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  • 1.
    Agreus, Lars
    et al.
    Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Talley, Nicholas J.
    Univ Newcastle, Fac Hlth & Med, Newcastle, NSW, Australia..
    Wallner, Bengt
    Umea Univ, Dept Surg, Umea, Sweden..
    Forsberg, Anna
    Karolinska Inst, Mol Med & Surg, Stockholm, Sweden..
    Vieth, Michael
    Klinikum Bayreuth, Inst Pathol, Bayreuth, Germany..
    Veits, Lothar
    Klinikum Bayreuth, Inst Pathol, Bayreuth, Germany..
    Björkegren, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Engstrand, Lars
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden..
    Andreasson, Anna
    Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.;Stockholm Univ, Stress Res Inst, Stockholm, Sweden..
    Towards a healthy stomach?: Helicobacter pylori prevalence has dramatically decreased over 23 years in adults in a Swedish community2016Ingår i: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, Vol. 4, nr 5, s. 686-696Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background In Western countries the prevalence of Helicobacter pylori (H. pylori) infection may be declining but there is a lack of recent longitudinal population studies. We evaluated the changing epidemiology over a 23-year period in Sweden.

    Materials and methods In 1989, the validated Abdominal Symptom Questionnaire (ASQ) was mailed to a random sample of inhabitants (ages 22-80 years) in a Swedish community, and 1097 (87%) responded. H. pylori serology was analysed in a representative subsample (n=145). Twenty-three years later, the ASQ was mailed again using similar selection criteria, and 388 out of 1036 responders had an upper endoscopy with assessment of H. pylori and corpus atrophy status.

    Results The prevalence of positive H. pylori serology decreased from 37.9% (1989) to 15.8% (2012), corresponding to a decrease in odds of 75% per decade (odds ratio (OR): 0.25; 95% confidence interval (CI): 0.11-0.59, p=0.001) independent of age, gender, body mass index (BMI) and level of education, with a pattern consistent with a birth cohort effect. The prevalence increased with increasing age (p=0.001). The prevalence of H. pylori on histology in 2012 was 11.4% (95% CI 8.6-15.0). The prevalence of corpus atrophy on serology and/or histology in 2012 was 3.2% (95% CI 1.8-5.5); all cases were 57 years old.

    Conclusion The stomach is healthier in 2012 compared with 1989. H. pylori prevalence in adults has decreased over the last two decades to a level where clinical management might be affected.

  • 2.
    Al-Saffar, Anas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi. Baghdad University/ College of Veterinary Medicine.
    Diaz, Hetzel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Gastrointestinal motility examined by wireless motility capsule (SmartPill®) and gut hormone profiles in inflammatory bowel diseases: Motility and hormones inIBDManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Background: Inflammatory bowel disease (IBD) is associated with vague gastrointestinal (GI) discomfort even when inflammation is in clinical remission. In Crohn’s disease (CD) and ulcerative colitis (UC) motility disorders have been described throughout the GI tract. In clinics, considerable patient discomfort relates to symtoms of dysmotility (e.g., intestinal cramping, distension or diarrhea), which present in active and inactive disease. Treatment requires diagnostic methods to identify pathologies throughout the gut during meals while also evaluating gut peptide hormone changes.

    Methods: SmartPill® wireless motility capsule (WMC) technique to identify pH and motility derangements along the GI tract. pH, luminal pressure, transit time and prandial peptide hormone changes were compared between either 10 CD patients or 10 UC patients relative 20 age- and sex-matched healthy controls.

    Results: Motility index was significantly reduced in the stomach and contraction frequency and peak pressures were reduced in CD. Small bowel motility index was reduced in UC. In CD, meal responses of ghrelin, GIP, PYY and leptin, and to a lesser extent GLP-1, showed elevated plasma levels. In UC, ghrelin, GIP and GLP-1, but not PYY and leptin were elevated. Neither had a clear relationship to the motility discrepancies.

    Conclusion: Enhanced endocrine meal responses may be a cause or result of motility disturbances in IBD, but cannot be broken down by individual peptides. These observations potentially give pathophysiological explanations for GI disturbances in IBD, opening the possibility for pharmacological treatment.

  • 3.
    Al-Saffar, Anas K.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi. Baghdad Univ, Coll Vet Medicine, Dept Surg & Obstet, Baghdad, Iraq..
    Halim, Md Abdul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hall, G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Small intestinal lactulose and sucralose hyper-permeability in inflammatory bowel disease2018Ingår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, s. S124-S124Artikel i tidskrift (Övrigt vetenskapligt)
  • 4.
    Al-Saffar, Anas Kh.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Gastrointestinal Permeability and Motility in Inflammatory Bowel Disease2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Mag-tarmkanalens glatta muskulatur är funktionellt integrerad med enteriska nervsystemet och endokrin signalering för ackommodation, blandning och passage genom mag-tarmkanalen. De intestinala epitelcellerna upprätthåller digestion och absorption, samtidigt med barriärfunktion mot skadliga agens.

    Avhandlingen utvärderar patofysiologiska barriärmekanismer vid inflammatorisk tarmsjukdom (IBD) beträffande permeabilitet, förändrad motilitet och hormonella mönster vid Crohns sjukdom (CD) och ulcerös colit (UC) genom att, 1) utvärdera mag-tarmkanalens motilitet med trådlös motilitetskapsel (WMC) och videokapsel endoskopi (VCE), 2) studera I-FABP som biomarkör vid CD avseende distribution i mag-tarmkanalen, samband med sjukdomsktivitet, parallellitet med  TNFα och Harvey-Bradshaw index (HBI) under anti-TNFα-behandling, 3) utvärdera intestinal permeabilitet vid IBD, 4) studera användning av WMC för att registrera motilitet vid måltidssvar och hormonella mönster.

    WMC registrerade pH, tryck och temperatur längs hela mag-tarmkanalen. Referensvärden för  ventrikeltömningstid och transittider för tunntarm, colon och totala mag-tarmkanalen etablerades. Dessa värden har använts för utvärdering av IBD. Mjukvaruberäknade värden var lika visuellt avlästa värden. Mätvärden för VCE under fasta visade snabb transit, medan WMC hade längre ventrikeltömningstid och transittid för tunntarm. Intra-individuell variation måste bedömas särskilt vid kliniska undersökningar.

    I-FABP lokaliserades till epitelet i tunntarmen, i mindre omfattning i ventrikel och colon. Cirkulerande I-FABP var förhöjt vid aktiv CD, som TNFα. Plasmanivåer av I-FABP följde parallellt TNFα och HBI under behandling och uppföljning. I-FABP kan användas som selektiv prognostisk markör för CD i jejunum och ileum vid monitorering av CD patienter.

    Ökad tunntarmspermeabilitet sågs både vid CD och UC med hyperpermeabilitet för laktulos, medan sukralos, som ersättning för laktulos, kunde mäta permeabilitet i både tunntarm och colon. Hyperpermeabiliteten medför ingen generell malabsorption eftersom absorptionen av riboflavin var normal, och beror av specifika transportmekanismer i tunntarmen.

    Med hjälp av WMC kunde endast begränsade avvikelser i motiliteten vid IBD registreras, även för pH. Hos enskilda individer kunde tydliga avvikelser ses. Dessutom noterades generellt förhöjda gastrointestinala och metabola peptidhormoner samtidigt med ett bevarat måltidssvar. Samband mellan hormonnivåer och motilitetsavvikelser saknades, men sannolikt har hormonnivåerna betydelse för hunger och mättnad.

    Den sammantagna bilden visar användbarheten av WMC och permeabilitetstest för att bedöma patofysiologiska funktioner i mag-tarmkanalen. I-FABP kan spåra sjukdomsaktivitet i tunntarmen, medan permeabilitetstest ger information selektivt om sjukdom i tunntarm och colon. Användning av WMC tillsammans med mönster av hormonfrisättning kan ge information om motilitetsstörningar och sannolikt förändrad aptitreglering.

    Delarbeten
    1. Validation of SmartPill® wireless motility capsule for gastrointestinaltransit time: Intra-subject variability, software accuracy and comparison with video capsule endoscopy
    Öppna denna publikation i ny flik eller fönster >>Validation of SmartPill® wireless motility capsule for gastrointestinaltransit time: Intra-subject variability, software accuracy and comparison with video capsule endoscopy
    Visa övriga...
    2017 (Engelska)Ingår i: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 29, nr 10, artikel-id e13107Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND: There is interest in ultimately combining endoscopy and motility assessments. Gastric emptying (GET), small bowel (SBTT), colon (CTT) and whole gut transit (WGTT) times are conveniently obtained by SmartPill® wireless motility capsule (WMC) that records luminal pH, temperature and pressure. Reproducibility within same subjects and accuracy of software derived times (MotiliGI® ) were investigated for diagnostic application. GET and SBTT were separately measured using video capsule endoscopy (VCE). The aim of this investigation was to assess same subject reproducibility of WMC, accuracy of software derived transit times and relate to Pillcam® SB (small bowel) VCE motility data.

    METHODS: Seventy three healthy adults ingested a 260 kcal mixed meal followed by WMC tests. Food intake was permitted after 6 hours. Regional transit data was obtained for GET, SBTT and CTT, the sum yielding WGTT. Nineteen subjects repeated WMC tests 2 or 4 weeks later; a separate 70 underwent VCE while fasted.

    KEY RESULTS: Visually derived data from WMC yielded GET 3.46±0.27, SBTT 5.15±0.21, CTT 20.76±1.19 and WGTT 29.53±1.28 hours (mean±SEM). Pearson's correlation coefficients (r) against software derived results were: GET 0.78 (P<.0001), SBTT 0.28 (P<.05), CTT 0.96 (P<.0001), WGTT 0.99 (P<.0001). VCE yielded lower GET (0.71±0.08 hours) and SBTT (4.15±0.13 hours).

    CONCLUSIONS AND INFERENCES: GET, SBTT, CTT and WGTT obtained by WMC are commensurate with literature values, including by other methods. Visually and software derived transit times have strongest correlations for CTT and WGTT. WMC yields longer GET and SBTT than VCE, perhaps due to meal related effects on motility.

    Nationell ämneskategori
    Gastroenterologi
    Identifikatorer
    urn:nbn:se:uu:diva-322579 (URN)10.1111/nmo.13107 (DOI)000410149700014 ()
    Forskningsfinansiär
    Svenska läkaresällskapet, SLS-503131Jerringfonden
    Tillgänglig från: 2017-05-26 Skapad: 2017-05-26 Senast uppdaterad: 2019-04-29
    2. Parallel Changes in Harvey-Bradshaw Index, TNFα, and Intestinal Fatty Acid Binding Protein  in Response to Infliximab in Crohn’s Disease
    Öppna denna publikation i ny flik eller fönster >>Parallel Changes in Harvey-Bradshaw Index, TNFα, and Intestinal Fatty Acid Binding Protein  in Response to Infliximab in Crohn’s Disease
    Visa övriga...
    2017 (Engelska)Ingår i: Gastroenterology Research and Practice, ISSN 1687-6121, E-ISSN 1687-630X, s. 1-8, artikel-id 1745918Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Intestinal fatty acid binding protein (I-FABP) indicates barrier integrity. Aims: determine if I-FABP is elevated in active Crohn's disease (CD) and if I-FABP parallels anti-TNF alpha antibody (infliximab) induced lowering of TNF alpha and Harvey-Bradshaw Index (HBI) as potential indicator of mucosal healing. I-FABP distribution along human gut was determined. Serum from 10 CD patients collected during first three consecutive infliximab treatments with matched pretreatment and follow-up samples one week after each treatment and corresponding HBI data were analyzed. I-FABP reference interval was established from 31 healthy subjects with normal gut permeability. I-FABP and TNF alpha were measured by ELISA; CRP was measured by nephelometry. Healthy tissue was used for I-FABP immunohistochemistry. Pretreatment CD patient TNF alpha was 1.6-fold higher than in-house reference interval, while I-FABP was 2.5-fold higher, which lowered at follow-ups. Combining all 30 infusion/follow-up pairs also revealed changes in I-FABP. HBI followed this pattern; CRP declined gradually. I-FABP was expressed in epithelium of stomach, jejunum, ileum, and colon, with the highest expression in jejunum and ileum. I-FABP is elevated in active CD with a magnitude comparable to TNF alpha. Parallel infliximab effects on TNF alpha, HBI, and I-FABP were found. I-FABP may be useful as an intestine selective prognostic marker in CD.

    Ort, förlag, år, upplaga, sidor
    Egypt: Hindawi Publishing Corporation, 2017
    Nationell ämneskategori
    Gastroenterologi
    Identifikatorer
    urn:nbn:se:uu:diva-334232 (URN)10.1155/2017/1745918 (DOI)000413557400001 ()
    Forskningsfinansiär
    Vetenskapsrådet, 7916Karolinska Institutets ForskningsstiftelseSveriges läkarförbund, SLS-411921; SLS-503131
    Anmärkning

    Title in WoS: Parallel Changes in Harvey-Bradshaw Index, TNF alpha, and Intestinal Fatty Acid Binding Protein in Response to Infliximab in Crohn's Disease

    Tillgänglig från: 2017-11-21 Skapad: 2017-11-21 Senast uppdaterad: 2019-04-29Bibliografiskt granskad
    3. Concurrent small and large intestinal permeability in inflammatory bowel disease: Hyper-permeability in IBD
    Öppna denna publikation i ny flik eller fönster >>Concurrent small and large intestinal permeability in inflammatory bowel disease: Hyper-permeability in IBD
    (Engelska)Manuskript (preprint) (Övrig (populärvetenskap, debatt, mm))
    Abstract [en]

    Hyper-permeability in inflammatory bowel disease (IBD) has mostly been explored in the colon, where symptomatic inflammation is prevalent. Relationships between small and large intestine barrier function were examined. Fasted (4h) IBD (19 ulcerative colitis, 11 Crohn's disease) and 25 healthy control subjects’ were investigated. Lactulose (10g), mannitol (5g), riboflavin (0.05g) and sucralose (5g) were ingested with 500 mL water. Urine lactulose and mannitol were measured by enzyme assays, riboflavin by intrinsic fluorescence and sucralose by HPLC. CRP was measured by nephelometry. In IBD, small intestine lactulose and sucralose % recoveries were 1.77 and 2.73 fold higher than controls; combined data revealed the two probes were correlated (R2=0.6). In IBD, large intestine sucralose % recovery was 2.6 fold higher than controls and correlated with small intestine sucralose % recovery (R2=0.6). Conclusions: Sucralose yields similar result as lactulose for small intestine permeability, while having higher S:N, implying sucralose is more sensitive. No evidence was found for riboflavin malabsorption in IBD. There is concurrent small and large intestine hyper-permeability in IBD. Small intestine hyper-permeability is presumably related to inflammation in the large intestine, but without obvious deficiency in transporter mediated micronutrient absorption (i.e., riboflavin) in the small intestine.

    Nyckelord
    Crohn’s disease; Ulcerative colitis; Sucralose; Tight junction; Permeability; Intestine
    Nationell ämneskategori
    Klinisk medicin Gastroenterologi
    Forskningsämne
    Medicinsk vetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-383487 (URN)
    Tillgänglig från: 2019-05-16 Skapad: 2019-05-16 Senast uppdaterad: 2019-05-17
    4. Gastrointestinal motility examined by wireless motility capsule (SmartPill®) and gut hormone profiles in inflammatory bowel diseases: Motility and hormones inIBD
    Öppna denna publikation i ny flik eller fönster >>Gastrointestinal motility examined by wireless motility capsule (SmartPill®) and gut hormone profiles in inflammatory bowel diseases: Motility and hormones inIBD
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Background: Inflammatory bowel disease (IBD) is associated with vague gastrointestinal (GI) discomfort even when inflammation is in clinical remission. In Crohn’s disease (CD) and ulcerative colitis (UC) motility disorders have been described throughout the GI tract. In clinics, considerable patient discomfort relates to symtoms of dysmotility (e.g., intestinal cramping, distension or diarrhea), which present in active and inactive disease. Treatment requires diagnostic methods to identify pathologies throughout the gut during meals while also evaluating gut peptide hormone changes.

    Methods: SmartPill® wireless motility capsule (WMC) technique to identify pH and motility derangements along the GI tract. pH, luminal pressure, transit time and prandial peptide hormone changes were compared between either 10 CD patients or 10 UC patients relative 20 age- and sex-matched healthy controls.

    Results: Motility index was significantly reduced in the stomach and contraction frequency and peak pressures were reduced in CD. Small bowel motility index was reduced in UC. In CD, meal responses of ghrelin, GIP, PYY and leptin, and to a lesser extent GLP-1, showed elevated plasma levels. In UC, ghrelin, GIP and GLP-1, but not PYY and leptin were elevated. Neither had a clear relationship to the motility discrepancies.

    Conclusion: Enhanced endocrine meal responses may be a cause or result of motility disturbances in IBD, but cannot be broken down by individual peptides. These observations potentially give pathophysiological explanations for GI disturbances in IBD, opening the possibility for pharmacological treatment.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Forskningsämne
    Medicinsk vetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-383491 (URN)
    Tillgänglig från: 2019-05-16 Skapad: 2019-05-16 Senast uppdaterad: 2019-05-17
  • 5.
    Al-Saffar, Anas Kh.
    et al.
    Baghdad University/ College of Veterinary Medicine.
    Halim, Abdul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Concurrent small and large intestinal permeability in inflammatory bowel disease: Hyper-permeability in IBDManuskript (preprint) (Övrig (populärvetenskap, debatt, mm))
    Abstract [en]

    Hyper-permeability in inflammatory bowel disease (IBD) has mostly been explored in the colon, where symptomatic inflammation is prevalent. Relationships between small and large intestine barrier function were examined. Fasted (4h) IBD (19 ulcerative colitis, 11 Crohn's disease) and 25 healthy control subjects’ were investigated. Lactulose (10g), mannitol (5g), riboflavin (0.05g) and sucralose (5g) were ingested with 500 mL water. Urine lactulose and mannitol were measured by enzyme assays, riboflavin by intrinsic fluorescence and sucralose by HPLC. CRP was measured by nephelometry. In IBD, small intestine lactulose and sucralose % recoveries were 1.77 and 2.73 fold higher than controls; combined data revealed the two probes were correlated (R2=0.6). In IBD, large intestine sucralose % recovery was 2.6 fold higher than controls and correlated with small intestine sucralose % recovery (R2=0.6). Conclusions: Sucralose yields similar result as lactulose for small intestine permeability, while having higher S:N, implying sucralose is more sensitive. No evidence was found for riboflavin malabsorption in IBD. There is concurrent small and large intestine hyper-permeability in IBD. Small intestine hyper-permeability is presumably related to inflammation in the large intestine, but without obvious deficiency in transporter mediated micronutrient absorption (i.e., riboflavin) in the small intestine.

  • 6.
    Al-Saffar, Anas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Meijer, Carl Hampus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Gannavarapu, Venkata Ram
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hall, Gustav
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Li, Yichen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Diaz Tartera, Hetzel O.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Lördal, Mikael
    Department of Medicine, Division of Gastroenterology and Hepatology, Danderyds Sjukhus, Danderyd, Sweden.
    Ljung, Tryggve
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi. Abbvie, Solna, Sweden.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Parallel Changes in Harvey-Bradshaw Index, TNFα, and Intestinal Fatty Acid Binding Protein  in Response to Infliximab in Crohn’s Disease2017Ingår i: Gastroenterology Research and Practice, ISSN 1687-6121, E-ISSN 1687-630X, s. 1-8, artikel-id 1745918Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Intestinal fatty acid binding protein (I-FABP) indicates barrier integrity. Aims: determine if I-FABP is elevated in active Crohn's disease (CD) and if I-FABP parallels anti-TNF alpha antibody (infliximab) induced lowering of TNF alpha and Harvey-Bradshaw Index (HBI) as potential indicator of mucosal healing. I-FABP distribution along human gut was determined. Serum from 10 CD patients collected during first three consecutive infliximab treatments with matched pretreatment and follow-up samples one week after each treatment and corresponding HBI data were analyzed. I-FABP reference interval was established from 31 healthy subjects with normal gut permeability. I-FABP and TNF alpha were measured by ELISA; CRP was measured by nephelometry. Healthy tissue was used for I-FABP immunohistochemistry. Pretreatment CD patient TNF alpha was 1.6-fold higher than in-house reference interval, while I-FABP was 2.5-fold higher, which lowered at follow-ups. Combining all 30 infusion/follow-up pairs also revealed changes in I-FABP. HBI followed this pattern; CRP declined gradually. I-FABP was expressed in epithelium of stomach, jejunum, ileum, and colon, with the highest expression in jejunum and ileum. I-FABP is elevated in active CD with a magnitude comparable to TNF alpha. Parallel infliximab effects on TNF alpha, HBI, and I-FABP were found. I-FABP may be useful as an intestine selective prognostic marker in CD.

  • 7.
    Amcoff, K.
    et al.
    Orebro Univ, Dept Gastroenterol, Fac Med & Hlth, Orebro, Sweden..
    Cao, Y.
    Univ Orebro, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden..
    Zhulina, Y.
    Orebro Univ, Dept Gastroenterol, Fac Med & Hlth, Orebro, Sweden..
    Lampinen, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Halfvarson, J.
    Orebro Univ, Dept Gastroenterol, Fac Med & Hlth, Orebro, Sweden..
    Carlson, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Prognostic significance of eosinophil granule proteins in inflammatory bowel disease2018Ingår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, s. S181-S182Artikel i tidskrift (Övrigt vetenskapligt)
  • 8.
    Amcoff, Karin
    et al.
    Univ Orebro, Fac Med & Hlth, Dept Gastroenterol, SE-70182 Orebro, Sweden..
    Stridsberg, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk endokrinologi.
    Lampinen, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Magnuson, Anders
    Univ Orebro, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden..
    Carlson, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Halfvarson, Jonas
    Univ Orebro, Fac Med & Hlth, Dept Gastroenterol, SE-70182 Orebro, Sweden..
    Clinical implications of assay specific differences in f-calprotectin when monitoring inflammatory bowel disease activity over time2017Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, nr 3, s. 344-350Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: With several faecal calprotectin (FC) assays on the market, it has been difficult to define a uniform threshold for discriminating between remission and active disease in patients with inflammatory bowel disease (IBD). We aimed to compare the results of different FC-assays in IBD patients, followed over time.Material and methods: IBD patients provided faecal samples and reported clinical activity every third month prospectively over a two year period. FC was measured with two ELISA - (Buhlmann and Immunodiagnostik) and one automated fluoroimmunoassay (Phadia).Results: In total, 13 patients provided 91 faecal samples. The median (IQR) concentration of FC was higher at active disease than at remission for all assays: Buhlmann 845 (1061-226) g/g versus 62 (224-39) g/g, Phadia 369 (975-122) g/g versus 11 (52-11) g/g, and Immundiagnostik 135 (302-69) g/g versus 8 (56-4) g/g. The Buhlmann assay produced the largest absolute difference but the corresponding relative difference seemed to be more pronounced when analysed by the Phadia - (ratio of means 8.5; 95% CI 3.3-21.9) or the Immundiagnostik assay (ratio of means 7.4; 95% CI 3.1-17.6) than by the Buhlmann assay (ratio of means 5.3; 95% CI 2.7-10.6). Consequently, the specificity for discriminating active disease from remission varied between assays (34-75%) when the cut-off 50g/g was used, whereas the differences in sensitivity were less pronounced.Conclusions: Cross-comparisons revealed overall poor agreement between the assays as well as differences in the dynamics of FC. These findings suggest that standardisation of the method is needed to implement FC as a disease monitoring tool at large-scale.

  • 9.
    Andersson, Hanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Frykholm, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Introducing the 6-4-0 fasting regimen and the incidence of prolonged preoperative fasting in children2018Ingår i: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 28, nr 1, s. 46-52Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Children often starve for longer than recommended by current preoperative fasting guidelines.

    Aims

    We studied the effects of implementing a more lenient fasting regimen on the duration of clear fluid fasting, as well as the incidence of extended fasting in children.

    Methods

    Preoperative duration of clear fluid fasting was recorded for patients scheduled for procedures in a unit applying the standard 6-4-2 fasting regimen. This group was compared with a cohort in the same unit 1year after transitioning to a 6-4-0 fasting regimen. The latter includes no limitations on clear fluid intake until the child is called to theater. A third cohort from a unit in which the 6-4-0 fasting regimen has been implemented for over a decade was also studied for comparison.

    Results

    Patients fasting according to the 6-4-2 fasting regimen (n=66) had a median fasting time for clear fluids of 4.0h and a 33.3% incidence of fasting more than 6h. After transitioning to the 6-4-0 fasting regimen (n=64), median duration of fasting for clear fluids decreased to 1.0h, and the incidence of fasting more than 6h decreased to 6.3%. In the second unit (n=73), median fasting time was 2.2h and the proportion of patients fasting more than 6h was 21.9%.

    Conclusion

    The introduction and implementation of the 6-4-0 fasting regimen reduces median fluid fasting duration and the number of children subjected to extended fasting.

  • 10.
    Angelison, L.
    et al.
    Helsingborg Hosp, Dept Med, Charlotte Yhlens Gata 10, S-25187 Helsingborg, Sweden..
    Almer, S.
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Eriksson, A.
    Sahlgrenska Univ Hospital Ostra, Dept Gastroenterol, Gothenburg, Sweden..
    Karling, P.
    Umea Univ, Dept Publ Hlth & Clin Med, Div Med, Umea, Sweden..
    Fagerberg, U.
    Vastmanlands Hosp, Clin Res Ctr, Vasteras, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Halfvarson, J.
    Univ Orebro, Dept Gastroenterol, Fac Med & Hlth, Orebro, Sweden..
    Thörn, Mari
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Björk, J.
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Hindorf, U.
    Lund Univ, Div Gastroenterol, Dept Clin Sci, Lund, Sweden..
    Löfberg, R.
    Karolinska Inst, Dept Med, IBD Unit, Stockholm Gastro Ctr, Stockholm, Sweden. Sodra Alvsborgs Sjukhus, Dept Med, Boras, Sweden..
    Bajor, A.
    Hjortswang, H.
    Linkoping Univ, Dept Gastroenterol, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Hammarlund, P.
    Angelholm Hosp, Dept Med, Angelholm, Sweden..
    Grip, O.
    Skane Univ Hosp, Dept Gastroenterol, Malmo, Sweden..
    Torp, J.
    Kristianstad Cent Hosp, Dept Med, Kristianstad, Sweden..
    Marsal, J.
    Hertervig, E.
    Skane Univ Hosp, Dept Gastroenterol, Lund, Sweden..
    Long-term outcome of infliximab treatment in chronic active ulcerative colitis: a Swedish multicentre study of 250 patients2017Ingår i: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 45, nr 4, s. 519-532Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Real-life long-term data on infliximab treatment in ulcerative colitis are limited. Aim To study the long-term efficacy and safety of infliximab in chronic active ulcerative colitis and possible predictors of colectomy and response were also examined. Methods A retrospective multi-centre study of infliximab treatment in 250 patients with chronic active ulcerative colitis with inclusion criteria: age 18 years, ambulatory treated, steroid-dependent or intolerant and/or immunomodulator refractory or intolerant. Results Steroid-free clinical remission was achieved by 123/250 patients (49.2%) at 12 months and in 126/250 patients at a median follow-up of 2.9 years (50.4%). Primary response at 3 months was achieved by 190/250 (76.0%) patients and associated with a high probability of response 168/190 (88.4%) at 12 months and 143/190 (75.3%) at follow-up. Long-term rate of colectomy in primary responders was 6/190 (3.2%) at 12 months and 27/190 (14.2%) at last follow-up. Failure to achieve response at 3 months was associated with a high risk of subsequent colectomy, 29/60 (48.3%) at 12 months and 41/60 (68.3%) at follow-up. Response at 12 months was associated with a low risk of subsequent colectomy, 14/181 (7.7%) compared with non-response 19/34 (55.9%) (P < 0.0001). Non-response at 3 months was an independent predictor of subsequent colectomy (HR = 9.40, 95% CI = 5.10-17.35, P < 0.001). Concomitant azathioprine therapy did not influence outcome in terms of colectomy. Conclusions Long-term efficacy of infliximab treatment in chronic active ulcerative colitis is excellent especially in patients who respond to induction treatment. Conversely, non-response at 3 months predicts a poor outcome, with a high risk of subsequent colectomy.

  • 11. Bergquist, Henrik
    et al.
    Agreus, Lars
    Tillander, Lotta
    Johnsson, Folke
    Sorngard, Helene
    Sjostedt, Svante
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Structured Diagnostic and Treatment Approach Versus the Usual Primary Care Approach in Patients With Gastroesophageal Reflux Disease: A Cluster-randomized Multicenter Study2013Ingår i: Journal of Clinical Gastroenterology, ISSN 0192-0790, E-ISSN 1539-2031, Vol. 47, nr 7, s. E65-E73Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Goals: To compare the clinical outcomes of gastroesophageal reflux disease (GERD) patients treated with an implemented new structured pathway (NSP) or according to existing local clinical practices [old clinical pathway (OCP)]. Background: GERD is a major challenge at the primary care level. Study: Primary care centers (n=24) were cluster randomized to handle patients suffering from symptoms suggestive of GERD according to the NSP (n=97) or the OCP (n=134). In the NSP, the GerdQ questionnaire score was used both for diagnosis and management including treatment. We used validated questionnaires to evaluate disease symptoms, quality of life, and costs at inclusion and at follow-up 2 to 6 months later. Results: On the basis of the Reflux Disease Questionnaire, 56% of the patients treated with the NSP reported total symptom relief at the follow-up compared with 33% in the OCP group (P=0.0013). The reflux symptoms after treatment affected daily activities to a lesser extent in the patients in the NSP group compared with the OCP group (10% vs. 13%, respectively, P=0.01). The utility score of the EuroQoL-5D questionnaire improved more in the NSP group than in the OCP group (0.05 vs. 0.02, respectively, P<0.001). The patients in the NSP group had an approximately 50% lower average total cost for GERD-related health care resources compared with the OCP group [301 Swedish Kronor (SEK) vs. 588 SEK, respectively, NS]. Conclusions: The management of GERD patients in primary care centers using a structured clinical pathway and the results of the GerdQ improves the clinical outcome compared with prevailing local routines (NCT00842387).

  • 12.
    Biglarnia, Alireza
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Yamamoto, Shinji
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Sedigh, Amir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Drachenberg, Cinthia
    Univ Maryland Hosp, Dept Pathol, Baltimore, MD 21201 USA..
    Wagner, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sund, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Berglund, David
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    von Zur-Muehlen, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Larsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Impact of duodenal cuff inflammation on outcome after clinical pancreas transplantation - a survey of a comprehensive follow-up strategy including serial protocol biopsy of the duodenal cuff2015Ingår i: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 22, s. S15-S15Artikel i tidskrift (Övrigt vetenskapligt)
  • 13.
    Biglarnia, AliReza
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Yamamoto, Shinji
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Sedigh, Amir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Drachenberg, Cinthia
    Univ Maryland Hosp, Dept Pathol, Baltimore, MD 21201 USA..
    Wagner, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sund, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Berglund, David
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    von Zur-Mühlen, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Larsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Impact Of Duodenal Cuff Inflammation On Outcome After Clinical Pancreas Transplantation - A Survey Of A Comprehensive Follow-Up Strategy Including Serial Protocol Biopsy Of The Duodenal Cuff.2015Ingår i: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 99, nr 11, s. S24-S24Artikel i tidskrift (Övrigt vetenskapligt)
  • 14.
    Blom, Kristin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Rubin, Jenny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Halfvarson, Jonas
    Torkvist, Leif
    Rönnblom, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sangfelt, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Lordal, Mikael
    Jönsson, Ulla-Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sjöqvist, Urban
    Håkansson, Lena Douhan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Carlson, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Eosinophil associated genes in the inflammatory bowel disease 4 region: Correlation to inflammatory bowel disease revealed2012Ingår i: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 18, nr 44, s. 6409-6419Artikel i tidskrift (Refereegranskat)
    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.

  • 15. Borssen, A. Danielsson
    et al.
    Lindgren, S.
    Bergquist, A.
    Almer, S.
    Sangfelt, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Werner, M.
    Risk For Hepatocellular Carcinoma In Autoimmune Hepatitis - Is There An Indication For Surveillance?2013Ingår i: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 58, nr Suppl. 1, s. S382-S383Artikel i tidskrift (Övrigt vetenskapligt)
  • 16. Borssen, Asa Danielsson
    et al.
    Almer, Sven
    Prytz, Hanne
    Wallerstedt, Sven
    Friis-Liby, Inga-Lill
    Bergquist, Annika
    Nyhlin, Nils
    Hultcrantz, Rolf
    Sangfelt, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Weiland, Ola
    Lindgren, Stefan
    Verbaan, Hans
    Werner, Marten
    Hepatocellular and extrahepatic cancer in patients with autoimmune hepatitis - a long-term follow-up study in 634 Swedish patients2015Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 50, nr 2, s. 217-223Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives. Cirrhosis is a well-known risk factor for hepatocellular cancer, but the true risk in autoimmune hepatitis (AIH) is scarcely studied. Other cancers may arise after prolonged use of immune-modulating drugs. The aim of this study was to investigate the cancer risk in a large cohort of AIH patients. Material and methods. Six hundred and thirty-four Swedish patients in a well-defined cohort were matched to the Cause of Death Registry and the Cancer Registry. Standard incidence ratios were calculated by relating the incidences in the cohort to an age-matched material from the Swedish background population. Results. A higher overall incidence of malignancies than the background population was found, counting from the date of diagnosis (standard incidence ratio (SIR) 2.08, 95% CI 1.68-2.55). The highest risk was found for hepatocellular carcinoma (HCC). We found 10 cases (4.0%) in 248 patients with cirrhosis, which gives an incidence rate of 0.3%. Standard incidence ratio for developing hepatobiliary cancer was 54.55 (95% CI 19.92-99.99). HCC only occurred in cirrhotic patients. There was also an increased risk for non-melanoma skin cancer (SIR 9.87, 95% CI 6.26-14.81). Conclusion. A slightly enhanced risk for malignancies in general compared to the background population was found. The risk of hepatobiliary cancer was increased, but the annual risk over the observational period was well under the postulated 1.5% when surveillance in cirrhotic patients is considered to be cost-effective.

  • 17.
    Borssen, Åsa D.
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Palmqvist, Richard
    Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden..
    Kechagias, Stergios
    Linkoping Univ, Dept Med & Hlth Sci, Dept Gastroenterol & Hepatol, Linkoping, Sweden..
    Marschall, Hanns-Ulrich
    Univ Gothenburg, Dept Mol & Clin Med, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden..
    Bergquist, Annika
    Karolinska Univ, Huddinge Hosp, Dept Med, Sect Hepatol & Gastroenterol,Karolinska Inst, Stockholm, Sweden..
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Weiland, Ola
    Karolinska Univ, Huddinge Hosp, Div Infect Dis, Dept Med,Karolinska Inst, Stockholm, Sweden..
    Verbaan, Hans
    Lund Univ, Gastroenterol Div, Dept Clin Sci, Univ Hosp Skane, Lund, Sweden..
    Nyhlin, Nils
    Orebro Univ, Dept Gastroenterol, Fac Med & Hlth, Orebro, Sweden..
    Nilsson, Emma
    Lund Univ, Gastroenterol Div, Dept Clin Sci, Univ Hosp Skane, Lund, Sweden..
    Werner, Mårten
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Histological improvement of liver fibrosis in well-treated patients with autoimmune hepatitis A cohort study2017Ingår i: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 96, nr 34, artikel-id e7708Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease that if left untreated may lead to the development of cirrhosis. Previous studies on AIH patients have suggested that fibrosis and even cirrhosis can be reversed by medical treatment. The aim of this study was to evaluate the efficacy of medical treatment for protection of developing fibrosis and cirrhosis. A total of 258 liver biopsies from 101 patients (72 women, 29 men) were analyzed by a single pathologist and classified according to the Ishak grading (inflammation) and staging (fibrosis) system. Liver histology was stratified according to the temporal changes of fibrosis stage (increased, decreased, or stable), and groups were compared. Complete or partial response to medical treatment was 94.9%. Reduction of fibrosis stage from the first to the last biopsy was seen in 63 patients (62.4%). We found an association between a reduction in the fibrosis stage and continuous glucocorticoid medication, as well as lowered scores of inflammation at last biopsy. Twenty-one patients had cirrhosis (Ishak stage 6) at least in one of the previous biopsies, but only 5 patients at the last biopsy. Histological improvement is common in AIH patients that respond to medical treatment, and a reduction or stabilization of fibrosis stage occurs in about 2/3 of such patients.

  • 18.
    Borssen, Åsa Danielsson
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden..
    Marschall, Hanns-Ulrich
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden..
    Bergquist, Annika
    Karolinska Univ Hosp Huddinge, Karolinska Inst, Sect Hepatol & Gastroenterol, Dept Med, Stockholm, Sweden..
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Weiland, Ola
    Karolinska Univ Hosp Huddinge, Karolinska Inst, Div Infect Dis, Dept Med, Stockholm, Sweden..
    Kechagias, Stergios
    Univ Hosp, Dept Gastroenterol & Hepatol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Nyhlin, Nils
    Orebro Univ, Fac Med & Hlth, Dept Gastroenterol, Orebro, Sweden..
    Verbaan, Hans
    Lund Univ, Univ Hosp Skane, Div Gastroenterol, Dept Clin Sci, Malmo, Sweden..
    Nilsson, Emma
    Lund Univ, Univ Hosp Skane, Div Gastroenterol, Dept Clin Sci, Lund, Sweden..
    Werner, Mårten
    Umea Univ, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden..
    Epidemiology and causes of death in a Swedish cohort of patients with autoimmune hepatitis2017Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, nr 9, s. 1022-1028Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Epidemiological studies of autoimmune hepatitis (AIH) show varying figures on prevalence and incidence, and data on the long-term prognosis are scarce.Objective To investigate the epidemiology, long-term prognosis and causes of death in a Swedish AIH cohort.Material and methods: Data collected from 634 AIH patients were matched to the Cause of Death Registry, and survival analyses were made. Prevalence and incidence were calculated for university hospitals with full coverage of cases and compared to the County of Vasterbotten in Northern Sweden.Results: AIH point prevalence was 17.3/100,000 inhabitants in 2009, and the yearly incidence 1990-2009 was 1.2/100,000 inhabitants and year. The time between diagnosis and end of follow-up, liver transplantation or death was in median 11.3 years (range 0-51.5 years). Men were diagnosed earlier (p<.001) and died younger than women (p=.002). No gender differences were found concerning transplant-free, overall survival and liver-related death. Cirrhosis at diagnosis was linked to an inferior survival (p<.001). Liver-related death was the most common cause of death (32.7%). The relative survival started to diverge from the general population 4 years after diagnosis but a distinct decline was not observed until after more than 10 years.Conclusions: Long-term survival was reduced in patients with AIH. No gender difference regarding prognosis was seen but men died younger, probably as a result of earlier onset of disease. Cirrhosis at diagnosis was a risk factor for poor prognosis and the overall risk of liver-related death was increased.

  • 19. Bryant, Eleanor J.
    et al.
    King, Neil A.
    Falken, Ylva
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hoist, Jens Juul
    Blundell, John E.
    Naslund, Erik
    Relationships among tonic and episodic aspects of motivation to eat, gut peptides, and weight before and after bariatric surgery2013Ingår i: Surgery for Obesity and Related Diseases, ISSN 1550-7289, E-ISSN 1878-7533, Vol. 9, nr 5, s. 802-808Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The interaction between motivation to eat, eating behavior traits, and gut peptides after Roux-en-Y gastric bypass (RYGB) surgery is not fully understood. Methods: Appetite and hormone responses to a fixed liquid preload were assessed in 12 obese (body mass index 45 +/- 1.9 kg/m(2)) participants immediately before and 3 days, 2 months, and 1 year after RYGB surgery. Subjective appetite and plasma levels of ghrelin, leptin, insulin, and glucagon-like peptide-1 (GLP-1) were measured for a 3-hour postprandial period. Eating behavior traits were also measured using the Three Factor Eating Questionnaire 18 (TFEQR18). Results: There was a decrease in TFEQR18 emotional eating (EE) and uncontrolled eating (UE) from presurgery to 1 year postsurgery but no significant change in cognitive restraint (CR). These changes occurred independently of change in weight. In addition, there was a reduction in subjective appetite ratings and alterations in appetite peptides favoring an anorectic response. Presurgery EE was significantly related to fasting and area under the curve (AUC) ghrelin; UE was associated with AUC desire to eat, and there was a significant association between fasting desire to eat and ghrelin (fasting and AUC). One year postsurgery, UE was positively related to fasting insulin, and CR was negatively associated with GLP-1. UE and subjective hunger were positively correlated, while the relationship between desire to eat and ghrelin remained. onclusion: The relationships among subjective appetite ratings, eating behavior traits, and appetite peptides in obese patients both before and at 1 year after RYGB surgery may contribute to the reduction in a propensity to overeat (as measured by TFEQR18 factors) and weight loss. 

  • 20. Caudwell, P.
    et al.
    Gibbons, C.
    Hopkins, M.
    Näslund, E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Finlayson, G.
    Blundell, J.
    Separating Satiety And Satiation In Appetite Control: Effect Of Exercise In Overweight And Obese Adults2013Ingår i: Annals of Nutrition and Metabolism, ISSN 0250-6807, E-ISSN 1421-9697, Vol. 63, nr Suppl. 1, s. 1053-1053Artikel i tidskrift (Övrigt vetenskapligt)
  • 21. Cesarini, M.
    et al.
    Collins, G.
    Rönnblom, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Santos, A.
    Sjöberg, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Parkes, M.
    Keshav, S.
    Travis, S.
    Predicting the risk of acute severe colitis (ASC) at diagnosis of Ulcerative Colitis (UC): external validation2015Ingår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 9, nr S1, s. S117-S118Artikel i tidskrift (Övrigt vetenskapligt)
  • 22.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    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 Diagnosis2017Ingår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 11, nr 3, s. 335-341Artikel i tidskrift (Refereegranskat)
    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.

  • 23. Costabel, Ulrich
    et al.
    Bendstrup, Elisabeth
    Cottin, Vincent
    Dewint, Pieter
    Egan, Jim J. J.
    Ferguson, James
    Groves, Richard
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Kreuter, Michael
    Maher, Toby M.
    Molina-Molina, Maria
    Nordlind, Klas
    Sarafidis, Alexandre
    Vancheri, Carlo
    Pirfenidone in Idiopathic Pulmonary Fibrosis: Expert Panel Discussion on the Management of Drug-Related Adverse Events2014Ingår i: Advances in Therapy, ISSN 0741-238X, E-ISSN 1865-8652, Vol. 31, nr 4, s. 375-391Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Pirfenidone is currently the only approved therapy for idiopathic pulmonary fibrosis, following studies demonstrating that treatment reduces the decline in lung function and improves progression-free survival. Although generally well tolerated, a minority of patients discontinue therapy due to gastrointestinal and skin-related adverse events (AEs). This review summarizes recommendations based on existing guidelines, research evidence, and consensus opinions of expert authors, with the aim of providing practicing physicians with the specific clinical information needed to educate the patient and better manage pirfenidone-related AEs with continued pirfenidone treatment. The main recommendations to help prevent and/or mitigate gastrointestinal and skin-related AEs include taking pirfenidone during (or after) a meal, avoiding sun exposure, wearing protective clothing, and applying a broad-spectrum sunscreen with high ultraviolet (UV) A and UVB protection. These measures can help optimize AE management, which is key to maintaining patients on an optimal treatment dose.

  • 24.
    Dahlgren, David
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Roos, Carl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Lundqvist, Anders
    AstraZeneca R&D, Gothenburg, Sweden..
    Abrahamsson, Bertil
    AstraZeneca R&D, Gothenburg, Sweden..
    Tannergren, Christer
    AstraZeneca R&D, Gothenburg, Sweden..
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sjögren, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Lennernäs, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Regional Intestinal Permeability of Three Model Drugs in Human2016Ingår i: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 13, nr 9, s. 3013-3021Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Currently there are only a limited number of determinations of human P-eff in the distal small intestine and none in the large intestine. This has hindered the validation of preclinical models with regard to absorption in the distal parts of the intestinal tract, which can be substantial for BCS class II-IV drugs, and drugs formulated into modified-release (MR) dosage forms. To meet this demand, three model drugs (atenolol, metoprolol, and ketoprofen) were dosed in solution intravenously, and into the jejunum, ileum, and colon of 14 healthy volunteers. The P-eff of each model drug was then calculated using a validated deconvolution method. The median P-eff of atenolol in the jejunum, ileum, and colon was 0.45, 0.15, and 0.013 X 10(-4) cm/s, respectively. The corresponding values for metoprolol were 1.72, 0.72, and 1.30 X 10(-4) cm/s, and for ketoprofen 8.85, 6.53, and 3.37 X 10(-4) cm/s, respectively. This is the first study where the human Peff of model drugs has been determined in all parts of the human intestinal tract in the same subjects. The jejunal values were similar to directly determined values using intestinal single-pass perfusion, indicating that the deconvolution method is a valid approach for determining regional P-eff. The values from this study will be highly useful in the validation of preclinical regional absorption models and in silico tools.

  • 25.
    Diaz Tartera, Hetzel O.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Al-Saffar, Anas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi. Uppsala University.
    Halim, Mohammed Abdul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Lindberg, G
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Gastroenterol & Hepatol Unit, Huddinge, Sweden.
    Sangfelt, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Validation of SmartPill® wireless motility capsule for gastrointestinaltransit time: Intra-subject variability, software accuracy and comparison with video capsule endoscopy2017Ingår i: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 29, nr 10, artikel-id e13107Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: There is interest in ultimately combining endoscopy and motility assessments. Gastric emptying (GET), small bowel (SBTT), colon (CTT) and whole gut transit (WGTT) times are conveniently obtained by SmartPill® wireless motility capsule (WMC) that records luminal pH, temperature and pressure. Reproducibility within same subjects and accuracy of software derived times (MotiliGI® ) were investigated for diagnostic application. GET and SBTT were separately measured using video capsule endoscopy (VCE). The aim of this investigation was to assess same subject reproducibility of WMC, accuracy of software derived transit times and relate to Pillcam® SB (small bowel) VCE motility data.

    METHODS: Seventy three healthy adults ingested a 260 kcal mixed meal followed by WMC tests. Food intake was permitted after 6 hours. Regional transit data was obtained for GET, SBTT and CTT, the sum yielding WGTT. Nineteen subjects repeated WMC tests 2 or 4 weeks later; a separate 70 underwent VCE while fasted.

    KEY RESULTS: Visually derived data from WMC yielded GET 3.46±0.27, SBTT 5.15±0.21, CTT 20.76±1.19 and WGTT 29.53±1.28 hours (mean±SEM). Pearson's correlation coefficients (r) against software derived results were: GET 0.78 (P<.0001), SBTT 0.28 (P<.05), CTT 0.96 (P<.0001), WGTT 0.99 (P<.0001). VCE yielded lower GET (0.71±0.08 hours) and SBTT (4.15±0.13 hours).

    CONCLUSIONS AND INFERENCES: GET, SBTT, CTT and WGTT obtained by WMC are commensurate with literature values, including by other methods. Visually and software derived transit times have strongest correlations for CTT and WGTT. WMC yields longer GET and SBTT than VCE, perhaps due to meal related effects on motility.

  • 26.
    Eberhardson, Michael
    et al.
    Karolinska Inst, Dept Med, Ctr Bioelect Med, Bioclinicum, Solna, Sweden;Karolinska Univ Hosp, Solna, Sweden.
    Hedin, Charlotte R. H.
    Karolinska Univ Hosp, Solna, Sweden;Karolinska Inst, Dept Med Solna, Solna, Sweden.
    Carlson, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Tarnawski, Laura
    Karolinska Inst, Dept Med, Ctr Bioelect Med, Bioclinicum, Solna, Sweden;Karolinska Univ Hosp, Solna, Sweden.
    Levine, Yaakov A.
    SetPoint Med, Valencia, CA USA.
    Olofsson, Peder S.
    Karolinska Inst, Dept Med, Ctr Bioelect Med, Bioclinicum, Solna, Sweden;Karolinska Univ Hosp, Solna, Sweden.
    Towards improved control of inflammatory bowel disease2019Ingår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 89, nr 3, artikel-id e12745Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Inflammatory bowel disease (IBD) is characterized by activation of both the innate and adaptive immune system in genetically susceptible individuals, resulting in chronic intestinal inflammation. The triggers that initiate and perpetuate this continuous inflammation are the subject of much speculation and research, although the central role of the intestinal microbiota is recognized, and is even a target for treatment in some circumstances. The mainstay of modern IBD treatment is suppression of the immune response towards as yet unspecified antigens, and conventional therapy includes corticosteroids, 5-aminosalicylic acid (5-ASA), thiopurines and methotrexate. Reducing activity of specific mediators has proven efficacious, including adhesion molecules, such as the gut-homing integrin alpha(4)beta(7) expressed on the surface of circulating immune cells, and cytokines, such as tumour necrosis factor alpha (TNF-alpha). This has been achieved using biologic agents including monoclonal antibodies. Recent discoveries in immunology and neuroscience have revealed that signals in the peripheral nervous system regulate inflammation, including levels of TNF-alpha. The understanding of the mechanisms of the neuro-immune communication involved in inflammation control in the gut is evolving, but is as yet incomplete. Clinical studies using implanted vagus nerve stimulators for treatment of IBD show encouraging results. Accordingly, the neural reflex control of inflammation is emerging as a potential therapeutic target in treatment of IBD. Here, we review current therapeutic options and neural reflex control of gut immunity in the context of intestinal inflammation.

  • 27.
    Efe, Cumali
    et al.
    Gazi Yasargil Educ & Res Hosp, Dept Gastroenterol, Diyarbakir, Turkey.
    Tascilar, Koray
    Istanbul Okmeydani Educ & Res Hosp, Dept Rheumatol, Istanbul, Turkey.
    Henriksson, Ida
    Orebro Univ, Fac Med & Hlth, Dept Gastroenterol, Orebro, Sweden.
    Lytvyak, Ellina
    Univ Alberta, Div Gastroenterol, Edmonton, AB, Canada;Univ Alberta, Liver Unit, Edmonton, AB, Canada.
    Alalkim, Fatema
    Univ British Columbia, Div Gastroenterol, Vancouver, BC, Canada;Vancouver Gen Hosp, Vancouver, BC, Canada.
    Trivedi, Hirsh
    Harvard Med Sch, Beth Israel Med Ctr, Div GI & Hepatol, Boston, MA 02115 USA.
    Eren, Fatih
    Uludag Univ, Med Fac, Dept Gastroenterol, Bursa, Turkey.
    Eliasson, Johanna
    Univ Copenhagen, Rigshosp, Dept Hepatol, Copenhagen, Denmark.
    Beretta-Piccoli, Benedetta Terziroli
    Epatoctr Ticino, Dept Internal Med, Lugano, Switzerland.
    Fischer, Janett
    Univ Clin Leipzig, Sect Hepatol, Clin Gastroenterol, Leipzig, Germany.
    Caliskan, Ali Riza
    Inonu Univ, Sch Med, Dept Gastroenterol, Malatya, Turkey.
    Chayanupatkul, Maneerat
    Mt Sinai Med Ctr, Div Liver Dis, New York, NY 10029 USA;Chulalongkorn Univ, Fac Med, Bangkok, Thailand.
    Coppo, Claudia
    Univ Bologna, Ctr Study & Treatment Autoimmune Dis Liver & Bili, Bologna, Italy.
    Ytting, Henriette
    Univ Copenhagen, Rigshosp, Dept Hepatol, Copenhagen, Denmark.
    Purnak, Tugrul
    Hacettepe Univ, Dept Gastroenterol, Ankara, Turkey.
    Muratori, Luigi
    Univ Bologna, Ctr Study & Treatment Autoimmune Dis Liver & Bili, Bologna, Italy.
    Werner, Mårten
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Muratori, Paolo
    Univ Bologna, Ctr Study & Treatment Autoimmune Dis Liver & Bili, Bologna, Italy.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Önnerhag, Kristina
    Skane Univ Hosp, Dept Gastroenterol & Hepatol, Malmo, Sweden.
    Günsar, Fulya
    Ege Univ, Dept Gastroenterol, Izmir, Turkey.
    Nilsson, Emma
    Lund Univ, Univ Hosp Skane, Dept Clin Sci, Gastroenterol Div, Lund, Sweden.
    Heurgue-Berlot, Alexandra
    CHU Reims, Dept Hepatogastroenterol, Reims, France.
    Güzelbulut, Fatih
    Haydarpasa Numune Educ & Res Hosp, Dept Gastroenterol, Istanbul, Turkey.
    Demir, Nurhan
    Gazi Yasargil Educ & Res Hosp, Dept Gastroenterol, Diyarbakir, Turkey.
    Gönen, Can
    Haydarpasa Numune Educ & Res Hosp, Dept Gastroenterol, Istanbul, Turkey.
    Semela, David
    Kantonsspital St Gallen, Div Gastroenterol & Hepatol, St Gallen, Switzerland.
    Aladag, Murat
    Inonu Univ, Sch Med, Dept Gastroenterol, Malatya, Turkey.
    Kiyici, Murat
    Uludag Univ, Med Fac, Dept Gastroenterol, Bursa, Turkey.
    Schiano, Thomas
    Mt Sinai Med Ctr, Div Liver Dis, New York, NY 10029 USA.
    Montano-Loza, Aldo
    Univ Alberta, Div Gastroenterol, Edmonton, AB, Canada;Univ Alberta, Liver Unit, Edmonton, AB, Canada.
    Berg, Thomas
    Univ Clin Leipzig, Sect Hepatol, Clin Gastroenterol, Leipzig, Germany.
    Ozaslan, Ersan
    Numune Res & Educ Hosp, Dept Gastroenterol, Ankara, Turkey.
    Yoshida, Eric
    Univ British Columbia, Div Gastroenterol, Vancouver, BC, Canada;Vancouver Gen Hosp, Vancouver, BC, Canada.
    Bonder, Alan
    Harvard Med Sch, Beth Israel Med Ctr, Div GI & Hepatol, Boston, MA 02115 USA.
    Marschall, Hanns-Ulrich
    Univ Gothenburg, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden.
    Wahlin, Staffan
    Karolinska Inst, Ctr Digest Dis, Hepatol Div, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Validation of Risk Scoring Systems in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis2019Ingår i: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 114, nr 7, s. 1101-1108Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Risk stratification based on biochemical variables is a useful tool for monitoring ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC). Several UDCA response criteria and scoring systems have been proposed for risk prediction in PBC, but these have not been validated in large external cohorts.

    METHODS: We performed a study on data of 1746 UDCA-treated patients with PBC from 25 centers in Europe, United States, and Canada. The prognostic performance of the risk scoring systems (GLOBE and UK-PBC) and the UDCA response criteria (Barcelona, Paris I, Paris II, Rotterdam, and Toronto) were evaluated. We regarded cirrhosis-related complications (ascites, variceal bleeding, and/or hepatic encephalopathy) as clinical end points.

    RESULTS: A total of 171 patients reached a clinical end point during a median 7 years (range 1-16 years) of follow-up. The 5-, 10- and 15-year adverse outcome-free survivals were 95%, 85%, and 77%. The GLOBE and UK-PBC scores predicted cirrhosis-related complications better than the UDCA response criteria. The hazard ratio (HR) for a 1 standard deviation increase was HR 5.05 (95% confidence interval (CI): 4.43-5.74, P < 0.001) for the GLOBE score and HR 3.39 (95% CI: 3.10-3.72, P < 0.001) for the UK-PBC score. Overall, the GLOBE and UK-PBC risk scores showed similar and excellent prognostic performance (C-statistic, 0.93; 95% CI: 0.91%-95% vs 0.94; 95% CI: 0.91%-0.96%).

    DISCUSSION: In our international, multicenter PBC cohort, the GLOBE and UK-PBC risk scoring systems were good predictors of future cirrhosis-related complications.

  • 28. Ejskjaer, N.
    et al.
    Wo, J.
    Esfandyari, T.
    Jamal, M.
    Dimcevski, G.
    Tarnow, L.
    Malik, R.
    Hellstrom, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Mondou, E.
    Quinn, J.
    Rousseau, F.
    Richard, M.
    Gastric emptying, glycaemia, and upper GI symptoms are independent factors in diabetic gastroparesis2013Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, s. S493-S493Artikel i tidskrift (Övrigt vetenskapligt)
  • 29. Ejskjaer, N.
    et al.
    Wo, J. M.
    Esfandyari, T.
    Mazen Jamal, M.
    Dimcevski, G.
    Tarnow, L.
    Malik, R. A.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Mondou, E.
    Quinn, J.
    Rousseau, F.
    Mccallum, R. W.
    A phase 2a, randomized, double-blind 28-day study of TZP-102 a ghrelin receptor agonist for diabetic gastroparesis2013Ingår i: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 25, nr 2, s. e140-e150Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Gastroparesis causes significant morbidity and treatment options are limited. TZP-102 a novel, macrocyclic, selective, oral ghrelin receptor agonist, was evaluated in a randomized, double-blind, placebo-controlled trial in patients with diabetic gastroparesis. Methods A total of 92 outpatients were randomized to once-daily administrations of 10-mg (n=22), 20-mg (n=21), 40-mg (n=23) TZP-102 or placebo (n=26). The primary endpoint was the change from baseline in gastric half-emptying time (T1/2) utilizing 13C-breath test methodology and secondary endpoints included symptom improvement using patient-reported gastroparesis symptom scores (PAGI-SYM questionnaire) and patient and physician overall treatment evaluations (OTE). Key Results Gastric T1/2 changes were not statistically significant between TZP-102 and placebo after 28days of treatment at any dose. Clinical improvements (-1.0 to -1.4 point mean decrease in symptom severity) occurred in the Gastroparesis Cardinal Symptom Index (GCSI) component of the PAGI-SYM, which was significant vs placebo for all TZP-102 doses combined. Improvements became evident after 1week of treatment. Significantly, more patients given TZP-102 (any dose) had a 50% reduction in baseline GCSI score (28.8%vs 7.7% placebo). Safety profiles were similar across groups. All TZP-102 doses were well-tolerated with no adverse cardiac, weight, or glucose control outcomes. Conclusions &amp; Inferences TZP-102 for 28days, at doses of 10-40mg once daily, was well-tolerated and resulted in a reduction in symptoms of gastroparesis. The lack of correlation between symptom improvement and gastric emptying change is consistent with previous studies in diabetic gastroparesis, and emphasizes the value of patient-defined outcomes in determining therapeutic benefit.

  • 30.
    Engström, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Lönnkvist, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Befrits, Ragnar
    Karolinska Univ Hosp Solna, Karolinska Inst, Dept Med Gastroenterol & Hepatol, Stockholm, Sweden.
    Ljung, Tryggve
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Diaz, Hetzel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Holst, Mikael
    Karolinska Univ Hosp Solna, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Comparison of fecal calprotectin and serum C-reactive protein in early prediction of outcome to infliximab induction therapy2019Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 54, nr 9, s. 1081-1088Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Fecal calprotectin (FC) and serum C-reactive protein (CRP) are biomarkers of disease activity in Crohn's disease (CD) and ulcerative colitis (UC). We assessed FC, CRP, Harvey-Bradshaw index (HBi), partial Mayo Clinic Scoring (pMCS) and a cytokine panel during infliximab induction to predict therapy outcome.

    Methods: FC, CRP and clinical indices were evaluated in 123 (76 CD, 47 UC) patients before infliximab induction and after 12 weeks. Responders were monitored 48 weeks for an 'incident' (dosage increase, shortened dosage interval, surgery). Cutoff values for FC and CRP were obtained using receiver-operating characteristics (ROC). Disease progression was analyzed with Kaplan-Meier survivals, log-rank test and logistic regression for combined biomarkers. Cytokines were analyzed with Luminex multiplexing system.

    Results: Following infliximab, FC and CRP declined (p < .0001) along with HBi for CD and pMCS for UC. Simultaneously, IL-6 and TNF-alpha decreased, while IL-10 increased. Optimal FC ROC cutoff was 221 mu g/g (sensitivity 66%, specificity 67%, AUC 0.71) and CRP ROC cutoff 2.1 mg/L (sensitivity 54%, specificity 60%, AUC 0.58). In CD, FC > 221 mu g/g (p < .0001), but not CRP > 2.1 mg/L predicted an 'incident'. However, combined FC and CRP also predicted an 'incident' (p < .042). In UC, both FC > 221 mu g/g (p < .0005) and CRP > 2.1 mg/L (p = .0334) predicted 'incident', as did combined biomarkers (p < .005).

    Conclusions: Clinical disease activity is reduced by treatment with infliximab. In CD, persistently high FC, but not CRP, predict a treatment 'incident', whereas in UC both high FC and high CRP predict 'incident'. Combined FC and CRP values also predict an 'incident'.

  • 31.
    Eriksson, Carl
    et al.
    Orebro Univ, Dept Gastroenterol, Fac Med & Hlth, SE-70182 Orebro, Sweden..
    Marsal, Jan
    Lund Univ, Immunol Sect, Lund, Sweden.;Skane Univ Hosp, Dept Gastroenterol, Lund, Sweden..
    Bergemalm, Daniel
    Orebro Univ, Dept Gastroenterol, Fac Med & Hlth, SE-70182 Orebro, Sweden..
    Vigren, Lina
    Ystad Hosp, Dept Internal Med, Ystad, Sweden..
    Bjork, Jan
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Digest Dis, Stockholm, Sweden..
    Eberhardson, Michael
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Digest Dis, Stockholm, Sweden..
    Karling, Pontus
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Soderman, Charlotte
    St Goran Hosp, Dept Internal Med, Stockholm, Sweden..
    Myrelid, Par
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.;Linkoping Univ Hosp, Dept Surg, Linkoping, Sweden..
    Cao, Yang
    Orebro Univ, Sch Med Sci, Dept Clin Epidemiol & Biostat, Orebro, Sweden.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Sjöberg, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Thörn, Mari
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Karlen, Per
    Danderyd Hosp, Dept Internal Med, Stockholm, Sweden..
    Hertervig, Erik
    Skane Univ Hosp, Dept Gastroenterol, Lund, Sweden..
    Strid, Hans
    Sodra Alvsborgs Sjukhus, Dept Internal Med, Boras, Sweden..
    Ludvigsson, Jonas F.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Orebro Univ Hosp, Dept Pediat, Orebro, Sweden..
    Almer, Sven
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Digest Dis, Stockholm, Sweden..
    Halfvarson, Jonas
    Orebro Univ, Dept Gastroenterol, Fac Med & Hlth, SE-70182 Orebro, Sweden..
    Long-term effectiveness of vedolizumab in inflammatory bowel disease: a national study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG)2017Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, nr 6-7, s. 722-729Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Clinical trials have demonstrated the efficacy of vedolizumab in inflammatory bowel disease (IBD). However, these findings may not reflect the clinical practice. Therefore, we aimed to describe a vedolizumab-treated patient population and assess long-term effectiveness.Materials and methods: Patients initiating vedolizumab between 1 June 2014 and 30 May 2015 were identified through the Swedish National Quality Registry for IBD. Prospectively collected data on treatment and disease activity were extracted. Clinical remission was defined as Patient Harvey Bradshaw index<5 in Crohn's disease (CD) and Patient Simple Clinical Colitis Activity index<3 in ulcerative colitis (UC).Results: Two-hundred forty-six patients (147CD, 92 UC and 7 IBD-Unclassified) were included. On study entry, 86% had failed TNF-antagonist and 48% of the CD patients had undergone1 surgical resection. After a median follow-up of 17 (IQR: 14-20) months, 142 (58%) patients remained on vedolizumab. In total, 54% of the CD- and 64% of the UC patients were in clinical remission at the end of follow-up, with the clinical activity decreasing (p<.0001 in both groups). Faecal-calprotectin decreased in CD (p<.0001) and in UC (p=.001), whereas CRP decreased in CD (p=.002) but not in UC (p=.11). Previous anti-TNF exposure (adjusted HR: 4.03; 95% CI: 0.96-16.75) and elevated CRP at baseline (adjusted HR: 2.22; 95% CI: 1.10-4.35) seemed to be associated with discontinuation because of lack of response. Female sex was associated with termination because of intolerance (adjusted HR: 2.75; 95% CI: 1.16-6.48).Conclusion: Vedolizumab-treated patients represent a treatment-refractory group. A long-term effect can be achieved, even beyond 1 year of treatment.

  • 32.
    Eriksson, Daniel
    et al.
    Karolinska Inst, Dept Med Solna, Ctr Mol Med, Stockholm, Sweden;Karolinska Univ Hosp, Dept Endocrinol Metab & Diabet, Stockholm, Sweden.
    Bacchetta, Rosa
    Stanford Univ, Dept Pediat, Sch Med, Div Stem Cell Transplantat & Regenerat Med, Stanford, CA 94305 USA.
    Gunnarsson, Hörður Ingi
    Karolinska Inst, Dept Med Solna, Ctr Mol Med, Stockholm, Sweden.
    Chan, Alice
    Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA.
    Barzaghi, Federica
    IRCCS San Raffaele Sci Inst, San Raffaele Telethon Inst Gene Therapy, Pediat Immunohematol & Bone Marrow Transplantat U, Milan, Italy.
    Ehl, Stephan
    Univ Freiburg, Freiburg Univ Hosp, Ctr Chron Immunodeficiency, Fac Med, Freiburg, Germany.
    Hallgren, Åsa
    Karolinska Inst, Dept Med Solna, Ctr Mol Med, Stockholm, Sweden.
    van Gool, Frederic
    Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
    Sardh, Fabian
    Karolinska Inst, Dept Med Solna, Ctr Mol Med, Stockholm, Sweden.
    Lundqvist, Christina
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden.
    Laakso, Saila M.
    Univ Helsinki, Childrens Hosp, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland.
    Rönnblom, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Ekwall, Olov
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden.
    Mäkitie, Outi
    Univ Helsinki, Childrens Hosp, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden;Folkhalsan Inst Genet, Helsinki, Finland;Univ Helsinki, Helsinki, Finland.
    Bensing, Sophie
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Husebye, Eystein S.
    Karolinska Inst, Dept Med Solna, Ctr Mol Med, Stockholm, Sweden;Univ Bergen, Dept Clin Sci, Bergen, Norway;Haukeland Hosp, Dept Med, Bergen, Norway;KG Jebsen Ctr Autoimmune Disorders, Bergen, Norway.
    Anderson, Mark
    Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
    Kämpe, Olle
    Karolinska Inst, Dept Med Solna, Ctr Mol Med, Stockholm, Sweden;Karolinska Univ Hosp, Dept Endocrinol Metab & Diabet, Stockholm, Sweden;KG Jebsen Ctr Autoimmune Disorders, Bergen, Norway.
    Landegren, Nils
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Med Solna, Ctr Mol Med, Stockholm, Sweden.
    The autoimmune targets in IPEX are dominated by gut epithelial proteins2019Ingår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 144, nr 1, s. 327-330Artikel i tidskrift (Övrigt vetenskapligt)
  • 33. Falken, Y.
    et al.
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Abraham-Nordling, M.
    Kressner, U.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Naslund, E.
    Intravenous ghrelin accelerates postoperative gastric emptying and time to first bowel movement in humans2013Ingår i: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 25, nr 6, s. 474-480Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Ghrelin has been shown to stimulate gastric emptying in healthy humans and patients with delayed gastric emptying. The aim of this study is to assess the effect of ghrelin on gastric emptying on day 2 after open colorectal surgery. Methods Twenty-four patients (mean age 69.2 +/- 1.4, BMI 25.8 +/- 0.8kgm2) were randomized to saline or ghrelin infusion (15pmolkg1min1) during 3h before and on day 2 after open colorectal surgery. Of these, 20 were assessed both before and after surgery. At start of infusion, a liquid meal (480kcal, 200mL) was administered together with 1.5g acetaminophen. Plasma was obtained at regular intervals together with visual analogue scales for hunger, satiety and nausea. Acetaminophen was analyzed as a marker of gastric emptying. Plasma glucose, insulin, acyl-ghrelin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinoptrophic peptide (GIP), pancreatic polypeptide and peptide YY (PYY) were analyzed. Key Results Gastric emptying was faster during ghrelin infusion compared to saline before and after surgery (P<0.02). In addition, plasma glucose was increased (P<0.05). With ghrelin infusion, plasma insulin was unchanged except for lower values postoperatively (P<0.05). Ghrelin did not alter plasma concentrations of gut peptides. After surgery, ghrelin shortened the time to first bowel movement compared to saline (2.1 +/- 0.3 vs 3.5 +/- 0.4days, P=0.02). Conclusions & Inferences A 3-h ghrelin infusion increased the gastric emptying rate and hastened the time to first bowel movement after surgery. Ghrelin/ghrelin receptor agonists have a therapeutic potential in postoperative ileus; Karolinska Clinical Trial Registry nr CT20110084.

  • 34.
    Farmer, A. D.
    et al.
    Aalborg Univ, Aalborg Univ Hosp, Aalborg & Clin Inst, Mech Sense,Dept Gastroenterol & Hepatol, Aalborg, Denmark.;Queen Mary Univ London, Neurogastroenterol Grp, Ctr Neurosci & Trauma, Blizard Inst,Wingate Inst Neurogastroenterol,Bart, London, England.;Univ Hosp North Midlands, Dept Gastroenterol, Stoke On Trent, Staffs, England..
    Wegeberg, A. -ML.
    Brock, B.
    Aarhus Univ Hosp, Dept Clin Biochem, Aarhus, Denmark..
    Hobson, A. R.
    Funct Gut Clin, London, England..
    Mohammed, S. D.
    Queen Mary Univ London, Neurogastroenterol Grp, Ctr Neurosci & Trauma, Blizard Inst,Wingate Inst Neurogastroenterol,Bart, London, England..
    Scott, S. M.
    Queen Mary Univ London, Neurogastroenterol Grp, Ctr Neurosci & Trauma, Blizard Inst,Wingate Inst Neurogastroenterol,Bart, London, England..
    Bruckner-Holt, C. E.
    Univ Hosp North Midlands, Dept Gastroenterol, Stoke On Trent, Staffs, England..
    Semler, J. R.
    Medtronic, Sunnyvale, CA USA..
    Hasler, W. L.
    Univ Michigan Hlth Syst, Div Gastroenterol, Ann Arbor, MI USA..
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Drewes, A. M.
    Aalborg Univ, Aalborg Univ Hosp, Aalborg & Clin Inst, Mech Sense,Dept Gastroenterol & Hepatol, Aalborg, Denmark..
    Brock, C.
    Aalborg Univ, Aalborg Univ Hosp, Aalborg & Clin Inst, Mech Sense,Dept Gastroenterol & Hepatol, Aalborg, Denmark.;Univ Copenhagen, Dept Pharmacotherapy & Dev, Copenhagen, Denmark..
    Regional gastrointestinal contractility parameters using the wireless motility capsule: inter-observer reproducibility and influence of age, gender and study country2018Ingår i: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 47, nr 3, s. 391-400Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background:

    The wireless motility capsule concurrently measures temperature, pH and pressure as it traverses the gastrointestinal tract. Aims: To describe normative values for motility/contractility parameters across age, gender and testing centres.

    Methods:

    Healthy participants underwent a standardised wireless motility capsule assessment following an overnight fast and consumption of a meal of known nutritional content. Traces were divided into regions of interest and analysed using 2 software packages (MotiliGI and GIMS Data Viewer). Inter-observer agreement was independently assessed by 2 investigators.

    Results:

    Normative data for motility/contractility parameters (maximum amplitude, mean peak amplitude, contraction frequency and motility index) are presented for 107 individuals (62 male, median age 40years, range 18-78). MotiliGI-Gastric, small bowel and colonic maximal contraction amplitude correlated with age (r = .24, P = .01; r = .22, P = .02; and r = .2, P = .04 respectively). Small bowel motility index was higher in females than males (150.412 vs 122 +/- 7.6, P = .04). Inter-observer agreement was excellent for transit times, pH and contractility/motility parameters. GIMS Data viewer-Gastric, small bowel and colonic log(e) motility index correlated with the respective area under the contraction curve, total contractions, sum of amplitudes and contraction frequency (all r>.35, P < .0003) but not with transit times.

    Conclusions:

    Our analysis provides normative data for motility/contractility parameters. Log motility index summarises a number of measures. In future, the measurement of contractile activity with the wireless motility capsule may potentially aid in the diagnosis of disease states such as visceral myopathic disorders.

  • 35. Farmer, Adam D
    et al.
    Ban, Vin F
    Coen, Steven J
    Sanger, Gareth J
    Barker, Gareth J
    Gresty, Michael A
    Giampietro, Vincent P
    Williams, Steven C
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hellström, Per M
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Andrews, Paul L R
    Aziz, Qasim
    Visually induced nausea causes characteristic changes in cerebral, autonomic and endocrine function in humans2015Ingår i: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 593, nr 5, s. 1183-1196Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    UNLABELLED: Nausea is a highly individual and variable experience. The reasons for this variability are incompletely understood although psychophysiological factors have been proposed. Herein we describe objective psychophysiological changes induced by the subjective sensation of motion sickness. In comparison to subjects who did not develop nausea, nausea-sensitive subjects demonstrated electrogastrographic and autonomic changes, which included an increase in sympathetic nervous system activity with a concomitant reduction in parasympathetic activity. Furthermore, differences were also evident in plasma ghrelin, and subcortical and cortical activity. These data have a number of important implications for future research examining the physiological mechanisms that underlie nausea: ○The physiological, hormonal and cortical patterns identified herein represent potential biomarkers of the physiological mechanisms of nausea. ○Reverse translation of the physiological factors identified may facilitate refinement of animal models used to investigate novel anti-emetic agents and emetic liability of candidate drugs, increasing their validity and translation of finding to humans.

    ABSTRACT: An integrated understanding of the physiological mechanisms involved in the genesis of nausea remains lacking. We aimed to describe the psychophysiological changes accompanying visually induced motion sickness, using a motion video, hypothesizing that differences would be evident between subjects who developed nausea in comparison to those who did not. A motion, or a control, stimulus was presented to 98 healthy subjects in a randomized crossover design. Validated questionnaires and a visual analogue scale (VAS) were used for the assessment of anxiety and nausea. Autonomic and electrogastrographic activity were measured at baseline and continuously thereafter. Plasma vasopressin and ghrelin were measured in response to the motion video. Subjects were stratified into quartiles based on VAS nausea scores, with the upper and lower quartiles considered to be nausea sensitive and resistant, respectively. Twenty-eight subjects were exposed to the motion vi