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Litrup E.,Statens Serum Institute | Torpdahl M.,Statens Serum Institute | Malorny B.,German Federal Institute for Risk Assessment | Huehn S.,German Federal Institute for Risk Assessment | And 3 more authors.
BMC Microbiology | Year: 2010

Background. Salmonella enterica subsp. enterica is one of the leading food-borne pathogens in the USA and European countries. Outcome of human Salmonella serotype Typhimurium infections ranges from mild self-limiting diarrhoea to severe diarrhoea that requires hospitalization. Increased knowledge of the mechanisms that are responsible for causing infection and especially the severity of infection is of high interest. Results. Strains were selected from patients with mild infections (n = 9) and patients with severe infections (n = 9) and clinical data allowed us to correct for known underlying diseases. Additionally, outbreak isolates (n = 3) were selected. Strains were analyzed on a DNA-DNA microarray for presence or absence of 281 genes covering marker groups of genes related to pathogenicity, phages, antimicrobial resistance, fimbriae, mobility, serotype and metabolism. Strains showed highly similar profiles when comparing virulence associated genes, but differences between strains were detected in the prophage marker group. The Salmonella virulence plasmid was present in 72% of the strains, but presence or absence of the virulence plasmid did not correspond to disease symptoms. A dendrogram clustered strains into four groups. Clustering confirmed DT104 as being a clonal phagetype. Clustering of the remaining strains was mainly correlated to presence or absence of the virulence plasmid and mobile elements such as transposons. Each of the four clusters in the tree represented an almost equal amount of strains causing severe or mild symptoms of infection. Conclusions. We investigated clinical significance of known virulence factors of Salmonella serotype Typhimurium strains causing different disease symptoms, and conclude that the few detected differences in Salmonella serotype Typhimurium do not affect outcome of human disease. © 2010 Litrup et al; licensee BioMed Central Ltd.

Schmiegelow M.D.,Gentofte University Hospital | Pedersen O.D.,Roskilde Sygehus | Kober L.,The Heart Center Rigshospitalet | Seibaek M.,Glostrup University Hospital | And 2 more authors.
BMC Cardiovascular Disorders | Year: 2011

Background: We examined the incidence of new-onset atrial fibrillation in patients with left ventricular dysfunction. Patients either had a recent myocardial infarction (with or without clinical heart failure) or symptomatic heart failure (without a recent MI). Patients were with and without treatment with the class III antiarrhythmic drug dofetilide over 36 months.Methods: The Danish Investigations of Arrhythmia and Mortality ON Dofetilide (DIAMOND) studies included 2627 patients without atrial fibrillation at baseline, who were randomised to treatment with either dofetilide or placebo.Results: The competing risk analyses estimated the cumulative incidences of atrial fibrillation during the 42 months of follow-up to be 9.6% in the placebo-treated heart failure-group, and 2.9% in the placebo-treated myocardial infarction-group.Cox proportional hazard regression found a 42% significant reduction in the incidence of new-onset AF when assigned to dofetilide compared to placebo (hazard ratio 0.58, 95% confidence interval 0.40-0.82) and there was no interaction with study (p = 0.89).In the heart failure-group, the incidence of atrial fibrillation was significantly reduced to 5.6% in the dofetilide-treated patients (hazard ratio 0.57, 95% confidence interval 0.38-0.86).In the myocardial infarction-group the incidence of atrial fibrillation was reduced to 1.7% with the administration of dofetilide. This reduction was however not significant (hazard ratio 0.61, 95% confidence interval 0.30-1.24).Conclusion: In patients with left ventricular dysfunction the incidence of AF in 42 months was 9.6% in patients with heart failure and 2.9% in patients with a recent MI. Dofetilide significantly reduced the risk of developing atrial fibrillation compared to placebo in the entire study group and in the subgroup of patients with heart failure. The reduction in the subgroup with recent MI was not statistically significant, but the hazard ratio was similar to the hazard ratio for the heart failure patients, and there was no difference between the effect in the two studies (p = 0.89 for interaction). © 2011 Schmiegelow et al; licensee BioMed Central Ltd.

Koningstein M.,Statens Serum Institute | Simonsen J.,Statens Serum Institute | Helms M.,Roskilde Sygehus | Molbak K.,Statens Serum Institute
Journal of Antimicrobial Chemotherapy | Year: 2010

Objectives: The use of antimicrobial drugs for food animals selects for resistant non-typhoid Salmonella strains, but human consumption of antimicrobial drugs may also increase the risk of subsequent infection. The aim of this study was to determine the risk of salmonellosis attributable to human consumption of antimicrobial drugs in a case-control study of 22602 laboratory-confirmed Salmonella infections, diagnosed in Denmark between 1997 and 2005. Methods: A population registry-based case-control study, using several Danish databases: the National Prescription Database; the National Registry for Enteric Pathogens; the Civil Registry System; and the Integrated Database on Labour Market Research. Results: Exposure to trimethoprim, sulphonamides, broad-spectrum penicillins, tetracyclines and fluoroquinolones, during the year prior to diagnosis, was associated with an increased risk of non-typhoid Salmonella infection. Overall, the highest risk was associated with the prior use of fluoroquinolones. This risk increased as the time window of exposure approached the infection date. Previous use of fluoroquinolones was associated with an odds ratio (OR) of 4.55 [95% confidence interval (CI): 3.78-5.47] for Salmonella serotypes other than Salmonella Typhimurium or Salmonella Enteritidis, an OR of 2.21 (95% CI: 1.70-2.86) for Salmonella Typhimurium and an OR of 2.07 (95% CI: 1.76-2.42) for Salmonella Enteritidis. In particular for fluoroquinolones, there was an interaction between the pathogen resistance pattern and a history of antibiotic drug use. Conclusions: The increasing use of antibiotics, particularly fluoroquinolones, is likely to result in increased incidence of foodborne infections with drug-resistant Salmonella. © The Author 2010.

Jensen M.K.,Copenhagen University | Havndrup O.,Roskilde Sygehus | Christiansen M.,Statens Serum Institute | Andersen P.S.,Statens Serum Institute | And 3 more authors.
International Journal of Cardiovascular Imaging | Year: 2015

Identification of the first echocardiographic manifestations of hypertrophic cardiomyopathy may be important for clinical management and our understanding of the pathogenesis. We studied the development of pre-diagnostic echocardiographic changes in young relatives to HCM patients during long-term years follow-up. HCM-relatives not fulfilling the diagnostic criteria for HCM and age of <18 years were included in this study. We performed echocardiographic evaluations at inclusion and after 12 ± 1 years follow-up. Based on family screening of 11 sarcomere genes, CRYAB, α-GAL, and titin, we evaluated: (1) non-carriers (known family mutation ruled out-controls), (2) carriers (phenotype negative gene mutation carriers) and (3) phenotype negative relatives with unknown genetic status (relatives from families without identified mutations). At inclusion (age 11 ± 5 years), there were no differences in echocardiographic chamber dimensions, systolic or diastolic function between the three groups. During follow-up (age 23 ± 5 years), carriers (n = 8) developed lower left ventricular end-diastolic dimension (LVEDd) compared to non-carriers (n = 23) (41 ± 4 vs. 46 ± 4 mm; p = 0.04) and a higher ratio of early left ventricular filling velocity and early diastolic velocity of lateral mitral annulus (E/e’ 6 ± 1 vs. 5 ± 1; p = 0.003). No significant differences in LVEDd or E/e’ were found between relatives with unknown genetic status (n = 24) and non-carriers though Z-scores for these parameters were >2 in a subset of relatives with unknown genetic status. Children carrying pathogenic sarcomere gene mutations develop reduced LVEDd and increased E/e’ as first pre-diagnostic echocardiographic manifestations during follow-up into adulthood. © 2015, Springer Science+Business Media Dordrecht.

Sondergaard E.S.,Roskilde Sygehus | Alamili M.,Koge Sygehus | Coskun M.,Herlev Hospital | Gogenur I.,Koge Sygehus
Trends in Anaesthesia and Critical Care | Year: 2015

Purpose: Sepsis is one of the leading causes of death after admission to the intensive care unit (ICU). The discovery of small non-coding microRNAs (miRs) and their correlation to sepsis has gained increasing interest. Our aim was to systematically review the literature examining the association between differential expression of miRs and sepsis. Methods: We performed a systematic search in the MEDLINE, Embase and Cochrane Library databases according to PRISMA-guidelines. We included all original English-language studies including human subjects admitted to the ICU with sepsis or systemic inflammatory response syndrome. The miR measures were done during the ICU-stay and the outcome was either death or survival. The identified miRs were combined with predicted human target genes, in order to identify target genes associated with the inflammatory response. Results: We found 245 papers. Eleven original studies were included into the systematic review. The included studies consisted of 12 case-control studies and one randomized controlled trial. 28 different miRs were associated with sepsis. However, we were unable to link the identified miRs with any predictive genes specific for sepsis, when searching the computational target prediction databases. Conclusion: Various miRs are associated with sepsis, but no corresponding predictor genes were found. © 2015 Elsevier Ltd.

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