| 1. |
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| 2. |
- Hugot, J-P, et al.
(author)
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Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease
- 2001
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 411:6837, s. 599-603
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Journal article (peer-reviewed)abstract
- Crohn's disease and ulcerative colitis, the two main types of chronic inflammatory bowel disease, are multifactorial conditions of unknown aetiology. A susceptibility locus for Crohn's disease has been mapped to chromosome 16. Here we have used a positional-cloning strategy, based on linkage analysis followed by linkage disequilibrium mapping, to identify three independent associations for Crohn's disease: a frameshift variant and two missense variants of NOD2, encoding a member of the Apaf-1/Ced-4 superfamily of apoptosis regulators that is expressed in monocytes. These NOD2 variants alter the structure of either the leucine-rich repeat domain of the protein or the adjacent region. NOD2 activates nuclear factor NF-?B, this activating function is regulated by the carboxy-terminal leucine-rich repeat domain, which has an inhibitory role and also acts as an intracellular receptor for components of microbial pathogens. These observations suggest that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-?B in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn's disease that can now be further investigated.
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| 3. |
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| 4. |
- Burisch, J., et al.
(author)
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Environmental factors in a population-based inception cohort of inflammatory bowel disease patients in Europe : An ECCO-EpiCom study
- 2014
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In: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 8:7, s. 607-616
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Journal article (peer-reviewed)abstract
- Background and Aims: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more "westernised" standard of Living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients.Methods: The EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1 million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors.Results: A total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p < 0.01). Daily consumption of fast food as well as appendectomy before the age of 20 was more frequent in Eastern European than in Western European UC patients (p < 0.01). Eastern European CD and UC patients had received more vaccinations and experienced fewer childhood infections than Western European patients (p < 0.01).Conclusions: In this European population-based inception cohort of unselected IBD patients, Eastern and Western European patients differed in environmental factors prior to diagnosis. Eastern European patients exhibited higher occurrences of suspected risk factors for IBD included in the Western lifestyle. (C) 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
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| 5. |
- Burisch, J., et al.
(author)
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Health care and patients' education in a European inflammatory bowel disease inception cohort : an ECCO-EpiCom study
- 2014
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In: Journal of Crohn's & Colitis. - : Oxford University Press (OUP). - 1873-9946 .- 1876-4479. ; 8:8, s. 811-818
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Journal article (peer-reviewed)abstract
- Background and Aims: The EpiCom study and inception cohort was initiated in 2010 in 31 centers from 14 Western and 8 Eastern European countries, covering a 10.1 million person background population. Our aim was to investigate whether there is a difference between Eastern and Western Europe in health care and education of patients with inflammatory bowel disease (IBD).Methods: A quality of care (QoC) questionnaire was developed in the EpiCom group consisting of 16 questions covering 5 items: time interval between the onset of symptoms and diagnosis, information, education, empathy and access to health care providers.Results: Of 1,515 patients, 947 (217 east/730 west) answered the QoC questionnaire. Only 23% of all patients had knowledge about IBD before diagnosis. In Eastern Europe, significantly more patients searched out information about IBD themselves (77% vs. 68%, p < 0.05), the main source was the Internet (92% vs. 88% p = 0.23). In Western Europe, significantly more patients were educated by nurses (19% vs. 1%, p < 0.05), while in Eastern Europe, gastroenterologists were easier to contact (80% vs. 68%, p < 0.05).Conclusion: Health care differed significantly between Eastern and Western Europe in all items, but satisfaction rates were high in both geographic regions. Because of the low awareness and the rising incidence of IBD, general information should be the focus of patient organizations and medical societies. In Western Europe IBD nurses play a very important role in reducing the burden of patient management. (c) 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
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| 6. |
- Burisch, J., et al.
(author)
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Health-related quality of life improves during one year of medical and surgical treatment in a European population-based inception cohort of patients with Inflammatory Bowel Disease : An ECCO-EpiCom study
- 2014
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In: Journal of Crohn's & Colitis. - Oxford, United Kingdom : Oxford University Press. - 1873-9946 .- 1876-4479. ; 8:9, s. 1030-1042
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Journal article (peer-reviewed)abstract
- Background & Aims: Health-related quality of life (HRQoL) is impaired in patients with Inflammatory Bowel Disease (IBD). The aim was prospectively to assess and validate the pattern of HRQoL in an unselected, population-based inception cohort of IBD patients from Eastern and Western Europe.Methods: The EpiCom inception cohort consists of 1560 IBD patients from 31 European centres covering a background population of approximately 10.1 million. Patients answered the disease specific Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and generic Short Form 12 (SF-12) questionnaire at diagnosis and after one year of follow-up.Results: In total, 1079 patients were included in this study. Crohn's disease (CD) patients mean SIBDQ scores improved from 45.3 to 55.3 in Eastern Europe and from 44.9 to 53.6 in Western Europe. SIBDQ scores for ulcerative colitis (UC) patients improved from 44.9 to 57.4 and from 48.8 to 55.7, respectively. UC patients needing surgery or biologicals had lower SIBDQ scores before and after compared to the rest, while biological therapy improved SIBDQ scores in CD. CD and UC patients in both regions improved all SF-12 scores. Only Eastern European UC patients achieved SF-12 summary scores equal to or above the normal population.Conclusion: Medical and surgical treatment improved HRQoL during the first year of disease. The majority of IBD patients in both Eastern and Western Europe reported a positive perception of disease-specific but not generic HRQoL. Biological therapy improved HRQoL in CD patients, while UC patients in need of surgery or biological therapy experienced lower perceptions of HRQoL than the rest.
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| 7. |
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| 8. |
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| 9. |
- Angelison, Leif, et al.
(author)
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Long-term outcome of infliximab treatment in chronic active ulcerative colitis : a Swedish multicentre study of 250 patients
- 2017
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In: Alimentary Pharmacology and Therapeutics. - : Wiley-Blackwell Publishing Inc.. - 0269-2813 .- 1365-2036. ; 45:4, s. 519-532
-
Journal article (peer-reviewed)abstract
- Background: Real-life long-term data on infliximab treatment in ulcerative colitis are limited.Aim: To study the long-term efficacy and safety of infliximab in chronic active ulcerative colitis and possible predictors of colectomy and response were also examined.Methods: A retrospective multi-centre study of infliximab treatment in 250 patients with chronic active ulcerative colitis with inclusion criteria: age ≥18 years, ambulatory treated, steroid-dependent or intolerant and/or immunomodulator refractory or intolerant.Results: Steroid-free clinical remission was achieved by 123/250 patients (49.2%) at 12 months and in 126/250 patients at a median follow-up of 2.9 years (50.4%). Primary response at 3 months was achieved by 190/250 (76.0%) patients and associated with a high probability of response 168/190 (88.4%) at 12 months and 143/190 (75.3%) at follow-up. Long-term rate of colectomy in primary responders was 6/190 (3.2%) at 12 months and 27/190 (14.2%) at last follow-up. Failure to achieve response at 3 months was associated with a high risk of subsequent colectomy, 29/60 (48.3%) at 12 months and 41/60 (68.3%) at follow-up. Response at 12 months was associated with a low risk of subsequent colectomy, 14/181 (7.7%) compared with non-response 19/34 (55.9%) (P < 0.0001). Non-response at 3 months was an independent predictor of subsequent colectomy (HR = 9.40, 95% CI = 5.10-17.35, P < 0.001). Concomitant azathioprine therapy did not influence outcome in terms of colectomy.Conclusions: Long-term efficacy of infliximab treatment in chronic active ulcerative colitis is excellent especially in patients who respond to induction treatment. Conversely, non-response at 3 months predicts a poor outcome, with a high risk of subsequent colectomy.
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| 10. |
- Burisch, J., et al.
(author)
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East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort
- 2014
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In: Gut. - : BMJ Publishing Group. - 0017-5749 .- 1468-3288. ; 63:4, s. 588-597
-
Journal article (peer-reviewed)abstract
- Objective The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East–West gradient in the incidence of IBD in Europe exists.Design A prospective, uniformly diagnosed, population based inception cohort of IBD patients in 31 centres from 14 Western and eight Eastern European countries covering a total background population of approximately 10.1 million people was created. One-third of the centres had previous experience with inception cohorts. Patients were entered into a low cost, web based epidemiological database, making participation possible regardless of socioeconomic status and prior experience.Results 1515 patients aged 15 years or older were included, of whom 535 (35%) were diagnosed with Crohn's disease (CD), 813 (54%) with ulcerative colitis (UC) and 167 (11%) with IBD unclassified (IBDU). The overall incidence rate ratios in all Western European centres were 1.9 (95% CI 1.5 to 2.4) for CD and 2.1 (95% CI 1.8 to 2.6) for UC compared with Eastern European centres. The median crude annual incidence rates per 100 000 in 2010 for CD were 6.5 (range 0–10.7) in Western European centres and 3.1 (range 0.4–11.5) in Eastern European centres, for UC 10.8 (range 2.9–31.5) and 4.1 (range 2.4–10.3), respectively, and for IBDU 1.9 (range 0–39.4) and 0 (range 0–1.2), respectively. In Western Europe, 92% of CD, 78% of UC and 74% of IBDU patients had a colonoscopy performed as the diagnostic procedure compared with 90%, 100% and 96%, respectively, in Eastern Europe. 8% of CD and 1% of UC patients in both regions underwent surgery within the first 3 months of the onset of disease. 7% of CD patients and 3% of UC patients from Western Europe received biological treatment as rescue therapy. Of all European CD patients, 20% received only 5-aminosalicylates as induction therapy.Conclusions An East–West gradient in IBD incidence exists in Europe. Among this inception cohort—including indolent and aggressive cases—international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Weismuller, T. J., et al.
(author)
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Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis
- 2017
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In: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 152:8
-
Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC. METHODS: We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. RESULTS: Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time to event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n = 594); patients of advanced age at diagnosis had an increased incidence compared with younger patients (incidence rate: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21-30 years old, 9.0 per 100 patient-years for patients 31-40 years old, 14.0 per 100 patient-years for patients 4150 years old, 15.2 per 100 patient-years for patients 51-60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohn's disease and no IBD (both vs ulcerative colitis) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62; P <.001 and HR, 0.90; P =.03, respectively) and malignancy (HR, 0.68; P =.008 and HR, 0.77; P =.004, respectively). Small-duct PSC was associated with a lower risk of LTD or malignancy compared with classic PSC (HR, 0.30 and HR, 0.15, respectively; both P <.001). Female sex was also associated with a lower risk of LTD or malignancy (HR, 0.88; P =.002 and HR, 0.68; P <.001, respectively). In multivariable analyses assessing the primary endpoint, small-duct PSC characterized a low-risk phenotype in both sexes (adjusted HR for men, 0.23; P <.001 and adjusted HR for women, 0.48; P =.003). Conversely, patients with ulcerative colitis had an increased risk of liver disease progression compared with patients with Crohn's disease (HR, 1.56; P <.001) or no IBD (HR, 1.15; P =.002). CONCLUSIONS: In an analysis of data from individual patients with PSC worldwide, we found significant variation in clinical course associated with age at diagnosis, sex, and ductal and IBD subtypes. The survival estimates provided might be used to estimate risk levels for patients with PSC and select patients for clinical trials.
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| 15. |
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| 16. |
- Bosma, M, et al.
(author)
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FNDC4 acts as an anti-inflammatory factor on macrophages and improves colitis in mice
- 2016
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 11314-
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Journal article (peer-reviewed)abstract
- FNDC4 is a secreted factor sharing high homology with the exercise-associated myokine irisin (FNDC5). Here we report that Fndc4 is robustly upregulated in several mouse models of inflammation as well as in human inflammatory conditions. Specifically, FNDC4 levels are increased locally at inflamed sites of the intestine of inflammatory bowel disease patients. Interestingly, administration of recombinant FNDC4 in the mouse model of induced colitis markedly reduces disease severity compared with mice injected with a control protein. Conversely, mice lacking Fndc4 develop more severe colitis. Analysis of binding of FNDC4 to different immune cell types reveals strong and specific binding to macrophages and monocytes. FNDC4 treatment of bone marrow-derived macrophages in vitro results in reduced phagocytosis, increased cell survival and reduced proinflammatory chemokine expression. Hence, treatment with FNDC4 results in a state of dampened macrophage activity, while enhancing their survival. Thus, we have characterized FNDC4 as a factor with direct therapeutic potential in inflammatory bowel disease and possibly other inflammatory diseases.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Hedström, Peter, et al.
(author)
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Load partitioning and strain-induced martensite formation during tensile loading of a metastable austenitic stainless steel
- 2009
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In: Metallurgical and Materials Transactions. A. - : Springer Science and Business Media LLC. - 1073-5623 .- 1543-1940. ; 40:5, s. 1039-1048
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Journal article (peer-reviewed)abstract
- In-situ high-energy X-ray diffraction and material modeling are used to investigate the strain-rate dependence of the strain-induced martensitic transformation and the stress partitioning between austenite and α′ martensite in a metastable austenitic stainless steel during tensile loading. Moderate changes of the strain rate alter the strain-induced martensitic transformation, with a significantly lower α′ martensite fraction observed at fracture for a strain rate of 10−2 s−1, as compared to 10−3 s−1. This strain-rate sensitivity is attributed to the adiabatic heating of the samples and is found to be well predicted by the combination of an extended Olson–Cohen strain-induced martensite model and finite-element simulations for the evolving temperature distribution in the samples. In addition, the strain-rate sensitivity affects the deformation behavior of the steel. The α′ martensite transformation at high strains provides local strengthening and extends the time to neck formation. This reinforcement is witnessed by a load transfer from austenite to α′ martensite during loading.
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| 22. |
- Hugot, JP, et al.
(author)
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Clustering of Crohn's disease within affected sibships
- 2003
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In: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 11:2, s. 179-184
-
Journal article (peer-reviewed)abstract
- Crohn's disease (CD) is a complex genetic disorder for which aetiology is unknown. Recently, genetic factors for susceptibility have been described. Several genetic loci have been mapped and partially explain the familial aggregations of the disease. However, environmental factors may also contribute to these aggregations. We considered that if the role of non-genetic factors was negligible, CD patients would be randomly distributed in sibships with multiple affected siblings. On the other hand if there was a significant environmental contribution, the siblings would be affected non-randomly over exposure status. In order to test this hypothesis, we studied 102 sibships with two or more affected siblings. A statistical test, named Cluster of Affected Sibling Test or CAST, was developed, based on the exact calculation of the probability of observing a given number of clusters of affected siblings in multiplex families. The null hypothesis of a random distribution of affected siblings was rejected (P=0,005). The observed excess of affected sibling clusters indicates that birth order influences the disease status. Considering that an adjacent order of birth is a global estimate of environmental sharing, this observation strongly suggests that environmental factors contribute to the observed familial aggregations of the disease. This observation provides evidence that familial CD is a relevant tool for further studies of environmental factors and gene-environment interaction. More generally, the CAST statistics may be widely applicable to estimate the involvement of environmental factors in the aetiology of other binary traits which may be observed in multiple members of the same sibship.
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| 23. |
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| 24. |
- Oden, Magnus, et al.
(author)
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In situ small-angle x-ray scattering study of nanostructure evolution during decomposition of arc evaporated TiAlN coatings
- 2009
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In: APPLIED PHYSICS LETTERS. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 94:5, s. 053114-
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Journal article (peer-reviewed)abstract
- Small-angle x-ray scattering was used to study in situ decomposition of an arc evaporated TiAlN coating into cubic-TiN and cubic-AlN particles at elevated temperature. At the early stages of decomposition particles with ellipsoidal shape form, which grow and change shape to spherical particles at higher temperatures. The spherical particles grow at a rate of 0.18 A/degrees C while coalescing.
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| 25. |
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| 26. |
- Thiébaut, R., et al.
(author)
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TNFSF15 polymorphisms are associated with susceptibility to inflammatory bowel disease in a new European cohort
- 2009
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In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 104:2, s. 384-391
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Inflammatory bowel disease (IBD), e.g., Crohn's disease (CD) and ulcerative colitis (UC), is a complex genetic disorder. Tumor necrosis factor (ligand) superfamily, member 15 (TNFSF15) has been previously identified as a susceptibility gene for CD in Japanese and UK cohorts. This replication study was designed in order to confirm and further validate the role of TNFSF15 in IBD. METHODS: A total of 666 IBD families (corresponding to 2,982 relatives) with European ancestry were genotyped for the rs6478108 and rs7869487 polymorphisms, which define the main TNFSF15 haplotypes previously associated with CD. An association between the main haplotypes and CD, UC and IBD was tested using the Genehunter TDT and Unphased statistics. Caspase recruitment domain 15 (CARD15)/TNFSF15 interaction and genotype/phenotype correlations were also studied. RESULTS: The previously reported "high-risk" haplotype (A) was associated with IBD (P=0.001) (OR=1.25 (1.05-1.50)) and CD (P=0.02) (OR=1.31 (1.03-1.67)) whereas the "protective" (B) haplotype was significantly less transmitted to IBD and CD patients. No interaction between CARD15 and TNFSF15 was detected. We also failed to define a clinical subgroup of CD patients specifically associated with TNFSF15 haplotype A. CONCLUSIONS: This study confirms that TNFSF15 or a closely linked gene is involved in the genetic predisposition to CD.
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| 27. |
- van Asseldonk, Dirk P, et al.
(author)
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Difficulties and possibilities with thiopurine therapy in inflammatory bowel disease-Proceedings of the first Thiopurine Task Force meeting
- 2011
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In: DIGESTIVE AND LIVER DISEASE. - : Elsevier Science B.V., Amsterdam. - 1590-8658. ; 43:4, s. 270-276
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Journal article (peer-reviewed)abstract
- Background: Thiopurines, such as azathioprine and mercaptopurine, are of pivotal importance in the treatment of inflammatory bowel disease. Although these drugs have been used for several decades, still many questions remain unanswered. Aim: To provide an overview of clinically and scientifically challenging topics concerning thiopurine therapy in inflammatory bowel disease treatment. Methods: The first meeting of the Thiopurine Task Force Interest Group was held during the 2009 United European Gastroenterology Week in London (GASTRO2009). The topics of this meeting were of particular clinical and scientific interest. Additional literature was identified by performing a Pubmed search using the search terms inflammatory bowel disease, azathioprine, 6-mercaptopurine and thioguanine. Results: The following topics were discussed: therapeutic drug monitoring; the synergy of thiopurines with aminosalicylates and allopurinol; serious adverse events such as opportunistic infections, hepatotoxicity, carcinogenicity and pancreatitis; prolongation of thiopurines during clinical remission; indications for thiopurines in the postoperative setting; and the potential use of thioguanine. Specific interesting and clinically relevant topics for potential future research are provided. Conclusions: Thiopurines remain central to inflammatory bowel disease treatment, although future studies are required to substantiate a more personalised medicine approach to their use.
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| 28. |
- Wang, Y.-D., et al.
(author)
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Grain-to-grain stress interactions in an electrodeposited iron coating
- 2005
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In: Advanced Materials. - : Wiley. - 0935-9648 .- 1521-4095. ; 17:10, s. 1221-1226
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Journal article (peer-reviewed)abstract
- The distribution of residual stresses, in an iron electrolytic coating with the thickness of 1 mm, was discussed. It was found that the coating minimizes the influence of crystallographic texture and stress gradients. Scanning electron microscopy observations indicate that some cracks are produced in the direct current deposited layer. The results show that the grain size in the electrolytic coating observed by transmission electron microscopy is around 20 nm with an aspect ratio of 5:1
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| 29. |
- Zouali, H, et al.
(author)
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CARD4/NOD1 is not involved in inflammatory bowel disease
- 2003
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In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 52:1, s. 71-74
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Journal article (peer-reviewed)abstract
- Background and aims: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex genetic disorders. CARD15/NOD2, a member of the Ced4 superfamily which includes Apaf-1 and CARD4/NOD1, has recently been associated with genetic predisposition to CD but additional genetic Factors remain to be identified. Because CARD4/NOD1 shares many structural and functional similarities with CARD15, we tested its putative role in IBD. Patients and methods: The 11 exons of CARD4 were screened for the presence of variants in 63 unrelated IBD patients. The only non-private genetic variation encoding for a substitution in the peptidic chain was genotyped in 381 IBD families (235 CD, 58 UC, 81 mixed, and seven indeterminate colitis families) using a polymerase chain reaction-restriction fragment length polymorphism procedure. Genotyping data were analysed by the transmission disequilibrium test. Results: Five of nine sequence variations identified in the coding sequence of the gene encoded for non-conservative changes (E266K, D372N, R705Q, T787M, and T787K). Four were present in only one family. The remaining variant (E266K), which exhibited an allele frequency of 0.28, was not associated with CD, UC, or IBD. Furthermore, IBD patients carrying sequence variations in their CARD4 gene had a similar phenotype to those with a normal sequence. Conclusion: Our results suggest that CARD4 does not play a major role in genetic susceptibility to IBD.
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| 30. |
- Zouali, H, et al.
(author)
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Genetic refinement and physical mapping of a chromosome 16q candidate region for inflammatory bowel disease
- 2001
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In: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 9:10, s. 731-742
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Journal article (peer-reviewed)abstract
- Crohn's disease (CD) is a complex genetic disorder for which a susceptibility gene, IBD1, has been mapped within the pericentromeric region of chromosome 16. In order to refine the location of IBD1, 77 multiplex CD families were genotyped for 26 microsatellite markers evenly spaced by approximately 1 cM. Nonparametric linkage analyses exhibited a maximum NPL score of 3.49 (P=2.37 ╫ 10-4) in a region centred by markers D16S3136, D16S3117 and D16S770. Simulation studies showed that the probability for IBD1 to be located in a 5 cM region around these markers was 70%. A 2.5 Mb YAC and BAC contig map spanning this genetic region on chromosome band 16q12 was built. TDT analyses demonstrated suggestive association between the 207 bp allele of D16S3136 (P<0.05) and a new biallellic marker hb27g11f-end (P=0.01). These markers were located in the hb27g11 and hb87b10 BAC clones from the contig. Taken together, the present results provide a crucial preliminary step before an exhaustive linkage disequilibrium mapping of putatively transcribed regions to identify IBD1.
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| 31. |
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| 32. |
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| 33. |
- Almer, J, et al.
(author)
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Microstructure and thermal stability of arc-evaporated Cr-C-N coatings
- 2004
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In: Philosophical Magazine. - : Informa UK Limited. - 1478-6435 .- 1478-6443. ; 84:7, s. 611-630
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Journal article (peer-reviewed)abstract
- The role of C incorporation in the microstructure and thermal stability of arc-evaporated Cr-C-N coatings is explored via reactive growth in a mixed C2H4-N2 environment. C is found to react more readily than N at both the Cr cathode and the coating surfaces, so that a C2H4-to-N2 flow ratio of only 1% yields a C-to-N ratio of approximately 10% within the coatings. The as-deposited microstructures consist primarily of the δ-Cr(C, N) phase and possess high compressive residual stresses, which decrease with increasing C content. Post-deposition annealing up to 700°C results in depletion of lattice defects, and concomitant reductions in stress and coating hardness, together with phase transformations which suggest metastable phase formation during growth. Apparent activation energies for this lattice defect are found to be in the range expected for bulk diffusion of N and C (2.4-2.8 eV). The results suggest that inclusion of small amounts of C in this system offers the ability to reduce internal stresses while maintaining defect-related hardness increases, permitting growth of thicker and thus more wear-resistant coatings.
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| 34. |
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| 35. |
- Almer, J, et al.
(author)
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Microstructure, stress and mechanical properties of arc-evaporated Cr-C-N coatings
- 2001
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In: Thin Solid Films. - 0040-6090 .- 1879-2731. ; 385:1-2, s. 190-197
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Journal article (peer-reviewed)abstract
- The relationships between coating microstructure and properties in the Cr-C-N system have been investigated as a function of composition and post-deposition annealing. Coatings of varying compositions were grown using arc-evaporation, by varying the reactive gas flow ratio fR = f(C2H4)/f(N2) from 0 to 0.2, and were found to consist primarily of the cubic d-Cr(C,N) phase. Changes in both the unstressed lattice parameter, ao, and X-ray diffraction background intensity indicate that both the carbon concentration within the d-phase and amorphous/crystalline content increases with fR. Increasing fR also decreases the magnitude of the compressive biaxial residual stress, from approximately 6 to 1 GPa, while increasing both the inhomogeneous stress and thermal stability. The elastic modulus and hardness of as-deposited coatings were determined from nanoindentation to be 320 and 23 GPa, respectively, for moderate carbon concentrations (fR=0.05). Concurrent variations in microstructure and hardness with post-deposition annealing indicate that the as-deposited hardness is significantly enhanced by the microstructure, primarily by lattice defects and related stresses (microstresses) rather than average stresses (macrostresses).
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| 36. |
- Almer, J., et al.
(author)
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Strain and texture analysis of coatings using high-energy x-rays
- 2003
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In: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 94:1, s. 697-702
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Journal article (peer-reviewed)abstract
- We investigate the internal strain and crystallographic orientation (texture) in physical-vapor deposited metal nitride coatings of TiN and CrN. A high-energy diffraction technique is presented that uses synchrotron x rays and an area detector, and which allows the strain and intensity distributions of multiple crystallographic planes to be measured by a single x-ray exposure. Unique texture states and nonlinear sin2 strain distributions are observed for all coatings investigated. Quantitative analysis indicates that existing micromechanical models can reasonably predict strain and corresponding stress for mixed-hkl reflections but are inadequate for fully describing measured data. Alternative mechanisms involving deposition-induced defects are proposed
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| 37. |
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| 38. |
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| 39. |
- Almer, Sven, et al.
(author)
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Modern läkemedelsterapi vid crohn - Nationella riktlinjer
- 2009
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In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 106:45, s. 2988-2993
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Journal article (peer-reviewed)abstract
- Lättanvända begrepp och definitioner på sjukdomsaktivitet och behandlingseffekt bör få ökad spridning inom sjukvården.Majoriteten av patienter med Crohns sjukdom behöver långvarig läkemedelsbehandling, och ungefär hälften genomgår en eller flera operationer någon gång under sjukdomstiden.Det är viktigt att tidigt i sjukdomsförloppet identifiera riskfaktorer för utveckling av komplicerad och aggressiv sjukdom och behandla intensivt i dessa fall.En aktiv strategi med regelbundet övervägande av tillgängliga behandlingsalternativ medför att de flesta patienter med Crohns sjukdom behåller en god livskvalitet.
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| 40. |
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| 41. |
- Andersson, Peter, et al.
(author)
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Low symptomatic load in Crohn's disease with surgery and medicine as complementary treatments
- 1998
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In: Scandinavian Journal of Gastroenterology. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 33:4, s. 423-429
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Journal article (peer-reviewed)abstract
- Background: The treatment of Crohn's disease has changed owing to the recognition of its chronicity. Medical maintenance treatment and limited resections have evolved as major concepts of management, regarded as complementary, and both aim at reducing the symptoms.Methods: We investigated the symptomatic load in Crohn's disease as reflected in a cross-sectional study of the symptom index, physicians' assessment, and the patients' perception of health. A cohort of 212 patients from the primary catchment area and 125 referred patients were studied.Results: Of catchment area patients, 83% were receiving medication, and the annual rate of abdominal surgery was 5.7%. Corresponding figures for the referred patients were 82% and 10.3%. According to the symptom index, 87% of catchment area patients were in remission or had only mild symptoms; according to the physicians' assessment, 90% were. The patients' median perception of health was 90% of perfect health according to the visual analogue scale. The figures were similar for referred patients, except that referrals were considered more diseased by the physician.Conclusion: The great majority of patients with Crohn's disease are able to live in remission or experience only mild symptoms.
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| 42. |
- Beccuti, A. G., et al.
(author)
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Hybrid control techniques for switched-mode DC-DC converters part II : The step-up topology
- 2007
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In: 2007 American Control Conference, Vols 1-13. - 1424409888 - 9781424409884 ; , s. 5464-5471
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Conference paper (peer-reviewed)abstract
- Several recent techniques from hybrid and optimal control are evaluated on a power electronics benchmark problem. The benchmark involves a number of practically interesting operating scenarios for a fixed-frequency step-up dc-dc converter. The specifications are defined such that good performance can only be obtained if the switched and nonlinear nature of the problem is respected during the design phase.
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| 43. |
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| 44. |
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| 45. |
- de Boer, NKH, et al.
(author)
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6-thioguanine treatment in inflammatory bowel disease : A critical appraisal by a European 6-TG working party
- 2006
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In: Digestion. - : S. Karger AG. - 0012-2823 .- 1421-9867. ; 73:1, s. 25-31
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Journal article (peer-reviewed)abstract
- Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity. Copyright (c) 2006 S. Karger AG, Basel.
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| 46. |
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| 47. |
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| 48. |
- Haglund, Sofie, et al.
(author)
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Pyrosequencing of TPMT Alleles in a General Swedish Population and in Patients with Inflammatory Bowel Disease
- 2004
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In: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 50:2, s. 288-295
-
Journal article (peer-reviewed)abstract
- Background: Interindividual differences in therapeutic efficacy in patients treated with thiopurines might be explained by the presence of thiopurine S-methyltransferase (TPMT) alleles that encode for reduced TPMT enzymatic activity. It is therefore of value to know an individual's inherent capacity to express TPMT. Method: We developed a pyrosequencing method to detect 10 single-nucleotide polymorphisms (SNPs) in TPMT. A Swedish population (n = 800) was examined for TPMT*3A, TPMT*3B, TPMT*3C, and TPMT*2. Patients with inflammatory bowel disease (n = 24) and healthy volunteers (n = 6), selected on the basis of TPMT enzymatic activity, were investigated for all 10 SNPs to determine the relationship between TPMT genotype and phenotype. Results: In the general population we identified the following genotypes with nonfunctional alleles: TPMT*1/*3A (*3A allelic frequency, 3.75%), TPMT*1/*3C (*3C allelic frequency, 0.44%), TPMT*1/*3B (*3B allelic frequency, 0.13%), and TPMT*1/*2 (*2 allelic frequency, 0.06%). All nine individuals with normal enzymatic activity were wild-type TPMT*1/*1. Thirteen individuals with intermediate activity were either TPMT*1/*3A (n = 12) or TPMT*1/*2 (n = 1). Eight individuals with low enzymatic activity were TPMT*3A/*3A (n = 4), TPMT*3A/*3C (n = 2), or TPMT*1/*3A (n = 2). Conclusion: Next to wild type, the most frequent alleles in Sweden are TPMT*3A and TPMT*3C. A previously established phenotypic cutoff for distinguishing normal from intermediate metabolizers was confirmed. To identify the majority of cases (90%) with low or intermediate TPMT activity, it was sufficient to analyze individuals for only 3 of the 10 SNPs investigated. Nevertheless, this investigation indicates that other mutations might be of relevance for decreased enzymatic activity. © 2004 American Association for Clinical Chemistry.
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| 49. |
- Hlebowicz, Joanna, et al.
(author)
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Effects of 1 and 3 g cinnamon on gastric emptying, satiety, and postprandial blood glucose, insulin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and ghrelin concentrations in healthy subjects.
- 2009
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In: American Journal of Clinical Nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 89, s. 815-821
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Journal article (peer-reviewed)abstract
- BACKGROUND: A previous study of healthy subjects showed that intake of 6 g cinnamon with rice pudding reduced postprandial blood glucose and the gastric emptying rate (GER) without affecting satiety. OBJECTIVE: The objective was to study the effect of 1 and 3 g cinnamon on GER, postprandial blood glucose, plasma concentrations of insulin and incretin hormones [glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)], the ghrelin response, and satiety in healthy subjects. DESIGN: GER was measured by using real-time ultrasonography after ingestion of rice pudding with and without 1 or 3 g cinnamon. Fifteen healthy subjects were assessed in a crossover trial. RESULTS: The addition of 1 or 3 g cinnamon had no significant effect on GER, satiety, glucose, GIP, or the ghrelin response. The insulin response at 60 min and the area under the curve (AUC) at 120 min were significantly lower after ingestion of rice pudding with 3 g cinnamon (P = 0.05 and P = 0.036, respectively, after Bonferroni correction). The change in GLP-1 response (DeltaAUC) and the change in the maximum concentration (DeltaC(max)) were both significantly higher after ingestion of rice pudding with 3 g cinnamon (P = 0.0082 and P = 0.0138, respectively, after Bonferroni correction). CONCLUSIONS: Ingestion of 3 g cinnamon reduced postprandial serum insulin and increased GLP-1 concentrations without significantly affecting blood glucose, GIP, the ghrelin concentration, satiety, or GER in healthy subjects. The results indicate a relation between the amount of cinnamon consumed and the decrease in insulin concentration.
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| 50. |
- Knutsson, Axel, et al.
(author)
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Microstructure evolution during annealing of TiAlN-coatings : A combined in-situ SAXS and phase field study
- 2011
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Other publication (other academic/artistic)abstract
- This paper describes in detail the microstructure evolution of Ti0.33Al0.67N and Ti0.50Al0.50N coatings during isothermal annealing studied by in-situ small angle x-ray scattering (SAXS) in combination with phase field simulations. We show that the decomposition occurs in two stages consistent with spinodal decomposition. During the initial stage, the phase segregation proceeds with a constant size of AlN- and TiN-rich domains with a radius of ~0.7 nm for 5 and 20 min at 900 and 850 ◦C respectively in the Ti0.50Al0.50N alloy. The length of the initial stage depends on the temperature as well as the composition, and is shorter for the higher Al content coating. Following the initial stage, the AlN- and TiN-rich domains coarsen. The decomposition process is discussed in terms of Gibbs free energy, diffusion, and gradient energies. Scanning transmission electron microscopy and energy dispersive x-ray spectroscopy of the post annealed coatings confirm a decomposed microstructure with coherent domains rich in AlN and TiN of the same size as determined by SAXS.
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