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Magerl M.,Charité - Medical University of Berlin | Rother M.,X pert Med GmbH | Bieber T.,University of Bonn | Biedermann T.,University of Tübingen | 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.

Greimel E.,Medical University of Graz | Nordin A.,Queen Elizabeth the Queen Mother Hospital | Lanceley A.,University College London | Creutzberg C.L.,Leiden University | And 15 more authors.
European Journal of Cancer | Year: 2011

Aim: A validation study was conducted to evaluate the psychometric properties of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Endometrial Cancer Module (EORTC QLQ-EN24). This module was designed to assess disease and treatment specific aspects of the quality of life (QoL) of patients with endometrial cancer. Methods: Two hundred and sixty-eight women with endometrial cancer were recruited in different phases of treatment: after pelvic surgery (Group 1); during adjuvant chemotherapy and/or radiotherapy (Group 2); after completion of treatment (Group 3). Patients completed the EORTC QLQ-C30, the endometrial cancer module and a short debriefing questionnaire. Results: Multi-trait scaling analyses confirmed the hypothesised scale structure of the QLQ-EN24. Internal consistency reliability was good with Cronbach's alpha coefficients ranging from 0.74 to 0.86 (lymphoedema 0.80, urological symptoms 0.75, gastrointestinal symptoms 0.74, body image problems 0.86 and sexual/vaginal problems 0.86). Convergent and discriminant validity did not show any scaling errors for the subscales. The QLQ-EN24 module discriminated well between clinically different groups of patients. All items exhibited a high completion rate with less than 2% missing values except for the sexuality items (19%). Conclusion: The validation study supports the reliability, the convergent and divergent validity of the EORTC QLQ-EN24. This newly developed QLQ-EN24 module is a useful instrument for the assessment of the QoL in patients treated for endometrial cancer in clinical trials. © 2010 Elsevier Ltd. All rights reserved.

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.

Schrader I.,Stadtisches Krankenhaus | Wilk D.,UK SH | Jansen O.,UK SH | Riedel C.,UK SH
RoFo Fortschritte auf dem Gebiet der Rontgenstrahlen und der Bildgebenden Verfahren | Year: 2013

Purpose: To evaluate how accurately final infarct volume in acute ischemic stroke can be predicted with perfusion CT (PCT) using a 64-MDCT unit and the toggling table technique. Materials and Methods: Retrospective analysis of 89 patients with acute ischemic stroke who underwent CCT, CT angiography (CTA) and PCT using the "toggling tableo" technique within the first three hours after symptom onset. In patients with successful thrombolytic therapy (n = 48) and in those without effective thrombolytic therapy (n = 41), the infarct volume and the volume of the penumbra on PCT were compared to the infarct size on follow-up images (CT or MRI) performed within 8 days. The feasibility of complete infarct volume prediction by 8 cm cranio-caudal coverage was evaluated. Results: The correlation between the volume of hypoperfusion on PCT defined by cerebral blood volume reduction and final infarct volume was strongest in patients with successful thrombolytic therapy with underestimation of the definite infarct volume by 8.5 ml on average. The CBV map had the greatest prognostic value. In patients without successful thrombolytic therapy, the final infarct volume was overestimated by 12.1 ml compared to the MTT map on PCT. All infarcts were detected completely. There were no false-positive or false-negative results. Conclusion: Using PCT and the "toggling tableo" technique in acute stroke patients is helpful for the rapid and accurate quantification of the minimal final infarct and is therefore a prognostic parameter which has to be evaluated in further studies to assess its impact on therapeutic decision. Key Points: Using PCT and the "toggling table techniqueo" allows accurate quantification of the infarct core and penumbra. It is possible to record dynamic perfusion parameters quickly and easily of almost the entire supratentorial brain volume on a 64-slice MDCT unit. The technique allows identification of those patients who could profit from thrombolytic therapy outside the established time intervals. Citation Format: Schrader I, Wilk D, Jansen O et al. Whole-Brain Perfusion CT Using a Toggling Table Technique to Predict Final Infarct Volume in Acute Ischemic Stroke. Fortschr Röntgenstr 2013; 185: 975-982. © Georg Thieme Verlag KG Stuttgart, New York.

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.,Charité - 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.

Szaszak M.,University of Lübeck | Steven P.,UK SH | Shima K.,University of Lübeck | Orzekowsky-Schroder R.,University of Lübeck | 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.

Acil Y.,UK SH | Gierloff M.,UK SH | Behrens C.,UK SH | Moller B.,UK SH | And 4 more authors.
Calcified Tissue International | Year: 2013

Radiotherapy can lead to a reduction of bone density with an increased risk of pathological fractures. Bisphosphonates may represent a preventive treatment option by increasing the density of anorganic bone mineral. Yet it is unknown how bisphosphonates act on irradiated collagen cross-links, which play an essential role for the mechanical stability of bone. The aim of this study was to evaluate the effects of zoledronate on bone collagens and their cross-links after irradiation. The right femur of 37 rats was irradiated with a single dose of 9.5 Gy at a high dose rate using an afterloading machine. Half of the rats (n = 18) received additionally a single dose zoledronate (0.1 mg/kg body weight). Fourteen and 100 days after irradiation the femora were collected for histologic evaluation and determination of the collagen cross-links lysylpyridinoline, hydroxylysylpyridinoline, and hydroxyproline. The collagen types were characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Fourteen days after treatment the lysylpyridinoline levels of all treatment groups were significantly lower compared to the untreated control. After 100 days, in the combined radiotherapy + zoledronate group significantly lower lysylpyridinoline values were determined (p = 0.009). Radiotherapy and/or zoledronate did not change significantly the level of hydroxylysylpyridinoline. The concentration of hydroxyproline was 14 days after irradiation significantly higher in the combined treatment group compared to the control. No significant differences were observed 100 days after treatment. Zoledronate does not have the ability to restore the physiological bone collagen cross-link levels after radiotherapy. However, this would be necessary for regaining the physiological mechanical stability of bone after irradiation and therefore to prevent effectively radiation-induced fractures. © 2012 Springer Science+Business Media New York.

PubMed | UK SH
Type: Journal Article | Journal: The Journal of cardiovascular surgery | Year: 2011

Doxorubicin-induced heart failure is a rare but serious illness due to the well-known treatment difficulties. Prevention strategies have not demonstrated the expected success and unfortunately, this specific type of heart failure does not respond well to the usual medical therapy as other kinds of heart failure. Therefore, surgical procedures may be necessary in some patients. Cardiac transplantation is performed in most cases but it requires the cure of the neoplastic disease. This usually requires a recurrence-free interval of several years which is associated with a high attrition rate in these patients due to their cardiac disease. Therefore, ventricular assist devices were implanted in selected patients. This review presents the most common procedures and discusses their efficacy as well as their clinical applicability.

PubMed | UK SH
Type: | Journal: BMJ case reports | Year: 2011

We present a case of dorsal cervical spinal cord injury in a 16-year-old boy caused by a screwdriver. Neurological deficits were hypaesthesia of the right body and neurovegetative functional deficits. Magnetic resonance imaging showed significant myelopathy and a subdural haematoma of the cervical spine. Surgical treatment was not necessary. Rheological infusions, lumbar puncture and rehabilitation resulted in full neurological recovery.

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