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  • 1. Abrahamsson, Hasse
    et al.
    Ostlund-Lindqvist, Ann-Margret
    Nilsson, Ralf
    Simren, Magnus
    Gillberg, Per-Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Altered bile acid metabolism in patients with constipation-predominant irritable bowel syndrome and functional constipation2008In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 43, no 12, p. 1483-1488Article in journal (Refereed)
    Abstract [en]

    Objective. Bile acids are derived from cholesterol and are potent physiological laxatives. The aim of this study was to investigate whether bile acid synthesis is altered in constipation. Material and methods. Female patients with constipation (23 IBS-C, 4 functional constipation (FC)) were studied and compared with non-constipated subjects (16 IBS-D, 20 healthy women). Body mass index (BMI), blood lipids, lanosterol, sitosterol, colonic transit (oro-anal transit time (OATT), reference=4.3 days) and stool frequency were measured. C4 (7--hydroxy-4-cholesten-3-one) levels reflecting bile acid synthesis were measured at 0800 h and 1300 h. Results. When all the groups of constipated and non-constipated subjects were compared, it was found that only stool frequency and OATT differed between groups (p 0.001). When constipated patients were categorized according to OATT, absence of the usual C4 increase at lunchtime was noted in 82% of patients with delayed OATT compared with 17% in subjects with normal OATT (p 0.001). Symptom severity did not differ between groups. A subset of the patients with severely delayed OATT had markedly elevated C4 levels. Conclusions. Patients with IBS-C and FC have marked changes in bile acid synthesis in relation to colonic transit. The diurnal rhythm is altered in the slow transit colon when there is no C4 peak at lunchtime. Alterations in bile acid metabolism may be implicated in the pathophysiology of constipation.

  • 2. Acosta, Stefan
    et al.
    Ögren, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Sternby, Nils-Herman
    Bergqvist, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Fatal colonic ischaemia: A population-based study2006In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 41, no 11, p. 1312-1319Article in journal (Refereed)
    Abstract [en]

    Objectives. To estimate the incidence of fatal colonic ischaemia (CI) and the cause-specific mortality of CI, and to describe the localization and extension of colonic infarction and quantify the risk factors associated with CI. Material and methods. Between 1970 and 1982 the autopsy rate in Malmo, Sweden, was 87%, creating the possibilities for a population-based study. Out of 23,446 clinical autopsies, 997 cases were coded for intestinal ischaemia in a database. In addition, 7569 forensic autopsy protocols were analysed. In a case-control study nested in the clinical autopsy cohort, four CI-free controls, matched for gender, age at death and year of death, were identified for each fatal CI case in order to evaluate the risk factors. Results. The cause-specific mortality ratio was 1.7/1000 autopsies. The overall incidence of autopsy-verified fatal CI was 1.7/100,000 person years, increasing with age up to 23/100,000 person years in octogenarians. Fatal cardiac failure (odds ratio (OR) 5.2), fatal valvular disease (OR 4.3), previous stroke (OR 2.5) and recent surgery (OR 3.4) were risk factors for fatal CI. Narrowing/occlusion of the inferior mesenteric artery (IMA) at the aortic origin was present in 68% of the patients. The most common segments affected by transmural infarctions were the sigmoid (83%) and the descending (77%) colon. Conclusions. Heart failure, atherosclerotic occlusion/stenoses of the IMA and recent surgery were the main risk factors causing colonic hypoperfusion and infarction. Segments of transmural infarctions were observed within the left colon in 94% of the patients. Awareness of the diagnosis and its associated cardiac comorbidities might help to improve survival.

  • 3. Albuquerque, Joaquim F. S.
    et al.
    Ferra, Maria A.
    Portela-Gomes, Guida M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Adaptive changes of the enterochromaffin and gastrin cells in the rat gastrointestinal tract following subtotal colectomy2006In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 41, no 8, p. 963-968Article in journal (Refereed)
    Abstract [en]

    Objective. Colectomized patients often have diarrhoea and increased gastric acid secretion. Although serotonin influences gastrointestinal (GI) motility and secretion, GI serotonin-producing enterochromaffin (EC) cells have not been investigated after colectomy, nor have the antral gastrin cells. The aim of this experimental study was to investigate the GI tract in rats 8 weeks after subtotal colectomy, with particular emphasis on the frequency and distribution of EC and gastrin cells. Material and methods. Immunohistochemical techniques were used to identify the two endocrine cell types. Results. The colectomized animals had diarrhoea. Body-weight was lower and the small intestine shorter in the colectomized animals compared with sham-operated and untreated controls. In the two surgically treated groups, the antral mucosa was thinner and the small intestinal mucosa was thicker compared with that of the untreated rats, whereas the thickness of the rectum of the colectomized rats was increased compared with that of the control groups. In the colectomized animals, the number of EC cells was increased in the small intestine and rectum, whereas the numbers of both EC and gastrin cells were decreased in the antrum. Conclusions. The results indicate that colectomy exerts a significant influence on the GI mucosa and on the endocrine cell systems studied. An increased number of EC cells can result in alterations in motility and secretion, which may be important in the pathogenesis of the diarrhoea that often occurs after colectomy.

  • 4. Aleman, Soo
    et al.
    Endalib, Sanam
    Stål, Per
    Lööf, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Lindgren, Stefan
    Sandberg-Gertzen, Hanna
    Almer, Sven
    Olsson, Sigvard
    Danielsson, Åke
    Wallerstedt, Sven
    Hultcrantz, Rolf
    Health check-ups and family screening allow detection of hereditary hemochromatosis with less advanced liver fibrosis and survival comparable with the general population2011In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 46, no 9, p. 1118-1126Article in journal (Refereed)
    Abstract [en]

    Objective. The information concerning the morbidity and mortality of hereditary hemochromatosis is based primarily on clinical cohorts of symptomatic patients. The major aim of this study was to analyze the long-term prognosis for Swedish patients with this condition, with respect to both clinical features and survival, in relation to the route by which the disease was detected.

    Patients and methods. 373 patients with hemochromatosis detected through routine health checkups (n = 153), family screening (n = 44), symptoms of arthralgia (n = 23), investigation of other diseases/symptoms (n = 108) or signs of liver disease (n = 45) were monitored for a mean period of 11.9 +/- 5.8 years. The degree of liver fibrosis and survival were analyzed.

    Results. Overall survival among these patients was not significantly different from that of a matched normal population. The patients diagnosed through health check-ups and family screening were detected at an earlier age and had the highest rate of survival. Liver biopsy at the time of diagnosis revealed cirrhosis in 9% of those detected through the health check-ups and 5% in the case of family screening, compared with 13% for the group with arthralgia, 17% for other diseases/symptoms and 42% for liver disease.

    Conclusion. Health check-ups and family screening allow detection of hereditary hemochromatosis at an earlier age and with less advanced liver fibrosis, although a few of these patients have already developed cirrhosis. Our study indicates that iron indices should be included in health check-ups, and if abnormal, should lead to further investigation.

  • 5.
    Amcoff, Karin
    et al.
    Univ Orebro, Fac Med & Hlth, Dept Gastroenterol, SE-70182 Orebro, Sweden..
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Magnuson, Anders
    Univ Orebro, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden..
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    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 time2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 3, p. 344-350Article in journal (Refereed)
    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.

  • 6. Aro, P.
    et al.
    Ronkainen, J.
    Storskrubb, T.
    Bolling-Sternevald, E.
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Talley, N.J.
    Junghard, O.
    Johansson, S.E.
    Wiklund, I.
    Agréus, L.
    Validation of the translation and cross-cultural adaptation into Finnish of the Abdominal Symptom Questionnaire, the Hospital Anxiety and Depression Scale and the Complaint Score Questionnaire2004In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 39, no 12, p. 1201-8Article in journal (Refereed)
  • 7.
    Atuma, C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Engstrand, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Physiology.
    Holm, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Physiology.
    Helicobacter pylori extracts reduce gastric mucosal blood flow by a nitric oxide-independent but mast cell- and platelet-activating factor receptor-dependent pathway in rats1999In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 34, no 12, p. 1183-1189Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We have previously shown that water extracts from Helicobacter pylori reduce gastric mucosal blood flow by approximately 15%. It has also been suggested that H. pylori can inhibit endogenous nitric oxide (NO) biosynthesis. Our aim was to examine whether the reduction in blood flow induced by H. pylori is the direct consequence of an NO synthase inhibition and the possible involvement of mast cell degranulation.

    METHODS: A water extract was produced from wildtype strain 88-23. The extract was applied on the exteriorized gastric corporal mucosa in inactin-anesthetized rats, after removing as much as possible of the mucus layer, during intravital microscopy. Blood flow was measured with laser-Doppler flowmetry.

    RESULTS: In rats pretreated with the NO synthase inhibitor N-nitro-L-arginine there was a 19% +/- 6% reduction in blood flow 40 min after application of the extract, and a 27% +/- 9% reduction after another 20 min with saline. The reduction was abolished by concomitant pretreatment with the mast cell stabilizer ketotifen or the platelet-activating factor (PAF) receptor antagonist WEB2086.

    CONCLUSION: The reduction in mucosal blood flow induced by the extract was probably mediated through an acute inflammatory response involving mast cell degranulation with consequent PAF secretion. The effect on blood flow was not the result of a decrease in vascular tone due to an inhibition of endogenous NO biosynthesis.

  • 8.
    Atuma, Christer
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Physiology.
    Engstrand, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Physiology.
    Holm, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Physiology.
    Extracts of Helicobacter pylori reduce gastric mucosal blood flow through a VacA- and CagA-independent pathway in rats1998In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 33, no 12, p. 1256-1261Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Helicobacter pylori may interfere with gastroduodenal protective mechanisms. Such effects could be due to a direct interaction with gastric epithelial cells but also to the action of a wide range of secreted and membrane-bound virulence factors. Our aim was to study the acute effects of water extracts produced from H. pylori on gastric mucosal blood flow and acid secretion and to relate them to VacA and CagA activity.

    METHOD: Extracts were produced from strains 88-23 and A5, both wild type; A5VacA, an isogenic mutant lacking expression of the vacuolating cytotoxin (VacA) and the immunodominant antigen (CagA); and Escherichia coli strain ATCC-25922. Bacterial extracts were applied on the exteriorized gastric corporal mucosa in inactin-anaesthetized rats after removal of as much as possible of the mucus layer, during intravital microscopy. Blood flow was measured by means of laser-Doppler flowmetry.

    RESULTS: All H. pylori extracts, including the extract from 88-23 heated to 100 degrees C for 30 min, significantly reduced blood flow by 15%-19%, whereas E. coli had no significant effect on blood flow.

    CONCLUSION: A factor or a combination of factors, other than VacA and CagA released from H. pylori, might compromise the natural defence of the gastric corporal mucosa by reducing mucosal blood flow. The factor is heat-stable and lacking or less potent in E. coli.

  • 9. Bajor, Antal
    et al.
    Gillberg, Per-Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Abrahamsson, Hasse
    Bile acids: short and long term effects in the intestine2010In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 45, no 6, p. 645-664Article, review/survey (Refereed)
    Abstract [en]

    Bile acids have secretory, motility and antimicrobial effects in the intestine. In patients with bile acid malabsorption the amount of primary bile acids in the colon is increased compared to healthy controls. Deoxycholic acid is affecting the intestinal smooth muscle activity. Chenodeoxycholic acid has the highest potency to affect intestinal secretion. Litocholic acid has little effect in the lumen of intestine compared to both deoxycholic acid and chenodeoxycholic acid. There is no firm evidence that clinically relevant concentrations of bile acids induce colon cancer. Alterations in bile acid metabolism may be involved in the pathophysiology of constipation.

  • 10.
    Bandstein, Marcus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Mwinyi, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Ernst, Barbara
    eSwiss Medical & Surgical Center, Interdisciplinary Obesity Center, St. Gallen, Switzerland..
    Thurnheer, Martin
    eSwiss Medical & Surgical Center, Interdisciplinary Obesity Center, St. Gallen, Switzerland..
    Schultes, Bernd
    eSwiss Medical & Surgical Center, Interdisciplinary Obesity Center, St. Gallen, Switzerland.
    Schiöth, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    A genetic variant in proximity to the gene LYPLAL1 is associated with lower hunger feelings and increased weight loss following Roux-en Y gastric bypass surgery2016In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 51, no 9, p. 1050-1055Article in journal (Refereed)
    Abstract [en]

    Objective: Bariatric surgery is the most efficient treatment of severe obesity. We investigated to what extent BMI- or waist-hip ratio (WHR)-related genetic variants are associated with excess BMI loss (EBMIL) two years after Roux-en-Y gastric bypass (RYGB) surgery, and elucidated the affected biological pathways.

    Methods: Two-hundred fifty-one obese patients (age: 4310.7, preoperative BMI: 45.16.1kg/m(2), 186 women) underwent RYGB surgery and were followed up after two years with regard to BMI. Patients were genotyped for 32 single-nucleotide polymorphisms (SNPs) that were investigated with regard to their impact on response to RYGB and preoperatively measured Three Factor Eating Questionnaire (TFEQ) scores.

    Results: Homozygous T carriers of the SNP rs4846567 in proximity to the Lysophospholipase-like 1 (LYPLAL1) gene showed a 7% higher EBMIL compared to wild-type and heterozygous carriers (p=0.031). TT-allele carriers showed furthermore lower scores for Hunger (74%, p<0.001), lower Disinhibition (53%, p<0.001), and higher Cognitive restraint (21%, p=0.017) than GG/GT carriers in the TFEQ. Patients within the lowest quartile of Hunger scores had a 32% greater EBMIL compared to patients in the highest quartile (p<0.001).

    Conclusion: The LYPLAL1 genotype is associated with differences in eating behavior and loss of extensive body weight following RYGB surgery. Genotyping and the use of eating behavior-related questionnaires may help to estimate the RYGB-associated therapy success.

  • 11. Benno, Peter
    et al.
    Bark, Johan
    Collinder, Eje
    Hellström, Per M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Midtvedt, Tore
    Norin, Elisabeth
    Major alterations in metabolic activity of intestinal microflora in Crohn's disease2012In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 47, no 2, p. 251-252Article in journal (Refereed)
  • 12. Bergström, M
    et al.
    Lu, L
    Marquez, M
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Catechol-O-Methyltransferase Inhibition Increases the Uptake of 11C-3-(3,4-Dihydroxyphenyl)-L-Alanine in the Rat PancreasRead1996In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 31, no 12, p. 1216-1222Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The objective of the present investigation was to evaluate the uptake and metabolism of 3-(3,4-dihydroxyphenyl-L-alanine) (L-DOPA) in the rat pancreas.

    METHODS:

    The procedure included intravenous injection of the positron-emitting radiotracer L-[beta-11C] DOPA (DOP) into unanaesthetized male Sprague-Dawley rats and evaluation of uptake of radioactivity in organs in animals only given the tracer and in animals given therapeutic doses of three different catechol-O-methyltransferase (COMT) inhibitors, OR-486, OR-611, or Ro 41-0960. Selected pancreati were homogenized, and the chemical form bearing the radioactivity was analysed with high-performance liquid chromatography (HPLC).

    RESULTS:

    The main finding was that the tracer uptake in the pancreas increased fourfold when the rats were pretreated with COMT inhibitors. Half maximum effect of OR-486 was found at a dose of 0.2 mg/kg. HPLC analysis showed that with COMT inhibitor, the radioactivity in the pancreas consisted of 90% DOPAC. When administering MAO-A and COMT inhibitor together, the pancreas radioactivity corresponded to dopamine. Also in the pig pancreas a significant increase of DOP was observed after COMT inhibition.

    CONCLUSIONS:

    This study has shown a high turnover of L-DOPA in the rat pancreas, which can be modulated to give enhanced levels of DOPAC or dopamine by COMT and MAO inhibition.

  • 13. Borssen, Asa Danielsson
    et al.
    Almer, Sven
    Prytz, Hanne
    Wallerstedt, Sven
    Friis-Liby, Inga-Lill
    Bergquist, Annika
    Nyhlin, Nils
    Hultcrantz, Rolf
    Sangfelt, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    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 patients2015In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 50, no 2, p. 217-223Article in journal (Refereed)
    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.

  • 14.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    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 hepatitis2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 9, p. 1022-1028Article in journal (Refereed)
    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.

  • 15.
    Chabok, Abbas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Smedh, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nilsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Stenson, Marianne
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    CT-colonography in the follow-up of acute diverticulitis: patient acceptance and diagnostic accuracy2013In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 48, no 8, p. 979-986Article in journal (Refereed)
    Abstract [en]

    Objective. The aim of this study was to assess CT-colonography (CTC) in the follow-up of diverticulitis regarding patient acceptance and diagnostic accuracy for diverticular disease, adenomas and cancer, with colonoscopy as a reference standard. Methods. A prospective comparative study where half of the patients underwent colonoscopy first, followed immediately by CTC. The other half had the examinations in the reverse order. Patient experiences and findings were registered after every examination, blinded to the examiner. Results. Of a total of 110 consecutive patients, 108 were included in the study, with a median age of 56 years (range 27-84). The success rate was 91% for colonoscopy and 86% for CTC. Examination time was 25 mm for both methods. The mean time for CTC evaluation was 20 mm. Eighty-three per cent of the patients received sedation during colonoscopy. Despite this, patients experienced colonoscopy as more painful (p < 0.001) and uncomfortable (p < 0.001). Diverticulosis and polyps were detected in 94% and 20% with colonoscopy and in 94% and 29% with CTC, respectively. Sensitivity and specificity for CTC in the detection of diverticulosis was 99% and 67%, with a good agreement (kappa = 0.71). Regarding detection of polyps, the sensitivity and specificity were 47% and 75%, with a poor agreement (kappa = 0.17). No cancer was found. Conclusion. CTC was less painful and unpleasant and can be used for colonic investigation in the follow-up of diverticulitis. CTC detected diverticulosis with good accuracy while the detection accuracy of small polyps was poor. CTC is a viable alternative, especially in case of incomplete colonoscopy or in a situation with limited colonoscopy resources.

  • 16.
    Chabok, Abbas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Tärnberg, Maria
    Smedh, Kennet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nilsson, Lennart E
    Lindberg, Christian
    Hanberger, Håkan
    Prevalence of fecal carriage of antibiotic-resistant bacteria in patients with acute surgical abdominal infections2010In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 45, no 10, p. 1203-1210Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Antibiotic resistance is increasing worldwide. The aims of the current study were to determine the fecal carriage of antibiotic-resistant bacteria and antibiotic treatment in surgical patients admitted to hospital due to acute intra-abdominal infections.

    MATERIALS AND METHODS:

    Eight Swedish surgical units participated in this prospective multicenter investigation. Rectal swabs were obtained on admission to hospital. Cultures were performed on chromogenic agar and antibiotic susceptibility testing was performed using the disk diffusion method. Extended-spectrum beta-lactamase (ESBL)-phenotype was confirmed by Etest.

    RESULTS:

    Rectal samples were obtained and analyzed from 208 patients with intra-abdominal surgical infections. Surgery was performed in 134 patients (65%). Cephalosporins were the most frequently used empirical antibiotic therapy. The highest rates of resistance among Enterobacteriaceae were detected for ampicillin (54%), tetracycline (26%), cefuroxime (26%) and trimethoprim-sulfamethoxazole (20%). The prevalence of decreased susceptibility (I + R) for the other antibiotics tested was for ciprofloxacin 20%, piperacillin-tazobactam 17%, cefotaxime 14%, ertapenem 12%, gentamicin 3% and imipenem 0%. ESBL-producing Enterobacteriaceae were found in samples from 10 patients (5%). Three patients had five E. coli isolates producing AmpC enzymes.

    CONCLUSIONS:

    This study shows a high rate of resistance among Enterobacteriaceae against antibiotics which are commonly used in Sweden and should have implications for the future choice of antibiotics for surgical patients.

  • 17. Darkahi, Bahman
    et al.
    Videhult, Per
    Sandblom, Gabriel
    Liljeholm, Haakan
    Ljungdahl, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Rasmussen, Ib Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Effectiveness of antibiotic prophylaxis in cholecystectomy: a prospective population-based study of 1171 cholecystectomies2012In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 47, no 10, p. 1242-1246Article in journal (Refereed)
    Abstract [en]

    Background.

    The aim of this study was to assess the benefit from antibiotic prophylaxis (AP) during cholecystectomy in a population-based cohort study.

    Methods.

    All cholecystectomies performed in Uppsala County, 2003-2005, were registered prospectively according to a standardized protocol. High-risk procedures (HP) were defined as operations for acute cholecystitis and procedures including exploration of the common bile duct. Infections requiring surgical or percutaneous drainage and non-surgical infections that prolonged hospital stay were defined as major infectious complications (IC).

    Results.

    Altogether 1171 patients underwent cholecystectomy. AP was given to 130 of 867 (15%) of the patients undergoing low-risk procedures (LP) and 205 of 304 (67%) of those undergoing H-R P. Major IC were seen in 6 of 205 (3%) of the patients undergoing H-R P with AP and 1 of 99 of the patients undergoing H-R P without AP. No major IC was seen after L-R P. Minor IC were seen after 5 of 205 (2%) HP with AP, 1 of 99 (1%) HP without AP, 0 of 130 (0%) LP with AP, and 2 of 737 (0.3%) LP without AP. In univariate logistic analysis, the overall risk for IC was found to be higher with AP (p < 0.05), but the increase did not remain significant if adjusting for age, gender, ASA class, H-R P/L-R P and surgical approach or limiting the analysis to major IC.

    Conclusion.

    There is no benefit from AP in uncomplicated procedures. The effectiveness of antibiotic prophylaxis in complicated cholecystectomy must be evaluated in randomized controlled trials.

  • 18.
    Emilsson, Össur Ingi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Univ Iceland, Fac Med, Reykjavik, Iceland.;Landspitali Univ Hosp, Dept Resp Med & Sleep, Reykjavik, Iceland..
    Benediktsdottir, Bryndis
    Univ Iceland, Fac Med, Reykjavik, Iceland.;Landspitali Univ Hosp, Dept Resp Med & Sleep, Reykjavik, Iceland..
    Olafsson, Isleifur
    Landspitali Univ Hosp, Dept Clin Biochem, Reykjavik, Iceland..
    Cook, Elizabeth
    Landspitali Univ Hosp, Dept Clin Biochem, Reykjavik, Iceland..
    Juliusson, Sigurdur
    Univ Iceland, Fac Med, Reykjavik, Iceland.;Landspitali Univ Hosp, Dept Ear Nose & Throat, Reykjavik, Iceland..
    Berg, Sören
    Lund Univ, Dept Otolaryngol & Head & Neck Surg, Lund, Sweden..
    Nordang, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Björnsson, Einar Stefan
    Univ Iceland, Fac Med, Reykjavik, Iceland.;Landspitali Univ Hosp, Dept Gastroenterol, Reykjavik, Iceland..
    Gudlaugsdottir, Sunna
    Landspitali Univ Hosp, Dept Gastroenterol, Reykjavik, Iceland..
    Gudmundsdottir, Anna Soffia
    Landspitali Univ Hosp, Dept Gastroenterol, Reykjavik, Iceland..
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Gislason, Thorarinn
    Univ Iceland, Fac Med, Reykjavik, Iceland.;Landspitali Univ Hosp, Dept Resp Med & Sleep, Reykjavik, Iceland..
    Definition of nocturnal gastroesophageal reflux for studies on respiratory diseases2016In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 51, no 5, p. 524-530Article in journal (Refereed)
    Abstract [en]

    Objective Nocturnal gastroesophageal reflux (nGER) has been associated with respiratory diseases. Our aim was to study a questionnaire method to identify nGER subjects with respiratory involvement in a general population. Material and methods A subgroup of Icelandic participants in the European Community Respiratory Health Survey III (ECRHS III) reporting symptoms of nGER (n =48) as well as age and gender paired controls (n =42) were studied further by a structured interview, questionnaires, laryngeal fibrescopy, and exhaled breath condensate. A subgroup underwent 24-h oesophageal pH impedance (24-h MII-pH) measurements. Symptoms of nGER were assessed with a modified version of the reflux disease questionnaire (RDQ), where symptoms were divided into daytime and nocturnal. A report of nGER both at baseline and at follow-up was defined as persistent nGER. Results Participants reporting persistent nGER had significantly more signs of laryngopharyngeal reflux according to the reflux finding score than those without nGER (Mean +/- SD: 5.1 +/- 2.3 vs. 3.9 +/- 2.2, p =0.02). Of the 16 persistent nGER subjects that underwent 24-h MII-pH, 11 had abnormal gastroesophageal reflux, but none of three control subjects (69% vs. 0%). Pepsin was more commonly found in exhaled breath condensate in the nGER group (67% vs. 45%, p =0.04). Conclusions Participants with nGER symptoms at least once a month, reported on two occasions, had a high level of positive 24-h MII-pH measurements, laryngeal inflammation and pepsin in exhaled breath condensate. This nGER definition identified a representable group for studies on nGER and respiratory diseases in a general population.

  • 19.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Thörn, Mari
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    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)2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 6-7, p. 722-729Article in journal (Refereed)
    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.

  • 20.
    Franck-Larsson, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Edebol Eeg-Olofsson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Axelson, Hans W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Rönnblom, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Physiological and structural anorectal abnormalities in patients with systemic sclerosis and fecal incontinence2014In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 49, no 9, p. 1073-1083Article in journal (Refereed)
    Abstract [en]

    Objective

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

    Materials and methods

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

    Results

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

    Conclusion

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

  • 21. Garcia Rodriguez, LA
    et al.
    Ruigomez, A
    Wallander, Mari-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Johansson, Saga
    Olbe, L
    Detection of colorectal tumor and inflammatory bowel disease duringfollow-up of patients with initial diagnosis of irritable bowel syndrome.2000In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 35, no 3, p. 306-311Article in journal (Refereed)
    Abstract [en]

    BACKGROUND

    We wanted to estimate the incidence of irritable bowel syndrome (IBS) and functional dyspepsia (FD) in the general population, and the detection of colorectal tumor (CRT) and inflammatory bowel disease (IBD) after the diagnosis of IBS and FD.

    METHODS

    Patients aged 20-79 years newly diagnosed with IBS (N = 2956) or FD (N = 9900), together with a comparison cohort randomly sampled from the general source population, were followed-up during a mean time of 3 years.

    RESULTS

    We found an overall incidence of 10.3 per 1000 person-years for FD and 2.6 per 1000 person-years for IBS. There was a greater prevalence of depression, stress, fatigue, and pain disorders among IBS and FD patients than in the general population. During the 1st year after a diagnosis of IBS the cumulative risk of detecting CRT was close to 1% in IBS patients. After the 1st year the risk of CRT in IBS patients was close to that in the general population. We found a significantly increased risk of detecting IBD among patients initially diagnosed as having IBS (relative risk (RR), 16.3; 95% confidence interval (CI), 6.6-40.7), which was constant during all the follow-up period. No association was found between dyspepsia and CRT, or IBD.

    CONCLUSION

    IBS and FD shared some comorbidity features, yet demographics and incidence rates were different. Unlike the detection of colorectal tumor, the excess risk of IBD after an initial diagnosis of IBS was cumulatively increased during all the follow-up period. The continuously increased risk of IBD detection in IBS patients favors a true association between IBS and IBD.

  • 22. Gillberg, L.
    et al.
    Varsanyi, M.
    Sjöström, M.
    Lördal, M.
    Lindholm, J.
    Hellström, Per M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Nitric oxide pathway-related gene alterations in inflammatory bowel disease2012In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 47, no 11, p. 1283-1297Article in journal (Refereed)
    Abstract [en]

    Objective: To reveal specific gene activation in nitric oxide (NO)-related inflammation we studied differential gene expression in inflammatory bowel disease (IBD). Methods. Total RNA was isolated from 20 biopsies of inflamed mucosa from Crohn's disease (CD) and ulcerative colitis (UC) patients each as well as from six controls, labeled with 32P-dCTP and hybridized to a human NO gene array. Significant genes were analyzed for functional gene interactions and heatmaps generated by hierarchical clustering. A selection of differentially expressed genes was further evaluated with immunohistochemical staining. Results. Significant gene expression differences were found for 19 genes in CD and 23 genes in UC compared to controls, both diseases with high expression of ICAM1 and IL-8. Correlation between microarray expression and corresponding protein expression was significant (r 0.47, p 0.002). Clustering analysis together with functional gene interaction analysis revealed clusters of coregulation and coexpression in CD and UC: transcripts involved in angiogenesis, inflammatory response mediated by the transcription factor hypoxia-inducible factor 1, and tissue fibrosis. Also, a fourth cluster with transcripts regulated by the transcription factor Sp1 was found in UC. Conclusions. Expression analysis in CD and UC revealed disease-specific regulation of NO-related genes, which might be involved in perpetuating inflammatory disease activity in IBD.

  • 23.
    Glimelius, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Cavalli-Bjorkman, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Metastatic colorectal cancer: Current treatment and future options for improved survival : Medical approach - present status2012In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 47, no 3, p. 296-314Article in journal (Refereed)
    Abstract [en]

    Background. Metastatic colorectal cancer has a poor prognosis, and the majority of patients are left with palliative measures. The development seen using medical treatments are reviewed.

    Material and methods. A systematic approach to the literature-based evidence of effects from palliative chemotherapy and targeted drugs was aimed at.

    Results. The continuous improvements during the past 20-25 years have been documented in several large conclusive trials. At the end of the 1980s, the evidence that chemotherapy should be used at all was very limited, whereas presently most patients can be offered three lines of chemotherapy with or without a targeted drug based upon good scientific evidence. Median survival in trials has gradually improved from about 6 months to above 24 months in the most recent trials. Survival in the populations has, however, not improved to the same extent. Several important issues remain to be solved, such as the best sequence of treatments, what regimens to use in various situations, when to start and when to stop if a response is seen, whether cure may be possible in a small subset of patients, and socioeconomic issues. Integration of surgery and other local methods have further improved outcome for some individuals, but must be fine-tuned.

    Conclusions. Progress has been rapid in advanced colorectal cancer. This is likely a result of well-designed trials in collaboration between academy and industry, showing a great interest in the disease. A multi-professional approach and future collaborations may hopefully introduce new treatment concepts, further improving outcome.

  • 24.
    Haenni, Arvo
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Sundberg, Birgitta
    Yazdanpanah, Nahid
    Viberg, Annika
    Olsson, Johan
    Effect of fat emulsion (Fabuless) on orocecal transit time in healthy men2009In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 44, no 10, p. 1186-1190Article in journal (Refereed)
    Abstract [en]

    Background. Given the growing prevalence of overweight and related health consequences, there is increased interest in the search for novel dietary strategies for weight control. A food ingredient, an emulsion based on palm and oat oil (Fabuless, previously known as Olibra), has been associated with short-term reductions of food intake, induction of satiety, alternation in the satiety hormones, as well as long-term effects on weight control. The mechanism by which it can exert these effects is so far unclear, though it has been suggested that the "ileal break'' may play a role in increasing gastrointestinal transit time. The aim of this study was to investigate the effects of this stable fat emulsion on orocecal transit time in healthy men. Material and methods. In a controlled, double-blind, cross-over-designed study, 15 healthy men (aged 20-59 years, body mass index (BMI) 22-28), randomly allocated to two treatments, consumed the stable fat emulsion or a milk fat in yoghurt during two days of investigation, with an interval of 1 week. Orocecal transit time was determined by following blood sulfapyridine levels, which is a metabolite of salazopyrine in the colon. Results. A statistically significant delay in the appearance of sulfapyridine in serum was obtained after active treatment versus control treatment, corresponding to a 45-min longer orocecal transit time due to fat emulsion consumption. Conclusions. This study provides the first evidence to suggest that this stable fat emulsion may affect the ileal brake mechanism by slowing down the gastrointestinal transit time, which might explain the weight control and appetite suppression previously observed in association with this emulsion.

  • 25.
    Hagström, Hannes
    et al.
    Karolinska Univ Hosp, Div Hepatol, Ctr Digest Dis, S-14186 Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Nasr, Patrik
    Linkoping Univ, Dept Gastroenterol & Hepatol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Ekstedt, Mattias
    Linkoping Univ, Dept Gastroenterol & Hepatol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Kechagias, Stergios
    Linkoping Univ, Dept Gastroenterol & Hepatol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Önnerhag, Kristina
    Skane Univ Hosp, Dept Gastroenterol & Hepatol, Malmo, Sweden..
    Nilsson, Emma
    Skane Univ Hosp, Dept Gastroenterol & Hepatol, Malmo, Sweden..
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Sheikhi, Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Marschall, Hanns-Ulrich
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden..
    Hultcrantz, Rolf
    Karolinska Univ Hosp, Div Hepatol, Ctr Digest Dis, S-14186 Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Stål, Per
    Karolinska Univ Hosp, Div Hepatol, Ctr Digest Dis, S-14186 Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Low to moderate lifetime alcohol consumption is associated with less advanced stages of fibrosis in non-alcoholic fatty liver disease2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 2, p. 159-165Article in journal (Refereed)
    Abstract [en]

    Background and aim: Moderate alcohol consumption has been associated with a lower risk of disease severity in non-alcoholic fatty liver disease (NAFLD). It is unclear if this reflects current or lifetime drinking, or can be attributed to confounders such as diet and exercise. We evaluated the impact of lifetime alcohol consumption on fibrosis severity in NAFLD. Methods: We prospectively enrolled 120 subjects with biopsy-proven NAFLD and through detailed questionnaires examined lifetime alcohol consumption, diet and physical activity. Main outcome measures were odds ratios (OR) for fibrosis stage, calculated through ordinal regression after adjustment for body mass index, diabetes mellitus type 2, smoking and age at biopsy. A biomarker for recent alcohol consumption, phosphatidyl ethanol (PEth) was sampled. Results: An increase in median weekly alcohol consumption to a maximum of 13 drinks per week was associated with lower fibrosis stage (adjusted OR for each incremental unit, 0.86; 95% CI, 0.76-0.97; p = .017). The lowest risk for fibrosis was found with the lowest odds seen in the top quartile of alcohol consumption (aOR 0.23; 95% CI 0.08-0.66; p = .006). Adding soft drink and coffee consumptions, and physical activity to the model did not change the estimates. Subjects with PEth >= 0.3 mu mol/L had higher ORs for a higher fibrosis stage (aOR 2.77; 95% CI 1.01-7.59; p = .047). Conclusion: Lifetime alcohol consumption with up to 13 units per week is associated with lower fibrosis stage in NAFLD. Elevated PEth is associated with higher stages of fibrosis.

  • 26.
    Haraldsson, Erik
    et al.
    Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden.;Karolinska Inst, CLINTEC, Div Surg, Stockholm, Sweden.;Skaraborg Hosp, Skovde, Sweden..
    Swahn, Fredrik
    Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden.;Karolinska Inst, CLINTEC, Div Surg, Stockholm, Sweden..
    Verbeke, Caroline
    Karolinska Inst, Dept Lab Med, Div Pathol, Stockholm, Sweden..
    Mattsson, Johanna S. M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Enochsson, Lars
    Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden.;Karolinska Inst, CLINTEC, Div Surg, Stockholm, Sweden..
    Ung, Kjell-Arne
    Skaraborg Hosp, Skovde, Sweden..
    Lundell, Lars
    Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden.;Karolinska Inst, CLINTEC, Div Surg, Stockholm, Sweden..
    Heuchel, Rainer
    Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden.;Karolinska Inst, CLINTEC, Div Surg, Stockholm, Sweden..
    Lohr, J. -Matthias
    Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden.;Karolinska Inst, CLINTEC, Div Surg, Stockholm, Sweden..
    Arnelo, Urban
    Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden.;Karolinska Inst, CLINTEC, Div Surg, Stockholm, Sweden..
    Endoscopic papillectomy and KRAS expression in the treatment of adenoma in the major duodenal papilla2015In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 50, no 11, p. 1419-1427Article in journal (Refereed)
    Abstract [en]

    Objective. The use of endoscopic papillectomy for resecting adenomas in the major duodenal papilla is increasing. This study focuses on the following three issues: Can endoscopic papillectomy be performed as a safe diagnostic and/or therapeutic procedure in biopsy-verified or suspected ampullary adenoma? Does expression of mutated KRAS in resected adenomatous tissue predict long-term outcome? What other factors may affect long-term outcome and should, therefore, be considered in decision making prior to endoscopic papillectomy? Material and methods. Thirty-six prospectively collected patients who underwent endoscopic papillectomy at Karolinska University Hospital between 2005 and 2014 were analyzed. Results. The rate of exact agreement between the histomorphological grading of the endoscopic biopsies and the papillectomy specimens was low (48%). Obstructive jaundice at presentation increased the risk of undetected adenocarcinoma (RR = 3.98; 95% CI = 1.46-10.85, p = 0.007). Lesions with malignancies were significantly larger (mean 30.6 mm) than those where only adenomas were found (mean 14.4 mm, p = 0.001). Mutated KRAS was detected in 9 of the 36 post-papillectomy specimens, including 4 of the 5 cases of ampullary adenocarcinoma. Eighteen cases were endoscopically cured after a mean follow-up period of 47 months (range 16-92 months). Conclusions. Endoscopic papillectomy is a valuable staging tool because of the limitations of endoscopic biopsy. Endoscopic papillectomy concomitantly offers a curative treatment for most patients with adenoma in the major duodenal papilla. Jaundice at presentation and large adenomas may indicate the presence of more advanced disease. Determination of mutated KRAS seems to be of limited value in predicting long-term outcome.

  • 27.
    Hellström, Per M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Hendolin, Panu
    Biohit Oyj, Clin Sci, Helsinki, Finland..
    Kaihovaara, Pertti
    Biohit Oyj, Clin Sci, Helsinki, Finland.;Univ Helsinki, Res Unit Acetaldehyde & Canc, Helsinki, Finland..
    Kronberg, Leif
    Abo Akad Univ, Johan Gadolin Proc Chem Ctr, Lab Organ Chem, Turku, Finland..
    Meierjohann, Axel
    Abo Akad Univ, Johan Gadolin Proc Chem Ctr, Lab Organ Chem, Turku, Finland..
    Millerhovf, Anders
    Univ Uppsala Hosp, Clin Trial Consultants, Uppsala, Sweden..
    Paloheimo, Lea
    Biohit Oyj, Clin Sci, Helsinki, Finland..
    Sundelin, Heidi
    Abo Akad Univ, Johan Gadolin Proc Chem Ctr, Lab Organ Chem, Turku, Finland..
    Syrjanen, Kari
    Biohit Oyj, Clin Sci, Helsinki, Finland..
    Webb, Dominic-Luc
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Salaspuro, Mikko
    Univ Helsinki, Res Unit Acetaldehyde & Canc, Helsinki, Finland..
    Slow-release L-cysteine capsule prevents gastric mucosa exposure to carcinogenic acetaldehyde: results of a randomised single-blinded, cross-over study of Helicobacter-associated atrophic gastritis2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 2, p. 230-237Article in journal (Refereed)
    Abstract [en]

    Introduction: Helicobacter-induced atrophic gastritis with a hypochlorhydric milieu is a risk factor for gastric cancer. Microbes colonising acid-free stomach oxidise ethanol to acetaldehyde, a recognised group 1 carcinogen. Objective: To assess gastric production of acetaldehyde and its inert condensation product, non-toxic 2-methyl-1,3-thiazolidine-4-carboxylic acid (MTCA), after alcohol intake under treatment with slow-release L-cysteine or placebo. Methods: Seven patients with biopsy-confirmed atrophic gastritis, low serum pepsinogen and high gastrin-17 were studied in a cross-over single-blinded design. On separate days, patients randomly received 200 mg slow-release L-cysteine or placebo with intragastric instillation of 15% (0.3 g/kg) ethanol. After intake, gastric concentrations of ethanol, acetaldehyde, L-cysteine and MTCA were analysed. Results: Administration of L-cysteine increased MTCA (p < .0004) and decreased gastric acetaldehyde concentrations by 68% (p < .0001). The peak L-cysteine level was 7552 +/- 2687 mu mol/L at 40 min and peak MTCA level 196 +/- 98 mu mol/L at 80 min after intake. Gastric L-cysteine and MTCA concentrations were maintained for 3 h. The AUC for MTCA was 11-fold higher than acetaldehyde, indicating gastric first-pass metabolism of ethanol. With placebo, acetaldehyde remained elevated also at low ethanol concentrations representing 'non-alcoholic' beverages and food items. Conclusions: After gastric ethanol instillation, slow-release L-cysteine eliminates acetaldehyde to form inactive MTCA, which remains in gastric juice for up to 3 h. High acetaldehyde levels indicate a marked gastric first-pass metabolism of ethanol resulting in gastric accumulation of carcinogenic acetaldehyde. Local exposure of the gastric mucosa to acetaldehyde can be mitigated by slow-release L-cysteine capsules.

  • 28. Håkansson, P
    et al.
    Andersson, Ingela
    AstraZeneca R&D Mo¨lndal, Discovery, Mo¨lndal, Sweden.
    Nyström, S
    Löfgren, L
    Amrot, L F
    Li, Hong
    Ontogenetic development and spatial distribution of the ileal apical sodium-dependent bile acid transporter and the ileal lipid-binding protein in apoE knockout and C57BL/6 mice2002In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 37, no 9, p. 1089-1096Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although apoE-/- mice are characterized by hypercholesterolemia, the bile acid enterohepatic circulation, which plays a crucial role in cholesterol homeostasis, has not been examined in these mice. The differences between apoE-/- and C57BL/6 mice in expression of the ileal ASBT and ILBP and in intestinal bile acid absorption were studied.

    METHODS: The intestinal tissues of the fetal, neonatal and post-weaning mice were processed for immunohistochemistry. Body retention and fecal excretion of 75SeHCAT were measured. The bile acid pool size and its composition were analysed by HPLC.

    RESULTS: In apoE-/- and C57BL/6 mice, the bile acid pool size was 75 +/- 13 and 78 +/- 13 micromol/ 100 g body weight, respectively, while the ratio of cholic acid/beta-muricholic acid was 1.8 +/- 0.3 and 1.4 +/- 0.3 (P < 0.05), respectively. The daily body retention of 75SeHCAT was 48% = 1.8% in C57 black mice and 58.4% +/- 2.7% in apoE-/- mice (P < 0.05). In both mouse strains, ASBT expression in the small intestine was found in the near-term fetal and post-weaning mice, while ILBP expression was found in all postnatal mice. In the post-weaning mice, ILBP expression was limited to the distal 25%-30% of the small intestine, while ASBT expression was limited to the distal 18%.

    CONCLUSIONS: The bile acid enterohepatic circulation in apoE-/- mice probably does not differ greatly from that in C57BL/6 mice.

  • 29. Ideström, Maja
    et al.
    Rubio, Carlos A
    Onelöv, Erik
    Henter, Jan-Inge
    Fagerberg, Ulrika L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Finkel, Yigael
    Pediatric Crohn's disease from onset to adulthood: granulomas are associated with an early need for immunomodulation2014In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 49, no 8, p. 950-7Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Childhood onset Crohn's disease (CD) is considered more aggressive than adult onset disease. Epithelioid cell granulomas in intestinal biopsies are one, non-obligate, criterion of CD. We investigated granulomas as markers of CD severity in children followed to adulthood.

    MATERIAL AND METHODS: Forty-five individuals with childhood onset CD were studied from diagnosis until attainment of final height, with data on disease location, medical and surgical management and with detailed growth data analyses. A blinded review of diagnostic biopsies was also performed.

    RESULTS: We found granulomas in 22/45 (49%) children at diagnosis, altogether in 28/45 (62%) patients during the disease course (median overall follow-up - 12.3 years, range 9.3-18). Granulomas were found in 9/11 (82%) with upper gastrointestinal involvement (cumulatively 17/20, 85%) (p = 0.017 and p = 0.006, respectively). The time from diagnosis to initiating immune modulating treatment (median 4.5 months, range 0-75) was shorter in the granuloma-positive group (16/22) compared to the granuloma-negative group (18/23) (median 33 months, range 2-105; p = 0.01). The median standard deviation score height at diagnosis and final adult height (both adjusted for target height) did not correlate to findings of granulomas.

    CONCLUSIONS: Epithelioid cell granulomas were associated with a shorter time to initiating immune modulating drugs, as a possible sign of more severe disease, but growth was not affected.

  • 30.
    Isacson, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Andreasson, Kalle
    Nikberg, Maziar
    Smedh, Kenneth
    Chabok, Abbas
    No antibiotics in acute uncomplicated diverticulitis: does it work?2014In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 49, no 12, p. 1441-1446Article in journal (Refereed)
    Abstract [en]

    Background. The first randomized multicenter study evaluating the need for antibiotic treatment in patients with acute uncomplicated diverticulitis (AUD) could not demonstrate any benefit gained from antibiotic use. The aim of this study was to review the application of the no antibiotic policy and its consequences in regard to complications and recurrence. Methods. This retrospective population-based cohort study included all patients diagnosed with all types of colonic diverticulitis during the year 2011 at Vastmanland Hospital Vasteras, Sweden. All medical records were carefully reviewed. Primary outcomes were the types of treatment adopted for diverticulitis, complications and recurrence. Results. In total, 246 patients with computer tomography-verified diverticulitis were identified, 195 with primary AUD and 51 with acute complicated diverticulitis. Age, sex, and temperature at admission were similar between the groups but there was a significant difference in white blood cell count, C-reactive protein, and length of hospital stay. In the AUD group, 178 (91.3%) patients were not treated with antibiotics. In this group, there were six (3.4%) readmissions but only two developed an abscess. Of the remaining 17 patients (8.7%) who were treated with antibiotics in the AUD group, one developed an abscess. Twenty-five (12.8%) patients in the AUD group presented with a recurrence within 1 year. Conclusion. The no-antibiotic policy for AUD is safe and applicable in clinical practice. The previous results of a low complication and recurrence rate in AUD are confirmed. There is no need for antibiotic treatment for AUD. What does this paper add to the literature? Despite published papers with excellent results, there are still doubts about patient safety against the policy to not use antibiotics in acute uncomplicated diverticulitis. This is the first paper, in actual clinical practice, to confirm that the no antibiotic policy for acute uncomplicated diverticulitis is applicable and safe.

  • 31. Janssen, Pieter
    et al.
    Nielsen, Maria Astin
    Hirsch, Ika
    Svensson, David
    Gillberg, Per-Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Hultin, Leif
    A novel method to assess gastric accommodation and peristaltic motility in conscious rats2008In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 43, no 1, p. 34-43Article in journal (Refereed)
    Abstract [en]

    Objective. To simultaneously study gastric accommodation and peristaltic motility in the whole stomach of conscious rats by measuring intragastric pressure (IGP) during test-meal infusion. Material and methods. After an overnight fast, a test-meal infusion system and a catheter to measure IGP were connected to a chronically implanted gastric fistula. IGP was measured during infusion of an X-ray-opaque, non-nutritious viscous test meal (0.25-2 ml min(-1)); gastric motility and emptying were assessed by X-ray fluoroscopy. Peristaltic motility-induced IGP waves were quantified as a motility index (wave amplitude divided by wavelength). Experiments were performed in Sprague-Dawley (SD) rats and in the high-anxiety Wistar Kyoto (WKY) rats. Moreover, the effects of 30 mg kg(-1) N-G-nitro-L-arginine methyl ester (L-NAME), 1 mg kg(-1) atropine or 20 mg kg(-1) molsidomine were tested in SD rats. Results. Compared with SD rats, IGP increased significantly faster during stomach distension in WKY rats, indicating impaired accommodation in the latter strain. Motility indices did not differ between the two strains. L-NAME significantly increased IGP during stomach distension, indicating decreased gastric accommodation. However, no change in motility indices was observed with L-NAME. Treatment with atropine significantly increased IGP and decreased motility indices, indicating decreased gastric accommodation and motility. Molsidomine significantly decreased IGP during stomach distension but did not affect motility. The results correspond to X-ray observations, and confirm literature data. Conclusions. We conclude that IGP measurement during test-meal infusion represents an efficient and novel method to compare gastric accommodation and peristaltic motility in the whole stomach of conscious rats.

  • 32. Jansson, C
    et al.
    Wallander, Mari-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Johansson, Saga
    Johnsen, R
    Hveem, K
    Stressful psychosocial factors and symptoms of gastroesophageal reflux disease: a population-based study in Norway2010In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 45, no 1, p. 21-29Article in journal (Refereed)
    Abstract [en]

    Objective. Adverse psychosocial factors, including work-related stress, are, like gastroesophageal reflux disease (GERD), increasing health problems in industrialized countries. The importance of clarifying the relation between psychosocial factors and GERD has been stressed, but there are few population-based studies. Material and methods. This was a population-based, cross-sectional, case-control study based on two health surveys conducted in the Norwegian county Nord-Trondelag in 1984-86 and 1995-97. GERD symptoms were assessed in the second survey, which included 65,333 participants, representing 70% of the county's adult population. The 3153 persons reporting severe GERD symptoms were defined as cases and the 40,2 10 persons without such symptoms were defined as controls. Data on psychosocial factors and potential confounders were collected using questionnaires. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Results. In models adjusted for age, sex, smoking, obesity and socioeconomic status, positive associations were observed between high job demands (OR 1.9, 95% CI 1.6-2.2), low job control (OR 1.1, 95% CI 1.0-1.2) and job strain (OR 1.9, 95% CI 1.6-2.4) and risk of GERD symptoms. Persons reporting low job satisfaction had a twofold (95% CI 1.6-2.5) increased risk of GERD compared to persons reporting high job satisfaction. Self pressure (OR 1.8, 95% CI 1.6-2.1) and time pressure (OR 2.0, 95% CI 1.7-2.4) were positively associated with GERD symptoms. These associations were attenuated after further adjustment for anxiety, depression, myocardial infarction, angina pectoris, stroke and insomnia, but remained statistically significant. Conclusions. This population-based study reveals a link between stressful psychosocial factors, including job strain, and GERD symptoms.

  • 33. Karling, Pontus
    et al.
    Abrahamsson, Hasse
    Dolk, Anders
    Hallböök, Olof
    Hellström, Per M.
    Knowles, Charles H
    Kjellström, Lars
    Lindberg, Greger
    Lindfors, Per-Johan
    Nyhlin, Henry
    Ohlsson, Bodil
    Schmidt, Peter T
    Sjölund, Kristina
    Sjövall, Henrik
    Walter, Susanne
    Function and dysfunction of the colon and anorectum in adults: Working team report of the Swedish Motility Group (SMoG)2009In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 44, no 6, p. 646-660Article in journal (Refereed)
    Abstract [en]

    Symptoms of fecal incontinence and constipation are common in the general population. These can, however, be unreliably reported and are poorly discriminatory for underlying pathophysiology. Furthermore, both symptoms may coexist. In the elderly, fecal impaction always must be excluded. For patients with constipation, colon transit studies, anorectal manometry and defecography may help to identify patients with slow-transit constipation and/or pelvic floor dysfunction. The best documented medical treatments for constipation are the macrogols, lactulose and isphagula. Evolving drugs include lubiprostone, which enhances colonic secretion by activating chloride channels. Surgery is restricted for a highly selected group of patients with severe slow-transit constipation and for those with large rectoceles that demonstrably cause rectal evacuatory impairment. For patients with fecal incontinence that does not resolve on antidiarrheal treatment, functional and structural evaluation with anorectal manometry and endoanal ultrasound or magnetic resonance (MR) of the anal canal may help to guide management. Sacral nerve stimulation is a rapidly evolving alternative when other treatments such as biofeedback and direct sphincter repair have failed. Advances in understanding the pathophysiology as a guide to treatment of patients with constipation and fecal incontinence is a continuing important goal for translational research. The content of this article is a summary of presentations given by the authors at the Fourth Meeting of the Swedish Motility Group, held in Gothenburg in April 2007.

  • 34. Karlsson, Mats
    et al.
    Linton, Ludvig
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Karlen, Per
    Glise, Hans
    Befrits, Ragnar
    Janczewska, Izabella
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Winqvist, Ola
    Eberhardson, Michael
    Naive T cells correlate with mucosal healing in patients with inflammatory bowel disease2014In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 49, no 1, p. 66-74Article in journal (Refereed)
    Abstract [en]

    Background. In previous studies, adaptive immune responses involving T-helper cells have been shown to play an important role in inflammatory bowel diseases (IBDs). Methods. The aim of this study was to investigate any correlation between the degree of mucosal inflammation and the phenotype of gut-infiltrating T-helper cells. Biopsies from intestinal mucosa were obtained and intestinal T cells were analyzed with regard to activity and maturation markers. Patients with active colitis (39 with Crohn's disease and 47 with ulcerative colitis) were included and treated with corticosteroids, biologicals or leukocytapheresis. Flow cytometry was used to analyze activation marker expression on gut-infiltrating T-helper cells. Results. Mucosal healing was reflected by almost 100% increase of CD62L expression in mucosal T cells in patients in remission compared to those with active inflammation (p < 0.01). The frequency of mucosal-naive CD4(+)CD45RA(+)T cells was reduced by 50% in mucosa displaying remission (5.3% compared to 12% of the total amount and CD4(+) T cells, p < 0.001). Surprisingly, the proportion of early activated T-helper cells (CD4(+)CD69(+)) did not differ between mucosa in remission and non-remission (43% and 42%, respectively). Moreover, no change in memory T-helper cells (CD4(+)CD45RO(+)) was observed (64% compared to 66%). The findings were independent of diagnosis (Crohn's disease or ulcerative colitis) or mode of treatment. Conclusion. This study suggests that a reduced recruitment of naive T-helper cells and increased frequency of T-helper cells with lymph node homing marker expression reflect mucosal healing in IBD. Surprisingly, the degree of activation of mucosal T-helper cells did not correlate with disease remission.

  • 35. Karlsson, Mats
    et al.
    Linton, Ludvig
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Karlen, Per
    Glise, Hans
    Befrits, Ragnar
    Janczewska, Izabella
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Winqvist, Ola
    Eberhardson, Michael
    Naive T cells in the gut: how to really find them?2014In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 49, no 4, p. 518-518Article in journal (Refereed)
  • 36.
    Kristjánsson, Gudjon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Serra, Jordi
    Lööf, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hällgren, Roger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kinetics of mucosal granulocyte activation after gluten challenge in coeliac disease2005In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 40, no 6, p. 662-669Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To elucidate the dynamics of the rectal inflammatory response to rectal gluten challenge in coeliac disease by measuring inflammatory mediators released by activated neutrophils, eosinophils and mast cells/basophils.

    MATERIAL AND METHODS: The release of myeloperoxidase (MPO), eosinophilic cationic protein (ECP) and histamine was measured continuously during the early challenge period (3-6 h after gluten challenge) in coeliac patients (n = 9) and healthy controls (n = 5). A segmental perfusion technique was used to carry out this part of the study. Another method, the mucosal patch technique, was used to enable studies of the late challenge period (5-48 h after gluten challenge) in coeliac patients (n = 10) and healthy controls (n = 15).

    RESULTS: During the early challenge period the MPO levels began to increase as early as 3 h after challenge and increased progressively (p < 0.001) during the next 3 h. A decline in MPO levels was seen 15 h after challenge and another phase of increasing levels at 24 h. The MPO values declined 48 h after challenge but still remained significantly increased (p < 0.05). The ECP levels started to increase 4 h after challenge and increased progressively during the next 2 h (p < 0.05). The ECP kinetics during the late challenge period was similar as for MPO but the relative increase in ECP was more modest. No increase in histamine was found except in one patient who had a transient, early increase of histamine (3-5 h after challenge). No signs of inflammatory reaction to gluten were seen in the controls.

    CONCLUSIONS: There is a pronounced neutrophil activation in coeliac patients after rectal gluten challenge. This activation is apparent 4 h after challenge and remains for at least 48 h. A more modest eosinophil activation defined by ECP levels starts 1-2 h later and also remains for at least 48 h. The biphasic pattern of MPO and ECP after challenge suggests a biphasic inflammatory reaction.

  • 37.
    Laurell, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Hansson, Lars-Erik
    Gunnarsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Diagnostic pitfalls and accuracy of diagnosis in acute abdominal pain2006In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 41, no 10, p. 1126-1131Article in journal (Refereed)
    Abstract [en]

    Objective. To identify the differential diagnostic difficulties in acute abdominal pain at the emergency department and during hospitalization. Material and methods. Patients with abdominal pain lasting for up to 7 days were registered during 1997-2000 and re-evaluated one year after discharge (n=2851). Results. Diagnoses with low sensitivity at the emergency department but markedly increased sensitivity at discharge were non-specific abdominal pain with a sensitivity value at the emergency department of 0.43, appendicitis 0.80, gallstones 0.68, constipation 0.74 and peptic ulcer 0.26. Corresponding K-values were 0.48, 0.74, 0.84, 0.88 and 0.93, respectively. Malignancy, gynaecological complaints, dyspepsia, urinary tract infection and diverticulitis displayed fairly good concordance between the preliminary and discharge judgements, but the predictive diagnostic value was still low at discharge. Sensitivity values at discharge were 0.40, 0.75, 0.73, 0.77 and 0.83, respectively. Among 479 surgically treated patients, 104 initially received a diagnosis usually not requiring surgery and had a median delay until operation of 22 h (95% CI 30-50 h), compared with 8 h (12-18 h) for referrals. Conclusions. Non-specific abdominal pain is the main differential diagnostic problem in the emergency department also for diagnoses requiring surgery. Constipation is a diagnostic pitfall and when making this diagnosis a careful re-evaluation is necessary.

  • 38.
    Laurell, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Hansson, Lars-Erik
    Gunnarsson, Ulf
    Is there an association between adult coeliac disease and non-specific abdominal pain?: Reply2007In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 42, no 7, p. 898-898Article in journal (Refereed)
  • 39. Lettesjö, Helene
    et al.
    Hansson, Tony
    Department of Rheumatology, karolinska Institute.
    Peterson, Christer
    Ung, Kjell-Arne
    Ringström, Gisela
    Abrahamsson, Hasse
    Simrén, Magnus
    Detection of inflammatory markers in stools from patients with irritable bowel syndrome and collagenous colitis2006In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 41, no 1, p. 54-59Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Irritable bowel syndrome (IBS) and collagenous colitis (CC) share chronically recurring symptoms of altered bowel habits associated with abdominal pain or discomfort. The aims of the present study were to investigate whether inflammatory markers could be detected in faeces from patients with IBS and CC, and to elucidate whether such analyses could be used as non-invasive tools to distinguish between these disorders.

    MATERIAL AND METHODS: Stool samples were obtained from 18 patients with CC, 46 patients with IBS and 20 healthy controls (HC). Eosinophil protein X (EPX), myeloperoxidase (MPO), tryptase, interleukin-1 beta (IL-1beta) and tumour necrosis factor alpha (TNFalpha) were measured in supernatants from processed faeces using immunoassays.

    RESULTS: EPX levels were enhanced in faeces from CC patients (median 3.8 microg/g (0.47-16.2)) compared to patients with IBS (0.44 microg/g (0.25-1.8)), p<0.001, and HC (0.46 microg/g (0.21-1.3)), p<0.001. In addition, MPO was increased in CC patients (11.7 microg/g (2.0-124)) compared to IBS patients (1.7 microg/g (0.81-5.2)), p<0.01, and HC (2.5 microg/g (1.1-6.3)), p<0.05. Tryptase was found in 9/18 patients with CC, 6/46 with IBS and 1/19 HC. IL-1beta was only enhanced in 2/11 CC patients and TNFalpha was not detected in any sample.

    CONCLUSIONS: Increased levels of EPX, MPO and tryptase were observed in stools from collagenous colitis patients, whereas the levels in IBS patients did not differ from healthy controls. Our data suggest that faecal markers could be used as part of the clinical work-up to determine which patients should be biopsied and evaluated for collagenous colitis.

  • 40.
    Lidén, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kristjánsson, Gudjón
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Valtýsdóttir, Sigrídur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hällgren, Roger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gluten sensitivity in patients with primary Sjögren's syndrome2007In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 42, no 8, p. 962-967Article in journal (Refereed)
    Abstract [en]

    Objective. To evaluate the rectal mucosal response to gluten as an indication of gluten sensitivity in patients with primary Sjögren's syndrome (pSS). Material and methods. Rectal challenges with wheat gluten were performed in 20 patients with pSS and 18 healthy control subjects. Fifteen hours after challenge the mucosal production of nitric oxide (NO) was measured. Results. Five patients with pSS had a significant increase in the luminal release of NO after the rectal gluten challenge, indicating gluten sensitivity. All were HLA-DQ2 and/or -DQ8-positive. Two of the patients with increased NO had antibodies against transglutaminase and a duodenal biopsy showed an absolutely flat mucosa consistent with coeliac disease in one of the patients. Before gluten challenge, 15 of the Sjögren's syndrome (SS) patients reported gastrointestinal symptoms, and 8 reported intolerance to various food products. No correlation was found between gluten sensitivity and self-reported food intolerance or gastrointestinal symptoms. Conclusions. Rectal mucosal inflammatory response after gluten challenge is often seen in patients with pSS, signifying gluten sensitivity. However, this reactivity is not necessarily linked to coeliac disease.

  • 41.
    Ljungdahl, Mikael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Österberg, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ransjö, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Engstrand, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Haglund, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Inflammatory response in patients with malignant obstructive jaundice2007In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 42, no 1, p. 94-102Article in journal (Refereed)
    Abstract [en]

    Objective. Surgery in patients with malignant obstructive jaundice is associated with increased risks for postoperative septic complications. The aim of this study was to investigate the inflammatory and the local cellular immune response in patients accepted for surgery because of tumours in the hepatic-pancreatic-biliary (HPB) tract. Material and methods. Patients with obstructive jaundice (group HPB+) were compared with those without (HPB-). Patients undergoing surgery for benign abdominal disorders served as controls. Obstructive jaundice was present in 18 out of 33 HPB patients. Preoperatively, blood was analysed for bacteria, endotoxins and cytokines (TNF-α, IL-6 and IL-10). At operation, mesenteric lymph nodes (MLNs) were excised for bacterial cultures using standard microbiological techniques, and immunohistochemistry, using antibodies CD4 and CD8 (mainly staining T lymphocytes), CD68 (macrophages), and anti-caspase-3 (to determine the rate of apoptosis). Results. Bacterial translocation was not demonstrated in any of the patients. Increased preoperative concentrations of endotoxins were found in group HPB+. The number of macrophages and the rate of apoptosis in MLNs were increased in jaundiced patients, while the number of T lymphocytes was decreased. Conclusions. Malignant obstructive jaundice causes increased blood concentrations of endotoxins and cytokines, an increased number of macrophages in MLNs, a higher rate of apoptosis in MLNs, but a decreased number of T lymphocytes in MLNs. The lymphocyte depletion is probably due to the increased rate of apoptosis, and might reduce the ability of jaundiced patients to eradicate infection.

  • 42. Lönnkvist, Maria H.
    et al.
    Theodorsson, Elvar
    Holst, Mikael
    Ljung, Tryggve
    Hellström, Per M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Blood chemistry markers for evaluation of inflammatory activity in Crohn's disease during infliximab therapy2011In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 46, no 4, p. 420-427Article in journal (Refereed)
    Abstract [en]

    Objective.

    There is a discrepancy between clinical activity and biomarkers in inflammatory bowel disease. The Harvey--Bradshaw index (HBi) is steadfast to evaluate disease activity. A set of biological markers (high sensitive C-reactive protein [hs-CRP], calprotectin, total nitrite, soluble urokinase Plasminogen Activator Receptor [suPAR], ghrelin and endothelin) are investigated to study inflammatory activity and correlation with HBi during infliximab therapy.

    Material and methods.

    Patients with Crohn'sdisease (n == 22) were assessed and blood samples drawn before and 1 week after infliximab infusion (5 mg/kg) and repeated after 6 months, and compared to healthy volunteers. Hs-CRP, calprotectin, suPAR, ghrelin and endothelin were analyzed with immunoassays, and total nitrite with Griess-reaction. Results were analyzed with Wilcoxon matched-pairs test, Mann--Whitney test and Spearman correlations.

    Results.

    After the first infusion visit, HBi and calprotectin values decreased while nitrite increased (p < 0.05). At the 6-month visit, pre-infusion index and biomarkers had returned to baseline levels. Post-infusion, again the values of HBi, hs-CRP and calprotectin decreased (p < 0.05). The suPAR levels did not change between pre- and post-infusion periods at either visit. Calprotectin, nitrite and suPAR differed from healthy controls throughout the study (p < 0.05). Endothelin decreased with each treatment but was, like ghrelin, not different from controls. We found HBi to correlate with hs-CRP (Spearman r == 0.32, p < 0.05), but calprotectin did not, neither did nitrate nor suPAR.

    Conclusions.

    Although infliximab ameliorates Crohn'sdisease symptoms, inflammatory markers are not persistently normalized, indicating a chronic inflammatory condition that may require continued infliximab therapy.

  • 43. Mohammadi, Mohammad
    et al.
    Song, Huan
    Cao, Yang
    Glimelius, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ekbom, Anders
    Ye, Weimin
    Smedby, Karin E
    Risk of lymphoid neoplasms in a Swedish population-based cohort of 337,437 patients undergoing appendectomy2016In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 51, no 5, p. 583-589Article in journal (Refereed)
    Abstract [en]

    Objective Appendectomy remains one of the most common surgical procedures, but possible long-term consequences for health and disease are incompletely investigated. The appendix forms part of the secondary lymphoid system and appendectomy has been associated with increased risks of hematolymphoproliferative malignancies in some studies. Materials and methods We examined the risk of lymphoid neoplasms in a large cohort of 337,437 appendectomised patients <60 years of age in Sweden 1975-2009. We estimated relative risks of non-Hodgkin lymphoma (NHL) and major subtypes, Hodgkin lymphoma (HL), chronic lymphocytic leukaemia (CLL), myeloma, and acute lymphoblastic leukaemia (ALL) versus the general population using standardised incidence ratios (SIRs) with 95% confidence intervals (CIs). Results There was no increased risk of NHL (SIR = 0.97, 95%CI 0.88-1.06), major NHL subtypes, CLL (SIR = 0.87, 95%CI 0.70-1.06), myeloma (SIR = 1.14, 95%CI 0.96-1.33) or ALL (SIR = 1.10, 95%CI 0.80-1.47) following appendectomy. An increased risk of HL was observed among patients diagnosed with appendicitis (SIR = 1.29, 95%CI 1.07-1.54, p=0.007), especially individuals aged <20 years at surgery (SIR = 1.43, 95%CI 1.11-1.82), and for the nodular sclerosis subtype of HL (SIR = 1.55, 95%CI 1.01-2.27). A marginally increased risk of myeloma was noted among men, but the association was limited to the first few years of follow-up. Conclusion Appendectomy is not associated with any notable increase in risk of lymphoid neoplasms. A small increased risk of HL following appendicitis (rather than appendectomy per se) could reflect a true association, or shared susceptibility to infection/inflammation among individuals prone to develop HL. The association observed for myeloma may be explained by chance or surveillance bias.

  • 44.
    Molinder, Herdis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Wallander, Mari-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Hallberg, Margareta
    Bodemar, G
    Dyspepsia - acid or stress?: a study of controversy -- abandoned by experts, finalized in clinical practice?1999In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 34, no 11, p. 1057-1064Article in journal (Refereed)
  • 45.
    Molinder, Herdis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Wallander, Mari-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Bodemar, G
    The introduction of H2-receptor antagonists to Scandinavia:  effects of experts' opinions1998In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 33, no 3, p. 224-230Article in journal (Refereed)
  • 46. Nylander, O
    et al.
    Holm, Lena
    Wilander, E
    Hällgren, A
    Exposure of the duodenum to high concentrations of hydrochloric acid. Effects on mucosal permeability, alkaline secretion, and blood flow.1994In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 29, no 5, p. 437-44Article in journal (Refereed)
    Abstract [en]

    Proximal duodenum was perfused with HCl for 5 min and the effects on blood-to-lumen clearance of 51Cr-EDTA (ED-Cl), morphology, luminal alkalinization, and blood flow determined in anesthetized rats. The rate of alkalinization was determined by back titration and blood flow assessed by laser Doppler flowmetry or by ultrasonic transit time flowmetry. Perfusion of duodenum with 30, 50 or 100 mM HCl for 5 min increased ED-Cl in a concentration-dependent manner and induced a small increase in alkalinization but had no effect on blood flow. At 55 min after cessation of perfusion with 100 mM HCl ED-Cl was 2.2-fold higher than control whereas the ED-Cl values in animals perfused with 30 or 50 mM HCl were not different from pre-acid control values. 100 mM HCl also induced an increase in 14C-mannitol and 14C-polyethylene glycol 4000 clearance, suggesting that HCl does indeed increase mucosal permeability. The 100 mM HCl-induced rise in mucosal permeability most probably reflects disturbance of mucosal integrity because three of five animals exhibited villous tip damage. The increases in ED-Cl in response to 100 mM HCl were the same in control rats as in rats with the renal pedicles ligated, indicating that the acid susceptibility is not affected by acute functional nephrectomy.

  • 47. Olsson, Karl Sigvard
    et al.
    walinder, Olof
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Science for Life Laboratory, SciLifeLab, Science for Life Laboratory, SciLifeLab.
    Williams, Roger
    Common local founder effects for Wilson's disease and hereditary hemochromatosis: mutation studies of a large family2012In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 47, no 8-9, p. 1014-1020Article in journal (Refereed)
    Abstract [en]

    Wilson's disease (WND) and hereditary hemochromatosis (HH) are two metal loading diseases of copper and iron, respectively, and are both recessively inherited. In central Sweden, where HH is common, 9 Wilson kindred (14 members) were identified. Aims of the study were to test whether nine WND families shared a common origin, a common mutation and if carrying HFE mutations affected their phenotype Results. The nine families were traced through 13 generations to a common founder origin in the mid-seventeenth century. Despite identity of descent, four different ATP7B mutations appeared with homozygosity in four, with two different mutations, W779X and T977M. There were three compound heterozygotes, W779X/T977M, R1319X/H1069Q and one T977M combined with a new, previously not described mutation, probably of Finnish origin. The founder family also included 26 descendant kindred (55 members) with HH as shown by HFE mutations. This admixture coincided with a migration out of the original parish into hemochromatosis-rich localities. One WND patient had iron overload (serum ferritin 672 mu g/l and raised liver enzymes), but lacked HFE mutations. In another family with serious hemochromatosis (two sons dying from bronze diabetes), the coinheritance of congenital spherocytosis was probably the cause rather than an additional effect of WND. Conclusions. WND though a rare disease may become aggregated like HH in certain areas due to local founder effects. Despite extensive pedigree studies leading back to the local founder family, the authors were unable to find a single defining mutation of the ATP7B gene.

  • 48.
    Rosenqvist, Kerstin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sheikhi, Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Sangfelt, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Ebeling Barbier, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Transjugular intrahepatic portosystemic shunt treatment of variceal bleeding in an unselected patient population.2018In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, no 1, p. 70-75Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate transjugular intrahepatic portosystemic shunt (TIPS) in variceal bleeding in a clinical setting.

    MATERIALS AND METHODS: Retrospective review of 131 patients (116 with liver cirrhosis) treated with TIPS with covered stent grafts in a single centre from 2002 to 2016.

    RESULTS: Survival at 1 and 2 years was 70% and 57% in patents with, and 100% at 2 years in patients without liver cirrhosis, respectively. A high Child-Pugh score and severe hepatic encephalopathy (HE) within 12 months post-TIPS were related to increased mortality. Re-bleeding occurred in 8% within 12 months and was related to TIPS dysfunction and a post-TIPS portosystemic gradient (PSG) of ≥5 mmHg. The main cause of TIPS dysfunction was that the stent did not fully reach the inferior vena cava. There was no correlation between the PSG and the occurrence of HE.

    CONCLUSIONS: TIPS was safe and prevented re-bleeding in patients with variceal bleeding, with or without liver cirrhosis, regardless of Child-Pugh class and of how soon after bleeding onset, the TIPS procedure was performed. A post-TIPS PSG of ≥5 mmHg was associated with an increased risk for re-bleeding and there was no correlation between the post-TIPS PSG and the occurrence of HE.

  • 49. Ruigomez, A
    et al.
    Wallander, Mari-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Lundborg, P
    Johansson, Saga
    Garcia Rodriguez, LA
    Gastroesophageal reflux disease in children and adolescents in primary care2010In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 45, no 2, p. 139-146Article in journal (Refereed)
    Abstract [en]

    Objectives. To determine the prevalence and incidence of a diagnosis of gastroesophageal reflux disease (GERD) in children and adolescents in UK primary care, and to assess comorbidities that are associated with a diagnosis of GERD. Material and methods. Incident GERD cases during 2000-05 were identified from The Health Improvement Network (THIN) UK primary care database via a computer search for diagnostic codes for GERD, followed by manual review of the patient records. Results. We identified 1700 children with a first diagnosis of GERD during 2000-05. The incidence of GERD was 0.84 per 1000 person-years. The incidence decreased with age from 1.48 per 1000 person-years among 1-year-old children until the age of 12 years, whereupon it increased to a maximum at 16-17 years of 2.26 per 1000 person-years for girls and 1.75 per 1000 person-years for boys. Pregnant adolescents were not included in the study. In addition to typical GERD symptoms (epigastric pain, heartburn, reflux, regurgitation), 21.2% of children reported nausea or vomiting. Children with neurological disorders were at increased risk of a GERD diagnosis. Hiatus hernia and congenital esophageal disorders were also associated with a diagnosis of GERD. Children and adolescents using antiepileptics, oral/inhaled steroids, beta-agonists and paracetamol had an increased risk of a GERD diagnosis. Conclusions. The incidence of a GERD diagnosis was age-dependent and was highest among very young children and older female adolescents. Children with neurological impairments and other comorbidities were at increased risk of a GERD diagnosis.

  • 50. Ruigomez, Ana
    et al.
    Lundborg, Per
    Johansson, Saga
    Wallander, Mari-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Garcia Rodriguez, Luis A.
    Follow-up of a cohort of children and adolescents with gastro-esophageal reflux disease who were free of reflux esophagitis at initial diagnosis2010In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 45, no 7-8, p. 814-821Article in journal (Refereed)
    Abstract [en]

    Objective. Few studies have examined the incidence of complications from gastro-esophageal reflux disease (GERD) in children and adolescents in primary care. Here we aimed to describe the natural history of GERD in a pediatric population with no reflux esophagitis at initial diagnosis, assessing diagnoses of new esophageal complications and extra-esophageal conditions. Material and methods. We used The Health Improvement Network UK primary care database (which includes data on more than 2 million patients) to identify individuals aged 1-17 years with a first diagnosis of gastro-esophageal reflux or heartburn in the period 2000-2005, via a computerized search followed by a manual review of the patient records. This search identified 1242 individuals with an incident diagnosis of GERD but no record of esophagitis. This cohort was followed-up to detect new diagnoses of esophageal complications and extra-esophageal conditions. Results. During a mean follow-up period of almost 4 years, 40 children and adolescents had a confirmed new diagnosis of reflux esophagitis (incidence: 10.9 per 1000 person-years). No cases of Barrett's esophagus, esophageal stricture or esophageal ulcer were reported. Individuals with GERD had double the risk of an extra-esophageal condition such as asthma, pneumonia, cough or chest pain compared with children and adolescents with no diagnosis of GERD. Conclusions. Children and adolescents with GERD may be at risk of developing reflux esophagitis and a range of other extra-esophageal conditions, but more severe esophageal complications are rare.

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