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  • 1.
    Blom, Kristin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Rubin, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Halfvarson, Jonas
    Torkvist, Leif
    Rönnblom, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Sangfelt, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Lordal, Mikael
    Jönsson, Ulla-Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sjöqvist, Urban
    Håkansson, Lena Douhan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Eosinophil associated genes in the inflammatory bowel disease 4 region: Correlation to inflammatory bowel disease revealed2012In: World Journal of Gastroenterology, ISSN 1007-9327, Vol. 18, no 44, 6409-6419 p.Article in journal (Refereed)
    Abstract [en]

    AIM: To study the association between inflammatory bowel disease (IBD) and genetic variations in eosinophil protein X (EPX) and eosinophil cationic protein (ECP). METHODS: DNA was extracted from ethylene diamine tetraacetic acid blood of 587 patients with Crohn's disease (CD), 592 with ulcerative colitis (UC) and 300 healthy subjects. The EPX405 (G > C, rs2013109), ECP434 (G > C, rs2073342) and ECP562 (G > C, rs2233860) gene polymorphisms were analysed, by the 5'-nuclease allelic discrimination assay. For determination of intracellular content of EPX and ECP in granulocytes, 39 blood samples was collected and extracted with a buffer containing cetyltrimethylammonium bromide. The intracellular content of EPX was analysed using an enzyme-linked immunosorbent assay. The intracellular content of ECP was analysed with the UniCAP (R) system as described by the manufacturer. Statistical tests for calculations of results were chi(2) test, Fisher's exact test, ANOVA, Student-Newman-Keuls test, and Kaplan-Meier survival curve with Log-rank test for trend, the probability values of P < 0.05 were considered statistically significant. RESULTS: The genotype frequency for males with UC and with an age of disease onset of >= 45 years (n = 57) was for ECP434 and ECP562, GG = 37%, GC = 60%, CC = 4% and GG = 51%, GC = 49%, CC = 0% respectively. This was significantly different from the healthy subject's genotype frequencies of ECP434 (GG = 57%, GC = 38%, CC = 5%; P = 0.010) and ECP562 (GG = 68%, GC = 29 /0,CC = 3%; P = 0.009). The genotype frequencies for females, with an age of disease onset of >= 45 years with CD (n = 62), was for the ECP434 and ECP562 genotypes GG = 37%, GC = 52%, CC = 11% and GG = 48%, GC = 47% and CC = 5% respectively. This was also statistically different from healthy controls for both ECP434 (P = 0.010) and ECP562 (P = 0.013). The intracellular protein concentration of EPX and ECP was calculated in mu g/10(6) eosinophils and then correlated to the EPX 405 genotypes. The protein content of EPX was highest in the patients with the CC genotype of EPX405 (GG = 4.65, GC = 5.93, and CC = 6.57) and for ECP in the patients with the GG genotype of EPX405 (GG = 2.70, GC = 2.47 and CC = 1.90). ANOVA test demonstrated a difference in intracellular protein content for EPX (P = 0.009) and ECP (P = 0.022). The age of disease onset was linked to haplotypes of the EPX405, ECP434 and ECP562 genotypes. Kaplan Maier curve showed a difference between haplotype distributions for the females with CD (P = 0.003). The highest age of disease onset was seen in females with the EPX405CC, ECP434GC, ECP562CC haplotype (34 years) and the lowest in females with the EPX405GC, ECP434GC, ECP562GG haplotype (21 years). For males with UC there was also a difference between the highest and lowest age of the disease onset (EPX405CC, ECP434CC, ECP562CC, mean 24 years vs EPX405GC, ECP434GC, ECP562GG, mean 34 years, P = 0.0009). The relative risk for UC patients with ECP434 or ECP562-GC/CC genotypes to develop dysplasia/cancer was 2.5 (95%CI: 1.2-5.4, P = 0.01) and 2.5 (95%CI: 1.1-5.4, P = 0.02) respectively, compared to patients carrying the GG-genotypes. CONCLUSION: Polymorphisms of EPX and ECP are associated to IBD in an age and gender dependent manner, suggesting an essential role of eosinophils in the pathophysiology of IBD.

  • 2. Cesarini, M.
    et al.
    Collins, G.
    Rönnblom, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Santos, A.
    Sjöberg, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Parkes, M.
    Keshav, S.
    Travis, S.
    Predicting the risk of acute severe colitis (ASC) at diagnosis of Ulcerative Colitis (UC): external validation2015In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 9, no S1, S117-S118 p.Article in journal (Other academic)
  • 3.
    Cesarini, Monica
    et al.
    Oxford Univ Hosp, Translat Gastroenterol Unit, Oxford, England.;Sapienza Univ Rome, Dipartimento Med Interna & Specialita Med, Rome, Italy..
    Collins, Gary S.
    Univ Oxford, Ctr Stat Med, Oxford, England..
    Rönnblom, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Santos, Antonieta
    Cambridge Univ Hosp, Gastroenterol Unit, Cambridge, England.;Hosp Amato Lusitano, Gastroenterol Unit, Castelo Branco, Portugal..
    Wang, Lai Mun
    Oxford Univ Hosp, Dept Cellular Pathol, Oxford, England..
    Sjöberg, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Parkes, Miles
    Oxford Univ Hosp, Translat Gastroenterol Unit, Oxford, England..
    Keshav, Satish
    Oxford Univ Hosp, Translat Gastroenterol Unit, Oxford, England..
    Travis, Simon P. L.
    Oxford Univ Hosp, Translat Gastroenterol Unit, Oxford, England..
    Predicting the Individual Risk of Acute Severe Colitis at Diagnosis2017In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 11, no 3, 335-341 p.Article in journal (Refereed)
    Abstract [en]

    Background and Aims: Acute severe colitis [ASC] is associated with major morbidity. We aimed to develop and externally validate an index that predicted ASC within 3 years of diagnosis. Methods: The development cohort included patients aged 16-89 years, diagnosed with ulcerative colitis [UC] in Oxford and followed for 3 years. Primary outcome was hospitalization for ASC, excluding patients admitted within 1 month of diagnosis. Multivariable logistic regression examined the adjusted association of seven risk factors with ASC. Backwards elimination produced a parsimonious model that was simplified to create an easy-to-use index. External validation occurred in separate cohorts from Cambridge, UK, and Uppsala, Sweden. Results: The development cohort [Oxford] included 34/111 patients who developed ASC within a median 14 months [range 1-29]. The final model applied the sum of 1 point each for extensive disease, C-reactive protein [CRP] >10 mg/l, or haemoglobin < 12 g/dl F or < 14 g/dl M at diagnosis, to give a score from 0/3 to 3/3. This predicted a 70% risk of developing ASC within 3 years [score 3/3]. Validation cohorts included different proportions with ASC [Cambridge = 25/96; Uppsala = 18/298]. Of those scoring 3/3 at diagnosis, 18/18 [Cambridge] and 12/13 [Uppsala] subsequently developed ASC. Discriminant ability [c-index, where 1.0 = perfect discrimination] was 0.81 [Oxford], 0.95 [Cambridge], 0.97 [Uppsala]. Internal validation using bootstrapping showed good calibration, with similar predicted risk across all cohorts. A nomogram predicted individual risk. Conclusions: An index applied at diagnosis reliably predicts the risk of ASC within 3 years in different populations. Patients with a score 3/3 at diagnosis may merit early immunomodulator therapy.

  • 4.
    Englund, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Jacobson, Annica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Artursson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rönnblom, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Efflux transporters in ulcerative colitis: decreased expression of BCRP (ABCG2) and Pgp (ABCB1)2007In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 13, no 3, 291-297 p.Article in journal (Refereed)
    Abstract [en]

    Background: Efflux transport proteins are important components of the intestinal barrier against bacterial toxins, carcinogens, and drugs. This investigation was conducted to determine the expression of Breast Cancer Resistance Protein (BCRP/ABCG2), P-glycoprotein (Pgp/MDR1/ABCB1), and Multidrug Resistance Protein 2 (MRP2/ABCC2) in the gut mucosa of patients with ulcerative colitis (UC). Methods: Patients were thoroughly diagnosed according to well-established clinical, endoscopic, and histologic criteria to be included in the group of patients with active UC (n = 16) or UC in remission (n = 17). Colonic and rectal mucosa from patients with UC were compared with tissues from control subjects (n = 15). The mRNA expression (TaqMan) of the efflux transporters and the proinflammatory cytokines interleukin (IL)-1β and IL-6 was determined. Western blot was used in the analysis of protein expression and the tissue localization of BCRP was determined with confocal microscopy. Results: BCRP and Pgp expression was strongly reduced in individuals with active inflammation compared with controls and was negatively correlated with the levels of IL-6 mRNA. The BCRP staining of colonic epithelium seen in healthy mucosa was diminished in inflamed tissues, with concurrent disruption of epithelial F-actin structure. Conclusions: Two of the efflux transporters of importance for the barrier function of the gut mucosa, Pgp and BCRP, are expressed at strongly reduced levels during active inflammation in patients with UC. Investigations are warranted to determine whether the low levels of efflux transporters during active UC contribute to altered transport and tissue exposure of carcinogens, bacterial toxins, and drugs.

  • 5.
    Englund, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rönnblom, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lazorova, Lucia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Gråsjö, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Artursson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Regional levels of drug transporters along the human intestinal tract: Co-expression of ABC and SLC transporters and comparison with Caco-2 cells2006In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 29, no 3-4, 269-277 p.Article in journal (Refereed)
    Abstract [en]

    A vast number of drugs are subjected to active or facilitated transport and multiple transport mechanism may contribute to the net flux during drug absorption. The main objective of this study was to quantify the regional mRNA expression and determine the co-expression of drug transporters from the ABC (Pgp, BCRP, MRP2, MRP3) and SLC (PEPT1, MCT1, OATPB, OCTN2, OCT1) families along the human intestine (duodenum, jejunum, ileum, and colon). A second objective was to compare the transporter expression between the different intestinal regions and Caco-2 cells. Eight out of nine of the investigated transporters exhibited significant regional differences in expression. OATPB was the only transporter that did not show a region-dependency in the expression along the human intestinal canal. The expression of Pgp, BCRP, OCTN2 and MCT1 differed along the small intestine, but the expression differences were greater than five-fold only for Pgp. The rank order of transcript prevalence was identical in the ileum and the jejunum. Between the ileum and colon, seven transcripts were differentially expressed, and MCT1, OCTN2 and MRP3 were expressed at higher levels in the colon than in the small intestine. The expression of transporters in Caco-2 was closest to the expression pattern in the small intestine, although the expression of OATPB, BCRP and MRP2 differed more than five-fold between the Caco-2 cells and ileum. In conclusion, this study provides quantitative data on the expression of transporters from the ABC and SLC families along the human intestine, which can be useful in the interpretation of clinical studies where more than one intestinal transporter contribute to the net transport and in the computer modelling of drug absorption.

  • 6.
    Franck-Larsson, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Edebol Eeg-Olofsson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Axelson, Hans W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Rönnblom, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Physiological and structural anorectal abnormalities in patients with systemic sclerosis and fecal incontinence2014In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 49, no 9, 1073-1083 p.Article in journal (Refereed)
    Abstract [en]

    Objective

    Fecal incontinence is common in systemic sclerosis (SSc), but the underlying mechanisms are not fully understood. The objectives of this study were to characterize anorectal physiological and morphological defects in SSc patients and to correlate the results with incontinence symptoms.

    Materials and methods

    Twenty-five SSc patients underwent anorectal neurophysiological investigations, anal manometry, and ultrasound.

    Results

    Eleven patients (44%) reported incontinence to solid or liquid feces, but no patient reported diarrhea. Increased fiber density (FD) was recorded in 78% of patients with and in 86% of patients without fecal incontinence not significant (NS). Incontinent patients had lower squeeze pressure (SP; median 49.5 mm Hg) in the high-pressure zone (HPZ) than continent patients (median 72 mm Hg; p = 0.01). In two of the incontinent patients, sonographic abnormalities of the internal anal sphincter (IAS) and the external anal sphincter (EAS) were present, whereas in another two patients isolated IAS abnormalities were seen. These four individuals had lower resting pressure at 1 cm and in the HPZ, and lower SP at 2 cm than patients with normal anorectal sonographic findings (p < 0.05).

    Conclusion

    Lower voluntary SP in incontinent patients and EAS sonographic abnormalities only in patients with incontinence suggest that the EAS is more important in maintaining fecal continence in SSc patients than has previously been reported. The finding of increased FD in most patients further supports involvement of the EAS function in SSc and could indicate previous nerve injury with consequent incomplete reinnervation.

  • 7.
    Lampinen, Maria
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Medicin.
    Rönnblom, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. OTM.
    Amin, Kawa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. klinisk kemi.
    Kristjansson, Gudjon
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. OTM.
    Rorsman, Fredrik
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. OTM.
    Sangfelt, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. OTM.
    Säfsten, Bengt
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. OTM.
    Wagner, Michael
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. OTM.
    Wanders, Alkwin
    Department of Genetics and Pathology. patologi.
    Winqvist, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Medicin.
    Carlson, Marie
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. OTM.
    Eosinophil granulocytes are activated during the remission phase of ulcerative colitis.2005In: Gut, ISSN 0017-5749Article in journal (Refereed)
  • 8.
    Ronnblom, A
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Danielsson, A
    Hereditary muscular diseases and symptoms from the gastrointestinal tract.2004In: Scand J Gastroenterol, ISSN 0036-5521, Vol. 39, no 1, 1-4 p.Article, review/survey (Other (popular scientific, debate etc.))
  • 9.
    Rönnblom, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Holmstrom, Tommy
    Tanghoj, Hans
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Sjoberg, Daniel
    Appearance of hepatobiliary diseases in a population-based cohort with inflammatory bowel diseases (Inflammatory Bowel Disease Cohort of the Uppsala Region)2015In: Journal of Gastroenterology and Hepatology, ISSN 0815-9319, E-ISSN 1440-1746, Vol. 30, no 8, 1288-1292 p.Article in journal (Refereed)
    Abstract [en]

    Background and AimTo prospectively follow the evolution of hepatobiliary diseases in a population-based cohort of patients with inflammatory bowel diseases. MethodsBetween 2005 and 2009, 790 incident cases of ulcerative colitis and Crohn's disease were registered in the Uppsala Health Region, corresponding to an average incidence of 20.0 and 9.9 new cases/100000 inhabitants/year, respectively. Liver function tests were analyzed in 97.1% and the results of ensuing investigations were summarized. ResultsSeventeen patients with primary sclerosing cholangitis were diagnosed corresponding to an overall prevalence of 2.2% (ulcerative colitis 1.7% and Crohn's disease 3.0%, respectively). The median age at diagnosis was 25 years (interquartile range: 17.0-34.0). Among the 92 patients below 17 years of age, three had autoimmune hepatitis and three primary sclerosing cholangitis, summing up to a prevalence of 6.5% immune-mediated hepatobiliary diseases among the pediatric patients. Three patients have undergone liver transplantation and one died of colonic carcinoma. Ten patients have demonstrated persistent elevation of alkaline phosphatases but had a normal magnetic resonance cholangiopancreatography (two patients) or refused further investigation (one patient). ConclusionIn this first large prospective population-based cohort of 526 patients with ulcerative colitis (UC) and 264 with Crohn's disease, 17 cases of primary sclerosing cholangitis were found, among whom three (17%) so far have been liver transplanted and one has died of colon carcinoma. The average age of those affected by primary sclerosing cholangitis is considerably lower than usually reported. Ten patients had or have had elevated alkaline phosphatase without confirmed liver or biliary disease.

  • 10.
    Rönnblom, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Holmstrom, Tommy
    Dept Internal Med, Mariehamn, Aland, Finland..
    Tanghoj, Hans
    Malar Hosp, Dept Internal Med, Eskilstuna, Sweden..
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sjoberg, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology. Uppsala Univ, Dept Med Sci, Uppsala, Sweden..
    Celiac disease, collagenous sprue and microscopic colitis in IBD. Observations from a population-based cohort of IBD (ICURE)2015In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 50, no 10, 1234-1240 p.Article in journal (Refereed)
    Abstract [en]

    Objective. Inflammatory bowel disease (IBD), microscopic colitis and celiac disease are all diseases with worldwide distribution and increased incidence has been reported from many areas. There is a shortage of studies investigating the occurrence of these diseases in the same individual and whether those affected demonstrate any particular phenotype. The aim of the study was to describe the concomitant incidence of microscopic colitis and celiac disease in a population-based IBD cohort. Methods. All 790 individuals in a prospective population-based cohort included 2005-09 from Uppsala region, Sweden, were reviewed regarding the appearance of microscopic or celiac disease before or after IBD diagnosis. Results. Fifty percent (396/790) of the patients had been examined for the possibility of celiac disease. Seventeen patients with celiac disease were found, representing 2.2% of the cohort. Patients with celiac disease were younger compared to the non-celiac patients and those with colitis had more often an extensive inflammation of the colon. Seventy-one percent (12/17) were women. The majority of the patients were diagnosed with celiac disease before IBD. Five patients with IBD had an earlier diagnosis of microscopic colitis or developed it after the IBD diagnosis. One teenager developed collagenous sprue, misinterpreted as a severe relapse of ulcerative colitis (UC) resulting in colectomy. Conclusions. The risk for celiac disease seems not to be increased in IBD, but those affected by both diseases seem to be predominantly women with extensive UC. There is a potential association between microscopic colitis and IBD.

  • 11.
    Rönnblom, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Holmström, Tommy
    Dept Internal Med, Mariehamn, Aland, Finland..
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Tanghöj, Hans
    Malar Hosp, Dept Internal Med, Eskilstuna, Sweden..
    Thörn, Mari
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Sjöberg, Daniel
    Falun Cent Hosp, Dept Internal Med, Falun, Sweden..
    Clinical course of Crohn's disease during the first 5 years. Results from a population-based cohort in Sweden (ICURE) diagnosed 2005-20092017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 1, 81-86 p.Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of the study was to describe the medical treatment, change in phenotype, need for surgery and IBD-associated mortality during the first 5 years after diagnosis. Material and Methods: Patients diagnosed with Crohn's disease including all age groups in the Uppsala healthcare region in the middle of Sweden 2005-2009 were included in the study. Medical notes were scrutinised and patients contacted. Out of 269 patients, 260 (96.3%) could be followed for 5 full years or until death. Results: The following drugs were used: 5-ASA 66.7%, systemic steroids 76.4%, antimetabolites 56.7% and anti-TNF 20.3%. Described with the Montreal classification, the proportion with inflammatory behaviour decreased from 78.1% to 74.0% from diagnosis to end of the observation, patients with stricturing behaviour increased from 13.0% to 15.4% and patients with penetrating behaviour increased from 8.9% to 10.6%. After the first year, 12.4% had been treated with intestinal resection or colectomy, a figure that increased to 14.8 after 5 years. Two patients suffered an IBD-related death. Conclusions: Compared to similar patient cohorts, the present study demonstrates that although the course of Crohn's disease seems difficult to change during the first year after diagnosis, the following years up to 5 years shows a more benign course than has usually been described earlier.

  • 12.
    Rönnblom, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Holmström, Tommy
    Dept Internal Med, Mariehamn, Finland..
    Tanghöj, Hans
    Malar Hosp, Dept Internal Med, Eskilstuna, Sweden..
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Thörn, Mari
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Sjöberg, Daniel
    Falun Cent Hosp, Dept Internal Med, Falun, Sweden..
    Low colectomy rate five years after diagnosis of ulcerative colitis. Results from a prospective population-based cohort in Sweden (ICURE) diagnosed during 2005-2009*2016In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 51, no 11, 1339-1344 p.Article in journal (Refereed)
    Abstract [en]

    Objective: The medical treatment of ulcerative colitis (UC) has seen a change towards a more active attitude during recent years, including both the use of more traditional drugs as well as new biological substances. In this epidemiological study we have evaluated the results of modern treatment of UC in a population-based cohort of patients including all age groups, with regard to relapse rate, colectomy and IBD-associated mortality.

    Material and methods: Patients diagnosed with UC in the Uppsala health care region in the middle of Sweden during 2005-2009 were included in the study. Out of 524 patients, 491 (93%) could be followed for five full years or until death.

    Results: Nineteen patients (3.9%) had died and two of these deaths could be attributed to UC (one postoperative death and one colonic carcinoma). The following drugs were used by the patients during the study period: 5-ASA (91%), systemic steroids (66%), immunomodulators (IMM), mainly thiopurines (26%) and anti-TNF (11%). During the observation period, 74% experienced at least one relapse and 5.3% were subjected to colectomy. Among patients<17 years at diagnosis, colectomy was performed in two (4.8%).

    Conclusions: Five years after diagnosis of ulcerative colitis, 5.3% had been subjected to colectomy and two patients (0.38%) had died because of the disease.

  • 13. Sjoberg, Daniel
    et al.
    Holmstrom, Tommy
    Larsson, Marit
    Nielsen, Anne-Lie
    Holmquist, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Ekbom, Anders
    Rönnblom, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Incidence and clinical course of Crohn's disease during the first year - Results from the IBD Cohort of the Uppsala Region (ICURE) of Sweden 2005-20092014In: Journal of Crohn's & Colitis, ISSN 1873-9946, Vol. 8, no 3, 215-222 p.Article in journal (Refereed)
    Abstract [en]

    Background and Aims: As a part of the Swedish ICURE study where the epidemiological results of ulcerative colitis and microscopic colitis recently have been published, we hereby present the corresponding figures for Crohn's disease. Methods: All patients diagnosed with Crohn's disease in Uppsala County (305,381 inhabitants) were prospectively registered during 2005-2006 and the same for all new patients with Crohn's disease in Uppsala Region (642,117 inhabitants) during 2007-2009. Results: 264 patients with Crohn's disease were included. The mean annual incidence was 9.9/100,000/year (95% CI: 7.1-12.6). Incidence among children <17 years was 10.0/100,000/year (95% CI: 3.8-16.3). 51% of the patients had ileal involvement (L1 n = 73, 28%. L2: n = 129, 49%. L3: n = 62, 23%, L4: n = 47, 18%) and 23% had a stricturing or penetrating disease (B1: n = 204, 77%. B2: n = 34, 13%. B3: n = 26, 10%. p: n = 27, 10%). Intestinal resection rate during the first year was 12.5%. Patients with complicated disease had longer symptom duration before diagnosis compared to patients with non-complicated disease (median months 12.0, IQR: 3.0-24.0 vs 4.0, IQR: 2.0-12.0, p = 0.0032). Patients 40 years or older had an increased risk for surgery (HR: 2.03, 95% CI: 1.01-4.08, p = 0.0457). Conclusions: The incidence of Crohn's disease in a region of Sweden is one of the highest reported in Europe. Long symptom duration precedes stricturing or penetrating behaviour. Old age is an independent risk factor for surgery. (C) 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  • 14. Sjoberg, Daniel
    et al.
    Holmstrom, Tommy
    Larsson, Marit
    Nielsen, Anne-Lie
    Holmquist, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Rönnblom, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Anemia in a Population-based IBD Cohort (ICURE): Still High Prevalence After 1 Year, Especially Among Pediatric Patients2014In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 20, no 12, 2266-2270 p.Article in journal (Refereed)
    Abstract [en]

    Background:Prevalence of anemia in patients with inflammatory bowel disease (IBD) is uncertain because of scarcity of population-based studies. The aim of this study was to evaluate prevalence of anemia in a population-based cohort of newly diagnosed patients with IBD to identify risk factors for anemia and to describe contemporary anemia-specific treatment during the first year.Methods:All patients with ulcerative colitis or Crohn's disease in the IBD Cohort of Uppsala Region cohort (n = 790) and hemoglobin levels at the time of diagnosis were eligible for inclusion. The WHO definition of anemia was used.Results:Seven hundred forty-nine (95%) of the patients with IBD were included. Five hundred eighty of 749 (77%) patients had measured hemoglobin levels at 12-month follow-up. The prevalence of anemia at the time of diagnosis was 227/749 (30%). After 1 year, it was 102/580 (18%). Anemia was more common among newly diagnosed patients with Crohn's disease compared with ulcerative colitis (42% versus 24%, P < 0.0001), but after 1 year, there was no difference (18% versus 18%, P = NS). Children had more often anemia compared with adults, both at diagnosis and after 1 year (diagnosis: 55% versus 27%, P < 0.0001; follow-up: 28% versus 16%, P < 0.05). Anemia was associated with colonic engagement in Crohn's disease and the extent of inflammation in ulcerative colitis. Only 46% of patients with anemia were treated with iron supplementation or blood transfusion.Conclusions:The overall prevalence of anemia in patients with IBD at the time of diagnosis was high. A large proportion was still anemic after 1 year. Children were more at risk compared with adults. More efforts are needed to treat patients with anemia.

  • 15.
    Sjöberg, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Larsson, Märit
    Nielsen, Anne-Lie
    Rönnblom, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Acute severe ulcerative colitis in a population based cohort (ICURE): Outcome and complications of medical and surgical treatmentArticle in journal (Refereed)
  • 16.
    Sköldberg, Filip
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Portela-Gomes, Guida M.
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Nilsson, Gunnar
    Perheentupa, Jaakko
    Betterle, Corrado
    Husebye, Eystein S.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Rönnblom, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Histidine decarboxylase, a pyridoxal phosphate-dependent enzyme, is an autoantigen of gastric enterochromaffin-like cells2003In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 88, no 4, 1445-1452 p.Article in journal (Refereed)
    Abstract [en]

    Patients with autoimmune polyendocrine syndrome type 1 often have autoantibodies against neurotransmitter synthesizing enzymes, including the pyridoxal phosphate-dependent enzymes glutamic acid decarboxylase and aromatic L-amino acid decarboxylase. Using a candidate approach, we have identified the histamine-synthesizing enzyme histidine decarboxylase, also pyridoxal phosphate dependent, as an autoantigen in this disorder. Anti-histidine decarboxylase antibodies reacting with in vitro translated antigen were found in 36/97 (37%) of autoimmune polyendocrine syndrome type 1 patients studied. The antibodies also reacted with the native enzyme in HMC-1 cell lysates and did not cross-react with the highly homologous aromatic L-amino acid decarboxylase. Anti-histidine decarboxylase antibodies were associated with a history of intestinal dysfunction (P = 0.017). Gastric and duodenal biopsies from a patient with anti-histidine decarboxylase antibodies were studied by immunohistochemistry. The oxyntic mucosa was found to lack the histamine producing enterochromaffin-like cells, suggestive of an autoimmune destruction. To our knowledge, this is the first report of autoantibodies against histidine decarboxylase and absence of gastric enterochromaffin-like cells.

  • 17.
    Thörn, Mari
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Rönnblom, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Sangfelt, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Eriksson, Britt-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Bondeson, Kåre
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Active cytomegalovirus infection diagnosed by real-time PCR in patients with inflammatory bowel disease: a prospective, controlled observational study2016In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 51, no 9, 1075-1080 p.Article in journal (Refereed)
    Abstract [en]

    Objective: It is assumed that cytomegaloviral (CMV) infection in inflammatory bowel disease (IBD) is caused by reactivation due to the immunosuppressive therapy, but the role of CMV as a pathophysiological factor and prognostic marker in IBD is unclear. The aim of this study was to investigate CMV infection in IBD, with real-time polymerase chain reaction (PCR) and immunohistochemistry, with emphasis on newly diagnosed disease.

    Materials and methods: In this prospective, controlled study, 67 patients with IBD and 34 control patients with irritable bowel syndrome (IBS) or rectal bleeding were included. Serology for CMV was analysed along with CMV DNA in plasma, mucosal biopsies, and faeces. Mucosal biopsies were further analysed with histopathology and CMV immunohistochemistry.

    Results: Detection of CMV IgM was more common in patients with IBD, compared to controls, 21% versus 3%. CMV DNA was found in 16% of patients with newly diagnosed, untreated IBD and in 38% of steroid-treated patients. Four of the five patients that needed urgent surgery were CMV-DNA positive in at least one of three sample types. None of the controls had detectable CMV DNA.

    Conclusions: Active CMV infection was found in high proportions of newly diagnosed untreated patients with IBD, in patients on immunosuppression and in patients in the need of surgery. Low CMV-DNA levels in non-immunosuppressed patients were not a risk factor for the development of more severe IBD, while the detection of CMV DNA in patients on immunosuppressive therapy may foresee disease progression.

  • 18.
    Thörn, Mari
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Sjöberg, Daniel
    Ekbom, Anders
    Holmstrom, Tommy
    Larsson, Märit
    Nielsen, Anne-Lie
    Holmquist, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Thelander, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Ronnblöm, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Microscopic colitis in Uppsala health region, a population-based prospective study 2005-20092013In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 48, no 7, 825-830 p.Article in journal (Refereed)
    Abstract [en]

    Objective

    The aim of this study is to report on the incidence of microscopic colitis (MC), any possible relation with inflammatory bowel disease (IBD), concomitant drug consumption, related diseases and the clinical course of the diseases.

    Methods

    Both new cases of IBD and MC were registered at the same time in the same geographical area. The study started in the county of Uppsala 2005-2006, and other parts of the surrounding health region were included 2007-2009. Established morphological criteria were used, i.e. a layer of subepithelial collagen band >= 10 mu m in collagenous colitis (CC) with concomitant inflammation and at least 20 lymphocytes per 100 epithelial cells in lymphocytic colitis (LC).

    Results

    The authors found 272 new cases of MC, 154 with CC and 118 with LC. The mean age-adjusted incidence was 7.0/1,000,000 for CC and 4.8/100,000 for LC. The clinical course was dominated by single episodes with diarrhea or intermittent symptoms, but 14% suffered from chronic diarrhea. In 10% of the cases, diagnosis was made in individuals without chronic watery diarrhea. Although not systematically tested, concomitant celiac disease was found in approximately 5% of the patients.

    Conclusions

    The incidence of MC in Uppsala health region is similar to other studied areas. The majority of patients had a self-limiting or easily treated condition, but 14% need a more or less continuous medication. Ten percent of the patients demonstrate other symptoms than chronic watery diarrhea. The possibility of concomitant celiac disease should be considered in new cases of MC.

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