| 1. |
- Beilmann-Lehtonen, Ines, et al.
(author)
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The Relationship between the Tissue Expression of TLR2, TLR4, TLR5, and TLR7 and Systemic Inflammatory Responses in Colorectal Cancer Patients
- 2021
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In: Oncology. - : S. Karger. - 0030-2414 .- 1423-0232. ; 99:12, s. 790-801
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Journal article (peer-reviewed)abstract
- Background: Colorectal cancer (CRC) is the third most commonly diagnosed malignancy globally. CRC patients with elevated plasma C-reactive protein (CRP) levels exhibit compromised prognoses. Toll-like receptors (TLRs), activating the innate and adaptive immune systems, may contribute to pro- and antitumorigenic inflammatory responses. We aimed to identify a possible link between local and systemic inflammatory responses in CRC patients by investigating the association between tissue TLRs and plasma CRP.Methods: Tissue expressions of TLR2, TLR4, TLR5, and TLR7 were assessed using immunohistochemistry of tissue microarray slides from 549 CRC patients surgically treated between 1998 and 2005. Blood samples were drawn preoperatively, centrifuged, aliquoted, and stored at −80°C until analysis. Plasma CRP was determined through high-sensitivity time-resolved immunofluorometric assay. We investigated the association of TLRs to clinicopathologic variables, plasma CRP, and survival.Results: High TLR2 expression (hazard ratio [HR] 0.59; 95% confidence interval [CI] 0.41–0.85; p = 0.005), high TLR5 expression (HR 0.60; 95% CI 0.45–0.83; p = 0.002), positive TLR7 expression (HR 0.49; 95% CI 0.33–0.72; p < 0.001), and low CRP (HR 1.48; 95% CI 1.08–2.11; p = 0.017) were associated with a better prognosis. A high TLR2 immunoexpression was associated with a better prognosis among low-CRP patients (HR 0.53; 95% CI 0.35–0.80; p = 0.002), high TLR4 expression among high-CRP patients (HR 2.04; 95% CI 1.04–4.00; p = 0.038), high TLR5 expression among low-CRP patients (HR 0.059; 95% CI 0.37–0.92; p = 0.021), and positive TLR7 expression among low-CRP patients (HR 0.53; 95% CI 0.28–1.00; p = 0.049). In multivariate analyses, no biomarkers emerged as significant independent variables.Conclusions: High tissue TLR2, TLR5, and TLR7 levels were associated with a better prognosis. Among low-CRP patients, those with high TLR2, TLR5, and TLR7 immunoexpressions exhibited a better prognosis. Among high CRP patients, a high TLR4 immunoexpression was associated with a better prognosis.
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| 2. |
- Karlgren, Maria, et al.
(author)
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Classification of Inhibitors of Hepatic Organic Anion Transporting Polypeptides (OATPs) : Influence of Protein Expression on Drug - Drug Interactions
- 2012
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:10, s. 4740-4763
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Journal article (peer-reviewed)abstract
- The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug-drug interactions. Predicting potential interactions with OATPs is, therefore, of value. Here, we developed in vitro and in silico models for identification and prediction of specific and general inhibitors of OATP1B1, OATP1B3, and OATP2B1, The maximal transport activity (MTA) of each OATP in human liver was predicted from transport kinetics and protein quantification. We then used MTA to predict the effects of a subset of inhibitors on atorvastatin uptake in vivo. Using a data set of 225 drug-like compounds, 91 OATP inhibitors were identified. In silico models indicated that lipophilicity and polar surface area are key molecular features of OATP inhibition. MTA predictions identified OATP1B1 and OATP1B3 as major determinants of atorvastatin uptake in vivo. The relative contributions to overall hepatic uptake varied with isoform specificities of the inhibitors.
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| 3. |
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| 4. |
- Bergknut, Magnus, et al.
(author)
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Identification of potentially toxic compounds in complex extracts of environmental samples using gas chromatography-mass spectrometry and multivariate data analysis
- 2007
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In: Environmental Toxicology and Chemistry. - New York : Pergamon. - 0730-7268 .- 1552-8618. ; 26:2, s. 208-217
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Journal article (peer-reviewed)abstract
- In this study, we examined 31 samples of varying chemical composition, including samples of soils from gasworks, coke production sites, and sites where wood preservatives were heavily used; ash and soot from municipal solid waste incinerators; antiskid sand; and dust from areas with heavy road traffic. The samples were comprehensively chemically characterized, especially their polycyclic aromatic compound contents, using gas chromatography-time-of-flight mass spectrometry, whereas their biological effects were assessed using dehydrogenase activity, root growth (Hordeum vulgare), reproduction of springtails (Folsomia candida), algal growth (Desmodesmus subspicatus), germinability (Sinapis alba), Vibrio fischeri, DR-CALUX, and Ames Salmonella assays. The number of compounds detected in the samples ranged from 123 to 527. Using the multivariate regression technique of partial-least-squares projections to latent structures, it was possible to find individual compounds that exhibited strong correlations with the different biological responses. Some of the results, however, indicate that a broader chemical characterization may be needed to identify all the compounds that may cause the measured biological responses.
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| 5. |
- Bergknut, Magnus, et al.
(author)
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Identification of potentially toxic compounds in complex extracts of environmental samples using GC-MS and multivariate data analysis
- 2007
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In: Environmental Toxicology and Chemistry. - 0730-7268 .- 1552-8618. ; 26:2, s. 208-17
-
Journal article (peer-reviewed)abstract
- In this study, we examined 31 samples of varying chemical composition, including samples of soils from gasworks, coke production sites, and sites where wood preservatives were heavily used; ash and soot from municipal solid waste incinerators; antiskid sand; and dust from areas with heavy road traffic. The samples were comprehensively chemically characterized, especially their polycyclic aromatic compound contents, using gas chromatography–time-of-flight mass spectrometry, whereas their biological effects were assessed using dehydrogenase activity, root growth (Hordeum vulgare), reproduction of springtails (Folsomia candida), algal growth (Desmodesmus subspicatus), germinability (Sinapis alba), Vibrio fischeri, DR-CALUX, and Ames Salmonella assays. The number of compounds detected in the samples ranged from 123 to 527. Using the multivariate regression technique of partial-least-squares projections to latent structures, it was possible to find individual compounds that exhibited strong correlations with the different biological responses. Some of the results, however, indicate that a broader chemical characterization may be needed to identify all the compounds that may cause the measured biological responses.
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| 6. |
- Bjerner, Tomas, et al.
(author)
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3D surface rendering of images from multiple MR pulse sequences in the pre-operative evaluation of hepatic lesions
- 1998
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In: Acta Radiologica. - 0284-1851 .- 1600-0455. ; 39:6, s. 698-700
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Journal article (peer-reviewed)abstract
- Segmentation and reconstruction took 1-2 h. To be able to combine the volumes from the different data sets, certain criteria had to be fulfilled: a) the field of view had to be constant; b) the same volume had to be scanned every time which meant that the slice thickness and the number of slices could be adjusted as long as the volume covered was the same; and c) the positioning of each volume had to be identical between every scan. The resulting 3D reconstruction gave the surgeon a clear appreciation of the different lesions and their relation to the different liver segments in the pre-operative planning of hepatic resections.
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| 7. |
- Edin, Sofia, et al.
(author)
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The Prognostic Importance of CD20+ B lymphocytes in Colorectal Cancer and the Relation to Other Immune Cell subsets
- 2019
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9:1
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Journal article (peer-reviewed)abstract
- The anti-tumour immune response is critical to patient prognosis in colorectal cancer (CRC). The aim of this study was to investigate infiltration of B lymphocytes into CRC tumours, and their clinical relevance, prognostic value and relation to other immune cell subsets. We used multiplexed immunohistochemistry and multispectral imaging to assay the amount of infiltrating CD20+ B lymphocytes along with infiltration of CD8+ cytotoxic T cells, FOXP3+ T regulatory cells, CD68+ macrophages and CD66b+ neutrophils, in 316 archival CRC tissue specimens. A higher density of infiltrating CD20+ B lymphocytes was associated with tumours of the right colon (P = 0.025) and of lower stages (P = 0.009). Furthermore, patients whose tumours were highly infiltrated by CD20+ B lymphocytes had a significantly improved disease-specific survival (HR = 0.45, 95% CI 0.28-0.73, P = 0.001), which remained significant in multivariable analysis. CD20+ B lymphocytes were highly and positively associated with CD8+ T lymphocytes (P < 0.001), and part of the prognostic role was found to be a cooperative effect between these lymphocyte subsets. Our results support a favourable prognostic value of tumour-infiltrating CD20+ B lymphocytes in CRC. Furthermore, a cooperative prognostic effect between CD20+ B lymphocytes and CD8+ T lymphocytes is suggested.
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| 8. |
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| 9. |
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| 10. |
- Esscher, Annika, 1968-, et al.
(author)
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Excess mortality in women of reproductive age from low-income countries : a Swedish national register study
- 2013
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In: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 23:2, s. 274-279
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Journal article (peer-reviewed)abstract
- Background: Cause-of-death statistics is widely used to monitor the health of a population. African immigrants have, in several European studies, shown to be at an increased risk of maternal death, but few studies have investigated cause-specific mortality rates in female immigrants. Methods: In this national study, based on the Swedish Cause of Death Register, we studied 27 957 women of reproductive age (aged 15-49 years) who died between 1988 and 2007. Age-standardized mortality rates per 100 000 person years and relative risks for death and underlying causes of death, grouped according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, were calculated and compared between women born in Sweden and in low-, middle- and high-income countries. Results: The total age-standardized mortality rate per 100 000 person years was significantly higher for women born in low-income (84.4) and high-income countries (83.7), but lower for women born in middle-income countries (57.5), as compared with Swedish-born women (68.1). The relative risk of dying from infectious disease was 15.0 (95% confidence interval 10.8-20.7) and diseases related to pregnancy was 6.6 (95% confidence interval 2.6-16.5) for women born in low-income countries, as compared to Swedish-born women. Conclusions: Women born in low-income countries are at the highest risk of dying during reproductive age in Sweden, with the largest discrepancy in mortality rates seen for infectious diseases and diseases related to pregnancy, a cause of death pattern similar to the one in their countries of birth. The World Bank classification of economies may be a useful tool in migration research.
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| 11. |
- Esscher, Annika, 1968-, et al.
(author)
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Maternal mortality in Sweden 1988-2007 : more deaths than officially reported
- 2013
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 92:1, s. 40-46
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To obtain more accurate calculations of maternal and pregnancy-related mortality ratios in Sweden from 1988 to 2007 by using information from national registers and death certificates.DESIGN: A national register-based study, supplemented by a review of death certificates.SETTING:Sweden, 1988 to 2007.POPULATION: The deaths of 27 957 women of reproductive age (15 to 49 years).METHODS:The Swedish Cause of Death Register, Medical Birth Register, and National Patient Register were linked. All women with a diagnosis related to pregnancy in at least one of these registers within one year prior to death were identified. Death certificates were reviewed to ascertain maternal deaths. Maternal mortality ratio, the number of maternal deaths/100 000 live births (excluding and including suicides); and pregnancy-related mortality ratio (number of deaths within 42 days after termination of pregnancy, irrespective of cause of death/100 000 live births) were calculated.MAIN OUTCOME MEASURES:Direct and indirect maternal deaths and pregnancy-related deaths.RESULTS: The maternal mortality ratio in Sweden, based on the current method of identifying maternal deaths, was 3.6. After linking registers and reviewing death certificates, we identified 64% more maternal deaths, resulting in a ratio of 6.0 (or 6.5 if suicides are included). The pregnancy-related mortality ratio was 7.3. A total of 478 women died within a year after being recorded with a diagnosis related to pregnancy.CONCLUSIONS: By including the 123 cases of maternal death identified in this study, the mean maternal mortality ratio from 1988-2007 was 64% higher than reported to the World Health Organization.
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| 12. |
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| 13. |
- Frühling, Petter, et al.
(author)
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Single-center nonrandomized clinical trial to assess the safety and efficacy of irreversible electroporation (IRE) ablation of liver tumors in humans : Short to mid-term results
- 2017
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In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 43:4, s. 751-757
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Journal article (peer-reviewed)abstract
- Introduction: A single-center nonrandomized clinical trial was performed to assess the safety and efficacy of IRE ablation of liver tumors in humans.Methods: 38 malignant liver tumors on 30 patients were treated with IRE between September 2011 and September 2014. Treatment was with curative intent, and the diagnoses were colorectal cancer with liver metastases (CRLM) (n = 23), hepatocellular carcinoma (HCC) (n = 8) and other metastasis (n = 7). Patients were selected when surgery, radiofrequency ablation (RFA) or microwave ablation (MWA) was not an option, and when they met inclusion criteria (tumor size < 3 cm, 1-2 tumors). Patients were followed-up at 1 and 6 months with a contrast-enhanced computed tomography (CE-CT), and contrast-enhanced ultrasound (CE-US) at 3 months.Results: Ablation success was defined as no evidence of residual tumor in the ablated area as confirmed by CE-CT and CE-US. At 3 months ablation success was 78.9%, and 65.8% at 6 months. There was no statistically significant difference between tumor volume (<5 cm(3) vs >5 cm(3), p = 0.518), and between diagnosis (CRLM vs HCC, p = 0.084) in terms of local recurrence. Complications were classified according to the standardized grading system of Society of Interventional Radiology (SIR). A minor complication occurred in six palients (20%), one patient (3.3%) suffered from a major complication (bile duct dilatation and stricture of the portal vein and bile duct). No mortalities occurred at 30 days.Conclusions: IRE appears to be a safe treatment modality for a selected group of patients with liver tumors and offers high local tumor control at 3 and 6 months.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Gkekas, Ioannis, 1981-, et al.
(author)
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Colon cancer patients with mismatch repair deficiency are more likely to present as acute surgical cases
- 2021
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In: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 157, s. 1-9
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Journal article (peer-reviewed)abstract
- Background: The effect of the genetic imprint on the emergency presentation of colon cancer remains unclear. The disparity between tumours evolving along different carcinogenetic pathways has not been studied systematically. This retrospective multicenter cohort study evaluates the association between mismatch repair status and the risk for acute surgery of colon cancer.Patients and methods: A retrospective multicenter cohort study including in total 870 patients from three different countries. Scandinavian cohort (Finland and Sweden), including a total of 412 patients operated between January 1, 1995 and December 31, 2010, was validated against a cohort from the Czech Republic, including a total of 458 patients, operated between January 1, 2018 and December 31, 2019. The proficiency or deficiency of mismatch repair was determined by immunohistochemistry. Primary outcome was the risk for acute colon cancer surgery given as the Odds Ratio (OR) in the univariable and multivariable analyses. Acute colon cancer surgery was defined as surgery performed during the same hospital admission as when the diagnosis of colon cancer was made.Results: Of the 870 patients (399 females [46%]) included in the analyses, median age at surgery was 69 [interquartile range, 61–76] years, deficient Mismatch Repair (dMMR) status was found in 190 patients (22%), and 179 patients (21%) underwent acute surgery during the same hospital admission as when the diagnosis of colon cancer was made. In the Scandinavian cohort, a significant association between dMMR status and acute surgery was seen in both the univariable (OR 1.82, 95% CI 1.11–3.02, P = 0.017) and the multivariable (OR = 2.21, 95% CI 1.28–3.95, P = 0.005) analyses. This was confirmed in the Czech validation cohort in both the univariable (OR = 1.94, 95% CI 1.09–3.26, P = 0.022) and the multivariable (OR = 1.77, 95% CI 1.15–3.18, P = 0.021) analyses.Conclusion: This multicenter study reveals a strong association between acute colon cancer surgery and dMMR tumour status.
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| 18. |
- Gkekas, Ioannis, 1981-, et al.
(author)
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Sporadic deficient mismatch repair in colorectal cancer increases the risk for non-colorectal malignancy : a European multicenter cohort study
- 2024
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In: Journal of Surgical Oncology. - : John Wiley & Sons. - 0022-4790 .- 1096-9098. ; 129:7, s. 1295-1304
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Journal article (peer-reviewed)abstract
- Background and Objectives: Disparities between tumors arising via different sporadic carcinogenetic pathways have not been studied systematically. This retrospective multicenter cohort study evaluated the differences in the risk for non-colorectal malignancy between sporadic colorectal cancer (CRC) patients from different DNA mismatch repair status.Methods: A retrospective European multicenter cohort study including in total of 1706 CRC patients treated between 1996 and 2019 in three different countries. The proficiency (pMMR) or deficiency (dMMR) of mismatch repair was determined by immunohistochemistry. Cases were analyzed for tumor BRAFV600E mutation, and BRAF mutated tumors were further analyzed for hypermethylation status in the promoter region of MLH1 to distinguish between sporadic and hereditary cases. Swedish and Finish patients were matched with their respective National Cancer Registries. For the Czech cohort, thorough scrutiny of medical files was performed to identify any non-colorectal malignancy within 20 years before or after the diagnosis of CRC. Poisson regression analysis was performed to identify the incidence rates of non-colorectal malignancies. For validation purposes, standardized incidence ratios were calculated for the Swedish cases adjusted for age, year, and sex.Results: Of the 1706 CRC patients included in the analysis, 819 were female [48%], median age at surgery was 67 years [interquartile range: 60–75], and sporadic dMMR was found in 188 patients (11%). Patients with sporadic dMMR CRC had a higher incidence rate ratio (IRR) for non-colorectal malignancy before and after diagnosis compared to patients with a pMMR tumor, in both uni- (IRR = 2.49, 95% confidence interval [CI] = 1.89–3.31, p = 0.003) and multivariable analysis (IRR = 2.24, 95% CI = 1.67–3.01, p = 0.004). This association applied whether or not the non-colorectal tumor developed before or after the diagnosis of CRC in both uni- (IRR = 1.91, 95% CI = 1.28–2.98, p = 0.004), (IRR = 2.45, 95% CI = 1.72–3.49, p = 0.004) and multivariable analysis (IRR = 1.67,95% CI = 1.05–2.65, p = 0.029), (IRR = 2.35, 95% CI = 1.63–3.42, p = 0.005), respectively.Conclusion: In this retrospective European multicenter cohort study, patients with sporadic dMMR CRC had a higher risk for non-colorectal malignancy than those with pMMR CRC. These findings indicate the need for further studies to establish the need for and design of surveillance strategies for patients with dMMR CRC.
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| 19. |
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| 20. |
- Gunnarsson, Ulf, et al.
(author)
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Association between local immune cell infiltration, mismatch repair status and systemic inflammatory response in colorectal cancer
- 2020
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In: Journal of Translational Medicine. - : BioMed Central. - 1479-5876. ; 18
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Journal article (peer-reviewed)abstract
- BACKGROUND: Systemic inflammatory response in colorectal cancer (CRC) has been established as a prognostic factor for impaired cancer-specific survival, predominantly in patients with right-sided tumors. On the other hand, defective mismatch repair (dMMR) tumors, primarily located in the right colon, are known to have favorable survival and dense local immune infiltration. The aim of this study was to see if there is any form of relationship between these seemingly diverse entities.METHODS: Complete clinical and long-term survival data were retrieved for 316 CRC patients operated at Helsinki University Hospital between the years 1998 and 2003. Tissue microarrays were prepared from surgical specimens and further processed and analyzed for local immune cell infiltration using multispectral imaging with a Vectra quantitative pathology imaging system and Inform software. Multiplex immunohistochemistry was applied using antibodies against CD66b, CD8, CD20, FoxP3, CD68 and pan-Cytokeratin. After exclusions, data on immune infiltration were available for 275 patients. Mismatch repair status was determined by immunohistochemistry.RESULTS: CRP was seen to be an independent predictor of cancer-specific survival but not overall survival in uni- and multivariable (HR 1.01 (1.00-1.02); p = 0.028) analyses of non-irradiated patients. There was no significant difference in CRP according to mismatch repair status, but all cases (n = 10) with CRP ≥ 75 mg/l had proficient mismatch repair (pMMR). There was a significant negative correlation between intratumor stromal infiltration by T-regulatory FOXP3+ cells and CRP (p = 0.006). There was significantly lower intratumor stromal infiltration by FOXP3+ cells (p = 0.043) in the right colon compared to the rectum, but no significant difference in CRP (p = 0.44). CRP was not a predictor of overall survival (HR 0.99, 95% CI 0.98-1.01) nor cancer-specific survival in irradiated patients (HR 0.94, 95% CI 0.94-1.02).CONCLUSIONS: There was a significant negative relationship between SIR, defined as an elevated CRP, and intratumor stromal infiltration by T-regulatory FOXP3+ cells. This and the fact that all cases with a CRP > 75 mg/l had pMMR suggests that SIR and dMMR are independent entities in CRC. Indeed, the general lack of difference in CRP between cases with dMMR and pMMR may be evidence of overlap in cases with a less pronounced SIR.
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| 21. |
- Gustafson, Elisabet K., et al.
(author)
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The Instant Blood-Mediated Inflammatory Reaction Characterized in Hepatocyte Transplantation
- 2011
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In: Transplantation. - 0041-1337 .- 1534-6080. ; 91:6, s. 632-638
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Journal article (peer-reviewed)abstract
- Background. Hepatocyte transplantation (HcTx) has proven to be a safe procedure, although the functional results have been unsatisfactory, probably due to insufficient engraftment or a loss of transplanted mass or function. In this study, we investigate whether hepatocytes in contact with blood induce an inflammatory reaction leading to, similar to what happens in clinical islet transplantation, an instant blood-mediated inflammatory reaction (IBMIR) resulting in an early loss of transplanted cells. Methods. By using an experimental model that mimics the portal vein blood flow, we could study different parameters reflecting the effects on the innate immunity elicited by hepatocytes in contact with ABO-matched human blood. Results. We report that all aspects of the IBMIR such as platelet and granulocyte consumption, coagulation, and complement activation were demonstrated. Addition of various specific inhibitors of coagulation allowed us to clearly delineate the various stages of the hepatocyte-triggered IBMIR and show that the reaction was triggered by tissue factor. Analysis of a case of clinical HcTx showed that hepatocyte-induced IBMIR also occurs in vivo. Both the inflammatory and the coagulation aspects were controlled by low-molecular-weight dextran sulfate. Conclusion. Isolated hepatocytes in contact with blood induce the IBMIR in vitro, and there are indications that these events are also relevant in vivo. According to these findings, HcTx would benefit from controlling a wider range of signals from the innate immune system.
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| 22. |
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| 23. |
- Haglund, Marie, et al.
(author)
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Kontrastnefropati efter datortomografi. Hydrering och anpassad kontrastmedelsdos ger bästa profylax
- 2005
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In: Läkartidningen. - 0023-7205. ; 102:40, s. 2864-2870
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Journal article (peer-reviewed)abstract
- Nefrotoxicitet efter kontrastmedelstillförsel, räknat som en 25-procentig stegring av kreatinin i plasma, förekom hos 12 procent i en oselekterad grupp patienter som genomgått datortomografi. Generell arterioskleros kan läggas till övriga kända riskfaktorer för utveckling av kontrastmedelsnefrotoxicitet. Uppskattning av njurfunktion, t ex med hjälp av lämplig formel, bör göras före kontrastmedelstillförsel, särskilt hos patienter över 70 års ålder. För att minimera risken för njurpåverkan bör kontrastmedelsdosen uttryckt i gram jod understiga det numeriska värdet av den glomerulära filtrationshastigheten (GFR) uttryckt i ml/min.
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| 24. |
- Haglund, Sofie, et al.
(author)
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The Role of Inosine-5'-Monophosphate Dehydrogenase in Thiopurine Metabolism in Patients With Inflammatory Bowel Disease.
- 2011
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In: Therapeutic Drug Monitoring. - : Lippincott Williams & Wilkins. - 0163-4356 .- 1536-3694. ; 33:2, s. 200-208
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Journal article (peer-reviewed)abstract
- BACKGROUND:: There is a large interindividual variability in thiopurine metabolism. High concentrations of methylthioinosine-5'-monophosphate (meTIMP) and low concentrations of 6-thioguanine nucleotides (6-TGNs) have been associated with a lower response rate and an increased risk of adverse events. In this study, the role of inosine-5'-monophosphate dehydrogenase (IMPDH) for differences in metabolite patterns of thiopurines was investigated. METHODS:: IMPDH activity and thiopurine metabolite concentrations were determined in patients with inflammatory bowel disease and a normal thiopurine methyltransferase (TPMT) phenotype and meTIMP/6-TGN concentration ratio > 20 (n = 26), in patients with a metabolite ratio ≤20 (n = 21), in a subgroup with a metabolite ratio <4 (n = 6), and in 10 patients with reduced TPMT activity. In vitro studies were conducted on human embryonic kidney cells (HEK293) with genetically engineered IMPDH and TPMT activities. RESULTS:: Patients with metabolite ratios >20 had lower IMPDH activity than those with ratios ≤20 (P < 0.001). Metabolic ratios >20 were only observed in patients with normal TPMT activity. Downregulation of IMPDH activity in HEK293 cells was associated with an increase in the concentration of meTIMP (fold change: 17 up to 93, P < 0.001) but, unexpectedly, also of 6-thioguanosine monophosphate (fold change: 2.6 up to 5.0, P < 0.001). CONCLUSIONS:: These data question the general view of IMPDH as the rate-limiting enzyme in the phosphorylation of thiopurines. Investigations of other mechanisms are needed to more fully explain the various metabolite patterns and outcomes in patients under treatment.
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| 25. |
- Haglund, Ulf, et al.
(author)
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Acute Cholecystitis
- 2001
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In: In: M Schein, L Wise (Eds), Controversis in Surgery. - : Springer Verlag, Berlin. ; , s. 109-
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Book chapter (other academic/artistic)abstract
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| 26. |
- Haglund, Ulf, et al.
(author)
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Appendix
- 2017. - 9
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In: Kirurgi. - : Liber. - 9789147112982 ; , s. 283-287
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Book chapter (peer-reviewed)
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| 27. |
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| 28. |
- Haglund, Ulf
(author)
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Evidens om hallux valgus
- 2001
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In: Läkartidningen. ; 98, s. 1364-
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Journal article (other academic/artistic)
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| 29. |
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| 30. |
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| 31. |
- Haglund, Ulf H., et al.
(author)
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Right hemihepatectomy
- 2008
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In: Journal of Gastrointestinal Surgery. - : Springer Science and Business Media LLC. - 1091-255X .- 1873-4626. ; 12:7, s. 1283-1287
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Journal article (peer-reviewed)abstract
- A right hemihepatectomy is frequently required for surgical removal of colorectal liver metastases. Today, this procedure can be performed quite safely provided the remaining liver is free from significant disease including steatohepatitis due to prolonged cytostatic treatment. Standard surgical techniques for liver resection are described in surgical textbooks. However, each center has developed its own modifications of important details. In this paper, we describe our technique to resect the right liver lobe using conventional surgical techniques as well as a vascular stapler and an ultrasonic dissector. This technique has proven to be quite safe, and blood loss is most often not significant despite we do not routinely apply the Pringle's manoeuvre during the division of the liver parenchyma.
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| 32. |
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| 33. |
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| 34. |
- Haglund, Ulf, et al.
(author)
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Invited commentary
- 1996
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In: World J Surg. ; 7
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Book chapter (other academic/artistic)
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| 35. |
- Haglund, Ulf, et al.
(author)
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Local consequences of reperfusion in the gut
- 1998
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In: Ischaemia-Reperfusion Injury, Eds: Pierce A Grace, Robert T Mathie. - : Blackwell Science Ltd, London. ; , s. 65-
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Book chapter (other academic/artistic)
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| 36. |
- Haglund, Ulf, et al.
(author)
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Mesenteric ischaemia
- 2002
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In: In: Critical Care Focus. The Gut. Ed: H F Galley.. - : BMJ Books. ; , s. 42-
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Book chapter (other academic/artistic)
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| 37. |
- Haglund, Ulf
(author)
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Reumatic Diseases - Surgical Treatment
- 1999
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In: Scandinavian Journal of Rheumatology, Suppl 110. - : Scandinavian University Press. ; 28
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Other publication (other academic/artistic)
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| 38. |
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| 39. |
- Haglund, Ulf
(author)
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Segmental liver resection
- 2001
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In: In: Liver Surgery. Operative techniques and avoidance of complications. Eds F Köckerling, SI Schwartz.. - : J A Barth Verlag. ; , s. 145-
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Book chapter (other academic/artistic)
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| 40. |
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| 41. |
- Haglund, Ulf, et al.
(author)
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Tunntarmen
- 2017. - 9
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In: Kir. - : Liber. - 9789147112982 ; , s. 273-282
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Book chapter (peer-reviewed)
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| 42. |
- Hamberger, Bertil, et al.
(author)
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Kirurgi
- 2002
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Book (other academic/artistic)
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| 43. |
- Holmberg, Linnéa, 1983-
(author)
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Konsten att producera lärande demokrater
- 2018
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Doctoral thesis (other academic/artistic)abstract
- This dissertation builds on the basic question of how individuals are formed and created as citizens in society today, and how individuals construct themselves as citizens in this society. It takes interest in how they are managed to govern themselves through specific constructions of citizenship, and looks at how the exercise of power establishes certain knowledge that affects their view of themselves and generates truths about how they are expected to live their lives. Simultaneously, the dissertation deals with the concept of freedom: what does it mean in contemporary society, how can one be free today, and what dangers might this liberty involve?In a broad sense, the analysis centres on the relationship between education and society; more specifically, it engages with the Swedish education system and its construction and production of desirable citizen subjects. The concrete example deals with the institution called leisure-time centre, with a purpose to investigate and problematise how institutionalised leisure-time is staged and legitimised in Sweden today. The studies take as a common starting point the following research question: how are children and personnel governed discursively in and through leisure-time centres?The first empirical contribution provides historical context for the study. In this, the `problematic leisure-time´ of today is outlined based on education policy documents relevant for children aged 6–13 years. These texts are discussed together with similar texts gathered from two other periods in history in order to give perspective on aspects of the leisure-time centre that may seem obvious in our own time.The first separate article investigates how talk about activities in leisure-time centres is couched in terms of meaningfulness and consists of an analysis of the ideological tension between democracy and authority, which the governmental authority, the Swedish Schools Inspectorate (Skolinspektionen), must address in its discursive work. The second article explores how the production of systematic reporting and documentation by personnel in leisure-time centres works through specific self-technologies in the form of confessional practices and which can be said to be primarily about constructing a free but loyal collective subject.The third article problematises the use of democracy as a method to produce specific citizen subjects in leisure-time centres. Children’s councils are analysed, focusing on how different nuances of influence are staged discursively by participating children and personnel. The article highlights how democracy – through pastoral care and in the name of children’s influence – becomes a governmentalising technology that produces an active, responsible and learning citizen.In summary, this dissertation highlights how leisure-time centres are staged and legitimised in Sweden today. The analysis shows how an administration of children and control of the development of society through the autonomous, competent, and voluntarily active individual is apparent; power operates through a perceived freedom in a way that makes the free choice the `right´ choice. With political ideas about forming a forward-looking mentality, children – and personnel – are constructed as a project of learning and improvement.
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| 44. |
- Hultman, Bo, et al.
(author)
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Phase II study of patients with peritoneal carcinomatosis from gastric cancer treated with preoperative systemic chemotherapy followed by peritonectomy and intraperitoneal chemotherapy
- 2013
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 52:4, s. 824-830
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Journal article (peer-reviewed)abstract
- BackgroundThe aim was to evaluate the feasibility and the effectiveness of neoadjuvant systemic chemotherapy followed by cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) in patients with peritoneal carcinomatosis (PC) from gastric cancer.Material and methodsEighteen patients (median age 57 years, range 38-74) were scheduled for three months' neoadjuvant systemic chemotherapy followed by CRS + HIPEC + EPIC.ResultsAt the time of surgery, the peritoneal tumor burden was extensive with tumor growth on the entire peritoneal cavity. Only eight patients received the entire treatment and OS was 14.3 months (range 6.1-34.3, 95% CI 6.6-20.3). Six patients had macroscopically radical (CC0) surgery and for this subgroup OS was 19.1 months (range 6.1-34.3, 95% CI 6.9-27.1). Postoperative 90-day mortality was 10% (one patient) and the perioperative grades II-IV adverse events (AE) rate was 62.5%.DiscussionNeoadjuvant chemotherapy followed by CRS + HIPEC + EPIC does not seem to be associated with prolonged OS in patients with extensive PC growth from gastric cancer unless macroscopically radical surgery is achieved. However, morbidity from this treatment is considerable and it cannot be recommended for routine care until a prospective randomized trial has been performed.
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| 45. |
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| 46. |
- Ihse, Ingemar, et al.
(author)
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Riktlinjer för handläggning av patienter med pankreascancer
- 2002
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In: Läkartidningen. - 0023-7205. ; 99:15, s. 1676-1683
-
Journal article (peer-reviewed)abstract
- The incidence of pancreatic cancer has fallen during the last ten years in Sweden. Early signs and symptoms of the disease are still undiscovered and when diagnosis is made the disease is incurable in most patients. Transabdominal ultrasonography is the first-line imaging test followed by spiral computed tomography (CT) and magnetic resonance imaging (MRI) if required for definite diagnosis. Spiral CT is also the imaging test of choice for assessment of resectability of the tumor. Surgical removal of the tumor is the only chance of cure. Markedly improved hospital mortality after pancreaticoduodenectomy is reported and an association between hospital volume and outcome of the operation has been established. Longterm survival after attempted curative resection continues to be dismal, however. Adjuvant treatment should not be given outside clinical studies. Palliative treatment has improved thanks to progress in the field of endoscopy, interventional radiology and in management of pain and nutrition. Palliative chemotherapy should only be given selectively outside clinical studies. Radiotherapy has no proven effects on survival. Special pancreatic cancer treatment teams with catchment areas of 2-4 million inhabitants are recommended by international authorities.
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| 47. |
- Ihse, Ingemar, et al.
(author)
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Riktlinjer för handläggning av patienter med pankreascancer [Guidelines for management of patients with pancreatic cancer]
- 2002
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In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 99:15, s. 1676-1685
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Journal article (other academic/artistic)abstract
- Transabdominellt ultraljud är förstahandsundersökning vid misstänkt pankreascancer, följt av spiral-DT eller MR för mer definitiv diagnos. Tumörmarkörer har ingen plats i rutindiagnostiken. Spiral-DT är basen i resektabilitetsbedömningen. Resektion av tumören är en förutsättning för bot. Ett samband har påvisats mellan antalet resektioner som görs vid ett sjukhus årligen och postoperativ mortalitet. Långtidsöverlevnaden efter resektion är oförändrat kort medan postoperativ mortalitet minskat dramatiskt vid enheter som rapporterat sina resultat. Adjuvant behandling efter resektion bör endast ges inom ramen för kliniska studier. Det palliativa omhändertagandet har förbättrats främst genom utveckling inom endoskopi, interventionell radiologi, smärt- och nutritionsbehandling. Palliativ cytostatikabehandling bör endast ges selektivt utanför kliniska studier. Radioterapi har ingen dokumenterad effekt på överlevnaden vid icke-resektabel pankreascancer. Internationellt rekommenderas speciella behandlingsteam för pankreascancer med tillräckliga upptagningsområden (2–4 miljoner invånare).
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| 48. |
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| 49. |
- Järnberg, Ulf, et al.
(author)
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Screening av klorparaffiner i den Svenska miljön
- 2005
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Reports (other academic/artistic)abstract
- Klorparaffiner, och i synnerhet kortkedjiga (SCCP) klorparaffiner är ämnen som klassificerats som prioriterade miljögifter på grund av stor produktionsvolym, toxiska egenskaper och persistens i miljön. Mycket höga halter har uppmätts tidigare i miljöprover i närhet av produktionsanläggningar men även i urban miljö. Naturvårdsverket beslutade därför att låta genomföra en screeningstudie på olika svenska miljöprover 2003-2004.Denna undersökning har genomförts dels genom en litteratursammanställning av uppgifter om användning i Sverige som erhållits från Kemikalieinspektionen, importörer och användare och dels som genom analys av miljöprover.I fältstudien har ingått:Beskrivning av spridning från en punktkälla: Spridning till luft och vattenmiljö; Tallbar, slam, sediment, fiskmuskel.Luftspridning, tidsvariation: urban luft (Rosenlundsgatan, Stockholm) och urban regional bakgrundsluft (Aspvreten, Nyköping). Från båda stationerna samlas regelbundet andra data på luftföroreningar, vind, temp, fukt, partikelhalt, trajektorier mm.Geografisk fördelning i biota: Fisk från stationer i miljöövervakningsprogrammet kust, insjö, hav.Spridning från reningsverk: Slam från Stockholms större reningsverk.
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| 50. |
- Karlson, Britt-Marie, et al.
(author)
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Intraarterial chemoembolisation with lipiodol and epirubicin in hepatocellular cancer : improved survival in some patients?
- 1999
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In: Annales Chirurgiae et Gynaecologiae. - 0355-9521. ; 88:4, s. 264-268
-
Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: Arterial chemoembolisation with lipiodol and a cytotoxic drug is reported to give equivocal results in irresectable primary hepatocellular cancer (HCC). In order to further elucidate the possible response to this treatment, we analysed the results of all patients with irresectable HCC treated with chemoembolisation at our hospital. MATERIAL AND METHODS: 58 consecutive patients with HCC were treated with lipiodolepirubicin chemoembolisation between February 1988 - October 1994 and followed until death or October 1998. RESULTS: The average survival was 11.7 months and median survival was 6 months. 17 patients had only one treatment mostly due to death within 6 weeks after the first treatment. Patients with an open portal system at inclusion (50% of all) were found to have significantly increased survival after 6 and 12 months compared to those with portal obstruction. The subgroup of patients displaying a decrease in tumour size as judged by repeated CT scan 6 months after inclusion had significantly increased survival; all survived more than 12 months (median survival 30 months). CONCLUSIONS: Chemoembolisation with lipiodol-epirubicin may have an impact on survival on selected patients with irresectable hepatocellular cancer. The treatment may justifiably be offered patients with an open portal venous system and without liver failure.
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