Universitaetsklinikum Ulm

Neu-Ulm, Germany

Universitaetsklinikum Ulm

Neu-Ulm, Germany
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Hoehler T.,Prosper Hospital Recklinghausen | Von Wichert G.,Universitaetsklinikum Ulm | Schimanski C.,University of Mainz | Kanzler S.,Leopoldina Krankenhaus | And 8 more authors.
British Journal of Cancer | Year: 2013

Background:Combined inhibition of platelet-derived growth factor receptor beta signalling and vascular endothelial growth factor promotes vascular normalisation in preclinical models and may lead to increased delivery of chemotherapy to tumour tissue. This phase I/II trial assessed the safety and efficacy of capecitabine plus oxaliplatin (XELOX) plus bevacizumab and imatinib in the first-line treatment of patients with metastatic colorectal cancer.Methods:Two dose levels (I/II) were defined: capecitabine 850/1000 mg m -2 twice daily on days 1-14; oxaliplatin 100/130 mg m -2 on day 1; bevacizumab 7.5 mg kg -1 on day 1; imatinib 300 mg day -1 on days 1-21 every 21 days. The primary study endpoint was safety. The phase II secondary endpoint was 6-month progression-free survival (PFS).Results:Dose level I was chosen for phase II testing because, even though further dose escalation was permitted by the protocol, gastrointestinal toxicities were considered to be clinically significant. A total of 49 patients were evaluated. The 6-month PFS rate was 76%, median PFS was 10.6 months and median overall survival was 23.2 months. Haematological toxicities were generally mild. Sensory neuropathy and diarrhoea were the most common grade 3 toxicities.Conclusion:The combination of XELOX with bevacizumab and imatinib is tolerable and has promising efficacy. © 2013 Cancer Research UK.

Xu S.,Anhui Medical University | Zhou Y.,Anhui Medical University | Du W.-D.,Anhui Medical University | Du W.-D.,Universitaetsklinikum Ulm | And 6 more authors.
Gene | Year: 2013

Human DOC-2/DAB2 interactive protein (hDAB2IP) gene is a novel member of the Ras GTPase-activating family and has been demonstrated to be a tumor-suppressor gene that inhibits cell survival and proliferation and induces cell apoptosis. It was reported that the expression level of hDAB2IP in gastric cancer tissue was highly correlated with tumor progression, however, whether hDAB2IP genetic variants are associated with the risk of gastric cancer remains yet unknown. In this case-control study, we conducted a genetic analysis for hDAB2IP variants in 311 patients with gastric cancer and 425 controls from the Chinese Han population. We found that the SNP rs2243421 of hDAB2IP gene with the minor allele C significantly revealed strong association with decreased gastric cancer susceptibility (P = 0.007, adjusted odds ratio [OR] = 0.734, 95%CI = 0.586-0.919). Haplotypes rs2243421 and rs10985332 (HaploType: CC, P = 0.012, aOR = 0.760) and haplotypes rs2243421 and rs555996 (HaploType: CG, P = 0.034, aOR = 0.788) represented the decreased risk of gastric cancer, respectively. On the contrary, rs2243421 and rs555996 showed an elevated susceptibility (HaploType: TG, P = 0.010, aOR = 1.320). Our results for the first time provided new insight into susceptibility factors of hDAB2IP gene variants in carcinogenesis of gastric cancer. © 2012 Elsevier B.V.

Zhou Y.,Anhui Medical University | Du W.-D.,Anhui Medical University | Du W.-D.,Universitaetsklinikum Ulm | Chen G.,Anhui Medical University | And 6 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2012

Purpose To investigate associations between genetic variants involved in microRNA networks (microRNA biogenesis, microRNA and microRNA binding sites) and risk of gastric cancer. Methods We genotyped 19 SNPs of the microRNArelated genes in a case-control study of 311 gastric cancers and 425 cancer-free controls in a Chinese Han population. Results We found that two of the SNPs were significantly associated with gastric cancer. Inhibitory effect of minor allele T of rs2071504 SNP within the exon of POLR2A gene was significantly associated with gastric carcinogenesis (p = 0.033, aOR = 0.742, 95%CI = 0.564-0.977) and the SNP rs895819 in the miR-27a gene with the minor allele C presented significantly reduced risk to gastric cancer (p = 0.037, aOR = 0.771, 95%CI = 0.604-0.985). Further stratified analysis with regard to clinical pathological parameters of the patients indicated that the SNP rs2071504 was associated with lymph node metastasis (p = 0.021, aOR = 0.529, 95%CI = 0.307-0.910) and TMN stage (p = 0.021, aOR = 0.532, 95%CI = 0.311- 0.908), respectively. Conclusions Our findings provided evidence that the SNP rs2071504 in the exon of POLR2A gene would not only confer a decreased risk of gastric cancer, but also influence lymph node metastasis and TMN stage of gastric cancer in the Chinese population. © Springer-Verlag 2012.

He X.-J.,Anhui Medical University | Ruan J.,Anhui Medical University | Du W.-D.,Anhui Medical University | Du W.-D.,Universitaetsklinikum Ulm | And 6 more authors.
Reproductive BioMedicine Online | Year: 2012

Protamine genes play important roles in DNA packaging within the sperm nucleus. In order to evaluate the association of PRM1, PRM2, KIT and KITLG variants with susceptibility to severely defective spermatogenesis, 309 male infertility patients (199 cases with non-obstructive azoospermia and 110 cases with severe oligozoospermia) and 377 controls were recruited in the Chinese Han population. This study genotyped 38 single-nucleotide polymorphisms (SNP) in PRM1, PRM2, KIT and KITLG using Sequenom iplex. The results showed that PRM1 variant rs35576928 (p.R34S) was significantly associated with severe oligozoospermia and played a protective role against the disease (P = 0.0079, Bonferroni correction, OR 0.426). The dominant model (variant-containing genotypes) of the SNP was confirmed to protect against the occurrence of oligozoospermia (P = 0.0078, Bonferroni correction, OR 0.387). Haplotype analysis of PRM1 and PRM2 in combination exhibited that haplotype TACCGGC exhibited a significant protective effect against the occurrence of oligozoospermia when compared with controls (P = 0.002, Bonferroni correction, OR 0.602). Haplotype TACCTGC was strongly associated with risk of the clinical phenotype severe oligozoospermia (P = 0.002, Bonferroni correction, OR 2.716). The findings indicated that PRM1 variant rs35576928 (p.R34S) was associated with severely defective spermatogenesis in the Chinese Han population. © 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Atanasov G.,Universitaetsklinik Leipzig | Benckert C.,Universitaetsklinik Leipzig | Thelen A.,Universitaetsklinik Leipzig | Tappe D.,University of Würzburg | And 6 more authors.
World Journal of Gastroenterology | Year: 2013

Human alveolar echinococcosis (AE) is a potentially deadly disease; recent studies have shown that the endemic area of Echinococcus multilocularis, its causative agent, is larger than previously known. This disease has low prevalence and remains underreported in Europe. Emerging clinical data show that diagnostic difficulties are still common. We report on a 76-year old patient suffering from AE lesions restricted to the left lobe of the liver who underwent a curative extended left hemihepatectomy. Prior to the resection a liver biopsy under the suspicion of an atypical malignancy was performed. After the intervention he developed a pseudoaneurysm of the hepatic artery that was successfully coiled. Surprisingly, during surgery, the macroscopic appearance of the tumour revealed a growth pattern that was rather typical for cystic echinococcosis (CE), i.e., a gross tumour composed of multiple large vesicles with several centimeters in diameter. In addition, there were neither extensive adhesions nor infiltrations of the neighboring pancreas and diaphragm as was expected from previous imaging results. The unexpected diagnosis of AE was confirmed by definite histopathology, specific polymerase chain reaction and serology results. This is a rare case of unusual macroscopic presentation of AE that posed immense diagnostic challenges and had an eventful course. To our knowledge this is the first case of an autochthonous infection in this particular geographic area of Germany, the federal state of Saxony. This report may provide new hints for an expanding area of risk for AE and emphasizes the risk of complications in the scope of diagnostic procedures and the limitations of modern radiological imaging. © 2013 Baishideng. All rights reserved.

In this study, we developed a novel protein biochip methodology that was characterized by dithiobis (succinimidyl undecanoate) (DSU) and specialized for detection of serum IgG and IgM antibodies against Treponema pallidum pathogens in the patients with syphilis, respectively. The biochips were validated by a dimension of atomic force microscope (AFM). The visualized detection limit of IgG antibody on the biochip was 0.39g/ml. Finally, 286 serum samples from the patients with syphilis were simultaneously tested on the rTpN15-17-47 coated biochips. The results were evaluated in comparison with the assays of T. pallidum particle agglutination (TPPA) and the toluidine red unheated serum test (TRUST). The result demonstrated that the relative positive rate in the 286 patients by biochip was 99.0%, similar to that by TPPA (97.9%, P>0.05) and higher than that by TRUST, (76.2%, P<0.01). The detection specificities were 100% for the biochip and the TPPA and 97.0% for the TRUST. Thus, the protein biochip would provide a useful platform not only for enabling concurrent detection of the infectious antibodies directed against T. pallidum on a larger scale, but also for monitoring therapy modality of the disease.

Otti A.,TU Munich | Guendel H.,Universitaetsklinikum Ulm | Henningsen P.,TU Munich | Zimmer C.,TU Munich | And 2 more authors.
Journal of Psychiatry and Neuroscience | Year: 2013

Background: Without stimulation, the human brain spontaneously produces highly organized, low-frequency fluctuations of neural activity in intrinsic connectivity networks (ICNs). Furthermore, without adequate explanatory nociceptive input, patients with somatoform pain disorder experience pain symptoms, thus implicating a central dysregulation of pain homeostasis. The present study aimed to test whether interactions among pain-related ICNs, such as the default mode network (DMN), cingular-insular network (CIN) and sensorimotor network (SMN), are altered in somatoform pain during resting conditions. Methods: Patients with somatoform pain disorder and healthy controls underwent resting functional magnetic resonance imaging that lasted 370 seconds. Using a data-driven approach, the ICNs were isolated, and the functional network connectivity (FNC) was computed. Results: Twenty-one patients and 19 controls enrolled in the study. Significant FNC (p < 0.05, corrected for false discovery rate) was detected between the CIN and SMN/anterior DMN, the anterior DMN and posterior DMN/SMN, and the posterior DMN and SMN. Interestingly, no group differences in FNC were detected. Limitations: The most important limitation of this study was the relatively short resting state paradigm. Conclusion: To our knowledge, our results demonstrated for the first time the resting FNC among pain-related ICNs. However, our results suggest that FNC signatures alone are not able to characterize the putative central dysfunction underpinning somatoform pain disorder. © 2013 Canadian Medical Association.

Anjum G.M.,Universitaetsklinikum Ulm | Du W.,Universitaetsklinikum Ulm | Klein R.,Universitaetsklinikum Ulm | Amara U.,Universitaetsklinikum Ulm | And 3 more authors.
Electrophoresis | Year: 2010

Forensic analysis of mitochondrial displacement loop (D-loop) sequences using Sanger sequencing or SNP detection by minisequencing is well established. Pyrosequencing has become an important alternative because it enables high-throughput analysis and the quantification of individual mitochondrial DNAs (mtDNAs) in samples originating from more than one individual. DNA typing of the mitochondrial D-loop region is usually the method of choice if STR analysis fails because of trace amounts of DNA and/or extensive degradation. The main aim of the present work was to optimize the efficiency of pyrosequencing. To do this, 31 SNPs within the hypervariable regions I and II of the D-loop of human mtDNA were simultaneously analyzed. As a novel approach, we applied two sets of amplification primers for the multiplexing assay. These went in combination with four sequencing primers for pyrosequencing. This method was compared with conventional sequencing of mtDNA from blood and biological trace materials. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.

Otti A.,TU Munich | Wohlschlaeger A.M.,TU Munich | Noll-Hussong M.,Universitaetsklinikum Ulm
PLoS ONE | Year: 2015

Background Successful social interaction relies on the ability to attribute mental states to other people. Previous functional neuroimaging studies have shown that this process, described as Theory of Mind (ToM) or mentalization, is reliably associated with activation of the medial prefrontal cortex (mPFC). However, this study presents a novel and surprising finding that provides new insight into the role of the mPFC in mentalization tasks. Methodology/Principal Findings Twenty healthy individuals were recruited from a wide range of ages and social backgrounds. Participants underwent functional magnetic resonance imaging (fMRI) while viewing a well-established ToM visual paradigm involving moving triangles. Functional MRI data were analyzed using a classical general linear model. No activation was detected in the medial prefrontal cortex (mPFC) during movement patterns that typically elicit ToM. However, increased activity was observed in the right middle occipital gyrus, right temporoparietal junction (TPJ), left middle occipital gyrus and right inferior frontal gyrus. No correlation was found between participants' age and BOLD response. Conclusions/Significance In contrast with previous neuroimaging research, our findings support the notion that mPFC function is not critical for reasoning about the mental states of others; furthermore, our data indicate that the right TPJ and right inferior frontal gyrus are able to perform mentalization without any contributions from the mPFC. © 2015 Otti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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