| 1. |
- Franzén, Lennart E., et al.
(författare)
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Characterization of colon carcinoma growth pattern by computerized morphometry : definition of a complexity index
- 2008
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Ingår i: International Journal of Molecular Medicine. - : Spandidos Publications. - 1107-3756 .- 1791-244X. ; 22:4, s. 465-472
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Tidskriftsartikel (refereegranskat)abstract
- The invasive front of carcinomas may vary in complexity from smooth to highly complex when the front splits up into small cell clusters or even single cancer cells. The degree of complexity is usually estimated visually and semiquantitatively by a pathologist, although more objective methods based on computer-assisted image analysis are available. In this study, we compared the visual estimation of the irregularity of the tumour invasion front of colon carcinomas to different quantitative image analytical techniques and defined a complexity index for the invasive margin. Sections from 29 archived colon carcinomas were stained immunohistochemically for cytokeratin 8. Images of the tumour invasion front were read into a computer and thresholded so that the tumour tissue became black and the background white or so that the tumour front was outlined by a single pixel line. The invasive front was visually classified into four degrees of irregularity by a pathologist. The complexity of the front was then assessed using four different image analysis techniques, i.e. the estimation of fractal dimension, tumour front length, number of tumour cell clusters and lacunarity. Fractal dimension and tumour cell clusters together gave the best correlation to visual grading using a discriminant analysis. A cluster analysis and a tree diagram analysis were then performed and were found to be superior to visual estimation. The clusters represent different degrees of complexity and the result of the tree diagram analysis can be used to assign complexity indices to colon tumours. The fractal dimension separated tumours up to a certain level (1.5-1.6) of complexity. When the tumour front split up into small cell clusters, the counting of tumour cell clusters separated the cells over and above the fractal dimension. This new technique can be used to objectively and quantitatively describe the complexity of the invasive front of tumours.
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| 2. |
- Franzén, Lennart E, et al.
(författare)
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Semiquantitative evaluation overestimates the degree of steatosis in liver biopsies : a comparison to stereological point counting.
- 2005
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Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952 .- 1530-0285. ; 18:7, s. 912-916
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Tidskriftsartikel (refereegranskat)abstract
- The degree of steatosis in liver biopsies is usually assessed by a morphological semiquantitative approach in which the histopathologist uses a four-graded scale: 0-3 or none, slight, moderate and severe. Scores 1-3 are considered to correspond to fat deposition in <33, 33-66 and >66% of the hepatocytes. There is a considerable inter- and intra-individual variation in such scoring methods and a more standardized and quantitative approach is preferable. In the present study, we compare the semiquantitative technique with the stereological point counting method in the assessment of hepatic steatosis. A total of 75 archived liver needle biopsies were used. They were selected according to the original routine diagnosis of slight, moderate or severe steatosis. In all, 10 randomly selected images from each biopsy were digitized into a computer, a point grid lattice was superimposed and the number of hits on fat globules was counted. A pathologist scored the specimens in a four-graded scale as described above. The mean liver biopsy area (volume) with fat in hepatocytes was 2.2% for grade 1, 9.2% for grade 2 and 23.1% for grade 3. The kappa value for the semiquantitative estimates was 0.71 for the unweigthed kappa and 0.87 for weighted kappa. The intraclass correlation coefficient (ICC) was 0.99 for images counted twice and 0.95 when two sets of images were captured from the same biopsy. These ICCs indicate excellent agreement and above that of the semiquantitative estimates. In conclusion, the area/volume of fat content of the hepatocytes is greatly overemphasized in semiquantitative estimation. Furthermore, the point counting technique has a better reproducibility than visual evaluation and should be preferred in estimates of liver steatosis in scientific studies and in clinical contexts when the amount of steatosis is important for treatment and prognosis, such as liver transplantation.
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| 3. |
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| 4. |
- Hahn-Strömberg, Victoria, et al.
(författare)
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Disturbed expression of E-cadherin, beta-catenin and tight junction proteins in colon carcinoma is unrelated to growth pattern and genetic polymorphisms
- 2008
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 116:4, s. 253-262
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Tidskriftsartikel (refereegranskat)abstract
- Adhesion proteins are responsible for the structural integrity of epithelial tissue and in tumors this integrity is often lost, resulting in a disorganization of the tissue. In the present study the complexity of the invasive front of colon carcinomas was correlated with cell adhesion protein expression and with polymorphisms in their genes. A complexity index was constructed from 32 colon carcinomas using computer-assisted morphometry estimating fractal dimension and tumor cell clusters followed by tree analysis. Immunohistochemical staining of beta-catenin, E-cadherin, occludin and claudin 2 was used for assessment of protein expression. Genetic screening of tissue from the tumor invasion front with laser microdissection was performed using SSCP and DNA sequencing. Adhesion protein distribution was significantly disturbed in most carcinomas. A single mutation in the gene of beta-catenin was found but there was no correlation between protein expression and genetic polymorphism. Nor was there any correlation between the complexity of the invasive border and protein distribution or genetic alterations. The results indicate that the complexity of colon carcinoma invasion is not dependent on genetic derangements in the genes of adhesion proteins or the protein distribution. Rather, aberrations in the function of other proteins related to the adhesive proteins could be responsible.
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| 5. |
- Hahn-Strömberg, Victoria, et al.
(författare)
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Tumor volume of colon carcinoma is related to the invasive pattern but not to the expression of cell adhesion proteins
- 2009
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley-Blackwell Publishing Inc.. - 0903-4641 .- 1600-0463. ; 117:3, s. 205-211
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Tidskriftsartikel (refereegranskat)abstract
- Tumor volume increases during growth and due to tumor progression various mutations appear that may cause phenotypic changes. The invasive pattern may thus be affected resulting in a more disorganized growth. This phenomenon might be due to mutations in the genome of the adhesion proteins, which are responsible for the structural integrity of epithelial tissue. Tumor volume was assessed in whole mount sections of 33 colon carcinomas using Cavalieri's principle. Images from the entire invasive border were captured and used for calculating the irregularity of the border (Complexity Index). The expression of the adhesion proteins E-cadherin, beta-catenin, Claudin 2 and Occludin was assessed after immunohistochemical staining of two randomly selected areas of the invasive front of the tumor. Statistical significance for differences in volume was obtained for tumor Complexity Index, tumor stage (pT) and lymph node status (pN). Expression of adhesion proteins was significantly perturbed in the tumors compared with normal mucosa but only infrequently correlated to tumor differentiation or invasive pattern. The results show that when tumor volume increases the invasive pattern becomes more irregular which is compatible with tumor progression. A direct contribution of adhesion protein derangement to this process appears to be insignificant.
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| 6. |
- Loogna, Peter, et al.
(författare)
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Cyclooxygenase-2 and Bcl-2 expression in the stomach mucosa of Wistar rats exposed to Helicobacter pylori, MNNG and bile
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Cyclooxygenase-2 (COX-2) and Bcl-2 may mirror different stages of gastric carcinogenesis, but the underlying mechanisms are not known. Thus the relation of COX-2 and Bcl-2 to known cell kinetics were studied in the glandular stomach mucosa of 104 Wistar rats given combinationsof H. pylori, MNNG (methyl-N'nitro-N-nitrosoguanidine) and bile.COX-2 expression, Bcl-2 and cell proliferation (Ki-67) in antral and corpus mucosa were determined immunohistochemically. Apoptotic cells were detected by using terminal uridine deoxynucleotidyl nick end labeling technique.Expression of COX-2 was found in the lower portion of glandular corpus epithelium and Bcl-2 positivity was mainly seen in the proliferative zone ofboth antmm and corpus mucosa. COX-2 in histologically normal-appearing corpus mucosa was associated with cell proliferation, atrophy and intestinal metaplasia in antmm and with Bcl-2 expression in corpus mucosa. No correlation was found between apoptosis and COX-2 or Bcl-2 expression. MNNG but not H. pylori significantly increased COX-2 in corpus mucosa. H.pylori, however, promoted the COX-2 expression in corpus when bile was added and Bcl-2 expression in antrum. These findings may indicate an early phase of gastric neoplasia in a state of increased cell proliferation.
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| 7. |
- Loogna, Peter, et al.
(författare)
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Effects of Helicobacter pylori and bile on N-methyl-N'-nitro-N'-nitrosoguanidine exposed antral mucosa of C57BL/6 mice
- 2001
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Ingår i: Virchows Archiv. - : Springer Science and Business Media LLC. - 0945-6317 .- 1432-2307. ; 439:5, s. 661-667
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the early influence of Helicobacter pylori infection on cell kinetics in the antral mucosa of mice exposed to N-methyl-N'-nitro-N'-nitrosoguanidine (MNNG) and bile alone or in combinations. Four hundred and one C57BL/6 male and female mice were assigned into seven treatment groups and one non-treated control group. The gastric antrums were assessed by histology and immunohistochemistry for studies of cell proliferation and apoptosis at 32 and 44 weeks. One female and one male mouse had developed dysplastic adenomas in the pylorus mucosa and one male animal had dysplastic proliferation in the antrum. Only one of these lesions occurred in a H. pylori colonized animal. H. pylori infection significantly increased the cell proliferation at 32 weeks and promoted the cell proliferation in the MNNG and bile group at 44 weeks. Female mice showed less increase in cell proliferation than did the males. No change in apoptosis was seen in any of the groups. Bile had no promotional effect on cell proliferation. These results indicate that H. pylori infection has the potential to alter epithelial cell kinetics as well as antrum mucosa of an animal species that is regarded as resistant to MNNG. However, this change is not sufficient to promote the early development of neoplastic lesions.
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| 8. |
- Loogna, Peter, et al.
(författare)
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Helicobacter pylori, N-methyl-N'-nitro-N'-nitrosoguanidine, and bile modulate gastric cell kinetics in experimental cancer
- 2001
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Ingår i: Virchows Archiv. - : Springer Science and Business Media LLC. - 0945-6317 .- 1432-2307. ; 439:5, s. 653-660
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori infection is a risk factor for gastric cancer. How the bacterium contributes to this process is still unclear. We present a new Wistar rat model that was used to evaluate the effect of H. pylori on early preneoplastic events as judged from epithelial cell turnover and histopathological changes. One hundred and four rats were colonized with H. pylori and exposed MNNG (N-methyl-N'-nitro-N'-nitrosoguanidine) and/or taurocholic acid. Inflammation, goblet cell-like metaplasia, atrophy, dysplasia, and adenocarcinoma were scored in a blinded manner. Apoptotic cells were counted after staining with terminal uridine deoxynucleotidyl nick end labeling, and epithelial cell proliferation was determined by means of the Ki-67 labeling index. No early tumor enhancement with H. pylori could be found in ordinary histology. However, H. pylori significantly enhanced the epithelial cell proliferation compared with the control group, and the combination with taurocholic acid appeared to have a synergistic effect. MNNG significantly increased the normal gastric epithelial apoptosis. This increase was reduced in antral mucosa with H. pylori infection. The findings suggest that H. pylori, especially when combined with bile. has an influence on cell kinetics, contributing to the development of gastric cancer. The reduced apoptosis of MNNG also observed in infected animals indicates a dual function of H. pylori.
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| 9. |
- Almer, Sven, 1953-, et al.
(författare)
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Leukocyte scintigraphy compared to intraoperative small bowel enteroscopy and laparotomy findings in Crohn's disease
- 2007
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998 .- 1536-4844. ; 13:2, s. 164-174
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Tidskriftsartikel (refereegranskat)abstract
- Background: Leukocyte scintigraphy is a noninvasive investigation to assess inflammation. We evaluated the utility of labeled leukocytes to detect small bowel inflammation and disease complications in Crohn's disease and compared it to whole small bowel enteroscopy and laparotomy findings.Methods: Scintigraphy with technetium-99m exametazime-labeled leukocytes was prospectively performed in 48 patients with Crohn's disease a few days before laparotomy; 41 also had an intraoperative small bowel enteroscopy. The same procedures were performed in 8 control patients. Independent grading of scans was compared with the results of enteroscopy and with surgical, histopathologic, and clinical data.Results: In the 8 control patients leukocyte scan, endoscopy, and histopathology were all negative for the small bowel. In patients with Crohn's disease and small bowel inflammation seen at enteroscopy and/or laparotomy (n = 39) the scan was positive in 33. In 8 patients without macroscopic small bowel inflammation, the scan was positive for the small bowel in 3 patients; at histology, 2 of 3 had inflammation. When combining results for patients and controls, the sensitivity of leukocyte scan for macroscopically evident small bowel inflammation was 0.85, specificity 0.81, accuracy 0.84, positive predictive value 0.92, and negative predictive value 0.68. Scintigraphy detected inflammatory lesions not known before laparotomy in 16 of 47 (34%) Crohn's disease patients and showed uptake in 25 of 35 (71%) bowel strictures. It was diagnostic regarding 4 of 8 abscesses and 9 of 15 fistulas. In 6 patients (13%) lesions first demonstrated by leukocyte scintigraphy were treated during the surgery performed.Conclusions: Leukocyte scintigraphy reliably detects small bowel inflammation in Crohn's disease. It gives additional information on the presence of inflammatory lesions in a fraction of patients planned for surgery.
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| 10. |
- Andrén, Ove, 1963-, et al.
(författare)
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How well does the Gleason score predict prostate cancer death? : A 20-year followup of a population based cohort in Sweden
- 2006
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Ingår i: Journal of Urology. - Baltimore : Williams and Wilkins Co.. - 0022-5347 .- 1527-3792. ; 175:4, s. 1337-1340
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Adenocarcinoma of the prostate is the most common cancer among men in Western countries. Although the prognostic heterogeneity of prostate cancer is enormous, clinically insignificant aggressive prostate cancers cannot be reliably distinguished. Therefore, identifying prognostic factors is increasingly important, notably among men diagnosed with localized prostate cancer, because many of them may not require aggressive treatment. Materials and Methods We analyzed a population based cohort of 253 men with early stage (T1a-b, Nx, M0) initially untreated prostate cancer diagnosed between 1977 and 1991, before PSA screening was available. Tissue samples were available for 240 patients diagnosed with transurethral resection. During complete followup through September 2003, standardized criteria were used to classify histopathological characteristics, progression and causes of death. Results Higher Gleason grade, higher nuclear grade and larger tumor volume were independent predictors of death in prostate cancer with monotonous and statistically significant trends (p <0.05). In contrast, the level of Ki-67 – strongly correlated to Gleason score – was not an independent predictor of prostate cancer death. Given a Gleason score of 7 or greater, the probability of dying of prostate cancer was 29%. The corresponding predictive value for Gleason score 8 or greater was 48%. Conclusions Although a high Gleason score is a determinant of prostate cancer death, its PPV is relatively low. Thus, further efforts in finding other or complementary indicators of prostate cancer outcome are needed.
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| 11. |
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| 12. |
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| 13. |
- Borch, Kurt, et al.
(författare)
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Benign gastric polyps - Morphological and functional origin
- 2003
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Ingår i: Digestive Diseases and Sciences. - 0163-2116 .- 1573-2568. ; 48:7, s. 1292-1297
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Tidskriftsartikel (refereegranskat)abstract
- The most common types of benign gastric polyps are fundic gland polyps, hyperplastic polyps, and adenomas. The aim of this study was to determine on which morphological and functional background benign gastric polyps develop. The study includes 85 consecutive patients with gastric polyps and sex and age-matched controls without polyps selected at random from a general population sample. The type of polyp was hyperplastic in 52 (61%), fundic gland in 18 (21%), adenoma in 10 (12%), carcinoid in 2 (2%), hamartoma in 2 ( 2%), and inflammatory fibroid in 1 (1%) of the cases. Routine biopsies from the gastric corpus and antrum were examined for presence of gastritis and H. pylori. Blood samples were analyzed for H. pylori antibodies, H+, K+-ATPase antibodies, gastrin, and pepsinogen I. Patients with hyperplastic polyps had increased P-gastrin concentrations and S-H+, K+-ATPase antibody titers and decreased S-pepsinogen I concentrations with a high prevalence of atrophic corpus gastritis or pangastritis. A similar pattern was observed among patients with adenomas, whereas patients with fundic gland polyps had normal serology and a lower prevalence of gastritis and H. pylori infection than controls. In conclusion, hyperplastic polyps and adenomas are generally associated with atrophic gastritis. Patients with fundic gland polyps seem to have a sounder mucosa than controls. Whereas the risk of malignant gastric neoplasia is increased in patients with hyperplastic polyps or adenomas, this does not seem to be the case in patients with fundic gland polyps.
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| 14. |
- Borch, Kurt, 1944-, et al.
(författare)
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Prevalence of gastroduodenitis and Helicobacter priori infection in a general population sample : relations to symptomatology and life-style
- 2000
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Ingår i: Digestive Diseases and Sciences. - 0163-2116 .- 1573-2568. ; 45:7, s. 1322-1329
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Tidskriftsartikel (refereegranskat)abstract
- Some benign and malignant diseases develop on the background of chronic gastritis or duodenitis. The present study was performed in order to determine the magnitude of these background changes with relations to symptomatology and life style in the general population. Examinations were performed in 501 volunteers (age 35–85 years). Fifty percent had gastritis; this was associated with H. pylori in 87%. H. pylori-negative gastritis was associated with regular use of NSAIDs [odds ratio 3.8 (1.6–9.9)]. Duodenitis, observed in 32%, was associated with H. pylori infection [odds ratio 2.3 (1.3–4.6)], previous cholecystectomy [odds ratio 3.6 (1.1–16.1)], and regular use of NSAIDs [odds ratio 3.0 (1.4–7.1)]. Neither gastritis nor duodenitis was associated with smoking or alcohol consumption. The rate of digestive symptoms did not differ between subjects with and without uncomplicated gastritis or duodenitis. In conclusion, half of this adult population had gastritis strongly associated with H. pylori infection. Gastritis without H. pylori infection was frequently associated with regular NSAID intake. One third had duodenitis, which was associated with H. pylori infection as well as with regular use of NSAIDs and previous cholecystectomy. Digestive symptoms were not overrepresented in uncomplicated gastritis or duodenitis.
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| 15. |
- Brynielsson, Joel, et al.
(författare)
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Enhanced situation awareness using random particles
- 2005
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Ingår i: Proceedingsof the Tenth International Command and Control Research and TechnologySymposium (ICCRTS).
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Konferensbidrag (refereegranskat)abstract
- Modern command and control systems present the current view of the situationthrough a situation picture that is being built up from fused sensor data. However,merely presenting a comprehensible description of the situation does not give thecommander complete awareness of the development of a situation. This articlepresents a generic tool for prediction of forthcoming troop movements. The techniqueis similar to particle filtering, a method used for approximate inference indynamic Bayesian networks.The prediction tool has been implemented and installed into an existent electronicwarfare system. The tool makes use of the system’s geographic informationsystem to extract geographic properties and calculate troop velocities in the terrainwhich is, in turn, being used for the construction of the tool’s transition model.Finally, the result is presented together with the situation picture.The prediction tool has been evaluated in field tests performed in cooperationwith the Swedish Armed Forces in an exercise in Sweden during the spring of2005. Officers and operators of the electronic warfare system were interviewedand exposed to the tool. Reactions were positive and prediction of future troopmovements was considered to be interesting for short-term tactical command andcontrol.
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| 16. |
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| 17. |
- Ekstedt, Mattias, et al.
(författare)
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Alcohol consumption is associated with progression of hepatic fibrosis in non-alcoholic fatty liver disease
- 2009
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 44:3, s. 366-374
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Moderate alcohol consumption has been reported to be inversely associated with cardiovascular disease and total mortality. The importance of non-alcoholic fatty liver disease (NAFLD) is increasing and many NAFLD patients suffer from cardiovascular disease. In these patients, moderate alcohol consumption could be beneficial. The aim of this study was to investigate whether low alcohol intake, consistent with the diagnosis of NAFLD, is associated with fibrosis progression in established NAFLD. Material and methods: Seventy-one patients originally referred because of chronically elevated liver enzymes and diagnosed with biopsy-proven NAFLD were re-evaluated. A validated questionnaire combined with an oral interview was used to assess weekly alcohol consumption and the frequency of episodic drinking. Significant fibrosis progression in NAFLD was defined as progression of more than one fibrosis stage or development of endstage liver disease during follow-up. Results: Mean follow-up (SD) was 13.8 (1.2) years between liver biopsies. At follow-up, 17 patients (24%) fulfilled the criteria for significant fibrosis progression. The proportion of patients reporting heavy episodic drinking at least once a month was higher among those with significant fibrosis progression (p=0.003) and a trend towards higher weekly alcohol consumption was also seen (p=0.061). In a multivariate binary logistic regression analysis, heavy episodic drinking (p0.001) and insulin resistance (p0.01) were independently associated with significant fibrosis progression. Conclusions: Moderate alcohol consumption, consistent with the diagnosis of NAFLD to be set, is associated with fibrosis progression in NAFLD. These patients should be advised to refrain from heavy episodic drinking.
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| 18. |
- Ekstedt, Mattias, et al.
(författare)
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Long-term follow-up of patients with NAFLD and elevated liver enzymes.
- 2006
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 44:4, s. 865-873
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Tidskriftsartikel (refereegranskat)abstract
- Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated liver enzymes in patients of developed countries. We determined the long-term clinical and histological courses of such patients. In a cohort study, 129 consecutively enrolled patients diagnosed with biopsy-proven NAFLD were reevaluated. Survival and causes of death were compared with a matched reference population. Living NAFLD patients were offered repeat liver biopsy and clinical and biochemical investigation. Mean follow-up (SD) was 13.7 (1.3) years. Mortality was not increased in patients with steatosis. Survival of patients with nonalcoholic steatohepatitis (NASH) was reduced (P = .01). These subjects more often died from cardiovascular (P = .04) and liver-related (P = .04) causes. Seven patients (5.4%) developed end-stage liver disease, including 3 patients with hepatocellular carcinoma. The absence of periportal fibrosis at baseline had a negative predictive value of 100% in predicting liver-related complications. At follow-up, 69 of 88 patients had diabetes or impaired glucose tolerance. Progression of liver fibrosis occurred in 41%. These subjects more often had a weight gain exceeding 5 kg (P = .02), they were more insulin resistant (P = .04), and they exhibited more pronounced hepatic fatty infiltration (P = .03) at follow-up. In conclusion, NAFLD with elevated liver enzymes is associated with a clinically significant risk of developing end-stage liver disease. Survival is lower in patients with NASH. Most NAFLD patients will develop diabetes or impaired glucose tolerance in the long term. Progression of liver fibrosis is associated with more pronounced insulin resistance and significant weight gain.
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| 19. |
- Ekstedt, Mattias, et al.
(författare)
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Low clinical relevance of the nonalcoholic fatty liver disease activity score (NAS) in predicting fibrosis progression
- 2012
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 47:1, s. 108-115
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims. The nonalcoholic fatty liver disease (NAFLD) activity score (NAS) is a newly proposed system to grade the necroinflammatory activity in liver biopsies of NAFLD patients. This study evaluates the usefulness of the NAS in predicting clinical deterioration and fibrosis progression in NAFLD. Methods. One hundred and twenty-nine patients with biopsy-proven NAFLD were included in a long-term histological follow-up study. Clinical course and change in fibrosis stage were compared between nonalcoholic steatohepatitis (NASH), “borderline NASH,” and “not NASH” patients. Significant fibrosis progression was defined as progression of more than one fibrosis stage or development of end-stage liver disease during follow-up. Results. Eighty-eight patients accepted reevaluation and 68 underwent repeat liver biopsy. Mean time between biopsies was 13.8 ± 1.2 years (range 10.3–16.3). At baseline, NASH was diagnosed in 2 (1.6%) patients, and at follow-up, in 1 (1.5%) patient. A trend toward higher baseline NAS was seen in patients (n = 7) who developed end-stage liver disease (3.1 ± 0.9 vs. 2.2 ± 1.0; p = 0.050). Baseline NAS was associated with progressive disease in a univariate binary logistic regression analysis (p = 0.024), but no difference was seen in the multivariate analysis including the NAS, portal inflammation, and perisinusoidal fibrosis. Moreover, 18% of patients without NASH progressed significantly in fibrosis stage. Conclusions. The ability of the NAS to predict progression of NAFLD is poor. The clinical usefulness of the score is limited due to the significant overlap in clinical development between NAS score groups. To use the NAS as endpoint in treatment trial is not justified.
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| 20. |
- Ekstedt, Mattias, et al.
(författare)
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Statins in non-alcoholic fatty liver disease and chronically elevated liver enzymes : a histopathological follow-up study.
- 2007
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Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 47:1, s. 135-141
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: The effect of statins on hepatic histology in non-alcoholic fatty liver disease (NAFLD) is not known. This study explores hepatic histology in NAFLD patients before and after initiation of statin therapy and compares histological outcome with NAFLD patients who had not been prescribed statins. Methods: Sixty-eight NAFLD patients were re-evaluated. Follow-up ranged from 10.3 to 16.3 years. Subjects were clinically investigated and a repeat liver biopsy was obtained. No patient was taking statins at baseline while 17 patients were treated with statins at follow-up. Results: At baseline, patients that later were prescribed statins had significantly higher BMI and more pronounced hepatic steatosis. At follow-up patients on medication with statins continued to have significantly higher BMI. Diabetes was significantly more common among patients on medication with statins and they had significantly more pronounced insulin resistance. However, they exhibited a significant reduction of liver steatosis at follow-up as opposed to patients not taking statins. Despite exhibiting a high risk profile for progression of liver fibrosis, only four patients on statin treatment progressed in fibrosis stage. Conclusions: Statins can be prescribed in patients with elevated liver enzymes because of NAFLD.
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| 21. |
- Ekstedt, Mattias, 1976-, et al.
(författare)
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The clinical relevance of the Nonalcoholic Fatty Liver Disease Activity Score (NAS) in predicting fibrosis progression
- 2008
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objective: The NAFLD activity score (NAS) is a newly proposed system to grade the necroinflammatory activity in liver biopsies of NAFLD patients. This study evaluates the usefulness of the NAS in predicting clinical deterioration and fibrosis progression in NAFLD. Methods: One hundred and twenty-nine patients with biopsy proven NAFLD were included in a long-term histological follow-up study. Clinical and histological course were compared between NASH, “borderline NASH”, and “not NASH” patients. Significant fibrosis progression in NAFLD was defined as progression of more than one fibrosis stage or development of end-stage liver disease during follow-up. Results: Eighty-eight patients accepted re-evaluation and 68 underwent repeat liver biopsy. Mean time between biopsies was 13.8 ± 1.2 years (range 10.3-16.3). At baseline, NASH was diagnosed in 2 (1.6%) patients, and at follow-up, in 1 (1.5%) patient. A trend towards higher baseline NAS was seen in patients (n = 7) that developed end-stage liver disease (3.1 ± 0.9 vs. 2.4 ± 1.0; P = 0.062). Baseline NAS was significantly higher in patients with progressive fibrosis (2.9 ± 0.9 vs. 2.2 ± 0.9; P = 0.017), and NAS was independently associated with significant fibrosis progression tested in a multivariate analysis (P = 0.023). However, 18% of patients without NASH progressed significantly in fibrosis stage. Conclusion: Although the NAS is independently associated with future risk of progressive fibrosis in NAFLD, the clinical usefulness of the score is limited due to the significant overlap in clinical development between NAS-score groups.
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| 22. |
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| 23. |
- Fälth-Magnusson, Karin, et al.
(författare)
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Infant feeding history shows distinct differences between Swedish celiac and reference children
- 1996
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Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 7:1, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- Infant feeding history was investigated in 72 celiac and 288 age-matched reference children in a retrospective questionnaire study. The reply rate was 100% in celiac and 91. 6% in reference children. The celiac children were breast-fed for a significantly shorter time than reference children, and they were less often breast-fed at the introduction of gluten. The age of the children at gluten introduction was similar, but the cellac children were significantly more often introduced by a gluten-containing follow-up formula, while the reference children more often started on a gluten-containing porridge. The results can be interpreted in two ways. First, it could be argued that breast milk per se protects against symptoms of celiac disease in childhood. It could, however, also be claimed that breast-feeding merely modulates the gluten introduction, causing a less abrupt introduction of gluten in the baby diet and thereby fewer overt symptoms of the disease.
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| 24. |
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| 25. |
- Hahn-Strömberg, Victoria, 1971-
(författare)
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Cell adhesion proteins in different invasive patterns of colon carcinomas : a morphometric and molecular genetic study
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colorectal carcinoma is the second most common type of cancer in both men and women in Sweden. Cancer of the colon and rectum are often considered together and their ten year survival rate is approximately 50 – 60 % depending on sex and location. Different histopathological characteristics of such cancers, including the complexity of growth, are of importance for prognosis. This thesis has compared different morphometric methods in order to achieve a quantitative and objective measurement of the invasive front of colon carcinoma. Since the growth pattern is dependent on the cell adhesiveness of different proteins we studied the distribution and localization of E-cadherin, Beta-catenin, Claudin 1,2,7 and Occludin as well as screened the genes for mutations. We found a perturbed protein expression of E-cadherin, Beta-catenin, Claudin 1,2,7 and Occludin in tumor sections compared to normal mucosa, but no relation to tumor volume or growth pattern could be seen. The tumor volume was found to be correlated to the growth pattern but not responsible to the perturbed protein expression. In the mutation screening we found a SNP in exon 13 the E-cadherin gene in the tumor, as well as in exon 2 of Claudin 1 and exon 4 of Claudin 7 in both tumor and normal mucosa. No correlation between mutations and growth pattern or tumor volume was found. In conclusion, this thesis shows that the computer image analysis with estimation of fractal dimension and number of free tumor cell clusters is superior to the semi quantitative visual grading of tumor invasive complexity. The aberrant expression of cell adhesion proteins in the tumor compared to normal mucosa as well as polymorphisms in the cell adhesion genes CLDN1 and CLDN7 in both tumor and normal mucosa can suggest that these aberrations are important in the tumorigenesis of colon carcinoma.
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| 26. |
- Jendle, Johan, 1963-, et al.
(författare)
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Delivery and Retention of an Insulin Aerosol Produced by a New Jet Nebulizer
- 1995
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Ingår i: Journal of Aerosol Medicine. - : Mary Ann Liebert. - 0894-2684 .- 1557-9026. ; 8:3, s. 243-254
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Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: This study describes the delivery and distribution of an aerosol generated by a jet nebulizer (MAXIN) in an experimental animal model. Anesthetised, intubated and ventilated piglets inhaled radiolabeled technetium diethylene-triamine-penta-acetic acid (99mTc-DTPA) through the endotracheal tube. The lungs were excised en bloc and scintigraphed, using a computerized gamma camera to evaluate the pattern of distribution. By nebulizing radiolabeled 125I-insulin and comparing the activity deposited on inspiratory and expiratory electrostatic filters, delivery and retention of nebulized insulin was assessed. The distribution of aerosol in the lungs was very even and reached the most peripheral parts. The delivery of nebulized insulin was calculated to be 88.9 +/- 5.3% and 36.1 +/- 8.8% of the insulin delivered to the respiratory tract was retained. The immediate local effects of insulin aerosol administration on the lungs were evaluated using light microscopy. No adverse effects were observed at histopathologic examination of the lung tissue.CONCLUSION: This study shows a high penetration of aerosol to the peripheral parts of the lung and efficient delivery of nebulized insulin when using the MAXIN-nebulizer.
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| 27. |
- Keita, Åsa, 1973-, et al.
(författare)
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Increased uptake of non-pathogenic E. coli via the follicle-associated epithelium in longstanding ileal Crohn's disease
- 2008
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 215:2, s. 135-144
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Tidskriftsartikel (refereegranskat)abstract
- In Crohn's disease (CD), inflammation is driven by luminal commensal micro-organisms, however, mechanisms of early phases of inflammation need further clarification. The earliest observable lesions of recurrent CD are microscopic erosions at the specialized follicle-associated epithelium (FAE), which lines the Peyer's patches. Therefore, our aim was to investigate the mucosal barrier to non-pathogenic bacteria in FAE of CD. The FAE of macroscopically normal ileum from patients with longstanding CD, ulcerative colitis, and controls was studied in Ussing chambers regarding electrophysiology and permeability to 51Cr-EDTA, horseradish peroxidase, and non-pathogenic E. coli strains. Transepithelial passage routes and uptake into dendritic cells were studied by confocal and electron microscopy. FAE of CD showed increased numbers of adherent bacteria, after E. coli exposure in Ussing chambers, as well as spontaneously in non-exposed archival surgical tissues. Further, we found increased uptake of fluorescent E. coli K-12 and HB101 across FAE of CD, but not in ulcerative colitis. Microscopy demonstrated intercellular and transcellular uptake of E. coli in CD, but only transcellular in controls. FAE exposed to E. coli demonstrated changes in conductance and 51Cr-EDTA permeability, suggesting that bacteria affected the paracellular pathway in CD mucosa. Following bacterial uptake, CD mucosa also demonstrated an increased percentage of E. coli co-localizing with dendritic cells, and augmented tissue release of TNF-α. Our data present novel insights into the pathophysiology of CD by demonstrating a previously unrecognized defect of FAE barrier to bacteria in ileal CD, leading to increased load of commensal bacteria to the inductive sites of mucosal immunity. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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| 28. |
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| 29. |
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| 30. |
- Kellokumpu-Lehtinen, Pirkko-Liisa, et al.
(författare)
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Docetaxel Versus Surveillance After Radical Radiotherapy for Intermediate- or High-risk Prostate Cancer-Results from the Prospective, Randomised, Open-label Phase III SPCG-13 Trial
- 2019
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 76:6, s. 823-830
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Tidskriftsartikel (refereegranskat)abstract
- Background: Docetaxel combined with androgen deprivation therapy (ADT) has improved patient survival for advanced prostate cancer (PCa). Objective: This randomised trial aimed to evaluate whether six courses of docetaxel improved biochemical disease-free survival (BDFS) after radical radiotherapy (RT) for intermediate- or high-risk PCa patients. Design, setting, and participants: A total of 376 patients were randomised in this multinational phase III study, and received either six cycles of adjuvant docetaxel 75 mg/m(2) every 3 wk without continuous prednisone (arm A, n =188) or surveillance (arm B, n = 188) after RT (NTC006653848). Neoadjuvant/adjuvant ADT was mandatory for all the patients. The primary endpoint was rising prostate-specific antigen (PSA) >= 2 ng/ml above the nadir PSA value. Intermediate- or high-risk PCa was defined as T2 with a Gleason score (GS) of 4 +3, PSA > 10; T2, GS 8-10, <= 70 ng/ml; or any T3. The patients were followed for 5 yr by assessing PSA levels every 3 mo for 2 yr and every 6 mo thereafter. Outcome measurements and statistical analysis: The study power was 89% to detect a difference in BDFS between groups, and the sample size calculation accounted for the T2/T3 distribution, where a 12%/15% difference in BDFS was assumed for the T2/T3 patients. Results and limitations: All six cycles were completed in 147 (78%) of the patients in arm A. The median age was 67 yr in both treatment groups, 75% had T3 disease, and 47% had GS 8-10. The median follow-up was 59 mo (range 1-111 mo). The primary endpoint was observed for 58 patients in arm A (docetaxel) and for 57 patients in arm B (surveillance). The Kaplan-Meier analysis showed no difference in the BDFS curves (p = 0.6) between the treatment groups. The 5-yr estimated biochemical progression rates were 31% for arm A and 28% for arm B. Febrile neutropenia occurred in 16% of the docetaxel patients.No deaths were related to the docetaxel treatment. There were 43 deaths during the trial, including 20 in arm A and 23 in arm B, of which nine and seven, respectively, were due to PCa. The hazard ratio from Cox multivariate analysis for PSA progression of arm A (docetaxel) versus arm B (surveillance) was 1.14 (95% confidence interval 0.79-1.64, p = 0.5). Conclusions: Adjuvant docetaxel without prednisone did not improve BDFS after radical RT with ADT for intermediate- or high-risk PCa. Patient summary: We compared six cycles of adjuvant docetaxel given after radical external radiotherapy plus androgen deprivation therapy to surveillance in intermediate- and high-risk localised prostate cancer. We found no overall benefit in this setting. (C) 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 31. |
- Kellokumpu-Lehtinen, P-L, et al.
(författare)
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Toxicity in patients receiving adjuvant docetaxel plus hormonal treatment after radical radiotherapy for intermediate or high-risk prostate cancer : a preplanned safety report of the SPCG-13 trial
- 2012
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Ingår i: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1365-7852 .- 1476-5608. ; 15:3, s. 303-307
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Radical radiotherapy (RD combined with androgen deprivation therapy is currently the standard treatment for elderly patients with localized intermediate- or high-risk prostate cancer (PC). To increase the recurrence-free and overall survival, we conducted an adjuvant, randomized trial using docetaxel (T) in PC patients (Scandinavian Prostate Cancer Group trial 13). METHODS: The inclusion criteria are the following: men > 18 and <= 75 years of age, WHO/ECOG performance status 0-1, histologically proven PC within 12 months before randomization and one of the following: T2, Gleason 7 (4 + 3), PSA > 10; T2, Gleason 8-10, any PSA; or any T3 tumors. Neoadjuvant/adjuvant hormone therapy is mandatory for all patients. The patients were randomized to receive six cycles of T (75 mg m(-2) d 1. cycle 21 d) or no docetaxel after radical RI (with a minimum tumor dose of 74 Gy). This study identifier number is NTC 006653848 (http://www.clinicaltrials.org). RESULTS: In this preplanned safety analysis of 100 patients, T treatment induced grade (G) 3 adverse events (AEs) in 15 patients (30%) and G4 AEs in 30 patients (60%), mainly due to bone marrow toxicity. Neutropenia G3-4 was observed in 72% of the patients, febrile neutropenia was found in 24% of patients, neutropenic infection in 10% of patients and G3 infection without neutropenia in 4% of patients. Nonhematological G3 AEs were rare: anorexia, diarrhea, mucositis, nausea, pain (1 patient each) and fatigue (5). Other severe serious AEs related to T were pulmonary embolism and renal failure. However, only three patients discontinued T before completing the planned six cycles. No deaths had occurred. No patients in the control arm experienced G3-4 toxicities at 12 weeks after the randomization. CONCLUSIONS: Adjuvant docetaxel chemotherapy after radiotherapy has a higher frequency of neutropenia than previous studies on patients with metastatic disease. Otherwise, the treatment was quite well tolerated.
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| 32. |
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| 33. |
- Lutgendorff, Femke, 1981-, et al.
(författare)
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Probiotics enhance pancreatic glutathione biosynthesis and reduce oxidative stress in experimental acute pancreatitis
- 2008
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Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 295:5
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Tidskriftsartikel (refereegranskat)abstract
- Factors determining severity of acute pancreatitis (AP) are poorly understood. Oxidative stress causes acinar cell injury and contributes to the severity, whereas prophylactic probiotics ameliorate experimental pancreatitis. Our objective was to study how probiotics affect oxidative stress, inflammation, and acinar cell injury during the early phase of AP. Fifty-three male Sprague-Dawley rats were randomly allocated into groups: 1) control, 2) sham procedure, 3) AP with no treatment, 4) AP with probiotics, and 5) AP with placebo. AP was induced under general anesthesia by intraductal glycodeoxycholate infusion (15 mM) and intravenous cerulein (5 μg·kg-1·h-1, for 6 h). Daily probiotics or placebo were administered intragastrically, starting 5 days prior to AP. After cerulein infusion, pancreas samples were collected for analysis including lipid peroxidation, glutathione, glutamate-cysteine-ligase activity, histological grading of pancreatic injury, and NF-κB activation. The severity of pancreatic injury correlated to oxidative damage (r = 0.9) and was ameliorated by probiotics (1.5 vs. placebo 5.5, P = 0.014). AP-induced NF-κB activation was reduced by probiotics (0.20 vs. placebo 0.53 OD 450nm/mg nuclear protein, P < 0.001). Probiotics attenuated AP-induced lipid peroxidation (0.25 vs. placebo 0.51 pmol malondialdehyde/mg protein, P < 0.001). Not only was AP-induced glutathione depletion prevented (8.81 vs. placebo 4.1 μmol/mg protein, P < 0.001), probiotic pretreatment even increased glutathione compared with sham rats (8.81 vs. sham 6.18 μmol/mg protein, P < 0.001). Biosynthesis of glutathione (glutamate-cysteine-ligase activity) was enhanced in probiotic-pretreated animals. Probiotics enhanced the biosynthesis of glutathione, which may have reduced activation of inflammation and acinar cell injury and ameliorated experimental AP, via a reduction in oxidative stress. Copyright © 2008 the American Physiological Society.
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| 34. |
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| 35. |
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| 36. |
- Norén, Bengt, 1955-, et al.
(författare)
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Separation of advanced from mild fibrosis in diffuse liver disease using 31P magnetic resonance spectroscopy
- 2008
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Ingår i: European Journal of Radiology. - : Elsevier. - 0720-048X .- 1872-7727. ; 66:2, s. 313-320
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Tidskriftsartikel (refereegranskat)abstract
- 31P-MRS using DRESS was used to compare absolute liver metabolite concentrations (PME, Pi, PDE, γATP, αATP, βATP) in two distinct groups of patients with chronic diffuse liver disorders, one group with steatosis (NAFLD) and none to moderate inflammation (n = 13), and one group with severe fibrosis or cirrhosis (n = 16). All patients underwent liver biopsy and extensive biochemical evaluation. A control group (n = 13) was also included. Absolute concentrations and the anabolic charge, AC = {PME}/({PME} + {PDE}), were calculated.Comparing the control and cirrhosis groups, lower concentrations of PDE (p = 0.025) and a higher AC (p < 0.001) were found in the cirrhosis group. Also compared to the NAFLD group, the cirrhosis group had lower concentrations of PDE (p = 0.01) and a higher AC (p = 0.009). No significant differences were found between the control and NAFLD group. When the MRS findings were related to the fibrosis stage obtained at biopsy, there were significant differences in PDE between stage F0–1 and stage F4 and in AC between stage F0–1 and stage F2–3.Using a PDE concentration of 10.5 mM as a cut-off value to discriminate between mild, F0–2, and advanced, F3–4, fibrosis the sensitivity and specificity were 81% and 69%, respectively. An AC cut-off value of 0.27 showed a sensitivity of 93% and a specificity of 54%.In conclusion, the results suggest that PDE is a marker of liver fibrosis, and that AC is a potentially clinically useful parameter in discriminating mild fibrosis from advanced.
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| 37. |
- Petersson, Fredrik, et al.
(författare)
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A morphometric study of antral G-cell density in a sample of adult general population : comparison of three different methods and correlation with patient demography, helicobacter pylori infection, histomorphology and circulating gastrin levels
- 2009
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Ingår i: International Journal of Clinical and Experimental Pathology. - 1936-2625. ; 2:3, s. 239-248
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori infection has been linked to hypergastrinemia and either decreased or normal G-cell content in the antral mucosa. To clarify this controversial issue, we quantitatively determined antral G-cell content on the same biopsy specimens with three different methods and examined whether these methods are intercorrelated and the relation of these methods to plasma gastrin concentrations, demography, the occurrence of H. pylori infection and chronic gastritis. Gastric antral mucosal biopsy sections from 273 adults (188 with and 85 without H pylori infection) from a general population sample were examined immunohistochemically for G-cells using cell counting, stereology (point counting) and computerized image analysis. Gastritis was scored according to the updated Sydney system. Basal plasma gastrin concentrations were measured by radioimmunoassay. The three methods for G-cell quantification were poorly correlated and the results showed no correlation with basal plasma gastrin concentrations. The antral G-cell density and scores for H. pylori colonization were positively related to age. Neither the scores for chronic inflammation, nor the scores for inflammatory activity, atrophy or intestinal metaplasia were consistently related to the antral G-cell content. In conclusion, the results of three techniques for G-cell quantification in the gastric antral mucosa were poorly intercorrelated and none of the methods correlated with plasma gastrin concentrations. Age and scores for H pylori colonization seem to be determinants of the G-cell density. That common morphometric techniques correlate poorly is of utmost importance to bear in mind when quantitative morphological studies are planned, compared or interpreted.
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| 38. |
- Petersson, Fredrik, et al.
(författare)
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Characterization of the gastric cardia in volunteers from the general population : type of mucosa, helicobacter pylori infection, inflammation, mucosal proliferative activity, p53 and p21 expression, and relations to gastritis
- 2010
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Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 0163-2116 .- 1573-2568. ; 55:1, s. 46-53
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this research was to characterize the mucosa of the gastric cardia in relation to infection with Helicobacter pylori and the occurrence of chronic gastritis in other parts of the stomach in a sample of the general population. In this study, 80 adult volunteers underwent esophagogastroscopy with biopsies from the gastric cardia, corpus, and antrum. Gastritis was classified according to the Sydney system. Chronic gastritis (cardia excepted) was diagnosed in 35 subjects, 30 with H. pylori infection. Epithelial proliferative activity (Ki-67), p53- and p21 expression were examined quantitatively with cell counting after immunohistochemical stainings. Esophagitis was diagnosed macroscopically. Fourty eight subjects had cardia-type and 32 corpus-type mucosa in the anatomical cardia. The prevalence of esophagitis (nine cases) did not differ between these groups. Carditis was more prevalent among subjects with cardia-type mucosa (73 vs. 28%, P < 0.0001). H. pylori was present in 48% of those with cardia-type and 25% of those with corpus-type mucosa (P = 0.06). Of the 44 subjects with carditis, 31 had H. pylori in this location. The group with H. pylori infection had significantly higher mucosal proliferative activity when compared to uninfected subjects. Among the subjects with H. pylori-associated carditis, more p53-positive epithelial cells were detected compared to both the non-infected group (P = 0.0004) and to subjects with non-H. pylori-associated carditis (P = 0.03). In subjects with cardia-type mucosa, and both carditis and gastritis, the degree of chronic inflammation was higher in the cardia compared to the corpus and antrum and the p53 expression was significantly higher in the cardia compared to the corpus, but similar to that in the antrum. The proliferative activity was significantly higher in the antrum compared to the cardia and corpus, respectively. In conclusion, H. pylori infection, carditis, and increased p53 expression are more common in subjects with cardia- than corpus-type mucosa in the gastric cardia. Carditis is mainly related to H. pylori infection. There are some differences regarding inflammation, proliferative activity, and p53 expression between the cardia and other regions of the stomach, yet the significance of these differences remains to be clarified.
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| 39. |
- Petersson, Fredrik, et al.
(författare)
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Gastric epithelial proliferation and p53 and p21 expression in a general population sample : relations to age, sex, and mucosal changes associated with H. pylori infection
- 2002
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Ingår i: Digestive Diseases and Sciences. - 0163-2116 .- 1573-2568. ; 47:7, s. 1558-1566
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 40. |
- Rezk, Mary, et al.
(författare)
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Associations between new-onset postoperative atrial fibrillation and long-term outcome in patients undergoing surgical aortic valve replacement.
- 2023
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Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - : Oxford University Press (OUP). - 1873-734X. ; 63:5
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Tidskriftsartikel (refereegranskat)abstract
- Data on prognostic implications of new-onset postoperative atrial fibrillation (POAF) after surgical aortic valve replacement (SAVR) is limited. We sought to explore associations between POAF, early-initiated oral anticoagulation (OAC), and long-term outcome after SAVR and combined SAVR+CABG.This is a retrospective, population-based study including all isolated SAVR (n=7038) and combined SAVR and CABG patients (n=3854) without a history of preoperative atrial fibrillation in Sweden 2007-2017. Individual patient data was merged from four nationwide registries. Inverse Probability of Treatment Weighting (IPTW) adjusted Cox regression models were employed separately in SAVR and SAVR+CABG patients. Median follow-up time was 4.7years (range 0-10years).POAF occurred in 44.5% and 50.7% of SAVR and SAVR+CABG patients, respectively. In SAVR patients, POAF was associated with increased long-term risk of death [adjusted hazard ratio (aHR) 1.21 (95% confidence interval 1.06-1.37)], ischaemic stroke [aHR 1.32 (1.08-1.59)], any thromboembolism, heart failure hospitalization, and recurrent atrial fibrillation. In SAVR+CABG, POAF was associated with death [aHR 1.31 (1.14-1.51)], recurrent atrial fibrillation, and heart failure, but not with ischaemic stroke [aHR 1.04 (0.84-1.29)] or thromboembolism. OAC was dispensed within 30days after discharge to 67.0% and 65.9% respectively of SAVR and SAVR+CABG patients with POAF. Early initiated OAC was not associated with reduced risk of death, ischaemic stroke or thromboembolism in any group of patients.POAF after SAVR is associated with an increased risk of long-term mortality and morbidity. Further studies are warranted to clarify the role of OAC in SAVR patients with POAF.
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| 41. |
- Sjöstedt, Camilla, 1970-, et al.
(författare)
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Atrophic gastritis is associated with increased sucrose permeability related to chronic inflammation
- 2005
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Ingår i: Digestion. - : S. Karger AG. - 0012-2823 .- 1421-9867. ; 72:4, s. 201-206
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Tidskriftsartikel (refereegranskat)abstract
- Background: Different theories have been presented to explain how atrophic gastritis may lead to gastric cancer development. One contributing factor could be impaired function of the gastric mucosal barrier. The aim of this study was to investigate if there are changes in gastric mucosal permeability to sucrose in atrophic gastritis. Methods: The study comprised 22 patients with atrophic gastritis and 21 normal controls. Gastritis was classified according to the Sydney system from endoscopic biopsies of the gastric corpus and antrum. All subjects were exposed to oral sucrose load (100 g), and the fraction of sucrose excreted in urine was measured by gas chromatography-mass spectrometry. Results: The fraction of sucrose excreted in urine after oral load was significantly increased in atrophic gastritis compared with controls (median 0.08 vs. 0.04%, p = 0.003). Sucrose excretion was positively related to the degree of chronic inflammation (median fraction excreted: mild inflammation 0.06%, moderate inflammation 0.08%, severe inflammation 0.18%, p = 0.04) rather than to the degree of atrophy in the gastric mucosa. Occurrence of intestinal metaplasia was also associated with significantly higher sucrose excretion. However, in multivariate analysis, including intestinal metaplasia, only the degree of inflammation was positively related to sucrose excretion. Conclusion: Atrophic gastritis is associated with increased sucrose permeability, suggesting paracellular leakage of the gastric mucosa. This leakage seems to be related to the degree of inflammation rather than the degree of atrophy. The findings may have implications for the diseases and complications associated with atrophic gastritis. Copyright © 2005 S. Karger AG.
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| 42. |
- Söderholm, Johan D, 1958-, et al.
(författare)
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Epithelial permeability to proteins in the noninflamed ileum of Crohn's disease?
- 1999
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Ingår i: Gastroenterology. - 0016-5085 .- 1528-0012. ; 117:1, s. 65-72
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 43. |
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| 44. |
- Taha, Amar, 1978, et al.
(författare)
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New-Onset Atrial Fibrillation After Coronary Artery Bypass Grafting and Long-Term Outcome: A Population-Based Nationwide Study From the SWEDEHEART Registry.
- 2021
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The long-term impact of new-onset postoperative atrial fibrillation (POAF) after coronary artery bypass grafting and the benefit of early-initiated oral anticoagulation (OAC) in patients with POAF are uncertain. Methods and Results All patients who underwent coronary artery bypass grafting without preoperative atrial fibrillation in Sweden from 2007 to 2015 were included in a population-based study using data from 4 national registries: SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies), National Patient Registry, Dispensed Drug Registry, and Cause of Death Registry. POAF was defined as any new-onset atrial fibrillation during the first 30 postoperative days. Cox regression models (adjusted for age, sex, comorbidity, and medication) were used to assess long-term outcome in patients with and without POAF, and potential associations between early-initiated OAC and outcome. In a cohort of 24523 patients with coronary artery bypass grafting, POAF occurred in 7368 patients (30.0%), and 1770 (24.0%) of them were prescribed OAC within 30days after surgery. During follow-up (median 4.5years, range 0‒9years), POAF was associated with increased risk of ischemic stroke (adjusted hazard ratio [aHR] 1.18 [95% CI, 1.05‒1.32]), any thromboembolism (ischemic stroke, transient ischemic attack, or peripheral arterial embolism) (aHR 1.16, 1.05‒1.28), heart failure hospitalization (aHR 1.35, 1.21‒1.51), and recurrent atrial fibrillation (aHR 4.16, 3.76‒4.60), but not with all-cause mortality (aHR 1.08, 0.98‒1.18). Early initiation of OAC was not associated with reduced risk of ischemic stroke or any thromboembolism but with increased risk for major bleeding (aHR 1.40, 1.08‒1.82). Conclusions POAF after coronary artery bypass grafting is associated with negative prognostic impact. The role of early OAC therapy remains unclear. Studies aiming at reducing the occurrence of POAF and its consequences are warranted.
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| 45. |
- Taha, Amar, 1978, et al.
(författare)
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Stroke Risk Stratification in Patients With Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting.
- 2022
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- Background The CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75years, diabetes, previous stroke or TIA [transient ischemic attack], vascular disease, age 65 to 74years, sex category female; 2 indicates 2 points, otherwise 1 point) scoring system is recommended to guide decisions on oral anticoagulation therapy for stroke prevention in patients with nonsurgery atrial fibrillation. A score ≥1 in men and ≥2 in women, corresponding to an annual stroke risk exceeding 1%, warrants long-term oral anticoagulation provided the bleeding risk is acceptable. However, in patients with new-onset postoperative atrial fibrillation, the optimal risk stratification method is unknown. The aim of this study was therefore to evaluate the CHA2DS2-VASc scoring system for estimating the 1-year ischemic stroke risk in patients with new-onset postoperative atrial fibrillation after coronary artery bypass grafting. Methods and Results All patients with new-onset postoperative atrial fibrillation and without oral anticoagulation after first-time isolated coronary artery bypass grafting performed in Sweden during 2007 to 2017 were eligible for this registry-based observational cohort study. The 1-year ischemic stroke rate at each step of the CHA2DS2-VASc score was estimated using a Kaplan-Meier estimator. Of the 6368 patients included (mean age, 69.9years; 81% men), >97% were treated with antiplatelet drugs. There were 147 ischemic strokes during the first year of follow-up. The ischemic stroke rate at 1year was 0.3%, 0.7%, and 1.5% in patients with CHA2DS2-VASc scores of 1, 2, and 3, respectively, and ≥2.3% in patients with a score ≥4. A sensitivity analysis, with the inclusion of patients on anticoagulants, was performed and supported the primary results. Conclusions Patients with new-onset atrial fibrillation after coronary artery bypass grafting and a CHA2DS2-VASc score <3 have such a low 1-year risk for ischemic stroke that oral anticoagulation therapy should probably be avoided.
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| 46. |
- Tillander, Bo, et al.
(författare)
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Carrageenan-induced subacromial bursitis caused changes in the rat's rotator cuff
- 2001
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Ingår i: Journal of Orthopaedic Research. - 0736-0266. ; 19:3, s. 441-447
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Tidskriftsartikel (refereegranskat)abstract
- This study was designed to investigate the histologic expression of the rat's supra- and infraspinatus tendons in carrageenan-induced subacromial bursitis. Thirty-two rats received subacromial injections with carrageenan (n = 28) or saline (n = 4). The tendons were analysed microscopically after staining with hematoxyline eosin, Van Giesons hematoxyline and immunofluorescent staining of fibronectin and fibrinogen. In the controls (saline × 10) and group A (carrageenan × 5) there were no changes in the tendons. In group B (carrageenan × 10) 3/8 rats showed macrophages between the collagen fibres and an increased staining of fibronectin. In group C (double dosis carrageenan) all rats had signs of fibrocartilaginous metaplasia in the supraspinatus tendon. In eight of these specimens even bony metaplasia was seen. The infraspinatus tendon showed fibrosis but no fibro-cartilaginous metaplasia. The results showed that iatrogenic bursitis after carrageenan subacromial injections was associated with marked changes of the supraspinatus tendon.
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| 47. |
- Tillander, Bo, et al.
(författare)
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Effect of steroid injections on the rotator cuff : An experimental study in rats
- 1999
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Ingår i: Journal of shoulder and elbow surgery. - 1058-2746. ; 8:3, s. 271-274
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the effects of repeated steroid injections into the subacromial space. Thirty rats were injected either 3 or 5 times with triamcinolone in a dosage equivalent to that given to human beings or 3 or 5 times with saline into the subacromial space. One rat received no injection. The supraspinatus and infraspinatus tendons were evaluated macroscopically and microscopically. Two different staining methods were used on each sample including hematoxylin eosin and Miller's elastin/van Gieson's solution. After 5 steroid injections, we found focal inflammation, necrosis, and fragmentation of collagen bundles in the tendon in 4 of 7 rats. The tendons of the controls showed a normal structure (P < .05). There were no pathologic changes among the rats that were injected with triamcinolone 3 times. These results show that repeated subacromial injections of triamcinolone may cause damage to the rotator cuff of the rat. This finding may indicate cautious use of subacromial steroid injections in human beings.
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| 48. |
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| 49. |
- Veress, Bela, et al.
(författare)
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Duodenal intraepithelial lymphocyte-count revisited
- 2004
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 39:2, s. 138-144
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Tidskriftsartikel (refereegranskat)abstract
- Background: The number of intraepithelial lymphocytes in the duodenum was determined 30 years ago, the suggested normal upper limit being 40 lymphocytes per 100 epithelial cells. Methods: Duodenal mucosa was analysed from 18 healthy individuals and 56 consecutive patients biopsied because of epigastralgia (17 cases), diarrhoea (10 cases), oesophagitis (10 cases), iron-deficiency (9 cases) and B12-deficiency (10 cases) showing normal histology, along with 10 cases of active coeliac disease. The biopsies were fixed in 4% formalin overnight and embedded in paraffin. Three micrometre thick sections were stained with haematoxylin and eosin and CD3. At least 300 epithelial cells were counted, the number of intraepithelial lymphocytes was given as the mean/100 epithelial cells. Extensive statistical analyses were performed. Results: In the healthy individuals the mean number (s) of intraepithelial lymphocytes/100 epithelial cells was 10.8 (2.6) and 13.2 (3.8) in H&E and CD3 stained sections, respectively. The upper limit of the confidence interval for CD3 staining was 29. There was no significant difference between normal individuals and the clinical groups, with the exception of coeliac disease. Conclusion: Two-step analysis of intraepithelial lymphocyte-determination is suggested: (a) semi-quantitative estimate on H&E-stained sections (normal ratio of 1:5 between lymphocytes and enterocytes, upper normal limit 20 lymphocytes) and (b) CD3-staining and counting if intraepithelial lymphocytosis is suspected. The upper normal range of intraepithelial lymphocytes is set at 25 CD3+ lymphocytes/100 epithelial cells. Values between 25 and 29 are regarded as 'borderline' and 30 or more represent pathologic intraepithelial lymphocytosis in the duodenum.
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