Straubing, Germany
Straubing, Germany

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Kaufmann S.G.,Universitatsklinikum Wurzburg | Westenbroek R.E.,University of Washington | Maass A.H.,University of Groningen | Lange V.,Hospital St Raphael | And 9 more authors.
Journal of Molecular and Cellular Cardiology | Year: 2013

Voltage-gated sodium channels composed of a pore-forming α subunit and auxiliary β subunits are responsible for the upstroke of the action potential in cardiac muscle. However, their localization and expression patterns in human myocardium have not yet been clearly defined. We used immunohistochemical methods to define the level of expression and the subcellular localization of sodium channel α and β subunits in human atrial myocytes. Nav1.2 channels are located in highest density at intercalated disks where β1 and β3 subunits are also expressed. Nav1.4 and the predominant Nav1.5 channels are located in a striated pattern on the cell surface at the z-lines together with β2 subunits. Nav1.1, Nav1.3, and Nav1.6 channels are located in scattered puncta on the cell surface in a pattern similar to β3 and β4 subunits. Nav1.5 comprised approximately 88% of the total sodium channel staining, as assessed by quantitative immunohistochemistry. Functional studies using whole cell patch-clamp recording and measurements of contractility in human atrial cells and tissue showed that TTX-sensitive (non-Nav1.5) α subunit isoforms account for up to 27% of total sodium current in human atrium and are required for maximal contractility. Overall, our results show that multiple sodium channel α and β subunits are differentially localized in subcellular compartments in human atrial myocytes, suggesting that they play distinct roles in initiation and conduction of the action potential and in excitation-contraction coupling. TTX-sensitive sodium channel isoforms, even though expressed at low levels relative to TTX-sensitive Nav1.5, contribute substantially to total cardiac sodium current and are required for normal contractility. This article is part of a Special Issue entitled "Na+ Regulation in Cardiac Myocytes". © 2013 Elsevier Ltd.

Brookman-May S.,University of Regensburg | Kendel F.,Charité - Medical University of Berlin | Hoschke B.,Carl Thiem Hospital Cottbus | Wieland W.F.,University of Regensburg | And 3 more authors.
Scandinavian Journal of Urology and Nephrology | Year: 2011

Objective. This study evaluated the impact of body mass index (BMI) and the influence of preoperative weight loss (WL) in each BMI category on survival in patients with surgically treated renal cell carcinoma (RCC). Material and methods. In total, 834 patients undergoing nephrectomy for RCC were retrospectively reviewed. Overall survival (OS) and cancer-specific survival (CSS) were estimated by Kaplan-Meier analysis. Univariate and multivariate analyses were accomplished to assess the influence of preoperatively assessed clinical parameters, including BMI and WL, on survival. The mean postsurgical follow-up was 85 months (median 79 months, range 12-191 months). Results. Of the patients studied, 251 (30%) presented with a BMI < 25 kg/m, while 362 patients (44%) were overweight (BMI ≥ 25 to < 30 kg/m) and 221 patients (26%) were obese (BMI ≥ 30 kg/m). Fifty-two patients (6.2%) experienced WL. While BMI did not significantly influence OS and CSS, WL had a significant impact on survival in patients with a BMI < 30 kg/m, in contrast to obese patients presenting with a BMI of ≥30 kg/m. Further analysis showed overweight to influence significantly disorders in wound healing, but neither other complications nor postoperative mortality. Conclusions. This is the first study providing information regarding the influence of BMI in relation to WL in patients with surgically treated RCC. While BMI did not significantly influence the survival of patients in the present series, WL had a significant impact on survival of patients presenting with a BMI < 30 kg/m. Hence, preoperative assessment of WL should be considered for the assessment of individual prognosis. © 2011 Informa Healthcare.

Maurer J.,University of Regensburg | Hipp M.,University of Regensburg | Schafer C.,Hospital St Elisabeth Straubing | Kolbl O.,University of Regensburg
Strahlentherapie und Onkologie | Year: 2011

Background: In the past, xerostomia was considered one of the most important determining factors of quality of life (QoL) after radiotherapy (RT) of the head and neck region. In addition, more recent studies have shown that RT-induced dysphagia has an essential influence on the QoL. Patients and Methods: Between September 2005 and August 2007, 35 patients with locally advanced squamous cell carcinoma of the head and neck region were included in the prospective study. Patients were treated by IMAT (intensity-modulated arc therapy) or IMRT (intensity-modulated radiotherapy) planned on 3D imaging. A total of 28 patients (80%) received concomitant chemotherapy. The evaluation of QoL (EORTC QLQ - C30, H&N C-35) and toxicities (CTC 2.0) were assessed at the beginning of, during, and after RT as well as up to 12 months after the end of therapy. Results: At the end of therapy, 86% of the patients experienced difficulties in swallowing (62% CTC II-III°). Twelve months after the end of treatment, 15% still suffered from dysphagia CTC II-III°. Concomitant chemotherapy exacerbated the incidence and gravity of dysphagia, resulting in increasing dietary problems. QoL (EORTC) was significantly affected by dysphagia. In particular, the global state of health and QoL were influenced at the end of treatment (p = 0.033) and at a later stage (p = 0.050). Conclusion: The findings of this study suggest that more emphasis should be placed on structured clinical diagnostics, therapy, and rehabilitation of deglutition problems. This means in particular to not only spare the parotids while planning the irradiation, but also to take into consideration the important structures for deglutition, like the retropharyngeal muscles. © 2011 Urban & Vogel.

Maurer J.,University of Regensburg | Schafer C.,Hospital St Elisabeth Straubing | Maurer O.,University of Regensburg | Kolbl O.,University of Regensburg
Strahlentherapie und Onkologie | Year: 2012

Background. Undergoing radiotherapy is often associated with severe impairment of quality of life in cancer patients. Especially psychosocial aspects like anxiety and depression play a major role. The aim of this study was to closely analyze anxiety and depression during the course of radiotherapy treatment.Methods. A total of 60 patients, who received radiotherapy because of a tumor disease between June 2005 and April 2006, were included in the prospective study; 57 (95%) patients were primarily treated with radiotherapy. In 72% of the cases the intention to treat was curable, in 18% palliative. Anxiety and depression (HADS-D) were assessed at three points in time: before (A) and after (B) radiotherapy treatment (RT), and 6 weeks after finishing RT at the follow-up appointment (C).Results. Before therapy (A), 41% of the treated patients showed positive or marginally positive symptoms of anxiety and 33% symptoms of depression. The symptoms of anxiety significantly decreased during the course of therapy. The proportion of patients with a positive score of anxiety dropped from 16% at the beginning of RT (A) to 9% after the RT (B; p=0.04). In addition, there was an increase in the number of patients who scored negatively with regard to anxiety from 59% (A) to 72% (B; p=0.04). With regard to the median score of anxiety, no statistically significant change (p<0.05) was observed during therapy, while for depression, the number of positively tested patients also decreased significantly during the course of therapy from the beginning of RT (A, 14%) to the first follow-up appointment (C, 9%; p=0.02). Furthermore, the number of negatively tested patients rose by 8% (p=0.02). During the whole course of the study, the median score of depression decreased from 6 (A) to 5 points (C; p=0.01).Conclusion. More than one third of the treated patients suffered from positive or marginally positive symptoms of anxiety and depression. This present study showed a decrease of anxiety and depression symptoms during the course of radiotherapy. © Springer-Verlag 2012.

Westenbroek R.E.,University of Washington | Bischoff S.,Universitatsklinikum Wurzburg | Fu Y.,University of Washington | Maier S.K.G.,Universitatsklinikum Wurzburg | And 3 more authors.
Journal of Molecular and Cellular Cardiology | Year: 2013

Voltage-gated sodium channels are responsible for the rising phase of the action potential in cardiac muscle. Previously, both TTX-sensitive neuronal sodium channels (NaV1.1, NaV1.2, NaV1.3, NaV1.4 and NaV1.6) and the TTX-resistant cardiac sodium channel (NaV1.5) have been detected in cardiac myocytes, but relative levels of protein expression of the isoforms were not determined. Using a quantitative approach, we analyzed z-series of confocal microscopy images from individual mouse myocytes stained with either anti-NaV1.1, anti-NaV1.2, anti-NaV1.3, anti-NaV1.4, anti-NaV1.5, or anti-NaV1.6 antibodies and calculated the relative intensity of staining for these sodium channel isoforms. Our results indicate that the TTX-sensitive channels represented approximately 23% of the total channels, whereas the TTX-resistant NaV1.5 channel represented 77% of the total channel staining in mouse ventricular myocytes. These ratios are consistent with previous electrophysiological studies in mouse ventricular myocytes. NaV1.5 was located at the cell surface, with high density at the intercalated disc, but was absent from the transverse (t)-tubular system, suggesting that these channels support surface conduction and inter-myocyte transmission. Low-level cell surface staining of NaV1.4 and NaV1.6 channels suggest a minor role in surface excitation and conduction. Conversely, NaV1.1 and NaV1.3 channels are localized to the t-tubules and are likely to support t-tubular transmission of the action potential to the myocyte interior. This quantitative immunocytochemical approach for assessing sodium channel density and localization provides a more precise view of the relative importance and possible roles of these individual sodium channel protein isoforms in mouse ventricular myocytes and may be applicable to other species and cardiac tissue types. © 2013 Elsevier Ltd.

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