Schlampp I.,University of Heidelberg |
Karger C.P.,German Cancer Research Center |
Jakel O.,German Cancer Research Center |
Jakel O.,University of Heidelberg |
And 10 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2011
Purpose: To identify predictors for the development of temporal lobe reactions (TLR) after carbon ion radiation therapy (RT) for radiation-resistant tumors in the central nervous system and to evaluate the predictions of the local effect model (LEM) used for calculation of the biologically effective dose. Methods and Materials: This retrospective study reports the TLR rates in patients with skull base chordomas and chondrosarcomas irradiated with carbon ions at GSI, Darmstadt, Germany, in the years 2002 and 2003. Calculation of the relative biological effectiveness and dose optimization of treatment plans were performed on the basis of the LEM. Clinical examinations and magnetic resonance imaging (MRI) were performed at 3, 6, and 12 months after RT and annually thereafter. Local contrast medium enhancement in temporal lobes, as detected on MRI, was regarded as radiation-induced TLR. Dose-volume histograms of 118 temporal lobes in 59 patients were analyzed, and 16 therapy-associated and 2 patient-associated factors were statistically evaluated for their predictive value for the occurrence of TLR. Results: Median follow-up was 2.5 years (range, 0.3 - 6.6 years). Age and maximum dose applied to at least 1 cm3 of the temporal lobe (Dmax,V - 1 cm3, maximum dose in the remaining temporal lobe volume, excluding the volume 1 cm3 with the highest dose) were found to be the most important predictors for TLR. Dose response curves of Dmax,V - 1 cm3 were calculated. The biologically equivalent tolerance doses for the 5% and 50% probabilities to develop TLR were 68.8 ± 3.3 Gy equivalents (GyE) and 87.3 ± 2.8 GyE, respectively. Conclusions: Dmax,V - 1 cm3 is predictive for radiation-induced TLR. The tolerance doses obtained seem to be consistent with published data for highly conformal photon and proton irradiations. We could not detect any clinically relevant deviations between clinical findings and expectations based on predictions of the LEM. © 2011 Elsevier Inc.
Hoffmann P.,Kliniken Essen Mitte |
Sturm A.,Charite Medical School Campus Virchow Clinic |
Stein J.,Elisabethen Hospital |
Dignass A.U.,Markus Hospital
Regulatory Peptides | Year: 2011
Introduction: Interferon γ (IFN γ) has been originally identified by its anti-viral activity and has been demonstrated to act as potent modulator of the immune system with a range of target cells limited largely to immune cell populations. Although IFN γ has been shown to directly affect the barrier function of intestinal epithelial cells, only limited information is available about other functional effects of IFN γ on intestinal epithelial cells. Methods: The effects on intestinal epithelial cell migration were studied using a previously described in-vitro model of epithelial restitution in confluent IEC-6 cell monolayers. Intestinal epithelial cell proliferation rates were assessed in various human and rat intestinal and colon epithelial cell lines using colorimetric MTT assays. Apoptosis of IEC-6 cells exposed to IFN γ was assessed by flow cytometry. In addition, transforming growth factor β mRNA expression after IFN γ treatment of IEC-6 cells was assessed by Northern blot analysis. Results: IFN γ significantly stimulated intestinal epithelial cell migration in an in-vitro wounding model. Furthermore, IFN γ caused a significant dose-dependent inhibition of epithelial cell proliferation in non-transformed small intestinal IEC-6 cells and human colon cancer-derived HT-29 cells and no significant rates of apoptosis were detected in the exposed epithelial cells. The effect of IFN γ on epithelial cell migration and proliferation could be completely blocked by neutralizing antibodies against TGF γ indicating that these effects are mediated through a TGFβ dependent pathway. In addition, increased expression of TGF γ1 mRNA by IEC-6 cells after treatment with IFN γ supports the hypothesis that IFN γ modulates intestinal epithelial cell function through a TGF γ-dependent pathway. Conclusion: These studies suggest that IFN γ produced by constituents of the mucosal immune system modulates epithelial cell functions with relevance for intestinal wound healing and may play a role in preserving the integrity of the intestinal epithelium following various forms of injuries. © 2011 Elsevier B.V.
Reuter K.C.,Goethe University Frankfurt |
Loitsch S.M.,Goethe University Frankfurt |
Dignass A.U.,Markus Hospital |
Steinhilber D.,Goethe University Frankfurt |
And 2 more authors.
PLoS ONE | Year: 2012
Introduction: Despite the excellent anti-inflammatory and immunosuppressive action of glucocorticoids (GCs), their use for the treatment of inflammatory bowel disease (IBD) still carries significant risks in terms of frequently occurring severe side effects, such as the impairment of intestinal tissue repair. The recently-introduced selective glucocorticoid receptor (GR) agonists (SEGRAs) offer anti-inflammatory action comparable to that of common GCs, but with a reduced side effect profile. Methods: The in vitro effects of the non-steroidal SEGRAs Compound A (CpdA) and ZK216348, were investigated in intestinal epithelial cells and compared to those of Dexamethasone (Dex). GR translocation was shown by immunfluorescence and Western blot analysis. Trans-repressive effects were studied by means of NF-κB/p65 activity and IL-8 levels, trans-activation potency by reporter gene assay. Flow cytometry was used to assess apoptosis of cells exposed to SEGRAs. The effects on IEC-6 and HaCaT cell restitution were determined using an in vitro wound healing model, cell proliferation by BrdU assay. In addition, influences on the TGF-β- or EGF/ERK1/2/MAPK-pathway were evaluated by reporter gene assay, Western blot and qPCR analysis. Results: Dex, CpdA and ZK216348 were found to be functional GR agonists. In terms of trans-repression, CpdA and ZK216348 effectively inhibited NF-κB activity and IL-8 secretion, but showed less trans-activation potency. Furthermore, unlike SEGRAs, Dex caused a dose-dependent inhibition of cell restitution with no effect on cell proliferation. These differences in epithelial restitution were TGF-β-independent but Dex inhibited the EGF/ERK1/2/MAPK-pathway important for intestinal epithelial wound healing by induction of MKP-1 and Annexin-1 which was not affected by CpdA or ZK216348. Conclusion: Collectively, our results indicate that, while their anti-inflammatory activity is comparable to Dex, SEGRAs show fewer side effects with respect to wound healing. The fact that SEGRAs did not have a similar effect on cell restitution might be due to a different modulation of EGF/ERK1/2 MAPK signalling. © 2012 Reuter et al.
Senf B.,Markus Hospital |
Senf B.,Goethe University Frankfurt |
Brandt H.,Goethe University Frankfurt |
Dignass A.,Markus Hospital |
And 2 more authors.
Supportive Care in Cancer | Year: 2010
Purpose: The identification of psychosocial stress in cancer patients has remained a challenging task especially in an acute care environment. The aims of the present study were to apply a short expert rating scale for the assessment of distress during the acute treatment phase and to identify potential sociodemographic and disease-related predictors. Methods: Four hundred seventy-eight ward cancer patients were assessed with the short form of the psycho-oncological basis documentation and its breast-cancer-specific version. In addition, they completed a self-rating questionnaire on stress in cancer patients. We recorded sociodemographic and disease-related variables and assessed their predictive value for psychosocial distress. Results: According to the expert rating scale, 56.3% of patients were rated distressed. While only 31.3% of patients were classified as distressed according to a patient selfrating, both approaches showed a good degree of concurrence with a consistent classification of 69% of patients. Younger age, current psychotropic medication, and past psychological treatment were associated with higher distress levels. Patients with metastases and those with a poorer functional status were more distressed. Interestingly, having an operation was associated with a better psychological well-being. Conclusions: This study demonstrated that a substantial proportion of cancer patients in acute care are psychosocially distressed. A short expert rating scale proved to be a feasible tool for the assessment of distress in an acute care setting. © Springer-Verlag 2010.
Frommer K.W.,Justus Liebig University |
Schaffler A.,Justus Liebig University |
Rehart S.,Markus Hospital |
Lehr A.,Markus Hospital |
And 2 more authors.
Annals of the Rheumatic Diseases | Year: 2014
Objectives: Due to their role in inflammatory metabolic diseases, we hypothesised that free fatty acids (FFA) are also involved in inflammatory joint diseases. To test this hypothesis, we analysed the effect of FFA on synovial fibroblasts (SF), human chondrocytes and endothelial cells. We also investigated whether the toll-like receptor 4(TLR4), which can contribute to driving arthritis, is involved in FFA signalling.Methods: Rheumatoid arthritis SF, osteoarthritis SF, psoriatic arthritis SF, human chondrocytes and endothelial cells were stimulated in vitro with different FFA. Immunoassays were used to quantify FFA-induced protein secretion. TLR4 signalling was inhibited extracellularly and intracellularly. Fatty acid translocase (CD36), responsible for transporting long-chain FFA into the cell, was also inhibited.Results: In rheumatoid arthritis synovial fibroblasts (RASF), FFA dose-dependently enhanced the secretion of the proinflammatory cytokine IL-6, the chemokines IL-8 and MCP-1, as well as the matrix-degrading enzymes pro-MMP1 and MMP3. The intensity of the response was mainly dependent on the patient rather than on the type of disease. Both saturated and unsaturated FFA showed similar effects on RASF, while responses to the different FFA varied for human chondrocytes and endothelial cells. Extracellular and intracellular TLR4 inhibition as well as fatty acid transport inhibition blocked the palmitic acid-induced IL-6 secretion of RASF.Conclusions: The data show that FFA are not only metabolic substrates but may also directly contribute to articular inflammation and degradation in inflammatory joint diseases. Moreover, the data suggest that, in RASF, FFA exert their effects via TLR4 and require extracellular and intracellular access to the TLR4 receptor complex.
Sohn M.,Markus Hospital |
Hatzinger M.,Markus Hospital |
Goldstein I.,Alvarado Hospital |
Krishnamurti S.,Andromeda Andrology Center
Journal of Sexual Medicine | Year: 2013
Introduction. The impact of penile blood supply on erectile function was recognized some 500 years ago. At the turn of the 20th century first results of penile venous ligation were published and in 1973 the first surgical attempts to restore penile arterial inflow were undertaken. Numerous techniques were published in the meantime, but inclusion criteria, patient selection, and success evaluation differed extremely between study groups. Aim. To develop evidence-based standard operating procedures (SOPs) for vascular surgery in erectile dysfunction, based on recent state of the art consensus reports and recently published articles in peer-reviewed journals. Methods. Based on the recent publication of the consensus process during the 2009 International Consultation on Sexual Medicine in Paris, recommendations are derived for diagnosis and surgical treatment of vascular erectile dysfunction. In addition several recent publications in this field not mentioned in the consensus statements are included in the discussion. Main Outcome Measure. The Oxford system of evidence-based review was systematically applied. Due to the generally low level of evidence in this field expert opinions were accepted, if published after a well-defined consensus process in peer-reviewed journals. Results. Referring to penile revascularization it may be concluded, that in the face of missing randomized trials, only recommendations grade D may be given: this kind of surgery may be offered to men less than 55 years, who are nonsmokers, nondiabetic, and demonstrate isolated arterial stenoses in the absence of generalized vascular disease. The evidence level for recommendations concerning penile venous ligations may be even lower. Too many unsolved controversies exist and universal diagnostic criteria for patient selection as well as operative technique selection have not been unequivocally established. This kind of surgery is still considered investigational but may be offered in special situations on an individualized basis in an investigational or research setting after obtaining written consent, using both pre- and postoperatively validated measuring instruments of success evaluation. Conclusions. SOPs for penile revascularization procedures can be developed, concerning a highly selected patient group with isolated arterial stenoses. Based on the available data it is not yet possible to define SOPs for surgical treatment of corporal veno-occlusive dysfunction. © 2012 International Society for Sexual Medicine.
Hatzinger M.,Markus Hospital |
Voge D.,Markus Hospital |
Stastny M.,Markus Hospital |
Moll F.,Cologne Medical Center at Holweide Hospital |
Sohn M.,Markus Hospital
Journal of Sexual Medicine | Year: 2012
Introduction. The phenomenon of castration is very closely associated with the baroque era. In a period that placed emphasis on pure sensual pleasure, castrati singers, with their angelic voices, were a perverted outcome of this ambition. It was the intention that these castrato voices with their supernatural sound would mesmerize audiences. At that time, it could be said that within certain society circles, an addiction to these voices existed. Equally, they were oblivious to the spiritual side of the lives of the castrati. Farinelli, Caffarelli, and Senesino, three of the most famous castrati, were the first musical superstars of the 18th century. Their voices moved decadent audiences to tears and standing ovations. The price for this fame was, however, high. Aim. The aim of this review is to provide an overview of castrati singers, especially in the baroque era, their sexuality and the effects of castration on their physical development. Methods. A literature search of relevant databases, books, and articles in journals was performed and compared with current data concerning androgen suppression and endocrine aspects of male sexual dysfunction. Results. The effects of castration on physical development were notoriously erratic. Much depended on the timing of the operation: boys pruned before the age of 10 or so very often grew up with feminine features; smooth, hairless bodies, incipient breasts, infantile penis, and often a complete lack of sex drive. Conclusion. The peak success of the castrati ended with the end of the 18th century. The last castrato was Alessandro Moreschi, a solo singer in the choir of the Sistine Chapel of the Vatican. Following the ban on castration, Pope Pius X sent him into retirement in 1912, thus putting an end to a very impressive part of the history of music. © 2012 International Society for Sexual Medicine.
PubMed | Markus Hospital
Type: | Journal: Circulation journal : official journal of the Japanese Circulation Society | Year: 2016
Clinical outcome after pulmonary vein isolation (PVI) may be linked to both durability of PVI and the antral lesion size. Data on balloon-guided technologies are scarce. We investigated the size of the isolated surface area (ISA) acutely after PVI achieved by cryoballoon (CB) or laser balloon (LB), both using voltage mapping.MethodsandResults:In 40 patients (73% male, mean age 669 years), a bipolar voltage map before and after PVI in sinus rhythm was acquired to delineate the isolated antral surface area (IASA, contiguous area of low voltage <0.5 mV) and the ISA (relative size of the low-voltage area in relation to the whole antral surface area including the posterior wall). IASA (CB: 5714 cmBalloon-guided PVI is associated with antral lesion formation. CB-guided PVI is associated with the largest ISA as compared with LB procedures. ISA size did not correlate with clinical outcome after a single procedure in the present study population.
Hatzinger M.,Markus Hospital
AMHA - Acta Medico-Historica Adriatica | Year: 2013
The early and unexpected death of Wolfgang Amadeus Mozart (Salzburg, 1756 - Vienna, 1791) was a mystery from the very first day and the subject of wildest speculations and adventurous assertions. Over the last 100 years, medical science has investigated the physical sufferings and the mysterious death of Mozart with increasing intensity. The aim of this article was to recreate Mozart's pathography relying on the his correspondence with father Leopold and sister Nannerl and on reports from his physicians and contemporaries. The rumour that Mozart was poisoned followed shortly after his death on 5 December 1791, at the age of 35, and has survived to this day. The alleged culprits were his physician van Swieten, Mozart's freemasons lodge, and the Imperial Chapel Master Salieri. Mozart however died of chronic kidney disease and ultimately of uraemia. If kidney damage reaches a critical point, even a minimum additional stress can lead to its failure. This usually occurs in the fourth decade of life. Next time we listen to Mozart, we should remember that this apparently happy person was actually a precocious boy, ripped of his childhood, whose short life was an endless chain of complaints, fatigue, misery, concern, and malady.
PubMed | Markus Hospital, Friedrich - Alexander - University, Erlangen - Nuremberg and Justus Liebig University
Type: Journal Article | Journal: Joint, bone, spine : revue du rhumatisme | Year: 2016
Osteoarthritis is not only characterized by cartilage degradation but also involves subchondral bone remodeling and osteophyte formation. Osteophytes are fibrocartilage-capped bony outgrowths originating from the periosteum. The pathophysiology of osteophyte formation is not completely understood. Yet, different research approaches are under way. Therefore, a histological osteophyte classification to achieve comparable results in osteophyte research was established for application to basic science research questions.The osteophytes were collected from knee joints of osteoarthritis patients (n=10, 94 osteophytes in total) after joint replacement surgery. Their size and origin in the respective joint were photo-documented. To develop an osteophyte classification, serial tissue sections were evaluated using histological (hematoxylin and eosin, Massons trichrome, toluidine blue) and immunohistochemical staining (collagen type II).Based on the histological and immunohistochemical evaluation, osteophytes were categorized into four different types depending on the degree of ossification and the percentage of mesenchymal connective tissue. Size and localization of osteophytes were independent from the histological stages.This histological classification system of osteoarthritis osteophytes provides a helpful tool for analyzing and monitoring osteophyte development and for characterizing osteophyte types within a single human joint and may therefore contribute to achieve comparable results when analyzing histological findings in osteophytes.