Institute of Medical Informatics

München, Germany

Institute of Medical Informatics

München, Germany

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Muehlmann M.,Ludwig Maximilians University of Munich | Koerte I.K.,Ludwig Maximilians University of Munich | Laubender R.P.,Institute of Medical Informatics | Steffinger D.,Ludwig Maximilians University of Munich | And 5 more authors.
Investigative Radiology | Year: 2013

Objectives: The aim of this study was to investigate the relationship between the pressure setting of the ventriculoperitoneal (VP) shunt valve and a magnetic resonance (MR)-based estimate of intracranial pressure (ICP) in children with shunt-treated hydrocephalus without clinical signs of shunt malfunction. Materials and Methods: Institutional review board approval was obtained before the study, and all subjects and/or their legal guardians provided written informed consent. In this prospective study, 15 consecutive patients (median age, 8.25 years; range, 2.2-18.4 years; 6 girls and 9 boys) with shunt-treated hydrocephalus without signs of shunt malfunction were examined with retrospectively gated phase contrast sequences to quantify arterial inflow, venous outflow, and cerebrospinal fluid (CSF) flow to and from the cranial vault. The ratio of the maximal intracranial volume change and the pulse pressure gradient change was used to derive MR-ICP. Spearman ρ was used to test for the association of setting of the shunt valve opening pressure and MR-ICP. Results: Shunt valve opening pressure settings and MR-ICP were positively correlated (Spearman ρ = 0.64, P < 0.01). Median MR-ICP was 8.67 mm Hg (interquartile range [IQR], 1.59 mm Hg) and median setting of the VP-shunt valve was 6.62 mm Hg (IQR, 1.47 mm Hg). The median MR-ICP was 1.9 mm Hg (IQR, 0.73 mm Hg) higher than the setting of the shunt valve. Conclusion: There is a positive correlation between MR-ICP and VP shunt valve opening pressure setting. The systematically higher assessment of MR-ICP is most likely a result of outflow resistance within the shunt tubing system and well within the known fluctuation rates of VP shunt systems. © 2013 by Lippincott Williams & Wilkins.


Crispin A.,Institute of Medical Informatics | Mansmann U.,Institute of Medical Informatics | Munte A.,Bavarian Association of Compulsory Health Insurance Physicians | Op Den Winkel M.,Ludwig Maximilians University of Munich | And 2 more authors.
Digestion | Year: 2013

Background/Aims: Surveillance colonoscopy is recommended after polypectomy of adenoma and surgery for colorectal cancer. The purpose of this study was to assess the frequency of advanced adenoma and cancer in colonoscopies performed for surveillance compared to screening colonoscopies. Methods: Analysis of relative frequencies of findings in colonoscopies performed for post-adenoma surveillance (post-ad), post-cancer surveillance (post-crc), screening, and follow-up of a positive fecal occult blood test (FOBT). Logistic regression was used to identify the risk for advanced adenoma (adenoma ≥10 mm, containing high-grade dysplasia, or villous histology) and cancer. Results: 324,912 colonoscopies were included in the analysis: 81,877 post-ad, 26,896 post-crc, 178,305 screening, 37,834 positive FOBT. Advanced adenoma (cancer) was diagnosed in 8.0% (0.4%) of post-ad, 5.0% (1.0%) of post-crc, 7.4% (1.1%) of screening, and 11.7% (3.6%) of positive FOBT colonoscopies. Compared to screening, the odds ratios for finding advanced adenoma were 0.93 (95% CI 0.88-0.98) for post-ad, 0.96 (0.86-1.08) for post-crc, and 1.18 (1.09-1.28) for positive FOBT colonoscopies. The odds ratios for the diagnosis of cancer were 0.29 (0.24-0.36) for post-ad, 0.81 (0.61-1.07) for post-crc, and 2.77 (2.43-3.17) for positive FOBT. Conclusion: Colonoscopy for post-ad surveillance but not colonoscopy for post-crc surveillance is associated with a lower risk of diagnosis of advanced adenoma and cancer. Copyright © 2013 S. Karger AG, Basel.


PubMed | Martin Luther University of Halle Wittenberg, University of Bonn, Institute of Medical Informatics, Life and Brain Center and University of Heidelberg
Type: Journal Article | Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics | Year: 2015

Transcription factor 4 (TCF4) is one of the most robust of all reported schizophrenia risk loci and is supported by several genetic and functional lines of evidence. While numerous studies have implicated common genetic variation at TCF4 in schizophrenia risk, the role of rare, small-sized variants at this locus-such as single nucleotide variants and short indels which are below the resolution of chip-based arrays requires further exploration. The aim of the present study was to investigate the association between rare TCF4 sequence variants and schizophrenia. Exon-targeted resequencing was performed in 190 German schizophrenia patients. Six rare variants at the coding exons and flanking sequences of the TCF4 gene were identified, including two missense variants and one splice site variant. These six variants were then pooled with nine additional rare variants identified in 379 European participants of the 1000 Genomes Project, and all 15 variants were genotyped in an independent German sample (n=1,808 patients; n=2,261 controls). These data were then analyzed using six statistical methods developed for the association analysis of rare variants. No significant association (P<0.05) was found. However, the results from our association and power analyses suggest that further research into the possible involvement of rare TCF4 sequence variants in schizophrenia risk is warranted by the assessment of larger cohorts with higher statistical power to identify rare variant associations.


Reulen H.-J.,Ludwig Maximilians University of Munich | Poepperl G.,Nuclear Medicine | Goetz C.,Ludwig Maximilians University of Munich | Gildehaus F.J.,Nuclear Medicine | And 5 more authors.
Journal of Neurosurgery | Year: 2015

Object The aim in this study was to present long-term results regarDing overall survival (OS), adverse effects, and toxicity following fractionated intracavitary radioimmunotherapy (RIT) with iodine-131? or yttrium-90?labeled anti-tenascin monoclonal antibody (131I-mAB or 90Y-mAB) for the treatment of patients with malignant glioma. Methods In 55 patients (15 patients with WHO Grade III anaplastic astrocytoma [AA] and 40 patients with WHO Grade IV glioblastoma multiforme [GBM]) following tumor resection and conventional radiotherapy, radioimmunoconjugate was introduced into the postoperative resection cavity. Patients received 5 cycles of 90Y-mAB (Group A, average dose 18 mCi/ cycle), 5 cycles of 131I-mAB (Group B, average dose 30 mCi/cycle), or 3 cycles of 131I-mAB (Group C, 50, 40, and 30 mCi). Results Median OS of patients with AA was 77.2 months (95% CI 30.8 to > 120). Five AA patients (33%) are currently alive, with a median observation time of 162.2 months. Median OS of all 40 patients with GBM was 18.9 months (95% CI 15.8-25.3), and median OS was 25.3 months (95% CI 18-30) for those patients treated with the 131I-mAB. Three GBM patients are currently alive. One-, 2-, and 3-year survival probabilities were 100%, 93.3%, and 66.7%, respectively, for AA patients and 82.5%, 42.5%, and 15.9%, respectively, for GBM patients. Restratification of GBM patients by recursive partitioning analysis (RPA) Classes III, IV, and V produced median OSs of 31.1, 18.9, and 14.5 months, respectively (p = 0.004), which was higher than expected. Multivariate analysis confirmed the role of RPA class, age, and treatment in predicting survival. No Grade 3 or 4 hematological, nephrologic, or hepatic toxic effects were observed; 4 patients developed Grade 3 neurological deficits. Radiological signs of radionecrosis were observed in 6 patients, who were all responDing well to steroids. Conclusions Median OS of GBM and AA patients treated with 131I-mABs reached 25.3 and 77.2 months, respectively, thus markedly exceeDing that of historical controls. Adverse events remained well controllable with the fractionated dosage regimen. © AANS, 2015.


Liu Y.-C.,National Cheng Kung University | Chen L.-C.,Academia Sinica, Taiwan | Liu C.-W.,National Cheng Kung University | Tseng V.S.,National Cheng Kung University | Tseng V.S.,Institute of Medical Informatics
International Journal of Data Mining and Bioinformatics | Year: 2014

In recent years, mass spectrometry data analysis has become an important protein identifi cation technique. The mass spectrometry technologies emerge as useful tools for biomarker discovery through studying protein profi les in various biological specimens. In mining mass spectrometry datasets, peak alignment is a critical issue among the preprocessing steps that affect the quality of analysis results. However, the existing peak alignment methods are sensitive to noise peaks across various mass spectrometry samples. In this paper, we proposed a novel algorithm named Two-Phase Clustering for peak Alignment (TPC-Align) to align mass spectrometry peaks across samples in the pre-processing phase. The TPC-Align algorithm sequentially considers the distribution of intensity values and the locations of mass-to-charge ratio values of peaks between samples. Moreover, TPC-Align algorithm can also report a list of signifi cantly differential peaks between samples, which serve as the candidate biomarkers for further biological study. The proposed peak alignment method was compared to the current peak alignment approach based on one-dimension hierarchical clustering through experimental evaluations and the results show that TPC-Align outperforms the traditional method on the real dataset. © 2014 Inderscience Enterprises Ltd.


Fortmeier D.,Institute of Medical Informatics | Fortmeier D.,University of Lübeck | Mastmeyer A.,Institute of Medical Informatics | Handels H.,Institute of Medical Informatics
Studies in Health Technology and Informatics | Year: 2014

Palpation is the first step for many medical interventions. To provide an immersive virtual training and planning environment, the palpation step has to be successfully modeled and simulated. Here, we present a multiproxy approach that calculates friction and surface resistance forces for multiple contact points on finger tips or virtual tools like ultrasound probes and displays the resulting force and torque on a 6DOF haptic device. No manual or time intensive segmentation of patient image data is needed to create a simulation based on CT data and thus our approach is usable for patient-specific simulation of palpation.© 2014 The authors and IOS Press. All rights reserved.


Stang A.,German Cancer Research Center | Jockel K.-H.,Institute of Medical Informatics
Cancer | Year: 2015

BACKGROUND: After a pilot study on skin cancer screening was performed between 2003 and 2004 in Schleswig-Holstein, Germany, the country implemented what to the authors' knowledge is the first nationwide skin cancer screening program in the world in 2008. The objective of the current study was to provide details regarding mortality trends in Schleswig-Holstein and Germany in relation to the screening. METHODS: Annual age-standardized mortality rates for skin melanoma (using the 10th Revision of the International Statistical Classification of Diseases and Related Health Problems [ICD-10] code C43) and malignant neoplasms of ill-defined, secondary, and unspecified sites (ICD-10 code C76-C80) were analyzed. The European Standard population was used for age standardization. A bias analysis was performed to estimate the number of skin melanoma deaths that may have been incorrectly counted as ICD-10 code C76-C80 when the skin melanoma mortality declined in Schleswig-Holstein. RESULTS: The observed mortality decline in Schleswig-Holstein 5 years after the pilot study was accompanied by a considerable increase in the number of deaths due to malignant neoplasms of ill-defined, secondary, and unspecified sites (ICD-10 code C76-C80) that is not explainable by an increase in the incidence of these neoplasms. Incorrect assignment of 8 to 35 and 12 to 23 skin melanoma deaths per year among men and women, respectively, as ICD-10 code C76-C80 during 2007 through 2010 could explain the transient skin melanoma mortality decline observed in Schleswig-Holstein. Five years after implementation of the program, the nationwide skin melanoma mortality increased (age-standardized rate change of +0.4 per 100,000 person-years [95% confidence interval, 0.2-0.6] in men and +0.1 per 100,000 person-years [95% confidence interval, -0.1 to 0.2] in women). CONCLUSIONS: Although the current analyses raise doubts that the skin cancer screening program in Germany can reduce the skin cancer mortality rate, the authors do not believe the program should be immediately stopped. Further in-depth evaluations are required. © 2015 American Cancer Society.


Varsier N.,Orange Group | Dahdouh S.,Orange Group | Dahdouh S.,Telecom ParisTech | Serrurier A.,Telecom ParisTech | And 9 more authors.
Physics in Medicine and Biology | Year: 2014

This paper analyzes the influence of pregnancy stage and fetus position on the whole-body and brain exposure of the fetus to radiofrequency electromagnetic fields. Our analysis is performed using semi-homogeneous pregnant woman models between 8 and 32 weeks of amenorrhea. By analyzing the influence of the pregnancy stage on the environmental whole-body and local exposure of a fetus in vertical position, head down or head up, in the 2100 MHz frequency band, we concluded that both whole-body and average brain exposures of the fetus decrease during the first pregnancy trimester, while they advance during the pregnancy due to the rapid weight gain of the fetus in these first stages. From the beginning of the second trimester, the whole-body and the average brain exposures are quite stable because the weight gains are quasi proportional to the absorbed power increases. The behavior of the fetus whole-body and local exposures during pregnancy for a fetus in the vertical position with the head up were found to be of a similar level, when compared to the position with the head down they were slightly higher, especially in the brain. © 2014 Institute of Physics and Engineering in Medicine.


Herbst A.,Ludwig Maximilians University of Munich | Rahmig K.,Ludwig Maximilians University of Munich | Stieber P.,Institute of Clinical Chemistry | Philipp A.,Ludwig Maximilians University of Munich | And 6 more authors.
American Journal of Gastroenterology | Year: 2011

Objectives: Colorectal cancer is the third most common cancer and a major cause of cancer-related deaths. Early detection of colonic lesions can reduce the incidence and mortality of colorectal cancer. Colonoscopy is the screening test for colorectal cancer with the highest efficacy, but its acceptance in the general public is rather low. To identify suitable tumor-derived markers that could detect colorectal cancer in blood samples, we analyzed the methylation status of a panel of genes in sera of affected patients. Methods: Using methylation-specific quantitative PCR, we analyzed the methylation of ten marker genes in sera of healthy individuals and patients with colorectal cancer. Results: Only HLTF, HPP1/TPEF, and NEUROG1 DNA methylation was detectable in at least 50% of patients with colorectal cancers. Whereas HLTF and HPP1/TPEF preferentially detected advanced and metastasized colorectal cancers, NEUROG1 methylation was detectable in UICC stages I-IV at a similar rate. Compared with other methylation markers, such as ALX4, SEPT9, and vimentin, NEUROG1 shows a higher sensitivity for colorectal cancer at UICC stages I and II. At a specificity of 91%, NEUROG1 reached a sensitivity of 61% (confidence interval, 50.4-70.6%) for the detection of colorectal cancers. Furthermore, detection of NEUROG1 methylation was independent of age and gender. Conclusions: Methylation of the NEUROG1 gene is frequently found in sera of patients with colorectal cancers independent of tumor stage. The quantitative detection of NEUROG1 DNA methylation in serum is a suitable approach for the non-invasive screening for asymptomatic colorectal cancer. © 2011 by the American College of Gastroenterology.


Lippert J.,University of Munster | Halfter H.,University of Munster | Heidbreder A.,University of Munster | Rohr D.,University of Munster | And 4 more authors.
PLoS ONE | Year: 2014

From single cell organisms to the most complex life forms, the 24-hour circadian rhythm is important for numerous aspects of physiology and behavior such as daily periodic fluctuations in body temperature and sleep-wake cycles. Influenced by environmental cues - mainly by light input -, the central pacemaker in the thalamic suprachiasmatic nuclei (SCN) controls and regulates the internal clock mechanisms which are present in peripheral tissues. In order to correlate modifications in the molecular mechanisms of circadian rhythm with the pathophysiology of idiopathic hypersomnia, this study aimed to investigate the dynamics of the expression of circadian clock genes in dermal fibroblasts of idiopathic hypersomniacs (IH) in comparison to those of healthy controls (HC). Ten clinically and polysomnographically proven IH patients were recruited from the department of sleep medicine of the University Hospital of Muenster. Clinical diagnosis was done by two consecutive polysomnographies (PSG) and Multiple Sleep Latency Test (MSLT). Fourteen clinical healthy volunteers served as control group. Dermal fibroblasts were obtained via punch biopsy and grown in cell culture. The expression of circadian clock genes was investigated by semiquantitative Reverse Transcriptase-PCR qRT-PCR analysis, confirming periodical oscillation of expression of the core circadian clock genes BMAL1, PER1/2 and CRY1/2. The amplitude of the rhythmically expressed BMAL1, PER1 and PER2 was significantly dampened in dermal fibroblasts of IH compared to HC over two circadian periods whereas the overall expression of only the key transcriptional factor BMAL1 was significantly reduced in IH. Our study suggests for the first time an aberrant dynamics in the circadian clock in IH. These findings may serve to better understand some clinical features of the pathophysiology in sleep - wake rhythms in IH. © 2014 Lippert et al.

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