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Svendborg, Denmark
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Vilming Elgaaen B.,University of Oslo | Olstad O.K.,OUH | Haug K.B.F.,OUH | Brusletto B.,OUH | And 6 more authors.
BMC Cancer | Year: 2014

Background: Improved insight into the molecular characteristics of the different ovarian cancer subgroups is needed for developing a more individualized and optimized treatment regimen. The aim of this study was to a) identify differentially expressed miRNAs in high-grade serous ovarian carcinoma (HGSC), clear cell ovarian carcinoma (CCC) and ovarian surface epithelium (OSE), b) evaluate selected miRNAs for association with clinical parameters including survival and c) map miRNA-mRNA interactions.Methods: Differences in miRNA expression between HGSC, CCC and OSE were analyzed by global miRNA expression profiling (Affymetrix GeneChip miRNA 2.0 Arrays, n = 12, 9 and 9, respectively), validated by RT-qPCR (n = 35, 19 and 9, respectively), and evaluated for associations with clinical parameters. For HGSC, differentially expressed miRNAs were linked to differentially expressed mRNAs identified previously.Results: Differentially expressed miRNAs (n = 78) between HGSC, CCC and OSE were identified (FDR < 0.01%), of which 18 were validated (p < 0.01) using RT-qPCR in an extended cohort. Compared with OSE, miR-205-5p was the most overexpressed miRNA in HGSC. miR-200 family members and miR-182-5p were the most overexpressed in HGSC and CCC compared with OSE, whereas miR-383 was the most underexpressed. miR-205-5p and miR-200 members target epithelial-mesenchymal transition (EMT) regulators, apparently being important in tumor progression. miR-509-3-5p, miR-509-5p, miR-509-3p and miR-510 were among the strongest differentiators between HGSC and CCC, all being significantly overexpressed in CCC compared with HGSC. High miR-200c-3p expression was associated with poor progression-free (p = 0.031) and overall (p = 0.026) survival in HGSC patients. Interacting miRNA and mRNA targets, including those of a TP53-related pathway presented previously, were identified in HGSC.Conclusions: Several miRNAs differentially expressed between HGSC, CCC and OSE have been identified, suggesting a carcinogenetic role for these miRNAs. miR-200 family members, targeting EMT drivers, were mostly overexpressed in both subgroups, among which miR-200c-3p was associated with survival in HGSC patients. A set of miRNAs differentiates CCC from HGSC, of which miR-509-3-5p and miR-509-5p are the strongest classifiers. Several interactions between miRNAs and mRNAs in HGSC were mapped. © 2014 Vilming Elgaaen et al.; licensee BioMed Central Ltd.


Dobloug G.C.,University of Oslo | Antal E.A.,OUH | Sveberg L.,OUH | Garen T.,University of Oslo | And 5 more authors.
European Journal of Neurology | Year: 2015

Background and purpose: Knowledge about the occurrence of sporadic inclusion body myositis (sIBM) in the general population is limited. Here, our aim was to identify and characterize every sIBM patient living in southeast Norway (population 2.64 million) from 2003 to 2012. Method: Two sIBM case finding strategies were applied. First, all hospital databases in southeast Norway were screened to identify cases with sIBM-compatible International Classification of Diseases 10 (ICD-10) codes. These cases were then manually chart reviewed. Secondly, all muscle histology reports encoded with inflammation were independently reviewed. Finally, cases were classified according to the 1997 and the 2011 European Neuro-Muscular Centre (ENMC) Research Diagnostic Criteria for sIBM. Results: The combined case finding strategy identified 3160 patients with sIBM compatible ICD-10 codes, and a largely overlapping cohort of 500 patients having muscle biopsies encoded with inflammation. Detailed retrospective review of chart and histology data showed that 95 patients met the 2011 ENMC sIBM criteria and 92 met the 1997 criteria. Estimated point prevalence of sIBM was 33/1 000 000, equal with both criteria sets. Mean age at diagnosis was 66.9 years and mean diagnostic delay was 5.6 years. Chart review revealed higher frequencies of dysphagia (94% vs. 65%) and anti-Sjøgren syndrome A antibodies (39% vs. 12%) in female sIBM patients (n = 40) than in males. Coexisting rheumatic diseases were present in 25% of sIBM cases, with Sjøgren's syndrome in 10%. Conclusion: An estimated point prevalence of sIBM seven times higher than previously observed in Europe is reported. Our data show considerable diagnostic delay, a major challenge with new sIBM treatments in the pipeline. © 2014 EAN.


Kleppa E.,University of Oslo | Ramsuran V.,University of KwaZulu - Natal | Karlsen G.H.,University of Aarhus | Bere A.,Emory University | And 9 more authors.
PLoS ONE | Year: 2014

Background: Schistosoma haematobium is a waterborne parasite that may cause female genital schistosomiasis (FGS), characterized by genital mucosal lesions. There is clinical and epidemiological evidence for a relationship between FGS and HIV. We investigated the impact of FGS on HIV target cell density and expression of the HIV co-receptor CCR5 in blood and cervical cytobrush samples. Furthermore we evaluated the effect of anti-schistosomal treatment on these cell populations. Design: The study followed a case-control design with post treatment follow-up, nested in an on-going field study on FGS. Methods: Blood and cervical cytobrush samples were collected from FGS negative and positive women for flow cytometry analyses. Urine samples were investigated for schistosome ova by microscopy and polymerase chain reaction (PCR). Results: FGS was associated with a higher frequency of CD14+ cells (monocytes) in blood (11.5% in FGS+ vs. 2.2% in FGS-, p = 0.042). Frequencies of CD4 + cells expressing CCR5 were higher in blood samples from FGS+ than from FGS- women (4.7% vs. 1.5%, p = 0.018). The CD14+ cell population decreased significantly in both compartments after anti-schistosomal treatment (p = 0.043). Although the frequency of CD4+ cells did not change after treatment, frequencies of CCR5 expression by CD4+ cells decreased significantly in both compartments (from 3.4% to 0.5% in blood, p = 0.036; and from 42.4% to 5.6% in genital samples, p = 0.025). Conclusions: The results support the hypothesis that FGS may increase the risk of HIV acquisition, not only through damage of the mucosal epithelial barrier, but also by affecting HIV target cell populations, and that anti-schistosomal treatment can modify this. © 2014 Kleppa et al.


Milano G.,Center Antoine Lacassagne | Uesaka K.,Shizuoka Cancer Center | Al-Batran S.-E.,UCT | Pfeiffer P.,OUH | And 2 more authors.
European Oncology and Haematology | Year: 2013

The European Society for Medical Oncology 15th World Congress of Gastrointestinal Cancer satellite symposium was held in Barcelona to discuss the oral fluoropyrimidine S-1. S-1 is a combination of three pharmacological compounds: tegafur, gimeracil and oteracil potassium. Tegafur is a prodrug of 5-fluorouracil (5-FU), an oral fluoropyrimidine, and has been developed as a replacement for infusional 5-FU therapy. S-1-based chemotherapy has become first-line treatment for unresectable advanced gastric cancer in Japan. It has also shown efficacy in the treatment of colorectal cancer, and a recent Japanese phase III clinical trial in pancreatic cancer showed that adjuvant treatment with S-1 substantially increases overall survival rates compared with treatment with the standard post-operative drug gemcitabin. Following a clinical trial in Western patients, S-1 has been approved in Europe and offers a tolerable and convenient treatment regimen with a tolerable safety profile. © Touch medical media 2013.


Kleppa E.,University of Oslo | Holmen S.D.,University of Oslo | Lillebo K.,University of Oslo | Kjetland E.F.,University of Oslo | And 5 more authors.
Sexually Transmitted Infections | Year: 2015

Objectives: It has been hypothesised that ectopy may be associated with increased susceptibility to sexually transmitted infections (STIs). In this cross-sectional study, we wanted to explore the association between STIs (including HIV) and cervical ectopy. Methods: We included 700 sexually active young women attending randomly selected high schools in a rural district in KwaZulu-Natal, South Africa. The district is endemic of HIV and has a high prevalence of STIs. We did computer-assisted measurements of the ectocervical area covered by columnar epithelium (ectopy) in colposcopic images and STI analyses on cervicovaginal lavage and serum samples. All participating women answered a questionnaire about sexual behaviour and use of contraceptives. Results: The mean age was 19.1 years. Ectopy was found in 27.2%, HIV in 27.8%, chlamydia in 25.3% and gonorrhoea in 15.6%. We found that age, parity, chlamydia and gonorrhoea, years since menarche, years since sexual debut and number of sexual partners were associated with ectopy. In multivariate analysis with chlamydia infection as the dependent variable, women with ectopy had increased odds of having chlamydia infection (adjusted OR 1.78, p=0.033). In women under 19 years of age, we found twofold higher odds of being HIV-positive for those with ectopy (OR 2.19, p=0.014). Conclusions: In conclusion, cervical ectopy is associated with Chlamydia trachomatis infection and HIV in the youngest women. © 2015, BMJ Publishing Group. All rights reserved.


PubMed | University of KwaZulu - Natal, University of Agder, OUH and University of Oslo
Type: Journal Article | Journal: Sexually transmitted infections | Year: 2015

It has been hypothesised that ectopy may be associated with increased susceptibility to sexually transmitted infections (STIs). In this cross-sectional study, we wanted to explore the association between STIs (including HIV) and cervical ectopy.We included 700 sexually active young women attending randomly selected high schools in a rural district in KwaZulu-Natal, South Africa. The district is endemic of HIV and has a high prevalence of STIs. We did computer-assisted measurements of the ectocervical area covered by columnar epithelium (ectopy) in colposcopic images and STI analyses on cervicovaginal lavage and serum samples. All participating women answered a questionnaire about sexual behaviour and use of contraceptives.The mean age was 19.1years. Ectopy was found in 27.2%, HIV in 27.8%, chlamydia in 25.3% and gonorrhoea in 15.6%. We found that age, parity, chlamydia and gonorrhoea, years since menarche, years since sexual debut and number of sexual partners were associated with ectopy. In multivariate analysis with chlamydia infection as the dependent variable, women with ectopy had increased odds of having chlamydia infection (adjusted OR 1.78, p=0.033). In women under 19years of age, we found twofold higher odds of being HIV-positive for those with ectopy (OR 2.19, p=0.014).In conclusion, cervical ectopy is associated with Chlamydia trachomatis infection and HIV in the youngest women.


Aalykke C.,OUH | Jensen M.D.,OUH | Fallingborg J.,OUH | Jess T.,OUH | And 6 more authors.
Danish medical journal | Year: 2015

The risk of colorectal cancer (CRC) and dysplasia in patients with inflammatory bowel disease (IBD) has been highly debated as risk estimates from different studies vary greatly. The present national Danish guideline on colonoscopy surveillance for dysplasia and colorectal cancer in patients with IBD is based on a thorough review of existing literature with particular focus on recent studies from Denmark revealing a lower risk of CRC than previously assumed. The overall risk of CRC in the Danish IBD population does not appear to be different from that of the background population; however, in some subgroups of patients the risk is increased. These subgroups of patients, who should be offered colonoscopy surveillance, include patients with ulcerative colitis having extensive disease and a long disease duration (10-13 years); early age at onset (less than 19 years of age) of ulcerative colitis; and patients with ulcerative colitis as well as Crohn's disease with a concomitant diagnosis of primary sclerosing cholangitis. A colonoscopy surveillance program is recommended in these subgroups with intervals ranging from every 3-6 months to every 5 years, using chromoendoscopy with targeted biopsies of the lesion and adjacent mucosa, instead of conventional colonoscopy with random biopsies. Preferably, the colonoscopy should be performed during clinical remission. If a lesion is detected the endoscopical resectability together with the pathology of the lesion and the adjacent mucosa determine how the lesion should be treated.


Robinson S.,Odense University Hospital | Zincuk A.,Odense University Hospital | Larsen U.L.,Odense University Hospital | Ekstrom C.,University of Southern Denmark | And 3 more authors.
Critical Care | Year: 2013

Introduction: Critically ill patients are predisposed to venous thromboembolism. We hypothesized that higher doses of enoxaparin would improve thromboprophylaxis without increasing the risk of bleeding. Peak anti-factor Xa (anti-Xa) levels of 0.1 to 0.4 IU/ml reflect adequate thromboprophylaxis for general ward patients. Studies conducted in orthopaedic patients demonstrated a statistically significant relationship between anti-Xa levels and wound haematoma and thrombosis. Corresponding levels for critically ill patients may well be higher, but have never been validated in large studies.Methods: Eighty critically ill patients weighing 50 to 90 kilograms were randomised in a double-blinded study to receive subcutaneous (sc) enoxaparin: 40 mg once daily (QD), 30 mg twice daily (BID), 40 mg BID, or 1 mg/kg QD, each administered for three days. Anti-Xa activity was measured at baseline, and daily at 4, 12, 16 and 24 hours post administration. Antithrombin, fibrinogen, and platelets were measured at baseline and twice daily thereafter.Results: Two patients were transferred prior to participation. On day 1, doses of 40 mg QD (n = 20) and 40 mg BID (n = 19) yielded mean peak anti-Xa of 0.20 IU/ml and 0.17 IU/ml respectively. A dose of 30 mg BID (n = 20) resulted in much lower levels (0.08 IU/ml). Patients receiving 1 mg/kg QD (n = 19) achieved near steady-state mean peak anti-Xa levels from day 1 (0.34 IU/ml). At steady state (day 3), mean peak anti-Xa levels of 0.13 IU/ml and 0.15 IU/ml were achieved with doses of 40 mg QD and 30 mg BID respectively. This increased significantly to 0.33 IU/ml and 0.40 IU/ml for doses of 40 mg BID and 1 mg/kg QD respectively. Thus anti-Xa response profiles differed significantly over the three days between enoxaparin treatment groups (P <0.0001). Doses of 40 mg BID and1 mg/kg QD enoxaparin yielded target anti-Xa levels for over 80% of the study period. There were no adverse effects.Conclusions: Doses of 40 mg QD enoxaparin (Europe) or 30 mg BID (North America) yield levels of anti-Xa which may be inadequate for critically ill patients. A weight-based dose yielded the best anti-Xa levels without bioaccumulation, and allowed the establishment of near steady-state levels from the first day of enoxaparin administration. Trial registration: Current Controlled Trials ISRCTN91570009. © 2013 Robinson et al.; licensee BioMed Central Ltd.

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