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Sökning: WFRF:(Willén Roger)

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  • Föregående 123[4]5Nästa
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  • Löfberg, Robert, et al. (författare)
  • Oral budesonide versus prednisolone in patients with extensive and left sided ulcerative colitis
  • 1996
  • Ingår i: Gastroenterology. - Elsevier. - 1528-0012. ; 110:6, s. 1713-1718
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Systemic glucocorticosteroids (GCSs) have proven efficacy in active ulcerative colitis but cause undesired systemic side effects. Therefore, new GCSs with high topical activity and a high rate of metabolism may be of clinical value in this condition. The aim of this study was to explore the efficacy and safety of the topically acting GCS budesonide in an oral controlled-release formulation in extensive or left-sided, mild to moderately active ulcerative colitis. METHODS: A 9-week, randomized, double-blind, controlled trial was performed, and treatments with 10 mg budesonide or 40 mg prednisolone daily, both gradually tapered, were compared. Endoscopic improvement and effect on endogenous plasma cortisol were assessed. RESULTS: Thirty-four patients were administered budesonide, and 38 patients were administered prednisolone. Mean endoscopic scores improved significantly in both groups but without difference between the groups. Five patients in the budesonide group and 7 patients in the prednisolone group deteriorated and were withdrawn from the study. Morning plasma cortisol levels were suppressed in the prednisolone group (entry, 449 nmol/L; 2 weeks, 116 nmol/L; 4 weeks, 195 nmol/L) but were unchanged in the budesonide group. CONCLUSIONS: The GCS budesonide administered in an oral controlled-release formulation seems to give an overall treatment result in active ulcerative colitis approaching that of prednisolone but without suppression of plasma cortisol levels. This concept merits further evaluation.
  • Marthinsen, Lars, et al. (författare)
  • Kolonspiroketos - behandlingsbart och värt att uppmärksamma : Erfarenheter från pediatrisk praktik
  • 2006
  • Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 103:46, s. 3600-3602
  • Forskningsöversikt (övrigt vetenskapligt)abstract
    • This article is written to raise awareness among clinicians and pathologists regarding the existence of colonic spirochetosis. Whether this is of clinical significance is still a matter of debate. We report a series of sixteen randomly selected patients, all of paediatric age; eight of them have been reported in a previous publication (10). In one patient, spirochetes were found both in the colon and in the liver. The colon organisms were Brachyspira aalborgi, documented by antigen test; however, due to lack of material, the spirochetes in the liver could not be typed. As 10 of 13 patients recovered or improved after antibiotic treatment with clarythromycin or metronidazole, our conclusion is that Brachyspira may be pathogenic. We suggest that when a rectosigmoidoscopy/colonoscopy is performed, colonic spirochetosis should be considered, especially in the differential diagnosis to microscopic colitis.
  • Nordengren, Johanna, et al. (författare)
  • High tumor tissue concentration of plasminogen activator inhibitor 2 (PAI-2) is an independent marker for shorter progression-free survival in patients with early stage endometrial cancer.
  • 2002
  • Ingår i: International Journal of Cancer. - John Wiley and Sons Inc.. - 0020-7136. ; 97:3, s. 379-385
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies including various tumor types have shown different associations between tumor tissue levels of plasminogen activator inhibitor 2 (PAI-2) and patient survival. High tumor tissue concentrations of PAI-2 have been associated with good prognosis in patients with breast cancer, small cell lung cancer and ovarian cancer, but with poor histologic differentiation and poor prognosis in patients with colorectal cancer. On the other hand, high tumor tissue concentrations of urokinase plasminogen activator (uPA), uPA receptor (R) and PAI-1 have more consistently been associated with poor histologic differentiation and poor prognosis. Our study quantified PAI-2 and uPAR using specific enzyme-linked immunosorbent assays in homogenates of 274 samples of endometrial cancer tissue. The prognostic power of each factor was analyzed in the subgroup of patients with early stage disease, i.e., International Federation of Gynecology and Oncology (FIGO) surgical stage I-II (n = 188). This group had a median follow-up time of 6.8 years (range 0.7-9.9), and 23 progressions were observed. The 80(th) percentile for PAI-2 and uPAR was used to dichotomize the material, and the results were analyzed for associations with clinical data including progression-free survival. The results were also compared with DNA ploidy status, S-phase fraction, uPA and PAI-1, which we reported in a previous study (Fredstorp Lidebring et al., Eur J Cancer 2001; in press). A high PAI-2 level was associated with shorter progression-free survival in univariate analysis and was an independent prognostic factor in bivariate analyses, which included PAI-1, uPA and DNA ploidy status. In contrast, a high level of uPAR had no association with prognosis in early stage endometrial cancer. The combination of high PAI-2 and PAI-1 levels in tumors revealed a small group of stage I-II patients with an accumulative progression rate of 50%.
  • Odin, Elisabeth, 1955-, et al. (författare)
  • Altered gene expression of folate enzymes in adjacent mucosa is associated with outcome of colorectal cancer patients.
  • 2003
  • Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1078-0432. ; 9:16 Pt 1, s. 6012-9
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: The purpose of this study was to analyze whether gene expression levels of folate enzymes in adjacent mucosa were associated with outcome of colorectal cancer patients. EXPERIMENTAL DESIGN: Real-time PCR was used to quantify expression levels of folate-associated genes including the reduced folate carrier (RFC-1), folylpolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH),and thymidylate synthase (TS) in tumor tissue and adjacent mucosa of patients with primary colorectal cancer (n=102). Furthermore, reduced folates in the tissues were measured with a binding-assay method. RESULTS: Mean gene expression levels of RFC-1, FPGS, GGH, and TS were significantly higher in tumor biopsies compared with mucosa. Univariate and multivariate analyses showed that the FPGS gene expression level in mucosa, but not in tumor, was a prognostic parameter independent of the clinicopathological factors with regard to survival. Patients with high FPGS levels (>0.92) in mucosa also showed significantly higher total folate concentrations (P=0.03) and gene expression levels of RFC-1 (P<0.01), GGH (P<0.01), and TS (P=0.04) compared with patients with low FPGS levels. The total reduced folate concentration correlated with the gene expression levels of RFC-1 and FPGS but not with TS or GGH. CONCLUSION: Our results suggest that normal-appearing colonic mucosa adjacent to primary colon cancer can show altered gene expression levels of FPGS that may have bearing on the development of aggressive metastatic behavior of the tumor and on tumor-specific survival.
  • Rangel, Ignacio, 1969-, et al. (författare)
  • Degree of colitis correlates with microbial composition and cytokine responses in colon and caecum of Gαi2-deficient mice
  • 2016
  • Ingår i: FEMS Microbiology Ecology. - Oxford, United Kingdom : Oxford University Press. - 0168-6496. ; 92:7
  • Tidskriftsartikel (refereegranskat)abstract
    • An altered immune response and gut microbiota have been associated with the pathology of Inflammatory Bowel Diseases (IBD). However, there is limited knowledge of how inflammation is associated with changes in the microbiota. We studied the microbiota in the intestine and faeces as well as the cytokine gene expressions in caecum and colon of a mouse model (Gαi2(-/-)) of colitis, and analysed them in relation to the degrees of inflammation in the colon. The degree of colitis was associated with general changes in the complexity of the microbiota and was corroborated by quantitative analyses of the Bacteroides and Lactobacillus High gene expression levels of IL-17 and IFN-γ in colon and caecum were detected in Gαi2(-/-) mice with moderate and severe colitis. High IL-27 gene expression in the colon of mice with moderate and severe colitis and in the caecum of mice with moderate colitis was also detected. Negative correlations between IL-27 and Bacteroides and Lactobacillus and between IFN-γ and Lactobacillus were detected in caecum. This research indicates that the degree of colitis in IBD correlates with the gene expression of cytokines and with disturbances in the gut microbiota. Furthermore, the caecum could have an important role in the pathology of IBD.
  • Sjunnesson, Håkan, et al. (författare)
  • Comparative study of Helicobacter pylori infection in guinea pigs and mice - elevation of acute-phase protein C3 in infected guinea pigs
  • 2001
  • Ingår i: Pathogens and Disease. - Wiley-Blackwell. - 2049-632X. ; 30:2, s. 167-172
  • Tidskriftsartikel (refereegranskat)abstract
    • Eighteen Dunkin-Hartley guinea pigs and 50 NMRI mice were inoculated with Helicobacter pylori and the infection followed by culture, histopathology, antibody response, and plasma levels of the acute-phase proteins albumin, C3, and transferrin for up to 7 weeks. The immune response to H. pylori surface proteins was studied by an enzyme immunoassay (EIA) and Western immunoblot and the plasma levels of albumin, C3, and transferrin were analyzed by single radial immunodiffusion. Guinea pigs had a more severe gastritis and a higher EIA immune response than NMRI mice. Serum C3 levels were elevated in infected guinea pigs after 3 and 7 weeks indicating a systemic inflammatory response and a possible link between H. pylori infection and extragastric manifestations such as vasculitis associated with atherosclerosis. Serum cholesterol levels were analyzed in guinea pigs at 7 weeks and indicated a higher level in H. pylori-infected than in control animals, but this difference was not statistically significant.
  • Solberg, Anna, et al. (författare)
  • Progress of tissue injury in appendicitis involves the serine proteases uPA and PAI-1.
  • 2009
  • Ingår i: Scandinavian journal of gastroenterology. - 1502-7708. ; 44:5, s. 579-84
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Serine proteases and the matrix metalloproteinases (MMPs) are key factors in the proteolytic cascade and participate in extracellular matrix (ECM) degradation. Fibrinolytic activators and inhibitors may have an effect on inflammatory cells, thereby modulating the inflammatory response. It is reasonable to assume that they may be implicated in the tissue injury in acute appendicitis that subsequently leads to appendix perforation. The purpose of this study was to investigate the expression and distribution of urokinase-type plasminogen activator (uPA) and plasminogen-activator inhibitor type 1 (PAI-1) in appendicitis. MATERIAL AND METHODS: Expression of uPA and expression of PAI-1 were measured in tissue specimens from patients with appendicitis (n=30) and in control specimens (n=9), using the quantitative ELISA technique. Distribution of enzymes was studied with immunohistochemistry. The uPA and PAI-1 levels in the subgroups of appendicitis and controls were compared. RESULTS: The overall expressions of uPA and PAI-1 were greater in appendicitis than in control specimens (p &lt;0.001 and p&lt;0.0001, respectively). Expressions of uPA and PAI-1 in phlegmonous (n=15), gangrenous (n=6) and perforated appendicitis (n=9) were all higher than those in controls (n=9), (p&lt;0.01). Moreover, the PAI-1 level was elevated in perforated appendicitis compared with phlegmonous appendicitis (p&lt;0.01). uPA staining was observed in connection with vascular endothelial cells and the serosa stained intensely in specimens from perforated appendicitis. CONCLUSIONS: The expression of uPA and especially the over-expression of PAI-1 seem to correlate to the progression of local inflammatory response in acute appendicitis.
  • Solberg, Anna, et al. (författare)
  • Tissue Proteolysis in Appendicitis with Perforation
  • 2011
  • Ingår i: Journal of Surgical Research. - 0022-4804 .- 1095-8673. ; 169:2, s. 194-201
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Matrix metalloproteinases (MMPs) and serine proteases are able to degrade the extracellular matrix (ECM) and modulate immune responses in the gastrointestinal tract. The purpose of this study was to investigate local proteolysis in perforated appendicitis and its association with the appendix perforation. MATERIALS AND METHODS: Biopsies were taken at the sites of perforation (n = 15) and with a gradually increased distance from it. The expression and distribution of MMP-1, -2, and -9, the tissue inhibitor of metalloproteinases type (TIMP-1), plasminogen activator inhibitor type1 (PAI-1), and urokinase plasminogen activator (uPA) were measured by ELISA. The distribution of MMP-9, TIMP-1, uPA, and PAI-1 in perforated, nonperforated, and uninflamed appendix was investigated by immunohistochemistry with monoclonal antibody technique. RESULTS: MMP-1 expression was highest close to the perforation and was gradually decreased in biopsies in more distal locations (P &lt; 0.01). MMP-9 showed a similar pattern being highest at the sites of perforation (P &lt; 0.05), while MMP-2 expression showed a trend in the opposite direction without statistically significance. The expression of TIMP-1 trended lower at the sites of perforation. PAI-1 was highest at the sites of perforation (P &lt; 0.01) and the uPA expression was similarly elevated close to and at the perforation. CONCLUSIONS: These data indicate a key role of MMP in the pathogenesis of appendix perforation. A local imbalance between MMP-9 and the inhibitor TIMP-1 could potentially contribute to the tissue injury leading to an appendix perforation. The overexpression of PAI-1 at the sites of perforation may also contribute to tissue damage.
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