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  • 101.
    Persson, Gunnar E.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Epidemiological and clinical aspects of non-acute gallstone disease1995Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    BACKGROUND

    Gallstones are common in many countries, but few patients develop severe complications. Fatal complications are rare and affect chiefly the very old. Gallstones may be an aetiological factor for gallbladder cancer, which has a poor prognosis but seldom occurs in young people. The risk of developing gallbladder cancer is small.The standard treatment for gallstone disease has been and still is cholecystectomy. Significant variations in cholecystectomy rates between different areas imply varying indications for gallstone surgery. Too little is known about the prognosis of non-acute gallstone disease to establish solid indications for cholecystectomy in these patients. Further studies on non-acute gallstone disease are therefore warranted.

    AIMS OF THE STUDY

    To analyse changes in the age- and sex-specific frequency and outcome of operation for gallstone disease over a 10-year period (I). To study anamnestic data and frequency of gallstones in people referred for oral cholecystography and to assess the number ofdays of sick leave and in-patient care during a 4 year period in patients referred for oral cholecystography (II,III). To study the physical and biochemical findings in patients with gallstones diagnosed by oral cholecystography and to study the prevalence of gallstones in patients with diabetes mellitus (IV,V). To study the outcome of expectant management of gallstone disease diagnosed by oral cholecystography and to analyse the risk factors for recurrent gallstone symptoms and complications (VI).

    RESULTS

    The reduction in the cholecystectomy rate observed in Sweden during the 1970s is to a large extent accounted for by a decline in the number of elective operations. Introduction of the endoscopic technique for treatment of bile duct stones has only to a limited extent changed the cholecystectomy rate. Gallstone surgery is today often performed on older patients as an acute procedure, yet this is associated with low postoperative morbidity and mortality.

    Patients referred for oral cholecystography often have other diseases and they present unspecific symptoms. This is reflected in increased sick leave during the years following cholecystography. Gallstone disease is responsible for only a small part of this sick leave.

    Gallstones diagnosed by oral cholecystography are associated with obesity and short stature in women, and high serum triglyceride and low cholesterol concentrations in both sexes.

    In patients with well controlled insulin dependent diabetes mellitus the risk of developing gallstones is not increased. In patients with gallstones diagnosed by oral cholecystography the prognosis with regard to the gallstone disease is generally good. However, the occurrence of a gallstone complication is a strong indication for cholecystectomy. In patients with uncomplicated gallstone disease and infrequent gallstone symptoms expectant management is advisable.

  • 102. Petersson, Fredrik
    et al.
    Borch, Kurt
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Franzén, L. E.
    Prevalence of subtypes of intestinal metaplasia in the general population and in patients with autoimmune chronic atrophic gastritis2002In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 37, no 3, p. 262-266Article in journal (Refereed)
    Abstract [en]

    Background: Gastric intestinal metaplasia (IM) is seen mostly in association with chronic gastritis, induced either by Helicobacter pylori infection or autoimmune mechanisms. IM can be categorized into three subtypes, where type III is associated with gastric carcinoma of intestinal type.

    Methods: Gastric biopsies from 475 subjects randomly selected from the general population and from 27 patients with autoimmune gastritis associated with pernicious anaemia were used. The criteria of Filipe & Jass were applied using different histochemical techniques in combination with haematoxylin and eosin stained material.

    Results: Twenty-three percent (109/475) of the subjects from the general population and 88% (24/27) in the group with autoimmune gastritis had IM. Type III IM occurred in 4% in both populations. Type III IM was located in the antrum in 90% in the general population. In the group with autoimmune gastritis, only one patient had type III IM, which was located in the corpus.

    Conclusions: This study reveals for the first time the prevalence and distribution of subtypes of IM in a general population from the Western world. The comparatively high prevalence of type III IM in the general population (4%) indicates that its role as a precursor of gastric carcinoma may have been overemphasized. A similar prevalence of type III IM in patients with autoimmune gastritis may be considered low and suggests that mechanisms for gastric carcinogenesis other than the atrophy - metaplasia-dysplasia sequence could also operate in this condition.

  • 103.
    Petersson, Fredrik
    et al.
    Pathology Research Department, Ryhov Hospital, Jönköping.
    Borch, Kurt
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Franzén, Lennart
    Department of Pathology, Medical Centre Hospital, Örebro, Sweden.
    Gastric epithelial proliferation and p53 and p21 expression in a general population sample: relations to age, sex, and mucosal changes associated with H. pylori infection2002In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 47, no 7, p. 1558-1566Article in journal (Refereed)
    Abstract [en]

    Helicobacter pylori infection is the main cause of chronic gastritis. The infection has been linked to altered proliferative activity and changes in various cell cycle regulating proteins. To determine, in a general population sample, the proliferative activity and expression of p53 and p21 in males and females of different age groups with and without H. pylori-associated chronic gastritis, gastric biopsies from 273 subjects (188 with and 85 without H. pylori infection) randomly selected from a general population were examined immunohistochemically for Ki-67, p53, and p21. One thousand epithelial cells, including the surface, neck, and glandular areas, were counted in both the corpus and the antrum. Results are expressed as the percentage of positive cells. Subjects with H. pylori infection showed significantly increased proliferative activity and expression of p53 compared to uninfected individuals. Regarding the expression of p21, no difference was detected. Multiple linear regression analysis showed significant associations between chronic inflammation or inflammatory activity, on the one hand, and the degree of proliferation in both the corpus and the antrum, on the other hand. In the antrum, the degree of H. pylori colonization was related to the expression of p53. H. pylori seems to cause increased proliferation and increased expression of p53 (but not p21) in the gastric mucosa, neither of which is age or sex dependent. The proliferative activity is related mainly to events associated with inflammation, while the expression of p53 in the antrum is associated with the degree of H. pylori infection. The action of p53 appears to be independent of p21 activity.

  • 104. Radecka, E
    et al.
    Brekkan, E
    Juhlin, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Nilsson, L
    Sundin, A
    Magnusson, A
    An unusual case of tumor thrombus in the inferior vena cava. A case report.2003In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 44, p. 160-161Article in journal (Refereed)
  • 105.
    Ragnarsson, G
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, GE: gastromed.
    Hallböök, Olof
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Bodemar, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, GE: gastromed.
    Postprandial increase in rectal sensitivity is not related to gastrointestinal symptoms in irritable bowel syndrom (IBS).1999In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 34, p. 250-258Article in journal (Refereed)
  • 106.
    Redéen, Stefan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Petersson, F
    Jönsson, K-Å
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Borch, Kurt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Relationship of gastroscopic features to histological findings in gastritis and Helicobacter pylori infection in a general population sample2003In: Endoscopy, ISSN 0013-726X, E-ISSN 1438-8812, Vol. 35, no 11, p. 946-950Article in journal (Refereed)
    Abstract [en]

    Background and study aim: Various gastroscopic features may be interpreted as signs of gastritis, but the significance of such features in relation to histomorphology is uncertain. The aim of this study was to determine how macroscopic findings were related to histomorphological changes and the presence of Helicobacter pylori in the gastric mucosa, in a sample of the general population. Subjects and methods: 488 adult individuals, randomly selected from a general population, were screened with gastroscopy and biopsy. The macroscopic features recorded were erythema (diffuse, spotty, linear), erosions, absence of rugae in the gastric corpus, and presence of visible vessels. Gastritis was classified microscopically according to the Sydney system. The presence of H. pylori was determined histologically and using the urease test on fresh biopsy specimens. Results: The sensitivity and specificity of absence of rugae for moderate to severe atrophic gastritis in the gastric corpus were 67% and 85%, respectively. Corresponding valuers for severe atrophy were 90% and 84%. The sensitivity and specificity of the presence of visible vessels for moderate to severe atrophy in the corpus were 48% and 87%, and for severe atrophy the values were 80% and 87%, respectively. Considering the antrum, the sensitivity and specificity of the presence of visible vessels for moderate to severe atrophy was 14% and 91%, respectively. With regard to chronic inflammation (moderate to severe in the corpus or antrum), none of the features, alone or in combination, showed a sensitivity of more than 56%. No endoscopic features (alone or in combination) showed a sensitivity of more than 57 % for H. pylori infection. Conclusions: Except for the absence of rugae and visible vessels in the gastric corpus, macroscopic features as observed during gastroscopy are of very limited value in the evaluation of whether or not gastritis or H. pylori infection are present. This is in accordance with most previous studies in patient populations, and it must be emphasized that the diagnosis of gastritis should be based on histological examination of the gastric mucosa.

  • 107.
    Ryn, Ann-Katrine
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Morren, Geert
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Hallböök, Olof
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Sjödahl, Rune
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Long-term results of electromyographic biofeedback training for fecal incontinence2000In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 43, no 9, p. 1262-1266Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim of this study was to examine the long-term results of electromyographic biofeedback training in fecal incontinence.

    METHODS: Thirty-seven patients (1 male) received a customised program of 2 to 11 (median, 3) biofeedback training sessions with an anal plug electromyometer. Nine patients had persistent incontinence after anal sphincter repair, a further 8 patients had postsurgical or partial obstetric damage of the sphincter but no sphincter repair, 9 patients had neurogenic sphincter damage, and 11 patients were classified as having idiopathic fecal incontinence. Duration of voluntary sphincter contraction was measured by anal electromyography (endurance score) before and after treatment. A postal questionnaire was used to investigate the following variables: 1) subjective rating on a four-grade Likert-scale of the overall result of the biofeedback training; 2) incontinence score (maximum score is 18, and 0 indicates no incontinence); and 3) rating of bowel dissatisfaction using a visual analog scale (0 to 10).

    RESULTS: Twenty-two patients (60 percent) rated the result as very good (n=8) or good (n=14) immediately after the treatment period. Median endurance score improved from 1 to 2 minutes (P<0.0001). Median incontinence score improved from 11 to 7, and bowel dissatisfaction rating improved from 5 to 2.8 (bothP<0.0001). After a median follow-up of 44 (range, 12–59) months, 15 patients (41 percent) still rated the overall result as very good (n=3) or good (n=12). The incontinence score did not change during follow-up. Median bowel dissatisfaction rating deteriorated from 2.8 to 4.2 but remained better than before treatment. Poor early subjective rating and the need for more than three biofeedback sessions were predictive of worsening during follow-up.

    CONCLUSION: We think it is encouraging that in this study biofeedback treatment for fecal incontinence with an intra-anal plug electrode resulted in a long-term success rate in nearly one-half of the patients.

  • 108. Sandblom, Gabriel
    et al.
    Gruber, Göran
    Kald, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Nilsson, Erik
    Audit and recurrence rates after hernia surgery2000In: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 166, no 2, p. 154-158Article in journal (Refereed)
    Abstract [en]

    Objective: To study the effect of quality assurance on the recurrence rate after hernia repair. Design: A prospective longitudinal cohort study. Setting: District hospital, Sweden. Subjects: All (n = 1232) patients aged 15-80 years operated upon for inguinal or femoral hernia in Motala 1984, 1986-1988, 1990, and 1992-1994. Intervention: A questionnaire enquiring about pain or a lump in the operated area was sent 3-6 years postoperatively to all patients, excluding those who had already been operated on for recurrence and those who had died. Selected cases were examined depending on the answers to the questionnaire. Main outcome measures: Recurrence rate estimated by adding already confirmed recurrences to those found at the clinical examination, reoperation for recurrence, hospital stay, and number of day cases. Cumulative incidence of reoperation was analysed by actuarial analysis of all patients operated on from 1986-1997. Results: The recurrence rate decreased from 18% in 1984 and 1986 to 3% in 1993 and 1994. The reoperation rate for recurrence at three years was 10.8% (95% confidence interval, CI: 9.3 to 12.2%), 3.6% (2.6 to 4.4%) and 2.2% (1.7 to 2.7%) for patients operated on between 1986-1988, 1989-1991 and 1992-1997, respectively. Differences between the first and the second and between the first and the third period were both highly significant (p < 0.001) whereas the difference between the second and third period was not (p = 0.09). Mean hospital stay decreased from 3.5 days in 1984 to 0.9 days in 1994. Conclusion: By recording recurrence rate or its surrogate endpoint, reoperation rate for recurrence, or both, hospital stay, and number of day cases, and presenting these results to participating surgeons, we provided incentives to improve outcome. This has resulted in a rapid decrease in recurrence rate and a shortened hospital stay, thereby improving cost-effectiveness.

  • 109.
    Sandstrom, Per
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Woods, C.M.
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Brooke-Smith, M.
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Saccone, G.T.P.
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Toouli, J.
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Svanvik, Joar
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Highly selective iNOS inhibition and sphincter of Oddi motility in the Australian possum2004In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 181, no 3, p. 321-331Article in journal (Refereed)
    Abstract [en]

    Aim:  Inducible nitric oxide synthase (iNOS) plays a major role in acute pancreatitis. Selective inhibitors of iNOS are being developed as therapeutic agents. Sphincter of Oddi (SO) dysfunction may cause pancreatitis and nitric oxide is necessary for SO relaxation. A new highly selective iNOS inhibitor, AR-C102222AA (AR-C), is evaluated together with the established iNOS inhibitor, l-N6-(1-iminoethyl)lysine (l-NIL), and the selective neuronal nitric oxide synthase (nNOS) blocker S-methyl-l-thiocitrulline (SMTC).

    Methods:  In anaesthetized Australian Brush-tailed possums, the effect of topical, i.v. or i.a. administration of these drugs was evaluated on spontaneous SO motility, blood pressure (BP) and pancreatic vascular perfusion. SO motility was recorded by manometry and pancreatic vascular perfusion by laser Doppler fluxmetry. Also, the effect of SMTC and AR-C on electrical field stimulation (EFS)-induced non-cholinergic non-adrenergic (NANC) SO relaxation in vitro was evaluated.

    Results:  Infusion of AR-C (0.1–30 μmol kg−1) increased SO contraction frequency (P = 0.026) only at the two highest doses. l-NIL infusion (0.15 to 14.7 μmol kg−1) also increased SO contraction frequency at 8.8 μmol kg−1 (P < 0.05) and reduced SO contraction amplitude at the two highest doses (P < 0.05). SMTC injections (0.5 nmol–2.4 μmol) produced a dose-dependent increase in SO contraction frequency (P = 0.009), but no effect was seen on the other parameters. In vitro SMTC (40–400 μm) inhibited EFS-induced NANC relaxation in a dose-dependent manner (P < 0.0005). In contrast AR-C (10–500 μm) had no effect on EFS-induced NANC relaxation (P > 0.05).

    Conclusions:  At low doses, AR-C does not effect SO motility or EFS-induced NO mediated relaxation. However, high doses of AR-C and L-NIL in vivo influenced SO motility by inhibiting nNOS activity and these effects need be considered in relation to therapeutic doses of this agent.

  • 110.
    Sandström, Per
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Nitric oxide, arginine and acute pancreatitis2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Acute pancreatitis is a serious inflammatory condition which is managed symptomatically as there is no causal treatment to offer. The main background causes are alcohol abuse and gallstone disease. The inducing factors lead to a premature activation of pancreatic enzymes in the acinar cells and their subsequent release into the pancreatic tissue. This activates the inflammatory cascade leading to reduced pancreatic vascular perfusion, cellular necrosis and in some cases systemic disease. Nitric oxide (NO) and the by-product citrulline are synthesised from the amino acid L-arginine by NO-synthases (NOS), which exist in three isoforms. Two are constitutive, being necessary for relaxation of vascular myogenic cells (eN OS) or for the relaxation of the sphincter of Oddi, (nNOS). The third, iNOS, is activated mainly during inflammation, producing high concentrations of NO, which may be harmful.

    We demonstrate that patients with acute pancreatitis, whatever the cause, have reduced sermn levels of arginine and citrulline, indicating a disturbed NO metabolism with possible negative effects on the outflow of pancreatic juice and on pancreatic blood perfusion. One possible reason for the reduced sermn levels could be an early high NO production via the iNOS route consuming L-arginine. Inhibition of iNOS may improve this imbalance and reduce the inflammation.

    In experimental studies, low doses of selective iNOS inhibition do not interfere with blood pressure, pancreatic vascular perfusion or the sphincter of Oddi in vivo. However, in high doses both in vivo and in vitro, the inhibitor stimulates the sphincter muscle by interfering with nNOS, indicating that high doses are harmful.

    The iNOS inhibitor was used in an experimental study of acute pancreatitis, and we showed that treatment with selective iNOS inhibition, two hours after induction, reduced inflammation in the pancreatic tissue and the need for fluid, stabilised blood pressure and improved the amino acid balance.

    High doses of L-arginine cause necrotising acute pancreatitis in rats within 48 hours. Sermn arginine and citrulline increased at 8 hours, but fell below control levels, at 24 hours. An early increase in pancreatic ATP dropped to control level at 24 hours. The ATP production correlated with histological swelling of mitochondria, seen as vacuole formation, followed by an increased apoptotic activity. Cell proliferation decreased. Full amino acid analysis at 24 hours showed reduction in 14 out of 22 amino acids, including the glutamate family. The process with apoptosis and the reduction of ATP, cell proliferation and amino acids precedes the development of inflammation and necrosis.

    List of papers
    1. Depletion of serum L-arginine in patients with acute pancreatitis
    Open this publication in new window or tab >>Depletion of serum L-arginine in patients with acute pancreatitis
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    2003 (English)In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 27, no 3, p. 261-266Article in journal (Refereed) Published
    Abstract [en]

    Introduction: Acute pancreatitis may be initiated by interference with the pancreatic outflow to the duodenum. This flow is normally regulated by reflex relaxation of the sphincter of Oddi in which nitric oxide is an important mediator.

    Aim: To test the hypothesis that acute pancreatitis involves a depletion in serum l-arginine resulting in impaired production of nitric oxide.

    Methods: We measured serum l-arginine and l-citrulline and urinary nitrite/nitrate concentrations 1 to 3 days after the onset of symptoms in 11 patients with gallstone pancreatitis, 10 patients with alcoholic pancreatitis, and 6 patients with idiopathic pancreatitis. We compared their results with those from control groups of 13 healthy blood donors, 9 patients fasting before hernia operations, 8 patients with acute cholecystitis, and 9 alcoholic subjects but no pancreatitis. Serum arginine and citrulline concentrations were measured with high performance liquid chromatography, and urinary nitrite/nitrate spectrophotometrically.

    Results: Patients with acute pancreatitis, of whatever cause, had lower serum l-arginine and l-citrulline concentrations than controls. Patients with gallstone and idiopathic pancreatitis also have reduced urinary concentrations of nitrite and nitrate but this was not seen in patients with alcoholic pancreatitis.

    Conclusions: L-arginine and l-citrulline concentrations are depleted in the serum of patients with acute pancreatitis. Reduced urinary nitrite and nitrate in gallstone pancreatitis indicate that there is a defect formation of nitric oxide. This may cause a functional obstruction of the outflow of pancreatic juice to the duodenum and so may be involved in the pathophysiology of acute pancreatitis.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25345 (URN)10.1097/00006676-200310000-00012 (DOI)9787 (Local ID)9787 (Archive number)9787 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    2. Highly selective iNOS inhibition and sphincter of Oddi motility in the Australian possum
    Open this publication in new window or tab >>Highly selective iNOS inhibition and sphincter of Oddi motility in the Australian possum
    Show others...
    2004 (English)In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 181, no 3, p. 321-331Article in journal (Refereed) Published
    Abstract [en]

    Aim:  Inducible nitric oxide synthase (iNOS) plays a major role in acute pancreatitis. Selective inhibitors of iNOS are being developed as therapeutic agents. Sphincter of Oddi (SO) dysfunction may cause pancreatitis and nitric oxide is necessary for SO relaxation. A new highly selective iNOS inhibitor, AR-C102222AA (AR-C), is evaluated together with the established iNOS inhibitor, l-N6-(1-iminoethyl)lysine (l-NIL), and the selective neuronal nitric oxide synthase (nNOS) blocker S-methyl-l-thiocitrulline (SMTC).

    Methods:  In anaesthetized Australian Brush-tailed possums, the effect of topical, i.v. or i.a. administration of these drugs was evaluated on spontaneous SO motility, blood pressure (BP) and pancreatic vascular perfusion. SO motility was recorded by manometry and pancreatic vascular perfusion by laser Doppler fluxmetry. Also, the effect of SMTC and AR-C on electrical field stimulation (EFS)-induced non-cholinergic non-adrenergic (NANC) SO relaxation in vitro was evaluated.

    Results:  Infusion of AR-C (0.1–30 μmol kg−1) increased SO contraction frequency (P = 0.026) only at the two highest doses. l-NIL infusion (0.15 to 14.7 μmol kg−1) also increased SO contraction frequency at 8.8 μmol kg−1 (P < 0.05) and reduced SO contraction amplitude at the two highest doses (P < 0.05). SMTC injections (0.5 nmol–2.4 μmol) produced a dose-dependent increase in SO contraction frequency (P = 0.009), but no effect was seen on the other parameters. In vitro SMTC (40–400 μm) inhibited EFS-induced NANC relaxation in a dose-dependent manner (P < 0.0005). In contrast AR-C (10–500 μm) had no effect on EFS-induced NANC relaxation (P > 0.05).

    Conclusions:  At low doses, AR-C does not effect SO motility or EFS-induced NO mediated relaxation. However, high doses of AR-C and L-NIL in vivo influenced SO motility by inhibiting nNOS activity and these effects need be considered in relation to therapeutic doses of this agent.

    Keywords
    Inducible nitric oxide synthase, Nitric oxide, Sphincter of Oddi motility
    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:liu:diva-45702 (URN)10.1111/j.1365-201X.2004.01296.x (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13Bibliographically approved
    3. Highly selective inhibition of inducible nitric oxide synthase ameliorates experimental acute pancreatitis
    Open this publication in new window or tab >>Highly selective inhibition of inducible nitric oxide synthase ameliorates experimental acute pancreatitis
    Show others...
    2005 (English)In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 30, no 1, p. 10-15Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES:

    Inducible nitric oxide synthase (iNOS) activity is increased in experimental acute pancreatitis. The aim of this study was to evaluate treatment with the selective iNOS inhibitors AR-C (AR-C102222AA) and L-NIL (L-N6-(1-iminoethyl)-lysine) in experimental acute pancreatitis.

    METHODS:

    Acute pancreatitis was induced in anesthetized Australian possums by topical administration of carbachol on the sphincter of Oddi. AR-C treatment was 2 intravenous infusions (2.5 micromol/kg over 15 minutes) at 2 and 4 hours after acute pancreatitis induction. L-NIL treatment was an intraarterial infusion (1 mg/kg/h) from 2 hours after acute pancreatitis induction. At 8 hours, pancreatic tissue was harvested and inflammation assessed (histologic score). Blood samples were collected for plasma amylase, lipase, and amino acid levels. Blood pressure, central venous pressure, supplementary fluids, and urine output were monitored.

    RESULTS:

    Treatment with AR-C or L-NIL reduced the plasma levels of amylase and the volume of supplementary fluids and improved the histological score (all P < 0.05). In animals with acute pancreatitis, plasma arginine levels were reduced (P < 0.05), while citrulline and ornithine levels increased (P < 0.05), consistent with increased nitric oxide production. Treatment with AR-C ameliorated the reduced arginine level.

    CONCLUSIONS:

    Treatment with AR-C or L-NIL, commencing 2 hours after the induction of acute pancreatitis, has significant and beneficial effects in experimental acute pancreatitis in Australian possums.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-30807 (URN)15632690 (PubMedID)16434 (Local ID)16434 (Archive number)16434 (OAI)
    Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13Bibliographically approved
    4. The influence of a load of L-arginine on serum amino acids and pancreatic apoptosis/proliferation and ATP levels in the rat
    Open this publication in new window or tab >>The influence of a load of L-arginine on serum amino acids and pancreatic apoptosis/proliferation and ATP levels in the rat
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    2004 (English)In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 29, no 4, p. 113-120Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES:

    Administration of high doses of amino acids like ethionine, methionine, and arginine causes pancreatic tissue damage. The initial mechanism behind these effects is not known. The aim of this study was to show the early effects of a load of L-arginine on programed cell death/proliferation and ATP levels in the pancreas.

    METHODS:

    We analyzed in rats the effects of intraperitoneal administration of L-arginine on serum amino acids, pancreatic cell apoptosis/proliferation, and ATP levels at 8, 16, and 24 hours. Serum amino acid concentrations were measured with HPLC, tissue ATP was measured fluorometrically, apoptosis was studied with caspase-3 activity and histone-associated DNA-fragments, and proliferation was studied with thymidine autoradiography.

    RESULTS:

    After a load of l-arginine, there were initially increased serum levels of L-arginine and L-citrulline, but these fell below control levels after 24 hours as well as amino acids in the glutamate family (ornithine, proline, histidine, and glutamine). Initially, increased ATP levels in the pancreatic tissue returned to control levels at 24 hours. The acinar cells proliferation was suppressed and the apoptosis rate strongly increased at 16 and 24 hours. Pancreatic histology showed vacuole formation in the acinar cells at 8 hours. At 16 hours, there was less vacuolization, but apoptotic bodies were seen, and at 24 hours there was cell degeneration but no necrosis.

    CONCLUSIONS:

    After a load of l-arginine, amino acid metabolism causes a high ATP production in the pancreatic tissue that may cause mitochondrial initiation of cell death.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-23748 (URN)15502637 (PubMedID)3258 (Local ID)3258 (Archive number)3258 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
  • 111.
    Sandström, Per
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Brooke-Smith, Mark E
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Thomas, Anthony C
    Department of Anatomical Pathology, Flinders Medical Centre, Flinders University of South Australia, Adelaide, SA, Australia.
    Grivell, Marlene B
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Saccone, Gino T P
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Toouli, James
    Department of General and Digestive Surgery, Centre for Neuroscience and the Centre for Digestive Sciences, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.
    Svanvik, Joar
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Highly selective inhibition of inducible nitric oxide synthase ameliorates experimental acute pancreatitis2005In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 30, no 1, p. 10-15Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    Inducible nitric oxide synthase (iNOS) activity is increased in experimental acute pancreatitis. The aim of this study was to evaluate treatment with the selective iNOS inhibitors AR-C (AR-C102222AA) and L-NIL (L-N6-(1-iminoethyl)-lysine) in experimental acute pancreatitis.

    METHODS:

    Acute pancreatitis was induced in anesthetized Australian possums by topical administration of carbachol on the sphincter of Oddi. AR-C treatment was 2 intravenous infusions (2.5 micromol/kg over 15 minutes) at 2 and 4 hours after acute pancreatitis induction. L-NIL treatment was an intraarterial infusion (1 mg/kg/h) from 2 hours after acute pancreatitis induction. At 8 hours, pancreatic tissue was harvested and inflammation assessed (histologic score). Blood samples were collected for plasma amylase, lipase, and amino acid levels. Blood pressure, central venous pressure, supplementary fluids, and urine output were monitored.

    RESULTS:

    Treatment with AR-C or L-NIL reduced the plasma levels of amylase and the volume of supplementary fluids and improved the histological score (all P < 0.05). In animals with acute pancreatitis, plasma arginine levels were reduced (P < 0.05), while citrulline and ornithine levels increased (P < 0.05), consistent with increased nitric oxide production. Treatment with AR-C ameliorated the reduced arginine level.

    CONCLUSIONS:

    Treatment with AR-C or L-NIL, commencing 2 hours after the induction of acute pancreatitis, has significant and beneficial effects in experimental acute pancreatitis in Australian possums.

  • 112.
    Sandström, Per
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Gasslander, Thomas
    Department of Surgery, Vrinnevi Hospital, Norrköping, Sweden.
    Sundqvist, Tommy
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Franke, Jonas
    Department of Surgery, Vrinnevi Hospital, Norrköping, Sweden.
    Svanvik, Joar
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Depletion of serum L-arginine in patients with acute pancreatitis2003In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 27, no 3, p. 261-266Article in journal (Refereed)
    Abstract [en]

    Introduction: Acute pancreatitis may be initiated by interference with the pancreatic outflow to the duodenum. This flow is normally regulated by reflex relaxation of the sphincter of Oddi in which nitric oxide is an important mediator.

    Aim: To test the hypothesis that acute pancreatitis involves a depletion in serum l-arginine resulting in impaired production of nitric oxide.

    Methods: We measured serum l-arginine and l-citrulline and urinary nitrite/nitrate concentrations 1 to 3 days after the onset of symptoms in 11 patients with gallstone pancreatitis, 10 patients with alcoholic pancreatitis, and 6 patients with idiopathic pancreatitis. We compared their results with those from control groups of 13 healthy blood donors, 9 patients fasting before hernia operations, 8 patients with acute cholecystitis, and 9 alcoholic subjects but no pancreatitis. Serum arginine and citrulline concentrations were measured with high performance liquid chromatography, and urinary nitrite/nitrate spectrophotometrically.

    Results: Patients with acute pancreatitis, of whatever cause, had lower serum l-arginine and l-citrulline concentrations than controls. Patients with gallstone and idiopathic pancreatitis also have reduced urinary concentrations of nitrite and nitrate but this was not seen in patients with alcoholic pancreatitis.

    Conclusions: L-arginine and l-citrulline concentrations are depleted in the serum of patients with acute pancreatitis. Reduced urinary nitrite and nitrate in gallstone pancreatitis indicate that there is a defect formation of nitric oxide. This may cause a functional obstruction of the outflow of pancreatic juice to the duodenum and so may be involved in the pathophysiology of acute pancreatitis.

  • 113. Santos, J
    et al.
    Yang, P-C
    Söderholm, Johan D
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Benjamin, M
    Perdue, MH
    Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat.2001In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 48, p. 630-636Article in journal (Refereed)
  • 114. Sayer, Brooke
    et al.
    Lu, Jun
    Green, Christina
    Söderholm, Johan D
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Akhtar, Mahmood
    McKay, Derek M
    Dextran sodium sulphate-induced colitis perturbs muscarinic cholinergic control of colonic epithelial ion transport2002In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 135, p. 1794-1800Article in journal (Refereed)
  • 115.
    Shabo, Ivan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery.
    Nordenskjöld, Kerstin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Svanvik, Joar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Incidensen av gallblåsecancer i Sverige har minskat. Den dåliga prognosen kan möjligen förbättras genom radikal kirurgi. [The incidence of gallbladder cancer in Sweden has decreased. The poor prognosis can possibly be improved by radical surgery.]2001In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 98, no 42, p. 4584-4589Article in journal (Other academic)
    Abstract [sv]

    Gallblåsecancer är en relativt sällsynt sjukdom som har dålig prognos med kort överlevnadstid. Sjukdomen drabbar framför allt kvinnor. Vi har inhämtat registerdata från cancerregistret och dödsorsaksregistret och studerat utvecklingen i Sverige mellan 1988 och 1997. Under de senaste åren har incidensen minskat, vilket möjligen kan förklaras av en hög kolecystektomifrekvens under 1950- och 1970-talen. Prognosen vid erhållen diagnos har tidigare varit dålig, med en medianöverlevnad på 3,5 månader, vilket beror på att diagnosen ofta har ställts först när sjukdomen blivit avancerad. Epidemiologiska data visar att dessa siffror kan ha förbättrats de senaste åren. I flera aktuella studier, framför allt från Japan, rapporteras bättre resultat och längre överlevnadstid efter utvidgad kirurgi. I ett material av elva patienter med gallblåsecancer, grad II–V enligt Nevin, som opererats med utvidgad kirurgi i Linköping finns hos tio inga tecken på recidiv efter en uppföljningstid på 1–8 år.

  • 116.
    Sjöberg, Folke
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, Anestesi. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery and Burns.
    Danielsson, Pär
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery and Burns.
    Andersson, L
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery and Burns.
    Steinwall, I
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery and Burns.
    Zdolsek, Joachim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery and Burns.
    Östrup, Leif
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery.
    Monafo, W
    Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
    Utility of an intervention scoring system in documenting effects of changes in burn treatment2000In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 26, no 6, p. 553-559Article in journal (Refereed)
    Abstract [en]

    The consequences of the introduction of a program of consistent use of topical antimicrobials and early aggressive excision of deep burn wounds by utilizing a comprehensive, computerized patient registry/therapeutic intervention scoring system, were investigated. Prospectively, the clinical course, mortality, outcome and hospital costs were compared for the year preceding (89 patients) and the 4 years following (226 patients) the introduction of the new treatment program. It was found that mortality decreased from 10.1 to 4.6% after change in therapy (P < 0.001), despite an increase in mean burn extent. The length of hospital stay per % burn surface area declined from 1.2 to 1.0 days (P < 0.001). The number and complexity of therapeutic interventions and the associated costs, also declined. Patients in the new treatment program had a better level of physical and psychosocial function at follow up. In conclusion, the introduction of a program of consistent use of topical antimicrobials and early, aggressive surgical excision was associated with an improved outcome at lesser cost. The combined registry-intervention scoring system permits ready analysis of results using data entered on a daily, near-real time basis.

  • 117.
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Comment NSAIDs and colorectal cancer.1999In: Int Hospital Pharmacy, ISSN 1354-5337, Vol. 9Article in journal (Refereed)
  • 118.
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Extent, mode, and dose dependence of anticancer effects2001In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 110, no 1 SUPPL. 1Article in journal (Refereed)
    Abstract [en]

    Regular intake of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a decreased incidence of colorectal, esophageal, gastric, and lung cancer. The relative risk of colorectal cancer is about 0.6 in large cohort studies - in other words, the risk is reduced by 40%. Also, in experimental models, the frequency of colonic cancer is reduced by NSAIDs. Both human and experimental tumors contain increased amounts of prostaglandin E2, which may have a role in the accelerated proliferation taking place in tumor tissue. This may be the result of activation of cyclooxygenase-2 (COX-2) in response to mitogens and growth factors, for example, which will result in an increased production of prostaglandins. The current theory is that the mechanism for the suppressor effect of NSAIDs on carcinogenesis is COX-2 inhibition. However, reliable data on the dose of aspirin or other NSAIDs for optimal benefit for tumor suppression are lacking, and it is still premature to give general recommendations on using NSAIDs for chemoprevention of gastrointestinal cancer.

  • 119.
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    The role of total mesorectal excision in rectal cancer surgery2001In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 27, no 5, p. 440-441Article in journal (Refereed)
    Abstract [en]

    A subtotal mesorectal excision with straight colorectal anastomosis should be done when the resection line is located 7 cm or more from the anal verge with a distal margin to the tumour of at least 3 cm. Subtotal TME combined with closure of the rectum and a colostomy (Hartmann's procedure) is performed at any level provided it is oncologically acceptable. TME with restorative surgery by a pouch-anal anastomosis is used for lower lesions not allowing an anastomosis at least 7 cm from the anal verge. TME with a low Hartmann's procedure is performed in patients with disseminated disease, other high risk patients, and when the anal sphincter function is inadequate. Abdomino-perineal resection (with the TME technique) is performed when the anal canal is infiltrated by tumour. TME is indicated in all rectal cancers which can be palpated.

  • 120.
    Sjödahl, Rune
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Johansen, Lars
    Wallin, Göran
    Kirurgernas jourverksamhet måste förändras för att klara nyrekryteringen2002In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 99, p. 311-313Article in journal (Other academic)
  • 121.
    Sjödahl, Rune
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Myrelid, Pär
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Söderholm, Johan D
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Anal and rectal cancer in Crohn's disease2003In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 5, no 5, p. 490-495Article in journal (Refereed)
    Abstract [en]

    Several epidemiological studies have been published regarding the risk of Crohn's disease- associated colorectal cancer. The findings are, however, contradictory and it has been particularly difficult to obtain indisputable information on the incidence of cancer limited to the rectum and the anus. During 1987-2000 rectal or anal cancer was diagnosed in 335 patients in Sweden (153 males, 182 females). In other words, approximately 3 Crohn patients per million inhabitants were diagnosed with rectal or anal cancer every year during that time period which is 1% of the total number of cases. At diagnosis of cancer 36% were aged below 50 years and 58% below 60 years. Corresponding figures for all cases of anal and rectal cancer were 5% and 18%, respectively. Present knowledge from the literature implies that there is an increased risk of rectal and anal cancer only in Crohn's disease patients with severe proctitis or severe chronic perianal disease. However, the rectal remnant must also be considered a risk factor. Multimodal treatment is similar to that in sporadic cancer but proctectomy and total or partial colectomy is added depending on the extent of the Crohn's disease. The outcome is the same as in sporadic cancer at a corresponding stage but the prognosis is often poor due to the advanced stage of cancer at diagnosis. We suggest that six high-risk groups should be recommended annual surveillance after a duration of Crohn's disease of 15 years including extensive colitis, chronic severe anorectal disese, rectal remnant, strictures, bypassed segments and sclerosing cholangitis.

  • 122.
    Skullman, Stefan
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Liver regeneration: With reference to malnutrition and growth factors1993Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The liver has a unique capacity to regenerate after damage, irrespective of cause. The regulatory mechanisms of this regeneration are not fully known. Liver regeneration· is associated with rapid growth and thereby increased demands for energy and synthesis of new compounds. These studies were undertaken to evaluate the impact of malnutrition on liver regeneration, to observe the consequences for energy metabolism and protein synthesis, and to investigate the potential effects of some growth factors and cholecystokinin on liver regeneration.

    Liver regeneration was studied in rats after 70 % liver resection. Malnutrition was induced by feeding with only 25 % of normal intake for one week. The regeneration rate was measured from incorporation of continuously infused radiolabelled thymidine and from liver DNA content and liver weight. Liver composition and contents of energy-rich substrateswere studied before and after regeneration. Protein synthesis was determined with a flooding dose method using labelled phenylalanine. The concentrations of epidermal growth factor (EGF), transfornting growth factor alpha (TGF-a) and insulin-like growth factor I (IGF-1) were measured in plasma and liver tissue. A constant endogenous increase in plasma cholecystokinin was induced by surgical pancreaticobiliary diversion.

    The studies showed that in malnourished rats the regeneration rate of hepatocytes was reduced and the rate of gain in liver weight, DNA and protein content decreased when expressed as absolute values. After 48 hours of regeneration, fat and water content had increased and glycogen and protein concentration decreased. Malnutrition was associated with a decrease in energy-rich phosphates and energy charge potential in the liver, but during regeneration in the malnourished state liver energy metabolism was given priority, with values rising to at least the same level as in the well-nourished group. Protein synthesis was stimulated during liver regeneration. After 48 hours of regeneration protein synthesis was greater in well-nourished than in malnourished rats. EGF concentrations were elevated in both plasma and liver tissue after 48 hours of liver regeneration indicating a role of EGF in that process. Levels of TGF-a were not then changed, suggesting that it is not important at this stage of regeneration. IGF-I concentrations were increased in regenerating hepatic tissue, implying a possible effect on regeneration. Malnutrition per se increased the plasma EGF levels, indicating involvement in the body's defense against malnutrition. Pancreaticobiliary diversion associated with increased cholecystokinin levels induced pancreatic hypertrophy and hyperplasia but no change was seen in the rate of liver regeneration.

  • 123.
    Smedh, Kennet
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Intrapperative and endoscopic surveillance after surgery in Chron's disease1994Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Crohn's disease is a chronic inflammatory bowel disease. There is no cure and the disease progresses to severe intestinal inflammation and stricture fonnation. Most patients will require intestinal resection of diseased bowel segments, but this is frequently followed by recurrent inflammation and symptoms.

    The study was undertaken to investigate a possible role for intraoperative endoscopy of the bowel in the surgical management of Crohn's disease, and to investigate various aspects of recurrent intestinal inflammation by colonoileoscopic surveillance after surgery. During surgery the relationship between intraoperative endoscopy of the bowel, transmural histopathology, and exterior inflammatory bowel wall changes, traditionally used to decide the extent of intestinal resection, were investigated, as was the influence intraoperative endoscopic findings had on surgical decision·making. At follow-up after surgery, the reliability of endoscopy was evaluated by studying the interobserver variation of endoscopic findings and the relationship between endoscopic inflammatory lesions and symptoms were investigated.

    Ileal ulcerations appeared soon after ileocolic resection, within three months, and with a high frequency. The lesions showed a time·related progression from aphthous ulcers to larger ulcers and stricture and excellent interobserver agreement was seen with some well· defined inflammatory lesions, even when investigator experience was limited. Ileal ulcers appeared prior to symptoms. Luminal pus and anastomotic stricture were related to symptoms and a stricture frrst produced symptoms when the diameter was less than 10 mm. The length of intestinal resection was as much related to symptoms as any endoscopically visualized inflammatory lesion. Endoscopically viewed inflammation correlated with bowel wall histopathology, whereas exterior bowel wall lesions, i.e. mural thickening, fat wrapping and serositis, had poorer correlation to both histology and endoscopy, the difference being attributable to cases with previous resection, fistula or abscess which causes exterior bowel wall changes mimicking Crohn's disease.

    In conclusion, intraoperative endoscopy offers better guidance as regards intestinal resection and selection of strictures for treaunent, and intraopemtive endoscopic findings intluenced surgical decision·making in the majority of the cases mainly by limiting intestinal resection. The findings underline the chronicity of Crohn's disease. This and the association of intestinal resection with symptoms emphasize the advisability of conservative surgery in Crohn's disease, which requires accurate intraoperative decisions. Intraoperative endoscopy enables more precise surgery.

  • 124.
    Smeds, Staffan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, GE: endokir.
    Trulsson, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery.
    Garovay, M
    Gumpert, M
    Clark, OH
    Survival of human parathyroid tissue transplanted in nude mice after 9 to 55 months' cryopreservation.1999In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 107, p. 445-450Article in journal (Refereed)
  • 125.
    Stenmark-Askmalm, Askmalm Marie
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Gentile, Massimiliano
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Wingren, Sten
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Arnesson, Lars-Gunnar
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Protein accumulation and gene mutation of p53 in bilateral breast cancer2001In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 40, no 1, p. 56-62Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the frequency of p53 alterations in bilateral breast cancer and to evaluate a possible clonal relationship between the paired tumours regarding p53 alteration and other pathobiological variables. Tumours from 34 patients were investigated with immunohistochemistry, single strand conformation polymorphism analysis and DNA-sequence analysis applied to exons 5-8. Fifteen percent of the 68 tumours showed positive immunoreaction and/or presence of mutation. The occurrence of p53 accumulation was 9% and the prevalence of gene mutation 10%. No significant concordance was found between the tumours in the same patient for p53 alterations, progesterone receptor status or DNA ploidy. S-phase fraction showed a weak correlation, not statistically significant. Oestrogen receptor status was the only variable that exhibited a significant concordance. No convincing evidence was found for other associations between the paired tumours or for a high prevalence of p53 alterations in bilateral breast cancer.

  • 126. Stenquist, Monika
    et al.
    Juhlin, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Åström, Gunnar
    Friberg, Ulla
    Case Report. Fourth branchial pouch sinus with recurrent deep cervical abscesses successfully treated with trichloroacetic acid cauterization2003In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 123, p. 879-882Article in journal (Refereed)
  • 127. Stenquist, Monika
    et al.
    Juhlin, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Åström, Gunnar
    Friberg, Ulla
    Fallbeskrivning: Anomali i fjärde gälfickan med recidiverande halsabscesser. Etsning med triklorättiksyra tillslöt fistelmynning och botade patienten2003In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 100, p. 1536-1539Article in journal (Other academic)
  • 128.
    Sun, Yi-Qian
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Experimental Helicobacter pylori infection in an animal model2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Helicobacter pylori is a microaerophilic Gram-negative bacterium colonizing the human stomach. The prevalence of this infection is between 20-90% depending on geographic location. Comprehensive studies have shown significant relationships between H. pylori infection and chronic gastritis, peptic ulcer and gastric carcinoma. The mechanisms behind these associations are still unclear in many aspects. The objective of this thesis was to elucidate some pathogenetic aspects of H. pylori infection based on an animal model using Mongolian gerbils.

    Aims: To determine bacterial profiles in the stomach of gerbils with and without H. pylori infection. To study the long-term morpho-functional development of H. pylori-induced gastritis. To investigate the gastric mucosal barrier function and to explore the effects of dietary antioxidant vitamin supplements on H. pylori-associated chronic gastritis.

    Methods and results: Mongolian gerbils were inoculated with H. pylori ATCC 43504 or culture broth (controls). The animals were killed at scheduled time points. The gastric microflora was profiled and identified by temporal temperature gradient gel electrophoresis (TTGE), cloning and pyrosequencing of 16S rDNA variable V3 region. TTGE and pyrosequencing revealed the presence of a mixed bacterial flora in the stomach of both H. pylori infected and control animals. In both cases, lactobacilli appeared to prevail. In H. pylori-infected gerbils, serum concentrations of anti-H. pylori IgG and gastrin increased over time. Mucosal epithelial proliferation quantified after immunohistochemical labeling with 5-bromo-2'-deoxy-uridine was increased in the antrum in short-term gastritis, followed by an increase in the corpus in the long-term. Gene expression of pro-inflammatory cytokines was quantitated by real-time RT-PCR. Interleukin-1beta and tumor necrosis factor-alpha expression was increased in H. pylori-infected gerbils. Beta-actin was not a reliable endogenous control for relative quantitative RT-PCR. Histological parameters of gastritis were semiquantitatively assessed and expressed as a "gastritis score". Gastritis scores increased over time and reached a peak 32 weeks after inoculation. With time there was an expansion of gastritis from the antrum to the corpus. Severe inflammation, ulcer development and pseudopyloric metaplasia (glandular atrophy) were characteristic features. Gastric mucosal samples were mounted in Ussing chambers and 51Cr-EDTA (paracellular probe) and horseradish peroxidase (HRP, protein antigen) were used as indicators of gastric mucosal barrier function. Short-term gastritis showed increased mucosal permeability to 51Cr-EDTA in the antrum. Long-standing gastritis was associated with increased 51Cr-EDTA permeation in both the antrum and corpus and an increased HRP flux in the antrum. In the vitamin supplement study, concentrations of 3-nitrotyrosine (nitrosative protein damage) and thiobarbituric acid reactive substances (TBARS) (oxidative lipid damage) in the gastric mucosa were determined with an immunodot blot and a fluorometric method, respectively. Mucosal concentrations of carbonyl carbons on proteins (oxidative protein damage) and 8-hydroxydeoxyguanosine (oxidative DNA damage) were determined by ELISA. Vitamin supplements had no effect on the colonization with H. pylori. Vitamin C as well as vitamin E supplements reduced mucosal 3-nitrotyrosine concentrations to normal levels in the infected animals. Vitamin E supplement induced decreased mucosal protein carbonyls and TBARS in short-term gastritis. In addition, vitamin C supplement caused attenuated mucosal oxidative DNA damage and milder mucosal inflammation in short-term gastritis.

    Conclusions: Lactobacilli, the prevailing indigenous bacterium in the stomach of gerbils, may have a probiotic impact on the colonization of H. pylori. The long-term morpho-functional development in the stomach of H. pylori-infected Mongolian gerbils resembles that of H. pylori-infected humans. H. pylori-induced gastritis in gerbils is associated with a long-standing gastric mucosal barrier dysfunction, which follows the extension of chronic gastritis from the antrum into the corpus over time. This impaired barrier function may contribute to perpetuation of chronic inflammation and may be involved in H. pylori-associated carcinogenesis. Vitamin C as well as vitamin E supplements lead to some short-term protective effects on H. pylori-induced stritis but these effects seem to subside over time when the infection persists.

    List of papers
    1. Profiling and identification of eubacteria in the stomach of Mongolian gerbils with and without Helicobacter pylori infection
    Open this publication in new window or tab >>Profiling and identification of eubacteria in the stomach of Mongolian gerbils with and without Helicobacter pylori infection
    Show others...
    2003 (English)In: Helicobacter, ISSN 1083-4389, E-ISSN 1523-5378, Vol. 8, no 2, p. 149-157Article in journal (Refereed) Published
    Abstract [en]

    Background. Mongolian gerbils are frequently used to study Helicobacter pylori-induced gastritis and its consequences. The presence of an indigenous bacterial flora with suppressive effect on H. pylori may cause difficulties with establishing this experimental model.

    Aim. The aim of the present study was to determine bacterial profiles in the stomach of Mongolian gerbils with and without (controls) H. pylori infection.

    Methods. Gastric tissue from H. pylori ATCC 43504 and CCUG 17874 infected and control animals were subjected to microbial culturing and histology. In addition, gastric mucosal samples from H. pylori ATCC 43504 infected and control animals were analyzed for bacterial profiling by temporal temperature gradient gel electrophoresis (TTGE), cloning and pyrosequencing of 16S rDNA variable V3 region derived PCR amplicons.

    Results. Oral administration of H. pylori ATCC 43504, but not CCUG 17874, induced colonization and gastric inflammation in the stomach of Mongolian gerbils. Temporal temperature gradient gel electrophoresis (TTGE) and partial 16S rDNA pyrosequencing revealed the presence of DNA representing a mixed bacterial flora in the stomach of both H. pylori ATCC 43504 infected and control animals. In both cases, lactobacilli appeared to be dominant.

    Conclusion. These findings suggest that indigenous bacteria, particularly lactobacilli, may have an impact on the colonization and growth of H. pylori strains in the stomach of Mongolian gerbils.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24966 (URN)10.1046/j.1523-5378.2003.00136.x (DOI)9377 (Local ID)9377 (Archive number)9377 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    2. Long-term morpho-functional development of Helicobacter pylori-induced gastritis in Mongolian gerbils
    Open this publication in new window or tab >>Long-term morpho-functional development of Helicobacter pylori-induced gastritis in Mongolian gerbils
    Show others...
    2005 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 40, no 10, p. 1157-1167Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE:

    Epidemiological studies have shown that Helicobacter pylori infection with associated chronic gastritis is the main risk factor for development of gastric cancer. The aim of this study was to investigate the long-term development of H. pylori-induced gastritis in Mongolian gerbils in terms of morphology, gastrin secretion, epithelial proliferation and gene expression of pro-inflammatory cytokines.

    MATERIAL AND METHODS:

    A total of 133 gerbils were inoculated with H. pylori and 62 served as controls. The gerbils were killed at different time-points between 6 and 94 weeks after inoculation. Serum concentrations of anti-H. pylori IgG and gastrin were determined by enzyme-linked immunoabsorbent assay (ELISA) and radioimmunoassay (RIA), respectively. Epithelial proliferation was evaluated immunohistochemically after labeling with 5-bromo-2'-deoxy-uridine. Gene expression of beta-actin, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) were measured by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Histological parameters of gastritis were assessed semiquantitatively and expressed as a "gastritis score".

    RESULTS:

    Serum concentrations of anti-H. pylori IgG and gastrin increased over time. Epithelial proliferation in the antrum was increased 6 weeks after inoculation, followed by increased proliferation in the corpus 32 weeks after inoculation. Gene expression of IL-1beta and TNF-alpha were increased in H. pylori-infected gerbils. Beta-actin was not a reliable endogenous control for RT-PCR. With time, gastritis expanded from the antrum to the corpus and the gastritis score increased to reach a peak 32 weeks after inoculation. Pseudopyloric metaplasia (loss of specialized cells) was a characteristic feature in the corpus mucosa. Gastric ulcers, but neither dysplasia nor carcinoma, were observed during 94 weeks of infection.

    CONCLUSIONS:

    Long-term H. pylori infection in Mongolian gerbils led to progressive gastritis, glandular atrophy, hypergastrinemia, increased epithelial proliferation and elevated gene expression of pro-inflammatory cytokines.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-30811 (URN)10.1080/00365520510023378 (DOI)16441 (Local ID)16441 (Archive number)16441 (OAI)
    Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13Bibliographically approved
    3. Long-standing gastric mucosal barrier dysfunction in Helicobacter pylori-induced gastritis in Mongolian gerbils
    Open this publication in new window or tab >>Long-standing gastric mucosal barrier dysfunction in Helicobacter pylori-induced gastritis in Mongolian gerbils
    2004 (English)In: Helicobacter, ISSN 1083-4389, E-ISSN 1523-5378, Vol. 9, no 3, p. 217-227Article in journal (Refereed) Published
    Abstract [en]

    Background and Aims. Helicobacter pylori infection causes chronic gastritis and leads to peptic ulcer and gastric adenocarcinoma. An impaired gastric mucosal barrier could be involved in these processes. Our aim was to investigate gastric barrier function in H. pylori-induced gastritis.

    Methods.  Stripped gastric mucosal tissues of H. pylori-infected Mongolian gerbils (4 weeks and 70 weeks after inoculation, respectively) and controls were mounted in Ussing chambers. 51Cr-EDTA (paracellular probe) and horseradish peroxidase (HRP, protein antigen) were used to assess mucosal barrier function. The electrophysiological parameters of the mucosa (transepithelial potential, short circuit current, and transepithelial resistance) were monitored as measurements of barrier integrity and viability. Tissue histology was performed to assess inflammation.

    Results.  In the antrum, both short-term gastritis [4.68 (3.88–5.74) × 10−6 vs. control 2.86 (2.34–3.77) × 10−6 cm/s, p < .001] and gastritis of long-standing [5.72 (3.88–10.94) × 10−6 cm/s, p < .001 vs. control] showed increased permeability to 51Cr-EDTA. In long-standing antral gastritis there was also an increased HRP flux [9.01 (2.98–45.02) vs. control 0.52 (0.06–1.20) pmol/h/cm2, p < .001]. In the corpus, permeability to 51Cr-EDTA was increased only in long-standing gastritis [4.63 (3.64–7.45) × 10−6 vs. control 2.86 (2.12–3.98) × 10−6 cm/s, p < .01]. Gastric mucosal permeability to 51Cr-EDTA was correlated to histological inflammation and inflammatory activity. The levels of serum anti-H. pylori immunoglobulin G were positively correlated to HRP flux and 51Cr-EDTA permeation.

    Conclusions. Helicobacter pylori-induced gastritis in Mongolian gerbils was associated with a long-standing gastric mucosal barrier dysfunction. The barrier defect extended from the antrum into the corpus over time. This impaired barrier function may contribute to perpetuation of chronic inflammation and may be involved in H. pylori-associated carcinogenesis.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-22344 (URN)10.1111/j.1083-4389.2004.00227.x (DOI)1545 (Local ID)1545 (Archive number)1545 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    4. Effects of antioxidant vitamin supplements on Helicobacter pylori-induced gastritis in Mongolian gerbils
    Open this publication in new window or tab >>Effects of antioxidant vitamin supplements on Helicobacter pylori-induced gastritis in Mongolian gerbils
    Show others...
    2005 (English)In: Helicobacter, ISSN 1083-4389, E-ISSN 1523-5378, Vol. 10, no 1, p. 33-42Article in journal (Refereed) Published
    Abstract [en]

    Background.  Epidemiological studies show that high intake of food-bound vitamin C and E reduces the risk of gastric cancer. Whether dietary supplementation with antioxidant micronutrients interferes with Helicobacter pylori infection and associated diseases is unclear. The aim of this study was to investigate if dietary vitamin C or E supplementation influences the progression of gastritis, gastric mucosal nitrosative and oxidative protein damage, gastric mucosal lipid peroxidation, or gastric mucosal oxidative DNA damage in H. pylori-infected Mongolian gerbils.

    Materials and methods.  Gerbils were divided into four groups: H. pylori-infected animals fed with vitamin C- or vitamin E-supplemented food, and infected and uninfected animals given standard rodent food. Subgroups of animals were killed at different time-points until 52 weeks postinfection. Concentrations of 3-nitrotyrosine and thiobarbituric acid-reactive substances (TBARS) in the gastric mucosa were determined with an immunodot blot and a fluorometric method, respectively. Mucosal concentrations of carbonyl carbons on proteins and 8-hydroxydeoxyguanosine were determined by enzyme-linked immunosorbent assay. Gastritis was scored semiquantitatively.

    Results.  Vitamin supplements had no effect on the colonization with H. pylori. Vitamin C as well as vitamin E supplements reduced mucosal 3-nitrotyrosine concentrations to normal levels in infected animals. Vitamin E supplements decreased mucosal protein carbonyls and TBARS in short-term gastritis. In addition, vitamin C supplements caused attenuated mucosal oxidative DNA damage and milder mucosal inflammation in short-term gastritis.

    Conclusion.  Vitamin C or vitamin E supplementation leads to some short-term protective effects on H. pylori-induced gastritis in Mongolian gerbils. These effects seem to subside over time when the infection persists.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-29786 (URN)10.1111/j.1523-5378.2005.00289.x (DOI)15197 (Local ID)15197 (Archive number)15197 (OAI)
    Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13Bibliographically approved
  • 129.
    Sun, Yi-Qian
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Girgensone, Ilze
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Leanderson, Per
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Petersson, Fredrik
    Pathology Research Department, Ryhov Hospital, Jönköping, Sweden.
    Borch, Kurt
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Effects of antioxidant vitamin supplements on Helicobacter pylori-induced gastritis in Mongolian gerbils2005In: Helicobacter, ISSN 1083-4389, E-ISSN 1523-5378, Vol. 10, no 1, p. 33-42Article in journal (Refereed)
    Abstract [en]

    Background.  Epidemiological studies show that high intake of food-bound vitamin C and E reduces the risk of gastric cancer. Whether dietary supplementation with antioxidant micronutrients interferes with Helicobacter pylori infection and associated diseases is unclear. The aim of this study was to investigate if dietary vitamin C or E supplementation influences the progression of gastritis, gastric mucosal nitrosative and oxidative protein damage, gastric mucosal lipid peroxidation, or gastric mucosal oxidative DNA damage in H. pylori-infected Mongolian gerbils.

    Materials and methods.  Gerbils were divided into four groups: H. pylori-infected animals fed with vitamin C- or vitamin E-supplemented food, and infected and uninfected animals given standard rodent food. Subgroups of animals were killed at different time-points until 52 weeks postinfection. Concentrations of 3-nitrotyrosine and thiobarbituric acid-reactive substances (TBARS) in the gastric mucosa were determined with an immunodot blot and a fluorometric method, respectively. Mucosal concentrations of carbonyl carbons on proteins and 8-hydroxydeoxyguanosine were determined by enzyme-linked immunosorbent assay. Gastritis was scored semiquantitatively.

    Results.  Vitamin supplements had no effect on the colonization with H. pylori. Vitamin C as well as vitamin E supplements reduced mucosal 3-nitrotyrosine concentrations to normal levels in infected animals. Vitamin E supplements decreased mucosal protein carbonyls and TBARS in short-term gastritis. In addition, vitamin C supplements caused attenuated mucosal oxidative DNA damage and milder mucosal inflammation in short-term gastritis.

    Conclusion.  Vitamin C or vitamin E supplementation leads to some short-term protective effects on H. pylori-induced gastritis in Mongolian gerbils. These effects seem to subside over time when the infection persists.

  • 130.
    Sun, Yi-Qian
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Monstein, Hans-Jürg
    Östergötlands Läns Landsting, LMÖ - Laboratoriemedicin i Östergötland.
    Nilsson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Petersson, Fredrik
    Pathology Research Department, Ryhov Hospital, Jönköping, Sweden.
    Borch, Kurt
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Profiling and identification of eubacteria in the stomach of Mongolian gerbils with and without Helicobacter pylori infection2003In: Helicobacter, ISSN 1083-4389, E-ISSN 1523-5378, Vol. 8, no 2, p. 149-157Article in journal (Refereed)
    Abstract [en]

    Background. Mongolian gerbils are frequently used to study Helicobacter pylori-induced gastritis and its consequences. The presence of an indigenous bacterial flora with suppressive effect on H. pylori may cause difficulties with establishing this experimental model.

    Aim. The aim of the present study was to determine bacterial profiles in the stomach of Mongolian gerbils with and without (controls) H. pylori infection.

    Methods. Gastric tissue from H. pylori ATCC 43504 and CCUG 17874 infected and control animals were subjected to microbial culturing and histology. In addition, gastric mucosal samples from H. pylori ATCC 43504 infected and control animals were analyzed for bacterial profiling by temporal temperature gradient gel electrophoresis (TTGE), cloning and pyrosequencing of 16S rDNA variable V3 region derived PCR amplicons.

    Results. Oral administration of H. pylori ATCC 43504, but not CCUG 17874, induced colonization and gastric inflammation in the stomach of Mongolian gerbils. Temporal temperature gradient gel electrophoresis (TTGE) and partial 16S rDNA pyrosequencing revealed the presence of DNA representing a mixed bacterial flora in the stomach of both H. pylori ATCC 43504 infected and control animals. In both cases, lactobacilli appeared to be dominant.

    Conclusion. These findings suggest that indigenous bacteria, particularly lactobacilli, may have an impact on the colonization and growth of H. pylori strains in the stomach of Mongolian gerbils.

  • 131.
    Sun, Yi-Qian
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Petersson, Fredrik
    Pathology Research Department, Ryhov Hospital, Jönköping.
    Monstein, Hans-Jürg
    Östergötlands Läns Landsting, LMÖ - Laboratoriemedicin i Östergötland.
    Söderholm, Johan D
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Rehfeld, Jens F
    Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen.
    Borch, Kurt
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Long-term morpho-functional development of Helicobacter pylori-induced gastritis in Mongolian gerbils2005In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 40, no 10, p. 1157-1167Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Epidemiological studies have shown that Helicobacter pylori infection with associated chronic gastritis is the main risk factor for development of gastric cancer. The aim of this study was to investigate the long-term development of H. pylori-induced gastritis in Mongolian gerbils in terms of morphology, gastrin secretion, epithelial proliferation and gene expression of pro-inflammatory cytokines.

    MATERIAL AND METHODS:

    A total of 133 gerbils were inoculated with H. pylori and 62 served as controls. The gerbils were killed at different time-points between 6 and 94 weeks after inoculation. Serum concentrations of anti-H. pylori IgG and gastrin were determined by enzyme-linked immunoabsorbent assay (ELISA) and radioimmunoassay (RIA), respectively. Epithelial proliferation was evaluated immunohistochemically after labeling with 5-bromo-2'-deoxy-uridine. Gene expression of beta-actin, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) were measured by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Histological parameters of gastritis were assessed semiquantitatively and expressed as a "gastritis score".

    RESULTS:

    Serum concentrations of anti-H. pylori IgG and gastrin increased over time. Epithelial proliferation in the antrum was increased 6 weeks after inoculation, followed by increased proliferation in the corpus 32 weeks after inoculation. Gene expression of IL-1beta and TNF-alpha were increased in H. pylori-infected gerbils. Beta-actin was not a reliable endogenous control for RT-PCR. With time, gastritis expanded from the antrum to the corpus and the gastritis score increased to reach a peak 32 weeks after inoculation. Pseudopyloric metaplasia (loss of specialized cells) was a characteristic feature in the corpus mucosa. Gastric ulcers, but neither dysplasia nor carcinoma, were observed during 94 weeks of infection.

    CONCLUSIONS:

    Long-term H. pylori infection in Mongolian gerbils led to progressive gastritis, glandular atrophy, hypergastrinemia, increased epithelial proliferation and elevated gene expression of pro-inflammatory cytokines.

  • 132.
    Sun, Yi-Qian
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Söderholm, Johan D
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Petersson, Fredrik
    Pathology Research Department, Ryhov Hospital, Jönköping, Sweden.
    Borch, Kurt
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Long-standing gastric mucosal barrier dysfunction in Helicobacter pylori-induced gastritis in Mongolian gerbils2004In: Helicobacter, ISSN 1083-4389, E-ISSN 1523-5378, Vol. 9, no 3, p. 217-227Article in journal (Refereed)
    Abstract [en]

    Background and Aims. Helicobacter pylori infection causes chronic gastritis and leads to peptic ulcer and gastric adenocarcinoma. An impaired gastric mucosal barrier could be involved in these processes. Our aim was to investigate gastric barrier function in H. pylori-induced gastritis.

    Methods.  Stripped gastric mucosal tissues of H. pylori-infected Mongolian gerbils (4 weeks and 70 weeks after inoculation, respectively) and controls were mounted in Ussing chambers. 51Cr-EDTA (paracellular probe) and horseradish peroxidase (HRP, protein antigen) were used to assess mucosal barrier function. The electrophysiological parameters of the mucosa (transepithelial potential, short circuit current, and transepithelial resistance) were monitored as measurements of barrier integrity and viability. Tissue histology was performed to assess inflammation.

    Results.  In the antrum, both short-term gastritis [4.68 (3.88–5.74) × 10−6 vs. control 2.86 (2.34–3.77) × 10−6 cm/s, p < .001] and gastritis of long-standing [5.72 (3.88–10.94) × 10−6 cm/s, p < .001 vs. control] showed increased permeability to 51Cr-EDTA. In long-standing antral gastritis there was also an increased HRP flux [9.01 (2.98–45.02) vs. control 0.52 (0.06–1.20) pmol/h/cm2, p < .001]. In the corpus, permeability to 51Cr-EDTA was increased only in long-standing gastritis [4.63 (3.64–7.45) × 10−6 vs. control 2.86 (2.12–3.98) × 10−6 cm/s, p < .01]. Gastric mucosal permeability to 51Cr-EDTA was correlated to histological inflammation and inflammatory activity. The levels of serum anti-H. pylori immunoglobulin G were positively correlated to HRP flux and 51Cr-EDTA permeation.

    Conclusions. Helicobacter pylori-induced gastritis in Mongolian gerbils was associated with a long-standing gastric mucosal barrier dysfunction. The barrier defect extended from the antrum into the corpus over time. This impaired barrier function may contribute to perpetuation of chronic inflammation and may be involved in H. pylori-associated carcinogenesis.

  • 133.
    Sund-Levander, Märtha
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology.
    Forsberg, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery.
    Wahren, Lis Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Welfare and Care (IVV), Science in Nursing.
    Normal oral, rectal, tympanic and axillary body temperature in adult men and women: A systematic literature review2002In: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 16, no 2, p. 122-128Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to investigate normal body temperature in adult men and women. A systematic review of data was performed. Searches were carried out in MEDLINE, CINAHL, and manually from identified articles reference lists. Studies from 1935 to 1999 were included. Articles were classified as (1) strong, (2) fairly strong and (3) weak evidence. When summarizing studies with strong or fairly strong evidence the range for oral temperature was 33.2-38.2░C, rectal: 34.4-37.8░C, tympanic: 35.4-37.8░C and axillary: 35.5-37.0░C. The range in oral temperature for men and women, respectively, was 35.7-37.7 and 33.2-38.1░C, in rectal 36.7-37.5 and 36.8-37.1░C, and in tympanic 35.5-37.5 and 35.7-37.5░C. The ranges of normal body temperature need to be adjusted, especially for the lower values. When assessing body temperature it is important to take place of measurement and gender into consideration. Studies with random samples are needed to confirm the range of normal body temperature with respect to gender and age.

  • 134.
    Svanvik, Joar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    För en säkrare vård: Analysera den "mänskliga faktorn"! [For safer health care: Analyse the "human factor"!]2001In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 98, p. 3770-3771Article in journal (Other academic)
    Abstract [sv]

    Genom att utnytja erfarenheter inom andra verksamheter med högt ställda säkerhetskrav bör vi kunna göra vården säkrare. Förebyggande riskhantering kan ske genom analys av mänskliga felhandlingar, dels som generell vetenskap dels som en erfarenhetsregistrering, på ett sätt som minskar risken för att misstag skall upprepas. Den tekniska utvecklingen har skapat möjligheter för övning av färdigheter i realistiska simuleringsmodeller. Detta är användbart för övning av bl a kirurger, ortopeder och anestesiologer och kan även användas för rehabilitering av patienter.

  • 135.
    Svanvik, Joar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Gallsten - riskfaktorer och komplikationer.2000In: Incitament, ISSN 1103-503X, Vol. 9, p. 575-580Article in journal (Other (popular science, discussion, etc.))
  • 136.
    Svanvik, Joar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Laparoscopic cholecystectomy for acute cholecystitis1999In: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 166, no Suppl. 585, p. 16-17Article in journal (Refereed)
    Abstract [en]

    Acute cholecystitis was initially considered a contra-indication for laparoscopic cholecystectomy, but today the laparoscopic route is generally used even for severe acute cholecystitis. Several studies have shown that this is possible, although the conversion and complication rates are high, but there are no randomised controlled trials that evaluate the complications and costs of this technique compared with conventional open techniques. The timing of a laparoscopic cholecystectomy for acute cholecystitis is also a matter of debate as well as its use in elderly patients with this condition.

  • 137.
    Svanvik, Joar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Arvidsson, Dag
    Evaluation of laparoscopic procedures in the treatment of biliary disease, gastro-eosophageal reflux and inguinal hernia. State-of-the-art-konferens.2000In: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 166Article in journal (Refereed)
  • 138.
    Söderholm, Johan D
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Holmgren Peterson, Kajsa
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Olaison, Gunnar
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Franzén, Lennart E.
    Department of Pathology, Lund University–MAS, Malmö.
    Weström, Björn
    Department of Animal Physiology, Lund University, Lund, Sweden.
    Magnusson, Karl-Eric
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Sjödahl, Rune
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Epithelial permeability to proteins in the noninflamed ileum of Crohn's disease?1999In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 117, no 1, p. 65-72Article in journal (Refereed)
    Abstract [en]

    Background & Aims: Crohn's disease (CD) is associated with a disturbed intestinal barrier. Permeability studies have focused on inert molecules, but little is known about transepithelial transport of macromolecules with antigenic potential in humans. The aim of this study was to quantify permeation and to characterize passage routes for macromolecules in ileal mucosa in CD.

    Methods: Noninflamed and inflamed ileal mucosa specimens from patients with CD (n = 12) and ileal specimens from patients with colon cancer (n = 7) were studied regarding transmucosal permeation of ovalbumin, dextran (mol wt, 40,000), and 51Cr-EDTA for 90 minutes in vitro in Ussing chambers. Transepithelial passage routes for fluorescent ovalbumin and dextran 40,000 were investigated by confocal microscopy.

    Results: Noninflamed ileum from CD patients showed increased permeation of ovalbumin compared with ileum from colon cancer patients (P < 0.05). Dextran permeation was equal in the three groups, whereas 51Cr-EDTA permeability was increased in inflamed ileum. Ovalbumin passed both transcellularly and paracellularly, but dextran followed a strictly paracellular route. Both markers were subsequently endocytosed by cells of the lamina propria.

    Conclusions: Noninflamed ileal mucosa from patients with CD shows increased epithelial permeability to ovalbumin, probably by augmented transcytosis. This increase in antigen load to the lamina propria could be an initiating pathogenic event in CD.

  • 139.
    Söderholm, Johan D
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Malm, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Hematology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Long-term endoscopic remission of Crohn disease after autologous stem cell transplantation for acute myeloid leukaemia2002In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 37, no 5, p. 613-616Article in journal (Refereed)
    Abstract [en]

    A favourable course of Crohn disease has been observed after allogeneic bone marrow transplantation, and there is now mounting evidence that autologous stem cell may be an effective treatment for severe autoimmune diseases. Here, we present the first long-term endoscopic follow-up of a patient with Crohn disease undergoing autologous stem cell transplantation for haematological disease. A 54-year-old woman developed Crohn disease and was submitted to ileocaecal resection. Four months after surgery, the patient contracted acute myeloid leukaemia. She was initially treated with chemotherapy, and subsequently underwent autologous stem cell transplantation. Following transplantation, the patient has remained in clinical remission regarding both diseases, without anti-inflammatory medication. She has undergone ileo-colonoscopy with normal findings at 1, 2, 3 and 5 years after transplantation. This case suggests that autologous stem cell transplantation can change not only the clinical course, but also the natural history of intestinal inflammation in Crohn disease. This has pathophysiological as well as therapeutic implications.

  • 140.
    Söderholm, Johan D
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Olaison, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Lindberg, E
    Hannestad, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Vindels, A
    Tysk, C
    Janerot, G
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Different intestinal permeability patterns in relative and spouses of patients with Crohn's disease: an inherited defect in mucosal defence?1999In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 44, p. 96-100Article in journal (Refereed)
  • 141.
    Söderholm, Johan D
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Olaison, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Peterson, KH
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Franzén, LE
    Lindmark, T
    Wirén, Mikael
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Augmented increase in tight junction permeability by luminal stimuli in the non-inflamed ileum of crohn's disease2002In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 50, no 3, p. 307-313Article in journal (Refereed)
    Abstract [en]

    Background: Crohn's disease is associated with deranged intestinal permeability in vivo, suggesting dysfunction of tight junctions. The luminal contents are important for development of neoinflammation following resection. Regulation of tight junctions by luminal factors has not previously been studied in Crohn's disease. Aims: The aim of the study was to investigate the effects of a luminal stimulus, known to affect tight junctions, on the distal ileum in patients with Crohn's disease. Patients: Surgical specimens from the distal ileum of patients with Crohn's disease (n=l 2) were studied, and ileal specimens from colon cancer patients (n=l 3) served as controls. Methods: Mucosal permeability to 51Cr-EDTA and electrical resistance were studied in Ussing chambers during luminal exposure to sodium caprate (a constituent of milk fat, affecting tight junctions) or to buffer only. The mechanisms involved were studied by mucosal ATP levels, and by electron and confocal microscopy. Results: Baseline permeability was the same in non-inflamed ileum of Crohn's disease and controls. Sodium caprate induced a rapid increase in paracellular permeability - that is, increased permeation of 51Cr-EDTA and decreased electrical resistance - which was more pronounced in non-inflamed ileum of Crohn's disease, and electron microscopy showed dilatations within the tight junctions. Moreover, sodium caprate induced disassembly of perijunctional filamentous actin was more pronounced in Crohn's disease mucosa. Mucosal permeability changes were accompanied by mitochondrial swelling and a fall in epithelial ATP content, suggesting uncoupling of oxidative phosphorylation. Conclusions: The tight junctions in the non-inflamed distal ileum of Crohn's disease were more reactive to luminal stimuli, possibly mediated via disturbed cytoskeletal contractility. This could contribute to the development of mucosal neoinflammation in Crohn's disease.

  • 142.
    Söderholm, Johan D
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Perdue, Mary H
    Stress and the gastrointestinal tract II. Stress and intestinal barrier function.2001In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 280Article in journal (Refereed)
  • 143.
    Söderholm, Johan D
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Yang, Ping-Chang
    Ceponis, Peter
    Vohra, Angeli
    Riddell, Robert
    Sherman, Philip M
    Perdue, Mary
    Chronic stress induces mast cell-dependent bacterial adherence and initiates mucosal inflammation in rat intestine2002In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 123, p. 1099-1108Article in journal (Refereed)
  • 144.
    Söderholm, Johan D
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Yates, Derrick
    Gareau, Mélanie
    Yang, Ping-Chang
    MacQueen, Glenda
    Perdue, Mary
    Neonatal maternal separation predisposes adult rats to colonic barrier dysfunction in response to mild stress2002In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 283, p. 1257-1263Article in journal (Refereed)
  • 145.
    Tibbling Grahn, Lita
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Blackadder, L
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Franzén, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Kullman, Eric
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Gastric bile monitoring: An in vivo and in vitro study of bilitec reliability2002In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 37, no 11, p. 1334-1337Article in journal (Refereed)
    Abstract [en]

    Background: It has been claimed that the combination of bile and hydrochloride acid (HCl) has a noxious effect on intestinal mucosa. The aim was to study the reliability of the Bilitec 2001 method in monitoring the presence of bile in repeated tests and at different pH and water dilutions. Methods: 24-h esophageal pH and gastric Bilitec monitoring were performed twice with an interval of 6 weeks in 23 patients with symptomatic gastroesophageal reflux (GER). In vitro tests of pH and Bilitec recordings were performed with different mixtures of bile, HCl and water. Results: Gastric bile was present in 37% of the recording time, 28% during day time and 47% during nights. No significant difference was found between the two test occasions. The maximum bile concentration in the stomach was significantly lower in patients with severe pathological GER than in those with normal GER. When concentrated bile was diluted with the same volume of HCl, the pH level fell below 4. The maximum absorption limit with Bilitec in concentrated bile was gradually reduced with decreasing pH. The Bilitec technique recorded the presence of bile even at a pH of 1.4, but not if the bile was diluted with water at a ratio of 1:100 or more. Conclusions: Bilitec gastric recordings show the same clinical result when repeated under standardized conditions. The Bilitec technique is not reliable for monitoring the amount and concentration of bile in the stomach. Bile reflux cannot be monitored with the pH recording technique.

  • 146.
    Tiveljung, Annika
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Söderholm, Johan D.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Olaison, Gunnar
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Jonasson, Jon
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Monstein, Hans-Jürg
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Presence of eubacteria in biopsies from Crohn's disease inflammatory lesions as determined by 16S rRNA gene-based PCR1999In: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 48, no 3, p. 263-268Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to search for putative microbial agents in Crohn's disease (CD) tissues by bacterial broad-range 16S rDNA PCR combined with genus- and species-specific DNA hybridisation analysis. Biopsies taken both surgically and endoscopically from the terminal ileum of 11 CD patients and 11 control patients were investigated. Significant amounts of eubacteria were demonstrated in biopsies taken endoscopically from both affected and unaffected individuals; the biopsies taken at surgery from control patients were negative. Three of five biopsies taken surgically from CD patients harboured Helicobacter spp.-, Mycobacterium paratuberculosis-, Listeria monocytogenes- and Escherichia coli-like 16S rDNA sequences. These findings show the importance of the sampling method chosen when combined with molecular typing of eubacteria in intestinal tissues. The mixed bacterial flora found in the surgical biopsies from CD patients supports the idea that the enteric microflora enters primary lesions where secondary bacterial colonisers may elicit a chronic inflammatory syndrome.

  • 147.
    Trulsson, Lena
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Influence of cholecystokinin and nitric oxide on growth regulation in exocrine pancreas of the rat2002Licentiate thesis, comprehensive summary (Other academic)
  • 148.
    Trulsson, Lena
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    The influence of nitric oxide and cholecystokinin on tissue homeostasis in exocrine pancreas: an experimental study in rats2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Growth of the pancreas is stimulated by cholecystokinin (CCK) in rats. Nitric oxide (NO), which is synthesized from the amino acid L-arginine by NO-synthases (NOS), interferes with CCK in modulating the pancreatic secretion. Both pro- and anti-apoptotic influences of NO have been observed in other tissues, but its importance for pancreatic tissue homeostasis has not been studied.

    Cell proliferation and death rates were studied in the rat pancreas during different experimental conditions. CCK-octapeptide (CCK-8) was given in different doses either intermittently or continuously for three days and the pancreatic growth response was studied. Exogenous CCK-8 caused dose-dependent pancreatic atrophy when given intermittently and hyperplasia when given continuously.

    The influence of NO on cell death and proliferation was studied during: 1) basal conditions, 2) CCK-8 induced hyperplasia, and 3) CCK-8 induced atrophy. The NO level was manipulated either by NOS inhibition (L-NNA) or by exogenous NO supply (SNAP). NO-metabolism was assessed in the basal situation by analysis of nitrite/nitrate excretion in urine (which was decreased by L-NNA and increased by SNAP), and L-arginine in serum (which increased by L-NNA) and L-citrulline in serum.

    1) During basal conditions NOS inhibition (NO↓) increased apoptosis and decreased cell proliferation.

    2) During CCK-8 induced hyperplasia NOS inhibition (NO↓) increased both apoptosis and cell proliferation. The apoptosis dominated as indicated by decreased DNA content. SNAP administration (NO↑) did neither influence apoptosis nor cell proliferation.

    3) During CCK-8 induced atrophy (DNA↓, apoptosis↑, cell proliferation↑, and cytoplasmic vacuolization) NOS inhibition further increased apoptosis, reduced cell proliferation and abolished vacuole formation. SNAP administration (NO↑) decreased the DNA content, and increased both apoptosis and cell proliferation. The vacuole formation was still present. Hence, NO influences both the basal and the disturbed homeostasis in hyperplastic and atrophic rat pancreatic tissue.

    Early events of a load of L-arginine, known to induce pancreatitis within 48 hrs, was studied at 8, 16 and 24 hrs by analysis of serum L-arginine and L-citrulline, pancreatic tissue ATP, apoptosis and cell proliferation. The initially increased serum L-arginine and L-citrulline decreased to levels below control at 24 hrs. Administration of L-arginine was correlated to a biphasic ATP production and formation of small vacuoles (mitochondrial swelling) in the acinar cells, most prominent at 8 hrs and followed by a gradually increased apoptosis rate. The cell proliferation decreased. At 24 hrs there was pronounced cell degeneration, but no evident necrosis. Another 20 amino acids in serum were also analysed at 24 hrs. Twelve amino acids (including the 'glutamate family') were significantly reduced. After an L-arginine load the augmented A TP production correlates to the initiation of pancreatic cell death. The disturbed amino acid metabolism seems to be of importance for development of experimental pancreatitis.

    List of papers
    1. Cholecystokinin octapeptide induces both proliferation and apoptosis in the rat pancreas
    Open this publication in new window or tab >>Cholecystokinin octapeptide induces both proliferation and apoptosis in the rat pancreas
    2001 (English)In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 98, no 1-2, p. 41-48Article in journal (Refereed) Published
    Abstract [en]

    Cholecystokinin-8 (CCK-8) causes exocrine pancreatic hypertrophy and hyperplasia. High doses of the CCK analogue cerulein causes necrosis and an inflammatory response in the pancreas. We have studied the pancreatic growth response in rats after administration of CCK-8 for 3 days, given either intermittently (20–80 μg/kg) twice a day, or continuously (2.4–48 μg/kg per 24 h). Plasma CCK-8 levels, pancreatic wet weight, water, protein and DNA contents and the pancreatic caspase-3 activity were measured. Cell proliferation was visualized by [3H]thymidine incorporation and apoptosis by TUNEL reaction. Continuous administration of CCK-8 dose-dependently increased the plasma CCK levels, the pancreatic wet weight, protein and DNA contents as well as thymidine labeling index, apoptotic index and caspase-3 activity. Intermittent injections of CCK-8 caused transient raises in plasma CCK, increased apoptotic index and caspase-3 activity, a dose-dependent increase in thymidine labeling but caused a dose-dependent reduction of pancreatic wet weight, protein, and DNA contents. It is concluded that CCK-8 causes both increased proliferation and apoptosis in the pancreas. In case of continuous administration of CCK-8, the proliferation outweighs the apoptosis causing hyperplasia but in the case of intermittent administration the opposite effect is seen.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25028 (URN)10.1016/S0167-0115(00)00223-8 (DOI)9451 (Local ID)9451 (Archive number)9451 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
    2. The influence of nitric oxide on basal and cholecystokinin-8-induced proliferation and apoptosis in the rat pancreas
    Open this publication in new window or tab >>The influence of nitric oxide on basal and cholecystokinin-8-induced proliferation and apoptosis in the rat pancreas
    2002 (English)In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 106, no 1-3, p. 97-104Article in journal (Refereed) Published
    Abstract [en]

    Nitric oxide (NO) is formed by different cell types in the pancreas. In this study, inhibition of endogenous nitric oxide by Nω-nitro-l-arginine (l-NNA) reduced the urinary excretion of NO2/NO3 and raised serum l-arginine and the NO donator S-nitroso-N-acetylpenicillamine (SNAP) increased the urinary excretion of NO2/NO3. The peptide cholecystokinin-8 (CCK-8) has a strong influence on exocrine pancreatic proliferation. Rat pancreas was excised and studied with regard to tissue weight, protein and DNA contents after 3 days of treatment with saline, l-NNA or SNAP given separately or combined with CCK-8. Further, proliferation of different pancreatic cells was studied with [3H]-thymidine incorporation and apoptotic activity was studied by analysing caspase-3 activity and histone-associated DNA fragments. The effects of l-NNA indicate that endogenous nitric oxide formation has a tonic inhibition on apoptosis in the pancreas during both basal condition and growth stimulation by CCK-8. In CCK-induced hyperplasia, NO inhibits the proliferation of acinar cells but stimulates ductal cells. Endogenous NO may regulate the balance between proliferation and apoptosis and in a situation of growth stimulation by CCK-8, it has a tonic inhibition on both mitogenesis and apoptosis thus slowing down the acinar cell turnover in the pancreas.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25029 (URN)10.1016/S0167-0115(02)00056-3 (DOI)9452 (Local ID)9452 (Archive number)9452 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
    3. Cholecystokinin-8-induced atrophy in the rat pancreas: influence of nitric oxide on proliferation, programmed cell death and NF-κB activation
    Open this publication in new window or tab >>Cholecystokinin-8-induced atrophy in the rat pancreas: influence of nitric oxide on proliferation, programmed cell death and NF-κB activation
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    The mechanisms involved in cholecystokinin-8-induced atrophy in the pancreas are not known and in this study the roles of nitric oxide (NO) and NF-κB were studied in rats. CCK-8 was injected for 4 days, in a mode known to cause atrophy, and the NO formation was either decreased by Nω-nitro-L-arginine (L-NNA) or increased by S-nitroso-N-acetylpencillamine (SNAP). Activation of NF-κB was quantified by ELISA detection, apoptosis with caspase-3 and histone associated DNA-fragmentation and mitotic activity in the acinar, centroacinar and ductal cells was visualized by incorporation of [3H]-thymidine. Pancreatic histology, weight, protein- and DNA contents were studied.

    Intermittent CCK injections reduced pancreatic weight, protein and DNA contents and increased apoptosis, acinar cell proliferation and NF-κB activation. It also caused vacuolisation of the acinar cells. Inhibition of endogenous NO formation by L-NNA further increased apoptosis and NF-κB activation but blocked the increased proliferation and vacuolisation of acinar cells. The DNA content was not further reduced. SNAP given together with CCK-8 increased both apoptosis and proliferation of acinar cells and strongly reduced the DNA content in the pancreas. Further, it caused vacuolisation in the acinar cells and these findings together indicate cell death by other pathways besides apoptosis. Histological examination showed no inflammation in any group.

    During CCK-8 induced pancreatic atrophy endogenous NO suppresses apoptosis and stimulates regeneration of acinar cells but increases cell death by non-apoptotic pathways. Exogenous NO enhances the acinar cell turnover by increases of both proliferation and apoptotic and non-apoptotic cell deaths. NF-κB activation, in this situation, seems not to inhibit apoptosis or promote cell proliferation.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-85071 (URN)
    Available from: 2012-11-01 Created: 2012-11-01 Last updated: 2012-11-01
    4. The influence of a load of L-arginine on serum amino acids and pancreatic apoptosis/proliferation and ATP levels in the rat
    Open this publication in new window or tab >>The influence of a load of L-arginine on serum amino acids and pancreatic apoptosis/proliferation and ATP levels in the rat
    Show others...
    2004 (English)In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 29, no 4, p. 113-120Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES:

    Administration of high doses of amino acids like ethionine, methionine, and arginine causes pancreatic tissue damage. The initial mechanism behind these effects is not known. The aim of this study was to show the early effects of a load of L-arginine on programed cell death/proliferation and ATP levels in the pancreas.

    METHODS:

    We analyzed in rats the effects of intraperitoneal administration of L-arginine on serum amino acids, pancreatic cell apoptosis/proliferation, and ATP levels at 8, 16, and 24 hours. Serum amino acid concentrations were measured with HPLC, tissue ATP was measured fluorometrically, apoptosis was studied with caspase-3 activity and histone-associated DNA-fragments, and proliferation was studied with thymidine autoradiography.

    RESULTS:

    After a load of l-arginine, there were initially increased serum levels of L-arginine and L-citrulline, but these fell below control levels after 24 hours as well as amino acids in the glutamate family (ornithine, proline, histidine, and glutamine). Initially, increased ATP levels in the pancreatic tissue returned to control levels at 24 hours. The acinar cells proliferation was suppressed and the apoptosis rate strongly increased at 16 and 24 hours. Pancreatic histology showed vacuole formation in the acinar cells at 8 hours. At 16 hours, there was less vacuolization, but apoptotic bodies were seen, and at 24 hours there was cell degeneration but no necrosis.

    CONCLUSIONS:

    After a load of l-arginine, amino acid metabolism causes a high ATP production in the pancreatic tissue that may cause mitochondrial initiation of cell death.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-23748 (URN)15502637 (PubMedID)3258 (Local ID)3258 (Archive number)3258 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
  • 149.
    Trulsson, Lena
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Gasslander, Thomas
    Department of Surgery, Vrinnevi Hospital, Norrköping, Sweden.
    Sundqvist, Tommy
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Svanvik, Joar
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    The influence of nitric oxide on basal and cholecystokinin-8-induced proliferation and apoptosis in the rat pancreas2002In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 106, no 1-3, p. 97-104Article in journal (Refereed)
    Abstract [en]

    Nitric oxide (NO) is formed by different cell types in the pancreas. In this study, inhibition of endogenous nitric oxide by Nω-nitro-l-arginine (l-NNA) reduced the urinary excretion of NO2/NO3 and raised serum l-arginine and the NO donator S-nitroso-N-acetylpenicillamine (SNAP) increased the urinary excretion of NO2/NO3. The peptide cholecystokinin-8 (CCK-8) has a strong influence on exocrine pancreatic proliferation. Rat pancreas was excised and studied with regard to tissue weight, protein and DNA contents after 3 days of treatment with saline, l-NNA or SNAP given separately or combined with CCK-8. Further, proliferation of different pancreatic cells was studied with [3H]-thymidine incorporation and apoptotic activity was studied by analysing caspase-3 activity and histone-associated DNA fragments. The effects of l-NNA indicate that endogenous nitric oxide formation has a tonic inhibition on apoptosis in the pancreas during both basal condition and growth stimulation by CCK-8. In CCK-induced hyperplasia, NO inhibits the proliferation of acinar cells but stimulates ductal cells. Endogenous NO may regulate the balance between proliferation and apoptosis and in a situation of growth stimulation by CCK-8, it has a tonic inhibition on both mitogenesis and apoptosis thus slowing down the acinar cell turnover in the pancreas.

  • 150.
    Trulsson, Lena M.
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Gasslander, Thomas
    Department of Surgery, Vrinnevi Hospital, Norrköping, Sweden.
    Svanvik, Joar
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Cholecystokinin-8-induced atrophy in the rat pancreas: influence of nitric oxide on proliferation, programmed cell death and NF-κB activationManuscript (preprint) (Other academic)
    Abstract [en]

    The mechanisms involved in cholecystokinin-8-induced atrophy in the pancreas are not known and in this study the roles of nitric oxide (NO) and NF-κB were studied in rats. CCK-8 was injected for 4 days, in a mode known to cause atrophy, and the NO formation was either decreased by Nω-nitro-L-arginine (L-NNA) or increased by S-nitroso-N-acetylpencillamine (SNAP). Activation of NF-κB was quantified by ELISA detection, apoptosis with caspase-3 and histone associated DNA-fragmentation and mitotic activity in the acinar, centroacinar and ductal cells was visualized by incorporation of [3H]-thymidine. Pancreatic histology, weight, protein- and DNA contents were studied.

    Intermittent CCK injections reduced pancreatic weight, protein and DNA contents and increased apoptosis, acinar cell proliferation and NF-κB activation. It also caused vacuolisation of the acinar cells. Inhibition of endogenous NO formation by L-NNA further increased apoptosis and NF-κB activation but blocked the increased proliferation and vacuolisation of acinar cells. The DNA content was not further reduced. SNAP given together with CCK-8 increased both apoptosis and proliferation of acinar cells and strongly reduced the DNA content in the pancreas. Further, it caused vacuolisation in the acinar cells and these findings together indicate cell death by other pathways besides apoptosis. Histological examination showed no inflammation in any group.

    During CCK-8 induced pancreatic atrophy endogenous NO suppresses apoptosis and stimulates regeneration of acinar cells but increases cell death by non-apoptotic pathways. Exogenous NO enhances the acinar cell turnover by increases of both proliferation and apoptotic and non-apoptotic cell deaths. NF-κB activation, in this situation, seems not to inhibit apoptosis or promote cell proliferation.

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  • asciidoc
  • rtf