Leffers H.C.,Copenhagen University |
Ostergaard M.,Copenhagen University |
Glintborg B.,Holbaek Hospital |
Krogh N.S.,Zitelab Aps |
And 9 more authors.
Annals of the Rheumatic Diseases | Year: 2011
Objectives: To describe drug survival, disease activity and clinical response in patients with rheumatoid arthritis (RA) treated with abatacept or tocilizumab in routine care, based on prospectively registered observational data from the nationwide Danish DANBIO registry. Methods: 150 Patients with RA treated with abatacept and 178 treated with tocilizumab were identified. Drug survival was investigated. Response data were available in 104 and 97 patients, respectively. Changes in 28-joint Disease Activity Score (DAS28) based on C-reactive protein (CRP) and European League Against Rheumatism (EULAR) response after 24 and 48 weeks were investigated. No direct comparison of drugs was made. Results: Median (IQR) disease duration was 8.5 (3-14)/9 (3-12) years (abatacept/tocilizumab). 95%/93% of patients had previously received one or more tumour necrosis factor inhibitor (TNFi). After 48 weeks, 54%/64% of patients (abatacept/tocilizumab) maintained treatment. Among patients with available response data, DAS28 was 5.3 (4.7-6.1), 3.4 (2.7-4.9) and 3.3 (2.5-4.3) at baseline, weeks 24 and 48, respectively, in the abatacept group and 5.4 (4.7-6.2), 2.9 (2.3-4.0) and 2.5 (1.9-4.5) in the tocilizumab group. At weeks 24 and 48, the remission rates for abatacept/tocilizumab were 19%/39% and 26%/58%, respectively. EULAR good-or-moderate response rates were 70%/88% and 77%/84%, respectively. The decline in DAS28 variables over time appeared similar between drugs, except for CRP, which seemed to decline more rapidly among tocilizumabtreated patients. Conclusions: In patients with RA (≥90% TNFi failures), a good-or-moderate EULAR response was achieved in ≥70% of patients treated with abatacept or tocilizumab for 24 weeks in routine care. Apparent declines in DAS28 variables over time were similar between drugs, except for the more rapid CRP decline among tocilizumab-treated patients, directly caused by interleukin 6 inhibition.
Bojesen A.,Vejle Hospital |
Bojesen A.,Aarhus University Hospital |
Birkebaek N.,Aarhus University Hospital |
Kristensen K.,Randers Hospital |
And 4 more authors.
Osteoporosis International | Year: 2011
Klinefelter syndrome (KS) patients have lower bone mineral density (BMD) at the spine, hip and forearm compared to healthy subjects, but frank osteoporosis is not common. Muscle strength and bone markers predicted BMD but KS itself and serum testosterone did not. Low vitamin D and high PTH were frequent among KS. Introduction: The long-term consequence of KS on bone health is not well described. The objective of this study is to investigate the regional BMD and its determinants in KS. Methods: This is a cross-sectional study. BMD at the spine, hip and forearm are measured by DXA and correlated to biochemical markers of bone turnover, vitamin D metabolites, PTH, sex hormones, growth factors as well as muscle strength and anthropometric measures. The setting is at a university clinical research centre. The study involves 70 adult KS patients and 71 age-matched healthy subjects. Results: In KS, BMD was universally lowered in all regions. Markers of bone formation or bone resorption were not altered in KS, but 25-OH-Dvitamin was lower (55 vs. 82 nmol/L, <0.0001) than in healthy subjects. Significantly more KS patients had low BMD (Z-scores below -2) at the forearm (15 KS vs. two healthy subjects, =0.001) but not at the spine or hip. Muscle strength (bicep and quadriceps) was lower among KS patients. Multivariate analysis revealed that muscle strength, treatment with testosterone (ever/never), age at diagnosis, SHBG, bone-specific alkaline phosphatase and 1CTP were all independent predictors of BMD, but androgens was not. Conclusions: KS patients had lower BMD at the spine, hip and forearm compared to age-matched healthy subjects, but frank osteoporosis was not common. Muscle strength, previous history of testosterone treatment, age at diagnosis and bone markers were predictors of BMD, but testosterone was not. Signs of secondary hyperparathyroidism were present among KS. Dietary intake of vitamin D or sun exposure may be lower in KS patients. © 2010 International Osteoporosis Foundation and National Osteoporosis Foundation.
Veno M.T.,University of Aarhus |
Bramsen J.B.,University of Aarhus |
Bendixen C.,University of Aarhus |
Panitz F.,University of Aarhus |
And 3 more authors.
RNA Biology | Year: 2012
Editing by ADAR enzymes is essential for mammalian life. Still, knowledge of the spatio-temporal editing patterns in mammals is limited. By use of 454 amplicon sequencing we examined the editing status of 12 regionally extracted mRNAs from porcine developing brain encompassing a total of 64 ADAR editing sites. In total 24 brain tissues, dissected from up to five regions from embryonic gestation day 23, 42, 60, 80, 100 and 115, were examined for editing. Generally, editing increased during embryonic development concomitantly with an increase in ADAR2 mRNA level. Notably, the Gria2 (GluR-B) Q/R site, reported to be ~100% edited in previous studies, is only 54% edited at embryonic day 23. Transcripts with multiple editing sites in close proximity to each other exhibit coupled editing and an extraordinary incidence of long-range coupling of editing events more than 32 kb apart is observed for the kainate glutamate receptor 2 transcript, Grik2. Our study reveals complex spatio-temporal ADAR editing patterns of coordinated editing events that may play important roles in the development of the mammalian brain. © 2012 Landes Bioscience.
Blechingberg J.,University of Aarhus |
Holm I.E.,Randers Hospital |
Nielsen A.L.,University of Aarhus
Gene | Year: 2012
The FET protein family consists of FUS (TLS), EWS (EWSR1), and TAF15. The FET proteins bind DNA and RNA and are involved in transcriptional regulation and RNA processing. Translocations involving the FET genes have been identified in human sarcomas, and mutations in the FUS and TAF15 genes are associated with Amyotrophic Lateral Sclerosis. We here describe the characterization of the porcine FET proteins and an expression analysis during embryonic brain development. The FET proteins are well conserved between pig and human. FET protein mutations associated with Amyotrophic Lateral Sclerosis affect evolutionary conserved amino acids. In cultured cells the porcine FET proteins have a nuclear localization with some specific cytoplasmic aggregation of TAF15 in neuronal progenitor cells. Immunohistochemical analyses supported a predominant nuclear localization, but also faint cytoplasmic localization. The FET proteins have similar expression profiles throughout the development of the embryonic porcine brain and most cell types appeared positive for expression. Quantitative RT-PCR analyses showed that the FET mRNA expression decreased during embryonic development of hippocampus and for FUS and EWS during embryonic development of cortex. FET mRNA expression was relatively constant in brain stem, basal ganglia, and cerebellum. Overall the FET protein localization and mRNA and protein expression analyses were concordant with previous analysis from the human brain. The presented results indicate that the porcine brain could be an alternative model for the future examination of the normal functions as well as neurological disease associated functions of the FET proteins. © 2011 Elsevier B.V.
Holm I.E.,Randers Hospital |
Holm I.E.,University of Aarhus |
Alstrup A.K.O.,Aarhus University Hospital |
Luo Y.,University of Aarhus
Journal of Pathology | Year: 2016
Increasing incidence of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease has become one of the most challenging health issues in ageing humans. One approach to combat this is to generate genetically modified animal models of neurodegenerative disorders for studying pathogenesis, prognosis, diagnosis, treatment, and prevention. Owing to the genetic, anatomic, physiologic, pathologic, and neurologic similarities between pigs and humans, genetically modified pig models of neurodegenerative disorders have been attractive large animal models to bridge the gap of preclinical investigations between rodents and humans. In this review, we provide a neuroanatomical overview in pigs and summarize and discuss the generation of genetically modified pig models of neurodegenerative disorders including Alzheimer's diseases, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, and ataxia-telangiectasia. We also highlight how non-invasive bioimaging technologies such as positron emission tomography (PET), computer tomography (CT), and magnetic resonance imaging (MRI), and behavioural testing have been applied to characterize neurodegenerative pig models. We further propose a multiplex genome editing and preterm recloning (MAP) approach by using the rapid growth of the ground-breaking precision genome editing technology CRISPR/Cas9 and somatic cell nuclear transfer (SCNT). With this approach, we hope to shorten the temporal requirement in generating multiple transgenic pigs, increase the survival rate of founder pigs, and generate genetically modified pigs that will more closely resemble the disease-causing mutations and recapitulate pathological features of human conditions. © 2015 Pathological Society of Great Britain and Ireland.
Johansen J.S.,Copenhagen University |
Christensen I.J.,Rigshospitalet |
Christensen I.J.,Copenhagen University |
Jorgensen L.N.,Bispebjerg Hospital |
And 7 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2015
The aim of the present study was to test the hypothesis that high serum YKL-40 associates with colorectal cancer in subjects at risk of colorectal cancer. We measured serum YKL-40 in a prospective study of 4,496 Danish subjects [2,064 men, 2,432 women, median age 61 years (range, 18-97)] referred to endoscopy due to symptoms or other risk factors for colorectal cancer. Blood samples were collected just before large bowel endoscopy. Serum YKL-40 was determined by ELISA. Serum YKL-40 was higher (P < 0.0001, unadjusted for confounding covariates) in subjects diagnosed with colon cancer (median 126 μg/L, 25%-75%: 80-206 μg/L) and rectal cancer (104, 72-204 μg/L) compared with subjects with adenoma (84, 53-154 μg/L), other nonmalignant findings (79, 49-138 μg/L), and no findings (62, 41-109 μg/L). Serum YKL-40 independently predicted colorectal cancer [OR, 1.53; 95% confidence interval (CI), 1.40-1.67; AUC = 0.68, P < 0.0001]. Restricting the analysis to subjects with no comorbidity increased the OR for serum YKL-40 to predict colorectal cancer (OR, 1.82; 1.58-2.08; AUC = 0.73, P < 0.0001). Combining serum YKL-40 and CEA demonstrated that both were significant [(YKL-40, OR, 1.27; 95% CI, 1.16-1.40); (CEA, OR, 1.92; 1.75-2.10; AUC = 0.75, P < 0.0001; OR for a 2-fold difference in marker level)]. Multivariable analysis (YKL-40, CEA, age, gender, body mass index, and center) showed that serum YKL-40 was a predictor for colorectal cancer in individuals without comorbidity (OR, 1.25; 95% CI, 1.05-1.40; P = 0.012), whereas this was not the case for those with comorbidity (OR, 0.98; 95% CI, 0.84-1.14; P = 0.80). In conclusion, high serum YKL-40 in subjects suspected of colorectal cancer and without comorbidity associates with colorectal cancer. Determination of serum YKL-40 may be useful in combination with other biomarkers in risk assessment for colorectal cancer. © 2015 AACR.
Jorgensen L.N.,Bispebjerg Hospital |
Sommer T.,Randers Hospital |
Assaadzadeh S.,Copenhagen University |
Strand L.,Frederikshavn Hospital |
And 3 more authors.
British Journal of Surgery | Year: 2013
Background: Many patients develop discomfort after open repair of a groin hernia. It was hypothesized that suture fixation of the mesh is a cause of these symptoms. Methods: This patient- and assessor-blinded randomized multicentre clinical trial compared a self-gripping mesh (Parietene Progrip®) and sutured mesh for open primary repair of uncomplicated inguinal hernia by the Lichtenstein technique. Patients were assessed before surgery, on the day of operation, and at 1 and 12 months after surgery. The primary endpoint was moderate or severe symptoms after 12 months, including a combination of chronic pain, numbness and discomfort. Results: The intention-to-treat population comprised 163 patients with self-gripping mesh and 171 with sutured mesh. The 12-month prevalence of moderate or severe symptoms was 17·4 and 20·2 per cent respectively (P = 0·573). There were no significant differences between the groups in postoperative complications (33·7 versus 40·4 per cent; P = 0·215), rate of recurrent hernia within 1 year (1·2 per cent in both groups) or quality of life. Conclusion: The avoidance of suture fixation using a self-gripping mesh was not accompanied by a reduction in chronic symptoms after inguinal hernia repair. Registration number: NCT00815698 (http://www.clinicaltrials.gov). Copyright © 2012 British Journal of Surgery Society Ltd.
Clemmensen K.,Aarhus University Hospital |
Akrawi N.,Randers Hospital |
Stawowy M.,Randers Hospital
Scandinavian Journal of Gastroenterology | Year: 2015
This article reports the first known case of permanent blindness due to irreversible unilateral optic neuritis (ON) related to infliximab (Remicade) treatment of a patient with ulcerative colitis. A young male, with a family history of inflammatory bowel disease, was diagnosed with ulcerative colitis at the age of 20. He was treated with steroids and a 5-aminosalicylic acid drug without considerable effect, and later admitted to our hospital due to a relapse during reduction of the prednisolone dosage. A new colonoscopy showed moderate ulcerative colitis activity and the patient was declared as a steroid nonresponder. A treatment of 400 mg intravenous infliximab was initiated along with 150 mg/day of azathioprine (Imurel). Three days after the second infliximab treatment the patient woke up with no vision on the left eye and with pain during ocular movement. Brain and orbitae magnetic resonance imaging showed ON on the left optical nerve without any abscess or thrombosis. The patient was treated with 1000 mg methylprednisolone (Solu-Medrol) intravenous for 3 days and afterward with 75 mg prednisolone orally without any effect. At the 3-month follow up, the patients vision had not improved, and he was declared permanently blind on the left eye. A neurologist also examined the patient, but no abnormality or cause of the ON was found. © 2015 Informa Healthcare.
Jorgensen S.P.,Aarhus University Hospital |
Agnholt J.,Aarhus University Hospital |
Glerup H.,Silkeborg Hospital |
Lyhne S.,Randers Hospital |
And 6 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2010
Aliment Pharmacol Ther 2010; 32: 377-383 SummaryBackground Vitamin D has immune-regulatory functions in experimental colitis, and low vitamin D levels are present in Crohn's disease. Aim To assess the effectiveness of vitamin D3 treatment in Crohn's disease with regard to improved disease course. Methods We performed a randomized double-blind placebo-controlled trial to assess the benefits of oral vitamin D3 treatment in Crohn's disease. We included 108 patients with Crohn's disease in remission, of which fourteen were excluded later. Patients were randomized to receive either 1200 IU vitamin D3 (n = 46) or placebo (n = 48) once daily during 12 months. The primary endpoint was clinical relapse. Results Oral vitamin D3 treatment with 1200 IU daily increased serum 25OHD from mean 69 nmolL [standard deviation (s.d.) 31 nmolL] to mean 96 nmolL (s.d. 27 nmolL) after 3 months (P < 0.001). The relapse rate was lower among patients treated with vitamin D3 (646 or 13%) than among patients treated with placebo (1448 or 29%), (P = 0.06). Conclusions Oral supplementation with 1200 IE vitamin D3 significantly increased serum vitamin D levels and insignificantly reduced the risk of relapse from 29% to 13%, (P = 0.06). Given that vitamin D3 treatment might be effective in Crohn's disease, we suggest larger studies to elucidate this matter further. ClinicalTrial.gov(NCT00122184). © 2010 Blackwell Publishing Ltd.
Sommer T.,Randers Hospital |
Elbroend H.,Randers Hospital |
Friis-Andersen H.,Horsens Hospital
Scandinavian Journal of Surgery | Year: 2010
Objective: To report the distribution and results of laparoscopic repair of perforated ulcer surgery in surgical departments in a major region in Denmark and compare it with the results from the national database regarding mortality and morbidity. Method: Case charts from all patients who underwent laparoscopic repair of perforated ulcer in Western Denmark in the period 1 January 2003 - 1 July 2007 were collected. Demographical data, surgical details, morbidity, 30-day mortality, and length of stay were recorded. For comparison, data from the National Health Registry (NIP) describing all patients who had an operation due to perforated ulcer in this period was obtained. Results: No more than 51 out of 818 patients undergoing operation for perforated ulcer in the region had a laparoscopic operation. Mortality in the laparoscopic group was 4% compared to 26% reported from the national database (NIP). The laparoscopic group had a higher reperforation rate but length of stay was equal. No formal criteria concerning surgeon or patients selection for laparoscopic surgery were met. Conclusion: Laparoscopic repair of perforated ulcer was done without any selection criteria in few surgical departments in Western Denmark and was associated with a low mortality but a higher risk of reperforation.