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  • 1.
    Al-Ayoubi, Fawzi
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Eriksson, Helene
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Hälsa, Aktivitet, Vård (HAV). Linköpings universitet, Hälsouniversitetet.
    Myrelid, Pär
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Wallon, Conny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Andersson, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Uneven distribution of emergency operations and lack of trauma: a call for reorganization of acute surgical care?2012Inngår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 20Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Subspecialisation within general surgery has today reached further than ever. However, on-call time, an unchanged need for broad surgical skills are required to meet the demands of acute surgical disease and trauma. The introduction of a new subspecialty in North America that deals solely with acute care surgery and trauma is an attempt to offer properly trained surgeons also during on-call time. To find out whether such a subspecialty could be helpful in Sweden we analyzed our workload for emergency surgery and trauma. METHODS: Linkoping University Hospital serves a population of 257 000. Data from 2010 for all patients, diagnoses, times and types of operations, surgeons involved, duration of stay, types of injury and deaths regarding emergency procedures were extracted from a prospectively-collected database and analyzed. RESULTS: There were 2362 admissions, 1559 emergency interventions; 835 were mainly abdominal operations, and 724 diagnostic or therapeutic endoscopies. Of the 1559 emergency interventions, 641 (41.1%) were made outside office hours, and of 453 minor or intermediate procedures (including appendicectomy, cholecystectomy, or proctological procedures) 276 (60.9%) were done during the evenings or at night. Two hundred and fifty-four patients were admitted with trauma and 29 (11.4%) required operation, of whom general surgeons operated on eight (3.1%). Thirteen consultants and 11 senior registrars were involved in 138 bowel resections and 164 cholecystectomies chosen as index operations for standard emergency surgery. The median (range) number of such operations done by each consultant was 6 (3--17) and 6 (1--22). Corresponding figures for senior registrars were 7 (0--11) and 8 (1--39). CONCLUSION: There was an uneven distribution of exposure to acute surgical problems and trauma among general surgeons. Some were exposed to only a few standard emergency interventions and most surgeons did not operate on a single patient with trauma. Further centralization of trauma care, long-term positions at units for emergency surgery and trauma, and subspecialisation in the fields of emergency surgery and trauma, might be options to solve problems of low volumes.

  • 2.
    Bringman, S.
    et al.
    Department of Surgery, Karolinska Institute, Huddinge University Hospital, S-141 86 Stockholm, Sweden.
    Ek, A.
    Ek, Å., Department of Surgery, Karlskoga Hospital, Karlskoga, Sweden.
    Haglind, E.
    Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Heikkinen, T.
    Department of Surgery, Karolinska Institute, Huddinge University Hospital, S-141 86 Stockholm, Sweden.
    Kald, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Kylberg, F.
    Department of Surgery, Karlskoga Hospital, Karlskoga, Sweden.
    Ramel, S.
    Department of Surgery, Karolinska Institute, Huddinge University Hospital, S-141 86 Stockholm, Sweden.
    Wallon, Conny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Anderberg, B.
    Department of Surgery, Karolinska Institute, Huddinge University Hospital, S-141 86 Stockholm, Sweden.
    Is a dissection balloon beneficial in totally extraperitoneal endoscopic hernioplasty (TEP)? A randomized prospective multicenter study2001Inngår i: Surgical Endoscopy, ISSN 0930-2794, E-ISSN 1432-2218, Vol. 15, nr 3, s. 266-270Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Laparoscopic hernioplasty has been criticized because of its technical complexity and increased costs. Disposable dissection balloons can be used to facilitate the creation of the initial working space in totally extraperitoneal endoscopic hernioplasty (TEP), but their use adds to the cost of the operation. Methods: A total of 322 men with unilateral, primary, or recurrent inguinal hernias were randomized to undergo TEP with or without a dissection balloon. Results: In the group with the balloon, three of 161 patients (2.5%) required conversion to transabdominal preperitoneal hernioplasty (TAPP), or open herniorraphy, whereas 17 of 161 patients (10.6%) were converted to TAPP or open herniorraphy in the group without the balloon (p = 0.002). The mean operation time was 55 min in the group with the balloon and 63 min in the group without the balloon (p = 0.004). There was no difference between them in postoperative morbidity, and there were no major complications in either group. The recurrence rate was 3.1% in the group with the balloon and 3.7 % in the group without the balloon (p = 0.8). Conclusion: The use of a dissection balloon in TEP reduces the conversion rate and may be especially beneficial early in the learning curve.

  • 3.
    Bringman, S
    et al.
    Huddinge Univ Hosp, Karolinska Inst, Dept Surg, S-14186 Huddinge, Sweden Karlskoga Hosp, Dept Surg, Karlskrona, Sweden Sahlgrens Univ Hosp, Dept Surg, S-41345 Gothenburg, Sweden Linkoping Univ Hosp, Dept Surg, S-58185 Linkoping, Sweden.
    Ek, Anna-Christina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Omvårdnad. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Akutkliniken.
    Haglind, E
    Huddinge Univ Hosp, Karolinska Inst, Dept Surg, S-14186 Huddinge, Sweden Karlskoga Hosp, Dept Surg, Karlskrona, Sweden Sahlgrens Univ Hosp, Dept Surg, S-41345 Gothenburg, Sweden Linkoping Univ Hosp, Dept Surg, S-58185 Linkoping, Sweden.
    Heikkinen, TJ
    Huddinge Univ Hosp, Karolinska Inst, Dept Surg, S-14186 Huddinge, Sweden Karlskoga Hosp, Dept Surg, Karlskrona, Sweden Sahlgrens Univ Hosp, Dept Surg, S-41345 Gothenburg, Sweden Linkoping Univ Hosp, Dept Surg, S-58185 Linkoping, Sweden.
    Kald, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Kylberg, F
    Huddinge Univ Hosp, Karolinska Inst, Dept Surg, S-14186 Huddinge, Sweden Karlskoga Hosp, Dept Surg, Karlskrona, Sweden Sahlgrens Univ Hosp, Dept Surg, S-41345 Gothenburg, Sweden Linkoping Univ Hosp, Dept Surg, S-58185 Linkoping, Sweden.
    Ramel, S
    Huddinge Univ Hosp, Karolinska Inst, Dept Surg, S-14186 Huddinge, Sweden Karlskoga Hosp, Dept Surg, Karlskrona, Sweden Sahlgrens Univ Hosp, Dept Surg, S-41345 Gothenburg, Sweden Linkoping Univ Hosp, Dept Surg, S-58185 Linkoping, Sweden.
    Wallon, Conny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Anderberg, B
    Huddinge Univ Hosp, Karolinska Inst, Dept Surg, S-14186 Huddinge, Sweden Karlskoga Hosp, Dept Surg, Karlskrona, Sweden Sahlgrens Univ Hosp, Dept Surg, S-41345 Gothenburg, Sweden Linkoping Univ Hosp, Dept Surg, S-58185 Linkoping, Sweden.
    Is a dissection balloon beneficial in bilateral, totally extraperitoneal, endoscopic hernioplasty? A randomized, prospective, multicenter study2001Inngår i: Surgical Laparoscopy, Endoscopy and Percutaneous Techniques, ISSN 1051-7200, E-ISSN 2331-2254, Vol. 11, nr 5, s. 322-326Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Laparoscopic hernioplasty has been criticized because of its technical complexity and increased costs. Disposable dissection balloons can be used to gain the initial working space in totally extraperitoneal endoscopic (TEP) hernioplasty, but this increases its cost. Forty-four men with bilateral, primary or recurrent inguinal hernias were randomized to undergo TEP with or without dissection balloon, There were two conversions to transabdominal preperitoneal hernioplasty, or open herniorrhaphy, in the group with balloon and four in the group without balloon. There was no difference in the postoperative morbidity or operation time between the two groups, and there were no major complications in either group. The recurrence rate was 4.3% in the group with the balloon and 7.1% in the group without the balloon. There were no statistically significant differences between the groups, Although our study population is too small to detect small differences between the groups, it seems that the use of a dissection balloon is not beneficial in a bilateral TEP.

  • 4.
    Keita, Åsa V
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Gullberg, Elisabet
    Department of Pharmacy, Uppsala University, BMC, Uppsala, Sweden.
    Ericson, Ann-Charlott
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Salim, Sa’ad Y
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Wallon, Conny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Kald, Anders
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Artursson, Per
    Department of Pharmacy, Uppsala University, BMC, Uppsala, Sweden.
    Söderholm, Johan D
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Characterization of antigen and bacterial transport in the follicle-associated epithelium of human ileum2006Inngår i: Laboratory investigation, ISSN 0023-6837, Vol. 86, nr 5, s. 504-516Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The follicle-associated epithelium (FAE), covering Peyer's patches, provides a route of entry for antigens and microorganisms. Animal studies showed enhanced antigen and bacterial uptake in FAE, but no study on barrier function of human FAE has been reported. Our aim was to characterize the normal barrier properties of human FAE. Specimens of normal ileum were taken from 30 patients with noninflammatory colonic disease. Villus epithelium (VE) and FAE were identified and mounted in Ussing chambers. Permeability to 51Cr-EDTA, transmucosal flux of the protein antigen, horseradish peroxidase (HRP), and transport of fluorescent Escherichia coli (chemically killed K-12 and live HB101) were measured. Uptake mechanisms were studied by confocal- and transmission electron microscopy, and by using pharmacological inhibitors in an in vitro coculture model of FAE and in human ileal FAE. HRP flux was substantially higher in FAE than in VE, and was reduced by an amiloride analog. Electron microscopy showed HRP-containing endosomes. Transport of E. coli K-12 and HB101 was also augmented in FAE and was confirmed by confocal microscopy. In vitro coculture experiments and electron microscopy revealed actin-dependent, mainly transcellular, uptake of E. coli K-12 into FAE. 51Cr-EDTA permeability was equal in FAE and VE. Augmented HRP flux and bacterial uptake but similar paracellular permeability, suggest functional variations of transcellular transport in the FAE. We show for the first time that FAE of human ileum is functionally distinct from regular VE, rendering the FAE more prone to bacterial–epithelial cell interactions and delivery of antigens to the mucosal immune system.

  • 5.
    Kurt Schultz, Johannes
    et al.
    Akershus University Hospital, Norway; University of Oslo, Norway.
    Yaqub, Sheraz
    Oslo University Hospital, Norway.
    Wallon, Conny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US. Linköpings universitet, Medicinska fakulteten.
    Blecic, Ljiljana
    Ostfold Hospital, Norway.
    Mjorud Forsmo, Havard
    Haukeland Hospital, Norway.
    Folkesson, Joakim
    Uppsala University, Sweden.
    Buchwald, Pamela
    Helsingborg Hospital, Sweden.
    Korner, Hartwig
    Stavanger University Hospital, Norway.
    Dahl, Fredrik A.
    Akershus University Hospital, Norway.
    Oresland, Tom
    Akershus University Hospital, Norway; University of Oslo, Norway.
    Laparoscopic Lavage vs Primary Resection for Acute Perforated Diverticulitis The SCANDIV Randomized Clinical Trial2015Inngår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 314, nr 13, s. 1364-1375Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    IMPORTANCE Perforated colonic diverticulitis usually requires surgical resection, which is associated with significant morbidity. Cohort studies have suggested that laparoscopic lavage may treat perforated diverticulitis with less morbidity than resection procedures. OBJECTIVE To compare the outcomes from laparoscopic lavage with those for colon resection for perforated diverticulitis. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized clinical superiority trial recruiting participants from 21 centers in Sweden and Norway from February 2010 to June 2014. The last patient follow-up was in December 2014 and final review and verification of the medical records was assessed in March 2015. Patients with suspected perforated diverticulitis, a clinical indication for emergency surgery, and free air on an abdominal computed tomography scan were eligible. Of 509 patients screened, 415 were eligible and 199 were enrolled. INTERVENTIONS Patients were assigned to undergo laparoscopic peritoneal lavage (n = 101) or colon resection (n = 98) based on a computer-generated, center-stratified block randomization. All patients with fecal peritonitis (15 patients in the laparoscopic peritoneal lavage group vs 13 in the colon resection group) underwent colon resection. Patients with a pathology requiring treatment beyond that necessary for perforated diverticulitis (12 in the laparoscopic lavage group vs 13 in the colon resection group) were also excluded from the protocol operations and treated as required for the pathology encountered. MAIN OUTCOMES AND MEASURES The primary outcome was severe postoperative complications (Clavien-Dindo score greater thanIlla) within 90 days. Secondary outcomes included other postoperative complications, reoperations, length of operating time, length of postoperative hospital stay, and quality of life. RESULTS The primary outcome was observed in 31 of 101 patients (30.7%) in the laparoscopic lavage group and 25 of 96 patients (26.0%) in the colon resection group (difference, 4.7% [95% CI, -7.9% to 17.0%]; P = .53). Mortality at 90 days did not significantly differ between the laparoscopic lavage group (14 patients [13.9%]) and the colon resection group (11 patients [11.5%]; difference, 2.4% [95% CI, -7.2% to 11.9%]; P = .67). The reoperation rate was significantly higher in the laparoscopic lavage group (15 of 74 patients [20.3%]) than in the colon resection group (4 of 70 patients [5.7%]; difference, 14.6% [95% CI, 3.5% to 25.6%]; P = .01) for patients who did not have fecal peritonitis. The length of operating time was significantly shorter in the laparoscopic lavage group; whereas, length of postoperative hospital stay and quality of life did not differ significantly between groups. Four sigmoid carcinomas were missed with laparoscopic lavage. CONCLUSIONS AND RELEVANCE Among patients with likely perforated diverticulitis and undergoing emergency surgery, the use of laparoscopic lavage vs primary resection did not reduce severe postoperative complications and led to worse outcomes in secondary end points. These findings do not support laparoscopic lavage for treatment of perforated diverticulitis.

  • 6.
    Münch, Andreas
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Gastroenterologi och hepatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken.
    Söderholm, Johan D
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Wallon, Conny
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Öst, Åke
    Medilab, Täby, Sweden.
    Olaison, Gunnar
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Ström, Magnus
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Gastroenterologi och hepatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Dynamics of mucosal permeability and inflammation in collagenous colitis before, during, and after loop ileostomy2005Inngår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 54, nr 8, s. 1126-1128Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Collagenous colitis has become a more frequent diagnosis but the aetiology of this disease is still unknown. We describe a female patient with intractable collagenous colitis who was treated with a temporary loop ileostomy. She was followed clinically, histopathologically, and functionally by measuring mucosal permeability before surgery, after ileostomy, and after bowel reconstruction. In our case report, active collagenous colitis was combined with increased transcellular and paracellular mucosal permeability. Diversion of the faecal stream decreased inflammation of the mucosa and normalised epithelial degeneration and mucosal permeability. After restoration of bowel continuity, mucosal permeability was altered prior to the appearance of a collagenous layer.

  • 7.
    Persborn, Mats
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Gerritsen, J
    Wageningen University, Netherlands .
    Wallon, Conny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Carlsson, Anders
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Akkermans, L M A .
    University of Medical Centre, Netherlands .
    Söderholm, Johan D.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    The effects of probiotics on barrier function and mucosal pouch microbiota during maintenance treatment for severe pouchitis in patients with ulcerative colitis2013Inngår i: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 38, nr 7, s. 772-783Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background less thanbrgreater than less thanbrgreater thanA total of 10-15% of patients with an ileoanal pouch develop severe pouchitis necessitating long-term use of antibiotics or pouch excision. Probiotics reduce the risk of recurrence of pouchitis, but mechanisms behind these effects are not fully understood. less thanbrgreater than less thanbrgreater thanAim less thanbrgreater than less thanbrgreater thanTo examine mucosal barrier function in pouchitis, before and after probiotic supplementation and to assess composition of mucosal pouch microbiota. less thanbrgreater than less thanbrgreater thanMethods less thanbrgreater than less thanbrgreater thanSixteen patients with severe pouchitis underwent endoscopy with biopsies of the pouch on three occasions: during active pouchitis; clinical remission by 4 weeks of antibiotics; after 8 weeks of subsequent probiotic supplementation (Ecologic 825, Winclove, Amsterdam, the Netherlands). Thirteen individuals with a healthy ileoanal pouch were sampled once as controls. Ussing chambers were used to assess transmucosal passage of Escherichia coli K12, permeability to horseradish peroxidase (HRP) and Cr-51-EDTA. Composition and diversity of the microbiota was analysed using Human Intestinal Tract Chip. less thanbrgreater than less thanbrgreater thanResults less thanbrgreater than less thanbrgreater thanPouchitis Disease Activity Index (PDAI) was significantly improved after antibiotic and probiotic supplementation. Escherichia coli K12 passage during active pouchitis [3.7 (3.4-8.5); median (IQR)] was significantly higher than in controls [1.7 (1.0-2.4); P andlt; 0.01], did not change after antibiotic treatment [5.0 (3.3-7.1); P = ns], but was significantly reduced after subsequent probiotic supplementation [2.2 (1.7-3.3); P andlt; 0.05]. No significant effects of antibiotics or probiotics were observed on composition of mucosal pouch microbiota; however, E. coli passage correlated with bacterial diversity (r = -0.40; P = 0.018). Microbial groups belonging to Bacteroidetes and Clostridium clusters IX, XI and XIVa were associated with healthy pouches. less thanbrgreater than less thanbrgreater thanConclusions less thanbrgreater than less thanbrgreater thanProbiotics restored the mucosal barrier to E. coli and HRP in patients with pouchitis, a feasible factor in prevention of recurrence during maintenance treatment. Restored barrier function did not translate into significant changes in mucosal microbiota composition, but bacterial diversity correlated with barrier function.

  • 8.
    Persborn, Mats
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Wallon, Conny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken i Östergötland.
    Carlsson, Anders
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Timmerman, Harro
    Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken i Östergötland.
    Söderholm, Johan D.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken i Östergötland.
    Effects of probiotics (Ecologic 825) on barrier function during maintenance treatment for severe pouchitisManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Background : About 10-15% of patients with an ileoanal pouch develop a severe, form of pouchitis that necessitates long and/or frequent use of antibiotics and in rare cases even pouch excision. Probiotics have been shown to reduce the risk of recurrence after induction treatment with antibiotics. The mechanisms behind the positive effects of probiotics are not fully understood. The aim of our study was to examine the mucosal barrier function in relation to pouchitis, before and after treatment with probiotics.

    Methods: 16 patients with a history of severe pouchitis underwent endoscopy with biopsies of the pouch on three occasions: Once during active pouchitis, second after 4 weeks of treatment with antibiotics until clinical remission and third after eight weeks of probiotic treatment. 13 controls with an ileoanal pouch with no recent history of pouchitis were used. The biopsies were mounted in Ussing chambers and mucosal barrier function was assessed by electrophysiology, transmucosal uptake of E coli K12, permeability to Cr-EDTA and Horseradish peroxidase (HRP). Pouchitis Disease Activity Index (PDAI) was used in all subjects.

    Results: PDAI was significantly improved after treatment with antibiotics and probiotics. There was a significant difference in E. coli K12 passage before treatment compared to controls (3.7 units (3.4-8.5) vs 1.7 units (1.0-2.4) p< 0.01). E. coli K12 passage did not change after antibiotic treatment (5.0 units (3.3-7.1) p = ns vs controls). In contrast a significant reduction in bacterial uptake was seen after probiotics (2.2 units (1.8-3.3) p< 0.05). Likewise, a significant normalization of HRP flux was seen after probiotic treatment. Pouchitis did not affect paracellular permability or electrophysiology.

    Conclusion: Probiotic treatment restored the increased permeation to E. coli and HRP in patients with chronic pouchitis. This could be an important factor behind the positive effects of probiotics in patients with chronic pouchitis.

  • 9.
    Velin Keita, Åsa
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Ericson, Ann-Charlott
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Braaf, Ylva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Wallon, Conny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Söderholm, Johan D
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Increased antigen and bacterial uptake in follicle-associated epithelium induced by chronic psychological stress in rats2004Inngår i: Gut, ISSN 0017-5749, Vol. 53, nr 4, s. 494-500Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Chronic stress affects the course of inflammatory bowel disease and experimental colitis, and may also initiate intestinal inflammation in rats.

    Aim: To investigate the effects of stress on the M cell containing follicle associated epithelium, specialised in antigen uptake.

    Subjects and methods: Wistar rats were submitted to acute water avoidance stress for one hour or chronic water avoidance stress for 1 hour/day for 10 consecutive days. Permeability to 51Cr-EDTA, horseradish peroxidase, and chemically killed Escherichia coli K-12 was studied in both villus and follicle associated epithelium in Ussing chambers. Segments were further examined by light, electron, and confocal microscopy.

    Results: Acute stress increased horseradish peroxidase flux in villus as well as in follicle associated epithelium. Chronic stress further increased permeability to horseradish peroxidase in villus and follicle associated epithelium, in the latter by almost fourfold. Moreover, chronic stress induced over 30 times increased E coli passage in follicle associated epithelium whereas there was no significant increase in villus epithelium. Bacterial uptake was confirmed by confocal microscopy showing fluorescent bacteria penetrating and passing through the epithelial surface.

    Conclusions: These results show that the barrier function of follicle associated epithelium can be modulated, and that chronic stress enhances the uptake of luminal antigens and bacteria via the follicle associated epithelium. This can increase antigen exposure in Peyer’s patches thereby having implications in the initiation of proinflammatory immune responses within the intestinal mucosa.

  • 10.
    Wallon, Conny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Neuro-immune regulation of macromolecular permeability in the normal human colon and in ulcerative colitis2007Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background and aim: Persistent stress and life events affect the course of ulcerative colitis (UC) by largely unknown mechanisms. Regulation of epithelial permeability to antigens is crucial for the balance between inflammation and immuno-surveillance, and increased intestinal permeability has been shown in patients with ulcerative colitis. Corticotropin releasing hormone (CRH) has been implicated as an important mediator of stress-induced abnormalities in intestinal mucosal function in animal models. Further cholinergic signalling during stress

    has been reported to increase bowel ion secretion in humans and uptake of HRP in rodents via activation of mast cells.

    The overall aim of this thesis was to examine the role of CRH-mediated and cholinergic signalling, and their interaction with mast cells and eosinophils, in the regulation of the mucosal barrier function in the normal human colon and in UC. In vivo studies or the use of surgical specimens for such studies have major shortcomings. Therefore a method with endoscopic biopsies in Ussing chambers was established for studies of protein antigen uptake and electrophysiology in human colonic biopsies, and used in subsequent investigations.

    Materials and methods: In the four studies a total of 91 healthy volunteers, 3 patients with rectal cancer, and 15 UC patients were included. Biopsies from the sigmoid colon were assessed for macromolecular permeability (Horseradish peroxidase (HRP), and 51Cr-EDTA), and electrophysiology during challenge with sodium caprate (C10), CRH or carbachol. Experiments were repeated with CRH receptor antagonists, carbachol receptor antagonists, mast cell stabilizers and nerve conductance blockers in Ussing chambers. The biopsies were examined by electron and light microscopy for endocytosis of HRP, morphological changes and receptor expression. Moreover, the human mast cell line, HMC-1; was used in studying expression of CRH receptors on mast cells.

    Results: Endoscopic biopsies of human colon were viable in Ussing chambers, and the technique was shown to be a reliable tool for studies of mucosal permeability to HRP. CRH stimulates transcellular uptake of HRP in human colon via CRH receptor subtypes R1 and R2 on subepithelial mast cells. Further, carbachol acts on muscarinic receptors, located on subepithelial eosinophils. Activated muscarinic M2 and M3 receptors on increased numbers of CRHproducing eosinophils in UC, lead to activation of mast cells and increased macromolecular uptake across the colonic mucosa. This signalling cascade is previously unrecognized, and may be involved in the inflammatory process in UC.

    Conclusions: In conclusion, we have demonstrated a chain of events leading to increased permeability to the protein antigen HRP in biopsies from healthy volunteers and patients with UC. The important steps begin with a cholinergic signal to muscarinic receptors on the CRH containing eosinophils. The next step includes activation of CRH receptors on mast cells leading to degranulation and increased macromolecular uptake across the epithelium. This explanatory model will have implications for understanding of the pathogenesis of UC and future treatment of the disease.

    Delarbeid
    1. Endoscopic biopsies in Ussing chambers evaluated for studies of macromolecular permeability in the human colon
    Åpne denne publikasjonen i ny fane eller vindu >>Endoscopic biopsies in Ussing chambers evaluated for studies of macromolecular permeability in the human colon
    Vise andre…
    2005 (engelsk)Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 40, nr 5, s. 586-595Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Objective Studies of mucosal permeability to protein antigens in humans are limited to in vitro techniques. The use of surgical specimens for such studies has major shortcomings. Endoscopic biopsies in Ussing chambers have been introduced as a means of studying secretion and transepithelial permeability, but have not been evaluated for studies of protein antigen uptake in human intestine.

    Material and methods Standard forceps biopsies from the sigmoid colon of 24 healthy volunteers were mounted in Ussing chambers with an exposed tissue area of 1.76 mm2. 51Cr-EDTA (paracellular probe) and horseradish peroxidase (HRP; 45 kDa protein antigen) were used as permeability markers. Mucosal permeability, electrophysiology, histology and energy contents of the biopsies were studied over time. To evaluate the ability of the technique to detect permeability changes, the mucosa was modulated with capric acid, a medium-chain fatty acid, known to affect tight junctions.

    Results In the Ussing chamber the mucosal biopsies were viable for 160 min with stable levels of ATP and lactate, and only minor changes in morphology. Steady-state permeability with low variability was seen for both markers during the 30-90 min period. Exposure to capric acid induced a rapid decrease in short-circuit current (Isc) and a slower reversible decrease in transepithelial resistance (TER), as well as an increased permeability to 51Cr-EDTA and HRP.

    Conclusions Endoscopic biopsies of human colon are viable in Ussing chambers and are reliable tools for studies of mucosal permeability to protein antigens. The technique offers a broad potential for studies of mucosal function in the pathophysiology of human gastrointestinal diseases.

    Emneord
    ATP; histology; horseradish peroxidase; intestinal absorption; intestinal mucosa; lactate; short-circuit current; sodium caprate; transepithelial electrical resistance
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-13152 (URN)10.1080/00365520510012235 (DOI)
    Tilgjengelig fra: 2008-04-07 Laget: 2008-04-07 Sist oppdatert: 2009-06-08
    2. Corticotropin releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro
    Åpne denne publikasjonen i ny fane eller vindu >>Corticotropin releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro
    Vise andre…
    2008 (engelsk)Inngår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 57, nr 1, s. 50-58Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Objective: Persistent stress and life events affect the course of ulcerativecolitis and irritable bowel syndrome by largely unknown mechanisms.Corticotropin-releasing hormone (CRH) has been implicated asan important mediator of stress-induced abnormalities in intestinalmucosal function in animal models, but to date no studies inhuman colon have been reported. The aim was to examine the effectsof CRH on mucosal barrier function in the human colon and toelucidate the mechanisms involved in CRH-induced hyper-permeability.

    Design: Biopsies from 39 volunteers were assessed for macromolecularpermeability (horseradish peroxidise (HRP), 51Cr-EDTA), andelectrophysiology after CRH challenge in Ussing chambers. Thebiopsies were examined by electron and confocal microscopy forHRP and CRH receptor localisation, respectively. Moreover, CRHreceptor mRNA and protein expression were examined in the humanmast cell line, HMC-1.

    Results: Mucosal permeability to HRP was increased by CRH (2.8±0.5pmol/cm2/h) compared to vehicle exposure (1.5±0.4 pmol/cm2/h),p = 0.032, whereas permeability to 51Cr-EDTA and transmucosalelectrical resistance were unchanged. The increased permeabilityto HRP was abolished by -helical CRH (9-41) (1.3±0.6pmol/cm2/h) and the mast cell stabiliser, lodoxamide (1.6±0.6pmol/cm2/h). Electron microscopy showed transcellular passageof HRP through colonocytes. CRH receptor subtypes R1 and R2were detected in the HMC-1 cell line and in lamina propria mastcells in human colon.

    Conclusions: Our results suggest that CRH mediates transcellular uptake ofHRP in human colonic mucosa via CRH receptor subtypes R1 andR2 on subepithelial mast cells. CRH-induced macromolecular uptakein human colon mucosa may have implications for stress-relatedintestinal disorders.

    sted, utgiver, år, opplag, sider
    London UK: BMJ Group, 2008
    Emneord
    CRH receptor subtypes, barrier function, electron microscopy, human mast cell line, intestinal mucosa
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-13153 (URN)10.1136/gut.2006.117549 (DOI)000251778400013 ()
    Tilgjengelig fra: 2008-04-07 Laget: 2008-04-07 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    3. Carbachol regulates transcellular antigen permeability in human sigmoid colon biopsies in vitro
    Åpne denne publikasjonen i ny fane eller vindu >>Carbachol regulates transcellular antigen permeability in human sigmoid colon biopsies in vitro
    Vise andre…
    Manuskript (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:liu:diva-13154 (URN)
    Tilgjengelig fra: 2008-04-07 Laget: 2008-04-07 Sist oppdatert: 2010-01-13
    4. Cholinergic stimulation-induced release of CRH from eosinophils mediates increased macromolecular permeability in ulcerative colitis
    Åpne denne publikasjonen i ny fane eller vindu >>Cholinergic stimulation-induced release of CRH from eosinophils mediates increased macromolecular permeability in ulcerative colitis
    Vise andre…
    Manuskript (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:liu:diva-13155 (URN)
    Tilgjengelig fra: 2008-04-07 Laget: 2008-04-07 Sist oppdatert: 2010-01-13
  • 11.
    Wallon, Conny
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Braaf, Ylva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Wolving, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet.
    Olaison, Gunnar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Söderholm, Johan D.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Endoscopic biopsies in Ussing chambers evaluated for studies of macromolecular permeability in the human colon2005Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 40, nr 5, s. 586-595Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective Studies of mucosal permeability to protein antigens in humans are limited to in vitro techniques. The use of surgical specimens for such studies has major shortcomings. Endoscopic biopsies in Ussing chambers have been introduced as a means of studying secretion and transepithelial permeability, but have not been evaluated for studies of protein antigen uptake in human intestine.

    Material and methods Standard forceps biopsies from the sigmoid colon of 24 healthy volunteers were mounted in Ussing chambers with an exposed tissue area of 1.76 mm2. 51Cr-EDTA (paracellular probe) and horseradish peroxidase (HRP; 45 kDa protein antigen) were used as permeability markers. Mucosal permeability, electrophysiology, histology and energy contents of the biopsies were studied over time. To evaluate the ability of the technique to detect permeability changes, the mucosa was modulated with capric acid, a medium-chain fatty acid, known to affect tight junctions.

    Results In the Ussing chamber the mucosal biopsies were viable for 160 min with stable levels of ATP and lactate, and only minor changes in morphology. Steady-state permeability with low variability was seen for both markers during the 30-90 min period. Exposure to capric acid induced a rapid decrease in short-circuit current (Isc) and a slower reversible decrease in transepithelial resistance (TER), as well as an increased permeability to 51Cr-EDTA and HRP.

    Conclusions Endoscopic biopsies of human colon are viable in Ussing chambers and are reliable tools for studies of mucosal permeability to protein antigens. The technique offers a broad potential for studies of mucosal function in the pathophysiology of human gastrointestinal diseases.

  • 12.
    Wallon, Conny
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Juhlin, Claes
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Melander, Helen
    Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Sjödahl, Rune
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Oplanerade återinläggningar på kirurgisk klinik2010Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, nr 23, s. 1548-1551Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    [No abstract available]

  • 13.
    Wallon, Conny
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken i Östergötland.
    Persborn, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Jönsson, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Wang, Arthur
    University of Calgary.
    Phan, Van
    University of Calgary.
    Lampinen, Maria
    Uppsala University.
    Vicario, Maria
    CIBERehd.
    Santos, Javier
    CIBERehd.
    Sherman, Philip M
    University of Toronto.
    Carlson, Marie
    Uppsala University.
    Ericson, Ann-Charlott
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    McKay, Derek M
    University of Calgary.
    Söderholm, Johan D
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken i Östergötland.
    Eosinophils Express Muscarinic Receptors and Corticotropin-Releasing Factor to Disrupt the Mucosal Barrier in Ulcerative Colitis2011Inngår i: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 140, nr 5, s. 1597-1607Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND andamp; AIMS: Altered intestinal barrier function has been implicated in the pathophysiology of ulcerative colitis (UC) in genetic, functional, and epidemiological studies. Mast cells and corticotropinreleasing factor (CRF) regulate the mucosal barrier in human colon. Because eosinophils are often increased in colon tissues of patients with UC, we assessed interactions among mast cells, CRF, and eosinophils in the mucosal barrier of these patients. METHODS: Transmucosal fluxes of protein antigens (horseradish peroxidase) and paracellular markers (51Cr-EDTA, fluorescein isothiocyanate-dextran 4000) were studied in noninflamed, colonic mucosal biopsy samples collected from 26 patients with UC and 53 healthy volunteers (controls); samples were mounted in Ussing chambers. We also performed fluorescence and electron microscopy of human tissue samples, assessed isolated eosinophils, and performed mechanistic studies using in vitro cocultured eosinophils (15HL-60), mast cells (HMC-1), and a colonic epithelial cell line (T84). RESULTS: Colon tissues from patients with UC had significant increases in permeability to protein antigens compared with controls. Permeability was blocked by atropine (a muscarinic receptor antagonist), alpha-helical CRF(9-41) (a CRF receptor antagonist), and lodoxamide (a mast-cell stabilizer). Eosinophils were increased in number in UC tissues (compared with controls), expressed the most M2 and M3 muscarinic receptors of any mucosal cell type, and had immunoreactivity to CRF. In coculture studies, carbachol activation of eosinophils caused production of CRF and activation of mast cells, which increased permeability of T84 epithelial cells to macromolecules. CONCLUSIONS: We identified a neuroimmune intercellular circuit (from cholinergic nerves, via eosinophils to mast cells) that mediates colonic mucosal barrier dysfunction in patients with UC. This circuit might exacerbate mucosal inflammation.

  • 14.
    Wallon, Conny
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Söderholm, Johan D
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Corticotropin-Releasing Hormone and Mast Cells in the Regulation of Mucosal Barrier Function in the Human Colon2009Inngår i: MOLECULAR STRUCTURE AND FUNCTION OF THE TIGHT JUNCTION: FROM BASIC MECHANISMS TO CLINICAL MANIFESTATIONS, ISSN 0077-8923, Vol. 1165, s. 206-210Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Corticotropin-releasing hormone (CRH) is an important neuro-endocrine mediator of the stress response. Local effects of CRH in the intestinal mucosa have become evident in recent years. We showed that CRH activates CRH receptor subtypes R1 and R2 on subepithelial mast cells, thereby inducing increased transcellular uptake of protein antigens in human colonic biopsies in Ussing chambers. Ongoing studies also implicate local cholinergic signaling in regulation of macromolecular permeability in the human colon. Since increased uptake of antigenic molecules is associated with mucosal inflammation, our findings may have implications for understanding stress-related intestinal disorders.

  • 15.
    Wallon, Conny
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Yang, P.
    Intestinal Disease Research Programme, McMaster University, Hamilton, Canada.
    Keita, Åsa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Ericson, Ann-Charlott
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    McKay, D. M.
    Department of Physiology and Biophysics, University of Calgary, Canada.
    Sherman, P. M.
    Departments of Paediatrics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
    Perdue, M. H.
    Intestinal Disease Research Programme, McMaster University, Hamilton, Canada.
    Söderholm, Johan D.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Corticotropin releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro2008Inngår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 57, nr 1, s. 50-58Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Persistent stress and life events affect the course of ulcerativecolitis and irritable bowel syndrome by largely unknown mechanisms.Corticotropin-releasing hormone (CRH) has been implicated asan important mediator of stress-induced abnormalities in intestinalmucosal function in animal models, but to date no studies inhuman colon have been reported. The aim was to examine the effectsof CRH on mucosal barrier function in the human colon and toelucidate the mechanisms involved in CRH-induced hyper-permeability.

    Design: Biopsies from 39 volunteers were assessed for macromolecularpermeability (horseradish peroxidise (HRP), 51Cr-EDTA), andelectrophysiology after CRH challenge in Ussing chambers. Thebiopsies were examined by electron and confocal microscopy forHRP and CRH receptor localisation, respectively. Moreover, CRHreceptor mRNA and protein expression were examined in the humanmast cell line, HMC-1.

    Results: Mucosal permeability to HRP was increased by CRH (2.8±0.5pmol/cm2/h) compared to vehicle exposure (1.5±0.4 pmol/cm2/h),p = 0.032, whereas permeability to 51Cr-EDTA and transmucosalelectrical resistance were unchanged. The increased permeabilityto HRP was abolished by -helical CRH (9-41) (1.3±0.6pmol/cm2/h) and the mast cell stabiliser, lodoxamide (1.6±0.6pmol/cm2/h). Electron microscopy showed transcellular passageof HRP through colonocytes. CRH receptor subtypes R1 and R2were detected in the HMC-1 cell line and in lamina propria mastcells in human colon.

    Conclusions: Our results suggest that CRH mediates transcellular uptake ofHRP in human colonic mucosa via CRH receptor subtypes R1 andR2 on subepithelial mast cells. CRH-induced macromolecular uptakein human colon mucosa may have implications for stress-relatedintestinal disorders.

  • 16.
    Yakymenko, Olena
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Schoultz, Ida
    Department of Medical Sciences, Faculty of Health and Medicine, Örebro University, Örebro, Sweden.
    Gullberg, Elisabet
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin.
    Ström, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Almer, Sven
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden / GastroCentrum, Karolinska University Hospital, Stockholm, Sweden.
    Wallon, Conny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Wang, Arthur
    Gastrointestinal Research Group, Cumming School of Medicine, University of Calgary, Calgary, Canada..
    Keita, Åsa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Campbell, Barry J.
    Gastroenterology Research Unit, Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool, UK.
    McKay, Derek M.
    Gastrointestinal Research Group, Cumming School of Medicine, University of Calgary, Calgary, Canada.
    Söderholm, Johan D
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Infliximab restores colonic barrier to adherent-invasive E. coli in Crohn's disease via effects on epithelial lipid rafts2018Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, nr 6, s. 677-684Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Infliximab is important in the therapeutic arsenal of Crohn’s disease (CD). However, its effect on mucosal barrier function is not fully understood. Adherent-invasive Escherichia coli (AIEC) are important in CD pathophysiology, but the transmucosal uptake routes are partly unknown. We investigated effects of infliximab on uptake of colon-specific AIEC HM427 across CD colonic mucosa.

    Materials and methods: Endoscopic biopsies from non-inflamed colon of seven patients with CD, before and after two infliximab infusions, and eight non-inflammation controls, were mounted in Ussing chambers. Paracellular permeability (51Cr-EDTA) and transmucosal passage of GFP-expressing HM427 were studied. Mechanisms of HM427 transepithelial transport were investigated in Caco-2 monolayers treated with TNF, in the presence of infliximab and/or endocytosis inhibitors.

    Results: Before infliximab treatment, colonic passage of HM427 [CD: 2475 CFU (450–3000); controls 1163(225–1950)] and 51Cr-EDTA permeability were increased in CD (p < .05), but were restored to control levels by infliximab (CD: 150 (18.8–1069)). In TNF-exposed Caco-2 monolayers HM427 transport and lipid rafts/HM427 co-localization was decreased by infliximab. The lipid raft inhibitor methyl-β-cyclodextrin decreased HM427 transport.

    Conclusion: Infliximab restored the colonic barrier to AIEC in CD; an effect partially mediated by blocking lipid rafts in epithelial cells. This ability likely contributes to infliximab’s clinical efficacy in colonic CD.

  • 17.
    Zdolsek, Johann
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Hand- och plastikkirurgiska kliniken US.
    Enebog, J.
    Wallon, Conny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Kald, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    A prospective evaluation of the PerFix® Plug technique for groin hernia repair2000Inngår i: Hernia, ISSN 1265-4906, E-ISSN 1248-9204, Vol. 4, nr 4, s. 311-315Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    The aim of the study was to prospectively evaluate complication rates, sick-leave, recurrence rate, and chronic post-operative pain after mesh-plug hernia repair. All 385 consecutive inguinal hernias (373 patients) operated at our department with the PerFix® Plug from September 1996 to December 1997 were included in the study. Follow-up included a questionnaire 3 and 12 months after the repair. Replies to the both of these questionnaires were obtained from 363 of 373 patients (98%). All patients who either reported a lump or sensory disturbance in the operated groin were offered a clinical examination. A third questionnaire focusing on chronic post-operative pain was completed by 77 of 90 patients reporting groin pain. The recurrence rate was 2% (9/385). After 25 months (17-36 months) 38 patients (10%) still experienced inguinal pain to some degree. In 7 male patients there was either pain or discomfort during sexual activities. In a patient with poorly controlled ascites the plug was removed. Day-case surgery was performed in 86% of patients with epidural or local anaesthesia, and 64% in general- or spinal anaesthesia. Employed/self-employed patients were off work for a median of 7 days (0-65). The median time to full recovery for all patients was 20 days. Conclusion: Mesh-plug hernia repair has a reasonably low complication rate together with quick recovery in a non-specialised surgical setting. Chronic inguinal pain is, however, still present to some degree in 10% of patients after two years.

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