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1.
HNO ; 69(4): 249-255, 2021 Apr.
Article in German | MEDLINE | ID: mdl-33215226

ABSTRACT

BACKGROUND: Etiologically, oropharyngeal squamous cell carcinoma (OPSCC) can be divided into OPSCC caused by noxious agents and human papillomavirus (HPV)-driven carcinoma. These types differ with regard to clinical features and prognosis-differences which are rooted in the underlying molecular biology of the tumor. OBJECTIVE: The aim of this work is to provide an overview of the molecular biological characteristics of the genetics, epigenetics, and immunology of OPSCC. MATERIALS AND METHODS: A literature review was performed on a selection of genetic, epigenetic, and immunological factors characterizing OPSCC. RESULTS: The understanding of genetic aberrations and their consequences for cancerogenesis and tumor biology is increasing. Epigenetic phenomena are complementing functional relationships. However, epigenetic mechanisms of gene regulation are complex and much research is still required in this field. Immunological aspects of cancer molecular biology have moved into the focus in light of recent advances in the field of immunotherapy. CONCLUSION: The tumor biology of OPSCC is primarily defined by its HPV status. Additionally, HPV-independent genetic, epigenetic, and immunological signatures are being defined. From these advances, rationales for new treatment concepts may evolve.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Oropharyngeal Neoplasms , Papillomavirus Infections , Biology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/therapy , Humans , Oropharyngeal Neoplasms/genetics , Oropharyngeal Neoplasms/therapy , Papillomavirus Infections/complications , Papillomavirus Infections/genetics , Prognosis
2.
Histochem Cell Biol ; 151(2): 101-114, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30488339

ABSTRACT

The detailed analysis of secondary envelopment of the Human betaherpesvirus 5/human cytomegalovirus (HCMV) from transmission electron microscopy (TEM) images is an important step towards understanding the mechanisms underlying the formation of infectious virions. As a step towards a software-based quantification of different stages of HCMV virion morphogenesis in TEM, we developed a transfer learning approach based on convolutional neural networks (CNNs) that automatically detects HCMV nucleocapsids in TEM images. In contrast to existing image analysis techniques that require time-consuming manual definition of structural features, our method automatically learns discriminative features from raw images without the need for extensive pre-processing. For this a constantly growing TEM image database of HCMV infected cells was available which is unique regarding image quality and size in the terms of virological EM. From the two investigated types of transfer learning approaches, namely feature extraction and fine-tuning, the latter enabled us to successfully detect HCMV nucleocapsids in TEM images. Our detection method has outperformed some of the existing image analysis methods based on discriminative textural indicators and radial density profiles for virus detection in TEM images. In summary, we could show that the method of transfer learning can be used for an automated detection of viral capsids in TEM images with high specificity using standard computers. This method is highly adaptable and in future could be easily extended to automatically detect and classify virions of other viruses and even distinguish different virion maturation stages.


Subject(s)
Capsid Proteins/analysis , Capsid Proteins/ultrastructure , Herpesviridae/chemistry , Herpesviridae/ultrastructure , Machine Learning , Humans , Microscopy, Electron, Transmission
4.
Leukemia ; 30(11): 2160-2168, 2016 11.
Article in English | MEDLINE | ID: mdl-27137476

ABSTRACT

We evaluated the frequency, genetic architecture, clinico-pathologic features and prognostic impact of RUNX1 mutations in 2439 adult patients with newly-diagnosed acute myeloid leukemia (AML). RUNX1 mutations were found in 245 of 2439 (10%) patients; were almost mutually exclusive of AML with recurrent genetic abnormalities; and they co-occurred with a complex pattern of gene mutations, frequently involving mutations in epigenetic modifiers (ASXL1, IDH2, KMT2A, EZH2), components of the spliceosome complex (SRSF2, SF3B1) and STAG2, PHF6, BCOR. RUNX1 mutations were associated with older age (16-59 years: 8.5%; ⩾60 years: 15.1%), male gender, more immature morphology and secondary AML evolving from myelodysplastic syndrome. In univariable analyses, RUNX1 mutations were associated with inferior event-free (EFS, P<0.0001), relapse-free (RFS, P=0.0007) and overall survival (OS, P<0.0001) in all patients, remaining significant when age was considered. In multivariable analysis, RUNX1 mutations predicted for inferior EFS (P=0.01). The effect of co-mutation varied by partner gene, where patients with the secondary genotypes RUNX1mut/ASXL1mut (OS, P=0.004), RUNX1mut/SRSF2mut (OS, P=0.007) and RUNX1mut/PHF6mut (OS, P=0.03) did significantly worse, whereas patients with the genotype RUNX1mut/IDH2mut (OS, P=0.04) had a better outcome. In conclusion, RUNX1-mutated AML is associated with a complex mutation cluster and is correlated with distinct clinico-pathologic features and inferior prognosis.


Subject(s)
Core Binding Factor Alpha 2 Subunit/genetics , Leukemia, Myeloid, Acute/genetics , Mutation , Adolescent , Age Factors , Disease-Free Survival , Epigenomics , Female , Humans , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Prognosis , Sex Factors , Spliceosomes/genetics , Survival Rate , Young Adult
6.
Med Phys ; 40(10): 102504, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24089925

ABSTRACT

PURPOSE: Calculation of the time-integrated activity coefficient (residence time) is a crucial step in dosimetry for molecular radiotherapy. However, available software is deficient in that it is either not tailored for the use in molecular radiotherapy and/or does not include all required estimation methods. The aim of this work was therefore the development and programming of an algorithm which allows for an objective and reproducible determination of the time-integrated activity coefficient and its standard error. METHODS: The algorithm includes the selection of a set of fitting functions from predefined sums of exponentials and the choice of an error model for the used data. To estimate the values of the adjustable parameters an objective function, depending on the data, the parameters of the error model, the fitting function and (if required and available) Bayesian information, is minimized. To increase reproducibility and user-friendliness the starting values are automatically determined using a combination of curve stripping and random search. Visual inspection, the coefficient of determination, the standard error of the fitted parameters, and the correlation matrix are provided to evaluate the quality of the fit. The functions which are most supported by the data are determined using the corrected Akaike information criterion. The time-integrated activity coefficient is estimated by analytically integrating the fitted functions. Its standard error is determined assuming Gaussian error propagation. The software was implemented using MATLAB. RESULTS: To validate the proper implementation of the objective function and the fit functions, the results of NUKFIT and SAAM numerical, a commercially available software tool, were compared. The automatic search for starting values was successfully tested for reproducibility. The quality criteria applied in conjunction with the Akaike information criterion allowed the selection of suitable functions. Function fit parameters and their standard error estimated by using SAAM numerical and NUKFIT showed differences of <1%. The differences for the time-integrated activity coefficients were also <1% (standard error between 0.4% and 3%). In general, the application of the software is user-friendly and the results are mathematically correct and reproducible. An application of NUKFIT is presented for three different clinical examples. CONCLUSIONS: The software tool with its underlying methodology can be employed to objectively and reproducibly estimate the time integrated activity coefficient and its standard error for most time activity data in molecular radiotherapy.


Subject(s)
Radiotherapy, Computer-Assisted/methods , Software , Time Factors
7.
Neurology ; 78(8): 569-77, 2012 Feb 21.
Article in English | MEDLINE | ID: mdl-22323746

ABSTRACT

OBJECTIVE: DNA damage accumulation in brain is associated with the development of Alzheimer disease (AD), but newly identified protein markers of DNA damage have not been evaluated in the diagnosis of AD and other forms of dementia. METHODS: Here, we analyzed the level of novel biomarkers of DNA damage and telomere dysfunction (chitinase activity, N-acetyl-glucosaminidase activity, stathmin, and EF-1α) in CSF of 94 patients with AD, 41 patients with non-AD dementia, and 40 control patients without dementia. RESULTS: Enzymatic activity of chitinase (chitotriosidase activity) and stathmin protein level were significantly increased in CSF of patients with AD and non-AD dementia compared with that of no dementia control patients. As a single marker, chitinase activity was most powerful for distinguishing patients with AD from no dementia patients with an accuracy of 85.8% using a single threshold. Discrimination was even superior to clinically standard CSF markers that showed an accuracy of 78.4% (ß-amyloid) and 77.6% (tau). Combined analysis of chitinase with other markers increased the accuracy to a maximum of 91%. The biomarkers of DNA damage were also increased in CSF of patients with non-AD dementia compared with no dementia patients, and the new biomarkers improved the diagnosis of non-AD dementia as well as the discrimination of AD from non-AD dementia. CONCLUSIONS: Taken together, the findings in this study provide experimental evidence that DNA damage markers are significantly increased in AD and non-AD dementia. The biomarkers identified outperformed the standard CSF markers for diagnosing AD and non-AD dementia in the cohort investigated.


Subject(s)
Alzheimer Disease/diagnosis , Alzheimer Disease/enzymology , Chitinases/cerebrospinal fluid , Adult , Aged , Aged, 80 and over , Alzheimer Disease/cerebrospinal fluid , Biomarkers/cerebrospinal fluid , DNA Damage/physiology , Dementia/cerebrospinal fluid , Dementia/diagnosis , Dementia/enzymology , Diagnosis, Differential , Female , Hexosaminidases/cerebrospinal fluid , Humans , Male , Middle Aged , Peptide Elongation Factor 1/cerebrospinal fluid , Stathmin/cerebrospinal fluid , Telomere/physiology
8.
Z Gastroenterol ; 48(8): 833-8, 2010 Aug.
Article in German | MEDLINE | ID: mdl-20687020

ABSTRACT

The marginal zone B-cell lymphoma, MALT-type (MZBL, MT) is a low-grade B-cell lymphoma which is predominantly localised in the stomach with a typical morphology and cytogenetic pattern. The coexistence of a diffuse large B-cell lymphoma (DLBCL) with an MZBL, MT in the gastrointestinal tract is defined as a composite lymphoma (ComL) and represents a fascinating model of lymphoma progression. In this review we focus on current aspects regarding the molecular characterisation of MZBL, MT and gastrointestinal DLBCL and their mutual relationships.


Subject(s)
Biomarkers, Tumor/metabolism , Lymphoma, B-Cell, Marginal Zone/metabolism , Lymphoma, B-Cell, Marginal Zone/pathology , Lymphoma, B-Cell/metabolism , Lymphoma, B-Cell/pathology , Neoplasm Proteins/metabolism , Diagnosis, Differential , Humans
9.
Dtsch Med Wochenschr ; 135(34-35): 1656-61, 2010 Aug.
Article in German | MEDLINE | ID: mdl-20721840

ABSTRACT

BACKGROUND AND OBJECTIVE: It was the aim of this study to compare the sensitivity and specificity of low-dose CT colonography (CTC) with that of optical colonoscopy (OC) in asymptomatic patients undergoing these tests in a screening program for colonic cancer. PATIENTS AND METHODS: 58 patients (mean age 62.6 years) were included. They underwent low dose CTC and, immediately afterwards, colonoscopy. The colonoscopists were unaware of the CTC findings. A "second look" was performed if a lesion seen in CTC had been missed in the first colonoscopy. RESULTS: A total of 150 lesions were detected and histologically confirmed. 136 were found to be polypoid lesions, classified as either hyperplastic polyps (n = 66) or polyps with intraepithelial neoplasia (n = 70). In the per-patient analysis only 22.4 % of patients had no polypoid lesion, 27.6 % had at least one hyperplastic and 50.0 % had at least one adenomatous lesion. Sensitivity for adenomas of all size categories was calculated 55.7 % for CTC and 92.9 % for OC. This marked difference (both for the detection of individual lesions and the per-patient analyses) does not reach significance in the two-sided McNemar test. CONCLUSIONS: There was a high prevalence of lesions with intraepithelial neoplasia in this screening group. OC had a higher sensitivity than CTC in the detection of lesions smaller than 10 mm.


Subject(s)
Colonic Polyps/diagnosis , Colonography, Computed Tomographic , Colonoscopy , Colorectal Neoplasms/diagnosis , Mass Screening , Video Recording , Adenoma/diagnosis , Adenoma/epidemiology , Adenoma/pathology , Adenoma/surgery , Aged , Carcinoma in Situ/diagnosis , Carcinoma in Situ/epidemiology , Carcinoma in Situ/pathology , Carcinoma in Situ/surgery , Colonic Polyps/epidemiology , Colonic Polyps/pathology , Colonic Polyps/surgery , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Cross-Sectional Studies , Diagnosis, Differential , Female , Humans , Hyperplasia , Male , Middle Aged , Prospective Studies , Sensitivity and Specificity
10.
Nuklearmedizin ; 46(5): 185-91, 2007.
Article in English | MEDLINE | ID: mdl-17938752

ABSTRACT

AIMS: We compared the intracoronary beta-brachytherapy using a liquid rhenium-188 filled balloon with the slow-release, polymer-based, paclitaxel-eluting Taxus-Express stent for treatment of in-stent restenoses. PATIENTS, METHODS: During the same study period, patients with restenoses in bare-metal stents were either treated with Taxus-Express stents (n = 50) or beta-brachytherapy after successful angioplasty (n = 51). For brachytherapy 30 Gy in 0.5 mm tissue depth were administered. The irradiated segment exceeded the traumatized segment 7.5 mm on both sides. Primary endpoint was the minimal lumen diameter (MLD) at the target lesion at six months follow-up. Angiographic follow-up was available in 78% (n = 79/101) and clinical follow-up in all patients. RESULTS: Baseline parameters did not differ statistically. The Taxus-Express stent resulted in a significantly larger MLD and a significantly lower percent diameter stenosis post intervention compared to beta-brachytherapy, which both maintained until angiographic follow-up (primary endpoint 2.44 +/- 0.74 mm versus 1.73 +/- 0.74 mm, p < 0.0001). Therefore, Taxus-Express stents were associated with a lower angiographic restenosis rate compared with beta-brachytherapy, both for the target lesion (6.1% versus 17.4%) and the total segment (9.1% versus 23.9%). Moreover, use of Taxus-stent was associated with a clinical benefit based on a significantly lower MACE rate compared with beta-brachytherapy (p < 0.05). CONCLUSIONS: Paclitaxel-eluting Taxus-Express stents resulted in superior clinical and angiographic outcomes compared to intracoronary beta-brachytherapy with a liquid (188)Re filled balloon for treatment of restenosis within a bare-metal stent.


Subject(s)
Brachytherapy/methods , Coronary Artery Disease/surgery , Coronary Restenosis/diagnostic imaging , Paclitaxel/therapeutic use , Radioisotopes , Rhenium , Stents/adverse effects , Aged , Coronary Restenosis/prevention & control , Female , Humans , Male , Middle Aged , Radionuclide Imaging
11.
Leukemia ; 21(12): 2463-9, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17728785

ABSTRACT

Primary mediastinal B-cell lymphoma (PMBL) is an aggressive extranodal B-cell non-Hodgkin's lymphoma with specific clinical, histopathological and genomic features. To characterize further the genotype of PMBL, we analyzed 37 tumor samples and PMBL cell lines Med-B1 and Karpas1106P using array-based comparative genomic hybridization (matrix- or array-CGH) to a 2.8k genomic microarray. Due to a higher genomic resolution, we identified altered chromosomal regions in much higher frequencies compared with standard CGH: for example, +9p24 (68%), +2p15 (51%), +7q22 (32%), +9q34 (32%), +11q23 (18%), +12q (30%) and +18q21 (24%). Moreover, previously unknown small interstitial chromosomal low copy number alterations (for example, -6p21, -11q13.3) and a total of 19 DNA amplifications were identified by array-CGH. For 17 chromosomal localizations (10 gains and 7 losses), which were altered in more than 10% of the analyzed cases, we delineated minimal consensus regions based on genomic base pair positions. These regions and selected immunohistochemistries point to candidate genes that are discussed in the context of NF-kappaB transcription activation, human leukocyte antigen class I/II defects, impaired apoptosis and Janus kinase/signal transducer and activator of transcription (JAK/STAT) activation. Our data confirm the genomic uniqueness of this tumor and provide physically mapped genomic regions of interest for focused candidate gene analysis.


Subject(s)
Chromosome Aberrations , Consensus Sequence , Gene Expression Profiling/methods , Lymphoma, B-Cell/genetics , Mediastinal Neoplasms/genetics , Adult , Apoptosis/genetics , Cell Line, Tumor/metabolism , Chromosome Deletion , Female , Gene Amplification , Gene Deletion , Gene Expression Regulation, Neoplastic , Humans , Janus Kinases/genetics , Janus Kinases/metabolism , Lymphoma, B-Cell/pathology , Male , Mediastinal Neoplasms/pathology , Middle Aged , NF-kappa B/metabolism , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , STAT Transcription Factors/genetics , STAT Transcription Factors/metabolism
12.
Clin Res Cardiol ; 96(2): 70-6, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17146605

ABSTRACT

BACKGROUND: The paclitaxel-eluting Taxus-Express stent is superior regarding angiographic and clinical outcome compared with its bare-metal platform for lesions in native coronary arteries. We studied the potential impact of the Taxus-Express stent in comparison with its bare-metal counterpart for treatment of lesions in saphenous vein grafts (SVGs). Furthermore, a meta-analysis was performed regarding use of drug-eluting (DES) vs bare-metal stents (BMS) in SVG lesions. METHODS: We analyzed 13 consecutive patients who underwent percutaneous revascularization in SVG lesions using the slow-release, paclitaxel-eluting Taxus-Express stent. These lesions were balanced with 26 patients with SVG lesions treated with the bare-metal Express stent (BMS) in the preceding period. Angiographic follow-up was performed after 6 months, clinical follow-up after 6 and 12 months. RESULTS: There were no statistically significant differences regarding clinical, procedural and angiographic parameters pre and post intervention. Binary restenoses occurred significantly less in the Taxus group compared with the BMS group (0% vs 34.6%; p=0.016). This translated into a significantly lower occurrence of major adverse cardiac events (death, Q-wave myocardial infarction, repeat target vessel revascularization) in the Taxus group compared with the BMS group at the 6-month (0% vs 26.9%, p=0.039) and 12-month follow-up (7.7% vs 38.5%, p=0.045). Multivariate predictors for freedom of binary restenosis were the reference diameter pre intervention and treatment with Taxus stents. Meta-analysis including 280 DES and 256 BMS patients revealed an odds ratio of 0.34 (95% confidence interval 0.21-0.54) for MACE and 0.26 (95% confidence interval 0.16-0.44) for target vessel revascularizations, both favoring DES. CONCLUSIONS: We conclude that the use of the slow-release Taxus-Express stent has the potential to be superior regarding angiographic and clinical outcome compared with its bare-metal counterpart for treatment of SVG lesions within a 12-month follow-up. A large, randomized trial including a long follow-up period is now required to prove the results of the meta-analysis.


Subject(s)
Coronary Restenosis/therapy , Graft Occlusion, Vascular/drug therapy , Paclitaxel/administration & dosage , Saphenous Vein/transplantation , Stents , Aged , Angioplasty, Balloon, Coronary , Coronary Angiography , Coronary Restenosis/diagnostic imaging , Drug Delivery Systems , Female , Follow-Up Studies , Graft Occlusion, Vascular/diagnostic imaging , Graft Occlusion, Vascular/etiology , Humans , Male , Metals , Odds Ratio , Treatment Outcome , Tubulin Modulators/administration & dosage
13.
J Pathol ; 211(3): 305-13, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17152084

ABSTRACT

The pathogenetic relationship of marginal zone B-cell lymphoma (MALT lymphoma) of the gastrointestinal (GI) tract and eventually co-existing aggressive B-cell lymphoma and primary aggressive B-cell lymphoma remains to be elucidated. The RNA of laser-microdissected cells was isolated and amplified from small and/or large cell compartments of eight MALT lymphomas (small cell lymphoma, SCL), 14 GI diffuse large B-cell lymphomas (large cell lymphoma, LCL), and ten GI B-cell lymphomas with composite small and large cell compartments (ComL) and expression analyses were performed using cDNA arrays. Hierarchical cluster analysis clearly separated SCL and LCL and the small and large cell compartments of ComL. Likewise, cluster analysis with all samples of SCL, LCL, and ComL yielded two main 'small cell' and 'large cell' branches. Furthermore, 60 genes were differentially expressed between SCL and LCL, and 82 genes between the small and large cell components of ComL; 26 genes were discriminators in both settings. Use of the profiles of ComL as training sets for class prediction resulted in 95% accuracy for the classification of SCL and LCL. Collectively, the data strongly suggest that both secondary and primary aggressive B-cell lymphomas of the GI tract are blastic marginal zone lymphomas.


Subject(s)
Gastrointestinal Neoplasms/genetics , Gene Expression Profiling , Lymphoma, B-Cell/genetics , Lymphoma, Large B-Cell, Diffuse/genetics , Oligonucleotide Array Sequence Analysis , Transcription, Genetic , Gastrointestinal Neoplasms/pathology , Genetic Markers , Humans , Immunohistochemistry/methods , In Situ Hybridization, Fluorescence , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Lymphoma, B-Cell/pathology , Lymphoma, Large B-Cell, Diffuse/pathology , Reverse Transcriptase Polymerase Chain Reaction
14.
Med Biol Eng Comput ; 42(6): 733-9, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15587463

ABSTRACT

Axillary lymph node status is a major prognostic factor in mammary carcinoma. It is clinically desirable to predict the axillary lymph node status from data from the mammary cancer specimen. In the study, the axillary lymph node status, routine histological parameters and flow-cytometric data were retrospectively obtained from 1139 specimens of invasive mammary cancer. The ten variables: age, tumour type, tumour grade, tumour size, skin infiltration, lymphangiosis carcinomatosa, pT4 category, percentage of tumour cells in G2/M- and S-phases of the cell cycle, and ploidy index were considered as predictor variables, and the single variable lymph node metastasis pN (0 for pN0, or 1 for pN1 or pN2) was used as an output variable. A stepwise logistic regression analysis, with the axillary lymph node as a dependent variable, was used for feature selection. Only lymphangiosis carcinomatosa and tumour size proved to be significant as independent predictor variables; the other variables were non-contributory. Three paradigms with supervised learning rules (multilayer perceptron, learning vector quantisation and support vector machines) were used for the purpose of prediction. If any of these paradigms was used with the information from all ten input variables, 73% of cases could be correctly predicted, with specificity ranging from 82 to 84% and sensitivity ranging from 60 to 63%. If only the two significant input variables were used, lymphangiosis carcinomatosa and tumour diameter, the prediction accuracy was no worse. Nearly identical results were obtained by two different techniques of cross-validation (leave-one-out against ten-fold cross validation). It was concluded that: artificial neural networks can be used for risk stratification on the basis of routine data in individual cases of mammary cancer; and lymphangiosis carcinomatosa and tumour size are independent predictors of axillary lymph node metastasis in mammary cancer.


Subject(s)
Breast Neoplasms/pathology , Flow Cytometry/methods , Algorithms , Axilla , Female , Humans , Lymphatic Metastasis/pathology , Neoplasm Invasiveness , Neural Networks, Computer , Ploidies , Predictive Value of Tests , Prognosis , Regression Analysis , Retrospective Studies
15.
Z Kardiol ; 93(9): 686-95, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15365736

ABSTRACT

UNLABELLED: Ejection fraction (EF) and end-diastolic and end-systolic volume index (EDVI/ ESVI) derived from ventriculography are important prognostic parameters. Cine magnetic resonance imaging (MRI) using a steady-state, free-precession sequence (SSFP) offers excellent delineation of the endocardial borders and highly reproducible and accurate results for cardiac volumes. We evaluated MRI volumetry against routine x-ray ventriculography. In 200 patients EF, EDVI and ESVI were measured with MRI volumetry and x-ray ventriculography. The same MRI protocol was applied to 102 healthy persons in order to establish reference values. In healthy subjects mean EF was 68.8% +/- 5.4% (range 59-84%), mean EDVI 69 +/- 10 (43-90) and mean ESVI 22 +/- 5.8 (10-35 ml). In the patients, overall correlation (Spearman's R) of MRI with ventriculography was 0.86 for EF, 0.77 for EDVI and 0.88 for ESVI. For postextrasystolic beats (38% of the measurements), R was 0.73/0.65/0.73 for EF/EDVI/ESVI. MRI correlated best with biplane ventriculography during sinus rhythm (0.96/0.85/0.93); the worst correlation (0.78/0.81/0.83) resulted from patients with wall motion abnormalities in comparison to monoplane x-ray ventriculography. CONCLUSION: Contemporary MRI volumetry compares well to invasive data obtained under optimal conditions. In view of the known limitations of single plane ventriculography, MRI seems to allow exact volumetry independent from regional wall motion abnormalities.


Subject(s)
Magnetic Resonance Imaging, Cine/methods , Ventricular Function, Left , Cardiac Catheterization , Electrocardiography , Heart Ventricles/diagnostic imaging , Humans , Image Processing, Computer-Assisted , Models, Cardiovascular , Observer Variation , Radiography , Reference Values , Ventricular Function, Left/physiology
16.
Urologe A ; 43(6): 669-74, 2004 Jun.
Article in German | MEDLINE | ID: mdl-15112041

ABSTRACT

Data emerging from DNA microarray experiments are usually difficult to interpret. While the level of expression of several thousand genes can be measured in a single experiment, only a few dozen experiments are normally carried out, leading to data sets of very high dimensionality and low cardinality. The computational analysis of gene expression data makes significant usage of machine learning and statistical methods. Nevertheless, caution should be used in the blind adoption of these methods, as this usually leads to an over-interpretation of the expression profiles. The following presentation provides an overview of up-to-date principles of biostatistical analysis. A potential application for the analysis of high-dimensional expression profiles of prostate cancer is given.


Subject(s)
Chromosome Aberrations , Computational Biology , Oligonucleotide Array Sequence Analysis , Prostatic Neoplasms/genetics , Expert Systems , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/physiology , Humans , Male , Neural Networks, Computer , Prognosis , Prostate/pathology , Prostatic Neoplasms/pathology
17.
BJU Int ; 93(3): 284-90, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14764124

ABSTRACT

OBJECTIVE: To identify significant predictive factors determining category T1a and T1b in incidental prostatic carcinoma with classical and neural multivariate data analysis methods. MATERIALS AND METHODS: Incidental prostatic carcinomas diagnosed in our department during 1990-99 (66 cases) were re-examined. Besides acquiring routine clinical and pathological data the tumours were assessed by scoring immunohistochemistry for proliferative activity and p53-overexpression. Tumour vascularization (angiogenesis) and epithelial texture variables were investigated by quantitative stereology. The data were evaluated by classical statistical methods (t-test, correlation analysis, logistic regression). Moreover, self-organizing feature maps (SOMs) were applied as an exploratory approach to unsupervised data analysis by artificial neural networks. RESULTS: The proliferative fraction, p53 overexpression of tumour cell nuclei, preoperative prostate-specific antigen value and density of capillary vascularization correlated with the Gleason score in incidental prostatic carcinoma. In a stepwise logistic regression analysis with the tumour categories T1a and T1b as dependent variables, the Gleason score and the volume fraction of epithelial cells were significant independent predictors of the tumour category. The cases could be grouped into clusters of different degrees of malignancy using SOMs. CONCLUSIONS: Texture variables of tumour cells are of central importance for the extent of propagation in the prostate in incidental prostatic adenocarcinomas. Gleason score and quantitative stereological estimates of the volume fraction of tumour cells are significant predictors of T1a and T1b categories of incidental prostatic carcinoma. Unsupervised clustering of T1 prostate carcinoma cases by SOMs correlates well with the dichotomous classification into T1a and T1b according to the UICC.


Subject(s)
Prostatic Neoplasms/pathology , Aged , Humans , Image Processing, Computer-Assisted , Immunohistochemistry , Incidental Findings , Male , Neural Networks, Computer , Predictive Value of Tests , Prostatic Neoplasms/blood supply , Regression Analysis , Sensitivity and Specificity , Tumor Suppressor Protein p53/metabolism
18.
Dtsch Med Wochenschr ; 128(24): 1333-7, 2003 Jun 13.
Article in German | MEDLINE | ID: mdl-12802741

ABSTRACT

BACKGROUND AND OBJECTIVE: In-vitro studies revealed that nitric oxide (NO) may affect rheological parameters. We studied the effect of highly-dosed NO-donor molsidomine on blood rheology and the impact of rheological parameters on the incidence of severe cardiovascular events. PATIENTS AND METHODS: In this randomized, placebo-controlled and double-blind trial 166 patients (60 +/- 10 years) with stable angina pectoris and coronary intervention received molsidomine 3 x 8 mg t. i. d. (controlled release tablets) or placebo for 6 months. Patients with inflammatory/neoplastic disorders or elevated values of C-reactive protein were excluded from analysis. A rheological profile (plasma viscosity, blood viscosity, aggregation and flexibility of erythrocytes, filtrability of leukocytes, fibrinogen levels) was done initially and after 6 months. Adverse cardiovascular events (death, myocardial infarction, stroke, coronary/peripheral revascularization) were recorded during 12 months. Furthermore, the impact of rheological parameters regarding the occurrence of severe cardiovascular events (death, myocardial infarction, stroke) was evaluated during a follow-up of median 38 months. RESULTS: The data of 137 patients (n = 71 placebo, n = 66 molsidomine) were analysed. The difference of rheological parameters between the two measurements did not vary between the two groups. Analysis of event-free survival with Kaplan-Meier technique revealed no difference between the two groups. Multivariate Cox regression analysis with adjustment for diabetes mellitus, smoking and therapy with statin showed a significant association of fibrinogen and plasma viscosity with the occurrence of severe cardiovascular events. CONCLUSION: Treatment with molsidomine 3 x 8 mg/day for 6 months does not improve blood rheology or reduce cardiovascular events. But elevated levels of fibrinogen and plasma viscosity were associated with the occurrence of severe cardiovascular events.


Subject(s)
Blood Viscosity/drug effects , Cardiovascular Diseases/prevention & control , Fibrinogen/analysis , Molsidomine/therapeutic use , Vasodilator Agents/therapeutic use , Cardiovascular Diseases/blood , Cardiovascular Diseases/epidemiology , Delayed-Action Preparations , Double-Blind Method , Erythrocyte Aggregation/drug effects , Erythrocyte Deformability/drug effects , Female , Fibrinogen/drug effects , Humans , Incidence , Leukocytes/cytology , Leukocytes/drug effects , Logistic Models , Male , Middle Aged , Molsidomine/administration & dosage , Molsidomine/pharmacology , Rheology/drug effects , Survival Analysis , Vasodilator Agents/administration & dosage , Vasodilator Agents/pharmacology
19.
Ann Hematol ; 82(6): 323-32, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12719886

ABSTRACT

Recently, DNA microarray technology has opened new avenues for the understanding of lymphomas. By hybridization of cDNA to arrays containing >10,000 different DNA fragments, this approach allows the simultaneous evaluation of the mRNA expression of thousands of genes in a single experiment. Using sophisticated bioinformatic tools, the huge amount of raw data can be clustered resulting in (1) tumor subclassification, (2) identification of pathogenetically relevant genes, or (3) biological predictors for the clinical course. This approach already has provided novel insights into different entities of B-cell non-Hodgkin's lymphomas. Genomic DNA chip hybridization (matrix-CGH) is a complementary approach focussing on genomic aberrations. In this review, we discuss the impact of this new technology both with regard to methodological aspects as well as to novel findings influencing our understanding of lymphomas.


Subject(s)
Lymphoma/genetics , Oligonucleotide Array Sequence Analysis/methods , Gene Expression Profiling/methods , Humans , Lymphoma, Non-Hodgkin/genetics
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