to treatment:. Thus, total costs of care might be reduced by efficient treatment.

  • 65.
    Momozawa, Yukihide
    et al.
    Grp Interdisciplinaire Genoprote Appliquee GIGA R.
    Mni, Myriam
    Grp Interdisciplinaire Genoprote Appliquee GIGA R.
    Nakamura, Kayo
    Grp Interdisciplinaire Genoprote Appliquee GIGA R.
    Coppieters, Wouter
    Grp Interdisciplinaire Genoprote Appliquee GIGA R.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Amininejad, Leila
    University Libre Bruxelles.
    Cleynen, Isabelle
    Catholic University Louvain.
    Colombel, Jean-Frederic
    Hop Calmette, Registre MICI Nord Quest France.
    de Rijk, Peter
    University Antwerp VIB.
    Dewit, Olivier
    Catholic University Louvain.
    Finkel, Yigael
    Karolinska Childrens Hospital.
    A Gassull, Miquel
    Hospital Badalona Germans Trias and Pujol.
    Goossens, Dirk
    University Antwerp VIB.
    Laukens, Debby
    University Ghent.
    Lemann, Marc
    University Paris 07.
    Libioulle, Cecile
    Grp Interdisciplinaire Genoprote Appliquee GIGA R.
    OMorain, Colm
    Adelaide and Meath Hospital.
    Reenaers, Catherine
    GIGA R.
    Rutgeerts, Paul
    Catholic University Louvain.
    Tysk, Curt
    Orebro Med Centre Hospital.
    Zelenika, Diana
    Centre Natl Genotypage, Evry.
    Lathrop, Mark
    Centre Natl Genotypage, Evry, France .
    Del-Favero, Jurgen
    University Antwerp VIB.
    Hugot, Jean-Pierre
    Hop Robert Debre.
    de Vos, Martine
    University Ghent.
    Franchimont, Denis
    University Libre Bruxelles.
    Vermeire, Severine
    Catholic University Louvain.
    Louis, Edouard
    GIGA R.
    Georges, Michel
    Grp Interdisciplinaire Genoprote Appliquee GIGA R.
    Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease2011In: NATURE GENETICS, ISSN 1061-4036, Vol. 43, no 1, p. 43-U58Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohns disease(1,2). However, common disease-associated SNPs explain at most similar to 20% of the genetic variance for Crohns disease. Several factors may account for this unexplained heritability(3-5), including rare risk variants not adequately tagged thus far in GWAS(6-8). That rare susceptibility variants indeed contribute to variation in multifactorial phenotypes has been demonstrated for colorectal cancer(9), plasma high-density lipoprotein cholesterol levels(10), blood pressure(11), type 1 diabetes(12), hypertriglyceridemia(13) and, in the case of Crohns disease, for NOD2 (refs. 14,15). Here we describe the use of high-throughput resequencing of DNA pools to search for rare coding variants influencing susceptibility to Crohns disease in 63 GWAS-identified positional candidate genes. We identify low frequency coding variants conferring protection against inflammatory bowel disease in IL23R, but we conclude that rare coding variants in positional candidates do not make a large contribution to inherited predisposition to Crohns disease.

  • 66.
    Myrelid, Pär
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Olaison, Gunnar
    Hvidovre University Hospital.
    Sjödahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Nystrom, Per-Olof
    Karolinska University Hospital .
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Andersson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Thiopurine Therapy Is Associated with Postoperative Intra-Abdominal Septic Complications in Abdominal Surgery for Crohns Disease2009In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 52, no 8, p. 1387-1394Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Thiopurines are important as maintenance therapy in Crohns disease, but there have been concerns whether thiopurines increase the risk for anastomotic complications. The present study was performed to assess whether thiopurines alone, or together with other possible risk factors, are associated with postoperative intra-abdominal septic complications after abdominal surgery for Crohns disease.

    METHODS: Prospectively registered data regarding perioperative factors were collected at a single tertiary referral center from 1989 to 2002. Data from 343 consecutive abdominal operations on patients with Crohns disease were entered into a multivariate analysis to evaluate risk factors for intra-abdominal septic complications. All operations involved either anastomoses, strictureplasties, or both; no operations, however, involved proximal diversion.

    RESULTS: Intra-abdominal septic complications occurred in 26 of 343 operations (8%). Thiopurine therapy was associated with an increased risk of intra-abdominal septic complications (16% with therapy; 6% without therapy; P = 0.044). Together with established risk factors such as pre-operative intra-abdominal sepsis (18% with sepsis; 6% without sepsis; P = 0.024) and colocolonic anastomosis (16% with such anastomosis; 6% with other types of anastomosis; P = 0.031), thiopurine therapy was associated with intra-abdominal septic complications in 24% if any 2 or all 3 risk factors were present compared with 13% if any 1 factor was present, and only 4% in patients if none of these factors were present (P andlt; 0.0001).

    CONCLUSIONS: Thiopurine therapy is associated with postoperative intra-abdominal septic complications. The risk for intra-abdominal septic complications was related to the number of identified risk factors. This increased risk should be taken into consideration when planning surgery for Crohns disease.

  • 67.
    Myrelid, Pär
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Svärm, Susanne
    Andersson, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Bodemar, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Olaison, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Azathioprine as a postoperative prophylaxis reduces symptoms in aggressive Crohn's disease2006In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 41, no 10, p. 1190-1195Article in journal (Refereed)
    Abstract [en]

    Objective. Recurrence of Crohn's disease (CD) after surgery is common. Azathioprine/6-mercaptopurine (Aza/6-MP) is effective in controlling medically induced remission but, so far, has only been sparsely investigated after surgically induced remission. This study comprises a subset of CD patients considered to have an aggressive disease course and chosen for treatment with Aza postoperatively. Material and methods. In 1989-2000, a total of 100 patients with CD were given Aza/6-MP as a postoperative prophylaxis. Fourteen Aza/6-MP-intolerant patients were compared with 28 Aza-tolerant patients, matched for gender, age, and duration of disease. Patients were prospectively registered for symptoms using a modified Crohn's disease activity index (CDAI) and perceived health was assessed on a visual analogue scale (VAS). The primary outcome variable was the modified CDAI postoperatively integrated over time, other variables were time to first relapse (modified CDAI ≥ 150), time to first repeated surgery, number of courses of steroids, and repeated surgery per year of follow-up. Patients were followed for a median of 84.7months (23.2-140). Results. The modified CDAI integrated over time was 93 for Aza-treated patients compared with 184 for controls (p = 0.01) and time to first relapse was 53 and 24 months, respectively (p < 0.05). Aza-treated patients needed fewer courses of corticosteroids (p = 0.05) compared with controls. Perceived health did not differ between the groups, nor did need of repeated surgery. Time to first repeat operation was 53 and 37 months, respectively. Conclusions. In CD patients considered to have an aggressive disease course, Aza reduced symptoms after surgery and prolonged the time to symptomatic relapse. The findings support a role for Aza as a postoperative maintenance treatment in CD. © 2006 Taylor & Francis.

  • 68.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Nayeri, Tayeb
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Xu, Junyang
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Lundström, Ingemar
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Åkerlind, Britt
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Liedberg, Bo
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Health Sciences.
    Hepatocyte growth factor (HGF) in fecal samples: rapid detection by surface plasmon resonance2005In: BMC Gastroenterology, ISSN 1471-230X, E-ISSN 1471-230X, Vol. 5, no 13Article in journal (Refereed)
    Abstract [en]

    Background

    The development of biosensors, based on surface plasmon resonance (SPR) technology, enables monitoring of a variety of biospecific interactions without the need for chemical-, biological- or radiological-labelled reagents.

    Method

    We utilised SPR to detect hepatocyte growth factor (HGF) in reconstituted faecal samples and studied samples from patients with infectious gastroenteritis (n = 20) and normal controls (n = 10). Mouse anti-human HGF monoclonal antibodies and recombinant human HGF receptor (c-Met)/Fc chimera were immobilised in flow cells of a CM5 biosensor chip.

    Results

    We found that infectious gastroenteritis produced a higher signal response compared to controls, due to binding of HGF to monoclonal anti-HGF antibody as well as binding of HGF to c-Met receptor (p < 0.01). The SPR signal response correlated with results from ELISA (r = 72%, p > 0.001). The signal response decreased significantly (p < 0.05) when samples were diluted with dextran, because of reduction in both specific as well as unspecific binding of HGF to dextran. The decrease in the specific response might imply that the dextran- binding site for HGF overlaps with the antibody binding epitope, or that dextran binding induces a conformational change of the HGF molecule. Bands corresponding to HGF were found by gel electrophoresis of purified faeces in an affinity chromatography column immobilised by HGF ligands.

    Conclusion

    Determination of HGF by SPR might be beneficial in diagnosis of acute situations that present with symptoms of gastroenteritis and may, possibly, guide appropriate medical treatments. This is to our knowledge the first report on the use of SPR for detection of HGF in faeces samples.

  • 69.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Department of Clinical Physiology, County Hospital, Kalmar.
    Nilsson, Ingela
    Department of Clinical Chemistry, County Hospital, Kalmar.
    Åkerlind, Britt
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    High hepatocyte growth factor levels in faeces during acute infectious gastroenteritis2003In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 35, no 11-12, p. 858-862Article in journal (Refereed)
    Abstract [en]

    Hepatocyte growth factor (HGF) is a potent mitogen of mature epithelial cells which is produced after organ injuries and acts as a trigger for regeneration in the impaired organ. The aim of the present study was to investigate local production of HGF during infectious gastroenteritis. We measured the concentration of HGF in serum and faeces in 49 patients with acute infectious gastroenteritis (bacterium=30, virus=10, amoebae=1, and probable infection=8) at the time of referral to hospital and at convalescence (n=31). The values were compared with normal healthy vaccination volunteers (n=11) as well as patients with acute non-infectious diarrhoea (n=10). The presence of HGF in faeces was confirmed by ELISA and Western immunoblot. HGF concentrations in faeces was significantly higher in the patients with infectious gastroenteritis compared to the control groups (p<0.0001). Using a cut-off concentration of 20 ng/g, the overall sensitivity of faeces HGF to distinguish infectious gastroenteritis (bacterial, viral, probable infection) was 98% with a specificity of 100%. At convalescence all patients had normal values. There was no significant correlation between HGF concentrations in faeces and serum. Determination of faeces HGF may identify cases of transmittable diarrhoea requiring isolation at an early stage.

  • 70.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Nilsson, I.
    Laboratories of Clinical Chemistry, Kalmar County Hospital Hospital, Kalmar, Sweden.
    Brudin, L.
    Department of Physiology, County Hospital, Kalmar, Sweden.
    Almer, Sven
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Stability of faecal hepatocyte growth factor determination2004In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 64, no 6, p. 589-597Article in journal (Refereed)
    Abstract [en]

    In order to evaluate the accuracy and reproducibility of determination of hepatocyte growth factor (HGF) levels in faeces, the stability of HGF in samples processed in different ways was investigated. An ELISA method was used for determination of HGF concentrations. Faeces samples from healthy controls and patients with infectious diarrhoea were studied. It was found that faeces HGF concentration remained stable irrespective of whether samples were freeze‐thawed several times, kept for 6, 12 or 24 h at room temperature or refrigerated for 6, 12, 24 or 36 h; the levels of HGF did not change significantly when samples were freeze‐dried. Adding protease inhibitor to the faeces samples did not affect the HGF levels. There were no significant differences between HGF levels using phosphate buffered saline (PBS) (pH 7.4) or NaCL as buffer, but it was observed that levels of HGF were significantly lower in the samples that were diluted in distilled water. Although both HGF and albumin through various mechanisms may increase in faeces during infectious diarrhoea, there was no significant correlation between faeces HGF levels and albumin levels, which might indicate local production of HGF in the bowel in response to infection. It is concluded that determination of faeces HGF levels is feasible with a high degree of stability. Increased HGF levels in faeces might represent a local production of HGF during bowel injury and might be of use as a diagnostic and monitoring assay.

  • 71.
    Norén, Bengt
    et al.
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Forsgren, Mikael
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Dahlström, Nils
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Kihlberg, Johan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Romu, Thobias
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Prospective Evaluation of a Novel Quantification Method for the Discrimination of Mild and Severe Hepatic Fibrosis Using Gd-EOB-DTPA2012Conference paper (Other academic)
  • 72.
    Norén, Bengt
    et al.
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Radiation Physics.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Ekstedt, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Franzén, Lennart
    Medilab, Täby, Sweden.
    Wirell, Staffan
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Separation of advanced from mild fibrosis in diffuse liver disease using 31P magnetic resonance spectroscopy2008In: European Journal of Radiology, ISSN 0720-048X, E-ISSN 1872-7727, Vol. 66, no 2, p. 313-320Article in journal (Refereed)
    Abstract [en]

    31P-MRS using DRESS was used to compare absolute liver metabolite concentrations (PME, Pi, PDE, γATP, αATP, βATP) in two distinct groups of patients with chronic diffuse liver disorders, one group with steatosis (NAFLD) and none to moderate inflammation (n = 13), and one group with severe fibrosis or cirrhosis (n = 16). All patients underwent liver biopsy and extensive biochemical evaluation. A control group (n = 13) was also included. Absolute concentrations and the anabolic charge, AC = {PME}/({PME} + {PDE}), were calculated.

    Comparing the control and cirrhosis groups, lower concentrations of PDE (p = 0.025) and a higher AC (p < 0.001) were found in the cirrhosis group. Also compared to the NAFLD group, the cirrhosis group had lower concentrations of PDE (p = 0.01) and a higher AC (p = 0.009). No significant differences were found between the control and NAFLD group. When the MRS findings were related to the fibrosis stage obtained at biopsy, there were significant differences in PDE between stage F0–1 and stage F4 and in AC between stage F0–1 and stage F2–3.

    Using a PDE concentration of 10.5 mM as a cut-off value to discriminate between mild, F0–2, and advanced, F3–4, fibrosis the sensitivity and specificity were 81% and 69%, respectively. An AC cut-off value of 0.27 showed a sensitivity of 93% and a specificity of 54%.

    In conclusion, the results suggest that PDE is a marker of liver fibrosis, and that AC is a potentially clinically useful parameter in discriminating mild fibrosis from advanced.

  • 73.
    Norén, Bengt
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dahlström, Nils
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Forsgren, Mikael
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Wirell, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Visual assessment of biliary excretion of Gd-EOB-DTPA in patients with suspected diffuse liver disease – a biopsy-controlled prospective study2015In: European Journal of Radiology Open, ISSN 2352-0477, Vol. 2, p. 19-25Article in journal (Refereed)
    Abstract [en]

    Objectives: To qualitatively evaluate late dynamic contrast phases, 10, 20 and 30 min, after administration of Gd-EOB-DTPA with regard to biliary excretion in patients presenting with elevated liver enzymes without any clinical signs of cirrhosis or hepatic decompensation and to compare the visual assessment of contrast agent excretion with histo-pathological fibrosis stage, contrast uptake parameters and blood tests.

    Methods: 29 patients were prospectively examined using 1.5-T MRI. The visually assessed presence (1) or absence (0) of contrast agent for each of five anatomical regions in randomly reviewed time-series was summarised on a four grade scale. The scores, including a total visual score, were related to the histo-pathological findings, the quantitative contrast agent uptake parameters and blood tests

    Results: No relationship between the fibrosis grade or contrast uptake parameters expressed as KHep or LSC_N could be established. A negative correlation between the visual assessment and ALP was found. Comparing a sub-group of cholestatic patients with fibrosis score and Gd-EOB-DTPAdynamic parameters did not add any additional significant correlation.

    Conclusions: In this prospective study with a limited number of patients we were not able to demonstrate a correlation between visually assessed biliary excretion of Gd-EOB-DTPA and  histo-pathological or contrast uptake parameters.

  • 74.
    Norén, Bengt
    et al.
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Forsgren, Mikael
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Dahlström, Nils
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Kihlberg, Johan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Romu, Thobias
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Separation of advanced from mild hepatic fibrosis by quantification of the hepatobiliary uptake of Gd-EOB-DTPA2012Conference paper (Other academic)
  • 75.
    Norén, Bengt
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Forsgren, Mikael Fredrik
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Dahlström, Nils
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Kihlberg, Johan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Romu, Thobias
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Separation of advanced from mild hepatic fibrosis by quantification of the hepatobiliary uptake of Gd-EOB-DTPA2013In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 23, no 1, p. 174-181Article in journal (Refereed)
    Abstract [en]

    Objectives

    To apply dynamic contrast-enhanced (DCE) MRI on patients presenting with elevated liver enzymes without clinical signs of hepatic decompensation in order to quantitatively compare the hepatocyte-specific uptake of Gd-EOB-DTPA with histopathological fibrosis stage.

    Methods

    A total of 38 patients were prospectively examined using 1.5-T MRI. Data were acquired from regions of interest in the liver and spleen by using time series of single-breath-hold symmetrically sampled two-point Dixon 3D images (non-enhanced, arterial and venous portal phase; 3, 10, 20 and 30 min) following a bolus injection of Gd-EOB-DTPA (0.025 mmol/kg). The signal intensity (SI) values were reconstructed using a phase-sensitive technique and normalised using multiscale adaptive normalising averaging (MANA). Liver-to-spleen contrast ratios (LSC_N) and the contrast uptake rate (KHep) were calculated. Liver biopsy was performed and classified according to the Batts and Ludwig system.

    Results

    Area under the receiver-operating characteristic curve (AUROC) values of 0.71, 0.80 and 0.78, respectively, were found for KHep, LSC_N10 and LSC_N20 with regard to severe versus mild fibrosis. Significant group differences were found for KHep (borderline), LSC_N10 and LSC_N20.

    Conclusions

    Liver fibrosis stage strongly influences the hepatocyte-specific uptake of Gd-EOB-DTPA. Potentially the normalisation technique and KHep will reduce patient and system bias, yielding a robust approach to non-invasive liver function determination.

  • 76.
    Norén, Bengt
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Medical Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology UHL.
    Lundberg, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Radiation Physics. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ressner, Marcus
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Wirell, Staffan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Medical Radiology.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Smedby, Örjan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Medical Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology UHL. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Absolute quantification of human liver metabolite concentrations by localized in vivo 31P NMR spectroscopy in diffuse liver disease2005In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 15, no 1, p. 148-157Article in journal (Refereed)
    Abstract [en]

    Phosphorus-31 NMR spectroscopy using slice selection (DRESS) was used to investigate the absolute concentrations of metabolites in the human liver. Absolute concentrations provide more specific biochemical information compared to spectrum integral ratios. Nine patients with histopathologically proven diffuse liver disease and 12 healthy individuals were examined in a 1.5-T MR scanner (GE Signa LX Echospeed plus). The metabolite concentration quantification procedures included: (1) determination of optimal depth for the in vivo measurements, (2) mapping the detection coil characteristics, (3) calculation of selected slice and liver volume ratios using simple segmentation procedures and (4) spectral analysis in the time domain. The patients had significantly lower concentrations of phosphodiesters (PDE), 6.3±3.9 mM, and ATP-β, 3.6±1.1 mM, (P<0.05) compared with the control group (10.0±4.2 mM and 4.2±0.3 mM, respectively). The concentrations of phosphomonoesters (PME) were higher in the patient group, although this was not significant. Constructing an anabolic charge (AC) based on absolute concentrations, [PME]/([PME] + [PDE]), the patients had a significantly larger AC than the control subjects, 0.29 vs. 0.16 (P<0.005). Absolute concentration measurements of phosphorus metabolites in the liver are feasible using a slice selective sequence, and the technique demonstrates significant differences between patients and healthy subjects.

  • 77. Nyblom, Helena
    et al.
    Björnsson, Einar
    Simrén, Magnus
    Aldenborg, Frank
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Olsson, Rolf
    The AST/ALT ratio as an indicator of cirrhosis in patients with PBC2006In: Liver international (Print), ISSN 1478-3223, E-ISSN 1478-3231, Vol. 26, no 7, p. 840-845Article in journal (Refereed)
    Abstract [en]

    Objectives: A non-invasive, simple and non-expensive test to predict cirrhosis would be highly desirable. The aspartate aminotransferase/ alanine aminotransferase (AST/ALT) ratio has been proven to be such an indicator of cirrhosis in alcoholic liver disease, hepatitis C. Aim: To test whether the AST/ALT ratio is a marker of cirrhosis also in patients with primary biliary cirrhosis (PBC). Methods: The study consisted of 160 patients. In 126 patients, we had clinical and laboratory data at the time of diagnosis and follow-up with outcome: liver-related death, liver transplantation and survival. In 121 patients, we had laboratory data and liver histology. Results: We found that the AST/ALT ratio was significantly higher in cirrhotic patients than in non-cirrhotic patients. A high AST/ALT ratio was significantly associated with esophageal varices and ascites. In a multivariate analysis, bilirubin and ALP were predictors of poor prognosis. Conclusion: The AST/ALT ratio seems to be of clinical value as a hint to the diagnosis of cirrhosis in patients with PBC but not as a prognostic factor. © 2006 Blackwell Munksgaard.

  • 78.
    Olaison, Gunnar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Andersen, Paul
    Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Language and Culture.
    Perianal Crohn's disease (Br J Surg 2004, 91: 801-814) [1]2004In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 91, no 10, p. 1381Other (Other academic)
    Abstract [en]

    [No abstract available]

  • 79.
    Olsson, Rolf
    et al.
    Sahlgrens University Hospital.
    Glaumann, Hans
    Karolinska University Hospital.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Broome, Ulrika
    Karolinska University Hospital.
    Lebrun, Barbro
    Karolinska University Hospital.
    Bergquist, Annika
    Karolinska University Hospital.
    Bjornsson, Einar
    Sahlgrens University Hospital.
    Prytz, Hanne
    Lund University Hospital.
    Danielsson, Ake
    Umeå University Hospital.
    Lindgren, Stefan
    Malmö University.
    High prevalence of small duct primary sclerosing cholangitis among patients with overlapping autoimmune hepatitis and primary sclerosing cholangitis2009In: EUROPEAN JOURNAL OF INTERNAL MEDICINE, ISSN 0953-6205, Vol. 20, no 2, p. 190-196Article in journal (Refereed)
    Abstract [en]

    Background: Overlap syndrome is a term used for overlapping features of autoimmune hepatitis and primary sclerosing cholangitis or primary biliary cirrhosis and for autoimmune cholangitis. We describe a high prevalence of small duct primary sclerosing cholangitis among patients with overlapping autoimmune hepatitis and primary sclerosing cholangitis.

    Methods: We sought to retrieve all patients with overlap syndrome between primary sclerosing cholangitis and autoimmune hepatitis in six university hospitals in Sweden. The revised autoimmune hepatitis scoring system proposed by the International Autoimmune Hepatitis Group was used to establish the diagnosis autoimmune hepatitis. Endoscopic retrograde cholangiography and/or magnetic resonance cholangiography were used to separate the primary sclerosing cholangitis cases diagnosed through liver biopsy into small and large primary sclerosing cholangitis. A histologocial diagnosis compatible with both autoimmune hepatitis and primary sclerosing cholangitis was required for inclusion.

    Results: 26 patients fulfilled our criteria for histological overlap of autoimmune hepatitis and primary sclerosing cholangitis, 7 (27%) of which had small duct primary sclerosing cholangitis. The reliability of the diagnosis small duct primary sclerosing cholangitis was supported by a very close similarity between small and large duct primary sclerosing cholangitis patients in clinical and laboratory data, and by a poor response to immunosuppressive therapy in the small duct primary sclerosing cholangitis patients. Patients with large duct overlap syndrome had a good response to immunosuppressive therapy. In both groups, our limited experience from ursodeoxycholic acid was largely poor.

    Conclusions: Small duct primary sclerosing cholangitis is prevalent in the overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis.

  • 80. Pettersson, B
    et al.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, EMK-magtarm.
    Albertioni, F
    Söderhäll, S
    Peterson, C
    Differences between children and adults in thiopurine methyltransferase activity and metabolite formation during thiopurine therapy: Possible role of concomitant methotrexate2002In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 24, no 3, p. 351-358Article in journal (Refereed)
    Abstract [en]

    This study examined the role of thiopurine methyltransferase (TPMT) polymorphism in the metabolism and clinical effects of azathioprine and 6-mercaptopurine in the treatment of inflammatory bowel disease and childhood leukemia. The current hypothesis is that the cytotoxic effects of thiopurines are caused by the incorporation of thioguanine nucleotides into DNA. In this context, S-methylation catalyzed by TPMT can be regarded as a competing metabolic pathway. The authors assayed the TPMT activity in red blood cells from 122 patients treated with azathioprine or 6-mercaptopurine (83 adults with inflammatory bowel disease and 39 children with acute lymphoblastic leukemia) and in 290 untreated controls (219 adult blood donors and 71 children). The concentrations of thioguanine nucleotides and methylthioinosine monophosphate were also assayed in red blood cells from the patients. The TPMT activity and the concentrations of methylthioinosine monophosphate and thioguanine nucleotides were higher in children than in adults. All children but no adult patient received concomitant methotrexate. Interaction between methotrexate and 6-mercaptopurine has been described, and may explain the results. Low TPMT activity in adult patients with inflammatory bowel disease correlated to an increased incidence of adverse drug reactions. However, there was no correlation between TPMT activity and the red blood cell concentrations of methylthioinosine monophosphate or thioguanine nucleotides, or between the concentrations of these metabolites and the occurrence of adverse effects. The results show that the role of thiopurine metabolism for drug effects is complex.

  • 81. Prytz, Hanne
    et al.
    Keiding, Susanne
    Björnsson, Einar
    Broomé, Ulrika
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Castedal, Maria
    Lajord Munk, Ole
    Dynamic FDG-PET is useful for detection of cholangiocarcinoma in patients with PSC listed for liver transplantation2006In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 44, no 6, p. 1572-1580Article in journal (Refereed)
    Abstract [en]

    Five to 15% of patients with primary sclerosing cholangitis (PSC) develop cholangiocarcinoma (CC) with a median survival of 5 to 7 months, an outcome not significantly improved by liver transplantation. However, if CC is found incidentally during the procedure or in the explanted liver, 5-year survival rates of 35% are reported. A noninvasive method to detect CC small enough to allow for intended curative surgery is needed. Unfortunately, computed tomography (CT) and ultrasonography (US) have poor sensitivity for detection of CC in PSC, however, positron emission tomography (PET) using 2-[ 18F]fluoro-2-deoxy-D-glucose (FDG) differentiates well between CC and nonmalignant tissue. We examined whether PET findings are valid using a blinded study design comparing pretransplantation FDG-PET results with histology of explanted livers. Dynamic FDG-PET was performed in 24 consecutive patients with PSC within 2 weeks after listing for liver transplantation and with no evidence of malignancy on CT, magnetic resonance imaging, or ultrasonography. The PET Center staff was blinded to clinical findings, and surgeons and pathologists were blinded to the PET results. Three patients had CC that was correctly identified by PET. PET was negative in 1 patient with high-grade hilar duct dysplasia. In 20 patients without malignancies, PET was false positive in 1 patient with epitheloid granulomas in the liver. In conclusion, dynamic FDG-PET appears superior to conventional imaging techniques for both detection and exclusion of CC in advanced PSC. FDG-PET may be useful for screening for CC in the pretransplant evaluation of patients with PSC. Copyright © 2006 by the American Association for the Study of Liver Diseases.

  • 82.
    Rajani, Rupesh
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Budd-Chiaris Syndrom2007Other (Other (popular science, discussion, etc.))
    Abstract [en]

          

  • 83.
    Rajani, Rupesh
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Letter: Incidence and prevalence rates in Budd-Chiari syndrome2009In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 58, no 6, p. 889-Article in journal (Other (popular science, discussion, etc.))
    Abstract [en]

    [No abstract available]

  • 84.
    Rajani, Rupesh
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Portavenstrombos2007Other (Other (popular science, discussion, etc.))
    Abstract [sv]

    Portaventrombos (PVT) är ett ovanligt tillstånd. Bakomliggande orsaker är vanligen leversjukdom (framförallt cirros), intraabdominell malignitet samt hyperkoagulabilitet. Två eller flera samtidiga riskfaktorer, oftast en lokal faktor kombinerat med en systemisk, förekommer i mer än hälften av fallen. Man bör ha diagnosen i åtanke vid oklar buksmärta, vid tecken på portal hypertension utan samtidig leversjukdom samt vid plötslig försämring hos en patient med känd leversjukdom. Asymtomatiska patienter är inte ovanliga. Randomiserade behandlingsstudier saknas. Behandlingen inriktas på att reversera och förhindra progression av trombosen samt att förebygga och behandla komplikationer såsom varixblödningar och kolangiopati. Rekanalisering kan ske i upptill 90% av fallen vid tidigt insättande av antikoagulantia. Prognosen är god om patienten inte har cirros, malignitet eller mesenterialventrombos; 1-, 5- och 10-års överlevnad är då på 95%, 89% och 81%.

  • 85.
    Rajani, Rupesh
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Bergquist, Annika
    Karolinska University Hospital.
    Melin, Tor
    Lund University Hospital.
    Friis-Liby, Ingalill
    Sahlgrens University Hospital.
    Kapraali, Marjo
    Danderyd Hospital.
    Werner, Marten
    Umea University Hospital.
    Sangfelt, Per
    Uppsala University.
    Wallerstedt, Sven
    Ostra Hospital, Gothenburg.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    INCREASED FACTOR VIII ACTIVITY IN PORTAL VEIN THROMBOSIS AND BUDD-CHIARI SYNDROME in HEPATOLOGY, vol 52, issue 4, pp 912A-912A2010In: HEPATOLOGY, John Wiley andamp; Sons, Ltd , 2010, Vol. 52, no 4, p. 912A-912AConference paper (Refereed)
    Abstract [en]

    n/a

  • 86.
    Rajani, Rupesh
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Björnsson, E
    Sahlgrenska University Hospital, Göteborg.
    Bergquist, A
    Karolinska University Hospital, Stockholm.
    Danielsson, A
    Umeå University Hospital, Umeå.
    Gustavsson, A
    Örebro University Hospital.
    Grip, O
    Malmö University Hospital, Malmö.
    Melin, T
    Lund University Hospital, Lund.
    Sangfelt, P
    Uppsala University Hospital. Uppsala.
    Wallerstedt, S
    Östra Hospital, Göteborg.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    The epidemiology and clinical features of portal vein thrombosis: a multicentre study2010In: ALIMENTARY PHARMACOLOGY and THERAPEUTICS, ISSN 0269-2813, Vol. 32, no 9, p. 1154-1162Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Reliable epidemiological data for portal vein thrombosis are lacking.

    AIMS: To investigate the incidence, prevalence and survival rates for patients with portal vein thrombosis.

    METHODS: Retrospective multicentre study of all patients registered with the diagnosis of portal vein thrombosis between 1995 and 2004.

    RESULTS: A total of 173 patients (median age 57 years, 93 men) with portal vein thrombosis were identified and followed up for a median of 2.5 years (range 0-9.7). The mean age-standardized incidence and prevalence rates were 0.7 per 100,000 per year and 3.7 per 100,000 inhabitants, respectively. Liver disease was present in 70 patients (40%), malignancy in 27%, thrombophilic factors in 22% and myeloproliferative disorders in 11%. Two or more risk factors were identified in 80 patients (46%). At diagnosis, 65% were put on anticoagulant therapy. Thrombolysis, TIPS, surgical shunting and liver transplantation were performed in 6, 3, 2 and 8 patients, respectively. The overall survival at 1 year and 5 years was 69% and 54%. In the absence of malignancy and cirrhosis, the survival was 92% and 76%, respectively.

    CONCLUSIONS: The incidence and prevalence rates of portal vein thrombosis were 0.7 per 100,000 inhabitants per year and 3.7 per 100,000 inhabitants, respectively. Concurrent prothrombotic risk factors are common. The prognosis is variable and highly dependent on underlying disease.

  • 87.
    Rajani, Rupesh
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Haglund, Sofie
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Bergquist, Annika
    Department of Gastroenterology & Hepatology, Karolinska University Hospital, Stockholm.
    Melin, Tor
    Division of Gastroenterology & Hepatology, University Hospital, Lund.
    Friis-Liby, Ingalill
    Department of Medicine, Sahlgrenska University Hospital, Gothenburg.
    Verbaan, Hans
    Department of Medicine, University Hospital, Malmö.
    Kapraali, Marjo
    Karolinska Institutet, Department of Clinical Sciences Danderyd Hospital, Division of Medicine, Stockholm.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    High prevalence of the germline JAK2 46/1 haplotype and V617-mutationin Swedish patients with Budd-Chiari syndrome and Portal Vein Thrombosis2010Manuscript (preprint) (Other academic)
    Abstract [en]

    Background & Aims: To determine the prevalence of the somatic JAK2 V617F mutation and distribution of the germline JAK2 46/1 haplotype in Budd-Chiari Syndrome (BCS) and portal vein thrombosis (PVT).

    Methods: Real-time PCR was performed to genotype for the JAK2V 617F mutation and the 46/1 haplotype (tag-SNPs rs12343867, T>C and rs12340895, C>G) in blood samples of 19 BCS and 91 PVT patients (without intra-abdominal malignancy), and 283 controls from a background population.

    Results: The prevalence of JAK2 V617F-mutation was 63% in BCS and 14% in PVT patients. 10% in BCS and 2% in PVT had V617F negative MPD. Conversely, V617F positive subjects without known MPD was found in 5% of the BCS and in 1% of PVT patients. The frequency of the JAK2 46/1 haplotype was significantly higher in BCS (53%) and PVT (36%) patients compared to controls (27%) (p=0.02; OR=3.0; 95% CI 1.5-5.9 and OR=1.51; 95% CI 1.1-2.1, respectively). In PVT patients the JAK2 haplotype was highly enriched in non-cirrhotic patients (41%) (p <0.01 ; OR=1.8; 95% CI 1.2-2.6) but not in cirrhotic patients (23%) (p=0.53 ; OR= 0.8; 95% CI 0.4-1.7). An increased JAK2 46/1 haplotype frequency was evident only in V617F mutation positive patients.

    Conclusions: The prevalence of JAK2 V617F was high in BCS (63%) and non-cirrhotic PVT (14%), facilitating detection of latent MPD. A negative result dose not rule out MPD. The occurrence of the JAK2 46/1 haplotype was significantly higher in V617F mutation positive patients but not in mutation negative patients, suggesting that the haplotype may not have an independent role separated from the V617F mutation in BCS and PVT patients.

  • 88.
    Rajani, Rupesh
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Jennersjö, Cecilia
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Health Care.
    Bergquist, Annika
    Department of Gastroenterology & Hepatology, Karolinska University Hospital, Stockholm.
    Melin, Tor
    Division of Gastroenterology & Hepatology, University Hospital, Lund.
    Friis-Liby, Ingalill
    Department of Medicine, Sahlgrenska University Hospital, Gothenburg.
    Kapraali, Marjo
    Karolinska Institutet, Department of Clinical Sciences Danderyd Hospital, Division of Medicine, Stockholm.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Increased Factor VIII Activity in Portal Vein Thrombosis and Budd-Chiari Syndrome2010Manuscript (preprint) (Other academic)
    Abstract [en]

    n/a

  • 89.
    Rajani, Rupesh
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Melin, Tor
    University Hospital, Lund .
    Bjornsson, Einar
    Sahlgrenska University Hospital, Göteborg.
    Broome, Ulrika
    Karolinska University Hospital, Stockholm.
    Sangfelt, Per
    University Uppsala Hospital, Uppsala.
    Danielsson, Ake
    Umea University Hospital, Umeå.
    Gustavsson, Anders
    University Hospital, Örebro.
    Grip, Olof
    Malmö University Hospital, Malmö.
    Svensson, Hans
    Vrinnevi Hospital, Norrköping.
    Loof, Lars
    Västerås City Hospital, Västerås.
    Wallerstedt, Sven
    Östra Hospital, Gothenberg.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Budd-Chiari syndrome in Sweden: epidemiology, clinical characteristics and survival - an 18-year experience2009In: Liver international (Print), ISSN 1478-3223, E-ISSN 1478-3231, Vol. 29, no 2, p. 253-259Article in journal (Refereed)
    Abstract [en]

    The exact incidence and prevalence of Budd-Chiari syndrome (BCS) is unknown in the general population. Published reports differ in terms of the clinical characteristics, effects of therapy and survival.

    To investigate the epidemiology, clinical presentation and survival in patients with BCS.

    Retrospective multicentre study in Sweden reviewing the medical records of all patients with BCS 1986-2003, identified from the computerised diagnosis database of 11 hospitals, including all university hospitals and liver transplantation centres.

    Forty-three patients with BCS were identified, of whom nine (21%) had concomitant portal vein thrombosis. The mean age-standardised incidence and prevalence rates in 1990-2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. Myeloproliferative disorders (38%), thrombophilic factors (31%) and oral contraceptives (30%) were common aetiological factors. Two or more risk factors were present in 44%. In 23%, no risk factor was evident. The median follow-up time was 2.7 years. Seventy-two percent were on anticoagulant therapy during follow-up. Transjugular intrahepatic portosystemic shunting, surgical shunting procedures and liver transplantation were performed in 4, 6 and 18 patients respectively. Nineteen patients died. The overall transplantation-free survival at 1, 5 and 10 years was 47, 28 and 17% respectively.

    Budd-Chiari syndrome is a rare disorder; the mean age-standardised incidence and prevalence rates in Sweden in 1990-2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. The presence of a myeloproliferative disorder was a common aetiological factor in our cohort and about half of the patients had a multifactorial aetiology. The transplantation-free survival was poor.

  • 90. Rampton, DS
    et al.
    Neurath, MF
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, GE: gastromed.
    D'Haens, G
    Petritsch, W
    Stange, EF
    Mycophenolate mofetil in Crohn's disease.2000In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 356, p. 163-164Article in journal (Refereed)
  • 91.
    Romu, Thobias
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Dahlqvist Leinhard, Olof
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Health Sciences.
    Forsgren, Mikael
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Dahlström, Nils
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, The Institute of Technology.
    Fat Water Classification of Symmetrically Sampled Two-Point Dixon Images Using Biased Partial Volume Effects2011In: Proceedings of the annual meeting of the International Society for Magnetic Resonance in Medicine (ISMRM 2011), 2011., 2011Conference paper (Refereed)
  • 92.
    Rydén, Ingvar
    et al.
    Department of Clinical Chemistry, Kalmar County Hospital, Sweden.
    Woxler, Per
    Linköping University, Department of Department of Health and Society. Linköping University, Faculty of Health Sciences.
    Bendtsen, Preben
    Linköping University, Department of Department of Health and Society. Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Påhlsson, Peter
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Increased α1-acid glycoprotein fucosylation in patients with high alcohol consumptionManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Changes in glycosylation of senun glycoproteins have been described in different pathologic conditions, and increased fucosylation has previously been reported in patients with liver disease. We analyzed serwn samples from patients admitted to hospital for detoxification of excessive alcohol consumption in order to study α1-acid glycoprotein (AGP) fucosylation and its correlation to other biochemical markers of alcoholism and liver damage.

    Methods: We used a novel lectin innmmoassay to analyze AGP fucosylation (AGP-F) in a prospective study of 21 consecutive patients admitted for treatment at Linköping University Hospital in the Southeast of Sweden. The results were compared with markers conunonly used for detecting alcoholism and liver cirrhosis, such as carbohydrate deficient transferrin, aminotransferase activity, including aspartate aminotransferase/alanine aminotransferase ratio (AST/ALT), and with hyaluronic acid (HA). In addition, ultrasonography of the liver was performed in 16 of the 21 patients.

    Results: AGP-F was significantly higher in the male study patients than in normal controls. In addition, in these patients AGP-F correlated to the levels of AST/ALT-ratio and HA No correlation was found between AGP-F and steatosis of the liver, as indicated by ultrasonography, or between AGP-F and CDT.

    Conclusion: We conclude that AGP-F is increased in men with a high alcohol intake and correlates with AST/ALT ratio and HA, which previously have been found to be indictors of liver cirrhosis. AGP-F should be further evaluated as a potential early indicator ofliver cirrhosis in this patient category.

  • 93.
    Schoultz, Ida
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Carlsson, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Gullberg, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Endocrinology and Gastroenterology.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Endocrinology and Gastroenterology.
    Lerm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    McKay, Derek M.
    Department of Physiology and Biophysics, University of Calgary, Calgary, Canada.
    Rhodes, Jonathan M.
    Department of Medicine, Henry Wellcome Laboratory of Molecular and Cellular Gastroenterology, University of Liverpool, Liverpool, United Kingdom.
    Söderholm, Johan D.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Infliximab reduces bacterial uptake in mucosal biopsies of Crohn’s colitis viamicrotubule-dependent pathwayManuscript (preprint) (Other academic)
    Abstract [en]

    Background: A defective intestinal barrier, shown by increased paracellular permeability is an importantpathogenic factor in Crohn’s disease (CD). TNFα is a key mediator in the regulation of the intestinal barrierfunction. Treatment with antibodies directed against TNFα, such as infliximab, has been established as animportant part of the therapeutic arsenal in severe Crohn’s disease, but the mechanisms of action have yet tobe elucidated. Part of infliximab’s effect has been suggested to be reduced apoptosis of epithelial cells andthereby reduced paracellular permeability. Our aim was to study how infliximab affects uptake of adherent E.coli across the colonic mucosa in CD.

    Method: Seven patients with active CD colitis were examined before and after a four week treatment withinfliximab. Control biopsies were taken from healthy volunteers (4) and patients undergoing controlexamination for colonic polyps (4), aged 36 (range 25-81), coloscopy. Biopsies were taken from macroscopicallynon-inflamed descending colon and were mounted in Ussing chambers to study barrier function. Transmucosalpassage of green fluorescent protein (GFP) incorporated E. coli HM427, an adherent bacteria isolated from thecolon of a CD patient, was studied by quantifying the translocated fluorescent bacteria using flow cytometry.

    Results: Bacterial passage across the colonic mucosa was increased in CD (2500 ± 300 arb. units) comparedwith controls (960 ± 280; p<0.05), and was reduced to 500 ± 200 units after the infliximab treatment (p<0.05).In biopsies treated with colchicine (a microtubuline inhibitor) uptake of E. coli HM427 was reduced by 2/3compared to non-treated biopsies.

    Conclusion: Patients with active Crohn’s disease showed a defect in the barrier to adherent E. coli, which waspartly mediated through a microtubule dependent uptake. The four week treatment with infliximab improvedthe intestinal barrier to these bacteria. This may constitute an important part of infliximab’s mechanisms ofaction in active colitis.

  • 94.
    Sjoberg, M
    et al.
    University of Örebro, Sweden .
    Magnuson, A
    Örebro University Hospital, Sweden .
    Bjork, J
    Karolinska University Hospital, Sweden .
    Benoni, C
    Skåne University Hospital, Sweden .
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology.
    Friis-Liby, I
    Sahlgrens University Hospital, Sweden .
    Hertervig, E
    Skåne University Hospital, Sweden .
    Olsson, M
    NAL Hospital, Sweden .
    Karlen, P
    Soder Sjukhuset, Sweden .
    Eriksson, A
    Ostra Hospital, Sweden .
    Midhagen, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Carlson, M
    University of Uppsala Hospital, Sweden .
    Lapidus, A
    Ersta Hospital, Sweden .
    Halfvarson, J
    University of Örebro, Sweden .
    Tysk, C
    University of Örebro, Sweden .
    Infliximab as rescue therapy in hospitalised patients with steroid-refractory acute ulcerative colitis: a long-term follow-up of 211 Swedish patients2013In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 38, no 4, p. 377-387Article in journal (Refereed)
    Abstract [en]

    BackgroundRescue therapy with infliximab (IFX) has been proven effective in a steroid-refractory attack of ulcerative colitis (UC). The long-term efficacy is not well described. less thanbrgreater than less thanbrgreater thanAimTo present a retrospective study of IFX as rescue therapy in UC. Primary end points were colectomy-free survival at 3 and 12months. less thanbrgreater than less thanbrgreater thanMethodsIn this multicentre study, 211 adult patients hospitalised between 1999 and 2010 received IFX 5mg/kg as rescue therapy due to a steroid-refractory, moderate-to-severe attack of UC. Exclusion criteria were duration of current flare for andgt;12weeks, corticosteroid treatment for andgt;8weeks before hospitalisation, previous IFX therapy or Crohns disease. less thanbrgreater than less thanbrgreater thanResultsProbability of colectomy-free survival at 3months was 0.71 (95% CI, 0.64-0.77), at 12months 0.64 (95% CI, 0.57-0.70), at 3years 0.59 (95% CI, 0.52-0.66) and at 5years 0.53 (95% CI, 0.44-0.61). Steroid-free, clinical remission was achieved in 105/211 (50%) and 112/209 (54%) patients at 3 and 12months respectively. Of 75 colectomies during the first year, 48 (64%) were carried out during the first 14days, 13 (17%) on days 15-90 and 14 (19%) between 3 and 12months. There were three (1.4%) deaths during the first 3months. less thanbrgreater than less thanbrgreater thanConclusionsInfliximab is an effective rescue treatment, both short- and long-term, in a steroid-refractory attack of UC. Most IFX failures underwent surgery during the first 14days, which calls for studies on how to optimise induction treatment with IFX. Serious complications, including mortality, were rare.

  • 95.
    Sjöwall, Christoffer
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Cardell, Kristina
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Bokarewa, Maria I
    University of Gothenburg.
    Enocsson, Helena
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ekstedt, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Lindvall, Liselott
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Frydén, Aril
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    High prevalence of autoantibodies to C-reactive protein in patients with chronic hepatitis C infection: association with liver fibrosis and portal inflammation2012In: Human Immunology, ISSN 0198-8859, E-ISSN 1879-1166, Vol. 73, no 4, p. 382-388Article in journal (Refereed)
    Abstract [en]

    The presence of autoantibodies against C-reactive protein (anti-CRP) has been reported in association with autoimmunity and histopathology in chronic hepatitis C virus (HCV) infection. Resistin could play a role in the pathogenesis of hepatitis, although results on HCV infection are ambiguous. Here we retrospectively analyzed anti-CRP and resistin levels in the sera of 38 untreated and well-characterized HCV patients at the time of their first liver biopsy. HCV activity and general health were assessed by a physician at least yearly until follow-up ended. Anti-CRP and resistin were also measured in patients with autoimmune hepatitis (AIH) and nonalcoholic fatty liver disease (NAFLD). Anti-CRP antibodies were registered in all HCV patients, whereas only a few AIH (11%) and NAFLD (12%) sera were positive. Anti-CRP levels were related to histopathological severity and were highest in patients with cirrhosis at baseline. Resistin levels were similar in HCV, AIH, and NAFLD patients, but high levels of resistin were associated with early mortality in HCV patients. Neither anti-CRP nor resistin predicted a response to interferon-based therapy or cirrhosis development or was associated with liver-related mortality. We conclude that anti-CRP antibodies are frequently observed in chronic HCV infection and could be a useful marker of advanced fibrosis and portal inflammation.

  • 96.
    Sjöwall, Christopher
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Autoantibodies to C-reactive protein is a common finding in SLE, but not in primary Sjögren’s syndrome, rheumatoid arthritis or inflammatory bowel disease2002In: Journal of Autoimmunity, ISSN 0896-8411, Vol. 19, no 3, p. 155-160Article in journal (Refereed)
    Abstract [en]

    The occurrence of antibodies to human C-reactive protein (CRP) was analysed by enzyme-linked immunosorbent assay (ELISA) in 56 patient sera known to contain antibodies to double-stranded DNA (dsDNA) and in 16 sera from patients with primary Sjögren's syndrome (SS), 15 rheumatoid arthritis, 31 Crohn's disease, and 37 ulcerative colitis. Eighty-seven per cent of the patients with anti-dsDNA antibodies had systemic lupus erythematosus (SLE) and the remaining had autoimmune hepatitis. The cut-off for positive anti-CRP test was set at the 95th percentile of 100 healthy blood donors. Twenty of 56 anti-dsDNA sera (36%) and two of 16 SS sera (13%) had antibodies reactive with human CRP, whereas all other samples were negative. Thirteen of 27 SLE patients (48%) were positive on at least one occasion. The sera containing anti-CRP antibodies only reacted with surface-bound antigen, but not with native CRP in solution. In conclusion, we found that autoantibodies to CRP are common in sera from patients with anti-dsDNA antibodies. It is not likely that this explains the relative failure of CRP response in patients with active SLE. However, it cannot be excluded that anti-CRP autoantibodies have other biological potentials of pathophysiological interest in SLE, for instance by binding to CRP deposited on cell and tissue surfaces.

  • 97.
    Skoglund, Karin
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Lindqvist Appell, Malin
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Almér, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Low expression of TPMT wild type alleles in a patient with absent TPMT activity2008Conference paper (Other academic)
  • 98.
    Skoglund, Karin
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Lindqvist Appell, Malin
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Almér, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Low Expression of TPMT wild type alleles in a patient with absent TPMT activity2008Conference paper (Other academic)
  • 99.
    Skoglund, Karin
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Lindqvist Appell, Malin
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Karlgren, Anna
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Kidhall, Irene
    Div of Gastroenterology and Hepatology, Danderyd Hospital.
    Almér, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Explaining TPMT Genotype/Phenotype Discrepancy by Identification of a Novel Sequence Variant, TPMT*232007Conference paper (Other academic)
  • 100.
    Soderman, Jan
    et al.
    Ryhov County Hospital, Sweden .
    Noren, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Ryhov County Hospital, Sweden.
    Christiansson, Malin
    Ryhov County Hospital, Sweden .
    Bragde, Hanna
    Ryhov County Hospital, Sweden .
    Thiebaut, Raphaele
    University of Paris Diderot, France University of Paris Diderot Sorbonne Paris Cite, France .
    Hugot, Jean-Pierre
    University of Paris Diderot, France University of Paris Diderot Sorbonne Paris Cite, France Hop Robert Debre, France .
    Tysk, Curt
    Örebro University, Sweden Örebro Uni, Sweden .
    OMorain, Colm A.
    Adelaide and Meath Hospital, Ireland Trinity Coll Dublin, Ireland .
    Gassull, Miquel
    Health Science Research Institute, Spain .
    Finkel, Yigael
    Sachs Childrens Hospital, Sweden .
    Colombel, Jean-Frederic
    Hop Calmette, France Icahn School Medical Mt Sinai, NY 10029 USA .
    Lemann, Marc
    Hop St Louis, France .
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology.
    Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease2013In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 19, no 30, p. 4935-4943Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate a possible genetic influence of claudin (CLDN) 1, CLDN2 and CLDN4 in the etiology of inflammatory bowel disease. METHODS: Allelic association between genetic regions of CLDN1, CLDN2 or CLDN4 and patients with inflammatory bowel disease, Crohns disease (CD) or ulcerative colitis were investigated using both a case-control study approach (one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls) and a family-based study (463 non-Swedish European inflammatory bowel disease-families). A nonsynonymous coding single nucleotide polymorphism in MORC4, located on the same linkage block as CLDN2, was investigated for association, as were two novel CLDN2 single nucleotide polymorphism markers, identified by resequencing. RESULTS: A single nucleotide polymorphism marker (rs12014762) located in the genetic region of CLDN2 was significantly associated to CD (case-control allelic OR = 1.98, 95% CI: 1.17-3.35, P = 0.007). MORC4 was present on the same linkage block as this CD marker. Using the case-control approach, a significant association (case control allelic OR = 1.61, 95% CI: 1.08-2.41, P = 0.018) was found between CD and a nonsynonymous coding single nucleotide polymorphism (rs6622126) in MORC4. The association between the CLDN2 marker and CD was not replicated in the family-based study. Ulcerative colitis was not associated to any of the single nucleotide polymorphism markers. CONCLUSION: These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.

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