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Köln, Germany

Linxweiler M.,Saarland University | Kadah B.A.,Saarland University | Bozzato A.,Saarland University | Bozzato V.,Saarland University | And 7 more authors.
European Archives of Oto-Rhino-Laryngology | Year: 2016

Confocal laser endomicroscopy (CLE) is an imaging technique that uses miniaturized fiberoptic probes to allow real-time histological imaging of human tissue. An application of CLE in otorhinolaryngology has hardly been investigated so far. In our study, we analyzed the applicability of CLE to visualize cancerous and healthy tissue of the head and neck region. Formalin-fixed tissue specimens from 135 head and neck squamous cell carcinoma (HNSCC) patients and 50 healthy controls were investigated using CLE with and without topical application of acriflavine. Four head and neck surgeons, four pathologists, and four laymen evaluated the CLE images of the HNSCC cases regarding the tumor localization and its border to healthy tissue. The tumor localization and the tumor border were correctly identified in 97 % by the pathologists, 85 % by the head and neck surgeons, and 70 % by the laymen. The main difference in evaluation results was seen in the correct identification of the tumor site (p < 0.05), while there was no significant difference in the identification of the tumor border. CLE is a valuable tool for real-time histological imaging of HNSCCs. It can help to visualize the tumor border and, thereby, facilitate a more precise tumor surgery. © 2016 Springer-Verlag Berlin Heidelberg Source

Warnke C.,Heinrich Heine University Dusseldorf | Stettner M.,Heinrich Heine University Dusseldorf | Lehmensiek V.,University of Ulm | Dehmel T.,Heinrich Heine University Dusseldorf | And 19 more authors.
Multiple Sclerosis | Year: 2015

Background: Natalizumab for multiple sclerosis (MS) increases the risk of progressive multifocal leukoencephalopathy (PML). Objective: We aimed to assess the effect of natalizumab on cellular composition and functional B cell parameters including patients with natalizumab-associated PML (n=37). Methods: Cellular composition by flow cytometry, levels of immunoglobulin (Ig)G/IgM by immunonephelometry, and oligoclonal bands by isoelectric focusing were studied in blood and cerebrospinal fluid. Results: In MS patients treated with natalizumab without PML (n=59) the proportion of CD19+ B cells was higher in blood, but lower in cerebrospinal fluid compared with MS patients not treated with natalizumab (n=17). The CD4/CD8-ratio in cerebrospinal fluid was lower, and IgG and IgM levels as well as the IgG index dropped in longitudinal samples during natalizumab therapy. Oligoclonal bands persisted, but the total amount of the intrathecally produced IgG fraction, and the polyclonal intrathecal IgG reactivity to measles, rubella, and zoster declined. At the time of diagnosis of PML patients with natalizumabassociated PML had low total IgG levels in blood and cerebrospinal fluid. Conclusions: Natalizumab impacts B and T cell distribution and exerts an inhibitory effect on surrogates of B cell function in periphery and in cerebrospinal fluid, potentially contributing to the increased risk of developing PML. Source

Warnke C.,Heinrich Heine University Dusseldorf | Von Geldern G.,U.S. National Institutes of Health | Markwerth P.,Heinrich Heine University Dusseldorf | Dehmel T.,Heinrich Heine University Dusseldorf | And 17 more authors.
Annals of Neurology | Year: 2014

Objective: Progressive multifocal leukoencephalopathy (PML), caused by JC virus (JCV), can occur in patients receiving natalizumab for multiple sclerosis (MS). JCV detection by quantitative polymerase chain reaction (qPCR) in cerebrospinal fluid (CSF), or brain biopsy, is required for probable or definite diagnosis of PML. However, in some patients only low levels of JCV DNA (<100 copies=ml) are present in CSF, making the diagnosis challenging. Our objective was to assess the complementary value of a CSF JCV antibody index (AIJCV) in the diagnosis of natalizumab-associated PMLMethods: AIJCV was assessed in 37 cases of natalizumab-associated PML and 89 MS-patients treated with natalizumab without PML. Sera and CSF were tested in a capture enzyme-linked immunosorbent assay, using JCV-VP1 fused to glutathione S-transferase as antigen. Albumin levels and total immunoglobulin G concentration were determined by immunonephelometry, and the AIJCV was calculated as publishedResults: Twenty-six of 37 (70%) patients with natalizumab-associated PML exhibited an AIJCV > 1.5, whereas this was seen in none of the controls (p < 0.0001). At time of the first positive qPCR for JCV DNA, 11 of 20 (55%) patients with natalizumab-associated PML had an AIJCV > 1.5. JCV DNA levels of <100 copies= ml were seen in 14 (70%) of these 20 patients, of whom 8 (57%) demonstrated an AIJCV > 1.5Interpretation: Determination of the AIJCV could be an added tool in the diagnostic workup for PML and should be included in the case definition of natalizumab-associated PML © 2014 American Neurological Association. Source

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