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  • 1.
    Cock, C.
    et al.
    Gastroenterology & Hepatology, Flinders Medical Centre, Bedford Park SA, Australia; School of Medicine, Flinders University of South Australia, Adelaide, Australia.
    Doeltgen, S. H.
    Speech Pathology, School of Health Sciences, Flinders University of South Australia, Adelaide, Australia.
    Omari, T.
    School of Medicine, Flinders University of South Australia, Adelaide, Australia; Human Physiology, Medical Science and Technology, Flinders University of South Australia, Adelaide, Australia.
    Savilampi, Johanna
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Anaesthesiology and Intensive Care, Örebro University Hospital, Örebro, Sweden.
    Effects of remifentanil on esophageal and esophagogastric junction (EGJ) bolus transit in healthy volunteers using novel pressure-flow analysis2018In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 30, no 2, article id e13191Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Remifentanil is associated with subjective dysphagia and an objective increase in aspiration risk. Studies of opioid effects have shown decreased lower esophageal sphincter relaxation. We assessed bolus transit through the esophagus and esophagogastric junction (EGJ) during remifentanil administration using objective pressure-flow analysis.

    METHODS: Data from 11 healthy young participants (23±3 years, 7 M) were assessed for bolus flow through the esophagus and EGJ using high-resolution impedance manometry (Manoscan™, Sierra Scientific Instruments, Inc., LES Angeles, CA, USA) with 36 pressure and 18 impedance segments. Data were analyzed for esophageal pressure topography and pressure-flow analysis using custom Matlab analyses (Mathworks, Natick, USA). Paired t tests were performed with a P-value of < .05 regarded as significant.

    KEY RESULTS: Duration of bolus flow through (remifentanil/R 3.0±0.3 vs baseline/B 5.0 ± 0.4 seconds; P < .001) and presence at the EGJ (R 5.1 ± 0.5 vs B 7.1 ± 0.5 seconds; P = .001) both decreased during remifentanil administration. Distal latency (R 5.2 ± 0.4 vs B 7.5 ± 0.2 seconds; P < .001) and distal esophageal distension-contraction latency (R 3.5 ± 0.1 vs B 4.7 ± 0.2 seconds; P < .001) were both reduced. Intrabolus pressures were increased in both the proximal (R 5.3 ± 0.9 vs B 2.6 ± 1.3 mm Hg; P = .01) and distal esophagus (R 8.6 ± 1.7 vs B 3.1 ± 0.8 mm Hg; P = .001). There was no evidence of increased esophageal bolus residue.

    CONCLUSIONS AND INFERENCES: Remifentanil-induced effects were different for proximal and distal esophagus, with a reduced time for trans-sphincteric bolus flow at the EGJ, suggestive of central and peripheral μ-opioid agonism. There were no functional consequences in healthy subjects.

  • 2.
    Cock, C.
    et al.
    Department of Gastroenterology & Surgery, Flinders University, Adelaide, Australia.
    Doeltgen, S.
    Department of Speech Pathology, Flinders University, Adelaide, Australia.
    Omari, T. I.
    Department of Gastroenterology & Surgery, Flinders University, Adelaide, Australia; Department of Human Physiology, Flinders University, Adelaide, Australia .
    Savilampi, Johanna
    Örebro University, School of Medical Sciences.
    Remifentanil induced changes in esophageal and esophagogastric junction (EGJ) bolus transport in healthy volunteers2016In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 28, no S1, p. 68-68Article in journal (Other academic)
  • 3.
    Dlugosz, A.
    et al.
    Department of Medicine and Center for Digestive Diseases, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Nowak, P.
    Department of Medicine, Unit of Infectious Diseases, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    D'Amato, M.
    Department of Biosciences and Nutrition, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Mohammadian Kermani, G.
    Department of Medicine and Center for Digestive Diseases, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Nyström, J.
    Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Abdurahman, Samir
    Örebro University, School of Science and Technology.
    Lindberg, G.
    Department of Medicine and Center for Digestive Diseases, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Increased serum levels of lipopolysaccharide and antiflagellin antibodies in patients with diarrhea-predominant irritable bowel syndrome2015In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 27, no 12, p. 1747-1754Article in journal (Refereed)
    Abstract [en]

    Background: Innate immune responses to conserved microbial products such as lipopolysaccharide (LPS) and flagellin are likely important in microbial-host interactions and intestinal homeostasis. We hypothesized that bacterial translocation and activation of mucosal immunity against common microbial antigens might be involved in the development of irritable bowel syndrome (IBS). We therefore compared serum levels of LPS, soluble CD14 (sCD14), and flagellin antibodies between patients with different subtypes of IBS and healthy controls.

    Methods: We analyzed serum obtained from 88 patients (74 females) aged 19(43)-73 years and 106 healthy volunteers (77 females) aged 19(38)-62 years. Diarrhea-predominant IBS (D-IBS) was present in 32 patients (36%), 23 patients (26%) had constipation-predominant IBS (C-IBS), and 33 patients (38%) had A-IBS. We used ELISA for sCD14 and antiflagellin immunoglobulin G and limulus amebocyte assay for LPS. Abdominal symptoms and psychiatric comorbidities were assessed using validated questionnaires.

    Key Results: We found a significantly higher serum level of LPS in patients with D-IBS compared to controls (p = 0.0155). The level of antibodies to flagellin was higher in patients with IBS than in controls (mainly driven by higher levels in D-IBS, p = 0.0018). The levels of sCD14 were lower in D-IBS patients compared to controls (p = 0.0498). We found a weak, but significant correlation between the levels of antiflagellin antibodies and anxiety among IBS patients ( = 0.38; p = 0.0045).

    Conclusions & Inferences: Our results support the concept that immune reactivity to luminal antigens may have a role in the development of D-IBS. The serum level of antiflagellin antibodies was found to correlate with patients' self-reported anxiety score.

  • 4.
    Sundin, Johanna
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Brummer, Robert
    Örebro University, School of Medicine, Örebro University, Sweden.
    Hultgren Hörnquist, Elisabet
    Örebro University, School of Medicine, Örebro University, Sweden.
    Rangel, Ignacio
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Increased number of double positive CD3+ CD8+ CD4+ lamina propria T lymphocyte in gut mucosa of post infectious IBS patients compared to healthy controls2012In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 24, no Suppl. 2, p. 104-105Article in journal (Other academic)
    Abstract [en]

    Objective: Irritable bowel syndrome (IBS) developed after a gastroenteritis is denoted post infectious IBS (PI-IBS) and is thought to represent a specific patho-physiological entity. Naive CD8+CD45RA+cytotoxic T lymphocytes recognize antigen derived from intracellular bacteria and viruses. Naive CD4+CD45RA+helper T lymphocytes are activated by the antigen from extracellular microorganisms with the help of antigen-presenting cells. Activated CD4+CD45RO+helper T lymphocytes help phagocytes to kill microbes and activate naive B lymphocytes.

    Aim: To characterize subsets of mucosal lymphocytes in PI-IBS with flow cytometry analysis as a lead in identifying new therapeutic methods.

    Methods: 5 PI-IBS patients and 6 healthy individuals were recruited. We performed a distal colonoscopy without bowel cleansing or other preparation. Lamina propria lymphocytes (LPL) and intra-epithelial lymphocytes (IEL) were isolated from sigmodal biopsies and sub classified by CD3, CD4, CD8, CD45RO and CD45RA with flow cytometry.

    Results: We observed a significant deference (P < 0.01, two-tailed Mann–Whitney test) in double positive CD3+CD8+CD4+LPL between PI-IBS patient and healthy controls. We also observed a trend towards increased frequency of CD3+CD4+LPL in PI-IBS patients. Additionally, PI-IBS patients showed an increased frequency of CD3+CD8+LPL and IEL. The proportion of memory / activated CD45RO+CD4+LPL was higher in PI-IBS patients, and its proportion of the CD8+population was lower compared with the healthy controls. On the contrary the proportion of naive CD45RA+CD4+LPL was lower in PI-IBS patients compared with healthy controls. However, we found no differences in the distribution naı¨ve / activated CD4+ and CD8+IEL between PI-IBS patients and healthy controls.

    Conclusion: The difference in double positive (DP) CD3+CD8+CD4+LPL seen between PI-IBS patient and healthy controls is consistent with findings of increased number DP T cells in target organs in immuno-inflammatory conditions. Our analysis revealed that the normal gut has a greater variation in the prevalence of CD3+CD4+and CD4+CD45RO+LPL than that of PI-IBS patients. These findings confirm aberrant mucosal subsets of lymphocytes. However, more subjects need to be included in the study in order to draw firm conclusions.

  • 5.
    Uusijärvi, A.
    et al.
    Astrid Lindgren's Childrens Hosp, Karolinska Univ Hosp, Stockholm, Sweden; Dept Clin Sci & Educ, Södersjukhuset, Karolinska Inst, Stockholm, Sweden.
    Bergström, A.
    Inst Environm Med, Karolinska Inst, Stockholm, Sweden.
    Simrén, M.
    Inst Med, Dept Internal Med, Sahlgrenska Acad, Univ Gothenburg, Gothenburg, Sweden.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Pediatric Department, Örebro University Hospital, Örebro, Sweden.
    Kull, I.
    Dept Clin Sci & Educ, Södersjukhuset, Karolinska Inst, Stockholm, Sweden; Inst Environm Med, Karolinska Inst, Stockholm, Sweden; Sachs Children & Youth Hosp, Södersjukhuset, Stockholm, Sweden.
    Wickman, M.
    Inst Environm Med, Karolinska Inst, Stockholm, Sweden; Sachs Children & Youth Hosp, Södersjukhuset, Stockholm, Sweden.
    Alm, J.
    Dept Clin Sci & Educ, Södersjukhuset, Karolinska Inst, Stockholm, Sweden; Sachs Children & Youth Hosp, Södersjukhuset, Stockholm, Sweden.
    Olén, O.
    Dept Clin Sci & Educ, Södersjukhuset, Karolinska Inst, Stockholm, Sweden; Dept Med, Clin Epidemiol Unit, Karolinska Inst, Stockholm, Sweden; Sachs Children & Youth Hosp, Södersjukhuset, Stockholm, Sweden.
    Use of antibiotics in infancy and childhood and risk of recurrent abdominal pain-a Swedish birth cohort study2014In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 26, no 6, p. 841-850Article in journal (Refereed)
    Abstract [en]

    Background: The etiology of recurrent abdominal pain of functional origin (AP) is largely unknown. Antibiotic treatment influences the intestinal microbiota, and a few studies have indicated an increased risk of AP in adults after antibiotic treatment. Corresponding data in children are lacking. The aim of this study was to explore the association between antibiotic treatment during childhood and AP at 12years.

    Methods: Two thousand seven hundred and thirty-two children from a Swedish, population-based birth cohort. Parents reported antibiotic use for the children between birth and 2years. Antibiotic use between 9 and 12years was collected from the Swedish Prescribed Drug Register. The children answered questionnaires regarding AP at age 12. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for AP at 12years as a function of antibiotic use.

    Key Results: Antibiotic treatment between 9 and 12years was not associated with AP at 12. Children who had received 3 courses, or broad-spectrum antibiotics between 9 and 12years had an increased risk of AP at 12, but these associations failed to reach statistical significance. Antibiotic treatment during both the first and the second year of life increased the risk of AP in girls at 12 (OR 1.65; 95% CI: 1.09-2.49), but not in boys or the whole cohort.

    Conclusions & Inferences: Antibiotic treatment does not seem to be a major risk factor for AP at 12years. However, we cannot exclude that repeated courses, especially to infant girls, or use of broad-spectrum antibiotics between 9 and 12years may be associated with an increased risk of AP.

  • 6. Vanhoutvin, S. A. L. W.
    et al.
    Troost, F. J.
    Kilkens, T. O. C.
    Lindsey, P. J.
    Hamer, H. M.
    Jonkers, D. M. A. E.
    Venema, K.
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences.
    The effects of butyrate enemas on visceral perception in healthy volunteers2009In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 21, no 9, p. 952-e76Article in journal (Refereed)
    Abstract [en]

    Fermentation of dietary fibres by colonic microbes leads to the production of short chain fatty acids (mainly propionate, butyrate and acetate), which are utilized by the colonic mucosa. Previous studies showed positive effects of butyrate on parameters of oxidative stress, inflammation and apoptosis. Recent studies in rats, however, showed that butyrate increased visceral sensitivity. The aim of this study was to determine the effects of physiologically relevant concentrations of butyrate on visceral perception in healthy human subjects. Eleven healthy volunteers participated in this randomized double-blind, placebo controlled cross-over study. The study consisted of three periods of 1 week each, in which the volunteers daily self-administered rectal enemas containing 100, 50 mmol L(-1) butyrate, or placebo (saline) prior to sleeping. A rectal barostat measurement was performed at the start and the end of each test period for the measurement of pain, urge and discomfort. Butyrate treatment resulted in a dose-dependent reduction of pain, urge and discomfort throughout the entire pressure range of the protocol. At a pressure of 4 mmHg, 50 and 100 mmol L(-1) butyrate concentrations resulted in a 23.9% and 42.1% reduction of pain scores, respectively, and the discomfort scores decreased by 44.2% and 69.0% respectively. At a pressure of 67 mmHg, 50 and 100 mmol L(-1) of butyrate decreased the pain scores by 23.8% and 42%, respectively, and discomfort scores 1.9% and 5.2% respectively. Colonic administration of butyrate, at physiologically relevant concentrations, dose-dependently decreases visceral sensitivity in healthy volunteers.

  • 7.
    Wall, Rebecca
    et al.
    Örebro University, School of Medical Sciences.
    Marques, Tatiana
    Örebro University, School of Medical Sciences.
    Edebol-Carlman, Hanna
    Örebro University, School of Medical Sciences.
    Sundin, J.
    University of Gothenburg, Gothenburg, Sweden.
    Vumma, R.
    Linnaeus University, Kalmar, Sweden.
    Rangel, Ignacio
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Altered expression of membrane transporters in colonic mucosa of patients with Irritable Bowel Syndrome (IBS) and Post-infectious (PI)-IBS compared to healthy subjects2017In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 29, no Suppl. 2, p. 107-108Article in journal (Other academic)
    Abstract [en]

    Background: Irritable bowel syndrome (IBS) affects 5%- 15% of adults in the general population, and is characterized by chronic recurrent abdominal pain and discomfort and associated with altered bowel habits. The pathophysiology of IBS is complex and not fully under-stood. Hence, treatment is often based on symptomatology rather than underlying physiological aberrancies.

    Objective: To compare the expression of membrane transporters in mucosal biopsies of healthy subjects, IBS patients and post- infectious (PI)- IBS patients.

    Methods: Mucosal biopsies were obtained from the unprepared sigmoid colon in 18 IBS patients, 9 PI- IBS patients and 10 healthy subjects. Total RNA was isolated and prepared for gene expression analyses using quantitative reverse- transcription polymerase chain reaction (qRT- PCR). We compared the expression of genes encoding membrane- spanning transporters, using GAPDH as a reference gene, and by using the comparative 2- ΔΔCt method.

    Results: Colonic expression of SCL7A5 and SLC3A2 (together com-prising the amino acid transporter LAT1+4F2hc) was significantly lower in IBS patients, but not in PI- IBS patients, compared to healthy controls (P<.001). The expression of SLC7A8 (LAT2) tended to be lower in IBS patients compared to controls (P=.06). Mucosal gene ex-pression of the short chain fatty acid transporter SMCT1 (SLC5A8) was lower in both IBS- patients and PI- IBS patients compared to healthy subjects (P<.01).

    Conclusions: The amino acid transporters LAT1 and LAT2 appeared to be affected in IBS patients, but not in PI- IBS patients, compared to healthy subjects, suggesting a possible alteration in amino acids transport in this patient group. Furthermore, our results suggest a lower uptake of short chain fatty acids in both IBS- and PI- IBS pa-tients. Altered expression of these transporters may be involved in the pathophysiology of IBS as well as being a potential biomarker of this aberration, and therefore deserves further study in IBS.

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