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Andres O.,University of Wurzburg | Strehl K.,Charite Childrens Hospital | Kolsch U.,Labor Berlin | Kolsch U.,Charite - Medical University of Berlin | And 7 more authors.
Pediatric Infectious Disease Journal | Year: 2013

A 9-month-old infant presented with fatal pneumococcal sepsis and attenuated inflammation indices. Even in septic conditions, flow cytometry-based CD62L shedding test on granulocytes proved to be a fast and reliable diagnostic tool for the detection of a defect in the innate immunity. Confirmatory immunologic and genetic assays identified an autosomalrecessive interleukin-1 receptor-associated kinase-4 deficiency due to compound heterozygous mutations. Copyright © 2013 by Lippincott Williams & Wilkins.

Swidsinski A.,Charite - Medical University of Berlin | Loening-Baucke V.,Charite - Medical University of Berlin | Swidsinski S.,Labor Berlin | Verstraelen H.,Ghent University
Archives of Gynecology and Obstetrics | Year: 2015

Purpose: Bacterial vaginosis is a recalcitrant polymicrobial biofilm infection that often resists standard antibiotic treatment. We therefore considered repeated treatment with octenidine, a local antiseptic that has previously been shown to be highly effective in several biofilm-associated infections.Methods: Twenty-four patients with recurrent BV were treated with a 7-day course of octenidine (octenidine dihydrochloride spray application with the commercial product Octenisept®). In case of treatment failure or relapse within 6 months, patients were re-treated with a 28-day course of octenidine. In case of recurrence within 6 months after the second treatment course, patients were treated again with a 28-day course followed by weekly applications for 2 months. Treatment effect was evaluated by assessment of the presence of the biofilm on voided vaginal epithelial cells through fluorescence in situ hybridisation.Results: The initial cure rate following a 7-day course of octenidine was as high as 87.5 %. The 6-month relapse rate was, however, as high as 66.6 %. Repeated treatment for 28 days led to an overall cure rate of 75.0 %; however, it was also associated with emergence of complete resistance to octenidine in a subset of women. The overall cure rate after three treatment courses with 1-year follow-up was 62.5 %, with 37.5 % of the patients showing complete resistance to octenidine.Conclusion: Our preliminary results showed that octenidine dihydrochloride was initially highly effective, but the efficacy of repeated and prolonged treatment dropped quickly as challenge with the antiseptic rapidly led to bacterial resistance in a considerable subset of women. © 2014, Springer-Verlag Berlin Heidelberg.

Swidsinski A.,Charite - Medical University of Berlin | Loening-Baucke V.,Charite - Medical University of Berlin | Mendling W.,Vivantes Kliniken fur Gynaekologie und Geburtshilfe | Dorffel Y.,Charite - Medical University of Berlin | And 5 more authors.
Histology and Histopathology | Year: 2014

BACKGROUND: We analysed data on bacterial vaginosis (BV) contradicting the paradigm of mono-infection. METHODOLOGY: Tissues and epithelial cells of vagina, uterus, fallopian tubes and perianal region were investigated using fluorescence in situ hybridization (FISH) in women with BV and controls. RESULTS: Healthy vagina was free of biofilms. Prolific structured polymicrobial (StPM) Gardnerella-dominated biofilm characterised BV. The intact StPM-Gardnerellabiofilm enveloped desquamated vaginal/prepuce epithelial cells and was secreted with urine and sperma. The disease involved both genders and occurred in pairs. Children born to women with BV were negative. Monotherapy with metronidazole, moxifloxacin or local antiseptics suppressed but often did not eradicate StPMGardnerella- biofilms. There was no BV without Gardnerella, but Gardnerella was not BV. Outside of StPM-biofilm, Gardnerella was also found in a subset of children and healthy adults, but was dispersed, temporal and did not transform into StPM-Gardnerella-biofilm. CONCLUSIONS: StPM-Gardnerella-biofilm is an infectious subject. The assembly of single players to StPM-Gardnerella-biofilm is a not trivial every day process, but probably an evolutionary event with a long history of growth, propagation and selection for viability and ability to reshape the environment. The evolutionary memory is cemented in the structural differentiation of StPM-Gardnerella-biofilms and imparts them to resist previous and emerging challenges.

Swidsinski A.,Charite - Medical University of Berlin | Verstraelen H.,Ghent University | Loening-Baucke V.,Charite - Medical University of Berlin | Swidsinski S.,Labor Berlin | And 2 more authors.
PLoS ONE | Year: 2013

Objective: To assess whether the bacterial vaginosis biofilm extends into the upper female genital tract. Study Design: Endometrial samples obtained during curettage and fallopian tube samples obtained during salpingectomy were collected. Endometrial and fallopian tube samples were analyzed for the presence of bacteria with fluorescence-in-situ-hybridisation (FISH) analysis with probes targeting bacterial vaginosis-associated and other bacteria. Results: A structured polymicrobial Gardnerella vaginalis biofilm could be detected in part of the endometrial and fallopian tube specimens. Women with bacterial vaginosis had a 50.0% (95% CI 24.0-76.0) risk of presenting with an endometrial Gardnerella vaginalis biofilm. Pregnancy (AOR = 41.5, 95% CI 5.0-341.9, p<0.001) and the presence of bacterial vaginosis (AOR = 23.2, 95% CI 2.6-205.9, p<0.001) were highly predictive of the presence of uterine or fallopian bacterial colonisation when compared to non-pregnant women without bacterial vaginosis. Conclusion: Bacterial vaginosis is frequently associated with the presence of a structured polymicrobial Gardnerella vaginalis biofilm attached to the endometrium. This may have major implications for our understanding of the pathogenesis of adverse pregnancy outcome in association with bacterial vaginosis. © 2013 Swidsinski et al.

Turkmen S.,Labor Berlin | Turkmen S.,Charite - Medical University of Berlin | Timmermann B.,Max Planck Institute For Molekulare Genetik | Bartels G.,Charite - Medical University of Berlin | And 9 more authors.
Genes Chromosomes and Cancer | Year: 2012

While the MLL "recombinome" is relatively well characterized in B-cell precursor acute lymphoblastic leukemia (BCP ALL), available data for adult acute T-lymphoblastic leukemia (T-ALL) are scarce. We performed fluorescence in situ hybridization (FISH) for an MLL split signal on 223 adult T-ALL samples obtained within the framework of the German Multicenter ALL 07/2003 therapy trial. Three biphenotypic leukemias (T-ALL/AML) were also included in the analysis. Samples showing any alteration by FISH were further investigated to characterize the MLL aberration. In addition, they were investigated for common genetic lesions known in T-ALL. Twenty-two cases (9.5%) showed an abnormal MLL signal by FISH analysis. Most of these appeared to be deletions or gains but in five cases (2.1%) a chromosomal translocation involving the MLL gene was identified. The translocation partners and chromosomal breakpoints were molecularly characterized. Three T-ALLs had an MLL-AF6/t(6;11) and two biphenotypic leukemias had an MLL-ELL/t(11;19). The chromosomal breakpoints in two of the MLL-AF6-positive cases were located outside the classical MLL major breakpoint cluster known from BCP ALL. In conclusion, the spectrum of MLL translocation partners in adult T-ALL much more resembles that of AML than that of BCP ALL and thus the mechanisms by which MLL contributes to leukemogenesis in adult T-ALL appear to differ from those in BCP ALL. Proposals are made for the diagnostic assessment of MLL fusion genes in adult T-ALL. © 2012 Wiley Periodicals, Inc.

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