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Lübeck, Germany

Kertzscher G.,Technical University of Denmark | Andersen C.E.,Technical University of Denmark | Siebert F.-A.,UK SH | Nielsen S.K.,Aarhus University Hospital | And 3 more authors.
Radiotherapy and Oncology | Year: 2011

Background and purpose: The feasibility of a real-time in vivo dosimeter to detect errors has previously been demonstrated. The purpose of this study was to: (1) quantify the sensitivity of the dosimeter to detect imposed treatment errors under well controlled and clinically relevant experimental conditions, and (2) test a new statistical error decision concept based on full uncertainty analysis. Materials and methods: Phantom studies of two gynecological cancer PDR and one prostate cancer HDR patient treatment plans were performed using tandem ring applicators or interstitial needles. Imposed treatment errors, including interchanged pairs of afterloader guide tubes and 2-20 mm source displacements, were monitored using a real-time fiber-coupled carbon doped aluminum oxide (Al 2O 3:C) crystal dosimeter that was positioned in the reconstructed tumor region. The error detection capacity was evaluated at three dose levels: dwell position, source channel, and fraction. The error criterion incorporated the correlated source position uncertainties and other sources of uncertainty, and it was applied both for the specific phantom patient plans and for a general case (source-detector distance 5-90 mm and position uncertainty 1-4 mm). Results: Out of 20 interchanged guide tube errors, time-resolved analysis identified 17 while fraction level analysis identified two. Channel and fraction level comparisons could leave 10 mm dosimeter displacement errors unidentified. Dwell position dose rate comparisons correctly identified displacements ≥5 mm. Conclusion: This phantom study demonstrates that Al 2O 3:C real-time dosimetry can identify applicator displacements ≥5 mm and interchanged guide tube errors during PDR and HDR brachytherapy. The study demonstrates the shortcoming of a constant error criterion and the advantage of a statistical error criterion. © 2011 Elsevier Ireland Ltd. All rights reserved.

Szaszak M.,University of Lubeck | Steven P.,UK SH | Shima K.,University of Lubeck | Orzekowsky-Schroder R.,University of Lubeck | And 4 more authors.
PLoS Pathogens | Year: 2011

Chlamydia trachomatis is an obligate intracellular bacterium that alternates between two metabolically different developmental forms. We performed fluorescence lifetime imaging (FLIM) of the metabolic coenzymes, reduced nicotinamide adenine dinucleotides [NAD(P)H], by two-photon microscopy for separate analysis of host and pathogen metabolism during intracellular chlamydial infections. NAD(P)H autofluorescence was detected inside the chlamydial inclusion and showed enhanced signal intensity on the inclusion membrane as demonstrated by the co-localization with the 14-3-3β host cell protein. An increase of the fluorescence lifetime of protein-bound NAD(P)H [τ 2-NAD(P)H] inside the chlamydial inclusion strongly correlated with enhanced metabolic activity of chlamydial reticulate bodies during the mid-phase of infection. Inhibition of host cell metabolism that resulted in aberrant intracellular chlamydial inclusion morphology completely abrogated the τ 2-NAD(P)H increase inside the chlamydial inclusion. τ 2-NAD(P)H also decreased inside chlamydial inclusions when the cells were treated with IFNγ reflecting the reduced metabolism of persistent chlamydiae. Furthermore, a significant increase in τ 2-NAD(P)H and a decrease in the relative amount of free NAD(P)H inside the host cell nucleus indicated cellular starvation during intracellular chlamydial infection. Using FLIM analysis by two-photon microscopy we could visualize for the first time metabolic pathogen-host interactions during intracellular Chlamydia trachomatis infections with high spatial and temporal resolution in living cells. Our findings suggest that intracellular chlamydial metabolism is directly linked to cellular NAD(P)H signaling pathways that are involved in host cell survival and longevity. © 2011 Szaszak et al.

Magerl M.,Charite - Medical University of Berlin | Rother M.,X pert Med GmbH | Bieber T.,University of Bonn | Biedermann T.,University of Tubingen | And 16 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2013

Background Chronic spontaneous urticaria (CSU), a mast cell-driven condition, is debilitating, common, and hard to treat. Miltefosine, a lipid raft modulator, can inhibit mast cell responses in vivo. Objective To study the safety and efficacy of systemic miltefosine treatment in CSU patients resistant to standard-dosed antihistamines. Methods In this investigator-initiated multicentre, randomized, double-blind, placebo-controlled study, CSU patients were treated for 4 weeks with daily doses of up to 150-mg miltefosine (n = 47) or placebo (n = 26). Disease activity was assessed using the urticaria activity score. Safety and tolerability of miltefosine were also assessed. Results After 4 weeks of treatment, Urticaria Activity Score (UAS7) levels were substantially more reduced in miltefosine-treated patients (-6.3 vs. -3.5 in placebo-treated patients; P = 0.05). Also, the number of weals, but not the intensity of pruritus, was significantly reduced in miltefosine-treated patients vs. placebo-treated patients (P = 0.02). In general, adverse events were frequent in both groups (miltefosine: 88%, placebo: 65% of patients) but mostly mild to moderate in severity. We did not observe any serious adverse events. Conclusions The results of this study indicate that miltefosine is an effective and safe treatment option for CSU patients who do not respond to standard-dosed antihistamines. © 2012 European Academy of Dermatology and Venereology.

Pneumonia is a relevant cause of high rates of mortality and morbidity in immunocompromized patients. While most important microbial pathogens of community-acquired pneumonia in immunocompetent adult patients are well characterized according to data from the multicenter study of CAPNETZ, immunocompromized patients often show infections with different, rare and opportunistic microbial pathogens. Especially respiratory viruses should be taken into consideration. Immune suppression can result from HIV infection with depletion of CD4 lymphocytes, in patients with lymphoma, leukemia or solid tumors regarding aggressive cytostatic chemotherapy or transplantation or from immunosuppressive therapy in rheumatic or autoimmune diseases. The diagnosis of viral pneumonia is difficult because of atypical symptoms, unspecific changes in inflammatory blood parameters and several possible types of X-ray changes. This makes it even more important to have a clear proof of viral infection, such as molecular biological diagnostics from respiratory specimens prior to treatment with antiviral therapy, as antiviral therapy is known to possibly cause severe side effects and should thereby be considered carefully. © 2013 Springer-Verlag Berlin Heidelberg.

Cnyrim C.D.,UK SH | Kupsch A.,Charite - Medical University of Berlin | Ebersbach G.,Neurological Hospital for Movement Disorders | Hoffmann K.-T.,University of Leipzig
Neurodegenerative Diseases | Year: 2013

Background: Differentiation between Parkinson's disease (PD) and atypical Parkinson syndromes (AP) is usually based on clinical examination, but can be challenging especially at early stages of the diseases. Diffusion tensor imaging (DTI) allows for differentiation between PD and AP with good specificity. It is a promising tool for clinical application, but has not been elaborated completely with respect to methodology and validity. Objective: In this study we evaluated differences of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) within white brain matter between patients with PD and multisystem atrophy of the parkinsonian type (MSAp). Materials and Methods: DTI data of 9 PD and 9 MSAp patients were compared by means of a hypothesis-free whole-brain analysis algorithm (TBSS) focusing on changes within white matter. Results: We found significantly higher values of the ADC in the MSAp group in the anterior limb of the inner capsule, superior parts of the corona radiata, and lateral periputaminal white matter. Group differences in FA values were not significant. Conclusion: Changes of the ADC close to the putamen proved most consistent and seem to be promising for the ongoing clinical implementation of DTI for the differentiation of hypokinetic-rigid movement disorders. Copyright © 2013 S. Karger AG, Basel.

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