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227 Publications visible to you, out of a total of 227
Impact of age on the efficacy of bone marrow mononuclear cell transplantation in experimental stroke
Genetical Statistics and Systems Biology

Abstract (Expand)

Bone marrow-derived mononuclear cells (BM MNC) have been effectively used to treat experimental stroke. Most of the preclinical trials have been performed in young and healthy laboratory animals, even … though age and hypertension are major risk factors for stroke. To determine the influence of age on the properties of BM MNCs after cerebral ischemia, we compared the efficacy of aged and young BM MNC in an in vitro model of cerebral hypoxia and in an adapted in vivo model of stroke. Human BM MNCs were obtained from healthy young or aged donors and either co-cultured with rat hippocampal slices exposed to oxygen glucose deprivation (OGD), or transplanted intravenously 24 h after permanent middle cerebral artery occlusion in aged (18 months) spontaneously hypertensive rats (SHR). Efficacy was examined by quantification of hippocampal cell death, or respectively, by neurofunctional tests and MR investigations. Co-cultivation with young, but not with aged BM MNCs significantly reduced the hippocampal cell death after OGD. Transplantation of both young and old BM MNCs did not reduce functional deficits or ischemic lesion volume after stroke in aged SHR. These results suggest a significant impact of age on the therapeutic efficacy of BM MNCs after cerebral ischemia.

Authors: Daniel-Christoph Wagner, Mitja Bojko, Myriam Peters, Marlene Lorenz, Cornelia Voigt, Alexander Kaminski, Dirk Hasenclever, Markus Scholz, Alexander Kranz, Gesa Weise, Johannes Boltze

Date Published: 1st Dec 2012

Publication Type: Journal article

Automated photoplethysmography-based determination of ankle-brachial index: a validation study against Doppler sonography
Genetical Statistics and Systems Biology

Abstract (Expand)

INTRODUCTION\backslashr\backslashnDetermination of ankle-brachial-index (ABI) by manual Doppler is well established to screen for lower extremity arterial disease (LEAD) and to predict cardiovascular … risk. A new generation of digital-controlled devices promises automated ABI determination. The aim of this study was to determine comparability of automated photoplethysmography (PPG)-derived ABI calculation with the Doppler-ABI algorithm commonly used in cohort studies.\backslashr\backslashnMETHODS\backslashr\backslashnAutomated PPG-based ABI measurements [Vascular Explorer (VE) and Vicorder (VI)] were recorded from 112 limbs of healthy subjects and 22 limbs of patients with confirmed LEAD. Validity was evaluated on the basis of receiver-operating characteristic (ROC) analysis of clinical status and concordance with Doppler-ABI. Differences between cuff inflation [inf]- and deflation [def]-based method were studied in VE.\backslashr\backslashnRESULTS\backslashr\backslashnPPG-based ABI values were higher compared to Doppler-ABI (VI +0.06, VEinf +0.15, VEdef +0.09, p \textless 0.001, respectively). The difference was pronounced in pathological (\textless0.9), borderline (0.9-0.99) and low normal (1.0-1.09) ABI, but less in ABI \geq1.1. However, ROC analysis revealed excellent diagnostic value for LEAD (sensitivity/specificity) and comparable area under the curve at method-adapted ABI thresholds for all methods: Doppler (95/90 %, 0.95), VI (75/96 %, 0.91), VEinf (85/89 %, 0.93) and VEdef (80/98 %, 0.94).\backslashr\backslashnCONCLUSIONS\backslashr\backslashnDigital-controlled PPG-based ABI determination is a useful diagnostic application for LEAD. However, the systematic higher ABI in PPG-based measurement compared to Doppler and remarkable differences between the deflationary and inflationary method are critical for the interpretation of borderline and low normal ABI values where precise reading is essential to detect mild LEAD and subclinical disease and to predict cardiovascular risk. INTRODUCTION Determination of ankle-brachial-index (ABI) by manual Doppler is well established to screen for lower extremity arterial disease (LEAD) and to predict cardiovascular risk. A new generation of digital-controlled devices promises automated ABI determination. The aim of this study was to determine comparability of automated photoplethysmography (PPG)-derived ABI calculation with the Doppler-ABI algorithm commonly used in cohort studies. METHODS Automated PPG-based ABI measurements [Vascular Explorer (VE) and Vicorder (VI)] were recorded from 112 limbs of healthy subjects and 22 limbs of patients with confirmed LEAD. Validity was evaluated on the basis of receiver-operating characteristic (ROC) analysis of clinical status and concordance with Doppler-ABI. Differences between cuff inflation [inf]- and deflation [def]-based method were studied in VE. RESULTS PPG-based ABI values were higher compared to Doppler-ABI (VI +0.06, VEinf +0.15, VEdef +0.09, p \textless 0.001, respectively). The difference was pronounced in pathological (\textless0.9), borderline (0.9-0.99) and low normal (1.0-1.09) ABI, but less in ABI \geq1.1. However, ROC analysis revealed excellent diagnostic value for LEAD (sensitivity/specificity) and comparable area under the curve at method-adapted ABI thresholds for all methods: Doppler (95/90 %, 0.95), VI (75/96 %, 0.91), VEinf (85/89 %, 0.93) and VEdef (80/98 %, 0.94). CONCLUSIONS Digital-controlled PPG-based ABI determination is a useful diagnostic application for LEAD. However, the systematic higher ABI in PPG-based measurement compared to Doppler and remarkable differences between the deflationary and inflationary method are critical for the interpretation of borderline and low normal ABI values where precise reading is essential to detect mild LEAD and subclinical disease and to predict cardiovascular risk.

Authors: Frank Beutner, Andrej Teren, Stephan Gielen, Gerhard Schuler, Kerstin Wirkner, Daniel Tiller, Markus Loeffler, Markus Scholz

Date Published: 1st Nov 2012

Publication Type: Journal article

"Real-time-3-dimensional-full-volume"-datensatz: Nutzen in der problemfokussierten intraoperativen transösophagealen echokardiographie
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND\backslashr\backslashnComprehensive intraoperative transesophageal echcardiography (TEE) includes various measurements for quantification of cardiac chambers and valves based on multiple two … dimensional (2D) standard views. Due to shortness of time during cardiac surgery most centres in Germany only carry out problem focussed intraoperative examinations which does not allow the complete repertoire of measurements to be exhausted. The aim of this study was to investigate which measurements for cardiac chamber and valve quantification can be performed with the acquisition of a real-time 3D full volume (RT-3D-FV) data set and to compare these measurements with those based on standard 2D views.\backslashr\backslashnMATERIALS AND METHODS\backslashr\backslashnIn patients undergoing elective surgical mitral valve repair a comprehensive 2D TEE examination according to the guidelines of the American Society of Echocardiography (ASE) and the Society of Cardiovascular Anesthesiologists (SCA) was performed after induction of anesthesia. Additionally, a RT-3D-FV TEE data set based on the midesophageal four chamber view was recorded (iE 33, Philips, Netherlands). All measurements of the 2D TEE and the RT-3D-FV dataset (Qlab) were performed offline by two independent examiners.\backslashr\backslashnRESULTS\backslashr\backslashnAfter approval by the local ethic committee and obtaining written informed consent 50 patients (31 male and 19 female) with a mean age of 59.4 \pm 11.5 years were enrolled in this study. All measurements recommended for chamber and valve quantification could be performed on the basis of the RT-3D-FV data set except for measurements of the sinus of Valsalva and the sinotubular junction. There was good correlation between the results of the two methods.\backslashr\backslashnCONCLUSIONS\backslashr\backslashnFor intraoperative problem focussed TEE examinations the acquisition of an additional RT-3D-FV TEE data set allows accurate measurement of most of the recommended chamber and valve quantification parameters.

Authors: A. Ender, S. Eibel, E. Hasheminejad, Markus Scholz, Udo X. Kaisers, Chirojit Mukherjee, Joerg Ender

Date Published: 1st Oct 2012

Publication Type: Journal article

A new evaluation and training system for micro-telemanipulation at the middle ear
Genetical Statistics and Systems Biology

Abstract (Expand)

In this article, a new surgical model for evaluating telemanipulators used in middle ear surgery is presented. The purpose of this work was to develop an evaluation and training system which imitates … a typical surgical task of middle ear surgery and which can easily be repeated in order to get significant result. The abstract task can be performed manually or by means of a microsurgical telemanipulator and guaranties stable experimental conditions between different subjects at any time. As a task the stapedotomy was chosen, due to the high demands in positioning and in applying forces to the delicate structures in the middle ear. The manual and telemanipulated performance of 15 ENT surgeons and 17 medical students was compared using this evaluation and training system. In this article, a new surgical model for evaluating telemanipulators used in middle ear surgery is presented. The purpose of this work was to develop an evaluation and training system which imitates a typical surgical task of middle ear surgery and which can easily be repeated in order to get significant result. The abstract task can be performed manually or by means of a microsurgical telemanipulator and guaranties stable experimental conditions between different subjects at any time. As a task the stapedotomy was chosen, due to the high demands in positioning and in applying forces to the delicate structures in the middle ear. The manual and telemanipulated performance of 15 ENT surgeons and 17 medical students was compared using this evaluation and training system.

Authors: Thomas Maier, Gero Strauss, Markus Scholz, Thomas Berger, Anne Kielhorn, Konrad Entsfellner, Christian Willim, Wolfgang Buscher, Andreas Dietz, Tim C. Lueth

Date Published: 1st Aug 2012

Publication Type: Journal article

Combined effects of different interleukin-28B gene variants on the outcome of dual combination therapy in chronic hepatitis C virus type 1 infection
Genetical Statistics and Systems Biology

Abstract (Expand)

In patients with chronic hepatitis C virus (HCV) infection, several variants of the interleukin-28B (IL28B) gene have been shown to correlate significantly with a sustained virologic response (SVR). … Recent evidence shows that determination of one single IL28B polymorphism, rs12979860, is sufficient for predicting treatment outcome. We examined whether the combined determination of the IL28B single-nucleotide polymorphisms (SNPs), rs12979860, rs8099917, rs12980275, and rs8103142, might improve the prediction of SVR in patients with HCV. In the study cohort, 54% of 942 patients with chronic HCV type 1 infection had SVR. The IL28B SNPs, rs12979860CC and rs8099917TT, correlated significantly with SVR (68% and 62%). The SNPs, rs12980275 and rs8103142, were in strong linkage disequilibrium with rs12979860 and were not included in further analysis. In homozygous carriers of the rs12979860 responder allele C, additional genotyping of the rs8099917 SNP had no effect on response prediction, whereas in carriers of the rs12979860 nonresponder allele, the rs8099917 SNP improved the response prediction. In heterozygous carriers of the rs12979860 nonresponder T allele, SVR rates were 55% in the presence of the rs8099917TT genotype and 40% in patients carrying the rs8099917 TG or GG genotype. Analysis of an independent confirmation cohort of 377 HCV type 1-infected patients verified the significant difference in SVR rates between the combined genotypes, rs12979860CT/rs8099917TT and rs12979860CT/rs8099917TG (38% versus 21%; P = 0.018). Conclusion: Treatment outcome prediction could not be improved in homozygous carriers of the IL28B rs12979860 C responder allele by the additional determination of the rs8099917 SNP. There is evidence that a significant proportion of heterozygous carriers of the rs12979860 T nonresponder allele can profit with respect to SVR prediction by further determination of the rs8099917 SNP. (HEPATOLOGY 2012;55:1700-1710).

Authors: Janett Fischer, Stephan Böhm, Markus Scholz, Tobias Müller, Heiko Witt, Jacob George, Christoph Sarrazin, Simone Susser, Eckart Schott, Vijayaprakash Suppiah, David R. Booth, Graeme J. Stewart, Florian van Bömmel, Annika Brodzinski, Balazs Fülöp, Pascal Migaud, Thomas Berg

Date Published: 1st Jun 2012

Publication Type: Journal article

Detection of novel genomic aberrations in anaplastic astrocytomas by GTG-banding, SKY, locus-specific FISH, and high density SNP-array
Genetical Statistics and Systems Biology

Abstract (Expand)

Astrocytomas represent the largest and most common subgroup of brain tumors. Anaplastic astrocytoma (WHO grade III) may arise from low-grade diffuse astrocytoma (WHO grade II) or as primary tumors … without any precursor lesion. Comprehensive analyses of anaplastic astrocytomas combining both cytogenetic and molecular cytogenetic techniques are rare. Therefore, we analyzed genomic alterations of five anaplastic astrocytomas using high-density single nucleotide polymorphism arrays combined with GTG-banding and FISH-techniques. By cytogenetics, we found 169 structural chromosomal aberrations most frequently involving chromosomes 1, 2, 3, 4, 10, and 12, including two not previously described alterations, a nonreciprocal translocation t(3;11)(p12;q13), and one interstitial chromosomal deletion del(2)(q21q31). Additionally, we detected previously not documented loss of heterozygosity (LOH) without copy number changes in 4/5 anaplastic astrocytomas on chromosome regions 5q11.2, 5q22.1, 6q21, 7q21.11, 7q31.33, 8q11.22, 14q21.1, 17q21.31, and 17q22, suggesting segmental uniparental disomy (UPD), applying high-density single nucleotide polymorphism arrays. UPDs are currently considered to play an important role in the initiation and progression of different malignancies. The significance of previously not described genetic alterations in anaplastic astrocytomas presented here needs to be confirmed in a larger series.

Authors: Heidrun Holland, Peter Ahnert, Ronald Koschny, Holger Kirsten, Manfred Bauer, Ralf Schober, Jürgen Meixensberger, Dominik Fritzsch, Wolfgang Krupp

Date Published: 1st Jun 2012

Publication Type: Journal article

Therapy of chronic myeloid leukaemia can benefit from the activation of stem cells: simulation studies of different treatment combinations
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Newly diagnosed patients with chronic myeloid leukaemia (CML) are currently treated with tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib or dasatinib. However, incomplete …e eradication of residual disease is a general problem of long-term TKI therapy. Activation of mouse haematopoietic stem cells by interferon-\textgreeka (IFN\textgreeka) stimulated the discussion of whether a combination treatment leads to accelerated eradication of the CML clone. METHODS We base our simulation approach on a mathematical model describing human CML as a competition phenomenon between normal and malignant cells. We amend this model to incorporate the description of IFN\textgreeka activity and simulate different scenarios for potential treatment combinations. RESULTS We demonstrate that the overall sensitivity of CML stem cells to IFN\textgreeka activation is a crucial determinant for the benefit of a potential combination therapy. We furthermore show that pulsed IFN\textgreeka together with continuous TKI administration is the most promising strategy for a combination treatment in which the therapeutic benefit prevails adverse side effects. CONCLUSION Our modelling approach is a highly beneficial tool to quantitatively address the competition between normal and leukaemic haematopoiesis in treated CML patients. We derive testable predictions for different experimental settings that are suggested before the clinical implementation of the combination treatment.

Authors: Ingmar Glauche, Katrin Horn, Matthias Horn, Lars Thielecke, M A G Essers, Andreas Trumpp, Ingo Roeder

Date Published: 1st May 2012

Publication Type: Journal article

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