German Diagnostic Clinic

Wiesbaden, Germany

German Diagnostic Clinic

Wiesbaden, Germany

Time filter

Source Type

Gockel I.,University Hospital Freiburg | Becker J.,University of Bonn | Wouters M.M.,Catholic University of Leuven | Niebisch S.,University Hospital Freiburg | And 46 more authors.
Nature Genetics | Year: 2014

Idiopathic achalasia is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. This ultimately leads to massive dilatation and an irreversibly impaired megaesophagus. We performed a genetic association study in 1,068 achalasia cases and 4,242 controls and fine-mapped a strong MHC association signal by imputing classical HLA haplotypes and amino acid polymorphisms. An eight-residue insertion at position 227-234 in the cytoplasmic tail of HLA-DQβ1 (encoded by HLA-DQB1*05:03 and HLA-DQB1*06:01) confers the strongest risk for achalasia (P = 1.73 × 10-19). In addition, two amino acid substitutions in the extracellular domain of HLA-DQα1 at position 41 (lysine encoded by HLA-DQA1*01:03; P = 5.60 × 10-10) and of HLA-DQβ1 at position 45 (glutamic acid encoded by HLA-DQB1*03:01 and HLA-DQB1*03:04; P = 1.20 × 109) independently confer achalasia risk. Our study implies that immune-mediated processes are involved in the pathophysiology of achalasia. © 2014 Nature America, Inc.


PubMed | University of Aarhus, University of Bonn, University of Würzburg, Protestant Hospital Castrop Rauxel and 14 more.
Type: Journal Article | Journal: Nature genetics | Year: 2014

Idiopathic achalasia is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. This ultimately leads to massive dilatation and an irreversibly impaired megaesophagus. We performed a genetic association study in 1,068 achalasia cases and 4,242 controls and fine-mapped a strong MHC association signal by imputing classical HLA haplotypes and amino acid polymorphisms. An eight-residue insertion at position 227-234 in the cytoplasmic tail of HLA-DQ1 (encoded by HLA-DQB1*05:03 and HLA-DQB1*06:01) confers the strongest risk for achalasia (P=1.7310(-19)). In addition, two amino acid substitutions in the extracellular domain of HLA-DQ1 at position 41 (lysine encoded by HLA-DQA1*01:03; P=5.6010(-10)) and of HLA-DQ1 at position 45 (glutamic acid encoded by HLA-DQB1*03:01 and HLA-DQB1*03:04; P=1.2010(-9)) independently confer achalasia risk. Our study implies that immune-mediated processes are involved in the pathophysiology of achalasia.


Disse S.C.,Justus Liebig University | Buelow A.,Justus Liebig University | Boedeker R.-H.,Justus Liebig University | Keller K.-M.,German Diagnostic Clinic | And 3 more authors.
Pediatric Obesity | Year: 2013

Background: Studies in animals and in man have demonstrated that excessive consumption of fructose can cause all components of the metabolic syndrome. Objective: To investigate the impact of a condition resulting in decreased absorption of fructose, on obesity. Methods: In a multicentre study, we analyzed a cohort of paediatric patients with suspected primary fructose malabsorption (FM). Patients with chronic intestinal diseases were excluded. The final cohort comprised 628 patients. Results: 302 patients were diagnosed with primary FM (48.1%). The proportion of obese patients was lower among FM patients, compared to non-FM patients (2.3 vs. 6.1%, P = 0.029). Logistic regression analysis with inclusion of various covariates showed that FM was negatively associated with obesity (OR 0.35, 95% CI [0.13; 0.97]). We discuss several mechanisms involving the metabolic, endocrine and gastrointestinal system. © 2013 The Authors.


Muller M.,German Diagnostic Clinic | Eckardt A.J.,German Diagnostic Clinic | Fisseler-Eckhoff A.,Dr. Horst Schmidt Kliniken | Haas S.,Dr. Horst Schmidt Kliniken | And 2 more authors.
World Journal of Gastroenterology | Year: 2012

AIM: To investigate endoscopic findings in patients with Schatzki rings (SRs) with a focus on evidence for eosinophilic esophagitis (EoE). METHODS: We consecutively approached all adult patients scheduled for elective outpatient upper endoscopy for a variety of indications at the German Diagnostic Clinic, Wiesbaden, Germany between July 2007 and July 2010. All patients with endoscopically diagnosed SRs, defned as thin, symmetrical, mucosal structures located at the esophagogastric junction, were prospectively registered. Additional endoscopic findings, clinical information and histopathological findings with a focus on esophageal eosinophilia (≥ 20 eosinophils/high power field) were recorded. The criteria for active EoE were defined as: (1) eosinophilic tissue infiltration ≥ 20 eosinophils/hpf; (2) symptoms of esophageal dysfunction; and (3) exclusion of other causes of esophageal eosinophilia. Gastroesophageal reflux disease was excluded by proton pump inhibitor treatment prior to endoscopy. The presence of ≥ 20 eosinophils/hpf in esophageal biopsies in patients that did not fulfil the criteria of EoE was defined as esophageal hypereosinophilia. RESULTS: A SR was diagnosed in 171 (3.3%; 128 males, 43 females, mean age 66 ± 12.9 years) of the 5163 patients that underwent upper gastrointestinalendoscopy. Twenty of the 116 patients (17%) from whom esophageal biopsies were obtained showed histological hypereosinophilia (≥ 20 eosinophils/hpf). Nine of these patients (8 males, 1 female, mean age 49 ± 10 years) did not fulfill all diagnostic criteria of EoE, whereas in 11 (9%) patients with ≥ 20 eosinophils/hpf, a defnite diagnosis of EoE was made. Three of the 11 patients (27%) with defnite EoE had no suspicious endoscopic features of EoE. In contrast, in the 25 patients in whom EoE was suspected by endoscopic features, EoE was only confrmed in 7 (28%) patients. Patients with EoE were younger (mean age 41.5 ± 6.5 vs 50.5 ± 11.5 years, P = 0.012), were more likely to have a history of allergies (73% vs 29%, P = 0.007) and complained more often of dysphagia (91% vs 34%, P = 0.004) and food impaction (36% vs 6%, P = 0.007) than patients without EoE. Endoscopically, additional webs were found significantly more often in patients with EoE than in patients without EoE (36% vs 11%, P = 0.04). Furthermore, the SR had a tendency to be narrower in patients with EoE than in those without EoE (36% vs 18%, P = 0.22). The percentage of males (73% vs 72%, P = 1.0) and frequency of heartburn (27% vs 27%, P = 1.0) were not signifcantly different in both groups. The 9 patients with esophageal hypereosinophilia that did not fulfil the diagnostic criteria of EoE were younger (mean age 49 ± 10 years vs 58 ± 6 years, P = 0.0008) and were more likely to have a history of allergies (78% vs 24%, P = 0.003) than patients with < 20 eosinophils/hpf. Predictors of EoE were younger age, presence of dysphagia or food impaction and a history of allergies. CONCLUSION: A significant proportion of patients with SRs also have EoE, which may not always be suspected according to other endoscopic features. © 2012 Baishideng. All rights reserved.


Werk M.,Martin Luther Hospital Berlin | Albrecht T.,Vivantes Clinic | Meyer D.-R.,Hubertus Hospital | Ahmed M.N.,Vivantes Clinic | And 9 more authors.
Circulation: Cardiovascular Interventions | Year: 2012

Background-Peripheral percutaneous transluminal angioplasty is fraught with a substantial risk of restenosis and reintervention. A drug-eluting balloon (DEB) based on a novel coating was compared with uncoated balloons in patients undergoing femoro-popliteal percutaneous transluminal angioplasty. Methods and Results-Patients with symptomatic femoro-popliteal atherosclerotic disease undergoing percutaneous transluminal angioplasty were randomized to paclitaxel-coated IN.PACT Pacific or uncoated Pacific balloons. The primary end point was late lumen loss at 6 months assessed by blinded angiographic corelab quantitative analyses. Secondary end points were binary restenosis and Rutherford class change at 6 months, and target lesion revascularization plus major adverse clinical events (major adverse events=death, target limb amputation, or target lesion revascularization) at 6 and 12 months. Eighty-five patients (91 cases=interventional procedures) were randomized in 3 hospitals (44 to DEB and 47 to uncoated balloons). Average lesion length was 7.0±5.3 and 6.6±5.5cm for DEB and control arm, respectively. Procedural success was obtained in all cases. Six-month quantitative angiography showed that DEB were associated with significantly lower late lumen loss (-0.01mm [95% CI, -0.29; 0.26] versus 0.65mm [0.37; 0.93], P=0.001) and fewer binary restenoses (3 [8.6%] versus 11 [32.4%], P=0.01). This translated into a clinically relevant benefit with significantly fewer major adverse events for DEB versus uncoated balloons up to 12 months (3 [7.1%] versus 15 [34.9%], P<0.01) as well as target lesion revascularizations (3 [7.1%] versus 12 [27.9%], P=0.02). Conclusions-Use of IN.PACT Pacific DEB is associated with significant reductions in late lumen loss and restenoses at 6 months, and reinterventions after femoro-popliteal percutaneous transluminal angioplasty up to 1 year of follow-up. © 2012 American Heart Association, Inc.


Lauenstein A-S.,German Diagnostic Clinic | Stettner M.,Heinrich Heine University Düsseldorf | Kieseier B.C.,Heinrich Heine University Düsseldorf | Lensch E.,German Diagnostic Clinic
BMJ Case Reports | Year: 2014

We present a 32-year-old female patient with fulminant neuromyelitis optica. After the initial treatment with the monoclonal antibody rituximab failed, therapy with the anti-IL-6 receptor antagonist tocilizumab was initiated. The patient experienced a clinically relevant improvement from severe tetraparesis to low-grade paresis, which is still maintained. On MRI of the spinal cord an almost complete restitution of a predescribed extensive myelopathy accompanied this clinical improvement. Meanwhile clinical stability was achieved for over 1 year without any side effects of the ongoing treatment with tocilizumab. Copyright 2014 BMJ Publishing Group. All rights reserved.


Zimmermann T.,Johannes Gutenberg University Mainz | Moehler M.,Johannes Gutenberg University Mainz | Gockel I.,University of Mainz | Gockel I.,Johannes Gutenberg University Mainz | And 8 more authors.
International Journal of Colorectal Disease | Year: 2010

Background: Chemokines and their receptors have been proposed to distinctly contribute to tumor growth, dissemination, and local immune escape. The aim of this study was to evaluate the relevance of the chemokine receptor CCR5 expression for the progression of human colorectal cancer. Methods: CCR5 expression was assessed by RT-PCR analysis in 103 colorectal cancer patients. Intensity of CCR5 expression was correlated with both tumor and patient characteristics. Infiltration of tumor margins with CD8+ T cells in the context of CCR5 expression was analyzed by immunohistochemistry in additional 18 colorectal cancer specimens. Results: Human colorectal cancer revealed variable intensities of CCR5 expression ranging from absent (48/103: 47%), weak (30/103: 29%), intermediate (13/103: 13%), to strong (12/103: 12%). Absent or weak CCR5 expression was significantly associated with advanced UICC stages (P = 0.02) and lymphatic metastasis (P=0.05). In addition, CCR5 expression positively correlated with CD8+ T-cell infiltration in tumor margins (P=0.001). Conclusion: In summary, intermediate and strong CCR5 expression was significantly associated with nonmetastatic colorectal cancer and increased CD8+ T-cell infiltration. © Springer-Verlag 2009.

Loading German Diagnostic Clinic collaborators
Loading German Diagnostic Clinic collaborators