Kretschmer C.,Research Group Surgical Oncology |
Sterner-Kock A.,University of Cologne |
Siedentopf F.,DRK Kliniken Berlin Westend |
Schoenegg W.,DRK Kliniken Berlin Westend |
And 2 more authors.
Molecular Cancer | Year: 2011
Background: The ductal carcinoma in situ (DCIS) of the mammary gland represents an early, pre-invasive stage in the development of invasive breast carcinoma. Since DCIS is a curable disease, it would be highly desirable to identify molecular markers that allow early detection. Mice transgenic for the WAP-SV40 early genome region were used as a model for DCIS development. Gene expression profiling was carried out on DCIS-bearing mice and control animals. Additionally, a set of human DCIS and invasive mammary tumors were analyzed in a similar fashion. Enhanced expression of these marker genes in human and murine samples was validated by quantitative RT-PCR. Besides, marker gene expression was also validated by immunohistochemistry of human samples. Furthermore in silico analyses using an online microarray database were performed.Results: In DCIS-mice seven genes were identified that were significantly up-regulated in DCIS: DEPDC1, NUSAP1, EXO1, RRM2, FOXM1, MUC1 and SPP1. A similar up-regulation of homologues of the murine genes was observed in human DCIS samples. Enhanced expression of these genes in DCIS and IDC (invasive ductal carcinoma) was validated by quantitative RT-PCR and immunohistochemistry.Conclusions: By comparing murine markers for the ductal carcinoma in situ (DCIS) of the mammary gland with genes up-regulated in human DCIS-samples we were able to identify a set of genes which might allow early detection of DCIS and invasive carcinomas in the future. The similarities between gene expression in DCIS and invasive carcinomas in our data suggest that the early detection and treatment of DCIS is of utmost relevance for the survival of patients who are at high risk of developing breast carcinomas. © 2011 Kretschmer et al; licensee BioMed Central Ltd.
Poretti A.,University of Zürich |
Poretti A.,Johns Hopkins University |
Hausler M.,RWTH Aachen |
Von Moers A.,DRK Kliniken Berlin Westend |
And 13 more authors.
Cerebellum | Year: 2014
Cerebellar cysts are rare findings in pediatric neuroimaging and rather characteristic for dystroglycanopathies and GPR56-related encephalopathy. We aim to report on seven children with cerebellar cysts showing absence of weakness and ruling out mutations within eight dystroglycanopathy genes and GPR56. Data about neurological and ophthalmological features, outcome, and creatine kinase values were collected from clinical histories and follow-up examinations. All MR images were qualitatively evaluated for infra- and supratentorial abnormalities. A SNP 6.0-Array was performed in three children. The POMT1, POMT2, POMGnT1, FKRP, FKTN, LARGE, ISPD, B3GALNT2, and GPR56 genes were screened in all patients by Sanger sequencing. Seven children from five families were studied. Ataxia, intellectual disability, and language impairment were found in all patients, ocular motor apraxia in five, and severe myopia in three. None of the patients had weakness, only three a minimally increased creatine kinase value. Qualitative neuroimaging evaluation showed cerebellar cysts and dysplasia in the cerebellar hemispheres and vermis in all children. Additional findings were an enlarged fourth ventricle in all children, vermian hypoplasia and brain stem morphological abnormalities in five. The SNP array showed no pathogenetic imbalances in all children evaluated. In all patients, no mutations were found in POMT1, POMT2, POMGnT1, FKRP, FKTN, LARGE, ISPD, B3GALNT2, and GPR56. The peculiar combination of the same clinical and neuroimaging findings in our patients highly suggests that this phenotype may represent a novel entity, possibly falling within the spectrum of dystroglycanopathies. © Springer Science+Business Media 2013.
Rosewich H.,University of Gottingen |
Thiele H.,University of Cologne |
Ohlenbusch A.,University of Gottingen |
Maschke U.,Catholic Hospital St Johann Nepomuk |
And 8 more authors.
The Lancet Neurology | Year: 2012
Background: Alternating hemiplegia of childhood (AHC) is a rare neurological disorder characterised by early-onset episodes of hemiplegia, dystonia, various paroxysmal symptoms, and developmental impairment. Almost all cases of AHC are sporadic but AHC concordance in monozygotic twins and dominant transmission in a family with a milder phenotype have been reported. Thus, we aimed to identify de-novo mutations associated with this disease. Methods: We recruited patients with clinically characterised AHC from paediatric neurology departments in Germany and with the aid of a parental support group between Sept, 2004, and May 18, 2012. We used whole-exome sequencing of three proband-parent trios to identify a disease-associated gene and then tested whether mutations in the gene were also present in the remaining patients and their healthy parents. We analysed genotypes and characterised their associations with the phenotypic spectrum of the disease. Findings: We studied 15 female and nine male patients with AHC who were aged 8-35 years. ATP1A3 emerged as the disease-associated gene in AHC. Whole-exome sequencing showed three heterozygous de-novo missense mutations. Sequencing of the 21 remaining affected individuals identified disease-associated mutations in ATP1A3 in all patients, including six de-novo missense mutations and one de-novo splice-site mutation. Because ATP1A3 is also the gene associated with rapid-onset dystonia-parkinsonism (DYT12, OMIM 128235) we compared the genotypes and phenotypes of patients with AHC in our cohort with those of patients with rapid-onset dystonia-parkinsonism reported in the scientific literature. We noted overlapping clinical features, such as abrupt onset of dystonic episodes often triggered by emotional stress, a rostrocaudal (face to arm to leg) gradient of involvement, and signs of brainstem dysfunction, as well as clearly differentiating clinical characteristics, such as episodic hemiplegia and quadriplegia. Interpretation: Mutation analysis of the ATP1A3 gene in patients who met clinical criteria for AHC allows for definite genetic diagnosis and sound genetic counselling. AHC and rapid-onset dystonia-parkinsonism are allelic diseases related to mutations in ATP1A3 and form a phenotypical continuum of a dystonic movement disorder. Funding: Eva Luise and Horst Köhler Foundation for Humans with Rare Diseases. © 2012 Elsevier Ltd.
Swidsinski A.,Charité - Medical University of Berlin |
Loening-Baucke V.,Charité - Medical University of Berlin |
Mendling W.,Vivantes Kliniken fur Gynaekologie und Geburtshilfe |
Dorffel Y.,Charité - 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.,Charité - Medical University of Berlin |
Verstraelen H.,Ghent University |
Loening-Baucke V.,Charité - 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.
Theben J.U.,St. Elisabeth Krankenhaus Hohenlind |
Schellong A.R.M.,University of Massachusetts Amherst |
Altgassen C.,DRK Kliniken Berlin Westend |
Kelling K.,University of Lübeck |
And 2 more authors.
Archives of Gynecology and Obstetrics | Year: 2013
Objective: The objective of this research was to identify the rate of unexpected malignancies after laparoscopic-assisted supracervical hysterectomies (LASH) and describe the therapy regime. Methods: The research is based on a retrospective chart analysis of patients undergoing a simple hysterectomy in the gynecological endoscopy department of a general hospital in Germany. Results: 2,577 simple hysterectomies conducted between March 2005 and March 2010 were sub-classified in different types of hysterectomies (vaginal-, abdominal-, total-, abdominal supracervical hysterectomy, LAVH, and LASH). This study focuses on the LASH sub-group of 1,584 patients and does not make any comparisons to other operative approaches. Out of the 1,584 patients, 87.8 % (n = 1,391) received preoperative screening to exclude dysplasia or malignancy based on the policy of the German Association for gynecology and obstetrics (DGGG). The screening includes cytology (Pap-smear) and preoperative ultrasound of the uterus or dilatation and curettage (d&c). Unexpected malignancies were found in 0.25 % (n = 4) of the patients pre-screened according to DGGG protocol. Out of the four malign patients, two had endometrial cancer. Two patients had leiomyosarcoma. Conclusion: The study shows that there is a small probability of unexpected malignancies even in correctly pre-screened patients for LASH procedures. Yet in the short-term (28-52 months), malign patients remain recurrence free after treatment. LASH is therefore a good procedure for assumed benign disease. © 2012 Springer-Verlag.
Amstutz C.A.,University of Zürich |
Bechrakis N.E.,Innsbruck Medical University |
Foerster M.H.,DRK Kliniken Berlin Westend |
Heufelder J.,Helmholtz Center Berlin |
Kowal J.H.,University Hospital Berne
International Journal of Radiation Oncology Biology Physics | Year: 2012
Purpose: External beam proton radiation therapy has been used since 1975 to treat choroidal melanoma. For tumor location determination during proton radiation treatment, surgical tantalum clips are registered with image data. This report introduces the intraoperative application of an opto-electronic navigation system to determine with high precision the position of the tantalum markers and their spatial relationship to the tumor and anatomical landmarks. The application of the technique in the first 4 patients is described. Methods and Materials: A navigated reference base was attached noninvasively to the eye, and a navigated pointer device was used to record the spatial position of the tantalum markers, the tumor, and anatomical landmarks. Measurement accuracy was assessed on ex vivo porcine eye specimen by repetitive recording of the tantalum marker positions. The method was applied intraoperatively on 4 patients undergoing routine tantalum clip surgery. The spatial position information delivered by the navigation system was compared to the geometric data generated by the EYEPLAN software. Results: In the ex vivo experiments, the maximum repetition error was 0.34 mm. For the intraoperative application, the root mean square error of paired-points matching of the marker positions from the navigation system and from the EYEPLAN software was 0.701-1.25 mm. Conclusions: Navigation systems are a feasible tool for accurate localization of tantalum markers and anatomic landmarks. They can provide additional geometric information, and therefore have the potential to increase the reliability and accuracy of external beam proton radiation therapy for choroidal melanoma. Copyright © 2012 Elsevier Inc. Printed in the USA. All rights reserved.
Recommendations for action for preclinical airway management: For emergency doctors and emergency medical service personnel [Handlungsempfehlung für das präklinische atemwegsmanagement: Für notärzte und rettungsdienstpersonal]
Timmermann A.,DRK Kliniken Berlin Westend |
Timmermann A.,Universitatsklinikum Gottingen |
Byhahn C.,Goethe University Frankfurt |
Wenzel V.,Innsbruck Medical University |
And 4 more authors.
Anasthesiologie und Intensivmedizin | Year: 2012
Successful management of the airway is one of the central tasks in emergency care medicine since the absence of adequate oxygenation and ventilation render all other measures void. Out-ofhospital airway management is markedly more difficult than in the hospital, since such factors as the state of the patient, the ambient situation, limited equipment and the individual experience of the medical personel all have a role to play. Tracheal intubation (ETI) continues to be regarded as the "gold standard" for airway securement, although data on the best procedure to use are not forthcoming. In addition there is a lack of evidence identifying the minimum number of successful in-hospital applications of a specific technique and the justification for its regular use ETI should be performed only by those who have mastered the technique. For such persons there should be documented evidence of supervised training involving at least 100 ETI's, and subsequently 10 ETI's a year performed in selected patients. Under pre-hospital conditions not more than two intubation attempts, each lasting not more than 30 seconds, should be undertaken. Between two attempts, mask ventilation should be applied. In the event of a failed ETI, or when the necessary requirements are absent, not more than two attempts to establish an extraglottic airway (EGA) should be made. EGA with a drainage channel should be applied and a gastric tube placed. After successful ETI and/or EGA, the airway should be secured via a coniotomy. When the airway has been secured, respiration must be monitored via capnography. In the event of circulatory failure, a second method should be used to detect an oesophageal misplacement. © Anästh Intensivmed 2012.
Carrizosa J.,University of Antioquia |
An I.,Pitie Salpetriere Hospital |
Appleton R.,Alder Hey Childrens Hospital |
Camfield P.,Dalhousie University |
Von Moers A.,DRK Kliniken Berlin Westend
Epilepsia | Year: 2014
Transition is a purposeful, planned process that addresses the medical, psychosocial, educational, and vocational needs of adolescents and young adults with chronic medical conditions, as they advance from a pediatric and family-centered to an adult, individual focused health care provider. This article describes some of the models for transition clinics or services for epilepsy in five countries (Canada, France, Colombia, Germany, and the United Kingdom). These models include joint adult and pediatric clinics, algorithm-driven service, and a check list system in the context of pediatric care. Evaluation of these models is limited, and it is not possible to choose an optimal program. The attitude and motivation of health care providers may be the most important elements. © 2014 International League Against Epilepsy.
PubMed | University of Bonn and DRK Kliniken Berlin Westend
Type: Clinical Trial | Journal: Anticancer research | Year: 2016
Complete cytoreduction is the most important prognostic factor in ovarian cancer. However, there exist conflicting data on whether the removal of microscopic tumor metastasis in macroscopically unsuspicious retroperitoneal lymph nodes is beneficial.Ovarian cancer tissues and tissues from lymph node metastasis of 30 patients with FIGO IIIC or IV disease undergoing neoadjuvant chemotherapy (NACT) were obtained and assessed using a validated regression score. Histopathological markers, size of largest tumor focus, and overall score were evaluated in lymph node and ovarian tissue. Regression and known prognostic factors were analyzed for influence on survival.No difference in the overall score between lymph nodes and ovarian tissue was shown, however, single parameters such as fibrosis and pattern of tumor infiltration, were significantly different.The pattern of tumor regression in lymph nodes and ovarian tissue are of prognostic value. Lymph node dissection even of unsuspicious nodes should, therefore, be performed.