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  • 1
    Language: English
    In: Respiratory Research, 01 July 2010, Vol.11(1), p.93
    Description: Abstract Background Legionella pneumophila is an important causative agent of severe pneumonia in humans. Human alveolar epithelium and macrophages are effective barriers for inhaled microorganisms and actively participate in the initiation of innate host defense. The beta defensin-3 (hBD-3), an antimicrobial peptide is an important component of the innate immune response of the human lung. Therefore we hypothesize that hBD-3 might be important for immune defense towards L. pneumophila. Methods We investigated the effects of L. pneumophila and different TLR agonists on pulmonary cells in regard to hBD-3 expression by ELISA. Furthermore, siRNA-mediated inhibition of TLRs as well as chemical inhibition of potential downstream signaling molecules was used for functional analysis. Results L. pneumophila induced release of hBD-3 in pulmonary epithelium and alveolar macrophages. A similar response was observed when epithelial cells were treated with different TLR agonists. Inhibition of TLR2, TLR5, and TLR9 expression led to a decreased hBD-3 expression. Furthermore expression of hBD-3 was mediated through a JNK dependent activation of AP-1 (c-Jun) but appeared to be independent of NF-κB. Additionally, we demonstrate that hBD-3 elicited a strong antimicrobial effect on L. pneumophila replication. Conclusions Taken together, human pulmonary cells produce hBD-3 upon L. pneumophila infection via a TLR-JNK-AP-1-dependent pathway which may contribute to an efficient innate immune defense.
    Keywords: Medicine
    ISSN: 1465-9921
    E-ISSN: 1465-993X
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  • 2
    Language: English
    In: Intensive Care Medicine, 2004, Vol.30(3), pp.430-436
    Description: Byline: Peter Schellongowski (1), Michael Benesch (2), Thomas Lang (2), Friederike Traunmuller (1), Christian Zauner (3), Klaus Laczika (1), Gottfried J. Locker (1), Michael Frass (1), Thomas Staudinger (1) Keywords: Scoring; Cancer; Critical care; Acute Physiology and Chronic Health Evaluation (APACHE) II; Simplified Acute Physiology Score (SAPS) II; Mortality Probability Model II Abstract: Objective To compare three scoring systems, the Acute Physiology and Chronic Health Evaluation (APACHE) II, the Simplified Acute Physiology Score (SAPS) II and a modified Mortality Probability Model II (ICU cancer mortality model, ICMM) for their prognostic value for mortality during hospital stay in a group of cancer patients admitted to a medical ICU. Design Prospective cohort study. Setting Medical ICU of a tertiary care hospital. Patients Two hundred forty-two consecutive cancer patients admitted to the ICU. Measurements and results Variables included in APACHE II, SAPS II and the ICMM scores as well as demographic data were assessed during the first 24 h of stay in the ICU. Hospital mortality was measured it was 44%. Calibration for all three scoring systems was acceptable, SAPS II yielded a significantly superior discrimination between survivors and non-survivors. The areas under the receiver operating characteristic curves were 0.776 for APACHE II, 0.825 for SAPS II and 0.698 for the ICMM. Conclusion The SAPS II was superior to APACHE II and ICMM. The newly developed ICMM does not improve mortality prediction in critically ill cancer patients. Author Affiliation: (1) Department of Internal Medicine I, University of Vienna, Waehringer Guertel 18--20, 1090, Vienna, Austria (2) Institute for Medical Statistics, University of Vienna, Schwarzspanierstrasse 17, 1090, Vienna, Austria (3) Department of Internal Medicine IV, University of Vienna, Waehringer Guertel 18--20, 1090, Vienna, Austria Article History: Registration Date: 01/01/2003 Received Date: 03/04/2003 Accepted Date: 29/09/2003 Online Date: 04/11/2003
    Keywords: Scoring ; Cancer ; Critical care ; Acute Physiology and Chronic Health Evaluation (APACHE) II ; Simplified Acute Physiology Score (SAPS) II ; Mortality Probability Model II
    ISSN: 0342-4642
    E-ISSN: 1432-1238
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  • 3
    In: Neurology, 2016, Vol.87(2), pp.168-177
    Description: OBJECTIVE:: This was a longitudinal single-center cohort study to comprehensively explore multimodal progression markers for Parkinson disease (PD) in patients with recently diagnosed PD (n = 123) and age-matched, neurologically healthy controls (HC; n = 106). METHODS:: Thirty tests at baseline and after 24 months covered nonmotor symptoms (NMS), cognitive function, and REM sleep behavior disorder (RBD) by polysomnography (PSG), voxel-based morphometry (VBM) of the brain by MRI, and CSF markers. Linear mixed-effect models were used to estimate differences of rates of change and to provide standardized effect sizes (d) with 95% confidence intervals (CI). RESULTS:: A composite panel of 10 informative markers was identified. Significant relative worsening (PD vs HC) was seen with the following markers: the Unified Parkinsonʼs Disease Rating Scale I (d 0.39; CI 0.09–0.70), the Autonomic Scale for Outcomes in Parkinsonʼs Disease (d 0.25; CI 0.06–0.46), the Epworth Sleepiness Scale (d 0.47; CI 0.24–0.71), the RBD Screening Questionnaire (d 0.44; CI 0.25–0.64), and RBD by PSG (d 0.37; CI 0.19–0.55) as well as VBM units of cortical gray matter (d −0.2; CI −0.3 to −0.09) and hippocampus (d −0.15; CI −0.27 to −0.03). Markers with a relative improvement included the Nonmotor Symptom (Severity) Scale (d −0.19; CI −0.36 to −0.02) and 2 depression scales (Beck Depression Inventory d −0.18; CI −0.36 to 0; Montgomery-Åsberg Depression Rating Scale d −0.26; CI −0.47 to −0.04). Unexpectedly, cognitive measures and select laboratory markers were not significantly changed in PD vs HC participants. CONCLUSIONS:: Current CSF biomarkers and cognitive scales do not represent useful progression markers. However, sleep and imaging measures, and to some extent NMS, assessed using adequate scales, may be more informative markers to quantify progression.
    Keywords: Neurologi ; Neurology ; Psykiatri ; Psychiatry ; Geriatrik ; Geriatrics;
    ISSN: 0028-3878
    E-ISSN: 1526632X
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  • 4
    Language: English
    In: Journal of the American College of Cardiology, 09 March 2010, Vol.55(10), pp.A43.E412-A43.E412
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/S0735-1097(10)60413-5 Byline: Nora F. Lang, Matthias Sigler, Elena Merkel, Franziska Fuchs, Dieter Schumann, Dieter Klemm, Friederike Kramer, Anja Meyer, Franz Freudenthal, Christian Schroeder, Susanne Mayer, Heinrich Netz, Rainer Kozlik-Feldmann
    Keywords: Medicine
    ISSN: 0735-1097
    E-ISSN: 1558-3597
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  • 5
    Language: English
    In: International Journal of Oncology, August 2011, Vol.39(2), pp.515-520
    Description: We performed this study in order to evaluate the impact of the chemokine CXCL12 and its single-nucleotide polymorphism (SNP) rs1801157 on clinicopathological parameters and survival in patients undergoing surgery for esophagogastric cancer. The expression pattern of CXCL12 and its polymorphisms were analyzed by RT-PCR and PCR-RFLP in 69 consecutive fresh-frozen samples of human esophagogastric junction and gastric adenocarcinomas and statistically analyzed. Expression of the CXCL12 (SNP rs1801157) polymorphisms GA/AA significantly correlated with distant metastasis (P=0.026), but not with prognosis. However, CXCL12 expression was not significantly associated with the tumor infiltration depth, lymphatic metastasis and grading. As CXCL12 polymorphisms mediate tumor cell dissemination in esophagogastric cancer, they could represent a marker indicating advanced disease. Antagonists targeting the CXCL12/ CXCR4 axis may be a novel therapeutic option in this entity.
    Keywords: Medicine;
    ISSN: 1019-6439
    E-ISSN: 17912423
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  • 6
    Language: English
    In: European Archives of Oto-Rhino-Laryngology, 2018, Vol.275(10), pp.2507-2513
    Description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s00405-018-5105-2 Byline: Kerstin Stahr (1), Laura Holtmann (1), Anke Schluter (1), Friederike Kaster (1), Michael Oeverhaus (2), Stephan Lang (1), Anja Eckstein (2), Stefan Mattheis (1) Keywords: Graves' orbitopathy; Orbital decompression; Nasal airflow; Olfactory performance; Surgical outcome Abstract: Purpose To determine the influence of anatomical changes after orbital decompression to nasal function. Methods We examined postoperative nasal function after orbital decompression in patients with GO in a prospective study. 25 patients were enrolled between 2014 and 2016. Sense of smell (Sniffin' Test) and nasal airflow (anterior rhinomanometry) were tested pre- and 6 weeks postoperatively. In addition, postoperative incidence of sinus infections, persistent pressure pain, and infraorbital hypoesthesia were assessed by means of a questionnaire. Results The olfactory performance showed a significant increase (p〈0.05) after surgery, while the nasal airflow significantly decreased (p〈0.05). Acute sinus infection occurred in three, infraorbital sensibility disorders in eight cases within the first 6 weeks after surgery. No persistent pain was recorded. Conclusion We demonstrate that decompression of the medial orbital wall leads to a decrease in nasal airflow, whereof patients should be informed before the procedure. This is most likely due to a medialization of the medial turbinate and the prolapse of orbital content into the nasal cavity. The increase of the olfactory performance is, in our opinion, more likely due to variation within the standard deviation than to anatomical changes. Author Affiliation: (1) 0000 0001 0262 7331, grid.410718.b, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany (2) 0000 0001 0262 7331, grid.410718.b, Department of Ophthalmology, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany Article History: Registration Date: 21/08/2018 Received Date: 08/06/2018 Accepted Date: 21/08/2018 Online Date: 30/08/2018
    Keywords: Graves’ orbitopathy ; Orbital decompression ; Nasal airflow ; Olfactory performance ; Surgical outcome
    ISSN: 0937-4477
    E-ISSN: 1434-4726
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  • 7
    In: Medicine, 2016, Vol.95(38), pp.e4602-e4602
    Description: ABSTRACT: We aimed to validate the liver fibrosis index FIB-4 as a model for risk stratification of hepatocellular carcinoma development in predominantly non-Asian patients with chronic hepatitis B infection seen at a tertiary referral center in Germany.We retrospectively analyzed 373 adult patients with chronic hepatitis B infection. Patient demographics, hepatitis B markers, antiviral treatment, laboratory parameters, results from liver imaging and histology were recorded. Patients were divided into 2 groups according to their FIB-4 levels and their hazard ratios for developing hepatocellular carcinoma were analyzed adjusted for age, sex, body mass index, alcohol consumption, and antiviral medication.Median follow-up was 8.7 years (range 1–21.3 years), 93% of patients were of non-Asian origin, and 64% were male. Compared with patients with a low FIB-4 (〈1.25) patients with FIB-4 ≥1.25 showed a hazard ratio for incidence of hepatocellular carcinoma of 3.03 (95% confidence interval (CI): 1.24–7.41) and an adjusted hazard ratio of 1.75 (95% CI: 0.64–4.74). Notably, 68% of patients with liver cirrhosis and 68% of those who developed HCC during observation had a low FIB-4 (〈1.25).We could not confirm that a FIB-4 value ≥1.25 is a reliable clinical indicator for incidence of hepatocellular carcinoma in predominantly non-Asian patients with chronic hepatitis B. Further studies in geographically and ethnically diverse populations are needed to prove its utility as a predictive tool.
    Keywords: Medicine;
    ISSN: 0025-7974
    E-ISSN: 15365964
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  • 8
    Language: English
    In: Experimental Hematology, September 2016, Vol.44(9), pp.S51-S52
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.exphem.2016.06.073 Byline: Friederike Herbst, Tonio Lang, Elias Eckert, Shayda Hemmati, Peer Wunsche, Oksana Zavidij, Manfred Schmidt, Claudia Ball, Hanno Glimm Author Affiliation: (1) Department of Translational Oncology, Heidelberg, Germany (2) National Center for Tumor Diseases (NCT), Heidelberg, Germany (3) German Cancer Research Center (DKFZ), Heidelberg, Germany Article Note: (miscellaneous) 2034
    Keywords: Medicine
    ISSN: 0301-472X
    E-ISSN: 1873-2399
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  • 9
    Language: English
    In: World journal of cardiology, 26 April 2014, Vol.6(4), pp.183-95
    Description: To investigate molecular phenotypes of myocardial B19V-infection to determine the role of B19V in myocarditis and dilated cardiomyopathy (DCM). Endomyocardial biopsies (EMBs) from 498 B19V-positive patients with myocarditis and DCM were analyzed using molecular methods and functional experiments. EMBs were obtained from the University Hospitals of Greifswald and Tuebingen and additionally from 36 German cardiology centers. Control tissues were obtained at autopsy from 34 victims of accidents, crime or suicide. Identification of mononuclear cell infiltrates in EMBs was performed using immunohistological staining. Anti-B19V-IgM and anti-B19V-IgG were analyzed by enzyme-linked immunosorbent assay (ELISA). B19V viral loads were determined using in-house quantitative real-time polymerase chain reaction (PCR). For B19V-genotyping a new B19V-genotype-specific restriction fragment length polymorphism (RFLP)-PCR was established. B19V-genotyping was verified by direct DNA-sequencing and sequences were aligned using BLAST and BioEdit software. B19V P6-promoter and HHV6-U94-transactivator constructs were generated for cell culture experiments. Transfection experiments were conducted using human endothelial cells 1. Luciferase reporter assays were performed to determine B19V-replication activity. Statistical analysis and graphical representation were calculated using SPSS and Prism5 software. The prevalence of B19V was significantly more likely to be associated with inflammatory cardiomyopathy (iCMP) compared to uninflamed DCM (59.6% vs 35.3%) (P 〈 0.0001). The detection of B19V-mRNA replication intermediates proved that replication of B19V was present. RFLP-PCR assays showed that B19V-genotype 1 (57.4%) and B19V-genotype 2 (36.7%) were the most prevalent viral genotypes. B19V-genotype 2 was observed more frequently in EMBs with iCMP (65.0%) compared to DCM (35%) (P = 0.049). Although there was no significant difference in gender-specific B19V-loads, women were more frequently infected with B19V-genotype 2 (44.6%) than men (36.0%) (P = 0.0448). Coinfection with B19V and other cardiotropic viruses was found in 19.2% of tissue samples and was associated with higher B19V viral load compared to B19V-monoinfected tissue (P = 0.0012). The most frequent coinfecting virus was human herpes virus 6 (HHV6, 16.5%). B19V-coinfection with HHV6 showed higher B19V-loads compared to B19V-monoinfected EMBs (P = 0.0033), suggesting that HHV6 had transactivated B19V. In vitro experiments confirmed a 2.4-fold increased B19V P6-promoter activity by the HHV6 U94-transactivator. The finding of significantly increased B19V loads in patients with histologically proven cardiac inflammation suggests a crucial role of B19V-genotypes and reactivation of B19V-infection by HHV6-coinfection in B19V-associated iCMP. Our findings suggest that B19V-infection of the human heart can be a causative event for the development of an endothelial cell-mediated inflammatory disease and that this is related to both viral load and genotype.
    Keywords: B19v Co-Infection ; B19v-Genotypes ; Dilated Cardiomyopathy ; Myocarditis ; Parvovirus B19
    ISSN: 1949-8462
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  • 10
    In: European Journal of Cardio-Thoracic Surgery, 2015, Vol. 47(6), pp.1013-1021
    Description: OBJECTIVES: Current materials for closure of cardiac defects such as ventricular septal defects (VSDs) are associated with compliance mismatch and a chronic inflammatory response. Bacterial nanocellulose (BNC) is a non-degradable biomaterial with promising properties such as high mechanical strength, favourable elasticity and a negligible inflammatory reaction. The aim of this study was the evaluation of a BNC patch for VSD closure and the investigation of its in vivo biocompatibility in a chronic pig model.METHODS: Young's modulus and tensile strength of BNC patches were determined before and after blood exposure. Muscular VSDs were created and closed with a BNC patch on the beating heart in an in vivo pig model. Hearts were explanted after 7, 30 or 90 days. Macropathology, histology and immunohistochemistry were performed.RESULTS: Young's modulus and tensile strength of the BNC patch decreased after blood contact from 6.3 ± 1.9 to 3.86 ± 2.2 MPa (P 〈 0.01) and 0.33 ± 0.06 to 0.26 ± 0.06 MPa (P 〈 0.01), respectively, indicating the development of higher elasticity. Muscular VSDs were closed with a BNC patch without residual shunting. After 90 days, a mild chronic inflammatory reaction was present. Moreover, there was reduced tissue overgrowth in comparison with polyester. Proceeding cellular organization characterized by fibromuscular cells, production of extracellular matrix, neoangiogenesis and complete neoendothelialization were found. There were no signs of thrombogenicity.CONCLUSIONS: BNC patches can close VSDs with good mid-term results and its biocompatibility can be considered as satisfactory. Its elasticity increases in the presence of blood, which might be advantageous. Therefore, it has potential to be used as an alternative patch material in congenital heart disease.
    Keywords: Ventricular Septal Defects ; Patch Material ; Biomaterial ; Biocompatibility
    ISSN: 1010-7940
    E-ISSN: 1873-734X
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