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PubMed | Internal Medicine, Ludwig Maximilians University of Munich, Cochin Hospital, University of Würzburg and 13 more.
Type: Journal Article | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2015

The clinical course of advanced adrenocortical carcinoma (ACC) is heterogeneous. Our study aimed primarily to refine and make headway in the prognostic stratification of advanced ACC.Patients with advanced ENSAT ACC (stage III or stage IV) at diagnosis registered between 2000 and 2009 in the ENSAT database were enrolled. The primary end point was overall survival (OS). Parameters of potential prognostic relevance were selected. Univariate and multivariate analyses were carried out: model 1 before surgery; model 2 post-surgery.Four hundred and forty-four patients with advanced ENSAT ACC (stage III: 210; stage IV: 234) were analyzed. After a median follow-up of 55.2 months, the median OS was 24 months. A modified ENSAT (mENSAT) classification was validated: stage III (invasion of surrounding tissues/organs or the vena renalis/cava) and stage IVa, IVb, IVc (2, 3 or >3 metastatic organs, including N, respectively). Two- or 5-year OS was 73%, 46%, 26% and 15% or 50%, 15%, 14% and 2% for stages III, IVa, IVb and IVc, respectively. In the multivariate analysis, mENSAT stages (stages IVa, IVb, or IVc, respectively) were significantly correlated with OS (P < 0.0001), as well as additional parameters: age 50 years (P < 0.0001), tumor- or hormone-related symptoms (P = 0.01 and 0.03, respectively) in model 1 but also the R status (P = 0.001) and Grade (Weiss >6 and/or Ki67 20%, P = 0.06) in model 2.The mENSAT classification and GRAS parameters (Grade, R status, Age and Symptoms) were found to best stratify the prognosis of patients with advanced ACC.


Monnig G.,University of Munster | Kobe J.,University of Munster | Loher A.,University of Munster | Wasmer K.,University of Munster | And 9 more authors.
Europace | Year: 2012

Aims The use of implantable cardioverter defibrillators (ICD) in patients with torsade de pointes (TdP) and ventricular fibrillation in the presence of acquired long QT syndrome (aLQTS) is under debate, partly due to the fact that aLQTS is potentially reversible and currently no long-term follow-up data are available. We aimed to evaluate the long-term follow-up of patients with acquired long QT syndrome (aLQTS) who had received an implantable cardioverter defibrillator (ICD) for secondary prevention of sudden cardiac arrest (SCA). Method and resultsOver a 10 year period, 43 patients with an ICD after survived cardiac arrest (SCA) due to an aLQTS were included [female n 27 (63%); mean age 61±16 years]. There was no clinical evidence for congenital LQTS (Schwartz score 1.25±0.8). Structural heart disease was present in 29 patients (47%; ischaemic n 13; dilated cardiomyopathy n 9; mean EF 41±12). The most common proarrhythmic trigger happened to be antiarrhythmic drugs (n 34; 79). Other triggers included contrast agent (n 1), haloperidol (n 2), severe hypokalaemia (n 2), drug abuse/alcohol (n 2), and mere severe bradycardia (n 2). Under trigger QTc interval measured 536±58 vs. 438±33 ms without trigger (P< 0.001). During a mean follow-up of 84 ± 55 months, appropriate shocks occurred in 19 patients (44%); inappropriate shocks in 13 patients (30; only inappropriate n 3). Appropriate shocks were almost as common in patients without as in those with structural heart disease (35 vs. 48%; P = 0.32). None of the patients were re-exposed to the initial trigger during the follow-up period. Beta-blocker medication did not prevent ICD shocks (12 of 19 vs. 11 of 24 on medication). ConclusionAppropriate ICD shocks are a common finding in patients with aLQTS and SCA irrespective of the underlying cause or structural heart disease. Thus, even in the presence of relevant acquired proarrhythmia ICD may be beneficial. © The Author 2011.


De Arellano M.L.B.,Endometriosis Research Center Berlin | Gericke J.,Endometriosis Research Center Berlin | Reichelt U.,Charit University Medicine Berlin | Okuducu A.F.,Breslauerstrasse | And 4 more authors.
Human Reproduction | Year: 2011

Background Smooth muscle cells (SMC) are common components of endometriotic lesions. SMC have been characterized previously in peritoneal, ovarian and deep infiltrating endometriotic lesions and adenomyosis. The aim of this retrospective study was to investigate the extent of differentiation in endometriosis-associated SMC (EMaSMC) in peritoneal endometriotic lesions. Methods We obtained biopsies from peritoneal endometriotic lesions (n = 60) and peritoneal sites distant from the endometriotic lesion (n = 60), as well as healthy peritoneum from patients without endometriosis (control tissue, n = 10). These controls were hysterectomy specimens from patients without endometriosis or adenomyosis. Histopathological examination of peritoneal specimens using antibodies against oxytocin receptor (OTR), vasopressin receptor (VPR), smooth muscle myosin heavy chain (SM-MHC), estrogen receptor (ER) or progesterone receptor (PR) was performed. To identify SMC and their level of differentiation, antibodies for smooth muscle actin desmin and caldesmon were used. Results SMC were detected in all endometriotic lesions. SMC were more abundant in unaffected peritoneum of women with endometriosis (38) compared with women without endometriosis (6; P < 0.0001). Depending on the level of differentiation, SMC stained for SM-MHC, OTR, VPR, ER and PR. OTR was only detected in fully differentiated SMC. Conclusions Identification of OTR, VPR, ER and PR leads to the hypothesis that the EMaSMC might be functionally active and possibly involved in the generation of pain associated with endometriosis. © 2011 The Author.


Haeusler K.G.,Charit University Medicine Berlin | Haeusler K.G.,Franklin University | Koch L.,Charit University Medicine Berlin | Ueberreiter J.,Franklin University | And 9 more authors.
Heart Rhythm | Year: 2011

Background Up to now there is little evidence about the safety and reliability of insertable cardiac monitors (ICMs) in patients undergoing magnetic resonance imaging (MRI). Objective The purpose of this prospective single-center study (MACPAF; clinicaltrials.gov NCT01061931), which we are currently performing, was to evaluate these issues for the ICM Reveal XT at a 3 Tesla MRI scanner in patients undergoing serial brain MRI. Methods We present an interim analysis including 62 brain MRI examinations in 24 patients with paroxysmal atrial fibrillation bearing the Reveal XT. All patients were interviewed for potential ICM-associated clinical symptoms during and after MRI examination. According to the study protocol, data from the Reveal XT were transmitted before and after the MRI examination. Results All patients were clinically asymptomatic during the MRI procedure. Moreover, the reliability (ability to detect signals, battery status) of the Reveal XT was unaffected, except for one MRI-induced artifact that was recorded by the ICM, mimicking a narrow complex tachycardia, as similarly recorded in a further study patient bearing the forerunner ICM Reveal DX. No loss of ICM data was observed after the MRI examination. Conclusions The 3 Tesla brain MRI scanning is safe for patients bearing the ICM Reveal XT and does not alloy reliability of the Reveal XT itself. MRI-induced artifacts occur rarely but have to be taken into account. © 2011 Heart Rhythm Society. All rights reserved.


Michaelis M.,Charit University Medicine Berlin | Michaelis M.,Leibniz Institute for Farm Animal Biology | Hofmann P.J.,Charit University Medicine Berlin | Gotz F.,Charit University Medicine Berlin | And 3 more authors.
Hormone and Metabolic Research | Year: 2012

A low-salt diet is known to decrease and salt excess to increase blood pressure in humans and rodents. Sex steroids seem to play a role in salt dependent hypertension. However, little is known about sex differences in mineralocorticoid receptor blockade between male and female rats. The objective of the work was at first to investigate the effects of a low-salt vs. a high-salt diet on blood pressure without the influence of gonadal steroids in male and female rats. Second, to determine the sex-specific effects of mineralocorticoid receptor blockade by spironolactone in high-salt and low-salt fed gonadectomized male and female animals. Normotensive male and female Wistar rats were gonadectomized and put on a low (NaCl<0.03%) or high (NaCl=4%) salt diet. On each diet animals received spironolactone or placebo. Blood pressure was measured by tail-cuff-method; 24-h urine samples were collected in metabolic cages and blood was collected for hormonal measurements. High-salt diet significantly increased systolic blood pressure in both sexes. This effect could be blocked effectively by spironolactone only in male rats. Spironolactone treatment significantly increased aldosterone levels in males and females independent of the sodium content of the diet. High sodium diet significantly increased relative kidney weight, which was not altered by spironolactone treatment. Independently of gonadal steroids a high-salt diet increased blood pressure in gonadectomized male and female rats. Spironolactone lowered blood pressure only in male not in female rats on a high-salt diet clearly indicating sex-specific effects of the mineralocorticoid antagonist spironolactone. © Georg Thieme Verlag KG Stuttgart · New York.


Muschalla B.,Charit University Medicine Berlin | Linden M.,Charit University Medicine Berlin
Psychopathology | Year: 2012

Objective: Job anxiety is a severe problem in many patients with chronic mental disorders, as it usually results in specific participation problems in the workplace and long-term sick leave. The aim of this study was to explore the development of sick leave in dependence on general psychosomatic complaints and job anxiety from admission to a psychosomatic inpatient treatment until 6 months after discharge. Method: A convenience sample of 91 patients, suffering from multiple mental disorders, filled in self-rating questionnaires on job anxiety (Job Anxiety Scale) and on general psychosomatic symptom load (Symptom Checklist-90-Revised) at the beginning, the end, and 6 months after discharge from an inpatient psychosomatic treatment. Additionally, sick leave status and employment status were assessed before and 6 months after the treatment. Results: 15.4% of 91 patients were on sick leave before inpatient treatment and at follow-up (SS group), 20.9% were fit for work at intake and follow-up (FF group), 6.6% were fit for work initially and on sick leave later (FS group), and 57.1% on sick leave first and working at follow-up (SF group). In regard to general psychosomatic complaints, there were initially high scores on the SCL, a marked reduction during inpatient treatment, and a bouncing back to initial levels at follow-up for all 4 patient groups. SS and FS patients showed the highest scores at intake and follow-up. Concerning job anxiety, SS patients had the highest scores at all three assessments, while FF patients had significantly lower scores, with only low variation between assessments. SF patients started with comparatively high scores of job anxiety, which even increased before reentering work, but decreased in the follow-up period when they were confronted with work again. FS patients started low (like the FF patients) at intake, reduced their job anxiety further till discharge, but increased to higher scores at follow-up. Conclusions: General psychosomatic symptom load and job anxiety show a different course during treatment and are differently related to sick leave. General psychosomatic symptom load can be understood as a measure of the degree of the chronic illness status, whereas job anxiety reflects specific additional context-related problems, i.e. problems with work. A core finding is that job anxiety is related to work avoidance, but work exposure may reduce job anxiety. This has direct consequences for putting patients on sick leave or not. Copyright © 2012 S. Karger AG, Basel.


Struthers A.D.,University of Dundee | Unger T.,Charit University Medicine Berlin
European Heart Journal, Supplement | Year: 2011

New adverse effects of aldosterone are now apparent: endothelial dysfunction, myocardial fibrosis and LV remodelling. Aldosterone blockade is able to reverse these adverse effects and so reduce mortality in heart failure. Pharmacological differences between spironolactone and eplerenone are discussed. © 2011 The Author.


Quinkler M.,Charit University Medicine Berlin | Born-Frontsberg E.,Charit University Medicine Berlin | Fourkiotis V.G.,Charit University Medicine Berlin
Hormone and Metabolic Research | Year: 2010

Patients presenting with primary aldosteronism experience more cardiovascular events than patients with essential hypertension independent of blood pressure. Therefore, the presence of primary aldosteronism should be detected, not only to determine the cause of hypertension, but also to prevent such complications. This review focuses on human data regarding increased end-organ damage and comorbidities in primary aldosteronism. Special emphasis is put on the effects of aldosterone excess on blood vessels, the heart, the kidney, and the brain. The data reviewed in our article demonstrate that primary aldosteronism is associated with a prevalence of cerebro-, cardiovascular and renal complications that are out of proportion to the blood pressure and benefits substantially from treatment in the long term. In this view, adrenalectomy and aldosterone antagonist treatment seem to be of considerable therapeutic value to control and limit the progression of comorbidities in primary aldosteronism. © Georg Thieme Verlag KG Stuttgart · New York.


Brockmann T.,Charit University Medicine Berlin | Steger C.,Charit University Medicine Berlin | Dawczynski J.,University of Leipzig
Ophthalmologica | Year: 2012

The purpose of this study was to evaluate photodynamic properties of indocyanine green (ICG), brilliant blue G (BBG) and trypan blue (TB) as currently used vital dyes for chromovitrectomy. Under consideration of intraoperative illumination intensities and dye concentrations, a simulative in vitro investigation was set up. Therefore, standardized dilutions of original ICG, BBG and TB vials were irradiated at a wavelength of 366 nm with an intensity of 14 μW/cm2 between 0 and 48 h. After this, all samples were measured spectroscopically in a 220-to 750-nm bandwidth. Analyzing the vital dyes over the time course, an exponential photolysis was observed for ICG, whereas BBG and TB presented photostable properties. Regarding ICG, 5% of the concentration was degraded to toxic metabolites every 20 min. For this reason, our study provides evidence that intraocular dye concentrations and modern endoillumination systems alone cannot fully prevent ICG photodegradation. © 2012 S. Karger AG, Basel.


PubMed | Charit University Medicine Berlin
Type: Journal Article | Journal: Cancer gene therapy | Year: 2016

Chemokines are key regulators of both innate and adaptive immune responses. CCL4 (macrophage inflammatory protein-1, MIP-1) is a CC chemokine that has a broad spectrum of target cells including immature dendritic cells, which express the cognate receptor CCR5. We asked whether a plasmid encoding CCL4 is able to improve tumor protection and immune responses in a Her2/neu+ mouse tumor model. Balb/c mice were immunized twice intramuscularly with plasmid DNA on days 1 and 15. On day 25, a tumor challenge was performed with 2 10(5) syngeneic Her2/neu+ D2F2/E2 tumor cells. Different groups of mice were vaccinated with pDNA(Her2/neu) plus pDNA(CCL4), pDNA(Her2/neu), pDNA(CCL4) or mock vector alone. Our results show that CCL4 is able to (i) improve tumor protection and (ii) augment a TH1-polarized immune response against Her2/neu. Although Her2/neu-specific humoral and T-cell immune responses were comparable with that induced in previous studies using CCL19 or CCL21 as adjuvants, tumor protection conferred by CCL4 was inferior. Whether this is due to a different spectrum of (innate) immune cells, remains to be clarified. However, combination of CCL19/21 with CCL4 might be a reasonable approach in the future, particularly for DNA vaccination in Her2/neu+ breast cancer in the situation of minimal residual disease.

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